@article {pmid40065797, year = {2025}, author = {Jayabalan, D and Donaghy, M and Charlesworth, C and Fysh, E and Lee, YCG}, title = {Miliary Mesothelioma.}, journal = {Respirology case reports}, volume = {13}, number = {3}, pages = {e70141}, doi = {10.1002/rcr2.70141}, pmid = {40065797}, issn = {2051-3380}, abstract = {Miliary spread of mesothelioma is a rare but important manifestation of late-stage disease, likely due to hematogenous dissemination. This case highlights characteristic CT imaging findings, emphasizing the need for awareness among clinicians and radiologists. Recognizing this pattern can aid in diagnosis, prognostication, and appropriate referral for palliative management.}, }
@article {pmid40061543, year = {2025}, author = {Barreto, I and Franckenberg, S and Frauenfelder, T and Opitz, I and Lauk, O}, title = {Potential advantage of magnetic resonance imaging in detecting thoracic wall infiltration in pleural mesothelioma: A retrospective single-center analysis.}, journal = {JTCVS open}, volume = {23}, number = {}, pages = {318-325}, pmid = {40061543}, issn = {2666-2736}, abstract = {OBJECTIVES: Thoracic wall infiltration in pleural mesothelioma determines the extent of resection and can be an important prognostic factor. Currently, standardized imaging for restaging after neoadjuvant systemic therapy comprises contrast-enhanced computed tomography or positron emission tomography. Additional thoracic magnetic resonance imaging could better discriminate chest wall infiltration preoperatively and increase staging accuracy. For this reason, the added benefit of magnetic resonance imaging was evaluated at our center.<br><br>METHODS: A retrospective analysis of the extended imaging protocol was performed from July 2018 to March 2024, including a descriptive analysis for the patient's sex, age, tobacco consumption, asbestos exposure, histological subtype, TNM stage, Modified Response Evaluation Criteria for Solid Tumors in solid tumors, and number of neoadjuvant therapy cycles. Preoperative restaging included routine imaging and magnetic resonance imaging. After histological diagnosis of pleural mesothelioma, neoadjuvant therapy was conducted, followed by intended macroscopic complete resection, with intraoperative biopsies of suspicious chest wall lesions. Computed tomography and magnetic resonance imaging results were compared with intraoperative biopsies.<br><br>RESULTS: Twenty-six patients (mean age, 65.50&#xa0;years, 11.50% female) with operable pleural mesothelioma were included. Of the 11 patients with histologically proven chest wall infiltration, 10 (90.91%) had a cT-stage 3 or greater and 4 (36.36%) underwent surgery that resulted in an R2 resection. Thoracic magnetic resonance imaging showed a high sensitivity (90.91%) for the detection of chest wall infiltration, especially when compared with the computed tomography scan (9.09%).<br><br>CONCLUSIONS: With the adjunctive use of magnetic resonance imaging, we demonstrated a higher sensitivity for detection of chest wall infiltration compared with conventional imaging before surgery. This may improve patient selection for surgery. Nevertheless, larger studies are required to confirm these results.}, }
@article {pmid40056733, year = {2025}, author = {Kinoshita, R and Takeda, N and Kiyotoshi, H and Sugihara, M and Kuriyama, M and Nakao, M and Tsuyuki, T and Muramatsu, H}, title = {Sarcomatoid pleural mesothelioma evaluated using diffusion-weighted whole-body imaging with background body signal suppression.}, journal = {Respiratory investigation}, volume = {63}, number = {3}, pages = {323-325}, doi = {10.1016/j.resinv.2025.02.013}, pmid = {40056733}, issn = {2212-5353}, abstract = {An 83-year-old man with a history of asbestos exposure presented with dyspnea. Thoracic computed tomography showed right-sided pleural effusion and heterogeneous pleural thickening with calcified plaques. Thoracentesis revealed exudative fluid, and the cytology results were negative for malignancy. He didn't want to undergo invasive biopsy for pathological diagnosis. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) detected signal enhancement in the pleural thickening, ruling out metastasis. The patient died after one month, and sarcomatoid pleural mesothelioma was confirmed by autopsy. DWIBS is free of radioactive materials and can be used to evaluate lesion spread and metastases in hospitals equipped with magnetic resonance imaging.}, }
@article {pmid40036898, year = {2025}, author = {DeBono, NL and Everest, L and Richardson, DB and Berriault, C and Yeo, RE and Meeds, MA and Arrandale, V and Demers, PA}, title = {Impact of Interventions to Prevent Asbestos-Related Respiratory Disease in an Exposed Worker Registry Using a Simplified G-computation.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwaf040}, pmid = {40036898}, issn = {1476-6256}, abstract = {The Ontario Asbestos Workers Registry is a regulatory exposure registry obligating employers to report the number of work hours with asbestos containing materials for each of their workers. Currently, each worker is notified of the need for a medical examination once they have accrued 2,000 reported hours of work with asbestos. We sought to evaluate the impact on disease prevention of alternative policies limiting asbestos work hours among registry participants. A cohort of 26,164 asbestos workers were followed for cancer and non-malignant disease diagnoses between 1986 and 2019. Analyses of the association between cumulative asbestos work hours and respiratory disease incidence rates showed substantially elevated disease rates well before reaching 2,000 asbestos work hours. Using a simplified application of parametric G-computation (G-POSH), limiting cumulative asbestos work hours to 100 hours would have prevented 76 asbestosis, 36 pulmonary fibrosis, 27 mesothelioma, and 79 lung cancer cases at the end of follow-up compared to the observed risk in the cohort. Limiting exposure to 2,000 asbestos work hours had a smaller but still substantial impact on disease prevention, particularly among workers in the construction industry. Regulatory agencies should intervene sooner to prevent respiratory disease among workers in the registry.}, }
@article {pmid40034201, year = {2025}, author = {Takano, T and Sato, S and Ito, I and Yamamoto, M and Tsukioka, K and Matsumura, Y and Kono, T}, title = {Rare Metastatic Mesothelioma Occupying Intra-Atrial Cavity, Released by an Emergency Surgery: A Case Report and Literature Review.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {40034201}, issn = {2198-7793}, abstract = {INTRODUCTION: Cardiac surgery for cardiovascular-associated mesothelioma has a poor prognosis. However, life-saving surgery is unavoidable to maintain circulation. This report describes a case in which metastatic intracardiac mesothelioma triggered sudden respiratory failure, which was reduced by surgical resection.<br><br>CASE PRESENTATION: An 81-year-old man with a history of asbestos exposure presented to our hospital with sudden onset of dyspnea. Prior to this event, the pleura was involved in an epithelial malignancy, which was immunohistochemically negatively stained with anti-D2-40, WT-1, or anti-calretinin antibodies, which are positive markers of mesothelioma. Transthoracic echocardiography revealed a fragile and mobile tumor occupying the right atrium, and the patient was admitted for surgical tumorectomy. The operation was performed urgently using a cardiopulmonary bypass via a full sternotomy. The pericardium is grossly intact and does not adhere to the heart. A 3 &#xd7; 5 cm tumor was tightly attached to the right atrium and was large enough to fit into the tricuspid valve. Therefore, the entire margin of the tumor stem attachment was resected from the lateral wall of the right atrium. Although the resected tumor was not positive for any of the three histopathological markers of mesothelioma, CDKN2A co-deletion revealed by fluorescence in situ hybridization led to a diagnosis of malignant mesothelioma.<br><br>CONCLUSIONS: Surgical removal of intracardiac tumors that cause circulatory and respiratory instability is essential for the prevention of sudden death, regardless of prognostic determinants. This case demonstrates that mesotheliomas can metastasize to the endocardium. Even when nuclear atypia and negative results for immunohistochemical tests for the three mesothelioma markers suggest carcinoma, mesothelioma should still be considered and p16/CDKN2A co-deletion should be evaluated.}, }
@article {pmid40017229, year = {2025}, author = {Prabhakaran, S and Hocking, AJ and Irani, Y and Hussey, M and Alexeyenko, A and Dobra, K and Micsik, T and Duhig, E and Walts, AE and Vanwalleghem, L and Chhut, V and Roden, AC and Roggli, VL and Hertoghs, M and Galateau-Salle, F and Brcic, L and Moffat, D and Klebe, S}, title = {An Evaluation Into the Robustness of Grading of Pleural Mesothelioma Outside of Specialist Centres.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {133}, number = {3}, pages = {e70006}, pmid = {40017229}, issn = {1600-0463}, support = {//Flinders University/ ; }, mesh = {Humans ; *Pleural Neoplasms/pathology/diagnosis ; *Neoplasm Grading ; *Mesothelioma/pathology/diagnosis ; Male ; Female ; Middle Aged ; Mesothelioma, Malignant/pathology/diagnosis ; Pathologists ; Aged ; Surveys and Questionnaires ; Prognosis ; Necrosis ; }, abstract = {The 2021 WHO classification of thoracic tumours recommends grading pleural mesothelioma to aid prognostication. Robustness of grading and morphological characterisation is key to its clinical utility, though validation of this grading system has largely been conducted by expert thoracic pathologists. We conducted a survey inviting pathologists across a range of practices and expertise to grade digitised images of 50 epithelioid pleural mesotheliomas that had been graded by an expert in thoracic pathology. We included slides that were considered potentially problematic such as small biopsies, focal necrosis, and rare subtypes that may affect grading (small cell and deciduoid features). Using the Sectra Uniview web viewer, participants were asked to score atypia, mitotic count, and necrosis and choose from a list of cytological and architectural features. Seventy-four pathologists anonymously participated. There was 90% agreement of consensus scores with expert opinion using the WHO 2-tier grade and 72% for the 3-tier nuclear grade but only 70% for nuclear atypia, 56% for mitoses, and 84% for necrosis. Both 3-tier nuclear grade and WHO 2-tier grading systems were significantly associated with survival. Our study affirms the overall robustness and utility of grading for pleural mesothelioma, reveals variances, and suggests the need for dedicated training.}, }
@article {pmid40009063, year = {2025}, author = {Brew, DW and Stevens, ME and Langer, AM and Paustenbach, DJ}, title = {A risk assessment of mechanics who changed chrysotile asbestos containing brakes and other vehicle components in the 1950s-early 2000s era: an update on the 2004 evaluation.}, journal = {Critical reviews in toxicology}, volume = {}, number = {}, pages = {1-50}, doi = {10.1080/10408444.2024.2427222}, pmid = {40009063}, issn = {1547-6898}, abstract = {For the past 50 years, there has been an ongoing interest in understanding the potential health hazards, if any, to vehicle mechanics who worked with asbestos-containing brakes in the 1950s-early 2000s era. Two reviews have been published on this topic, one by Langer (2003) ("Reduction of the biological potential of chrysotile asbestos arising from conditions of service on brake pads") and another by Paustenbach, et al. (2004) ("Environmental and occupational health hazards associated with the presence of asbestos in brake linings and pads (1900 to present): a 'state-of-the-art' review"). This analysis is an update on those papers since a considerable amount of research has been published over the past 20 years on this topic. The following important aspects are addressed in this review: new information on the toxicology of chrysotile, toxicology studies of brake dust associated with grinding, additional epidemiology studies and meta-analyses published on auto mechanics of the era, previously unfound data on how brakes (during the era when chrysotile was used) were manufactured, and new work describing the transformation of chrysotile to various degradation products during vehicle braking. This update also addresses questions about the health hazards associated with asbestos in vehicle clutches, transmissions, and gaskets. The exposure data indicate that the airborne concentrations of chrysotile fibers associated with vehicle mechanic work when asbestos was in auto brakes were, on average, less than 0.04 f/cm[3] (8-h TWA) and the average lifetime cumulative dose was in the vicinity of 0.5-3 f/cm[3]-year for mechanics of that era. Although many of these fibers may have no toxicity due to thermal degradation and the conversion to degradation products, 31 epidemiology studies have evaluated the risks of mesothelioma for vehicle mechanics of this era and all but one indicate that there was no increased incidence of this disease in these workers. The weight of evidence continues to indicate that the asbestos-related health risks to vehicle mechanics from asbestos-containing components were de minimis. The risks associated with take-home and bystander exposure of a mechanic were also addressed and they were found to pose a de minimis or zero health risk to those potentially exposed. Based on our evaluation, there is no indication that asbestos from asbestiform tremolite was present at detectable concentrations in bulk samples of brakes or in the air during brake work. The recent U.S. Environmental Protection Agency (EPA) risk assessment of 2024 on chrysotile and their views of the hazards of asbestos-containing brakes were discussed. Their analyses did not alter our views that exposures to mechanics posed no increased risk of asbestos related disease. The latest knowledge about the role of genetic susceptibility on the development of mesothelioma is also addressed.}, }
@article {pmid40006597, year = {2025}, author = {Stebletsova, IA and Larin, AA and Matnurov, EM and Ananyev, IV and Babak, MV and Fershtat, LL}, title = {Exploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma.}, journal = {Pharmaceutics}, volume = {17}, number = {2}, pages = {}, doi = {10.3390/pharmaceutics17020230}, pmid = {40006597}, issn = {1999-4923}, support = {9211315//Pneumoconiosis Compensation Fund Board of Hong Kong/ ; 19-73-20074-P//Russian Science Foundation/ ; }, abstract = {Background: Nitric oxide (NO) has been linked to the pathogenesis of asbestos-related pleural diseases, including an extremely aggressive cancer called malignant pleural mesothelioma (MPM). Given that MPM cells are characterized by a higher expression of NO synthases and elevated NO production relative to normal cells, the use of NO-donor compounds could potentially saturate the cancerous cells with NO, triggering their death. Methods: We developed a novel class of NO prodrugs by merging two NO-releasing components, 1,2,5-oxadiazole 2-oxides (furoxans) and 1,2,4-oxadiazoles, and studied their NO-releasing characteristics in a time-dependent manner using the Griess assay. The cytotoxicity against two human MPM cell lines and non-cancerous lung fibroblasts was evaluated using a colorimetric MTT assay. Results: All compounds exhibited excellent NO-donating properties, surpassing the capacity of two reference NO donor compounds, 3-carbamoyl-4-(hydroxymethyl)furoxan (CAS-1609) and 4-ethoxy-3-phenylsulphonylfuroxan (CHF-2363), by at least 1.5-3 times. All oxadiazole hybrids demonstrated high cytotoxicity against MPM cell lines in a low micromolar range, comparable or higher than the cytotoxicity of the standard-of-care drug cisplatin. Conclusions: Notably, the novel compounds displayed a markedly greater selectivity towards cancerous cells than cisplatin when compared with non-cancerous lung fibroblasts, aligning with the intended design.}, }
@article {pmid40003441, year = {2025}, author = {Singh, R and Fitzgerald, S and Dada, R and Frank, AL}, title = {Marble Waste Dump Yard in Rajasthan, India Revealed as a Potential Asbestos Exposure Hazard.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, doi = {10.3390/ijerph22020215}, pmid = {40003441}, issn = {1660-4601}, mesh = {India ; *Asbestos/analysis ; Humans ; Environmental Exposure ; Waste Disposal Facilities ; Asbestos, Amphibole/analysis/toxicity ; Dust/analysis ; }, abstract = {Asbestos is a fibrous variety of certain minerals, some of which occur naturally as an accessory to a wide variety of mineral resources. Although asbestos itself has been historically mined for various useful properties, the negative health effects of asbestos dust have greatly diminished it as a useful earth material, as many countries have banned the use of these fibrous minerals based on those health concerns. Resulting regulations of asbestos have focused primarily on intentionally mined material used in product manufacturing, such as building materials made with beneficiated asbestos and their derivative exposures, e.g., airborne asbestos in schools with asbestos-containing materials. The hazards of asbestos as unintended byproducts have not been as extensively considered, although this "contamination" has been repeatedly observed in common earth materials including talc, vermiculite, sand, and gravel. This study reveals such contamination of ornamental and dimension stone commonly referred to as "marble". Asbestos types that can be associated with certain Indian marble reserves include asbestiform tremolite, actinolite, anthophyllite, and chrysotile asbestos. This case reveals such contamination in a marble reserve in Rajsamand, Rajasthan. At this location, marble dust in slurry is disposed at waste collection points, unfortunately including a location now open to the public that has become a tourist destination. Using Transmission Electron Microscopy (TEM) in this study, dust from this location revealed abundant tremolite asbestos fibres in the disaggregated dust. This poses potential health risks to the workers, bystanders, and tourists that may be exposed to this recognized carcinogen, a known cause of mesothelioma, lung cancer, and other asbestos-related diseases.}, }
@article {pmid40002287, year = {2025}, author = {Suraya, R and Nagano, T and Tachihara, M}, title = {Recent Advances in Mesothelioma Treatment: Immunotherapy, Advanced Cell Therapy, and Other Innovative Therapeutic Modalities.}, journal = {Cancers}, volume = {17}, number = {4}, pages = {}, doi = {10.3390/cancers17040694}, pmid = {40002287}, issn = {2072-6694}, abstract = {Mesothelioma is a highly malignant condition arising from the pleura and peritoneum that is closely related to asbestos exposure. The prognosis for this condition has traditionally been poor due to the difficulty physicians have faced in diagnosing and treating this disease, even in its early phase. Fortunately, recent advances in both the molecular understanding of the development of this disease and innovative and novel treatment modalities have accelerated the discovery of new ways to treat mesothelioma. In this review, we first summarize the mechanism of mesothelioma pathophysiology and then relate it to emerging treatment modalities. These include immunotherapy or immune checkpoint inhibitors (ICIs), molecular targeted therapies, and cell-based therapies (such as CAR-T cells or dendritic cells). The scientific basis for the utilization of these treatment modalities, alongside the current clinical evidence for each option, will be explored in detail later on. The hope is that this review can elucidate how these emerging therapeutic options work clinically to help accelerate further developments in novel mesothelioma treatment modalities.}, }
@article {pmid39989419, year = {2025}, author = {Angelini, A and Ricci, P and Mirabelli, D}, title = {[Risk apportionment to remote and recent asbestos exposures for pleural mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {49}, number = {1}, pages = {In press}, doi = {10.19191/EP25.1.A762.002}, pmid = {39989419}, issn = {1120-9763}, mesh = {Humans ; *Asbestos ; *Mesothelioma/epidemiology/etiology ; *Pleural Neoplasms/epidemiology/etiology ; *Occupational Exposure/adverse effects ; Italy/epidemiology ; *Occupational Diseases/epidemiology/etiology ; Incidence ; Risk Assessment ; Middle Aged ; Time Factors ; Adult ; Male ; Aged ; Lung Neoplasms/epidemiology/etiology ; Female ; Aged, 80 and over ; }, abstract = {BACKGROUND: the exposure-response relationship between pleural mesothelioma and asbestos has been traditionally described by models that predicted incidence to increase indefinitely by latency. Studies with long observation showed that the increase flattens out beyond 40 years of latency. It has been, therefore, proposed to introduce an exponential decay function into the models Objectives: to show characteristics and implications as to the relevance of remote and recent exposures, by conducting a simulation exercise based on data available from the literature.<br><br>METHODS: the traditional and decay models that best fit mortality from pleural cancer during the initial 40 years of observation in the Italian pooled cohort of asbestos workers were selected. The mesothelioma incidence predicted by such models as a function of age at first exposure, exposure duration, and age at risk was compared. It was also compared the proportional weight assigned to remote, intermediate, and recent exposure, by dividing the whole exposure period in three parts of equal duration.<br><br>RESULTS: the decay, but not the traditional, model fits well the trend observed after 40 years. According to the traditional model, remote exposures have maximum and recent exposures minimum weight: for instance, following an exposure starting at age 20 and lasting 18 years, the incidence at age 80 would be attributed to remote exposures by 47% and by 21% to the recent ones. The decay model predicts only minor differences and even of reversed weight: 34% and 31%, respectively, in this case.<br><br>CONCLUSIONS: remote exposures do not necessarily have overwhelming weight in determining pleural mesothelioma risk. The balance between different exposure periods depends on the time-distribution of exposure.}, }
@article {pmid39984959, year = {2025}, author = {Piccioni, M and Di Meo, F and Valentino, A and Campani, V and Arigoni, M and Tanori, M and Mancuso, M and Cuciniello, R and Tomasetti, M and Monaco, F and Goteri, G and Spugnini, EP and Calogero, RA and De Rosa, G and Peluso, G and Baldi, A and Crispi, S}, title = {miRNA-503 inhibition exerts anticancer effects and reduces tumor growth in mesothelioma.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {44}, number = {1}, pages = {65}, pmid = {39984959}, issn = {1756-9966}, support = {PNRR P2022RLH39//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; P2022RZ8WM//Ministero dell'Universit&#xe0; e della Ricerca/ ; G46C2000000009//Regione Basilicata/ ; F/180022/04/X43//Ministero dello Sviluppo Economico/ ; DBA.AD005.225//Consiglio Nazionale delle Ricerche/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare and aggressive form of cancer that affects the mesothelial surfaces, associated with exposure to asbestos fibres. To date, no cure is available for MM and therapeutically approved treatments are based on the use of platinum compounds often used in combination with other drugs. We have previously analysed the efficacy of a cisplatin/piroxicam (CDDP/P) combined treatment showing that this treatment was able to reduce in vivo tumor growth. Several studies reported that platinum-drug sensitivity in cancer is connected to modulation of the expression of non-coding RNAs. In this study we analysed if the CDDP/P treatment was able to modulate miRNAs expression in MM.<br><br>METHODS: miRNA sequencing performed on MSTO-211&#xa0;H cells treated with CDDP with CDDP/P led us to identify miRNA-503 - downregulated by CDDP/P - as a novel miRNA that acts as an oncomiR in MM. The effect of miRNA-503 inhibition was evaluated in vitro in mesothelioma cells analysing apoptosis induction and reduction of cancer properties. Inhibition of miR-503 expression in vivo, was analysed in ectopic mouse model of MM by using LNP encapsulating anti-mir-503 and miR-503 expression was evaluated in human MM samples.<br><br>RESULTS: In vitro and in vivo analysis confirmed miR-503 acts as oncogene in MM since its inhibition was able to reduce cell cancer properties and tumor growth in ectopic mouse model of MM. Its expression was found upregulated in human MM patients compared to normal pleura. Bioinformatic analysis indicated BTG1, CCNG1, EDG1, and TIMP2 as putative target genes of miRNA-503. These genes showed an opposite expression compared to miR-503 levels both in cells and in MM samples. Finally, microarray analysis indicated that miR-503 inhibition affected the expression of the well-known MM biomarkers: CXCL8, SERPINE1 and Osteopontin.<br><br>CONCLUSIONS: Our study is the first reporting an oncomiR role for miR-503 in MM and suggests that its inactivation could have a clinical value in MM patients. This study reveals that miRNA-503 acts as an oncomiR in MM suggesting that its inhibition, through LNP delivery, has the potential to be considered as a novel therapeutic strategy in MM.}, }
@article {pmid39983469, year = {2025}, author = {Fukui, T and Sumitomo, R and Menju, T and Kobayashi, M and Sakai, H and Date, H}, title = {M2-like tumor-associated macrophages may promote tumor progression in malignant pleural mesothelioma.}, journal = {Translational oncology}, volume = {54}, number = {}, pages = {102324}, doi = {10.1016/j.tranon.2025.102324}, pmid = {39983469}, issn = {1936-5233}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with an unfavorable prognosis. Asbestos-activated macrophages may contribute to both oncogenesis and progression of MPM. This study aimed to clarify the biological and clinical significance of M2-like tumor-associated macrophages (TAMs) in MPM.<br><br>METHODS: This retrospective study included 101 MPM patients who were diagnosed and started treatment between 1998 and 2010. The distribution of M2-like TAMs in the intratumoral and peritumoral regions was evaluated by immunohistochemistry using CD163 staining. Tumor proliferation was evaluated by Ki-67 staining.<br><br>RESULTS: Intratumoral M2-like TAM density was significantly correlated with the pretreatment C-reactive protein level (r = 0.283, P = 0.004) and Ki-67 proliferation index (r = 0.498, P < 0.001). Peritumoral M2-like TAM density was also significantly correlated with the pretreatment C-reactive protein level (r = 0.255, P = 0.010) and Ki-67 proliferation index (r = 0.435, P < 0.001). Additionally, intratumoral M2-like TAM density was associated with histological subtype (P < 0.001), with higher densities observed in sarcomatoid tumors compared to epithelioid tumors. The overall survival rate was significantly worse in the intratumoral and peritumoral M2-like TAM-high groups (P = 0.044 and P = 0.046, respectively), particularly in patients with advanced-stage MPM. Multivariable analysis identified peritumoral M2-like TAM status (hazard ratio = 1.700, 95&#x202f;% confidence interval: 1.034-2.796, P = 0.037), clinical stage, and histology as significant prognostic factors for overall survival.<br><br>CONCLUSIONS: During MPM progression, M2-like TAMs may induce tumor cell proliferation and aggressiveness, contributing to the poor prognosis in MPM patients.}, }
@article {pmid39981889, year = {2025}, author = {Andreikos, D and Spandidos, DA and Georgakopoulou, VE}, title = {Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).}, journal = {International journal of oncology}, volume = {66}, number = {3}, pages = {}, doi = {10.3892/ijo.2025.5729}, pmid = {39981889}, issn = {1791-2423}, mesh = {Humans ; *Telomerase/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; *Telomere/genetics/metabolism ; *Mesothelioma, Malignant/genetics/pathology/drug therapy ; Mesothelioma/genetics/pathology ; Lung Neoplasms/genetics/pathology ; Prognosis ; Polymorphism, Single Nucleotide ; Mutation ; Promoter Regions, Genetic ; }, abstract = {Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.}, }
@article {pmid39973732, year = {2025}, author = {Tuncer, K and Gomleksiz, M}, title = {Improving asbestos knowledge among demolition workers through training after earthquakes.}, journal = {Work (Reading, Mass.)}, volume = {}, number = {}, pages = {10519815241305009}, doi = {10.1177/10519815241305009}, pmid = {39973732}, issn = {1875-9270}, abstract = {BACKGROUND: Asbestos was widely used as insulation material in Türkiye's construction. It poses severe health risks, including mesothelioma, a type of lung cancer that is often fatal.<br><br>OBJECTIVE: This study aimed to determine and improve the knowledge about asbestos among employees of a building demolition workers in Elaz&#x131;&#x11f;.<br><br>METHODS: Out of 82 employees in the demolition workers, 75 volunteered for the study after ethical approval was obtained. Training materials and survey forms were developed through a review of the literature. Surveys were conducted before and after the training sessions. Data were analyzed using SPSS 22.0, and a p-value of less than 0.05 indicated statistical significance.<br><br>RESULTS: The participants were exclusively male, with an average age of 39.06 years. Among them, 40% were current smokers. Most had not received prior training on asbestos. Before the training, nearly half of the respondents (49.4%) were unaware of the procedures for asbestos check and removal prior to demolition. knowledge across all surveyed areas. The knowledge of demolition workers increased significantly after training.<br><br>CONCLUSION: Training significantly improved asbestos-related knowledge which was low before among the demolition workers, a group at high risk for asbestos exposure.}, }
@article {pmid39960454, year = {2025}, author = {Kanno, J}, title = {Carcinogenicity assessment: "Modern Toxicology" considerations from an experience in the evaluation of a carbon nanotube.}, journal = {Journal of occupational health}, volume = {}, number = {}, pages = {}, doi = {10.1093/joccuh/uiaf013}, pmid = {39960454}, issn = {1348-9585}, abstract = {The novel properties and functions of nanomaterials have naturally alerted the toxicologists to the fact that such materials may also have novel effects on the human body and living organisms. In particular, materials with high stability or biopersisteny have been shown to have a tendency to accumulate in the body, leading to chronic toxicity including carcinogenicity. However, at the early stages of toxicity research, the information is often limited to the effects of short-term exposure studies, and findings on chronic effects are very much delayed. In this context, it was rather exceptional that studies on multiwall carbon nanotubes (MWCNTs) have started with the verification of their potential to induce mesothelioma. This toxicological endpoint was expected on the basis of existing knowledge of asbestos and asbestos-like fiber particles. This movement has led to the achievement of the original mission of the "Modern Toxicology", which is "to achieve a win-win situation where both industrial promotion and safety assurance are ensured by communicating and sharing toxicity information to developers and consumers at a stage before mass production and consumption begins, that is, before massive exposure of the general public begins". Inaccurate toxicity assessments of asbestos in the 1980s and 1990s allowed its spread to our living environment, which is difficult to decontaminate, and the damage still continues to this day. However, the case described here could be an example of realizing the proposition that 'nanomaterials, the flagship of high technology, must not repeat the same mistakes.'}, }
@article {pmid39958414, year = {2024}, author = {Salvado, A and Capone, L and Zamorano, P and Samudio, M and Garcia-de-Dávila, MT and Ernst, G}, title = {A comprehensive multidisciplinary approach for identifying asbestos exposure among underground workers.}, journal = {Revista brasileira de medicina do trabalho : publicacao oficial da Associacao Nacional de Medicina do Trabalho-ANAMT}, volume = {22}, number = {4}, pages = {e20241271}, pmid = {39958414}, issn = {1679-4435}, abstract = {INTRODUCTION: Inhalation of asbestos fibers can lead to a range of diseases, including asbestosis, pleural plaques, lung cancer, and malignant mesothelioma. Despite regulatory efforts, asbestos-related diseases remain a significant public health issue.<br><br>OBJECTIVES: This study aimed to assess the characteristics and prevalence of asbestos-related diseases among exposed workers.<br><br>METHODS: We conducted a descriptive cohort study with underground workers in Buenos Aires, Argentina, from March 2018 to March 2023. A comprehensive screening and surveillance program, including medical examinations, was implemented to identify exposure-related signs and symptoms. Histological sections from paraffin-embedded tissue blocks were analyzed using light and polarization microscopy for lung cancer cases.<br><br>RESULTS: A total of 2,690 participants were included, of whom 2.8% (n = 77) had asbestos-related diseases and 0.22% (n = 6) had lung cancer. Occupational exposure exceeding 20 years was significantly associated with an elevated risk of asbestos-related diseases (odd ratio: 3.02; 95%CI 1.7-5.3).<br><br>CONCLUSIONS: The prevalence of occupational diseases among underground workers was consistent with findings from other surveillance programs for asbestos-exposed workers. Occupational exposure exceeding 20 years emerged as a significant risk factor, markedly increasing the likelihood of asbestos-related diseases.}, }
@article {pmid39947731, year = {2025}, author = {Rao D, P and Vijayan, S and Vananjakar, SS and T, PK}, title = {Malignant pleural mesothelioma.}, journal = {BMJ case reports}, volume = {18}, number = {2}, pages = {}, doi = {10.1136/bcr-2024-263562}, pmid = {39947731}, issn = {1757-790X}, mesh = {Humans ; Female ; *Mesothelioma, Malignant/diagnosis/pathology/therapy ; *Pleural Neoplasms/diagnosis/therapy ; Aged ; *Pleurodesis ; Mesothelioma/diagnosis/therapy/pathology ; Lung Neoplasms/diagnosis/pathology/therapy ; Palliative Care ; Talc/adverse effects/administration &amp; dosage ; Thoracoscopy/methods ; Pleural Effusion, Malignant/etiology/therapy/diagnosis/diagnostic imaging ; Tomography, X-Ray Computed ; Dyspnea/etiology ; }, abstract = {Malignant pleural mesothelioma is a rare and aggressive tumour of the pleura, commonly linked to asbestos exposure. However, its diagnosis is challenging, especially without known exposure. We present the case of a woman in her early 70s with no history of asbestos exposure, who presented with progressive breathlessness and left-sided chest pain. Radiological assessment revealed a large pleural effusion and nodular pleural thickening. Malignant pleural mesothelioma was confirmed through histopathological analysis of biopsies obtained via medical thoracoscopy. The patient was initiated on a palliative chemotherapy regimen, underwent talc slurry pleurodesis for recurrent effusion, and is currently under follow-up. This case emphasises the importance of a high index of suspicion for malignant pleural mesothelioma in patients with unexplained pleural effusion, even in the absence of typical risk factors, and the need for a timely diagnosis due to the disease's dismal prognosis.}, }
@article {pmid39939955, year = {2025}, author = {Shi, H and Yu, TK and Johnson, B and Selvamani, SP and Zhuang, L and Lee, K and Klebe, S and Smith, S and Wong, K and Chen, K and Clark, G and Rath, EM and Pearson, H and Ortega, DG and Linton, A and Kao, S and Silveira, P and Cheng, YY}, title = {A combination of PD-1 and TIGIT immune checkpoint inhibitors elicits a strong anti-tumour response in mesothelioma.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {44}, number = {1}, pages = {51}, pmid = {39939955}, issn = {1756-9966}, abstract = {BACKGROUND: Finding effective and curative treatment for mesothelioma remains challenging. While the introduction of immunotherapy combinations using ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have offered hope for some patients, a large proportion of mesothelioma cases, particularly the epithelial subtype, have minimal benefit from this.<br><br>METHODS: Our study was inspired by the results of the AdvanTG-105 phase I clinical trial, which showed partial response with anti-TIGIT/PD-1 treatment in two epithelioid mesothelioma patients. Here, we conducted a comprehensive in vivo experiment involving eight animal treatment groups administered with either PBS (control group), cisplatin/pemetrexed, anti-PD-1, anti-PD-1&#x2009;+&#x2009;anti-CTLA-4, anti-TIGIT, anti-PD-1&#x2009;+&#x2009;anti-TIGIT, anti-PD-1&#x2009;+&#x2009;anti-CTLA-4&#x2009;+&#x2009;anti-TIGIT, and cisplatin/pemetrexed&#x2009;+&#x2009;anti-PD-1&#x2009;+&#x2009;anti-TIGIT.<br><br>RESULTS: Our results indicate that animals receiving anti-PD-1&#x2009;+&#x2009;TIGIT exhibited a superior anti-tumour response, with 90% of the treatment group exhibiting an objective response, compared to 60%, 20% and 40% for the standard-of-care anti-PD-1&#x2009;+&#x2009;CTLA-4, single-agent anti-PD-1 and cisplatin/pemetrexed treatment groups, respectively. Animals receiving anti-PD-1&#x2009;+&#x2009;TIGIT displayed a significantly reduced average tumour size, with improved weight and survival rates, and fewer adverse effects than those receiving anti-PD-1&#x2009;+&#x2009;CTLA-4 treatment. Anti-PD-1&#x2009;+&#x2009;TIGIT-treated animals achieved complete tumour regression, with heightened effector CD8&#x2009;+&#x2009;T cell and NK cell activity, remaining tumour-free for over 300&#xa0;days without immune-related adverse events. After initial tumour elimination, anti-PD-1&#x2009;+&#x2009;TIGIT-treated animals showed no tumour regrowth in the rechallenge experiment.<br><br>CONCLUSION: These findings provide rationale for the development of an anti-PD-1&#x2009;+&#x2009;TIGIT combination immunotherapy trial for mesothelioma patients.}, }
@article {pmid39934006, year = {2025}, author = {Lopci, E}, title = {"Current Status of Staging and Restaging Malignant Pleural Mesothelioma".}, journal = {Seminars in nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.semnuclmed.2025.01.003}, pmid = {39934006}, issn = {1558-4623}, abstract = {Malignant pleural mesothelioma (MPM) is the most frequent aggressive tumor affecting the pleura, accounting for over 38,000 deaths worldwide. It originates from the mesothelial cells and is mostly associated to asbestos exposure. Depending on the extent of the disease, the management of MPM varies from surgical intervention to a combination of systemic chemotherapy, immunotherapy, and radiation therapy. Major International scientific societies provide continuous updates on proper management of the disease, including recommendations on the optimal imaging algorithms, which are crucial for determining effective treatment options and optimizing clinical outcomes. However, despite the continuous efforts to improve patients' prognosis, median overall survival remains poor, ranging from 8 to 14 months. And even in case of initial response to treatment, local or distant recurrences represent almost a certainty, requiring appropriate imaging for the assessment of tumor sites. The aim of the present article is to illustrate the current status of imaging for staging and restaging of MPM, not forgetting most recent novelties in the diagnostic work-up of the disease.}, }
@article {pmid39921204, year = {2025}, author = {Pandey, K and Faridi, P and Ayala, R and Lee, YCG and Rouse, E and Krishna, SSG and Dick, I and Redwood, A and Robinson, B and Creaney, J and Purcell, AW}, title = {Multiple classes of antigen contribute to the antigenic landscape of mesothelioma.}, journal = {Molecular &amp; cellular proteomics : MCP}, volume = {}, number = {}, pages = {100925}, doi = {10.1016/j.mcpro.2025.100925}, pmid = {39921204}, issn = {1535-9484}, abstract = {Mesothelioma is an incurable, asbestos-exposure related cancer that typically affects the lining or pleura of the lungs. Symptoms typically develop many decades after initial exposure to asbestos, leaving an enduring legacy of disease. Current disease burden is peaking worldwide and thus there is a massive unmet clinical need for curative therapies. Recently, immune checkpoint blockade-based therapy has been adopted as a first-line of treatment for mesothelioma. Vaccine-induced augmentation of immune responses unleashed during checkpoint blockade may provide further clinical benefit in mesothelioma. In this study we explore the human leukocyte antigen class I landscape (or immunopeptidome) of mesothelioma in patient derived cell line and clinical material (pleural effusion samples). We identify a range of peptide antigens derived from targets including cancer testis antigens, endogenous retroviruses as well as novel post-translational modification of peptides. This information will facilitate the characterization of the immune response to these antigens to determine which class of antigen is most immunogenic and has the potential to be tested in future vaccine studies.}, }
@article {pmid39911320, year = {2025}, author = {Korchevskiy, AA and Wylie, AG}, title = {Habit of elongate amphibole particles as a predictor of mesothelial carcinogenicity.}, journal = {Toxicology reports}, volume = {14}, number = {}, pages = {101908}, pmid = {39911320}, issn = {2214-7500}, abstract = {INTRODUCTION: Amphiboles are a class of minerals that are abundantly present in the environment. Amphiboles may exist in several habits, with asbestiform particles behaving like typical amphibole asbestos and non-asbestiform (or massive) reported to be less biologically active.<br><br>MATERIALS AND METHODS: The available dimensional information for 16 testing sets (8 asbestiform and 8 non-asbestiform types of tremolite) was combined. In addition, three validation sets (an asbestiform sample from Eastern New York and non-asbestiform samples from Quebec and Falls Village, Connecticut) were tested by Transmission Electron Microscopy (TEM) to determine dimensional distribution. Mathematical modeling was utilized to determine the classification method for amphiboles with various habits.<br><br>RESULTS: The decision boundary method was developed to distinguish asbestiform vs. non-asbestiform samples (with error rate of 0&#x202f;% for single-sourced tremolite and 3&#x202f;% for potentially mixed samples). All validation datasets were correctly classified. A new empirical dimensional coefficient of carcinogenicity (DCC) was proposed, with DCC = 1 - exp(-0.11 Surface Area /(1000width[3] + 1)). For several mineral types (crocidolite, amosite, Libby amphiboles, anthophyllite, chrysotile, and erionite), it was demonstrated that mesothelioma potency factors can be predicted based on DCC and biosolubility with a high level of accuracy (R=0.98, R[2]=0.96, p&#x202f;<&#x202f;0.006). It was demonstrated that modeled mesothelioma potency correlates with relative potency for pleural instillation in Wistar rats, and correlates inversely with membranolytic toxicity index HC50. Mesothelioma potency was demonstrated to be negligible in all non-asbestiform sets.<br><br>CONCLUSIONS: The habit of amphibole particles is predictive of biological behavior that can be estimated from the dimensional data for the particles.}, }
@article {pmid39871092, year = {2025}, author = {Toyokuni, S and Kong, Y}, title = {Decoding the Molecular Enigma Behind Asbestos and Fibrous Nanomaterial-induced carcinogenesis.}, journal = {Journal of occupational health}, volume = {}, number = {}, pages = {}, doi = {10.1093/joccuh/uiae064}, pmid = {39871092}, issn = {1348-9585}, abstract = {OBJECTIVES: Natural fibrous mineral, asbestos, has been useful in industry for many centuries. In the 1960's, epidemiology had recognized the association between asbestos exposure and mesothelioma and the IARC designated all kinds of asbestos as Group 1 in 1987. However, various scientific enigmas remained regarding the molecular mechanisms of asbestos-induced mesothelial carcinogenesis. This review article was undertaken to reveal and summarize the recent discoveries how the enigma has been resolved.<br><br>METHODS: We collected recent important findings of our own laboratory and the others to explain why mesothelial cells are the target for asbestos-induced carcinogenesis and what is the key molecular mechanisms.<br><br>RESULTS: Long incubation period of 30&#x2009;~&#x2009;40&#xa0;years for mesothelial carcinogenesis after asbestos exposure is responsible for the asbestos fibers to go through the pulmonary parenchyma from the central to peripheral portions finally to reach the parietal mesothelium by piercing visceral pleura. Asbestos fibers have affinity for hemoglobin and histones, thus accumulating iron on the surface while travelling through the lung. The other important point is that mesothelial cells are phagocytic cells, engulfing iron-coated asbestos fibers. Accordingly, homozygous deletion of p16INK4a tumor suppressor gene, a signature of excess iron-induced carcinogenesis, is acquired through oxidative DNA damage. Recently, exosome-dependent iron transfer from asbestos-fed macrophages to mesothelial cells was reported. Similar molecular mechanisms are observed in multiwalled carbon nanotube of ~50-nm-diameter.<br><br>CONCLUSION: Physical dimension, biopersistence and affinity to iron/histones are essential for fibrous material to be carcinogenic to mesothelial cells. Therefore, local iron reduction maybe a strategy to prevent mesothelial carcinogenesis.}, }
@article {pmid39867168, year = {2025}, author = {Jadhav, AV and Gawde, N and Veerappan, R and Choi, Y and Frank, AL}, title = {Understanding exposure risk using soil testing and GIS around an abandoned asbestos mine.}, journal = {Annals of global health}, volume = {91}, number = {1}, pages = {2}, pmid = {39867168}, issn = {2214-9996}, mesh = {*Mining ; Humans ; *Geographic Information Systems ; *Environmental Exposure/analysis ; India/epidemiology ; *Asbestos/analysis ; *Soil Pollutants/analysis ; Dust/analysis ; Soil/chemistry ; Asbestos, Serpentine/analysis ; Environmental Monitoring/methods ; Microscopy, Electron, Scanning ; }, abstract = {Background: Abandoned asbestos mines are a potential source of environmental contamination and exposure for nearby residents. The asbestos exposure risk may persist even after the cessation of mining activity if the mine is not properly closed. One such abandoned mine is at Roro Hills in the Jharkhand state of India. There are limited studies examining soil contamination and asbestos exposure to nearby residents due to abandoned mines. Objectives: The aim of this study is to examine the presence of asbestos in the residential areas of villages surrounding an abandoned asbestos mine and to understand the spread of visible asbestos dust using geographic information system map analysis. Methods: This study examined the presence of asbestos in soil samples from four villages surrounding an abandoned asbestos mine using the scanning electron microscopy technique. The study also compared satellite images taken 13 years apart to determine whether the mine waste containing asbestos had spread over time. Findings: The soil sample testing indicated that, out of 16 soil samples from residential areas, 12 showed the presence of chrysotile asbestos. It was found in the map analysis that asbestos-containing areas had enlarged by around 20% in those years. Conclusion: The evidence indicated the presence of asbestos in the soil of nearby residential areas around the mine, and this contamination has spread over the years. Similar studies at other mine locations are needed, and timely interventions are warranted to protect nearby residents.}, }
@article {pmid39447855, year = {2024}, author = {Opitz, I and Lauk, O and Werner, R and Matter, A and Hebeisen, M and Battilana, B and Batirel, H and Pass, H and Flores, R and Wolf, A and de Perrot, M and Hoda, MA and Klepetko, W and Klikovits, T and Hashimoto, M and Hasegawa, S and Richards, WG and Bueno, R}, title = {Characteristics of Long-term Survivors With Malignant Pleural Mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.athoracsur.2024.10.004}, pmid = {39447855}, issn = {1552-6259}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is a cancer with a usually dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centers around the world.<br><br>METHODS: This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival &#x2265;5 years from surgery) treated within a multimodality therapy approach, including macroscopic complete resection. Overall survival was calculated with Kaplan-Meier analysis, and patients were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis.<br><br>RESULTS: There were 276 long-term survivors (166 men [63%]), with a median age of 59 years (range 21-83 years) at the time of diagnosis. The histology was epithelioid for 246 patients and nonepithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients had died, 104 were alive, and 10 were lost to follow-up. Pathologic tumor stages were: pT1 (n&#xa0;= 50), pT2 (n&#xa0;= 63), pT3 (n&#xa0;= 90), or pT4 (n&#xa0;= 16) and pN0 (n&#xa0;= 150), pN1 (n&#xa0;= 20), and pN2 (n&#xa0;= 39). The matched control data set included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, we found moderate evidence that a low white blood cell count before surgery was more often observed in long-term survivors.<br><br>CONCLUSIONS: The data show that long-term survival in PM is possible in a subgroup of surgically treated patients. Histologic subtype and white blood cell count seem to be prognosticators for longer survival.}, }
@article {pmid39833869, year = {2025}, author = {Ahmad, Z and Jehanzeb, H and Hussain, SN and Umar, M and Saleem, H}, title = {A synchronous occurrence of breast cancer and pleural mesothelioma: a case report.}, journal = {Journal of medical case reports}, volume = {19}, number = {1}, pages = {25}, pmid = {39833869}, issn = {1752-1947}, mesh = {Humans ; Female ; *Pleural Neoplasms/therapy/pathology/diagnosis ; Adult ; *Breast Neoplasms/pathology ; *Neoplasms, Multiple Primary/pathology ; *Mesothelioma, Malignant/pathology ; Lung Neoplasms/pathology ; Tomography, X-Ray Computed ; Paclitaxel/therapeutic use ; Mesothelioma/pathology/diagnosis ; }, abstract = {BACKGROUND: Malignant mesotheliomas are aggressive forms of tumors arising from mesothelial cells. The most common type is malignant pleural mesothelioma, which progresses rapidly and leads to pleural effusion. It typically affects older men and is strongly associated with asbestos exposure. However, a few studies have reported cases of malignant pleural mesothelioma resulting from non-asbestos factors, including radiotherapy for breast cancer, viruses, chronic inflammation, and BRCA1-associated protein-1-associated genetic mutations. Breast cancer is the most common sporadic cancer among women, and a small percentage of cases are related to genetic factors, such as BRCA1/2 and BRCA1-associated protein-1 mutations. While breast cancer can be linked with other primary malignancies through germline mutations, the synchronous occurrence of breast cancer with pleural mesothelioma is extremely rare.<br><br>CASE PRESENTATION: We present the case of a 40-year-old Pashtun woman diagnosed with primary breast cancer. She underwent surgery followed by chemotherapy (paclitaxel). During chemotherapy, she developed right-sided chest pain and dyspnea. A computed tomography scan revealed pleural thickening, and a pleural biopsy confirmed the diagnosis of malignant pleural mesothelioma, with positive results for the diagnostic markers WT1 and D240.<br><br>CONCLUSION: This case represents a rare occurrence of synchronous breast cancer and pleural mesothelioma in a 40-year-old female, and is the first case reported in Khyber Pakhtunkhwa, Pakistan. These findings demonstrate the importance of comprehensive diagnostic testing and the potential role of genetic mutations in concurrent cancers. The challenge of simultaneously treating these cancers highlights the need for further research and the importance of multidisciplinary approaches.}, }
@article {pmid39831243, year = {2024}, author = {Vinci, L and Wanner, M and Karavasiloglou, N and Dressel, H and Barresi, F and Korol, D and Rohrmann, S}, title = {Incidence, mortality and survival of pleural mesothelioma in Zurich between 1981 and 2019, Switzerland.}, journal = {Journal of thoracic disease}, volume = {16}, number = {12}, pages = {8240-8249}, doi = {10.21037/jtd-24-766}, pmid = {39831243}, issn = {2072-1439}, abstract = {BACKGROUND: Pleural mesothelioma is mainly caused by (occupational) asbestos exposure. Since 1990, the import and use of asbestos is prohibited in Switzerland. However, due to the long latency time between exposure and the development of disease, incidence in Switzerland was expected to further increase for years after the ban. The aim of the present study was to analyse incidence, mortality, and survival of patients diagnosed with malignant pleural mesothelioma in the canton of Zurich in Switzerland.<br><br>METHODS: Population-based cancer registry data and cause of death statistics of the canton of Zurich from 1981 to 2019 were used to calculate age-standardized incidence and mortality rates. Time trends were investigated with joinpoint regression and net survival was computed using the Pohar-Perme method.<br><br>RESULTS: In men, the incidence rate increased from 1981 to 2002 {annual percentage change (APC) 4.7 [95% confidence interval (CI): 2.6 to 6.8]} and then decreased until 2019 [APC: -2.3 (95% CI: -4.2 to -0.3)], while in women it increased over the whole period [APC 6.2 (95% CI: -1.3 to 14.4)]. Mortality rates were stable in men and women. Three-year net survival was 9.7% (95% CI: 7.8% to 12.2%) for men and 22.1% (95% CI: 15.3% to 32.1%) for women. Men with stage I or II pleural mesothelioma had a net survival of 25.4% (95% CI: 17.2% to 37.5%) after three years whereas men with stage III or IV experienced a net survival of 7.4% (95% CI: 3.9% to 13.8%) after three years.<br><br>CONCLUSIONS: Malignant pleural mesothelioma incidence seems to have reached the peak in the canton of Zurich in men, but not yet in women. Mortality rates were stable in men and women, and net survival was poor for both sexes, particularly in men.}, }
@article {pmid39831064, year = {2024}, author = {Jaurand, MC and Murphy, F and Felley-Bosco, E}, title = {Editorial: Asbestos and disease genomics: is mesothelioma a genomic paradigm?.}, journal = {Frontiers in toxicology}, volume = {6}, number = {}, pages = {1536344}, doi = {10.3389/ftox.2024.1536344}, pmid = {39831064}, issn = {2673-3080}, }
@article {pmid39818191, year = {2025}, author = {Imai, H}, title = {Current drug therapy for pleural mesothelioma.}, journal = {Respiratory investigation}, volume = {63}, number = {2}, pages = {200-209}, doi = {10.1016/j.resinv.2024.12.017}, pmid = {39818191}, issn = {2212-5353}, abstract = {Pleural mesothelioma (PM) is a rare and highly aggressive malignancy originating from the pleural lining, with a median overall survival of merely 1 year. This cancer primarily arises from mesothelial cells following exposure to carcinogenic, biopersistent mineral fibers, particularly asbestos. The histological subtypes of mesothelioma are epithelioid (approximately 60%), sarcomatoid (20%), and biphasic (20%), exhibiting epithelioid and sarcomatoid characteristics. Classification is important for prognosis and guides the therapeutic strategy. Due to the typical late presentation, most patients with PM are ineligible for localized treatments such as surgery or radiotherapy. Systemic therapy, including cytotoxic chemotherapy, targeted therapies, and immunotherapy, is thus critical for managing advanced PM. For unresectable PM, decisions regarding systemic treatment are guided by patient suitability and histological characteristics. First-line therapies for advanced PM currently include the cisplatin-pemetrexed combination and the nivolumab-ipilimumab regimen. Historically, cisplatin-pemetrexed has been administered as first-line treatment, though recent advancements have introduced new therapies that significantly prolong patient survival. Innovative approaches combining immunotherapy and chemotherapy offer promising avenues for further improvement. Future treatment strategies should incorporate novel paradigms, such as combination chemo-immunotherapy, targeted agents, and potential cellular therapies, alongside companion biomarkers tailored to the histologic and molecular diversity of mesothelioma. This review explores the latest advancements in drug therapy for PM and provides an overview of current systemic treatment options.}, }
@article {pmid39791266, year = {2025}, author = {Kadariya, Y and Sementino, E and Hua, X and Kappes, DJ and Testa, JR}, title = {Modeling Malignant Mesothelioma in Genetically Engineered Mice.}, journal = {Current protocols}, volume = {5}, number = {1}, pages = {e70086}, doi = {10.1002/cpz1.70086}, pmid = {39791266}, issn = {2691-1299}, mesh = {Animals ; *Mesothelioma/genetics/chemically induced/pathology ; Mice ; *Disease Models, Animal ; *Mesothelioma, Malignant/genetics/pathology ; *Lung Neoplasms/genetics/chemically induced/pathology ; Humans ; Asbestos/toxicity ; Mice, Transgenic ; Genetic Engineering ; }, abstract = {Mesothelioma is a lethal cancer of the serosal lining of the body cavities. Risk factors include environmental and genetic factors. Asbestos exposure is considered the principal environmental risk factor, but other carcinogenic mineral fibers, such as erionite, also have a causal role. Pathogenic germline (heritable) mutations of specific genes, especially BAP1, are thought to predispose the individual to mesothelioma in about 10% of cases. Somatic mutations and deletions of specific tumor suppressor genes, particularly BAP1, CDKN2A/B, and NF2, occur frequently in human mesothelioma, and asbestos-exposed mice with heterozygous deletions of any one of these genes have been shown to develop mesothelioma more often and at an accelerated rate than in control animals. Autochthonous mesothelioma mouse models, which are genetically engineered to carry multiple genetic lesions matching those observed in the human disease counterpart, closely resemble the disease phenotype and the extensive inflammatory responses that characterize human mesothelioma. Because autochthonous mice do not require asbestos exposure and form tumors rapidly, these models are invaluable for assessing novel therapeutic strategies in an immunocompetent setting. The overlapping genetic, epigenetic, and immune environments of the tumors observed in these genetically engineered mouse models (GEMMs) and human primary mesothelioma specimens support the clinical relevance of these preclinical models. This article presents protocols for studies of asbestos-induced mesothelioma in GEMMs and non-carcinogenic conditional knockout models of mesothelioma, including an example of a preclinical application. These models are invaluable for understanding the biological underpinnings of mesothelioma and for testing new therapeutics and chemoprevention or interception agents. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Generation of a genetically engineered mouse model (GEMM) with a germline Bap1 knockout allele Basic Protocol 2: Generation of GEMMs with germline Bap1 knock-in alleles Basic Protocol 3: Asbestos carcinogenicity investigations with GEMMs Basic Protocol 4: Preclinical chemoprevention and chemotherapy studies using a GEMM with asbestos-induced mesothelioma Basic Protocol 5: Generation of a GEMM with conditional knockout of Bap1 Basic Protocol 6: Generation of a conditional knockout model of mesothelioma.}, }
@article {pmid39776006, year = {2025}, author = {Franzoi, IG and Sauta, MD and Bonafede, M and Francioso, G and De Luca, A and Barbagli, F and Granieri, A}, title = {Psychological Distress in Patients With Asbestos-Related Diseases and Their Families: A Systematic Literature Review.}, journal = {Psycho-oncology}, volume = {34}, number = {1}, pages = {e70051}, doi = {10.1002/pon.70051}, pmid = {39776006}, issn = {1099-1611}, mesh = {Humans ; *Caregivers/psychology ; *Asbestos ; *Psychological Distress ; Quality of Life/psychology ; Mesothelioma, Malignant/psychology ; Anxiety/psychology ; Depression/psychology ; Stress, Psychological/psychology ; Occupational Exposure/adverse effects ; }, abstract = {BACKGROUND: Exposure to asbestos in the workplace is currently recognized as one of the leading causes of work-related deaths, with more than half of deaths attributable to cancer.<br><br>AIMS: The aim of this systematic literature review was to investigate the mental health and psychological distress of patients affected by asbestos-related diseases and their caregivers.<br><br>METHODS: The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The studies were identified in October 2023 by searching four electronic databases: Scopus, Web of Science, PubMed and PsycInfo/PsycArtcicles. Risk of bias was assessed using the JBI checklist.<br><br>RESULTS: Fourteen articles were identified. The studies focused exclusively on the psychological distress of patients with malignant mesothelioma (MM) and their caregivers. MM appears to have traumatic effects on both patients and caregivers, who may experience anxiety and depression, an impoverished emotional life, somatization, social withdrawal, and a deterioration in their quality of life. In addition, a need for information about MM, its progression and associated care tasks was identified, and patients and caregivers reported frequently seeking information from online sources.<br><br>CONCLUSIONS: Our review has shown that there are still few studies addressing psychological distress in MM patients and their caregivers, and none addressing distress in the context of other asbestos-related diseases. The somatopsychic consequences of MM in patients and caregivers should encourage institutions and health professionals to develop assessment and intervention models that are tailored to the specific suffering and needs of MM patients and their caregivers and promote their residual vitality.}, }
@article {pmid39773018, year = {2025}, author = {Pyana Kitenge, J and Dubbeldam, A and Said-Hartley, Q and Ronsmans, S and Jeebhay, M and Nemery, B}, title = {Asbestos-related diseases in Africa: sentinel cases of mesothelioma and asbestosis from DR Congo.}, journal = {Pulmonology}, volume = {31}, number = {1}, pages = {2449268}, doi = {10.1080/25310429.2024.2449268}, pmid = {39773018}, issn = {2531-0437}, }
@article {pmid39765992, year = {2024}, author = {Ferrante, P}, title = {Respiratory Diseases with High Occupational Fraction in Italy: Results from the Italian Hospital Discharge Registry (2010-2021).}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {24}, pages = {}, doi = {10.3390/healthcare12242565}, pmid = {39765992}, issn = {2227-9032}, abstract = {OBJECTIVES: Occupational respiratory diseases represent a major public health concern worldwide. This study analyses the hospitalization costs and characteristics of four major occupational respiratory diseases: malignant mesothelioma (MM), sinonasal cancer (SNC), pneumoconiosis (PN), and hypersensitivity pneumonitis (HP). The findings are situated within the context of Italy's population trends and healthcare system, offering insights into the economic and clinical burden of these diseases.<br><br>STUDY DESIGN: This retrospective, population-based study examines Italian hospitalizations for MM, SNC, PN, and HP during the period 2010-2021. The primary outcomes were the number of hospitalizations, length of stay, and associated cost. Costs were derived from charges linked to diagnosis-related groups (version 24) and major diagnostic category coding systems.<br><br>RESULTS: Though the Italian population is rapidly aging, the annual number and rate of hospitalizations declined by 35% over the study period. SNC hospitalizations aligned with the overall trend, PN and MM experienced faster declines, whereas HP admissions remained steady. MM emerged as the most resource-intensive (EUR 25 million yearly, with 86% attributable to occupation), followed by PN (EUR 10 million, entirely occupational), SNC (EUR 5 million, with EUR 650,000 occupational), and HP (EUR 2 million, with EUR 370,000 occupational). All studied diseases had an average length of stay exceeding the national one. The SNC admissions were the shortest (6.5 days) and least expensive (EUR 3647). In contrast, MM, PN, and HP had a mean length of stay exceeding 10 days, with admission costs averaging EUR 4700 for MM and EUR 4000 for PN and HP. The median age was the highest for PN (78 years) and MM (71 years), while SNC and HP patients had a median age of approximately 65 years.<br><br>CONCLUSIONS: Consistent with their anticipated benefits, Italian workplace health regulations over the last three decades, including the 1992 asbestos ban and D.lgs. 81/2008, are associated with significant reductions in the hospitalization burden and an increased median age at discharge for MM and PN. In contrast, fewer conclusions can be drawn for SNC and HP due to their lower occupational fractions (10-20%). This finding suggests adding an occupational exposure flag in hospital records for acknowledged occupational diseases to enhance surveillance. Finally, this study provides the first estimate of the occupational fraction of hospitalization costs for the studied diseases in Italy.}, }
@article {pmid39758284, year = {2025}, author = {Bertolotti, M and Tamburro, M and Salzo, A and Cassinari, A and Crivellari, S and Bertolina, C and Farotto, M and Adesso, C and Di Palma, MA and Natale, A and Torregiani, F and Pacileo, G and Maconi, A and Ripabelli, G}, title = {Knowledge and awareness of asbestos risk among General Practitioners: Validation of a questionnaire in an area with a high incidence of asbestos-related diseases.}, journal = {Preventive medicine reports}, volume = {49}, number = {}, pages = {102940}, pmid = {39758284}, issn = {2211-3355}, abstract = {OBJECTIVE: Given the critical role of general practitioners (GPs) in the early diagnosis and management of asbestos-related diseases (ARDs), and the significant history of asbestos fibres pollution in Alessandria Local Health Authority (ASL AL), this project aimed to assess the knowledge and awareness of asbestos risks, as well as the experience in diagnosing ARDs among GPs working in Alessandria province, Northern Italy.<br><br>METHODS: A questionnaire was administered to 216 GPs from all ASL AL territorial districts during 26 Territorial Assistance Equipes (EATs) meetings, held from September 2022 to January 2023. It contained 29 questions covering three main areas: 'knowledge and awareness', 'competence and experience', 'sociodemographic characteristics and workload'.<br><br>RESULTS: Although GPs were aware of the health hazards of asbestos (94&#xa0;%) and the increased risk of mesothelioma from asbestos exposure (92.6&#xa0;%), significant disparities and heterogeneity of knowledge were observed among territorial districts and by comparing Casale Monferrato district with all the others, particularly regarding asbestos exposure routes, reporting of occupational diseases, and mesothelioma latency.<br><br>CONCLUSIONS: This project provides a comprehensive overview of GPs' knowledge, awareness and experience in managing ARDs, providing indications of customised training requirements. This evaluation could be extended to all areas with a history of previous asbestos exposure and provide a useful tool for policy makers to define and plan strategic actions on asbestos. This work could also be adapted to different realities with a history of environmental pollutant exposure other than asbestos, which pose a risk for the development of several diseases.}, }
@article {pmid39751851, year = {2025}, author = {D'Alonzo, RA and Keam, S and Gill, S and Rowshanfarzad, P and Nowak, AK and Ebert, MA and Cook, AM}, title = {Fractionated low-dose radiotherapy primes the tumor microenvironment for immunotherapy in a murine mesothelioma model.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {74}, number = {2}, pages = {44}, pmid = {39751851}, issn = {1432-0851}, support = {APP1197652//National Health &amp; Medical Research Council with a Centre of Research Excellence/ ; APP1197652//National Health &amp; Medical Research Council with a Centre of Research Excellence/ ; APP1197652//National Health &amp; Medical Research Council with a Centre of Research Excellence/ ; 1163065//Cancer Australia Priority-driven Collaborative Cancer Research Scheme/ ; 1163065//Cancer Australia Priority-driven Collaborative Cancer Research Scheme/ ; }, mesh = {Animals ; Mice ; *Tumor Microenvironment/immunology/radiation effects ; *Immunotherapy/methods ; *Mesothelioma/radiotherapy/immunology/therapy/pathology ; *Disease Models, Animal ; Dose Fractionation, Radiation ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Female ; Mice, Inbred C57BL ; Humans ; Cell Line, Tumor ; Combined Modality Therapy/methods ; }, abstract = {Combination immune checkpoint inhibitors (nivolumab and ipilimumab) are currently a first-line treatment for mesothelioma; however, not all patients respond. The efficacy of treatment is influenced by the tumor microenvironment. Murine mesothelioma tumors were irritated with various radiotherapy doses. Radiotherapy induced vasculature changes were monitored by power Doppler and photoacoustic ultrasound and analyzed via mixed-effects models. Tissue staining was used to investigate the immune cell infiltrate of tumors. The optimal radiotherapy schedule was combined with immune checkpoint inhibitors, and the survival of mice was analyzed. Using low-dose, low-fraction radiotherapy allowed favorable modification of the murine mesothelioma tumor microenvironment. Irradiating tumors with 2 Gy × 5 fractions significantly improved blood flow and reduced hypoxia, consequently increasing the presence of CD8[+] and regulatory T cells in the tumor. Understanding the transient nature of these changes is crucial for optimizing the timing of therapeutic delivery. The combination of radiotherapy with dual immunotherapy (anti-PD-1 plus anti-CTLA-4) proved highly curative when administered concurrently. A diminishing rate of cures was noted with an increasing delay between radiotherapy and subsequent immunotherapy. Concurrent low-dose, low-fraction radiotherapy emerges as a translatable approach for improving the efficacy of immune checkpoint inhibitors in patients.}, }
@article {pmid39747518, year = {2025}, author = {Nielsen, DM and Hsu, M and Zapata, M and Ciavarra, G and van Zyl, L}, title = {Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {169}, pmid = {39747518}, issn = {2045-2322}, abstract = {Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.}, }
@article {pmid39737233, year = {2024}, author = {Franzoi, IG}, title = {Rediscovering one's own voice in a brief psychoanalytic group intervention aimed at malignant mesothelioma patients and their families.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1471057}, pmid = {39737233}, issn = {1664-1078}, abstract = {Occupational and/or environmental exposure to asbestos can lead to clinical manifestation of a variety of diseases, including malignant mesothelioma (MM), a rare cancer with a particularly high incidence rate in areas with a long history of asbestos processing. This paper aims to describe brief psychoanalytic groups (BPGs), which is an intervention model aimed at MM patients and their families in the early stages of the disease, shortly after diagnosis. The BPG model comprises 12 weekly sessions of 1 h each, co-led by two psychoanalytically oriented psychotherapists who are trained in working with cancer patients and their families and in the specifics of the BPG setting. Reflections in this paper on the BPGs will attempt to trace the voice of the group in clinical material, paying attention to its horizontal unfolding as a melodic development over time and its vertical unfolding as a harmonic interweaving between the different individual voices, which, even when opposed to each other, can find a generative interlocking of meaning. In the BPG, then, it is possible to set in motion transformations that allow one to embrace the different and diverse affective colorations of experience, evolve toward a thinking that is capable of incorporating intense emotions related to death and grief, follow healthier paths of interaction on an intrapsychic and interpersonal level, and find traces of one's own vitality.}, }
@article {pmid39731918, year = {2024}, author = {Chin, WL and Cook, AM and Chee, J and Principe, N and Hoang, TS and Kidman, J and Hmon, KPW and Yeow, Y and Jones, ME and Hou, R and Denisenko, E and McDonnell, AM and Hon, CC and Moody, J and Anderson, D and Yip, S and Cummins, MM and Stockler, MR and Kok, PS and Brown, C and John, T and Kao, SC and Karikios, DJ and O'Byrne, KJ and Hughes, BGM and Lake, RA and Forrest, ARR and Nowak, AK and Lassmann, T and Lesterhuis, WJ}, title = {Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {101882}, doi = {10.1016/j.xcrm.2024.101882}, pmid = {39731918}, issn = {2666-3791}, abstract = {Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54). Single-cell RNA-seq and T cell receptor sequencing (TCR-seq) reveal that CD8[+] T effector memory (TEM) cells with stem-like properties are more abundant in peripheral blood of responders and that this population expands upon treatment. These peripheral blood changes are linked to the transcriptional state of the tumor microenvironment. Combining information from both compartments, rather than individually, is most predictive of response. Our study highlights complex interactions between the tumor and immune cells in peripheral blood during objective tumor responses to chemoimmunotherapy. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616001170415.}, }
@article {pmid39697085, year = {2024}, author = {Kurzhunbaeva, Z and Dzhusupov, K and Spinazzè, A and Visonà, SD and Sulaimanova, C and Kasymov, O and Belluso, E and Colosio, C}, title = {Human Exposure to Asbestos in Central Asian Countries and Health Effects: A Narrative Review.}, journal = {La Medicina del lavoro}, volume = {115}, number = {6}, pages = {e2024042}, doi = {10.23749/mdl.v115i6.15453}, pmid = {39697085}, issn = {0025-7818}, mesh = {Humans ; *Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Occupational Exposure/adverse effects ; Asia, Central/epidemiology ; Asbestosis/epidemiology/etiology ; Kazakhstan/epidemiology ; Mesothelioma/etiology/epidemiology ; }, abstract = {The discovery of the detrimental effects of asbestos on human health came long after its widespread use, with the first scientific evidence of asbestos-related diseases emerging in the late 19th and early 20th centuries. Despite efforts to ban its use, asbestos continues to be mined and used in Central Asia (as well as in Russia, China, and other countries). To gain a deeper understanding of the situation in Central Asia, we have conducted a systematic review of scientific literature on the use of asbestos, exposure assessment, and health consequences of asbestos exposure in this geographic area. This review encompasses studies about exposure assessments, epidemiological data, and biochemical or clinical surveys conducted in Kazakhstan, Uzbekistan, Tajikistan, Turkmenistan, and Kyrgyzstan. A total of 18 articles met the inclusion criteria, and their content is summarised in this review, which represents the first attempt to systematically examine research on asbestos and its impact on the health of workers and the general population in Central Asia countries, including literature published in Russian and English. The findings here highlighted the substantial limitations of the currently available knowledge about the impact of asbestos on health in this geographical area.}, }
@article {pmid39686704, year = {2024}, author = {Meisenkothen, C}, title = {Underestimation of Chrysotile Health Risk due to Under-ascertainment of Mesothelioma: Evidence from a Century of Connecticut's Experience with the "Magic Mineral".}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {}, number = {}, pages = {10482911241303469}, doi = {10.1177/10482911241303469}, pmid = {39686704}, issn = {1541-3772}, abstract = {Over a century ago, Connecticut industry began using chrysotile asbestos. Chrysotile found a home in several factories that used it exclusively or predominantly. The occurrence of mesothelioma in 4 of those factories is the subject of this paper-2 have been reported previously and are updated here with new information; one was the subject of a prior internal corporate study that was never published; one is reported here for the first time. Twenty-four cases of mesothelioma have been identified among these workers, including several who had no known amphibole exposure. It is likely that additional cases of mesothelioma have been missed. The full scale of the hazard may never be completely known, but reports such as the present one add to the weight of evidence that chrysotile causes mesothelioma in humans and that the full extent of the epidemic is probably wider than retrospective studies have revealed. Continued vigilance is required.}, }
@article {pmid39682143, year = {2024}, author = {Stella, S and Ceresoli, GL and Dallari, B and Barile, R and Maisenti, F and Rugarli, S and Marinaccio, A and Consonni, D and Mensi, C}, title = {Mesothelioma of the Tunica Vaginalis Testis: Diagnostic and Therapeutic Management. A Comprehensive Review, 1982-2024.}, journal = {Cancers}, volume = {16}, number = {23}, pages = {}, doi = {10.3390/cancers16233956}, pmid = {39682143}, issn = {2072-6694}, support = {BRIC INAIL ID 66/2022 [Grant PB-0184]//INAIL: Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro/ ; }, abstract = {BACKGROUND: Mesothelioma of the tunica vaginalis testis (MTVT) is an extremely rare and aggressive cancer. The diagnosis and management of MTVT is complex, and no standard treatment protocol is available.<br><br>METHODS: We conducted a systematic literature review from 1 January 1982 to 14 March 2024 using PubMed to collect all the available case reports and case series. A descriptive analysis of patient characteristics with clinical presentation, diagnostic work-up, therapeutic management, and past asbestos exposure was performed. Survival times of patients treated with different therapeutic approaches were evaluated.<br><br>RESULTS: Overall, 289 patients with MTVT were included in our analysis. The most common clinical presentations were scrotal/testicular swelling or mass (187 patients, 65%) and the presence of hydrocele (159, 55%). Imaging evaluation, mostly with ultrasonography or CT scan, was reported in two-thirds of cases. Radical surgery (216 patients, 75%) with orchiectomy and, in select cases, hemiscrotectomy and inguinal lymphadenectomy was the most frequent therapeutic approach. A minority of patients (49, 17%) received adjuvant therapy after surgery (radiotherapy, chemotherapy, or a combination of the two), with no evidence of survival improvement.<br><br>CONCLUSIONS: No standard guidelines for MTVT are available so far. Radical surgery following accurate radiological staging should be the mainstay of treatment. The role of adjuvant treatments remains undefined. Due to its rarity, MTVT should be treated in referral centers, and patients' data should be collected in a dedicated register in order to improve the knowledge of this exceedingly rare disease and establish optimal diagnostic and therapeutic management.}, }
@article {pmid39679483, year = {2024}, author = {Taiano, L and Porzio, A and Massari, S and Iavicoli, I and Palladino, R and Menegozzo, S and Mensi, C and Binazzi, A and Menegozzo, M and Marinaccio, A}, title = {[Mortality due to mesothelioma and asbestosis in Campania Region (Southern Italy): perspectives for reducing asbestos exposure].}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {6}, pages = {429-437}, doi = {10.19191/EP24.6.A754.134}, pmid = {39679483}, issn = {1120-9763}, mesh = {Humans ; Italy/epidemiology ; *Asbestosis/mortality ; Female ; Male ; *Mesothelioma/mortality ; *Asbestos/adverse effects ; Aged ; Middle Aged ; Environmental Exposure/adverse effects ; Lung Neoplasms/mortality ; Aged, 80 and over ; Adult ; }, abstract = {OBJECTIVES: to provide an overview of the geographical distribution of mesothelioma and asbestosis deaths in the Campania Region (Southern Italy) occurred from 2005 to 2018 and to identify areas at higher risk.<br><br>DESIGN: for each municipality, Standardized Mortality Ratios (SMRs) for mesothelioma and asbestosis have been estimated from the mortality data provided by the Italian National Institute of Statistics (Istat). Deaths for which mesothelioma and asbestosis were identified as the underlying causes, according to the classification system ICD-10 codes (C45 and J61, respectively), were included. Expected cases were estimated applying age- and gender-specific mortality rates in Campania on resident populations of each municipality. Furthermore, the association between the municipal SMR and the local socioeconomic deprivation index based on the 2011 General Census of Population and Housing was also analysed.<br><br>SETTING AND PARTICIPANTS: Campania Region.<br><br>MAIN OUTCOMES MEASURES: the study outcomes were standardized mortality ratios for mesothelioma and asbestosis and the identification of territorial subareas.<br><br>RESULTS: a total of 998 deaths attributed to mesothelioma and 62 to asbestosis were identified. No cases of death due to mesothelioma or asbestosis were reported in the province of Benevento. A significant increase in mortality due to mesothelioma was observed across 34 municipalities. These findings show that several municipalities within the province of Naples display a high increase in mortality due to mesothelioma and asbestosis, with 506 deaths in total and 246 cases recorded in the municipality of Naples against 178,37 expected (SMR 1,38; 90%CI 1.24-1.53). In 15 municipalities, a notable increase in mortality for asbestosis was recorded; in Naples, 28 cases occurred (SMR 2,51; 90%CI 1.84-3.42). The overlap between mortality maps for mesothelioma and asbestosis confirms the existence of areas subjected to definite and prolonged asbestos exposure. Additionally, a correlation with the deprivation index was noted: the pooled SMR by quintiles increases with higher quintiles of the deprivation index, for both mesothelioma and asbestosis.<br><br>CONCLUSIONS: results highlight the crucial need for epidemiological surveillance of asbestos-related diseases in Campania. Actively searching out for new cases of mesothelioma in the entire region is a crucial task in primary prevention of occupational, environmental, and domestic exposures to asbestos.}, }
@article {pmid39668371, year = {2024}, author = {Tibaldi, E and Gnudi, F and Mandrioli, D and Bruno, C and Zona, A and Fazzo, L and Comba, P}, title = {Pathological characterization of lung fibrosis in Sprague-Dawley rats treated with fluoro-edenite fibres by intrapleural injection.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {19}, number = {1}, pages = {45}, pmid = {39668371}, issn = {1745-6673}, abstract = {BACKGROUND: An increased incidence of pleural mesotheliomas in Biancavilla (Italy) was attributed to the environmental exposure to fluoro-edenite (FE). Results from the Ramazzini Institute (RI) in vivo long-term study confirmed the evidence that exposure to FE fibres is correlated with an increase of malignant pleural mesotheliomas in Sprague-Dawley rats. Recently asbestosis-like features were substantiated in Biancavilla residents without known occupational exposures. Aim of this work was to establish whether FE induce lung fibrosis with a pathogenetic mechanism similar to other asbestiform fibres.<br><br>METHODS: Original slides from the RI study were systematically re-examined to characterize the FE-induced lesions. Quantitative analysis of lung fibrosis was assessed following the Ashcroft method. Immunohistochemical analysis of protein involved in fibrotic responses and histochemical staining for FE-fibres identification were performed.<br><br>RESULTS: Like asbestos, FE caused fibrotic lesions, pleural plaques or nodules and mesotheliomas. A significant increase of lung fibrosis (p&#x2009;<&#x2009;0.001) was observed in the FE-treated groups compared to untreated controls. In the fibrotic responses to FE, vimentin was the most expressed protein, followed by collagen-I and alpha-SMA. Finally, ferruginous bodies, characterized by iron deposits and ferritin expression, were observed in FE-induced lesions.<br><br>CONCLUSIONS: This study confirmed that FE exposure promotes the onset of fibrotic lesions at pleural level, as fibrous plaques or nodules and fibrosis, through a mechanism similar to other form of asbestos. These results combined with epidemiological study reported in Biancavilla residents, corroborate the need to promote health and epidemiological surveillance plans of respiratory diseases in population living in FE contaminated sites.}, }
@article {pmid39611075, year = {2024}, author = {Fadl, L and Fadl, M and Fadl, O and Thaplar G Gouda, SG and Mirza, H}, title = {A Case Report of Peritoneal Mesothelioma as an Acute Abdomen Mimic: A Rare Presentation and Diagnostic Challenges.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74598}, pmid = {39611075}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer often linked to asbestos exposure. This case report presents a 60-year-old man with a history of asbestos exposure who developed MPM, initially presenting with acute abdominal pain, an uncommon mimic of the acute abdomen. Diagnosing MPM is challenging due to its vague symptoms, often leading to delayed diagnosis. Additionally, the patient developed internal jugular vein thrombosis, a rare complication associated with malignancies. This case highlights the rare presentation of peritoneal mesothelioma as an acute abdomen mimic, the diagnostic complexities associated with MPM, and the rare type of thromboembolic event in this case.}, }
@article {pmid39609252, year = {2024}, author = {Visonà, SD and Untalan, M and Bertoglio, B and Capella, S and Belluso, E and Billò, M and Ivic-Pavlicic, T and Taioli, E}, title = {Asbestos Burden in Lungs of Subjects Deceased From Mesothelioma Who Lived in Proximity to an Asbestos Factory: A Topographic Post-Mortem SEM-EDS Study.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23680}, pmid = {39609252}, issn = {1097-0274}, support = {//The authors received no specific funding for this work./ ; }, abstract = {BACKGROUND: Asbestos exposure and its pathological consequences, especially malignant mesothelioma (MM) still represent a major public health problem on a global scale. After the ban of asbestos in most western countries, nonoccupational exposure plays an essential role in MM pathogenesis. However, few studies have quantified asbestos lung burden after environmental exposure. The main objective of this work is to understand if asbestos lung content is different between occupationally and environmentally exposed individuals, and if the distance between the subjects' residences and the source of exposure is significantly associated with the asbestos lung burden.<br><br>METHODS: In this retrospective, observational study we quantified, with analytical scanning electron microscopy, asbestos content in lungs of individuals deceased from MM between 2005 and 2019, who were exposed to asbestos (occupationally and/or environmentally) in Broni, a small town in northern Italy where an important asbestos-cement plant operated until 1993.<br><br>RESULTS: We analyzed asbestos lung content of 77 subjects. We found that the asbestos lung content in MM patients who lived around the asbestos factory was as high as that seen in occupationally exposed individuals; this holds true in residents up to 10&#x2009;km radius from the factory. We found no significant associations between the residence duration/distance ratio and asbestos lung burden.<br><br>CONCLUSIONS: This study suggests that heavy asbestos pollution involves not only the area adjacent to the factory, but the entire town of Broni and the surroundings. This is alarming if we consider that most asbestos factories still active in some countries are located close to towns and dwellings.}, }
@article {pmid39607779, year = {2024}, author = {Faccioli, E and Dell'Amore, A and Lorenzoni, G and Schiavon, M and Canu, G and Pasello, G and Zambello, G and Sepulcri, M and Sambataro, V and Labella, F and Giraudo, C and Gregori, D and Calabrese, F and Rea, F}, title = {Surgery for pleural mesothelioma in multimodality setting: comparison between surgical techniques in a high-volume center.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {}, number = {}, pages = {}, doi = {10.1093/ejcts/ezae431}, pmid = {39607779}, issn = {1873-734X}, abstract = {OBJECTIVES: Pleural mesothelioma (PM) is an aggressive disease linked to asbestos exposure, presenting significant treatment challenges. The recommended approach is multimodal treatment, even if the concept of resectable PM and the superiority of one surgical technique over the other [(extended) pleurectomy decortication [(E)PD] vs extra-pleural pneumonectomy (EPP)] are matter of debates. The aim of this study is to compare the two techniques in terms of short- and long-term outcomes at a high-volume center.<br><br>METHODS: Clinical data from PM patients who underwent radical surgery [(E)PD and EPP] between 1994 and 2022 were collected. A propensity score weighting approach was used for non-random intervention allocation. Survival distribution was estimated using Kaplan-Meier method and the association with outcomes was evaluated using a weighted Cox Proportional Hazard Models.<br><br>RESULTS: Among 254 patients, 125 (49%) underwent EPP and 129 (51%) (E)PD. The 90-day mortality was higher in the EPP group (7.2% vs 0%; p&#x2009;=&#x2009;0.01). No difference in 1-,3- and 5-year survival was found: 65.8%, 26%, 17% for EPP and 75.5%, 39.7% and 21.3% for (E)PD; p&#x2009;=&#x2009;0.39). The multivariable weighted Cox model identified no increased risk of death (HR 1.25; p&#x2009;=&#x2009;0.49) or recurrence (HR 1.05; p&#x2009;=&#x2009;0.858) in the EPP group. Pre-operative total lung capacity (TLC) was significantly associated with a reduced risk of death (HR 0.96; p&#x2009;=&#x2009;0.023) and recurrence (HR 0.97; p&#x2009;=&#x2009;0.019) at follow-up while preoperative disease burden to a higher risk of recurrence (HR 1.01; p&#x2009;=&#x2009;0.02).<br><br>CONCLUSIONS: Our experience showed acceptable short- and long-term outcomes in both procedures, making EPP still an option only for carefully selected patients at high volume center. Surgery, although recently debated, should be performed exclusively in expert centers to minimize post-operative risks. The identification of new prognostic factors is crucial for better selecting patients who may benefit from surgery within the context of multimodal treatment.}, }
@article {pmid39604235, year = {2024}, author = {Chen, YQ and Gao, ZB and Shen, W and Ying, SB and He, XL and Zhang, X and Jiang, ZQ and Lou, JL}, title = {[The prognostic value of BAP1 protein loss in patients with malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {11}, pages = {815-820}, doi = {10.3760/cma.j.cn121094-20240112-00016}, pmid = {39604235}, issn = {1001-9391}, support = {KYYB202113//The Basic Scientific Research Business Fee and Basic Scientific Research Plan of Hangzhou Medical College/ ; 81973011//The National Natural Science Foundation of China/ ; //The Key Discipline of Zhejiang Province in Public Health and Preventive Medicine (First Class, Category A) of Hangzhou Medical College/ ; }, mesh = {Humans ; *Ubiquitin Thiolesterase/metabolism ; Female ; *Tumor Suppressor Proteins/metabolism ; Male ; Middle Aged ; *Mesothelioma, Malignant/metabolism ; Prognosis ; *Lung Neoplasms/metabolism ; Aged ; *Mesothelioma/metabolism ; Survival Rate ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Adult ; }, abstract = {Objective: To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) . Methods: A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate. Results: Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ(2)=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery (P<0.05). Multivariate model results showed that positive expression of BAP1 protein (HR=3.75, 95%CI: 2.23-6.30, P<0.001) and age ≥57 years (HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion: Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.}, }
@article {pmid39569577, year = {2024}, author = {Angelini, A and Martini, A and Masala, G}, title = {[Update. Inventory of occupational exposure to asbestos with particular reference to Tuscan worker].}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {6}, pages = {1-128}, doi = {10.19191/EP24.6.S1.128}, pmid = {39569577}, issn = {1120-9763}, mesh = {Italy/epidemiology ; *Asbestos/adverse effects ; Humans ; *Occupational Exposure/adverse effects ; Occupational Diseases/epidemiology ; Lung Neoplasms/epidemiology/etiology/chemically induced ; Asbestosis/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Carcinogens ; Population Surveillance ; }, abstract = {This Catalogue is a collection of information on the use of raw asbestos and asbestos-containing materials used in several industries and occupational activities, with particular attention to the situation of Tuscany, a region of Central Italy. The work was developed at the Institute for Cancer Research, Prevention and Clinical Network (ISPRO) of Florence, where epidemiologic research and surveillance activities have been developing since 1988 and where the coordination and evaluation of the regional health surveillance programme provided to past asbestos workers started in 2016 and is still ongoing. The Catalogue aims at being a working tool for all health professionals engaged in examining and classifying the occupational asbestos exposures of subjects both affected by diseases that could be associated to this carcinogen and examined within the regional health surveillance programme. It is necessary for the health personnel engaged in the above-mentioned activities to know or to have the possibility to find exact and detailed data on asbestos exposure by occupational sector. These data are briefly described in the 29 factsheets this Catalogue consists of. In each factsheet, the presence and every use of asbestos are described, with reference to a precise occupational sector. Several occupational sectors can be considered together because of analogies on asbestos exposure. Occupations are considered on the basis of existing evidence on the use of raw asbestos or asbestos-containing materials (as semi-finished or finished products or as auxiliary materials in production processes). Besides the presence and use of asbestos, a description of the possible exposures of workers is reported. Sources of information were scientific and grey literature as well as the 8,097 occupational histories of mesothelioma registered by the specific Tuscan registry. Some factsheets have been revised and enhanced by Italian experts on the asbestos exposure with a specific competence in the examined sectors. Each factsheet includes also questions to be addressed to workers in order to examine in depth their possible asbestos exposure. For those who would like to expand their knowledge on this topic, references are reported both at the end of each factsheet and at the end of the volume. In all industrialized countries, also in those which have not already banned asbestos use, a decrease in the use of this material and in the relative exposure have been observing since the end of the Seventies, few years after the general consensus within the scientific community on asbestos carcinogenicity. This decreasing trend has been becoming greater and greater since the end of the Eighties, when more restrictive regulations have been approved and applied, especially in occupational settings. Nevertheless, nowadays asbestos-related diseases are still diagnosed due to past exposures, although during next decade a decreasing incidence of malignant mesothelioma - the cancer most specifically related to this carcinogen and characterized by a very bad prognosis and the longest latency - could be observed. Particular attention will be paid to jobs regarding renovation of old buildings containing asbestos and to decontamination activities. In conclusion, this Catalogue is a working tool - although it is not exhaustive and could be upgraded with new information - for all professionals engaged in asbestos risk prevention activities as health personnel, personnel of insurance companies, employers, and employee representatives.}, }
@article {pmid39568634, year = {2024}, author = {Yilmaz, ME and Rashidfarokhi, M and Pollard, K and Durmus, N and Keserci, S and Sterman, DH and Arslan, AA and Shao, Y and Reibman, J}, title = {Mesothelioma Cases in the World Trade Center Survivors.}, journal = {Annals of case reports}, volume = {9}, number = {2}, pages = {}, pmid = {39568634}, issn = {2574-7754}, abstract = {OBJECTIVES: The destruction of the World Trade Center (WTC) towers in New York City on September 11, 2001 (9/11), released approximately 1 million tons of pulverized particulate matter throughout southern Manhattan and areas in Brooklyn, exposing community members and responders to high levels of potentially toxic environmental particles. Asbestos exposure was a health concern because of its use in certain sections of the WTC towers. Malignant mesothelioma, originating from the lining cells (mesothelium) of the peritoneal and pleural cavities, is one complication associated with asbestos exposure.<br><br>METHODS: The WTC Environmental Health Center (WTC EHC) is a treatment and surveillance program for community members (Survivors) exposed to WTC dust and fumes.<br><br>RESULTS: In this report, we describe four cases of mesothelioma in the WTC EHC as of July 1st, 2023. Two of our patients have been diagnosed with peritoneal mesothelioma and two patients have been diagnosed with pleural mesothelioma.<br><br>CONCLUSION: Given the known delay in the development of mesotheliomas after asbestos exposure, we provide information on these early mesothelioma cases to enhance the understanding of the adverse health effects of WTC exposures on the local community.}, }
@article {pmid39558529, year = {2024}, author = {Willis, VJ and Levin, JL and Nessim, DE}, title = {A Review of Job Assignments and Asbestos Workplace Exposure Measurements for TAWP Mesothelioma Deaths Through 2011.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23675}, pmid = {39558529}, issn = {1097-0274}, support = {//This study was supported by the Jesse Jones Distinguished Professorship of Occupational Health Sciences Endowment, University of Texas at Tyler Health Science Center Occupational and Environmental Medicine Residency Program./ ; }, abstract = {INTRODUCTION: Asbestos workers have a higher risk of developing mesothelioma; however, few studies have looked at specific jobs and job locations within asbestos factories. The purpose of this study was to investigate asbestos exposure in different job locations of the Tyler, Texas asbestos plant to determine if there was a relationship between the duration of exposure and air fiber concentration burden in workers who developed pleural versus peritoneal mesothelioma.<br><br>METHODS: This study used a patient information database to compile secondary data on 23 workers who died from mesothelioma through 2011. The airborne fiber exposure burdens for each of the 23 workers were estimated and then stratified by job location category and by type of mesothelioma for analysis.<br><br>RESULTS: Most of the worker cases were assigned to the forming area which had the overall highest fiber concentration of all the plant's job locations. Workers who developed pleural mesothelioma spent the most time in the packing and miscellaneous locations, whereas workers who developed peritoneal mesothelioma worked mostly in the forming and miscellaneous locations. There were significant differences in days worked and estimated airborne exposure fiber burden between the pleural and peritoneal mesothelioma cases in the forming and curing locations.<br><br>CONCLUSION: Results from this study reiterate the association between occupational asbestos exposure and mesothelioma, emphasizing the importance of concentration of respirable asbestos dust levels and duration of exposure.}, }
@article {pmid39539262, year = {2024}, author = {Ebrahimi, A and Ak, G and Özel, C and İzgördü, H and Ghorbanpoor, H and Hassan, S and Avci, H and Metintaş, M}, title = {Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review.}, journal = {ACS pharmacology &amp; translational science}, volume = {7}, number = {11}, pages = {3299-3333}, doi = {10.1021/acsptsci.4c00324}, pmid = {39539262}, issn = {2575-9108}, abstract = {Pleural mesothelioma (PM), a rare malignant tumor explicitly associated with asbestos and erionite exposures, has become a global health problem due to limited treatment options and a poor prognosis, in which the median life expectancy varies depending on the method of treatment. However, the importance of early diagnosis is emphasized, and the practical methods have not matured yet. This study provides a critical overview of PM, addressing various aspects like epidemiology, etiology, diagnosis, treatment options, and the potential use of advanced technologies like microfluidic chip-based models for research and diagnosis. It initially begins with fundamentals of clinical aspects and then discusses the identification of disease-specific biomarkers in patients' serum or plasma samples, which could potentially be used for early diagnosis. A detailed investigation of the sophisticated preclinical models is highlighted. Recent three-dimensional (3D) model accomplishments, including microarchitecture modeling by transwell coculture, spheroids, organoids, 3D bioprinting constructs, and ex vivo tumor slices, are discussed comprehensively. On-chip models that imitate physiological processes, such as detection chips and therapeutic screening chips, are assessed as potential techniques. The review concludes with a critical and constructive discussion of the growing interest in the topic and its limitations and suggestions.}, }
@article {pmid39534944, year = {2024}, author = {Wu, Y and Zhao, Y and Yu, L and Wang, R and Feng, W and Wu, Y and Wang, L and Chen, H and He, Z and Wang, Q}, title = {Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib.}, journal = {The Journal of international medical research}, volume = {52}, number = {11}, pages = {3000605241287320}, doi = {10.1177/03000605241287320}, pmid = {39534944}, issn = {1473-2300}, mesh = {Humans ; *Crizotinib/therapeutic use ; Female ; *Anaplastic Lymphoma Kinase/genetics ; *Mesothelioma, Malignant/drug therapy/genetics/pathology ; *Mutation ; *Lung Neoplasms/genetics/drug therapy/pathology ; *Pleural Neoplasms/genetics/drug therapy/pathology ; *Protein Kinase Inhibitors/therapeutic use ; *Mesothelioma/genetics/drug therapy/pathology ; Pyridines/therapeutic use ; Receptor Protein-Tyrosine Kinases/genetics ; Pyrazoles/therapeutic use ; Molecular Targeted Therapy ; Middle Aged ; Gene Fusion ; }, abstract = {Malignant mesothelioma is a rare highly invasive tumour originating from the mesothelial cells of the pleura, peritoneum and pericardium. Malignant pleural mesothelioma (MPM) is the most common type in all malignant mesothelioma. The onset of MPM is associated with exposure to asbestos and it can have an incubation period of up to 40 years. The incidence of MPM has been increasing worldwide in recent years, so more attention has been focused on its diagnosis, treatment and prognosis. Activating mutations, amplifications and fusions/rearrangements of the anaplastic lymphoma kinase receptor tyrosine kinase (ALK) gene are commonly seen in patients with non-small cell lung cancer. However, it is rare in MPM. This current case report describes a female patient with advanced MPM with an ALK gene fusion mutation. In this particular case, treatment with crizotinib demonstrated some initial efficacy, which suggests that this might be a promising strategy for patients with advanced MPM with an ALK gene mutation. This required further research and evaluation in the future.}, }
@article {pmid39516654, year = {2023}, author = {Gold, LT and Bray, SE and Kernohan, NM and Henderson, N and Nowicki, M and Masson, GR}, title = {The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma.}, journal = {BJC reports}, volume = {1}, number = {1}, pages = {4}, pmid = {39516654}, issn = {2731-9377}, support = {119615//Tenovus/ ; }, abstract = {BACKGROUND: Malignant mesothelioma is a tumour that is strongly associated with a history of asbestos exposure, and which derives from mesothelial cells that line the serous cavities of the body. The tumour most commonly arises in the pleural cavity, but can also arise in the pericardium, peritoneum, and tunica vaginalis. At present the lesion has a very poor prognosis and is an incurable form of cancer with median survival times of up to 19 months being quoted for some histological subtypes. A large proportion of mesotheliomas have been shown to be arginine auxotrophic, leading to new research for therapeutics which might exploit this potential vulnerability.<br><br>METHODS: We measured the levels of General Control Non-derepressible 2 (GCN2) protein in malignant mesothelioma tumour samples and determined whether these levels correlate with clinical outcomes.<br><br>RESULTS: We observed that the expression levels of GCN2 correlated with patient survival and was an independent prognostic variable in pairwise comparisons with all available clinical data.<br><br>CONCLUSION: These findings suggest that GCN2 levels provides prognostic information and may allow for stratification of care pathways. It may suggest that targeting GCN2 is a viable strategy for mesothelioma therapy development.}, }
@article {pmid39514167, year = {2024}, author = {Guglielmo, P and Crivellaro, C and Castello, A and Della Corte, CM and Pagano, M and Marchesi, S and Occhipinti, M and Zucali, PA and Evangelista, L}, title = {Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [[18]F]FDG Alternatives.}, journal = {Molecular diagnosis &amp; therapy}, volume = {}, number = {}, pages = {}, pmid = {39514167}, issn = {1179-2000}, abstract = {Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([[18]F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation. However, it has some limitations, including lower sensitivity after pleurodesis and poor accuracy for involved lymph node evaluation. Thus, there is the need to explore other agents. The aim of the present review is to analyze the current literature on the use of alternative radiopharmaceuticals for PET imaging in patients with mesothelioma. A comprehensive search of scientific databases (PubMed, Scopus, and Web of Science) for studies published in the last decade was performed by using the following keywords: "mesothelioma" AND "PET" AND "PET/CT" "radiopharmaceuticals", "[[18]F]FDG alternatives". Articles focused solely on [[18]F]FDG, non-English publications or preclinical studies, reviews, meeting abstracts, letters to the editors, and editorials were excluded. A qualitative assessment was made by using the Critical Appraisal Skills Programme (CASP) checklist for diagnostic test studies, when applicable. In total, 14 papers were selected; in seven articles more than five patients were enrolled, while the other seven were only clinical cases (enrolling up to two subjects). [[18]F]/gallium-68 ([[68]Ga])-labeled fibroblast activation protein inhibitor (FAPI) compounds, [[18]F]Fluorothymidine ([[18]F]FLT), methionine labeled with carbon-11 ([[11]C]MET), and fluoromisonidazole labeled with fluorine-18 ([[18]F]FMISO) PET/CT were the alternative agents used most often. In 12 articles, [[18]F]FDG PET/CT was used as a comparator imaging modality. Detection rate of [[18]F]FDG was similar to the other radiopharmaceuticals ([[68]Ga]/[18F]-labeled FAPI compounds, [[18]F]FLT, [[18]F]FMISO, [[11]C]MET, and [[68]Ga]-Pentaxifor), although radiolabeled FAPI seems to exhibit a higher diagnostic performance. [[18]F]FDG is still a valuable agent in patients with mesothelioma. However, radiolabeled FAPI appears to be promising and its theranostic properties should therefore be further assessed.}, }
@article {pmid39507169, year = {2024}, author = {Lief, S and Patibandla, S and Ansari, AZ and Bhatt, N and Gulraiz, A and Beauti, SM and Ali, R}, title = {Ascites as a Rare Manifestation of Malignant Peritoneal Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e70982}, doi = {10.7759/cureus.70982}, pmid = {39507169}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that originates from the mesothelial cells lining the parietal peritoneum or visceral peritoneum and extensively spreads within the abdominal cavity. It is a rare malignancy characterized by an insidious onset and poor prognosis. We present the case of a 79-year-old Caucasian male who experienced escalating abdominal pain for six weeks and acute abdominal distension. His medical history was significant for hypertension, gastroesophageal reflux disease (GERD), hypercholesterolemia, and prior coronary artery bypass grafting (CABG). The patient had a 30-pack-year smoking history and worked as a plumber and roofer until retirement. We also confirmed with the patient that he has never been diagnosed with asbestosis. He reported no family history of mesothelioma or related conditions. A computed tomography (CT) scan revealed a prior sternotomy, mild pleural calcifications, mild hepatic steatosis, diffuse peritoneal ascites, diffuse omental edema, and pelvic phleboliths. MPM was confirmed through histopathological examination, which revealed atypical mesothelial cells with high nucleus-to-cytoplasm ratios, prominent nucleoli, and irregular nuclear membranes. It also revealed tumor cells positive for p53, calretinin, WT1, and podoplanin (D2-40). This case highlights the importance of considering MPM in the differential diagnosis for patients with ascites and possible asbestos exposure, particularly with respect to occupational hazards, as it is a rare manifestation of the disease.}, }
@article {pmid39481034, year = {2024}, author = {Gilbert, A and Wieland, R and Zacher, N and Rieger, K and Berry, GJ and Novoa, R}, title = {Metastatic Mesothelioma of the Tunica Vaginalis Presenting as Scrotal and Abdominal Nodules: A Case Report and Review of the Literature.}, journal = {The American Journal of dermatopathology}, volume = {}, number = {}, pages = {}, doi = {10.1097/DAD.0000000000002848}, pmid = {39481034}, issn = {1533-0311}, abstract = {Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.}, }
@article {pmid39474071, year = {2024}, author = {Behrouzfar, K and Mutsaers, SE and Chin, WL and Patrick, K and Ng, IT and Pixley, FJ and Morahan, G and Lake, RA and Fisher, SA}, title = {Mesothelioma survival prediction based on a six-gene transcriptomic signature.}, journal = {iScience}, volume = {27}, number = {10}, pages = {111011}, pmid = {39474071}, issn = {2589-0042}, abstract = {Mesothelioma is a lethal cancer. Despite promising outcomes associated with immunotherapy, durable responses remain restricted to a minority of patients, highlighting the need for improved strategies that better predict outcome. Here, we described the development of a mesothelioma-specific gene signature that accurately predicts survival. Comprehensive gene expression analysis of asbestos exposed MexTAg Collaborative Cross mouse tumors revealed distinct tumor clusters characterized by epithelial mesenchymal transition/extracellular matrix, or immune infiltrate related gene expression profiles. Weighted gene co-expression network analysis (WGCNA) identified 20 hub genes that drove differential gene expression. Human homologues of these 20 hub genes were refined through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to identify a six-gene mesothelioma-specific prognostic signature that accurately predicted patient survival across four independent human mesothelioma datasets. Furthermore, this six-gene signature demonstrated the potential to predict treatment response, thus advancing the management of this challenging malignancy.}, }
@article {pmid39472148, year = {2024}, author = {Mei, W and Yang, SJ and Zhang, YP}, title = {[Establishment and research progress of early diagnosis system for pleural mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {10}, pages = {793-800}, doi = {10.3760/cma.j.cn121094-20230915-00060}, pmid = {39472148}, issn = {1001-9391}, support = {202301BA070001-26, 202301BA070001-027//Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities/ ; 81560458, 31601155//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Mesothelioma/diagnosis ; *Pleural Neoplasms/diagnosis ; *Early Detection of Cancer/methods ; MicroRNAs/blood ; Lung Neoplasms/diagnosis ; Biomarkers, Tumor/blood ; Breath Tests ; Early Diagnosis ; Mesothelioma, Malignant/diagnosis ; }, abstract = {Pleural mesothelioma (PMe) was associated with asbestos exposure.The Diagnosis of PMe is difficult due to the lack of specificity of clinical signs and symptoms, although there are many tools available for early diagnosis of mesothelioma. Most PMe patients are diagnosed at an advanced stage. This article reviews advances in strategies for early diagnosis of mesothelioma, focusing on breath analysis, early diagnosis of pleural effusion cytology in patients with mesothelioma, serum biomarkers and miRNA.}, }
@article {pmid39469233, year = {2024}, author = {Santos, C and Sacadura-Leite, E and Feijó, S and Dixe, MDA and Astoul, P and Sousa-Uva, A}, title = {Translation, Cultural Adaptation, and Content Validation of a Pleural Mesothelioma Questionnaire to Portuguese Context - A Key Tool for Epidemiological Surveillance.}, journal = {Portuguese journal of public health}, volume = {42}, number = {2}, pages = {101-110}, pmid = {39469233}, issn = {2504-3145}, abstract = {OBJECTIVE: The main objective of this study was to describe the translation, cultural adaptation, and content validation process of the French National Surveillance Programme for Pleural Mesothelioma (FNSPPM) questionnaire for the Portuguese context.<br><br>METHODS: A search was conducted in the PubMed database and Web of Science, in the period from January 1, 1960, to December 31, 2022, to select the questionnaire. Forward and reverse translations, calculation of the content validity index (CVI) by a panel of experts (n = 9), and cognitive interviewing with individuals with at least one exposure to asbestos (n = 10) were performed. Experts rated items on a Likert scale (1-4) based on their relevance. The item-level content validity index (I-CVI), scale-level content validity index based on the average method (S-CVI/Ave), and scale-level content validity index based on the universal agreement method (S-CVI/UA) were calculated.<br><br>RESULTS: The final version of the FNSPPM questionnaire for the Portuguese context resulted from a translation and content validation process. The panel of experts considered the questionnaire relevant, with an I-CVI of up to 0.78 in 68 of 69 of the questions, an S-CVI/Ave of 0.98, and an S-CVI/UA of 0.90. The participants in the cognitive interviews reported an understanding of the questionnaire.<br><br>CONCLUSION: A validated FNSPPM questionnaire for the Portuguese context is now available to study individuals with pleural mesothelioma (PM) and asbestos exposure.}, }
@article {pmid39469260, year = {2023}, author = {Santos, C and Dixe, MDA and Sacadura-Leite, E and Astoul, P and Sousa-Uva, A}, title = {Asbestos Exposure and Malignant Pleural Mesothelioma: A Systematic Review of Literature.}, journal = {Portuguese journal of public health}, volume = {40}, number = {3}, pages = {188-202}, pmid = {39469260}, issn = {2504-3145}, abstract = {BACKGROUND: The relationship between exposure to asbestos and malignant pleural mesothelioma (MPM) is already well established. Nevertheless, much remains to be known about exposure thereto and the incidence and mortality from MPM.<br><br>OBJECTIVE: This systematic review aims to map the relationship between asbestos and MPM by studying the exposure to asbestos and the incidence and mortality of MPM.<br><br>METHODS: A systematic review was conducted relating asbestos and MPM. Exposure to asbestos, incidence, and mortality by MPM was reviewed. PubMed, Web of Science, Cochrane Library, RCAAP, DART-Europe, and the reference lists of included studies were searched, from January 1, 1960, to December 31, 2020. Methodological quality was checked, the risk of bias analysis was performed, a level of evidence grade was assigned, and descriptive data analysis was performed.<br><br>RESULTS: 3,484 unique citations were identified, which included seventeen observational studies that met inclusion criteria with a total of 1,104 patients. Heterogeneity is present between the included studies which range from a case series of 16 retrospective studies and 1 prospective study. Studies were mostly conducted in Europe, particularly in Italy (6), and were published between 1969 and 2020. The mean age of patients is approximately 66 years with a latency period between the first exposure and diagnosis of approximately 42 years. 14 studies present data regarding the occupational context and chrysotile and crocidolite are the most studied types of fibre. The incidence of cases occurred between the interval 1966 and 2014 and in 9 studies the mortality rate was 100% of patients.<br><br>CONCLUSION: There is high evidence to support the relationships between asbestos and MPM. However, the relatively scant information provided by the studies reinforces the need for well-conducted research and implementation of National Mesothelioma Surveillance Centres at a global level.}, }
@article {pmid39447016, year = {2024}, author = {Stevens, ME and Tuttle, BP and Brew, DW and Paustenbach, DJ}, title = {An evaluation of trends for mesothelioma mortality in American women: Addressing the content of a recent Morbidity and Mortality Weekly Report (MMWR).}, journal = {Toxicology and industrial health}, volume = {}, number = {}, pages = {7482337241293201}, doi = {10.1177/07482337241293201}, pmid = {39447016}, issn = {1477-0393}, abstract = {Mesothelioma is a fatal disease that has historically been associated with exposure to airborne asbestos. Because occupational asbestos exposures dropped dramatically in the late 1960s and early 1970s, far fewer cases of mesothelioma today are due to these fibers but, instead, are usually a result of the aging process or genetic predisposition. In May of 2022, a Morbidity and Mortality Weekly Report (MMWR) was issued by the Centers for Disease Control and Prevention (CDC) regarding malignant mesothelioma incidence in women from 1999 to 2020. While this MMWR alerted citizens to the continued presence of the disease, after reading this article one might have thought that the CDC was suggesting that the disease was increasing in women due to asbestos exposures (which it is not). In the present analysis, we investigate several factors related to the interpretation of epidemiological data for mesothelioma, including the role of asbestos as a risk factor over time. The authors conducted a review of the scientific community's understanding of mesothelioma incidence and asbestos exposures amongst women, as well as an investigation of the methods and references in the MMWR article. Although various articles have recently discussed the incidence of both peritoneal and pleural mesothelioma in women, it is fortunate that the age-adjusted rates for mesothelioma have remained flat (neither increased nor decreased significantly) in women for the past 50 years. Incredibly few women in the U. S. have had appreciable cumulative exposures to any type of asbestos (chrysotile, amosite, or crocidolite) in the workplace or from the ambient environment, especially since about 1965-1970. In this paper, we highlight six factors that should be considered when evaluating the incidence of mesothelioma amongst American women in the current era. Without sufficient consideration of these factors, improper conclusions have been drawn over the past several years.}, }
@article {pmid39445262, year = {2024}, author = {Paremuzyan, A and Onwubuya, E and Mathews, J}, title = {A Case of Malignant Pleural Mesothelioma With Unknown Asbestos Exposure.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69966}, pmid = {39445262}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, locally invasive tumor that develops from mesothelial cells lining the lung's pleura. It is mostly associated with prolonged asbestos exposure. The long latency period between asbestos exposure and clinical symptoms makes diagnosing MPM challenging. This report describes a 57-year-old Hispanic female who presented with a persistent nonproductive cough and was ultimately diagnosed with advanced-stage pleural mesothelioma after extensive work-up. It highlights the difficulties in diagnosing MPM in patients without apparent asbestos exposure independent of age or gender.}, }
@article {pmid39441675, year = {2024}, author = {Suehiro, T and Ahmad, KM and Hoang, NTD and Xu, B and Komatsu, H and Kurachi, K and Nikawa, H and Mine, Y and Matsuki, T and Asano, K and Fujii, M}, title = {Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells.}, journal = {Journal of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1093/jb/mvae068}, pmid = {39441675}, issn = {1756-2651}, abstract = {The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.}, }
@article {pmid39439640, year = {2024}, author = {Guerra, J and Pina, JM and Andrade, V and Cassis, J and Campos Pinheiro, L}, title = {Malignant Mesothelioma of the Tunica Vaginalis: About a Rare Clinical Case.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69897}, pmid = {39439640}, issn = {2168-8184}, abstract = {Malignant mesothelioma (MM) of the tunica vaginalis is an exceedingly rare neoplasm, with fewer than 300 cases reported in the medical literature. Due to its rarity, epidemiology, and risk factors are still unclear, and it is unknown whether asbestos or chronic inflammatory conditions play a role in etiology. This case study presents a 70-year-old male patient with MM of the tunica vaginalis, detailing the diagnostic challenges, treatment procedures, and eventual progression to palliative care. The study underscores the importance of accurate diagnosis and the aggressive nature of the disease despite treatment efforts.}, }
@article {pmid39434641, year = {2024}, author = {Visonà, SD and Pace, MC and Consonni, D and Mensi, C}, title = {Accuracy of the Lombardy Mesothelioma Registry: comparison with the autopsy database of Pavia University (Lombardy Region, Northern Italy).}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {4-5}, pages = {320-325}, doi = {10.19191/EP24.4-5.A736.096}, pmid = {39434641}, issn = {1120-9763}, mesh = {Humans ; Italy/epidemiology ; *Registries ; *Autopsy ; *Mesothelioma/mortality/pathology/epidemiology ; Male ; *Sensitivity and Specificity ; *Databases, Factual ; Female ; Aged ; Middle Aged ; Incidence ; Asbestos/adverse effects ; Universities ; }, abstract = {OBJECTIVES: to evaluate the accuracy (completeness of case recording and diagnostic quality) of the Lombardy Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) through a comparison with the autopsy database of Pavia University (years 2000-2016).<br><br>DESIGN: validation study.<br><br>SETTING AND PARTICIPANTS: all mesothelioma records with incidence date between 01.01.2000 and 16.09.2016 were extracted from the RML. They were cross-referenced with deaths from any asbestos-related disease subjected to a forensic autopsy extracted from the archive of the Department of Public Health, Experimental and Forensic Medicine of Pavia University.<br><br>MAIN OUTCOMES MEASURES: using the postmortem diagnosis by Pavia University as the gold standard, RML sensitivity and specificity and their 95% confidence intervals (95%CI) were calculated using the Agresti-Coull formula.<br><br>RESULTS: based on 141 deaths, the RML showed very good accuracy: specificity was 100% (95%CI 87%-100%; 32/32 deaths) and sensitivity 94% (95%CI 87%-97%; 102/109 deaths). The 7 false negative cases either were missed by the RML (N. 4) or had been wrongly classified as non-mesotheliomas (N. 3) because the diagnosis was made or confirmed only postmortem after a forensic autopsy.<br><br>CONCLUSIONS: RML accuracy (completeness and diagnostic quality) was very high. No false positive was found and the few false negatives were due to lack of notification of mesotheliomas diagnosed postmortem to the registry. Forensic pathologists should be made aware that mesothelioma notification to the regional mesothelioma registry is important and compulsory.}, }
@article {pmid39430319, year = {2024}, author = {Ye, L and Ryu, H and Granadier, D and Nguyen, LT and Simoni, Y and Dick, I and Firth, T and Rouse, E and Chiang, P and Lee, YCG and Robinson, BW and Creaney, J and Newell, EW and Redwood, AJ}, title = {Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.}, journal = {Translational lung cancer research}, volume = {13}, number = {9}, pages = {2352-2372}, pmid = {39430319}, issn = {2218-6751}, abstract = {BACKGROUND: Anti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8[+] T cells include less differentiated stem-like exhausted T (Tex[stem]) cells and terminally exhausted T (Tex[term]) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort.<br><br>METHODS: Pre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Tex[stem] and Tex[term] CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire.<br><br>RESULTS: Higher frequency of Tex[stem] was associated with significantly increased OS [median 9.9 vs. 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16-0.79, P=0.01]. The frequency of Tex[term] was not associated with OS. These findings were validated in the mesothelioma cohort (high vs. low Tex[stem], median OS 32.1 vs. 19.8 months, HR 0.31, 95% CI: 0.10-0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Tex[stem] cells also contained 'bystander' virus-specific T cells.<br><br>CONCLUSIONS: This study demonstrates that PE CD8 Tex[stem] cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.}, }
@article {pmid39410011, year = {2024}, author = {Stella, GM and Lisini, D and Pedrazzoli, P and Galli, G and Bortolotto, C and Melloni, G and D'Ambrosio, G and Klersy, C and Grosso, A and Paino, F and Tomaselli, S and Saracino, L and Alessandri, G and Pessina, A and Grignani, E and Rosti, V and Corsico, AG and Comoli, P and Agustoni, F}, title = {Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design.}, journal = {Cancers}, volume = {16}, number = {19}, pages = {}, doi = {10.3390/cancers16193391}, pmid = {39410011}, issn = {2072-6694}, support = {PLAGENCELL//Fondazione Regionale per la Ricerca Biomedica , PLAGENCELL project - A network for cell and gene therapies for devastating diseases (grant to A.G.C. and P.C.)/ ; }, abstract = {Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction. The experimental pre-clinical background and rationale are discussed as well.}, }
@article {pmid39409190, year = {2024}, author = {Chiec, L and Bruno, DS}, title = {Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, doi = {10.3390/ijms251910861}, pmid = {39409190}, issn = {1422-0067}, mesh = {Humans ; *Immunotherapy/methods ; *Pleural Neoplasms/therapy/immunology/pathology ; *Mesothelioma/therapy/immunology/pathology ; Immune Checkpoint Inhibitors/therapeutic use ; Mesothelioma, Malignant/therapy/pathology ; Clinical Trials as Topic ; }, abstract = {Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%. Outcomes may vary according to stage at time of diagnosis and histologic subtype. Most recently, clinical trials utilizing dual checkpoint inhibitor regimens and chemotherapy in combination with immune oncologic agents have demonstrated impactful changes in outcomes. In this article, we review studies that have led to the successful implementation of immunotherapy in clinical practice for the treatment of this disease and highlight ongoing clinical trials exploring the use of different immunotherapy strategies for the treatment of pleural mesothelioma. We also discuss the challenges of immunotherapy-based approaches in the context of mesothelioma and future strategies currently being investigated to overcome them.}, }
@article {pmid39407894, year = {2024}, author = {Jain, M and Crites, MK and Rich, P and Bajantri, B}, title = {Malignant Pleural Mesothelioma: A Comprehensive Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {19}, pages = {}, doi = {10.3390/jcm13195837}, pmid = {39407894}, issn = {2077-0383}, abstract = {Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body's external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant mesothelioma, characterized by recurrent inflammation, disruption of cell division, activation of proto-oncogenes, and generation of free radicals. In pleural mesothelioma, BAP1, CDKN2A, and NF are the most often mutated genes. Accurate diagnosis and assessment usually require the use of chest computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.}, }
@article {pmid39400365, year = {2024}, author = {Arrandale, VH and Berriault, C and Song, C and DeBono, N and Demers, PA}, title = {Surveillance of asbestos related disease among workers enrolled in an exposure registry.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23668}, pmid = {39400365}, issn = {1097-0274}, support = {//Ontario Ministry of Labour, Immigration, Training and Skills Development/ ; }, abstract = {INTRODUCTION: Contemporary asbestos exposure occurs during construction, remediation, and maintenance involving asbestos-containing materials (ACM), as compared to the historical exposure scenarios of asbestos mining and milling. The Ontario Asbestos Workers Register (AWR) was established in 1986 to track asbestos exposure among construction workers. This study reports on the risk of asbestos-related diseases (ARD) among workers in the AWR.<br><br>METHODS: AWR registrants were linked probabilistically with administrative health databases (1986-2019) to identify cases of ARD including both cancer and chronic respiratory disease. Follow-up began at AWR enrollment and continued prospectively. Incidence rates were compared to the general population using standardized incidence ratios (SIRs). Associations between ACM exposure and ARD were estimated among AWR registrants using Poisson regression.<br><br>RESULTS: In total, 26,204 (81%) registrants were linked successfully. Common industries of employment were construction (62%), manufacturing (19%) and education (8%). Among men and women mesothelioma (M:SIR 6.83 [95% CI&#x2009;=&#x2009;5.56-8.31]; W:SIR 19.2 [3.86-56.1]) and pulmonary fibrosis (M:SIR 14.1 [12.2-16.2]; W:SIR 9.25 [2.49-23.7]) rates were higher than the general population. Asbestosis risk was elevated among men (M:SIR 11.2 [9.59-13.1]). Workers with longer reported exposures (&#x2265;140&#x2009;h) had increased rates of lung cancer (RR 1.34 [1.10-1.63]), mesothelioma (RR 2.83 [1.75-4.58]), asbestosis (RR 3.07 [2.12-4.43]), chronic obstructive pulmonary disease (RR 1.42 [1.29-1.57]), and pulmonary fibrosis (RR 1.88 [1.35-2.62]).<br><br>CONCLUSION: Exposure to asbestos in construction and building maintenance continues to contribute to ARD incidence. Despite a Canadian ban on asbestos in new products, exposures to existing ACM will persist from construction activities. The AWR offers an opportunity for ongoing surveillance of resulting ARD in Ontario.}, }
@article {pmid39394704, year = {2024}, author = {Li, R and Yu, WK and Wang, Q and Zhu, LJ and Zhang, FF}, title = {[Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {9}, pages = {668-672}, doi = {10.3760/cma.j.cn121094-20240112-00014}, pmid = {39394704}, issn = {1001-9391}, support = {LQY18H260001, LGD21C040008//Natural Science Foundation of Zhejiang Province/ ; YS2022012//Special Plan Project of Hangzhou Medical College Institute/ ; }, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Epithelial-Mesenchymal Transition/drug effects ; *Asbestos, Serpentine/toxicity ; Epithelial Cells/metabolism/drug effects ; Asbestos/toxicity ; Mesothelioma/genetics/chemically induced ; Cell Line, Tumor ; Cadherins/genetics/metabolism ; Vimentin/metabolism/genetics ; Cell Line ; Pleural Neoplasms/genetics/chemically induced/metabolism ; }, abstract = {Objective: To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells. Methods: In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm(2) chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet-t test. Results: Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased (P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased (P<0.05) . Conclusion: Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.}, }
@article {pmid39377019, year = {2024}, author = {Rezvani, A and Shahriarirad, R and Jahanshahi, S and Fouladi, D and Tavallali, M and Ziaian, B and Fallahi, MJ}, title = {The aftermath of asbestos prohibition in industry and its association with malignant mesothelioma in the south of Iran: An enduring predicament yet to be resolved.}, journal = {Health science reports}, volume = {7}, number = {10}, pages = {e70117}, pmid = {39377019}, issn = {2398-8835}, abstract = {PURPOSE: Malignant Mesothelioma (MM) is a rare malignancy of the serosa membranes with a high mortality rate and long latent period. The relationship between a group of mineral fibers known as asbestos and mesothelioma is now well accepted in which people can be exposed to these fibers by various means during their lifetime and has been its usage has banned in many countries, such as Iran, which announced its gradual elimination from 1999 over a period of 7 years by using safe substitutes. However, the mineral particles are able to sustain itself in the environment, air, water, and soil and on the other hand, symptoms may take up to half a century to develop in exposed individuals. Also, there remains a shortage of comprehensive investigation on the effects of asbestos exposure within the familial context (household or domestic exposure) or on individuals residing in proximity to asbestos mines or factories (environmental exposure). Based on the high number of MM cases in Iran, and also our hypothesis that residuals of asbestos in the environment and petroleum products may be the etiological factor for MM, we conducted this study to evaluate the clinic epidemiological features of MM in the south of Iran its relation to possible asbestos exposure.<br><br>METHODS: In this study, we analyzed the demographic features and occupations of confirmed cases of MM in Shiraz, southern Iran along with the follow-up of the patients' disease from 2008 to 2018, while also comparing the features of our patients with a control group compromising of 105 non-MM patients.<br><br>RESULTS: Among the 35 confirmed cases of MM, with an average age of 61 years, 9 (25.7%) were female, and 26 (74.3%) were male. During our assessment, 12 patients had already died, with a mean time of 11.26 months post-diagnosis. Our findings revealed a higher prevalence of MM among housekeepers and employees of oil companies. In comparison to the control group, individuals with occupational exposure and those residing near refinery locations were at a heightened risk of developing MM. However, based on regression analysis, only occupations associated with refineries exhibited a significant correlation with MM (p&#x2009;=&#x2009;0.028; OR: 14.602; 95% CI: 1.328-160.499).<br><br>CONCLUSION: Both occupational and para-occupational exposure demonstrated a significant correlation with MM, whereas our regression analysis did not affirm geographical and environmental factors as contributors to MM. Despite the industry's prohibition of direct asbestos usage, the persistent existence of asbestos particles in the environment for decades, coupled with the long latency period of MM, warrants further investigation. Health authorities and policymakers should recognize this potential hazard, prompting an enhancement of early detection within at-risk groups.}, }
@article {pmid39371847, year = {2024}, author = {R, PD and Grace Priyadarshini, S and P, J}, title = {Malignant Mesothelioma: Overcoming Diagnostic Hurdles.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e68718}, pmid = {39371847}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma, an aggressive neoplasm frequently linked to asbestos exposure, is often detected at an advanced stage. This report details the case of a 58-year-old mason who presented with left-sided chest pain, and shortness of breath, accompanied by weight loss for a month. A positron emission tomography (PET) scan revealed increased uptake along the pleural surface, as well as in several mediastinal lymph nodes and the left supraclavicular lymph node. Thoracoscopy revealed the presence of multiple nodules on the costal pleura. Despite repeated negative results from pleural effusion cytology, cell block analysis, and pleural biopsies, the diagnosis of malignant mesothelioma (MM) was ultimately established through an ultrasound-guided (USG) biopsy of the left supraclavicular lymph node, with immunohistochemical confirmation using calretinin.}, }
@article {pmid39337157, year = {2024}, author = {Porzio, A and Feola, A and Salzillo, C and Corbi, G and Campobasso, CP}, title = {Colorectal Cancer and Asbestos Exposure: A Women's Health Perspective.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {18}, pages = {}, pmid = {39337157}, issn = {2227-9032}, abstract = {BACKGROUND: Colorectal cancer (CRC) is considered a "man's disease". However, emerging data show that females may have a higher prevalence of certain risk factors. A potential causal role of asbestos in CRC carcinogenesis has been suggested. This relationship is controversial, and only a few studies have focused on exposed female populations. The aim of this study was to review the scientific literature related to asbestos-related CRC incidence and mortality rates in female populations to address gender bias in the existing research.<br><br>METHODS: A systematic review was performed following PRISMA statement.<br><br>RESULTS: Fourteen studies reporting 92 cases in total were included. Most women were aged 50 years or older and were employed in occupational activities with high asbestos exposure (steel, textile, and asbestos-cement industry) for at least 10 years. In one single case, household asbestos exposure was reported. The colon was the primary location of the tumor in 47 out of 92 cases. Three women were also affected by synchronous or metachronous peritoneal mesotheliomas.<br><br>CONCLUSIONS: This study revealed a general methodological "gender bias" in scientific research. A significantly higher representation of women in clinical studies is needed to clarify the link between asbestos exposure and the development of colorectal cancer.}, }
@article {pmid39329996, year = {2024}, author = {Roca, E and Aujayeb, A and Astoul, P}, title = {Diagnosis of Pleural Mesothelioma: Is Everything Solved at the Present Time?.}, journal = {Current oncology (Toronto, Ont.)}, volume = {31}, number = {9}, pages = {4968-4983}, pmid = {39329996}, issn = {1718-7729}, mesh = {Humans ; *Pleural Neoplasms/diagnosis/therapy ; *Mesothelioma, Malignant/diagnosis/therapy/pathology ; Mesothelioma/diagnosis/therapy ; Lung Neoplasms/diagnosis/therapy ; Biopsy/methods ; Thoracic Surgery, Video-Assisted/methods ; }, abstract = {Ranked high in worldwide growing health issues, pleural diseases affect approximately one million people globally per year and are often correlated with a poor prognosis. Among these pleural diseases, malignant pleural mesothelioma (PM), a neoplastic disease mainly due to asbestos exposure, still remains a diagnostic challenge. Timely diagnosis is imperative to define the most suitable therapeutic approach for the patient, but the choice of diagnostic modalities depends on operator experience and local facilities while bearing in mind the yield of each diagnostic procedure. Since the analysis of pleural fluid cytology is not sufficient in differentiating historical features in PM, histopathological and morphological features obtained via tissue biopsies are fundamental. The quality of biopsy samples is crucial and often requires highly qualified expertise. Since adequate tissue biopsy is essential, medical or video-assisted thoracoscopy (MT or VATS) is proposed as the most suitable approach, with the former being a physician-led procedure. Indeed, MT is the diagnostic gold standard for malignant pleural pathologies. Moreover, this medical or surgical approach can allow diagnostic and therapeutic procedures: it provides the possibility of video-assisted biopsies, the drainage of high volumes of pleural fluid and the administration of sterile calibrated talcum powder under visual control in order to achieve pleurodesis, placement of indwelling pleural catheters if required and in a near future potential intrapleural therapy. In this context, dedicated diagnostic pathways remain a crucial need, especially to quickly and properly diagnose PM. Lastly, the interdisciplinary approach and multidisciplinary collaboration should always be implemented in order to direct the patient to the best customised diagnostic and therapeutic pathway. At the present time, the diagnosis of PM remains an unsolved problem despite MDT (multidisciplinary team) meetings, mainly because of the lack of standardised diagnostic work-up. This review aims to provide an overview of diagnostic procedures in order to propose a clear strategy.}, }
@article {pmid39316223, year = {2024}, author = {Pacella, A and Ballirano, P and Di Carlo, MC and Altieri, A and Paccapelo, M and Skogby, H and Campopiano, A and Bruno, MR and Croce, A and Piersante, C and Apollaro, C and Malvasi, G and Bruni, BM and Bloise, A}, title = {Geological and mineralogical characterization of fibrous tremolite from Iacolinei quarry (Basilicata, Italy).}, journal = {Environmental geochemistry and health}, volume = {46}, number = {11}, pages = {429}, pmid = {39316223}, issn = {1573-2983}, support = {B87G23000090005//National Institute for Insurance against Accidents at Work (INAIL) - BRIC 2022 project/ ; }, mesh = {Italy ; *Asbestos, Amphibole/analysis ; X-Ray Diffraction ; Geologic Sediments/chemistry ; Environmental Monitoring ; }, abstract = {Naturally Occurring Asbestos (NOA) has drawn the attention worldwide when investigation revealed an increased incidence of malignant mesothelioma in population living near NOA sites. In Basilicata region (South Italy), population living in the villages of Castelluccio Superiore and Inferiore, Lauria, Latronico, Episcopia, San Severino Lucano, and Francavilla in Sinni may be considered at high risk of asbestos exposure because these villages are either surrounded by or built on NOA-rich ophiolitic outcrops. In this work we investigated an asbestos tremolite sample coming from the ophiolitic rocks outcropping in the quarry of Iacolinei, widely used in the past to extract aggregates for various applications. A detailed mineralogical characterization has been attained by using a multi-analytical approach (EMPA, SEM-EDS, TEM-EDS, Mössbauer, µ-Raman, X-ray powder diffraction, and thermal analysis). Morphological investigation highlighted that the sample is composed of long fibers (> 5 µm) with a significant fraction (ca. 55%) having width below 0.25 µm, considered the most biologically active fibers. Moreover, the crystal chemical characterization showed that Fe occurs at the octahedral sites of the tremolite structure. It should be noted that Fe plays a primary role in the toxicity of asbestos. Based on these results, the investigated asbestos tremolite may be considered a potent mesothelial carcinogen, requiring therefore special attention for public health protection purposes. Investigations using sentinel animals to assess the diffusion of the tremolite fibers into the environment from the serpentinite rocks and soils of Iacolinei quarry are in progress.}, }
@article {pmid39312698, year = {2024}, author = {Khosla, D and Singh, PK and Chhabria, BA and Kataria, V and Singh, N and Kapoor, R}, title = {Malignant pleural mesothelioma: The disdained member of thoracic oncology!.}, journal = {World journal of experimental medicine}, volume = {14}, number = {3}, pages = {91739}, pmid = {39312698}, issn = {2220-315X}, abstract = {Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure. The ban on asbestos has helped to lower the incidence, but in developing countries like India, it is expected to rise. It has an extended latency period usually progressing over decades and presents with nonspecific symptoms. It has a median survival ranging between 10-22 months. The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT, with the last two predicting the resectability of the tumor better than CT alone. A pleural biopsy along with an array of immunohistochemical markers, such as p16, BRCA1 associated protein 1, and claudin-4, are required for a definitive diagnosis. Several genetic alterations have prognostic significance as well. The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored. The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes. However, the latter continues to be a robust treatment option for patients with the epithelioid subtype. Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant, adjuvant, and palliative settings along with systemic treatment. This review article provides an overview of epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and genetic markers), staging, and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery, chemotherapy, immunotherapy, and radiotherapy. It also sheds light on some recent studies (EMPHACIS, CALGB30901, Checkmate-743, etc.) that have led to significant developments in recent years with clinically meaningful results.}, }
@article {pmid39290927, year = {2024}, author = {Reddy, S and M G, K and Gattu, R and P, A and Kuthadi, M}, title = {Challenging the Norm: Occurrence of Synchronous Pleural and Peritoneal Mesothelioma in a Female Patient.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67118}, pmid = {39290927}, issn = {2168-8184}, abstract = {Here, we present a unique case involving a female patient in her 40s with synchronous malignant pleural and peritoneal mesothelioma, despite lacking a history of asbestos exposure. The patient's initial symptoms included dyspnoea, chest pain, cough, fever, appetite loss, and weight loss over a month. Clinical evaluation led to the identification of right-sided pleural effusion, prompting consideration of differential diagnoses, such as tubercular or malignant pleural effusion. A thoracoscopy-guided biopsy, followed by histopathological examination and immunohistochemical staining, confirmed the diagnosis of mesothelioma. Chemotherapy was initiated as part of the treatment plan. The prognosis for this condition is generally bad; however, unusual cases of extended survival have been documented. The complexities of our case underscore the critical necessity for a thorough and aggressive evaluation of pleural effusion cases to unveil rare underlying causes, such as mesothelioma.}, }
@article {pmid39281715, year = {2024}, author = {Huang, Q and Chen, Y and Lian, L and Lei, Q and Chen, J and Wu, L and Hemminki, K and Ji, J and Chen, T}, title = {Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029.}, journal = {Journal of the National Cancer Center}, volume = {4}, number = {3}, pages = {214-222}, pmid = {39281715}, issn = {2667-0054}, abstract = {OBJECTIVE: To provide the most up-to-date data on the burden of malignant mesothelioma (MM) and the projections through 2029 in China.<br><br>METHODS: Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease (GBD) 2019 database, including annual cases and deaths data and age-standardized rates of incidence, mortality, and disability-adjusted life-years (DALYs) associated with MM among different age groups. Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95% confidence interval (CI), while the projections through 2029 were calculated by the Bayesian age-period-cohort model. Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.<br><br>RESULTS: We observed a significant elevation in incident new cases and deaths over the last 3 decades, increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases. We found a roughly 6% increase in the proportion of incident cases for those aged >70 years (30% in 2019 versus 24% in 1990), while for the proportion of deaths similar elevation for those aged >70 years was found. Additionally, men had significantly higher DALYs due to MM across age groups compared with women. Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons. By 2029, the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.<br><br>CONCLUSION: We found, for the first time using GBD data on the Chinese population, that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade, suggesting an urgent need for a complete ban on chrysotile asbestos in China.}, }
@article {pmid39269499, year = {2024}, author = {Sheema, AN and Naiki-Ito, A and Kakehashi, A and Ahmed, OHM and Alexander, DB and Alexander, WT and Numano, T and Kato, H and Goto, Y and Takase, H and Hirose, A and Wakahara, T and Miyazawa, K and Takahashi, S and Tsuda, H}, title = {Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long-term study after 2-week intra-tracheal intrapulmonary administration.}, journal = {Archives of toxicology}, volume = {}, number = {}, pages = {}, pmid = {39269499}, issn = {1432-0738}, support = {JPMH20316858//Ministry of Health, Labour and Welfare/ ; JPMH16769893//Ministry of Health, Labour and Welfare/ ; }, abstract = {Fullerene whiskers (FLW)s are thin rod-like structures composed of C60 and C70 fullerene (FL). The shape of FLWs suggests potential toxic effects including carcinogenicity to the lung and pleura, similar to effects elicited by asbestos and multi-walled carbon nanotubes (MWCNT)s. However, no long-term carcinogenic studies of FL or FLW have been conducted. In the present study we investigated the pulmonary and pleural carcinogenicity of FL and FLW. Twelve-week-old male F344 rats were administered 0.25 or 0.5 mg FL, FLW, MWCNT-7, and MWCNT-N by intra-tracheal intra-pulmonary spraying (TIPS). Acute lung lesions and carcinogenicity were analyzed at 1 and 104 weeks after 8 doses/15 days TIPS administration. At week 1, FLW, MWCNT-7, and MWCNT-N significantly increased alveolar macrophage infiltration. Expression of Ccl2 and Ccl3, reactive oxygen species production, and cell proliferation were significantly increased by administration of MWCNT-7 and MWCNT-N but not FL or FLW. At week 104, the incidence of bronchiolo-alveolar adenoma plus adenocarcinoma was significantly increased in the MWCNT-7 and MWCNT-N groups, and the incidence of mesothelioma was significantly increased in the MWCNT-7 group. No significant induction of pulmonary or pleural tumorigenesis was observed in the FL or FLW groups. The number of 8-OHdG-positive cells in the alveolar epithelium was significantly increased in the MWCNT-7 and MWCNT-N groups but not in the FL or FLW groups. FL and FLW did not exert pulmonary or pleural carcinogenicity in our study. In addition, oxidative DNA damage was implicated in MWCNT-induced lung carcinogenesis, suggesting that it may be a useful initial marker of carcinogenicity.}, }
@article {pmid39265763, year = {2024}, author = {Feng, L and Li, T and Xu, B and Huang, J and Xia, H and Jiang, Z and Chen, J and Pan, S and Zhang, X and Jiang, H and Lou, J}, title = {Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {362}, number = {}, pages = {124928}, doi = {10.1016/j.envpol.2024.124928}, pmid = {39265763}, issn = {1873-6424}, abstract = {Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulfite sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.}, }
@article {pmid39258522, year = {2024}, author = {Kinsman, N and Del Monaco, A and Dimitriadis, C and Xie, S and Benke, G and Sim, MR and Walker-Bone, K}, title = {Bauxite mine and alumina refinery workers: mortality and cancer risk.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {7}, pages = {508-513}, pmid = {39258522}, issn = {1471-8405}, support = {//Alcoa of Australia Ltd/ ; }, mesh = {Humans ; Male ; Female ; *Occupational Exposure/adverse effects ; *Aluminum Oxide/adverse effects ; *Occupational Diseases/mortality/epidemiology ; Australia/epidemiology ; *Mining/statistics &amp; numerical data ; Middle Aged ; *Neoplasms/mortality/epidemiology ; Adult ; Incidence ; Risk Factors ; Mesothelioma/mortality/epidemiology ; Aged ; Melanoma/mortality/epidemiology ; Metallurgy ; Prostatic Neoplasms/mortality/epidemiology ; }, abstract = {BACKGROUND: Aluminium industry workers are at risk of long-term health consequences.<br><br>AIMS: To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers.<br><br>METHODS: A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment.<br><br>RESULTS: Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11-4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60-3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06-1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66-6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36-3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02-3.65]. Overall cancer incidence was otherwise similar to the general Australian population.<br><br>CONCLUSIONS: Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation.}, }
@article {pmid39237806, year = {2024}, author = {Duraffour, F and Ramos-Bonilla, JP and Lysaniuk, B}, title = {Use of agent-based modeling to analyze potential non-occupational exposures to asbestos of the general population of Sibaté (Colombia).}, journal = {Environmental monitoring and assessment}, volume = {196}, number = {10}, pages = {900}, pmid = {39237806}, issn = {1573-2959}, support = {ANR-18-CE03-0001-01//Agence Nationale de la Recherche/ ; ANR-18-CE03-0001-01//Agence Nationale de la Recherche/ ; ANR-18-CE03-0001-01//Agence Nationale de la Recherche/ ; }, mesh = {*Asbestos/analysis ; Humans ; *Environmental Exposure/statistics &amp; numerical data ; Environmental Monitoring/methods ; Mesothelioma/epidemiology/chemically induced ; }, abstract = {Previous studies conducted in the municipality of Sibaté (Colombia) have revealed alarming findings regarding asbestos exposure in the region, as it is the site of the country's first mesothelioma cluster. Non-occupational asbestos exposure events were identified in this population, and the young age of the mesothelioma cases at the time of diagnosis suggests that asbestos exposure occurred during their childhood. The creation of landfilled zones in the 1980s and 1990s, utilizing friable asbestos among other disposed materials, may have been a significant asbestos exposure event contributing to the elevated number of mesothelioma cases. The objective of this study was to model various historical exposure scenarios related to the creation and interaction of the population with asbestos-contaminated landfilled zones, in light of the absence of asbestos monitoring in the region. The models utilized a multi-agent simulation process, focusing on a 10-year period (1986-1995). Various relevant variables were incorporated into the modeling process, including, for example, the number of children playing in the landfilled zones and the percentage of children carrying asbestos fibers on their clothes to their homes. A range of values for input data for the models were utilized, spanning from very conservative numbers to exposure-promoting values. The average number of exposed individuals estimated over 750 simulation runs, considering all scenarios, was 571, with a range between 31 and 3800 exposed individuals. The use of multi-agent simulation models can assist the understanding of past asbestos exposure events, especially when there is a lack of environmental surveillance data.}, }
@article {pmid39204360, year = {2024}, author = {Favaron, C and Gaiaschi, L and Casali, C and De Luca, F and Gola, F and Cavallo, M and Ramundo, V and Aldieri, E and Milanesi, G and Visonà, SD and Ravera, M and Bottone, MG}, title = {Unraveling Novel Strategies in Mesothelioma Treatments Using a Newly Synthetized Platinum(IV) Compound.}, journal = {Pharmaceutics}, volume = {16}, number = {8}, pages = {}, pmid = {39204360}, issn = {1999-4923}, support = {FRG Fondo ricerca e Giovani Maria Grazia Bottone//University of Pavia: Fondi Ricerca Giovani (FRG 2021)./ ; }, abstract = {Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed. In this view, the purpose of this study was to evaluate the therapeutic potential of the newly synthetized platinum prodrug Pt(IV)Ac-POA compared to cisplatin (CDDP) on human biphasic mesothelioma cell line MSTO-211H using different complementary techniques, such as flow-cytometry, transmission electron microscopy (TEM), and immunocytochemistry. Healthy mesothelial cell lines Met-5A were also employed to assess the cytotoxicity of the above-mentioned compounds. Our in vitro results showed that Pt(IV)Ac-POA significantly interfere with iron metabolisms and more importantly is able to trigger cell death, through different pathways, including ferroptosis, necroptosis, and apoptosis, in neoplastic cells. On the other hand, CDDP triggers mainly apoptotic and necrotic cell death. In conclusion, Pt(IV)Ac-POA may represent a new promising pharmacological agent in the treatment of malignant mesothelioma.}, }
@article {pmid39189372, year = {2024}, author = {Giacomino, F and Marinelli, F and Bisceglia, I and Cacchi, M and Storchi, C and Pinto, C and Mangone, L and Romanelli, A and Morabito, F}, title = {Trends in Asbestos Exposure and Malignant Mesothelioma Incidence in Emilia-Romagna Italy: A Retrospective Study 1996-2023.}, journal = {La Medicina del lavoro}, volume = {115}, number = {4}, pages = {e2024028}, pmid = {39189372}, issn = {0025-7818}, mesh = {Humans ; Italy/epidemiology ; Male ; Retrospective Studies ; Female ; *Asbestos/adverse effects ; Aged ; *Mesothelioma, Malignant/epidemiology ; Incidence ; *Occupational Exposure/statistics &amp; numerical data/adverse effects ; Middle Aged ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; Environmental Exposure/adverse effects/statistics &amp; numerical data ; Adult ; Aged, 80 and over ; Occupational Diseases/epidemiology ; }, abstract = {Malignant mesothelioma (MM) is a rare but lethal cancer strongly associated with asbestos exposure. This retrospective study examines trends in asbestos exposure in Emilia-Romagna, Northern Italy. Between 1996 and 2023, 3,513 cases of MM were recorded, predominantly in males (72%) and in older than 65 years (79%). Occupational exposure accounted for 82% of cases, with a significant increase observed over time from 71% to 88% in the most recent period. A greater definition of professional exposure indicates that certain exposure has gone from 49% in the first period to 62% and 58% in the last two periods; probable exposure showed a decrease from 21% to 16% while possible exposure decreased from 16% to 13%. Familiar exposure remained relatively constant at around 8%, environmental exposure showed a slight decrease from 4% to 2%, while non-occupational exposure remained stable at 2%. Among patients with exclusively occupational exposure (1,826 cases), 87% were male and aged between 65 and 75 years (36%) and 75+ (41%). The exposure rates for the province of residence see the province of Reggio Emilia with the highest occupational exposure rate (2.5 x 100,000 residents), followed by Ravenna (2.3 x 100,000 residents) and Parma and Piacenza which have similar exposure rates with 2.2 x 100,000 residents. Professional sectors such as construction, railway maintenance and metalworking are identified as high-risk industries. Despite efforts to mitigate exposure, non-occupational and environmental exposures persist. The study highlights the importance of continuous surveillance and exposure monitoring to guide effective interventions and legal recognition of MM.}, }
@article {pmid39181447, year = {2024}, author = {Kindler, HL and Rosenthal, A and Giroux, DJ and Nowak, AK and Billè, A and Gill, RR and Pass, H and Rice, D and Ripley, RT and Wolf, A and Blyth, KG and Cedres, S and Rusch, V and , }, title = {The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2024.08.022}, pmid = {39181447}, issn = {1556-1380}, abstract = {INTRODUCTION: The International Association for the Study of Lung Cancer developed a global multicenter database to propose evidence-based revisions for the ninth edition of the TNM classification of pleural mesothelioma (PM). This study analyzes the M category to validate eighth edition M category recommendations.<br><br>METHODS: Cases were submitted electronically or by transfer of existing institutional databases for patients with histologically or cytologically confirmed PM. The presence and number of metastases (single versus multiple) in each of eight organ systems were reported for patients with M1 disease at diagnosis. Overall survival (OS) was calculated by the Kaplan-Meier method. Differences in OS were assessed by log-rank test.<br><br>RESULTS: Of 7338 submitted cases, 3598 were eligible and 3221 had sufficient data for clinical staging; 228 cases (7%) were M1. Median overall estimated survival was inferior for M1 compared with M0 patients: 10.5 months versus 21.5 months, respectively (p < 0.0001); estimated 1-year survival was 46% versus 71%, respectively. OS differences between M categories were preserved within histologic subgroups. Among 158 patients with organ-specific documentation of M1 disease, there was no statistically significant difference in OS between those with intrathoracic versus more distant metastatic disease (14.4 mo versus 10.9 mo, p&#xa0;= 0.64). No significant survival difference was detected between patients with metastatic disease in a single-organ system versus multiple-organ systems (12.6 mo versus 8.8 mo, p&#xa0;= 0.45).<br><br>CONCLUSIONS: This evidence-based analysis of the M category for PM conforms with the eighth edition M descriptors. No changes are proposed in the ninth edition of the mesothelioma M category.}, }
@article {pmid39168966, year = {2024}, author = {Zhang, M and Bzura, A and Baitei, EY and Zhou, Z and Spicer, JB and Poile, C and Rogel, J and Branson, A and King, A and Barber, S and Kamata, T and Dzialo, J and Harber, J and Greystoke, A and Nusrat, N and Faulkner, D and Sun, Q and Nolan, L and Hahne, JC and Scotland, M and Walter, H and Darlison, L and Morgan, B and Bajaj, A and Brookes, C and Hollox, EJ and Lubawska, D and Jama, M and Griffiths, G and Nakas, A and Kutywayo, K and Luo, JL and Klampatsa, A and Cooper, A and Halder, K and Wells-Jordan, P and Zhou, H and Dudbridge, F and Thomas, A and Richards, CJ and Pritchard, C and Yang, H and Barer, M and Fennell, DA}, title = {A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {7187}, pmid = {39168966}, issn = {2041-1723}, support = {C10604/A25151//Cancer Research UK (CRUK)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Bevacizumab/therapeutic use/pharmacology ; Male ; *B7-H1 Antigen/metabolism/antagonists &amp; inhibitors ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Female ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Middle Aged ; Aged ; Mesothelioma, Malignant/drug therapy ; Vascular Endothelial Growth Factor A/metabolism ; Mesothelioma/immunology/drug therapy/microbiology/pathology ; Tumor Microenvironment/immunology ; Lung Neoplasms/drug therapy/immunology/pathology/genetics/microbiology ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68[+] monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8[+] T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68[+] monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.}, }
@article {pmid39163890, year = {2024}, author = {Little, LD and Barnett, SE and Issitt, T and Bonsall, S and Carolan, VA and Allen, E and Cole, LM and Cross, NA and Coulson, JM and Haywood-Small, SL}, title = {Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts.}, journal = {Journal of breath research}, volume = {18}, number = {4}, pages = {}, pmid = {39163890}, issn = {1752-7163}, mesh = {*Volatile Organic Compounds/analysis ; *Chorioallantoic Membrane ; Animals ; Humans ; *Mesothelioma, Malignant/pathology ; *Gas Chromatography-Mass Spectrometry ; *Pleural Neoplasms/pathology ; *Lung Neoplasms/pathology/metabolism ; Biomarkers, Tumor/analysis ; Mesothelioma/pathology ; Cell Line, Tumor ; Heterografts ; Breath Tests/methods ; Solid Phase Microextraction/methods ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM is often diagnosed late, at a point where limited treatment options are available, but early intervention could improve the chances of successful treatment for MPM patients. Biomarkers to detect MPM in at-risk individuals are needed to implement early diagnosis technologies. Volatile organic compounds (VOCs) have previously shown diagnostic potential as biomarkers when analysed in MPM patient breath. In this study, chorioallantoic membrane (CAM) xenografts of MPM cell lines were used as models of MPM tumour development for VOC biomarker discovery with the aim of generating targets for investigation in breath, biopsies or other complex matrices. VOC headspace analysis of biphasic or epithelioid MPM CAM xenografts was performed using solid-phase microextraction and gas chromatography-mass spectrometry. We successfully demonstrated the capture, analysis and separation of VOC signatures from CAM xenografts and controls. A panel of VOCs was identified that showed discrimination between MPM xenografts generated from biphasic and epithelioid cells and CAM controls. This is the first application of the CAM xenograft model for the discovery of VOC biomarkers associated with MPM histological subtypes. These findings support the potential utility of non-invasive VOC profiling from breath or headspace analysis of tissues for detection and monitoring of MPM.}, }
@article {pmid39143249, year = {2024}, author = {Mayoral, M and Araujo-Filho, JAB and Tan, KS and Ortiz, E and Adusumilli, PS and Rusch, V and Zauderer, M and Ginsberg, MS}, title = {Are there features that can predict the unresectability of pleural mesothelioma?.}, journal = {European radiology}, volume = {}, number = {}, pages = {}, pmid = {39143249}, issn = {1432-1084}, abstract = {INTRODUCTION: The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM.<br><br>METHODS: Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling.<br><br>RESULTS: Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p&#x2009;=&#x2009;0.005), neoadjuvant treatment (p&#x2009;=&#x2009;0.001), clinical T-stage (p&#x2009;<&#x2009;0.0001), all pleural thickness measurements (p&#x2009;<&#x2009;0.05), pleural thickness pattern (p&#x2009;<&#x2009;0.0001) and degree (p&#x2009;=&#x2009;0.033), lung invasion (p&#x2009;=&#x2009;0.004), extrapleural space obliteration (p&#x2009;<&#x2009;0.0001), extension to subphrenic space (p&#x2009;=&#x2009;0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p&#x2009;=&#x2009;0.002) and mediastinal invasion (p&#x2009;<&#x2009;0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC)&#x2009;>&#x2009;0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC&#x2009;=&#x2009;0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC&#x2009;=&#x2009;0.879).<br><br>CONCLUSION: Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM.<br><br>CLINICAL RELEVANCE STATEMENT: A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments.<br><br>KEY POINTS: About half of pleural mesothelioma patients are reported to receive an incorrect disease stage&#xa0;preoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.}, }
@article {pmid39138009, year = {2024}, author = {Nash, J and Stone, E and Vinod, S and Leong, T and Dawkins, P and Stirling, RG and Harden, S and Bolton, A and McWilliams, A and O'Byrne, K and Wright, GM and Brunelli, VN and Guan, T and Philpot, S and Navani, N and Brims, F and , }, title = {Lung cancer (internet-based) Delphi (LUCiD): A modified eDelphi consensus process to establish Australasian clinical quality indicators for thoracic cancer.}, journal = {Respirology (Carlton, Vic.)}, volume = {}, number = {}, pages = {}, doi = {10.1111/resp.14812}, pmid = {39138009}, issn = {1440-1843}, abstract = {BACKGROUND AND OBJECTIVE: Approximately 16,000 new cases of lung cancer are diagnosed each year in Australia and Aotearoa New Zealand, and it is the leading cause of cancer death in the region. Unwarranted variation in lung cancer care and outcomes has been described for many years, although clinical quality indicators to facilitate benchmarking across Australasia have not been established. The purpose of this study was to establish clinical quality indicators applicable to lung and other thoracic cancers across Australia and Aotearoa New Zealand.<br><br>METHODS: Following a literature review, a modified three round eDelphi consensus process was completed between October 2022 and June 2023. Participants included clinicians from all relevant disciplines, patient advocates, researchers and other stakeholders, with representatives from all Australian states and territories and Aotearoa New Zealand. Consensus was set at a threshold of 70%, with the first two rounds conducted as online surveys, and the final round held as a hybrid in person and virtual consensus meeting.<br><br>RESULTS: The literature review identified 422 international thoracic oncology indicators, and a total of 71 indicators were evaluated over the course of the Delphi consensus. Ultimately, 27 clinical quality indicators reached consensus, covering the continuum of thoracic oncologic care from diagnosis to first line treatment. Indicators benchmarking supportive care were poorly represented. Attendant numeric quality standards were developed to facilitate benchmarking.<br><br>CONCLUSION: Twenty-seven clinical quality indicators relevant to thoracic oncology care in Australasia were developed. Real world implementation will now be explored utilizing a prospective dataset collected across Australia.}, }
@article {pmid39133306, year = {2024}, author = {Thunold, S and Hernes, E and Farooqi, S and Öjlert, &#xc5;K and Francis, RJ and Nowak, AK and Szejniuk, WM and Nielsen, SS and Cedres, S and Perdigo, MS and Sørensen, JB and Meltzer, C and Mikalsen, LTG and Helland, &#xc5; and Malinen, E and Haakensen, VD}, title = {Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {}, number = {}, pages = {}, pmid = {39133306}, issn = {1619-7089}, support = {2020077//Helse S&#xf8;r-&#xd8;st RHF/ ; 2021083//Helse S&#xf8;r-&#xd8;st RHF/ ; }, abstract = {PURPOSE: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy.<br><br>METHODS: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response.<br><br>RESULTS: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5.<br><br>CONCLUSION: MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response.<br><br>STUDY REGISTRATION: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic.<br><br>CLINICALTRIALS: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&amp;cntry=NO&amp;draw=2&amp;rank=4.}, }
@article {pmid39129543, year = {2024}, author = {Delhaise, J and Gustin, M}, title = {[Erionite, an exposure factor linked to pleural mesothelioma].}, journal = {Revue medicale de Liege}, volume = {79}, number = {7-8}, pages = {478-484}, pmid = {39129543}, issn = {0370-629X}, mesh = {Humans ; *Pleural Neoplasms/etiology/diagnosis ; *Mesothelioma/etiology/chemically induced ; Male ; Zeolites/adverse effects ; Environmental Exposure/adverse effects ; Mesothelioma, Malignant/pathology ; }, abstract = {Mesotheliomas are neoplasia developed from the mesothelium, a layer covering the viscera (visceral layer) and the cavity where the organs are (parietal layer). The best known, and the most frequently encountered is the pleural mesothelioma. This disease has a close link with exposure to asbestos, a mineral fibre now banned in several countries. However, other exposure factors have also been incriminated, including another one recognised as a certain carcinogenic agent for several years now : erionite. We present the case of a patient with pleural mesothelioma whose exposure to erionite could be demonstrated. The presentation of this clinical case will be complemented by a literature review on this less known and mostly environmental exposure, contrary to asbestos which is mostly professional.}, }
@article {pmid39114201, year = {2024}, author = {Al-Moussally, F and Alamin, F and Khan, S and Gopalan, PK}, title = {Sarcomatoid Mesothelioma With New Pancreatic Lesions Presenting As Acute Pancreatitis: A Case Report.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64088}, pmid = {39114201}, issn = {2168-8184}, abstract = {Sarcomatoid mesothelioma is a rare, aggressive malignancy that usually follows asbestos exposure. It is the least common subtype of mesotheliomas, following epithelial and biphasic subtypes. Pleural mesothelioma can metastasize, with the liver, kidneys, adrenal glands, and opposite lungs being the most commonly reported sites for metastasis. Metastasis of the pancreas is extremely rare, which is why the authors of this case report intend to present the case of a 78-year-old male who was found to have acute pancreatitis, most likely secondary to metastatic lesions.}, }
@article {pmid39111017, year = {2024}, author = {Otte, N and Fraune, E and Cetiner, Y and Felten, MK and Dirrichs, T and Krabbe, J and Kraus, T}, title = {Asbestos Surveillance Program Aachen (ASPA): Cancer mortality among asbestos exposed power industry workers.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {195}, number = {}, pages = {107899}, doi = {10.1016/j.lungcan.2024.107899}, pmid = {39111017}, issn = {1872-8332}, mesh = {Humans ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects ; Male ; *Lung Neoplasms/mortality/etiology/epidemiology ; Middle Aged ; Female ; Aged ; Adult ; Mesothelioma/mortality/etiology ; Occupational Diseases/mortality/epidemiology ; Follow-Up Studies ; }, abstract = {BACKGROUND: The time between initial asbestos exposure and asbestos-related disease can span several decades. The Asbestos Surveillance Program aims to detect early asbestos-related diseases in a cohort of 8,565 power industry workers formerly exposed to asbestos.<br><br>RESEARCH QUESTION: How does asbestos exposure patterns affect cancer mortality and the duration of latency until death?<br><br>METHODS: A mortality follow-up was conducted with available vital status for 8,476 participants (99 %) and available death certificates for 89.9 % of deceased participants. Standardised mortality ratios (SMR) were calculated for asbestos-related cancers. The SMR of mesothelioma and lung cancer were stratified by exposure duration, cumulative asbestos exposure and smoking. The effect of age at first exposure, cumulative asbestos exposure and smoking on the duration of latency until death was examined using multiple linear regression analysis.<br><br>RESULTS: The mortality risk of mesothelioma (n&#xa0;=&#xa0;104) increased with cumulative asbestos exposure but not with exposure duration; the highest mortality (SMR: 23.20; 95&#xa0;% CI: 17.62-29.99) was observed in participants who performed activities with short extremely high exposures (steam turbine revisions). Lung cancer mortality (n&#xa0;=&#xa0;215) was not increased (SMR: 1.03; 95&#xa0;% CI: 0.89-1.17). Median latency until death was 46 (15-63) years for mesothelioma and 44 (15-70) years for lung cancer and deaths occurred between age 64 and 82&#xa0;years. Latency until death was not influenced by age at first exposure, cumulative exposure, or smoking.<br><br>CONCLUSION: Cumulative dose seems to be more appropriate than exposure duration for estimating the risk of mesothelioma death. Additionally, exposure with high cumulative doses in short time should be considered. Since only lung cancer mortality, not incidence, was recorded in this study, lung cancer risk associated with asbestos exposure could not be assessed and the lung cancer mortality was lower than expected probably due to screening effects and improved treatments. The critical time window of death from asbestos-related cancer is between the seventh and ninth decade of life. Future studies should further explore the concept of latency, especially since large ranges are reported throughout the literature.}, }
@article {pmid39083122, year = {2024}, author = {Kraus, T and Jonigk, D}, title = {[Mesothelioma-30 years after the asbestos ban in Germany].}, journal = {Pathologie (Heidelberg, Germany)}, volume = {45}, number = {5}, pages = {305-308}, pmid = {39083122}, issn = {2731-7196}, mesh = {Humans ; Germany/epidemiology ; *Asbestos/adverse effects ; *Mesothelioma/epidemiology/history/etiology ; Occupational Diseases/epidemiology/history/prevention &amp; control ; Occupational Exposure/legislation &amp; jurisprudence/history/adverse effects/prevention &amp; control ; Incidence ; Pleural Neoplasms/epidemiology/history/etiology ; Asbestosis/epidemiology/history/prevention &amp; control/etiology ; }, abstract = {In 1993, a total asbestos ban was introduced in Germany. Thirty years later, mesothelioma is still one of the most frequent occupational diseases. Recent data on incidence, mortality, recognized occupational diseases, early detection, and assessment are presented in this article.}, }
@article {pmid39060158, year = {2024}, author = {Gislard, A and Gramond, C and Clin, B and Paris, C and Delva, F and Brochard, P and Laurent, F and Benoist, J and Andujar, P and Chouaïd, C and Thaon, I and Boudet, L and Pairon, JC}, title = {[Compensation of occupational diseases during monitoring of the ARDCO cohort].}, journal = {Revue des maladies respiratoires}, volume = {41}, number = {7}, pages = {472-487}, doi = {10.1016/j.rmr.2024.06.010}, pmid = {39060158}, issn = {1776-2588}, mesh = {Humans ; France/epidemiology ; *Occupational Diseases/epidemiology/diagnosis/etiology ; Male ; Middle Aged ; Female ; *Occupational Exposure/adverse effects/statistics &amp; numerical data ; Aged ; *Asbestosis/epidemiology/diagnosis ; Cohort Studies ; *Lung Neoplasms/epidemiology/diagnosis/etiology ; *Workers' Compensation/statistics &amp; numerical data ; *Asbestos/adverse effects ; Adult ; Aged, 80 and over ; Tomography, X-Ray Computed/statistics &amp; numerical data ; Mesothelioma/epidemiology/diagnosis/etiology ; }, abstract = {INTRODUCTION: Questions concerning under-reporting of occupational diseases (OD) linked to asbestos exposure are regularly voiced in France. Monitoring of the French multicenter Asbestos-Related Disease Cohort (ARDCO), which ensures post-occupational medical surveillance of subjects having been exposed to asbestos, provides information on (1) the medico-legal steps taken following screening by computed tomography (CT) for benign thoracic diseases, and (2) recognition of OD as a causal factor in malignant diseases.<br><br>METHODS: OD recognition -&#xa0;and possible compensation&#xa0;- was analyzed in July 2021 among 13,289 volunteers in the cohort recruited between 2003 and 2005.<br><br>RESULTS: Fifteen percent of the subjects in the cohort were found to have at least one recognized asbestos-related OD (78.2% benign pleural disease, 10.3% asbestosis, 14.2% lung cancer, and 6.0% mesothelioma). Only 58% of pleural plaques reported by the radiologist who performed the CT resulted in their recognition as ODs. On a parallel track, 88.7% of the mesotheliomas identified based on French National health insurance data and 46.9% of lung cancers were recognized as ODs.<br><br>CONCLUSIONS: This study confirms the feasibility of a system designed to facilitate recognition, leading to possible compensation, of asbestos-related occupational diseases. The system could be improved by better training of the medical actors involved.}, }
@article {pmid39015660, year = {2024}, author = {Neilly, MDJ and Pearson, J and Thu, AW and MacRae, C and Blyth, KG}, title = {Contemporary management of mesothelioma.}, journal = {Breathe (Sheffield, England)}, volume = {20}, number = {2}, pages = {230175}, pmid = {39015660}, issn = {1810-6838}, abstract = {Pleural mesothelioma (PM) is an aggressive asbestos-associated thoracic malignancy with a median survival of 12-18 months. Due to continued asbestos use in many nations, global incidence is rising. Causes due to non-occupational, environmental exposure are also rising in many countries despite utilisation bans. For many years, platinum--pemetrexed chemotherapy was the solitary licensed therapy, but first-line combination immune checkpoint blockade has recently demonstrated improved outcomes, with both regimes tested in predominantly late-stage cohorts. In the second-line setting, single-agent nivolumab has been shown to extend survival and is now available for routine use in some regions, while second-line chemotherapy has no proven role and opportunities for clinical trials should be maximised in relapsed disease. Surgery for "technically resectable" disease has been offered for decades in many expert centres, but the recent results from the phase III MARS2 trial have challenged this approach. There remains no robustly proven standard of care for early-stage PM. The clinical trial landscape for PM is complex and increasingly diverse, making further development of specialist PM multidisciplinary teams an important priority in all countries. The observation of improving outcomes in centres that have adopted this service model emphasises the importance of high-quality diagnostics and equitable access to therapies and trials. Novel therapies targeting a range of aberrations are being evaluated; however, a better understanding of the molecular drivers and their associated vulnerabilities is required to identify and prioritise treatment targets.}, }
@article {pmid39015649, year = {2024}, author = {Cravero, JC and Yakubik, T and Wahab, L and Giang, T and Lopez, LM and Newman, MG}, title = {Primary Peritoneal Mesothelioma Affecting the Greater Omentum That Mimicked an Omental Infarction: A Case Report.}, journal = {Case reports in oncology}, volume = {17}, number = {1}, pages = {596-601}, pmid = {39015649}, issn = {1662-6575}, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is a rare cancer that is associated with asbestos exposure. The diagnosis can be difficult given the nonspecific nature of presenting symptoms and the presence of concomitant confounding findings.<br><br>CASE PRESENTATION: We report a 71-year-old male who presented with right lower quadrant pain and new-onset ascites. CT imaging of the abdomen/pelvis demonstrated omental stranding concerning for a possible omental infarction. Subsequent imaging showed persistent omental edema but no identifiable soft tissue mass. A biopsy of the omentum showed atypical mesothelial proliferation, but pathology was unable to determine if proliferation was a neoplastic versus reactive process. Surgical oncology performed a diagnostic laparoscopy that showed peritoneal studding of the omentum. Subsequent immunohistochemical staining of the omentum demonstrated preservation of BAP1 expression and loss of MTAP expression, consistent with peritoneal mesothelioma.<br><br>CONCLUSION: MPM is a rare and aggressive cancer with an overall poor prognosis. The diagnosis of MPM can be difficult based on the nonspecific clinical presentation, insufficient imaging and laboratory testing, and the presence of concomitant confounding findings, such as with this patient and his admitting diagnosis of omental infarction. This case demonstrates the importance of developing a broad differential while maintaining an awareness of heuristics that can influence clinical decision-making.}, }
@article {pmid39014872, year = {2024}, author = {Khan, S and Malik, A and Qureshi, S and Cohen, B and Nadir, A}, title = {Incidental Diagnosis of Malignant Peritoneal Mesothelioma During Liver Transplantation Surgery: A Case Report.}, journal = {The American journal of case reports}, volume = {25}, number = {}, pages = {e943787}, pmid = {39014872}, issn = {1941-5923}, mesh = {Humans ; *Liver Transplantation ; Female ; *Peritoneal Neoplasms/diagnosis ; Middle Aged ; *Incidental Findings ; *Mesothelioma, Malignant/diagnosis ; Mesothelioma/diagnosis ; Lung Neoplasms/diagnosis ; }, abstract = {BACKGROUND Malignant peritoneal mesothelioma (MPM) is a rare, lethal tumor of serous membranes. The most common factor reported in association with MPM is asbestos exposure, while viral infections, genetic predisposition, paraneoplastic syndrome, and altered immunity have been described as well. The diagnosis can be challenging among those with lower tumor burden as well as nonspecific symptoms, and it is not unusual to discover the diagnosis incidentally. CASE REPORT A middle-aged woman with decompensated cirrhosis underwent extensive pre-transplant workup, showing no evidence of malignancy. She had a personal history of asbestos exposure and family history of MPM in the extended family. During transplant surgery, a few peritoneal nodules were noted, leading to termination of the procedure. Pathological analysis confirmed malignant MPM. A multidisciplinary discussion led to following a conservative treatment approach without any intervention, due to higher risk of worsening hepatic decompensation associated with peritonectomy and intraperitoneal chemotherapy. The patient's hepatic decompensation resolved 6 months after the aborted liver transplant operation. Since the diagnosis of MPM, positron emission tomography scans have shown no recurrence of MPM for 3 consecutive years. CONCLUSIONS This is the first case of MPM diagnosed incidentally during a liver transplantation surgery. This case highlights the challenges in the diagnosis and management of MPM in a patient with decompensated liver disease. A multidisciplinary approach and following a consensus decision led to prolonged survival in the described patient.}, }
@article {pmid39011477, year = {2024}, author = {Costa, A and Forte, IM and Pentimalli, F and Iannuzzi, CA and Alfano, L and Capone, F and Camerlingo, R and Calabrese, A and von Arx, C and Benot Dominguez, R and Quintiliani, M and De Laurentiis, M and Morrione, A and Giordano, A}, title = {Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1418951}, pmid = {39011477}, issn = {2234-943X}, abstract = {INTRODUCTION: Diffuse pleural mesothelioma (DPM) of the pleura is a highly aggressive and treatment-resistant cancer linked to asbestos exposure. Despite multimodal treatment, the prognosis for DPM patients remains very poor, with an average survival of 2 years from diagnosis. Cisplatin, a platinum-based chemotherapy drug, is commonly used in the treatment of DPM. However, the development of resistance to cisplatin significantly limits its effectiveness, highlighting the urgent need for alternative therapeutic strategies. New selective inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have shown promise in various malignancies by inhibiting cell cycle progression and suppressing tumor growth. Recent studies have indicated the potential of abemaciclib for DPM therapy, and a phase II clinical trial has shown preliminary encouraging results.<br><br>METHODS: Here, we tested abemaciclib, palbociclib, and ribociclib on a panel of DPM cell lines and non-tumor mesothelial(MET-5A) cells.<br><br>RESULTS: Specifically, we focused on abemaciclib, which was the mosteffective cytotoxic agent on all the DPM cell lines tested. Abemaciclib reduced DPM cell viability, clonogenic potential, and ability to grow as three-dimensional (3D) spheroids. In addition, abemaciclib induced prolonged effects, thereby impairing second-generation sphere formation and inducing G0/G1 arrest and apoptosis/ necrosis. Interestingly, single silencing of RB family members did not impair cell response to abemaciclib, suggesting that they likely complement each other in triggering abemaciclib's cytostatic effect. Interestingly, abemaciclib reduced the phosphorylation of AKT, which is hyperactive in DPM and synergized with the pharmacological AKT inhibitor (AKTi VIII). Abemaciclib also synergized with cisplatin and reduced the viability of DPM cells with acquired resistance to cisplatin.<br><br>DISCUSSION: Overall, our results suggest that CDK4/6 inhibitors alone or in combination with standard of care should be further explored for DPM therapy.}, }
@article {pmid39006698, year = {2024}, author = {Sonobe, H and Omote, R and Habara, T and Washio, K and Yamazoe, N and Matsumoto, S and Nabeshima, K and Toda, H}, title = {A Rare Case of Pleural Epithelioid Mesothelioma With a Prominent Myxoid Stroma Reported With Morphology, Fluorescent In Situ Hybridization, and Ultrastructural Findings.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62212}, pmid = {39006698}, issn = {2168-8184}, abstract = {Herein, we report a rare case of pleural epithelioid malignant mesothelioma with a prominent myxoid stroma. To date, detailed morphological or molecular pathological findings have not been reported for this type of tumor. Hence, we aimed to describe the cytological, histological, immuno-cytohistological, electron-microscopic, and molecular pathological findings using fluorescence in situ hybridization (FISH) in such a case. The patient was a male in his mid-sixties with a history of asbestos exposure and had originally visited the hospital with a persistent cough and fever. Chest radiography revealed left pleural effusion, and laboratory examination revealed a high titer for hyaluronic acid in the effusion. Additionally, computed tomography revealed diffuse multinodular or cystic lesions in the left parietal pleura, and pleural effusion cytology revealed large epithelioid cells with mild nuclear atypia, which were considered reactive mesothelial cells. Cytologically, Giemsa staining revealed that these cells harbored variously sized intracytoplasmic vacuoles that were Alcian-blue-positive, suggesting hyaluronan production. Biopsy revealed large epithelioid cells that loosely proliferated against a prominent myxoid background. These cells were immuno-positive for calretinin, Wilms' tumor 1, D2-40, vimentin, and cytokeratin AE1/AE3 but not for carcinoembryonic antigen, Ber-EP4, or desmin. BRCA 1 associated protein 1 immunostaining showed nuclear loss, and FISH showed homozygous deletion of cyclin-dependent kinase inhibitor 2A (p16) on chromosome 9p21. Based on these findings, the lesion was diagnosed as an epithelioid mesothelioma with a prominent myxoid stroma. Electron-microscopy demonstrated a dense microvillus pattern on the surface of the tumor cells, indicating a mesothelial cell origin, and variously sized vacuoles in the cytoplasm, confirming the presence of intracytoplasmic vacuoles demonstrated on cytology. The tumor tissues obtained during surgery harbored prominent myxoid stroma, which proved that the present tumor was consistent with this type of mesothelioma. After informed consent was obtained, the patient and family wished for total resection of the tumor and postoperative chemotherapy, and the patient eventually died eight months after surgery.}, }
@article {pmid39003938, year = {2024}, author = {van Zandwijk, N and Frank, AL and Reid, G and Dimitri Røe, O and Amos, CI}, title = {Asbestos-Related lung Cancer: An underappreciated oncological issue.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {194}, number = {}, pages = {107861}, doi = {10.1016/j.lungcan.2024.107861}, pmid = {39003938}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms/etiology/epidemiology ; *Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Incidence ; Air Pollution/adverse effects ; Occupational Exposure/adverse effects ; Particulate Matter/adverse effects ; }, abstract = {Asbestos, a group of class I (WHO) carcinogenic fibers, is the main cause of mesothelioma. Asbestos inhalation also increases the risk to develop other solid tumours with lung cancer as the most prominent example [91]. The incidence of asbestos-related lung cancer (ARLC) is estimated to be to six times larger than the mesothelioma incidence thereby becoming an important health issue [86]. Although the pivotal role of asbestos in inducing lung cancer is well established, the precise causal relationships between exposures to asbestos, tobacco smoke, radon and 'particulate' (PM2.5) air pollution remain obscure and new knowledge is needed to establish appropriate preventive measures and to tailor existing screening practices[22,61,65]. We hypothesize that a part of the increasing numbers of lung cancer diagnoses in never-smokers can be explained by (historic and current) exposures to asbestos as well as combinations of different forms of air pollution (PM2.5, asbestos and silica).}, }
@article {pmid38995135, year = {2024}, author = {Mirabelli, D and Terracini, B}, title = {Carcinogenicity of asbestos-free talc and talcum powder: A systematic review of the epidemiological evidence after the 2006 monograph of the International Agency for Research on Cancer.}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {3}, pages = {220-232}, doi = {10.19191/EP24.3.A688.057}, pmid = {38995135}, issn = {1120-9763}, mesh = {Female ; Humans ; Male ; Carcinogens/toxicity ; Case-Control Studies ; Cosmetics ; Endometrial Neoplasms/epidemiology/chemically induced ; Lung Neoplasms/epidemiology/chemically induced/etiology ; Neoplasms/epidemiology/chemically induced/etiology ; *Occupational Diseases/epidemiology/chemically induced ; *Occupational Exposure/adverse effects ; Ovarian Neoplasms/epidemiology/chemically induced ; *Talc/adverse effects ; }, abstract = {BACKGROUND: in 2006, the International Agency for Research on Cancer (IARC) concluded that the evidence of carcinogenicity for asbestos-free talc was inadequate (group 3), whereas perineal use of talcum powder was classified as possibly carcinogenic (group 2B).<br><br>OBJECTIVES: to assess whether later studies provide more solid information on the carcinogenic risk from asbestos-free talc and talcum powder and a better characterization of exposure.<br><br>DESIGN: systematic review.<br><br>METHODS: cohort studies of talc miners and millers exposed to asbestos-free talc, as well as cohort and case-control studies reporting cancer risk in talc powder consumers published from 2006 onwards were identified through PubMed and reference lists. Pooled analyses were included, but not reviews and meta-analyses. In the case of repeatedly reported studies, the article with the longest follow-up or the largest number of observed cases was selected for data abstraction. Notice was taken of studies which were both reported individually and included in pooled analyses.<br><br>RESULTS: publications meeting inclusion criteria were: 2 cohort studies on talc miners and millers, 10 cohort studies on talcum powder users (4 of which estimated ovarian cancer risk), and 14 case-control studies (13 on ovarian and 1 on endometrial cancer) on the risk from talcum powder use. No excess cancer mortality has been reported among asbestos-free talc miners and millers. Case-control studies consistently led to estimates of ovarian cancer excesses associated with the use of perineal talcum powder (odds ratios up to 1.5). Most studies quantifying exposure also provided evidence of a dose-response relationship. Individual cohort studies estimated hazard ratios (HR) just above 1. In an analysis of pooled cohorts for a total of 3,112 cases, the HR for women with patent reproductive tract was 1.13 (95%CI 1.01-1.26) with a correlation between HR and frequency of use (p for trend 0.03). In all cohort studies, the perineal use of talcum powder was measured only once in the early phases of follow-up, thus producing an inaccurate measure of cumulative exposure. Results of epidemiological studies regarding cancer risk in other organs are limited and inconsistent.<br><br>CONCLUSIONS: epidemiological studies updated or published after IARC 2006 evaluation indicate that: no increase in cancer risk is apparent among miners and millers of asbestos-free talc; risk for ovarian cancer increases following the perineal use of commercial talcum powder. A correlation between indicators of quantity of use and cancer risk is suggested by a number of studies. The composition of talcum powders considered in such studies is not known.}, }
@article {pmid38990952, year = {2024}, author = {Novelli, F and Yoshikawa, Y and Vitto, VAM and Modesti, L and Minaai, M and Pastorino, S and Emi, M and Kim, JH and Kricek, F and Bai, F and Onuchic, JN and Bononi, A and Suarez, JS and Tanji, M and Favaron, C and Zolondick, AA and Xu, R and Takanishi, Y and Wang, Z and Sakamoto, G and Gaudino, G and Grzymski, J and Grosso, F and Schrump, DS and Pass, HI and Atanesyan, L and Smout, J and Savola, S and Sarin, KY and Abolhassani, H and Hammarström, L and Pan-Hammarström, Q and Giorgi, C and Pinton, P and Yang, H and Carbone, M}, title = {Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {29}, pages = {e2405231121}, pmid = {38990952}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; S10 OD028515/OD/NIH HHS/United States ; 853057/ERC_/European Research Council/International ; IG-19803//Italian Association for Cancer Research/ ; PRIN2017E5L5P3 t//AROSE, Progetti di Rilevante Interesse Nazionale/ ; C-1792//Welch Foundation (The Welch Foundation)/ ; GR-2013-02356747//Italian Ministry of Health/ ; R01 ES030948/ES/NIEHS NIH HHS/United States ; 5U01CA214195-04//the Early Detection Research Network NCI/ ; 1R01ES030948-01//HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; IG-23670//Italian Association for Cancer Research/ ; 1R01CA237235-01A1//HHS | NIH | National Cancer Institute (NCI)/ ; 1R01CA198138//US Department of Defence/ ; R01 CA237235/CA/NCI NIH HHS/United States ; PHY-2019745//NSF/ ; U01 CA214195/CA/NCI NIH HHS/United States ; PRIN20177E9EPY//AROSE, Progetti di Rilevante Interesse Nazionale/ ; }, mesh = {Humans ; *DNA Repair/genetics ; *Tumor Suppressor Proteins/genetics/metabolism ; *Germ-Line Mutation ; *Ubiquitin-Protein Ligases/genetics/metabolism ; *Mesothelioma/genetics ; *Genetic Predisposition to Disease ; *Calcium Signaling/genetics ; Female ; Male ; Middle Aged ; Tumor Suppressor Protein p53/genetics/metabolism ; Apoptosis/genetics ; Fibroblasts/metabolism ; Asbestos/toxicity ; Genomic Instability ; }, abstract = {We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 (BARD1) gene that were predicted to be damaging by computational analyses. We conducted functional assays, essential for accurate interpretation of missense variants, in primary fibroblasts that we established in tissue culture from a patient carrying the heterozygous BARD1[V523A] mutation. We found that these cells had genomic instability, reduced DNA repair, and impaired apoptosis. Investigating the underlying signaling pathways, we found that BARD1 forms a trimeric protein complex with p53 and SERCA2 that regulates calcium signaling and apoptosis. We validated these findings in BARD1-silenced primary human mesothelial cells exposed to asbestos. Our study elucidated mechanisms of BARD1 activity and revealed that heterozygous germline BARD1 mutations favor the development of mesothelioma and increase the susceptibility to asbestos carcinogenesis. These mesotheliomas are significantly less aggressive compared to mesotheliomas in asbestos workers.}, }
@article {pmid38970770, year = {2024}, author = {Cedres, S and Calvete, J and Taylor-Stokes, G and Ayerza, N&#xc1; and Larena, DV and Daumont, M}, title = {Treatment patterns and humanistic burden of malignant pleural mesothelioma in Spain.}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {38970770}, issn = {1699-3055}, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer with long latency and poor prognosis. The real-world treatment patterns and humanistic burden of MPM in an international cohort of patients were recently published. Spanish data are currently lacking and are reported here.<br><br>METHODS/PATIENTS: Data were collected from three sources: physician-abstracted demographic, clinical and treatment characteristics of patients with MPM; patient-completed questionnaires on treatment satisfaction, symptoms, caregiver use, and impact of the disease; and caregiver-completed questionnaire reporting their activity and its impact on their daily life.<br><br>RESULTS: The 241 patients in Spain were primarily elderly (median age: 67 years), male, retired/unemployed/on long-term sick leave, and diagnosed at stage IV with unresectable disease. Exposure to asbestos was detected (54%, 101/188). First-line treatment (1L) consisted primarily of doublet chemotherapy (86%, 207/241). Of 102 patients who completed 1L at data abstraction, 67 were receiving maintenance therapy, most commonly singlet chemotherapy with pemetrexed. Best supportive care was given to 29 patients, primarily after 1L (86.2%, 25/29). Symptom burden was high and health-related quality of life was poor and declined with progression: mean (SD) EQ-5D score and EQ-5D visual analogue scale score were 0.615 (0.285) and 60.8 (17.1) in 1L and 0.497 (0.370) and 56.1 (19.5) in second line. Overall, 67% of patients (162/241) required daily assistance from their caregiver, who reported an impact on their psychological well-being.<br><br>CONCLUSIONS: Patients with MPM in Spain were overall treated according to treatment guidelines at the time. Nevertheless, a considerable burden of disease was reported by patients and caregivers.}, }
@article {pmid38968839, year = {2024}, author = {Andersson, EM and Barregard, L and Akerstrom, M and Sallsten, G and Järvholm, B and Nilsson, RI}, title = {Cancer incidence in Swedish oil refinery workers exposed to benzene.}, journal = {International journal of hygiene and environmental health}, volume = {261}, number = {}, pages = {114420}, doi = {10.1016/j.ijheh.2024.114420}, pmid = {38968839}, issn = {1618-131X}, mesh = {Humans ; *Benzene/toxicity ; Sweden/epidemiology ; *Occupational Exposure/adverse effects ; Male ; Incidence ; *Oil and Gas Industry ; Middle Aged ; Adult ; *Leukemia/epidemiology/chemically induced ; Occupational Diseases/epidemiology/chemically induced ; Retrospective Studies ; Neoplasms/epidemiology/chemically induced ; Air Pollutants, Occupational ; }, abstract = {BACKGROUND: Oil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers' exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma.<br><br>AIM: The objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries.<br><br>METHODS: Cancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35-47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated.<br><br>RESULTS: In total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95-1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18-4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9&#xa0;ppm-years (median 4.9, range 0.1-31.1).<br><br>DISCUSSION: The study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure.<br><br>CONCLUSION: The present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.}, }
@article {pmid38955483, year = {2024}, author = {Berge, LAM and Shala, NK and Barone-Adesi, F and Hosgood, HD and Samuelsen, SO and Bråtveit, M and Kirkeleit, J and Silverman, D and Friesen, MC and Babigumira, R and Grimsrud, TK and Veierød, MB and Stenehjem, JS}, title = {Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort.}, journal = {Occupational and environmental medicine}, volume = {81}, number = {7}, pages = {331-338}, doi = {10.1136/oemed-2024-109424}, pmid = {38955483}, issn = {1470-7926}, mesh = {Humans ; Norway/epidemiology ; *Occupational Exposure/adverse effects ; Male ; *Asbestos/adverse effects ; Middle Aged ; *Mesothelioma/epidemiology/etiology/chemically induced ; *Pleural Neoplasms/epidemiology/etiology/chemically induced ; *Occupational Diseases/epidemiology/chemically induced/etiology ; Adult ; Aged ; *Ceramics/adverse effects ; *Petroleum/adverse effects ; Cohort Studies ; Mesothelioma, Malignant/epidemiology/etiology ; Risk Factors ; Oil and Gas Industry ; Lung Neoplasms/epidemiology/etiology/chemically induced ; Mineral Fibers/adverse effects ; Case-Control Studies ; Proportional Hazards Models ; }, abstract = {OBJECTIVES: Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers.<br><br>METHODS: Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965-1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999-2022). A case-cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure.<br><br>RESULTS: An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95%&#x2009;CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95%&#x2009;CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95%&#x2009;CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma.<br><br>CONCLUSIONS: Associations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.}, }
@article {pmid38954660, year = {2024}, author = {Zhao, Z and Li, J and Tan, F and Xue, Q and Gao, S and He, J}, title = {Assessing the global burden of mesothelioma: trends, socioeconomic influences, and asbestos exposure: a retrospective cohort study.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000001900}, pmid = {38954660}, issn = {1743-9159}, abstract = {INTRODUCTION: Mesothelioma is an uncommon type of cancer which has received little attention. This study aims to evaluate the global disease burden; trends of mesothelioma by age, sex, and geographic locations; and its risk factors on the population level.<br><br>METHODS: The Global Cancer Observatory in 2022 and 2019 Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. Multivariable linear regression analyses was conducted to explore the associations between mesothelioma incidence and key predictors including Human Development Index (HDI), Gross Domestic Product (GDP) per capita, and occupational asbestos exposure, adjusting for age and sex across global regions.<br><br>RESULTS: This study identified 30,870 global cases of mesothelioma in 2022, with a higher age-standardized incidence rate (ASR) in males (0.25 per 100,000) compared to females (0.39 per 100,000). Geographical analysis indicated the highest disease burden in Northern Europe, with particular prevalence in more developed regions. The incidence was also significantly associated with higher Human Development Index (HDI), with a beta coefficient of 0.133 overall, and Gross Domestic Product (GDP) per capita, with a beta coefficient of 0.101. These socioeconomic factors exhibited stronger associations in the elderly population, especially with HDI (&#x3b2;=0.512) and GDP (&#x3b2;=0.389), than in adults. Additionally, occupational exposure to asbestos remained a significant risk factor across all groups, except for the younger adult population, with an overall beta of 0.122 for incidence. The temporal trend analysis revealed a general decrease in mesothelioma incidence, particularly in the 15-49 years age group.<br><br>CONCLUSIONS: The analysis indicates a higher mesothelioma incidence in males and in developed regions, with marked disparities noted particularly in Northern Europe. Significant correlations with socioeconomic indicators-HDI and GDP-and occupational asbestos exposure were identified, particularly affecting the elderly. Despite a decline in global incidence, especially among younger individuals, persistent cases in females highlight the need for continued public health measures addressing both occupational and environmental exposures.}, }
@article {pmid38952736, year = {2024}, author = {De Maria, L and Pentimone, F and Cavone, D and Caputi, A and Sponselli, S and Fragassi, F and Dicataldo, F and Luisi, V and Delvecchio, G and Giannelli, G and Cafaro, F and Sole, S and Ronghi, C and Zagaria, S and Loiacono, G and Sifanno, G and Ferri, GM and Vimercati, L}, title = {Clinical investigation of former workers exposed to asbestos: the health surveillance experience of an Italian University Hospital.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1411910}, pmid = {38952736}, issn = {2296-2565}, mesh = {Humans ; Italy/epidemiology ; *Occupational Exposure/adverse effects ; Male ; *Asbestos ; *Hospitals, University ; Female ; Middle Aged ; *Asbestosis/epidemiology ; Aged ; Mesothelioma, Malignant ; Adult ; Lung Neoplasms/epidemiology/etiology ; Population Surveillance ; Pleural Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; }, abstract = {BACKGROUND: The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992.<br><br>OBJECTIVES: We describe the results of the health surveillance of former workers exposed to asbestos, conducted over 27 years, from 1994 to 2020, at the Operative Unit of Occupational Medicine of the University Hospital of Bari.<br><br>MATERIALS AND METHODS: We adopted the health surveillance protocol, which was validated at the national level in 2018.<br><br>RESULTS: A total of 1,405 former workers exposed to asbestos were examined. We proceeded with diagnosing pathologies in 339 cases (24% of the cohort subjected to surveillance), with diagnoses of some cases involving multiple pathologies. Specifically, pleural plaques were diagnosed in 49.2% of the 339 cases, asbestosis in 35.9%, malignant pleural mesothelioma (MPM) in 20.3%, mesothelioma of the vaginal tunic of the testis (MTVT) in 9.1%, lung cancer in 5.8%, and laryngeal cancer in 0.8%.<br><br>CONCLUSION: Despite the 1992 asbestos ban, asbestos-related diseases remain a serious public health issue. It is important to establish criteria that ensure the health surveillance of formerly exposed workers minimizes costs, reduces the number of invasive examinations, and optimizes achievable results.}, }
@article {pmid38951010, year = {2024}, author = {Sherborne, V and Ejegi-Memeh, S and Tod, AM and Taylor, B and Hargreaves, S and Gardiner, C}, title = {Living with mesothelioma: a systematic review of mental health and well-being impacts and interventions for patients and their informal carers.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e075071}, pmid = {38951010}, issn = {2044-6055}, mesh = {Humans ; *Mesothelioma/psychology/therapy ; *Caregivers/psychology ; *Mental Health ; Quality of Life ; Anxiety/etiology ; Depression/etiology ; }, abstract = {OBJECTIVES: Mesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review's aims were to identify/synthesise international evidence on mesothelioma's MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness.<br><br>DESIGN: Systematic review.<br><br>DATA SOURCES: Databases, searched March 2022 and March 2024, were MEDLINE; CINAHL; PsycINFO; Cochrane Library; ASSIA.<br><br>ELIGIBILITY CRITERIA: We included study designs focusing on psychological impacts of living with mesothelioma and MHWB interventions used by patients and informal carers, published in English since January 2002.<br><br>DATA EXTRACTION AND SYNTHESIS: A team of reviewers screened included studies using standardised methods. Quality was assessed using validated tools: Mixed-Methods Appraisal tool for primary research and Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews.<br><br>RESULTS: Forty-eight studies met the inclusion criteria: 20 qualitative, 16 quantitative, nine reviews, two mixed-methods, one combined systematic review/qualitative study. UK studies predominated. Many MHWB impacts were reported, including traumatic stress, depression, anxiety and guilt. These were influenced by mesothelioma's causation, communication issues and carer-patient relational interactions. Participants used wide-ranging MHWB interventions, including religious/spiritual practice; talking to mental-health professionals; meaning-making. Some strategies were presented as unhelpful, for example, denial. Participants reported lack of access to support.<br><br>CONCLUSIONS: Most qualitative studies were rated high quality. The quality of the quantitative studies and reviews varied. The sparse literature regarding MHWB in mesothelioma means more research is needed into impacts on patients and carers, including trauma. To enable access to evidence-based support, research is recommended concerning MHWB interventions' effectiveness in mesothelioma.<br><br>PROSPERO REGISTRATION NUMBER: CRD42022302187.}, }
@article {pmid38943482, year = {2024}, author = {Girardi, P and Rigoni, S and Ferrante, D and Silvestri, S and Angelini, A and Cuccaro, F and Oddone, E and Vicentini, M and Barone-Adesi, F and Tunesi, S and Migliore, E and Roncaglia, F and Sala, O and Pirastu, R and Chellini, E and Miligi, L and Perticaroli, P and Bressan, V and Merler, E and Azzolina, D and Marinaccio, A and Massari, S and Magnani, C}, title = {Asbestos exposure and asbestosis mortality in Italian cement-asbestos cohorts: Dose-response relationship and the role of competing death causes.}, journal = {American journal of industrial medicine}, volume = {67}, number = {9}, pages = {813-822}, doi = {10.1002/ajim.23629}, pmid = {38943482}, issn = {1097-0274}, support = {//Istituto Superiore di Sanit&#xe0;/ ; //Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; //The Italian National Institute of Health (ISS)/ ; //The INAIL/ ; }, mesh = {Humans ; *Asbestosis/mortality ; Italy/epidemiology ; *Occupational Exposure/adverse effects/analysis ; Male ; *Asbestos ; Middle Aged ; *Construction Materials/adverse effects ; Female ; *Cause of Death ; Aged ; Cohort Studies ; *Lung Neoplasms/mortality ; Pleural Neoplasms/mortality ; Proportional Hazards Models ; Peritoneal Neoplasms/mortality ; Occupational Diseases/mortality ; Adult ; Dose-Response Relationship, Drug ; }, abstract = {OBJECTIVES: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks.<br><br>METHODS: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death.<br><br>RESULTS: The cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death.<br><br>CONCLUSIONS: Asbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.}, }
@article {pmid38920665, year = {2024}, author = {Zhand, S and Liao, J and Castorina, A and Yuen, ML and Ebrahimi Warkiani, M and Cheng, YY}, title = {Small Extracellular Vesicle-Derived Circular RNA hsa_circ_0007386 as a Biomarker for the Diagnosis of Pleural Mesothelioma.}, journal = {Cells}, volume = {13}, number = {12}, pages = {}, pmid = {38920665}, issn = {2073-4409}, support = {2023/24 ideas to action//NSW Dust Diseases board (iCare)/ ; }, mesh = {Humans ; *RNA, Circular/genetics/metabolism ; *Extracellular Vesicles/metabolism/genetics ; *Biomarkers, Tumor/genetics/metabolism ; *Mesothelioma/genetics/diagnosis ; Cell Line, Tumor ; Pleural Neoplasms/genetics/diagnosis ; Gene Expression Regulation, Neoplastic ; Mesothelioma, Malignant/genetics/diagnosis ; }, abstract = {Pleural mesothelioma (PM) is a highly aggressive tumor that is caused by asbestos exposure and lacks effective therapeutic regimens. Current procedures for PM diagnosis are invasive and can take a long time to reach a definitive result. Small extracellular vesicles (sEVs) have been identified as important communicators between tumor cells and their microenvironment via their cargo including circular RNAs (circRNAs). CircRNAs are thermodynamically stable, highly conserved, and have been found to be dysregulated in cancer. This study aimed to identify potential biomarkers for PM diagnosis by investigating the expression of specific circRNA gene pattern (hsa_circ_0007386) in cells and sEVs using digital polymerase chain reaction (dPCR). For this reason, 5 PM, 14 non-PM, and one normal mesothelial cell line were cultured. The sEV was isolated from the cells using the gold standard ultracentrifuge method. The RNA was extracted from both cells and sEVs, cDNA was synthesized, and dPCR was run. Results showed that hsa_circ_0007386 was significantly overexpressed in PM cell lines and sEVs compared to non-PM and normal mesothelial cell lines (p < 0.0001). The upregulation of hsa_circ_0007386 in PM highlights its potential as a diagnostic biomarker. This study underscores the importance and potential of circRNAs and sEVs as cancer diagnostic tools.}, }
@article {pmid38902063, year = {2024}, author = {Couchman, E and Ejegi-Memeh, S and Mitchell, S and Gardiner, C}, title = {Rethinking continuity in primary care for people with mesothelioma.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {74}, number = {suppl 1}, pages = {}, doi = {10.3399/bjgp24X737373}, pmid = {38902063}, issn = {1478-5242}, mesh = {Humans ; *Continuity of Patient Care ; *Primary Health Care ; *Mesothelioma/therapy ; Male ; Female ; State Medicine ; United Kingdom ; Middle Aged ; Qualitative Research ; Aged ; Lung Neoplasms/therapy ; Attitude of Health Personnel ; }, abstract = {BACKGROUND: Mesothelioma is a terminal disease that is linked to asbestos exposure. Continuity is difficult for GPs, and other healthcare professionals (HCPs), to provide within the current NHS primary care system, but is highly valued by people with mesothelioma.<br><br>AIM: To understand the experiences of continuity in primary care among people with mesothelioma, their close persons, and their HCPs; how they achieve this (or not); and how it affects their healthcare service use.<br><br>METHOD: Realist case studies of patient journeys through the healthcare system (involving longitudinal interviews with people with mesothelioma, their close persons, and HCPs; and exploration of the organisational context). Data analysis allowed understanding of hidden mechanisms (resources and reasoning), triggered in certain contexts, leading to specific outcomes.<br><br>RESULTS: Forty-eight interviews (involving 9 patients, 8 close persons, and 12 HCPs) were undertaken (totalling 30.8 hours/1848 minutes). Context-Mechanism-Outcome configurations related to: challenges unique to mesothelioma; capacity of patients/close persons/HCPs to facilitate continuity; multidisciplinary (MDT) approach differs from the family doctor model; and 'the NHS primary care system is broken'.<br><br>CONCLUSION: Patients perceive their continuity needs to be unmet by the inflexible primary care system, which needs to adapt to a society in which people receive increasingly novel treatments and live longer with complex healthcare needs. A societal perspective shift is required to understand that an MDT now shares responsibility for care, rather than an individual family doctor. Policy documents continue to focus on access, and still do not advocate strongly enough for continuity, despite unequivocal evidence demonstrating its worth.}, }
@article {pmid38891178, year = {2024}, author = {Santos, C and Sacadura-Leite, E and Ferreira, J and Dixe, MDA and Astoul, P and Sousa-Uva, A}, title = {The Pleural Mesothelioma Cases and Mortality in Portugal in 2014-2020: A Descriptive Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {38891178}, issn = {2227-9032}, abstract = {BACKGROUND: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known.<br><br>OBJECTIVE: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020.<br><br>METHODS: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System.<br><br>RESULTS: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%).<br><br>CONCLUSION: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases.}, }
@article {pmid38886298, year = {2024}, author = {Lin, RT and Boonhat, H and Lin, YY and Klebe, S and Takahashi, K}, title = {Health Effects of Occupational and Environmental Exposures to Nuclear Power Plants: A Meta-Analysis and Meta-Regression.}, journal = {Current environmental health reports}, volume = {11}, number = {3}, pages = {329-339}, pmid = {38886298}, issn = {2196-5412}, support = {CMU112-MF-76 and CMU111-MF-82//China Medical University, Taiwan/ ; 111-2314-B-039-020-MY2 and 110-2314-B-039-058//National Science and Technology Council, Taiwan/ ; }, mesh = {*Nuclear Power Plants ; Humans ; *Occupational Exposure/adverse effects/analysis ; *Radiation Exposure/adverse effects ; *Environmental Exposure/adverse effects ; Neoplasms, Radiation-Induced/epidemiology/etiology ; }, abstract = {PURPOSE OF REVIEW: Numerous epidemiological studies have shown increased health risks among workers and residents living near nuclear power plants exposed to radiation levels meeting regulatory dose limits. This study aimed to evaluate the association between radiation exposure and disease risks among these populations exposed to radiation levels meeting the current regulatory dose limits.<br><br>RECENT FINDINGS: We searched four databases (Cochrane Library, PubMed, ScienceDirect, and Web of Science) for studies published before August 2023, screened eligible studies (inclusion and exclusion criteria based on population, exposure, comparator, and outcome framework), and collected data on exposure indicators and disease risks. We applied random-effects models of meta-analysis to estimate the pooled effects and meta-regression to assess the dose-response relationship (radiation dose rate for workers and distance for residents). We identified 47 studies, 13 with worker and 34 with resident samples, covering 175 nuclear power plants from 17 countries, encompassing samples of 480,623 workers and 7,530,886 residents. Workers had a significantly lower risk for all-cancer and a significantly higher risk for mesothelioma. Residents had significantly higher risks for all-cancer, thyroid cancer, and leukemia. Notably, children under 5 years old showed the highest risk for all-cancer. Our meta-regression showed a significantly positive dose-response relationship between cumulative dose of radiation exposure and risk for circulatory disease among workers. Our findings demonstrated higher risks for mesothelioma for workers and all-cancer, thyroid cancer, and leukemia for residents exposed to low-dose radiation from nuclear power plants. Some included studies did not adjust for cancer risk confounders, which could overestimate the association between radiation exposure and cancer risk and increase the risk of bias.}, }
@article {pmid38880927, year = {2024}, author = {Fu, F and Zhang, Y and Shen, H}, title = {[Advances in Targeted Therapy for Malignant Pleural Mesothelioma].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {27}, number = {5}, pages = {391-398}, pmid = {38880927}, issn = {1999-6187}, mesh = {Humans ; *Mesothelioma, Malignant/drug therapy/therapy ; *Mesothelioma/drug therapy/therapy ; *Lung Neoplasms/drug therapy/therapy/genetics ; *Molecular Targeted Therapy ; Pleural Neoplasms/drug therapy/therapy ; Animals ; Endoplasmic Reticulum Chaperone BiP ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .}, }
@article {pmid38858710, year = {2024}, author = {Huh, DA and Choi, YH and Kim, L and Park, K and Lee, J and Hwang, SH and Moon, KW and Kang, MS and Lee, YJ}, title = {Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea.}, journal = {Environmental health : a global access science source}, volume = {23}, number = {1}, pages = {56}, pmid = {38858710}, issn = {1476-069X}, mesh = {Humans ; Male ; Republic of Korea/epidemiology ; *Lung Neoplasms/mortality ; Female ; Aged ; Middle Aged ; *Mesothelioma, Malignant/mortality ; *Air Pollutants/adverse effects/analysis ; Follow-Up Studies ; *Air Pollution/adverse effects ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Particulate Matter/adverse effects/analysis ; Aged, 80 and over ; Adult ; Mesothelioma/mortality/epidemiology ; }, abstract = {BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer.<br><br>METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter&#x2009;<&#x2009;10&#xa0;&#x3bc;m, and fine particulate matter with a diameter&#x2009;<&#x2009;2.5&#xa0;&#x3bc;m-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality.<br><br>RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30).<br><br>CONCLUSION: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.}, }
@article {pmid38857841, year = {2024}, author = {Chornkrathok, S and Carbone, M and Yang, H and Rouf, M and Dodson, RF and Dera, P}, title = {Mineralogical investigation of asbestos contamination of soil near old vermiculite processing plant in Honolulu, Hawai'i.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {356}, number = {}, pages = {124350}, doi = {10.1016/j.envpol.2024.124350}, pmid = {38857841}, issn = {1873-6424}, mesh = {*Aluminum Silicates ; Hawaii ; *Soil Pollutants/analysis ; *Asbestos/analysis ; *Environmental Monitoring ; *Mining ; *Soil/chemistry ; Asbestos, Amphibole ; }, abstract = {From 1954 to 1983, a vermiculite processing facility operated near the Honolulu airport and processed raw material from the Libby, Montana mine, which is now well known for the high asbestos content of its clay deposits. The factory was closed in 1983 due to health hazard concerns, and remediation was performed in 2001 as part of the Libby mine superfund project. However, because of close proximity of the closed-down facility to residential areas of metropolitan Honolulu, some concerns remain regarding the possible environmental persistence of the harmful contaminant. To assess the dispersion of asbestos-contaminated vermiculite and explore the impact of trade winds on its distribution, air samples, and soil samples were collected from multiple locations near the former vermiculite plant. Polarized light microscopy was employed to identify elongated minerals, including potential asbestos. Quantitative mineralogical analysis utilizing X-ray powder diffraction and Rietveld refinement revealed an average content of approximately 7% vermiculite and 4% tremolite at the site. The asbestiform nature of tremolite was confirmed through X-ray micro-diffraction. Detailed analysis of airborne samples using transmission electron microscopy revealed no detectable levels of asbestos fibers in the vicinity of the former processing facilities, but the possibility of asbestos fibers becoming airborne due to mechanical disturbance during dry weather cannot be ruled out.}, }
@article {pmid38854177, year = {2024}, author = {Potesta, MA and Guld, E and Laman, J}, title = {Dual Malignancies Discovered: A Rare Case of Malignant Peritoneal Epithelioid Mesothelioma and Lung Adenocarcinoma.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e59962}, pmid = {38854177}, issn = {2168-8184}, abstract = {Clinicians diagnosing malignant peritoneal epithelioid mesothelioma (MPM or MPeM) have historically had challenges due to the low incidence of the disease, as well as the often vague symptomatology that patients present with. Newer advances in technology, specifically in immunocytochemistry, have provided a clearer path to diagnosis. Additionally, malignant mesotheliomas must be differentiated from carcinomas. This is done via histology, immunocytochemistry, as well as a careful incorporation of the patient's clinical history. In this case, we present an asymptomatic 73-year-old non-smoker female with no past medical history of asbestos exposure. She was diagnosed with MPM following a routine abdominal hernia repair. Subsequent workup revealed a lung infiltrate that was successfully biopsied and resected, evidently found to be adenocarcinoma. A careful review of the resulting pathology, as well as the interpretation of immunocytochemistry, supported the notion that the patient had two independent malignant processes occurring at once. This case underscores the rarity of two similar, yet distinct cancers, as well as epidemiology, symptomatology, histology, immunocytochemistry, and prognosis.}, }
@article {pmid38806867, year = {2024}, author = {Chen, Z and Cai, Y and Ou, T and Zhou, H and Li, H and Wang, Z and Cai, K}, title = {Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990-2019.}, journal = {Journal of cancer research and clinical oncology}, volume = {150}, number = {5}, pages = {282}, pmid = {38806867}, issn = {1432-1335}, support = {2022A028//the Dean Research Funding of Nanfang Hospital, Southern Medical University, China/ ; }, mesh = {Humans ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects ; Male ; Female ; *Global Burden of Disease ; Middle Aged ; Aged ; Adult ; Mesothelioma/epidemiology/mortality/etiology ; Mesothelioma, Malignant/epidemiology/mortality/etiology ; Disability-Adjusted Life Years ; Lung Neoplasms/epidemiology/etiology/mortality ; Aged, 80 and over ; Global Health/statistics &amp; numerical data ; Occupational Diseases/epidemiology/mortality/etiology ; }, abstract = {Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312-28,622) deaths and 569,429 (95% UI 509,956-617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25-74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure.}, }
@article {pmid38806807, year = {2024}, author = {Albano, GD and Rodolico, V and Di Franco, S and Re, GL and Midiri, M and Malta, G and Cannizzaro, E and Argo, A and Zerbo, S}, title = {Asbestos exposure determined 357 days after death through autopsy: a report of a multidisciplinary approach.}, journal = {Forensic science, medicine, and pathology}, volume = {}, number = {}, pages = {}, pmid = {38806807}, issn = {1556-2891}, abstract = {Asbestosis is an interstitial lung disease caused by the inhalation of asbestos fibers and poses a significant risk to individuals working in construction, shipping, mining, and related industries. In a forensic context, postmortem investigations are crucial for accurate diagnosis, for which the gold standard is the histopathological examination. This case report describes the autopsy and related investigations conducted on an 84-year-old man, nearly one year (357 days) after his death. After a post-mortem CT scan, an autoptic investigation was performed, followed by histopathological, immunohistochemical, and scanning electron microscopy examinations. The integration of the evidence from these examinations with previously available personal and clinical information conclusively confirmed the diagnosis of asbestosis. We demonstrated the efficacy and reliability of our diagnostic protocol in detecting asbestosis and asbestos fibers and excluding mesothelioma even in decomposed tissues. According to our findings autopsy remains the diagnostic gold standard in cases of suspected asbestosis within a forensic context, even 1 year after death, therefore it is always highly recommended, even in cases where the body has decomposed.}, }
@article {pmid38806763, year = {2024}, author = {Yaşar, S and Yılmaz, F and Utkan, G and Algın, E and Bayram, D and Tamam, S and Öksüzoğlu, &#xd6;B&#xc7; and İlhan, A and Erdat, EC and Ünal, AE and Yalçın, &#x15e;}, title = {Analysis of Treatment Strategies and Outcomes in Malignant Peritoneal Mesothelioma: Insights From a Multi-Center Study.}, journal = {Annals of surgical oncology}, volume = {31}, number = {9}, pages = {6228-6236}, pmid = {38806763}, issn = {1534-4681}, mesh = {Humans ; *Peritoneal Neoplasms/therapy/secondary/mortality ; Female ; Male ; Middle Aged ; Retrospective Studies ; *Cytoreduction Surgical Procedures ; *Mesothelioma, Malignant/therapy/pathology ; Survival Rate ; Prognosis ; Aged ; Follow-Up Studies ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Hyperthermic Intraperitoneal Chemotherapy ; Adult ; Combined Modality Therapy ; Lung Neoplasms/therapy/pathology/mortality ; }, abstract = {BACKGROUND: This study aimed to evaluate the demographic," clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population.<br><br>METHODS: A retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients' diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study.<br><br>RESULTS: The study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason.<br><br>CONCLUSIONS: According to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable.}, }
@article {pmid38803090, year = {2024}, author = {Altshuler, PC and Newman, AL and Garibay, JA}, title = {Rapid Progression of Malignant Peritoneal Mesothelioma Mimicking a Postoperative Complication in a Young Woman: A Case Report.}, journal = {The American journal of case reports}, volume = {25}, number = {}, pages = {e942948}, pmid = {38803090}, issn = {1941-5923}, mesh = {Humans ; Female ; Adult ; *Peritoneal Neoplasms/diagnosis ; *Postoperative Complications/diagnosis ; *Ovarian Neoplasms/diagnosis/pathology ; *Mesothelioma, Malignant/diagnosis ; Fatal Outcome ; Diagnosis, Differential ; Disease Progression ; Teratoma/diagnosis/surgery ; Salpingo-oophorectomy ; Mesothelioma/diagnosis ; }, abstract = {BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results. Causes include industrial pollutants, primarily asbestos, and certain genetic mutations, such as BAP1. Due to the nonspecific symptoms, it is often incidentally diagnosed during or after other surgical procedures. CASE REPORT A 35-year-old healthy woman underwent an uncomplicated laparoscopic left salpingo-oophorectomy for a symptomatic large ovarian mature cystic teratoma. She subsequently presented with late-onset postoperative fever, leukocytosis, and multiple intra-abdominal masses. Following an exploratory laparotomy, extensive infectious disease evaluation, and multiple biopsies requiring interdisciplinary collaboration, malignant peritoneal mesothelioma was diagnosed by positive histologic staining of an omental biopsy for D2-40 and CK5/6. This first specimen was positive for BAP1, with the second, a liver biopsy, testing negative for BAP1. The tumor cell testing was also notable for mutations in NF2, MLL2, and ARID1A, and the hereditary cancer genetic testing was overall unremarkable. Her disease progressed rapidly, and she died 6 months after her initial procedure. CONCLUSIONS This case of rapidly developing malignant peritoneal mesothelioma following surgical management of an ovarian mature teratoma highlights the complexity in diagnosing a rare disease that presents with nonspecific symptoms in an otherwise young and healthy woman. The rapid disease course was likely accelerated by expansive intraperitoneal spread and multiple somatic oncogenic mutations in BAP1, NF2, MLL2, and ARID1A. Gynecologists should keep a broad differential for postoperative complications, as occult malignancies can present with symptoms that mimic postoperative complications.}, }
@article {pmid38798778, year = {2024}, author = {Singh, R and Frank, AL}, title = {Analysis of mesothelioma cases and National Cancer Registry data to assess asbestos exposure in India.}, journal = {Public health action}, volume = {14}, number = {1}, pages = {30-33}, pmid = {38798778}, issn = {2220-8372}, abstract = {SETTING: Asbestos exposure can cause mesothelioma, a form of cancer which should be recorded by cancer registries. However, such registries currently cover only a small fraction (16%) of the population in India. Because India still uses asbestos, it is important to understand its health impact, especially the number of mesothelioma cases.<br><br>OBJECTIVE: To assess the number of mesothelioma cases in India and compare these to the number reported to the National Cancer Registry.<br><br>DESIGN: We used the Right to Information Act 2005 to gather data for 83 hospitals across India from 2012 to 2022-2023.<br><br>RESULTS: From a total of 83 hospitals, there were 2,213 cases of mesothelioma from 2012 onwards. During the 2012-2016 period, the number of reported cases in the Cancer Registry was 54, whereas 1,126 cases were reported by these hospitals for this period. Only 21 (25%) of the hospitals assessed in this study were part of the population-based national cancer registry programme. Overall, cases of mesothelioma occur far more frequently than are reported in cancer registries.<br><br>CONCLUSION: National record-keeping is inadequate and the system needs to be expanded and improved across all of India. This will provide more effective reporting and help to highlight the risk of exposure to asbestos.}, }
@article {pmid38791896, year = {2024}, author = {Hintermair, S and Iser, S and Varga, A and Biesinger, M and Bohanes, T and Celik, A and Sayan, M and Kankoç, A and Akyurek, N and Öğüt, B and Stubenberger, E and Ghanim, B}, title = {Ki67 Tumor Expression Predicts Treatment Benefit Achieved by Macroscopic Radical Lung-Preserving Surgery in Pleural Mesothelioma-A Retrospective Multicenter Analysis.}, journal = {Cancers}, volume = {16}, number = {10}, pages = {}, pmid = {38791896}, issn = {2072-6694}, abstract = {Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5-55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7-14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy.}, }
@article {pmid38789301, year = {2024}, author = {Hassan, A and Prabhakaran, S and Pulford, E and Hocking, AJ and Godbolt, D and Ziad, F and Pandita, A and Wessels, A and Hussey, M and Russell, PA and Klebe, S}, title = {The significance of BAP1 and MTAP/CDKN2A expression in well-differentiated papillary mesothelial tumour: a series of 21 cases and a review of the literature.}, journal = {Pathology}, volume = {56}, number = {5}, pages = {662-670}, doi = {10.1016/j.pathol.2024.02.016}, pmid = {38789301}, issn = {1465-3931}, mesh = {Humans ; *Ubiquitin Thiolesterase/metabolism ; *Tumor Suppressor Proteins/metabolism ; Male ; Female ; Middle Aged ; Aged ; Adult ; *Cyclin-Dependent Kinase Inhibitor p16/metabolism ; *Mesothelioma/pathology/metabolism/diagnosis ; *Biomarkers, Tumor/metabolism/analysis ; Purine-Nucleoside Phosphorylase/metabolism ; Young Adult ; Mesothelioma, Malignant/pathology/diagnosis/metabolism ; Neoplasms, Mesothelial/pathology/metabolism/diagnosis ; Lung Neoplasms/pathology/metabolism/diagnosis ; Pleural Neoplasms/pathology/metabolism/diagnosis ; Immunohistochemistry ; }, abstract = {The nomenclature and diagnostic criteria of well-differentiated papillary mesothelial tumour (WDPMT) have been changed in the 2021 World Health Organization (WHO) classification of thoracic tumours, and a new entity, mesothelioma in situ (MIS), introduced. Histologically these two entities may be similar. However, MIS is regarded as a precursor to invasive mesothelioma and requires demonstration of loss of BAP1 and/or MTAP/CDKN2A for diagnosis, whereas performance of these ancillary tests is desirable but not essential for a diagnosis of WDPMT, in which the significance of BAP1 and/or MTAP/CDKN2A loss is not well understood or well defined. Against this backdrop, we undertook an investigation of 21 cases of WDPMT, identified from our case files and diagnosed according to 2021 WHO criteria, to explore the relationship between histology and BAP1 and MTAP/CDKN2A expression with clinical features including asbestos exposure, focality of tumours and clinical outcome. There were 18 women and three men, with ages ranging from 23-77 years (median 62 years), in which six had a history of asbestos exposure, two had no exposure, and in 13 exposure history was unavailable. Of 20 peritoneal tumours and one pleural tumour, 13 were detected incidentally at the time of surgery for unrelated conditions and eight peritoneal tumours were multifocal at the time of diagnosis. BAP1 immunohistochemistry (IHC) was performed in all 21 tumours, with nine tumours showing BAP1 expression loss. MTAP/CDKN2A testing was performed in 14 tumours, comprising MTAP IHC in 12 and CDKN2A fluorescence in situ hybridisation (FISH) in two, with three tumours showing MTAP/CDKN2A expression loss. Two tumours with MTAP/CDKN2A loss also showed BAP1 expression loss. Four patients progressed to invasive mesothelioma, including one male with a pleural tumour and asbestos exposure, and three females with multifocal peritoneal tumours, two with asbestos exposure and one without exposure. BAP1 expression loss was seen in all tumours from the four patients who progressed to invasive mesothelioma, whilst two of these tumours showed retained MTAP IHC and two were not tested. There was one patient with a tumour with MTAP loss and retained BAP1 who died from unrelated causes 5 months after diagnosis. Eight patients received WDPMT-specific treatment in addition to the initial excision. Survival for all patients ranged from 4-218 months, with one patient dying of mesothelioma at 49 months. Based on our results in this series of 21 patients with WDPMT diagnosed according to 2021 WHO criteria, we propose that WDPMT with BAP1 expression loss may best be regarded as papillary MIS and that a history of asbestos exposure and the presence of multifocal tumours in patients diagnosed with WDPMT should prompt ancillary testing with BAP1 IHC. Further we propose that BAP1 IHC should be essential in the diagnosis of WDPMT, with the diagnosis restricted to those tumours which show retained BAP1 expression. However more studies in larger cohorts of patients are needed to explore the relationship between BAP1 expression and MTAP loss in WDPMT, which will help to define this entity and separate it more clearly from MIS and invasive mesothelioma.}, }
@article {pmid38784478, year = {2024}, author = {Testa, JR and Kadariya, Y and Friedberg, JS}, title = {Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma.}, journal = {Oncoscience}, volume = {11}, number = {}, pages = {53-57}, pmid = {38784478}, issn = {2331-4737}, abstract = {Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.}, }
@article {pmid38781764, year = {2024}, author = {Broggi, G and Massimino, M and Failla, M and Filetti, V and Rapisarda, V and Ledda, C and Lombardo, C and Loreto, C and Vigneri, P and Caltabiano, R}, title = {Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series.}, journal = {Pathology, research and practice}, volume = {259}, number = {}, pages = {155350}, doi = {10.1016/j.prp.2024.155350}, pmid = {38781764}, issn = {1618-0631}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Asbestos, Amphibole ; Biomarkers, Tumor/genetics/analysis/metabolism ; *Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Gene Deletion ; Homozygote ; *Immunohistochemistry ; *Mesothelioma/genetics/pathology/chemically induced/metabolism ; Mesothelioma, Malignant/pathology/genetics ; *Pleural Neoplasms/genetics/pathology/chemically induced/metabolism ; Purine-Nucleoside Phosphorylase/genetics ; }, abstract = {Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.}, }
@article {pmid38763755, year = {2024}, author = {Takata, A and Yamauchi, H and Yamashita, K and Aminaka, M and Hitomi, T and Toya, T and Kohyama, N}, title = {Mesothelioma carcinogenesis of chrysotile and forsterite compared and validated by intraperitoneal injection in rat.}, journal = {Industrial health}, volume = {}, number = {}, pages = {}, doi = {10.2486/indhealth.2024-0025}, pmid = {38763755}, issn = {1880-8026}, abstract = {Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1000°C and 1500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2'-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.}, }
@article {pmid38737188, year = {2024}, author = {Hong Lee, AH and Macalister, SJ and Yap, KK}, title = {Pleural small cell lung cancer masquerading as malignant mesothelioma: A case report.}, journal = {Radiology case reports}, volume = {19}, number = {8}, pages = {2969-2972}, pmid = {38737188}, issn = {1930-0433}, abstract = {Nodular soft tissue pleural thickening on imaging is highly suggestive of malignancy, of which pleural malignant mesothelioma and metastatic disease are differentials. We present the case of a 71-year-old male who presented with acute worsening of shortness of breath associated with a recurrent left pleural effusion post-pleurocentesis. He was an ex-smoker with previous asbestos exposure. Computed tomography performed demonstrated left-sided pleural thickening in the hemithorax and hemidiaphragm with complex pleural effusion. [18]F-2-deoxy-d-glucose whole body PET scan revealed extensive uptake throughout the left hemithorax in multiple pleural masses. The imaging findings and clinical case were typical of malignant mesothelioma. However, histopathology results revealed small cell lung cancer. We need to be cognisant of this atypical presentation of a common disease entity. Even when all clinical and imaging findings point towards a certain diagnosis, histopathological assessment cannot be ignored.}, }
@article {pmid38736489, year = {2024}, author = {Lapidot, M and Mazzola, E and Bueno, R}, title = {Prolonged survival and novel prognostic factors in women with pleural mesothelioma treated with extended pleurectomy decortication.}, journal = {Translational lung cancer research}, volume = {13}, number = {4}, pages = {811-820}, pmid = {38736489}, issn = {2218-6751}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is an uncommon and extremely aggressive malignancy associated with past exposure to asbestos. The low representation of women among PM patients is likely due to differences in occupational asbestos exposure. Due to the controversial role of female sex as a prognostic factor in PM, the study aims to evaluate the survival of females treated with lung-sparing surgery. We present a cohort of 114 consecutive female patients with PM who underwent intended extended pleurectomy decortication (ePD) over 11 years in a high-volume single institution.<br><br>METHODS: All women from 2007-2017 who underwent intended ePD were enrolled in the study. Data on clinical, operative, and outcome were collected. Kaplan-Meier estimators and log-rank tests were employed to assess the overall survival, and Cox regression models were utilized to analyze prognostic factors.<br><br>RESULTS: During the study period, 454 patients underwent thoracotomy with intended ePD in a single institution. There were 114 females (25%), and macroscopic complete resection (MCR) was achieved in 97 (85.1%). The median age was 65 years, histology was epithelioid in 81 (71.0%), biphasic in 31 (27.2%), and sarcomatoid in 2 (1.8%). The 30- and 90-day mortality were 3.5% and 6.1%, respectively. Median survival in females was 38 months, and 5-year survival was 28.2%. The median survival and 5-year survival rate for patients with epithelioid histology and MCR were 44.4 months and 36.4%, respectively. In a univariate analysis, several factors were found to be associated with patient overall survival including MCR [hazard ratio (HR): 0.3, P<0.001], early T status (HR: 1.6, P=0.03), adjuvant therapy (HR: 0.5, P=0.006), intraoperative heated chemotherapy (IOHC) (HR: 0.8, P=0.03), age (HR: 1.02, P=0.03) and epithelioid histology (HR: 0.5, P=0.009).<br><br>CONCLUSIONS: For women with epithelioid PM undergoing intended ePD within a multimodal setting, prolonged survival is anticipated.}, }
@article {pmid38734073, year = {2024}, author = {Bille, A and Ripley, RT and Giroux, DJ and Gill, RR and Kindler, HL and Nowak, AK and Opitz, I and Pass, HI and Wolf, A and Rice, D and Rusch, VW and , }, title = {The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the "N" Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {9}, pages = {1326-1338}, pmid = {38734073}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Neoplasm Staging/standards ; *Pleural Neoplasms/pathology/classification ; *Lung Neoplasms/pathology/classification/surgery/mortality ; *Mesothelioma/pathology/classification/mortality/surgery ; Male ; Female ; Mesothelioma, Malignant/pathology/classification/mortality ; Aged ; Middle Aged ; }, abstract = {INTRODUCTION: The International Association for the Study of Lung Cancer developed an international database to inform potential revisions in the ninth edition of the TNM classification of diffuse pleural mesothelioma (PM). This study analyzed the clinical and pathologic N categories to determine whether revisions were indicated relative to the eighth edition staging system.<br><br>METHODS: Of 7338 PM cases diagnosed from 2013 to 2022 and 3598 met&#xa0;all inclusion criteria for planned analyses. Data on 2836 patients without metastases were included in this study. Overall survival (OS) was measured from date of diagnosis. Patients were included regardless of whether they received neoadjuvant treatment. For the pathologic N analysis, patients who underwent resection (extrapleural pneumonectomy or pleurectomy/decortication) were included. N subgroups were analyzed and OS assessed by the Kaplan-Meier method.<br><br>RESULTS: The existing eighth edition N categories were performed adequately in the ninth edition data set. A median OS advantage was noted for clinical and pathologic N0 versus N1 patients: 23.2 versus 18.5 and 33.8 versus 25.0 months, respectively. Patients with resected pN0 had a 3-year OS of 48%. No difference in OS was noted for single- versus multiple-station nodal metastases. The number of nodal stations sampled at the time of resection was not associated with a difference in OS.<br><br>CONCLUSIONS: Data regarding clinical and pathologic N categories corroborate those used in the eighth edition. No changes in the N categories are recommended in the ninth edition of PM staging system.}, }
@article {pmid38729555, year = {2024}, author = {Gugnoni, M and Lorenzini, E and Torricelli, F and Donati, B and Manicardi, V and Vitale, E and Muccioli, S and Piana, S and Lococo, F and Zamponi, R and Gandellini, P and Ciarrocchi, A}, title = {Linc00941 fuels ribogenesis and protein synthesis by supporting robust cMYC translation in malignant pleural mesothelioma.}, journal = {Cancer letters}, volume = {592}, number = {}, pages = {216950}, doi = {10.1016/j.canlet.2024.216950}, pmid = {38729555}, issn = {1872-7980}, mesh = {Humans ; *Mesothelioma, Malignant/genetics/pathology/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; *Protein Biosynthesis ; *Eukaryotic Initiation Factor-4G/genetics/metabolism ; *Mesothelioma/genetics/pathology/metabolism ; Cell Line, Tumor ; *Proto-Oncogene Proteins c-myc/genetics/metabolism ; *Lung Neoplasms/genetics/pathology/metabolism ; *Gene Expression Regulation, Neoplastic ; Pleural Neoplasms/genetics/pathology/metabolism ; Ribosomes/metabolism/genetics ; Retrospective Studies ; Prognosis ; Cell Proliferation ; }, abstract = {Malignant pleural mesothelioma is a rare and lethal cancer caused by exposure to asbestos. The highly inflammatory environment caused by fibers accumulation forces cells to undergo profound adaptation to gain survival advantages. Prioritizing the synthesis of essential transcripts is an efficient mechanism coordinated by multiple molecules, including long non-coding RNAs. Enhancing the knowledge about these mechanisms is an essential weapon in combating mesothelioma. Linc00941 correlates to bad prognosis in various cancers, but it is reported to partake in distinct and apparently irreconcilable processes. In this work, we report that linc00941 supports the survival and aggressiveness of mesothelioma cells by influencing protein synthesis and ribosome biogenesis. Linc00941 binds to the translation initiation factor eIF4G, promoting the selective protein synthesis of cMYC, which, in turn, enhances the expression of key genes involved in translation. We analyzed a retrospective cohort of 97 mesothelioma patients' samples from our institution, revealing that linc00941 expression strongly correlates with reduced survival probability. This discovery clarifies linc00941's role in mesothelioma and proposes a unified mechanism of action for this lncRNA involving the selective translation of essential oncogenes, reconciling the discrepancies about its function.}, }
@article {pmid38724155, year = {2024}, author = {Bluhm, M and Atmeh, B and Boehm, S and Rüschoff, JH and Bode, P and Dommann-Scherrer, C}, title = {Pleural Effusion Caused by an Unusual Mass in the Right Hemithorax.}, journal = {Chest}, volume = {165}, number = {5}, pages = {e151-e155}, doi = {10.1016/j.chest.2024.01.025}, pmid = {38724155}, issn = {1931-3543}, mesh = {Humans ; Female ; Aged, 80 and over ; *Tomography, X-Ray Computed ; Pleural Effusion/etiology/diagnosis ; Diagnosis, Differential ; Pleural Neoplasms/complications/diagnosis ; }, abstract = {An 80-year-old woman presented with complaints of weakness and dizziness. She had a medical history of subacute cerebral ischemia, vertigo, hypertension, and thalassemia minor. The patient was born and raised in Turkey and has lived in Switzerland for 50 years. Her sister died of a mesothelioma caused by asbestos exposure at the age of 60 years but had lived in Turkey until her death. The patient had neither a history of TB nor B symptoms. She has never smoked.}, }
@article {pmid38722058, year = {2024}, author = {Stirpe, E and Bardaro, F and Köhl, J}, title = {Gluteal muscle metastases from malignant pleural mesothelioma: a case report.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {}, number = {}, pages = {}, doi = {10.4081/monaldi.2024.2629}, pmid = {38722058}, issn = {2532-5264}, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy arising from the mesothelial or subthelial layer of the pleura, and it has increased in recent decades, mainly associated with asbestos exposure. Sarcomatoid mesothelioma is the second-most common subtype of MPM. It is usually difficult to differentiate MPM from benign mesothelial pleural proliferations or other cancers. Because of its nonspecific symptoms, MPM is often diagnosed at a late stage with distal metastases. However, it is extremely rare to see a metastatic lesion within subcutaneous tissue and muscles, which is most likely caused by hematogenous spread. We present a case of sarcomatoid mesothelioma with a metastatic lesion of the right gluteal muscles.}, }
@article {pmid38711818, year = {2024}, author = {Syed Ahmad, SD and Kirk, F and Wijesinghe, W and He, C and Stroebel, A}, title = {A peculiar presentation of tamponade: pericardial mesothelioma.}, journal = {Journal of surgical case reports}, volume = {2024}, number = {5}, pages = {rjae279}, pmid = {38711818}, issn = {2042-8812}, abstract = {Pericardial mesothelioma (PM) is rare with only 200 cases recorded, and a post-mortem prevalence of <0.0022%. It is the third most common cardiac/pericardial tumour, behind angiosarcoma and rhabdomyosarcoma. PM incidence increases with age, typically incidentally diagnosed between 50 and 70 years, with a 3:1 male predominance. Occasional PM can cause chest pain, dyspnoea, cough and even dysphagia. PMs are often misdiagnosed with only 25% of cases being antemortem diagnoses. Unlike pleural mesothelioma, the link between asbestos exposure and malignancy is less convincing, with only 20% of cases having known exposure. 6 There are three histological types: epithelioid, fibrous (spindle cell), and biphasic (mixed). The average life-expectancy post diagnosis is 3-10 months. Due to the heterogeneity of the presentation and rarity there is no standardized management algorithm, and the diagnostic imaging or laboratory investigations are scarcely described. We are presenting one of the cases diagnosed in our unit here in the Gold Coast.}, }
@article {pmid38702329, year = {2024}, author = {Chin, WL and Zemek, RM and Tilsed, CM and Forrest, ARR and Fear, VS and Forbes, C and Boon, L and Bosco, A and Guo, BB and Millward, MJ and Nowak, AK and Lake, RA and Lesterhuis, WJ and Lassmann, T}, title = {Time-course RNAseq data of murine AB1 mesothelioma and Renca renal cancer following immune checkpoint therapy.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {448}, pmid = {38702329}, issn = {2052-4463}, support = {APP1154524//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Animals ; Mice ; *Carcinoma, Renal Cell/drug therapy/genetics ; *Immune Checkpoint Inhibitors/therapeutic use ; *Kidney Neoplasms/drug therapy/genetics ; *Mesothelioma/drug therapy/genetics ; RNA-Seq ; Sequence Analysis, RNA ; Single-Cell Analysis ; *Tumor Microenvironment ; }, abstract = {Time-critical transcriptional events in the immune microenvironment are important for response to immune checkpoint blockade (ICB), yet these events are difficult to characterise and remain incompletely understood. Here, we present whole tumor RNA sequencing data in the context of treatment with ICB in murine models of AB1 mesothelioma and Renca renal cell cancer. We sequenced 144 bulk RNAseq samples from these two cancer types across 4 time points prior and after treatment with ICB. We also performed single-cell sequencing on 12 samples of AB1 and Renca tumors an hour before ICB administration. Our samples were equally distributed between responders and non-responders to treatment. Additionally, we sequenced AB1-HA mesothelioma tumors treated with two sample dissociation protocols to assess the impact of these protocols on the quality transcriptional information in our samples. These datasets provide time-course information to transcriptionally characterize the ICB response and provide detailed information at the single-cell level of the early tumor microenvironment prior to ICB therapy.}, }
@article {pmid38699968, year = {2024}, author = {Lombardo, C and Maugeri, G and D'Amico, AG and Broggi, G and Caltabiano, R and Filetti, V and Matera, S and D'Agata, V and Loreto, C}, title = {Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report.}, journal = {European journal of histochemistry : EJH}, volume = {68}, number = {2}, pages = {}, pmid = {38699968}, issn = {2038-8306}, mesh = {Humans ; *Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism ; Male ; *Mesothelioma/metabolism/pathology/chemically induced ; Middle Aged ; *Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I/metabolism ; Female ; *Pleural Neoplasms/metabolism/pathology/chemically induced ; Aged ; Asbestos, Amphibole/toxicity ; Mesothelioma, Malignant/metabolism/pathology ; Lung Neoplasms/metabolism/pathology/chemically induced ; Immunohistochemistry ; Biomarkers, Tumor/metabolism ; }, abstract = {Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.}, }
@article {pmid38694815, year = {2024}, author = {Fisher, SA and Patrick, K and Hoang, T and Marcq, E and Behrouzfar, K and Young, S and Miller, TJ and Robinson, BWS and Bueno, R and Nowak, AK and Lesterhuis, WJ and Morahan, G and Lake, RA}, title = {The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop.}, journal = {Frontiers in toxicology}, volume = {6}, number = {}, pages = {1373003}, pmid = {38694815}, issn = {2673-3080}, abstract = {Objectives: This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown. Here we report a study designed to rapidly identify genes associated with mesothelioma susceptibility by combining the Collaborative Cross (CC) resource with the well-characterised MexTAg mesothelioma mouse model. Methods: The CC is a powerful mouse resource that harnesses over 90% of common genetic variation in the mouse species, allowing rapid identification of genes mediating complex traits. MexTAg mice rapidly, uniformly, and predictably develop mesothelioma, but only after asbestos exposure. To assess the influence of host genetics on ARD, we crossed 72 genetically distinct CC mouse strains with MexTAg mice and exposed the resulting CC-MexTAg (CCMT) progeny to asbestos and monitored them for traits including overall survival, the time to ARD onset (latency), the time between ARD onset and euthanasia (disease progression) and ascites volume. We identified phenotype-specific modifier genes associated with these traits and we validated the role of human orthologues in asbestos-induced carcinogenesis using human mesothelioma datasets. Results: We generated 72 genetically distinct CCMT strains and exposed their progeny (2,562 in total) to asbestos. Reflecting the genetic diversity of the CC, there was considerable variation in overall survival and disease latency. Surprisingly, however, there was no variation in disease progression, demonstrating that host genetic factors do have a significant influence during disease latency but have a limited role once disease is established. Quantitative trait loci (QTL) affecting ARD survival/latency were identified on chromosomes 6, 12 and X. Of the 97-protein coding candidate modifier genes that spanned these QTL, eight genes (CPED1, ORS1, NDUFA1, HS1BP3, IL13RA1, LSM8, TES and TSPAN12) were found to significantly affect outcome in both CCMT and human mesothelioma datasets. Conclusion: Host genetic factors affect susceptibility to development of asbestos associated disease. However, following mesothelioma establishment, genetic variation in molecular or immunological mechanisms did not affect disease progression. Identification of multiple candidate modifier genes and their human homologues with known associations in other advanced stage or metastatic cancers highlights the complexity of ARD and may provide a pathway to identify novel therapeutic targets.}, }
@article {pmid38692809, year = {2024}, author = {Li, H and Husain, AN and Moffat, D and Klebe, S}, title = {Nonmesothelial Spindle Cell Tumors of Pleura and Pericardium.}, journal = {Surgical pathology clinics}, volume = {17}, number = {2}, pages = {257-270}, doi = {10.1016/j.path.2024.01.001}, pmid = {38692809}, issn = {1875-9157}, mesh = {Humans ; *Pericardium/pathology ; *Pleural Neoplasms/pathology/diagnosis ; Diagnosis, Differential ; Heart Neoplasms/pathology/diagnosis ; Mesothelioma/pathology/diagnosis ; Sarcoma/pathology/diagnosis ; Biomarkers, Tumor/analysis ; Pleura/pathology ; }, abstract = {Spindle cell lesions of the pleura and pericardium are rare. Distinction from sarcomatoid mesothelioma, which has a range of morphologic patterns, can be difficult, but accurate diagnosis matters. This article provides practical guidance for the diagnosis of pleural spindle cell neoplasms, focusing on primary lesions.}, }
@article {pmid38692064, year = {2024}, author = {Nuvoli, B and Sacconi, A and Bottillo, G and Sciarra, F and Libener, R and Maconi, A and Carosi, M and Piperno, G and Mastropasqua, E and Papale, M and Camera, E and Galati, R}, title = {DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {175}, number = {}, pages = {116662}, doi = {10.1016/j.biopha.2024.116662}, pmid = {38692064}, issn = {1950-6007}, mesh = {Humans ; *Estradiol/blood ; Male ; *Biomarkers, Tumor/blood ; *Androstenedione/blood ; *Asbestos/toxicity/adverse effects ; Female ; Middle Aged ; *Occupational Exposure/adverse effects ; Aged ; *Mesothelioma, Malignant/blood/diagnosis ; *Lung Neoplasms/blood/diagnosis ; Mesothelioma/blood/diagnosis/chemically induced ; Pleural Neoplasms/blood/diagnosis/chemically induced ; Dehydroepiandrosterone/blood ; Case-Control Studies ; Early Detection of Cancer/methods ; }, abstract = {17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.}, }
@article {pmid38671450, year = {2024}, author = {Gogou, E and Hatzoglou, C and Siachpazidou, D and Zarogiannis, SG and Gourgoulianis, KI}, title = {Asbestos ban policies and mesothelioma mortality in Greece.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1177}, pmid = {38671450}, issn = {1471-2458}, mesh = {Humans ; Greece/epidemiology ; Male ; Female ; *Asbestos ; *Mesothelioma/mortality ; Middle Aged ; Aged ; Adult ; Mesothelioma, Malignant/mortality ; Aged, 80 and over ; Environmental Exposure/adverse effects ; Lung Neoplasms/mortality ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005, however, the public was already aware of this substance in the 1980s. This research aims to present an overview of Greece's mesothelioma age-standardized mortality rates (ASMR) from 1983 to 2019 by age, gender, and geographic region and to determine whether the actions to ban asbestos impacted these rates.<br><br>METHODS: Data were retrieved by the Hellenic Statistical Authority (HSA) from death certificates that mentioned mesothelioma as the cause of death from 1983 to 2019 with details on the residence, gender, and age. Statistical analysis was performed using PRISM 6.0 software, a two-way ANOVA test, Trend analysis was conducted using Joinpoint Regression Program 5.0 software. The linear and non-linear model was used to calculate the age-standardized rates of annual percentage change (APC) and its 95% confidential interval (95% CI).<br><br>RESULTS: From 1983 to 2019, 850 total mesothelioma deaths were recorded, the majority of whom were males (634). A rate of 74.6% accounts for males and 25.4% for females, and the ratio of Males: Females was 3:1. Males' ASMR and the whole population's ASMR reached their highest levels in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). To look for potential changes between the first two decades of the 21st century, we compared the mean ASMR of each geographic region in Greece between two different 10-year subperiods (2000-2009 and 2010-2019). Except for Epirus, all regions of Greece had elevated regional ASMRs, particularly in those with the highest asbestos deposits. Notably, the ASMR in Epirus decreased from 0.54/100000person-years (2000-2009) to 0.31/100000person-years (2010-2019). After 2011, the ASMR for men and the general population stabilized. This stability is important since mesothelioma in men is associated with occupational asbestos exposure. The intriguing discovery of a lower ASMR in Epirus emphasizes the need to raise awareness of the condition and implement effective public health measures.<br><br>CONCLUSIONS: In Greece, the annual ASMR for males and the whole population reached its highest level in 2011, which is positive and encouraging and may be a sign that the rate will stabilize during the following years. Moreover, this study showed that the actions made in the 1980s regarding public awareness and surveillance directly impacted the decrease in Epirus rates. Future research, continual awareness, information, and recording are needed to monitor the mesothelioma epidemic. The possible benefit of a mesothelioma registry and the epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, need to be addressed.<br><br>TRIAL REGISTRATION: Not applicable.}, }
@article {pmid38662022, year = {2024}, author = {Feder, IS and Fruth, E and Tannapfel, A}, title = {[Asbestos: detection and characterization in tissue].}, journal = {Pathologie (Heidelberg, Germany)}, volume = {45}, number = {5}, pages = {333-338}, pmid = {38662022}, issn = {2731-7196}, mesh = {Humans ; *Asbestos/adverse effects/analysis ; *Asbestosis/pathology/diagnosis ; *Lung/pathology/drug effects ; Mesothelioma/diagnosis/chemically induced/pathology/etiology ; Occupational Exposure/adverse effects/analysis ; Lung Neoplasms/diagnosis/pathology ; Microscopy/methods ; }, abstract = {BACKGROUND: When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease.<br><br>OBJECTIVES: The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods.<br><br>MATERIALS AND METHODS: Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented.<br><br>RESULTS: Assessing asbestos-related diseases requires recognition of the person's occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM).<br><br>CONCLUSION: The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains a&#xa0;concern.}, }
@article {pmid38642958, year = {2024}, author = {Gómez Herrero, H and Álvarez Galván, B}, title = {Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.}, journal = {Radiologia}, volume = {66 Suppl 1}, number = {}, pages = {S3-S9}, doi = {10.1016/j.rxeng.2023.03.005}, pmid = {38642958}, issn = {2173-5107}, mesh = {Male ; Humans ; Female ; Aged ; *Mesothelioma/diagnostic imaging/etiology ; *Pleural Neoplasms/diagnostic imaging/etiology ; *Asbestos/adverse effects ; *Pleural Effusion/chemically induced/complications/pathology ; Diagnostic Imaging ; }, abstract = {BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography.<br><br>MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis.<br><br>RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%.<br><br>CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.}, }
@article {pmid38640636, year = {2024}, author = {Ejegi-Memeh, S and Sherborne, V and Mayland, C and Tod, A and Taylor, BH}, title = {Mental health and wellbeing in mesothelioma: A qualitative study exploring what helps the wellbeing of those living with this illness and their informal carers.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {70}, number = {}, pages = {102572}, doi = {10.1016/j.ejon.2024.102572}, pmid = {38640636}, issn = {1532-2122}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Qualitative Research ; *Caregivers/psychology ; Aged ; *Mesothelioma/psychology ; *Mental Health ; United Kingdom ; Quality of Life ; Adult ; Social Support ; Adaptation, Psychological ; Aged, 80 and over ; Interviews as Topic ; }, abstract = {PURPOSE: Mesothelioma is an incurable, asbestos related cancer with a poor prognosis. Little is known about how patients and carers living with the condition manage their mental health and wellbeing needs. This paper reports findings on interventions being used by patients and informal carers living with mesothelioma and those which they find most helpful.<br><br>METHODS: In-depth interviews with patients (n&#xa0;=&#xa0;10) and (informal) carers (n&#xa0;=&#xa0;11) living with mesothelioma in the UK. We analysed our data inductively using a reflexive thematic analysis approach.<br><br>RESULTS: Participants described the importance of both smaller and larger actions and strategies which helped with their mental health. This included spending more time with family and friends and going on holidays. Professionals who participants said supported their mental health journey included not only specialist nurses and mental health professionals but also legal and Asbestos Support Group professionals. The latter demonstrates the unique needs and support required for this population. Exposure to asbestos as the cause of mesothelioma, has led to a social justice aspect of the experience of living with this cancer. Participants reported the importance of collective action to their mental health and wellbeing. The data indicate that patients and carers may have distinct mental health and wellbeing requirements and need to manage these in different ways at different times.<br><br>CONCLUSIONS: Findings have implications for nurses and other key professionals working in healthcare, community and legal settings supporting this client group, and for those living with mesothelioma who want to understand ways to enhance their own wellbeing.}, }
@article {pmid38634609, year = {2024}, author = {Liu, RA and Wang, BY and Chen, X and Pu, YQ and Zi, JJ and Mei, W and Zhang, YP and Qiu, L and Xiong, W}, title = {Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.}, journal = {Genetic testing and molecular biomarkers}, volume = {28}, number = {5}, pages = {189-198}, doi = {10.1089/gtmb.2023.0532}, pmid = {38634609}, issn = {1945-0257}, mesh = {Humans ; *Simian virus 40/genetics ; China/epidemiology ; Male ; Female ; Middle Aged ; Aged ; *Pleural Neoplasms/epidemiology/virology/genetics ; *Asbestos, Crocidolite ; Mesothelioma/virology/epidemiology/genetics ; Polyomavirus Infections/epidemiology ; Tumor Virus Infections/epidemiology ; Cell Line, Tumor ; Mesothelioma, Malignant/genetics ; Lung Neoplasms/virology/genetics/epidemiology ; Adult ; }, abstract = {Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.}, }
@article {pmid38630790, year = {2024}, author = {Yang, SR and Jayakumaran, G and Benhamida, J and Febres-Aldana, CA and Fanaroff, R and Chang, J and Gedvilaite, E and Villafania, LB and Sauter, JL and Offin, M and Zauderer, MG and Ladanyi, M}, title = {Diffuse Pleural Mesotheliomas with Genomic Near-Haploidization: A Newly Recognized Subset with Distinct Clinical, Histologic, and Molecular Features.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {30}, number = {13}, pages = {2780-2789}, pmid = {38630790}, issn = {1557-3265}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30-CA008748//National Cancer Institute (NCI)/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Pleural Neoplasms/genetics/pathology/mortality ; Mutation ; Loss of Heterozygosity ; Mesothelioma/genetics/pathology ; Adult ; DNA Copy Number Variations ; Genomics/methods ; Biomarkers, Tumor/genetics ; Prognosis ; Aged, 80 and over ; Mesothelioma, Malignant/genetics/pathology ; Lung Neoplasms/genetics/pathology/mortality ; }, abstract = {PURPOSE: Diffuse pleural mesotheliomas (DPM) with genomic near-haploidization (GNH) represent a novel subtype first recognized by The Cancer Genome Atlas project; however, its clinicopathologic and molecular features remain poorly defined.<br><br>EXPERIMENTAL DESIGN: We analyzed clinical genomic profiling data from 290 patients with DPM using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. Allele-specific copy number analysis was performed using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm.<br><br>RESULTS: A total of 210 patients were evaluable for loss of heterozygosity (LOH) analysis using FACETS from MSK-IMPACT tumor:normal sequencing data. In this cohort, GNH, defined as LOH across >80% of the genome, was detected in 10 cases (4.8%). Compared with non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor-infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, whereas SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, P = 0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Of three patients with GNH DPMs who received immune checkpoint blockade, two achieved a clinician-assessed partial response.<br><br>CONCLUSIONS: GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary immune checkpoint blockade response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.}, }
@article {pmid38629360, year = {2024}, author = {Mirra, L and Beretta, GL and Lisini, D and Marcianti, A and Spampinato, E and Corno, C and Costantino, M and Corsico, A and Stella, GM and Perego, P}, title = {Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673268206240405084558}, pmid = {38629360}, issn = {1875-533X}, abstract = {Pleural mesothelioma is a rare neoplastic disease with aggressive features. Patient survival is poor due to the lack of early symptoms and the absence of effective therapeutic strategies. The development of pleural mesothelioma is mainly associated with asbestos exposure and related chronic inflammation. From a molecular-based perspective, this disease is a heterogeneous tumor lacking actionable alterations. The median overall survival of patients affected by this tumor does not exceed 16 months from diagnosis. Molecular and biochemical approaches have shown that this disease is characterized by resistance to drug-induced apoptosis associated with the activation of cell survival pathways and expression of anti-apoptotic proteins. Thus, there is an urgent need to develop efficient and safe therapeutic strategies. Here, we review the pharmacological options available for the treatment of this disease with specific reference to the antitumor agents used in systemic therapies. In addition, novel pharmacological approaches, such as drug delivery tools, to improve pleural mesothelioma treatment are discussed.}, }
@article {pmid38619810, year = {2024}, author = {Gibson, AEJ and Ahmed, W and Longworth, L and Bennett, B and Daumont, M and Darlison, L}, title = {Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.}, journal = {The patient}, volume = {17}, number = {5}, pages = {551-563}, pmid = {38619810}, issn = {1178-1661}, mesh = {Humans ; *Quality of Life ; Male ; Female ; *Caregivers/psychology ; Middle Aged ; *Mesothelioma, Malignant/psychology ; Aged ; United Kingdom ; Qualitative Research ; Australia ; Pleural Neoplasms/psychology ; Interviews as Topic ; Adult ; Aged, 80 and over ; Lung Neoplasms/psychology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers.<br><br>METHODS: This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models.<br><br>RESULTS: Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving.<br><br>CONCLUSIONS: This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.}, }
@article {pmid38619498, year = {2024}, author = {Miller, E and Beckett, EM and Cheatham, D and Comerford, CE and Lewis, RC and Krevanko, C and Mandava, N and Pierce, JS}, title = {A review of the mesotheliogenic potency of cleavage fragments found in talc.}, journal = {Toxicology and industrial health}, volume = {40}, number = {7}, pages = {398-424}, doi = {10.1177/07482337241246924}, pmid = {38619498}, issn = {1477-0393}, mesh = {*Talc/chemistry ; Humans ; Animals ; *Asbestos, Amphibole ; Mesothelioma/chemically induced ; Occupational Exposure/adverse effects ; }, abstract = {It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.}, }
@article {pmid38592450, year = {2024}, author = {Kadariya, Y and Sementino, E and Ruan, M and Cheung, M and Hadikhani, P and Osmanbeyoglu, HU and Klein-Szanto, AJ and Cai, K and Testa, JR}, title = {Low Exposures to Amphibole or Serpentine Asbestos in Germline Bap1-mutant Mice Induce Mesothelioma Characterized by an Immunosuppressive Tumor Microenvironment.}, journal = {Cancer research communications}, volume = {4}, number = {4}, pages = {1004-1015}, pmid = {38592450}, issn = {2767-9764}, support = {R00 CA207871/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Mesothelioma, Malignant ; Asbestos, Serpentine ; Asbestos, Amphibole ; Asbestos, Crocidolite/toxicity ; Tumor Microenvironment/genetics ; *Mesothelioma/chemically induced ; *Neoplasms, Mesothelial ; Adenosine ; Immunosuppressive Agents ; Germ Cells ; }, abstract = {UNLABELLED: Asbestos and BAP1 germline mutations are risk factors for malignant mesothelioma (MM). While it is well accepted that amphibole asbestos is carcinogenic, the role of serpentine (chrysotile) asbestos in MM has been debated. To address this controversy, we assessed whether minimal exposure to chrysotile could significantly increase the incidence and rate of MM onset in germline Bap1-mutant mice. With either crocidolite or chrysotile, and at each dose tested, MMs occurred at a significantly higher rate and earlier onset time in Bap1-mutant mice than in wild-type littermates. To explore the role of gene-environment interactions in MMs from Bap1-mutant mice, we investigated proinflammatory and protumorigenic factors and the tumor immune microenvironment (TIME). IHC and immunofluorescence staining showed an increased number of macrophages in granulomatous lesions and MMs. The relative number of CD163-positive (CD163+) M2 macrophages in chrysotile-induced MMs was consistently greater than in crocidolite-induced MMs, suggesting that chrysotile induces a more profound immunosuppressive response that creates favorable conditions for evading immune surveillance. MMs from Bap1-mutant mice showed upregulation of CD39/CD73-adenosine and C-C motif chemokine ligand 2 (Ccl2)/C-C motif chemokine receptor 2 (Ccr2) pathways, which together with upregulation of IL6 and IL10, promoted an immunosuppressive TIME, partly by attracting M2 macrophages. Interrogation of published human MM RNA sequencing (RNA-seq) data implicated these same immunosuppressive pathways and connections with CD163+ M2 macrophages. These findings indicate that increased M2 macrophages, along with upregulated CD39/CD73-adenosine and Ccl2/Ccr2 pathways, contribute to an immunosuppressive TIME in chrysotile-induced MMs of Bap1-mutant mice, suggesting that immunotherapeutic strategies targeting protumorigenic immune pathways could be beneficial in human BAP1 mutation carriers who develop MM.<br><br>SIGNIFICANCE: We show that germline Bap1-mutant mice have enhanced susceptibility to MM upon minimal exposure to chrysotile asbestos, not only amphibole fibers. Chrysotile induced a more profound immune tumor response than crocidolite in Bap1-mutant mice by upregulating CD39/CD73-adenosine and Ccl2/Ccr2 pathways and recruiting more M2 macrophages, which together contributed to an immunosuppressive tumor microenvironment. Interrogation of human MM RNA-seq data revealed interconnected immunosuppressive pathways consistent with our mouse findings.}, }
@article {pmid38583132, year = {2024}, author = {Stevens, ME and Paustenbach, DJ and Lockhart, NJ and Busboom, DE and Deckard, BM and Brew, DW}, title = {The presence of erionite in North American geologies and the estimated mesothelioma potency by region.}, journal = {Inhalation toxicology}, volume = {36}, number = {3}, pages = {158-173}, doi = {10.1080/08958378.2024.2322496}, pmid = {38583132}, issn = {1091-7691}, mesh = {Humans ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Asbestos, Amosite/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant/complications ; *Asbestos/toxicity ; *Zeolites ; Montana ; *Lung Neoplasms/epidemiology ; }, abstract = {OBJECTIVE: Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers.<br><br>MATERIALS AND METHODS: Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined.<br><br>RESULTS AND DISCUSSION: The model predicted potency factors ranged from 0.19 to 11.25 (average &#x223c;3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor &#x223c;0.5.<br><br>CONCLUSION: The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).}, }
@article {pmid38552427, year = {2024}, author = {Lanfranco, A and Rakhshan, S and Alberti, D and Renzi, P and Zarechian, A and Protti, N and Altieri, S and Crich, SG and Deagostino, A}, title = {Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes.}, journal = {European journal of medicinal chemistry}, volume = {270}, number = {}, pages = {116334}, doi = {10.1016/j.ejmech.2024.116334}, pmid = {38552427}, issn = {1768-3254}, mesh = {Mice ; Animals ; *Carbonic Anhydrases ; *Boron Neutron Capture Therapy ; *Mesothelioma/drug therapy ; *Glioma/drug therapy ; *Melanoma/drug therapy ; Boron Compounds/therapeutic use ; }, abstract = {Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer.}, }
@article {pmid38538248, year = {2024}, author = {Mei, W and Zhang, YP and Yang, SJ}, title = {[Research progress on pathogenesis of malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {3}, pages = {232-240}, doi = {10.3760/cma.j.cn121094-20221226-00604}, pmid = {38538248}, issn = {1001-9391}, support = {82160516//National Natural Science Foundation of China/ ; 2022J0716//Science Research Foundation of Education Department of Yunnan Province/ ; 202301BA070001-26, 202301BA070001-027//The Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities/ ; }, mesh = {Humans ; *Mesothelioma, Malignant/complications ; *Lung Neoplasms/genetics/pathology ; *Pleural Neoplasms/genetics ; *Mesothelioma/genetics/diagnosis ; *Asbestos ; }, abstract = {The occurrence of malignant mesothelioma is related to exposure of asbestos. And many researchers have conducted in-depth analysis of the molecular changes of mesothelioma, showed that its molecular characteristics were chromosome changes, including chromosome rearrangement, gene mutation and gene deletion. Recent studies have strengthened our understanding of molecular characterization of mesothelioma, such as targeted mutations of tumor suppressor genes, differential gene expression, changes of miRNA and signal pathways. It is of great significance for the early diagnosis, clinical treatment and prognosis of malignant mesothelioma to explore the pathogenesis and development of malignant mesothelioma. This article reviews the research progress on the pathogenesis and carcinogenesis-related molecules of malignant mesothelioma.}, }
@article {pmid38538239, year = {2024}, author = {Wang, ZZ and Zhang, JJ and Song, PP and Zhang, H and Luo, LM and Luan, T}, title = {[Survival analysis of 37 cases of malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {3}, pages = {191-195}, doi = {10.3760/cma.j.cn121094-20230109-00012}, pmid = {38538239}, issn = {1001-9391}, mesh = {Humans ; Aged ; Middle Aged ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy ; Retrospective Studies ; *Pleural Neoplasms ; Prognosis ; Survival Analysis ; *Lung Neoplasms ; Survival Rate ; }, abstract = {Objective: To explore the relationship between clinicopathological features, treatment and prognosis of patients with malignant mesothelioma, and provide theoretical basis for the prevention and treatment of malignant mesothelioma. Methods: In November 2022, the clinical data of 37 patients with malignant mesothelioma diagnosed in Qingdao Central Hospital from July 2014 to November 2022 were retrospectively analyzed, and the prognostic factors were analyzed by Kaplan-Meier and log-rank tests. Results: The median age of the 37 patients was 66 years old, all patients were confirmed by pathology. The median survival time of all patients was 30.00 months. The 1-year, 2-year, 3-year and 5-year cumulative survival rates were 70.27% (26/37), 48.65% (18/37), 16.22% (6/37) and 13.51% (5/37), respectively. Compared with different treatments, the median survival time of palliative care patients was 5.00 months, which was significantly lower than that of operation group (30.33 months), chemotherapy group (30.00 months), surgery combined with chemotherapy group (30.00 months) and chemotherapy combined with bevacizumab targeted therapy group (47.42 months) (P<0.05). Gender, age (≥60 years old or <60 years old), smoking history, occupational exposure history, disease site, and surgical history were not factors affecting the survival of malignant mesothelioma patients (P>0.05) . Conclusion: The clinical symptoms of malignant mesothelioma are not specific, but early initiation of treatment can still prolong survival, and chemotherapy combined with anti-vascular targeted therapy shows better therapeutic effect.}, }
@article {pmid38532179, year = {2024}, author = {Mirabelli, D and Somigliana, AB and Azzolina, D and Consonni, D and Barbieri, PG}, title = {Lung fibre burden and risk of malignant mesothelioma in shipyard workers: a necropsy-based case-control study.}, journal = {Annals of work exposures and health}, volume = {68}, number = {5}, pages = {476-485}, doi = {10.1093/annweh/wxae018}, pmid = {38532179}, issn = {2398-7316}, mesh = {Humans ; Male ; Case-Control Studies ; *Occupational Exposure/adverse effects ; *Mesothelioma/pathology/etiology/epidemiology ; Italy/epidemiology ; Middle Aged ; *Lung Neoplasms/pathology/etiology/epidemiology ; *Ships ; Aged ; *Mesothelioma, Malignant ; Mineral Fibers/analysis/adverse effects ; Occupational Diseases/epidemiology/etiology ; Lung/pathology ; Pleural Neoplasms/etiology/pathology/epidemiology ; Adult ; Odds Ratio ; Autopsy ; Asbestos/analysis/adverse effects ; Asbestos, Amphibole/analysis/adverse effects ; Asbestos, Serpentine/analysis/adverse effects ; Risk Factors ; }, abstract = {OBJECTIVES: In Italy, the highest pleural cancer mortality and incidence have been observed among Italian regions where the 2 largest Italian shipyards were (and are) located. The objective of this study was to assess the exposure-response relationship for mesothelioma among male workers employed in the Monfalcone, Italy, shipyard.<br><br>METHODS: We conducted a necropsy-based case-control study. Cases (N = 102) were mesothelioma decedents and controls were those with lung cancer (N = 84). Complete job histories were available; the lung fibre content was measured using a scanning electron microscope with X-ray fluorescence, after sample preparation according to the European Respiratory Society guidelines. Odds ratios and 95% confidence intervals of mesothelioma by fibre type and lung fibre burden, as a categorical or continuous variable, were assessed by unconditional logistic regression, adjusted for age and time since exposure cessation. Analyses for the amphibole and chrysotile lung fibre burden were mutually adjusted. We calculated a cumulative exposure index by applying a job-exposure matrix to the job histories of study cases and assessed its correlation with the lung fibre burden.<br><br>RESULTS: We found an odds ratio of 22.0 (confidence intervals 5.66-85.7) for the highest lung fibre burden category (mean 43.8 million total asbestos fibres per gram of dry tissue) compared with the reference (mean 0.48). Using log10-transformed lung fibre burden, we found that the odds ratio was 3.71 (confidence intervals 2.03-6.79) for a 10-fold lung fibre burden increase. Results for the amphibole lung fibre burden were similar. Odds ratios increased over chrysotile lung fibre burden categories (P-trend = 0.025), and the odds ratio for a 10-fold increase was 4.73 (confidence intervals 0.32-70.4).<br><br>CONCLUSIONS: The cumulative exposure index was correlated with total and amphibole lung fibre burden, but not with chrysotile lung fibre burden. Mesothelioma risk was proportional to total, amphibole, and chrysotile lung fibre burden in shipyard workers.}, }
@article {pmid38522452, year = {2024}, author = {Burki, T}, title = {EPA ruling to ban chrysotile asbestos.}, journal = {The Lancet. Oncology}, volume = {25}, number = {5}, pages = {537}, doi = {10.1016/S1470-2045(24)00155-4}, pmid = {38522452}, issn = {1474-5488}, mesh = {*Asbestos, Serpentine/adverse effects ; Humans ; *United States Environmental Protection Agency/legislation &amp; jurisprudence ; United States ; Mesothelioma/chemically induced ; Occupational Exposure/legislation &amp; jurisprudence/adverse effects/prevention &amp; control ; Lung Neoplasms ; }, }
@article {pmid38522172, year = {2024}, author = {Sherborne, V and Wood, E and Mayland, CR and Gardiner, C and Lusted, C and Bibby, A and Tod, A and Taylor, B and Ejegi-Memeh, S}, title = {The mental health and well-being implications of a mesothelioma diagnosis: A mixed methods study.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {70}, number = {}, pages = {102545}, doi = {10.1016/j.ejon.2024.102545}, pmid = {38522172}, issn = {1532-2122}, mesh = {Humans ; Male ; Female ; *Mesothelioma/diagnosis/psychology ; Cross-Sectional Studies ; Middle Aged ; Aged ; *Quality of Life ; *Caregivers/psychology ; Adult ; Mental Health ; Depression/epidemiology/diagnosis ; Anxiety/epidemiology/diagnosis ; Aged, 80 and over ; Stress Disorders, Post-Traumatic/diagnosis/epidemiology ; Surveys and Questionnaires ; Mesothelioma, Malignant/diagnosis ; }, abstract = {PURPOSE: Mesothelioma is an incurable, asbestos-related cancer with a poor prognosis. There is scant evidence about the mental health and well-being impacts on patients and carers living with the illness. This study aimed to investigate mesothelioma's impact on mental health and well-being and the scale of mental health conditions in patients and informal carers.<br><br>METHODS: A mixed-methods design was used: a cross-sectional survey of mesothelioma patients and informal carers plus semi-structured interviews with patients and carers. The survey used validated scales collecting data on mental health aspects of mesothelioma: the EQ5D to assess health-related quality-of-life; the Hospital Anxiety and Depression scale; the PCL-5 to assess Posttraumatic Stress; and the Posttraumatic Growth Inventory. The datasets were integrated during analysis.<br><br>RESULTS: 96 useable survey responses were received. A clinical level of depression was reported by 29 participants (30.21%), of anxiety by 48 (50%), of posttraumatic distress disorder by 32 (33.33%), and of posttraumatic growth by 34 (35.42%). Carers had worse scores than patients. Three main themes were developed from interviews with 10 patients and 11 carers: 'Prognosis', 'Support from services', and 'Social connections and communication'.<br><br>CONCLUSIONS: Healthcare professionals delivering a mesothelioma diagnosis require regular training in communication skills plus updating in current treatment options, so they provide an appropriate mix of realism and hope. Better signposting to mental health support is needed for patients and carers. Our introduction of posttraumatic growth into the mesothelioma literature is novel. We recommend specialist nurses are trained to recognise, understand, and foster posttraumatic growth.}, }
@article {pmid38521202, year = {2024}, author = {Gill, RR and Nowak, AK and Giroux, DJ and Eisele, M and Rosenthal, A and Kindler, H and Wolf, A and Ripley, RT and Billé, A and Rice, D and Opitz, I and Rimner, A and de Perrot, M and Pass, HI and Rusch, VW and , }, title = {The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for Revisions of the "T" Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {9}, pages = {1310-1325}, pmid = {38521202}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Neoplasm Staging/standards/methods ; *Pleural Neoplasms/pathology/classification ; *Lung Neoplasms/pathology/classification ; Male ; Female ; *Mesothelioma/pathology/classification ; Aged ; Middle Aged ; Mesothelioma, Malignant/pathology/classification ; Prognosis ; Prospective Studies ; }, abstract = {INTRODUCTION: The primary tumor (T) component in the eighth edition of pleural mesothelioma (PM) staging system is based on pleural involvement and extent of invasion. Quantitative assessment of pleural tumor has been found to be prognostic. We explored quantitative and qualitative metrics to develop recommendations for T descriptors in the upcoming ninth edition of the PM staging system.<br><br>METHODS: The International Association for the Study of Lung Cancer prospectively collected data on patients with PM. Sum of maximum pleural thickness (Psum) was recorded. Optimal combinations of Psum and eighth edition cT descriptors were assessed using recursive binary splitting algorithm, with bootstrap resampling to correct for the adaptive nature of the splitting algorithm, and validated in the eighth edition data. Overall survival (OS) was calculated by the Kaplan-Meier method and differences in OS assessed by the log-rank test.<br><br>RESULTS: Of 7338 patients submitted, 3598 were eligible for cT analysis and 1790 had Psum measurements. Recursive partitioning identified optimal cutpoints of Psum at 12 and 30 mm, which, in combination with extent of invasion, yielded four prognostic groups for OS. Fmax greater than 5 mm indicated poor prognosis. cT4 category (based on invasion) revealed similar performance to eighth edition. Three eighth edition descriptors were eliminated based on low predictive accuracy. Eighth edition pT descriptors remained valid in ninth edition analyses.<br><br>CONCLUSION: Given reproducible prognostication by Psum, size criteria will be incorporated into cT1 to T3 categories in the ninth edition. Current cT4 category and all pT descriptors will be maintained, with reclassification of fissural invasion as pT2.}, }
@article {pmid38515807, year = {2023}, author = {Singh, S and Roy Pradhan, S and Yadav, A and Singh, PK}, title = {Banning asbestos in talcum powder: Time for action in India.}, journal = {Dialogues in health}, volume = {3}, number = {}, pages = {100158}, pmid = {38515807}, issn = {2772-6533}, abstract = {Long-term use of asbestos-contaminated talcum power has been reported to be the main causative agent for carcinogenesis in many research studies. In recent developments Johnson &amp; Johnson has lost multimillion-dollar lawsuits for being associated with the development of mesothelioma and ovarian cancer by its talc-based baby powder. In May 2020, the company announced, the end of the sale of its baby powder in the USA and Canada and in August 2022, announced the global discontinuation by 2023. However, in India vast proportions of people are using talc-based baby powder and the products are readily available in the market. The purpose of this communication is to create awareness and draw attention of authorities for effective regulation, including prohibition of sale and retraction of the contaminated talc-based products from the Indian market at the earliest.}, }
@article {pmid38511037, year = {2024}, author = {Singh, A and Bansal, C and Singla, D and More, S and Chabhra, S and Bashir, S}, title = {Peritoneal Malignant Mesothelioma Metastasizing to Lymph Node in Young Male-a Case Report.}, journal = {Indian journal of surgical oncology}, volume = {15}, number = {1}, pages = {145-148}, pmid = {38511037}, issn = {0975-7651}, abstract = {Peritoneal malignant mesothelioma is an uncommon neoplasm with a poor prognosis. We hereby report a case of a 20-year-old male, first diagnosed on biopsy with axillary lymph node metastasis. He presented with abdominal pain and axillary lymphadenopathy, with no history of asbestos exposure. CECT showed peritoneal thickening and ascites. Ascitic fluid cytology showed reactive morphology. The diagnosis of metastatic deposits of malignant mesothelioma was made on histopathology and confirmed by immunohistochemistry. Tumor cells were immune-reactive for CK 5/6, calretinin, D2-40, and WT1 and negative for TTF1, CK 20, and CD 3. This case report has two important highlights-(i) unusual presentation with axillary lymph node metastasis leading to diagnostic dilemma in a young male with no asbestos exposure history and (ii) confirmatory diagnostic role of IHC in Peritoneal malignant mesothelioma.}, }
@article {pmid38505910, year = {2024}, author = {Tuncel, T and Ak, G and Güneş, HV and Metintaş, M}, title = {Complex Genomic Rearrangement Patterns in Malignant Pleural Mesothelioma due to Environmental Asbestos Exposure.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {43}, number = {2}, pages = {13-27}, doi = {10.1615/JEnvironPatholToxicolOncol.2023046200}, pmid = {38505910}, issn = {2162-6537}, mesh = {Humans ; *Mesothelioma, Malignant/genetics/complications ; *Mesothelioma/chemically induced/genetics ; *Lung Neoplasms/chemically induced/genetics ; *Asbestos/toxicity ; Genomics ; Nucleotides ; Xeroderma Pigmentosum Group D Protein ; X-ray Repair Cross Complementing Protein 1 ; DEAD-box RNA Helicases ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare type of cancer, and its main risk factor is exposure to asbestos. Accordingly, our knowledge of the genomic structure of an MPM tumor is limited when compared to other cancers. In this study, we aimed to characterize complex genomic rearrangement patterns and variations to better understand the genomics of MPM tumors. We comparatively scanned 3 MPM tumor genomes by Whole-Genome Sequencing and High-Resolution SNP array. We also used various computational algorithms to detect both CNAs and complex chromosomal rearrangements. Genomic data obtained from each bioinformatics tool are interpreted comparatively to better understand CNAs and cancer-related Nucleotide variations in MPM tumors. In patients 1 and 2, we found pathogenic nucleotide variants of BAP1, RB1, and TP53. These two MPM genomes exhibited a highly rearranged chromosomal rearrangement pattern resembling Chromomanagesis particularly in the form of Chromoanasynthesis. In patient 3, we found nucleotide variants of important cancer-related genes, including TGFBR1, KMT2C, and PALLD, to have lower chromosomal rearrangement complexity compared with patients 1 and 2. We also detected several actionable nucleotide variants including XRCC1, ERCC2. We also discovered the SKA3-DDX10 fusion in two MPM genomes, which is a novel finding for MPM. We found that MPM genomes are very complex, suggesting that this highly rearranged pattern is strongly related to driver mutational status like BAP1, TP53 and RB1.}, }
@article {pmid38502527, year = {2024}, author = {Rota, M and Viscardi, A and Maghin, F and Placidi, D and Conti, A}, title = {Mesothelioma among seamen: a systematic review and meta-analysis.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {33}, number = {5}, pages = {438-447}, doi = {10.1097/CEJ.0000000000000875}, pmid = {38502527}, issn = {1473-5709}, mesh = {Humans ; *Mesothelioma/epidemiology/mortality/etiology ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects/toxicity ; *Ships ; Occupational Diseases/epidemiology/etiology/mortality ; Military Personnel/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: Navy personnel and seafarers live and work 24 h per day in the shipboard environment and they are exposed to asbestos fibers released into the confined spaces aboard ships. We conducted a systematic review and meta-analysis to quantify the mesothelioma risk of seamen working aboard ships, either commercial or naval vessels, as compared to that of the general population.<br><br>METHODS: We carried out a literature search in MEDLINE through PubMed and EMBASE, from inception to 31 December 2021, of all studies on seamen working aboard ships, either commercial or naval vessels, characterized by exposure to asbestos and providing mesothelioma risk estimates. The Newcastle-Ottawa Scale was used to assess the quality of the studies included. The pooled standardized mortality ratio (SMR) was computed across eligible studies. The study protocol was registered on PROSPERO and reporting followed the preferred reporting items for systematic reviews and meta-analyses guidelines.<br><br>RESULTS: A total of 10 studies published from 1990 to 2020 were considered eligible and included in the systematic review and meta-analysis. All the included studies were of good quality, with a median score of seven out of nine. Overall, there were 235 mesothelioma cases/deaths in the included studies versus 115.6 expected, with a pooled SMR of 2.11 (95% confidence intervals, 1.70-2.62), in the absence of a significant between-study heterogeneity (I2 &#x2005;=&#x2005;39%, P &#x2005;=&#x2005;0.11).<br><br>CONCLUSION: A more than double excess risk for mesothelioma among seamen working aboard ships emerged from our meta-analysis.}, }
@article {pmid38502172, year = {2024}, author = {Dodson, RF and Moline, J and Salinas, CD and Poye, LW}, title = {Elongated particulate burden in an individual who died of mesothelioma and had an occupational history as a talc "mucker".}, journal = {Inhalation toxicology}, volume = {36}, number = {3}, pages = {205-216}, doi = {10.1080/08958378.2024.2329935}, pmid = {38502172}, issn = {1091-7691}, mesh = {Male ; Humans ; Aged ; Talc ; *Mesothelioma/chemically induced ; Asbestos, Amphibole ; *Mesothelioma, Malignant/complications ; *Asbestos/toxicity ; *Lung Neoplasms/chemically induced ; Dust ; }, abstract = {INTRODUCTION: Tissue from a 77-year-old man diagnosed with mesothelioma was referred with a request for identification of the presence of fibrous structures in tissue samples. The individual's work history including working as a "mucker" at a specific "industrial" talc mine.<br><br>METHODS: Ferruginous bodies in the tissue digests as well as asbestos fibers were found. A bulk sample of a talc containing product from that mine was also analyzed.<br><br>DISCUSSIONS/CONCLUSIONS: The correlation between the unique asbestos mineral/fibrous content of the talc to which he was exposed and findings of the same type of asbestos found in his lung is discussed. The type of asbestos found (tremolite) is a "non-commercial" type of asbestos that has been identified in some talc deposits. Tremolite, like all forms of asbestos is a causative agent for mesothelioma-the disease from which this individual suffered.}, }
@article {pmid38500093, year = {2024}, author = {Miao, X and Yao, T and Dong, C and Chen, Z and Wei, W and Shi, Z and Xu, T and Shao, J and Niu, Q and Rui, D and Hu, Y and Yan, Y}, title = {Global, regional, and national burden of non-communicable diseases attributable to occupational asbestos exposure 1990-2019 and prediction to 2035: worsening or improving?.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {832}, pmid = {38500093}, issn = {1471-2458}, support = {RCZK2021B28//The Shihezi University High-level Talents Program/ ; ZZZC202125//The Shihezi University self-funded project/ ; SRP2023085//The Shihezi University 2023 College Student Research and Training Program SRP Project/ ; }, mesh = {Male ; Humans ; Aged ; Quality-Adjusted Life Years ; *Noncommunicable Diseases/epidemiology ; Global Burden of Disease ; *Occupational Exposure/adverse effects ; *Asbestos/toxicity ; Global Health ; }, abstract = {Understanding the burden associated with occupational asbestos exposure on a global and regional scale is necessary to implement coordinated prevention and control strategies. By the GBD Study 2019, we conducted a comprehensive assessment of the non-communicable diseases burden attributable to occupational asbestos exposure. In 2019, 239,330 deaths and 4,189,000 disability-adjusted life years (DALYs) worldwide due to occupational asbestos exposure occurred. 1990-2019, deaths and DALYs attributed to occupational asbestos exposure increased by 65.65% and 43.66%, respectively. Age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased, with the most rapid declines in high Socio-Demographic Index (SDI) regions, with average annual percent change (AAPC) of - 1.05(95%CI: -1.2, -0.89) and -1.53(95%CI: -1.71, -1.36), respectively. Lung cancer, mesothelioma and ovarian cancer were the top three contributors to the increase in deaths and DALYs, accounting for more than 96%. AAPCs of ASMR and ASDR were positively associated with SDI. Global deaths from occupational asbestos exposure were predicted to increase and ASMR to decrease by 2035, mostly in males. Due consideration should be given to the susceptibility of the elderly, the lag of asbestos onset, and the regional differences, and constantly improve the prevention and control measures of occupational asbestos exposure and related diseases.}, }
@article {pmid38490630, year = {2024}, author = {Frank, AL}, title = {To the Editor-environmental research this letter is a critique of the paper by regarding chronological trends of the fiber burden in mesothelioma cases.}, journal = {Environmental research}, volume = {251}, number = {Pt 1}, pages = {117352}, doi = {10.1016/j.envres.2023.117352}, pmid = {38490630}, issn = {1096-0953}, mesh = {Humans ; *Mesothelioma/epidemiology ; Asbestos ; }, }
@article {pmid38482789, year = {2024}, author = {Chellini, E}, title = {[Is the epidemiological surveillance of malignant mesothelioma implemented in Italy still valid and necessary?].}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {1}, pages = {78-84}, doi = {10.19191/EP24.1.A561.024}, pmid = {38482789}, issn = {1120-9763}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/epidemiology/etiology ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology/etiology ; Italy/epidemiology ; *Asbestos/toxicity ; }, abstract = {The register of malignant mesotheliomas can still play an informative role in the context of both remediation activities and the health surveillance of former asbestos-exposed persons, and become an epidemiological surveillance system on the harmful effects of exposure to asbestos. It must, however, maintain and improve the level of quality achieved, resolve the problems that have emerged in the interaction between the local level (where cases and their exposure histories are identified, registered, assessed, and medical insurance procedures activated) and the central insurance body that also manages the national register, and become an active participant in research, including clinical research. All this is important to meet the social and welfare justice needs of individual cases.}, }
@article {pmid38465395, year = {2024}, author = {Costantino, C and Ledda, C and Riccò, M and Costagliola, E and Balsamo, F and Belluzzo, M and Bonaccorso, N and Carubia, A and D'Azzo, L and Sciortino, M and Vitello, T and Zagra, L and Fruscione, S and Ilardo, S and Trapani, E and Calamusa, G and Rapisarda, V and Mazzucco, W}, title = {Decade-long insights: tracking asbestos-related health impacts among formerly exposed workers in Palermo, Italy.}, journal = {Annali di igiene : medicina preventiva e di comunita}, volume = {36}, number = {5}, pages = {525-536}, doi = {10.7416/ai.2024.2619}, pmid = {38465395}, issn = {1120-9135}, mesh = {Humans ; Italy/epidemiology ; *Occupational Exposure/adverse effects ; *Asbestosis/epidemiology/etiology ; *Asbestos/adverse effects ; Male ; *Lung Neoplasms/epidemiology/etiology ; Middle Aged ; Female ; Aged ; *Occupational Diseases/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Adult ; Time Factors ; Pleural Neoplasms/epidemiology/etiology ; Smoking/epidemiology/adverse effects ; }, abstract = {BACKGROUND: Asbestos is a foremost occupational carcinogen globally. Despite the prohibition under Law 257/1992, Italy persists as one of the European nations most burdened by asbestos-related diseases (ARDs). This research assessed ARD cases in asbestos-exposed workers from the Province of Palermo, Italy, spanning 2010-2021.<br><br>METHODS: Data acquisition utilized the epidemiological dataset from the 'Service of Prevention and Safety on Work Environment' under the Prevention Department of Palermo's Local Health Authority (LHA).<br><br>RESULTS: Between 2010 and 2021, we identified 245 ARD instances, comprising 163 Asbestosis/Pleural plaques, 41 Lung Cancers, 38 Mesotheliomas, and 3 unspecified cases. Multivariate analysis indicated a notable decline in temporal exposure for mesothelioma (HR=0.933; 95% CI=0.902-0.965) and lung cancer (HR=0.93; 95% CI=0.90-0.978) relative to pleural plaques/asbestosis. Tobacco use displayed a pronounced correlation with lung cancer (smoker HR=64.520 95% CI=13,075-318.390; former smoker HR=20.917 95% CI=4,913-89.048). A significant link was observed between mesothelioma and pleural plaques/asbestosis in those employed in shipbuilding and repair (HR=0.371 95% CI=0.155-0.892).<br><br>CONCLUSIONS: ARDs persist in clinical observations, even following the 1992 cessation of asbestos-related activities, emphasizing an enduring public health challenge. Enhancing prevention strategies is paramount, focusing on amplifying anamnestic and occupational data collection, thereby facilitating superior early diagnosis strategies for these maladies in the occupationally exposed cohort.}, }
@article {pmid38462627, year = {2024}, author = {Liu, J and Lu, Y and Liu, Y and Zhang, W and Xian, S and Wang, S and Zheng, Z and Lin, R and Jin, M and Zhang, M and Qian, W and Tang, J and Lu, B and Yang, Y and Liu, Z and Qu, M and Ma, H and Wu, X and Chang, Z and Zhang, J and Zhang, Y}, title = {A gene signature linked to fibroblast differentiation for prognostic prediction of mesothelioma.}, journal = {Cell &amp; bioscience}, volume = {14}, number = {1}, pages = {33}, pmid = {38462627}, issn = {2045-3701}, support = {82002923//National Natural Science Foundation of China/ ; 201940306//Shanghai Municipal Health Commission/ ; }, abstract = {BACKGROUND: Malignant mesothelioma is a type of infrequent tumor that is substantially related to asbestos exposure and has a terrible prognosis. We tried to produce a fibroblast differentiation-related gene set for creating a novel classification and prognostic prediction model of MESO.<br><br>METHOD: Three databases, including NCBI-GEO, TCGA, and MET-500, separately provide single-cell RNA sequencing data, bulk RNA sequencing profiles of MESO, and RNA sequencing information on bone metastatic tumors. Dimensionality reduction and clustering analysis were leveraged to acquire fibroblast subtypes in the MESO microenvironment. The fibroblast differentiation-related genes (FDGs), which were associated with survival and subsequently utilized to generate the&#xa0;MESO categorization and prognostic prediction model, were selected in combination with pseudotime analysis and survival information from the TCGA database. Then, regulatory network was constructed for each MESO subtype, and candidate inhibitors were predicted. Clinical specimens were collected for further validation.<br><br>RESULT: A total of six fibroblast subtypes, three differentiation states, and 39 FDGs were identified. Based on the expression level of FDGs, three MESO subtypes were distinguished in the fibroblast differentiation-based classification&#xa0;(FDBC). In the multivariate prognostic prediction model, the risk score that was dependent on the expression level of several&#xa0;important FDGs,&#xa0;was verified to be an independently effective prognostic factor and worked well in internal cohorts. Finally, we predicted 24 potential drugs for the treatment of MESO. Moreover, immunohistochemical staining and statistical analysis provided further validation.<br><br>CONCLUSION: Fibroblast differentiation-related genes&#xa0;(FDGs), especially those in low-differentiation states, might&#xa0;participate in the proliferation and invasion of MESO. Hopefully, the raised clinical subtyping of MESO would provide references for clinical practitioners.}, }
@article {pmid38459714, year = {2024}, author = {Rigon, M and Mutti, L and Campanella, M}, title = {Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer.}, journal = {Molecular oncology}, volume = {18}, number = {4}, pages = {797-814}, pmid = {38459714}, issn = {1878-0261}, support = {2019//Gruppo Italiano Mesotelioma G.I.Me Charity/ ; COG2018-819600_FIRM//H2020 European Research Council/ ; ARCLEADER2022020004901//Fondation ARC pour la Recherche sur le Cancer/ ; MFAG21903//Associazione Italiana per la Ricerca sul Cancro/ ; }, mesh = {Humans ; *Mesothelioma/genetics/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms/genetics ; *Asbestos ; *Lung Neoplasms/pathology ; }, abstract = {Mesothelioma is a type of late-onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it mainly targets the lining of the lungs, making pleural mesothelioma (PMe) the most common and widely studied mesothelioma type. PMe is caused by exposure to fibres of asbestos, which when inhaled leads to inflammation and scarring of the pleura. Despite the ban on asbestos by most Western countries, the incidence of PMe is on the rise, also facilitated by a lack of specific symptomatology and diagnostic methods. Therapeutic options are also limited to mainly palliative care, making this disease untreatable. Here we present an overview of biological aspects underlying PMe by listing genetic and molecular mechanisms behind its onset, aggressive nature, and fast-paced progression. To this end, we report on the role of deubiquitinase BRCA1-associated protein-1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation.}, }
@article {pmid38447601, year = {2024}, author = {Roggli, VL and Pavlisko, EN and Glass, CH and Green, CL and Liu, B and Carney, JM}, title = {Response to the editor-Environmental Research this letter is a critique of the paper by Roggli et al. (1) regarding chronological trends of the fiber burden in mesothelioma cases.}, journal = {Environmental research}, volume = {251}, number = {Pt 1}, pages = {118620}, doi = {10.1016/j.envres.2024.118620}, pmid = {38447601}, issn = {1096-0953}, mesh = {Humans ; *Mesothelioma/epidemiology/chemically induced ; Asbestos ; }, }
@article {pmid38447379, year = {2024}, author = {Haakensen, VD and Öjlert, &#xc5;K and Thunold, S and Farooqi, S and Nowak, AK and Chin, WL and Grundberg, O and Szejniuk, WM and Cedres, S and Sørensen, JB and Dalen, TS and Lund-Iversen, M and Bjaanæs, M and Helland, &#xc5;}, title = {UV1 telomerase vaccine with ipilimumab and nivolumab as second line treatment for pleural mesothelioma - A phase II randomised trial.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {202}, number = {}, pages = {113973}, doi = {10.1016/j.ejca.2024.113973}, pmid = {38447379}, issn = {1879-0852}, mesh = {Humans ; Nivolumab/adverse effects ; Ipilimumab/adverse effects ; *Telomerase ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Mesothelioma, Malignant/drug therapy ; *Mesothelioma/drug therapy ; *Pleural Neoplasms/drug therapy/etiology ; }, abstract = {PURPOSE: The NIPU-trial investigates the effect of adding the telomerase vaccine UV1 to treatment with ipilimumab and nivolumab for patients with pleural mesothelioma (PM).<br><br>METHODS: In this phase 2 open-label trial, patients with PM progressing after first-line chemotherapy were randomised to receive ipilimumab and nivolumab alone (arm B) or combined with UV1 (arm A). The primary endpoint was progression-free survival (PFS) as determined by BICR. It was estimated that 69 PFS events were needed to detect a hazard ratio (HR) of 0.60 with 80% power and a one-sided alpha level of 0.10.<br><br>RESULTS: 118 patients were randomised. The median PFS determined by blinded independent central review (BICR) was 4.2 months (95%CI 2.9-9.8) in arm A and 4.7 months (95%CI 3.9-7.0) in arm B (HR 1.01, 80%CI 0.75-1.36&#xa0;P&#xa0;=&#xa0;0.979), after a median follow-up of 12.5 months (95%CI 9.7-15.6). The investigator-determined median PFS was 4.3 months (95%CI 3.0-6.8) in arm A and 2.9 months (95%CI 2.4-5.5) in arm B (HR 0.60, 80%CI 0.45-0.81&#xa0;P&#xa0;=&#xa0;0.025). Confirmed objective response rate (ORR) by BICR was 31% in arm A and 16% in arm B (odds ratio 2.44 80%CI 1.35-4.49&#xa0;P&#xa0;=&#xa0;0.056). After a median follow-up time of 17.3 months (95%CI 15.8-22.9), the OS was 15.4 months (95%CI 11.1-22.6) in arm A and 11.1 months (95%CI 8.8-18.1) in arm B, (HR 0.73, 80%CI 0.53-1.0, P&#xa0;=&#xa0;0.197).<br><br>CONCLUSION: The primary endpoint was not met. Predefined analyses of response rates are in favour of adding the vaccine.}, }
@article {pmid38426158, year = {2024}, author = {Amakusa, Y and Suzuki, T and Hikosaka, Y and Takemura, M and Oguri, T}, title = {Successful treatment of simultaneous malignant pleural mesothelioma and pulmonary adenocarcinoma: A case report.}, journal = {Oncology letters}, volume = {27}, number = {4}, pages = {155}, pmid = {38426158}, issn = {1792-1082}, abstract = {The present report described the case of a 74-year-old male patient with asbestos exposure whose chest computed tomography revealed a right lower lobe nodule and right pleural effusion. Pleural biopsy led to the diagnosis of epithelial malignant pleural mesothelioma (cT2N0M0, stage IB). Combination therapy with cisplatin + pemetrexed led to the complete remission of malignant pleural mesothelioma; however, the right lower lobe nodule grew in size over time. The patient was subsequently diagnosed with lung adenocarcinoma (cT1aN0M0, stage IA1) by computed tomography-guided biopsy performed 18 months after chemotherapy initiation and achieved remission of lung adenocarcinoma with stereotactic radiotherapy. The patient was alive without recurrence at the 12-month follow-up. The present case illustrated that multiple active regimens are currently available for malignant pleural mesothelioma and lung cancer that can aid in the treatment of complex cases.}, }
@article {pmid38423601, year = {2024}, author = {Shimizu, D and Ishibashi, M and Yamada, T and Toda, Y and Hosogi, S and Ashihara, E}, title = {POLD1 Is Required for Cell Cycle Progression by Overcoming DNA Damage in Malignant Pleural Mesothelioma.}, journal = {Cancer genomics &amp; proteomics}, volume = {21}, number = {2}, pages = {158-165}, pmid = {38423601}, issn = {1790-6245}, mesh = {Humans ; *Mesothelioma, Malignant ; DNA Polymerase III/genetics ; *Lung Neoplasms/pathology ; *Pleural Neoplasms/genetics/pathology ; *Mesothelioma/genetics ; RNA, Small Interfering/genetics ; Cell Line, Tumor ; Cell Cycle/genetics ; DNA Damage ; RNA, Messenger ; }, abstract = {BACKGROUND/AIM: The prognosis of patients with malignant pleural mesothelioma (MPM) remains poor due to lack of effective therapeutic targets. DNA damage caused by long-time exposure to asbestos fibers has been associated with the development of MPM, with mutations at genes encoding DNA damage repair (DDR)-related molecules frequently expressed in patients with MPM. The present study was designed to identify novel therapeutic targets in MPM using large public databases, such as The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression project (GTEx) focused on DDR pathways.<br><br>MATERIALS AND METHODS: The correlations between mRNA expression levels of DDR-related genes and overall survival (OS) were analyzed in mesothelioma patients in TCGA mesothelioma (TCGA-MESO) datasets. The anti-tumor effects of small interfering RNAs (siRNA) against DDR-related genes associated with OS were subsequently tested in MPM cell lines.<br><br>RESULTS: High levels of mRNA encoding DNA polymerase delta 1, catalytic subunit (POLD1) were significantly associated with reduced OS in patients with MPM (p<0.001, Log-rank test). In addition, siRNA targeting POLD1 (siPOLD1) caused cell cycle arrest at the G1/S checkpoint and induced apoptosis involving accumulation of DNA damage in MPM cell lines.<br><br>CONCLUSION: POLD1 plays essential roles in overcoming DNA damage and cell cycle progression at the G1/S checkpoint in MPM cells. These findings suggest that POLD1 may be a novel therapeutic target in MPM.}, }
@article {pmid38413635, year = {2024}, author = {Elkahwagy, DM and Kiriacos, CJ and Sobeih, ME and Khorshid, OMR and Mansour, M}, title = {The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4823}, pmid = {38413635}, issn = {2045-2322}, mesh = {Humans ; Biomarkers ; Biomarkers, Tumor/genetics ; Egypt ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; *RNA, Long Noncoding/genetics ; }, abstract = {Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30-40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.}, }
@article {pmid38412661, year = {2024}, author = {Kalla, C and Ott, G and Finotello, F and Niewola-Staszkowska, K and Conza, GD and Lahn, M and van der Veen, L and Schüler, J and Falkenstern-Ge, R and Kopecka, J and Riganti, C}, title = {The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition.}, journal = {Translational oncology}, volume = {43}, number = {}, pages = {101857}, pmid = {38412661}, issn = {1936-5233}, abstract = {Targeting aberrantly expressed kinases in malignant pleural mesothelioma (MPM) is a promising therapeutic strategy. We here investigated the effect of the novel and highly selective Phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib (IOA-244) on MPM cells and on the immune cells in MPM microenvironment. To this aim, we analyzed the expression of PI3K-δ by immunohistochemistry in specimens from primary MPM, cell viability and death in three different MPM cell lines treated with roginolisib alone and in combination with ipatasertib (AKT inhibitor) and sapanisertib (mTOR inhibitor). In a co-culture model of patient-derived MPM cells, autologous peripheral blood mononuclear cells and fibroblasts, the tumor cell viability and changes in immune cell composition were investigated after treatment of roginolisib with nivolumab and cisplatin. PI3K-δ was detected in 66/89 (74%) MPM tumors and was associated with reduced overall survival (12 vs. 25 months, P=0.0452). Roginolisib induced apoptosis in MPM cells and enhanced the anti-tumor efficacy of AKT and mTOR kinase inhibitors by suppressing PI3K-δ/AKT/mTOR and ERK1/2 signaling. Furthermore, the combination of roginolisib with chemotherapy and immunotherapy re-balanced the immune cell composition, increasing effector T-cells and reducing immune suppressive cells. Overall, roginolisib induces apoptosis in MPM cells and increases the antitumor immune cell effector function when combined with nivolumab and cisplatin. These results provide first insights on the potential of roginolisib as a therapeutic agent in patients with MPM and its potential in combination with established immunotherapy regimen.}, }
@article {pmid38410609, year = {2024}, author = {Congedo, MT and West, EC and Evangelista, J and Mattingly, AA and Calabrese, G and Sassorossi, C and Nocera, A and Chiappetta, M and Flamini, S and Abenavoli, L and Margaritora, S and Boccuto, L and Lococo, F}, title = {The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review.}, journal = {Journal of thoracic disease}, volume = {16}, number = {1}, pages = {671-687}, pmid = {38410609}, issn = {2072-1439}, abstract = {BACKGROUND AND OBJECTIVE: Malignant pleural mesothelioma (MPM) is a very aggressive primary tumor of the pleura whose main risk factor is exposure to asbestos. However, only a minority of exposed people develops MPM and the incidence of MPM cases without an apparent association with asbestos exposure has been increasing in recent years, suggesting that genetic predisposing factors may play a crucial role. In addition, several studies reported familial cases of MPM, suggesting that heredity may be an important and underestimated feature in MPM development. Several candidate genes have been associated with a predisposition to MPM and most of them play a role in DNA repair mechanisms: overall, approximately 20% of MPM cases may be related to genetic predisposition. A particular category of patients with high susceptibility to MPM is represented by carriers of pathogenic variants in the BAP1 gene. Germline variants in BAP1 predispose to the development of MPM following an autosomal dominant pattern of inheritance in the familial cases. MPMs in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. In the present narrative review, we presented a comprehensive overview of genetic susceptibility in the development of MPM.<br><br>METHODS: The narrative review is based on a selective literature carried out in PubMed in 2023. Inclusion criteria were original articles in English language, and clinical trials (randomized, prospective, or retrospective).<br><br>KEY CONTENT AND FINDINGS: We summarized the somatic and germline variants and the differences in terms of clinicopathological features and prognosis between gene-related MPM (GR-MPM) and asbestos-related MPM (AR-MPM). We also discussed the indications for screening, genetic testing, and surveillance of patients with BAP1 germline variants.<br><br>CONCLUSIONS: In this narrative review, we have emphasized that the BAP1 gene's harmful germline variations are inherited in an autosomal dominant manner in familial cases. MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.}, }
@article {pmid38409016, year = {2024}, author = {Nazar, T and Gopalakrishnabhaktan, A and Tashrifwala, FAA and Sathish, A and Dave, T}, title = {Testicular mesothelioma disguised as hydrocele: a case report.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {114}, pmid = {38409016}, issn = {1752-1947}, mesh = {Male ; Humans ; Middle Aged ; *Mesothelioma, Malignant/complications ; *Mesothelioma/diagnostic imaging/surgery ; *Testicular Hydrocele/diagnosis/surgery/etiology ; *Testicular Neoplasms/diagnosis/surgery/complications ; }, abstract = {BACKGROUND: Testicular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis.<br><br>CASE PRESENTATION: We present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1&#xa0;month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up.<br><br>CONCLUSION: Although hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants.}, }
@article {pmid38406142, year = {2024}, author = {Qasim, A and Allu, SVV and Schmidt, P and Parikh, HR and Moore, S and Yapor, L and Soliman, M}, title = {Comprehensive Review of Mesothelioma Cases: From Diagnosis to Therapeutic Strategies.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52859}, pmid = {38406142}, issn = {2168-8184}, abstract = {Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.}, }
@article {pmid38404135, year = {2024}, author = {Barnes, H and Hoy, RF}, title = {Changing trends in mesothelioma: Important lessons for an occupational disease registry.}, journal = {Respirology (Carlton, Vic.)}, volume = {29}, number = {4}, pages = {269-270}, doi = {10.1111/resp.14692}, pmid = {38404135}, issn = {1440-1843}, mesh = {Humans ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/epidemiology ; Registries ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects ; *Pleural Neoplasms ; }, }
@article {pmid38402124, year = {2024}, author = {Mukhopadhyay, D and Cocco, P and Orrù, S and Cherchi, R and De Matteis, S}, title = {The role of MicroRNAs as early biomarkers of asbestos-related lung cancer: A systematic review and meta-analysis.}, journal = {Pulmonology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pulmoe.2024.02.002}, pmid = {38402124}, issn = {2531-0437}, abstract = {BACKGROUND: Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is still poor especially at advanced stage, so early diagnosis biomarkers are needed. MicroRNAs (miRNAs) have been proposed as potential early diagnostic biomarkers of asbestos-related LC and MPM.<br><br>AIM: To evaluate the role of miRNAs as diagnostic and prognostic biomarkers of asbestos-related LC and MPM by performing a literature systematic review and meta-analysis.<br><br>METHODS: MEDLINE, EMBASE via Ovid, PUBMED and Cochrane library databases were systematically searched up to April 2023 to identify relevant articles. A grey literature search was also conducted using the Google Scholar platform. MeSH and free text terms for 'asbestos', 'occupational exposure', 'lung cancer', 'mesothelioma' and 'miRNAs' were used to search the literature. Our systematic review protocol was registered in the PROSPERO database. Study quality was assessed via the Newcastle-Ottawa Scale.<br><br>RESULTS: From the search, 331 articles were retrieved, and, after applying our selection criteria, and exclusion of one study for poor quality, 27 studies were included in the review. Most of the studies were hospital-based case-control, conducted in Europe, and evaluated MPM among men only. MiRNAs expression was measured mainly in plasma or serum. MiR-126, miR-132-3p, and miR-103a-3p were the most promising diagnostic biomarkers for MPM, and we estimated a pooled area under the curve (AUC) of 85 %, 73 %, and 50 %, respectively. In relation to MPM prognosis, miR-197&#x2011;3p resulted associated with increased survival time. MiR-126, alone and combined with miR-222, was confirmed associated also to LC diagnosis, together with miR-1254 and miR-574-5p; no miRNA was found associated to LC prognosis.<br><br>CONCLUSION: Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.}, }
@article {pmid38397189, year = {2024}, author = {Oliveto, S and Ritter, P and Deroma, G and Miluzio, A and Cordiglieri, C and Benvenuti, MR and Mutti, L and Raimondi, MT and Biffo, S}, title = {The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells.}, journal = {Genes}, volume = {15}, number = {2}, pages = {}, pmid = {38397189}, issn = {2073-4425}, support = {PRIN2020//PRIN/ ; WCR2022//WCR/ ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/metabolism/pathology ; Collagen ; Cell Movement/genetics ; }, abstract = {Malignant mesothelioma is a type of cancer that affects the mesothelium. It is an aggressive and deadly form of cancer that is often caused by exposure to asbestos. At the molecular level, it is characterized by a low number of genetic mutations and high heterogeneity among patients. In this work, we analyzed the plasticity of gene expression of primary mesothelial cancer cells by comparing their properties on 2D versus 3D surfaces. First, we derived from primary human samples four independent primary cancer cells. Then, we used Nichoids, which are micro-engineered 3D substrates, as three-dimensional structures. Nichoids limit the dimension of adhering cells during expansion by counteracting cell migration between adjacent units of a substrate with their microarchitecture. Tumor cells grow effectively on Nichoids, where they show enhanced proliferation. We performed RNAseq analyses on all the samples and compared the gene expression pattern of Nichoid-grown tumor cells to that of cells grown in a 2D culture. The PCA analysis showed that 3D samples were more transcriptionally similar compared to the 2D ones. The 3D Nichoids induced a transcriptional remodeling that affected mainly genes involved in extracellular matrix assembly. Among these genes responsible for collagen formation, COL1A1 and COL5A1 exhibited elevated expression, suggesting changes in matrix stiffness. Overall, our data show that primary mesothelioma cells can be effectively expanded in Nichoids and that 3D growth affects the cells' tensegrity or the mechanical stability of their structure.}, }
@article {pmid38396947, year = {2024}, author = {Okado, S and Kato, T and Hanamatsu, Y and Emoto, R and Imamura, Y and Watanabe, H and Kawasumi, Y and Kadomatsu, Y and Ueno, H and Nakamura, S and Mizuno, T and Takeuchi, T and Matsui, S and Chen-Yoshikawa, TF}, title = {CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396947}, issn = {1422-0067}, mesh = {Humans ; *Asbestos/toxicity ; Biomarkers, Tumor/genetics/metabolism ; *Mesothelioma, Malignant/diagnosis/genetics ; Survival Analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.}, }
@article {pmid38384604, year = {2024}, author = {Bairos Menezes, M and Pedroso de Lima, R and Dunões, I and Inácio, M and Dinis, R}, title = {A Complete Response to Pembrolizumab in Malignant Peritoneal Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52716}, pmid = {38384604}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the peritoneum with a poor prognosis and nonspecific clinical course. We discuss a case of MPeM in a 59-year-old male who presented with abdominal pain and distension, without any known previous asbestos exposure. The diagnosis was made after a second biopsy finally confirmed epithelioid MPeM in an advanced stage with pleural effusion. The patient underwent six cycles of chemotherapy with cisplatin and pemetrexed, experienced disease progression, and was then started on pembrolizumab as a second-line treatment. The patient achieved a complete response after two years of treatment with pembrolizumab and has been disease-free for almost four years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Despite the lack of evidence to support the treatment with immunotherapy for MPeM, our case report encourages its use, highlighting its ability to enable a complete response with pembrolizumab with an excellent quality of life.}, }
@article {pmid38378028, year = {2024}, author = {Mervic, A and Goricar, K and Blagus, T and Franko, A and Trebusak-Podkrajsek, K and Fikfak, MD and Dolzan, V and Kovac, V}, title = {Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {58}, number = {1}, pages = {87-98}, pmid = {38378028}, issn = {1581-3207}, mesh = {Humans ; *Telomerase/genetics ; Case-Control Studies ; Retrospective Studies ; Polymorphism, Single Nucleotide ; Biomarkers ; Telomere/genetics ; Disease Progression ; }, abstract = {BACKGROUND: Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).<br><br>SUBJECTS AND METHODS: We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.<br><br>RESULTS: Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).<br><br>CONCLUSIONS: Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.}, }
@article {pmid38377382, year = {2024}, author = {Tian, T and Xie, H and Huang, M}, title = {Epithelial Malignant Pleural Mesothelioma Mimics Lymphoma on 18 F-FDG PET/MRI : A Case Report.}, journal = {Clinical nuclear medicine}, volume = {49}, number = {4}, pages = {359-360}, doi = {10.1097/RLU.0000000000005095}, pmid = {38377382}, issn = {1536-0229}, mesh = {Male ; Humans ; Middle Aged ; *Mesothelioma, Malignant ; Fluorodeoxyglucose F18 ; *Lymphoma ; *Mesothelioma/diagnostic imaging ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; }, abstract = {Malignant pleural mesothelioma is a rare tumor with a poor prognosis. We describe a case of 55-year-old man without asbestos exposure history presenting with extensive lymph nodes with high 18 F-FDG uptake in PET/MRI but atypical pleural manifestations thereby being misdiagnosed for lymphoma. Pathological examination concludes for an epithelioid mesothelioma-associated lymph node metastasis. This case emphasizes that with the extensive lymph node abnormalities shown in PET imaging, in addition to the general consideration of lymphoma, it is still necessary to be vigilant about the possibility of mesothelioma and emphasizes the necessity of pathological examination.}, }
@article {pmid38350880, year = {2024}, author = {Tilsed, CM and Morales, MLO and Zemek, RM and Gordon, BA and Piggott, MJ and Nowak, AK and Fisher, SA and Lake, RA and Lesterhuis, WJ}, title = {Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {203}, pmid = {38350880}, issn = {1471-2407}, mesh = {Humans ; Animals ; Mice ; *Tretinoin/pharmacology/therapeutic use ; Cyclophosphamide ; CD8-Positive T-Lymphocytes ; Combined Modality Therapy ; *Mesothelioma/drug therapy ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Chemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects. Therefore, there is a need for alternative immunomodulatory drugs that enhance chemotherapy.<br><br>METHODS: We used gene expression data from cyclophosphamide (CY) responders and non-responders to identify existing clinically approved drugs that could phenocopy a chemosensitive tumor microenvironment (TME), and tested combination treatments in multiple murine cancer models.<br><br>RESULTS: The vitamin A derivative tretinoin was the top predicted upstream regulator of response to CY. Tretinoin pre-treatment induced an inflammatory, interferon-associated TME, with increased infiltration of CD8&#x2009;+&#x2009;T cells, sensitizing the tumor to subsequent chemotherapy. However, while combination treatment significantly improved survival and cure rate in a CD4[+] and CD8[+] T cell dependent manner in AB1-HA murine mesothelioma, this effect was model-selective, and could not be replicated using other cell lines.<br><br>CONCLUSIONS: Despite the promising data in one model, the inability to validate the efficacy of combination treatment in multiple cancer models deprioritizes tretinoin/cyclophosphamide combination therapy for clinical translation.}, }
@article {pmid38341199, year = {2024}, author = {Mizuhashi, K and Okamoto, K and Nabeshima, K and Kishimoto, T}, title = {Detailed clinical course of a patient with rapidly progressing sarcomatoid pleural mesothelioma without p16 deletion with systemic haematogenous metastasis to soft tissues.}, journal = {BMJ case reports}, volume = {17}, number = {2}, pages = {}, pmid = {38341199}, issn = {1757-790X}, mesh = {Humans ; Male ; *Asbestos ; Disease Progression ; *Lung Neoplasms/pathology ; *Mesothelioma/diagnosis/genetics/pathology ; *Mesothelioma, Malignant ; *Pleural Effusion ; *Pleural Neoplasms/pathology ; Aged, 80 and over ; }, abstract = {Sarcomatoid mesothelioma is difficult to differentiate from other mesotheliomas. Here, we describe the case of a man in his early 80s with sarcomatoid mesothelioma and a history of asbestos exposure. He initially presented with right-sided chest pain and was examined. Right-sided pleural effusion was detected; therefore, he was hospitalised. Based on the observed pleural effusion and biopsy result, the presence of a malignant tumour was excluded; hence, he was diagnosed with benign asbestos pleurisy. He subsequently developed left-sided pleural effusion, masses and lung nodules, and died 9.5 months after the initial examination. A definitive diagnosis of sarcomatoid mesothelioma with rapid systemic progression was established after detailed investigations using autopsy specimens. This rare case of mesothelioma-without p16 deletion (detected using fluorescence in situ hybridisation)-presented differently from the usual sarcomatoid mesothelioma.}, }
@article {pmid38341059, year = {2024}, author = {Xiong, X and Zhang, S and Liao, X and Du, J and Zheng, W and Hu, S and Wei, Q and Yang, L}, title = {An umbrella review of the evidence associating occupational carcinogens and cancer risk at 19 anatomical sites.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {345}, number = {}, pages = {123531}, doi = {10.1016/j.envpol.2024.123531}, pmid = {38341059}, issn = {1873-6424}, mesh = {Humans ; *Mesothelioma ; *Lung Neoplasms/chemically induced/epidemiology ; *Asbestos ; Carcinogens/toxicity ; *Occupational Exposure/adverse effects ; Formaldehyde/*adverse effects ; *Respiratory Hypersensitivity ; }, abstract = {Occupational exposure to carcinogens of increasing cancer risk have been extensively suggested. A robust assessment of these evidence is needed to guide public policy and health care. We aimed to classify the strength of evidence for associations of 13 occupational carcinogens (OCs) and risk of cancers. We searched PubMed and Web of Science up to November 2022 to identify potentially relevant studies. We graded the evidence into convincing, highly suggestive, suggestive, weak, or not significant according to a standardized classification based on: random-effects p value, number of cancer cases, 95% confidence interval of largest study, heterogeneity between studies, 95% prediction interval, small study effect, excess significance bias and sensitivity analyses with credibility ceilings. The quality of meta-analysis was evaluated by AMSTAR 2. Forty-eight articles yielded 79 meta-analyses were included in current umbrella review. Evidence of associations were convincing (class I) or highly suggeastive (class II) for asbestos exposure and increasing risk of lung cancer among smokers (RR = 8.79, 95%CI: 5.81-13.25 for cohort studies and OR = 8.68, 95%CI: 5.68-13.24 for case-control studies), asbestos exposure and increasing risk of mesothelioma (RR = 4.61, 95%CI: 2.57-8.26), and formaldehyde exposure and increasing risk of sinonasal cancer (RR = 1.68, 95%CI: 1.38-2.05). Fifteen associations were supported by suggestive evidence (class III). In summary, the current umbrella review found strong associations between: asbestos exposure and increasing risk of lung cancer among smokers; asbestos exposure and increasing risk of mesothelioma; and formaldehyde exposure and higher risk of sinonasal cancer. Other associations might be genuine, but substantial uncertainty remains.}, }
@article {pmid38323897, year = {2024}, author = {Järvholm, B and Burdorf, A}, title = {Asbestos and disease - a public health success story?.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {50}, number = {2}, pages = {53-60}, pmid = {38323897}, issn = {1795-990X}, mesh = {Humans ; Public Health ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects/analysis ; *Neoplasms ; *Occupational Health ; *Mesothelioma/epidemiology ; *Lung Neoplasms/epidemiology ; *Asbestosis/epidemiology ; }, abstract = {OBJECTIVE: This paper discusses the failure and success of society to decrease the adverse health effects of asbestos exposure on workers' health in relation to scientific knowledge.<br><br>METHODS: The findings are based on a narrative literature review.<br><br>RESULTS: Early warnings of the adverse health effects of workplace exposure to asbestos were published already in the 1930s. Serious health effects, such as malignancies and fibrosis due to occupational asbestos exposure, were highlighted in major medical journals and textbooks in late 1960s. New technologies could detect also asbestos fibers in the lung of non-occupational exposed persons in the 1970s. The first bans for using asbestos came in the early 1970s, and more general bans by authorities came in the 1980s and continue until today.<br><br>CONCLUSIONS: The rather late recognition of adverse effects of asbestos exposure in the general population and measures to decrease the exposure through more general bans came rather late. However, the very strong measures such as general bans in many countries have been a success. A Swedish study showed that the general ban and other measures have decreased the risk of malignancies due to occupational exposure. The effect of the bans on adverse effects in the general population has yet to be studied. Analysis of fibers in the lungs of persons born after the bans could be an efficient method.}, }
@article {pmid38318560, year = {2024}, author = {Subahi, EA and Fadul, A and Mohamed, A and Alsayed, A and Ali, EA and Sayed, S and Mustafa, S and Wazwaz, B and Fadul, MH}, title = {Biphasic Peritoneal Mesothelioma Is a Rare Tumor and a Diagnostic Challenge: A Case Report.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51725}, pmid = {38318560}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare subtype of mesothelioma. There are three main histological subtypes of mesothelioma: epithelioid, sarcomatoid, and biphasic (mixed). Risk factors include asbestos exposure, previous radiation, and some germline mutations. Treatment includes surgical resection of amenable tumors or cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We present a 34-year-old male who presented with weight loss, night sweats, and pleuritic chest pain and was found to have ascites with peritoneal nodularity on abdominal imaging. He had a history of tuberculosis contact, but no history of asbestos exposure. After a long challenging and interesting diagnostic process, he was subsequently diagnosed with biphasic MPM. The diagnostic challenge stems from not only the rarity of the tumor but also from the absence of risk factors, the unavailability of some special laboratory investigations, in addition to the potentially misleading effect of tuberculosis exposure history, a top differential diagnosis in the case. This is a case report of a really challenging and totally unexpected diagnosis of biphasic peritoneal mesothelioma in a patient with tuberculosis exposure, constitutional symptoms, but no history of asbestos exposure. It highlights the diagnostic process as well as the importance of early diagnosis to improve the overall survival of such malignancies.}, }
@article {pmid38301599, year = {2024}, author = {Fitzgerald, SM}, title = {Resolving asbestos and ultrafine particulate definitions with carcinogenicity.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {189}, number = {}, pages = {107478}, doi = {10.1016/j.lungcan.2024.107478}, pmid = {38301599}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms ; *Asbestos ; Minerals ; *Calcinosis ; }, abstract = {As asbestos fibers and other fine particles have been studied extensively to correlate physical and chemical properties with their potential for negative human health impact on inhalation, there remains no concise definitions for the individual particle types nor collective considerations of combined variabilities. Extensive studies relating negative health to asbestos morphology, chemistry, surface effects, and biodurability form general qualitative bins of what is more likely causative or less, but do not provide enough information to quantitatively dismiss particles with parameters outside any given range. Further, natural mineral species and accessory mineralization makes standardization of universally applicable reference materials nearly unobtainable. With modern advent of engineered nanoparticles, we are adding even more unknowns to the universe of the microscopic size fraction and its potential for human disease, and our paradigm is challenged.}, }
@article {pmid38297314, year = {2024}, author = {Reamon-Buettner, SM and Rittinghausen, S and Klauke, A and Hiemisch, A and Ziemann, C}, title = {Malignant peritoneal mesotheliomas of rats induced by multiwalled carbon nanotubes and amosite asbestos: transcriptome and epigenetic profiles.}, journal = {Particle and fibre toxicology}, volume = {21}, number = {1}, pages = {3}, pmid = {38297314}, issn = {1743-8977}, support = {BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; }, mesh = {Humans ; Rats ; Animals ; *Mesothelioma, Malignant/complications/genetics ; Asbestos, Amosite/toxicity ; *Nanotubes, Carbon/toxicity ; *Mesothelioma/chemically induced/genetics ; Transcriptome ; Rats, Wistar ; *Asbestos/toxicity ; Carcinogenesis/chemically induced/genetics ; DNA Methylation ; Epigenesis, Genetic ; *Lung Neoplasms/chemically induced/genetics/pathology ; GADD45 Proteins ; Antigens, Differentiation/toxicity ; }, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive cancer that often originates in the pleural and peritoneal mesothelium. Exposure to asbestos is a frequent cause. However, studies in rodents have shown that certain multiwalled carbon nanotubes (MWCNTs) can also induce malignant mesothelioma. The exact mechanisms are still unclear. To gain further insights into molecular pathways leading to carcinogenesis, we analyzed tumors in Wistar rats induced by intraperitoneal application of MWCNTs and amosite asbestos. Using transcriptomic and epigenetic approaches, we compared the tumors by inducer (MWCNTs or amosite asbestos) or by tumor type (sarcomatoid, epithelioid, or biphasic).<br><br>RESULTS: Genome-wide transcriptome datasets, whether grouped by inducer or tumor type, showed a high number of significant differentially expressed genes (DEGs) relative to control peritoneal tissues. Bioinformatic evaluations using Ingenuity Pathway Analysis (IPA) revealed that while the transcriptome datasets shared commonalities, they also showed differences in DEGs, regulated canonical pathways, and affected molecular functions. In all datasets, among highly- scoring predicted canonical pathways were Phagosome Formation, IL8 Signaling, Integrin Signaling, RAC Signaling, and TREM1 Signaling. Top-scoring activated molecular functions included cell movement, invasion of cells, migration of cells, cell transformation, and metastasis. Notably, we found many genes associated with malignant mesothelioma in humans, which showed similar expression changes in the rat tumor transcriptome datasets. Furthermore, RT-qPCR revealed downregulation of Hrasls, Nr4a1, Fgfr4, and Ret or upregulation of Rnd3 and Gadd45b in all or most of the 36 tumors analyzed. Bisulfite sequencing of Hrasls, Nr4a1, Fgfr4, and Ret revealed heterogeneity in DNA methylation of promoter regions. However, higher methylation percentages were observed in some tumors compared to control tissues. Lastly, global 5mC DNA, m6A RNA and 5mC RNA methylation levels were also higher in tumors than in control tissues.<br><br>CONCLUSIONS: Our findings may help better understand how exposure to MWCNTs can lead to carcinogenesis. This information is valuable for risk assessment and in the development of safe-by-design strategies.}, }
@article {pmid38292909, year = {2024}, author = {Tagarakis, G and Tsolaki, F and Tagarakis, I}, title = {Commentary: The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1336545}, pmid = {38292909}, issn = {2296-2565}, mesh = {Humans ; Polymorphism, Single Nucleotide ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; Iron ; Homeostasis ; }, }
@article {pmid38292377, year = {2023}, author = {Fazzo, L and Grande, E and Zona, A and Minelli, G and Crialesi, R and Iavarone, I and Grippo, F}, title = {Mortality rates from asbestos-related diseases in Italy during the first year of the COVID-19 pandemic.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1243261}, pmid = {38292377}, issn = {2296-2565}, mesh = {Adult ; Humans ; Female ; Male ; Aged, 80 and over ; *Mesothelioma, Malignant ; *Asbestosis/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; Pandemics ; *Lung Neoplasms ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; *Asbestos/adverse effects ; Italy/epidemiology ; }, abstract = {BACKGROUND AND AIM: Patients with interstitial lung diseases, including asbestosis, showed high susceptibility to the SARS-CoV-2 virus and a high risk of severe COVID-19 symptoms. Italy, highly impacted by asbestos-related diseases, in 2020 was among the European countries with the highest number of COVID-19 cases. The mortality related to malignant mesotheliomas and asbestosis in 2020 and its relationship with COVID-19 in Italy are investigated.<br><br>METHODS: All death certificates involving malignant mesotheliomas or asbestosis in 2010-2020 and those involving COVID-19 in 2020 were retrieved from the National Registry of Causes of Death. Annual mortality rates and rate ratios (RRs) of 2020 and 2010-2014 compared to 2015-2019 were calculated. The association between malignant pleural mesothelioma (MPM) and asbestosis with COVID-19 in deceased adults &#x2265;80 years old was evaluated through a logistic regression analysis (odds ratios: ORs), using MPM and asbestosis deaths COVID-19-free as the reference group. The hospitalization for asbestosis in 2010-2020, based on National Hospital Discharge Database, was analyzed.<br><br>RESULTS: In 2020, 746,343 people died; out of them, 1,348 involved MPM and 286 involved asbestosis. Compared to the period 2015-2019, the mortality involving the two diseases decreased in age groups below 80 years; meanwhile, an increasing trend was observed in subjects aged 80 years and older, with a relative mortality risks of 1.10 for MPM and 1.17 for asbestosis. In subjects aged &#x2265;80 years, deaths with COVID-19 were less likely to have MPM in both genders (men: OR = 0.22; women: OR = 0.44), while no departure was observed for asbestosis. A decrease in hospitalization in 2020 with respect to those in 2010-2019 in all age groups, both considering asbestosis as the primary or secondary diagnosis, was observed.<br><br>CONCLUSIONS: The increasing mortality involving asbestosis and, even if of slight entity, MPM, observed in people aged over 80 years during the 1[st] year of the COVID-19 pandemic, aligned in part with the previous temporal trend, could be due to several factors. Although no positive association with COVID-19 mortality was observed, the decrease in hospitalizations for asbestosis among individuals aged over 80 years, coupled with the increase in deaths, highlights the importance of enhancing home-based assistance during the pandemic periods for vulnerable patients with asbestos-related conditions.}, }
@article {pmid38250976, year = {2023}, author = {Kang, MS and Chae, WR and Lee, YJ and Moon, KW}, title = {Occupational and Environmental Asbestos Exposure and Survival of Patients with Asbestos-Related Cancer: A Follow-Up Study on Patients with Malignant Mesothelioma and Asbestos-Related Lung Cancer in Korea.}, journal = {Toxics}, volume = {12}, number = {1}, pages = {}, pmid = {38250976}, issn = {2305-6304}, abstract = {Malignant mesothelioma and asbestos-related lung cancer are typically associated with a poor prognosis. However, it has been observed that some patients with these cancers survive significantly longer than the average survival period. While many preliminary studies have investigated factors influencing patient survival, the specific impact of asbestos exposure has not been thoroughly explored. We followed up with 546 patients with malignant mesothelioma and 902 patients with asbestos-related lung cancer, all identified as asbestos victims between 2009 and 2021. In both malignant mesothelioma and asbestos-related lung cancer, patients with occupational asbestos exposure exhibited not only shorter median survival times but also lower 3- and 5-year survival rates compared to those with environmental exposure. Additionally, a longer duration of occupational exposure and closer proximity to the source of asbestos were linked to shorter survival times and lower survival rates. Among the patients with occupational asbestos exposure, the highest hazard ratios (HRs) were observed in those who worked in the production of asbestos-containing products across both cancer types. In contrast, significant HRs were only noted in mesothelioma patients who lived near asbestos industries, slate houses, and redevelopment areas, within the environmentally exposed group.}, }
@article {pmid38249898, year = {2023}, author = {Visonà, SD and Capella, S and Borrelli, P and Villani, S and Favaron, C and Kurzhunbaeva, Z and Colosio, C and Belluso, E}, title = {Asbestos burden in lungs of non-occupationally exposed women from Broni (Pavia, Italy): a postmortem SEM-EDS study.}, journal = {Journal of thoracic disease}, volume = {15}, number = {12}, pages = {6555-6569}, pmid = {38249898}, issn = {2072-1439}, abstract = {BACKGROUND: In Italy the incidence of malignant mesothelioma (MM) among women is remarkably high, due to the several contexts in which women had been exposed to asbestos. However, very few studies in literature focus on the inorganic lung content in women. The aim of this retrospective, observational study is to investigate the asbestos lung burden, in terms of concentration, dimensions and type of asbestos, in 42 women who died from MM and had been non-occupationally exposed to asbestos during the activity of the asbestos-cement plant located in Broni (Pavia, Northern Italy) where mainly chrysotile, crocidolite and amosite were used.<br><br>METHODS: Lung samples taken during forensic autopsies have been digested using sodium hypochlorite and filtered through a cellulose-ester membrane. The filter was examined using a scanning electron microscope and the chemical composition of the fibers was analyzed using an electron dispersive spectroscopy. The number of detected inorganic fibers, asbestos fibers and asbestos bodies (ABs) were normalized to 1 gram of dry tissue.<br><br>RESULTS: In six samples no asbestos has been detected. Overall, the most represented kind of asbestos was amosite, followed by crocidolite, tremolite/actinolite asbestos and chrysotile. The concentration of all inorganic fibers was significantly higher in women with environmental and household exposures compared with those with only environmental exposure (P=0.025), as well as the concentration of asbestos fibers (P=0.019) and ABs (P=0.049). We found a significant correlation between the concentration of asbestos fibers and the duration of exposure (rho =0.413, P=0.008), as well as with the latency of MM (rho =0.427, P=0.005). The distance of the residential address from the factory and the time spent daily in contact with asbestos did not influence the lung asbestos burden.<br><br>CONCLUSIONS: These results suggest the relevance of the lung clearance of asbestos, regarding mainly chrysotile. As a consequence, although scanning electron microscopy -energy dispersive X-ray spectroscopy (SEM-EDS) is considered the most reliable tool for assessing previous exposure to asbestos, its results should be interpreted with caution, especially in a legal context. In addition, our data confirm the relevance of environmental and household exposure in determining asbestos concentration in lungs and highlight the importance of household exposure.}, }
@article {pmid38247448, year = {2024}, author = {Schüz, J and Kovalevskiy, E and Olsson, A and Moissonnier, M and Ostroumova, E and Ferro, G and Feletto, E and Schonfeld, SJ and Byrnes, G and Tskhomariia, I and Straif, K and Morozova, T and Kromhout, H and Bukhtiyarov, I}, title = {Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study).}, journal = {Journal of the National Cancer Institute}, volume = {116}, number = {6}, pages = {866-875}, pmid = {38247448}, issn = {1460-2105}, support = {001/WHO_/World Health Organization/International ; /NH/NIH HHS/United States ; //Ministry of Health of the Russian Federation/ ; 2009-2014//National System of Chemical and Biological Safety of the Russian Federation/ ; //Federal State Budgetary Scientific Institution/ ; //Izmerov Research Institute of Occupational Health/ ; //International Agency for Research on Cancer/ ; 2015-2023/WHO_/World Health Organization/International ; /CA/NCI NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; Male ; *Asbestos, Serpentine/adverse effects ; Female ; *Occupational Exposure/adverse effects ; *Lung Neoplasms/mortality/epidemiology ; Middle Aged ; Russia/epidemiology ; Cohort Studies ; *Occupational Diseases/mortality/epidemiology ; Adult ; Dust ; Aged ; Miners/statistics &amp; numerical data ; Mining/statistics &amp; numerical data ; }, abstract = {BACKGROUND: We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.<br><br>METHODS: This historical cohort study included all workers employed for at least 1&#x2009;year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.<br><br>RESULTS: A total of 30&#x200a;445 (32% women) workers accumulated 721&#x200a;312 person-years at risk and 11&#x200a;110 (36%) died. Of the workers, 54% had more than 30&#x2009;years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR&#x2009;=&#x2009;7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR&#x2009;=&#x2009;4.56, 95% CI = 0.94 to 22.1, to at least 150&#x2009;mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.<br><br>CONCLUSION: In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.}, }
@article {pmid38239857, year = {2024}, author = {Behers, BM and Guske, CW and Behers, BJ and Kortum, SB and Bermingham, IG and Warner, CL and Carey, RI}, title = {Malignant Epithelioid Mesothelioma of the Tunica Vaginalis Testis Presenting as Hydrocele in a Kidney Transplant Recipient.}, journal = {Case reports in urology}, volume = {2024}, number = {}, pages = {9227764}, pmid = {38239857}, issn = {2090-696X}, abstract = {Mesotheliomas of the tunica vaginalis testis are rare malignant tumors that can present as a scrotal mass or hydrocele. These tumors are typically aggressive with high rates of recurrence and metastasis. Suspected risk factors for malignant mesothelioma include asbestos exposure, chronic inflammation, trauma, and persistent hydrocele. We report the case of a malignant epithelioid mesothelioma of the tunica vaginalis testis that presented as a finding at hydrocelectomy and was ultimately treated with radical inguinal orchiectomy. This patient was on chronic immunosuppression therapy with tacrolimus and mycophenolate mofetil secondary to a kidney transplant but had none of the common risk factors for mesothelioma formation. To our knowledge, this is the first case describing a possible connection between chronic immunosuppression and mesothelioma of the tunica vaginalis. However, future studies are needed to investigate this association and discern whether this could have played a role in our patient or if his mesothelioma formation was coincidental.}, }
@article {pmid38201520, year = {2023}, author = {Iser, S and Hintermair, S and Varga, A and Çelik, A and Sayan, M and Kankoç, A and Akyürek, N and Öğüt, B and Bertoglio, P and Capozzi, E and Solli, P and Ventura, L and Waller, D and Weber, M and Stubenberger, E and Ghanim, B}, title = {Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma.}, journal = {Cancers}, volume = {16}, number = {1}, pages = {}, pmid = {38201520}, issn = {2072-6694}, support = {ATU 67837709//Karl Landsteiner University of Health Sciences/ ; }, abstract = {Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers' prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.}, }
@article {pmid38192052, year = {2024}, author = {Carney, JM and Sporn, TA and Roggli, VL and Pavlisko, EN}, title = {The diagnosis of asbestosis in the 21[st] century: a clinicopathological correlation of 102 cases.}, journal = {Ultrastructural pathology}, volume = {48}, number = {2}, pages = {137-148}, doi = {10.1080/01913123.2023.2299874}, pmid = {38192052}, issn = {1521-0758}, mesh = {Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; *Asbestosis/pathology ; *Asbestos ; Lung/pathology ; *Mesothelioma/complications/pathology ; Asbestos, Amosite ; *Lung Neoplasms/pathology ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21[st] century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.}, }
@article {pmid38190277, year = {2024}, author = {Hung, YP and Chirieac, LR}, title = {Molecular and Immunohistochemical Testing in Mesothelioma and Other Mesothelial Lesions.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {148}, number = {5}, pages = {e77-e89}, doi = {10.5858/arpa.2023-0213-RA}, pmid = {38190277}, issn = {1543-2165}, mesh = {Humans ; *Mesothelioma/diagnosis/genetics/metabolism/pathology ; *Immunohistochemistry ; *Biomarkers, Tumor/genetics/metabolism/analysis ; Neoplasms, Mesothelial/diagnosis/genetics/metabolism/pathology ; Mesothelioma, Malignant/diagnosis/genetics/pathology/metabolism ; Mutation ; *Tumor Suppressor Proteins ; *Ubiquitin Thiolesterase ; }, abstract = {CONTEXT.&#x2014;: Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most diffuse mesotheliomas lack oncogenic kinase mutations and instead harbor alterations involving tumor suppressors and chromatin regulators, a minor subset of tumors is characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion.<br><br>OBJECTIVE.&#x2014;: To provide updates on the salient molecular features of diffuse mesothelioma, mesothelioma in situ, and other mesothelial lesions: well-differentiated papillary mesothelial tumor, adenomatoid tumor, peritoneal inclusion cyst, and others. We consider the diagnostic, prognostic, and predictive utility of molecular testing in mesothelial lesions.<br><br>DATA SOURCES.&#x2014;: We performed a literature review of recently described genetic features, molecular approaches, and immunohistochemical tools, including BAP1, MTAP, and merlin in mesothelioma and other mesothelial lesions.<br><br>CONCLUSIONS.&#x2014;: Our evolving understanding of the molecular diversity of diffuse mesothelioma and other mesothelial lesions has led to considerable changes in pathology diagnostic practice, including the application of immunohistochemical markers such as BAP1, MTAP, and merlin (NF2), which are surrogates of mutation status. In young patients and/or those without significant asbestos exposure, unusual mesothelioma genetics such as germline mutations, ALK rearrangement, and ATF1 rearrangement should be considered.}, }
@article {pmid38182448, year = {2024}, author = {Carney, JM and Roggli, VL and Glass, CH and Piña-Oviedo, S and Pavlisko, EN}, title = {The over diagnosis of diffuse mesothelioma: An analysis of 311 cases with recommendations for the avoidance of pitfalls.}, journal = {Annals of diagnostic pathology}, volume = {68}, number = {}, pages = {152248}, doi = {10.1016/j.anndiagpath.2023.152248}, pmid = {38182448}, issn = {1532-8198}, mesh = {Humans ; Overdiagnosis ; *Pleural Neoplasms/diagnosis/metabolism/pathology ; Biomarkers, Tumor/analysis ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant/diagnosis ; *Carcinoma/pathology ; *Lung Neoplasms/diagnosis/pathology ; Diagnosis, Differential ; }, abstract = {BACKGROUND: The diagnosis of mesothelioma may be challenging. We investigated a large database of cases in order to determine the frequency with which a diagnosis of mesothelioma was made incorrectly and the most frequent causes of error.<br><br>DESIGN: A database including more than 4000 consultation cases of histologically confirmed mesothelioma was examined to identify cases in which mesothelioma was diagnosed by at least one pathologist when the available information pointed towards a different diagnosis.<br><br>RESULTS: There were 311 cases misdiagnosed as mesothelioma. The most common category was metastatic carcinoma to the pleura or peritoneum (129 cases: 73 lung carcinomas, 15 renal cell carcinomas). The next most common category was primary lung cancer (111 cases: 55 sarcomatoid carcinoma, 56 pseudomesotheliomatous carcinoma). The third most common category was primary malignancies arising from or near the serosal membranes (33 cases). The fourth most common category was fibrous pleurisy (38 cases). The most common errors were failure to consider important radiographic information regarding the gross distribution of tumor, lack of awareness or consideration of another malignancy, overreliance on certain immunohistochemical results, and failure to perform certain diagnostic histochemical, immunohistochemical, or ultrastructural studies.<br><br>CONCLUSIONS: There are a number of diagnostic pitfalls that can lead to the over diagnosis of mesothelioma. Careful attention to clinical and radiographic information as well as performance of appropriate ancillary tests can help to prevent such misdiagnoses. Detailed examples will be presented to assist in the avoidance of these pitfalls with emphasis on the most commonly observed errors.}, }
@article {pmid38176439, year = {2024}, author = {van der Linde, LIS and Hantzsch-Kuhn, B and Ellebrecht, D and Stellmacher, F and Welker, L}, title = {[Interdisciplinary diagnostics and therapy of malignant mesothelioma].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {78}, number = {4}, pages = {262-268}, doi = {10.1055/a-2202-5445}, pmid = {38176439}, issn = {1438-8790}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/therapy/drug therapy ; *Pleural Neoplasms/diagnosis/therapy/pathology ; Prognosis ; Combined Modality Therapy ; }, abstract = {The asbestos-related malignant mesothelioma (MM) is one of the common occupational cancers in Germany with approximately 1000 new cases per year. Provided that the appropriate diagnostic criteria are fulfilled, MM can be diagnosed with high specificity from both histological and cytological specimens. However, many MM are detected cyto-/histologically only at advanced stages. Clinical/radiological aspects complement each other and enable interdisciplinary assessment of tumor stage and individualized decisions on the best possible therapeutic options. Diagnostically, video-assisted thoracoscopy (VATS) has the highest priority. Therapy planning is based on the MM subtype, tumor spread and stage, and the patient's clinical condition. MM has generally a very unfavorable prognosis. Accordingly, the standard therapy aims at a macroscopic radical tumor resection in terms of cytoreduction within the framework of a suitable multimodal therapy concept (chemotherapy, radiotherapy, psychooncology). The aim of palliative measures should be primarily symptom control. Overall, interdisciplinary diagnosis and therapy of MM is crucial for the best possible care of MM patients.}, }
@article {pmid38166430, year = {2024}, author = {Shaker, N and Blankenship, H and Shaker, N and Ben Musa, R and Niu, S and Alrohaibani, A and Mansoor, I and Abu Shakra, R and Sangueza, OP}, title = {Malignant Para-Testicular Mesothelioma: A Rare Presentation in the Tunica Vaginalis of an Elderly Male With No Prior Asbestos Exposure.}, journal = {International journal of surgical pathology}, volume = {32}, number = {6}, pages = {1117-1122}, doi = {10.1177/10668969231215426}, pmid = {38166430}, issn = {1940-2465}, mesh = {Humans ; Male ; Aged ; *Testicular Neoplasms/pathology/diagnosis ; *Mesothelioma, Malignant/pathology/diagnosis ; *Biomarkers, Tumor/analysis/metabolism ; Diagnosis, Differential ; Mesothelioma/diagnosis/pathology ; Testis/pathology ; Lung Neoplasms/diagnosis/pathology ; }, abstract = {Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.}, }
@article {pmid38153786, year = {2024}, author = {Brims, F and Kumarasamy, C and Menon, L and Olsen, N and de Klerk, N and Franklin, P}, title = {The Western Australian Mesothelioma Registry: Analysis of 60 years of cases.}, journal = {Respirology (Carlton, Vic.)}, volume = {29}, number = {4}, pages = {288-294}, doi = {10.1111/resp.14648}, pmid = {38153786}, issn = {1440-1843}, support = {1197652//National Health and Medical Research Council/ ; //Western Australia Department of Health/ ; }, mesh = {Male ; Female ; Humans ; Western Australia/epidemiology ; Australia/epidemiology ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Pleural Neoplasms/etiology/complications ; Registries ; Incidence ; }, abstract = {BACKGROUND AND OBJECTIVE: Australia introduced a partial ban on asbestos consumption in 1984. There is continuing concern about exposure to asbestos in the built environment and non-occupational exposures. The aim of this study was to describe epidemiological trends of mesothelioma in Western Australia (WA) over the 60 years since the first case was recorded.<br><br>METHODS: Every case of mesothelioma notified to the WA Cancer Registry is reviewed by an expert panel. Data include demographic and clinical variables including principal mode of asbestos exposure and age at first exposure. Trends over time for survival, latency and pathological subtype of mesothelioma where analysed. Incidence rates for cases exposed during home renovation where calculated.<br><br>RESULTS: Two thousand seven hundred ninety-six cases of mesothelioma were identified with males comprising the majority (n&#x2009;=&#x2009;2368, 84.7%). The median (IQR) age at diagnosis was 70 (62-78) years, and median latency of 47 (38-55) years. Pleural mesothelioma was recorded in 2620 (93.7%) cases with the epithelioid subtype most prevalent (n&#x2009;=&#x2009;1730, 61.9%). Overall, median survival was 298 (128-585) days and latency 46 (37-54) years, both effectively doubling over the study period. Non-occupational exposures were proportionally higher in females (52.6%), compared with males (9.5%). Home renovation was the primary exposure in 227 (8.1%) cases, with number of cases and incidence rate ratio peaking in 2005/09 but subsequently decreasing.<br><br>CONCLUSION: The annual number of cases of mesothelioma in WA may have hit a plateau. The majority of females have non-occupational exposures and incidence rates from home renovation exposure may have peaked, suggesting the ban on asbestos has been effective.}, }
@article {pmid38136442, year = {2023}, author = {Weber, DG and Casjens, S and Wichert, K and Lehnert, M and Taeger, D and Rihs, HP and Brüning, T and Johnen, G and The MoMar Study Group, }, title = {Tasks and Experiences of the Prospective, Longitudinal, Multicenter MoMar (Molecular Markers) Study for the Early Detection of Mesothelioma in Individuals Formerly Exposed to Asbestos Using Liquid Biopsies.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136442}, issn = {2072-6694}, abstract = {Mesothelioma is an aggressive cancer, strongly associated with prior exposure to asbestos. Commonly, tumors are detected at late stages of the disease. Detection at early stages might be meaningful, because therapies might be more effective when the tumor burden is relatively low and the tumor has not spread to distant sites. Circulating biomarkers in blood might be a promising tool to improve the early detection of mesothelioma, but for screening in asymptomatic subjects, candidate biomarkers need to be validated in appropriate studies. This study was conducted to assess the performance of biomarkers in liquid biopsies to detect mesothelioma at early stages. Over a period of 10 years, 2769 volunteers formerly exposed to asbestos were annually examined and liquid biopsies were collected. A follow-up was completed 17 months after the last blood collection. The article provides a detailed overview of our lessons learned and experiences of conducting a prospective, longitudinal, multicenter study. The existing cohort of individuals at risk is highly suitable for the validation of blood-based biomarkers for the early detection of mesothelioma as well as lung cancer.}, }
@article {pmid38136353, year = {2023}, author = {Bertin, B and Zugman, M and Schvartsman, G}, title = {The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136353}, issn = {2072-6694}, abstract = {The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.}, }
@article {pmid38136333, year = {2023}, author = {Cedres, S and Valdivia, A and Iranzo, P and Callejo, A and Pardo, N and Navarro, A and Martinez-Marti, A and Assaf-Pastrana, JD and Felip, E and Garrido, P}, title = {Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136333}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4-8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM; however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy for different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20-40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.}, }
@article {pmid38136262, year = {2023}, author = {Cerbone, L and Orecchia, S and Bertino, P and Delfanti, S and de Angelis, AM and Grosso, F}, title = {Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136262}, issn = {2072-6694}, abstract = {Mesothelioma comprises a group of rare cancers arising from the mesothelium of the pleura, peritoneum, tunica vaginalis testis and pericardium. Mesothelioma is generally associated with asbestos exposure and has a dismal prognosis, with few therapeutic options. Several next generation sequencing (NGS) experiments have been performed on mesothelioma arising at different sites. These studies highlight a genomic landscape mainly characterized by a high prevalence (>20%) of genomic aberrations leading to functional losses in oncosuppressor genes such as BAP1, CDKN2A, NF2, SETD2 and TP53. Nevertheless, to date, evidence of the effect of targeting these alterations with specific drugs is lacking. Conversely, 1-2% of mesothelioma might harbor activating mutations in oncogenes with specifically approved drugs. The goal of this review is to summarize NGS applications in mesothelioma and to provide insights into target therapy of mesothelioma guided by NGS.}, }
@article {pmid38134842, year = {2024}, author = {Ledda, C and Loreto, C and Lombardo, C and Cardile, V and Rapisarda, V}, title = {Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers.}, journal = {Translational oncology}, volume = {40}, number = {}, pages = {101872}, pmid = {38134842}, issn = {1936-5233}, abstract = {Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.}, }
@article {pmid38126124, year = {2023}, author = {Beckett, EM and Abelmann, A and Roberts, B and Lewis, RC and Cheatham, D and Miller, EW and Hall, E and Pierce, JS}, title = {An updated evaluation of reported no-observed adverse effect levels for chrysotile, amosite, and crocidolite asbestos for lung cancer and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {53}, number = {10}, pages = {611-657}, doi = {10.1080/10408444.2023.2283169}, pmid = {38126124}, issn = {1547-6898}, mesh = {Humans ; Asbestos, Crocidolite/toxicity/analysis ; Asbestos, Serpentine/toxicity ; Asbestos, Amosite/analysis ; *Lung Neoplasms/chemically induced/epidemiology ; No-Observed-Adverse-Effect Level ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant/chemically induced/complications ; Asbestos, Amphibole/toxicity/analysis ; *Asbestos/toxicity/analysis ; }, abstract = {This analysis updates two previous analyses that evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. We reviewed recently published studies, as well as updated information from previous studies. Based on the 16 studies considered for chrysotile (<10% amphibole), we identified the "no-observed adverse effect level" (NOAEL) for lung cancer and/or mesothelioma; it should be noted that smoking or previous or concurrent occupational exposure to amphiboles (if it existed) was not controlled for. NOAEL values ranged from 2.3-<11.5 f/cc-years to 1600-3200 f/cc-years for lung cancer and from 100-<400 f/cc-years to 800-1599 f/cc-years for mesothelioma. The range of best-estimate NOAELs was estimated to be 97-175 f/cc-years for lung cancer and 250-379 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased risk at any exposure level, while all but one of the six studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Only eight cases of peritoneal mesothelioma were reported in all studies on predominantly chrysotile-exposed cohorts combined. This analysis also proposed best-estimate amosite and crocidolite NOAELs for mesothelioma derived by the application of relative potency estimates to the best-estimate chrysotile NOAELs for mesothelioma and validated by epidemiology studies with exposure-response information. The best-estimate amosite and crocidolite NOAELs for mesothelioma were 2-5 f/cc-years and 0.6-1 f/cc-years, respectively. The rate of peritoneal mesothelioma in amosite- and crocidolite-exposed cohorts was between approximately 70- to 100-fold and several-hundred-fold higher than in chrysotile-exposed cohorts, respectively. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile, amosite, and crocidolite exposures.}, }
@article {pmid38090310, year = {2023}, author = {Liu, B and Niu, L and Lee, FF}, title = {Utilizing residential histories to assess environmental exposure and socioeconomic status over the life course among mesothelioma patients.}, journal = {Journal of thoracic disease}, volume = {15}, number = {11}, pages = {6126-6139}, pmid = {38090310}, issn = {2072-1439}, support = {R21 CA235153/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Exposure misclassification based solely on the address at cancer diagnosis has been widely recognized though not commonly assessed.<br><br>METHODS: We linked 1,015 mesothelioma cases diagnosed during 2011-2015 from the New York State Cancer Registry to inpatient claims and LexisNexis administrative data and constructed residential histories. Percentile ranking of exposure to ambient air toxics and socioeconomic status (SES) were based on the National Air Toxic Assessment and United States Census data, respectively. To facilitate comparisons over time, relative exposures (REs) were calculated by dividing the percentile ranking at individual census tract by the state-level average and subtracting one. We used generalized linear regression models to compare the RE in the past with that at cancer diagnosis, adjusting for patient-level characteristics.<br><br>RESULTS: Approximately 43.7% of patients had residential information available for up to 30 years, and 96.0% up to 5 years. The median number of unique places lived was 4 [interquartile range (IQR), 2-6]. The time-weighted-average RE from all addresses available had a median of -0.11 (IQR, -0.50 to 0.30) for air toxics and -0.28 (IQR, -0.65 to 0.25) for SES. RE associated with air toxics (but not SES) was significantly higher for earlier addresses than addresses at cancer diagnosis for the 5-year [annual increase =1.24%; 95% confidence interval (CI): 0.71-1.77%; n=974] and 30-year (annual increase =0.36%; 95% CI: 0.25-0.48%; n=444) look-back windows, respectively.<br><br>CONCLUSIONS: Environmental exposure to non-asbestos air toxics among mesothelioma patients may be underestimated if based solely on the address at diagnosis. With geospatial data becoming more readily available, incorporating cancer patients' residential history would lead to reduced exposure misclassification and accurate health risk estimates.}, }
@article {pmid38089107, year = {2023}, author = {Tibaduiza Torres, AL and Betancur Romero, JE and Silva Aparicio, A and Rico Mendoza, MA}, title = {[Malignant mesothelioma in Colombia: burden of disease, overview, and subnational sociodemographic index, 2015-2020Mesotelioma maligno na Colômbia: carga de morbidade, visão geral e índice sociodemográfico subnacional, entre 2015 e 2020].}, journal = {Revista panamericana de salud publica = Pan American journal of public health}, volume = {47}, number = {}, pages = {e95}, pmid = {38089107}, issn = {1680-5348}, abstract = {OBJECTIVE: Establish the disease burden of malignant mesothelioma (MM) in Colombia between 2015 and 2020, and its association with the subnational sociodemographic development index (SDI) and with asbestos sites.<br><br>METHODS: Mixed ecological study of the Colombian population diagnosed with MM (according to ICD-10) from 2015 to 2020. The global burden of disease (GBD) was estimated using the methodology proposed by Murray and Lopez, based on prevalence and mortality data obtained from official sources. The subnational (departmental level) SDI was estimated as a measure of socioeconomic development. Linear regressions were established with the GBD, SDI, and documented asbestos sites.<br><br>RESULTS: The estimated GBD of MM in Colombia during 2015-2020 was 51.71 disability-adjusted life years (DALYs) per 1 000 000 inhabitants (15 375.79 total DALYs), with predominance in people over 50 years of age (91.1%) and males (66.4%).Bogot&#xe1; and Valle del Cauca were the departments with the highest number of adjusted DALYs. Bogot&#xe1; had the highest SDI and Guain&#xed;a and Cesar had the lowest. There was evidence of an association between DALYs and SDI, explaining 22.8% of DALYs.<br><br>CONCLUSION: Malignant mesothelioma is the cause of a large number of DALYs, predominantly in the departments with greater socioeconomic development and with companies that used to use asbestos. However, possible underdiagnosis of MM limits analysis of the information.}, }
@article {pmid38076518, year = {2023}, author = {Shenouda, M and Gudmundsson, E and Li, F and Straus, CM and Kindler, HL and Dudek, AZ and Stinchcombe, T and Wang, X and Starkey, A and Armato, SG}, title = {Convolutional Neural Networks for Segmentation of Malignant Pleural Mesothelioma: Analysis of Probability Map Thresholds (CALGB 30901, Alliance).}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {38076518}, issn = {2331-8422}, support = {U10 CA180821/CA/NCI NIH HHS/United States ; U10 CA180882/CA/NCI NIH HHS/United States ; UG1 CA189863/CA/NCI NIH HHS/United States ; UG1 CA233253/CA/NCI NIH HHS/United States ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common form of malignant mesothelioma, with exposure to asbestos being the primary cause of the disease. To assess response to treatment, tumor measurements are acquired and evaluated based on a patient's longitudinal computed tomography (CT) scans. Tumor volume, however, is the more accurate metric for assessing tumor burden and response. Automated segmentation methods using deep learning can be employed to acquire volume, which otherwise is a tedious task performed manually. The deep learning-based tumor volume and contours can then be compared with a standard reference to assess the robustness of the automated segmentations. The purpose of this study was to evaluate the impact of probability map threshold on MPM tumor delineations generated using a convolutional neural network (CNN). Eighty-eight CT scans from 21 MPM patients were segmented by a VGG16/U-Net CNN. A radiologist modified the contours generated at a 0.5 probability threshold. Percent difference of tumor volume and overlap using the Dice Similarity Coefficient (DSC) were compared between the standard reference provided by the radiologist and CNN outputs for thresholds ranging from 0.001 to 0.9. CNN annotations consistently yielded smaller tumor volumes than radiologist contours. Reducing the probability threshold from 0.5 to 0.1 decreased the absolute percent volume difference, on average, from 43.96% to 24.18%. Median and mean DSC ranged from 0.58 to 0.60, with a peak at a threshold of 0.5; no distinct threshold was found for percent volume difference. The CNN exhibited deficiencies with specific disease presentations, such as severe pleural effusion or disease in the pleural fissure. No single output threshold in the CNN probability maps was optimal for both tumor volume and DSC. This study emphasized the importance of considering both figures of merit when evaluating deep learning-based tumor segmentations across probability thresholds. This work underscores the need to simultaneously assess tumor volume and spatial overlap when evaluating CNN performance. While automated segmentations may yield comparable tumor volumes to that of the reference standard, the spatial region delineated by the CNN at a specific threshold is equally important.}, }
@article {pmid38072464, year = {2023}, author = {Turati, F and Rossi, M and Spinazzè, A and Pira, E and Cavallo, DM and Patel, L and Mensi, C and La Vecchia, C and Negri, E}, title = {Occupational asbestos exposure and ovarian cancer: updated systematic review.}, journal = {Occupational medicine (Oxford, England)}, volume = {73}, number = {9}, pages = {532-540}, doi = {10.1093/occmed/kqad122}, pmid = {38072464}, issn = {1471-8405}, support = {ARL_2/2018//'Fondazione Regionale per la Ricerca Biomedica'-'Bando Progetto Speciale 2017 su Patologie Amianto-Correlate'/ ; }, mesh = {Humans ; Female ; *Asbestos/adverse effects ; *Ovarian Neoplasms/etiology ; Risk ; *Occupational Exposure/adverse effects ; Time Factors ; *Mesothelioma/etiology ; *Occupational Diseases/diagnosis/etiology ; *Lung Neoplasms ; }, abstract = {BACKGROUND: The association between asbestos exposure and ovarian cancer has been questioned given the possible misdiagnosis of peritoneal mesothelioma as ovarian cancer.<br><br>AIMS: To update a systematic review on ovarian cancer risk in women occupationally exposed to asbestos, exploring the association with the time since first exposure and the duration of exposure.<br><br>METHODS: We searched PubMed from 2008 onwards, screened previous systematic reviews, combined standardized mortality ratios (SMR) using random effect models and quantified heterogeneity using the I2 statistic. To assess tumour misclassification, we compared the distribution of observed excess ovarian cancers (OEOC) to that expected (EEOC) from the distribution of peritoneal cancers in strata of latency and exposure duration.<br><br>RESULTS: Eighteen publications (20 populations), including a pooled analysis of 21 cohorts, were included. The pooled SMR was 1.79 (95% confidence interval 1.38-2.31), with moderate heterogeneity between studies (I2&#x2005;=&#x2005;42%), based on 144 ovarian cancer deaths/cases. The risk was increased for women with indirect indicators of higher exposure, longer duration and latency, and lower for chrysotile than for crocidolite exposure. The effect of duration and latency could not be completely disentangled, since no multivariate analysis was available for time-related variables. The dissimilarity index between OEOC and EEOC for the time since first exposure was small suggesting a similar pattern of risk.<br><br>CONCLUSIONS: While some misclassification between ovarian and peritoneal cancers cannot be excluded, the observed excess risk of ovarian cancer should be added to the overall disease burden of asbestos.}, }
@article {pmid38069464, year = {2024}, author = {Visonà, SD and Bertoglio, B and Capella, S and Belluso, E and Austoni, B and Colosio, C and Kurzhunbaeva, Z and Ivic-Pavlicic, T and Taioli, E}, title = {Asbestos burden in lungs of mesothelioma patients with pleural plaques, lung fibrosis and/or ferruginous bodies at histology: a postmortem SEM-EDS study.}, journal = {Carcinogenesis}, volume = {45}, number = {3}, pages = {131-139}, doi = {10.1093/carcin/bgad090}, pmid = {38069464}, issn = {1460-2180}, mesh = {Humans ; *Pulmonary Fibrosis/complications/pathology ; *Mesothelioma, Malignant/complications/pathology ; *Asbestos/toxicity/analysis ; *Mesothelioma/chemically induced ; Lung/pathology ; *Lung Neoplasms/etiology/pathology ; *Occupational Exposure ; }, abstract = {The causal attribution of asbestos-related diseases to past asbestos exposures is of crucial importance in clinical and legal contexts. Often this evaluation is made based on the history of exposure, but this method presents important limitations. To assess past asbestos exposure, pleural plaques (PP), lung fibrosis and histological evidence of ferruginous bodies (FB) can be used in combination with anamnestic data. However, such markers have never been associated with a threshold value of inhaled asbestos. With this study we attempted to shed light on the dose-response relationship of PP, lung fibrosis and FBs, investigating if their prevalence in exposed individuals who died from malignant mesothelioma (MM) is related to the concentration of asbestos in lungs assessed using scanning electron microscopy equipped with energy dispersive spectroscopy. Moreover, we estimated the values of asbestos concentration in lungs associated with PP, lung fibrosis and FB. Lung fibrosis showed a significant positive relationship with asbestos lung content, whereas PP and FB did not. We identified, for the first time, critical lung concentrations of asbestos related to the presence of PP, lung fibrosis and FB at histology (respectively, 19 800, 26 400 and 27 400 fibers per gram of dry weight), that were all well-below the background levels of asbestos identified in our laboratory. Such data suggest that PP, lung fibrosis and FB at histology should be used with caution in the causal attribution of MM to past asbestos exposures, while evaluation of amphibole lung content using analytical electron microscopy should be preferred.}, }
@article {pmid38064629, year = {2024}, author = {Yang, D and Zhou, Y and Lv, K}, title = {Analysis of Ki67 Protein Expression and Clinicopathological Features in Patients with Peritoneal Mesothelioma.}, journal = {Alternative therapies in health and medicine}, volume = {30}, number = {9}, pages = {202-209}, pmid = {38064629}, issn = {1078-6791}, mesh = {Humans ; *Ki-67 Antigen/metabolism ; *Peritoneal Neoplasms/metabolism/genetics ; *Mesothelioma/pathology/metabolism/mortality ; Male ; Female ; Prognosis ; Middle Aged ; *Biomarkers, Tumor/metabolism/genetics ; Aged ; Adult ; }, abstract = {BACKGROUND: At present, there are many treatments for peritoneal mesothelioma, but the treatment of peritoneal mesothelioma is still facing great challenges. Distant metastasis is the main cause of poor prognosis and death of patients with peritoneal mesothelioma. Ki67 is a cell proliferation marker. In recent years, it has been found to be used as a molecular marker for the diagnosis, treatment and prognosis of different tumor cells. Ki67 has been shown to play a crucial role in the occurrence and development of a variety of cancers. However, the clinical significance and biological function of Ki67 in peritoneal mesothelioma remain poorly understood.<br><br>PURPOSE: To clarify the expression of Ki67 in peritoneal mesothelioma (PC), and to explore the relationship between the expression level of Ki67 and the clinicopathological parameters and prognosis of patients with PC, and to explore the potential of Ki67 as a therapeutic target and prognostic biomarker for PC.<br><br>METHODS: TIMER database was used to compare the expression levels of Ki67 mRNA and protein in mesothelioma tissues and adjacent tissues. The relationship between the expression level of Ki67 in mesothelioma and clinicopathological characteristics, and the relationship between the expression level of Ki67 and the level of immune infiltration in mesothelioma were analyzed. The prognostic value of Ki67 in mesothelioma patients was predicted, and the overall survival curve was drawn according to the follow-up data. LinkedOmics database and GSEA were used to perform co-expression analysis and enrichment analysis of Ki67, respectively.<br><br>RESULTS: Bioinformatics analysis showed that Ki67 was highly expressed in peritoneal mesothelioma (P < .01). Immunohistochemistry showed that the positive rate of Ki67 in peritoneal mesothelioma was high, and the number of Ki67 positive cases was 62.0% (31/50 cases). Univariate analysis showed that TNM stage (P = .007), asbestos (P < .001), chemotherapy (P < .001), and Ki67 expression level (P = .029) were associated with prognosis. Multivariate analysis showed that Ki67 expression level (P = .039) and TNM stage (P = .029) were independent risk factors for the prognosis of peritoneal mesothelioma. Peritoneal mesothelioma patients with high Ki67 expression have poor OS. In addition, Ki67 is also associated with the immune infiltration of mesothelioma.<br><br>CONCLUSION: Ki67 is highly expressed in peritoneal mesothelioma. Ki67 protein plays an important role in the development of peritoneal mesothelioma and is one of the important factors to evaluate the prognosis of patients with peritoneal mesothelioma.}, }
@article {pmid38063957, year = {2024}, author = {Martella, S and Aiello, MM and Bertaglia, V and Cau, R and Denaro, N and Cadoni, A and Novello, S and Scartozzi, M and Novello, G and Soto Parra, HJ and Saba, L and Solinas, C and Porcu, M}, title = {Malignant Pleural Mesothelioma: Staging and Radiological Response Criteria in Patients Treated with Immune Checkpoint Inhibitors.}, journal = {Targeted oncology}, volume = {19}, number = {1}, pages = {13-28}, pmid = {38063957}, issn = {1776-260X}, mesh = {Humans ; *Mesothelioma, Malignant/drug therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Artificial Intelligence ; *Pleural Neoplasms/diagnostic imaging/drug therapy ; *Lung Neoplasms/diagnostic imaging/drug therapy ; Combined Modality Therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically, platinum-based chemotherapy has been the primary approach, but recent developments have introduced immunotherapy as a promising alternative for the treatment of this disease. Nevertheless, the unique growth patterns and occasionally ambiguous progressive characteristics of MPM make the interpretation of radiological assessments complex. Immunotherapy further complicates matters by introducing unconventional treatment response patterns such as hyperprogression and pseudoprogression. Consequently, there is a growing imperative to integrate the standard RECIST criteria with the mesothelioma-specific mRECIST criteria (version 1.1), as outlined in iRECIST. This comprehensive review is driven by the intent to provide a valuable resource for radiologists and clinicians engaged in the diagnosis, treatment, and monitoring of MPM in the era of immunotherapy. Specifically, the current imaging methods employed for staging and follow-up will be exposed and discussed, with a focus on the technical specificities and the mRECIST 1.1 methodology. Furthermore, we will provide a discussion about major clinical trials related to the use of immunotherapy in MPM patients. Finally, the latest advancements in radiomics, the applications of artificial intelligence in MPM, and their potential impact on clinical practice for prognosis and therapy, are discussed.}, }
@article {pmid38054089, year = {2023}, author = {Wang, D and Wang, YH and Chu, SC}, title = {Case Report: Early diagnosis and bevacizumab-based chemotherapy for primary pericardial mesothelioma: a case with occupational asbestos exposure history.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1257373}, pmid = {38054089}, issn = {2297-055X}, abstract = {BACKGROUND: Primary pericardial mesothelioma (PPM) is an exceedingly rare malignant cancer and has a poor prognosis, which has been partly attributed to its frequently delayed diagnosis due to its nonspecific syndromes, its similar presentation to benign pericardial diseases, and its non-definitive etiology. In many PPM cases, the time from presentation to definite diagnosis may last for several months or even over one year. Unlike pleural mesothelioma, the relationship between PPM and asbestos exposure remains unsettled. To date, there is no consensus on the treatment of PPM.<br><br>CASE REPORT: The patient is a 57-year-old male who had nonspecific syndromes and inconclusive image findings. The occupational long-term asbestos exposure history of this patient raised our concerns regarding potential malignancy when confronted with unexplained pericardial effusion accompanied by cardiac tamponade. The heightened suspicion prompted us to perform pericardiocentesis and biopsy on the third day after admission to our department. An early diagnosis of PPM was established by the pathological and immunohistochemical evaluation of the biopsy specimen two weeks after admission. Positron emission tomography-computed tomography revealed that the lesion was localized at the anterior part of the mediastinum without distant metastasis. This patient refused to receive cardiac surgery. He subsequently underwent six cycles of chemotherapy (cisplatin plus pemetrexed) in combination with bevacizumab (a humanized anti-VEGF antibody) as the first-line treatment, resulting in complete relief of symptoms and satisfactory outcomes with no complications. Four months after the first course, the patient initiated a second course of chemotherapy with a similar regimen, but he opted to discontinue the medical treatment after the initiation of the second course. The patient was transferred to the hospice care unit and unfortunately expired one year after the initial presentation.<br><br>CONCLUSION: We present a case of an early multidisciplinary clinical approach to diagnose and manage PPM with consideration of occupational asbestos exposure history and clinical symptoms. Bevacizumab-based chemotherapy remains an option for the treatment of PPM.}, }
@article {pmid38044849, year = {2024}, author = {Klebe, S and Judge, M and Brcic, L and Dacic, S and Galateau-Salle, F and Nicholson, AG and Roggli, V and Nowak, AK and Cooper, WA}, title = {Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).}, journal = {Histopathology}, volume = {84}, number = {4}, pages = {633-645}, doi = {10.1111/his.15106}, pmid = {38044849}, issn = {1365-2559}, mesh = {Humans ; Peritoneum ; Pleura ; Retrospective Studies ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; Pericardium ; *Pathology, Clinical/methods ; }, abstract = {AIMS: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers.<br><br>METHODS AND RESULTS: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading.<br><br>CONCLUSION: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).}, }
@article {pmid38041166, year = {2023}, author = {Visonà, SD and Bertoglio, B and Favaron, C and Capella, S and Belluso, E and Colosio, C and Villani, S and Ivic-Pavlicic, T and Taioli, E}, title = {A postmortem case control study of asbestos burden in lungs of malignant mesothelioma cases.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {875}, pmid = {38041166}, issn = {1479-5876}, mesh = {Humans ; Female ; Male ; *Mesothelioma, Malignant/complications ; Asbestos, Serpentine ; Case-Control Studies ; *Mesothelioma/pathology ; *Lung Neoplasms/etiology/pathology ; *Asbestos ; Lung/pathology ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends.<br><br>METHODS: Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM-EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023.<br><br>RESULTS: Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011.<br><br>DISCUSSION: The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011.}, }
@article {pmid38038422, year = {2023}, author = {Zupanc, C and Franko, A and Strbac, D and Kovac, V and Dolzan, V and Goricar, K}, title = {The association of genetic factors with serum calretinin levels in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {57}, number = {4}, pages = {473-486}, pmid = {38038422}, issn = {1581-3207}, mesh = {Humans ; *Asbestos/adverse effects ; *Asbestosis/genetics ; *Calbindin 2/blood ; *Mesothelioma, Malignant/genetics ; }, abstract = {BACKGROUND: Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.<br><br>SUBJECTS AND METHODS: The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis.<br><br>RESULTS: Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2 rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335 genotypes.<br><br>CONCLUSIONS: The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.}, }
@article {pmid38036250, year = {2024}, author = {McNamee, N and Harvey, C and Gray, L and Khoo, T and Lingam, L and Zhang, B and Nindra, U and Yip, PY and Pal, A and Clay, T and Arulananda, S and Itchins, M and Pavlakis, N and Kao, S and Bowyer, S and Chin, V and Warburton, L and Pires da Silva, I and John, T and Solomon, B and Alexander, M and Nagrial, A}, title = {Brief Report: Real-World Toxicity and Survival of Combination Immunotherapy in Pleural Mesothelioma-RIOMeso.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {4}, pages = {636-642}, doi = {10.1016/j.jtho.2023.11.014}, pmid = {38036250}, issn = {1556-1380}, mesh = {Humans ; Male ; Aged ; Female ; Nivolumab/adverse effects ; Ipilimumab/adverse effects ; Retrospective Studies ; *Lung Neoplasms/drug therapy/etiology ; Australia ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy/etiology ; *Pleural Neoplasms/drug therapy/etiology ; Immunotherapy/adverse effects ; *Asbestos ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; }, abstract = {BACKGROUND: Australia has one of the highest rates of asbestos-associated diseases. Mesothelioma remains an area of unmet need with a 5-year overall survival of 10%. First-line immunotherapy with ipilimumab and nivolumab is now a standard of care for unresectable pleural mesothelioma following the CheckMate 743 trial, with supportive data from the later line single-arm MAPS2 trial. RIOMeso evaluates survival and toxicity of this regimen in real-world practice.<br><br>METHODS: Demographic and clinicopathologic data of Australian patients treated with ipilimumab and nivolumab in first- and subsequent-line settings for pleural mesothelioma were collected retrospectively. Survival was reported using the Kaplan-Meier method and compared between subgroups with the log-rank test. Toxicity was investigator assessed using Common Terminology Criteria for Adverse Events version 5.0.<br><br>RESULTS: A total of 119 patients were identified from 11 centers. The median age was 72 years, 83% were male, 92% had Eastern Cooperative Oncology Group less than or equal to 1, 50% were past or current smokers, and 78% had known asbestos exposure. In addition, 50% were epithelioid, 19% sarcomatoid, 14% biphasic, and 17% unavailable. Ipilimumab and nivolumab were used first line in 75% of patients. Median overall survival (mOS) was 14.5 months (95% confidence interval [CI]: 13.0-not reached [NR]) for the entire cohort. For patients treated first line, mOS was 14.5 months (95% CI: 12.5-NR) and in second- or later-line patients was 15.4 months (95% CI: 11.2-NR). There was no statistically significant difference in mOS for epithelioid patients compared with nonepithelioid (19.1 mo [95% CI: 15.4-NR] versus 13.0 mo [95% CI: 9.7-NR], respectively, p&#xa0;= 0.064). Furthermore, 24% of the patients had a Common Terminology Criteria for Adverse Events grade greater than or equal to 3 adverse events, including three treatment-related deaths. Colitis was the most frequent adverse event.<br><br>CONCLUSIONS: Combination immunotherapy in real-world practice has poorer survival outcomes and seems more toxic compared with clinical trial data. This is the first detailed report of real-world survival and toxicity outcomes using ipilimumab and nivolumab treatment of pleural mesothelioma.}, }
@article {pmid38032359, year = {2024}, author = {Geyer, SJ}, title = {A cluster of mesotheliomas reported in a case series does not implicate chrysotile asbestos-containing friction products as the cause of mesotheliomas.}, journal = {American journal of industrial medicine}, volume = {67}, number = {1}, pages = {81-82}, doi = {10.1002/ajim.23554}, pmid = {38032359}, issn = {1097-0274}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; Friction ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; *Lung Neoplasms/etiology ; }, }
@article {pmid38030592, year = {2024}, author = {Miller, A}, title = {Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.}, journal = {American journal of industrial medicine}, volume = {67}, number = {1}, pages = {73-80}, doi = {10.1002/ajim.23553}, pmid = {38030592}, issn = {1097-0274}, mesh = {Humans ; *Asbestos/toxicity ; Asbestos, Amphibole/toxicity ; *Asbestosis/diagnostic imaging/pathology ; Fibrosis ; Pain ; Pleura/diagnostic imaging/pathology ; *Pleural Diseases/diagnostic imaging/etiology ; *Pleurisy/pathology ; }, abstract = {Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.}, }
@article {pmid38017544, year = {2023}, author = {Yoshida, M and Jimbo, N and Tsukamoto, R and Itoh, T and Kawahara, K and Mitsui, S and Tanaka, Y and Maniwa, Y}, title = {Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma.}, journal = {Diagnostic pathology}, volume = {18}, number = {1}, pages = {126}, pmid = {38017544}, issn = {1746-1596}, support = {23K08317//JSPS KAKENHI/ ; 23K08317//JSPS KAKENHI/ ; }, mesh = {Male ; Humans ; Aged ; In Situ Hybridization, Fluorescence ; Homozygote ; *Lung Neoplasms/diagnosis/genetics/pathology ; Sequence Deletion ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/genetics/pathology ; *Pleural Neoplasms/diagnosis/genetics/pathology ; *Pleural Effusion/genetics ; *Sarcoma/genetics ; Biomarkers, Tumor/genetics/analysis ; Ubiquitin Thiolesterase/analysis/genetics ; }, abstract = {BACKGROUND: Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts.<br><br>CASE PRESENTATION: This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9&#xa0;months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12&#xa0;months after the diagnosis of the sarcomatoid morphology of mesothelioma.<br><br>CONCLUSION: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.}, }
@article {pmid38015374, year = {2023}, author = {Nash, A and Creaney, J}, title = {Genomic Landscape of Pleural Mesothelioma and Therapeutic Aftermaths.}, journal = {Current oncology reports}, volume = {25}, number = {12}, pages = {1515-1522}, pmid = {38015374}, issn = {1534-6269}, support = {1197652//National Health and Medical Research Council/ ; CA190450//U.S. Department of Defense/ ; }, mesh = {Humans ; *Lung Neoplasms/genetics/therapy/pathology ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/therapy/pathology ; *Pleural Neoplasms/genetics/therapy/pathology ; Genomics ; Tumor Microenvironment ; }, abstract = {PURPOSE OF REVIEW: In this article, we provide a comprehensive analysis of recent progress in the genetic characterisation of pleural mesothelioma, and the translation of these findings to clinical practice.<br><br>RECENT FINDINGS: Advancements in sequencing technology have allowed the identification of driver mutations and improved our understanding of how these mutations may shape the mesothelioma tumour microenvironment. However, the identification of frequently mutated regions including CDKN2A, BAP1 and NF2 have, to date, not yet yielded targeted therapy options that outperform standard chemo- and immunotherapies. Similarly, the association between mutational profile and the immune microenvironment or immunotherapy response is not well characterised. Further research into the link between tumour mutational profile and response to therapy is critical for identifying targetable vulnerabilities and stratifying patients for therapy.}, }
@article {pmid38002620, year = {2023}, author = {Sorino, C and Mondoni, M and Marchetti, G and Agati, S and Inchingolo, R and Mei, F and Flamini, S and Lococo, F and Feller-Kopman, D}, title = {Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers.}, journal = {Journal of clinical medicine}, volume = {12}, number = {22}, pages = {}, pmid = {38002620}, issn = {2077-0383}, abstract = {Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.}, }
@article {pmid38000500, year = {2024}, author = {Nel, AE and Pavlisko, EN and Roggli, VL}, title = {The Interplay Between the Immune System, Tumor Suppressor Genes, and Immune Senescence in Mesothelioma Development and Response to Immunotherapy.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {4}, pages = {551-564}, doi = {10.1016/j.jtho.2023.11.017}, pmid = {38000500}, issn = {1556-1380}, mesh = {Humans ; United States ; Aged ; Phylogeny ; *Lung Neoplasms/genetics/therapy ; *Mesothelioma/genetics/therapy ; *Mesothelioma, Malignant/genetics ; Genes, Tumor Suppressor ; *Asbestos ; Tumor Microenvironment ; }, abstract = {Despite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable at approximately 2500 cases annually. This trend is not unique to the United States but is also a global phenomenon, associated with increased aging of populations worldwide. Although geoeconomic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging. Recognizing that mesothelioma shares genetic instability and immune system effects with other age-related cancers is crucial because the impact of aging on mesothelioma is frequently assessed in the context of disease latency after asbestos exposure. Nevertheless, the long latency period, often cited as a reason for mesothelioma's elderly predominance, should not overshadow the shared mechanisms. This communication focuses on the role of immune surveillance in mesothelioma, particularly exploring the impact of immune escape resulting from altered TSG function during aging, contributing to the phylogenetic development of gene mutations and mesothelioma oncogenesis. The interplay between the immune system, TSGs, and aging not only shapes the immune landscape in mesothelioma but also contributes to the development of heterogeneous tumor microenvironments, significantly influencing responses to immunotherapy approaches and survival rates. By understanding the complex interplay between aging, TSG decline, and immune senescence, health care professionals can pave the way for more effective and personalized immunotherapies, ultimately offering hope for better outcomes in the fight against mesothelioma.}, }
@article {pmid37995092, year = {2023}, author = {Somigliana, AB and Barbieri, PG and Cavallo, A and Colombo, R and Consonni, D and Mirabelli, D}, title = {Lung asbestos fiber burden analysis: effects of the counting rules for legal medicine evaluations.}, journal = {Inhalation toxicology}, volume = {35}, number = {11-12}, pages = {300-307}, doi = {10.1080/08958378.2023.2285789}, pmid = {37995092}, issn = {1091-7691}, mesh = {Humans ; *Asbestos/toxicity/analysis ; Lung/chemistry ; Asbestos, Amphibole/toxicity/analysis ; Asbestos, Serpentine/toxicity ; *Lung Neoplasms ; Forensic Medicine ; }, abstract = {OBJECTIVES: The work shows the effect of counting rules, such as analysis magnification and asbestos fiber dimension to be count (with length ≥5 µm or also asbestos fibers with length <5 µm) in the lung asbestos fiber burden analysis for legal medicine evaluations.<br><br>METHODS: On the same lung tissue samples, two different analyses were carried out to count any asbestos fibers with length &#x2265;1&#x2009;&#xb5;m and with length &#x2265;5&#x2009;&#xb5;m. Results of the amphibole burden of the two analyses were compared by linear regression analysis on log10-transformed values.<br><br>RESULTS: The analysis should be carried out at an appropriate magnification and on samples prepared in such a way as they allow the counting of very fine fibers. If the analysis is limited to the asbestos fibers with length &#x2265;5&#x2009;&#xb5;m, there is a high risk of not detecting possible residual chrysotile fiber burden and thinner crocidolite asbestos fibers.<br><br>CONCLUSIONS: On average we estimated that 1 amphibole fiber with length &#x2265;5&#x2009;&#xb5;m corresponds to &#x223c;8 amphibole fibers with length &#x2265;1&#x2009;&#xb5;m in the lung. The values of the Helsinki criteria should be updated taking this into account.}, }
@article {pmid37977032, year = {2023}, author = {Salman, A and Abdel Mageed, SS and Fathi, D and Elrebehy, MA and Abulsoud, AI and Elshaer, SS and Khidr, EG and Al-Noshokaty, TM and Khaled, R and Rizk, NI and Elballal, MS and Sayed, GA and Abd-Elmawla, MA and El Tabaa, MM and Mohammed, OA and Ashraf, A and El-Husseiny, AA and Midan, HM and El-Dakroury, WA and Abdel-Reheim, MA and Doghish, AS}, title = {Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma.}, journal = {Pathology, research and practice}, volume = {252}, number = {}, pages = {154947}, doi = {10.1016/j.prp.2023.154947}, pmid = {37977032}, issn = {1618-0631}, mesh = {Humans ; *Mesothelioma, Malignant ; *MicroRNAs/genetics ; *Mesothelioma/diagnosis ; *Pleural Neoplasms/pathology ; Hedgehog Proteins ; *Lung Neoplasms/pathology ; Signal Transduction/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/β-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.}, }
@article {pmid37975977, year = {2023}, author = {John, A and O'Sullivan, H and Popat, S}, title = {Updates in Management of Malignant Pleural Mesothelioma.}, journal = {Current treatment options in oncology}, volume = {24}, number = {12}, pages = {1758-1789}, pmid = {37975977}, issn = {1534-6277}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/etiology/therapy ; Pemetrexed/therapeutic use ; *Lung Neoplasms/pathology ; *Pleural Neoplasms/diagnosis/etiology/therapy ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated thoracic malignancy that is usually incurable. As demonstrated in the landmark MARS2 trial, surgical resection does not improve survival outcomes and its role in managing MPM is limited. Whilst platinum-pemetrexed chemotherapy in combination with bevacizumab was the standard first-line approach for unresectable disease, landmark phase 3 trials have now established the role of immune checkpoint inhibitors (CPIs) in the upfront management of unresectable disease: either nivolumab-ipilimumab or carboplatin-pemetrexed-pembrolizumab. Patient selection for optimal strategy remains an ongoing question. For relapsed disease novel genomic-based therapies targeting a range of aberrations including losses of the tumour suppressor genes BAP1, CDKN2A and NF2, are being evaluated. Nonetheless, the future of MPM therapeutics holds promise. Here we overview current treatment strategies in the management of MPM.}, }
@article {pmid37963950, year = {2023}, author = {Gun, RT and Kendall, GM}, title = {Asbestos-related cancer in naval personnel: findings from participants in the British nuclear tests 1952-1967.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {18842}, pmid = {37963950}, issn = {2045-2322}, mesh = {Humans ; Australia/epidemiology ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/etiology ; *Asbestosis/complications ; *Lung Neoplasms/epidemiology/etiology ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology ; }, abstract = {Asbestos-containing materials (ACM) were present in British and Australian naval vessels throughout the twentieth century. The aim of this study was to identify and quantify the incidence of cancer in naval personnel from onboard asbestos exposure. Subjects were four cohorts of subjects who had served in the armed forces of the United Kingdom and Australia in the 1950s and 1960s. All cohorts had previously been studied, three of them in relation to radiation exposures from British nuclear testing. Comparisons of SIRs between services were made to identify cancers attributable to asbestos exposure. Excess mesotheliomas were found in naval personnel in all cohorts. In all but one cohort the lung cancer incidence was highest in navy personnel. Comparison of other smoking-related conditions indicated that the excess in navy personnel was not smoking-related. The relatively high SIRs for mesothelioma and the occurrence of deaths from asbestosis were indicative of high levels of asbestos exposure, with an expectation of cases of asbestos-related lung cancer. The findings are consistent with the occurrence of significant excesses of mesotheliomas. In addition, notwithstanding some inconsistencies in the results between the cohorts, we estimated that approximately 27% of lung cancers in Australian seamen and 12% in British seamen were related to onboard asbestos exposure.}, }
@article {pmid37942251, year = {2023}, author = {Grignani, P and Visonà, SD and Fronda, MV and Borrelli, P and Monti, MC and Bertoglio, B and Conti, A and Fattorini, P and Previderè, C}, title = {The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1236558}, pmid = {37942251}, issn = {2296-2565}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; Polymorphism, Single Nucleotide ; *Occupational Exposure ; *Mesothelioma/genetics ; *Asbestos/adverse effects ; Iron/metabolism ; Homeostasis ; Tumor Microenvironment ; }, abstract = {Asbestos-related diseases still represent a major public health problem all over the world. Among them, malignant mesothelioma (MM) is a poor-prognosis cancer, arising from the serosal lining of the pleura, pericardium and peritoneum, triggered by asbestos exposure. Literature data suggest the key role of iron metabolism in the coating process leading to the formation of asbestos bodies, considered to be both protective and harmful. Two sample sets of individuals were taken into consideration, both residing in Broni or neighboring cities (Northwestern Italy) where an asbestos cement factory was active between 1932 and 1993. The present study aims to compare the frequency of six SNPs involved in iron trafficking, previously found to be related to protection/predisposition to MM after asbestos exposure, between 48 male subjects with documented asbestos exposure who died of MM and 48 male subjects who were exposed to asbestos but did not develop MM or other neoplastic respiratory diseases (Non-Mesothelioma Asbestos Exposed - NMAE). The same analysis was performed on 76 healthy male controls. The allelic and genotypic frequencies of a sub-group of 107 healthy Italian individuals contained in the 1000 genomes database were considered for comparison. PCR-multiplex amplification followed by SNaPshot mini-sequencing reaction was used. The findings presented in this study show that the allelic and genotypic frequencies for six SNP markers involved in iron metabolism/homeostasis and the modulation of tumor microenvironment are not significantly different between the two sample sets of MM and NMAE. Therefore, the SNPs here considered do not seem to be useful markers for individual susceptibility to mesothelioma. This finding is not in agreement with previous literature.}, }
@article {pmid37921373, year = {2023}, author = {Esteban Porcar, A and García Gómez, M and Santana Yllobre, L and Gómez Pajares, F and Esteban Buedo, V and Usó Talamantes, R}, title = {[Reconocimiento del mesotelioma de pleura como enfermedad profesional en la Comunidad Valenciana de 2012 a 2018.].}, journal = {Revista espanola de salud publica}, volume = {97}, number = {}, pages = {}, pmid = {37921373}, issn = {2173-9110}, mesh = {Humans ; Pleura ; Retrospective Studies ; Spain/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Pleural Neoplasms/etiology/complications ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology/etiology ; }, abstract = {OBJECTIVE: Pleural mesothelioma is a neoplasm almost exclusively attributed to occupational exposure to asbestos and is legally considered an occupational disease. Nevertheless, only a few cases achieve that official recognition. The objective of this work was to describe and analyse this issue, and to identify the major obstacles to its recognition.<br><br>METHODS: A descriptive and retrospective epidemiological study of data was carried out, including figures and some characteristics, of all patients with pleural mesothelioma registered in the official health and labor registries of the Valencian Community from 2012 to 2018, using frequencies, proportions, and incidence rates.<br><br>RESULTS: There were large differences between the two sets of data collected in the different registries, especially regarding the number of cases. During the seven years of data examined, 590 pleural mesotheliomas were diagnosed in the Valencian public health system. Of these, the number of cases that were related to occupational exposure was at least 437. Despite the legal duty of doctors to report such cases, only 31 were reported as suspected occupational disease (7.09%), of which only 13 were ultimately officially recognized as such. It was estimated that the annual economic overcost to the public system of unrecognised patients with this occupational disease by was 2,2270,520 euros.<br><br>CONCLUSIONS: Only a small proportion of occupational mesotheliomas are officially recognized as such. This has important health care and economic repercussions for the individuals involved as well as for the public health system.}, }
@article {pmid37916370, year = {2023}, author = {Aydogdu, G and Özekinci, S}, title = {Contribution of BAP1 loss and p16 (CDKN2A) deletion analysis to the definitive diagnosis of mesothelioma in effusion cytology.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {20}, pages = {10001-10007}, doi = {10.26355/eurrev_202310_34180}, pmid = {37916370}, issn = {2284-0729}, mesh = {Female ; Humans ; Male ; Middle Aged ; Biomarkers, Tumor/analysis ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor Proteins ; Homozygote ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/genetics ; *Mesothelioma/diagnosis/genetics/metabolism ; *Mesothelioma, Malignant ; *Pleural Neoplasms ; Sequence Deletion ; Tumor Suppressor Proteins/genetics/analysis ; Ubiquitin Thiolesterase/genetics ; Adult ; Aged ; Aged, 80 and over ; }, abstract = {OBJECTIVE: The cytological diagnosis of mesothelioma is a controversial issue, and definitive diagnosis often requires ancillary tests. The aim of this study was to investigate the contribution of BRCA1-associated protein (1) (BAP1) loss and p16 (CDKN2A) homozygous deletion (HD) on the early diagnosis of mesothelioma in effusion fluids.<br><br>MATERIALS AND METHODS: Between 2019-2022, 21 pleural and peritoneal fluid samples diagnosed with atypical mesothelial proliferation in our institution were included in the study. The slides of the cases that underwent BAP1 immunohistochemistry (IHC) were retrieved from the archive and re-examined. Homozygous deletion (HD) of p16 (CDKN2A) was investigated by the fluorescence in situ hybridization (FISH) method in cell blocks of cytology samples. At least 100 atypical mesothelial cells were counted in each case, and the HD threshold value was >10%.<br><br>RESULTS: The mean age of the cases was 63.47 years (34-90 years), female/male ratio was 3/1. Of the pleural mesothelioma cases, 16 were epithelioid, 2 were biphasic, and 1 were sarcomatoid. Two cases were diagnosed with peritoneal well-differentiated papillary mesothelioma (WDPM). BAP1 loss was observed in 11 (69%) of 16 cases. HD deletion of p16 (CDKN2A) was seen in 11 (58%) patients with FISH. The HD threshold value was 10-20% in 6 of the cases, 30-50% in 3 cases, and above 90% in 2 cases. While HD deletion was observed in p16 (CDKN2A) in all biphasic and sarcomatoid cases (n=3), no deletion was observed in peritoneal WDPM (n=2). Positivity was observed with at least one method in 12 (86%) of 14 pleural mesotheliomas who underwent both BAP1 IHC and p16 (CDKN2A) FISH. Due to technical reasons, the FISH signal could not be obtained in two cell blocks, so no results could be obtained.<br><br>CONCLUSIONS: Asbestos exposure in areas where mesothelioma is endemic and/or the presence of proliferating mesothelial cells in cytological examination are important clues for diagnosis. In controversial cases, BAP1 IHC should be the first step in an ancillary test. Although the FISH method applied to cell blocks has cytology-specific limitations and difficulties, investigating the p16 (CDKN2A) deletion with FISH in selected cases will contribute to the diagnosis.}, }
@article {pmid37901248, year = {2023}, author = {Qualiotto, AN and Baldavira, CM and Balancin, M and Ab'Saber, A and Takagaki, T and Capelozzi, VL}, title = {Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1268927}, pmid = {37901248}, issn = {1664-3224}, mesh = {Humans ; Male ; Female ; *Mesothelioma, Malignant ; B7-H1 Antigen/metabolism ; *Mesothelioma/drug therapy ; Mesothelin ; Tumor Microenvironment ; Collagen Type I ; *Pleural Neoplasms/drug therapy ; *Lung Neoplasms/pathology ; Neoplasm Recurrence, Local ; Risk Factors ; }, abstract = {BACKGROUND: The combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts.<br><br>METHODS: The discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin &amp; eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database.<br><br>RESULTS: Most patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15-10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09-6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58-9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival.<br><br>CONCLUSION: Tumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM.}, }
@article {pmid37899647, year = {2023}, author = {Yu, M and Yang, D and Chen, C and Xia, H}, title = {Effects of SETD2 on telomere length and malignant transformation property of Met-5A after one-month crocidolite exposure.}, journal = {Journal of environmental science and health. Part C, Toxicology and carcinogenesis}, volume = {41}, number = {3-4}, pages = {121-134}, doi = {10.1080/26896583.2023.2271822}, pmid = {37899647}, issn = {2689-6591}, mesh = {Humans ; *Aminobenzoates/metabolism/pharmacology ; *Asbestos, Crocidolite/toxicity/metabolism ; Cell Transformation, Neoplastic/chemically induced/metabolism/pathology ; Epithelium/metabolism/pathology ; Naphthalenes/metabolism/pharmacology ; *Histone-Lysine N-Methyltransferase/metabolism ; *Telomere Homeostasis ; }, abstract = {Crocidolite is a carcinogen contributing to the pathogenesis of malignant mesothelioma. This study aimed to characterize the possible telomere-related events mediating the malignant transformation of mesothelial cells with and without SETD2 under crocidolite exposure. The crocidolite concentration resulting in 90% viable SETD2 knockout Met-5A (Met-5A[SETD2-KO]) and Met-5A were estimated to be 0.71 μg/cm[2] and 1.8 μg/cm[2], respectively, during 72 h of exposure, which was further employed in chronical crocidolite exposure during a 72 h exposure interval per time up to 1 month. Chronical crocidolite-exposed Met-5A[SETD2-KO] (chronical Cro-Met-5A[SETD2-KO]) had higher colony formation and increased telomerase reverse transcriptase (TERT) protein levels than chronical crocidolite-exposed Met-5A (chronical Cro-Met-5A) and Met-5A[SETD2-KO]. Chronical Cro-Met-5A[SETD2-KO] had longer telomere length (TL) than chronical Cro-Met-5A, although there were no changes in TL for either chronical Cro-Met-5A or chronical Cro-Met-5A[SETD2-KO] compared with their corresponding cells without crocidolite exposure. BIBR 1532, an inhibitor targeting TERT, partially reduced colony formation and TL for chronical Cro-Met-5A[SETD2-KO], while BIBR 1532 reduced TL but had no effect on colony formation for chronical Cro-Met-5A. Therefore, SETD2 deficient mesothelial cells are susceptible to malignant transformation during chronical crocidolite exposure, and TERT-dependent TL modification likely partially drives SETD2 loss-mediated early onset of mesothelial malignant transformation.}, }
@article {pmid37898984, year = {2024}, author = {May, IJ and Nowak, AK and Francis, RJ and Ebert, MA and Dhaliwal, SS}, title = {The prognostic value of F18 Fluorothymidine positron emission tomography for assessing the response of malignant pleural mesothelioma to chemotherapy - A prospective cohort study.}, journal = {Journal of medical imaging and radiation oncology}, volume = {68}, number = {1}, pages = {57-66}, doi = {10.1111/1754-9485.13592}, pmid = {37898984}, issn = {1754-9485}, support = {//National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Humans ; *Mesothelioma, Malignant/diagnostic imaging ; Prognosis ; Prospective Studies ; Fluorodeoxyglucose F18 ; Talc ; Radiopharmaceuticals ; Positron-Emission Tomography/methods ; *Mesothelioma/diagnostic imaging/drug therapy ; Positron Emission Tomography Computed Tomography/methods ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is difficult to prognosticate. F18-Fluorodeoxyglucose positron emission tomography (FDG PET) shows promise for response assessment but is confounded by talc pleurodesis. F18-Fluorothymidine (FLT) PET is an alternative tracer specific for proliferation. We compared the prognostic value of FDG and FLT PET and determined the influence of talc pleurodesis on these parameters.<br><br>METHODS: Overall, 29 prospectively recruited patients had FLT PET, FDG PET and CT-scans performed prior to and post one chemotherapy cycle; 10 had prior talc pleurodesis. Patients were followed for overall survival. CT response was assessed using mRECIST. Radiomic features were extracted using the MiM software platform. Changes in maximum SUV (SUVmax), mean SUV (SUVmean), FDG total lesion glycolysis (TLG), FLT total lesion proliferation (TLP) and metabolic tumour volume (MTV) after one chemotherapy cycle.<br><br>RESULTS: Cox univariate analysis demonstrated FDG PET radiomics were confounded by talc pleurodesis, and that percentage change in FLT MTV was predictive of overall survival. Cox multivariate analysis showed a 10% increase in FLT tumour volume corresponded with 9.5% worsened odds for overall survival (P&#x2009;=&#x2009;0.028, HR&#x2009;=&#x2009;1.095, 95% CI [1.010, 1.187]). No other variables were significant on multivariate analysis.<br><br>CONCLUSION: This is the first prospective study showing the statistical significance of FLT PET tumour volumes for measuring mesothelioma treatment response. FLT may be better than FDG for monitoring mesothelioma treatment response, which could help optimise mesothelioma treatment regimes.}, }
@article {pmid37894824, year = {2023}, author = {Leinardi, R and Petriglieri, JR and Pochet, A and Yakoub, Y and Lelong, M and Lescoat, A and Turci, F and Lecureur, V and Huaux, F}, title = {Distinct Pro-Inflammatory Mechanisms Elicited by Short and Long Amosite Asbestos Fibers in Macrophages.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37894824}, issn = {1422-0067}, mesh = {Mice ; Animals ; *Asbestos, Amosite/toxicity ; Toll-Like Receptor 4 ; Macrophages ; *Asbestos/toxicity ; Apoptosis ; }, abstract = {While exposure to long amphibolic asbestos fibers (L > 10 µm) results in the development of severe diseases including inflammation, fibrosis, and mesothelioma, the pathogenic activity associated with short fibers (L < 5 µm) is less clear. By exposing murine macrophages to short (SFA) or long (LFA) fibers of amosite asbestos different in size and surface chemistry, we observed that SFA internalization resulted in pyroptotic-related immunogenic cell death (ICD) characterized by the release of the pro-inflammatory damage signal (DAMP) IL-1α after inflammasome activation and gasdermin D (GSDMD)-pore formation. In contrast, macrophage responses to non-internalizable LFA were associated with tumor necrosis factor alpha (TNF-α) release, caspase-3 and -7 activation, and apoptosis. SFA effects exclusively resulted from Toll-like receptor 4 (TLR4), a pattern-recognition receptor (PRR) recognized for its ability to sense particles, while the response to LFA was elicited by a multifactorial ignition system involving the macrophage receptor with collagenous structure (SR-A6 or MARCO), reactive oxygen species (ROS) cascade, and TLR4. Our findings indicate that asbestos fiber size and surface features play major roles in modulating ICD and inflammatory pathways. They also suggest that SFA are biologically reactive in vitro and, therefore, their inflammatory and toxic effects in vivo should not be underestimated.}, }
@article {pmid37889448, year = {2023}, author = {Lee, FW and Chen, YH and Tran, ND and Lin, CK and Pham, LA}, title = {Association between Asbestos Exposure and the Incidence of Kidney Cancer: a Weight-of-Evidence Evaluation and Meta-analysis.}, journal = {Current environmental health reports}, volume = {10}, number = {4}, pages = {394-409}, pmid = {37889448}, issn = {2196-5412}, mesh = {Humans ; *Mesothelioma/chemically induced/epidemiology ; Incidence ; *Asbestos/toxicity ; Asbestos, Amphibole ; *Occupational Exposure/adverse effects ; *Kidney Neoplasms/chemically induced/epidemiology/complications ; }, abstract = {PURPOSE OF REVIEW: Occupational asbestos exposure has been extensively linked to various cancers, with ongoing debates regarding its association with kidney cancer. This study aims to investigate the correlation between occupational asbestos exposure and kidney cancer incidence. Additionally, potential influencing factors are analyzed to enhance the comprehension of the relationship between asbestos exposure and kidney cancer.<br><br>RECENT FINDING: While asbestos has established strong associations with malignant mesothelioma and lung cancer, its connection to other malignancies such as gastric, colorectal, and kidney cancers remains under scrutiny. The current study presents mixed opinions on the relationship between asbestos exposure and kidney cancer. Our analysis revealed a potential association between asbestos exposure and the incidence of kidney cancer. Notably, among different types of asbestos, exposure to amphibole appeared to be particularly linked to a higher incident risk of kidney cancer.}, }
@article {pmid37880686, year = {2023}, author = {Carbone, M and Minaai, M and Takinishi, Y and Pagano, I and Yang, H}, title = {Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {749}, pmid = {37880686}, issn = {1479-5876}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; 1R01ES030948-01/ES/NIEHS NIH HHS/United States ; 1R01CA237235-01A1/CA/NCI NIH HHS/United States ; 1R01CA198138/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Asbestos/toxicity ; Carcinogenesis ; *HMGB1 Protein ; *Lung Neoplasms/genetics ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant/complications ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Mesothelioma is a cancer typically caused by asbestos. Mechanistically, asbestos carcinogenesis has been linked to the asbestos-induced release of HMGB1 from the nucleus to the cytoplasm, where HMGB1 promotes autophagy and cell survival, and to the extracellular space where HMGB1 promotes chronic inflammation and mesothelioma growth. Targeting HMGB1 inhibited asbestos carcinogenesis and the growth of mesothelioma. It is hoped that targeting HMGB1 will be a novel therapeutic strategy that benefits mesothelioma patients. Severe restrictions and/or a complete ban on the use of asbestos were introduced in the 80 and early 90s in the Western world. These measures have proven effective as the incidence of mesothelioma/per 100,000 persons is decreasing in these countries. However, the overall number of mesotheliomas in the Western world has not significantly decreased. There are several reasons for that which are discussed here: (1) the presence of asbestos in old constructions; (2) the development of rural areas containing asbestos or other carcinogenic mineral fibers in the terrain; (3) the discovery of an increasing fraction of mesotheliomas caused by germline genetic mutations of BAP1 and other tumor suppressor genes; (4) mesotheliomas caused by radiation therapy; (5) the overall increase in the population and of the fraction of older people who are much more susceptible to develop all types of cancers, including mesothelioma. In summary, the epidemiology of mesothelioma is changing, the ban on asbestos worked, there are opportunities to help mesothelioma patients especially those who develop in a background of germline mutations and there is the opportunity to prevent a mesothelioma epidemic in the developing world, where the use of asbestos is increasing exponentially. We hope that restrictive measures similar to those introduced in the Western world will soon be introduced in developing countries to prevent a mesothelioma epidemic.}, }
@article {pmid37878258, year = {2023}, author = {Vimercati, L and Cavone, D and Negrisolo, O and Pentimone, F and De Maria, L and Caputi, A and Sponselli, S and Delvecchio, G and Cafaro, F and Chellini, E and Binazzi, A and Di Marzio, D and Mensi, C and Consonni, D and Migliore, E and Brentisci, C and Martini, A and Negro, C and D'Agostin, F and Grappasonni, I and Pascucci, C and Benfatto, L and Malacarne, D and Casotto, V and Comiati, V and Storchi, C and Mangone, L and Murano, S and Rossin, L and Tallarigo, F and Vitale, F and Verardo, M and Eccher, S and Madeo, G and Staniscia, T and Carrozza, F and Cozzi, I and Romeo, E and Pelullo, P and Labianca, M and Melis, M and Cascone, G and Ferri, GM and Serio, G}, title = {Mesothelioma Risk Among Maritime Workers According to Job Title: Data From the Italian Mesothelioma Register (ReNaM).}, journal = {La Medicina del lavoro}, volume = {114}, number = {5}, pages = {e2023038}, pmid = {37878258}, issn = {0025-7818}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; *Mesothelioma/epidemiology/etiology ; *Military Personnel ; Italy/epidemiology ; *Asbestos/adverse effects ; }, abstract = {The study describes the 466 cases of malignant mesotheliomas (MM) collected by the National Mesothelioma Register (ReNaM) in Italy in the period 1993-2018 relating to subjects with exclusive asbestos exposure in merchant or military navy. The cases among maritime workers represent 1.8% of the total cases with defined exposure registred in the ReNaM, of which 212 cases (45.4%) among merchant maritime workers and 254 cases (54.5%) among navy. The distribution by site of mesothelioma showed 453 (97.2%) MM cases of the pleura, 11 (2.3%) of the peritoneum and 2 (0.4%) of the tunica vaginalis of the testis. With regard to occupational exposure, it was classified as certain in 318 (68.2%) cases, probable in 69 (14.8%) cases and possible in 79 (16.9%) cases. Among the 23 classified jobs, the highest percentages of certain exposures are among naval engineers, motor mechanics, machine captains and sailors. Machine crew accounted for 49.3% of the cases, deck crew for 27.6%. All cases began exposure on board between 1926 and 1988. Seamen were exposed to asbestos while at sea by virtue of living onboard ships and from continual release of asbestos fibers due to the motion of a vessel. Epidemiological surveillance through the ReNaM has allowed us to verify among cases in the maritime, navy and merchant marine sectors, that in the past, subjects were exposed regardless of the ship's department where have provided service therefore all these cases must be considered as occupational diseases.}, }
@article {pmid37873988, year = {2023}, author = {Bolgeo, T and Di Matteo, R and Crivellari, S and Gatti, D and Cassinari, A and Riccio, C and De Angelis, A and Delfanti, S and Ferrero, E and Gnani, C and Riili, G and Maconi, A}, title = {Quality of life in patients with PICC diagnosed with mesothelioma: Results of a multicenter epidemiological survey (LifePICC).}, journal = {The journal of vascular access}, volume = {}, number = {}, pages = {11297298231202046}, doi = {10.1177/11297298231202046}, pmid = {37873988}, issn = {1724-6032}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is a rare and aggressive cancer. PICC devices are widely used in cancer patients. The aim of the study is to evaluate the quality of life of patients with PICC diagnosed with PM treated at the Hospital of Casale Monferrato and Alessandria (Italy), an area with a high incidence of asbestos-related diseases.<br><br>STUDY DESIGN AND METHODS: Longitudinal prospective observational study with data collection at PICC insertion (T0), after 3&#x2009;months (T1), 6&#x2009;months (T2), and 9&#x2009;months (T3). Participants were aged >18&#x2009;years, diagnosed with PM, eligible for PICC insertion. Questionnaires used: EORTC QLQ-C30, EORTC QLQ-LC13, and HADS rating scale.<br><br>RESULTS: Twenty-eight patients were enrolled. The mean age was 68.93&#x2009;years (SD 9.13), mostly male (57.1%). The most frequent cancer stage at diagnosis was III (39.3%), then I (32.1%), and IV (21.4%). 85.7% were treated with chemotherapy, 14.3% also with immunotherapy. 96.4% of patients reported no complications during PICC implantation. The perception of health status and quality of life, measured on a scale of 1-7, was in line with an average score of 5 during the evaluation period. The total anxiety and depression score remained normal for most patients (0-7).<br><br>CONCLUSIONS: The PICC management involved a multidisciplinary team with different skills: study findings revealed the key role that dedicated nurses play in PICC placement and ensuring patient problems are promptly addressed. From our study results, PICC placement does not seem to negatively impact the patient's quality of life.}, }
@article {pmid37855384, year = {2024}, author = {Ferrante, D and Angelini, A and Barbiero, F and Barbone, F and Bauleo, L and Binazzi, A and Bovenzi, M and Bruno, C and Casotto, V and Cernigliaro, A and Ceppi, M and Cervino, D and Chellini, E and Curti, S and De Santis, M and Fazzo, L and Fedeli, U and Fiorillo, G and Franchi, A and Gangemi, M and Giangreco, M and Rossi, PG and Girardi, P and Luberto, F and Massari, S and Mattioli, S and Menegozzo, S and Merlo, DF and Michelozzi, P and Migliore, E and Miligi, L and Oddone, E and Pernetti, R and Perticaroli, P and Piro, S and Addario, SP and Romeo, E and Roncaglia, F and Silvestri, S and Storchi, C and Zona, A and Magnani, C and Marinaccio, A}, title = {Cause specific mortality in an Italian pool of asbestos workers cohorts.}, journal = {American journal of industrial medicine}, volume = {67}, number = {1}, pages = {31-43}, doi = {10.1002/ajim.23546}, pmid = {37855384}, issn = {1097-0274}, support = {//This work was supported by the 'INAIL BRIC project 2019-2021"; INAIL (Piano Ricerca 2016-2018, "Programma Speciale Amianto, BRIC id 55 and BRIC id 59) and 'Asbestos Project' organized by the Italian National Institute of Health (ISS) (Ricerca corrente 2012: Progetto amianto)./ ; }, mesh = {Male ; Humans ; Female ; Cause of Death ; *Mesothelioma/etiology ; Cohort Studies ; *Occupational Exposure/adverse effects ; *Occupational Diseases/etiology ; Construction Materials ; *Asbestos/adverse effects ; *Pleural Neoplasms ; *Peritoneal Neoplasms ; *Ovarian Neoplasms ; Italy/epidemiology ; *Lung Neoplasms/etiology ; }, abstract = {BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers.<br><br>METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period.<br><br>RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men&#x2009;=&#x2009;1.04, 95% confidence interval [CI] 1.03-1.05; women&#x2009;=&#x2009;1.15, 95% CI 1.11-1.18), all malignancies (SMR: men&#x2009;=&#x2009;1.21, 95% CI 1.18-1.23; women&#x2009;=&#x2009;1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR&#x2009;=&#x2009;10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR&#x2009;=&#x2009;27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men&#x2009;=&#x2009;1.28, 95% CI 1.24-1.32; women&#x2009;=&#x2009;1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR&#x2009;=&#x2009;1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter.<br><br>CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.}, }
@article {pmid37850051, year = {2023}, author = {Nishida, S and Toriyama, K and Yomota, M and Hosomi, Y}, title = {Malignant pleural mesothelioma with resolution of pleural effusion.}, journal = {Respirology case reports}, volume = {11}, number = {11}, pages = {e01234}, pmid = {37850051}, issn = {2051-3380}, abstract = {In malignant pleural mesothelioma patients, pleural effusion may improve during the course of the disease. Pleural effusion with nodular shadows bordering the pleura should be followed up even if the pleural effusion improves.}, }
@article {pmid37846453, year = {2023}, author = {Silvestri, S and Carnevale, F and Cavariani, F and Deidda, B}, title = {[The assessment of asbestos exposure of mesothelioma cases registered in Italy: which problems more than thirty years after the birth of the first regional archives].}, journal = {Epidemiologia e prevenzione}, volume = {47}, number = {4-5}, pages = {298-305}, doi = {10.19191/EP23.4-5.A617.070}, pmid = {37846453}, issn = {1120-9763}, mesh = {Humans ; *Occupational Exposure/adverse effects ; Population Surveillance ; Italy/epidemiology ; Registries ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Asbestos/toxicity ; *Pleural Neoplasms/diagnosis/epidemiology/etiology ; }, abstract = {More than 30 years have passed since the beginning of the epidemiological surveillance of mesothelioma (MM). The Italian National Mesothelioma Register (ReNaM), part of the research department of the National Institute for insurance against industrial injuries (INAIL), has published 7 reports with the description of the cas-es concerning the assessment of diagnoses and exposures to asbestos suffered mainly during working activities but also environmental, in the family premises and during personal activities.Today we are witnessing a reduction in the commitment by some regions which negatively affects those who develop the pathology. Reading the ReNaM reports it emerges, among others, the problem of the delay in reporting new cases which limits the collection of information directly from patients. This contribution, discussing various topics, invites to develop a debate that should allow to update and resolve the critical aspects that arise after decades of activity regarding, in particular, the asbestos exposure assessment. It is the primary interest of the authors to give continuity and improve the ReNaM which remains the most prestigious MM register among those active in other countries.}, }
@article {pmid37846448, year = {2023}, author = {Angelini, A and Martini, A and Begliomini, B and Silvestri, S}, title = {[Malignant mesothelioma in two married couples exposed to asbestos].}, journal = {Epidemiologia e prevenzione}, volume = {47}, number = {4-5}, pages = {257-262}, doi = {10.19191/EP23.4-5.A623.065}, pmid = {37846448}, issn = {1120-9763}, mesh = {Humans ; Female ; *Mesothelioma, Malignant ; *Mesothelioma/chemically induced/diagnosis/epidemiology ; Spouses ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology ; Italy/epidemiology ; *Asbestos/toxicity ; *Lung Neoplasms/chemically induced/diagnosis/epidemiology ; *Occupational Diseases/epidemiology ; }, abstract = {BACKGROUND: the relationship between past asbestos exposure and the onset of malignant mesothelioma (MM) is well established. However, defining the exposure is not always easy, as it occurs decades before the onset of the disease.<br><br>OBJECTIVES: this report describes four cases of MM diagnosed in two different married couples, both exposed to asbestos fibers: husbands at work and wives for cohabiting and washing their work overalls.<br><br>DESIGN: case report.<br><br>METHODS: the information was collected through interviews using a semi-structured questionnaire and analyzed by occupational hygienists during the activity of epidemiological surveillance of this disease. The results of the mineral content of asbestos fibers performed on lung parenchymal from one of the female cases are available.<br><br>RESULTS: these two cases show a longer latency in the lesser exposed confirming what an occupational epidemiological study has recently highlighted.<br><br>CONCLUSIONS: whenever good quality information collected during interviews are available, skilled occupational hygienists are able to reconstruct past exposures in quali-quantitative terms.}, }
@article {pmid37845104, year = {2023}, author = {Kaplan, MA and Şendur, MAN and Cangır, AK and Fırat, P and Göker, E and Kılıçkap, S and Oyan, B and Büge Öz, A and Özdemir, F and Özyiğit, G}, title = {Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group.}, journal = {Current problems in cancer}, volume = {47}, number = {6}, pages = {101017}, doi = {10.1016/j.currproblcancer.2023.101017}, pmid = {37845104}, issn = {1535-6345}, mesh = {Humans ; Immunotherapy ; *Mesothelioma/therapy/drug therapy ; Pleura/pathology ; *Pleural Neoplasms/therapy/drug therapy ; Turkey/epidemiology ; }, abstract = {Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.}, }
@article {pmid37813485, year = {2023}, author = {Marinaccio, A and Di Marzio, D and Mensi, C and Consonni, D and Gioscia, C and Migliore, E and Genova, C and Rossetto Giaccherino, R and Eccher, S and Murano, S and Comiati, V and Casotto, V and Negro, C and Mangone, L and Miligi, L and Piro, S and Angelini, A and Grappasonni, I and Madeo, G and Cozzi, I and Ancona, L and Staniscia, T and Carrozza, F and Cavone, D and Vimercati, L and Labianca, M and Tallarigo, F and Cascone, G and Melis, M and Bonafede, M and Scarselli, A and Binazzi, A}, title = {Incidence of mesothelioma in young people and causal exposure to asbestos in the Italian national mesothelioma registry (ReNaM).}, journal = {Occupational and environmental medicine}, volume = {80}, number = {11}, pages = {603-609}, doi = {10.1136/oemed-2023-108983}, pmid = {37813485}, issn = {1470-7926}, mesh = {Humans ; Adolescent ; Middle Aged ; *Mesothelioma, Malignant/complications ; Incidence ; *Mesothelioma/epidemiology/etiology ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects ; Italy/epidemiology ; Registries ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {INTRODUCTION: The epidemiological surveillance of mesothelioma incidence is a crucial key for investigating the occupational and environmental sources of asbestos exposure. The median age at diagnosis is generally high, according to the long latency of the disease. The purposes of this study are to analyse the incidence of mesothelioma in young people and to evaluate the modalities of asbestos exposure.<br><br>METHODS: Incident malignant mesothelioma (MM) cases in the period 1993-2018 were retrieved from Italian national mesothelioma registry and analysed for gender, incidence period, morphology and exposure. Age-standardised rates have been calculated and the multiple correspondence analysis has been performed. The association between age and asbestos exposure has been tested by &#x3c7;[2] test.<br><br>RESULTS: From 1993 to 2018, 30&#x2009;828 incident MM cases have been collected and 1278 (4.1%) presented diagnosis at early age (&#x2264;50 years). There is a substantial association between age at diagnosis and the type of asbestos exposure and a significantly lower frequency of cases with occupational exposure to asbestos (497 cases vs 701 expected) in young people has been documented. Paraoccupational and environmental exposure to asbestos have been found more frequent in young MM cases (85 and 93 observed cases vs 52 and 44 expected cases, respectively).<br><br>CONCLUSIONS: Mesothelioma incidence surveillance at population level and the anamnestic individual research of asbestos exposure is a fundamental tool for monitoring asbestos exposure health effects, supporting the exposure risks prevention policies. Clusters of mesothelioma incident cases in young people are a significant signal of a potential non-occupational exposure to asbestos.}, }
@article {pmid37824368, year = {2024}, author = {Tuncel, T and Metintas, M and Güntülü, AK and Güneş, HV}, title = {Whole-Genome Comparative Copy Number Alteration Profiling between Malignant Pleural Mesothelioma and Asbestos-Induced Chronic Pleuritis.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {43}, number = {1}, pages = {31-44}, doi = {10.1615/JEnvironPatholToxicolOncol.2023047755}, pmid = {37824368}, issn = {2162-6537}, mesh = {Humans ; *Mesothelioma, Malignant ; DNA Copy Number Variations ; *Asbestos/toxicity ; *Pleurisy/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is rare and aggressive cancer. The most important risk factor for MPM is exposure to asbestos. In this study, we scanned the genomes of individuals MPM and asbestos-induced chronic pleuritis (AICP) to compare and determine copy number alterations (CNAs) between two asbestos-related diseases. We used high-resolution SNP arrays to compare CNA profiles between MPM (n = 55) and AICP (n = 18). DNAs extracted from pleural tissues in both groups. SNP array analysis revealed common losses at 1p, 3p, 6q, 9p, 13q, 14q, 15q, 16q, 22q and frequent gains at chromosomes 1, 3, 5, 7, 8, and 6p, 12q, 15q, 17p, 20q in MPMs (frequencies max 67%-min 30%; these alterations were not detected in AICPs. Besides detecting well-known MPM-associated CNAs, our high -resolution copy number profiling also detected comparatively rare CNAs for MPMs including losses like 9q33.3, 16q and gains of 1p, 1q, 3p, 3q, 6p, 7q, 15q, 12q, 17p, 20q at significant frequencies in the MPM cohort. We also observed Copy Number gains clustered on the NF2 locus in AICPs, whereas this region was commonly deleted in MPMs. According to this distinct genomic profiles between the two groups, AICPs genomes can be clearly distinguished from highly altered MPM genomes. Hence, we can suggest that SNP arrays can be used as a supporting diagnostic tool in terms of discriminating asbestos-related malignant disease such as MPM and benign pleural lesions, which can be challenging in most instances.}, }
@article {pmid37811036, year = {2023}, author = {Mehta, K and Mehta, S and Joshi, M and Bharadwaj, HR and Ardeshana, G and Tenkorang, PO}, title = {Challenging diagnosis of sarcomatoid hepatic mesothelioma: a case report with review of literature.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {10}, pages = {5123-5126}, pmid = {37811036}, issn = {2049-0801}, abstract = {INTRODUCTION: Mesothelioma is a rare and aggressive cancer that is primarily caused by asbestos exposure. However, cases of mesothelioma without asbestos exposure suggest the involvement of other risk factors. Sarcomatoid mesothelioma, which is characterized by spindle-shaped cells, is a particularly aggressive subtype with limited treatment options.<br><br>CASE PRESENTATION: The authors present a case of a 72-year-old man with no history of asbestos exposure who presented with abdominal pain, fatigue, and weight loss. Imaging revealed a large cystic mass in the liver. A Liver biopsy confirmed the diagnosis of sarcomatoid mesothelioma. Immunohistochemistry results further supported this diagnosis. Due to the advanced stage and tumor size, surgical resection was not feasible. Palliative chemotherapy was initiated, but the patient's condition deteriorated rapidly, leading to his demise.<br><br>CONCLUSION: This case highlights the complexity of mesothelioma and the need for further research to identify the nonasbestos-related risk factors. Understanding alternative causative agents and mechanisms is crucial for the early detection, the development of targeted therapies, and improving patient outcomes. The presented case contributes to the existing literature and aligns with the Surgical CAse REport (SCARE) Criteria.}, }
@article {pmid37810608, year = {2023}, author = {Ramos-Bonilla, JP and Giraldo, M and Marsili, D and Pasetto, R and Terracini, B and Mazzeo, A and Magnani, C and Comba, P and Lysaniuk, B and Cely-García, MF and Ascoli, V}, title = {An Approach to Overcome the Limitations of Surveillance of Asbestos Related Diseases in Low- and Middle-Income Countries: What We Learned from the Sibaté Study in Colombia.}, journal = {Annals of global health}, volume = {89}, number = {1}, pages = {64}, pmid = {37810608}, issn = {2214-9996}, mesh = {Humans ; Colombia/epidemiology ; Developing Countries ; *Occupational Exposure/adverse effects ; *Asbestos ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Respiratory Distress Syndrome ; }, abstract = {INTRODUCTION: The asbestos industry began its operations in Colombia in 1942 with the establishment of an asbestos-cement facility in Sibaté, located in the Department of Cundinamarca. Despite extensive asbestos use and production in Colombia, the country lacks a reliable epidemiological surveillance system to monitor the health effects of asbestos exposure. The Colombian health information system, known as SISPRO, did not report mesothelioma cases diagnosed in the municipality, posing a significant challenge in understanding the health impacts of asbestos exposure on the population of Sibaté.<br><br>METHODS: To address this issue, an active surveillance strategy was implemented in Sibat&#xe9;. This strategy involved conducting door-to-door health and socioeconomic structured interviews to identify Asbestos-Related Diseases (ARDs). Validation strategies included a thorough review of medical records by a panel of physicians, and the findings were communicated to local, regional, and national authorities, as well as the general population.<br><br>RESULTS: The active surveillance strategy successfully identified a mesothelioma cluster in Sibat&#xe9;, revealing the inadequacy of the existing health information system in monitoring asbestos-related diseases. The discovery of this cluster underscores the critical importance of implementing active surveillance strategies in Colombia, where governmental institutions and resources are often limited.<br><br>CONCLUSION: The findings of this study emphasize the urgent need for Colombia to establish a reliable epidemiological surveillance system for asbestos-related diseases (ARDs). Active surveillance strategies can play a crucial role in identifying mesothelioma clusters and enhancing our understanding of the health effects of asbestos exposure in low- and middle-income countries.}, }
@article {pmid37802348, year = {2024}, author = {Takefuji, Y}, title = {An urgent call to action: The absolute necessity to ban asbestos production and sales.}, journal = {The Science of the total environment}, volume = {906}, number = {}, pages = {167557}, doi = {10.1016/j.scitotenv.2023.167557}, pmid = {37802348}, issn = {1879-1026}, mesh = {Humans ; *Occupational Exposure ; *Asbestos ; *Mesothelioma/epidemiology ; Health Policy ; Dust ; }, abstract = {The issue with asbestos highlights the shortcomings in the global management of health policies for dangerous substances. The perils of asbestos dust were identified about a century ago. A significant number of individuals succumb to asbestos-related diseases worldwide annually. A considerable portion of occupational cancer fatalities are believed to be due to asbestos. A large population across the globe is exposed to asbestos in their workplaces. To address issues like asbestos, it is crucial for policymakers to prioritize public interest, and third parties should actively participate in scrutinizing the actions of these policymakers.}, }
@article {pmid37800384, year = {2023}, author = {Sahin, ER and Koksal, D}, title = {Asbestos: Mineralogical features and fiber analysis in biological materials.}, journal = {Archives of environmental &amp; occupational health}, volume = {78}, number = {6}, pages = {369-378}, doi = {10.1080/19338244.2023.2264764}, pmid = {37800384}, issn = {2154-4700}, mesh = {Humans ; *Asbestos ; *Mesothelioma/chemically induced ; *Asbestosis/etiology ; *Lung Neoplasms/chemically induced ; *Mesothelioma, Malignant/complications ; }, abstract = {Asbestos is a mineral with unique physical and chemical properties that make it highly resistant to heat, fire, and corrosion. Nevertheless, exposure to asbestos fibers has been linked to serious health problems, including lung cancer, mesothelioma, and asbestosis. Despite the ban on asbestos usage, asbestos-related diseases are still a major cause of morbidity and mortality worldwide. Analyzing the mineralogical features and fiber analysis of asbestos in biological materials is critical for scenarios where an asbestos exposure history cannot be obtained, a clinical diagnosis cannot be made, or legal aspects necessitate further investigation. This review outlines the mineralogical features and fiber analysis techniques of asbestos in biological materials.}, }
@article {pmid37793939, year = {2023}, author = {Ibnian, AM and Khan, OU and Chan, R and Bangalore Lakshminarayana, U and Kiran, F and Abed, S and Abbas, R and Amir, A and Al-Kofahi, NK}, title = {Gelatinous Pleural Effusion: A Diagnostic Challenge for Pleural Mesothelioma in an 80-Year-Old Man.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e941263}, pmid = {37793939}, issn = {1941-5923}, mesh = {Male ; Humans ; Aged, 80 and over ; *Mesothelioma/diagnosis/pathology ; *Pleural Neoplasms/diagnosis ; *Pleural Effusion/diagnostic imaging/etiology ; Pleura/pathology ; *Asbestos ; *Pleural Diseases ; }, abstract = {BACKGROUND Gelatinous pleural effusion, due to raised hyaluronic acid, can be associated with pleural infection and malignancies, such as tuberculosis, metastatic pleural disease, and mesothelioma. This report is of an 80-year-old man presenting with a gelatinous pleural effusion and diagnosis of pleural mesothelioma. CASE REPORT An 80-year-old man with diabetes mellitus, ischemic heart disease, metastatic prostate cancer, 30-pack-year smoking history, and 5-year history of asbestos exposure (during his 30s), presented with a 4-week history of breathlessness and was found to have right-sided pleural effusion. Thoracic computed tomography (CT) showed mild right-sided pleural thickening. Pleural tap revealed exudative fluid, with a pH of 7.4, and unremarkable cytology and microbiology analyses. The patient was treated for pneumonia and para-pneumonic effusion and discharged home. He came back 5 weeks later with worsening of symptoms and re-accumulation of pleural fluid. Repeated thorax CT showed extensive right-sided pleural lobular thickening. Pleural tap again yielded an exudative fluid, with a pH of 7.37. Cytology and microbiology did not reveal any positive signs for malignancy or infection. This time the pleural fluid appeared gelatinous in consistency. Pleural biopsy showed atypical epithelioid mesothelial cells arranged in trabeculae, with a tubulo-papillary configuration. Also, immunohistochemistry panel showed tumor cells expressed calretinin, EMA, WT1, and D2-40, with negative TTF1, CEA, and BerEp4. Final diagnosis was epithelioid mesothelioma. CONCLUSIONS This report has shown that a gelatinous pleural effusion can be associated with malignant and inflammatory pleural diseases. In this case, imaging and pleural biopsy with histopathology confirmed a diagnosis of pleural mesothelioma.}, }
@article {pmid37730104, year = {2023}, author = {Schelch, K and Emminger, D and Zitta, B and Johnson, TG and Kopatz, V and Eder, S and Ries, A and Stefanelli, A and Heffeter, P and Hoda, MA and Hoetzenecker, K and Dome, B and Berger, W and Reid, G and Grusch, M}, title = {Targeting YB-1 via entinostat enhances cisplatin sensitivity of pleural mesothelioma in vitro and in vivo.}, journal = {Cancer letters}, volume = {574}, number = {}, pages = {216395}, doi = {10.1016/j.canlet.2023.216395}, pmid = {37730104}, issn = {1872-7980}, support = {DOC 59/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {*Cisplatin/pharmacology ; Animals ; Humans ; *Pyridines/pharmacology ; *Benzamides/pharmacology ; Cell Line, Tumor ; *Y-Box-Binding Protein 1/metabolism/genetics ; *Pleural Neoplasms/drug therapy/pathology/genetics/metabolism ; *Xenograft Model Antitumor Assays ; *Drug Synergism ; *Mesothelioma/drug therapy/pathology/metabolism/genetics ; Mice ; Cell Proliferation/drug effects ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Mice, Nude ; Antineoplastic Agents/pharmacology ; Acetylation ; Female ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {Pleural mesothelioma (PM) is characterized by poor prognosis and limited therapeutic options. Y-box-binding protein 1 (YB-1) was shown to drive growth and migration of PM cells. Here, we evaluated the effect of genetic and pharmacological targeting of YB-1 on PM growth and response to cisplatin and radiation treatment. YB-1 knockdown via siRNA resulted in reduced PM cell growth, which significantly correlated with wt BAP1 and mutant NF2 and P53 status. Entinostat inhibited YB-1 deacetylation and its efficacy correlated with YB-1 knockdown-induced growth inhibition in 20 PM cell lines. Tumor growth inhibition by siRNA as well as entinostat was confirmed in mouse xenotransplant models. Furthermore, both YBX1-targeting siRNA and entinostat enhanced sensitivity to cisplatin and radiation. In particular, entinostat showed strong synergistic interactions with cisplatin which was linked to significantly increased cellular platinum uptake in all investigated cell models. Importantly, in a mouse model, the combination of cisplatin and entinostat also resulted in stronger growth inhibition than each treatment alone. Our study highlights YB-1 as an attractive target in PM and demonstrates that targeting YB-1 via entinostat is a promising approach to enhance cisplatin and radiation sensitivity.}, }
@article {pmid37729199, year = {2023}, author = {Suarez, JS and Novelli, F and Goto, K and Ehara, M and Steele, M and Kim, JH and Zolondick, AA and Xue, J and Xu, R and Saito, M and Pastorino, S and Minaai, M and Takanishi, Y and Emi, M and Pagano, I and Wakeham, A and Berger, T and Pass, HI and Gaudino, G and Mak, TW and Carbone, M and Yang, H}, title = {HMGB1 released by mesothelial cells drives the development of asbestos-induced mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {39}, pages = {e2307999120}, pmid = {37729199}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; S10 OD028515/OD/NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Mesothelioma, Malignant ; Tumor Necrosis Factor-alpha/genetics ; *HMGB1 Protein/genetics ; *Mesothelioma/chemically induced/genetics ; *Asbestos/toxicity ; Inflammation ; Tumor Microenvironment ; }, abstract = {Asbestos is the main cause of malignant mesothelioma. Previous studies have linked asbestos-induced mesothelioma to the release of HMGB1 from the nucleus to the cytoplasm, and from the cytoplasm to the extracellular space. In the cytoplasm, HMGB1 induces autophagy impairing asbestos-induced cell death. Extracellularly, HMGB1 stimulates the secretion of TNFα. Jointly, these two cytokines kick-start a chronic inflammatory process that over time promotes mesothelioma development. Whether the main source of extracellular HMGB1 were the mesothelial cells, the inflammatory cells, or both was unsolved. This information is critical to identify the targets and design preventive/therapeutic strategies to interfere with asbestos-induced mesothelioma. To address this issue, we developed the conditional mesothelial HMGB1-knockout (Hmgb1[ΔpMeso]) and the conditional myelomonocytic-lineage HMGB1-knockout (Hmgb1[ΔMylc]) mouse models. We establish here that HMGB1 is mainly produced and released by the mesothelial cells during the early phases of inflammation following asbestos exposure. The release of HMGB1 from mesothelial cells leads to atypical mesothelial hyperplasia, and in some animals, this evolves over the years into mesothelioma. We found that Hmgb1[ΔpMeso], whose mesothelial cells cannot produce HMGB1, show a greatly reduced inflammatory response to asbestos, and their mesothelial cells express and secrete significantly reduced levels of TNFα. Moreover, the tissue microenvironment in areas of asbestos deposits displays an increased fraction of M1-polarized macrophages compared to M2 macrophages. Supporting the biological significance of these findings, Hmgb1[ΔpMeso] mice showed a delayed and reduced incidence of mesothelioma and an increased mesothelioma-specific survival. Altogether, our study provides a biological explanation for HMGB1 as a driver of asbestos-induced mesothelioma.}, }
@article {pmid37722697, year = {2024}, author = {Febres-Aldana, CA and Fanaroff, R and Offin, M and Zauderer, MG and Sauter, JL and Yang, SR and Ladanyi, M}, title = {Diffuse Pleural Mesothelioma: Advances in Molecular Pathogenesis, Diagnosis, and Treatment.}, journal = {Annual review of pathology}, volume = {19}, number = {}, pages = {11-42}, doi = {10.1146/annurev-pathol-042420-092719}, pmid = {37722697}, issn = {1553-4014}, mesh = {Humans ; *Mesothelioma ; Risk Factors ; }, abstract = {Diffuse pleural mesothelioma (DPM) is a highly aggressive malignant neoplasm arising from the mesothelial cells lining the pleural surfaces. While DPM is a well-recognized disease linked to asbestos exposure, recent advances have expanded our understanding of molecular pathogenesis and transformed our clinical practice. This comprehensive review explores the current concepts and emerging trends in DPM, including risk factors, pathobiology, histologic subtyping, and therapeutic management, with an emphasis on a multidisciplinary approach to this complex disease.}, }
@article {pmid37712235, year = {2023}, author = {Bruno, C and Di Stefano, R and Ricceri, V and La Rosa, M and Cernigliaro, A and Ciranni, P and Di Maria, G and Mandrioli, D and Zona, A and Comba, P and Scondotto, S}, title = {Fluoro-edenite non-neoplastic diseases in Biancavilla (Sicily, Italy): pleural plaques and/or pneumoconiosis?.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {59}, number = {3}, pages = {187-193}, doi = {10.4415/ANN_23_03_03}, pmid = {37712235}, issn = {2384-8553}, mesh = {Humans ; Sicily/epidemiology ; *Asbestosis/diagnostic imaging/epidemiology ; Asbestos, Amphibole/toxicity ; Italy/epidemiology ; *Pneumoconiosis/diagnostic imaging/epidemiology ; *Mesothelioma/diagnostic imaging/epidemiology ; }, abstract = {BACKGROUND: A mesothelioma cluster in Biancavilla (Sicily, Italy), drew attention to fluoro-edenite, a fibre classified by International Agency for Research on Cancer as carcinogenic to humans. Significant excesses in mortality and morbidity were observed for respiratory diseases and a significant excess of pneumoconiosis hospitalizations was reported.<br><br>OBJECTIVE: Aim of this study is to assess the characters of the lung damage in Biancavilla residents hospitalized with pneumoconiosis or asbestosis diagnoses.<br><br>METHODOLOGY: Medical records, available radiographs and computed tomography scans were collected. The obtained imaging was reviewed by a panel of three specialists and focused on pleural and parenchymal abnormalities. Cases with an ILO-BIT or ICOERD score equal or greater than 2 were considered positive for a pneumoconiosis-like damage, cases with a score lower than 2 or insufficient quality of imaging were considered inconclusive. If no pneumoconiotic aspects were present the cases were classified as negative.<br><br>RESULTS: Out of 38 cases, diagnostic imaging for 25 cases were found. Ten cases out of 25 showed asbestosis-like features, nine subjects were considered negative. In six patients' results were inconclusive.<br><br>CONCLUSIONS: Asbestosis-like features were substantiated in Biancavilla residents without known occupational exposure to asbestos. Further studies to estimate population respiratory health are required. Experimental studies on the fibrogenic potential of fluoro-edenite are needed.}, }
@article {pmid37692737, year = {2023}, author = {Alsalihi, Y and Kandaswamy, C}, title = {A Worsening Cough: An Unusual Presentation of Malignant Mesothelioma.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e43205}, pmid = {37692737}, issn = {2168-8184}, abstract = {Localized malignant pleural mesothelioma (LMPM) is a rare cancer with poor survival rates. Often affecting males with asbestos exposure, we report a case of a 56-year-old female with no history of occupational exposure presenting with a worsening cough. A radiological examination revealed left pleural effusion and pleural thickening. Cytological and pathological reports of pleural samples were consistent with malignant mesothelioma of epithelioid type, with the histological examination via video-assisted thoracoscopic surgery (VATS) consistent with a clear cell epithelioid mesothelioma. We discuss the rapid presentation of the disease with emphasis on considering the disease in young patients with no prior asbestos exposure.}, }
@article {pmid37683624, year = {2023}, author = {Zwijsen, K and Schillebeeckx, E and Janssens, E and Cleemput, JV and Richart, T and Surmont, VF and Nackaerts, K and Marcq, E and van Meerbeeck, JP and Lamote, K}, title = {Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results.}, journal = {Journal of breath research}, volume = {17}, number = {4}, pages = {}, doi = {10.1088/1752-7163/acf7e3}, pmid = {37683624}, issn = {1752-7163}, mesh = {Humans ; Breath Tests ; *Mesothelioma/diagnostic imaging ; *Pleural Neoplasms/diagnostic imaging ; *Asbestos/adverse effects ; *Body Fluids ; }, abstract = {Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).}, }
@article {pmid37676382, year = {2024}, author = {Gabelloni, M and Faggioni, L and Brunese, MC and Picone, C and Fusco, R and Aquaro, GD and Cioni, D and Neri, E and Gandolfo, N and Giovagnoni, A and Granata, V}, title = {An overview on multimodal imaging for the diagnostic workup of pleural mesothelioma.}, journal = {Japanese journal of radiology}, volume = {42}, number = {1}, pages = {16-27}, pmid = {37676382}, issn = {1867-108X}, mesh = {Humans ; Neoplasm Staging ; *Mesothelioma/diagnostic imaging/etiology ; *Pleural Neoplasms/diagnostic imaging/pathology ; Risk Factors ; Multimodal Imaging ; }, abstract = {Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic and therapeutic viewpoint. Despite recent improvements in patient care, PM typically carries a poor outcome, especially in advanced stages. Therefore, a timely and effective diagnosis taking advantage of currently available imaging techniques is essential to perform an accurate staging and dictate the most appropriate treatment strategy. Our aim is to provide a brief, but exhaustive and up-to-date overview of the role of multimodal medical imaging in the management of PM.}, }
@article {pmid37673586, year = {2023}, author = {Eastwood, M and Marc, ST and Gao, X and Sailem, H and Offman, J and Karteris, E and Fernandez, AM and Jonigk, D and Cookson, W and Moffatt, M and Popat, S and Minhas, F and Robertus, JL}, title = {Malignant Mesothelioma subtyping via sampling driven multiple instance prediction on tissue image and cell morphology data.}, journal = {Artificial intelligence in medicine}, volume = {143}, number = {}, pages = {102628}, doi = {10.1016/j.artmed.2023.102628}, pmid = {37673586}, issn = {1873-2860}, support = {30731/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Mesothelioma, Malignant ; Neural Networks, Computer ; Recognition, Psychology ; }, abstract = {Malignant Mesothelioma is a difficult to diagnose and highly lethal cancer usually associated with asbestos exposure. It can be broadly classified into three subtypes: Epithelioid, Sarcomatoid, and a hybrid Biphasic subtype in which significant components of both of the previous subtypes are present. Early diagnosis and identification of the subtype informs treatment and can help improve patient outcome. However, the subtyping of malignant mesothelioma, and specifically the recognition of transitional features from routine histology slides has a high level of inter-observer variability. In this work, we propose an end-to-end multiple instance learning (MIL) approach for malignant mesothelioma subtyping. This uses an adaptive instance-based sampling scheme for training deep convolutional neural networks on bags of image patches that allows learning on a wider range of relevant instances compared to max or top-N based MIL approaches. We also investigate augmenting the instance representation to include aggregate cellular morphology features from cell segmentation. The proposed MIL approach enables identification of malignant mesothelial subtypes of specific tissue regions. From this a continuous characterisation of a sample according to predominance of sarcomatoid vs epithelioid regions is possible, thus avoiding the arbitrary and highly subjective categorisation by currently used subtypes. Instance scoring also enables studying tumor heterogeneity and identifying patterns associated with different subtypes. We have evaluated the proposed method on a dataset of 234 tissue micro-array cores with an AUROC of 0.89±0.05 for this task. The dataset and developed methodology is available for the community at: https://github.com/measty/PINS.}, }
@article {pmid37667155, year = {2023}, author = {Yang, YX and Zhang, DK and Lu, HY and Zhao, XL and Yu, H}, title = {[Change trends and related risk factors of disease burden on mesothelioma in Jiangsu Province from 1990 to 2019].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {8}, pages = {594-600}, doi = {10.3760/cma.j.cn121094-20220815-00400}, pmid = {37667155}, issn = {1001-9391}, support = {H2017018//Medical Research Topic of Jiangsu Commission of Health/ ; }, mesh = {Female ; Male ; Humans ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Risk Factors ; Cost of Illness ; *Occupational Exposure ; }, abstract = {Objective: To analyze the change trends and risk factors of mesothelioma disease burden in Jiangsu Province from 1990 to 2019. Methods: In January 2022, using the 2019 Global Burden of Disease Study Data, the Joinpoint regression model was used to analyze the change trends of incidence, mortality, disable-adjusted life years (DALY) and premature mortality of mesothelioma residents in Jiangsu Province from 1990 to 2019, and the attribution level of mesothelioma risk factors was estimated by population attributing fraction. Results: The standardized incidence rates of mesothelioma in Jiangsu Province from 1990 to 2019 ranged from 0.07/10(5) to 0.09/10(5), with an average annual percentage change (AAPC) of -1.1% (t=-13.56, P<0.001). AAPCs in males and females were -0.3% (t=-2.18, P=0.029) and -1.6% (t=-11.39, P<0.001), respectively. The standardized mortality rates of mesothelioma ranged from 0.07/10(5) to 0.09/10(5), the AAPC was -1.1% (t=-12.23, P<0.001), AAPC was -1.6% (t=-14.09, P<0.001) for females, and there was no significant change in males (t=-1.83, P=0.068). The premature mortality was 0.004%-0.006%, the AAPC was -1.0% (t=-4.40, P<0.001), AAPC was -1.7% (t=-13.72, P<0.001) for females, and there was no significant change in males (t=-0.68, P=0.495). The standardized DALY rates ranged from 1.86/10(5) to 2.32/10(5), the AAPC was -0.9% (t=-11.08, P<0.001), AAPC was -1.6% (t=-11.05, P<0.001) for females, and there was no significant change in males (t=-0.95, P=0.343). Both the standardized years of life lost (YLL) rate and the standardized years lived with disability (YLD) rate showed a decreasing trend, and the AAPCs were -0.9% (t=-7.66, P<0.001) and -1.0% (t=-12.88, P<0.001), respectively. The proportion of YLL in DALY was more than 98.5%. Among the risk factors for mesothelioma burden attribution, the AAPC attributed to occupational asbestos exposure of DALY was 1.4% (t=3.43, P=0.001). The AAPC of DALY rate of standardized attribution was -1.7% (t=-12.11, P<0.001) . Conclusion: The overall burden of mesothelioma in Jiangsu Province is decreasing, occupational asbestos exposure is still the main risk factor of mesothelioma in Jiangsu Province, and early diagnosis and treatment should be strengthened.}, }
@article {pmid37664365, year = {2023}, author = {Sousa, B and Silva, J and Monteiro, N and Romano, M and Araújo, E}, title = {Malignant Peritoneal Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e42902}, pmid = {37664365}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare tumor of the serous membranes of the peritoneum and has been linked to exposure to asbestos and other risk factors. The clinical manifestations are vague, with a wide clinical spectrum, predominantly related to the abdominal involvement of the disease. Localized mesothelioma is an uncommon manifestation of the disease. Common symptoms include abdominal pain or abdominal distention, nausea, anorexia, and weight loss. Rarely, patients present with paraneoplastic syndrome. Due to the nonspecific symptoms, many patients already have advanced disease at the time of diagnosis. The authors report a case of a 75-year-old female patient who presented with symptoms of asthenia, anorexia, progressive paleness, and weight loss lasting five months. She reports later new-onset symptoms of diffuse abdominal pain and diarrhea associated with nausea. Laboratory tests showed anemia, mild leukocytosis, thrombocytosis, elevated C-reactive protein (CRP), and elevated liver enzymes. An abdominal and pelvic computed tomography (CT) scan revealed marked tissue thickening of an irregular and striated configuration of the leaflets and peritoneal reflections in an omental cake pattern, and a chest CT scan showed multiple bilateral pulmonary nodules, suggesting diffuse malignant disease. A CT-guided biopsy of a peritoneal implant was performed, establishing the diagnosis of malignant peritoneal mesothelioma. Due to rapid clinical deterioration, the patient did not receive any systemic treatment, surgery, or radiotherapy and was transitioned to comfort care. As in the presented case, most cases of MPM have diffuse peritoneal involvement at the time of diagnosis, although extra-abdominal involvement is very rare. This disease presentation is associated with high morbidity and mortality compared to cases of localized disease. There is no specific imaging diagnostic modality or valuable tumor markers for MPM. Although a CT scan remains important in the diagnostic approach, the changes found are not specific. Radiographically, MPM may present as mesenteric or parietal peritoneal nodules, visceral peritoneal thickening, ascites, or omental masses. Although these features may raise suspicion of MPM, a biopsy is necessary to confirm the diagnosis. Therefore, due to the rarity of this disease and its nonspecific signs or symptoms, MPM is difficult to diagnose, and the prognosis remains poor.}, }
@article {pmid37658846, year = {2023}, author = {Qin, C and Xia, Q and Chen, ZJ and Zhou, Q and Zheng, X}, title = {En bloc resection of the recurrent pleural mesothelioma and reconstruction of the chest wall after immunotherapy: A case report.}, journal = {Thoracic cancer}, volume = {14}, number = {30}, pages = {3063-3066}, pmid = {37658846}, issn = {1759-7714}, mesh = {Female ; Humans ; Adult ; *Mesothelioma, Malignant/pathology ; *Thoracic Wall/surgery/pathology ; Nivolumab ; Ipilimumab ; *Mesothelioma/surgery/pathology ; *Pleural Neoplasms/surgery/pathology ; Immunotherapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is associated with previous asbestos exposure, while more clinical insights into this disease have come from other case studies. Maximal cytoreduction is critical in disease control and might help to improve the prognosis. Here, a 41-year-old female presented with a 6-month history of a mass detected in the chest wall following resection of a right pleural mesothelioma 2 years previously. A fluorodeoxyglucose positron emission tomography/computed tomography scan showed a right chest wall mass with a blurred boundary 8.9 cm × 3.7 cm in size. The patient had received one cycle of bevacizumab, carboplatin, and pemetrexed, and two cycles of nivolumab, ipilimumab, and gemcitabine 5 months before admission. We subsequently resected the tumor, the involved diaphragm, and the fifth and sixth ribs, and titanium mesh and continuous suture were used to close the thoracic cage. The fixed paraffin-embedded tissues showed epithelioid pleural mesothelioma. The patient received nivolumab and ipilimumab postoperatively, and no recurrence was detected 16 months after surgery. En bloc resection with reconstructive surgery effectively removed the locally advanced malignancy and restored the biological function of the thorax with a favorable prognosis. Neoadjuvant immunotherapy might therefore be conducive to radical resection and perioperative immunotherapy might improve the prognosis.}, }
@article {pmid37648326, year = {2023}, author = {Endo, I and Amatya, VJ and Kushitani, K and Kambara, T and Nakagiri, T and Aoe, K and Takeshima, Y}, title = {FOXM1 Promotes Mesothelioma Cell Migration and Invasion via Activation of SMAD Signaling.}, journal = {Anticancer research}, volume = {43}, number = {9}, pages = {3961-3968}, doi = {10.21873/anticanres.16583}, pmid = {37648326}, issn = {1791-7530}, mesh = {Humans ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Carcinogenesis ; Cell Transformation, Neoplastic ; Cell Movement ; Forkhead Box Protein M1/genetics ; }, abstract = {BACKGROUND/AIM: Forkhead box M1 (FOXM1) is a transcription factor closely associated with various human malignancies and is considered an attractive target for cancer therapy. Mesothelioma is a malignancy primarily due to asbestos exposure and certain genetic factors, requiring a better understanding of tumorigenesis for improved treatment. Asbestos-exposed human mesothelial cells have been reported to up-regulate FOXM1 expression in a dose-dependent manner.<br><br>MATERIALS AND METHODS: FOXM1 expression was evaluated in mesothelioma tissues and cell lines. FOXM1 small interfering RNA was transfected into mesothelioma cell lines to analyze its biological functions and regulatory mechanisms.<br><br>RESULTS: FOXM1 was over-expressed in mesothelioma tissues and cell lines. Knock-down of FOXM1 in mesothelioma cell lines inhibited cell proliferation, migration, and invasion. These results suggest that up-regulation of FOXM1 expression promotes mesothelioma tumorigenesis and progression. We previously reported that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes the proliferation, migration, and invasion of mesothelioma cell lines. In this study, IGF2BP3 knock-down suppressed FOXM1 expression in mesothelioma cell lines. Our results suggest that IGF2BP3, an upstream regulator, contributes to increased FOXM1 expression. Furthermore, IGF2BP3 and FOXM1 knock-down suppressed SMAD signaling by inhibiting SMAD2/3 phosphorylation in mesothelioma cell lines.<br><br>CONCLUSION: IGF2BP3/FOXM1 promotes mesothelioma cell migration and invasion via SMAD signaling, highlighting IGF2BP3/FOXM1 as a potential target for mesothelioma treatment.}, }
@article {pmid37642305, year = {2023}, author = {Zhang, C and Sun, Q and Zhao, J and Jiang, N and Hao, Y and Luo, J and Karim, S and Wu, L and de Perrot, M and Peng, C and Zhao, X}, title = {JSI-124 inhibits cell proliferation and tumor growth by inducing autophagy and apoptosis in murine malignant mesothelioma.}, journal = {Molecular carcinogenesis}, volume = {62}, number = {12}, pages = {1888-1901}, doi = {10.1002/mc.23623}, pmid = {37642305}, issn = {1098-2744}, support = {//Taishan Mountain Scholars of Shandong Province/ ; //Second hospital of Shandong University/ ; 2022YP104//Youth Talent Innovation Foundation of the Second Hospital of Shandong University/ ; //Special Construction Project Fund for Taishan Mountain Scholars of Shandong Province/ ; }, mesh = {Humans ; Animals ; Mice ; *Mesothelioma, Malignant ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis ; Autophagy ; }, abstract = {Malignant pleural mesothelioma (MPM), mainly caused by asbestos exposure, has a poor prognosis and lacks effective treatment compared with other cancer types. The intracellular transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed and hyperactivated in most human cancers. In this study, the role of STAT3 in murine MPM was examined. Inhibition of the Janus kinase 2 (JAK2)/STAT3 pathway with the selective inhibitor JSI-124 has an antitumor effect in murine MPM. Specifically, we demonstrated that JSI-124 inhibits murine MPM cell growth and induces apoptotic and autophagic cell death. Exposure of RN5 and AB12 cells to JSI-124 resulted in apoptosis via the Bcl-2 family of proteins. JSI-124 triggered autophagosome formation, accumulation, and conversion of LC3I to LC3II. Autophagy inhibitors, Chloroquine (CQ) and Bafilomycin A1 (Baf-A1), inhibited autophagy and sensitized RN5 and AB12 cells to JSI-124-induced apoptosis. Our data indicate that JSI-124 is a promising therapeutic agent for MPM treatment.}, }
@article {pmid37637041, year = {2023}, author = {Deboever, N and Zhou, N and McGrail, DJ and Tomczak, K and Oliva, JL and Feldman, HA and Parra, E and Zhang, J and Lee, PP and Antonoff, MB and Hofstetter, WL and Mehran, RJ and Rajaram, R and Rice, DC and Roth, JA and Swisher, SS and Vaporciyan, AA and Altan, M and Weissferdt, A and Tsao, AS and Haymaker, CL and Sepesi, B}, title = {Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1216999}, pmid = {37637041}, issn = {2234-943X}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).<br><br>METHODS: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria.<br><br>RESULTS: In this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was -16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62-5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55-4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001).<br><br>CONCLUSION: Poor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.}, }
@article {pmid37628748, year = {2023}, author = {Ramundo, V and Zanirato, G and Palazzo, ML and Riganti, C and Aldieri, E}, title = {APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37628748}, issn = {1422-0067}, support = {ALDE_RILO_19_01//University of Turin/ ; }, mesh = {Animals ; *Mesothelioma, Malignant ; Epithelial-Mesenchymal Transition ; Oxidative Stress ; Cell Proliferation ; Carcinogenesis ; Hyperplasia ; Endonucleases ; *Hominidae ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and epithelial mesenchymal transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos-related primary oxidative damage is counteracted in the lungs by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet been fully understood. Moreover, asbestos exposure has been associated with induced EMT events, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells; as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Taken as a whole, these results show, for the first time, crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, thus improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.}, }
@article {pmid37626858, year = {2023}, author = {Fiorilla, I and Martinotti, S and Todesco, AM and Bonsignore, G and Cavaletto, M and Patrone, M and Ranzato, E and Audrito, V}, title = {Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma.}, journal = {Cells}, volume = {12}, number = {16}, pages = {}, pmid = {37626858}, issn = {2073-4409}, mesh = {Humans ; *Mesothelioma, Malignant ; Reactive Oxygen Species ; Oxidative Stress ; Carcinogenesis ; Inflammation ; Tumor Microenvironment ; }, abstract = {Malignant pleural mesothelioma (MPM) is a lethal and rare cancer, even if its incidence has continuously increased all over the world. Asbestos exposure leads to the development of mesothelioma through multiple mechanisms, including chronic inflammation, oxidative stress with reactive oxygen species (ROS) generation, and persistent aberrant signaling. Together, these processes, over the years, force normal mesothelial cells' transformation. Chronic inflammation supported by "frustrated" macrophages exposed to asbestos fibers is also boosted by the release of pro-inflammatory cytokines, chemokines, growth factors, damage-associated molecular proteins (DAMPs), and the generation of ROS. In addition, the hypoxic microenvironment influences MPM and immune cells' features, leading to a significant rewiring of metabolism and phenotypic plasticity, thereby supporting tumor aggressiveness and modulating infiltrating immune cell responses. This review provides an overview of the complex tumor-host interactions within the MPM tumor microenvironment at different levels, i.e., soluble factors, metabolic crosstalk, and oxidative stress, and explains how these players supporting tumor transformation and progression may become potential and novel therapeutic targets in MPM.}, }
@article {pmid37608979, year = {2023}, author = {Moitra, S and Tabrizi, AF and Khadour, F and Henderson, L and Melenka, L and Lacy, P}, title = {Exposure to insulating materials and risk of coronary artery diseases: a cross-sectional study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1235189}, pmid = {37608979}, issn = {2296-2565}, mesh = {Adult ; Male ; Humans ; Middle Aged ; Female ; *Coronary Artery Disease/epidemiology/etiology ; Cross-Sectional Studies ; *Heart Diseases ; Heart ; *Mesothelioma, Malignant ; }, abstract = {BACKGROUND: Although previous reports link exposure to insulating materials with an increased risk of mesothelioma and chronic respiratory diseases, studies evaluating their associations with the risk of coronary artery diseases (CAD) are lacking.<br><br>AIMS: We aimed at evaluating the associations between exposure to insulating materials and the 10-year risk of CAD among insulators.<br><br>METHODS: In this cross-sectional study, we recruited 643 adults (&#x2265;18 years), full-time insulators from the Local 110 Heat and Frost Insulators and Allied Workers Union in Edmonton, Alberta. We obtained demographic information, personal and family history, and job-exposure history, including experience (years) and types of exposure to insulating materials. Clinical profiling including Framingham risk scores (FRS) was assessed.<br><br>RESULTS: Of all insulators, 89% were men (mean &#xb1; SD age: 47 &#xb1; 12 years), 27% had a parental history of cardiac diseases, and 22% had a comorbid chronic respiratory disease. In total, 53% reported exposure to asbestos, while 61, 82, and 94% reported exposure to ceramic fibers, fiberglass, and mineral fibers, respectively. In single-exposure multivariable regression models adjusted for experience, marital status, and body mass index (BMI), asbestos was found to be associated with higher FRS (&#x3b2;: 1.004; 95%CI: 0.003-2.00). The association remained consistent in multi-exposure models and a higher association was found between asbestos exposure and FRS among insulators with comorbid chronic respiratory disease.<br><br>CONCLUSION: Our study demonstrates that apart from cancer and chronic respiratory diseases, asbestos exposure may also have a cardiac effect, thus warranting the need for systematic surveillance to protect workers from the adverse effects of these materials.}, }
@article {pmid37605147, year = {2023}, author = {Welch, H and Harris, J and Pufulete, M and Dimagli, A and Benedetto, U and Maskell, N}, title = {Does previous asbestos exposure increase the risk of a post coronary artery bypass graft (CABG) pleural effusion - a routine data study?.}, journal = {BMC pulmonary medicine}, volume = {23}, number = {1}, pages = {307}, pmid = {37605147}, issn = {1471-2466}, mesh = {Humans ; *Asbestosis/epidemiology ; Prospective Studies ; *Pleural Effusion/epidemiology/etiology ; *Asbestos/adverse effects ; *Pleural Diseases/epidemiology/etiology ; Coronary Artery Bypass/adverse effects ; }, abstract = {BACKGROUND: Development of pleural effusion (PE) following CABG is common. Post-CABG PE are divided into early- (within 30 days of surgery) and delayed-onset (30 days-1 year) which are likely due to distinct pathological processes. Some experts suggest asbestos exposure may confer an independent risk for late-onset post-CABG PE, however no large studies have explored this potential association.<br><br>RESEARCH QUESTION: To explore possible association between asbestos exposure and post-CABG PE using routine data.<br><br>METHODS: All patients who underwent CABG 01/04/2013-31/03/2018 were identified from the Hospital Episode Statistics (HES) Database. This England-wide population was evaluated for evidence of asbestos exposure, pleural plaques or asbestosis and a diagnosis of PE or PE-related procedure from 30 days to 1 year post-CABG. Patients with evidence of PE three months prior to CABG were excluded, as were patients with a new mesothelioma diagnosis.<br><br>RESULTS: 68,150 patients were identified, of whom 1,003 (1%) were asbestos exposed and 2,377 (3%) developed late-onset PE. After adjusting for demographic data, Index of Multiple Deprivation and Charlson Co-morbidity Index, asbestos exposed patients had increased odds of PE diagnosis or related procedure such as thoracentesis or drainage (OR 1.35, 95% CI 1.03-1.76, p&#x2009;=&#x2009;0.04). In those with evidence of PE requiring procedure alone, the adjusted OR was 1.66 (95% CI 1.14-2.40, p&#x2009;=&#x2009;0.01). Additional subgroup analysis of the 518 patients coded for pleural plaques and asbestosis alone revealed an adjusted OR of post-CABG PE requiring a procedure of 2.16 (95% CI 1.38-3.37, p&#x2009;=&#x2009;0.002).<br><br>INTERPRETATION: This large-scale study demonstrates prior asbestos exposure is associated with modestly increased risk of post-CABG PE development. The risk association appears higher in patients with assigned clinical codes indicative of radiological evidence of asbestos exposure (pleural plaques or asbestosis). This association may fit with a possible inflammatory co-pathogenesis, with asbestos exposure 'priming' the pleura resulting in greater propensity for PE evolution following the physiological insult of CABG surgery. Further work, including prospective studies and clinicopathological correlation are suggested to explore this further.}, }
@article {pmid37571934, year = {2022}, author = {Nasirzadeh, N and Soltanpour, Z and Mohammadian, Y and Pourhasan, B}, title = {Lung Cancer and Pleural Mesothelioma Risk Assessment for the General Population Exposed to Asbestos in Different Regions of Tehran, Iran.}, journal = {Journal of research in health sciences}, volume = {22}, number = {4}, pages = {e00563}, pmid = {37571934}, issn = {2228-7809}, mesh = {Humans ; Iran/epidemiology ; Cross-Sectional Studies ; *Mesothelioma/epidemiology/etiology ; *Asbestos/toxicity ; *Lung Neoplasms/epidemiology/etiology ; *Pleural Neoplasms/epidemiology/etiology ; Risk Assessment ; *Occupational Exposure/adverse effects/analysis ; }, abstract = {BACKGROUND: Asbestos is a natural fiber leading to health risks like chronic lung diseases. The current study aimed to estimate pleural mesothelioma and lung cancer risk for population exposure to asbestos in Tehran, Iran.<br><br>STUDY DESIGN: A cross-sectional study.<br><br>METHODS: According to the annual report of Air Quality Control Company (AQCC), from 2011-2020, carcinogenic risk and mesothelioma were assessed based on the Environmental Protection Agency (EPA) method using the Monte Carlo simulation (MCS). The relative risk (RR) of mortality cancer was calculated based on Camus and colleagues' model. Moreover, mesothelioma risk was estimated by Bourgault and colleagues' model.<br><br>RESULTS: The mean concentration and health risk of asbestos in ambient air generally reduced from 2011 to 2020. The highest mortality risk for lung cancer was 8.4 per 100000 persons in 2011 and reduced to 1.8 in 2017. For mesothelioma, the corresponding values were 8.96 per 100000 persons in 2011 and reduced to 1.92 in 2017.<br><br>CONCLUSION: The findings of this study could be helpful to health policymakers in the management of asbestos risk.}, }
@article {pmid37567753, year = {2023}, author = {Stella, S and Consonni, D and Migliore, E and Stura, A and Cavone, D and Vimercati, L and Miligi, L and Piro, S and Landi, MT and Caporaso, NE and Curti, S and Mattioli, S and Brandi, G and Gioscia, C and Eccher, S and Murano, S and Casotto, V and Comiati, V and Negro, C and D'Agostin, F and Genova, C and Benfatto, L and Romanelli, A and Grappasonni, I and Madeo, G and Cozzi, I and Romeo, E and Tommaso, S and Carrozza, F and Labianca, M and Tallarigo, F and Cascone, G and Melis, M and Marinaccio, A and Binazzi, A and Mensi, C and , }, title = {Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018.}, journal = {BMJ open}, volume = {13}, number = {8}, pages = {e073480}, pmid = {37567753}, issn = {2044-6055}, mesh = {Humans ; Male ; *Construction Industry ; Case-Control Studies ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; Logistic Models ; Italy/epidemiology ; }, abstract = {OBJECTIVES: Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.<br><br>DESIGN: Case-control study.<br><br>SETTING: Cases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies.<br><br>METHODS: We selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.<br><br>RESULTS: The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.<br><br>CONCLUSIONS: We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.}, }
@article {pmid37553196, year = {2023}, author = {Ferguson, K and Neilson, M and Mercer, R and King, J and Marshall, K and Welch, H and Tsim, S and Maskell, NA and Rahman, NM and Evison, M and Blyth, KG}, title = {Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance.}, journal = {BMJ open}, volume = {13}, number = {8}, pages = {e067780}, pmid = {37553196}, issn = {2044-6055}, support = {29372/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; Feasibility Studies ; Prospective Studies ; Retrospective Studies ; *Mesothelioma, Malignant ; *Mesothelioma/pathology ; *Pleural Neoplasms/epidemiology ; *Asbestos ; *Lung Neoplasms/pathology ; }, abstract = {OBJECTIVES: To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI).<br><br>DESIGN: A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size.<br><br>SETTING: 4 UK pleural disease centres (February 2019-January 2020).<br><br>PARTICIPANTS: Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required &#x2265;2&#x2009;years follow-up.<br><br>OUTCOME MEASURES: A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6&#x2009;months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95%&#x2009;CI). Baseline predictors of evolution were identified using logistic regression.<br><br>RESULTS: 296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)).<br><br>CONCLUSIONS: Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN12840870.}, }
@article {pmid37547483, year = {2023}, author = {Damiran, N and Frank, AL}, title = {Mongolia: Failure of Total Banning of Asbestos.}, journal = {Annals of global health}, volume = {89}, number = {1}, pages = {50}, pmid = {37547483}, issn = {2214-9996}, mesh = {Humans ; Mongolia ; *Occupational Exposure/adverse effects/prevention &amp; control/analysis ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/prevention &amp; control ; *Mesothelioma, Malignant ; *Lung Neoplasms ; }, abstract = {The primary uses of asbestos in Mongolia are in thermal power plants, construction and at railway companies. There is, however, limited data on both asbestos consumption and asbestos related disease (ARD) in Mongolia. The purpose of this paper is to report on the failure to completely ban asbestos in Mongolia. To write this paper, available asbestos related literature, published nationally and internationally, and legal regulations, national standards and guidelines on asbestos control were reviewed. Mongolia consumed a total of 44,421.9 metric tons of asbestos containing materials (AMCs) between 1996 and 2014. As a key indicator of ARD, 54 cases of mesothelioma were diagnosed at the National Cancer Center by pathological testing of tissue samples between 1994 and 2013. In 2010, The government made the decision to stop all types of asbestos use under the Law on Toxic and Hazardous Substances. However, there was no nationwide action plan to gradually reduce asbestos use, promote substitutes and raise awareness of health hazards and economic burdens in the future from asbestos use. There was also no planning for safe removal of asbestos currently in place. After the banning of asbestos, thermal power plants told the government that they could not produce electricity without insulation of AMCs and substitution materials were economically not feasible. Due to pressure from the energy sector and inadequate awareness of asbestos hazards, the government changed the legal status on asbestos in 2011 as a restricted chemical. Asbestos is still allowed to be used, and workers and the general community are still unnecessarily exposed to this carcinogen.}, }
@article {pmid37529811, year = {2023}, author = {Kuramochi, M and Muraoka, T and Shinonaga, M and Ohtani, H and Kuraoka, S}, title = {Malignant Pleural Mesothelioma (MPM) Presenting as Hydropneumothorax.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e41243}, pmid = {37529811}, issn = {2168-8184}, abstract = {An 86-year-old man presented with bilateral lower limb edema and was found to have hydropneumothorax on chest radiography. CT revealed a substantial pleural effusion and plaques. The patient had a history of working in a stone workshop, but the extent of asbestos exposure remained unknown. Thoracic drainage and subsequent thoracoscopic surgery confirmed the presence of biphasic malignant mesothelioma through pathological examination. Hydropneumothorax as a presentation of malignant pleural mesothelioma (MPM) is rare, with only a few similar cases reported. Remarkably, despite the coexistence of plural effusion and pneumothorax, the patient did not experience dyspnea. The examination also revealed tumor rupture and disruption of the pleura. Considering the possibility of MPM in patients with asymptomatic hydropneumothorax is essential for early diagnosis and appropriate management.}, }
@article {pmid37528762, year = {2023}, author = {Frank, AL}, title = {Four mesothelioma cases from a single automotive dealership: A case series.}, journal = {American journal of industrial medicine}, volume = {66}, number = {10}, pages = {904-906}, doi = {10.1002/ajim.23521}, pmid = {37528762}, issn = {1097-0274}, mesh = {Humans ; Asbestos, Serpentine ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; *Asbestos ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; }, abstract = {BACKGROUND: Four cases of mesothelioma were noted in a workplace of some 110 persons at a tractor dealership between 2006 and 2023. Each worker had a different job title.<br><br>METHODS: Medical-legal case material was reviewed and abstracted from four cases from the same dealership, all supplied via one law firm.<br><br>RESULTS: Four mesotheliomas are reported from this single facility that used chrysotile asbestos automotive products. Two of the four cases had no other known exposures to asbestos.<br><br>DISCUSSION: Automotive products containing chrysotile do appear capable of causing mesothelioma. Job category is not a good surrogate for exposure.}, }
@article {pmid37524680, year = {2023}, author = {Zhang, GZ and Zheng, GQ and Wei, F and Liu, YY and Song, H and Liang, YF}, title = {[Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {7}, pages = {541-546}, doi = {10.3760/cma.j.cn121094-20211203-00597}, pmid = {37524680}, issn = {1001-9391}, abstract = {Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.}, }
@article {pmid37517251, year = {2023}, author = {Rouabeh, W and Cherif, T and Mgarrech, I and Ajmi, N and Kortas, C and Jerbi, S}, title = {Case report and analysis of the literature on sarcomatous mesothelioma of the left atrium.}, journal = {International journal of surgery case reports}, volume = {109}, number = {}, pages = {108537}, pmid = {37517251}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Primary intracardiac malignant mesothelioma is an extremely uncommon condition with a terrible prognosis. Because of its rarity, there have been extremely few examples described in the literature.<br><br>CASE PRESENTATION: We are reporting the instance of a 44-year-old lady who was referred to the department of cardiology for worsening dyspnea, palpitations, and a recent syncopal episode. On examination, the patient had signs of global heart failure. Cardiac imaging showed a tissue mass infiltrating the atrioventricular sulcus at the mitral valve level, responsible for severe mitral stenosis. Pleural effusion without an intrapleural mass was also noted. Urgent surgery was performed, including excision of the tumor mass, mechanical replacement of the mitral valve, and tricuspid plasty. The anatomo-pathological study concluded in cardiac mesothelioma. The patient was transferred back to the cardiology department 9&#xa0;months after surgery due to severe left heart failure. TTE and TOE were performed and revealed tumor recurrence responsible for severe mitral stenosis. The course was marked by the onset of cardiogenic shock refractory to treatment, followed by the death of the patient. The case we are reporting seems to be the initial instance documented as exclusively primary intracardiac mesothelioma especially its lack of association with any other pleural sarcomatoid mesothelioma or asbestos exposure.<br><br>CLINICAL DISCUSSION: In cases where a large atrial tumor is present, prompt surgical intervention is recommended to mitigate the risk of catastrophic embolization or valve orifice obstruction. The objective of surgical intervention is to excise the entire neoplasm with sufficient surrounding tissue, a feat that is infrequently achievable. Palliative debulking may be a beneficial intervention for patients who do not necessitate complete resection, particularly those experiencing relevant or rapidly escalating symptoms. Cardiac transplantation remains a viable option in the event of an unresectable malignant tumor.<br><br>CONCLUSION: The short-term prognosis is poor. Surgical treatment remains the best treatment for this type of tumor. Total excision should be considered, but may not be feasible in all cases. Adjuvant chemotherapy may be considered.}, }
@article {pmid37483507, year = {2023}, author = {Wang, J and Huang, X and Ma, R and Zhang, Q and Wu, N and Du, X and Ye, Q}, title = {The incidence of malignancies in asbestosis with chrysotile exposure: a large Chinese prospective cohort study.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1172496}, pmid = {37483507}, issn = {2234-943X}, abstract = {BACKGROUND: Asbestos exposure is closely related to the occurrence and development of various malignancies. This prospective cohort study aimed to evaluate the incidence rate and potential risk factors in a cohort of asbestosis patients in China.<br><br>METHODS: The incidence of malignancies was determined in patients who had been exposed to chrysotile asbestos and diagnosed with asbestosis sequentially at Beijing Chaoyang Hospital from 1 January 2007 to 31 December 2019. Cox regression analyses were used to analyze the correlations between clinical variables and asbestosis combined with malignancies.<br><br>RESULTS: A total of 618 patients with asbestosis were identified, of whom 544 were eligible for analysis. Among them, 89 (16.36%) were diagnosed with various malignancies. The standardized incidence ratios (SIRs) of patients with asbestosis combined with malignancies were 16.61, 175, 5.23, and 8.77 for lung cancer, mesothelioma, breast cancer, and endometrial carcinoma, respectively. The risks of all malignancies and lung cancer increased with initial exposure before 17 years old, longer asbestos exposure, and smoking.<br><br>CONCLUSIONS: The SIRs of patients with asbestosis-related malignancies were significantly increased in lung cancer, mesothelioma, breast cancer, and endometrial carcinoma in a hospital-based Chinese cohort. Smoking and the duration of asbestos exposure increased the risk of lung cancer.}, }
@article {pmid37476375, year = {2023}, author = {Shi, H and Zhang, L and Yu, TK and Zhuang, L and Ke, H and Johnson, B and Rath, E and Lee, K and Klebe, S and Kao, S and Qin, KL and Pham, HNT and Vuong, Q and Cheng, YY}, title = {Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1162027}, pmid = {37476375}, issn = {2234-943X}, abstract = {Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender[®] (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender[®] daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender[®]. Significantly enhanced tumor apoptosis was observed in the Defender[®]-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender[®] were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.}, }
@article {pmid37469419, year = {2023}, author = {Sahu, RK and Ruhi, S and Jeppu, AK and Al-Goshae, HA and Syed, A and Nagdev, S and Widyowati, R and Ekasari, W and Khan, J and Bhattacharjee, B and Goyal, M and Bhattacharya, S and Jangde, RK}, title = {Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1204722}, pmid = {37469419}, issn = {2234-943X}, abstract = {The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.}, }
@article {pmid37466108, year = {2023}, author = {Lombardo, C and Broggi, G and Vitale, E and Ledda, C and Loreto, C and Matera, S and Hagnas, M and Caltabiano, R and Filetti, V}, title = {Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report.}, journal = {Histology and histopathology}, volume = {38}, number = {11}, pages = {1249-1256}, pmid = {37466108}, issn = {1699-5848}, support = {2020/2022//Interdepartment "PIA.CE.RI" Research Plan of University of Catania/ ; }, mesh = {Humans ; *Asbestos/toxicity/analysis ; Biomarkers/analysis ; *Lung Neoplasms/pathology ; *Mesothelioma/diagnosis/metabolism ; *Mesothelioma, Malignant ; Sicily ; Stathmin ; }, abstract = {BACKGROUND: Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoro-edenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables.<br><br>AIM: The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data.<br><br>MATERIAL AND METHODS: Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression.<br><br>RESULTS: Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients.<br><br>CONCLUSION: Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options.}, }
@article {pmid37460925, year = {2023}, author = {Torricelli, F and Donati, B and Reggiani, F and Manicardi, V and Piana, S and Valli, R and Lococo, F and Ciarrocchi, A}, title = {Spatially resolved, high-dimensional transcriptomics sorts out the evolution of biphasic malignant pleural mesothelioma: new paradigms for immunotherapy.}, journal = {Molecular cancer}, volume = {22}, number = {1}, pages = {114}, pmid = {37460925}, issn = {1476-4598}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/therapy ; Transcriptome ; Ecosystem ; *Pleural Neoplasms/genetics/therapy ; *Lung Neoplasms/genetics ; Prognosis ; Biomarkers, Tumor/genetics ; Immunotherapy ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place.<br><br>METHODS: We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx&#x2122;Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis.<br><br>RESULTS: Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability.<br><br>CONCLUSIONS: Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.}, }
@article {pmid37441092, year = {2023}, author = {Farahmand, P and Gyuraszova, K and Rooney, C and Raffo-Iraolagoitia, XL and Jayasekera, G and Hedley, A and Johnson, E and Chernova, T and Malviya, G and Hall, H and Monteverde, T and Blyth, K and Duffin, R and Carlin, LM and Lewis, D and Le Quesne, J and MacFarlane, M and Murphy, DJ}, title = {Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma.}, journal = {Frontiers in toxicology}, volume = {5}, number = {}, pages = {1200650}, pmid = {37441092}, issn = {2673-3080}, support = {23983/CRUK_/Cancer Research UK/United Kingdom ; 25006/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration. Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy. Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit.}, }
@article {pmid37421230, year = {2024}, author = {Jama, M and Zhang, M and Poile, C and Nakas, A and Sharkey, A and Dzialo, J and Dawson, A and Kutywayo, K and Fennell, DA and Hollox, EJ}, title = {Gene fusions during the early evolution of mesothelioma correlate with impaired DNA repair and Hippo pathways.}, journal = {Genes, chromosomes &amp; cancer}, volume = {63}, number = {1}, pages = {e23189}, doi = {10.1002/gcc.23189}, pmid = {37421230}, issn = {1098-2264}, support = {//British Lung Foundation/ ; //Mesothelioma UK/ ; }, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; Hippo Signaling Pathway ; *Lung Neoplasms/genetics/pathology ; *Mesothelioma/genetics ; *Asbestos ; DNA Repair/genetics ; Gene Fusion ; }, abstract = {Malignant pleural mesothelioma (MPM), a rare cancer a long latency period (up to 40 years) between asbestos exposure and disease presentation. The mechanisms coupling asbestos to recurrent somatic alterations are poorly defined. Gene fusions arising through genomic instability may create novel drivers during early MPM evolution. We explored the gene fusions that occurred early in the evolutionary history of the tumor. We conducted multiregional whole exome sequencing (WES) of 106 samples from 20 patients undergoing pleurectomy decortication and identified 24 clonal nonrecurrent gene fusions, three of which were novel (FMO9P-OR2W5, GBA3, and SP9). The number of early gene fusion events detected varied from zero to eight per tumor, and presence of gene fusions was associated with clonal losses involving the Hippo pathway genes and homologous recombination DNA repair genes. Fusions involved known tumor suppressors BAP1, MTAP, and LRP1B, and a clonal oncogenic fusion involving CACNA1D-ERC2, PARD3B-NT5DC2, and STAB2-NT5DC2 fusions were also identified as clonal fusions. Gene fusions events occur early during MPM evolution. Individual fusions are rare as no recurrent truncal fusions event were found. This suggests the importance of early disruption of these pathways in generating genomic rearrangements resulting in potentially oncogenic gene fusions.}, }
@article {pmid37399948, year = {2023}, author = {Coccè, V and Bonelli, M and La Monica, S and Alfieri, R and Doneda, L and Martegani, E and Alessandri, G and Lagrasta, CA and Giannì, A and Sordi, V and Petrella, F and Roncoroni, L and Paino, F and Pessina, A}, title = {Mesenchymal stromal cells loaded with Paclitaxel (PacliMES) a potential new therapeutic approach on mesothelioma.}, journal = {Biochemical pharmacology}, volume = {214}, number = {}, pages = {115678}, doi = {10.1016/j.bcp.2023.115678}, pmid = {37399948}, issn = {1873-2968}, mesh = {Humans ; Paclitaxel ; *Mesothelioma, Malignant ; Cell Line, Tumor ; *Mesothelioma/drug therapy ; *Mesenchymal Stem Cells ; }, abstract = {Malignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone. An in vivo approach to treat in situ mesothelioma xenografts using a minimal amount of 10[6] mesenchymal stromal cells loaded with Paclitaxel showed the same efficacy of a systemic administration of 10 mg/kg of Paclitaxel. These data strongly support drug delivery system by mesenchymal stromal cells as a useful approach against many solid tumors. We look with interest at the favourable opinion recently expressed by the Italian Drug Agency on the procedure for the preparation of mesenchymal stromal cells loaded with Paclitaxel in large-scale bioreactor systems and their storage until clinical use. This new Advanced Medicinal Therapy Product, already approved for a Phase I clinical trial on mesothelioma patients, could pave the way for mesenchymal stromal cells use as drug delivery system on other solid tumors for adjuvant therapy associated with surgery and radiotherapy.}, }
@article {pmid37398648, year = {2023}, author = {Digifico, E and Erreni, M and Mannarino, L and Marchini, S and Ummarino, A and Anfray, C and Bertola, L and Recordati, C and Pistillo, D and Roncalli, M and Bossi, P and Zucali, PA and D'Incalci, M and Belgiovine, C and Allavena, P}, title = {Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1116430}, pmid = {37398648}, issn = {1664-3224}, mesh = {Animals ; Humans ; Mice ; Cytokines/therapeutic use ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; *Osteopontin/genetics/metabolism ; *Pleural Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.<br><br>METHODS: Expression and quantification of Osteopontin (OPN) was detected in tumor and plasma samples of MPM patients by mRNA, immunohistochemistry and ELISA. The functional role of OPN was investigated in mouse MPM cell lines in vivo using an orthotopic syngeneic mouse model.<br><br>RESULTS: In patients with MPM, the protein OPN was significantly more expressed in tumors than in normal pleural tissues and predominantly produced by mesothelioma cells; plasma levels were elevated in patients and associated with poor prognosis. However, modulation of OPN levels was not significantly different in a series of 18 MPM patients receiving immunotherapy with durvalumab alone or with pembrolizumab in combination with chemotherapy, some of whom achieved a partial clinical response. Two established murine mesothelioma cell lines: AB1 and AB22 of sarcomatoid and epithelioid histology, respectively, spontaneously produced high levels of OPN. Silencing of the OPN gene (Spp1) dramatically inhibited tumor growth in vivo in an orthotopic model, indicating that OPN has an important promoting role in the proliferation of MPM cells. Treatment of mice with anti-CD44 mAb, blocking a major OPN receptor, significantly reduced tumor growth in vivo.<br><br>CONCLUSION: These results demonstrate that OPN is an endogenous growth factor for mesothelial cells and inhibition of its signaling may be helpful to restrain tumor progression in vivo. These findings have translational potential to improve the therapeutic response of human MPM.}, }
@article {pmid37361656, year = {2023}, author = {Mishra, K and Siddiquee, S and Mislang, AR}, title = {A rare presentation of malignant mesothelioma of the tunica vaginalis managed with immunotherapy and review of the literature.}, journal = {Clinical case reports}, volume = {11}, number = {6}, pages = {e7610}, pmid = {37361656}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: We describe the first case in literature of malignant mesothelioma of the tunica vaginalis that has shown partial response to systemic immunotherapy (ipilimumab-nivolumab) post orchiectomy, warranting further investigation in a trial setting.<br><br>ABSTRACT: We present a case report of an 80-year-old ex-smoker with a rare diagnosis of metastatic mesothelioma of the tunica vaginalis, managed with immunotherapy. The patient, with no known history of asbestos exposure, presented with a left scrotal mass and pain. Scrotal ultrasound confirmed a large paratesticular mass, and computed tomography (CT) of the chest, abdomen, and pelvis revealed a bilobed mass in the left scrotal compartment without associated inguinal or abdominopelvic lymphadenopathy, and an indeterminate, subcentimeter, bi-basal subpleural nodules. He underwent a left orchiectomy, and histopathology confirmed the diagnosis of a paratesticular mesothelioma. Postoperatively, the patient had a positron emission tomography (PET) scan showing a new right pleural effusion as well as increasing size of the lobar and pleural nodules bilaterally, all metabolically active and suggestive of progressive metastatic disease. The patient was commenced on ipilimumab and nivolumab immunotherapy, a regimen indicated for malignant pleural mesothelioma; however, the efficacy on paratesticular mesothelioma is not known. After 6&#x2009;months of treatment, the patient demonstrated a partial response to immunotherapy, with a reduction in the size of known pleural nodules and effusion.Literature review suggests that diagnosis requires a high index of suspicion and patients commonly have metastatic disease at the time of diagnosis. Orchiectomy is a common management modality. However, the role, regimen, and benefits of systemic therapy are unclear, warranting further studies investigating management strategies.}, }
@article {pmid37359917, year = {2023}, author = {Charlaix Hidalgo, AL and Roux, A and Charissoux, A and Mathonnet, M and Descazeaud, A and Durand Fontanier, S and Taibi, A}, title = {First Case of Abdominal and Tunica Vaginalis Multicystic Benign Mesothelioma: Management and Review of Literature.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {Suppl 1}, pages = {92-96}, pmid = {37359917}, issn = {0975-7651}, abstract = {Multicystic benign mesothelioma is a rare tumor that affects the serosa. Most cases present with peritoneal lesions exclusively. Some identified risk factors are chronic abdominal inflammation, woman of childbearing age, and asbestos exposure. The symptomatology is not specific and can delay the diagnosis. There are no guidelines for the treatment of this pathology. We describe one male patient with abdominal and tunica vaginalis localizations of multicystic benign mesothelioma. The diagnosis was suspected on imaging and confirmed with histological examination. The treatment on an expert center was complete cytoreduction surgery and HIPEC, but the patient had two recurrences during the 2-year of follow-up. This is the first case of simultaneous rare localizations of multicystic benign mesothelioma. No new risk factors were identified. The case underlines the importance of regular examination of all serosa localizations.}, }
@article {pmid37359063, year = {2023}, author = {Singh, R and Frank, AL}, title = {Analysis of the Indian Government's position on the use of asbestos and its health effects.}, journal = {Public health action}, volume = {13}, number = {2}, pages = {50-52}, pmid = {37359063}, issn = {2220-8372}, abstract = {Based on WHO guidance, all forms of asbestos are a health risk. In India, the mining of asbestos has been stopped, but chrysotile (a type of asbestos) is still imported and processed in large quantities. Chrysotile is mainly used for asbestos-cement roofing, and the manufacturers claim its use to be safe. We sought to understand the Indian Government's position on the use of asbestos. To do so, we have analysed the replies of the executive wing of the Indian Government to questions on asbestos in the Indian Parliament. This revealed that, despite a mining ban, the government has defended the import, processing and continued use of asbestos.}, }
@article {pmid37347449, year = {2024}, author = {Mejia-Garcia, A and Bonilla, DA and Ramirez, CM and Escobar-Díaz, FA and Combita, AL and Forero, DA and Orozco, C}, title = {Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies.}, journal = {Biochemical genetics}, volume = {62}, number = {1}, pages = {352-370}, pmid = {37347449}, issn = {1573-4927}, support = {CV2022-CSD-B-12516//Fundaci&#xf3;n Universitaria del Area Andina/ ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/metabolism ; Phosphatidylinositol 3-Kinases ; *Pleural Neoplasms/genetics/metabolism ; *Lung Neoplasms/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.}, }
@article {pmid37309879, year = {2023}, author = {Vimercati, L and Cavone, D and De Maria, L and Caputi, A and Pentimone, F and Sponselli, S and Delvecchio, G and Chellini, E and Binazzi, A and Di Marzio, D and Mensi, C and Consonni, D and Migliore, E and Mirabelli, D and Angelini, A and Martini, A and Negro, C and D'Agostin, F and Grappasonni, I and Pascucci, C and Benfatto, L and Malacarne, D and Casotto, V and Comiati, V and Storchi, C and Mangone, L and Murano, S and Rossin, L and Tallarigo, F and Vitale, F and Verardo, M and Eccher, S and Madeo, G and Staniscia, T and Carrozza, F and Cozzi, I and Romeo, E and Pelullo, P and Labianca, M and Melis, M and Cascone, G and Marinaccio, A and Ferri, GM and Serio, G}, title = {Mesothelioma Risk among Construction Workers According to Job Title: Data from the Italian Mesothelioma Register.}, journal = {La Medicina del lavoro}, volume = {114}, number = {3}, pages = {e2023025}, pmid = {37309879}, issn = {0025-7818}, mesh = {Humans ; *Construction Industry ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Health ; Registries ; }, abstract = {BACKGROUND: An increased risk of mesothelioma has been reported in various countries for construction workers. The Italian National Mesothelioma Registry, from 1993 to 2018, reported exposure exclusively in the construction sector in 2310 cases. We describe the characteristics of these cases according to job title.<br><br>METHODS: We converted into 18 groups the original jobs (N=338) as reported by ISTAT codes ('ATECO 91'). The exposure level was attributed at certain, probable and possible in accordance with the qualitative classification of exposure as reported in the Registry guidelines. Descriptive analysis by jobs highlights the total number of subjects for each single job and certain exposure, in descending order, insulator, plumbing, carpenter, mechanic, bricklayer, electrician, machine operator, plasterer, building contractor, painter and labourer.<br><br>RESULTS: The cases grow for plumbing in the incidence periods 1993-2018, while, as expected, it decreases for insulator. Within each period considered the most numerous cases are always among bricklayers and labourers, these data confirm the prevalence of non-specialised "interchangeable" jobs in Italian construction sector in the past.<br><br>CONCLUSIONS: Despite the 1992 ban, the construction sector still presents an occupational health prevention challenge, circumstances of exposure to asbestos may still occur due to incomplete compliance with prevention and protection measures.}, }
@article {pmid37306905, year = {2023}, author = {Tamanna, MT and Egbune, C}, title = {Traditional Treatment Approaches and Role of Immunotherapy in Lung Malignancy and Mesothelioma.}, journal = {Cancer treatment and research}, volume = {185}, number = {}, pages = {79-89}, pmid = {37306905}, issn = {0927-3042}, mesh = {Humans ; B7-H1 Antigen ; *Carcinoma, Non-Small-Cell Lung ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; *Mesothelioma, Malignant ; Nivolumab ; Programmed Cell Death 1 Receptor ; Receptors, Death Domain ; }, abstract = {There is no denying that many revolutions took place in the fight against cancer during the last decades. However, cancers have always managed to find new ways to challenge humankinds. Variable genomic epidemiology, socio-economic differences and limitations of widespread screening are the major concerns in cancer diagnosis and early treatment. A multidisciplinary approach is essentially to manage a cancer patient efficiently. Thoracic malignancies including lung cancers and pleural mesothelioma are accountable for little more than 11.6% of the global cancer burden [4]. Mesothelioma is one of the rare cancers, but concern is the incidences are increasing globally. However, the good news is first-line chemotherapy with the combination of immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and mesothelioma has showed promising respond and improved overall survival (OS) in pivotal clinical trials [10]. ICIs are commonly referred as immunotherapy are antigens on the cancer cells, and inhibitors are the antibodies produce by the T cell defence system. By inhibiting immune checkpoints, the cancer cells become visible to be identified as abnormal cells and attack by the body's defence system [17]. The programmed death receptor-1 (PD-1) and programmed death receptor ligand-1 (PD-L1) inhibitors are commonly used immune checkpoint blockers for anti-cancer treatment. PD-1/PD-L1 are proteins produced by immune cells and mimic by cancer cells that are implicated in inhibiting T cell response to regulate our immune system, which results tumour cells escaping the defence mechanism to achieve immune surveillance. Therefore, inhibiting immune checkpoints as well as monoclonal antibodies can lead to effective apoptosis of tumour cells [17]. Mesothelioma is an industrial disease caused by significant asbestos exposure. It is the cancer of the mesothelial tissue which presents in the lining of the mediastinum of pleura, pericardium and peritoneum, most commonly affected sites are pleura of the lung or chest wall lining [9] as route of asbestos exposure is inhalation. Calretinin is a calcium binding protein, typically over exposed in malignant mesotheliomas and the most useful marker even while initial changes take place [5]. On the other hand, Wilm's tumour 1 (WT-1) gene expression on the tumour cells can be related to prognosis as it can elicit immune response, thereby inhibit cell apoptosis. A systematic review and meta-analysis study conducted by Qi et al. has suggested that expression of WT-1 in a solid tumour is fatal however, it gives the tumour cell a feature of immune sensitivity which then acts positively towards the treatment with immunotherapy. Clinical significance of WT-1 oncogene in treatment is still hugely debatable and needs further attention [21]. Recently, Japan has reinstated Nivolumab in patients with chemo-refractory mesothelioma. According to NCCN guidelines, the salvage therapies include Pembrolizumab in PD-L1 positive patients and Nivolumab alone or with Ipilimumab in cancers irrespective of PD-L1 expression [9]. The checkpoint blockers have taken over the biomarker-based research and demonstrated impressive treatment options in immune sensitive and asbestos-related cancers. It can be expected that in near future the immune checkpoint inhibitors will be considered as approved first-line cancer treatment universally.}, }
@article {pmid37305461, year = {2023}, author = {Peña-Castro, M and Montero-Acosta, M and Saba, M}, title = {A critical review of asbestos concentrations in water and air, according to exposure sources.}, journal = {Heliyon}, volume = {9}, number = {5}, pages = {e15730}, pmid = {37305461}, issn = {2405-8440}, abstract = {Asbestos, a group of minerals with unique physical and chemical properties, has been widely used in various industries. However, extensive exposure to asbestos fibers, present in the environment, has been linked to several types of cancer, mesothelioma, and asbestosis. Despite worldwide regulations prohibiting or regulating the use of this material, the uncertainty surrounding the concentrations of asbestos fibers in the environment (air and water) from different sources of exposure persists. The objective of this review paper is to identify the levels of asbestos in air and water reported in the literature based on the source of exposure in diverse contexts to assess conformity with the reference limits for this mineral. Initially, the review delineates various forms of exposure and the origin of fiber generation in the environment, whether direct or indirect. Regarding the presence of asbestos in the environment, high concentrations were identified in natural water bodies known as Naturally Occurring Asbestos (NOA), and there is a risk in the process of distributing drinking water due to the presence of asbestos-cement pipes. In the air, studies to determine asbestos concentrations vary based on the sources of exposure in each region or city studied. The presence of asbestos mines around the city and the intensity of vehicular traffic are some of the most relevant sources found to be related to high concentrations of asbestos fibers in the air. The present review paper features a critical review section in each chapter to highlight critical points found in the literature and suggest new methodologies/ideas to standardize future research. It emphasizes the necessity to standardize methods for measuring asbestos concentrations in air and water arising from diverse sources of exposure to enable comparisons between different regions and countries.}, }
@article {pmid37302119, year = {2023}, author = {Torén, K and Neitzel, RL and Eriksson, HP and Andersson, E}, title = {Cancer incidence among workers in soft paper mills: A cohort study.}, journal = {American journal of industrial medicine}, volume = {66}, number = {9}, pages = {728-735}, doi = {10.1002/ajim.23508}, pmid = {37302119}, issn = {1097-0274}, mesh = {Male ; Humans ; Female ; Cohort Studies ; Incidence ; *Occupational Diseases/epidemiology/etiology ; *Neoplasms/chemically induced/epidemiology ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Pleural Neoplasms ; *Occupational Exposure/adverse effects ; *Sarcoma/complications ; Dust ; }, abstract = {OBJECTIVES: To elucidate whether occupational exposure to soft paper dust increases the incidence of cancer.<br><br>METHODS: We studied 7988 workers in Swedish soft paper mills from 1960 to 2008, of whom 3233 (2 187 men and 1046 women) had more than 10 years of employment. They were divided into high exposure (>5&#x2009;mg/m[3] for >1 year) or lower exposure to soft paper dust based on a validated job-exposure matrix. They were followed from 1960 to 2019, and person-years at risk were stratified according to gender, age, and calendar-year. The expected numbers of incident tumors were calculated using the Swedish population as the reference, and standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were assessed.<br><br>RESULTS: Among high-exposure workers with more than 10 years of employment, there was an increased incidence of colon cancer (SIR 1.66, 95% CI 1.20-2.31), small intestine cancer (SIR 3.27, 95% CI 1.36-7.86), and thyroid gland cancer (SIR 2.68, 95% CI 1.11-6.43), as well as lung cancer (SIR 1.56, 95% CI 1.12-2.19). Among the lower-exposed workers there was an increased incidence of connective tissue tumors (sarcomas) (SIR 2.26, 95% CI 1.13-4.51) and pleural mesothelioma (SIR 3.29, 95% CI 1.37-7.91).<br><br>CONCLUSION: Workers in soft paper mills with high exposure to soft paper dust have an increased incidence of large and small intestine tumors. Whether the increased risk is caused by paper dust exposure or some unknown associated factors is unclear. The increased incidence of pleural mesothelioma is probably linked to asbestos exposure. The reason for increased incidence of sarcomas is unknown.}, }
@article {pmid37297561, year = {2023}, author = {Fazzo, L and Minelli, G and De Santis, M and Ceccarelli, E and Iavarone, I and Zona, A}, title = {The Epidemiological Surveillance of Mesothelioma Mortality in Italy as a Tool for the Prevention of Asbestos Exposure.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {11}, pages = {}, pmid = {37297561}, issn = {1660-4601}, mesh = {Male ; Female ; Humans ; *Mesothelioma, Malignant ; *Mesothelioma/epidemiology ; *Asbestos ; Italy/epidemiology ; Asbestos, Amphibole ; *Occupational Exposure ; }, abstract = {As part of a surveillance plan active since the early 1990s, this study evaluates malignant mesothelioma (MM) mortality for the time-window 2010-2019 in Italy, a country that banned asbestos in 1992. National and regional mortality rates for MM, and municipal standardized mortality ratios (all mesotheliomas, pleural (MPM) and peritoneal (MPeM)), by gender and age group were calculated. A municipal clustering analysis was also performed. There were 15,446 deaths from MM (11,161 males, 3.8 × 100,000; 4285 females, 1.1 × 100,000), of which 12,496 were MPM and 661 were MPeM. In the study period, 266 people ≤50 years died from MM. A slightly decreasing rate among males since 2014 was observed. The areas at major risk hosted asbestos-cement plants, asbestos mines (chrysotile in Balangero), shipyards, petrochemical and chemical plants, and refineries. Female mortality excesses particularly were found in municipalities with a fluoro-edenite-contaminated mine (Biancavilla) and textile facilities. Excesses were also found in a region with the presence of natural asbestos fibres and in males living in two small islands. The Italian National Prevention Plan stated recommendations to eliminate asbestos exposures and to implement health surveillance and healthcare for people exposed to asbestos.}, }
@article {pmid37296902, year = {2023}, author = {Rondon, L and Fu, R and Patel, MR}, title = {Success of Checkpoint Blockade Paves the Way for Novel Immune Therapy in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {15}, number = {11}, pages = {}, pmid = {37296902}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a malignancy associated with asbestos exposure and is typically categorized as an orphan disease. Recent developments in immunotherapy with anti-PD-1 and anti-CTLA-4 antibodies, specifically with agents nivolumab and ipilimumab, have demonstrated an improvement in overall survival over the previous standard chemotherapy leading to their FDA-approval as first-line therapy for unresectable disease. For quite some time, it has been known that these proteins are not the only ones that function as immune checkpoints in human biology, and the hypothesis that MPM is an immunogenic disease has led to an expanding number of studies investigating alternative checkpoint inhibitors and novel immunotherapy for this malignancy. Early trials are also supporting the notion that therapies that target biological molecules on T cells, cancer cells, or that trigger the antitumor activity of other immune cells may represent the future of MPM treatment. Moreover, mesothelin-targeted therapies are thriving in the field, with forthcoming results from multiple trials signaling an improvement in overall survival when combined with other immunotherapy agents. The following manuscript will review the current state of immune therapy for MPM, explore the knowledge gaps in the field, and discuss ongoing novel immunotherapeutic research in early clinical trials.}, }
@article {pmid37295554, year = {2023}, author = {Schaefer, IM and Mariño-Enríquez, A and Hammer, MM and Padera, RF and Sholl, LM}, title = {Recurrent Tumor Suppressor Alterations in Primary Pericardial Mesothelioma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {36}, number = {9}, pages = {100237}, pmid = {37295554}, issn = {1530-0285}, support = {K08 CA241085/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Aged ; *Lung Neoplasms/pathology ; Neoplasm Recurrence, Local ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis ; *Pleural Neoplasms/pathology ; *Heart Neoplasms/genetics ; *Thymus Neoplasms ; Ubiquitin Thiolesterase/genetics/metabolism ; Biomarkers, Tumor/genetics/metabolism ; }, abstract = {Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be determined. Here, we report the clinicopathologic, immunohistochemical, and molecular genetic findings of 3 pericardial mesotheliomas without pleural involvement. Three cases diagnosed between 2004 and 2022 were included in the study and analyzed by immunohistochemistry and targeted next-generation sequencing (NGS); corresponding nonneoplastic tissue was sequenced in all cases. Two patients were female and 1 was male, aged between 66 and 75 years. Two patients each had prior asbestos exposure and were smokers. Histologic subtypes were epithelioid in 2 cases and biphasic in 1 case. Immunohistochemical staining identified expression of cytokeratin AE1/AE3 and calretinin in all cases, D2-40 in 2 cases, and WT1 in 1 case. Staining for tumor suppressors revealed loss of p16, MTAP, and Merlin (NF2) expression in 2 cases and loss of BAP1 and p53 in 1 case. Abnormal cytoplasmic BAP1 expression was observed in an additional case. Protein expression abnormalities correlated with NGS results, which showed concurrent complete genomic inactivation of CDKN2A/p16, CDKN2B, MTAP, and NF2 in 2 mesotheliomas and of BAP1 and TP53 in 1 mesothelioma each, respectively. In addition, 1 patient harbored a pathogenic BRCA1 germline mutation, which resulted in biallelic inactivation in the mesothelioma. All mesotheliomas were mismatch repair proficient and showed several chromosomal gains and losses. All patients died from disease. Our study demonstrates that pericardial mesotheliomas share common morphologic, immunohistochemical, and molecular genetic features with pleural mesothelioma, including recurrent genomic inactivation of canonical tumor suppressors. Our study adds new insights into the genetic landscape of primary pericardial mesothelioma and highlights BRCA1 loss as a potential contributing factor in a subset of cases, thereby contributing to refined precision diagnostics for this rare cancer.}, }
@article {pmid37293522, year = {2023}, author = {Tagliaferri, AR and Melki, G and Rezkalla, A and Baddoura, W}, title = {Diffuse malignant peritoneal mesothelioma presenting as small bowel obstruction.}, journal = {Radiology case reports}, volume = {18}, number = {8}, pages = {2681-2684}, pmid = {37293522}, issn = {1930-0433}, abstract = {Mesotheliomas are aggressive malignant tumors which can occur most commonly in the pleural space, however can occur in the peritoneum in those with an extensive history of asbestos exposure. Primary peritoneal mesothelioma is relatively rare and is a fatal diagnosis. The prognosis of primary peritoneal mesothelioma is very poor and individuals are at high risk of developing mesothelioma in another cavity within the first year after initial diagnosis. Herein, we present a case of primary peritoneal mesothelioma, presenting as small bowel obstruction.}, }
@article {pmid37292347, year = {2023}, author = {Migliore, M and Fiore, M and Filippini, T and Tumino, R and Sabbioni, M and Spatola, C and Polosa, R and Vigneri, P and Nardini, M and Castorina, S and Basile, F and Ferrante, M and , }, title = {Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16685}, pmid = {37292347}, issn = {2405-8440}, abstract = {Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6-80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12-25) in Group A and 28 months (95% CI 0-56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0-34) in Group A and 45 months (95% CI 0-107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.}, }
@article {pmid37254056, year = {2023}, author = {Ito, F and Kato, K and Yanatori, I and Maeda, Y and Murohara, T and Toyokuni, S}, title = {Matrigel-based organoid culture of malignant mesothelioma reproduces cisplatin sensitivity through CTR1.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {487}, pmid = {37254056}, issn = {1471-2407}, support = {JP18J13646, JP20K22805 and JP21K15484//Japan Society for the Promotion of Science/ ; JP20K17145, JP22K08123//Japan Society for the Promotion of Science/ ; JP19H05462 and JP20H05502//Japan Society for the Promotion of Science/ ; JPMJCR19H4//Core Research for Evolutional Science and Technology/ ; 19-25126//Princess Takamatsu Cancer Research Fund/ ; }, mesh = {Animals ; Humans ; Mice ; *Cisplatin/pharmacology ; Collagen/metabolism ; *Mesothelioma, Malignant/metabolism ; Organoids/pathology ; *Copper Transporter 1/metabolism ; }, abstract = {Organoids are a three-dimensional (3D) culture system that simulate actual organs. Therefore, tumor organoids are expected to predict precise response to chemotherapy in patients. However, to date, few studies have studied the drug responses in organoids of malignant mesothelioma (MM). The poor prognosis of MM emphasizes the importance of establishing a protocol for generating MM-organoid for research and clinical use. Here, we established murine MM organoids from p53[+/-] or wild-type C57BL/6 strain by intraperitoneal injection either with crocidolite or carbon nanotube. Established MM-organoids proliferated in Matrigel as spheroids. Subcutaneous injection assays revealed that the MM-organoids mimicked actual tissue architecture and maintained the original histological features of the primary MM. RNA sequencing and pathway analyses revealed that the significant expressional differences between the 2D- and 3D-culture systems were observed in receptor tyrosine kinases, including IGF1R and EGFR, glycosylation and cholesterol/steroid metabolism. MM-organoids exhibited a more sensitive response to cisplatin through stable plasma membrane localization of a major cisplatin transporter, copper transporter 1/Slc31A1 (Ctr1) in comparison to 2D-cultures, presumably through glycosylation and lipidation. The Matrigel culture system facilitated the localization of CTR1 on the plasma membrane, which simulated the original MMs and the subcutaneous xenografts. These results suggest that the newly developed protocol for MM-organoids is useful to study strategies to overcome chemotherapy resistance to cisplatin.}, }
@article {pmid37253383, year = {2023}, author = {Nash, A and Firth Née Phan, T and Creaney, J}, title = {New Markers for Management of Mesothelioma.}, journal = {Seminars in respiratory and critical care medicine}, volume = {44}, number = {4}, pages = {491-501}, doi = {10.1055/s-0043-1769097}, pmid = {37253383}, issn = {1098-9048}, mesh = {Humans ; *Mesothelioma, Malignant ; *Lung Neoplasms/diagnosis/drug therapy/genetics ; *Mesothelioma/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/drug therapy ; Biomarkers, Tumor/genetics ; }, abstract = {In this review, we provide an update on the status of cancer biomarkers for the clinical management of pleural mesothelioma, an aggressive cancer associated with asbestos exposure. Mesothelioma can be difficult to diagnose, and response to treatment is transient, even with recently adopted immune checkpoint inhibitor (ICI) combinations. Identification of mesothelioma-specific biomarkers could facilitate early diagnosis and tailor treatment strategies. Mesothelioma is characterized by frequent loss or alteration of the tumor suppressor genes cyclin-dependent kinase inhibitor 2A (CDKN2A) and BRCA1-associated protein-1 (BAP1). Accumulating data show these genes and/or their related protein products will be valuable tissue-based biomarkers for mesothelioma. Loss of BAP1, CDKN2A, p16, or methylthioadenosine phosphorylase provide pathologists with a reliable means of differentiating between mesothelioma and reactive mesothelial cell proliferations. This can aid diagnosis in difficult cases and is requisite for the identification of the new pathological entity malignant mesothelioma in situ. However, limited progress in identifying clinically useful soluble biomarkers in this cancer type has been made, with mesothelin remaining the benchmark. To date, results from studies to identify predictive biomarkers for ICI response have been disappointing. A recent retrospective study demonstrated BAP1 loss was predictive of improved survival following combination pemetrexed- and platinum-based chemotherapy. Validation of this result could have important clinical implications. Clinical trials aimed at targeting therapy based on biomarker expression are generally in the early phase setting, with overall results being moderate. The identification of biomarkers for mesothelioma remains a key research question due to their potential to improve patient outcomes in this deadly cancer.}, }
@article {pmid37248188, year = {2023}, author = {Zhao, F and Zhang, YL and Liu, X and Chen, TH and Li, J}, title = {[A case of malignant peritoneal mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {4}, pages = {307-309}, doi = {10.3760/cma.j.cn121094-20220328-00158}, pmid = {37248188}, issn = {1001-9391}, mesh = {Humans ; *Mesothelioma, Malignant/drug therapy ; *Mesothelioma/diagnosis ; Pemetrexed/therapeutic use ; Cisplatin/therapeutic use ; *Peritoneal Neoplasms/diagnosis ; *Pleural Neoplasms ; *Lung Neoplasms/drug therapy ; }, abstract = {Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.}, }
@article {pmid37247334, year = {2023}, author = {Ntlailane, L and Sebola, L and Singo, D and Nthoke, T and Mizan, G}, title = {Managing the risks of an asbestos bulk storage facility at a research institute.}, journal = {Annals of work exposures and health}, volume = {67}, number = {7}, pages = {907-911}, doi = {10.1093/annweh/wxad028}, pmid = {37247334}, issn = {2398-7316}, mesh = {Humans ; *Mesothelioma ; *Occupational Exposure ; *Asbestos ; Asbestos, Crocidolite ; Academies and Institutes ; }, abstract = {The South African National Institute for Occupational Health (NIOH), formerly the Pneumoconiosis Research Unit, has previously milled about 544 kg of anthophyllite, crocidolite, amosite and chrysotile asbestos fibre materials. This endeavour came about in an attempt to address a recommendation, made by the International Union Against Cancer (UICC), to make asbestos standard reference samples available for research. Some of these reference samples, as well as the bulk, unprocessed materials are still within the care of the NIOH and can be obtained for the purpose of Public Health research under strict terms and conditions. Considering the hazardous nature of asbestos and regulated prohibitions imposed on this mineral, the NIOH asbestos storage facility is being subjected to various occupational and environmental control measures to ensure that any potential fibre release, and subsequent risk of exposure, are prevented.}, }
@article {pmid37232345, year = {2023}, author = {Broggi, G and Filetti, V and Magro, G and Morante, B and Garro, R and Ledda, C and Rapisarda, V and Lombardo, C and Loreto, C and Caltabiano, R}, title = {Immunohistochemical expression of cAMP in fluoroedenite‑induced malignant pleural mesothelioma: Preliminary results.}, journal = {Molecular medicine reports}, volume = {28}, number = {1}, pages = {}, doi = {10.3892/mmr.2023.13019}, pmid = {37232345}, issn = {1791-3004}, mesh = {Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; *Mesothelioma, Malignant ; *Mesothelioma/chemically induced/metabolism ; *Lung Neoplasms/pathology ; *Asbestos ; }, abstract = {Despite advances in understanding of the biology of malignant pleural mesothelioma (MPM), the prognosis of this malignancy remains poor. Although asbestos still remains the main pathogenic agent of MPM, other asbestos‑like fibers such as fluoro‑edenite (FE) fibers, induce MPM. Notable incidence and mortality rates of MPM have been found in Biancavilla, Italy, where FE fibers have been extracted from building materials for >50 years. Cyclic adenosine monophosphate (cAMP) is a secondary messenger that plays a key role in several physiological and pathological mechanisms regulating protein kinase A (PKA) and the CREB pathway. Hyperactivation of the cAMP/PKA/CREB pathway is involved in many neoplastic processes, including tumor cell proliferation, invasion and metastatic spread. The present study investigated immunohistochemical expression of cAMP in patients with FE‑induced MPM, which included six males and four females with an age range of 50‑93 years. There was high immunoexpression of cAMP in 5 out of 10 tumors while the remaining 5 cases showed low immunoexpression. In addition, there was a correlation between cAMP overexpression and decreased survival times (mean overall survival times, 7.5 months in high expression group vs. 18 months in low expression group).}, }
@article {pmid37220527, year = {2023}, author = {Wang, D and Zhu, J and Li, N and Lu, H and Gao, Y and Zhuang, L and Chen, Z and Mao, W}, title = {GC-MS-based untargeted metabolic profiling of malignant mesothelioma plasma.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15302}, pmid = {37220527}, issn = {2167-8359}, mesh = {Humans ; *Mesothelioma, Malignant ; Gas Chromatography-Mass Spectrometry ; Metabolomics ; Alanine ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma.<br><br>METHODS: By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers.<br><br>RESULTS: Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid.<br><br>CONCLUSIONS: To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.}, }
@article {pmid37220304, year = {2023}, author = {Korchevskiy, AA and Wylie, AG}, title = {Toxicological and epidemiological approaches to carcinogenic potency modeling for mixed mineral fiber exposure: the case of fibrous balangeroite and chrysotile.}, journal = {Inhalation toxicology}, volume = {35}, number = {7-8}, pages = {185-200}, doi = {10.1080/08958378.2023.2213720}, pmid = {37220304}, issn = {1091-7691}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; Mineral Fibers/toxicity ; Carcinogens/toxicity ; Asbestos, Amphibole/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Lung Neoplasms/chemically induced/epidemiology ; *Asbestos/analysis ; }, abstract = {CONTEXT: Excess mesothelioma risk was observed among chrysotile miners and millers in Balangero, Italy. The mineral balangeroite has been identified in an asbestiform habit from the Balangero chrysotile mine (Italy). Previous studies did not contain a detailed description of the fiber dimensions, thus limiting possible approaches to estimating their carcinogenic potential.<br><br>OBJECTIVES: To reconstruct excess mesothelioma risk based on characteristics of mixed fiber exposure.<br><br>METHODS: The lengths and widths of particles from a sample of balangeroite were measured by transmission electron microscopy (TEM). Statistical analysis and modeling were applied to assess the toxicological potential of balangeroite.<br><br>RESULTS: Balangeroite fibers are characterized as asbestiform, with geometric mean length of 10 &#x3bc;m, width of 0.54 &#x3bc;m, aspect ratio of 19, and specific surface area of 13.8 (1/&#x3bc;m). Proximity analysis shows dimensional characteristics of balangeroite close to asbestiform anthophyllite. Modeling estimates the average potency of balangeroite as 0.04% (95% CI 0.0058, 0.16) based on dimensional characteristics and 0.05% (95% CI-0.04, 0.24) based on epidemiological data. The available estimate of the fraction of balangeroite in the Balangero mine is very approximate. There were no data for airborne balangeroite fibers from the Balangero mine and no lung burden data are available. All estimates were performed using weight fractions of balangeroite and chrysotile. However, based on reasonable assumptions, of the seven cases of mesothelioma in the cohort, about three cases (43%) can be attributed to fibrous balangeroite.<br><br>CONCLUSION: The presence of different types of mineral fibers in aerosolized materials even in small proportions can explain observed cancer risks.}, }
@article {pmid37217834, year = {2023}, author = {Zambrano, E and Matoso, A and Reyes-Múgica, M}, title = {Mesotheliomas in Children.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {4}, pages = {275-279}, doi = {10.1097/PAP.0000000000000403}, pmid = {37217834}, issn = {1533-4031}, mesh = {Adult ; Humans ; Child ; *Mesothelioma/genetics/pathology ; *Asbestos ; }, abstract = {Mesotheliomas are rare and aggressive tumors that originate from mesothelial cells. Although exceedingly rare, these tumors may occur in children. Different from adult mesotheliomas, however, environmental exposures particularly to asbestos do not appear to play a major role in mesotheliomas in children, in whom specific genetic rearrangements driving these tumors have been identified in recent years. These molecular alterations may increasingly offer opportunities for targeted therapies in the future, which may provide better outcomes for these highly aggressive malignant neoplasms.}, }
@article {pmid37210180, year = {2023}, author = {Carbone, M and Yang, H and Pass, HI and Taioli, E}, title = {Did the Ban on Asbestos Reduce the Incidence of Mesothelioma?.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {18}, number = {6}, pages = {694-697}, doi = {10.1016/j.jtho.2023.03.013}, pmid = {37210180}, issn = {1556-1380}, support = {R01 ES030948/ES/NIEHS NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Incidence ; *Lung Neoplasms/epidemiology/prevention &amp; control/complications ; *Mesothelioma/epidemiology/prevention &amp; control/etiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects/prevention &amp; control ; }, }
@article {pmid37199503, year = {2023}, author = {Giacobbe, C and Moliterni, A and Di Giuseppe, D and Malferrari, D and Wright, JP and Mattioli, M and Raneri, S and Giannini, C and Fornasini, L and Mugnaioli, E and Ballirano, P and Gualtieri, AF}, title = {The crystal structure of the killer fibre erionite from Tuzköy (Cappadocia, Turkey).}, journal = {IUCrJ}, volume = {10}, number = {Pt 4}, pages = {397-410}, pmid = {37199503}, issn = {2052-2525}, support = {20173X8WA4//PRIN: Progetti di Ricerca di Rilevante Interesse Nazionale-Bando 2017-Prot/ ; }, abstract = {Erionite is a non-asbestos fibrous zeolite classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen and is considered today similar to or even more carcinogenic than the six regulated asbestos minerals. Exposure to fibrous erionite has been unequivocally linked to cases of malignant mesothelioma (MM) and this killer fibre is assumed to be directly responsible for more than 50% of all deaths in the population of the villages of Karain and Tuzköy in central Anatolia (Turkey). Erionite usually occurs in bundles of thin fibres and very rarely as single acicular or needle-like fibres. For this reason, a crystal structure of this fibre has not been attempted to date although an accurate characterization of its crystal structure is of paramount importance for our understanding of the toxicity and carcinogenicity. In this work, we report on a combined approach of microscopic (SEM, TEM, electron diffraction), spectroscopic (micro-Raman) and chemical techniques with synchrotron nano-single-crystal diffraction that allowed us to obtain the first reliable ab initio crystal structure of this killer zeolite. The refined structure showed regular T-O distances (in the range 1.61-1.65 Å) and extra-framework content in line with the chemical formula (K2.63Ca1.57Mg0.76Na0.13Ba0.01)[Si28.62Al7.35]O72·28.3H2O. The synchrotron nano-diffraction data combined with three-dimensional electron diffraction (3DED) allowed us to unequivocally rule out the presence of offretite. These results are of paramount importance for understanding the mechanisms by which erionite induces toxic damage and for confirming the physical similarities with asbestos fibres.}, }
@article {pmid37194050, year = {2023}, author = {RanYue, W and ChunYan, W and Likun, H and LiPing, Z and JieLu, L and ZhengWei, D}, title = {Diffuse intrapulmonary mesothelioma mimicking pulmonary lepidic adenocarcinoma: a rare case report and review of the literature.}, journal = {Diagnostic pathology}, volume = {18}, number = {1}, pages = {64}, pmid = {37194050}, issn = {1746-1596}, mesh = {Humans ; In Situ Hybridization, Fluorescence ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant/diagnosis ; *Lung Neoplasms/diagnosis/pathology ; *Pleural Neoplasms/pathology ; *Adenocarcinoma of Lung/diagnosis ; *Lung Diseases, Interstitial/diagnosis ; Biomarkers, Tumor/metabolism ; Diagnosis, Differential ; }, abstract = {Mesothelioma, with various clinical manifestations, radiological features, and histomorphological types, can be divided into epithelioid, sarcomatoid, and biphasic types, according to their histomorphological characteristics. There is a rare growth pattern of pleural mesothelioma: diffuse intrapulmonary mesothelioma (DIM), with a distinctive pattern of predominantly intrapulmonary growth, has no or minimal pleural involvement, and simulates interstitial lung disease(ILD) clinically and radiologically. A 59-year-old man presented to the hospital with recurrent pleural effusions for 4 years and a history of asbestos exposure. Computed tomography (CT) showed bilateral pure ground-glass opacity lesions, and the tumor cells showed a lepidic growth pattern pathologically. Immunohistochemical staining was positive for CK, WT-1, calretinin, D2-40, CK5/6, and Claudin4, while TTF-1, CEA, EMA, CK7, CK20, and other epithelial markers were negative. BAP1 loss its expression, and MTAP was positive in cytoplasm. CDKN2A was negative tested by Fluorescence in situ hybridization (FISH). The final diagnosis was DIM. In conclusion, we should recognize this rare disease to avoid misdiagnosis and delayed treatment.}, }
@article {pmid37190292, year = {2023}, author = {Ahmadzada, T and Vijayan, A and Vafaee, F and Azimi, A and Reid, G and Clarke, S and Kao, S and Grau, GE and Hosseini-Beheshti, E}, title = {Small and Large Extracellular Vesicles Derived from Pleural Mesothelioma Cell Lines Offer Biomarker Potential.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190292}, issn = {2072-6694}, support = {Corporate/private financial support//Turner Freeman Lawyers/ ; TBC//Dust Diseases Board/ ; }, abstract = {Pleural mesothelioma, previously known as malignant pleural mesothelioma, is an aggressive and fatal cancer of the pleura, with one of the poorest survival rates. Pleural mesothelioma is in urgent clinical need for biomarkers to aid early diagnosis, improve prognostication, and stratify patients for treatment. Extracellular vesicles (EVs) have great potential as biomarkers; however, there are limited studies to date on their role in pleural mesothelioma. We conducted a comprehensive proteomic analysis on different EV populations derived from five pleural mesothelioma cell lines and an immortalized control cell line. We characterized three subtypes of EVs (10 K, 18 K, and 100 K), and identified a total of 4054 unique proteins. Major differences were found in the cargo between the three EV subtypes. We show that 10 K EVs were enriched in mitochondrial components and metabolic processes, while 18 K and 100 K EVs were enriched in endoplasmic reticulum stress. We found 46 new cancer-associated proteins for pleural mesothelioma, and the presence of mesothelin and PD-L1/PD-L2 enriched in 100 K and 10 K EV, respectively. We demonstrate that different EV populations derived from pleural mesothelioma cells have unique cancer-specific proteomes and carry oncogenic cargo, which could offer a novel means to extract biomarkers of interest for pleural mesothelioma from liquid biopsies.}, }
@article {pmid37190163, year = {2023}, author = {Collatuzzo, G and Turati, F and Malvezzi, M and Negri, E and La Vecchia, C and Boffetta, P}, title = {Attributable Fraction of Cancer Related to Occupational Exposure in Italy.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190163}, issn = {2072-6694}, support = {22987//Italian Association for Cancer Research/ ; }, abstract = {BACKGROUND: Exposure to occupational carcinogens is an important and avoidable cause of cancer. We aimed to provide an evidence-based estimate of the burden of occupation-related cancers in Italy.<br><br>METHODS: The attributable fraction (AF) was calculated based on the counterfactual scenario of no occupational exposure to carcinogens. We included exposures classified as IARC group 1 and with reliable evidence of exposure in Italy. Relative risk estimates for selected cancers and prevalences of exposure were derived from large-scale studies. Except for mesothelioma, a 15-20-year latency period between exposure and cancer was considered. The data on cancer incidence in 2020 and mortality in 2017 in Italy were obtained from the Italian Association of Cancer Registries.<br><br>RESULTS: The most prevalent exposures were UV radiation (5.8%), diesel exhaust (4.3%), wood dust (2.3%) and silica dust (2.1%). Mesothelioma had the largest AF to occupational carcinogens (86.6%), followed by sinonasal cancer (11.8%) and lung cancer (3.8%). We estimated that 0.9% of cancer cases (N~3500) and 1.6% of cancer deaths (N~2800) were attributable to occupational carcinogens in Italy. Of these, about 60% were attributable to asbestos, 17.5% to diesel exhaust, followed by chromium and silica dust (7% and 5%).<br><br>CONCLUSIONS: Our estimates provide up-to-date quantification of the low, but persistent, burden of occupational cancers in Italy.}, }
@article {pmid37189132, year = {2023}, author = {Kauschke, V and Philipp-Gehlhaar, M and Schneider, J}, title = {Expression of microRNAs in leukocytes and serum of asbestosis patients.}, journal = {European journal of medical research}, volume = {28}, number = {1}, pages = {175}, pmid = {37189132}, issn = {2047-783X}, mesh = {Humans ; *MicroRNAs ; *Asbestosis/genetics ; Biomarkers ; *Asbestos ; Leukocytes/metabolism ; }, abstract = {BACKGROUND: Although asbestos use is banned in many countries, long latency of asbestos-related diseases like pleural plaques or asbestosis mean it is still a public health issue. People suffering from these diseases have a higher risk of developing mesothelioma or lung cancer, which can progress quickly and aggressively. MicroRNAs were suggested as potential biomarkers in several diseases. However, in asbestosis, blood microRNAs are less explored. Since miR-32-5p, miR-143-3p, miR-145-5p, miR-146b-5p, miR-204-5p and miR-451a are involved in fibrotic processes and in cancer, expression of these microRNAs was analyzed in leukocytes and serum of asbestosis patients.<br><br>METHODS: MicroRNA expression was analyzed in leukocytes and serum of 36 patients (26 affected by pleural plaques and 10 by asbestosis) and 15 healthy controls by real-time RT-PCR. Additionally, data analyses were performed regarding disease severity based on ILO classification.<br><br>RESULTS: MicroRNA miR-146b-5p was significantly down-regulated in leukocytes of patients suffering from pleural plaques with a large effect indicated by &#x3b7;[2]p&#x2009;=&#x2009;0.150 and Cohen's f&#x2009;=&#x2009;0.42, a value of difference of 0.725 and a 95% confidence interval of 0.070-1.381. In patients suffering from asbestosis miR-146b-5p was not significantly regulated. However, data analyses considering disease severity only, revealed that miR-146b-5p was significantly down-regulated in leukocytes of mildly diseased patients compared to controls with a large effect indicated by &#x3b7;[2]p&#x2009;=&#x2009;0.178 and Cohen's f&#x2009;=&#x2009;0.465, a value of difference of 0.848 and a 95% confidence interval of 0.097-1.599. Receiver operating characteristic (ROC) curve and an area under the ROC curve value of 0.757 for miR-146b-5p indicated acceptable discrimination ability between patients suffering from pleural plaques and healthy controls. Less microRNAs were detectable in serum than in leukocytes, showing no significant expression differences in all participants of this study. Moreover, miR-145-5p was regulated significantly differently in leukocytes and serum. An R[2] value of 0.004 for miR-145-5p indicated no correlation in microRNA expression between leukocytes and serum.<br><br>CONCLUSION: Leukocytes seem more suitable than serum for microRNA analyses regarding disease and potentially cancer risk assessment of patients suffering from asbestos-related pleural plaques or asbestosis. Long-term studies may reveal whether down-regulation of miR-146b-5p in leukocytes might be an early indicator for an increased cancer risk.}, }
@article {pmid37180489, year = {2023}, author = {Sekido, Y and Sato, T}, title = {NF2 alteration in mesothelioma.}, journal = {Frontiers in toxicology}, volume = {5}, number = {}, pages = {1161995}, pmid = {37180489}, issn = {2673-3080}, abstract = {The NF2 tumor suppressor gene is a frequent somatically mutated gene in mesothelioma, with 30%-40% mesotheliomas showing NF2 inactivation. NF2 encodes merlin, a member of the ezrin, radixin, and moesin (ERM) family of proteins that regulate cytoskeleton and cell signaling. Recent genome analysis revealed that NF2 alteration may be a late event in mesothelioma development, suggesting that NF2 mutation confers a more aggressive phenotype to mesothelioma cells and may not be directly caused by asbestos exposure. The Hippo tumor-suppressive and mTOR prooncogenic signaling pathways are crucial cell-signaling cascades regulated by merlin. Although the exact role and timing of NF2 inactivation in mesothelioma cells remain to be elucidated, targeting the NF2/merlin-Hippo pathway may be a new therapeutic strategy for patients with mesothelioma.}, }
@article {pmid37178944, year = {2023}, author = {Brown, JS}, title = {Comparison of Oncogenes, Tumor Suppressors, and MicroRNAs Between Schizophrenia and Glioma: The Balance of Power.}, journal = {Neuroscience and biobehavioral reviews}, volume = {151}, number = {}, pages = {105206}, doi = {10.1016/j.neubiorev.2023.105206}, pmid = {37178944}, issn = {1873-7528}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Schizophrenia/genetics ; Oncogenes ; *Glioma/genetics ; }, abstract = {The risk of cancer in schizophrenia has been controversial. Confounders of the issue are cigarette smoking in schizophrenia, and antiproliferative effects of antipsychotic medications. The author has previously suggested comparison of a specific cancer like glioma to schizophrenia might help determine a more accurate relationship between cancer and schizophrenia. To accomplish this goal, the author performed three comparisons of data; the first a comparison of conventional tumor suppressors and oncogenes between schizophrenia and cancer including glioma. This comparison determined schizophrenia has both tumor-suppressive and tumor-promoting characteristics. A second, larger comparison between brain-expressed microRNAs in schizophrenia with their expression in glioma was then performed. This identified a core carcinogenic group of miRNAs in schizophrenia offset by a larger group of tumor-suppressive miRNAs. This proposed "balance of power" between oncogenes and tumor suppressors could cause neuroinflammation. This was assessed by a third comparison between schizophrenia, glioma and inflammation in asbestos-related lung cancer and mesothelioma (ALRCM). This revealed that schizophrenia shares more oncogenic similarity to ALRCM than glioma.}, }
@article {pmid37175892, year = {2023}, author = {Cugliari, G}, title = {FKBP5, a Modulator of Stress Responses Involved in Malignant Mesothelioma: The Link between Stress and Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175892}, issn = {1422-0067}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/pathology ; *Pleural Neoplasms/pathology ; *Asbestos/toxicity ; *Lung Neoplasms/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare tumour characterized by a long latency period after asbestos exposure and poor survival [...].}, }
@article {pmid37172528, year = {2023}, author = {Du, X and Li, X and Zhang, B and Hao, Z and Gao, Y and Jiang, X and Yang, Z and Chen, Y}, title = {The clinicopathological significance of TOP2A expression in malignant peritoneal mesothelioma.}, journal = {Annals of diagnostic pathology}, volume = {65}, number = {}, pages = {152155}, doi = {10.1016/j.anndiagpath.2023.152155}, pmid = {37172528}, issn = {1532-8198}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Asbestos ; Ki-67 Antigen/metabolism ; *Lung Neoplasms/pathology ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms ; *Pleural Neoplasms/metabolism/pathology ; Prognosis ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. TOP2A expression is associated with cell proliferation and cell cycle progression. We aimed to demonstrate the expression profile of TOP2A in MPM and its correlation with clinicopathological features.<br><br>METHODS: Clinicopathological information from 100 MPM cases was collected at Beijing Shijitan Hospital, Capital Medical University. Immunohistochemistry (IHC) was performed to evaluate TOP2A levels. The associations between TOP2A levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to determine correlations among the pathological prognostic factors using the Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models.<br><br>RESULTS: Among the 100 MPM patients, there were 48 males and 52 females, with a median age of 54&#xa0;years (range: 24-72&#xa0;years). The cutoff curve was used to find the boundary value of the TOP2A-positive rate. TOP2A positive rate&#xa0;&#x2265;&#xa0;11.97&#xa0;% accounted for 48&#xa0;% in tumor tissue. The TOP2A-positive rate was not associated with sex, age, asbestos exposure, peritoneal carcinomatosis index (PCI) score, or completeness of cytoreduction (CC) score in MPM. Univariate analysis revealed survival-related pathological parameters, including asbestos exposure, CA125, histological type, PCI score, CC score, Ki-67 index, and TOP2A positive rate. Multivariate analysis identified that asbestos exposure history, PCI score, Ki-67 proliferation index and TOP2A positive rate in tissue are independent prognostic factors.<br><br>CONCLUSIONS: High expression of TOP2A is linked to better prognosis of MPM.}, }
@article {pmid37168168, year = {2023}, author = {Singh, R and Frank, AL}, title = {Does the Presence of Asbestos-Containing Materials in Buildings Post-construction and Before Demolition Have an Impact on the Exposure to Occupants in Non-occupational Settings?.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e37305}, pmid = {37168168}, issn = {2168-8184}, abstract = {This narrative review aims to determine if asbestos-containing materials in buildings pose a hazard to building occupants in non-occupational settings. This paper is limited to the post-construction and pre-demolition stages of a building. The researchers selected 19 studies from the 126 studies screened, concerning exposure to asbestos fibers in non-occupational building settings, with a focus on post-construction and pre-demolition phases. The literature review found that certain conditions, such as the measurement techniques, standards, and previous data availability, prevent a conclusive answer to the research question. Some studies have pointed towards an effect of asbestos-containing materials on health of occupants in non-occupational settings. But, there are some that do not suggest a positive relationship between non-occupational exposure and the presence of asbestos-containing materials, and therefore these provide scope for further research, as these studies also do not rule out the relationship completely. The present study highlights the gaps in current knowledge and indicates areas for further research. Until conclusive evidence based on revised threshold standards and accurate measurement techniques is available, asbestos-containing materials may be considered unsafe for use in non-occupational settings, especially ones that young people and children occupy.}, }
@article {pmid37167572, year = {2023}, author = {Hathaway, F and Martins, R and Sorscher, S and Bzura, A and Dudbridge, F and Fennell, DA}, title = {Family Matters: Germline Testing in Thoracic Cancers.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {43}, number = {}, pages = {e389956}, doi = {10.1200/EDBK_389956}, pmid = {37167572}, issn = {1548-8756}, mesh = {Humans ; *Lung Neoplasms/diagnosis/epidemiology/etiology ; ErbB Receptors/genetics ; *Carcinoma, Non-Small-Cell Lung ; Mutation ; Tumor Suppressor Proteins/genetics/metabolism ; Protein Kinase Inhibitors ; *Mesothelioma ; *Mesothelioma, Malignant ; *Asbestos ; Germ-Line Mutation ; Germ Cells/metabolism ; Genetic Predisposition to Disease ; }, abstract = {Most thoracic cancers arise via a series of stepwise somatic alterations driven by a well-defined carcinogen (ie, tobacco or asbestos for lung cancer and mesothelioma, respectively). A small proportion can emerge on a background of pathogenic germline variants (PGVs), which have the property of heritability. In general, PGVs may be initially suspected on the basis of the presence of specific clinical features. Such gene × environment interactions significantly increase the risk of developing lung cancer (1.5- to 3.2-fold). PGVs have been discovered involving the actionable driver oncogene, epidermal growth factor receptor (EGFR), with an EGFR T790M PGV rate of 0.3%-0.9% in the nonsquamous non-small-cell lung cancer subtype. Its appearance during routine somatic DNA sequencing in those patients who have not had a previous tyrosine kinase inhibitor should raise suspicion. In patients with sporadic mesothelioma, BAP1 is the most frequently mutated tumor driver, with a PGV rate between 2.8% and 8%, associated with a favorable prognosis. BAP1 PGVs accelerate mesothelioma tumorigenesis after asbestos exposure in preclinical models and may be partly predicted by clinical criteria. At present, routine germline genetic testing for thoracic cancers is not a standard practice. Expert genetic counseling is, therefore, required for patients who carry a PGV. Ongoing studies aim to better understand the natural history of patients harboring PGVs to underpin future cancer prevention, precise counseling, and cancer management with the goal of improving the quality and length of life.}, }
@article {pmid37165917, year = {2023}, author = {Sato, T and Akao, K and Sato, A and Tsujimura, T and Mukai, S and Sekido, Y}, title = {Aberrant expression of NPPB through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations.}, journal = {Cancer medicine}, volume = {12}, number = {12}, pages = {13586-13598}, pmid = {37165917}, issn = {2045-7634}, mesh = {Humans ; Hippo Signaling Pathway ; *Mesothelioma, Malignant ; *Mesothelioma/genetics ; *Pleural Effusion ; Protein Serine-Threonine Kinases/genetics/metabolism ; Tumor Suppressor Proteins/metabolism ; }, abstract = {BACKGROUND: Mesothelioma is a neoplastic disease associated with asbestos exposure. It is highly malignant and has a poor prognosis; thus, early detection is desirable. Recent whole-genome analysis has revealed that mesothelioma is characterized by a high frequency of mutations in a set of genes involved in the Hippo pathway, such as NF2 and LATS2. However, a rapid, simple, and precise method for finding mesothelioma with these mutations has not yet been established.<br><br>METHODS: Clustering of Hippo pathway gene alteration groups and the differential expression of each gene in mesothelioma patients were analyzed using The Cancer Genome Atlas database. Gene expression levels in various tumors and normal tissues were analyzed using public databases. Knockdown or transient expression of YAP1 or TAZ was performed to evaluate the regulation of gene expression by these genes. NT-proBNP was measured in the pleural effusions of 18 patients and was compared with NF2 expression in five cases where cell lines had been successfully established.<br><br>RESULTS: NPPB mRNA expression was markedly higher in the group of mesothelioma patients with Hippo pathway gene mutations than in the group without them. NPPB expression was low in all normal tissues except heart, and was highest in mesothelioma. Mesothelioma patients in the high NPPB expression group had a significantly worse prognosis than those in the low NPPB expression group. NPPB expression was suppressed by knockdown of YAP1 or TAZ. NT-proBNP was abundant in the effusions of mesothelioma patients and was particularly high in those with impaired NF2 expression.<br><br>CONCLUSIONS: NPPB, whose levels can be measured in pleural effusions of mesothelioma patients, has the potential to act as a biomarker to detect NF2-Hippo pathway gene alterations and/or predict patient prognosis. Additionally, it may provide useful molecular insights for a better understanding of mesothelioma pathogenesis and for the development of novel therapies.}, }
@article {pmid37158685, year = {2023}, author = {Moline, J}, title = {Response to the Letter to the Editor From Jeffrey Brent, MD, PhD. Re: Mesothelioma Associated With the Use of Cosmetic Talc.}, journal = {Journal of occupational and environmental medicine}, volume = {65}, number = {5}, pages = {e361}, doi = {10.1097/JOM.0000000000002840}, pmid = {37158685}, issn = {1536-5948}, mesh = {Humans ; Talc/adverse effects ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; }, }
@article {pmid37150820, year = {2023}, author = {Avramescu, ML and Potiszil, C and Kunihiro, T and Okabe, K and Nakamura, E}, title = {An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma.}, journal = {Particle and fibre toxicology}, volume = {20}, number = {1}, pages = {19}, pmid = {37150820}, issn = {1743-8977}, mesh = {Animals ; Mice ; *Mesothelioma, Malignant/pathology ; Smoking/adverse effects ; *Asbestos/toxicity/analysis ; Lung ; *Lung Neoplasms/chemically induced/pathology ; *Mesothelioma/chemically induced/pathology ; }, abstract = {BACKGROUND: Asbestos is a fibrous mineral that was widely used in the past. However, asbestos inhalation is associated with an aggressive type of cancer known as malignant mesothelioma (MM). After inhalation, an iron-rich coat forms around the asbestos fibres, together the coat and fibre are termed an "asbestos ferruginous body" (AFB). AFBs are the main features associated with asbestos-induced MM. Whilst several studies have investigated the external morphology of AFBs, none have characterised the internal morphology. Here, cross-sections of multiple AFBs from two smokers and two non-smokers are compared to investigate the effects of smoking on the onset and growth of AFBs. Morphological and chemical observations of AFBs were undertaken by transmission electron microscopy, energy dispersive x-ray spectroscopy and selected area diffraction.<br><br>RESULTS: The AFBs of all patients were composed of concentric layers of 2-line or 6-line ferrihydrite, with small spherical features being observed on the outside of the AFBs and within the cross-sections. The spherical components are of a similar size to Fe-rich inclusions found within macrophages from mice injected with asbestos fibres in a previous study. As such, the spherical components composing the AFBs may result from the deposition of Fe-rich inclusions during frustrated phagocytosis. The AFBs were also variable in terms of their Fe, P and Ca abundances, with some layers recording higher Fe concentrations (dense layers), whilst others lower Fe concentrations (porous layers). Furthermore, smokers were found to have smaller and overall denser AFBs than non-smokers.<br><br>CONCLUSIONS: The AFBs of smokers and non-smokers show differences in their morphology, indicating they grew in lung environments that experienced disparate conditions. Both the asbestos fibres of smokers and non-smokers were likely subjected to frustrated phagocytosis and accreted mucopolysaccharides, resulting in Fe accumulation and AFB formation. However, smokers' AFBs experienced a more uniform Fe-supply within the lung environment compared to non-smokers, likely due to Fe complexation from cigarette smoke, yielding denser, smaller and more Fe-rich AFBs. Moreover, the lack of any non-ferrihydrite Fe phases in the AFBs may indicate that the ferritin shell was intact, and that ROS may not be the main driver for the onset of MM.}, }
@article {pmid37147569, year = {2023}, author = {Liang, Y and Li, C and Liu, Y and Tian, L and Yang, D}, title = {Prognostic role of CD74, CD10 and Ki-67 immunohistochemical expression in patients with diffuse malignant peritoneal mesothelioma: a retrospective study.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {406}, pmid = {37147569}, issn = {1471-2407}, support = {2016-304//Cangzhou Finance Bureau/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; Prognosis ; Retrospective Studies ; Ki-67 Antigen/metabolism ; *Mesothelioma/pathology ; *Percutaneous Coronary Intervention ; Biomarkers, Tumor/metabolism ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Diagnosis and treatment of diffuse malignant peritoneal mesothelioma (DMPM) are still challenging. The aim of the present study was to explore the correlation between CD74, CD10, Ki-67 and clinicopathological parameters, and identify independent prognostic factors of DMPM.<br><br>METHODS: Seventy patients with pathologically proven DMPM were retrospectively reviewed. The expression of CD74, CD10 and Ki-67 in peritoneal tissues was detected by immunohistochemical analysis using standard avidin biotin complex (ABC) immunostaining technique. Kaplan-Meier survival analysis and multivariate Cox regression analyses were performed to assess prognostic factors. The nomogram based on the Cox hazards regression model was established. C-index and calibration curve were performed to evaluate the accuracy of nomogram models.<br><br>RESULTS: The median age of DMPM was 62.34&#xa0;years, and the male-to-female ratio was 1: 1.80. CD74 expression was identified in 52 (74.29%) of 70 specimens, CD10 in 34 (48.57%) specimens, and higher Ki-67 in 33(47.14%) specimens. CD74 was negatively associated with asbestos exposure(r&#x2009;=&#x2009;-0.278), Ki-67(r&#x2009;=&#x2009;-0.251) and TNM stage(r&#x2009;=&#x2009;-0.313). All patients were effectively&#xa0;followed&#xa0;up in the survival analysis. Univariate analysis revealed that PCI, TNM stage, treatment, Ki-67, CD74 and ECOG PS were associated with DMPM prognosis. CD74 (HR&#x2009;=&#x2009;0.65, 95%Cl:0.46-0.91, P&#x2009;=&#x2009;0.014), Ki-67(HR&#x2009;=&#x2009;2.09, 95%Cl:1.18-3.73, P&#x2009;=&#x2009;0.012),TNM stage (HR&#x2009;=&#x2009;1.89, 95%Cl:1.16-3.09, P&#x2009;=&#x2009;0.011), ECOG PS(HR&#x2009;=&#x2009;2.12, 95%Cl:1.06-4.25, P&#x2009;=&#x2009;0.034), systemic chemotherapy (HR&#x2009;=&#x2009;0.41, 95%Cl:0.21-0.82, P&#x2009;=&#x2009;0.011) and intraperitoneal chemotherapy (HR&#x2009;=&#x2009;0.34, 95%Cl:0.16-0.71, P&#x2009;=&#x2009;0.004) were independent predictors by multivariate Cox analysis. The C&#x2011;index of the nomogram for predicting overall survival (OS) was 0.81. The OS calibration curve showed good agreement between nomogram-predicted and observed survival.<br><br>CONCLUSIONS: CD74, Ki-67, TNM stage, ECOG PS and treatment were independent factors affecting prognosis of DMPM. Reasonable chemotherapy treatment might improve the prognosis of patients. The proposed nomogram was a visual tool to effectively predict the OS of DMPM patients.}, }
@article {pmid37147272, year = {2023}, author = {Yang, D and Chen, C and Xia, H and Chen, J and Yu, M}, title = {Characteristics of transcription profile, adhesion and migration of SETD2-loss Met-5A mesothelial cells exposed with crocidolite.}, journal = {Journal of applied toxicology : JAT}, volume = {43}, number = {10}, pages = {1511-1521}, doi = {10.1002/jat.4493}, pmid = {37147272}, issn = {1099-1263}, mesh = {Humans ; Asbestos, Crocidolite/toxicity/metabolism ; Epithelium ; *Asbestos/toxicity ; *Mesothelioma ; Silicates ; Cell Adhesion Molecule-1/metabolism ; }, abstract = {Asbestos is a fibrous silicate mineral exhibiting biopersistence and carcinogenic properties and contributes to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with SET domain containing 2 (SETD2) loss and asbestos exposure remains obscure. Herein, CRISPR/Cas9-mediated SETD2 knockout Met-5A mesothelial cells (Met-5A[SETD2-KO]) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5A[SETD2-KO] appeared to dramatically decrease with ≥2.5 μg/cm[2] crocidolite exposure as compared with Met-5A, although no cytotoxicity and apoptosis changes of Met-5A[SETD2-KO] and Met-5A was evident with 1.25 μg/cm[2] crocidolite exposure for 48 h. RNA sequencing uncovered top 50 differentially expressed genes (DEGs) between 1.25 μg/cm[2] crocidolite exposed Met-5A[SETD2-KO] (Cro-Met-5A[SETD2-KO]) and 1.25 μg/cm[2] crocidolite exposed Met-5A (Cro-Met-5A), and ITGA4, THBS2, MYL7, RAC2, CADM1, and CLDN11 appeared to be the primary DEGs involved with adhesion in gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Cro-Met-5A[SETD2-KO] had strong migration but mild adhesion behavior as compared with Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5A[SETD2-KO] but inhibited migration of Met-5A when compared with their corresponding cells without crocidolite exposure, although no further adhesion property changes was evident for both cells in response to crocidolite. Therefore, crocidolite may affect adhesion-related gene expression and modify adhesion and migration behavior for SETD2-depleted Met-5A, which could provide preliminary insight regarding the potential role of SETD2 in the cell behavior of asbestos-related malignant mesothelial cell.}, }
@article {pmid37146474, year = {2023}, author = {Tada, A and Minami, T and Kitai, H and Higashiguchi, Y and Tokuda, M and Higashiyama, T and Negi, Y and Horio, D and Nakajima, Y and Otsuki, T and Mikami, K and Takahashi, R and Nakamura, A and Kitajima, K and Ohmuraya, M and Kuribayashi, K and Kijima, T}, title = {Combination therapy with anti-programmed cell death 1 antibody plus angiokinase inhibitor exerts synergistic antitumor effect against malignant mesothelioma via tumor microenvironment modulation.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {180}, number = {}, pages = {107219}, doi = {10.1016/j.lungcan.2023.107219}, pmid = {37146474}, issn = {1872-8332}, mesh = {Humans ; Female ; Animals ; Mice ; Cell Line, Tumor ; Mice, Inbred C57BL ; *Mesothelioma, Malignant/drug therapy ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Indoles/therapeutic use ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; *Protein Kinase Inhibitors/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; *Antibodies, Monoclonal/therapeutic use ; Allografts ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related fatal malignant neoplasm. Although there has been no reliable chemotherapeutic regimen other than combination therapy of cisplatin and pemetrexed for two decades, combination of ipilimumab plus nivolumab brought about a better outcome in patients with MPM. Thus, cancer immunotherapy using immune checkpoint inhibitor (ICI) is expected to play a central role in the treatment of MPM. To maximize the antitumor effect of ICI, we evaluated whether nintedanib, an antiangiogenic agent, could augment the antitumor effect of anti-programmed cell death 1 (PD-1) antibody (Ab). Although nintedanib could not inhibit the proliferation of mesothelioma cells in vitro, it significantly suppressed the growth of mesothelioma allografts in mice. Moreover, combination therapy with anti-PD-1 Ab plus nintedanib reduced tumor burden more dramatically compared with nintedanib monotherapy via inducing remarkable necrosis in MPM allografts. Nintedanib did not promote the infiltration of CD8[+] T cells within the tumor when used alone or in combination with anti-PD-1 Ab but it independently decreased the infiltration of tumor-associated macrophages (TAMs). Moreover, immunohistochemical analysis and ex vivo study using bone marrow-derived macrophages (BMDMs) showed that nintedanib could polarize TAMs from M2 to M1 phenotype. These results indicated that nintedanib had a potential to suppress protumor activity of TAMs both numerically and functionally. On the other hand, ex vivo study revealed that nintedanib upregulated the expression of PD-1 and PD-ligand 1 (PD-L1) in BMDMs and mesothelioma cells, respectively, and exhibited the impairment of phagocytic activity of BMDMs against mesothelioma cells. Co-administration of anti-PD-1 Ab may reactivate phagocytic activity of BMDMs by disrupting nintedanib-induced immunosuppressive signal via binding between PD-1 on BMDMs and PD-L1 on mesothelioma cells. Collectively, combination therapy of anti-PD-1 Ab plus nintedanib enhances the antitumor activity compared with respective monotherapy and can become a novel therapeutic option for patients with MPM.}, }
@article {pmid37146029, year = {2023}, author = {Orozco Morales, ML and Rinaldi, CA and de Jong, E and Lansley, SM and Lee, YCG and Zemek, RM and Bosco, A and Lake, RA and Lesterhuis, WJ}, title = {Geldanamycin treatment does not result in anti-cancer activity in a preclinical model of orthotopic mesothelioma.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0274364}, pmid = {37146029}, issn = {1932-6203}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy/genetics ; *Pleural Neoplasms/pathology ; Cell Proliferation ; *Lung Neoplasms/drug therapy/genetics/pathology ; }, abstract = {Mesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a non-invasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples. Invasive pleural tumours were characterised by a transcriptomic signature enriched for genes associated with MEF2C and MYOCD signaling, muscle differentiation and myogenesis. Further analysis using the CMap and LINCS databases identified geldanamycin as a potential antagonist of this signature, so we evaluated its potential in vitro and in vivo. Nanomolar concentrations of geldanamycin significantly reduced cell growth, invasion, and migration in vitro. However, administration of geldanamycin in vivo did not result in significant anti-cancer activity. Our findings show that myogenesis and muscle differentiation pathways are upregulated in pleural mesothelioma which may be related to the invasive behaviour. However, geldanamycin as a single agent does not appear to be a viable treatment for mesothelioma.}, }
@article {pmid37139482, year = {2023}, author = {Ma, GY and Shi, S and Sang, YZ and Wang, P and Zhang, ZG}, title = {High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {6575194}, pmid = {37139482}, issn = {2314-6141}, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; Zinc Finger Protein GLI1/genetics/metabolism ; Lymphatic Metastasis ; Signal Transduction ; Hedgehog Proteins/genetics ; *Mesothelioma/genetics/pathology ; Prognosis ; RNA, Messenger/genetics ; Biomarkers, Tumor/genetics/metabolism ; Smoothened Receptor/genetics ; }, abstract = {BACKGROUND: To investigate the value of SMO and GLI1 genes in the hedgehog pathway in malignant mesothelioma specimens. Further study on the expression and prognosis of SMO and GLI1 in malignant mesothelioma tissues and the relationship between the two and the molecular mechanisms of mesothelioma immunity and to further investigate the prognostic value of mesothelioma expression.<br><br>MATERIALS AND METHODS: Immunohistochemistry and RT-qPCR were applied to detect the expression of SMO and GLI1 proteins and mRNA in biopsy specimens and plasma cavity effusion specimens from malignant mesothelioma (n = 130) and benign mesothelial tissues (n = 50) and to analyze the clinicopathological significance and survival risk factors of SMO and GLI1 protein expression in mesothelioma. The mechanisms of mesothelioma cell expression and immune cell infiltration were investigated using bioinformatics methods.<br><br>RESULTS: SMO and GLI1 in mesothelioma tissues detected high concordance between the diagnostic results of mesothelioma biopsy specimens and plasma cavity effusion specimens. The expression levels of SMO and GLI1 protein and mRNA in mesothelioma tissues were higher than those in benign mesothelioma tissues. The expression levels of SMO and GLI1 protein were correlated with the age, site, and asbestos exposure history of patients with mesothelioma. The expression levels of SMO and GLI1 protein were correlated with the expressions of ki67 and p53 (P < 0.05). SMO and GLI1 gene expression levels were negatively correlated with good prognosis in mesothelioma patients (P < 0.05). Cox proportional risk model indicated that protein expressions of invasion, lymph node metastasis, distant metastasis, staging, and genes were independent prognostic factors of mesothelioma. The GEPIA database showed the overall survival rate and the disease-free survival rate of mesothelioma patients in the high SMO and GLI1 expression groups; the UALCAN database analysis showed lower SMO expression levels in mesothelioma patients with more pronounced TP53 mutations (P = 0.001); GLI1 gene expression levels were strongly correlated with lymph node metastasis in mesothelioma patients (P = 0.009). Timer database analysis showed that the mechanism of immune cell infiltration was closely related to SMO and GLI1 expression. The degree of immune cell infiltration was strongly correlated with the prognosis of mesothelioma patients (P < 0.05).<br><br>CONCLUSION: The expression levels of both SMO and GLI1 proteins were higher than those of normal mesothelial tissues, and the mRNA expression levels also changed in the same direction. SMO and GLI1 gene expressions in mesothelioma were negatively correlated with age, site of occurrence, and history of asbestos exposure. Positive expression of SMO and GLI1 was negatively correlated with patient survival. The Cox proportional risk model showed that gender, history of asbestos exposure, site of occurrence, SMO, and GLI1 were independent prognostic factors for mesothelioma. The mechanism of immune cell infiltration in mesothelioma is closely related to the gene expression of both and the survival prognosis of mesothelioma patients.}, }
@article {pmid37131285, year = {2023}, author = {Abdelghafar, M and Anand, K and Paiva-Correia, A and Smith, EP and Salle, FG and Joshi, V}, title = {Well-Differentiated Papillary Mesothelial Tumor: An Unusual Radiologic Presentation: A Case Report.}, journal = {Journal of chest surgery}, volume = {56}, number = {3}, pages = {220-223}, pmid = {37131285}, issn = {2765-1606}, abstract = {Well-differentiated papillary mesothelial tumor (WDPMT) is an uncommon tumor, formerly named well-differentiated papillary mesothelioma in the 2015 World Health Organization classification. It has a characteristic papillary architecture, bland cytologic features, a tendency toward superficial spread without invasion, and a good prognosis due to its clinically indolent behavior with prolonged survival. Rare cases with superficial invasion are termed WDPMT with invasive foci. WDPMT occurs primarily in the peritoneum of reproductive-age women, but also rarely in the pleura. We report a case of a 60-year-old woman who developed WDPMT with minimal invasion in the pleura with atypical radiological features and a family history of mesothelioma and indirect asbestos exposure.}, }
@article {pmid37128670, year = {2024}, author = {Marshall, T and Lane, J and Lahorra, J}, title = {A Rare Presentation of Minimally Invasive Mesothelioma as a Large Tension Pneumothorax.}, journal = {International journal of surgical pathology}, volume = {32}, number = {1}, pages = {109-114}, doi = {10.1177/10668969231167492}, pmid = {37128670}, issn = {1940-2465}, mesh = {Male ; Humans ; Aged, 80 and over ; *Pneumothorax/diagnosis/etiology/surgery ; *Mesothelioma/complications/diagnosis/surgery ; *Mesothelioma, Malignant/complications ; Pleura/surgery ; *Pleural Effusion/complications ; *Pleural Neoplasms/complications/diagnosis/surgery ; }, abstract = {Development of mesothelioma is associated with asbestos exposure. Common presentations are with pleural-based plaques invading the chest wall and/or pleural effusion on chest imaging. The intent of this case report is to describe a rare presentation of mesothelioma, which presented atypically as a large tension pneumothorax. A 93-year-old male presented with a history of dyspnea that started after a coughing episode. On physical examination he was hemodynamically stable, but was hypoxic requiring 2L of supplemental oxygen. Computed tomography of the chest revealed a large right tension pneumothorax. A chest tube was placed and connected to suction (-20cmH20), but he continued to have an unresolving air leak over the following 2-week period. Upon video-assisted thoracotomy there were no blebs or adhesions seen. Right apical wedge resection and talc pleurodesis were performed. Pathologic examination revealed an atypical mesothelial cell proliferation with minimal, focal invasion into the pulmonary parenchyma. Tumor spread along the visceral pleura was thought to be the underlying cause of the pneumothorax. The surgical margins were uninvolved by the tumor, and the patient was later discharged home in stable condition. This was a rare presentation of what could best be described as minimally invasive mesothelioma arising in a background of probable mesothelioma in situ, which presented atypically as a large tension pneumothorax. This case highlighted the importance of establishing a pathologic diagnosis from pleural effusion cytology and/or pleural biopsy in persons presenting with spontaneous pneumothorax, and the difficulty in confirming a pathologic diagnosis of early mesothelial neoplasia.}, }
@article {pmid37104724, year = {2023}, author = {Arrossi, AV}, title = {Pericardial Mesotheliomas.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {4}, pages = {253-258}, doi = {10.1097/PAP.0000000000000399}, pmid = {37104724}, issn = {1533-4031}, mesh = {Humans ; Prospective Studies ; *Mesothelioma, Malignant/complications ; *Mesothelioma/diagnosis/pathology ; *Pleural Neoplasms/diagnosis/etiology/pathology ; *Sarcoma/pathology ; *Heart Neoplasms/diagnosis ; }, abstract = {Primary pericardial mesothelioma (PM) is a rare tumor arising from the mesothelial cells of the pericardium. It has an incidence of <0.05% and comprises <2% of all mesotheliomas; however, it is the most common primary malignancy of the pericardium. PM should be distinguished from secondary involvement by the spread of pleural mesothelioma or metastases, which are more common. Although data are controversial, the association between asbestos exposure and PM is less documented than that with other mesotheliomas. Late clinical presentation is common. Symptoms may be nonspecific but are usually related to pericardial constriction or cardiac tamponade, and diagnosis can be challenging usually requiring multiple imaging modalities. Echocardiography, computed tomography, and cardiac magnetic resonance demonstrate heterogeneously enhancing thickened pericardium, usually encasing the heart, with findings of constrictive physiology. Tissue sampling is essential for diagnosis. Histologically, similar to mesotheliomas elsewhere in the body, PM is classified as epithelioid, sarcomatoid, or biphasic, with the biphasic type being the most common. Combined with morphologic assessment, the use of immunohistochemistry and other ancillary studies is helpful for distinguishing mesotheliomas from benign proliferative processes and other neoplastic processes. The prognosis of PM is poor with about 22% 1-year survival. Unfortunately, the rarity of PM poses limitations for comprehensive and prospective studies to gain further insight into the pathobiology, diagnosis, and treatment of PM.}, }
@article {pmid37101434, year = {2022}, author = {Vicari, K and Ribeiro, IM and Aguiar, BF and Brey, C and Boller, S and Miranda, FMD}, title = {Occupational characterization of workers exposed to asbestos: an integrative review.}, journal = {Revista brasileira de medicina do trabalho : publicacao oficial da Associacao Nacional de Medicina do Trabalho-ANAMT}, volume = {20}, number = {4}, pages = {650-658}, pmid = {37101434}, issn = {1679-4435}, abstract = {Asbestos is a mineral fiber abundant in nature and classified as a carcinogen since 1987. The present study aimed to identify, in the scientific literature, what are the occupation and activities developed by sick workers and which categories would be affected with asbestos-related diseases. Through a literature review performed in the following databases: PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and Regional Portal of the Virtual Health Library, 23 studies published from 2015 to 2020 were selected and evaluated. The occupations that showed greater illness due to exposure to asbestos were general asbestos workers (40%), miners (22%), and textile workers (9%), followed by naval, automotive, carpentry, doll-making, construction, and upholstery workers, as well as workers involved in the rescue, recovery, cleaning, and restoration of the World Trade Center (4%). Of the disease associated with exposure to asbestos, the most described is malignant mesothelioma (43%). Evidence found corroborate pre-existing information in the literature showing that exposure to asbestos may be harmful to health. Moreover, the importance of using personal protective equipment was emphasized, in order to prevent the development of asbestos-related diseases.}, }
@article {pmid37095543, year = {2023}, author = {Tomasetti, M and Monaco, F and Strogovets, O and Volpini, L and Valentino, M and Amati, M and Neuzil, J and Santarelli, L}, title = {ATG5 as biomarker for early detection of malignant mesothelioma.}, journal = {BMC research notes}, volume = {16}, number = {1}, pages = {61}, pmid = {37095543}, issn = {1756-0500}, mesh = {Humans ; *Mesothelioma, Malignant ; Mesothelin ; *Mesothelioma/diagnosis ; GPI-Linked Proteins/adverse effects ; *Pleural Neoplasms/diagnosis ; Biomarkers, Tumor/metabolism ; *Asbestos/adverse effects ; *MicroRNAs ; Early Diagnosis ; *Lung Neoplasms/diagnosis ; Autophagy-Related Protein 5 ; }, abstract = {OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups.<br><br>RESULTS: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.}, }
@article {pmid37090283, year = {2023}, author = {Razzak, AN and Syed, A and Procknow, ER and Bequest, A and Jha, P}, title = {Modern Malignant Mesothelioma Manifestation.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36479}, pmid = {37090283}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) involves the uncontrolled growth of mesothelial cells that form the lining of pleural serous layers. MPM has been linked with asbestos exposure in mining and manufacturing occupations with an unforgiving prognosis of 4-18 months. In this case report, we present a 56-year-old male with a significant past medical history of hypertension, hyperlipidemia, hepatic steatosis, and ulcerative colitis who presented to the emergency department for worsening cough, eight-pound weight loss over the previous year, night sweats, and fatigue. The patient was admitted due to right pleural effusion with lower lobe collapse seen on imaging; upon diagnostic workup including pleural biopsy, results were consistent with malignant mesothelioma of the epithelioid type. Over the course of six months post-diagnosis, the patient underwent multiple hospital admissions due to acute hypoxic respiratory failure from the segmental left upper lobe and subsegmental right upper lobe pulmonary emboli, recurrent pleural effusion, and anemia. Given the aggressive nature of MPM, the patient was determined not to be a surgical candidate and underwent palliative chemotherapy sessions until his passing. As the patient worked in heating/ventilation/air conditioning with asbestos exposure, taking a full occupational history was crucial. MPM is relatively rare; however, the incidence has increased over the last decade due to tumor development lag time post-asbestos exposure and an increase in do-it-yourself projects. There is no cure for MPM. Multimodal treatment approaches with surgery, chemotherapy, radiotherapy, and immunotherapy have been noted in the literature.}, }
@article {pmid37089484, year = {2023}, author = {Marsh, GM and Kruchten, A}, title = {A reevaluation of selected mortality risks in the updated NCI/NIOSH acrylonitrile cohort study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1122346}, pmid = {37089484}, issn = {2296-2565}, mesh = {United States/epidemiology ; Humans ; Cohort Studies ; *Acrylonitrile ; National Institute for Occupational Safety and Health, U.S. ; *Occupational Exposure/adverse effects ; *Lung Neoplasms ; *Asbestos ; *Urinary Bladder Neoplasms ; }, abstract = {OBJECTIVES: The study aimed to determine whether the National Cancer Institute's (NCI) recent suggestion of associations between acrylonitrile (AN) exposure and mortality in lung and bladder cancer and pneumonitis is robust to alternative methods of data analysis.<br><br>MATERIALS AND METHODS: We used the Richardson method to indirectly adjust risk ratios (RRs) in relation to AN exposure for potential confounding by smoking and asbestos. We repeated key analyses omitting workers from Plant 4 to account for possible local, historical shipyard-related asbestos exposures.<br><br>RESULTS: The adjustment of lung cancer RRs for confounding by both smoking and asbestos and omitting Plant 4 workers yielded mostly decreased RRs and much less evidence of a positive association with cumulative AN exposure.<br><br>CONCLUSION: Overall, our reanalysis provided little evidence to support NCI's suggestion of associations between AN exposure and mortality in lung and bladder cancer and pneumonitis.}, }
@article {pmid37087784, year = {2023}, author = {Barbieri, PG and Consonni, D and Magnani, C and Mensi, C and Mirabell, D and Ricci, P and Terracini, B}, title = {Is mesothelioma related to "initial dose" rather than to "cumulative dose"? Critical remarks on Maghin et al. Assessment protocol of mesothelioma and relevance of SEM-EDS analysis through a case studies of legal medicine of Brescia (Italy). Legal Medicine 2022;57:102076.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {63}, number = {}, pages = {102262}, doi = {10.1016/j.legalmed.2023.102262}, pmid = {37087784}, issn = {1873-4162}, mesh = {Humans ; *Mesothelioma/diagnosis ; *Occupational Exposure ; Forensic Medicine ; Italy ; }, }
@article {pmid37081052, year = {2023}, author = {Di Mauro, G and Frontini, F and Torreggiani, E and Iaquinta, MR and Caselli, A and Mazziotta, C and Esposito, V and Mazzoni, E and Libener, R and Grosso, F and Maconi, A and Martini, F and Bononi, I and Tognon, M}, title = {Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6501}, pmid = {37081052}, issn = {2045-2322}, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; *Circulating MicroRNA ; *Mesothelioma/pathology ; *Lung Neoplasms/pathology ; *Pleural Neoplasms/pathology ; *Asbestos/adverse effects ; *MicroRNAs/genetics ; Epigenesis, Genetic ; }, abstract = {The epigenetic role of microRNAs is established at both physiological and pathological levels. Dysregulated miRNAs and their targets appear to be a promising approach for innovative anticancer therapies. In our previous study, circulating miR-197-3p tested dysregulated in workers ex-exposed to asbestos (WEA). Herein, an epigenetic investigation on this circulating miRNA was carried out in sera from malignant pleural mesothelioma (MPM) patients. MiR-197-3p was quantified in MPM (n = 75) sera and comparatively analyzed to WEA (n = 75) and healthy subject (n = 75) sera, using ddPCR and RT-qPCR techniques. Clinicopathological characteristics, occupational, non-occupational information and overall survival (OS) were evaluated in correlation studies. MiR-197-3p levels, analyzed by ddPCR, were significantly higher in MPM than in WEA cohort, with a mean copies/µl of 981.7 and 525.01, respectively. Consistently, RT-qPCR showed higher miR-197-3p levels in sera from MPM with a mean copies/µl of 603.7, compared to WEA with 336.1 copies/µl. OS data were significantly associated with histologic subtype and pleurectomy. Circulating miR-197-3p is proposed as a new potential biomarker for an early diagnosis of the MPM onset. Indeed, miR-197-3p epigenetic investigations along with chest X-ray, computed tomography scan and spirometry could provide relevant information useful to reach an early and effective diagnosis for MPM.}, }
@article {pmid37077094, year = {2023}, author = {Bulutay, P and Vatansever, D and Taskiran, C and Mericoz, CA and Tokat, F and Kapucuoglu, N and Kulac, I}, title = {STRN-ALK rearranged malignant peritoneal mesothelioma-Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {66}, number = {2}, pages = {392-395}, doi = {10.4103/ijpm.ijpm_360_21}, pmid = {37077094}, issn = {0974-5130}, mesh = {Adolescent ; Female ; Humans ; Calmodulin-Binding Proteins/genetics ; *Cystadenocarcinoma, Serous/diagnosis/genetics ; Membrane Proteins/genetics ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant ; Nerve Tissue Proteins/genetics/metabolism ; *Ovarian Neoplasms/diagnosis/pathology ; Receptor Protein-Tyrosine Kinases/genetics ; *Anaplastic Lymphoma Kinase/genetics ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.}, }
@article {pmid37062308, year = {2023}, author = {Bolan, S and Kempton, L and McCarthy, T and Wijesekara, H and Piyathilake, U and Jasemizad, T and Padhye, LP and Zhang, T and Rinklebe, J and Wang, H and Kirkham, MB and Siddique, KHM and Bolan, N}, title = {Sustainable management of hazardous asbestos-containing materials: Containment, stabilization and inertization.}, journal = {The Science of the total environment}, volume = {881}, number = {}, pages = {163456}, doi = {10.1016/j.scitotenv.2023.163456}, pmid = {37062308}, issn = {1879-1026}, abstract = {Asbestos is a group of six major silicate minerals that belong to the serpentine and amphibole families, and include chrysotile, amosite, crocidolite, anthophyllite, tremolite and actinolite. Weathering and human disturbance of asbestos-containing materials (ACMs) can lead to the emission of asbestos dust, and the inhalation of respirable asbestos fibrous dust can lead to 'mesothelioma' cancer and other diseases, including the progressive lung disease called 'asbestosis'. There is a considerable legacy of in-situ ACMs in the built environment, and it is not practically or economically possible to safely remove ACMs from the built environment. The aim of the review is to examine the three approaches used for the sustainable management of hazardous ACMs in the built environment: containment, stabilization, and inertization or destruction. Most of the asbestos remaining in the built environment can be contained in a physically secured form so that it does not present a significant health risk of emitting toxic airborne fibres. In settings where safe removal is not practically feasible, stabilization and encapsulation can provide a promising solution, especially in areas where ACMs are exposed to weathering or disturbance. Complete destruction and inertization of asbestos can be achieved by thermal decomposition using plasma and microwave radiation. Bioremediation and chemical treatment (e.g., ultrasound with oxalic acid) have been found to be effective in the inertization of ACMs. Technologies that achieve complete destruction of ACMs are found to be attractive because the treated products can be recycled or safely disposed of in landfills.}, }
@article {pmid37058192, year = {2023}, author = {Bardelli, F and Giacobbe, C and Ballirano, P and Borelli, V and Di Benedetto, F and Montegrossi, G and Bellis, D and Pacella, A}, title = {Closing the knowledge gap on the composition of the asbestos bodies.}, journal = {Environmental geochemistry and health}, volume = {45}, number = {7}, pages = {5039-5051}, pmid = {37058192}, issn = {1573-2983}, support = {BRIC2019, ID57//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; }, mesh = {Humans ; *Asbestosis/etiology/pathology ; *Asbestos/toxicity/analysis ; Lung/chemistry ; }, abstract = {Asbestos bodies (AB) form in the lungs as a result of a biomineralization process initiated by the alveolar macrophages in the attempt to remove asbestos. During this process, organic and inorganic material deposit on the foreign fibers forming a Fe-rich coating. The AB start to form in months, thus quickly becoming the actual interface between asbestos and the lung tissue. Therefore, revealing their composition, and, in particular, the chemical form of Fe, which is the major component of the AB, is essential to assess their possible role in the pathogenesis of asbestos-related diseases. In this work we report the result of the first x-ray diffraction measurements performed on single AB embedded in the lung tissue samples of former asbestos plant workers. The combination with x-ray absorption spectroscopy data allowed to unambiguously reveal that Fe is present in the AB in the form of two Fe-oxy(hydroxides): ferrihydrite and goethite. The presence of goethite, which can be explained in terms of the transformation of ferrihydrite (a metastable phase) due to the acidic conditions induced by the alveolar macrophages in their attempt to phagocytose the fibers, has toxicological implications that are discussed in the paper.}, }
@article {pmid37057081, year = {2023}, author = {Sundaralingam, A and Aujayeb, A and Jackson, KA and Pellas, EI and Khan, II and Chohan, MT and Joosten, R and Boersma, A and Kerkhoff, J and Bielsa, S and Porcel, JM and Rozman, A and Marc-Malovrh, M and Welch, H and Symonds, J and Anevlavis, S and Froudrakis, M and Mei, F and Zuccatosta, L and Gasparini, S and Gonnelli, F and Dhaliwal, I and Mitchell, MA and Fjaellegaard, K and Petersen, JK and Ellayeh, M and Rahman, NM and Burden, T and Bodtger, U and Koegelenberg, CFN and Maskell, NA and Janssen, J and Bhatnagar, R}, title = {Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database.}, journal = {ERJ open research}, volume = {9}, number = {2}, pages = {}, pmid = {37057081}, issn = {2312-0541}, abstract = {INTRODUCTION: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis.<br><br>METHODS: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis.<br><br>RESULTS: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2&#x2005;months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09).<br><br>DISCUSSION: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.}, }
@article {pmid37047661, year = {2023}, author = {Boumya, S and Fallarini, S and Siragusa, S and Petrarolo, G and Aprile, S and Audrito, V and La Motta, C and Garavaglia, S and Moro, L and Pinton, G}, title = {A Selective ALDH1A3 Inhibitor Impairs Mesothelioma 3-D Multicellular Spheroid Growth and Neutrophil Recruitment.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047661}, issn = {1422-0067}, support = {FAR#2019//University of Eastern Piedmont Amadeo Avogadro/ ; MFAG-2021 #26004 to V.A.//Associazione Italiana di Ricerca sul Cancro/ ; }, mesh = {Humans ; Aldehyde Dehydrogenase ; Cell Line, Tumor ; Enzyme Inhibitors/therapeutic use ; *Lung Neoplasms/genetics ; *Mesothelioma/drug therapy/genetics/metabolism ; *Mesothelioma, Malignant ; Neutrophil Infiltration ; *Pleural Neoplasms/pathology ; Spheroids, Cellular/metabolism ; Tumor Microenvironment ; Retinal Dehydrogenase/metabolism ; }, abstract = {Aldehyde dehydrogenase 1A3 (ALDH1A3), one of the three members of the aldehyde dehydrogenase 1A subfamily, has been associated with increased progression and drug resistance in various types of solid tumours. Recently, it has been reported that high ALDH1A3 expression is prognostic of poor survival in patients with malignant pleural mesothelioma (MPM), an asbestos-associated chemoresistant cancer. We treated MPM cells, cultured as multicellular spheroids, with NR6, a potent and highly selective ALDH1A3 inhibitor. Here we report that NR6 treatment caused the accumulation of toxic aldehydes, induced DNA damage, CDKN2A expression and cell growth arrest. We observed that, in CDKN2A proficient cells, NR6 treatment induced IL6 expression, but abolished CXCL8 expression and IL-8 release, preventing both neutrophil recruitment and generation of neutrophil extracellular traps (NETs). Furthermore, we demonstrate that in response to ALDH1A3 inhibition, CDKN2A loss skewed cell fate from senescence to apoptosis. Dissecting the role of ALDH1A3 isoform in MPM cells and tumour microenvironment can open new fronts in the treatment of this cancer.}, }
@article {pmid37047331, year = {2023}, author = {Hager, T and Borchert, S and Wessolly, M and Mathilakathu, A and Mairinger, E and Kollmeier, J and Mairinger, T and Hegedus, B and Greimelmaier, K and Wohlschlaeger, J and Herrmann, K and Mairinger, FD}, title = {One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047331}, issn = {1422-0067}, mesh = {Humans ; *Mesothelioma, Malignant ; Mesothelin ; *Mesothelioma/drug therapy/radiotherapy/diagnosis ; Positron Emission Tomography Computed Tomography ; GPI-Linked Proteins/genetics/metabolism ; *Pleural Neoplasms/metabolism ; *Lung Neoplasms/metabolism ; Receptors, CXCR4/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a mainly asbestos-related tumour associated with a very poor prognosis. Therapeutic approaches include multimodal therapy and chemotherapeutics, with cisplatin being the drug of choice, but response rates of only up to 14% indicate very poor outcomes. Effective treatment options are lacking. Besides the diagnostic usage of radioligands in positron emission tomography (PET)/computed tomography (CT), the endo-radioligand therapy with Lu177 has been proven as a powerful tool in cancer therapy. Mesothelin (MSLN) and C-XC chemokine receptor 4 (CXCR4) are membrane-bound proteins, expressed in certain cancers, and thus are promising targets for endo-radiotherapy. A significant portion of high MSLN- or CXCR4-expressing tumors within the MPM may open the field for this sophisticated treatment approach in the near future. Formalin-fixed, paraffin-embedded (FFPE) tumour specimens from 105 patients suffering from MPM and treated at the Lung Cancer Centre of Essen and at the Helios Klinikum Emil von Behring Berlin were screened. The tumour samples were arranged in tissue microarrays. We immunohistochemically stained the tumour samples against MSLN and CXCR4. The protein expressions of the stainings were scored by a pathologist by using a semiquantitative method. The data obtained were correlated with the clinical outcome. Overall, 77.1% of the analysed tumours showed CXCR4 protein expression (25.7% of them at high expression level (Score 3)). 48.6% of all samples showed an overall strong staining (Score ≥ 2), 59% of the investigated tumours showed MSLN protein expression (10.5% of them at high expression (Score 3)), and 36.2% of all samples showed an overall strong staining (Score ≥ 2). Our results show significant tissue expression levels, for both CXCR4 and MSLN protein, in a major portion of clinical MPM samples. One-third of patients showed outstanding immunoexpression of at least one of these markers, making them interesting candidates for radioligand-based PET/CT diagnostics and follow-up and furthermore may profit from endo-radiotherapy.}, }
@article {pmid37040900, year = {2023}, author = {Chu, GJ and Linton, A and Kao, S and Klebe, S and Adelstein, S and Yeo, D and Rasko, JEJ and Cooper, WA}, title = {High mesothelin expression by immunohistochemistry predicts improved survival in pleural mesothelioma.}, journal = {Histopathology}, volume = {83}, number = {2}, pages = {202-210}, pmid = {37040900}, issn = {1365-2559}, support = {//CSR Ltd/ ; //Li Ka Shing Foundation/ ; //Royal College of Pathologists of Australasia/ ; //Sydney Local Health District/ ; PW18-030//Cancer Council of NSW/ ; RG20-07//Cancer Council of NSW/ ; APP1169460//National Health and Medical Research Council/ ; 1177305//National Health and Medical Research Council/ ; }, mesh = {Humans ; GPI-Linked Proteins/metabolism ; Immunohistochemistry ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; *Receptors, Chimeric Antigen ; }, abstract = {AIMS: Mesothelin (MSLN) is a cancer-associated antigen that is overexpressed in malignancies such as mesothelioma, pancreatic and ovarian cancer. It is also a target for novel personalised therapies, including antibodies, antibody-drug conjugates and chimeric antigen receptor T cells. Immunohistochemistry may predict those who would best respond to anti-mesothelin therapies and guide decisions in therapeutic strategy. This study aimed to assess the intensity and distribution of MSLN immunostaining in mesothelioma, and to determine the prognostic value of MSLN expression by histochemical-score (H-score).<br><br>METHODS AND RESULTS: The MN1 anti-MSLN antibody was used to stain a formalin-fixed paraffin-embedded tissue microarray of histologically confirmed mesothelioma from 75 consecutive patients who had undergone pleurectomy with or without decortication. MSLN positivity, the staining intensity, distribution of staining and H-score were evaluated. The correlation of H-score with prognosis was investigated. Sixty-six per cent of epithelioid tumours were MSLN-positive (with expression in >&#x2009;5% tumour cells). Of MSLN-expressing epithelioid tumours, 70.4% had moderate (2+) or strong (3+) intensity MSLN immunostaining, although only 37% of samples had staining in &#x2265;&#x2009;50% of tumour cells. In multivariate analysis, MSLN H-score as a continuous variable and an H-score&#x2009;&#x2265;&#x2009;33 were independent predictors of improved survival (P&#x2009;=&#x2009;0.04 and P&#x2009;<&#x2009;0.001, respectively).<br><br>CONCLUSIONS: MSLN expression was more heterogenous in epithelioid mesothelioma than reported previously. Therefore, it would be appropriate to perform an immunohistochemical assessment of MSLN expression to stratify and assess patient suitability for mesothelin-targeted personalised therapies, such as chimeric antigen receptor T cells.}, }
@article {pmid37027032, year = {2023}, author = {Akarsu, M and Ak, G and Dündar, E and Metintaş, M}, title = {Genetic analysis of familial predisposition in the pathogenesis of malignant pleural mesothelioma.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {10}, pages = {7767-7778}, pmid = {37027032}, issn = {1432-1335}, mesh = {Humans ; *Mesothelioma, Malignant ; Genetic Predisposition to Disease ; *Lung Neoplasms/pathology ; *Mesothelioma/genetics/pathology ; *Asbestos/toxicity ; *Pleural Neoplasms/genetics/pathology ; }, abstract = {PURPOSE: Mesothelioma is the primary tumor of the mesothelial cell membrane. The most important etiology is asbestos exposure. The development of malignant mesothelioma in very few of the population exposed to asbestos and its frequent occurrence in some families may be significant in terms of genetic predisposition. Again, the presence of relatives with mesothelioma who did not have asbestos contact strengthens this argument. This disease, which has limited treatment options and has a poor prognosis, revealing a genetic predisposition, if any, may prolong survival with early diagnosis and effective treatment.<br><br>METHODS: Based on the genetic predisposition idea, we diagnosed and followed a total of ten individuals of relatives with mesothelioma. DNA was isolated from peripheral blood and whole genome sequencing analysis was done. Common gene mutations in ten individuals were filtered using bioinformatics. After this filter, from the remaining variants, very rare in the population and damaging mutations are selected.<br><br>RESULTS: Eight thousand six hundred and twenty-two common variants have been identified in ten individuals with this analysis. In total, 120 variants were found on 37 genes in 15 chromosomes. These genes are PIK3R4, SLC25A5, ITGB6, PLK2, RAD17, HLA-B, HLA-DRB1, HLA-DQB1, GRM, IL20RA, MAP3K7, RIPK2, and MUC16.<br><br>CONCLUSION: Our finding, PIK3R4 gene, is directly associated with mesothelioma development. Twelve genes, which are associated with cancer, were detected in literature. Additional studies, which scan first-degree relatives of individual, are needed to find the specific gene region.}, }
@article {pmid37010194, year = {2023}, author = {Kitamura, Y and Zha, L and Liu, R and Shima, M and Nakaya, T and Kurumatani, N and Kumagai, S and Goji, J and Sobue, T}, title = {Association of mesothelioma deaths with neighborhood asbestos exposure due to a large-scale asbestos-cement plant.}, journal = {Cancer science}, volume = {114}, number = {7}, pages = {2973-2985}, pmid = {37010194}, issn = {1349-7006}, support = {15H04774//Japan Society for the Promotion of Science/ ; }, mesh = {Male ; Female ; Humans ; Case-Control Studies ; Environmental Exposure/adverse effects ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; *Mesothelioma, Malignant/chemically induced ; *Pleural Neoplasms/epidemiology ; }, abstract = {A causal relationship between mesothelioma and occupational asbestos exposure is well known, while some studies have shown a relationship to non-occupational exposures. The aim of this study was to quantify the risk of mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, adjusting properly risk factors including occupational exposures. We conducted a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with the neighborhood exposure were estimated by a conditional logistic-regression model. For quantitative assessments for neighborhood exposure, we adopted cumulative indices for individuals' residential histories at each residence-specific asbestos concentration multiplied by the duration during the potential exposure period of 1957-1975 (crocidolite). We observed an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrating that ORs in the highest quintile category were 21.4 (95% confidence interval [CI] 5.8-79.2) for all, 23.7 (95% CI 3.8-147.2) for males, and 26.0 (95% CI 2.8-237.5) for females compared to the lowest quintile, respectively. A quantitative assessment for risk of mesothelioma deaths, adjusting for occupational and non-occupational exposures separately, showed a dose-dependent association with neighborhood exposure and no substantial gender differences in magnitude.}, }
@article {pmid36981857, year = {2023}, author = {Gaitens, JM and Culligan, M and Friedberg, JS and Glass, E and Reback, M and Scilla, KA and Sachdeva, A and Atalla, A and McDiarmid, MA}, title = {Laying the Foundation for a Mesothelioma Patient Registry: Development of Data Collection Tools.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {6}, pages = {}, pmid = {36981857}, issn = {1660-4601}, support = {U24 OH009077/OH/NIOSH CDC HHS/United States ; 75D30119P05558/CC/CDC HHS/United States ; }, mesh = {United States/epidemiology ; Humans ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; *Asbestos/toxicity ; *Occupational Exposure/adverse effects ; Registries ; Surveys and Questionnaires ; Incidence ; }, abstract = {Mesothelioma, a cancer of mesothelial cells that line the chest, lungs, heart, and abdomen, is a relatively rare disease. In the United States, approximately 3000 individuals are diagnosed with mesothelioma annually. The primary risk factor for mesothelioma is occupational asbestos exposure which can occur decades prior to disease development, though in approximately 20% of cases, known asbestos exposure is lacking. While several other countries have developed mesothelioma registries to collect key clinical and exposure data elements to allow better estimation of incidence, prevalence, and risk factors associated with disease development, no national mesothelioma registry exists in the U.S. Therefore, as part of a larger feasibility study, a patient exposure questionnaire and a clinical data collection tool were created using a series of key informant interviews. Findings suggest that risk factor and clinical data collection via an on-line questionnaire is feasible, but specific concerns related to confidentiality, in the context of employer responsibility for exposure in the unique U.S. legal environment, and timing of enrollment must be addressed. Lessons learned from piloting these tools will inform the design and implementation of a mesothelioma registry of national scope.}, }
@article {pmid36981000, year = {2023}, author = {Doyle, E and Blanchon, D and Wells, S and de Lange, P and Lockhart, P and Waipara, N and Manefield, M and Wallis, S and Berry, TA}, title = {Internal Transcribed Spacer and 16S Amplicon Sequencing Identifies Microbial Species Associated with Asbestos in New Zealand.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36981000}, issn = {2073-4425}, mesh = {*Siderophores ; New Zealand ; *Asbestos ; Iron/metabolism ; Bacteria/genetics/metabolism ; Soil ; }, abstract = {Inhalation of asbestos fibres can cause lung inflammation and the later development of asbestosis, lung cancer, and mesothelioma, and the use of asbestos is banned in many countries. In most countries, large amounts of asbestos exists within building stock, buried in landfills, and in contaminated soil. Mechanical, thermal, and chemical treatment options do exist, but these are expensive, and they are not effective for contaminated soil, where only small numbers of asbestos fibres may be present in a large volume of soil. Research has been underway for the last 20 years into the potential use of microbial action to remove iron and other metal cations from the surface of asbestos fibres to reduce their toxicity. To access sufficient iron for metabolism, many bacteria and fungi produce organic acids, or iron-chelating siderophores, and in a growing number of experiments these have been found to degrade asbestos fibres in vitro. This paper uses the internal transcribed spacer (ITS) and 16S amplicon sequencing to investigate the fungal and bacterial diversity found on naturally-occurring asbestos minerals, asbestos-containing building materials, and asbestos-contaminated soils with a view to later selectively culturing promising species, screening them for siderophore production, and testing them with asbestos fibres in vitro. After filtering, 895 ITS and 1265 16S amplicon sequencing variants (ASVs) were detected across the 38 samples, corresponding to a range of fungal, bacteria, cyanobacterial, and lichenized fungal species. Samples from Auckland (North Island, New Zealand) asbestos cement, Auckland asbestos-contaminated soils, and raw asbestos rocks from Kahurangi National Park (South Island, New Zealand) were comprised of very different microbial communities. Five of the fungal species detected in this study are known to produce siderophores.}, }
@article {pmid36980631, year = {2023}, author = {Mensi, C and Stella, S and Dallari, B and Rugarli, S and Pesatori, AC and Ceresoli, GL and Consonni, D}, title = {Second Primary Cancers in a Population-Based Mesothelioma Registry.}, journal = {Cancers}, volume = {15}, number = {6}, pages = {}, pmid = {36980631}, issn = {2072-6694}, support = {BRiC 55/2019//Istituto Nazionale per l'Assicurazione Contro gli Infortuni sul Lavoro/ ; }, abstract = {BACKGROUND: The presence of a second primary cancer (SPC) in patients with pleural mesothelioma (PM) may impact overall survival and suggest a common mechanism of carcinogenesis or an underlying germline genetic alteration.<br><br>METHODS: We evaluated the occurrence of SPCs within PM cases collected from 2000 to 2018 by the Lombardy Mesothelioma Registry and their prognostic implications. Kaplan-Meier analysis was performed to estimate median survival times, together with univariate and multivariate Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of death.<br><br>RESULTS: The median overall survival (OS) of the entire study population (N = 6646) was 10.9 months (95% CI: 10.4-11.2); patient age and histotype were the strongest prognostic factors. No substantial survival difference was observed by the presence of an SPC (10.5 months in 1000 patients with an SPC vs. 10.9 months in 5646 patients in the non-SPC group, HR 1.03, p = 0.40). Shorter OS in the SPC group was only observed in 150 patients with the non-epithelioid subtype (median OS of 5.4 vs. 7.1 months, HR 1.21, p = 0.03).<br><br>CONCLUSIONS: The diagnosis of an SPC did not influence the outcome of PM patients in the overall study population but was associated with shorter OS in non-epithelioid cases. Further studies are needed to clarify the role of SPCs as markers of genetic susceptibility in mesothelioma.}, }
@article {pmid36974955, year = {2023}, author = {Dement, JM and Loomis, D}, title = {Manufactured doubt and the EPA 2020 chrysotile asbestos risk assessment.}, journal = {American journal of industrial medicine}, volume = {66}, number = {7}, pages = {543-553}, doi = {10.1002/ajim.23476}, pmid = {36974955}, issn = {1097-0274}, mesh = {United States ; Humans ; Asbestos, Serpentine/toxicity/analysis ; United States Environmental Protection Agency ; *Lung Neoplasms ; *Asbestos/toxicity/analysis ; Asbestos, Amphibole/toxicity/analysis ; Asbestos, Crocidolite/analysis/toxicity ; Risk Assessment ; *Mesothelioma/epidemiology ; }, abstract = {While all forms of asbestos have been determined to be carcinogenic to humans by the International Agency for Research on Cancer (IARC) as well as other authoritative bodies, the relative carcinogenic potency of chrysotile continues to be argued, largely in the context of toxic tort litigation. Relatively few epidemiologic studies have investigated only a single form of asbestos; however, one study that included an asbestos textile plant located in Marshville, North Carolina that processed chrysotile asbestos was used by the United States Environmental Protection Agency (EPA) in 2020 to help inform the agency's chrysotile asbestos risk assessment. During the EPA proceedings toxic tort defense consultants submitted comments to the EPA docket and made public presentations asserting that the Marshville plant had processed amphibole asbestos types and should not be used for the chrysotile risk assessment. A detailed evaluation of defense consultant assertions and supporting information and a full assessment of the available information concerning asbestos types used at the Marshville plant was undertaken. The preponderance of evidence continues to support the conclusion that neither amosite nor crocidolite were likely to have been processed in the Marshville textile plant. Defense consultants' assertions about chrysotile use are not supported by the preponderance of evidence and constitute an example of manipulation of information to cast uncertainty and doubt rather than to seek truth and contribute to the body of scientific evidence.}, }
@article {pmid36966347, year = {2023}, author = {Marcu, A and McGregor, F and Egan, B and Hill, K and Cook, T and Arber, A}, title = {Developing sustainable patient and public involvement in mesothelioma research: multi-method exploration with researchers, patients, carers, and patient organisations.}, journal = {Research involvement and engagement}, volume = {9}, number = {1}, pages = {15}, pmid = {36966347}, issn = {2056-7529}, support = {JH-18-10//June Hancock Mesothelioma Research Fund/ ; JH-18-10//June Hancock Mesothelioma Research Fund/ ; JH-18-10//June Hancock Mesothelioma Research Fund/ ; JH-18-10//June Hancock Mesothelioma Research Fund/ ; }, abstract = {BACKGROUND: Rare diseases where prognosis is poor provide limited scope for patient and public involvement (PPI). One such disease is mesothelioma, a cancer of the lung pleura or of the peritoneum caused by exposure to asbestos, where PPI is poorly documented. We undertook to explore how PPI could be facilitated in mesothelioma research.<br><br>METHODS: An online survey with mesothelioma researchers (n&#x2009;=&#x2009;23) assessed the perceived benefits and challenges of PPI in mesothelioma. Six online workshops and thirteen in-depth interviews with patients and the public explored their views on how PPI could be increased in mesothelioma and their motivations to become PPI representatives in the future. The survey data were analysed using descriptive statistics and the interviews, using Thematic Analysis.<br><br>RESULTS: In the survey, 26% (n&#x2009;=&#x2009;6) of the researchers did not include PPI in their research, while 74% (n&#x2009;=&#x2009;17) did, finding it most beneficial at the stages of applying for funding and dissemination. The main perceived benefits of PPI were clarifying the research question and outcome measures, making research more credible and relevant to patients' needs, and increasing its impact. The main perceived challenges to PPI were the general poor prognosis in mesothelioma, and funding timescales which hindered timely recruitment of PPI representatives. The analysis of the interviews with the patients and public revealed three main themes: "Motivations to become a PPI representative in the future", "Understanding the nature of PPI during the project", and "Perceived challenges to PPI in mesothelioma". Altruism and the need for hope were the main reasons to wish to become involved in PPI in the future. For many participants, the project proved to be a journey of understanding the nature of PPI, a concept that was not easy to grasp from the start. The participants perceived certain barriers to PPI such as high symptom burden in mesothelioma, the abstract concept of PPI, and the use of scientific language.<br><br>CONCLUSIONS: The present research provides a detailed picture of the benefits and challenges of PPI in mesothelioma. We recommend long-term engagement with mesothelioma support groups so that researchers achieve meaningful and sustainable PPI in mesothelioma research.}, }
@article {pmid36965810, year = {2023}, author = {Gao, Y and Mazurek, JM and Li, Y and Blackley, D and Weissman, DN and Burton, SV and Amin, W and Landsittel, D and Becich, MJ and Ye, Y}, title = {Industry, occupation, and exposure history of mesothelioma patients in the U.S. National Mesothelioma Virtual Bank, 2006-2022.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115085}, pmid = {36965810}, issn = {1096-0953}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; U24 OH009077/OH/NIOSH CDC HHS/United States ; U24OH009077/ACL/ACL HHS/United States ; }, mesh = {Female ; Humans ; Male ; *Mesothelioma, Malignant/chemically induced ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; Industry ; Occupations ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma is associated with environmental and occupational exposure to certain mineral fibers, especially asbestos. This study aims to examine work histories of mesothelioma patients and their survival time.<br><br>METHOD: Using the NIOSH Industry and Occupation Computerized Coding System, we mapped occupations and industries recorded for 748 of 1444 patients in the U.S. National Mesothelioma Virtual Bank (NMVB) during the period 2006-2022. Descriptive and survival analyses were conducted.<br><br>RESULTS: Among the 1023 industries recorded for those having mesothelioma, the most frequent cases were found for those in manufacturing (n&#xa0;=&#xa0;225, 22.0%), construction (138, 13.5%), and education services (66, 6.5%); among the 924 occupation records, the most frequent cases were found for those in construction and extraction (174, 18.8%), production (145, 15.7%), and management (84, 9.1%). Males (583) or persons aged >40 years (658) at the time of diagnosis tended to have worked in industries traditionally associated with mesothelioma (e.g., construction), while females (163) or persons aged 20-40 years (27) tended to have worked in industries not traditionally associated with mesothelioma (e.g., health care). Asbestos, unknown substances, and chemical solvents were the most frequently reported exposure, with females most often reporting an unknown substance. A multi-variable Cox Hazard Regression analysis showed that significant prognostic factors associated with decreased survival in mesothelioma cases are sex (male) and work experience in utility-related industry, while factor associated with increased survival are epithelial or epithelioid histological type, prior history of surgery and immunotherapy, and industry experience in accommodation and food services.<br><br>CONCLUSION: The NMVB has the potential of serving as a sentinel surveillance mechanism for identifying industries and occupations not traditionally associated with mesothelioma. Results indicate the importance of considering all potential sources of asbestos exposures including occupational, environmental, and extra-occupational exposures when evaluating mesothelioma patients and advising family members.}, }
@article {pmid36965809, year = {2023}, author = {Lieberman-Cribbin, W and Taioli, E}, title = {Epidemiologic roadblocks in studying elongated mineral particles and mesothelioma risk.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115086}, doi = {10.1016/j.envres.2022.115086}, pmid = {36965809}, issn = {1096-0953}, mesh = {Humans ; Silicates ; Iron ; *Occupational Exposure/adverse effects/analysis ; *Air Pollutants, Occupational/analysis ; *Lung Neoplasms/chemically induced/epidemiology ; Minerals/analysis ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; }, abstract = {Elongated mineral particles (EMPs) are a type of both occupational and environmental exposures that have generated interest in the scientific community due to their potential health effects. Their possible association with mesothelioma represents an area of concern. We provide an overview of the current challenges around epidemiological assessments of EMP exposure and mesothelioma risk, including methodological aspects that need to be addressed when designing and analyzing a study on EMP exposure and mesothelioma. Future work is needed to investigate the relationship between EMPs and mesothelioma, focused on an improved definition of EMP exposure and accounting for other concomitant sources of carcinogen exposure.}, }
@article {pmid36965808, year = {2023}, author = {Bogen, KT}, title = {Ultrasensitive dose-response for asbestos cancer risk implied by new inflammation-mutation model.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115047}, doi = {10.1016/j.envres.2022.115047}, pmid = {36965808}, issn = {1096-0953}, mesh = {Animals ; Humans ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/genetics ; Inflammation/chemically induced/metabolism ; *Lung Neoplasms/chemically induced/genetics ; *Carcinogens, Environmental/toxicity ; Mutation ; }, abstract = {Alterations in complex cellular phenotype each typically involve multistep activation of an ultrasensitive molecular switch (e.g., to adaptively initiate an apoptosis, inflammasome, Nrf2-ARE anti-oxidant, or heat-shock activation pathway) that triggers expression of a suite of target genes while efficiently limiting false-positive switching from a baseline state. Such switches exhibit nonlinear signal-activation relationships. In contrast, a linear no-threshold (LNT) dose-response relationship is expected for damage that accumulates in proportion to dose, as hypothesized for increased risk of cancer in relation to genotoxic dose according to the multistage somatic mutation/clonal-expansion theory of cancer, e.g., as represented in the Moolgavkar-Venzon-Knudsen (MVK) cancer model by a doubly stochastic nonhomogeneous Poisson process. Mesothelioma and lung cancer induced by exposure to carcinogenic (e.g., certain asbestos) fibers in humans and experimental animals are thought to involve modes of action driven by mutations, cytotoxicity-associated inflammation, or both, rendering ambiguous expectations concerning the nature of model-implied shape of the low-dose response for above-background increase in risk of incurring these endpoints. A recent Inflammation Somatic Mutation (ISM) theory of cancer posits instead that tissue-damage-associated inflammation that epigenetically recruits, activates and orchestrates stem cells to engage in tissue repair does not merely promote cancer, but rather is a requisite co-initiator (acting together with as few as two somatic mutations) of the most efficient pathway to any type of cancer in any reparable tissue (Dose-Response 2019; 17(2):1-12). This theory is reviewed, implications of this theory are discussed in relation to mesothelioma and lung cancer associated with chronic asbestos inhalation, one of the two types of ISM-required mutations is here hypothesized to block or impede inflammation resolution (e.g., by doing so for GPCR-mediated signal transduction by one or more endogenous autacoid specialized pro-resolving mediators or SPMs), and supporting evidence for this hypothesis is discussed.}, }
@article {pmid36965804, year = {2023}, author = {Sanchez, MS and McGrath-Koerner, M and McNamee, BD}, title = {Characterization of elongate mineral particles including talc, amphiboles, and biopyriboles observed in mineral derived powders: Comparisons of analysis of the same talcum powder samples by two laboratories.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114791}, doi = {10.1016/j.envres.2022.114791}, pmid = {36965804}, issn = {1096-0953}, mesh = {*Asbestos, Amphibole/toxicity ; Talc/toxicity ; Powders ; Laboratories ; Minerals/toxicity ; *Asbestos ; }, abstract = {Elongate mineral particles, including asbestos, have long been screened in talc and other mineral powders. In recent years, there has been a renewed scrutiny of talc containing asbestos due to allegations in civil litigation in the United States as well as reports, proposals, and white papers by international laboratories and government bodies related to this subject. This study demonstrates the importance of the fundamental understanding of both mineralogy and its application, using microscopy with empirical examples from conflicting analyses of the same talc powders by two independent laboratories in civil litigation in the United States. Methods include polarized light microscopy (PLM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) in the accurate measurement of morphological, optical, compositional, and structural data to characterize mineral-based samples. Discussions in this study include: 1) contrasting the interlaboratory findings of amphibole and amphibole asbestos by PLM and TEM using various preparation techniques, 2) the use of multiple analytical tools on a singular particle for identification, 3) the misidentification of anthophyllite asbestos by inexpert use of electron diffraction using TEM, and 4) the misidentification of chrysotile in talc by PLM. These examples emphasize the importance of not only maintaining the existing requirements, but of the need for even more rigorous analytical requirements in routine monitoring of elongate mineral particles that may occur in mineral-based powders.}, }
@article {pmid36965802, year = {2023}, author = {Darnton, L}, title = {Quantitative assessment of mesothelioma and lung cancer risk based on Phase Contrast Microscopy (PCM) estimates of fibre exposure: an update of 2000 asbestos cohort data.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114753}, doi = {10.1016/j.envres.2022.114753}, pmid = {36965802}, issn = {1096-0953}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; Asbestos, Amosite ; Asbestos, Crocidolite/toxicity ; Microscopy, Phase-Contrast ; *Occupational Exposure ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; Asbestos, Amphibole/toxicity ; *Occupational Diseases ; }, abstract = {An earlier meta-analysis of mortality studies of asbestos-exposed worker populations, quantified excess mesothelioma and lung cancer risks in relation to cumulative exposure to the three main commercial asbestos types. The aim of this paper was to update these analyses incorporating new data based on increased follow-up of studies previously included, as well as studies of worker populations exposed predominantly to single fibre types published since the original analysis. Mesothelioma as a percentage of expected mortality due to all causes of death, percentage excess lung cancer and mean cumulative exposure were abstracted from available mortality studies of workers exposed predominantly to single asbestos types. Average excess mesothelioma and lung cancer per unit of cumulative exposure were summarised for groupings of studies by fibre type; models for pleural and peritoneal mesothelioma risk and lung cancer risk in terms of cumulative exposure for the different fibre types were fitted using Poisson regression. The average mesothelioma risks (per cent of total expected mortality) per unit cumulative exposure (f/cc.yr), RM, were 0.51 for crocidolite, 0.12 for amosite, and 0.03 for the Libby mixed amphiboles cohort. Significant heterogeneity was present for cohorts classed as chrysotile, with RM values of 0.01 for chrysotile textiles cohorts and 0.0011 for other chrysotile-exposed cohorts. Average percentage excess lung cancer risks per unit cumulative exposure, RL, were 4.3 for crocidolite and amosite combined, 0.82 for Libby. Very significant heterogeneity was present for chrysotile-exposed cohorts with RL values spanning two orders of magnitude from 0.053 for the Balangero mine to 4.8 for the South Carolina textiles cohort. Best fitting models suggest a non-linear exposure-response in which the peritoneal mesothelioma risk is proportional to approximately the square of cumulative exposure. Pleural mesothelioma and lung cancer risk were proportion to powers of cumulative exposure slightly less than one and slightly higher than one respectively.}, }
@article {pmid36965801, year = {2023}, author = {Nel, A}, title = {Carbon nanotube pathogenicity conforms to a unified theory for mesothelioma causation by elongate materials and fibers.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114580}, doi = {10.1016/j.envres.2022.114580}, pmid = {36965801}, issn = {1096-0953}, mesh = {Humans ; *Nanotubes, Carbon/toxicity ; Virulence ; *Mesothelioma/chemically induced ; *Asbestos/toxicity ; Inflammation/pathology ; }, abstract = {The purpose of this review is to elucidate how dimensional and durability characteristics of high aspect ratio nanomaterials (HARN), including carbon nanotubes (CNT) and metal nanowires (MeNW), contribute to understanding the fiber pathogenicity paradigm (FPP), including by explaining the structure-activity relationships (SAR) of a diverse range of natural and synthetic elongate materials that may or may not contribute to mesothelioma development in the lung. While the FPP was originally developed to explain the critical importance of asbestos and synthetic vitreous fiber length, width, aspect ratio and biopersistence in mesothelioma development, there are a vast number of additional inhalable materials that need to be considered in terms of pathogenic features that may contribute to mesothelioma or lack thereof. Not only does the ability to exert more exact control over the length and biopersistence of HARNs confirm the tenets of the FPP, but could be studied by implementating more appropriate toxicological tools for SAR analysis. This includes experimentation with carefully assembled libraries of CNTs and MeNWs, helping to establish more precise dimensional features for interfering in lymphatic drainage from the parietal pleura, triggering of lysosomal damage, frustrated phagocytosis and generation of chronic inflammation. The evidence includes data that long and rigid, but not short and flexible multi-wall CNTs are capable of generating mesotheliomas in rodents based on an adverse outcome pathway requiring access to pleural cavity, obstruction of pleural stomata, chronic inflammation and transformation of mesothelial cells. In addition to durability and dimensional characteristics, bending stiffness of CNTs is a critical factor in determining the shape and rigidity of pathogenic MWCNTs. While no evidence has been obtained in humans that CNT exposure leads to a mesothelioma outcome, it is important to monitor exposure levels and health effect impacts in workers to prevent adverse health outcomes in humans.}, }
@article {pmid36965800, year = {2023}, author = {Roggl, VL and Green, CL and Liu, B and Carney, JM and Glass, CH and Pavlisko, EN}, title = {Chronological trends in the causation of malignant mesothelioma: Fiber burden analysis of 619 cases over four decades.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114530}, pmid = {36965800}, issn = {1096-0953}, support = {UL1 TR002553/TR/NCATS NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; Asbestos/toxicity ; Asbestosis/etiology/complications ; Lung/pathology ; *Lung Neoplasms/chemically induced/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; Mesothelioma, Malignant/complications/pathology ; *Occupational Exposure ; }, abstract = {Malignant mesothelioma is a relatively rare malignancy with a strong association with prior asbestos exposure. A percentage of cases is not related to asbestos, and fiber analysis of lung tissue is a useful methodology for identifying idiopathic or spontaneous cases. We have performed fiber analyses in more than 600 cases of mesothelioma over the past four decades and were interested in looking for trends in terms of fiber types and concentrations as well as percentages of cases not related to asbestos. Demographic information was also considered including patient age, gender, and tumor location (pleural vs. peritoneal). The histologic pattern of the tumor and the presence or absence of pleural plaques or asbestosis were noted. Fiber analysis was performed in 619 cases, using the sodium hypochlorite technique for digestion of lung tissue samples. Asbestos bodies were counted by light microscopy (LM) and coated and uncoated fibers by scanning electron microscopy (EM). The results were stratified over four decades. Trends that were observed included increasing patient age, increasing percentage of women, increasing percentage of peritoneal cases, and increasing percentage of epithelial histological type. There was a decreasing trend in the percentage of patients with concomitant asbestosis (p < 0.001). The percentage of cases with an elevated lung asbestos content decreased from 90.5% in the 1980s to 54.1% in the 2010s (p < 0.001). This trend also held when the analysis was limited to 490 cases of pleural mesothelioma in men (91.8% in the 1980s vs. 65.1% in the 2010s). There was a decrease in the median asbestos body count by LM from 1390 asbestos bodies per gram of wet lung in the 1980s to 38 AB/gm in the 2010s. Similar trends were observed for each of the asbestos fiber types as detected by EM. We conclude that there has been a progressive decrease in lung fiber content of mesothelioma patients during the past four decades, with an increasing percentage of cases not related to asbestos and an increase in median patient age.}, }
@article {pmid36965799, year = {2023}, author = {Moolgavkar, S and Chang, ET and Luebeck, EG}, title = {Multistage carcinogenesis: Impact of age, genetic, and environmental factors on the incidence of malignant mesothelioma.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114582}, doi = {10.1016/j.envres.2022.114582}, pmid = {36965799}, issn = {1096-0953}, mesh = {Humans ; *Mesothelioma, Malignant/complications ; Incidence ; *Carcinogens, Environmental/toxicity ; Syndrome ; *Lung Neoplasms/chemically induced/epidemiology ; Genetic Predisposition to Disease ; *Asbestos/toxicity ; Carcinogenesis/chemically induced/genetics ; }, abstract = {The current paradigm of carcinogenesis as a cellular evolutionary process driven by mutations of a few critical driver genes has immediate logical implications for the epidemiology of cancer. These include the impact of age on cancer risk, the role played by inherited tumor predisposition syndromes, and the interaction of genetics and environmental exposures on cancer risk. In this paper, we explore the following logical epidemiological consequences of carcinogenesis as a clonal process of mutation accumulation, with special emphasis on asbestos-related cancers, specifically malignant mesothelioma:1 All cancers, including mesothelioma, can and do occur spontaneously, i.e., in the absence of exposure to any environmental carcinogens. 2. Age is an important determinant of cancer risk, with or without exposure to environmental carcinogens. 3. Genetic tumor predisposition syndromes, such as the BAP1 syndrome, increase enormously the risk of cancer even in the absence of exposure to environmental carcinogens. We illustrate these concepts by applying a multistage clonal expansion model to U.S. Surveillance, Epidemiology, and End Results cancer registry data for pleural and peritoneal malignant mesotheliomas in 1975-2018.}, }
@article {pmid36965798, year = {2023}, author = {Wylie, AG and Korchevskiy, AA}, title = {Dimensions of elongate mineral particles and cancer: A review.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114688}, doi = {10.1016/j.envres.2022.114688}, pmid = {36965798}, issn = {1096-0953}, mesh = {Humans ; Mineral Fibers/toxicity ; Minerals/toxicity/analysis ; *Mesothelioma/chemically induced/epidemiology ; Asbestos, Amphibole ; *Lung Neoplasms/chemically induced/epidemiology ; Carcinogens/analysis ; Dust/analysis ; *Asbestos ; }, abstract = {CONTEXT: Based on a decade-long exploration, dimensions of elongate mineral particles are implicated as a pivotal component of their carcinogenic potency. This paper summarizes current understanding of the discovered relationships and their importance to the protection of public health.<br><br>OBJECTIVES: To demonstrate the relationships between cancer risk and dimensions (length, width, and other derivative characteristics) of mineral fibers by comparing the results and conclusions of previously published studies with newly published information.<br><br>METHODS: A database including 59 datasets comprising 341,949 records were utilized to characterize dimensions of elongate particles. The descriptive statistics, correlation and regression analysis, combined with Monte Carlo simulation, were used to select dimensional characteristics most relevant for mesothelioma and lung cancer risk prediction.<br><br>RESULTS: The highest correlation between mesothelioma potency factor and weight fraction of size categories is achieved for fibers with lengths >5.6&#xa0;&#x3bc;m and widths &#x2264;0.26&#xa0;&#x3bc;m (R&#xa0;=&#xa0;0.94, P&#xa0;<&#xa0;0.02); no statistically significant potency was found for lengths <5&#xa0;&#x3bc;m. These results are consistent with early published estimations, though are derived from a different approach. For combinations of amphiboles and chrysotile (with a consideration of a correction factor between mineral classes), the potency factors correlated most highly with a fraction of fibers longer than 5&#xa0;&#x3bc;m and thinner than 0.2&#xa0;&#x3bc;m for mesothelioma, and longer than 5&#xa0;&#x3bc;m and thinner than 0.3&#xa0;&#x3bc;m for lung cancer. Because the proportion of long, thin particles in asbestiform vs. non-asbestiform dusts is higher, the cancer potencies of the former are predicted at a significantly higher level. The analysis of particle dimensionality in human lung burden demonstrates positive selection for thinner fibers (especially for amosite and crocidolite) and prevailing fraction of asbestiform habit.<br><br>CONCLUSION: Dimensions of mineral fibers can be confirmed as one of the main drivers of their carcinogenicity. The width of fibers emerges as a primary potency predictor, and fibers of all widths with lengths shorter than 5&#xa0;&#x3bc;m seem to be non-impactful for cancer risk. The mineral dust with a fibrous component is primarily carcinogenic if it contains amphibole fibers longer than 5&#xa0;&#x3bc;m and thinner than 0.25&#xa0;&#x3bc;m.}, }
@article {pmid36965797, year = {2023}, author = {Goodman, JE and Becich, MJ and Bernstein, DM and Case, BW and Mandel, JH and Nel, AE and Nolan, R and Odo, NU and Smith, SR and Taioli, E and Gibbs, G}, title = {Non-asbestiform elongate mineral particles and mesothelioma risk: Human and experimental evidence.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114578}, pmid = {36965797}, issn = {1096-0953}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; U24 OH009077/OH/NIOSH CDC HHS/United States ; U24OH009077/ACL/ACL HHS/United States ; }, mesh = {Humans ; Epigenesis, Genetic ; *Air Pollutants, Occupational ; *Occupational Exposure ; *Lung Neoplasms/chemically induced/epidemiology ; Minerals/analysis ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; Tumor Microenvironment ; }, abstract = {The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.}, }
@article {pmid36965795, year = {2023}, author = {Chatfield, EJ}, title = {Asbestiform fibers and cleavage Fragments: Conceptual approaches for differentiation in laboratory practice and data analysis.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114529}, doi = {10.1016/j.envres.2022.114529}, pmid = {36965795}, issn = {1096-0953}, mesh = {Animals ; *Occupational Exposure/analysis ; *Air Pollutants, Occupational/analysis ; Particle Size ; Minerals/analysis ; *Asbestos ; Asbestos, Amphibole ; Dust/analysis ; Data Analysis ; }, abstract = {The respirable fractions from 46 different crushed amphibole samples were separated by water elutriation. The dimensions of approximately 200 elongate mineral particles (EMPs) longer than 5 μm in each of these fractions were measured by transmission electron microscopy (TEM). The data were used to address three questions: 1. Can amphiboles be classified on a scale that represents the level of inhalation hazard they present? 2. Can prismatic amphibole be discriminated from amphibole asbestos on the basis of EMP size distributions and concentration measurements? 3. How do different exposure indices (Phase Contrast Microscopy Equivalent (PCME), Berman &amp; Crump protocol fibers, Chatfield extra-criteria EMPs) compare when applied to these amphibole samples? For each sample, the number of respirable EMPs longer than 5 μm per gram of respirable dust and the number of extra-criteria EMPs per gram of respirable dust were calculated. The number of respirable EMPs longer than 5 μm per gram of respirable dust and the proportion of those with dimensions associated with mesothelioma in animal studies were considered to be contributors to the inhalation hazard presented by amphibole dust. In addition to these concentration measurements, the median EMP width, median aspect ratio and the aspect ratio geometric standard deviation (GSD) were considered to be relevant parameters in discriminating prismatic amphibole from asbestiform amphibole. A plot of the aspect ratio GSD against either the concentration of respirable EMPs per gram of respirable dust, the median aspect ratio or the median width allowed discrimination. The data showed a close correspondence between exposures in terms of Chatfield extra-criteria EMPs and Berman and Crump protocol structures for all of the amphibole samples. However, although for commercial asbestos varieties exposures in terms of PCME fibers were comparable to those of the other two metrics, they greatly exceeded those for non-asbestiform amphiboles.}, }
@article {pmid36965793, year = {2023}, author = {Cox, LA and Bogen, KT and Conolly, R and Graham, U and Moolgavkar, S and Oberdörster, G and Roggli, VL and Turci, F and Mossman, B}, title = {Mechanisms and shapes of causal exposure-response functions for asbestos in mesotheliomas and lung cancers.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115607}, doi = {10.1016/j.envres.2023.115607}, pmid = {36965793}, issn = {1096-0953}, mesh = {Humans ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; Lung/pathology ; Asbestos, Amphibole/toxicity ; Inflammation/metabolism ; }, abstract = {This paper summarizes recent insights into causal biological mechanisms underlying the carcinogenicity of asbestos. It addresses their implications for the shapes of exposure-response curves and considers recent epidemiologic trends in malignant mesotheliomas (MMs) and lung fiber burden studies. Since the commercial amphiboles crocidolite and amosite pose the highest risk of MMs and contain high levels of iron, endogenous and exogenous pathways of iron injury and repair are discussed. Some practical implications of recent developments are that: (1) Asbestos-cancer exposure-response relationships should be expected to have non-zero background rates; (2) Evidence from inflammation biology and other sources suggests that there are exposure concentration thresholds below which exposures do not increase inflammasome-mediated inflammation or resulting inflammation-mediated cancer risks above background risk rates; and (3) The size of the suggested exposure concentration threshold depends on both the detailed time patterns of exposure on a time scale of hours to days and also on the composition of asbestos fibers in terms of their physiochemical properties. These conclusions are supported by complementary strands of evidence including biomathematical modeling, cell biology and biochemistry of asbestos-cell interactions in vitro and in vivo, lung fiber burden analyses and epidemiology showing trends in human exposures and MM rates.}, }
@article {pmid36965792, year = {2023}, author = {Smith, SR}, title = {An updated review of diffuse mesothelioma of the pleura - A sentinel health event of potential elongate mineral particle pathogenicity.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115608}, doi = {10.1016/j.envres.2023.115608}, pmid = {36965792}, issn = {1096-0953}, mesh = {Humans ; Asbestos/toxicity ; Asbestos, Amphibole/toxicity ; *Lung Neoplasms/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; Minerals/adverse effects ; *Occupational Exposure/adverse effects ; Particle Size ; Particulate Matter/adverse effects ; Pleura ; Sentinel Surveillance ; Virulence ; }, abstract = {There are approximately 400 inorganic minerals in the Earth's crust, some of which can be encountered as elongate mineral particles [EMPs] with dimensional characteristics similar to the six minerals known as asbestos and other asbestiform amphiboles with established human pathogenicity. In addition, the rapidly developing field of nanotechnology is producing an ever-increasing array of high aspect ratio engineered nanomaterials [HARNs] with physical dimensions and biodurability similar to the asbestos fiber types with recognized pathogenic potential. Many of these non-asbestos/non-asbestiform EMPs and HARNs with the potential for aerosolization into the breathing zones of workers and in individuals in non-occupational environments have not yet been thoroughly studied with respect to their potential human pathogenicity, a fact which obviously poses concerns for both occupational health and public health professionals. On the basis of dose-response considerations it seems reasonable to infer that if any of these non-regulated EMPs or HARNs actually are pathogenic, then those mineral fiber exposure-induced disorders associated with the lowest cumulative exposure doses of the commercial amphibole types of asbestos, that is, diffuse mesothelioma of the pleura, and its non-malignant correlate of benign parietal pleural plaques, are those which are most likely to occur following inhalational exposures to any of the non-regulated EMPs and HARNs. Because of that observation, this paper reviews certain aspects of diffuse mesothelioma, including a summary of recent changes in the nomenclature of diffuse mesothelioma of the pleura; of both the descriptive and the analytical epidemiology of the disease; of the etiologies of mesothelioma, both "exposure" related and endogenous in nature; and of the asbestos population attributable fraction for diffuse mesotheliomas in the USA, both historically and in the future.}, }
@article {pmid36944283, year = {2023}, author = {Belcaid, L and Bertelsen, B and Wadt, K and Tuxen, I and Spanggaard, I and Højgaard, M and Benn Sørensen, J and Ravn, J and Lassen, U and Cilius Nielsen, F and Rohrberg, K and Westmose Yde, C}, title = {New pathogenic germline variants identified in mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {179}, number = {}, pages = {107172}, doi = {10.1016/j.lungcan.2023.03.008}, pmid = {36944283}, issn = {1872-8332}, mesh = {Humans ; Genetic Predisposition to Disease ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Germ-Line Mutation ; Germ Cells ; DNA Helicases/genetics ; }, abstract = {BACKGROUND: Mesothelioma (MM) is associated with asbestos exposure, tumor heterogeneity and aggressive clinical behavior. Identification of germline pathogenic variants (PVs) in mesothelioma is relevant for identifying potential actionable targets and genetic counseling.<br><br>METHODS: 44 patients underwent whole exome sequencing (WES) or whole genome sequencing (WGS). Germline variants were selected according to association with inherited cancer using a 168-gene in silico panel, and variants classified according to ACMG/AMP classification as pathogenic (class 5) or likely pathogenic (class 4).<br><br>RESULTS: In total, 16 patients (36%) were found to carry pathogenic or likely pathogenic variants in 13 cancer associated genes (ATM, BAP1, BRCA2, CDKN2A, FANCA, FANCC, FANCD2, FANCM, MUTYH, NBN, RAD51B, SDHA and XPC). The germline PVs occurred in DNA repair pathways, including homologous recombination repair (HRR) (75%), nucleotide excision repair (6%), cell cycle regulatory (7%), base excision repair (6%), and hypoxic pathway (6%). Five (31%) patients with a germline PV had a first or second degree relative with mesothelioma compared to none for patients without a germline PV. Previously undiagnosed BRCA2 germline PVs were identified in two patients. Potential actionable targets based on the germline PVs were found in four patients (9%).<br><br>CONCLUSION: This study revealed a high frequency of germline PVs in patients with mesothelioma. Furthermore, we identified germline PVs in two genes (NBN &amp; RAD51B) not previously associated with mesothelioma. The data support germline testing in mesothelioma and provide a rationale for additional investigation of the HRR pathway as a potential actionable target.}, }
@article {pmid36932968, year = {2023}, author = {Taioli, E and Wolf, A and Alpert, N and Rosenthal, D and Flores, R}, title = {Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.}, journal = {Journal of surgical oncology}, volume = {128}, number = {1}, pages = {134-141}, doi = {10.1002/jso.27243}, pmid = {36932968}, issn = {1096-9098}, mesh = {Humans ; Female ; Male ; Aged ; United States/epidemiology ; *Mesothelioma, Malignant ; Medicare ; *Mesothelioma/epidemiology/therapy ; *Pleural Neoplasms/epidemiology/therapy ; Prognosis ; *Lung Neoplasms/epidemiology/therapy ; SEER Program ; }, abstract = {BACKGROUND: Pleural mesothelioma is rare cancer linked to asbestos exposure. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.<br><br>MATERIALS AND METHODS: Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders.<br><br>RESULTS: Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy.<br><br>CONCLUSIONS: The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.}, }
@article {pmid36924064, year = {2023}, author = {Spaziani, E and Di Filippo, AR and Valle, G and Spaziani, M and Francioni, P and Caruso, G and Tamagnini, GT and Mosciatti, E and Picchio, M and De Cesare, A}, title = {A rare case of primary gastric Burkitt's lymphoma associated with malignant pleural mesothelioma.}, journal = {Annali italiani di chirurgia}, volume = {12}, number = {}, pages = {}, pmid = {36924064}, issn = {2239-253X}, mesh = {Humans ; Male ; Aged ; *Mesothelioma, Malignant/complications ; *Burkitt Lymphoma/complications/diagnosis ; *Mesothelioma/complications/diagnosis/pathology ; *Pleural Neoplasms/complications/diagnosis/pathology ; *Pleural Effusion ; *Respiratory Insufficiency/complications ; Dyspnea/complications ; }, abstract = {BACKGROUND: Primary gastric Burkitt lymphoma (PG BL) and malignant pleural mesothelioma (MPM) are rare and aggressive tumors with poor prognosis. HIV and EBV infection have a link in the aetiology of PG BL, while MPM is usually associated with asbestos exposure. Endoluminal bleeding from massive solid tumor, and dyspnea usually due to pleural effusion, are the typical clinical manifestations respectively of PG BL and MPM. In most patients just palliative treatment is indicated.<br><br>CASE REPORT: A caucasian elderly male, negative for the proven risk factors, presenting respiratory failure due to massive left pleural effusion with severe mediastinal shift. Contrast enhanced - Computed Tomography (CE-CT) showed a large mass causing circumferential thickening of the gastric fundus, infiltrating the left diaphragmatic dome and the ipsilateral crus. Macroscopically, on endoscopy the gastric fundus appeared completely occupied by an ulcerated large mass protunding in the gastric lumen. Histopathological examination from biopsy specimens taken during esophagogastroduodenoscopy and thoracoscopy allowed to make diagnosis of PG BL and MPM. The patient first underwent a placement of a chest tube drainage for the pleural effusion and then a thoracoscopic talc insufflation (TTI) in the left hemithorax. A surgical treatment of the gastric lesion was planned, due to the rapid growth and the high risk of bleeding. The patient died because of fatal cardiac arrhythmia, before undergoig abdominal surgery.<br><br>CONCLUSIONS: This report presents an unique case of PG BL associated with MPM and highlights the real challenge for the physicians to identify them in early stage, especially in patients without the proved risk factors. The onset symptoms make it a very singular case, characterized by severe dyspnea up to respiratory failure, due to massive left pleural effusion and contralateral mediastinal fluttering, without an active bleeding from the gastric mass, while CE-CT findings were instead negative for pleural thickening and positive for circumferential thickening of the gastric fundus.<br><br>KEY WORDS: Burkitt Lymphoma, Case Report, Gastric, Pleural Mesothelioma, Pleural Effusion, Respiratory Failure.}, }
@article {pmid36902544, year = {2023}, author = {Borgeaud, M and Kim, F and Friedlaender, A and Lococo, F and Addeo, A and Minervini, F}, title = {The Evolving Role of Immune-Checkpoint Inhibitors in Malignant Pleural Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, pmid = {36902544}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer usually caused by asbestos exposure and associated with a very poor prognosis. After more than a decade without new therapeutic options, immune checkpoint inhibitors (ICIs) demonstrated superiority over standard chemotherapy, with improved overall survival in the first and later-line settings. However, a significant proportion of patients still do not derive benefit from ICIs, highlighting the need for new treatment strategies and predictive biomarkers of response. Combinations with chemo-immunotherapy or ICIs and anti-VEGF are currently being evaluated in clinical trials and might change the standard of care in the near future. Alternatively, some non-ICI immunotherapeutic approaches, such as mesothelin targeted CAR-T cells or denditric-cells vaccines, have shown promising results in early phases of trials and are still in development. Finally, immunotherapy with ICIs is also being evaluated in the peri-operative setting, in the minority of patients presenting with resectable disease. The goal of this review is to discuss the current role of immunotherapy in the management of malignant pleural mesothelioma, as well as promising future therapeutic directions.}, }
@article {pmid36901302, year = {2023}, author = {Buralli, RJ and Pinheiro, RDC and Susviela, LL and Duracenko, SRC and De Capitani, EM and Savaris, A and Algranti, E}, title = {The Brazilian System for Monitoring Workers and General Population Exposed to Asbestos: Development, Challenges, and Opportunities for Workers' Health Surveillance.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36901302}, issn = {1660-4601}, mesh = {Humans ; *Asbestosis/epidemiology ; Brazil ; Quality of Life ; *Occupational Exposure ; Population Surveillance ; *Asbestos ; *Mesothelioma/epidemiology ; *Lung Neoplasms/epidemiology ; }, abstract = {UNLABELLED: The lack of safe levels of asbestos exposure and the long latency of asbestos-related disease (ARD) makes workers' health surveillance challenging, especially in lower-income countries. This paper aims to present the recently developed Brazilian system for monitoring workers and general population exposed to asbestos (Datamianto), and to discuss the main challenges and opportunities for workers' health surveillance.<br><br>METHODS: a descriptive study of the Datamianto development process, examining all the stages of system planning, development, improvement, validation, availability, and training of health services for its use, in addition to presenting the main challenges and opportunities for its implementation.<br><br>RESULTS: The system was developed by a group of software developers, workers' health specialists, and practitioners, and it was recently incorporated by the Ministry of Health to be used for workers' health surveillance. It can facilitate the monitoring of exposed individuals, epidemiological data analysis, promote cooperation between health services, and ensure periodical medical screening guaranteed to workers by labor legislation. Moreover, the system has a Business Intelligence (BI) platform to analyze epidemiologic data and produce near real-time reports.<br><br>CONCLUSIONS: Datamianto can support and qualify the healthcare and surveillance of asbestos-exposed workers and ARD, promoting a better quality of life for workers and improving companies' compliance with legislation. Even so, the system's significance, applicability, and longevity will depend on the efforts aimed at its implementation and improvement.}, }
@article {pmid36900330, year = {2023}, author = {Al Khatib, MO and Pinton, G and Moro, L and Porta, C}, title = {Benefits and Challenges of Inhibiting EZH2 in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900330}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer that is mainly associated with prior exposure to asbestos fibers. Despite being a rare cancer, its global rate is increasing and the prognosis remains extremely poor. Over the last two decades, despite the constant research of new therapeutic options, the combination chemotherapy with cisplatin and pemetrexed has remained the only first-line therapy for MPM. The recent approval of immune checkpoint blockade (ICB)-based immunotherapy has opened new promising avenues of research. However, MPM is still a fatal cancer with no effective treatments. Enhancer of zeste homolog 2 (EZH2) is a histone methyl transferase that exerts pro-oncogenic and immunomodulatory activities in a variety of tumors. Accordingly, a growing number of studies indicate that EZH2 is also an oncogenic driver in MPM, but its effects on tumor microenvironments are still largely unexplored. This review describes the state-of-the-art of EZH2 in MPM biology and discusses its potential use both as a diagnostic and therapeutic target. We highlight current gaps of knowledge, the filling of which will likely favor the entry of EZH2 inhibitors within the treatment options for MPM patients.}, }
@article {pmid36896837, year = {2023}, author = {Scarselli, A and Corfiati, M and Marinaccio, A}, title = {Occupational exposure register-based cohort study on mortality among asbestos-related workers in Italy after the ban.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {32}, number = {3}, pages = {281-285}, doi = {10.1097/CEJ.0000000000000786}, pmid = {36896837}, issn = {1473-5709}, mesh = {Male ; Humans ; Cohort Studies ; *Asbestos/toxicity ; *Mesothelioma ; *Occupational Exposure/adverse effects ; Carcinogens ; Italy/epidemiology ; *Lung Neoplasms/etiology ; }, abstract = {OBJECTIVE: Asbestos is a human carcinogen and can cause some types of cancer, including mesothelioma. A relevant number of workers are still engaged in asbestos removal and disposal activities, whose actual risk of asbestos-related diseases is still scarcely recognized. The main objective of this study is to assess the cause-specific mortality among workers involved in asbestos removal and disposal after the ban in Italy.<br><br>METHODS: Data from the Information System on Occupational Exposure to carcinogens (SIREP) in the period 1996-2018 were selected. Proportionate mortality ratios (PMRs) by cause of death were calculated by linking exposure occupational information to national mortality statistics (2005-2018), assuming a Poisson distribution of the data.<br><br>RESULTS: A total of 142 deaths (all men) were identified among 13&#x2009;715 asbestos removal and disposal workers. A significant excess (P &#x2009;<&#x2009;0.05) of mesothelioma deaths was found among male workers, about five-fold the expected. A significant increase in the mortality ratio was also found for malignant melanoma of skin.<br><br>CONCLUSIONS: A risk of mesothelioma has been found among workers involved in asbestos removal and disposal. Epidemiological surveillance and promotion of prevention action plans are highly recommended for workers engaged in asbestos removal and disposal activities, to ensure compliance with regulatory requirements and reduce the still relevant risk of contracting the related tumor pathology.}, }
@article {pmid36883200, year = {2023}, author = {Janosikova, M and Nakladalova, M and Stepanek, L}, title = {Current causes of mesothelioma: how has the asbestos ban changed the perspective?.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {167}, number = {2}, pages = {99-108}, pmid = {36883200}, issn = {1804-7521}, mesh = {Humans ; Female ; Adolescent ; *Nanotubes, Carbon ; *Lung Neoplasms/chemically induced ; *Mesothelioma/chemically induced/complications ; *Mesothelioma, Malignant/chemically induced/complications ; *Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Minerals ; *Pleural Neoplasms/chemically induced/complications ; }, abstract = {The association of mesothelioma, a lethal lung disease, with asbestos has led to an absolute ban on asbestos in at least 55 countries worldwide. The purpose of this paper is to review residual exposure to asbestos as well as other emerging causes of mesothelioma outside asbestos. The review provides detailed description of asbestos minerals, their geographical locations, mesothelioma in these areas, as well as contemporary possible sources of asbestos exposure. Second, we examine other emerging causes of mesothelioma including: ionizing radiation as the second most important risk factor after asbestos, particularly relevant to patients undergoing radiotherapy, third, carbon nanotubes which are under investigation and fourth, Simian virus 40. In the case of asbestos per se, the greatest risk is from occupational exposure during mining and subsequent processing. Of the non-occupational exposures, environmental exposure is most serious, followed by exposure from indoor asbestos minerals and secondary familial exposure. Overall, asbestos is still a major risk factor, but alternative causes should not be neglected, especially in young people, in women and those with a history of radiotherapy or living in high-risk locations.}, }
@article {pmid36876393, year = {2023}, author = {Walther, D and Hunziker, S and Boichat Burdy, S and Ruf, F and Rossi, I and Vernez, D}, title = {[Asbestos related cancers: burden and recognition as occupational diseases].}, journal = {Revue medicale suisse}, volume = {19}, number = {816}, pages = {422-425}, doi = {10.53738/REVMED.2023.19.816.422}, pmid = {36876393}, issn = {1660-9379}, mesh = {Humans ; *Asbestos ; Health Personnel ; *Lung Neoplasms ; *Occupational Diseases ; }, abstract = {Although asbestos has been banned in Switzerland since 1989, diseases caused by asbestos are still present and increasing today. In Switzerland, per year, occupational exposure to asbestos is responsible for approximately 135 deaths from mesothelioma and 930 deaths from lung cancer, though the latter is rarely recognized as an occupational disease. Taking an occupational history is essential for all such diagnosis, especially in smokers, whose risk of lung cancer increases due to the synergistic effect of asbestos and tobacco exposure. The medical practitioner can play an important role in occupational diseases being recognized as such, which is essential for the reimbursement of medical expenses by the accident insurance companies and the allocation of indemnities and pensions for the patient or their family.}, }
@article {pmid36857650, year = {2023}, author = {Han, J and Park, S and Yon, DK and Lee, SW and Woo, W and Dragioti, E and Koyanagi, A and Jacob, L and Kostev, K and Radua, J and Lee, S and Shin, JI and Smith, L}, title = {Global, Regional, and National Burden of Mesothelioma 1990-2019: A Systematic Analysis of the Global Burden of Disease Study 2019.}, journal = {Annals of the American Thoracic Society}, volume = {20}, number = {7}, pages = {976-983}, doi = {10.1513/AnnalsATS.202209-802OC}, pmid = {36857650}, issn = {2325-6621}, mesh = {Male ; Humans ; Female ; *Global Burden of Disease ; Quality-Adjusted Life Years ; Risk Factors ; Morbidity ; Incidence ; *Mesothelioma/epidemiology ; Global Health ; }, abstract = {Rationale: Mesothelioma has become a major health burden since World War II because of the use of asbestos. Although many countries have imposed bans on asbestos, there remain significant mortality and morbidity from mesothelioma because of its long latent period and aggressiveness. Also, the use of asbestos is increasing in low-income countries, potentiating risk of mesothelioma in the coming decades. Assessment of the global burden of mesothelioma is required to take proper measures against the disease. Objectives: To assess the burden of mesothelioma from 1990 to 2019 at the global, regional, and national levels and to investigate patterns according to sex, age, sociodemographic index, and risk factors. Methods: The numbers, rates, and age-standardized rates of incidence, death, and disability-adjusted life years (DALYs) of mesothelioma in 204 countries and territories from 1990 to 2019 were estimated using vital registration and cancer registry data. The relationship between sociodemographic index and age-standardized DALY rate was determined, and DALYs attributable to occupational exposure to asbestos were calculated. Results: In 2019, there were 34,511 (95% uncertainty interval [UI], 31,199 to 37,771) incident cases of mesothelioma globally, with an age-standardized rate of 0.43 per 100,000 persons (95% UI, 0.38 to 0.47), which decreased between 1990 and 2019 by -12.6% (95% UI, -21.8% to -2.3%). Mesothelioma was responsible for 29,251 (95% UI, 26,668 to 31,006) deaths in 2019, with an age-standardized rate of 0.36 deaths per 100,000 persons (95% UI, 0.33 to 0.39), which decreased between 1990 and 2019 by -9.6% (95% UI, -17.8% to -1.1%). The age-standardized incidence rate increased in central Europe between 1990 and 2019 by 46.1% (95% UI, 16.6% to 72.4%). The Netherlands, Australia, and the United Kingdom had the highest age-standardized incidence rates. Incidence rates were higher in men than in women ages 45-49 to 90-94 years, peaking at 85-89 years. Occupational exposure to asbestos contributed to 85.2% (95% UI, 82.1% to 88.1%) of DALYs. Conclusions: The global burden of mesothelioma is decreasing in terms of age-standardized incidence and mortality rates. Mesothelioma remains a substantial public health challenge in many parts of the world.}, }
@article {pmid36833533, year = {2023}, author = {Lai, H and Hu, C and Qu, M and Liu, X and Xue, Y and Xu, P and Hao, D}, title = {Mesothelioma Due to Workplace Exposure: A Comprehensive Bibliometric Analysis of Current Situation and Future Trends.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {4}, pages = {}, pmid = {36833533}, issn = {1660-4601}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma ; Workplace ; *Lung Neoplasms ; Bibliometrics ; }, abstract = {Background: This article provides an overview of the current status and research progress of mesothelioma. Methods: A total of 2638 documents published from 1 January 2004 to 30 November 2022 were retrieved from the Web of Science Core Collection and analyzed via Microsoft Office Excel 2019, VOSviewer 1.6.18, and Tableau 2022.2. Results: There was an obvious increase in the number of publications regarding mesothelioma in the last 18 years, with the United States dominating the research field with 715 publications and 23,882 citations, while the University of Turin contributed the most (118). Occupational &amp; Environmental Medicine was the most popular journal (80), with Corrado Magnani being the most prolific author (52) and Michele Carbone obtaining the most citations (4472). "Oncology" and "Health Science of Environment &amp; Occupation" were the two main subjects, while the keywords "asbestos", "lung cancer", "gene expression", "apoptosis", "survival", and "cisplatin" were the most popular. Conclusions: The containment of mesothelioma calls for more participation from low- and middle-income countries, and further attention needs to be paid to clinical research.}, }
@article {pmid36831074, year = {2023}, author = {Filetti, V and Lombardo, C and Loreto, C and Dounias, G and Bracci, M and Matera, S and Rapisarda, L and Rapisarda, V and Ledda, C and Vitale, E}, title = {Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers.}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36831074}, issn = {2227-9059}, support = {20722142130//University of Catania/ ; }, abstract = {Environmental exposure to fibers of respirable size has been identified as a risk for public health. Experimental evidence has revealed that a variety of fibers, including fluoro-edenite, can develop chronic respiratory diseases and elicit carcinogenic effects in humans. Fluoro-edenite (FE) is a silicate mineral first found in Biancavilla (Sicily, Italy) in 1997. Environmental exposure to its fibers has been correlated with a cluster of malignant pleural mesotheliomas. This neoplasm represents a public health problem due to its long latency and to its aggression not alerted by specific symptoms. Having several biomarkers providing us with data on the health state of those exposed to FE fibers or allowing an early diagnosis on malignant pleural mesothelioma, still asymptomatic patients, would be a remarkable goal. To these purposes, we reported the miRNA transcriptome in human normal mesothelial cell line (MeT-5A) and in the human malignant mesothelioma cell line (JU77) exposed and not exposed to FE fibers. The results showed a difference in the number of deregulated miRNAs between tumor and nontumor samples both exposed and not exposed to FE fibers. As a matter of fact, the effect of exposure to FE fibers is more evident in the expression of miRNA in the tumor samples than in the nontumor samples. In the present paper, several pathways involved in the pathogenesis of malignant pleural mesothelioma have been analyzed. We especially noticed the involvement of pathways that have important functions in inflammatory processes, angiogenesis, apoptosis, and necrosis. Besides this amount of data, further studies will be designed for the selection of the most significant miRNAs to test and validate their diagnostic potential, alone or in combination with other protein biomarkers, in high-risk individuals' liquid biopsy to have a noninvasive tool of diagnosis for this neoplasm.}, }
@article {pmid36825373, year = {2023}, author = {Zona, A and Fazzo, L and Benedetti, M and Bruno, C and Vecchi, S and Pasetto, R and Minichilli, F and De Santis, M and Nannavecchia, AM and Di Fonzo, D and Contiero, P and Ricci, P and Bisceglia, L and Manno, V and Minelli, G and Santoro, M and Gorini, F and Ancona, C and Scondotto, S and Soggiu, ME and Scaini, F and Beccaloni, E and Marsili, D and Villa, MF and Maifredi, G and Magoni, M and Iavarone, I and , }, title = {[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report].}, journal = {Epidemiologia e prevenzione}, volume = {47}, number = {1-2 Suppl 1}, pages = {1-286}, doi = {10.19191/EP23.1-2-S1.003}, pmid = {36825373}, issn = {1120-9763}, mesh = {Pregnancy ; Adolescent ; Young Adult ; Humans ; Female ; Male ; Child ; Adult ; Middle Aged ; Aged ; Infant, Newborn ; Infant ; Child, Preschool ; *Stomach Neoplasms/complications ; Cross-Sectional Studies ; Italy/epidemiology ; *Mesothelioma/etiology ; *Asbestos ; *Breast Neoplasms ; *Lymphoma, Non-Hodgkin ; *Lung Neoplasms/epidemiology ; *Urinary Bladder Neoplasms/complications ; *Liver Neoplasms ; *Colorectal Neoplasms ; }, abstract = {INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest.<br><br>METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources.<br><br>RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males: pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered.<br><br>LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources.<br><br>CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.}, }
@article {pmid36819965, year = {2023}, author = {Gariazzo, C and Gasparrini, A and Marinaccio, A}, title = {Asbestos Consumption and Malignant Mesothelioma Mortality Trends in the Major User Countries.}, journal = {Annals of global health}, volume = {89}, number = {1}, pages = {11}, pmid = {36819965}, issn = {2214-9996}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; *Asbestos ; *Mesothelioma/epidemiology ; World Health Organization ; Linear Models ; *Lung Neoplasms ; *Pleural Neoplasms ; *Occupational Exposure ; }, abstract = {BACKGROUND: The causal association between mesothelioma and asbestos exposure is conclusive, and many studies have proved that the trend in asbestos use is a strong predictor of the pattern in mesothelioma cases with an adequate latency time (generally around 30-40 years or more). Recently, a novel approach for predicting malignant pleural mesothelioma, based on asbestos consumption trend and using distributed non-linear models, has been applied.<br><br>OBJECTIVES: The purpose of this study is to analyse trends in asbestos consumption and malignant mesothelioma mortality in the major asbestos-user countries. Furthermore, we applied distributed non-linear models to estimate and compare epidemiological relationships between asbestos consumption and mesothelioma mortality across these countries.<br><br>METHODS: The study involves major asbestos-user countries in which historical asbestos consumption and mesothelioma mortality data are available. Data on asbestos consumption were derived from worldwide asbestos supply and mesothelioma mortality data from World Health Organization (WHO) mortality archives. A quasi-Poisson generalized linear model was used to model past asbestos exposure and male mesothelioma mortality rates in each country. Exposure-response associations have been modelled using distributed lag non-linear models.<br><br>FINDINGS AND CONCLUSIONS: According to the criteria defined above, we selected 18 countries with raw asbestos cumulative consumptions higher than two million tons in the period 1933-2012. Overall, a clear linear relationship can be observed between total consumption and total deaths for mesothelioma. Country-specific exposure, lag and age-response relationships were identified and common functions extracted by a meta-analysis procedure. Non-linear models appear suitable and flexible tools for investigating the association between mesothelioma mortality and asbestos consumption. There is a need to improve the global epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, and the absence of reliable data for some major asbestos-user countries is a real concern. A reliable assessment of mesothelioma mortality is a fundamental step towards increasing the awareness of related risks and the need of an international ban on asbestos.}, }
@article {pmid36808895, year = {2023}, author = {Sejben, A and Pancsa, T and Tiszlavicz, L and Furák, J and Paróczai, D and Zombori, T}, title = {Highlighting the immunohistochemical differences of malignant mesothelioma subtypes via case presentations.}, journal = {Thoracic cancer}, volume = {14}, number = {10}, pages = {857-863}, pmid = {36808895}, issn = {1759-7714}, mesh = {Humans ; *Mesothelioma, Malignant/diagnosis ; *Mesothelioma/pathology ; Mesothelin ; Calbindin 2 ; Biomarkers, Tumor/metabolism ; Immunohistochemistry ; Diagnosis, Differential ; *Lung Neoplasms/pathology ; }, abstract = {Malignant mesothelioma (MM) is a rare tumor of mesothelial cells, with an increasing incidence both in developed and developing countries. MM has three major histological subtypes, in order of frequency, according to the World Health Organization (WHO) Classification of 2021: epithelioid, biphasic, and sarcomatoid MM. Distinction may be a challenging task for the pathologist, due to the unspecific morphology. Here, we present two cases of diffuse MM subtypes to emphasize the immunohistochemical (IHC) differences, and to facilitate diagnostic difficulties. In our first case of epithelioid mesothelioma, the neoplastic cells showed cytokeratin 5/6 (CK5/6), calretinin, and Wilms-tumor-1 (WT1) expression, while remaining negative with thyroid transcription factor-1 (TTF-1). BRCA1 associated protein-1 (BAP1) negativity was seen in the neoplastic cells' nucleus, reflecting loss of the tumor suppressor gene. In the second case of biphasic mesothelioma, expression of epithelial membrane antigen (EMA), CKAE1/AE3, and mesothelin was observed, while WT1, BerEP4, CD141, TTF1, p63, CD31, calretinin, and BAP1 expressions were not detected. Due to the absence of specific histological features, the differentiation between MM subtypes could be a challenging task. In routine diagnostic work, IHC may be the proper method in distinction. According to our results and literature data, CK5/6, mesothelin, calretinin, and Ki-67 should be applied in subclassification.}, }
@article {pmid36800547, year = {2023}, author = {Hocking, AJ and Thomas, EM and Prabhakaran, S and Jolley, A and Woods, SL and Soeberg, MJ and Klebe, S}, title = {Molecular Characterization of Testicular Mesothelioma and the Role of Asbestos as a Causative Factor.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {147}, number = {12}, pages = {1446-1450}, doi = {10.5858/arpa.2022-0283-OA}, pmid = {36800547}, issn = {1543-2165}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Mesothelioma/genetics ; *Testicular Neoplasms/genetics/pathology ; }, abstract = {CONTEXT.&#x2014;: Mesothelioma of the tunica vaginalis testis (TVT) is an extremely rare form of mesothelioma.<br><br>OBJECTIVE.&#x2014;: To compare the clinical and molecular characteristics of mesothelioma of the TVT with those of mesothelioma at other more common sites, including the relationship with exposure to asbestos.<br><br>DESIGN.&#x2014;: We present clinical and pathological data for 9 cases of primary TVT mesothelioma. We performed whole-genome sequencing on 3 cases for the first time.<br><br>RESULTS.&#x2014;: The majority (7 of 9 cases) of TVT mesotheliomas were epithelioid, with the remaining 2 cases showing biphasic morphology. Morphology and immunohistochemical profiles were indistinguishable from mesothelioma elsewhere. Asbestos exposure was documented for 7 of the 9 cases, with no information for 2 cases. The 3 TVT mesothelioma cases that underwent whole-genome sequencing displayed a mutational profile similar to that of mesothelioma at other sites, including NF2 and TP53 mutations.<br><br>CONCLUSIONS.&#x2014;: The clinical and molecular profile of TVT mesothelioma is similar to that of mesothelioma elsewhere.}, }
@article {pmid36785667, year = {2023}, author = {Kapila, D and Panwar, S and Raja, MKMM and Mondal, T and Rafi, SM and Singh, SP and Kumar, B}, title = {Applications of Neural Network-Based Plan-Cancer Method for Primary Diagnosis of Mesothelioma Cancer.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {3164166}, pmid = {36785667}, issn = {2314-6141}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/pathology ; Artificial Intelligence ; *Asbestos/toxicity ; Neural Networks, Computer ; }, abstract = {"Malignant mesothelioma (MM)" is an uncommon although fatal form of cancer. The proper MM diagnosis is crucial for efficient therapy and has significant medicolegal implications. Asbestos is a carcinogenic material that poses a health risk to humans. One of the most severe types of cancer induced by asbestos is "malignant mesothelioma." Prolonged shortness of breath and continuous pain are the most typical symptoms of the condition. The importance of early treatment and diagnosis cannot be overstated. The combination "epithelial/mesenchymal appearance of MM," however, makes a definite diagnosis difficult. This study is aimed at developing a deep learning system for medical diagnosis MM automatically. Otherwise, the sickness might cause patients to succumb to death in a short amount of time. Various forms of artificial intelligence algorithms for successful "Malignant Mesothelioma illness" identification are explored in this research. In relation to the concept of traditional machine learning, the techniques support "Vector Machine, Neural Network, and Decision Tree" are chosen. SPSS has been used to analyze the result regarding the applications of Neural Network helps to diagnose MM.}, }
@article {pmid36781903, year = {2023}, author = {Vasuri, F and Deserti, M and Corradini, AG and Tavolari, S and Relli, V and Palloni, A and Frega, G and Curti, S and Mattioli, S and Cescon, M and D'Errico, A and Brandi, G}, title = {Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2580}, pmid = {36781903}, issn = {2045-2322}, mesh = {Humans ; Pilot Projects ; *Asbestos/toxicity ; *Cholangiocarcinoma/etiology/chemically induced ; Risk Factors ; Bile Ducts, Intrahepatic/pathology ; *Bile Duct Neoplasms/etiology/chemically induced ; }, abstract = {Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype. Forty patients with surgically removed iCCA were prospectively enrolled: asbestos exposure was assessed according to the Italian National Mesothelioma Register questionnaire. From the surgical iCCA specimens the main histopathological variables were collected, including the small duct (sd-iCCA, 32 patients) and large duct subtypes (ld-iCCA, 8 patients). Five sd-iCCA cases had a definite/probable occupational exposure to asbestos, while no cases of ld-iCCA were classified as being occupationally exposed (definite/probable). Other kind of asbestos exposure (i.e. possible occupational, familial, environmental) were recorded in 16 sd-iCCA and 3 ld-iCCA. Cases with unlikely exposure to asbestos were 11 sd-iCCA (35.5%) and 5 ld-iCCA (62.5%). In conclusion, these findings seem to indicate that sd-iCCA might be more frequently associated to asbestos exposure rather than ld-iCCA, suggesting that asbestos fibres might represent a parenchymal, rather than a ductal risk factor for iCCA. This pilot study must be confirmed by further case-control studies or large independent cohorts.}, }
@article {pmid36781827, year = {2023}, author = {Iwadare, T and Kimura, T and Nagata, Y and Suzuki, H and Kunimoto, H and Kitabatake, H and Seki, A and Ochi, Y and Hara, E and Umemura, T}, title = {A case of malignant peritoneal mesothelioma with a Fitz-Hugh-Curtis syndrome-like imaging finding.}, journal = {Clinical journal of gastroenterology}, volume = {16}, number = {3}, pages = {372-376}, pmid = {36781827}, issn = {1865-7265}, mesh = {Male ; Female ; Humans ; Middle Aged ; *Pelvic Inflammatory Disease/diagnosis ; *Hepatitis/diagnosis ; *Peritonitis/diagnosis ; *Peritoneal Neoplasms/diagnostic imaging/drug therapy ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/diagnostic imaging ; }, abstract = {Malignant peritoneal mesothelioma (MPeM) is a rare disease with a poor prognosis that develops in the mesothelial cells of the peritoneum. We encountered a 48-year-old man with no prior asbestos exposure who visited our hospital with abdominal pain. Laboratory findings showed elevated C-reactive protein of 15.5 mg/dL. Contrast-enhanced computed tomography (CT) detected a Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface and thickening of the peritoneum. Blood culture, Mycobacterium tuberculosis-specific IFN-γ release assay, Chlamydia trachomatis and Neisseria gonorrhoeae DNA testing, and antinuclear antibody were all negative. CA125 was high at 124.8 U/mL. The laparoscopy for diagnostic purposes revealed adhesions between the liver surface and peritoneum in addition to numerous small and large white nodules on the peritoneum. Biopsy of the nodules confirmed the diagnosis of epithelial-type MPeM. Treatment was initiated with combined cisplatin and pemetrexed, and CT 6 months later showed a reduced contrast effect on the liver surface and improved peritoneal thickening. A Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface on contrast-enhanced CT may help identify MPeM.}, }
@article {pmid36775192, year = {2023}, author = {Huang, J and Chan, SC and Pang, WS and Chow, SH and Lok, V and Zhang, L and Lin, X and Lucero-Prisno, DE and Xu, W and Zheng, ZJ and Elcarte, E and Withers, M and Wong, MCS and , }, title = {Global Incidence, Risk Factors, and Temporal Trends of Mesothelioma: A Population-Based Study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {18}, number = {6}, pages = {792-802}, doi = {10.1016/j.jtho.2023.01.095}, pmid = {36775192}, issn = {1556-1380}, mesh = {Female ; Humans ; Male ; Incidence ; *Lung Neoplasms/complications ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; Risk Factors ; }, abstract = {INTRODUCTION: Mesothelioma is an uncommon type of cancer which has received little attention. This study aims to evaluate the global disease burden; trends of mesothelioma by age, sex, and geographic locations; and its risk factors on the population level.<br><br>METHODS: The Global Cancer Observatory, Cancer Incidence in Five Continents Plus, and Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. The associations between mesothelioma incidence and asbestos were evaluated for each country by multivariable linear regression analysis by sex and age. Average annual percentage change (AAPC) was calculated using Joinpoint regression to evaluate the epidemiologic trends of mesothelioma.<br><br>RESULTS: The age-standardized rate of mesothelioma was 0.30 per 100,000 persons with Northern Europe reporting the highest incidence rates. The incidence rate of the male population was much higher than that of the females. Countries with higher human development index (&#x3b2;&#xa0;= 0.119, confidence interval [CI]: 0.073-0.166, p < 0.001), gross domestic product per capita (&#x3b2;&#xa0;= 0.133, CI: 0.106-0.161, p < 0.001), and asbestos exposure (&#x3b2;&#xa0;= 0.087, CI: 0.073-0.102, p < 0.001) had higher mesothelioma. The overall trend of mesothelioma incidence was decreasing, although an increase was observed in Bulgaria (AAPC: 5.56, 95% CI: 2.94-8.24, p&#xa0;= 0.001) and Korea (AAPC: 3.24, 95% CI: 0.08-6.49, p&#xa0;= 0.045).<br><br>CONCLUSIONS: There was a substantial declining incidence trend of mesothelioma in the past decade possibly related to the restriction of the use of asbestos in some countries. Meanwhile, the increasing trend in mesothelioma incidence observed in females might be indicative of an increase in environmental exposure to mineral fibers.}, }
@article {pmid36765599, year = {2023}, author = {Palstrøm, NB and Overgaard, M and Licht, P and Beck, HC}, title = {Identification of Highly Sensitive Pleural Effusion Protein Biomarkers for Malignant Pleural Mesothelioma by Affinity-Based Quantitative Proteomics.}, journal = {Cancers}, volume = {15}, number = {3}, pages = {}, pmid = {36765599}, issn = {2072-6694}, support = {NA//Odense University Hospital/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-associated, highly aggressive cancer characterized by late-stage diagnosis and poor prognosis. Gold standards for diagnosis are pleural biopsy and cytology of pleural effusion (PE), both of which are limited by low sensitivity and markedly inter-observer variations. Therefore, the assessment of PE biomarkers is considered a viable and objective diagnostic tool for MPM diagnosis. We applied a novel affinity-enrichment mass spectrometry-based proteomics method for explorative analysis of pleural effusions from a prospective cohort of 84 patients referred for thoracoscopy due to clinical suspicion of MPM. Protein biomarkers with a high capability to discriminate MPM from non-MPM patients were identified, and a Random Forest algorithm was applied for building classification models. Immunohistology of pleural biopsies confirmed MPM in 40 patients and ruled out MPM in 44 patients. Proteomic analysis of pleural effusions identified panels of proteins with excellent diagnostic properties (90-100% sensitivities, 89-98% specificities, and AUC 0.97-0.99) depending on the specific protein combination. Diagnostic proteins associated with cancer growth included galactin-3 binding protein, testican-2, haptoglobin, Beta ig-h3, and protein AMBP. Moreover, we also confirmed previously reported diagnostic accuracies of the MPM markers fibulin-3 and mesothelin measured by two complementary mass spectrometry-based methods. In conclusion, a novel affinity-enrichment mass spectrometry-based proteomics identified panels of proteins in pleural effusion with extraordinary diagnostic accuracies, which are described here for the first time as biomarkers for MPM.}, }
@article {pmid36765038, year = {2023}, author = {Yang, H and Gao, Y and Xu, D and Xu, K and Liang, SQ and Yang, Z and Scherz, A and Hall, SRR and Forster, S and Berezowska, S and Yao, F and Ochsenbein, AF and Marti, TM and Kocher, GJ and Schmid, RA and Dorn, P and Peng, RW}, title = {MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {55}, pmid = {36765038}, issn = {2058-7716}, support = {KFS-4851-08-2019//Krebsliga Schweiz (Ligue Suisse Contre le Cancer)/ ; 310030_192648//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a lethal malignancy etiologically caused by asbestos exposure, for which there are few effective treatment options. Although asbestos carcinogenesis is associated with reactive oxygen species (ROS), the bona fide oncogenic signaling pathways that regulate ROS homeostasis and bypass ROS-evoked apoptosis in MPM are poorly understood. In this study, we demonstrate that the mitogen-activated protein kinase (MAPK) pathway RAS-RAF-MEK-ERK is hyperactive and a molecular driver of MPM, independent of histological subtypes and genetic heterogeneity. Suppression of MAPK signaling by clinically approved MEK inhibitors (MEKi) elicits PARP1 to protect MPM cells from the cytotoxic effects of MAPK pathway blockage. Mechanistically, MEKi induces impairment of homologous recombination (HR) repair proficiency and mitochondrial metabolic activity, which is counterbalanced by pleiotropic PARP1. Consequently, the combination of MEK with PARP inhibitors enhances apoptotic cell death in vitro and in vivo that occurs through coordinated upregulation of cytotoxic ROS in MPM cells, suggesting a mechanism-based, readily translatable strategy to treat this daunting disease. Collectively, our studies uncover a previously unrecognized scenario that hyperactivation of the MAPK pathway is an essential feature of MPM and provide unprecedented evidence that MAPK signaling cooperates with PARP1 to homeostatically maintain ROS levels and escape ROS-mediated apoptosis.}, }
@article {pmid36757881, year = {2023}, author = {Bonde, A and Singh, R and Prasad, SR and Kamireddy, D and Aggarwal, A and Ramani, N and Saboo, S and Shanbhogue, K and Dasyam, AK and Katabathina, VS}, title = {Mesotheliomas and Benign Mesothelial Tumors: Update on Pathologic and Imaging Findings.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {43}, number = {3}, pages = {e220128}, doi = {10.1148/rg.220128}, pmid = {36757881}, issn = {1527-1323}, mesh = {Humans ; *Adenomatoid Tumor ; Positron Emission Tomography Computed Tomography ; *Mesothelioma/diagnostic imaging/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; *Neoplasms, Mesothelial ; Biomarkers, Tumor ; }, abstract = {A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics. While malignant mesotheliomas are biologically aggressive malignancies that occur primarily in patients exposed to asbestos with attendant poor survival rates, well-differentiated papillary mesothelial tumors and adenomatoid tumors charter a benign clinical course with an excellent prognosis. Mesothelioma in situ is a newly characterized entity represented by recurrent unexplained pleural effusions without any identifiable mass at imaging or thoracoscopy. Immunohistochemical markers based on BAP1, MTAP, CDKN2A, and TRAF7 gene mutations help differentiate diffuse mesotheliomas from benign mesothelial proliferations and localized mesotheliomas. Cross-sectional imaging modalities, including US, CT, MRI, and fluorine 18-fluorodeoxyglucose (FDG) PET/CT, permit diagnosis and play a major role in staging and assessing surgical resectability. Imaging studies are invaluable in providing noninvasive and quantitative assessment of tumor response in patients with unresectable disease. Owing to significant overlap in patient characteristics and pathomorphology, accurate diagnosis based on advanced histopathology techniques and genetic abnormalities is imperative for optimal management and prognostication. While patients with nonepithelioid pleural mesotheliomas benefit from immunotherapy, novel targeted therapies for CDKN2A-, NF2-, and BAP1-altered mesotheliomas are under consideration. [©] RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.}, }
@article {pmid36754595, year = {2023}, author = {Walker-Bone, K and Benke, G and MacFarlane, E and Klebe, S and Takahashi, K and Brims, F and Sim, MR and Driscoll, TR}, title = {Incidence and mortality from malignant mesothelioma 1982-2020 and relationship with asbestos exposure: the Australian Mesothelioma Registry.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {4}, pages = {186-191}, doi = {10.1136/oemed-2022-108669}, pmid = {36754595}, issn = {1470-7926}, mesh = {Male ; Humans ; Female ; Aged, 80 and over ; *Mesothelioma, Malignant/chemically induced/complications ; Incidence ; Australia/epidemiology ; *Mesothelioma/etiology ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects ; Registries ; }, abstract = {OBJECTIVES: Malignant mesothelioma is an uncommon cancer associated with asbestos exposure, predominantly occupational. Asbestos has been banned in Australia since 2003 but mesothelioma has a long latency and incident cases continue to present. The Australian Mesothelioma Registry was incepted to collect systematic data about incidence and mortality alongside asbestos exposure.<br><br>METHODS: Benefiting from the Australian national system of cancer notification, all incident cases of mesothelioma in all states and territories are fast-tracked and notified regularly. Notified patients are contacted asking for consent to collect exposure information, initially by postal questionnaire and subsequently by telephone interview. Age-standardised annual incidence rates and mortality rates were calculated. Asbestos exposure was categorised as occupational, non-occupational, neither or, both; and as low, or high, probability of exposure.<br><br>RESULTS: Mesothelioma incidence appears to have peaked. The age-standardised incidence rates have declined steadily since the early 2000s (peaking in males at 5.9/100 000 and in all-persons at 3.2/100 000), driven by rates in males, who comprise the majority of diagnosed cases. Rates in women have remained fairly stable since that time. Age-standardised mortality rates have followed similar trends. Mesothelioma remains the most common in those aged over 80 years. Nearly all (94%) cases were linked with asbestos exposure (78% occupational in men; 6.8% in women).<br><br>CONCLUSIONS: With effective control of occupational asbestos use, the decline in age-standardised incidence and death rates has occurred. Incidence rates among women, in whom occupational asbestos exposure is rarely detectable, remain unchanged, pointing to the role of household and /or environmental asbestos exposure.}, }
@article {pmid36740402, year = {2023}, author = {Cunningham, R and Jia, S and Purohit, K and Salem, O and Hui, NS and Lin, Y and Carragher, NO and Hansen, CG}, title = {YAP/TAZ activation predicts clinical outcomes in mesothelioma and is conserved in in vitro model of driver mutations.}, journal = {Clinical and translational medicine}, volume = {13}, number = {2}, pages = {e1190}, pmid = {36740402}, issn = {2001-1326}, support = {19-0238/AICR_/Worldwide Cancer Research/United Kingdom ; 204804/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Hippo Signaling Pathway ; *Mesothelioma/genetics/metabolism/pathology ; Mutation/genetics ; Protein Serine-Threonine Kinases/metabolism ; *Transcription Factors/genetics/metabolism ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; YAP-Signaling Proteins ; }, abstract = {The Hippo signalling pathway is dysregulated across a wide range of cancer types and, although driver mutations that directly affect the core Hippo components are rare, a handful is found within pleural mesothelioma (PM). PM is a deadly disease of the lining of the lung caused by asbestos exposure. By pooling the largest-scale clinical datasets publicly available, we here interrogate associations between the most prevalent driver mutations within PM and Hippo pathway disruption in patients, while assessing correlations with a variety of clinical markers. This analysis reveals a consistent worse outcome in patients exhibiting transcriptional markers of YAP/TAZ activation, pointing to the potential of leveraging Hippo pathway transcriptional activation status as a metric by which patients may be meaningfully stratified. Preclinical models recapitulating disease are transformative in order to develop new therapeutic strategies. We here establish an isogenic cell-line model of PM, which represents the most frequently mutated genes and which faithfully recapitulates the molecular features of clinical PM. This preclinical model is developed to probe the molecular basis by which the Hippo pathway and key driver mutations affect cancer initiation and progression. Implementing this approach, we reveal the role of NF2 as a mechanosensory component of the Hippo pathway in mesothelial cells. Cellular NF2 loss upon physiological stiffnesses analogous to the tumour niche drive YAP/TAZ-dependent anchorage-independent growth. Consequently, the development and characterisation of this cellular model provide a unique resource to obtain molecular insights into the disease and progress new drug discovery programs together with future stratification of PM patients.}, }
@article {pmid36729166, year = {2023}, author = {Slavik, CE and Demers, PA and Tamburic, L and Warden, H and McLeod, C}, title = {Do patterns of past asbestos use and production reflect current geographic variations of cancer risk?: mesothelioma in Ontario and British Columbia, Canada.}, journal = {Cancer causes &amp; control : CCC}, volume = {34}, number = {4}, pages = {349-360}, pmid = {36729166}, issn = {1573-7225}, support = {RS2018-SP27//WorkSafeBC/ ; }, mesh = {Humans ; British Columbia/epidemiology ; Ontario/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Asbestos/adverse effects ; Environmental Exposure ; Incidence ; *Occupational Exposure/adverse effects ; }, abstract = {PURPOSE: Canada was a major global asbestos producer and consumer. Geographic patterns of Canadian asbestos use and mesothelioma, a highly fatal cancer linked to asbestos exposure, have not been previously reported. This study summarized key trends in mesothelioma incidence by geography and time in two Canadian provinces, Ontario and British Columbia (BC), and explored how past workforce characteristics and geographic trends in asbestos production and use may shape variations in regional rates of mesothelioma.<br><br>METHODS: We report trends in mesothelioma incidence (1993-2016) for Ontario and British Columbia using population-based incidence data that were age-standardized to the 2011 Canadian population. Historical records of asbestos production and use were analyzed to geo-locate industrial point sources of asbestos in Ontario and BC. The prevalence of occupations in regions with the highest and lowest rates of mesothelioma in Ontario and BC were calculated using labor force statistics from the 1981 Canadian Census.<br><br>RESULTS: Regional mesothelioma rates varied in both provinces over time; more census divisions in both Ontario and BC registered mesothelioma rates in the highest quintile of incidences during the period 2009 to 2016 than in any prior period examined. Certain occupations such as construction trades workers were more likely to be overrepresented in regions with high mesothelioma rates.<br><br>CONCLUSION: This work explored how studying asbestos exposure and mesothelioma incidence at small-scale geographies could direct cancer surveillance and research to more targeted areas. Findings indicated that regional variations in mesothelioma could signal important differences in past occupational and potentially environmental exposures.}, }
@article {pmid36724751, year = {2023}, author = {Endo, I and Amatya, VJ and Kushitani, K and Nakagiri, T and Aoe, K and Takeshima, Y}, title = {miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {90}, number = {4}, pages = {270-280}, doi = {10.1159/000528670}, pmid = {36724751}, issn = {1423-0291}, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; Cell Movement/genetics ; Cell Line, Tumor ; *Mesothelioma/genetics ; *MicroRNAs/genetics/metabolism ; RNA, Small Interfering/metabolism ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; }, abstract = {INTRODUCTION: Malignant mesothelioma is an aggressive cancer associated with asbestos exposure. Currently, the efficacy of therapeutics is limited in malignant mesothelioma, and developing more effective therapies is the need of the hour. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have attracted attention as therapeutic targets. To explore potential therapeutic targets, we focused on miR-142-3p expression, which was found to be significantly downregulated in mesothelioma cell lines in our previous study.<br><br>METHODS: Mesothelioma cell lines and tissues were validated for expression of miR-142-3p or integrin subunit alpha-V (ITGAV). We transfected mesothelioma cell lines with miR-142-3p mimic and ITGAV siRNA and analyzed their biological functions.<br><br>RESULTS: We found that miR-142-3p was significantly downregulated in mesothelioma tissues. Transfection with miR-142-3p mimic significantly suppressed cell proliferation, migration, and invasion. Bioinformatics analysis of potential targets of miR-142-3p identified ITGAV. Membrane ITGAV expression in mesothelioma cell lines was confirmed using immunocytochemistry. ITGAV was significantly upregulated in mesothelioma tissues. Moreover, transfection of miR-142-3p mimics into mesothelioma cell lines significantly suppressed ITGAV expression, indicating that miR-142-3p targets ITGAV. Next, ITGAV siRNA transfection into mesothelioma cell lines inhibited cell proliferation, migration, and invasion. Further investigation of cell adhesion mechanisms showed that the miR-142-3p/ITGAV axis specifically affects mesothelioma cell adhesion via vitronectin in the extracellular matrix.<br><br>CONCLUSION: This study proposed that the miR-142-3p/ITGAV axis is involved in tumor progression in malignant mesothelioma.}, }
@article {pmid36720634, year = {2023}, author = {Del Monaco, A and Dimitriadis, C and Xie, S and Benke, G and Sim, MR and Walker-Bone, K}, title = {Workers in Australian prebake aluminium smelters: update on risk of mortality and cancer incidence in the Healthwise cohort.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {3}, pages = {160-169}, doi = {10.1136/oemed-2022-108605}, pmid = {36720634}, issn = {1470-7926}, mesh = {Humans ; Male ; Aluminum/adverse effects ; Incidence ; Cohort Studies ; *Occupational Diseases/etiology ; Australia/epidemiology ; *Neoplasms ; *Mesothelioma/etiology ; *Lung Neoplasms ; Cause of Death ; *Mesothelioma, Malignant/complications ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: To investigate mortality and the rates of incident cancer among a cohort of aluminium industry workers.<br><br>METHODS: Among 4507 male employees who worked in either of two Australian prebake smelters for at least 3 months, data linkage was undertaken with the Australian National Death Index and Australian Cancer Database. Standardised Mortality Ratios (SMRs) and Standardised Incidence Rates (SIRs) were estimated for the whole cohort and for: production; maintenance and office workers. SMRs and SIRs were calculated by time since first employment.<br><br>RESULTS: Among production workers, there was an excess risk of mortality from mesothelioma (SMR 2.8, 95%&#x2009;CI 1.3 to 5.2), lung (SMR 1.4, 95%&#x2009;CI 1.0 to 1.8), prostate (SMR 1.9, 95%&#x2009;CI 1.3 to 2.7) and liver cancer (SMR 2.0, 95%&#x2009;CI 1.1 to 3.4) and the SIR was also increased for overall respiratory cancers, specifically lung cancers. An excess risk of death from stomach cancer (SMR 2.9, 95%&#x2009;CI 1.2 to 6.1) and Alzheimer's disease (SMR 3.4, 95%&#x2009;CI 1.1 to 7.9) was seen among maintenance workers. The overall risk of death was similar to that of the Australian general population, as was mortality from cancers overall and non-malignant respiratory disease.<br><br>CONCLUSIONS: No excess risk of death from bladder cancer or non-malignant respiratory disease was found. Excess lung cancer mortality and incidence may be explained by smoking and excess mortality from mesothelioma may be explained by asbestos exposure. An excess risk of mortality from liver and prostate cancer has been shown in production workers and requires further investigation.}, }
@article {pmid36705549, year = {2022}, author = {Di Genova, A and Mangiante, L and Sexton-Oates, A and Voegele, C and Fernandez-Cuesta, L and Alcala, N and Foll, M}, title = {A molecular phenotypic map of malignant pleural mesothelioma.}, journal = {GigaScience}, volume = {12}, number = {}, pages = {}, pmid = {36705549}, issn = {2047-217X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/pathology ; *Lung Neoplasms/genetics/pathology ; *Pleural Neoplasms/genetics/pathology ; Phenotype ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare understudied cancer associated with exposure to asbestos. So far, MPM patients have benefited marginally from the genomics medicine revolution due to the limited size or breadth of existing molecular studies. In the context of the MESOMICS project, we have performed the most comprehensive molecular characterization of MPM to date, with the underlying dataset made of the largest whole-genome sequencing series yet reported, together with transcriptome sequencing and methylation arrays for 120 MPM patients.<br><br>RESULTS: We first provide comprehensive quality controls for all samples, of both raw and processed data. Due to the difficulty in collecting specimens from such rare tumors, a part of the cohort does not include matched normal material. We provide a detailed analysis of data processing of these tumor-only samples, showing that all somatic alteration calls match very stringent criteria of precision and recall. Finally, integrating our data with previously published multiomic MPM datasets (n = 374 in total), we provide an extensive molecular phenotype map of MPM based on the multitask theory. The generated map can be interactively explored and interrogated on the UCSC TumorMap portal (https://tumormap.ucsc.edu/?p=RCG_MESOMICS/MPM_Archetypes).<br><br>CONCLUSIONS: This new high-quality MPM multiomics dataset, together with the state-of-art bioinformatics and interactive visualization tools we provide, will support the development of precision medicine in MPM that is particularly challenging to implement in rare cancers due to limited molecular studies.}, }
@article {pmid36687288, year = {2023}, author = {Romano, M and Pinto, P and Afonso, R and Fontes, J and Ferreira, M}, title = {Pleural Mesothelioma: A Rapid Evolution of an Indolent Disease.}, journal = {Cureus}, volume = {15}, number = {1}, pages = {e33965}, pmid = {36687288}, issn = {2168-8184}, abstract = {Mesothelioma is a rare and insidious neoplasm and is characterized by its highly malignant and aggressive nature. The most common etiology is asbestos exposure, but there are some reports without known asbestos exposure and other factors leading to malignant pleural mesothelioma (MPM). Here, we present the case of a 58-year-old woman with pleuritic chest pain, dyspnea, and fever on presentation to the emergency department (ED), which caused several admissions to the ED in 20 days. The patient was then admitted to the internal medicine department with a diagnosis of community-acquired pneumonia with parapneumonic effusion. During hospitalization, a positron emission tomography (PET) scan, thoracic computed tomography (CT), and pleural biopsy were performed and a final diagnosis of malignant epithelioid pleural mesothelioma was made. Six weeks after the onset of symptoms, the patient presented with an exponential disease progression, dying two months after the diagnosis, despite the initiation of chemotherapy. MPM remains a diagnostic and therapeutic challenge with a very poor prognosis. However, studies show that mesothelioma patients who undergo treatment live at least twice as long as patients who do not receive treatment. This case report is particularly significant because, although it was epithelioid mesothelioma, multiple solid masses were noted on CT and the patient exhibited rapid disease progression, dying a few weeks after starting treatment.}, }
@article {pmid36673690, year = {2023}, author = {Magnani, C and Mensi, C and Binazzi, A and Marsili, D and Grosso, F and Ramos-Bonilla, JP and Ferrante, D and Migliore, E and Mirabelli, D and Terracini, B and Consonni, D and Degiovanni, D and Lia, M and Cely-García, MF and Giraldo, M and Lysaniuk, B and Comba, P and Marinaccio, A}, title = {The Italian Experience in the Development of Mesothelioma Registries: A Pathway for Other Countries to Address the Negative Legacy of Asbestos.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {2}, pages = {}, pmid = {36673690}, issn = {1660-4601}, mesh = {Female ; Humans ; *Lung Neoplasms/epidemiology ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Carcinogens, Environmental ; Registries ; Italy/epidemiology ; }, abstract = {Asbestos (all forms, including chrysotile, crocidolite, amosite, tremolite, actinolite, and anthophyllite) is carcinogenic to humans and causally associated with mesothelioma and cancer of the lung, larynx, and ovary. It is one of the carcinogens most diffuse in the world, in workplaces, but also in the environment and is responsible for a very high global cancer burden. A large number of countries, mostly with high-income economies, has banned the use of asbestos which, however, is still widespread in low- and middle-income countries. It remains, thus, one of the most common occupational and environmental carcinogens worldwide. Italy issued an asbestos ban in 1992, following the dramatic observation of a large increase in mortality from mesothelioma and other asbestos-related diseases in exposed workers and also in subjects with non-occupational exposure. A mesothelioma registry was also organized and still monitors the occurrence of mesothelioma cases, conducting a case-by-case evaluation of asbestos exposure. In this report, we describe two Italian communities, Casale Monferrato and Broni, that faced an epidemic of mesothelioma resulting from the production of asbestos cement and the diffuse environmental exposure; we present the activity and results of the Italian mesothelioma registry (ReNaM), describe the risk-communication activities at the local and national level with a focus on international cooperation and also describe the interaction between mesothelioma registration and medical services specialized in mesothelioma diagnosis and treatment in an area at high risk of mesothelioma. Finally, we assess the potential application of the solutions and methods already developed in Italy in a city in Colombia with high mesothelioma incidence associated with the production of asbestos-cement materials and the presence of diffuse environmental asbestos pollution.}, }
@article {pmid36653798, year = {2023}, author = {Moline, J and Patel, K and Frank, AL}, title = {Exposure to cosmetic talc and mesothelioma.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {18}, number = {1}, pages = {1}, pmid = {36653798}, issn = {1745-6673}, abstract = {AIM: Mesothelioma is associated with asbestos exposure. In this case series, we present 166 cases of individuals who had substantial asbestos exposure to cosmetic talc products as well as some who had potential or documented additional exposures to other asbestos-containing products and who subsequently developed mesothelioma.<br><br>METHODS: Data were gathered for all subjects referred to an occupational and environmental medicine specialist as part of medicolegal review. Years of total cosmetic talcum powder usage was noted as well as the latency from the onset of talcum powder use to the mesothelioma diagnosis. Alternate asbestos exposure in addition to the exposure from cosmetic talc was categorized as none, possible, likely, and definite.<br><br>RESULTS: In 122 cases, the only known exposure to asbestos was from cosmetic talc. For 44 cases, potential or documented alternate exposures in addition to the cosmetic talc were described.<br><br>CONCLUSION: Cumulative exposure to asbestos leads to mesothelioma; for individuals with mixed exposures to asbestos, all exposures should be considered. Use of cosmetic talc is often overlooked as a source of asbestos exposure. All individuals with mesothelioma should have a comprehensive history of asbestos exposure, including cosmetic talc exposure.}, }
@article {pmid36646495, year = {2022}, author = {Piao, ZH and Zhou, XC and Zhang, X}, title = {[Updates in the pathological diagnosis of Pleural Malignant Mesothelioma in the WHO classification of thoracic tumors (5(th) edition)].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {40}, number = {12}, pages = {956-960}, doi = {10.3760/cma.j.cn121094-20211105-00546}, pmid = {36646495}, issn = {1001-9391}, support = {2022-F30//China-Japan Project for the Improvement of Diagnosis of Asbestos-related Cancer/ ; //Project of NiNGBO leading Medical &amp; Health Discipline/ ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis ; *Mesothelioma/diagnosis ; Prognosis ; World Health Organization ; *Lung Neoplasms/diagnosis/pathology ; }, abstract = {The WHO Classification of Thoracic Tumors (5(th) edition) mainly has the following changes in the chapter of pleural malignant mesothelioma. (1) The concept of mesothelioma in situ and its diagnostic method have been established for the first time; (2) The tumour grading of pleural malignant mesothelioma was added, it was divided into low grade and high grade according to the cellular atypia, mitotic activity and presence of necrosis. (3) The morphological features of pleural malignant mesothelioma was classified into architectural pattern, cellular and stromal features, the correlation between histological features and prognosis was refined, and some of the controversial cellular types have been reclassified. In this review, we introduced the changes of related pathologic diagnosis, in the WHO Classification of Thoracic Tumors (5(th) edition) and discussed its clinical significance.}, }
@article {pmid36636687, year = {2022}, author = {Neff, D and Padberg Sgier, BC and Dietze, H and Müller, J and Früh, M}, title = {Unusually Aggressive Presentation of Malignant Peritoneal Mesothelioma: Two Case Reports.}, journal = {Case reports in oncology}, volume = {15}, number = {3}, pages = {1001-1008}, pmid = {36636687}, issn = {1662-6575}, abstract = {Malignant peritoneal mesothelioma is a rare disease. Patients mainly present with abdominal distension, pain, nausea, and weight loss with or without an exposure history of asbestos. Diagnosis may be difficult from a clinical and histopathologic perspective. Treatment options are surgery in early stages, radiotherapy and/or intraperitoneal or systemic therapy. Prognosis depends on TNM stage and histologic subtype with epithelioid subtype being the most favorable one but in general remains poor. We present a 59-year-old male (patient 1) and a 79-year-old female (patient 2) with progressive dyspnea. PET-CT of patient 1 revealed metastatic spread in the pleura and extensive peritoneal carcinomatosis. PET-CT of patient 2 displayed FDG-avid lymph nodes on both sides of the diaphragm, polyserositis, and FDG uptake along the peritoneum. Both patients were eventually diagnosed with malignant peritoneal mesothelioma. Patient 1 was treated with carboplatin and gemcitabine, and patient 2 received no systemic therapy. Even though the epithelioid subtype was found, both patients succumbed due to rapid tumor progression in a matter of a few weeks only. Presentation with polyserositis even in the absence of relevant asbestos exposure may represent malignant peritoneal mesothelioma if ascites is present, and rapid invasive diagnostic (excision biopsy) should be performed. These two unusual cases emphasize that even in epithelioid subtype, clinicians ought to be aware of possible rapid clinical deterioration, and timely diagnosis with initiation of therapy is crucial. Further research is necessary to better understand tumor biology, establish predictive markers, and develop new treatment options.}, }
@article {pmid36636360, year = {2022}, author = {Dusseault, SK and Okobi, OE and Thakral, N and Sankar, V and Gunawardene, I and Dawkins, B and Abu, Y and Davis, B}, title = {Primary Peritoneal Mesothelioma: Diagnostic Challenges of This Lethal Imposter.}, journal = {Case reports in gastroenterology}, volume = {16}, number = {3}, pages = {588-594}, pmid = {36636360}, issn = {1662-0631}, abstract = {Primary Peritoneal Mesothelioma is a rapidly aggressive and rare neoplasm that arises from the lining of mesothelial cells of the peritoneum and spreads extensively within the confines of the abdominal cavity. The pathogenesis of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Characteristically, asbestos exposure has a strong relationship with mesothelioma of the pleura, but the peritoneal cavity is the second most commonly affected site. Additionally, in contrast to pleural mesothelioma, which has a male predominance (male-female ratio of between four and five to one), women comprise approximately one-half of all cases of malignant peritoneal mesothelioma. A thorough history of occupational/paraoccupational exposure along with histopathology is the key to timely diagnosis and treatment.}, }
@article {pmid36635096, year = {2023}, author = {Kurth, L and Mazurek, JM and Blackley, DJ}, title = {Malignant mesothelioma among US Medicare beneficiaries: incidence, prevalence and therapy, 2016-2019.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {2}, pages = {86-92}, pmid = {36635096}, issn = {1470-7926}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Humans ; Aged ; United States/epidemiology ; *Medicare ; *Mesothelioma, Malignant ; Prevalence ; Incidence ; Fee-for-Service Plans ; }, abstract = {OBJECTIVES: Mesothelioma is a rare, aggressive cancer caused by exposure to asbestos fibres. Mesothelioma patients who receive trimodal therapy (chemotherapy, surgical resection and radiation) survive longer than those who receive two or fewer therapy modalities. This study analyses the 2016-2019 Medicare claims data to estimate the burden of malignant mesothelioma and describe therapy patterns (when available) among continuously enrolled fee-for-service (FFS; Medicare parts A and B) beneficiaries.<br><br>METHODS: We analysed claims and enrolment information from 42 529 117 FFS Medicare beneficiaries using three mesothelioma case definitions (broad, intermediate and narrow) with varying levels of diagnostic requirements. Results are presented as ranges of values for the three definitions.<br><br>RESULTS: Among FFS beneficiaries, 8213-19&#x2009;036 beneficiaries with mesothelioma were identified depending on the case definition. The annual prevalence per 100&#x2009;000 beneficiaries ranged from 8.8 in 2016 (narrow) to 31.3 in 2019 (broad) and annual incidence per 100&#x2009;000 beneficiaries ranged from 4.5 in 2019 (narrow) to 12.6 in 2017 (broad). Depending on the mesothelioma case definition, 41.8%-81.5% had available therapy claim information indicating that 7.6%-11.3% received chemotherapy alone, 1.3%-1.5% received radiation alone, and 14.3%-27.0% underwent surgery only, with 4.6%-10.5% receiving all three therapy modalities.<br><br>CONCLUSIONS: Mesothelioma was a prevalent disease among FFS Medicare beneficiaries during 2016-2019, and a limited proportion of beneficiaries received all three therapy modalities. Medicare data build on findings from cancer registry data to enhance our understanding of the mesothelioma burden and therapy patterns.}, }
@article {pmid36630203, year = {2023}, author = {Caceres, JD and Venkata, AN}, title = {Asbestos-associated pulmonary disease.}, journal = {Current opinion in pulmonary medicine}, volume = {29}, number = {2}, pages = {76-82}, pmid = {36630203}, issn = {1531-6971}, mesh = {Humans ; *Mesothelioma/etiology/pathology ; *Asbestos/toxicity ; *Pleural Diseases/diagnostic imaging/etiology ; *Lung Diseases/complications ; *Asbestosis/complications/diagnostic imaging/pathology ; *Pleural Effusion/etiology ; *Lung Neoplasms/chemically induced ; *Mesothelioma, Malignant/complications ; }, abstract = {PURPOSE OF REVIEW: Exposure to asbestos can cause both benign and malignant, pulmonary and pleural diseases. In the current era of low asbestos exposure, it is critical to be aware of complications from asbestos exposure; as they often arise after decades of exposure, asbestos-related pulmonary complications include asbestosis, pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions and malignant pleural mesothelioma.<br><br>RECENT FINDINGS: Multiple recent studies are featured in this review, including a study evaluating imaging characteristics of asbestos with other fibrotic lung diseases, a study that quantified pleural plaques on computed tomography imaging and its impact on pulmonary function, a study that examined the risk of lung cancer with pleural plaques among two large cohorts and a review of nonasbestos causes of malignant mesothelioma.<br><br>SUMMARY: Asbestos-related pulmonary and pleural diseases continue to cause significant morbidity and mortality. This review summarizes the current advances in this field and highlights areas that need additional research.}, }
@article {pmid36622824, year = {2022}, author = {Moscadelli, A and Martini, A and Angelini, A and Baldassarre, A and Lorini, C and Bonaccorsi, G and Cacciarini, V and Rosselli, A and Chellini, E}, title = {[Mortality study in a cohort of entertainment workers].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {44}, number = {3}, pages = {360-359}, pmid = {36622824}, issn = {1592-7830}, mesh = {Humans ; Male ; Female ; Cohort Studies ; *Mesothelioma ; *Occupational Diseases/etiology ; Cause of Death ; *Asbestos ; *Occupational Exposure/adverse effects ; }, abstract = {Introduction. Malignant mesotheliomas have been observed in entertainment workers in the last decades. They have been evaluated as occupationally exposed to asbestos contained in tools used for fireproof and sound-absorbing purposes. Aim of the study. To evaluate the mortality of workers engaged in a Florentine theatre where a large quantity of asbestos was found in the '80s, put in place 20 years earlier. Methods. It is a cohort study on entertainment workers with follow-up period ranged from 1-1-1970 till 31-12-2018. Standardized Mortality Ratios (SMRs) and their 95% Confidence Intervals (95% IC) were calculated by gender and job ("manual workers" and "all other jobs"), using age and sex specific mortality rates of Tuscan population. Results. The cohort includes 826 workers (389 manual workers and 437 engaged in other jobs) engaged by the Florentine theatre between 01/01/1937 and 31/12/1990. Excesses of mortality for all causes are observed in manual workers, either males (301 cases; SMR 304,0; 95% IC 271,5-340,3) or females (86 cases; SMR 429,8; 95% IC 348,0-531,0). The group of the other workers presents deficits of mortality by all causes, cancers and cardiovascular diseases in both genders. One death for pleural cancer is observed in a manual worker. Discussion. The results are in line with previous observations in similar occupations. In the examined Florentine theatre the asbestos exposures were important only for the manual workers who worked in the technical rooms characterized by the presence of friable asbestos sprinkled and in a bad state of maintenance.}, }
@article {pmid36612385, year = {2022}, author = {Mutetwa, B and Moyo, D and Brouwer, D}, title = {Prediction of Asbestos-Related Diseases (ARDs) and Chrysotile Asbestos Exposure Concentrations in Asbestos-Cement (AC) Manufacturing Factories in Zimbabwe.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612385}, issn = {1660-4601}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; *Asbestosis/epidemiology ; Zimbabwe/epidemiology ; *Asbestos ; *Mesothelioma/epidemiology ; *Lung Neoplasms/epidemiology ; *Occupational Exposure ; *Mesothelioma, Malignant ; }, abstract = {The use of historical asbestos measurement data in occupational exposure assessment is essential as it allows more quantitative analysis of possible exposure response relationships in asbestos-related disease (ARD) occurrence. The aim of this study was to predict possible ARDs, namely lung cancer, mesothelioma, gastrointestinal cancer, and asbestosis, in two chrysotile asbestos cement (AC) manufacturing factories. Prediction of ARDs was done using a specific designed job-exposure matrix for airborne chrysotile asbestos fibre concentrations obtained from the Harare and Bulawayo AC factories and through application of OSHA's linear dose effect model in which ARDs were estimated through extrapolation at 1, 10, 20, and 25 years of exposure. The results show that more cancer and asbestosis cases are likely to be experienced among those exposed before 2008 as exposure levels and subsequently cumulative exposure were generally much higher than those experienced after 2008. After a possible exposure period of 25 years, overall cancer cases predicted in the Harare factory were 325 cases per 100,000 workers, while for the Bulawayo factory, 347 cancer cases per 100,000 workers exposed may be experienced. Possible high numbers of ARDs are likely to be associated with specific tasks/job titles, e.g., saw cutting, kollergang, fettling table, ground hard waste, and possibly pipe-making operations, as cumulative exposures, though lower than reported in other studies, may present higher risk of health impairment. The study gives insights into possible ARDs, namely lung cancer, mesothelioma, gastrointestinal cancer, and asbestosis, that may be anticipated at various cumulative exposures over 1, 10, 20, and 25 years of exposure in AC manufacturing factories in Zimbabwe. Additionally, results from the study can also form a basis for more in-depth assessment of asbestos cancer morbidity studies in the AC manufacturing industries.}, }
@article {pmid36612122, year = {2022}, author = {Casalone, E and Birolo, G and Pardini, B and Allione, A and Russo, A and Catalano, C and Mencoboni, M and Ferrante, D and Magnani, C and Sculco, M and Dianzani, I and Grosso, F and Mirabelli, D and Filiberti, RA and Rena, O and Sacerdote, C and Rodriguez-Barranco, M and Smith-Byrne, K and Panico, S and Agnoli, C and Johnson, T and Kaaks, R and Tumino, R and Huerta, JM and Riboli, E and Heath, AK and Trobajo-Sanmartín, C and Schulze, MB and Saieva, C and Amiano, P and Agudo, A and Weiderpass, E and Vineis, P and Matullo, G}, title = {Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.}, journal = {Cancers}, volume = {15}, number = {1}, pages = {}, pmid = {36612122}, issn = {2072-6694}, support = {001/WHO_/World Health Organization/International ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.}, }
@article {pmid36601180, year = {2022}, author = {Mankidy, B and Sparkman, J and Boddu, S and Huang, Q and Sharma, M}, title = {Simultaneous Use of Endobronchial and Endoscopic Ultrasound Guidance as Primary Tools in the Diagnosis of Malignant Pleural Mesothelioma.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32110}, pmid = {36601180}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is related to exposure to asbestos. It is insidious in nature and is generally diagnosed at an advanced stage. MPM is aggressive and portends a poor prognosis. Definitive diagnosis is usually established by obtaining pathological samples of the pleura by medical or surgical thoracoscopy. However, these procedures are invasive and carry a risk of seeding of biopsy sites with tumors. We herein report an infrequently encountered case of simultaneous use of endobronchial ultrasound and endoscopic ultrasound-guided biopsy of malignant pleural mesothelioma in a 48-year-old female patient.}, }
@article {pmid38299094, year = {2023}, author = {Alratrout, H and Boumarah, DN and Alghusnah, ES and Alabbad, A and Alsaffar, AH and Alsafwani, NS and Foula, MS}, title = {Synchronous Malignant Peritoneal Mesothelioma and Sigmoid Adenocarcinoma: a Challenging Clinical Entity.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {77}, number = {5}, pages = {400-404}, pmid = {38299094}, issn = {1986-5961}, mesh = {Humans ; Female ; Aged ; *Mesothelioma/diagnosis/pathology/surgery ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/diagnosis ; *Colonic Neoplasms/diagnosis ; *Adenocarcinoma/diagnosis/surgery ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) represents a rare clinical entity. The synchronous existence of MPM with other malignancies as colonic adenocarcinoma have been rarely reported. Its diagnosis and management are challenging given its complexity and rarity.<br><br>OBJECTIVE: Herein, we report a case of epithelioid subtype of MPM occurring synchronously with sigmoid colonic adenocarcinoma, along with review of the literature.<br><br>CASE PRESENTATION: An elderly female patient was referred as case of rectosigmoid mass. She reported history of abdominal pain, per-rectal bleeding, anorexia, and significant weight loss. Her computed-tomography scan of the abdomen revealed a fistulizing sigmoid mass and multiple enlarged lymphnodes with omental nodulation. The colonoscopy revealed a large fungating mass and the endoscopic biopsies were reported as colonic adenocarcinoma. The patient was scheduled laparoscopic low anterior resection. However, the diagnostic laparoscopy revealed several nodules disseminated all over the peritoneum, suggestive of peritoneal mesothelioma. Therefore, the decision was changed to create transverse colostomy after examination obtaining multiple biopsies from the omental and peritoneal nodules. The histopathological revealed MPM and the final diagnosis was sigmoid adenocarcinoma with synchronous MPM. The patient was started on palliative chemotherapy (capecitabine) without active management of MPM because of her general condition. She was followed up with a good clinical course.<br><br>CONCLUSION: MPM is an overlooked entity with vague clinical presentation. Synchronous MPM with colorectal cancer is rare with only few published case reports. Its diagnosis is challenging, and its management should be tailored according to the patient. This case is the first reported case in Saudi Arabia and the Middle East.}, }
@article {pmid36556334, year = {2022}, author = {Caraballo-Arias, Y and Zunarelli, C and Caffaro, P and Roccuzzo, F and Nocilla, MR and Imperiale, MC and Romano, C and Boffetta, P and Violante, FS}, title = {Quantitative Assessment of Asbestos Fibers in Normal and Pathological Peritoneal Tissue-A Scoping Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {36556334}, issn = {2075-1729}, abstract = {Peritoneal tissue is the second most affected site by malignant mesothelioma linked to asbestos exposure. This scoping review aims to summarize the findings of the studies in which asbestos fibers in the peritoneum were quantified by electron microscopy, occasionally associated with spectroscopy, both in neoplastic and non-neoplastic tissue. The 9 studies selected comprised 62 cases, out of whom 100 samples were analyzed. Asbestos fibers were detected in 58 samples (58%). In addition, 28 cases had diagnosis of peritoneal mesothelioma. For 32 cases, a lung tumor sample was available: 28/32 samples analyzed presented asbestos fibers; 18/32 reported amphiboles with a range from not detected to 14.2 million fibers per gram of dry tissue (mfgdt); 18/32 reported chrysotile, with a range of 0 to 90 mfgdt. The studies were heterogeneous for type of samples, analytical technology, and circumstances of exposure to asbestos. To evaluate asbestos fibers in the peritoneum and to better understand the association between asbestos exposure and malignant peritoneal mesothelioma, it is desirable that the search for asbestos fibers becomes a routine process every time peritoneal tissue is accessible.}, }
@article {pmid36554530, year = {2022}, author = {Gardner, M and Cross, M and Reed, S and Davidson, M and Hughes, R and Oosthuizen, J}, title = {Pathogenic Potential of Respirable Spodumene Cleavage Fragments following Application of Regulatory Counting Criteria for Asbestiform Fibres.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {24}, pages = {}, pmid = {36554530}, issn = {1660-4601}, mesh = {Humans ; Minerals ; *Mesothelioma ; *Mesothelioma, Malignant ; *Lung Neoplasms ; *Occupational Exposure ; }, abstract = {Health risks from exposure to lithium-bearing spodumene cleavage fragments are unknown. While asbestiform fibres can lead to fibrosis, mesothelioma and lung cancer, controversy remains whether non-asbestiform cleavage fragments, having equivalent dimensions, elicit similar pathologic responses. The mineralogy of respirable particles from two alpha (α)-spodumene concentrate grades (chemical and technical) were characterised using semi-quantitative X-ray diffraction (XRD). Particles were measured using scanning electron microscopy (SEM) and the dimensions (length [L], diameter [D], aspect ratio [AR]) applied to regulatory counting criteria for asbestiform fibres. Application of the current World Health Organization (WHO) and National Occupational Health and Safety Commission (NOHSC) counting criteria, L ˃ 5 µm, D ˂ 3 µm, AR ˃ 3:1, to 10 SEM images of each grade identified 47 countable particles in the chemical and 37 in the technical concentrate test samples. Of these particles, 17 and 16 in the chemical and technical test samples, respectively, satisfied the more rigorous, previously used Mines Safety and Inspection Regulations 1995 (Western Australia [WA]) criteria, L ˃ 5 µm and D ≤ 1 µm. The majority of the countable particles were consistent with α-spodumene cleavage fragments. These results suggest elongated α-spodumene particles may pose a health risk. It is recommended the precautionary principle be applied to respirable α-spodumene particles and the identification and control of dust hazards in spodumene extraction, handling and processing industries be implemented.}, }
@article {pmid36553016, year = {2022}, author = {Moro, J and Sobrero, S and Cartia, CF and Ceraolo, S and Rapanà, R and Vaisitti, F and Ganio, S and Mellone, F and Rudella, S and Scopis, F and La Paglia, D and Cacciatore, CC and Ruffini, E and Leo, F}, title = {Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {36553016}, issn = {2075-4418}, abstract = {Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease.}, }
@article {pmid36552335, year = {2022}, author = {Rihs, HP and Casjens, S and Raiko, I and Kollmeier, J and Lehnert, M and Nöfer, K and May-Taube, K and Kaiser, N and Taeger, D and Behrens, T and Brüning, T and Johnen, G and , }, title = {Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany.}, journal = {Biology}, volume = {11}, number = {12}, pages = {}, pmid = {36552335}, issn = {2079-7737}, abstract = {Malignant mesothelioma (MM) is a severe disease mostly caused by asbestos exposure. Today, one of the best available biomarkers is the soluble mesothelin-related protein (SMRP), also known as mesothelin. Recent studies have shown that mesothelin levels are influenced by individual genetic variability. This study aimed to investigate the influence of three mesothelin (MSLN) gene variants (SNPs) in the 5′-untranslated promoter region (5′-UTR), MSLN rs2235503 C > A, rs3764246 A > G, rs3764247 A > C, and one (rs1057147 G > A) in the 3′-untranslated region (3′-UTR) of the MSLN gene on plasma concentrations of mesothelin in 410 asbestos-exposed males without cancer and 43 males with prediagnostic MM (i.e., with MM diagnosed later on) from the prospective MoMar study, as well as 59 males with manifest MM from Germany. The mesothelin concentration differed significantly between the different groups (p < 0.0001), but not between the prediagnostic and manifest MM groups (p = 0.502). Five to eight mutations of the four SNP variants studied were associated with increased mesothelin concentrations (p = 0.001). The highest mesothelin concentrations were observed for homozygous variants of the three promotor SNPs in the 5′-UTR (p < 0.001), and the highest odds ratio for an elevated mesothelin concentration was observed for MSLN rs2235503 C > A. The four studied SNPs had a clear influence on the mesothelin concentration in plasma. Hence, the analysis of these SNPs may help to elucidate the diagnostic background of patients displaying increased mesothelin levels and might help to reduce false-positive results when using mesothelin for MM screening in high-risk groups.}, }
@article {pmid36543384, year = {2022}, author = {Chimed-Ochir, O and Rath, EM and Kubo, T and Yumiya, Y and Lin, RT and Furuya, S and Brislane, K and Klebe, S and Nowak, AK and Kang, SK and Takahashi, K}, title = {Must countries shoulder the burden of mesothelioma to ban asbestos? A global assessment.}, journal = {BMJ global health}, volume = {7}, number = {12}, pages = {}, pmid = {36543384}, issn = {2059-7908}, mesh = {Humans ; Shoulder ; *Mesothelioma/epidemiology/etiology ; *Asbestos/adverse effects ; Policy ; Global Burden of Disease ; }, abstract = {INTRODUCTION: Mesothelioma is a key asbestos-related disease (ARD) but can be difficult to diagnose. Countries presumably ban asbestos to reduce future ARD burdens, but it is unknown if countries ban asbestos as a consequence of ARD burdens. We assessed if and to what extent mesothelioma burden has an impact on a country banning asbestos and obtaining targets for preventative strategies.<br><br>METHODS: We analysed the status of asbestos ban and mesothelioma burden during 1990-2019 in 198 countries. We assessed mesothelioma burden by age-adjusted mortality rates (MRs) estimated by the Global Burden of Disease Study (GBD) and mesothelioma identification by the WHO mortality database. For GBD-estimated mesothelioma MR, the pre-ban period in the asbestos-banned countries was compared with the 1990-2019 period in the not-banned countries. For mesothelioma identification, the 1990-2019 period was applied to both banned and not-banned countries.<br><br>RESULTS: The association of mesothelioma MR with ban status increased as the ban year approached. Logistic regression analyses showed that the odds of a country banning asbestos increased 14.1-fold (95% CI 5.3 to 37.9) for mesothelioma identification combined with a 26% (12% to 42%) increase per unit increase of mesothelioma MR (one death per million per year) during the period 1-5&#x2009;year before ban (model p<0.0001).<br><br>CONCLUSION: Mesothelioma burden had an impact on, and together with its identification, explained the banning of asbestos in many countries. Asbestos-banned countries likely learnt lessons from their historical policies of using asbestos because mesothelioma burden and identification follow historical asbestos use. Prevention targets for ARD elimination should combine asbestos ban with mesothelioma identification.}, }
@article {pmid36541514, year = {2023}, author = {Luo, Y and Akatsuka, S and Motooka, Y and Kong, Y and Zheng, H and Mashimo, T and Imaoka, T and Toyokuni, S}, title = {BRCA1 haploinsufficiency impairs iron metabolism to promote chrysotile-induced mesothelioma via ferroptosis resistance.}, journal = {Cancer science}, volume = {114}, number = {4}, pages = {1423-1436}, pmid = {36541514}, issn = {1349-7006}, support = {JP16H06276 [AdAMS]//Japan Society for the Promotion of Science/ ; JP21H03601//Japan Society for the Promotion of Science/ ; JP19H05462//Japan Society for the Promotion of Science/ ; JP20H05502//Japan Society for the Promotion of Science/ ; JP16H06276//Japan Society for the Promotion of Science/ ; JPMJCR19H4//Core Research for Evolutional Science and Technology/ ; SPRING JPMJSP2125//Japan Science and Technology Agency/ ; }, mesh = {Animals ; Female ; Male ; Rats ; *Asbestos/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; BRCA1 Protein/genetics ; Carcinogenesis/genetics ; Comparative Genomic Hybridization ; DNA ; Ferric Compounds/metabolism ; *Ferroptosis/genetics ; Haploinsufficiency ; Iron/metabolism ; *Lung Neoplasms/chemically induced/genetics ; *Mesothelioma, Malignant/chemically induced/genetics ; }, abstract = {Malignant mesothelioma (MM) is still a social burden associated with asbestos exposure. Local iron accumulation thereby represents the major pathogenesis, followed by oxidative DNA strand breaks and genomic alterations in the mesothelium. BRCA1 is a critical component of homologous recombination repair directed to DNA double-stranded breaks, whereas BRCA1 germline mutation is an established risk for breast/ovarian cancer, its role in MM development remains to be elucidated. Murine Brca1 mutant models so far have not reproduced human phenotypes. However, a rat Brca1 mutant model (Mut; L63X/+) recently reproduced them at least partially. Here we describe the differential induction of MM in Brca1 mutant rats by intraperitoneal injection of chrysotile or crocidolite. Only Mut males injected with chrysotile revealed a promotional effect on mesothelial carcinogenesis in comparison with wild-type and/or females, with all the MMs Brca1 haploinsufficient. Array-based comparative genomic hybridization of MMs disclosed a greater extent of chromosomal deletions in Brca1 mutants, including Cdkn2a/2b accompanied by Tfr2 amplification, in comparison with wild-type tumors. Mutant MMs indicated iron metabolism dysregulation, such as an increase in catalytic Fe(II) and Ki67-index as well as a decrease in Fe(III) and ferritin expression. Simultaneously, mutant MMs revealed ferroptosis resistance by upregulation of Slc7A11 and Gpx4. At an early carcinogenic stage of 4 weeks, induced Brca1 expression in mesothelial cells was significantly suppressed in chrysotile/Mut in comparison with crocidolite/Mut, whereas significant preference to iron with a decrease in Fe(III) has been already established. In conclusion, chrysotile exposure can be a higher risk for MM in BRCA1 mutant males, considering the rat results.}, }
@article {pmid36525994, year = {2023}, author = {Gazzano, E and Petriglieri, JR and Aldieri, E and Fubini, B and Laporte-Magoni, C and Pavan, C and Tomatis, M and Turci, F}, title = {Cytotoxicity of fibrous antigorite from New Caledonia.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115046}, doi = {10.1016/j.envres.2022.115046}, pmid = {36525994}, issn = {1096-0953}, mesh = {Humans ; Mice ; Animals ; *Asbestos, Serpentine/toxicity ; New Caledonia ; *Asbestos/toxicity ; Minerals/toxicity ; Silicates ; }, abstract = {Exposure to asbestos and asbestos-like minerals has been related to the development of severe lung diseases, including cancer and malignant mesothelioma (MM). A high incidence of non-occupational MM was observed in New Caledonia (France) in people living in proximity of serpentinite outcrops, containing chrysotile and fibrous antigorite. Antigorite is a magnesium silicate, which shares with chrysotile asbestos the chemical formula. To achieve information on antigorite toxicity, we investigated the physico-minero-chemical features relevant for toxicity and cellular effects elicited on murine macrophages (MH-S) and alveolar epithelial cells (A549) of three fibrous antigorites (f-Atg) collected in a Caledonian nickel lateritic ore and subjected to supergene alteration. Field Atg were milled to obtain samples suitable for toxicological studies with a similar particle size distribution. UICC chrysotile (Ctl) and a non-fibrous antigorite (nf-Atg) were used as reference minerals. A high variability in toxicity was observed depending on shape, chemical alteration, and surface reactivity. The antigorites shared with Ctl a similar surface area (16.3, 12.1, 20.3, 13.4, and 15.6 m[2]/g for f-Atg1, 2, 3, nf-Atg, and Ctl). f-Atg showed different level of pedogenetic weathering (Ni depletion f-Atg1 ≪ f-Atg2 and 3) and contained about 50% of elongated mineral particles, some of which exhibited high aspect ratios (AR > 10 μm, 20%, 26%, 31% for f-Atg1, 2, and 3, respectively). The minerals differed in bio-accessible iron at pH 4.5 (f-Atg1 ≪ f-Atg3, < f-Atg2, nf-Atg < Ctl), and surface reactivity (ROS release in solution, f-Atg1 ≪ f-Atg2, 3, nf-Atg, and Ctl). f-Atg2 and f-Atg3 induced oxidative stress and pro-inflammatory responses, while the less altered, poorly reactive sample (f-Atg1) induced negligible effects, as well nf-Atg. The slow dissolution kinetics observed in simulated body fluids may signal a high biopersistence. Overall, our work revealed a significative cellular toxicity of f-Atg that correlates with fibrous habit and surface reactivity.}, }
@article {pmid36519024, year = {2022}, author = {Klotz, LV and Hoffmann, H and Shah, R and Eichhorn, F and Gruenewald, C and Bulut, EL and Griffo, R and Muley, T and Christopoulos, P and Baum, P and Huber, P and Safi, S and Kriegsmann, M and Thomas, M and Bischoff, H and Winter, H and Eichhorn, ME}, title = {Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach.}, journal = {Translational lung cancer research}, volume = {11}, number = {11}, pages = {2230-2242}, pmid = {36519024}, issn = {2218-6751}, abstract = {BACKGROUND: The exact role and type of surgery for malignant pleural mesothelioma (MPM) remains controversial. This study aimed at analyzing a 20-year single center perioperative experience in MPM surgery at our high-volume thoracic surgery center and comparing the overall survival after trimodal extrapleural pneumonectomy (EPP) and extended pleurectomy and decortication combined with hyperthermic intrathoracic chemoperfusion (EPD/HITOC) and adjuvant chemotherapy with that after chemotherapy (CTx) alone.<br><br>METHODS: Patients with epithelioid MPM treated with neoadjuvant chemotherapy, EPP and adjuvant radiotherapy within a trimodal concept or EPD/HITOC in combination with adjuvant chemotherapy between 2001 and 2018 were included in this retrospective analysis. Surgical cohorts were compared to patients treated with standard chemotherapy.<br><br>RESULTS: Overall, 182 patients (69 EPP, 57 EPD/HITOC, 56 CTx) were analyzed. Due to occupational exposure to asbestos for most of the patients, 154 patients (84.6%) were male. The patients in the surgical cohorts were significantly younger than those in the CTx cohort. There was no significant difference between the proportion of patient age and side. The median overall survival of the EPD/HITOC cohort with 38.1 months was significantly longer than that of the EPP and CTx cohorts (24.0 and 15.8 months). Better survival was significantly associated with an ECOG 0 performance status, age below 70 years, and negative lymph node status. In the multivariate analysis, EPD/HITOC was significantly associated with improved overall survival. Perioperative morbidity was lower in the EPD/HITOC group than in the EPP cohort.<br><br>CONCLUSIONS: EPD/HITOC is feasible and safe for localized epithelioid pleural mesothelioma. Changing the surgical approach to a less radical lung-sparing technique may improve overall survival compared to trimodal EPP.}, }
@article {pmid36506969, year = {2022}, author = {Guglielmucci, F and Bonafede, M and Azzolina, D and Marinaccio, A and Franzoi, IG and Migliore, E and Mensi, C and Chellini, E and Romeo, E and Grosso, F and Granieri, A}, title = {Preliminary validation of a brief PROM assessing psychological distress in patients with malignant mesothelioma: The mesothelioma psychological distress tool-Patients.}, journal = {Frontiers in psychology}, volume = {13}, number = {}, pages = {974982}, pmid = {36506969}, issn = {1664-1078}, abstract = {OBJECTIVE: Psychological suffering in malignant mesothelioma (MM) differs from that in other cancers because of its occupational etiology, and we aimed to develop specific patient-reported outcome measures to assess it.<br><br>METHODS: We used a multi-method prospective observational multicentric study (N&#x2009;=&#x2009;149), and a preliminary questionnaire validation was performed through a Bayesian approach.<br><br>RESULTS: Item analysis showed a good internal consistency and reliability (Cronbach alpha&#x2009;=&#x2009;0.79 [95% CI&#x2009;=&#x2009;0.74-0.93]. Twenty of the 41 initial items were selected as posterior 95% highest density interval factor loading standardized effect size fell outside of the region of practical equivalence. Bayesian exploratory factor analysis showed a two-factor structure: (1) Trauma-related reactions (TR, 13 items) and (2) Claim for justice (CJ, 7 items), confirmed by the Bayesian confirmatory factor analysis. Latent factors were poorly correlated (Posterior median: 0.13; 95% CI&#x2009;=&#x2009;-0.079 to 0.323). The 90% root mean square error of approximation posterior median was 0.04 [90% CI&#x2009;=&#x2009;0.03-0.58]; the 90% chi-square posterior median was 242 [90% CI&#x2009;=&#x2009;209-287].<br><br>CONCLUSION: Psychological suffering in MM patients implies negative cognitive, emotional, and somatic reactions related to the traumatic impact of the disease and the need to obtain justice through economic compensation. Our findings provide preliminary evidence that the Mesothelioma Psychological Distress Tool-Patients could be a promising and reliable instrument to assess MM patients' psychological distress.}, }
@article {pmid36499762, year = {2022}, author = {Munson, P and Shukla, A}, title = {Potential Roles of Exosomes in the Development and Detection of Malignant Mesothelioma: An Update.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499762}, issn = {1422-0067}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; W81XWH-13-PRCRP-IA//Department of Defence/ ; ES021110/NH/NIH HHS/United States ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/pathology ; *Lung Neoplasms/pathology ; *Asbestos/toxicity ; *Exosomes/pathology ; }, abstract = {Malignant mesothelioma (MM) is a devastating cancer of mesothelial cells, caused by asbestos exposure. Limited knowledge regarding the detection of asbestos exposure and the early diagnosis of MM, as well as a lack of successful treatment options for this deadly cancer, project an immediate need to understand the mechanism(s) of MM development. With the recent discovery of nano-vesicles, namely exosomes, and their enormous potential to contain signature molecules representative of different diseases, as well as to communicate with distant targets, we were encouraged to explore their role(s) in MM biology. In this review, we summarize what we know so far about exosomes and MM based on our own studies and on published literature from other groups in the field. We expect that the information contained in this review will help advance the field of MM forward by revealing the mechanisms of MM development and survival. Based on this knowledge, future therapeutic strategies for MM can potentially be developed. We also hope that the outcome of our studies presented here may help in the detection of MM.}, }
@article {pmid36498008, year = {2022}, author = {Huh, DA and Chae, WR and Choi, YH and Kang, MS and Lee, YJ and Moon, KW}, title = {Disease Latency according to Asbestos Exposure Characteristics among Malignant Mesothelioma and Asbestos-Related Lung Cancer Cases in South Korea.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36498008}, issn = {1660-4601}, mesh = {Humans ; *Mesothelioma, Malignant ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/etiology ; *Lung Neoplasms/chemically induced/epidemiology ; Republic of Korea/epidemiology ; *Occupational Exposure ; }, abstract = {Korea was one of the major consumers of asbestos in the late 1900s, and asbestos-related disease patients have been reported continuously to date, owing to long disease latency. Several studies have been conducted to predict the future incidence of malignant mesothelioma and lung cancer in Korea, but little is understood about the latency time. Therefore, the aim of this study is to estimate the latency period of malignant mesothelioma and asbestos-related lung cancer in Korea and its determinants. We obtained information from the Environmental Health Centers for Asbestos in Korea on the history of asbestos exposure and demographic characteristics of 1933 patients with malignant mesothelioma and asbestos-related lung cancer. In our study, the latency periods for malignant mesothelioma and lung cancer were 33.7 and 40.1 years, respectively. Regardless of the disease type, those with a history of exposure related to the production of asbestos-containing products or asbestos factories had the shortest latency period. In addition, we observed that those who worked in or lived near asbestos mines tended to have a relatively long disease latency. Smoking was associated with shorter latency, but no linear relationship between the lifetime smoking amount (expressed in pack years) and latent time was observed. In addition, the age of initial exposure showed a negative linear association with the latency period for mesothelioma and lung cancer.}, }
@article {pmid36475505, year = {2022}, author = {Ferrari, L and Iodice, S and Cantone, L and Dallari, B and Dioni, L and Bordini, L and Palleschi, A and Mensi, C and Pesatori, AC}, title = {Identification of a new potential plasmatic biomarker panel for the diagnosis of malignant pleural mesothelioma.}, journal = {La Medicina del lavoro}, volume = {113}, number = {6}, pages = {e2022052}, pmid = {36475505}, issn = {0025-7818}, mesh = {Humans ; *Mesothelioma, Malignant ; *HMGB1 Protein ; Reproducibility of Results ; *MicroRNAs ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare highly aggressive tumor strongly associated with asbestos exposure and characterized by poor prognosis. Currently, diagnosis is based on invasive techniques, thus there is a need of identifying non-invasive biomarkers for early detection of the disease among asbestos-exposed subjects. In the present study, we measured the plasmatic concentrations of Mesothelin, Fibulin-3, and HMGB1 protein biomarkers, and of hsa-miR-30e-3p and hsa-miR-103a-3p Extracellular-Vesicles- embedded micro RNAs (EV-miRNAs). We tested the ability of these biomarkers to discriminate between MPM and PAE subjects alone and in combination.<br><br>METHODS: the study was conducted on a population of 26 patients with MPM and 54 healthy subjects with previous asbestos exposure (PAE). Mesothelin, Fibulin-3, and HMGB1 protein biomarkers were measured by the enzyme-linked immunosorbent assay (ELISA) technique; the levels of hsa-miR-30e-3p and hsa-miR-103a-3p EV-miRNAs was assessed by quantitative real-time PCR (qPCR).<br><br>RESULTS: the most discriminating single biomarker resulted to be Fibulin-3 (AUC 0.94 CI 95% 0.88-1.0; Sensitivity 88%; Specificity 87%). After investigating the different possible combinations, the best performance was obtained by the three protein biomarkers Mesothelin, Fibulin-3, and HMGB1 (AUC 0.99 CI 95% 0.97-1.0; Sensitivity 96%; Specificity 93%).<br><br>CONCLUSIONS: the results obtained contribute to identifying new potential non-invasive biomarkers for the early diagnosis of MPM in high-risk asbestos-exposed subjects. Further studies are needed to validate the evidence obtained, in order to assess the reliability of the proposed biomarker panel.}, }
@article {pmid36466911, year = {2022}, author = {Graham, PT and Nowak, AK and Cornwall, SMJ and Larma, I and Nelson, DJ}, title = {The STING agonist, DMXAA, reduces tumor vessels and enhances mesothelioma tumor antigen presentation yet blunts cytotoxic T cell function in a murine model.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {969678}, pmid = {36466911}, issn = {1664-3224}, mesh = {Mice ; Animals ; T-Lymphocytes, Cytotoxic ; Antigen Presentation ; Disease Models, Animal ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy ; Ovalbumin ; Antigens, Neoplasm ; }, abstract = {We assessed the murine Stimulator of Interferon Genes (STING) agonist, DMXAA, for anti-mesothelioma potential using the AE17-sOVA model that expresses ovalbumin (OVA) as a neo tumor antigen. Dose response experiments alongside testing different routes of administration identified a safe effective treatment regimen that induced 100% cures in mice with small or large tumors. Three doses of 25mg/kg DMXAA given intra-tumorally every 9 days induced tumor regression and long-term survival (>5 months). Re-challenge experiments showed that tumor-free mice developed protective memory. MTT and propidium-iodide assays showed that DMXAA exerted direct cytotoxic effects at doses >1mg/ml on the murine AE17 and AB1 mesothelioma cell lines. In-vivo studies using a CFSE-based in-vivo proliferation assay showed that DMXAA improved tumor-antigen presentation in tumor-draining lymph nodes, evidenced by OVA-specific OT-1 T cells undergoing more divisions. An in-vivo cytotoxic T lymphocyte (CTL) assay showed that DMXAA blunted the lytic quality of CTLs recognizing the dominant (SIINFEKL) and a subdominant (KVVRFDKL) OVA epitopes. DMXAA reduced tumor vessel size in-vivo and although the proportion of T cells infiltrating tumors reduced, the proportion of tumor-specific T cells increased. These data show careful dosing and treatment protocols reduce mesothelioma cell viability and modulate tumor vessels such that tumor-antigen specific CTLs access the tumor site. However, attempts to enhance DMXAA-induced anti-tumor responses by combination with an agonist anti-CD40 antibody or IL-2 reduced efficacy. These proof-of-concept data suggest that mesothelioma patients could benefit from treatment with a STING agonist, but combination with immunotherapy should be cautiously undertaken.}, }
@article {pmid36465873, year = {2022}, author = {Patel, JP and Brook, MS and Kah, M and Hamilton, A}, title = {Global geological occurrence and character of the carcinogenic zeolite mineral, erionite: A review.}, journal = {Frontiers in chemistry}, volume = {10}, number = {}, pages = {1066565}, pmid = {36465873}, issn = {2296-2646}, abstract = {As with the six regulated asbestos minerals (chrysotile, amosite, crocidolite, anthophyllite, tremolite, and actinolite), the zeolite mineral, erionite, can exhibit a fibrous morphology. When fibrous erionite is aerosolized and inhaled, it has been linked to cases of lung cancers, such as malignant mesothelioma. Importantly, fibrous erionite appears to be more carcinogenic than the six regulated asbestos minerals. The first health issues regarding erionite exposure were reported in Cappadocia (Turkey), and more recently, occupational exposure issues have emerged in the United States. Erionite is now classified as a Group 1 carcinogen. Thus, identifying the geological occurrence of erionite is a prudent step in determining possible exposure pathways, but a global review of the geological occurrence of erionite is currently lacking. Here, we provide a review of the >100 global locations where erionite has been reported, including: 1) geological setting of host rocks; 2) paragenetic sequence of erionite formation, including associated zeolite minerals; 3) fiber morphological properties and erionite mineral series (i.e., Ca, K, Na); and 4) a brief overview of the techniques that have been used to identify and characterize erionite. Accordingly, erionite has been found to commonly occur within two major rock types: felsic and mafic. Within felsic rocks (in particular, tuffaceous layers within lacustrine paleoenvironments), erionite is disseminated through the layer as a cementing matrix. In contrast, within mafic (i.e., basaltic) rocks, erionite is typically found within vesicles. Nevertheless, aside from detailed studies in Italy and the United States, there is a paucity of specific information on erionite geological provenance or fiber morphology. The latter issue is a significant drawback given its impact on erionite toxicity. Future erionite studies should aim to provide more detailed information, including variables such as rock type and lithological properties, quantitative geochemistry, and fiber morphology.}, }
@article {pmid36429481, year = {2022}, author = {Handra, CM and Chirila, M and Smarandescu, RA and Ghita, I}, title = {Near Missed Case of Occupational Pleural Malignant Mesothelioma, a Case Report and Latest Therapeutic Options.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {22}, pages = {}, pmid = {36429481}, issn = {1660-4601}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/chemically induced/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/therapy/complications ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects ; }, abstract = {Asbestos use started to be gradually banned in Europe from 1991 onwards, and there are currently strict occupational exposure limits for asbestos. However, malignant mesothelioma has a long latency time (in some cases up to 50-60 years), so the risks related to asbestos exposure should not be forgotten. Considering the increased risk of lung cancer following the inhalation of asbestos fibers, lifetime health monitoring should be considered in people occupationally exposed to asbestos, with an emphasis on the respiratory system. An assessment of their occupational history should be performed rigorously, especially in the areas with a history of asbestos production/use, as this is a key element for an early diagnosis and appropriate treatment. This case report presents a near-missed case of occupational pleural malignant mesothelioma. The latency time between the first asbestos exposure and the diagnosis of occupational pleural malignant mesothelioma was 49 years. The accurate diagnosis was made two years after the first symptoms appeared.}, }
@article {pmid36420194, year = {2022}, author = {Keam, S and MacKinnon, KM and D'Alonzo, RA and Gill, S and Ebert, MA and Nowak, AK and Cook, AM}, title = {Effects of Photon Radiation on DNA Damage, Cell Proliferation, Cell Survival, and Apoptosis of Murine and Human Mesothelioma Cell Lines.}, journal = {Advances in radiation oncology}, volume = {7}, number = {6}, pages = {101013}, pmid = {36420194}, issn = {2452-1094}, abstract = {PURPOSE: To characterize the cellular responses of murine and human mesothelioma cell lines to different doses of photon radiation with a long-term aim of optimizing a clinically relevant in vivo model in which to study the interaction of radiation therapy and immunotherapy combinations.<br><br>METHODS AND MATERIALS: Two murine mesothelioma cell lines (AB1 and AE17) and 3 human cell lines (BYE, MC, and JU) were used in the study. Cells were treated with increasing doses of photon radiation. DNA damage, DNA repair, cell proliferation, and apoptosis at different time points after irradiation were quantified by flow cytometry, and cell survival probability was examined using clonogenic survival assay.<br><br>RESULTS: DNA damage increased with escalating dose in all cell lines. Evident G2/M arrest and reduced cell proliferation were observed after irradiation with 8 Gy. DNA repair was uniformly less efficient at higher compared with lower radiation-fraction doses. The apoptosis dose response varied between cell lines, with greater apoptosis observed at 16 Gy with human BYE and murine AB1 cell lines but less for other studied cell lines, regardless of dose and time. The &#x3b1;/&#x3b2; ratio from the cell survival fraction of human mesothelioma cell lines was smaller than from murine ones, suggesting human cell lines in our study were more sensitive to a change of dose per fraction than were murine mesothelioma cell lines. However, in all studied cell lines, colony formation was completely inhibited at 8 Gy.<br><br>CONCLUSIONS: A threshold dose of 8 Gy appeared to be appropriate for hypofractionated radiation therapy. However, the radiation therapy doses between 4 and 8 Gy remain to be systematically analyzed. These observations provide an accurate picture of the in vitro response of mesothelioma cell lines to photon irradiation and characterize the heterogeneity between human and murine cell lines. This information may guide in vivo experiments and the strengths and limitations of extrapolation from murine experimentation to potential human translation.}, }
@article {pmid36420072, year = {2022}, author = {Yabuuchi, Y and Hiroshima, K and Oshima, H and Kanazawa, J and Hayashihara, K and Nakagawa, T and Shimanouchi, M and Usui, S and Oh-Ishi, S and Saito, T and Hizawa, N and Minami, Y}, title = {Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report.}, journal = {Oncology letters}, volume = {24}, number = {6}, pages = {440}, pmid = {36420072}, issn = {1792-1082}, abstract = {Mesothelioma in situ (MIS) is defined as a preinvasive mesothelioma that forms a single layer of mild atypical mesothelial cells lining on the serosa surface of pleura. The atypical mesothelial cells present loss of BRCA-1 associated protein-1 (BAP-1) and/or methylthioadenosine phosphorylase as examined by immunohistochemistry (IHC) and/or homozygous deletion of cyclin-dependent kinase inhibitor 2A/p16 as examined by fluorescence in situ hybridization. It is difficult to diagnose because of the unremarkable clinical findings except for pleural effusion. The present report describes a case in which MIS was diagnosed at the time of sampling due to the presence of clearly malignant mesothelial cells in the pleural fluid. In 2016, a 74-year-old man with a history of past exposure to asbestos was admitted to Ibaraki Higashi National Hospital (Tokai-mura, Japan) with dyspnea. Chest CT indicated only right pleural effusion. Malignant mesothelial cells were suspected in a cell block made using pleural effusion; therefore, right pleural biopsy was performed. Pathologically, there was proliferation of mesothelial cells with mild atypia that formed a single-flat layer on the pleural surface; however, there was no invasion. Furthermore, IHC revealed loss of BAP-1 in cells from the biopsied pleura and pleural effusion. MIS was suspected at the time; however, the patient arbitrarily quit his medical check-ups. After 44 months, the patient was readmitted to our hospital complaining of dyspnea. CT indicated a large right pleural mass. A specimen of the mass obtained via CT-guided needle biopsy revealed malignant mesothelioma. The patient continued to deteriorate and eventually died. This case indicated that pleural effusion could be used to demonstrate overtly malignant mesothelial cells and diagnose MIS at the time of sampling. To the best of our knowledge, this is first report of MIS with overtly malignant mesothelial cells in pleural effusion. Pleural effusion may serve an important role in MIS diagnosis.}, }
@article {pmid36410050, year = {2022}, author = {Walter, M and Schenkeveld, WDC and Tomatis, M and Schelch, K and Peter-Vörösmarty, B and Geroldinger, G and Gille, L and Bruzzoniti, MC and Turci, F and Kraemer, SM and Grusch, M}, title = {The Potential Contribution of Hexavalent Chromium to the Carcinogenicity of Chrysotile Asbestos.}, journal = {Chemical research in toxicology}, volume = {35}, number = {12}, pages = {2335-2347}, pmid = {36410050}, issn = {1520-5010}, mesh = {Humans ; Asbestos, Serpentine/toxicity/chemistry ; Hydrogen Peroxide ; *Asbestos ; Chromium/toxicity ; Carcinogens/analysis ; *Lung Neoplasms/chemically induced ; }, abstract = {Chrysotile asbestos is a carcinogenic mineral that has abundantly been used in industrial and consumer applications. The carcinogenicity of the fibers is partly governed by reactive Fe surface sites that catalyze the generation of highly toxic hydroxyl radicals (HO[•]) from extracellular hydrogen peroxide (H2O2). Chrysotile also contains Cr, typically in the low mass permille range. In this study, we examined the leaching of Cr from fibers at the physiological lung pH of 7.4 in the presence and absence of H2O2. Furthermore, we investigated the potential of cells from typical asbestos-burdened tissues and cancers to take up Cr leached from chrysotile in PCR expression, immunoblot, and cellular Cr uptake experiments. Finally, the contribution of Cr to fiber-mediated H2O2 decomposition and HO[•] generation was studied. Chromium readily dissolved from chrysotile fibers in its genotoxic and carcinogenic hexavalent redox state upon oxidation by H2O2. Lung epithelial, mesothelial, lung carcinoma, and mesothelioma cells expressed membrane-bound Cr(VI) transporters and accumulated Cr up to 10-fold relative to the Cr(VI) concentration in the spiked medium. Conversely, anion transporter inhibitors decreased cellular Cr(VI) uptake up to 45-fold. Finally, chromium associated with chrysotile neither decomposed H2O2 nor contributed to fiber-mediated HO[•] generation. Altogether, our results support the hypothesis that Cr may leach from inhaled chrysotile in its hexavalent state and subsequently accumulate in cells of typically asbestos-burdened tissues, which could contribute to the carcinogenicity of chrysotile fibers. However, unlike Fe, Cr did not significantly contribute to the adverse radical production of chrysotile.}, }
@article {pmid36387076, year = {2022}, author = {Chang, F and Keam, S and Hoang, TS and Creaney, J and Gill, S and Nowak, AK and Ebert, M and Cook, AM}, title = {Immune marker expression of irradiated mesothelioma cell lines.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1020493}, pmid = {36387076}, issn = {2234-943X}, abstract = {BACKGROUND: Though immune checkpoint inhibition has recently shown encouraging clinical efficacy in mesothelioma, most patients do not respond. Combining immune checkpoint inhibition with radiotherapy presents an attractive option for improving treatment responses owing to the various immunomodulatory effects of radiation on tumors. However, the ideal dosing and scheduling of combined treatment remains elusive, as it is poorly studied in mesothelioma. The present study characterizes the dose- and time-dependent changes to expression of various immune markers and cytokines important to antitumor responses following irradiation of mesothelioma cell lines.<br><br>METHODS: Two murine (AB1, AE17) and two human (BYE, JU77) mesothelioma cell lines were treated with titrated gamma-radiation doses (1-8 Gy) and the expression of MHC class-I, MHC class-II and PD-L1 was measured over a series of post-irradiation timepoints (1-72 hours) by flow cytometry. Levels of cytokines IL-1&#x3b1;, IL-1&#x3b2;, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-&#x3b2;, IFN-&#x3b3;, TNF-&#x3b1;, and GM-CSF were measured by multiplex immunoassay in murine cell lines following 8 Gy radiation.<br><br>RESULTS: Following irradiation, a dose-dependent upregulation of MHC-I and PD-L1 was observed on three of the four cell lines studied to varying extents. For all cell lines, the increase in marker expression was most pronounced 72 hours after radiation. At this timepoint, increases in levels of cytokines IFN-&#x3b2;, MCP-1 and IL-6 were observed following irradiation with 8 Gy in AB1 but not AE17, reflecting patterns in marker expression.<br><br>CONCLUSIONS: Overall, this study establishes the dose- and time-dependent changes in immune marker expression of commonly studied mesothelioma cell lines following radiation and will inform future study into optimal dosing and scheduling of combined radiotherapy and immune checkpoint inhibition for mesothelioma.}, }
@article {pmid36362413, year = {2022}, author = {Crovella, S and Moura, RR and Brandão, L and Vita, F and Schneider, M and Zanconati, F and Finotto, L and Zacchi, P and Zabucchi, G and Borelli, V}, title = {Variant Enrichment Analysis to Explore Pathways Disruption in a Necropsy Series of Asbestos-Exposed Shipyard Workers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362413}, issn = {1422-0067}, support = {(Bando di Ricerca sanitaria 2017-programma 5 per mille anno 2015) and Municipality of Monfalcone (Gorizia)//Italian League for the Fight Against Cancer (LILT), ASSOCIAZIONE ISONTINA LILT/ ; decree 1124/SPS, 09/20/2016, N&#xb0; 1299//Regione Autonoma Friuli-Venezia Giulia, Assessorato alla Salute e Protezione Sociale, LR 22/2001/ ; BioHub 03/20//Institute for Maternal and Child Health IRCCS "Burlo Garofolo/Italian Ministry of Health"/ ; 311415/2020-2//Interreg Italia-Slovenia, ISE-EMH 07/2019; and by CNPq/ ; }, mesh = {Humans ; Autopsy ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/genetics ; *Mesothelioma, Malignant ; *Lung Neoplasms/chemically induced/genetics ; *Occupational Exposure/adverse effects ; }, abstract = {The variant enrichment analysis (VEA), a recently developed bioinformatic workflow, has been shown to be a valuable tool for whole-exome sequencing data analysis, allowing finding differences between the number of genetic variants in a given pathway compared to a reference dataset. In a previous study, using VEA, we identified different pathway signatures associated with the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic radiation therapy. Here, we used VEA to discover novel pathways altered in individuals exposed to asbestos who developed or not asbestos-related diseases (lung cancer or mesothelioma). A population-based autopsy study was designed in which asbestos exposure was evaluated and quantitated by investigating objective signs of exposure. We selected patients with similar exposure to asbestos. Formalin-fixed paraffin-embedded (FFPE) tissues were used as a source of DNA and whole-exome sequencing analysis was performed, running VEA to identify potentially disrupted pathways in individuals who developed thoracic cancers induced by asbestos exposure. By using VEA analysis, we confirmed the involvement of pathways considered as the main culprits for asbestos-induced carcinogenesis: oxidative stress and chromosome instability. Furthermore, we identified protective genetic assets preserving genome stability and susceptibility assets predisposing to a worst outcome.}, }
@article {pmid36362209, year = {2022}, author = {Paajanen, J and Bueno, R and De Rienzo, A}, title = {The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362209}, issn = {1422-0067}, mesh = {Humans ; *Lung Neoplasms/drug therapy/genetics/chemically induced ; *Mesothelioma/drug therapy/genetics/chemically induced ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/genetics ; *Asbestos/adverse effects ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20-40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.}, }
@article {pmid36361401, year = {2022}, author = {Vorster, T and Mthombeni, J and teWaterNaude, J and Phillips, JI}, title = {The Association between the Histological Subtypes of Mesothelioma and Asbestos Exposure Characteristics.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {21}, pages = {}, pmid = {36361401}, issn = {1660-4601}, mesh = {Humans ; Female ; *Mesothelioma, Malignant ; *Asbestos ; *Mesothelioma/epidemiology ; Asbestos, Crocidolite/toxicity ; Mining ; *Occupational Exposure ; *Occupational Diseases/epidemiology ; *Lung Neoplasms/pathology ; }, abstract = {Asbestos mining operations have left South Africa with a legacy of asbestos contamination and asbestos-related diseases continue to be a problem. The large-scale mining of three types of asbestos presents a unique opportunity to study malignant mesothelioma of the pleura (mesothelioma) in South Africa. This study aimed to describe the demographics of deceased individuals diagnosed with mesothelioma and explore any associations between the histological morphology of mesothelioma and asbestos characteristics. We reviewed the records of all deceased miners and ex-miners from the Pathology Automation System (PATHAUT) database of the National Institute of Occupational Health (NIOH) that were histologically diagnosed with mesothelioma in the period from January 2006-December 2016 (11 years). The study population does not include all cases of mesothelioma in South Africa but rather those that reached the compensation system. Crocidolite asbestos fibres were identified in the majority of mesothelioma cases (n = 140; 53.4%). The epithelioid subtype was most commonly present in both occupational and environmental cases. Cases with the sarcomatous subtype were older at death and fewer female cases were diagnosed with this subtype. No relationship between mesothelioma subtype and asbestos type or asbestos burden or fibre size was established.}, }
@article {pmid36357176, year = {2023}, author = {Azzolina, D and Consonni, D and Ferrante, D and Mirabelli, D and Silvestri, S and Luberto, F and Angelini, A and Cuccaro, F and Nannavecchia, AM and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Tunesi, S and Chellini, E and Miligi, L and Perticaroli, P and Pettinari, A and Bressan, V and Merler, E and Girardi, P and Bisceglia, L and Marinaccio, A and Massari, S and Magnani, C and , }, title = {Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.}, journal = {Thorax}, volume = {78}, number = {8}, pages = {808-815}, doi = {10.1136/thorax-2021-217862}, pmid = {36357176}, issn = {1468-3296}, mesh = {Humans ; *Asbestos/toxicity ; Cohort Studies ; Italy/epidemiology ; *Lung Neoplasms/epidemiology/mortality ; *Mesothelioma/epidemiology/mortality ; Mortality/trends ; *Occupational Diseases/epidemiology/mortality ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/mortality ; Risk Assessment ; Male ; Female ; Construction Industry ; Adult ; Middle Aged ; Aged ; }, abstract = {INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy.<br><br>METHOD: The cohort study included 12&#x2009;578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE).<br><br>RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE.<br><br>CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.}, }
@article {pmid36355620, year = {2022}, author = {Kadariya, Y and Sementino, E and Shrestha, U and Gorman, G and White, JM and Ross, EA and Clapper, ML and Neamati, N and Miller, MS and Testa, JR}, title = {Inflammation as a chemoprevention target in asbestos-induced malignant mesothelioma.}, journal = {Carcinogenesis}, volume = {43}, number = {12}, pages = {1137-1148}, pmid = {36355620}, issn = {1460-2180}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; HHSN261201500032I/NH/NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Mesothelioma, Malignant ; Interleukin-6/genetics ; Sulindac ; Interleukin 1 Receptor Antagonist Protein/adverse effects ; Cytokine Receptor gp130/metabolism ; *Asbestos/toxicity ; Carcinogenesis ; Inflammation/drug therapy/pathology ; Chemoprevention ; *Mesothelioma/chemically induced/prevention &amp; control/genetics ; }, abstract = {Malignant mesothelioma (MM) is an incurable cancer of the serosal lining that is often caused by exposure to asbestos. Therefore, novel agents for the prevention and treatment of this disease are urgently needed. Asbestos induces the release of pro-inflammatory cytokines such as IL-1β and IL-6, which play a role in MM development. IL-6 is a component of the JAK-STAT3 pathway that contributes to inflammation-associated tumorigenesis. Glycoprotein 130 (gp130), the signal transducer of this signaling axis, is an attractive drug target because of its role in promoting neoplasia via the activation of downstream STAT3 signaling. The anticancer drug, SC144, inhibits the interaction of gp130 with the IL-6 receptor (IL6R), effectively blunting signaling from this inflammatory axis. To test whether the inflammation-related release of IL-6 plays a role in the formation of MM, we evaluated the ability of SC144 to inhibit asbestos-induced carcinogenesis in a mouse model. The ability of sulindac and anakinra, an IL6R antagonist/positive control, to inhibit MM formation in this model was tested in parallel. Asbestos-exposed Nf2+/-;Cdkn2a+/- mice treated with SC144, sulindac or anakinra showed significantly prolonged survival compared to asbestos-exposed vehicle-treated mice. STAT3 activity was markedly decreased in MM specimens from SC144-treated mice. Furthermore, SC144 inhibited STAT3 activation by IL-6 in cultured normal mesothelial cells, and in vitro treatment of MM cells with SC144 markedly decreased the expression of STAT3 target genes. The emerging availability of newer, more potent SC144 analogs showing improved pharmacokinetic properties holds promise for future trials, benefitting individuals at high risk of this disease.}, }
@article {pmid36346299, year = {2022}, author = {Fassio, F and Bussa, M and Oddone, E and Ferraro, OE and Puci, MV and Morandi, A and Castaldo, F and Broi, M and Uberti, F and Villani, S and Montomoli, C and Monti, MC}, title = {Health status of petrochemical workers: a narrative review.}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {44}, number = {1}, pages = {51-58}, pmid = {36346299}, issn = {1592-7830}, mesh = {Male ; Humans ; *Petroleum/toxicity ; *Mesothelioma ; *Occupational Exposure/adverse effects ; Health Status ; *Leukemia/complications ; *Occupational Diseases/epidemiology/etiology ; }, abstract = {Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial.}, }
@article {pmid36325490, year = {2022}, author = {Ge, T and Phung, AL and Jhala, G and Trivedi, P and Principe, N and De George, DJ and Pappas, EG and Litwak, S and Sanz-Villanueva, L and Catterall, T and Fynch, S and Boon, L and Kay, TW and Chee, J and Krishnamurthy, B and Thomas, HE}, title = {Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor.}, journal = {Clinical &amp; translational immunology}, volume = {11}, number = {11}, pages = {e1425}, pmid = {36325490}, issn = {2050-0068}, abstract = {OBJECTIVES: Immune checkpoint inhibitors have achieved clinical success in cancer treatment, but this treatment causes immune-related adverse events, including type 1 diabetes (T1D). Our aim was to test whether a JAK1/JAK2 inhibitor, effective at treating spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice, can prevent diabetes secondary to PD-L1 blockade.<br><br>METHODS: Anti-PD-L1 antibody was injected into NOD mice to induce diabetes, and JAK1/JAK2 inhibitor LN3103801 was administered by oral gavage to prevent diabetes. Flow cytometry was used to study T cells and beta cells. Mesothelioma cells were inoculated into BALB/c mice to induce a transplantable tumour model.<br><br>RESULTS: Anti-PD-L1-induced diabetes was associated with increased immune cell infiltration in the islets and upregulated MHC class I on islet cells. Anti-PD-L1 administration significantly increased islet T cell proliferation and islet-specific CD8[+] T cell numbers in peripheral lymphoid organs. JAK1/JAK2 inhibitor treatment blocked IFN&#x3b3;-mediated MHC class I upregulation on beta cells and T cell proliferation mediated by cytokines that use the common &#x3b3; chain receptor. As a result, anti-PD-L1-induced diabetes was prevented by JAK1/JAK2 inhibitor administered before or after checkpoint inhibitor therapy. Diabetes was also reversed when the&#xa0;JAK1/JAK2 inhibitor was administered after the onset of anti-PD-L1-induced hyperglycaemia. Furthermore, JAK1/JAK2 inhibitor intervention after checkpoint inhibitors did not reverse or abrogate the antitumour effects in a transplantable tumour model.<br><br>CONCLUSION: A JAK1/JAK2 inhibitor can prevent and reverse anti-PD-L1-induced diabetes by blocking IFN&#x3b3; and &#x3b3;c cytokine activities. Our study provides preclinical validation of JAK1/JAK2 inhibitor use in checkpoint inhibitor-induced diabetes.}, }
@article {pmid36318367, year = {2022}, author = {Caporali, S and Butera, A and Amelio, I}, title = {BAP1 in cancer: epigenetic stability and genome integrity.}, journal = {Discover oncology}, volume = {13}, number = {1}, pages = {117}, pmid = {36318367}, issn = {2730-6011}, abstract = {Mutations in BAP1 have been identified in a hereditary cancer predisposition syndrome and in sporadic tumours. Individuals carrying familiar BAP1 monoallelic mutations display hypersusceptibility to exposure-associated cancers, such as asbestos-driven mesothelioma, thus BAP1 status has been postulated to participate in gene-environment interaction. Intriguingly, BAP1 functions display also a high degree of tissue dependency, associated to a peculiar cancer spectrum and cell types of specific functions. Mechanistically, BAP1 functions as an ubiquitin carboxy-terminal hydrolase (UCH) and controls regulatory ubiquitination of histones as well as degradative ubiquitination of a range of protein substrates. In this article we provide an overview of the most relevant findings on BAP1, underpinning its tissue specific tumour suppressor function. We also discuss the importance of its epigenetic role versus the control of protein stability in the regulation of genomic integrity.}, }
@article {pmid36305648, year = {2023}, author = {Allione, A and Viberti, C and Cotellessa, I and Catalano, C and Casalone, E and Cugliari, G and Russo, A and Guarrera, S and Mirabelli, D and Sacerdote, C and Gentile, M and Eichelmann, F and Schulze, MB and Harlid, S and Eriksen, AK and Tjønneland, A and Andersson, M and Dollé, MET and Van Puyvelde, H and Weiderpass, E and Rodriguez-Barranco, M and Agudo, A and Heath, AK and Chirlaque, MD and Truong, T and Dragic, D and Severi, G and Sieri, S and Sandanger, TM and Ardanaz, E and Vineis, P and Matullo, G}, title = {Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort.}, journal = {International journal of cancer}, volume = {152}, number = {4}, pages = {725-737}, doi = {10.1002/ijc.34339}, pmid = {36305648}, issn = {1097-0215}, support = {1000143/MRC_/Medical Research Council/United Kingdom ; C8221/A29017/CRUK_/Cancer Research UK/United Kingdom ; MR/N003284/1/MRC_/Medical Research Council/United Kingdom ; MR/M012190/1/MRC_/Medical Research Council/United Kingdom ; G0401527/MRC_/Medical Research Council/United Kingdom ; G1000143/MRC_/Medical Research Council/United Kingdom ; 14136/CRUK_/Cancer Research UK/United Kingdom ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; 001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Child, Preschool ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/genetics/pathology ; DNA Methylation ; Case-Control Studies ; Prospective Studies ; *Pleural Neoplasms/diagnosis/genetics/pathology ; Biomarkers, Tumor/metabolism ; *Asbestos/adverse effects ; Genetic Markers ; Blood Cells ; *Lung Neoplasms/diagnosis/genetics/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.}, }
@article {pmid36304150, year = {2022}, author = {Lam, SK and Yan, S and Lam, JS and Feng, Y and Khan, M and Chen, C and Ko, FC and Ho, JC}, title = {Disturbance of the Warburg effect by dichloroacetate and niclosamide suppresses the growth of different sub-types of malignant pleural mesothelioma in vitro and in vivo.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1020343}, pmid = {36304150}, issn = {1663-9812}, abstract = {Background: Inhalation of asbestos fibers is the most common cause of malignant pleural mesothelioma (MPM). In 2004, the United States Food and Drug Administration approved a combination of cisplatin with pemetrexed to treat unresectable MPM. Nonetheless novel treatment is urgently needed. The objective of this study is to report the combination effect of dichloroacetate (DCA) or niclosamide (Nic) Nic in MPM. Materials and methods: The effect of a combination of DCA and Nic was studied using a panel of MPM cell lines (H28, MSTO-211H, H226, H2052, and H2452). Cell viability was monitored by MTT assay. Glycolysis, oxidative phosphorylation, glucose, glycogen, pyruvate, lactate, citrate, succinate and ATP levels were determined by corresponding ELISA. Apoptosis, mitochondrial transmembrane potential, cell cycle analysis, hydrogen peroxide and superoxide were investigated by flow cytometry. Cell migration and colony formation were investigated by transwell migration and colony formation assays respectively. The in vivo effect was confirmed using 211H and H226 nude mice xenograft models. Results and conclusion: Cell viability was reduced. Disturbance of glycolysis and/or oxidative phosphorylation resulted in downregulation of glycogen, citrate and succinate. DCA and/or Nic increased apoptosis, mitochondrial transmembrane depolarization, G2/M arrest and reactive oxygen species. Moreover, DCA and/or Nic suppressed cell migration and colony formation. Furthermore, a better initial tumor suppressive effect was induced by the DCA/Nic combination compared with either drug alone in both 211H and H226 xenograft models. In H226 xenografts, DCA/Nic increased median survival of mice compared with single treatment. Single drug and/or a combination disturbed the Warburg effect and activated apoptosis, and inhibition of migration and proliferation in vivo. In conclusion, dichloroacetate and/or niclosamide showed a tumor suppressive effect in MPM in vitro and in vivo, partially mediated by disturbance of glycolysis/oxidative phosphorylation, apoptosis, ROS production, G2/M arrest, and suppression of migration and proliferation.}, }
@article {pmid36293328, year = {2022}, author = {Chernova, T and Grosso, S and Sun, XM and Tenor, AR and Cabeza, JZ and Craxton, A and Self, EL and Nakas, A and Cain, K and MacFarlane, M and Willis, AE}, title = {Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293328}, issn = {1422-0067}, support = {29372/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/4/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/5 (RG94521)/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/7/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Cancer-Associated Fibroblasts/metabolism ; YAP-Signaling Proteins ; Cell Line, Tumor ; *Mesothelioma/pathology ; *Extracellular Vesicles/metabolism ; Carcinogenesis/metabolism ; Simvastatin ; Tumor Microenvironment ; }, abstract = {Malignant mesothelioma is an aggressive tumour of the pleura (MPM) or peritoneum with a clinical presentation at an advanced stage of the disease. Current therapies only marginally improve survival and there is an urgent need to identify new treatments. Carcinoma-associated fibroblasts (CAFs) represent the main component of a vast stroma within MPM and play an important role in the tumour microenvironment. The influence of CAFs on cancer progression, aggressiveness and metastasis is well understood; however, the role of CAF-derived extracellular vesicles (CAF-EVs) in the promotion of tumour development and invasiveness is underexplored. We purified CAF-EVs from MPM-associated cells and healthy dermal human fibroblasts and examined their effect on cell proliferation and motility. The data show that exposure of healthy mesothelial cells to EVs derived from CAFs, but not from normal dermal human fibroblasts (NDHF) resulted in activating pro-oncogenic signalling pathways and increased proliferation and motility. Consistent with its role in suppressing Yes-Associated Protein (YAP) activation (which in MPM is a result of Hippo pathway inactivation), treatment with Simvastatin ameliorated the pro-oncogenic effects instigated by CAF-EVs by mechanisms involving both a reduction in EV number and changes in EV cargo. Collectively, these data determine the significance of CAF-derived EVs in mesothelioma development and progression and suggest new targets in cancer therapy.}, }
@article {pmid36282034, year = {2022}, author = {Mangone, L and Storchi, C and Pinto, C and Giorgi Rossi, P and Bisceglia, I and Romanelli, A}, title = {Incidence of malignant mesothelioma and asbestos exposure in the Emilia-Romagna region, Italy.}, journal = {La Medicina del lavoro}, volume = {113}, number = {5}, pages = {e2022047}, pmid = {36282034}, issn = {0025-7818}, mesh = {Female ; Humans ; Male ; Middle Aged ; *Asbestos/adverse effects ; Incidence ; Italy/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {BACKGROUND: The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021.<br><br>METHODS: The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos.<br><br>RESULTS: 3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure.<br><br>CONCLUSIONS: This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.}, }
@article {pmid36275913, year = {2022}, author = {Quigley, N and Lang-Lazdunski, L and Boily-Daoust, C and Couture, C and Fortin, M}, title = {An unusual isolated anterior mediastinal lesion.}, journal = {Respirology case reports}, volume = {10}, number = {11}, pages = {e01059}, pmid = {36275913}, issn = {2051-3380}, abstract = {Malignant pleural mesothelioma (MPM) is an infrequent tumour of poor prognosis with a strong association with asbestos exposure. Pleural effusion or thickening is the most common radiological finding. Thoracoscopic biopsy is the diagnostic modality of choice. In our report, we present the case of a career welder who consulted with vocal cord palsy and an atypical anterior mediastinal lesion. An EBUS-TBNA-guided biopsy and a thorough cytological assessment led to an unexpected diagnosis of epithelioid MPM. A localized anterior mediastinal lesion is an extremely infrequent presentation of MPM that deserves clinical recognition.}, }
@article {pmid36240245, year = {2022}, author = {Jiménez-Ramírez, C and Gilbert Weber, D and Aguilar-Madrid, G and Brik, A and Juárez-Pérez, CA and Casjens, S and Raiko, I and Brüning, T and Johnen, G and Cabello-López, A}, title = {Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275936}, pmid = {36240245}, issn = {1932-6203}, mesh = {*Asbestos/adverse effects ; Bilirubin ; Biomarkers, Tumor/genetics ; Calbindin 2/genetics ; Creatinine ; Female ; GPI-Linked Proteins/genetics ; Glucose ; Humans ; Leukocytes/pathology ; *Lung Neoplasms/pathology ; Male ; Mesothelin ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; *MicroRNAs/genetics ; Middle Aged ; *Pleural Neoplasms/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.}, }
@article {pmid36232554, year = {2022}, author = {Gesmundo, I and Pedrolli, F and Vitale, N and Bertoldo, A and Orlando, G and Banfi, D and Granato, G and Kasarla, R and Balzola, F and Deaglio, S and Cai, R and Sha, W and Papotti, M and Ghigo, E and Schally, AV and Granata, R}, title = {Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232554}, issn = {1422-0067}, support = {2017HRTZYA//Italian Ministry of Instruction and Research PRIN 2017/ ; 2017S55RXB_002//Italian Ministry of Instruction and Research PRIN 2017/ ; 2019-2022//Fondazione Buzzi Unicem/ ; }, mesh = {Cell Line, Tumor ; Cisplatin/pharmacology/therapeutic use ; Cyclin D1 ; Cyclooxygenase 2 ; Growth Hormone-Releasing Hormone ; *HMGB1 Protein ; Humans ; Insulin-Like Growth Factor I/therapeutic use ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9/genetics ; *Mesothelioma/drug therapy/pathology ; *Mesothelioma, Malignant ; NF-kappa B/metabolism ; Pemetrexed/pharmacology/therapeutic use ; *Pleural Neoplasms/drug therapy/pathology ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.}, }
@article {pmid36230710, year = {2022}, author = {Johnson, B and Zhuang, L and Rath, EM and Yuen, ML and Cheng, NC and Shi, H and Kao, S and Reid, G and Cheng, YY}, title = {Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230710}, issn = {2072-6694}, support = {RSP-080-19/20//Tour de Cure/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a deadly thoracic malignancy and existing treatment options are limited. Chemotherapy remains the most widely used first-line treatment regimen for patients with unresectable MPM, but is hampered by drug resistance issues. The current study demonstrated a modest enhancement of MPM cell sensitivity to chemotherapy drug treatment following microRNA (miRNA) transfection in MPM cell lines, albeit not for all tested miRNAs. This effect was more pronounced for FAK (PND-1186) small molecule inhibitor treatment; consistent with previously published data. We previously established that MPM response to survivin (YM155) small molecule inhibitor treatment is unrelated to basal survivin expression. Here, we showed that MPM response to YM155 treatment is enhanced following miRNA transfection of YM155-resistant MPM cells. We determined that YM155-resistant MPM cells secrete a higher level of exosomes in comparison to YM155-sensitive MPM cells. Despite this, an exosome inhibitor (GW4896) did not enhance MPM cell sensitivity to YM155. Additionally, our study showed no evidence of a correlation between the mRNA expression of inhibitor of apoptosis (IAP) gene family members and MPM cell sensitivity to YM155. However, two drug transporter genes, ABCA6 and ABCA10, were upregulated in the MPM cell lines and correlated with poor sensitivity to YM155.}, }
@article {pmid36221913, year = {2022}, author = {Hariharan, A and Qi, W and Rehrauer, H and Wu, L and Ronner, M and Wipplinger, M and Kresoja-Rakic, J and Sun, S and Oton-Gonzalez, L and Sculco, M and Serre-Beinier, V and Meiller, C and Blanquart, C and Fonteneau, JF and Vrugt, B and Rüschoff, JH and Opitz, I and Jean, D and de Perrot, M and Felley-Bosco, E}, title = {Heterogeneous RNA editing and influence of ADAR2 on mesothelioma chemoresistance and the tumor microenvironment.}, journal = {Molecular oncology}, volume = {16}, number = {22}, pages = {3949-3974}, pmid = {36221913}, issn = {1878-0261}, mesh = {Animals ; Mice ; RNA Editing/genetics ; Tumor Microenvironment/genetics ; Drug Resistance, Neoplasm/genetics ; RNA-Binding Proteins/genetics/metabolism ; Adenosine Deaminase/genetics/metabolism ; *Mesothelioma, Malignant ; *Mesothelioma/genetics ; }, abstract = {We previously observed increased levels of adenosine-deaminase-acting-on-dsRNA (Adar)-dependent RNA editing during mesothelioma development in mice exposed to asbestos. The aim of this study was to characterize and assess the role of ADAR-dependent RNA editing in mesothelioma. We found that tumors and mesothelioma primary cultures have higher ADAR-mediated RNA editing compared to mesothelial cells. Unsupervised clustering of editing in different genomic regions revealed heterogeneity between tumor samples as well as mesothelioma primary cultures. ADAR2 expression levels are higher in BRCA1-associated protein 1 wild-type tumors, with corresponding changes in RNA editing in transcripts and 3'UTR. ADAR2 knockdown and rescue models indicated a role in cell proliferation, altered cell cycle, increased sensitivity to antifolate treatment, and type-1 interferon signaling upregulation, leading to changes in the microenvironment in vivo. Our data indicate that RNA editing contributes to mesothelioma heterogeneity and highlights an important role of ADAR2 not only in growth regulation in mesothelioma but also in chemotherapy response, in addition to regulating inflammatory response downstream of sensing nucleic acid structures.}, }
@article {pmid36209608, year = {2023}, author = {Gualtieri, AF}, title = {Journey to the centre of the lung. The perspective of a mineralogist on the carcinogenic effects of mineral fibres in the lungs.}, journal = {Journal of hazardous materials}, volume = {442}, number = {}, pages = {130077}, doi = {10.1016/j.jhazmat.2022.130077}, pmid = {36209608}, issn = {1873-3336}, mesh = {Humans ; Mineral Fibers/toxicity ; Asbestos, Crocidolite ; Asbestos, Serpentine ; *Zeolites/chemistry ; Asbestos, Amphibole/toxicity ; Lung ; *Lung Neoplasms/chemically induced ; *Asbestos/toxicity ; }, abstract = {This work reviews the bio-chemical mechanisms leading to adverse effects produced when mineral fibres are inhaled and transported in the lungs from the perspective of a mineralogist. The behaviour of three known carcinogenic mineral fibres (crocidolite, chrysotile, and fibrous-asbestiform erionite) during their journey through the upper respiratory tract, the deep respiratory tract and the pleural cavity is discussed. These three fibres have been selected as they are the most socially and economically relevant mineral fibres representative of the classes of chain silicates (amphiboles), layer silicates (serpentine), and framework silicates (zeolites), respectively. Comparison of the behaviour of these fibres is made according to their specific crystal-chemical assemblages and properties. Known biological and subsequent pathologic effects which lead and contribute to carcinogenesis are critically reviewed under the mineralogical perspective and in relation to recent progress in this multidisciplinary field of research. Special attention is given to the understanding of the cause-effect relationships for lung cancer and malignant mesothelioma. Comparison with interstitial pulmonary fibrosis, or "asbestosis", will also be made here. This overview highlights open issues, data gaps, and conflicts in the literature for these topics, especially as regards relative potencies of the three mineral fibres under consideration for lung cancer and mesothelioma. Finally, an attempt is made to identify future research lines suitable for a general comprehensive model of the carcinogenicity of mineral fibres.}, }
@article {pmid36187519, year = {2022}, author = {Kazi, M and Vispute, T and Shah, P and Ramadwar, M and Bhandare, MS and Shrikhande, SV and Chaudhari, VA}, title = {Localized gastric mesothelioma with nodal metastasis-an exceptionally rare entity.}, journal = {Indian journal of surgical oncology}, volume = {13}, number = {3}, pages = {612-615}, pmid = {36187519}, issn = {0975-7651}, abstract = {Localized mesothelioma is a rare disease with very few reports of presentation in visceral organs. We report a case of localized gastric mesothelioma with lymph node metastasis in a 32-year-old man without asbestos exposure. A failed attempt at resection was made before presentation at another center. He was given perioperative chemotherapy that was followed by a D2 radical subtotal gastrectomy and hyperthermic intraperitoneal chemotherapy. Histopathology showed epithelioid mesothelioma with nodal metastasis but without visceral peritoneal involvement. Cytoreductive surgery and regional chemotherapy are standard in diffuse mesothelioma. Management of localized mesothelioma is anecdotal; however aggressive surgery plays a central role with selective use of perioperative chemotherapy.}, }
@article {pmid36181042, year = {2022}, author = {Cimen, F and Agackiran, Y and Düzgün, S and Aloglu, M and Senturk, A and Atikcan, S}, title = {Factors affecting the life expectancy in malignant pleural mesothelioma: Our 10 years of studies and experience.}, journal = {Medicine}, volume = {101}, number = {39}, pages = {e30711}, pmid = {36181042}, issn = {1536-5964}, mesh = {Female ; Fluorodeoxyglucose F18 ; Humans ; Life Expectancy ; *Lung Neoplasms/pathology ; Male ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Diseases ; *Pleural Neoplasms/pathology ; Positron Emission Tomography Computed Tomography/methods ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. In our study, we aimed to investigate the specific clinical, laboratory, and radiological features of the tumor and the prognostic effect of SUVmax (maximum standardized uptake values) according to PET/CT (positron emission tomography). Demographic, therapeutic, clinical, and survival information of patients diagnosed with histologically-validated pleural mesothelioma in our hospital between January 2010 to December 2019 will be retrospectively scanned from the hospital records. A total of 116 patients, 61 men (52.6%), and 55 women (47.4%), were analyzed. Thirty five patients (30.2%) were over the age of 65. Percentage of patients over 65 years of age, neutrophil count, and PET SUV Max values, asbestos exposure and pleural thickening rate were significantly higher in the deceased patients' group than in the living patients' group (P = .042, P = .039, P = .002, P = .004, P = .037). T stage (tumor stage), N stage (lymph nodes stage), metastasis stage, and Grade distribution were significantly higher in the deceased patients' group than in the living patients' group (P < .000, P < .000, P = .003, P < .000). The rates of chemotherapy and surgical treatment, right lung location, and epithelioid pathology were significantly lower in the deceased patients' group compared to the living patients' group (P = .016, P = .030, P = .018, P = .008). The mean follow-up time was 13 months. Key determinants of survival in MPM include age, male gender, neutrophil increase, pleural thickening, high PET SUV max values, stage, histological type, asbestos exposure, and treatment regimen.}, }
@article {pmid36174024, year = {2022}, author = {Wang, X and Katz, S and Miura, J and Karakousis, G and Roshkovan, L and Walker, S and McNulty, S and Ciunci, C and Cengel, K and Langer, CJ and Marmarelis, ME}, title = {A single-center retrospective cohort study of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0275187}, pmid = {36174024}, issn = {1932-6203}, mesh = {Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Humans ; *Mesothelioma, Malignant ; Middle Aged ; *Peritoneal Neoplasms/drug therapy/surgery ; Peritoneum ; Platinum ; Retrospective Studies ; }, abstract = {BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare variant of malignant mesothelioma, representing 10-15% of malignant mesothelioma cases. The preferred therapeutic approach is cytoreductive surgery (CRS) accompanied by hyperthermic intraperitoneal chemotherapy (HIPEC); the role of systemic chemotherapy is not well established. While some limited retrospective studies report worse outcomes with neoadjuvant chemotherapy, our institution has favored the use of neoadjuvant chemotherapy for symptom relief and surgical optimization. The aim of our study was to assess the outcomes of patients receiving neoadjuvant chemotherapy, compared to those receiving adjuvant or no perioperative chemotherapy.<br><br>PATIENTS AND METHODS: We conducted a single-center retrospective cohort study of treatment-na&#xef;ve, non-papillary DMPM patients seen at our institution between 1/1/2009 and 9/1/2019. We explored the effect of type of systemic therapy on clinical outcomes and estimated median overall survival (mOS) using Kaplan-Meier curves. Hazard ratios (HR) calculated by Cox proportional hazard model were used to estimate effect of the exposures on overall survival.<br><br>RESULTS: 47 patients were identified with DMPM (median age at diagnosis 61.2 years, 76.6% epithelioid histology, 74.5% white race, 55.3% known asbestos exposure). CRS was performed in 53.2% of patients (25/47); 76.0% of surgical patients received HIPEC (19/25). The majority received systemic chemotherapy (37/47, 78.7%); among patients receiving both CRS and chemotherapy, neoadjuvant chemotherapy was more common than adjuvant chemotherapy (12 neoadjuvant, 8 adjuvant). Overall mOS was 84.1 months. Among neoadjuvant patients, 10/12 underwent surgery, and 2 were lost to follow-up; the majority (9/10) had clinically stable or improved disease during the pre-operative period. There were numerical more issues with chemotherapy with the adjuvant patients (4/8: 2 switches in platinum agent, 2 patients stopped therapy) than with the neoadjuvant patients (2/10: 1 switch in platinum agent, 1 delay due to peri-procedural symptoms). Neoadjuvant chemotherapy was not associated with worse mOS compared to adjuvant chemotherapy (mOS NR vs 95.1 mo, HR 0.89, 95% CI 0.18-4.5, p = 0.89).<br><br>CONCLUSIONS: When used preferentially, the use of neoadjuvant chemotherapy in DMPM patients was not associated with worse outcomes compared to adjuvant chemotherapy. It was well-tolerated and did not prevent surgical intervention.}, }
@article {pmid36165817, year = {2022}, author = {Han, Y and Zhang, T and Chen, H and Yang, X}, title = {Global magnitude and temporal trend of mesothelioma burden along with the contribution of occupational asbestos exposure in 204 countries and territories from 1990 to 2019: Results from the Global Burden of Disease Study 2019.}, journal = {Critical reviews in oncology/hematology}, volume = {179}, number = {}, pages = {103821}, doi = {10.1016/j.critrevonc.2022.103821}, pmid = {36165817}, issn = {1879-0461}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Asbestos/adverse effects ; Global Burden of Disease ; Global Health ; Humans ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; Quality-Adjusted Life Years ; Risk Factors ; }, abstract = {Understanding the burden of mesothelioma with the contribution of occupational asbestos exposure globally provides essential foundations for cancer control, policy decisions and resource allocation. Globally, 34,511 incident cases, 29,251 deaths and 668,104 disability-adjusted life years (DALYs) of mesothelioma were estimated in 2019. The age-standardized rates of incidence, mortality and DALYs all showed a slightly declining trend over the past 30 years, but the latest absolute number of mesothelioma burden almost doubled since 1990. The burden rate decreased among the population aged under 70 years, but increased among the population aged over 80 years, especially in the High socio-demographic index (SDI) region. The burden rate of mesothelioma attributable to asbestos exposure was positively associated with SDI at the national level. This study depicted a continuous increase in mesothelioma burden globally over the past 30 years. Controlling occupational asbestos exposure will reduce the mesothelioma burden, especially for higher SDI regions.}, }
@article {pmid36161345, year = {2022}, author = {Golka, K and Böthig, R and Weistenhöfer, W and Jungmann, OP and Bergmann, S and Zellner, M and Schöps, W}, title = {[Occupation-related cancer in urology-Current knowledge including environmental medical aspects].}, journal = {Urologie (Heidelberg, Germany)}, volume = {61}, number = {11}, pages = {1198-1207}, pmid = {36161345}, issn = {2731-7072}, mesh = {Male ; Humans ; Female ; *Trichloroethylene ; *Urology ; *Mesothelioma/etiology ; Occupations ; *Kidney Neoplasms/chemically induced ; }, abstract = {Occupation-related cancers are of considerable importance, which is not yet adequately recognized in the field of urology. The three numerically most significant entities are tumors of the urinary tract caused by carcinogenic aromatic amines or polycyclic aromatic hydrocarbons, renal cell cancer after high exposure to the solvent trichloroethylene, and mesotheliomas of the tunica vaginalis of the testis after exposure to asbestos; however, these can only be recognized as occupation-related if an occupational history regarding the hazard relevant to the organ bearing the tumor is documented from the beginning of employment, e.g. by a questionnaire. This is because the relevant exposures generally date back several decades. With the exception of high exposure to trichloroethylene, the substances mentioned can also environmentally trigger the same tumors. In the context of environmental risk factors, it is of considerable importance that smoking is now considered to be a trigger for some 50% of all bladder cancers in men and women; however, smoking cessation results in a reduction in smoking-related cancer risk of over 30% after only 3-4 years. Work and commuting accidents, which are considered occupational risks, can lead to urological sequelae. For example, increased tumors of the bladder can occur after spinal cord injury lasting longer than 10 years.}, }
@article {pmid36156859, year = {2022}, author = {Algranti, E and Santana, VS and Campos, F and Salvi, L and Saito, CA and Cavalcante, F and Correa-Filho, HR}, title = {Analysis of Mortality from Asbestos-Related Diseases in Brazil Using Multiple Health Information Systems, 1996-2017.}, journal = {Safety and health at work}, volume = {13}, number = {3}, pages = {302-307}, pmid = {36156859}, issn = {2093-7911}, abstract = {BACKGROUND: In Brazil, asbestos was intensively used from the 1960s until its ban in 2017. Mesothelioma, asbestosis, and pleural plaques are typical asbestos-related diseases (ARD-T). To create an ARD-T national database, death records from 1996-2017 were retrieved from several health information systems (HIS).<br><br>METHODS: All national HIS containing coded diagnoses (ICD-10) and death information were obtained. Linkage was performed to create a single database of ARD-T death records, either as underlying or contributory causes, in adults aged 30 years and older.<br><br>RESULTS: A total of 3,057 ARD-T death records were found, 2,405 (76.4%) of which being malignant mesotheliomas (MM). Pleural MM (n&#xa0;=&#xa0;1,006; 41.8%) and unspecified MM (n&#xa0;=&#xa0;792; 32.9%) prevailed. Male to female MM ratio (M:F) was 1.4:1, and higher ratios were found for non-malignant ARD-T: 3.5:1 for asbestosis and 2.4:1 for pleural plaques. Male crude annual mesothelioma mortality (CMmm x1,000,000) was 0.98 in 1996 and 2.26 in 2017, a 131.1% increment, while for females it was 1.04 and 1.25, a 20.2% increase, correspondingly. The small number of deaths with asbestosis and pleural plaques records precluded conclusive interpretations.<br><br>CONCLUSIONS: Even with the linkage of several HIS, ARD-T in death records remained in low numbers. MM mortality in men was higher and showed a rapid increase and, along with non-malignant ARD-T, higher M:F ratios suggested a predominant pattern of work-related exposure. The monitoring of workplace and environmental asbestos exposure needs to be improved, as well as the workers surveillance, following the recent Brazilian ban.}, }
@article {pmid36139575, year = {2022}, author = {Tedesco, J and Jaradeh, M and Vigneswaran, WT}, title = {Malignant Pleural Mesothelioma: Current Understanding of the Immune Microenvironment and Treatments of a Rare Disease.}, journal = {Cancers}, volume = {14}, number = {18}, pages = {}, pmid = {36139575}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma is a rare disease with an annual incidence of around 3000 cases a year in the United States. Most cases are caused by asbestos exposure, with a latency period of up to 40 years. Pleural mesothelioma is an aggressive disease process with overall survival of roughly 6-12 months after the time of diagnosis. It is divided into three subtypes: epithelioid, mixed type, and sarcomatoid type, with the epithelioid subtype having the best overall survival. Often, the treatment is multimodality with surgery, chemotherapy, and radiation. The survival benefit is improved but remains marginal. New treatment options involving targeted immune therapies appear to offer some promise. The tumor microenvironment is the ecosystem within the tumor that interacts and influences the host immune system. Understanding this complex interaction and how the host immune system is involved in the progression of the disease process is important to define and guide potential treatment options for this devastating and rare disease.}, }
@article {pmid36109807, year = {2022}, author = {Hoang, NTD and Hassan, G and Suehiro, T and Mine, Y and Matsuki, T and Fujii, M}, title = {BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {984}, pmid = {36109807}, issn = {1471-2407}, support = {16K15922//Japan Society for the Promotion of Science/ ; }, mesh = {Activins ; Animals ; Cell Proliferation/genetics ; *Connective Tissue Growth Factor/genetics ; Cyclin D3 ; Cyclin-Dependent Kinases ; Humans ; *Membrane Proteins/genetics ; *Mesothelioma, Malignant ; Mice ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive mesothelial cell cancer type linked mainly to asbestos inhalation. MM characterizes by rapid progression and resistance to standard therapeutic modalities such as surgery, chemotherapy, and radiotherapy. Our previous studies have suggested that tumor cell-derived connective tissue growth factor (CTGF) regulates the proliferation of MM cells as well as the tumor growth in mouse xenograft models.<br><br>METHODS: In this study, we knock downed the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and CTGF in MM cells and investigated the relationship between both and their impact on the cell cycle and cell proliferation.<br><br>RESULTS: The knockdown of CTGF or BAMBI reduced MM cell proliferation. In contrast to CTGF knockdown which decreased BAMBI, knockdown of BAMBI increased CTGF levels. Knockdown of either BAMBI or CTGF reduced expression of the cell cycle regulators; cyclin D3, cyclin-dependent kinase (CDK)2, and CDK4. Further, in silico analysis revealed that higher BAMBI expression was associated with shorter overall survival rates among MM patients.<br><br>CONCLUSIONS: Our findings suggest that BAMBI is regulated by CTGF promoting mesothelioma growth by driving cell cycle progression. Therefore, the crosstalk between BAMBI and CTGF may be an effective therapeutic target for MM treatment.}, }
@article {pmid36091141, year = {2022}, author = {Shi, H and Rath, EM and Lin, RCY and Sarun, KH and Clarke, CJ and McCaughan, BC and Ke, H and Linton, A and Lee, K and Klebe, S and Maitz, J and Song, K and Wang, Y and Kao, S and Cheng, YY}, title = {3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {973576}, pmid = {36091141}, issn = {2234-943X}, abstract = {Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics in vivo conditions and pathological conditions such as cancer. In comparison to biospecimens taken from in vivo tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma - an aggressive cancer with very limited effective treatment options. In this study, we examined the veracity of the 3D mesothelioma cell culture model to study cell-to-cell interaction, gene expression and drug response from 3D cell culture, and compared them to 2D cell and tumor samples. We confirmed via SEM analysis that 3D cells grown using the spheroid methods expressed highly interconnected cell-to-cell junctions. The 3D spheroids were revealed to be an improved mini-tumor model as indicated by the TEM visualization of cell junctions and microvilli, features not seen in the 2D models. Growing 3D cell models using decellularized lung scaffold provided a platform for cell growth and infiltration for all cell types including primary cell lines. The most time-effective method was growing cells in spheroids using low-adhesive U-bottom plates. However, not every cell type grew into a 3D model using the the other methods of hanging drop or poly-HEMA. Cells grown in 3D showed more resistance to chemotherapeutic drugs, exhibiting reduced apoptosis. 3D cells stained with H&amp;E showed cell-to-cell interactions and internal architecture that better represent that of in vivo patient tumors when compared to 2D cells. IHC staining revealed increased protein expression in 3D spheroids compared to 2D culture. Lastly, cells grown in 3D showed very different microRNA expression when compared to that of 2D counterparts. In conclusion, 3D cell models, regardless of which method is used. Showed a more realistic tumor microenvironment for architecture, gene expression and drug response, when compared to 2D cell models, and thus are superior preclinical cancer models.}, }
@article {pmid36077838, year = {2022}, author = {Trassl, L and Stathopoulos, GT}, title = {KRAS Pathway Alterations in Malignant Pleural Mesothelioma: An Underestimated Player.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077838}, issn = {2072-6694}, support = {Translational Research Project to GTS and LT//German Center for Lung Research/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, incurable cancer of the mesothelial cells lining the lungs and the chest wall that is mainly caused by asbestos inhalation. The molecular mechanisms of mesothelial carcinogenesis are still unclear despite comprehensive studies of the mutational landscape of MPM, and the most frequently mutated genes BAP1, NF2, CDKN2A, TP53, and TSC1 cannot cause MPM in mice in a standalone fashion. Although KRAS pathway alterations were sporadically detected in older studies employing targeted sequencing, they have been largely undetected by next generation sequencing. We recently identified KRAS mutations and copy number alterations in a significant proportion of MPM patients. Here, we review and analyze multiple human datasets and the published literature to show that, in addition to KRAS, multiple other genes of the KRAS pathway are perturbed in a significant proportion of patients with MPM.}, }
@article {pmid36077664, year = {2022}, author = {Ranzato, E and Bonsignore, G and Martinotti, S}, title = {ER Stress Response and Induction of Apoptosis in Malignant Pleural Mesothelioma: The Achilles Heel Targeted by the Anticancer Ruthenium Drug BOLD-100.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077664}, issn = {2072-6694}, abstract = {Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer is strongly related to asbestos exposure and shows a very inauspicious prognosis, because there are scarce therapeutic options for this rare disease. Thus, there is an urgent need to develop novel therapeutic approaches to treat this form of cancer. To explore the biology of malignant pleural mesothelioma (MPM), we previously observed that MPM cell lines show high expression of the GRP78 protein, which is a chaperone protein and the master regulator of the unfolded protein response (UPR) that resides in the endoplasmic reticulum (ER). Based on our previous studies showing the importance of GRP78 in MPM, we observed that BOLD-100, a specific modulator of GRP78 and the UPR, shows cytotoxicity against MPM cells. Our studies demonstrated that BOLD-100 increases ROS production and Ca[2+] release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM.}, }
@article {pmid36077483, year = {2022}, author = {Pietrofesa, RA and Chatterjee, S and Kadariya, Y and Testa, JR and Albelda, SM and Christofidou-Solomidou, M}, title = {Synthetic Secoisolariciresinol Diglucoside (LGM2605) Prevents Asbestos-Induced Inflammation and Genotoxic Cell Damage in Human Mesothelial Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077483}, issn = {1422-0067}, support = {1P30 ES013508-02/NH/NIH HHS/United States ; Office of the Vice Provost for Research//University of Pennsylvania School of Medicine/ ; NIH-R03 CA180548/NH/NIH HHS/United States ; 3P42ES023720-04S2/NH/NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos/toxicity ; Butylene Glycols ; Cytokines ; DNA Damage ; Glucosides ; *HMGB1 Protein ; Humans ; Inflammasomes ; Inflammation/pathology/prevention &amp; control ; Interleukin-18 ; Interleukin-6 ; Reactive Oxygen Species ; Tumor Necrosis Factor-alpha ; }, abstract = {Although alveolar macrophages play a critical role in malignant transformation of mesothelial cells following asbestos exposure, inflammatory and oxidative processes continue to occur in the mesothelial cells lining the pleura that may contribute to the carcinogenic process. Malignant transformation of mesothelial cells following asbestos exposure occurs over several decades; however, amelioration of DNA damage, inflammation, and cell injury may impede the carcinogenic process. We have shown in an in vitro model of asbestos-induced macrophage activation that synthetic secoisolariciresinol diglucoside (LGM2605), given preventively, reduced inflammatory cascades and oxidative/nitrosative cell damage. Therefore, it was hypothesized that LGM2605 could also be effective in reducing asbestos-induced activation and the damage of pleural mesothelial cells. LGM2605 treatment (50 µM) of huma n pleural mesothelial cells was initiated 4 h prior to exposure to asbestos (crocidolite, 20 µg/cm2). Supernatant and cells were evaluated at 0, 2, 4, and 8 h post asbestos exposure for reactive oxygen species (ROS) generation, DNA damage (oxidized guanine), inflammasome activation (caspase-1 activity) and associated pro-inflammatory cytokine release (IL-1β, IL-18, IL-6, TNFα, and HMGB1), and markers of oxidative stress (malondialdehyde (MDA) and 8-iso-prostaglandin F2a (8-iso-PGF2α). Asbestos induced a time-dependent ROS increase that was significantly (p < 0.0001) reduced (29.4%) by LGM2605 treatment. LGM2605 pretreatment also reduced levels of asbestos-induced DNA damage by 73.6% ± 1.0%. Although levels of inflammasome-activated cytokines, IL-1β and IL-18, reached 29.2 pg/mL ± 0.7 pg/mL and 43.9 pg/mL ± 0.8 pg/mL, respectively, LGM2605 treatment significantly (p < 0.0001) reduced cytokine levels comparable to baseline (non-asbestos exposed) values (3.8 pg/mL ± 0.2 pg/mL and 5.4 pg/mL ± 0.2 pg/mL, respectively). Furthermore, levels of IL-6 and TNFα in asbestos-exposed mesothelial cells were high (289.1 pg/mL ± 2.9 pg/mL and 511.3 pg/mL ± 10.2 pg/mL, respectively), while remaining undetectable with LGM2605 pretreatment. HMGB1 (a key inflammatory mediator and initiator of malignant transformation) release was reduced 75.3% ± 0.4% by LGM2605. Levels of MDA and 8-iso-PGF2α, markers of oxidative cell injury, were significantly (p < 0.001) reduced by 80.5% ± 0.1% and 76.6% ± 0.3%, respectively. LGM2605, given preventively, reduced ROS generation, DNA damage, and inflammasome-activated cytokine release and key inflammatory mediators implicated in asbestos-induced malignant transformation of normal mesothelial cells.}, }
@article {pmid36054746, year = {2022}, author = {Mai, HL and Deshayes, S and Nguyen, TV and Dehame, V and Chéné, AL and Brouard, S and Blanquart, C}, title = {IL-7 is expressed in malignant mesothelioma and has a prognostic value.}, journal = {Molecular oncology}, volume = {16}, number = {20}, pages = {3606-3619}, pmid = {36054746}, issn = {1878-0261}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/diagnosis ; *Pleural Neoplasms/genetics ; Interleukin-7 ; Prognosis ; *Asbestos ; *Lung Neoplasms/pathology ; Receptors, Interleukin-7 ; Biomarkers ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL-7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL-7R/IL-7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL-7R, IL-7 had no effect on their intracellular signaling. Accordingly, the addition of IL-7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumors was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL-7 concentration was not a good diagnostic biomarker. However, we observed that high IL-7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL-7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL-7R/IL-7 signaling pathway is not functional in MPM cells, IL-7 expression in PEs may have prognostic value in MPM patients.}, }
@article {pmid36039621, year = {2022}, author = {Kenchetty, PK and Balasundaram, S and Rao, K}, title = {An uncommon aetiology for a common clinical problem: Primary pericardial mesothelioma.}, journal = {The National medical journal of India}, volume = {35}, number = {1}, pages = {14-16}, doi = {10.25259/NMJI_273_20}, pmid = {36039621}, issn = {2583-150X}, mesh = {*Asbestos ; *Heart Neoplasms/complications/diagnostic imaging ; Humans ; Male ; *Mesothelioma/etiology/pathology/therapy ; Middle Aged ; Pericardium/diagnostic imaging/pathology ; *Peritoneal Neoplasms ; }, abstract = {Mesothelioma is a tumour arising from the mesothelial cells lining the pleura, pericardium, peritoneum, or the tunica vaginalis of testes. Primary pericardial mesothelioma is a rare tumour that can have varied manifestations and survival in patients with malignant pericardial tumours is generally dismal. The role of asbestos in pericardial mesotheliomas is less well established compared to that in pleural or peritoneal mesotheliomas. The prognosis is generally poor with the treatment options available. We present a middle-aged man with large pericardial effusion secondary to primary pericardial mesothelioma with no previous exposure to asbestos.}, }
@article {pmid36039211, year = {2022}, author = {Kerosky, ZP and Powell, CR and Lindholm, PC}, title = {Malignant Peritoneal Mesothelioma Presenting with High Protein, High Serum-Ascites Albumin Gradient.}, journal = {Cureus}, volume = {14}, number = {7}, pages = {e27286}, pmid = {36039211}, issn = {2168-8184}, abstract = {Mesothelioma is a difficult-to-detect neoplasm that rarely develops in the peritoneum. In patients with unexplained ascites, pleural fluid analysis and ultrasonography is often the first step to achieving a diagnosis. This case report shares a unique presentation in which a patient who presented with unexplained ascites, was initially thought to have cirrhosis but was later found to have malignant peritoneal mesothelioma after cross-sectional imaging and tissue acquisition. This case illustrates the importance of a high clinical index of suspicion for mesothelioma given its variety of clinical presentations, as well as the utility of early cross-sectional imaging in such cases.}, }
@article {pmid36012262, year = {2022}, author = {Setlai, BP and Mkhize-Kwitshana, ZL and Mehrotra, R and Mulaudzi, TV and Dlamini, Z}, title = {Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012262}, issn = {1422-0067}, mesh = {*Asbestos/adverse effects ; Epigenomics ; Humans ; Immunity ; *Lung Neoplasms/genetics ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Microbiota ; }, abstract = {Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome-epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.}, }
@article {pmid36000688, year = {2022}, author = {Gregório, PHP and Terra, RM and Lima, LP and Pêgo-Fernandes, PM}, title = {Mesothelioma in a developing country: a retrospective analysis of the diagnostic process.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {48}, number = {5}, pages = {e20220064}, pmid = {36000688}, issn = {1806-3756}, mesh = {*Asbestos/toxicity ; Developing Countries ; Humans ; *Lung Neoplasms/chemically induced/diagnosis/therapy ; *Mesothelioma/diagnosis/etiology/therapy ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/diagnosis/therapy ; Retrospective Studies ; }, abstract = {OBJECTIVE: To evaluate the process of diagnosing patients with malignant pleural mesothelioma (MPM) at a tertiary care hospital.<br><br>METHODS: This was a retrospective study involving patients referred to a tertiary-care cancer center in Brazil between 2009 and 2020. The diagnostic process was divided into four steps: onset of symptoms, referral to a specialist visit, histopathological diagnosis, and beginning of treatment. The intervals between each phase and the factors for delays were evaluated. Data including clinical status, radiological examinations, staging, treatment modalities, and survival outcomes were collected.<br><br>RESULTS: During the study period, 66 patients (mean age = 64 years) were diagnosed with MPM and underwent treatment. Only 27 (41%) of the patients had knowledge of prior exposure to asbestos. The median number of months (IQR) between the onset of symptoms and the first specialist visit, between the specialist visit and histopathological characterization, and between definite diagnosis and beginning of treatment was, respectively, 6.5 (2.0-11.4), 1.5 (0.6-2.1), and 1.7 (1.2-3.4). The knowledge of prior asbestos exposure was associated with a shorter time to referral to a specialist (median: 214 vs. 120 days; p = 0.04). A substantial number of nondiagnostic procedures and false-negative biopsy results (the majority of which involved the use of Cope needle biopsy) were found to be decisive factors for the length of waiting time. The mean overall survival was 11.9 months.<br><br>CONCLUSIONS: The unfamiliarity of health professionals with MPM and the patient's lack of knowledge of prior asbestos exposure were the major factors to cause a long time interval between the onset of symptoms and beginning of treatment. An overall survival shorter than 1 year is likely to have been due to the aforementioned delays.}, }
@article {pmid35987988, year = {2022}, author = {Muti, P and Sacconi, A and Pulito, C and Orlandi, G and Donzelli, S and Morrone, A and Jiulian, J and Cox, GP and Kolb, M and Pond, G and Kavsak, P and Levine, MN and Blandino, G and Strano, S}, title = {Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {41}, number = {1}, pages = {255}, pmid = {35987988}, issn = {1756-9966}, mesh = {*Asbestos/toxicity ; Biomarkers, Tumor ; *Cynara scolymus ; GPI-Linked Proteins/genetics ; Humans ; *Lung Neoplasms/etiology ; Male ; Mesothelin ; *Mesothelioma/drug therapy/genetics ; *Mesothelioma, Malignant ; *MicroRNAs/genetics ; *Pleural Neoplasms/drug therapy/genetics ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set.<br><br>METHODS: In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model.<br><br>RESULTS: We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants.<br><br>CONCLUSIONS: We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT02076672 . Registered 03/03/2014.}, }
@article {pmid35978837, year = {2022}, author = {Jiang, Z and Chen, J and Chen, J and Feng, L and Jin, M and Zhong, H and Ju, L and Zhu, L and Xiao, Y and Jia, Z and Xu, C and Yu, D and Zhang, X and Lou, J}, title = {Mortality due to respiratory system disease and lung cancer among female workers exposed to chrysotile in Eastern China: A cross-sectional study.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {928839}, pmid = {35978837}, issn = {2234-943X}, abstract = {Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (P trend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.}, }
@article {pmid35941734, year = {2022}, author = {Silvestri, S and Ciapini, C and Innocenti, A}, title = {Past Asbestos Exposure in Rolling Stock Manufacturing in the Absence of Environmental Monitoring: An Original Method.}, journal = {Journal of occupational and environmental medicine}, volume = {64}, number = {10}, pages = {e635-e640}, doi = {10.1097/JOM.0000000000002656}, pmid = {35941734}, issn = {1536-5948}, mesh = {*Asbestos ; Cohort Studies ; Environmental Monitoring ; Humans ; *Mesothelioma ; *Occupational Diseases ; *Occupational Exposure/adverse effects/analysis ; }, abstract = {OBJECTIVE: The aim of this study is the reconstruction of asbestos exposure in absence of environmental monitoring data, to use the results in a cohort study of railway rolling stock workers.<br><br>METHODS: To reconstruct past exposures, the production data (number of rolling stock and asbestos content) and working methods were reconstructed with former employees and company documentation, literature data, and author expertise.<br><br>RESULTS: The result of the work is a job/exposure matrix from 1956 to 1979, when sprayed asbestos was used as insulator of the metal bodies. Annual exposure estimate varies from 0.08 to 4.9 fb/mL depending on the specific jobs. Thirty-one mesotheliomas with occupational exposure, one with environmental and one with family exposures, were identified.<br><br>CONCLUSIONS: The originality of the study consists on the use of company production data to establish frequency duration of asbestos exposure.}, }
@article {pmid35940275, year = {2023}, author = {Chun, CP and Song, LX and Zhang, HP and Guo, DD and Xu, GX and Li, Y and Xin, X and Cao, J and Li, F}, title = {Malignant peritoneal mesothelioma.}, journal = {The American journal of the medical sciences}, volume = {365}, number = {1}, pages = {99-103}, doi = {10.1016/j.amjms.2022.07.008}, pmid = {35940275}, issn = {1538-2990}, mesh = {Male ; Humans ; Aged ; *Mesothelioma, Malignant/complications ; Ascites/diagnostic imaging/etiology ; *Mesothelioma/diagnosis/etiology/pathology ; *Asbestos/toxicity ; *Pleural Neoplasms/diagnosis ; *Peritoneal Neoplasms/diagnosis/etiology/pathology ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare, life-threatening malignant tumor. We present a report of a rare case of a 67-year-old male patient with MPM and severe abdominal pain, bloating, and bloody ascites as manifestations. The diagnosis was confirmed by cytology of ascites aspiration fluid and further verified by laparoscopic exploratory biopsy. The characteristics of signs and clinical manifestations in this case are less common. As everyone knows, asbestos exposure is usually associated with pleural mesothelioma, but only 6%-10% of malignant mesothelioma cases originate from the peritoneum, which is far less than pleural mesothelioma. Generally, its non-specificity provides a huge challenge to medical professionals in its diagnosis, and this is also the main reason for delayed diagnosis. Patients should be vigilant, even though no clear risk factor is observed.}, }
@article {pmid35937383, year = {2022}, author = {Shobana, M and Balasraswathi, VR and Radhika, R and Oleiwi, AK and Chaudhury, S and Ladkat, AS and Naved, M and Rahmani, AW}, title = {Classification and Detection of Mesothelioma Cancer Using Feature Selection-Enabled Machine Learning Technique.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {9900668}, pmid = {35937383}, issn = {2314-6141}, mesh = {Algorithms ; Bayes Theorem ; Humans ; *Machine Learning ; *Mesothelioma/classification/diagnosis ; Mesothelioma, Malignant/diagnosis ; Multiple Myeloma/diagnosis ; }, abstract = {Cancer of the mesothelium, sometimes referred to as malignant mesothelioma (MM), is an extremely uncommon form of the illness that almost always results in death. Chemotherapy, surgery, radiation therapy, and immunotherapy are all potential treatments for multiple myeloma; however, the majority of patients are identified with the disease at an advanced stage, at which time it is resistant to these therapies. After obtaining a diagnosis of advanced multiple myeloma, the average length of time that a person lives is one year after hearing this news. There is a substantial link between asbestos exposure and mesothelioma (MM). Using an approach that enables feature selection and machine learning, this article proposes a classification and detection method for mesothelioma cancer. The CFS correlation-based feature selection approach is first used in the feature selection process. It acts as a filter, selecting just the traits that are relevant to the categorization. The accuracy of the categorization model is improved as a direct consequence of this. After that, classification is carried out with the help of naive Bayes, fuzzy SVM, and the ID3 algorithm. Various metrics have been utilized during the process of measuring the effectiveness of machine learning strategies. It has been discovered that the choice of features has a substantial influence on the accuracy of the categorization.}, }
@article {pmid35931425, year = {2022}, author = {Røe, OD and Creaney, J and , }, title = {Response to "Revisiting 'BAP1ness' in Malignant Pleural Mesothelioma".}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {e69-e70}, doi = {10.1016/j.jtho.2022.05.013}, pmid = {35931425}, issn = {1556-1380}, mesh = {Humans ; *Lung Neoplasms/genetics/pathology ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; }, }
@article {pmid35931423, year = {2022}, author = {Yang, H and Gaudino, G and Bardelli, F and Carbone, M}, title = {Does the Amount of Asbestos Exposure Influence Prognosis?.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {949-952}, doi = {10.1016/j.jtho.2022.06.003}, pmid = {35931423}, issn = {1556-1380}, mesh = {*Asbestos/adverse effects ; Humans ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; *Occupational Exposure/adverse effects ; Prognosis ; }, }
@article {pmid35911327, year = {2022}, author = {Tachibana, M and Nozawa, M and Kamimura, K and Tsutsumi, Y}, title = {Synchronous Jejunal Sarcomatoid Carcinoma and Incidentally Associated Localized Peritoneal Malignant Mesothelioma.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e26270}, pmid = {35911327}, issn = {2168-8184}, abstract = {Sarcomatoid carcinoma (SCA) of the small bowel is a rare aggressive variant of small intestinal cancer accompanying a poor prognosis. The tumor primarily affects middle-aged and elderly patients. We report herein a 67-year-old Japanese male who manifested anemia. He had a history of asbestos exposure 30 years earlier. An abdominal computed tomography (CT) scan showed a 6.5-cm aneurysmal, dilated mass of the small intestine. Capsule endoscopy revealed a large circumferential hemorrhagic ulcerative lesion in the jejunum. Biopsy indicated sarcomatoid carcinoma, and partial resection of the small bowel and adjacent transverse colon and omentum was performed. In addition to the T3N0M0 jejunal giant sarcomatoid carcinoma (SCA), a 3-mm small localized peritoneal (omental) malignant mesothelioma (LMM) was also incidentally included. Synchronous presentation of small intestinal and mesothelial malignancies is extremely rare, and the avoidance of incorrect clinical staging is critically important. Surgical resection is still considered the best first-line therapy, because of a poor response to chemotherapy and radiotherapy. Dual-color fluorescent in situ hybridization (FISH) for p16/CDKN2A and chromosome 9 indicated homologous deletion of p16/CDKN2A in SCA and a normal pattern in LMM. Methylthioadenosine phosphorylase (MTAP) was negative in SCA but positive in LMM. Both tumors consistently expressed BRCA1-associated protein 1 (BAP1). Tumor necrosis factor receptor-associated factor 7 (TRAF7) was suppressed, and neural cell adhesion molecule L1 precursor (NCAML1/L1CAM) was agitated in both tumors. Diffuse and strong expression of programmed death-ligand 1 (PD-L1) and the association of tumor-infiltrating lymphocytes in SCA may indicate a potential for PD-L1-targeted immunotherapy for treating this type of aggressive cancer. PD-L1 was focally expressed in LMM. The postoperative course was uneventful for two years.}, }
@article {pmid35908620, year = {2022}, author = {Parvathaneni, V and Chilamakuri, R and Kulkarni, NS and Wang, X and Agarwal, S and Gupta, V}, title = {Repurposing clofazimine for malignant pleural mesothelioma treatment - In-vitro assessment of efficacy and mechanism of action.}, journal = {Life sciences}, volume = {306}, number = {}, pages = {120843}, doi = {10.1016/j.lfs.2022.120843}, pmid = {35908620}, issn = {1879-0631}, mesh = {*Antineoplastic Agents/pharmacology/therapeutic use ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Clofazimine/pharmacology/therapeutic use ; Drug Repositioning ; Humans ; *Lung Neoplasms/pathology ; *Mesothelioma/drug therapy/metabolism ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/metabolism/pathology ; beta Catenin ; }, abstract = {AIMS: Malignant pleural mesothelioma (MPM) is a rare cancer of lungs' pleural cavity, with minimally effective therapies available. Thus, there exists a necessity for drug repurposing which is an attractive strategy for drug development in MPM. Repurposing of an old FDA-approved anti-leprotic drug, Clofazimine (CFZ), presents an outstanding opportunity to explore its efficacy in treating MPM.<br><br>MAIN METHODS: Cytotoxicity, scratch assay, and clonogenic assays were employed to determine CFZ's ability to inhibit cell viability, cell migration, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of CFZ in MSTO-211H cell line. Gene expression analysis was performed using RT-qPCR assays to determine the CFZ's effect of key genes. Western blot studies were performed to determine CFZ's ability to induce apoptosis its effect to induce autophagy marker.<br><br>KEY FINDINGS: CFZ showed significant cytotoxicity against both immortalized and primary patient-derived cell lines with IC50 values ranging from 3.4&#xa0;&#x3bc;M (MSTO-211H) to 7.1&#xa0;&#x3bc;M (HAY). CFZ significantly impaired MPM cell cloning efficiency, migration, and tumor spheroid formation. 3D Spheroid model showed that CFZ resulted in reduction in spheroid volume. RT-qPCR data showed downregulation of genes &#x3b2;-catenin, BCL-9, and PRDX1; and upregulation of apoptosis markers such as PARP, Cleaved caspase 3, and AXIN2. Additionally, immunoblot analysis showed that CFZ down-regulates the expression of &#x3b2;-catenin (apoptosis induction) and up-regulates p62, LC3B protein II (autophagy inhibition).<br><br>SIGNIFICANCE: It can be concluded that CFZ could be a promising molecule to repurpose for MPM treatment which needs numerous efforts from further studies.}, }
@article {pmid35906513, year = {2022}, author = {Dubois, F and Bazille, C and Levallet, J and Maille, E and Brosseau, S and Madelaine, J and Bergot, E and Zalcman, G and Levallet, G}, title = {Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP.}, journal = {Targeted oncology}, volume = {17}, number = {4}, pages = {407-431}, pmid = {35906513}, issn = {1776-260X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Asbestos ; Bevacizumab/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy ; *Mesothelioma/drug therapy/pathology ; *Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; *Pleural Neoplasms/drug therapy/pathology ; }, abstract = {Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12-18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma's carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway's member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.}, }
@article {pmid35885614, year = {2022}, author = {Sculco, M and La Vecchia, M and Aspesi, A and Clavenna, MG and Salvo, M and Borgonovi, G and Pittaro, A and Witel, G and Napoli, F and Listì, A and Grosso, F and Libener, R and Maconi, A and Rena, O and Boldorini, R and Giachino, D and Bironzo, P and Maffè, A and Alì, G and Elefanti, L and Menin, C and Righi, L and Tampieri, C and Scagliotti, GV and Dianzani, C and Ferrante, D and Migliore, E and Magnani, C and Mirabelli, D and Matullo, G and Dianzani, I}, title = {Diagnostics of BAP1-Tumor Predisposition Syndrome by a Multitesting Approach: A Ten-Year-Long Experience.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35885614}, issn = {2075-4418}, support = {21390//Italian Association for Cancer Research/ ; 23760//Italian Association for Cancer Research/ ; //This research was funded by the offer of compensation to the inhabitants of Casale Monferrato deceased or affected by mesothelioma - HERMES (HEreditary Risk in MESothelioma)/ ; //The APC was funded by the Italian Ministry of Education, University and Research (MIUR) program &quot;Departments of Excellence 2018-2022&quot;, FOHN Project - Department of Health Sciences, Universit&#xe0; del Piemonte Orientale/ ; }, abstract = {Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of BAP1-TPDS, along with a clinical update and cascade genetic testing of previously reported BAP1-TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected BAP1-TPDS and validated pathogenic variants (PVs) by assessing BAP1 somatic loss in matching tumor specimens. Overall, we identified seven patients (7/101, 6.9%) carrying six different germline BAP1 PVs, including one novel variant. Consistently, cascade testing revealed a total of seven BAP1 PV carriers. In addition, we explored the mutational burden of BAP1-TPDS tumors by targeted next-generation sequencing. Lastly, we found that certain tumors present in PV carriers retain a wild-type BAP1 allele, suggesting a sporadic origin of these tumors or a functional role of heterozygous BAP1 in neoplastic development. Altogether, our findings have important clinical implications for therapeutic response of BAP1-TPDS patients.}, }
@article {pmid35883451, year = {2022}, author = {Pandey, SK and Machlof-Cohen, R and Santhanam, M and Shteinfer-Kuzmine, A and Shoshan-Barmatz, V}, title = {Silencing VDAC1 to Treat Mesothelioma Cancer: Tumor Reprograming and Altering Tumor Hallmarks.}, journal = {Biomolecules}, volume = {12}, number = {7}, pages = {}, pmid = {35883451}, issn = {2218-273X}, mesh = {Animals ; Apoptosis ; Humans ; Inflammation ; *Mesothelioma/genetics/therapy ; Mice ; *Nanotubes, Carbon ; RNA, Small Interfering/metabolism ; Tumor Microenvironment ; Voltage-Dependent Anion Channel 1/genetics/metabolism ; }, abstract = {Mesothelioma, an aggressive cancer with a poor prognosis, is linked to asbestos exposure. However, carbon nanotubes found in materials we are exposed to daily can cause mesothelioma cancer. Cancer cells reprogram their metabolism to support increased biosynthetic and energy demands required for their growth and motility. Here, we examined the effects of silencing the expression of the voltage-dependent anion channel 1 (VDAC1), controlling the metabolic and energetic crosstalk between mitochondria and the rest of the cell. We demonstrate that VDAC1 is overexpressed in mesothelioma patients; its levels increase with disease stage and are associated with low survival rates. Silencing VDAC1 expression using a specific siRNA identifying both mouse and human VDAC1 (si-m/hVDAC1-B) inhibits cell proliferation of mesothelioma cancer cells. Treatment of xenografts of human-derived H226 cells or mouse-derived AB1 cells with si-m/hVDAC1-B inhibited tumor growth and caused metabolism reprogramming, as reflected in the decreased expression of metabolism-related proteins, including glycolytic and tricarboxylic acid (-)cycle enzymes and the ATP-synthesizing enzyme. In addition, tumors depleted of VDAC1 showed altered microenvironments and inflammation, both associated with cancer progression. Finally, tumor VDAC1 silencing also eliminated cancer stem cells and induced cell differentiation to normal-like cells. The results show that silencing VDAC1 expression leads to reprogrammed metabolism and to multiple effects from tumor growth inhibition to modulation of the tumor microenvironment and inflammation, inducing differentiation of malignant cells. Thus, silencing VDAC1 is a potential therapeutic approach to treating mesothelioma.}, }
@article {pmid35880098, year = {2022}, author = {Di Marzio, N and Ananthanarayanan, P and Guex, AG and Alini, M and Riganti, C and Serra, T}, title = {Sound-based assembly of a microcapillary network in a saturn-like tumor model for drug testing.}, journal = {Materials today. Bio}, volume = {16}, number = {}, pages = {100357}, pmid = {35880098}, issn = {2590-0064}, abstract = {The tumor microenvironment (TME), consisting of extracellular matrix, proteins, stromal cells, and a vascular system, is reported to have a key role in cancer progression and prognosis. Thereby, the interaction between the vascular network and tumor mass is an important feature of the TME since the anticancer agents which are delivered to the TME can trigger the vascular response and influence the therapeutic outcome of the treatment. To identify and develop new therapeutic strategies, 3D in vitro models that recapitulate the complexity of the TME are urgently needed. Among them, vascularized tumor models are a promising approach, allowing to target tumor angiogenesis and reduce tumor growth. By using sound patterning, cells can be condensed locally into highly reproducible patterns through the action of mild hydrodynamic forces. Here, we use a soundwave-driven cell assembly approach to create a ring-shaped microcapillary network in fibrin hydrogel. Then, we generate a 3D vascularized tumor model by combining a tumor heterotypic spheroid, consisting of fibroblasts and Malignant Pleural Mesothelioma (MPM) cells, with the surrounding vascular ring. Based on its shape, we name it Saturn-like vascularized Tumor Model (STM). The growth of the microcapillary network is monitored over time by fluorescence imaging. The area covered by the microcapillary network, and its continuous increase in presence of the heterotypic tumor spheroid was monitored. Interestingly, this effect is enhanced when treating the STM with the anticancer agent Cisplatin. Overall, we show the use of sound patterning as a fast and cell-friendly approach to spatially organize and condense cells, to generate a 3D in vitro platform from which simple readouts of drug tests can be extracted by image analysis, with the potential to provide a model system for tailored tumor therapy.}, }
@article {pmid35876593, year = {2022}, author = {Urban, M and Pelclová, D and Urban, P and Vít, M and Urban, P and Fenclová, Z}, title = {Asbestos danger in central Europe is not yet over - the situation in the Czech Republic.}, journal = {Central European journal of public health}, volume = {30}, number = {2}, pages = {67-73}, pmid = {35876593}, issn = {1210-7778}, mesh = {*Asbestos/toxicity ; Asbestosis/epidemiology ; Czech Republic/epidemiology ; Humans ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; Retrospective Studies ; }, abstract = {OBJECTIVES: In the Czech Republic, asbestos has been classified as a known human carcinogen since 1984. The use of asbestos-containing products was limited to scenarios where the use of other materials was not possible. Since 1997, the manufacture of asbestos materials has been forbidden, and in 1999, the import, manufacture and distribution of all types of asbestos fibres was legally banned by Act No. 157/1998 Coll. Although the use of asbestos is forbidden, the risk of exposure still exists given the ongoing demolition and reconstruction of buildings in which asbestos has been used. In addition, a novel risk has arisen through the quarrying of asbestos-containing aggregates and their subsequent use. The aim of this paper was to describe and evaluate asbestos in terms of history, legislation, current risk of occupational exposure and its health consequences in the Czech Republic over the last three decades.<br><br>METHODS: This retrospective descriptive study used the collected data on occupational exposure and occupational diseases. The counts of workers occupationally exposed to asbestos were obtained from the Registry of Work Categorization; the numbers and structure of occupational diseases caused by asbestos were taken from the Czech National Registry of Occupational Diseases. Data on the total number of mesothelioma cases recorded in the Czech National Cancer Registry was provided by the Institute of Health Information and Statistics of the Czech Republic.<br><br>RESULTS: A total of 13,112 subjects were registered as occupationally exposed to asbestos during the period 2001-2020. A total of 687 cases of asbestos-related occupational diseases were reported in the period 1991-2020 in the Czech Republic, comprising 178 cases of asbestosis, 250 cases of pleural hyalinosis, 168 cases of pleural or peritoneal mesothelioma, 90 cases of lung cancer, and one case of laryngeal cancer. The data from the Czech National Cancer Registry, available for a shorter period (1991-2018), reveal 1,389 cases of mesothelioma, of which only ~11% were recognised as occupational, despite the fact that the occupational causality of mesotheliomas is estimated to be up to 90% of mesotheliomas. Moreover, the latency of mesotheliomas since the last occupational exposure reached up to 50 years and this trend is still slightly increasing, unlike asbestosis, where a high cumulative dose of inhaled asbestos is needed. The real proportion of occupational lung cancers may obviously be even higher, especially in smokers, where occupational causes including asbestos are not suspected by most physicians.<br><br>CONCLUSION: Czech data on asbestos-related occupational diseases, especially cancers, are grossly underestimated, which is most apparent through the low proportion of mesotheliomas diagnosed as occupational. Asbestos materials in older buildings remained in situ and may represent a danger during reconstruction works. The current source of exposure appears to be quarrying of asbestos-containing aggregate and its subsequent use. Awareness of the professional community is therefore crucial, not only for the possibility of compensating those affected, but also for the early detection of the diseases through the dispensary of exposed persons.}, }
@article {pmid35874636, year = {2022}, author = {Mazzoni, E and Bononi, I and Rotondo, JC and Mazziotta, C and Libener, R and Guaschino, R and Gafà, R and Lanza, G and Martini, F and Tognon, M}, title = {Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {7249912}, pmid = {35874636}, issn = {1687-8450}, abstract = {Malignant pleural mesothelioma (MPM), a fatal tumor, is mainly linked to the asbestos exposure. It has been reported that together with the inhalation of asbestos fibers, other factors are involved in the MPM onset, including simian virus 40 (SV40). SV40, a polyomavirus with oncogenic potential, induces (i) in vitro the mesenchymal cell transformation, whereas (ii) in vivo the MPM onset in experimental animals. The association between MPM and SV40 in humans remains to be elucidated. Sera (n = 415) from MPM-affected patients (MPM cohort 1; n = 152) and healthy subjects (HSs, n = 263) were investigated for their immunoglobulin G (IgG) against simian virus 40 large tumor antigen (Tag), which is the transforming protein. Sera were investigated with an indirect enzyme-linked immunosorbent assay (ELISA) using two synthetic peptides from SV40 Tag protein. SV40 Tag protein was evaluated by immunohistochemical (IHC) staining on MPM samples (MPM cohort 2; n = 20). Formalin-fixed and paraffin-embedded (FFPE) samples were obtained from MPM patients unrelated to MPM serum donors. The proportion of sera, from MPM patients, showing antibodies against SV40 Tag (34%) was significantly higher compared to HSs (20%) (odds ratio 2.049, CI 95% 1.32-3.224; p=0.0026). Immunohistochemical staining (IHS) assays showed SV40 Tag expression in 8/20, 40% of MPM specimens. These results indicate that SV40 is linked to a large fraction of MPM. It is worth noting that the prevalence of SV40 Tag antibodies detected in sera from cohort 1 of MPM patients is similar to the prevalence of SV40 Tag found to be expressed in FFPE tissues from MPM cohort 2.}, }
@article {pmid35863303, year = {2022}, author = {Thives, LP and Ghisi, E and Thives Júnior, JJ and Vieira, AS}, title = {Is asbestos still a problem in the world? A current review.}, journal = {Journal of environmental management}, volume = {319}, number = {}, pages = {115716}, doi = {10.1016/j.jenvman.2022.115716}, pmid = {35863303}, issn = {1095-8630}, mesh = {*Asbestos ; Commerce ; Humans ; International Cooperation ; *Mesothelioma/epidemiology/etiology ; *Occupational Exposure ; }, abstract = {Asbestos has been used by automobile, construction, manufacturing, power, and chemical industries for many years due to its particular properties, i.e. high tensile strength, non-flammable, thermal and electrical resistance and stability, and chemical resistance. However, such a mineral causes harmful effects to human health, including different types of cancer (e.g., mesothelioma). As a result, the use of asbestos has been banned since the 1980s in many countries. Nonetheless, asbestos is still part of the daily life of the population as asbestos-containing materials (ACMs) are still present in many buildings constructed and renovated before the 1990s. This work aims to present a current literature review about asbestos. The literature review was composed mainly of research articles published in international journals from the medical and engineering disciplines to provide an overview of asbestos use effects reported in interdisciplinary areas. The literature review comprised asbestos characteristics and its relationship to the risks of human exposure, countries where asbestos use is permitted or banned, reducing asbestos in the built environment, and environmental impact due to use and disposal of asbestos. The main findings were that ACMs are still responsible for severe human diseases, particularly in areas where there is a lack of coordinated asbestos management plans, reduced awareness about asbestos health risks, or even a delay in the implementation of asbestos-ban. Such issues may be more prevailing in developing countries. The current research in many countries contemplates several methodologies and techniques to process ACMs into inert and recyclable materials. The identification and coordinated management of ACM hazardous waste is a significant challenge to be faced by countries, and its inadequate disposal causes severe risk of exposure to asbestos fibres. Based on this work, it was concluded that banning asbestos is indicated in all countries in the world.}, }
@article {pmid35859704, year = {2022}, author = {Kumar, N and Natrayan, L and Kasirajan, G and Kaliappan, S and Raj Kamal, MD and Patil, PP and Chewaka, MD}, title = {Development of Novel Bio-mulberry-Reinforced Polyacrylonitrile (PAN) Fibre Organic Brake Friction Composite Materials.}, journal = {Bioinorganic chemistry and applications}, volume = {2022}, number = {}, pages = {6426763}, pmid = {35859704}, issn = {1565-3633}, abstract = {Natural fibre reinforcement is used in important sectors such as medical, aerospace, automobile, and many other fields. Many articles have reported that natural fibre has the potential to replace synthetic fibres. Natural fibre reinforcement has given good results as a brake friction material. It has already been proven that asbestos causes lung cancer and mesothelioma in brakes. Many people died from the effects of asbestos. According to the World Health Organization's trending brake report, this material leads to serious health issues. This work is going on for the replacement of these materials. Mulberry fibre is a unique material, and PAN fibre is combined with mulberry fibre and used as a brake reinforcement material to replace Kevlar fibre. The brake pads were fabricated with the various wt% of mulberry fibres and PAN fibre [3-12%] with an equal ratio and aramid fibre [3-6%] in the hydraulic hind brake moulding machine. The mechanical, chemical, physical, tribological, and thermal properties were evaluated. MF-2 [6 wt%] mulberry-PAN-fibre-based brake pad composites have shown better results for ultimate shear strength and proof stress, tensile strength, compressive strength, and impact energy.}, }
@article {pmid35852497, year = {2022}, author = {Price, B}, title = {Projection of future numbers of mesothelioma cases in the US and the increasing prevalence of background cases: an update based on SEER data for 1975 through 2018.}, journal = {Critical reviews in toxicology}, volume = {52}, number = {4}, pages = {317-324}, doi = {10.1080/10408444.2022.2082919}, pmid = {35852497}, issn = {1547-6898}, mesh = {*Asbestos/toxicity ; Humans ; Incidence ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/epidemiology/etiology/pathology ; Prevalence ; }, abstract = {Historically, mesothelioma, which is almost exclusively a cancer of the pleura or peritoneum, has been referred to as a sentinel disease for asbestos exposure meaning that the disease is an epidemiologic marker for asbestos. This description of mesothelioma often has been misinterpreted to mean that the only risk factor for mesothelioma is asbestos. In addition to a few risk factors other than asbestos, in the US, background mesotheliomas, i.e. mesothelioma cases that are a consequence of spontaneous tumor formation, are the most prevalent number of cases after asbestos-associated cases.[1] My analysis of SEER data for 1973 through 2005 published in 2009 projected that around 2040 virtually all mesothelioma cases in the US will be background cases. The update here, which is based on the most current SEER data, 1975 through 2018, and the same methods used in 2009 shows that the pattern of mesothelioma incidence is unchanged. Further, in general agreement with the analysis published in 2009, after 2040 virtually all mesothelioma cases, currently estimated to be approximately 1600 per year, will be background cases.}, }
@article {pmid35840292, year = {2022}, author = {Henshall, C and Dawson, P and Rahman, N and Ball, H and Sundralingam, A and Shahidi, M and McKeown, E and Park, J and Walthall, H and Davey, Z}, title = {Understanding clinical decision-making in mesothelioma care: a mixed methods study.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35840292}, issn = {2052-4439}, mesh = {*COVID-19 ; Clinical Decision-Making ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; State Medicine ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is a rare, incurable cancer arising from previous asbestos exposure; patients have a poor prognosis, with a median survival rate of 8-14 months. Variation in mesothelioma clinical decision-making remains common with a lack of multidisciplinary knowledge sharing, leading to inconsistencies in treatment decisions. The study aimed to explore which factors impacted on clinicians' decision-making in mesothelioma care, with a view to optimising the mesothelioma care pathway.<br><br>METHODS: This mixed methods study consisted of documentary analysis of local and national guidelines, policies or documents pertaining to mesothelioma care pathways, secondary analysis of mesothelioma patient data, and interviews with clinicians attending lung cancer and/or mesothelioma-specific multidisciplinary team meetings. The study took place at three National Health Service trusts in England. Documentations relating to patients' treatment pathways were collated and reviewed qualitatively. Records of patients with mesothelioma were extracted from hospital patient records and data collected on diagnosis date, treatment, mortality rates, survival postdiagnosis, age and clinical care team. Data were statistically analysed. Interviews with clinicians explored influences on clinical decision-making, including challenges or barriers involved. Data were thematically analysed. The Strengthening the Reporting of Observational Studies in Epidemiology reporting checklist was used.<br><br>RESULTS: There were differences in the structure and delivery of mesothelioma treatment and care between trusts. Four main themes were identified: 'collaboration and communication', 'evidence base and knowledge', 'role of the clinician' and 'role of the patient'. Two cross-cutting themes relating to the role of the mesothelioma nurse specialist and the impact of COVID-19 were identified.<br><br>DISCUSSION: There is a need to review the structure of mesothelioma multidisciplinary team meetings to ensure patients are reviewed by clinicians with appropriate knowledge, expertise and understanding of how, why and when decisions should be made. There is a need for expert clinicians in mesothelioma care to promote an up-to-date evidence and knowledge base within the wider multidisciplinary team.}, }
@article {pmid35815188, year = {2022}, author = {Ma, GY and Shi, S and Wang, P and Wang, XG and Zhang, ZG}, title = {Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion.}, journal = {Biomedical reports}, volume = {17}, number = {2}, pages = {66}, pmid = {35815188}, issn = {2049-9442}, abstract = {The diagnostic value of the 9P21 gene determined using fluorescence in situ hybridization (FISH) combined with BRCA1-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) expression detection by immunohistochemistry, was investigated in serous effusion samples of malignant mesothelioma. A total of 70 serous disease samples with serous effusion were collected from June 2017 to June 2020. Following biopsy specimen pathological diagnosis, samples were divided into malignant mesothelioma and benign mesothelioma. Differential expression of BAP1 and MTAP genes were identified in mesothelioma and mesenchymal hyperplasia. The 9P21 gene fragment was lost in mesothelioma. The positive rates of FISH, BAP1 and MTAP in biopsy specimens were 98.00, 94.00 and 90.00%. The specificity of the three were 96.00, 85.71 and 77.27%, the sensitivity were 90.00, 95.92 and 93.75%, and the positive rate of the combined detection of the three was 93.33%. The positive rate of serous fluid samples detected by the three methods (9P21 FISH probe combined with BAP1 and MTAP expression detected immunohistochemically) was 96.00, 92.00 and 88.00%, the specificity were 90.00, 77.27 and 71.43%, the sensitivity was 96.00, 93.75 and 89.80%, and the positive rate of the three combined detections was 91.33%. It was demonstrated that there was a high consistency between serous fluid samples and biopsy samples. According to clinicopathological analysis, sex, age, lesion site, Ki67 had little association with the occurrence and development of malignant mesothelioma, while asbestos exposure history was closely associated to the occurrence of mesothelioma. A high level of BAP1 gene was positively associated with the prognosis of mesothelioma, while a high level of MTAP gene was negatively associated with the prognosis of mesothelioma (P<0.05). Therefore, 9P21 FISH probe combined with BAP1 and MTAP can be used as a new method for the detection of malignant mesothelioma, and provide an important basis for the early diagnosis of mesothelioma.}, }
@article {pmid35804954, year = {2022}, author = {Janssens, E and Schillebeeckx, E and Zwijsen, K and Raskin, J and Van Cleemput, J and Surmont, VF and Nackaerts, K and Marcq, E and van Meerbeeck, JP and Lamote, K}, title = {External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {14}, number = {13}, pages = {}, pmid = {35804954}, issn = {2072-6694}, support = {grants KOTK UA/2016/10710/1 and 'Emmanuel van der Schueren'//Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society/ ; }, abstract = {During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, we performed the first external validation of a VOC-based prediction model for MPM. The external validation cohort was prospectively recruited, consisting of 47 MPM patients and 76 asbestos-exposed (AEx) controls. The predictive performance of the previously developed model was assessed by determining the degree of agreement between the predicted and actual outcome of the participants (patient/control). Additionally, to optimise the performance, the model was updated by refitting it to the validation cohort. External validation revealed a poor performance of the original model as the accuracy was estimated at only 41%, indicating poor generalisability. However, subsequent updating of the model improved the differentiation between MPM patients and AEx controls significantly (73% accuracy, 92% sensitivity, and 92% negative predictive value), substantiating the validity of the original predictors. This updated model will be more generalisable to the target population and exhibits key characteristics of a potential screening test for MPM, which could significantly impact MPM management.}, }
@article {pmid35804881, year = {2022}, author = {Song, Y and Baxter, SS and Dai, L and Sanders, C and Burkett, S and Baugher, RN and Mellott, SD and Young, TB and Lawhorn, HE and Difilippantonio, S and Karim, B and Kadariya, Y and Pinto, LA and Testa, JR and Shoemaker, RH}, title = {Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability.}, journal = {Cancers}, volume = {14}, number = {13}, pages = {}, pmid = {35804881}, issn = {2072-6694}, support = {HHSN261201500003C/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; CA06927/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA148805/CA/NCI NIH HHS/United States ; }, abstract = {Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. We characterized an orthotopic model using MMe cells derived from Cdkn2a[+/-];Nf2[+/-] mice chronically injected with asbestos. These MMe cells were tumorigenic upon intraperitoneal injection. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting.}, }
@article {pmid35795882, year = {2022}, author = {Tanaka, T and Asakura, S and Hisamatsu, K and Fujimoto, N}, title = {Thrombocytopenia as an Immune-Related Adverse Event in Malignant Pleural Mesothelioma: A Case Report.}, journal = {JTO clinical and research reports}, volume = {3}, number = {7}, pages = {100351}, pmid = {35795882}, issn = {2666-3643}, abstract = {A 69-year-old man presented with a pulmonary opacity at a regular medical check-up. He had been exposed to asbestos in a chemical fiber manufacturing setting. Result of positron emission tomography with computed tomography (CT) revealed fluorodeoxyglucose accumulations along the right pleura in areas with multiple nodules and irregular pleural thickening. On the basis of analysis of a CT-guided needle biopsy result, he had been diagnosed with having epithelioid malignant pleural mesothelioma. He received neoadjuvant chemotherapy, and subsequently, a pleurectomy and decortication. After 6 months, malignant pleural mesothelioma recurred with multiple tumors in the pleural cavity. Nivolumab was administered as salvage immunotherapy. A CT scan result revealed marked tumor reduction; however, his platelet count was low (8000/μL), and he was diagnosed with having nivolumab-induced immune thrombocytopenia. Oral prednisone and thrombopoietin receptor agonist were delivered, and the platelet count improved; therefore, a sustained cycle of nivolumab was resumed. This case revealed that nivolumab could be readministered for continued antitumor effects, with careful management of immune-related adverse events.}, }
@article {pmid35785199, year = {2022}, author = {Kuryk, L and Rodella, G and Staniszewska, M and Pancer, KW and Wieczorek, M and Salmaso, S and Caliceti, P and Garofalo, M}, title = {Novel Insights Into Mesothelioma Therapy: Emerging Avenues and Future Prospects.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {916839}, pmid = {35785199}, issn = {2234-943X}, abstract = {Malignant mesothelioma is a rare and aggressive cancer that develops in the thin layer surrounding the mesothelium and is mainly caused by asbestos exposure. Despite improvements in patient prognosis with conventional cancer treatments, such as surgery, chemotherapy, and radiotherapy, there are still no curative treatment modalities for advanced disease. In recent years, new therapeutic avenues have been explored. Improved understanding of the mechanisms underlying the dynamic tumor interaction with the immune system has led to the development of immunotherapeutic approaches. Numerous recent clinical trials have shown a desire to develop more effective treatments that can be used to fight against the disease. Immune checkpoint inhibitors, oncolytic adenoviruses, and their combination represent a promising strategy that can be used to synergistically overcome immunosuppression in the mesothelioma tumor microenvironment. This review provides a synthesized overview of the current state of knowledge on new therapeutic options for mesothelioma with a focus on the results of clinical trials conducted in the field.}, }
@article {pmid35778611, year = {2022}, author = {Fennell, DA and Dulloo, S and Harber, J}, title = {Immunotherapy approaches for malignant pleural mesothelioma.}, journal = {Nature reviews. Clinical oncology}, volume = {19}, number = {9}, pages = {573-584}, pmid = {35778611}, issn = {1759-4782}, support = {21400/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; Immunotherapy/methods ; *Lung Neoplasms/drug therapy ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/pathology ; Tumor Microenvironment ; *Vaccines/therapeutic use ; }, abstract = {Over the past decade, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. In mesothelioma, a rare cancer with a dismal prognosis generally caused by exposure to asbestos, treatment with single or dual ICIs results in robust improvements in overall survival over previous standard-of-care therapies, both in the first-line and relapsed disease settings. Predictive biological features that underpin response to ICIs remain poorly understood; however, insights into the immune microenvironment and genomic landscape of mesothelioma as well as into their association with response or acquired resistance to ICIs are emerging. Several studies of rational combinations involving ICIs with either another ICI or a different agent are ongoing, with emerging evidence of synergistic antitumour activity. Non-ICI-based immunotherapies, such as peptide-based vaccines and mesothelin-targeted chimeric antigen receptor T cells, have demonstrated promising efficacy. Moreover, results from pivotal trials of dendritic cell vaccines and viral cytokine delivery, among others, are eagerly awaited. In this Review, we comprehensively summarize the key steps in the development of immunotherapies for mesothelioma, focusing on strategies that have led to randomized clinical evaluation and emerging predictors of response. We then forecast the future treatment opportunities that could arise from ongoing research.}, }
@article {pmid35748766, year = {2022}, author = {Locher, BN and Barresi, F and Kuhn, BK and Vrugt, B and Bopp, M and Dressel, H}, title = {Occupations and geographical distribution of mesothelioma in Switzerland 1989-2018 - record linkage of an asbestos-exposed population with the Swiss National Cohort.}, journal = {Swiss medical weekly}, volume = {152}, number = {}, pages = {w30164}, doi = {10.4414/smw.2022.w30164}, pmid = {35748766}, issn = {1424-3997}, mesh = {*Asbestos/toxicity ; Humans ; *Mesothelioma/epidemiology/etiology/pathology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; Occupations ; *Pleural Neoplasms/epidemiology/etiology/pathology ; Switzerland/epidemiology ; }, abstract = {OBJECTIVE: We investigated the possibility of linking the data of the Swiss Laboratory for Particle Analysis (Silag), a valuable but incomplete data source in the field of asbestos-related diseases, to the Swiss National Cohort (SNC). With the resulting comprehensive dataset, we intended to provide a source for further research in the field. We also conducted preliminary analyses of data focusing on occupations and regional distribution of malignant pleural mesothelioma cases.<br><br>METHODS: Data of asbestos-exposed individuals available from the Silag were anonymously linked with the SNC by means of deterministic record linkage. From this linkage, data on occupation classified according to the international standard classification of occupations (ISCO) as well as the canton of residence in Switzerland could be retrieved.<br><br>RESULTS: Of 838 eligible individuals from the Silag data, 788 (94.0%) could be linked to the SNC database, including 476 mesothelioma cases. In 340 cases of the latter, data on occupation and industries were available. Although the majority of them were blue-collar workers, a significant proportion (n = 44, 12.9%) had executive professions. The Canton of residence in 1990 was established in 430 of subjects with mesothelioma. A cluster could be identified in eastern Switzerland, especially in the canton of Glarus.<br><br>CONCLUSIONS: It was possible to link the datasets to a large extent thereby creating a data source for further research. Of note, the linkage provided data on occupation of a selection of mesothelioma cases in Switzerland.}, }
@article {pmid35743451, year = {2022}, author = {Nagamatsu, Y and Sakyo, Y and Barroga, E and Koni, R and Natori, Y and Miyashita, M}, title = {Depression and Complicated Grief, and Associated Factors, of Bereaved Family Members of Patients Who Died of Malignant Pleural Mesothelioma in Japan.}, journal = {Journal of clinical medicine}, volume = {11}, number = {12}, pages = {}, pmid = {35743451}, issn = {2077-0383}, support = {16H05579, and 21H03241//Japan Society for the Promotion of Science/ ; 210901-01//Grants-in-Aid from the Ministry of Health, Labor and Welfare, Japan,/ ; }, abstract = {OBJECTIVES: we investigated the prevalence and associated factors of depression and complicated grief (CG) among bereaved family members of malignant pleural mesothelioma (MPM) patients in Japan.<br><br>METHODS: Bereaved family members of MPM patients (n = 72) were surveyed. The Japanese version of the Patient Health Questionnaire-9 (PHQ-9) and the Japanese version of the Brief Grief Questionnaire (BGQ) were used to assess depression and complicated grief (CG), respectively. Socio-economic factors, anger toward asbestos, care satisfaction, achievement of good death, and quality of end-of-life care were assessed in relation to depression and CG.<br><br>RESULTS: In the family members of MPM patients, the frequencies of depression and CG were 19.4% and 15.3%, respectively. The bereaved family members who were not compensated by the asbestos-related health-damage relief system (p = 0.018) and who felt the financial impacts of the patient's MPM on the family (p = 0.006) had a higher likelihood of depression. The bereaved family members who were not satisfied with the care given when the patient became critical (p = 0.034), who were not compensated by the asbestos-related health-damage relief system (p = 0.020), who felt the financial impact of the patient's MPM on the family (p = 0.016), and whose deceased relative underwent surgery (p = 0.030) had a higher likelihood of CG.<br><br>CONCLUSIONS: For bereaved family members of MPM patients, routine screening for depression and CG and the provision of grief care are suggested. In addition, for family members of MPM patients, financial support, including the promotion of the asbestos-related health-damage relief system, and improved care for patients who undergo surgery and when patients become critical, are recommended.}, }
@article {pmid35743417, year = {2022}, author = {Bellini, A and Mazzarra, S and Sterrantino, S and Argnani, D and Stella, F}, title = {Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {11}, number = {12}, pages = {}, pmid = {35743417}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.}, }
@article {pmid35741021, year = {2022}, author = {Pellavio, G and Martinotti, S and Patrone, M and Ranzato, E and Laforenza, U}, title = {Aquaporin-6 May Increase the Resistance to Oxidative Stress of Malignant Pleural Mesothelioma Cells.}, journal = {Cells}, volume = {11}, number = {12}, pages = {}, pmid = {35741021}, issn = {2073-4409}, mesh = {Aquaporin 6/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; *Mesothelioma/diagnosis/drug therapy/genetics ; *Mesothelioma, Malignant ; Oxidative Stress ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural surface and is associated with previous asbestos exposure. The chemotherapy drug is one of the main treatments, but the median survival ranges from 8 to 14 months from diagnosis. The redox homeostasis of tumor cells should be carefully considered since elevated levels of ROS favor cancer cell progression (proliferation and migration), while a further elevation leads to ferroptosis. This study aims to analyze the functioning/role of aquaporins (AQPs) as a hydrogen peroxide (H2O2) channel in epithelial and biphasic MPM cell lines, as well as their possible involvement in chemotherapy drug resistance. Results show that AQP-3, -5, -6, -9, and -11 were expressed at mRNA and protein levels. AQP-6 was localized in the plasma membrane and intracellular structures. Compared to normal mesothelial cells, the water permeability of mesothelioma cells is not reduced by exogenous oxidative stress, but it is considerably increased by heat stress, making these cells resistant to ferroptosis. Functional experiments performed in mesothelioma cells silenced for aquaporin-6 revealed that it is responsible, at least in part, for the increase in H2O2 efflux caused by heat stress. Moreover, mesothelioma cells knocked down for AQP-6 showed a reduced proliferation compared to mock cells. Current findings suggest the major role of AQP-6 in providing mesothelioma cells with the ability to resist oxidative stress that underlies their resistance to chemotherapy drugs.}, }
@article {pmid35723508, year = {2022}, author = {Lee, JT and Mittal, DL and Warby, A and Kao, S and Dhillon, HM and Vardy, JL}, title = {Dying of mesothelioma: A qualitative exploration of caregiver experiences.}, journal = {European journal of cancer care}, volume = {31}, number = {5}, pages = {e13627}, pmid = {35723508}, issn = {1365-2354}, support = {//Dust Diseases Board NSW/ ; }, mesh = {Adaptation, Psychological ; *Bereavement ; Caregivers ; Humans ; *Mesothelioma/therapy ; Palliative Care ; Qualitative Research ; }, abstract = {OBJECTIVE: To explore the experience of family caregivers of people with mesothelioma with focus on end-of-life issues.<br><br>METHODS: A qualitative sub-study using semi-structured interviews and thematic analysis.<br><br>RESULTS: Fourteen caregivers were interviewed; 11 were bereaved. The overarching theme was the impact of patients' diagnosis, treatment and death on caregivers and families. Three main themes were identified: (i) information provision and decision-making; (ii) grief and bereavement; and (iii) involvement and timing of palliative care. Caregivers initially had minimal knowledge of mesothelioma and wanted more information. Prognostic uncertainty caused distress. Grief and bereavement sub-themes were (i) coping and personal priorities; (ii) reflections on dying; and (iii) reflections on care. Caregivers highlighted the importance of creating meaningful events, having hope, 'doing something' and support from family and external sources. Reflections on dying contrasted regret after a 'bad', often unexpected death, with 'good' deaths. Care was made difficult by challenges navigating the health system and perceived gaps. Caregivers reported late referral to palliative care.<br><br>CONCLUSION: Lack of information caused challenges for caregivers. Grief and bereavement outcomes varied and may have been adversely impacted by lack of engagement with palliative care. Integrated care with lung cancer coordinators and improved palliative care access may reduce caregiver burden.}, }
@article {pmid35717324, year = {2022}, author = {Migliore, E and Consonni, D and Peters, S and Vermeulen, RCH and Kromhout, H and Baldassarre, A and Cavone, D and Chellini, E and Magnani, C and Mensi, C and Merler, E and Musti, M and Marinaccio, A and Mirabelli, D}, title = {Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM).}, journal = {Environmental health : a global access science source}, volume = {21}, number = {1}, pages = {60}, pmid = {35717324}, issn = {1476-069X}, mesh = {*Asbestos ; Case-Control Studies ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/epidemiology/etiology ; *Occupational Exposure/adverse effects ; Occupations ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {BACKGROUND: The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases' exposures but cannot provide relative risk estimates.<br><br>OBJECTIVES: i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure-response relationship.<br><br>METHODS: A population-based mesothelioma case-control study was conducted in 2012-2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI).<br><br>RESULTS: Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR&#x2009;=&#x2009;3.43), manufacture of railroad equipment (OR&#x2009;=&#x2009;8.07), shipbuilding and repairing (OR&#x2009;=&#x2009;2.34), iron and steel mills (OR&#x2009;=&#x2009;2.15), and construction (OR&#x2009;=&#x2009;1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR&#x2009;=&#x2009;15.8, men; OR&#x2009;=&#x2009;8.80, women), possible occupational (OR&#x2009;=&#x2009;2.82, men; OR&#x2009;=&#x2009;3.70, women), sharing home with an exposed worker (OR&#x2009;=&#x2009;2.55, men; OR&#x2009;=&#x2009;10.3, women), residential (OR&#x2009;=&#x2009;2.14, men; OR&#x2009;=&#x2009;3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR&#x2009;=&#x2009;1.28, CI 1.16-1.42).<br><br>CONCLUSIONS: Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure-response relationship.}, }
@article {pmid35713639, year = {2022}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Miranda, RN and Raghav, KP and Fournier, KF and Ramalingam, P}, title = {Localized Malignant Peritoneal Mesothelioma (LMPeM) in Women: A Clinicopathologic Study of 18 Cases.}, journal = {The American journal of surgical pathology}, volume = {46}, number = {10}, pages = {1352-1363}, doi = {10.1097/PAS.0000000000001924}, pmid = {35713639}, issn = {1532-0979}, mesh = {Adult ; Aged ; *Asbestos/adverse effects ; Female ; Homozygote ; Humans ; *Mesothelioma ; *Mesothelioma, Malignant ; Middle Aged ; MutS Homolog 2 Protein ; *Peritoneal Neoplasms/genetics ; Sequence Deletion ; }, abstract = {Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients' median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.}, }
@article {pmid35703172, year = {2022}, author = {Bernstein, DM}, title = {The health effects of short fiber chrysotile and amphibole asbestos.}, journal = {Critical reviews in toxicology}, volume = {52}, number = {2}, pages = {89-112}, doi = {10.1080/10408444.2022.2056430}, pmid = {35703172}, issn = {1547-6898}, mesh = {*Asbestos ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung ; *Lung Neoplasms/epidemiology ; *Mesothelioma/epidemiology ; }, abstract = {The potential toxic effects of short chrysotile and amphibole asbestos fibers with lengths <5 to ∼10 µm have been debated over the years. This stems from the large database of epidemiology, toxicology, and in-vitro studies, each of which often provides different information in understanding and differentiating the effects of short fibers. The epidemiology studies in which the cancer potency estimates were based upon relatively high exposure concentrations provide a conservative assessment that shorter fibers would have little if any effect, especially under controlled exposure or environmental conditions that may occur today. The QSAR models have shown that fiber aspect ratio and Mg content are excellent predictors of cancer potency and that short fibers/particles of amphibole would have no effect. The studies of motor vehicle mechanics and in particular workers who serviced chrysotile containing brakes with the majority of the fibers being short provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma. Several inhalation toxicology studies clearly differentiated that short chrysotile and amphibole asbestos fibers did not produce a significant carcinogenic effect in the lung or pleural cavity. Because of dosing and lack of sensitivity to biosolubility, in vitro studies can be difficult to interpret; however, a number have differentiated short chrysotile and amphibole asbestos fibers from long fibers. Integral to understanding the importance of fiber length in determining possible health effects is an understanding of the biological and physiological function of the respiratory system. Short asbestos fibers, like innocuous dust, can be cleared through the tracheobronchial ciliated mucous transport, phagocytized by macrophages and cleared via the bronchial tree, and can also be removed through the lymphatic system. While the first two methods can remove them from the lung, with lymphatic transport through one-way valves, fibers are removed from the active area of the lung where the fiber-related disease has been shown to develop and can accumulate in lymphatic sumps and lymph nodes. While short asbestos fibers are present in most occupational or environmental exposures, the large body of studies strongly supports that they do not contribute to the health effects of asbestos exposure.}, }
@article {pmid35670855, year = {2022}, author = {Napoli, F and Rapa, I and Izzo, S and Rigutto, A and Libener, R and Riganti, C and Bironzo, P and Taulli, R and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Correction to: Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {481}, number = {2}, pages = {331}, doi = {10.1007/s00428-022-03355-y}, pmid = {35670855}, issn = {1432-2307}, }
@article {pmid35665561, year = {2022}, author = {Dermawan, JK and Torrence, D and Lee, CH and Villafania, L and Mullaney, KA and DiNapoli, S and Sukhadia, P and Benayed, R and Borsu, L and Agaram, NP and Nash, GM and Dickson, BC and Benhamida, J and Antonescu, CR}, title = {EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity.}, journal = {Genes, chromosomes &amp; cancer}, volume = {61}, number = {10}, pages = {592-602}, pmid = {35665561}, issn = {1098-2264}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; P50 CA217694/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Epigenesis, Genetic ; Epigenomics ; Female ; Humans ; Male ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Middle Aged ; *Peritoneal Neoplasms/genetics/pathology ; RNA-Binding Protein EWS/genetics ; YY1 Transcription Factor/genetics/metabolism ; Young Adult ; }, abstract = {Mesothelioma is a rare, aggressive malignant neoplasm of mesothelial origin. A small subset of peritoneal mesothelioma is driven by recurrent gene fusions, mostly EWSR1/FUS::ATF1 fusions, with predilection for young adults. To date, only two cases of mesothelioma harboring EWSR1::YY1 fusions have been described. We present three additional cases of EWSR1::YY1-fused peritoneal mesotheliomas, two localized and one diffuse, all occurring in the peritoneum of middle-aged adults (2 females and 1 male), and discovered incidentally by imaging or during surgery performed for unrelated reasons. None presented with symptoms or had a known history of asbestos exposure. All three cases were cellular epithelioid neoplasms with heterogeneous architectural patterns comprising mostly solid nests and sheets with variably papillary and trabecular areas against collagenous stroma. Cytologically, the cells were monomorphic, polygonal, epithelioid cells with dense eosinophilic cytoplasm and centrally located nuclei. Overt mitotic activity or tumor necrosis was absent. All cases showed strong diffuse immunoreactivity for pancytokeratin, CK7, and nuclear WT1, patchy to negative calretinin, retained BAP1 expression, and were negative for Ber-EP4 and MOC31. RNA-sequencing confirmed in-frame gene fusion transcripts involving EWSR1 exon 7/8 and YY1 exon 2/3. By unsupervised clustering analysis, the methylation profiles of EWSR1::YY1-fused mesotheliomas clustered similarly with EWSR1/FUS::ATF1-fused mesotheliomas and conventional mesotheliomas, suggesting a mesothelioma epigenetic signature. All three patients underwent surgical resection or cytoreductive surgery of the masses. On follow-up imaging, no recurrence or progression of disease was identified. Our findings suggest that EWSR1::YY1-fusion defines a small subset of peritoneal epithelioid mesothelioma in middle-aged adults without history of asbestos exposure.}, }
@article {pmid35664766, year = {2022}, author = {Usuda, K and Niida, Y and Ishikawa, M and Iwai, S and Yamagata, A and Iijima, Y and Motono, N and Yamada, S and Uramoto, H}, title = {Genomics of Tumor Origin and Characteristics for Adenocarcinoma and Malignant Pleural Mesothelioma: A Case Report.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {858094}, pmid = {35664766}, issn = {2234-943X}, abstract = {A female underwent a right middle lobectomy for a pulmonary adenocarcinoma (AD). She eventually died of a right malignant pleural mesothelioma (MPM; sarcomatoid type) 4 years and 7 months after the removal of the AD even though she did not have any history of asbestos exposure, smoking, or radiation exposure. Her chest CT revealed multiple pulmonary nodules and bilateral pleural effusion with a right pleural tumor directly invading into the abdominal cavity. The genomics of tumor origin and characteristics were examined for the AD and the MPM. As a result, 50 somatic variants were detected in the AD, and 29 somatic variants were detected in the MPM. The variants which were common in both the AD and the MPM were not present, which suggested that the AD and the MPM had occurred independently in different origins. The MPM had two driver oncogenes of TP53 and EP300, but the AD did not. Two driver oncogenes of TP53 and EP300 were hypothesized to make the MPM aggressive. The speed at which the MPM progressed without the patient having a history of asbestos exposure, smoking, or radiation exposure was alarming.}, }
@article {pmid35659582, year = {2022}, author = {Barbieri, PG and Consonni, D and Somigliana, A}, title = {Asbestos Lung Burden Does Not Predict Survival in Malignant Pleural Mesothelioma: A Necropsy-Based Study of 185 Cases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {1042-1049}, doi = {10.1016/j.jtho.2022.05.010}, pmid = {35659582}, issn = {1556-1380}, mesh = {*Asbestos ; Humans ; Italy/epidemiology ; Lung/pathology ; *Lung Neoplasms/pathology ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Occupational Exposure ; *Pleural Neoplasms/pathology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is an asbestos-related disease with poor survival. The prognostic role of histologic subtype is well established. Some studies (without a biological hypothesis) suggested that higher asbestos lung burden is associated with reduced survival.<br><br>METHODS: We selected subjects from two series of necropsies: residents in Brescia province (North-West Italy) and workers (or persons living with them) employed in the Monfalcone shipyards (North-East Italy). Asbestos fibers and asbestos bodies in lung samples were counted using a scanning electron and an optical microscope, respectively. Separately in the two series, we analyzed median survival time and fitted multivariable Cox regression models (adjusted for sex, period and age at diagnosis, and histopatholocical diagnosis) to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for three levels of asbestos fiber counts (reference: <1 million fibers/g of dry lung tissue).<br><br>RESULTS: We analyzed 185 necropsies, 83 in Brescia and 102 in Monfalcone. Despite a much higher lung burden in Monfalcone patients, median survival was slightly shorter in Brescia (8.3 mo) than in Monfalcone (10.2 mo). In Brescia, medium (1.0-9.9) and high (10+) fiber burden HRs were 0.91 (95% CI: 0.54-1.53) and 1.23 (95% CI: 0.41-3.70), respectively. In Monfalcone, the corresponding HRs were 1.18 (95% CI: 0.59-2.35) and 1.63 (95% CI: 0.77-3.45), respectively.<br><br>CONCLUSIONS: No relationship between asbestos lung burden and survival was found. Histologic subtype was the strongest prognostic determinant.}, }
@article {pmid35650101, year = {2022}, author = {Tomita, R and Nishijo, N and Hayama, T and Fujioka, T}, title = {Discrimination of Malignant Pleural Mesothelioma Cell Lines Using Amino Acid Metabolomics with HPLC.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {45}, number = {6}, pages = {724-729}, doi = {10.1248/bpb.b21-00972}, pmid = {35650101}, issn = {1347-5215}, mesh = {Amino Acids ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Humans ; *Mesothelioma/metabolism ; *Mesothelioma, Malignant ; Metabolomics ; *Pleural Neoplasms/diagnosis/metabolism/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a malignancy closely associated with asbestos exposure. Although early diagnosis provides a chance of effective treatment and better prognosis, invasive biopsy and cytological procedure are required for definitive diagnosis. In this study, we developed a method to differentiate between MPM and control cell lines, named "amino acid metabolomics," consisting in the assessment of the balance of their amino acid levels in the cell culture medium. Culture media of MESO-1 (MPM cell line) and Met-5A (control) cells were used in this study to evaluate amino acid levels using HPLC, following the fluorescence derivatization method. The time-dependent changes in amino acid levels were visualized on the score plot following principal component analysis, and the results revealed differential changes in amino acid levels between the two cell culture supernatants. A discriminative model based on linear discriminant analysis could distinguish MPM and control cells.}, }
@article {pmid35649637, year = {2022}, author = {Johnson, M and Allmark, P and Tod, A}, title = {Living beyond expectations: a qualitative study into the experience of long-term survivors with pleural mesothelioma and their carers.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35649637}, issn = {2052-4439}, mesh = {Caregivers ; Cross-Sectional Studies ; Humans ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Motivation ; Survivors ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is characterised by poor prognosis and limited treatment options. However, a minority of patients can survive well beyond these bleak estimates. Little is known about the specific experiences and needs of long-term survivors and families.<br><br>STUDY PURPOSE: The study aimed to gain in-depth understanding of the experiences of patients diagnosed with MPM 3 or more years, along with their main carer, and to determine the care and support needs of this group.<br><br>PARTICIPANTS AND SETTING: People diagnosed with MPM 3 or more years were recruited via asbestos and mesothelioma social media and support groups. Potential participants were asked to identify someone who acted as their main carer.<br><br>METHOD: The study employed a cross-sectional qualitative interview design. A topic guide aided a conversational interview style, conducted remotely and recorded. Patient and carer pairs were interviewed jointly when possible, but were given an option for separate interviews if preferred. Fifteen patients, with 14 identifying a main carer, consented to participation.<br><br>ANALYSIS: Recorded interviews were transcribed verbatim, and then anonymised by the interviewer. Framework analysis was used to analyse the data iteratively and to develop final themes.<br><br>FINDINGS: Three themes were developed. Participants 'Living beyond expectations' remained acutely aware that MPM was incurable, but developed a range of coping strategies. Periods of disease stability were punctuated with crises of progression or treatment ending, straining coping. 'Accessing treatment' was important for patients and carers, despite the associated challenges. They were aware options were limited, and actively sought new treatments and clinical trials. 'Support needs' were met by healthcare professionals, voluntary groups and social media networks.<br><br>CONCLUSIONS: Managing patients via regional MPM multidisciplinary teams, facilitating equal access to treatment and trials, could reduce patient and carer burden. Greater awareness and support around crisis points for this group could improve care.}, }
@article {pmid35642773, year = {2022}, author = {Taeger, D and Wichert, K and Lehnert, M and Casjens, S and Pesch, B and Weber, DG and Brüning, T and Johnen, G and Behrens, T}, title = {Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.}, journal = {American journal of industrial medicine}, volume = {65}, number = {8}, pages = {652-659}, doi = {10.1002/ajim.23401}, pmid = {35642773}, issn = {1097-0274}, mesh = {*Asbestos/adverse effects ; Humans ; Lung ; *Lung Neoplasms/chemically induced/etiology ; Male ; *Mesothelioma/chemically induced/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/chemically induced/etiology ; *Occupational Exposure/adverse effects ; *Pleural Diseases/chemically induced/etiology ; *Pleural Neoplasms/epidemiology/etiology ; Prospective Studies ; }, abstract = {BACKGROUND: Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases.<br><br>METHODS: Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI).<br><br>RESULTS: We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen.<br><br>CONCLUSIONS: Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.}, }
@article {pmid35637829, year = {2022}, author = {Rhazari, M and Moueqqit, O and Gartini, S and El Morabit, S and Diani, S and Aharmim, M and Thouil, A and Kouismi, H and El Bourkadi, JE}, title = {Unexplained Pleural Effusion Leads to the Revelation of a Malignant Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24478}, pmid = {35637829}, issn = {2168-8184}, abstract = {Malignant mesothelioma is a rare and aggressive cancer that usually affects subjects with prior asbestos exposure, a major risk factor that has been widely known as carcinogenic, and its use is now controlled if not banned in many areas of the world. Malignant mesothelioma originates from mesothelial surface cells covering the serous cavities, and the pleura is its most common site. Malignant pleural mesothelioma (MPM) typically presents with pleural effusion and chest wall pain with wide pleural thickening at radiological investigation. Although the histological examination along with immunohistochemistry helps yield the diagnosis, clinicians and experts face many challenges in diagnosing malignant mesothelioma not only due to the rarity of the disease but also due to the similarities that the disease share with other malignancies. Here, we report a case of a 55-year-old male patient with a history of chronic asbestos work exposure for 12 years who initially presented with unexplained pleural effusion and chest wall pain and was lost to follow-up but came back later with a worsening clinical state. This case is specially presented to raise awareness against cases of unexplained pleural effusion and chest pain.}, }
@article {pmid35637530, year = {2022}, author = {Creaney, J and Patch, AM and Addala, V and Sneddon, SA and Nones, K and Dick, IM and Lee, YCG and Newell, F and Rouse, EJ and Naeini, MM and Kondrashova, O and Lakis, V and Nakas, A and Waller, D and Sharkey, A and Mukhopadhyay, P and Kazakoff, SH and Koufariotis, LT and Davidson, AL and Ramarao-Milne, P and Holmes, O and Xu, Q and Leonard, C and Wood, S and Grimmond, SM and Bueno, R and Fennell, DA and Pearson, JV and Robinson, BW and Waddell, N}, title = {Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {58}, pmid = {35637530}, issn = {1756-994X}, mesh = {Genomics ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Pleural Neoplasms/genetics/pathology ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.<br><br>METHODS: We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study. This was combined with RNA-seq analysis to characterize the tumour immune environment.<br><br>RESULTS: The comprehensive genome analysis identified 12 driver genes, including new candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed SBS5/40 were dominant in 93% of samples, and defects in homologous recombination repair were infrequent in our cohort. The tumour immune environment contained high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immune suppressive environment. The expression of TGFB1 was associated with overall survival. A small subset of samples (less than 10%) had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a 'hot' immune environment independent of the somatic mutations.<br><br>CONCLUSIONS: We propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future.}, }
@article {pmid35636988, year = {2022}, author = {Porcel, JM}, title = {Pleural mesothelioma.}, journal = {Medicina clinica}, volume = {159}, number = {5}, pages = {240-247}, doi = {10.1016/j.medcli.2022.03.007}, pmid = {35636988}, issn = {1578-8989}, mesh = {Biomarkers, Tumor/metabolism ; Homozygote ; Humans ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/diagnosis/genetics/therapy ; *Mesothelioma/diagnosis/genetics/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/genetics/therapy ; Sequence Deletion ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {The diagnosis of diffuse pleural mesothelioma requires in most cases a pleural biopsy, performed either under imaging guidance (ultrasound or computed tomography) or thoracoscopy. Loss of BAP1 or MTAP expression (immunohistochemistry) and homozygous deletion of CDKN2A (fluorescence in situ hybridization) are the basic molecular markers for the diagnosis of mesothelioma. The histologic type and patient's performance status are the most important prognostic factors. Pleural effusion can be managed by the insertion of tunneled pleural catheters, either as a stand-alone measure (e.g., patients not amenable to multimodality therapy who have been diagnosed by pleural fluid cytology or image-guided biopsy) or combined with the administration of aerosolized talc during a diagnostic thoracoscopy. Immunotherapy is one of the front-line approaches in inoperable patients, particularly in biphasic or sarcomatous histologic varieties.}, }
@article {pmid35634282, year = {2022}, author = {Principe, N and Aston, WJ and Hope, DE and Tilsed, CM and Fisher, SA and Boon, L and Dick, IM and Chin, WL and McDonnell, AM and Nowak, AK and Lake, RA and Chee, J and Lesterhuis, WJ}, title = {Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {872295}, pmid = {35634282}, issn = {1664-3224}, mesh = {Animals ; CD8-Positive T-Lymphocytes ; Fluorouracil/therapeutic use ; Humans ; *Immune Checkpoint Inhibitors ; Mice ; *Neoplasms/therapy ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha/therapeutic use ; }, abstract = {Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB. We investigated 10 chemotherapies from the main canonical classes dosed at the clinically relevant maximum tolerated dose in combination with anti-CTLA-4/anti-PD-L1 ICB. We screened these chemo-immunotherapy combinations in two murine mesothelioma models from two different genetic backgrounds, and identified chemotherapies that produced additive, neutral or antagonistic effects when combined with ICB. Using flow cytometry and bulk RNAseq, we characterized the tumor immune milieu in additive chemo-immunotherapy combinations. 5-fluorouracil (5-FU) or cisplatin were additive when combined with ICB while vinorelbine and etoposide provided no additional benefit when combined with ICB. The combination of 5-FU with ICB augmented an inflammatory tumor microenvironment with markedly increased CD8[+] T cell activation and upregulation of IFNγ, TNFα and IL-1β signaling. The effective anti-tumor immune response of 5-FU chemo-immunotherapy was dependent on CD8[+] T cells but was unaffected when TNFα or IL-1β cytokine signaling pathways were blocked. Our study identified additive and non-additive chemotherapy/ICB combinations and suggests a possible role for increased inflammation in the tumor microenvironment as a basis for effective combination therapy.}, }
@article {pmid35602795, year = {2022}, author = {Shrestha, B and Handa, R and Poudel, B and Hingorani, R}, title = {Pericardial Mesothelioma Presenting as Constrictive Pericarditis.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24270}, pmid = {35602795}, issn = {2168-8184}, abstract = {This case report presents a 60-year-old gentleman with a significant smoking history and possible asbestos exposure who was referred to the emergency department for atrial fibrillation with a rapid ventricular rate and symptoms of heart failure. Labs showed normal brain natriuretic peptide and troponin I. His echocardiography finding suggested constrictive pericarditis with an ejection fraction of 60%. A computed tomography scan was concerning for a pericardial mass. Left and right heart catheterization hinted more toward constrictive physiology; however, some findings were concerning for restrictive physiology. Hence, cardiac magnetic resonance imaging was done, which established the diagnosis of constrictive pericarditis. Pericardiectomy was planned with a maze procedure for atrial fibrillation. However, a malignant neoplasm was seen on a frozen biopsy. Hence, surgery was limited to partial pericardiectomy, as the patient had advanced infiltrative neoplasm that had resulted in constrictive pericarditis. The final pathology report confirmed the diagnosis of malignant pericardial mesothelioma mixed type. Malignancy is usually diagnosed in an advanced stage, like in our case, due to nonspecific initial presentation. A literature review suggests that there is a lack of established consensus on treatment. The response to therapy also seems to be poor and results only in palliation of symptoms, with a median survival of six months from diagnosis despite optimum medical management.}, }
@article {pmid35582652, year = {2022}, author = {Mielgo-Rubio, X and Cardeña Gutiérrez, A and Sotelo Peña, V and Sánchez Becerra, MV and González López, AM and Rosero, A and Trujillo-Reyes, JC and Couñago, F}, title = {Tsunami of immunotherapy reaches mesothelioma.}, journal = {World journal of clinical oncology}, volume = {13}, number = {4}, pages = {267-275}, pmid = {35582652}, issn = {2218-4333}, abstract = {Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte-associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.}, }
@article {pmid35566667, year = {2022}, author = {Nagamatsu, Y and Sakyo, Y and Barroga, E and Koni, R and Natori, Y and Miyashita, M}, title = {Bereaved Family Members' Perspectives of Good Death and Quality of End-of-Life Care for Malignant Pleural Mesothelioma Patients: A Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {9}, pages = {}, pmid = {35566667}, issn = {2077-0383}, support = {16H05579//the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI)/ ; 16H05579//the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI)/ ; }, abstract = {OBJECTIVE: This study investigated whether malignant pleural mesothelioma (MPM) patients achieved good deaths and good quality of end-of-life care compared with other cancer patients from the perspective of bereaved family members in Japan.<br><br>METHODS: This cross-sectional study was part of a larger study on the achievement of good deaths of MPM patients and the bereavement of their family members. Bereaved family members of MPM patients in Japan (n = 72) were surveyed. The Good Death Inventory (GDI) was used to assess the achievement of good death. The short version of the Care Evaluation Scale (CES) version 2 was used to assess the quality of end-of-life care. The GDI and CES scores of MPM patients were compared with those of a Japanese cancer population from a previous study.<br><br>RESULTS: MPM patients failed to achieve good deaths. Only 12.5% of the MPM patients were free from physical pain. The GDI scores of most of the MPM patients were significantly lower than those of the Japanese cancer population. The CES scores indicated a significantly poorer quality of end-of-life care for the MPM patients than the Japanese cancer population. The total GDI and CES scores were correlated (r = 0.55).<br><br>CONCLUSIONS: The quality of end-of-life care for MPM patients remains poor. Moreover, MPM patients do not achieve good deaths from the perspective of their bereaved family members.}, }
@article {pmid35565374, year = {2022}, author = {Holzknecht, A and Illini, O and Hochmair, MJ and Krenbek, D and Setinek, U and Huemer, F and Bitterlich, E and Kaindl, C and Getman, V and Akan, A and Weber, M and Leobacher, G and Valipour, A and Mueller, MR and Watzka, SB}, title = {Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients.}, journal = {Cancers}, volume = {14}, number = {9}, pages = {}, pmid = {35565374}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients’ survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4−20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.}, }
@article {pmid35564776, year = {2022}, author = {Vidican, P and Perol, O and Fevotte, J and Fort, E and Treilleux, I and Belladame, E and Zavadil, J and Fervers, B and Charbotel, B}, title = {Frequency of Asbestos Exposure and Histological Subtype of Ovarian Carcinoma.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {9}, pages = {}, pmid = {35564776}, issn = {1660-4601}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Asbestos/toxicity ; *Carcinoma ; Carcinoma, Ovarian Epithelial ; Child ; Female ; Humans ; *Mesothelioma/epidemiology ; Middle Aged ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Ovarian Neoplasms/epidemiology ; }, abstract = {The International Agency for Research on Cancer established a causal link between asbestos exposure and ovarian cancer. However, the exposure frequency and histological characteristics of asbestos-associated ovarian cancers remain to be investigated in detail. This multicenter case-case study assessed the asbestos exposure in ovarian carcinoma (OC) patients, alongside its association with histological subtype. Women were recruited in four hospitals in Lyon, France. Histological reports were reviewed by a pathologist. Patient and family members' data were collected by phone-based questionnaires. Asbestos exposure was defined as direct (occupational and environmental) and indirect (via parents, partners, and children). An industrial hygienist assessed the probability and level of exposure. The 254 enrolled patients (mean age 60 years) reported having an average of 2.3 different jobs (mean working duration 29 years). The prevalence of direct and indirect asbestos exposure was 13% (mean exposure duration 11 years) and 46%, respectively. High-grade serous carcinoma accounted for 73% of all OCs and 82% of histological subtypes in women with direct exposure. After adjustment on a familial history of OC, no significant associations between asbestos exposure (direct and/or indirect) and high-grade serous carcinoma were found. Women with OC had a high prevalence of asbestos exposure. Establishing risk profiles, as reported here, is important in facilitating compensation for asbestos-related OCs and for the surveillance of women at risk.}, }
@article {pmid35559971, year = {2021}, author = {Murphy, F and Dekkers, S and Braakhuis, H and Ma-Hock, L and Johnston, H and Janer, G and di Cristo, L and Sabella, S and Jacobsen, NR and Oomen, AG and Haase, A and Fernandes, T and Stone, V}, title = {An integrated approach to testing and assessment of high aspect ratio nanomaterials and its application for grouping based on a common mesothelioma hazard.}, journal = {NanoImpact}, volume = {22}, number = {}, pages = {100314}, doi = {10.1016/j.impact.2021.100314}, pmid = {35559971}, issn = {2452-0748}, mesh = {*Asbestos/toxicity ; Humans ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; *Nanostructures/adverse effects ; Risk Assessment/methods ; }, abstract = {Here we describe the development of an Integrated Approach to Testing and Assessment (IATA) to support the grouping of different types (nanoforms; NFs) of High Aspect Ratio Nanomaterials (HARNs), based on their potential to cause mesothelioma. Hazards posed by the inhalation of HARNs are of particular concern as they exhibit physical characteristics similar to pathogenic asbestos fibres. The approach for grouping HARNs presented here is part of a framework to provide guidance and tools to group similar NFs and aims to reduce the need to assess toxicity on a case-by-case basis. The approach to grouping is hypothesis-driven, in which the hypothesis is based on scientific evidence linking critical physicochemical descriptors for NFs to defined fate/toxicokinetic and hazard outcomes. The HARN IATA prompts users to address relevant questions (at decision nodes; DNs) regarding the morphology, biopersistence and inflammatory potential of the HARNs under investigation to provide the necessary evidence to accept or reject the grouping hypothesis. Each DN in the IATA is addressed in a tiered manner, using data from simple in vitro or in silico methods in the lowest tier or from in vivo approaches in the highest tier. For these proposed methods we provide justification for the critical descriptors and thresholds that allow grouping decisions to be made. Application of the IATA allows the user to selectively identify HARNs which may pose a mesothelioma hazard, as demonstrated through a literature-based case study. By promoting the use of alternative, non-rodent approaches such as in silico modelling, in vitro and cell-free tests in the initial tiers, the IATA testing strategy streamlines information gathering at all stages of innovation through to regulatory risk assessment while reducing the ethical, time and economic burden of testing.}, }
@article {pmid35558518, year = {2022}, author = {Martens, M and Kreidl, F and Ehrhart, F and Jean, D and Mei, M and Mortensen, HM and Nash, A and Nymark, P and Evelo, CT and Cerciello, F}, title = {A Community-Driven, Openly Accessible Molecular Pathway Integrating Knowledge on Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {849640}, pmid = {35558518}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy mainly triggered by exposure to asbestos and characterized by complex biology. A significant body of knowledge has been generated over the decades by the research community which has improved our understanding of the disease toward prevention, diagnostic opportunities and new treatments. Omics technologies are opening for additional levels of information and hypotheses. Given the growing complexity and technological spread of biological knowledge in MPM, there is an increasing need for an integrating tool that may allow scientists to access the information and analyze data in a simple and interactive way. We envisioned that a platform to capture this widespread and fast-growing body of knowledge in a machine-readable and simple visual format together with tools for automated large-scale data analysis could be an important support for the work of the general scientist in MPM and for the community to share, critically discuss, distribute and eventually advance scientific results. Toward this goal, with the support of experts in the field and informed by existing literature, we have developed the first version of a molecular pathway model of MPM in the biological pathway database WikiPathways. This provides a visual and interactive overview of interactions and connections between the most central genes, proteins and molecular pathways known to be involved or altered in MPM. Currently, 455 unique genes and 247 interactions are included, derived after stringent manual curation of an initial 39 literature references. The pathway model provides a directly employable research tool with links to common databases and repositories for the exploration and the analysis of omics data. The resource is publicly available in the WikiPathways database (Wikipathways : WP5087) and continues to be under development and curation by the community, enabling the scientists in MPM to actively participate in the prioritization of shared biological knowledge.}, }
@article {pmid35552365, year = {2022}, author = {Mazurek, JM and Blackley, DJ and Weissman, DN}, title = {Malignant Mesothelioma Mortality in Women - United States, 1999-2020.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {71}, number = {19}, pages = {645-649}, pmid = {35552365}, issn = {1545-861X}, mesh = {*Asbestos/adverse effects ; Data Collection ; Female ; Humans ; Male ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; United States/epidemiology ; }, abstract = {Inhalation of asbestos fibers can cause malignant mesothelioma, a rapidly progressing and lethal cancer of the mesothelium, the thin layer of tissues surrounding internal organs in the chest and abdomen. Patients with malignant mesothelioma have a poor prognosis, with a median survival of 1 year from diagnosis. The estimated median interval from initial occupational asbestos exposure to death is 32 years (range = 13-70 years) (1). Occupational asbestos exposure is most often reported in men working in industries such as construction and manufacturing; however, women are also at risk for exposure to asbestos fibers, and limited data exist on longer-term trends in mesothelioma deaths among women. To characterize deaths associated with mesothelioma and temporal trends in mesothelioma mortality among women in the United States, CDC analyzed annual Multiple Cause of Death records from the National Vital Statistics System for 1999-2020, the most recent years for which complete data are available. The annual number of mesothelioma deaths among women increased significantly, from 489 in 1999 to 614 in 2020; however, the age-adjusted death rate per 1 million women declined significantly, from 4.83 in 1999 to 4.15 in 2020. The largest number of deaths was associated with the health care and social assistance industry (89; 15.7%) and homemaker occupation (129; 22.8%). Efforts to limit exposure to asbestos fibers, including among women, need to be maintained.}, }
@article {pmid35547634, year = {2022}, author = {Li, X and Wang, D and Liu, A and Hu, W and Sun, X}, title = {Epidemiological Characteristics of Occupational Cancers Reported - China, 2006-2020.}, journal = {China CDC weekly}, volume = {4}, number = {17}, pages = {370-373}, pmid = {35547634}, issn = {2096-7071}, abstract = {INTRODUCTION: Occupational cancers are a major threat to workers' health in China. The latest version of the Classification and Catalogue of the Occupational Diseases includes 11 occupational cancers. This study analyzed the epidemiological characteristics of occupational cancers in China reported to the National Occupational Disease Reporting System during 2006-2020.<br><br>METHODS: Occupational cancers reported during 2016-2020 were obtained from the National Occupational Disease Reporting System. Epidemiological characteristics were analyzed by year, region, industry, gender, age at diagnosis, and exposure duration to occupational hazards.<br><br>RESULTS: Overall, a total of 1,116 cases of occupational cancers were reported between 2006 and 2020. The main types reported were leukemia caused by benzene exposure (511, 45.79%), lung cancer caused by coke oven exhaust exposure (266, 23.84%), and lung cancer and mesothelioma caused by asbestos exposure (226, 20.25%). There were 6 provincial-level administrative divisions (PLADs) that had reported over 50 new cases in the last 15 years. Most cases (913, 81.18%) were distributed in the manufacturing industry. There were 870 (77.96%) male cases and 246 (22.04%) female cases. The average age at diagnosis of all reported cases was 51.91&#xb1;15.85 years, and the median exposure duration to occupational hazards was 12 (5.29-23.25) years.<br><br>CONCLUSIONS: There is a large discrepancy between the high morbidity of occupational cancers and a low number of cases diagnosed and reported cases. Occupational cancers in China may be underestimated, and comprehensive measures should be taken to improve the diagnosis and reporting of occupational cancers.}, }
@article {pmid35533249, year = {2022}, author = {Anobile, DP and Montenovo, G and Pecoraro, C and Franczak, M and Ait Iddouch, W and Peters, GJ and Riganti, C and Giovannetti, E}, title = {Splicing deregulation, microRNA and notch aberrations: fighting the three-headed dog to overcome drug resistance in malignant mesothelioma.}, journal = {Expert review of clinical pharmacology}, volume = {15}, number = {3}, pages = {305-322}, doi = {10.1080/17512433.2022.2074835}, pmid = {35533249}, issn = {1751-2441}, mesh = {Drug Resistance, Neoplasm/genetics ; Humans ; *Mesothelioma, Malignant/genetics ; *MicroRNAs/genetics ; Neoplasm Recurrence, Local ; Prognosis ; *RNA Splicing/genetics ; *Receptors, Notch/metabolism ; }, abstract = {INTRODUCTION: Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeutic targets.<br><br>AREAS COVERED: Chemoresistance is frequently elicited by microRNA (miRNA) alterations and splicing deregulations. Indeed, several miRNAs, such as miR-29c, have been shown to exert oncogenic or oncosuppressive activity. Alterations in the splicing machinery might also be involved in chemoresistance. Moreover, the Notch signaling pathway, often deregulated in MMe, plays a key role in cancer stem cells formation and self-renewal, leading to drug resistance and relapses.<br><br>EXPERT OPINION: The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.}, }
@article {pmid35524457, year = {2022}, author = {Almeida, GC and Santos, UP and Parente, YDM and Colares, PFB and Mizutani, RF and Bernardi, FDC and Terra, RM and Terra-Filho, M}, title = {Mesothelioma in situ with regressive malignant pleural effusion and an unexpected evolution: A case report.}, journal = {American journal of industrial medicine}, volume = {65}, number = {7}, pages = {620-623}, doi = {10.1002/ajim.23358}, pmid = {35524457}, issn = {1097-0274}, mesh = {Aged ; *Asbestos/toxicity ; Humans ; Male ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Pleural Effusion, Malignant/complications ; *Pleural Neoplasms/etiology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that originates from hyperplasia and metaplasia of the mesothelial cells that cover the pleural cavity. Previous exposure to asbestos is the main risk factor. Since MPM is often diagnosed at an advanced stage with rapid evolution and resistance to treatment, it is associated with an unfavorable outcome. Mesothelioma in situ (MIS) has been postulated as a preinvasive phase of MPM; however, its diagnostic criteria have been defined only recently. Diagnosis of MIS may represent an opportunity for early therapies with better results, but the optimal approach has not been defined thus far. Here, we report on a case of a 74-year-old man with right-sided pleural effusion and a previous history of occupational exposure to asbestos for 9 years who was diagnosed with MIS after a latency of 36 years. During follow-up, spontaneous disease regression was observed 5 months after the initial diagnosis; however, it recurred in the form of invasive epithelioid MPM. There is a paucity of literature on MIS and its evolution; however, our case provides relevant knowledge of this unusual behavior, which is important to define follow-up and therapeutic strategies for future cases.}, }
@article {pmid35501851, year = {2022}, author = {Malakoti, F and Targhazeh, N and Abadifard, E and Zarezadeh, R and Samemaleki, S and Asemi, Z and Younesi, S and Mohammadnejad, R and Hadi Hossini, S and Karimian, A and Alemi, F and Yousefi, B}, title = {DNA repair and damage pathways in mesothelioma development and therapy.}, journal = {Cancer cell international}, volume = {22}, number = {1}, pages = {176}, pmid = {35501851}, issn = {1475-2867}, abstract = {Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.}, }
@article {pmid35497939, year = {2022}, author = {Kambara, T and Amatya, VJ and Kushitani, K and Fujii, Y and Endo, I and Takeshima, Y}, title = {Downregulation of FTL decreases proliferation of malignant mesothelioma cells by inducing G1 cell cycle arrest.}, journal = {Oncology letters}, volume = {23}, number = {6}, pages = {174}, pmid = {35497939}, issn = {1792-1082}, abstract = {Pleural malignant mesothelioma is a malignant tumor with a poor prognosis that is strongly associated with asbestos exposure during its development. Because there is no adequate treatment for malignant mesothelioma, investigation of its molecular mechanism is important. The ferritin light chain (FTL) is a subunit of ferritin, and its high expression in malignant tumors, including malignant mesothelioma, has recently been reported; however, its role in malignant mesothelioma is unclear. The purpose of the present study was to clarify the function of FTL in malignant mesothelioma. The expression levels of FTL in malignant mesothelioma were examined using the Cancer Cell Line Encyclopedia database and our previous data. The short interfering (si)RNA against FTL was transfected into two mesothelioma cell lines, ACC-MESO-1 and CRL-5915, and functional analysis was performed. Expression of p21, p27, cyclin-dependent kinase 2 (CDK2) and phosphorylated retinoblastoma protein (pRb) associated with the cell cycle were examined as candidate genes associated with FTL. The expression levels of the FTL mRNA were higher in malignant mesothelioma compared with other tumors in the Cancer Cell Line Encyclopedia database, and among other genes in our previous study. Reverse transcription-quantitative PCR and western blotting demonstrated suppression of FTL expression in two cell lines transfected with FTL siRNA compared with cells transfected with negative control (NC) siRNA. In the two cell lines transfected with FTL siRNA, proliferation was significantly suppressed, and cell cycle arrest was observed in the G1 phase. The levels of p21 and p27 were increased, while those of CDK2 and pRb were decreased compared with NC. However, no significant differences in invasion and migration ability were revealed between FTL siRNA-transfected cells and NC. In conclusion, FTL may increase the proliferative capacity of malignant mesothelioma cells by affecting p21, p27, CDK2 and pRb, and promoting the cell cycle at the G1 phase.}, }
@article {pmid35489694, year = {2022}, author = {Louw, A and Panou, V and Szejniuk, WM and Meristoudis, C and Chai, SM and van Vliet, C and Lee, YCG and Dick, IM and Firth, T and Lynggaard, LA and Asghari, AB and Vyberg, M and Hansen, J and Creaney, J and Røe, OD}, title = {BAP1 Loss by Immunohistochemistry Predicts Improved Survival to First-Line Platinum and Pemetrexed Chemotherapy for Patients With Pleural Mesothelioma: A Validation Study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {7}, pages = {921-930}, doi = {10.1016/j.jtho.2022.04.008}, pmid = {35489694}, issn = {1556-1380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Australia/epidemiology ; Humans ; Immunohistochemistry ; *Lung Neoplasms/pathology ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; Platinum/therapeutic use ; *Pleural Neoplasms/pathology ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {INTRODUCTION: Pleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumor BAP1 status is a predictive biomarker for survival in patients receiving first-line combination platinum and pemetrexed therapy.<br><br>METHODS: PM cases (n&#xa0;= 114) from Aalborg, Denmark, were stained for BAP1 on tissue microarrays. Demographic, clinical, and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n&#xa0;= 234).<br><br>RESULTS: BAP1 loss was found in 62% and 60.3% of all Danish and Australian samples, respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histological subtype, performance status, age, sex, and treatment (hazard ratio&#xa0;= 2.49, p < 0.001, and 1.48, p&#xa0;= 0.01, respectively). First-line platinum and pemetrexed-treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 versus 7.3 mo, p < 0.001) and Australian cohorts (19.6 versus 11.1 mo, p < 0.01). Survival in patients with BAP1 retained and treated with platinum and pemetrexed was similar as in those with best supportive care. There was a higher OS in patients with best supportive care with BAP1 loss, but it was significant only in the Australian cohort (16.8 versus 8.3 mo, p < 0.01).<br><br>CONCLUSIONS: BAP1 is a predictive biomarker for survival after first-line combination platinum and pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumor is a promising clinical tool for treatment stratification.}, }
@article {pmid35472827, year = {2022}, author = {Maghin, F and Antonietti, A and Cerri, N and Lancini, LM and Maccarinelli, A and Manzoni, S and Restori, M and Rota, M and Ruffini, D and Verzeletti, A and Conti, A}, title = {Assessment protocol of mesothelioma and relevance of SEM-EDS analysis through a case studies of legal medicine of Brescia (Italy).}, journal = {Legal medicine (Tokyo, Japan)}, volume = {57}, number = {}, pages = {102076}, doi = {10.1016/j.legalmed.2022.102076}, pmid = {35472827}, issn = {1873-4162}, mesh = {*Asbestos/adverse effects ; Autopsy ; Humans ; Italy ; *Mesothelioma/chemistry/diagnosis/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/complications ; Retrospective Studies ; }, abstract = {INTRODUCTION: This study evaluates the assessment protocol that allows the correlation between the development of mesothelioma to a specific exposure, with particular focus on investigations with Scanning Electron Microscope with Energy Dispersion Spectroscopy.<br><br>METHODS: This retrospective study includes 80 subjects who died from mesothelioma in the period 2001-2019. A judicial autopsy was performed for each case to confirm cause of death and correlate the disease with specific asbestos exposure. In 28 cases investigations were carried out to determine the pulmonary load of the asbestos fibres and corpuscles in the lung tissue through microscopic investigations, in order to confirm the suspicion of occupational exposure.<br><br>RESULTS: Our data agree with the scientific literature reported, but it is interesting to underline how the present study uses a different systematic approach than others, which are mainly based on epidemiological and environmental studies without considering the lung content of fibres and corpuscles.<br><br>CONCLUSION: It would be desirable that the use of the microscopic analysis was introduced in the evaluation protocol: it should always be carried out if the suspicion of asbestos-related disease is raised and not only as a possible integration to the less expensive anamnestic evaluation, even more so if the work or personal history should be suggestive of exposure to asbestos fibres.}, }
@article {pmid35462085, year = {2022}, author = {Carbone, M and Pass, HI and Ak, G and Alexander, HR and Baas, P and Baumann, F and Blakely, AM and Bueno, R and Bzura, A and Cardillo, G and Churpek, JE and Dianzani, I and De Rienzo, A and Emi, M and Emri, S and Felley-Bosco, E and Fennell, DA and Flores, RM and Grosso, F and Hayward, NK and Hesdorffer, M and Hoang, CD and Johansson, PA and Kindler, HL and Kittaneh, M and Krausz, T and Mansfield, A and Metintas, M and Minaai, M and Mutti, L and Nielsen, M and O'Byrne, K and Opitz, I and Pastorino, S and Pentimalli, F and de Perrot, M and Pritchard, A and Ripley, RT and Robinson, B and Rusch, V and Taioli, E and Takinishi, Y and Tanji, M and Tsao, AS and Tuncer, AM and Walpole, S and Wolf, A and Yang, H and Yoshikawa, Y and Zolondick, A and Schrump, DS and Hassan, R}, title = {Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {7}, pages = {873-889}, pmid = {35462085}, issn = {1556-1380}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, mesh = {Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; *Lung Neoplasms/diagnosis/genetics/surgery ; *Melanoma/genetics ; *Mesothelioma/diagnosis/genetics/surgery ; *Mesothelioma, Malignant ; Quality of Life ; *Skin Neoplasms/genetics ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, substantial medical, social, and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life, and being cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges, and our recommendations of how to best care for these patients and their family members, including the potential economic and psychosocial impact.}, }
@article {pmid35461395, year = {2022}, author = {Napoli, F and Rapa, I and Izzo, S and Rigutto, A and Libener, R and Riganti, C and Bironzo, P and Taulli, R and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {481}, number = {2}, pages = {233-244}, pmid = {35461395}, issn = {1432-2307}, support = {IG 2019 - ID 23760//Associazione Italiana per la Ricerca sul Cancro/ ; GR-2011-02348356//Regione Piemonte/ ; }, mesh = {Cell Line, Tumor ; *Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; *Mesothelioma, Malignant/genetics/pathology ; *MicroRNAs/genetics ; *Pleural Neoplasms/genetics/pathology ; *Thymidylate Synthase/genetics/metabolism ; }, abstract = {The standard front-line treatment for pleural mesothelioma (PM) is pemetrexed-based chemotherapy, whose major target is thymidylate synthase (TS). In several cancer models, miR-215 and miR-375 have been shown to target TS, while information on these miRNAs in PM are still limited although suggest their role in epithelial to mesenchymal transition. Seventy-one consecutive PM tissues (4 biphasic, 7 sarcomatoid, and 60 epithelioid types) and 16 commercial and patient-derived PM cell lines were screened for TS, miR-215, and miR-375 expression. REN and 570B cells were selected for miR-215 and miR-375 transient transfections to test TS modulation. ZEB1 protein expression in tumor samples was also tested. Moreover, genetic profile was investigated by means of BAP1 and p53 immunohistochemistry. Expression of both miR-215 and miR-375 was significantly higher in epithelioid histotype. Furthermore, inverse correlation between TS protein and both miR-215 and miR-375 expression was found. Efficiently transfected REN and 570B cell lines overexpressing miR-215 and miR-375 showed decreased TS protein levels. Epithelioid PM with a mesenchymal component highlighted by reticulin stain showed significantly higher TS and ZEB1 protein and lower miRNA expression. A better survival was recorded for BAP1 lost/TS low cases. Our data indicate that miR-215 and miR-375 are involved in TS regulation as well as in epithelial-to-mesenchymal transition in PM.}, }
@article {pmid35443624, year = {2022}, author = {Ziółkowska, B and Cybulska-Stopa, B and Papantoniou, D and Suwiński, R}, title = {Systemic treatment in patients with malignant pleural mesothelioma - real life experience.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {432}, pmid = {35443624}, issn = {1471-2407}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Female ; Humans ; *Lung Neoplasms/pathology ; Male ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/therapeutic use ; *Pleural Neoplasms ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural cavity linked to asbestos exposure. The combination of pemetrexed and platinum is a standard first-line therapy for malignant pleural mesothelioma. Despite some progress, almost all MPM patients experience progression after first-line therapy. The second-line treatment is still being under discussion and there are very limited data available on the second-line and subsequent treatments.<br><br>METHODS: The retrospective analysis included 57 patients (16 females and 41 males) from two Polish oncological institutions treated for advanced mesothelioma between 2013 and 2019. We analysed the efficacy of first-line and second-line therapy: progression-free survival (PFS), overall survival (OS), overall response rate (ORR).<br><br>RESULTS: In the first-line treatment, 55 patients received pemetrexed-based chemotherapy (PBC) and two cisplatin in monotherapy. Patients' characteristics at baseline: median age was 64.2&#xa0;years, ECOG PS&#x2009;&#x2264;&#x2009;1 (86.2%), epithelial histology (85.7%). Median PFS and OS were 7.6&#xa0;months and 14&#xa0;months, respectively. Patients with ECOG PS&#x2009;&#x2264;&#x2009;1 vs&#x2009;>&#x2009;1 had a longer median OS (14.8&#xa0;months vs 9.7&#xa0;months, p&#x2009;=&#x2009;0.057). One-year OS and PFS were 60.9% and 32.0%, respectively. Disease control rate (DCR) was 82.5%. Response to first-line therapy: PFS&#x2009;&#x2265;&#x2009;6&#xa0;months and PFS&#x2009;&#x2265;&#x2009;12&#xa0;months had a significant impact on median OS. Twelve patients received second-line therapy (seven PBC and five other cytotoxic single agents: navelbine, gemcitabine, or adriamycin/vincristine/methotrexate triplet).&#xa0;Median PFS and OS were 3.7&#xa0;months and 7.2&#xa0;months, respectively. DCR was 83%. One-year OS and PFS were 37% and 16.7%, respectively. In the group receiving PBC, OS was prolonged by 4.5&#xa0;months compared to the non-PBC group (6.0&#xa0;months vs 10.5&#xa0;months, p&#x2009;=&#x2009;0.47).<br><br>CONCLUSION: Patients who benefited from first-line therapy and had prolonged PFS at first-line and achieve PFS longer than 6&#xa0;months at first-line should be offered second-line treatment. Consideration of retreatment with the same cytotoxic agent could to be a viable option when no other treatment are available.}, }
@article {pmid35439870, year = {2022}, author = {Jin, MY and Jiang, ZQ}, title = {[Research progress on the role of lncRNA in the occurrence and development of malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {40}, number = {3}, pages = {231-235}, doi = {10.3760/cma.j.cn121094-20210413-00205}, pmid = {35439870}, issn = {1001-9391}, support = {2019RC142//Zhejiang Medical and Health Science and Technology Program/ ; 11-ZC02//Zhejiang Medical Support Discipline Labor Hygiene/ ; KYYB202113//Basic Scientific Research Projects of Hangzhou Medical College/ ; }, mesh = {*Asbestos ; Epigenesis, Genetic ; Humans ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Prognosis ; *RNA, Long Noncoding/genetics ; }, abstract = {Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.}, }
@article {pmid35431929, year = {2022}, author = {Robinson, BWS and Redwood, AJ and Creaney, J}, title = {How Our Continuing Studies of the Pre-clinical Inbred Mouse Models of Mesothelioma Have Influenced the Development of New Therapies.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {858557}, pmid = {35431929}, issn = {1663-9812}, abstract = {Asbestos-induced preclinical mouse models of mesothelioma produce tumors that are very similar to those that develop in humans and thus represent an ideal platform to study this rare, universally fatal tumor type. Our team and a number of other research groups have established such models as a stepping stone to new treatments, including chemotherapy, immunotherapy and other approaches that have been/are being translated into clinical trials. In some cases this work has led to changes in mesothelioma treatment practice and over the last 30 years these models and studies have led to trials which have improved the response rate in mesothelioma from less than 10% to over 50%. Mouse models have had a vital role in that improvement and will continue to play a key role in the future success of mesothelioma immunotherapy. In this review we focus only on these original inbred mouse models, the large number of preclinical studies conducted using them and their contribution to current and future clinical therapy for mesothelioma.}, }
@article {pmid35410957, year = {2023}, author = {Dawson, AG and Kutywayo, K and Mohammed, SB and Fennell, DA and Nakas, A}, title = {Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review.}, journal = {Thorax}, volume = {78}, number = {4}, pages = {409-417}, doi = {10.1136/thoraxjnl-2021-218214}, pmid = {35410957}, issn = {1468-3296}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/surgery ; Cisplatin/therapeutic use ; Cytoreduction Surgical Procedures ; *Pleural Neoplasms/drug therapy/surgery ; Combined Modality Therapy ; }, abstract = {INTRODUCTION: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval.<br><br>METHODS: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed.<br><br>RESULTS: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications.<br><br>CONCLUSION: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose.<br><br>PROSPERO REGISTRATION NUMBER: CRD42019129002.}, }
@article {pmid35409711, year = {2022}, author = {Berry, TA and Belluso, E and Vigliaturo, R and Gieré, R and Emmett, EA and Testa, JR and Steinhorn, G and Wallis, SL}, title = {Asbestos and Other Hazardous Fibrous Minerals: Potential Exposure Pathways and Associated Health Risks.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {7}, pages = {}, pmid = {35409711}, issn = {1660-4601}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos/toxicity ; *Asbestosis/epidemiology ; Carcinogens/toxicity ; Humans ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Zeolites ; }, abstract = {There are six elongate mineral particles (EMPs) corresponding to specific dimensional and morphological criteria, known as asbestos. Responsible for health issues including asbestosis, and malignant mesothelioma, asbestos has been well researched. Despite this, significant exposure continues to occur throughout the world, potentially affecting 125 million people in the workplace and causing thousands of deaths annually from exposure in homes. However, there are other EMPS, such as fibrous/asbestiform erionite, that are classified as carcinogens and have been linked to cancers in areas where it has been incorporated into local building materials or released into the environment through earthmoving activities. Erionite is a more potent carcinogen than asbestos but as it is seldom used for commercial purposes, exposure pathways have been less well studied. Despite the apparent similarities between asbestos and fibrous erionite, their health risks and exposure pathways are quite different. This article examines the hazards presented by EMPs with a particular focus on fibrous erionite. It includes a discussion of the global locations of erionite and similar hazardous minerals, a comparison of the multiple exposure pathways for asbestos and fibrous erionite, a brief discussion of the confusing nomenclature associated with EMPs, and considerations of increasing global mesothelioma cases.}, }
@article {pmid35409322, year = {2022}, author = {Henzi, T and Diep, KL and Oberson, A and Salicio, V and Bochet, CG and Schwaller, B}, title = {Forchlorfenuron and Novel Analogs Cause Cytotoxic Effects in Untreated and Cisplatin-Resistant Malignant Mesothelioma-Derived Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409322}, issn = {1422-0067}, mesh = {Animals ; *Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cisplatin/metabolism/pharmacology ; Halogens/metabolism ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; Mice ; Phenylurea Compounds/pharmacology ; Pyridines ; Septins/metabolism ; }, abstract = {Malignant mesothelioma (MM) is a currently incurable, aggressive cancer derived from mesothelial cells, most often resulting from asbestos exposure. The current first-line treatment in unresectable MM is cisplatin/pemetrexed, which shows very little long-term effectiveness, necessitating research for novel therapeutic interventions. The existing chemotherapies often act on the cytoskeleton, including actin filaments and microtubules, but recent advances indicate the 'fourth' form consisting of the family of septins, representing a novel target. The septin inhibitor forchlorfenuron (FCF) and FCF analogs inhibit MM cell growth in vitro, but at concentrations which are too high for clinical applications. Based on the reported requirement of the chloride group in the 2-position of the pyridine ring of FCF for MM cell growth inhibition and cytotoxicity, we systematically investigated the importance (cell growth-inhibiting capacity) of the halogen atoms fluorine, chlorine, bromine and iodine in the 2- or 3-position of the pyridine ring. The MM cell lines ZL55, MSTO-211H, and SPC212, and-as a control-immortalized Met-5A mesothelial cells were used. The potency of the various halogen substitutions in FCF was mostly correlated with the atom size (covalent radius); the small fluoride analogs showed the least effect, while the largest one (iodide) most strongly decreased the MTT signals, in particular in MM cells derived from epithelioid MM. In the latter, the strongest effects in vitro were exerted by the 2-iodo and, unexpectedly, the 2-trifluoromethyl (2-CF3) FCF analogs, which were further tested in vivo in mice. However, FCF-2-I and, more strongly, FCF-2-CF3 caused rapidly occurring strong symptoms of systemic toxicity at doses lower than those previously obtained with FCF. Thus, we investigated the effectiveness of FCF (and selected analogs) in vitro in MM cells which were first exposed to cisplatin. The slowly appearing population of cisplatin-resistant cells was still susceptible to the growth-inhibiting/cytotoxic effect of FCF and its analogs, indicating that cisplatin and FCF target non-converging pathways in MM cells. Thus, a combination therapy of cisplatin and FCF (analogs) might represent a new avenue for the treatment of repopulating chemo-resistant MM cells in this currently untreatable cancer.}, }
@article {pmid35402250, year = {2022}, author = {Tilsed, CM and Casey, TH and de Jong, E and Bosco, A and Zemek, RM and Salmons, J and Wan, G and Millward, MJ and Nowak, AK and Lake, RA and Lesterhuis, WJ}, title = {Retinoic Acid Induces an IFN-Driven Inflammatory Tumour Microenvironment, Sensitizing to Immune Checkpoint Therapy.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {849793}, pmid = {35402250}, issn = {2234-943X}, abstract = {With immune checkpoint therapy (ICT) having reshaped the treatment of many cancers, the next frontier is to identify and develop novel combination therapies to improve efficacy. Previously, we and others identified beneficial immunological effects of the vitamin A derivative tretinoin on anti-tumour immunity. Although it is known that tretinoin preferentially depletes myeloid derived suppressor cells in blood, little is known about the effects of tretinoin on the tumour microenvironment, hampering the rational design of clinical trials using tretinoin in combination with ICT. Here, we aimed to identify how tretinoin changed the tumour microenvironment in mouse tumour models, using flow cytometry and RNAseq, and we sought to use that information to establish optimal dosing and scheduling of tretinoin in combination with several ICT antibodies in multiple cancer models. We found that tretinoin rapidly induced an interferon dominated inflammatory tumour microenvironment, characterised by increased CD8+ T cell infiltration. This phenotype completely overlapped with the phenotype that was induced by ICT itself, and we confirmed that the combination further amplified this inflammatory milieu. The addition of tretinoin significantly improved the efficacy of anti-CTLA4/anti-PD-L1 combination therapy, and staggered scheduling was more efficacious than concomitant scheduling, in a dose-dependent manner. The positive effects of tretinoin could be extended to ICT antibodies targeting OX40, GITR and CTLA4 monotherapy in multiple cancer models. These data show that tretinoin induces an interferon driven, CD8+ T cell tumour microenvironment that is responsive to ICT.}, }
@article {pmid35394203, year = {2022}, author = {Nakashima, K and Sakai, Y and Hoshino, H and Umeda, Y and Kawashima, H and Sekido, Y and Ishizuka, T and Kobayashi, M}, title = {Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {200}, number = {3}, pages = {339-346}, pmid = {35394203}, issn = {1432-1750}, mesh = {*Adenocarcinoma of Lung/diagnosis ; Antibodies, Monoclonal ; Humans ; *Lung Neoplasms/diagnosis ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/pathology ; Polysaccharides ; Sulfates ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is a malignant neoplasm of the pleura caused by asbestos exposure. For diagnosis of MPM, immunohistochemistry using multiple markers is recommended to rule out differential diagnoses, such as pulmonary adenocarcinoma. However, the specificity of currently used markers is not fully satisfactory. We previously developed a monoclonal antibody named S1, which recognizes 6-sulfo sialyl Lewis x, an L-selectin ligand expressed on high endothelial venules. During the screening process, we discovered that this antibody stained normal pleural mesothelium. This finding prompted us to hypothesize that the epitope recognized by S1 might serve as a new diagnostic marker for MPM.<br><br>METHODS: To test this hypothesis, we immunostained human MPM (n&#x2009;=&#x2009;22) and lung adenocarcinoma (n&#x2009;=&#x2009;25) tissues using S1 antibody.<br><br>RESULTS: 77.3% of MPM were S1 positive, and if limited to epithelioid type, the positivity rate was 100%, while that of lung adenocarcinoma was only 36.0%. Statistical analysis revealed a significant difference in the S1 positivity rate between each disease. Furthermore, immunohistochemistry using a series of anti-carbohydrate antibodies combined with glycosidase digestion revealed the structure of sulfated glycans expressed in MPM to be 6-sulfo sialyl N-acetyllactosamine attached to core 2-branched O-glycans.<br><br>CONCLUSION: We propose that the S1 glycoepitope could serve as a new diagnostic marker for MPM.}, }
@article {pmid35378379, year = {2022}, author = {Cameron, JK and Aitken, J and Reid, A and Mengersen, K and Cramb, S and Preston, P and Armstrong, B and Baade, P}, title = {Geographic distribution of malignant mesothelioma incidence and survival in Australia.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {167}, number = {}, pages = {17-24}, doi = {10.1016/j.lungcan.2022.03.017}, pmid = {35378379}, issn = {1872-8332}, mesh = {*Asbestos ; Australia/epidemiology ; Bayes Theorem ; Humans ; Incidence ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {OBJECTIVES: To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia.<br><br>MATERIALS AND METHODS: Generalised linear models and Bayesian spatial models were fitted using population registry data. Area-level covariates were socioeconomic quintile, remoteness category and state or territory. The maximised excess events test was used to test for spatial heterogeneity.<br><br>RESULTS: There was strong evidence of spatial differences in standardised incidence rates for malignant mesothelioma but survival was uniformly poor. Incidence rates varied by state or territory and were lower in remote areas. Patterns in the geographic distribution of modelled incidence counts for malignant mesothelioma differed substantially from patterns of standardised incidence rates.<br><br>CONCLUSIONS: Geographic variation in the modelled incidence counts of malignant mesothelioma demonstrates varying demand for diagnostic and management services. The long latency period for this cancer coupled with migration complicates any associations with patterns of exposure, however some of the geographic distribution of diagnoses can be explained by the location of historical mines and asbestos-related industries.}, }
@article {pmid35367351, year = {2022}, author = {Laaksonen, S and Kettunen, E and Sutinen, E and Ilonen, I and Vehmas, T and Törmäkangas, T and Räsänen, J and Wolff, H and Myllärniemi, M}, title = {Pulmonary Asbestos Fiber Burden Is Related to Patient Survival in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {1032-1041}, doi = {10.1016/j.jtho.2022.03.012}, pmid = {35367351}, issn = {1556-1380}, mesh = {*Asbestos/adverse effects ; Humans ; Lung/pathology ; *Lung Neoplasms/pathology ; *Mesothelioma/complications ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/pathology ; Retrospective Studies ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is associated with poor prognosis and is strongly associated with occupational asbestos exposure. Given the importance of asbestos exposure in MPM pathogenesis, we retrospectively analyzed the types and concentrations of asbestos fibers within the lung tissues of patients with MPM and investigated their effects on all-cause mortality.<br><br>METHODS: We formed a national data set of patients with MPM identified from the Finnish Cancer Registry and Statistics Finland. These data were merged with pulmonary asbestos fiber analysis results received from the Finnish Institute of Occupational Health.<br><br>RESULTS: We identified 590 patients with MPM who underwent pulmonary asbestos fiber analysis. The median asbestos concentration within dry lung tissue was 3.20 million fibers/gram (range: 0 - 1700 million fibers/gram). Crocidolite and anthophyllite were the most prevalent asbestos fiber types detected in lung tissue. The multivariable risk of death analyses, where changes over time were accounted for, revealed that total asbestos fiber concentration was associated with increased mortality. Nevertheless, no difference in mortality was noted between different fiber types.<br><br>CONCLUSIONS: Our study revealed that pulmonary fiber concentrations correlated with the manner of asbestos usage. Anthophyllite was identified as the sole fiber in a sizable proportion of cases, supporting its independent role in the pathogenesis of MPM. Our findings suggest that asbestos fiber burden, but not fiber type, may have an impact on the prognosis of MPM.}, }
@article {pmid35360426, year = {2022}, author = {Idkedek, M and Tahayneh, KS and Abu-Akar, F and Bakri, IA}, title = {Case Report and Review of Literature: Familial Malignant Pleural Mesothelioma in a 39 Years Old Patient With an Inconclusive [18]F-FDG PET/CT Result.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {819596}, pmid = {35360426}, issn = {2296-875X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare yet aggressive neoplasm that was linked only to asbestos exposure for decades, although familial clusters were diagnosed with MPM without a known history of asbestos exposure most likely due to genetic susceptibility. Here, we describe a case of familial malignant mesothelioma in a 39 years old patient with a confirmed BAP1 mutation in addition to a known family history with the same mutation. The patient presented with progressive shortness of breath and recurrent pleural effusions and diagnosis was made through biopsies taken during uniportal Video-Assisted Thoracoscopic Surgery. After the inconclusive result of [18]F-FDG PET/CT scan, subxiphoid uniportal Video-Assisted Thoracoscopic Surgery left pleural and laparoscopic peritoneal biopsies were obtained for staging and evaluating contralateral lung and peritoneal cavity. Finally, two important educational values should be acquired from this case: genetic predisposition and BAP1 tumor suppressor gene mutation might affect the age of presentation and overall prognosis of the disease. Also, [18]F-FDG PET/CT scan may not be the best modality for staging and confirming the diagnosis of malignant pleural mesothelioma.}, }
@article {pmid35358455, year = {2022}, author = {Kindler, HL and Novello, S and Bearz, A and Ceresoli, GL and Aerts, JGJV and Spicer, J and Taylor, P and Nackaerts, K and Greystoke, A and Jennens, R and Calabrò, L and Burgers, JA and Santoro, A and Cedrés, S and Serwatowski, P and Ponce, S and Van Meerbeeck, JP and Nowak, AK and Blumenschein, G and Siegel, JM and Kasten, L and Köchert, K and Walter, AO and Childs, BH and Elbi, C and Hassan, R and Fennell, DA}, title = {Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial.}, journal = {The Lancet. Oncology}, volume = {23}, number = {4}, pages = {540-552}, pmid = {35358455}, issn = {1474-5488}, support = {ZID BC011540/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Humans ; Arthrogryposis ; *Immunoconjugates/adverse effects ; Maytansine/analogs &amp; derivatives ; Mesothelin ; *Mesothelioma, Malignant/drug therapy ; Neoplasm Recurrence, Local/pathology ; Vinorelbine/adverse effects ; }, abstract = {BACKGROUND: Few treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab.<br><br>METHODS: In this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged &#x2265;18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6&#xb7;5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m[2] once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed.<br><br>FINDINGS: Between Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4&#xb7;0 months [IQR 1&#xb7;4-5&#xb7;5]) versus 43 (52%) of 82 patients treated with vinorelbine (3&#xb7;9 months [1&#xb7;4-5&#xb7;4]) had disease progression or died (median progression-free survival 4&#xb7;3 months [95% CI 4&#xb7;1-5&#xb7;2] vs 4&#xb7;5 months [4&#xb7;1-5&#xb7;8]; hazard ratio 1&#xb7;22 [0&#xb7;85-1&#xb7;74]; log-rank p=0&#xb7;86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia).<br><br>INTERPRETATION: Anetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma.<br><br>FUNDING: Bayer Healthcare Pharmaceuticals.}, }
@article {pmid35341441, year = {2022}, author = {Ierardi, AM and Best, EA and Marsh, GM}, title = {Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers.}, journal = {Inhalation toxicology}, volume = {34}, number = {5-6}, pages = {135-144}, doi = {10.1080/08958378.2022.2053251}, pmid = {35341441}, issn = {1091-7691}, mesh = {Cohort Studies ; Cosmetics ; *Extraction and Processing Industry ; Humans ; Italy/epidemiology ; *Mesothelioma/epidemiology ; Mining ; *Occupational Diseases/epidemiology ; Risk Assessment ; *Talc/toxicity ; }, abstract = {OBJECTIVES: To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data.<br><br>METHODS: Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on an a priori one-sided significance level of 0.05, and exact Poisson and approximate distribution probabilities. To evaluate the confidence interval function for the observed pooled mesothelioma standardized mortality ratios (SMRs), we calculated the probability for the upper 100(1-2&#x3b1;)% confidence limit that equals various SMRs of interest.<br><br>RESULTS: The pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively.<br><br>CONCLUSIONS: Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.}, }
@article {pmid35339776, year = {2022}, author = {Ejegi-Memeh, S and Sherborne, V and Harrison, M and Taylor, B and Senek, M and Tod, A and Gardiner, C}, title = {Patients' and informal carers' experience of living with mesothelioma: A systematic rapid review and synthesis of the literature.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {58}, number = {}, pages = {102122}, doi = {10.1016/j.ejon.2022.102122}, pmid = {35339776}, issn = {1532-2122}, mesh = {Adaptation, Psychological ; *Asbestos ; Caregivers/psychology ; Health Personnel ; Humans ; *Mesothelioma/therapy ; Qualitative Research ; }, abstract = {PURPOSE: Mesothelioma is a rare and incurable cancer linked to asbestos exposure. It primarily affects the pleura. This systematic rapid review aimed to identify what is known about the experience of living with mesothelioma, from the perspective of patients and their informal carers.<br><br>METHODS: Medline, PsycInfo, Scopus and the Cumulative Index to Nursing and Allied Health Literature were searched for empirical studies published between December 2008 and October 2020. Google Scholar was searched. The inclusion criteria stated that studies were peer-reviewed, reported the experience of living with mesothelioma from the perspective of patients and carers and written in English. The Mixed-Methods Appraisal Tool was used to assess quality. The review protocol is registered on PROSPERO: CRD42020204726.<br><br>RESULTS: Twenty-five studies met the inclusion criteria. Following data extraction, a narrative synthesis identified three themes: the impact on the individual; the impact on informal carers and relationships; and interactions with professionals and systems. The physical and psychological symptom burden of mesothelioma on patients' lives was reported as high. Both the qualitative and quantitative literature highlighted that patients and carers may have different needs throughout the mesothelioma journey. Differences included psychological experiences and preferences regarding the timing of information and support provision. Patients and carers expected their health care professionals to be knowledgeable about mesothelioma or refer to those who were. Health care professionals that were compassionate, honest and supportive also positively influenced the experience of patients and carers living with mesothelioma. A lack of communication or misinformation was damaging to the patient-healthcare professional relationship. Continuity of care, coordinated care and good communication between treatment centres were widely reported as important in the literature. Fragmented care was identified as detrimental to the patient experience, increasing anxiety in patients. However, relationships with professionals were not only important in terms of co-ordinating care. There was also evidence that good relationships with healthcare professionals were beneficial to coping with the mesothelioma diagnosis.<br><br>CONCLUSION: The volume of mesothelioma experience research has grown over the past decade. This has led to our growing understanding of the complex needs and experiences of mesothelioma patients and carers. However, this review identified several evidence gaps.}, }
@article {pmid35329341, year = {2022}, author = {Saito, CA and Bussacos, MA and Salvi, L and Mensi, C and Consonni, D and Fernandes, FT and Campos, F and Cavalcante, F and Algranti, E}, title = {Sex-Specific Mortality from Asbestos-Related Diseases, Lung and Ovarian Cancer in Municipalities with High Asbestos Consumption, Brazil, 2000-2017.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329341}, issn = {1660-4601}, mesh = {Adult ; *Asbestos/toxicity ; *Asbestosis ; Brazil/epidemiology ; Carcinoma, Ovarian Epithelial ; Cities ; Female ; Humans ; Italy ; Lung ; *Lung Neoplasms ; Male ; *Mesothelioma ; *Occupational Exposure ; *Ovarian Neoplasms ; }, abstract = {The aim of this study is to compare the mortality rates for typical asbestos-related diseases (ARD-T: mesothelioma, asbestosis, and pleural plaques) and for lung and ovarian cancer in Brazilian municipalities where asbestos mines and asbestos-cement plants had been operating (areas with high asbestos consumption, H-ASB) compared with in other municipalities. The death records for adults aged 30+ years were retrieved from multiple health information systems. In the 2000-2017 time period, age-standardized mortality rates (standard: Brazil 2010) and standardized rate ratios (SRR; H-ASB vs. others) were estimated. The SRRs for ARD-T were 2.56 for men (257 deaths in H-ASB municipalities) and 1.19 for women (136 deaths). For lung cancer, the SRRs were 1.33 for men (32,604 deaths) and 1.19 for women (20,735 deaths). The SRR for ovarian cancer was 1.34 (8446 deaths). Except for ARD-T and lung cancer in women, the SRRs were higher in municipalities that began using asbestos before 1970 than in municipalities that began utilizing asbestos from 1970 onwards. In conclusion, the mortality rates for ARD-T, and lung and ovarian cancer in municipalities with a history of asbestos mining and asbestos-cement production exceed those of the whole country. Caution is needed when interpreting the results of this ecological study. Analytical studies are necessary to document the impact of asbestos exposure on health, particularly in the future given the long latency of asbestos-related cancers.}, }
@article {pmid35329152, year = {2022}, author = {Stoppa, G and Mensi, C and Fazzo, L and Minelli, G and Manno, V and Consonni, D and Biggeri, A and Catelan, D}, title = {Spatial Analysis of Shared Risk Factors between Pleural and Ovarian Cancer Mortality in Lombardy (Italy).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329152}, issn = {1660-4601}, mesh = {*Asbestos/adverse effects ; Bayes Theorem ; Carcinoma, Ovarian Epithelial ; Female ; Humans ; Italy/epidemiology ; *Mesothelioma/epidemiology ; *Occupational Exposure/adverse effects ; *Ovarian Neoplasms/epidemiology ; *Pleural Neoplasms/complications/epidemiology ; Risk Factors ; Spatial Analysis ; }, abstract = {BACKGROUND: Asbestos exposure is a recognized risk factor for ovarian cancer and malignant mesothelioma. There are reports in the literature of geographical ecological associations between the occurrence of these two diseases. Our aim was to further explore this association by applying advanced Bayesian techniques to a large population (10 million people).<br><br>METHODS: We specified a series of Bayesian hierarchical shared models to the bivariate spatial distribution of ovarian and pleural cancer mortality by municipality in the Lombardy Region (Italy) in 2000-2018.<br><br>RESULTS: Pleural cancer showed a strongly clustered spatial distribution, while ovarian cancer showed a less structured spatial pattern. The most supported Bayesian models by predictive accuracy (widely applicable or Watanabe-Akaike information criterion, WAIC) provided evidence of a shared component between the two diseases. Among five municipalities with significant high standardized mortality ratios of ovarian cancer, three also had high pleural cancer rates. Wide uncertainty was present when addressing the risk of ovarian cancer associated with pleural cancer in areas at low background risk of ovarian cancer.<br><br>CONCLUSIONS: We found evidence of a shared risk factor between ovarian and pleural cancer at the small geographical level. The impact of the shared risk factor can be relevant and can go unnoticed when the prevalence of other risk factors for ovarian cancer is low. Bayesian modelling provides useful information to tailor epidemiological surveillance.}, }
@article {pmid35329075, year = {2022}, author = {Spinazzè, A and Consonni, D and Borghi, F and Rovelli, S and Cattaneo, A and Zellino, C and Dallari, B and Pesatori, AC and Kromhout, H and Peters, S and Riboldi, L and Cavallo, DM and Mensi, C}, title = {Asbestos Exposure in Patients with Malignant Pleural Mesothelioma included in the PRIMATE Study, Lombardy, Italy.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329075}, issn = {1660-4601}, mesh = {Animals ; *Asbestos/adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; Primates ; Surveys and Questionnaires ; }, abstract = {The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational asbestos exposure (cumulative exposure expressed in fibers per mL (f/mL)). The performance of SYN-JEM was evaluated against the experts' evaluation. According to experts' evaluation, occupational asbestos exposure was recognized in 73.6% of men and 23.6% of women; furthermore, 29 men (7.8%) and 70 women (36.9%) had non-occupational exposure to asbestos. When applying SYN-JEM, 225 men (60.5%) and 25 women (13.2%) were classified as occupationally exposed, with a median cumulative exposure higher for men (1.7 f/mL-years) than for women (1.2 f/mL-years). The concordance between the two methods (Cohen's kappa) for occupational exposure assessment was 0.46 overall (0.41 in men, and 0.07 in women). Sensitivity was higher in men (0.73) than in women (0.18), while specificity was higher in women (0.88) than in men (0.74). Overall, both methods can be used to reconstruct past occupational exposure to asbestos, each with its own advantages and limitations.}, }
@article {pmid35328844, year = {2022}, author = {Anaya-Aguilar, C and Bravo, M and Magan-Fernandez, A and Del Castillo-Salmerón, R and Rodríguez-Archilla, A and Montero, J and Rosel, E and Puche, P and Anaya-Aguilar, R}, title = {Prevention of Occupational Hazards Due to Asbestos Exposure in Dentistry. A Proposal from a Panel of Experts.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35328844}, issn = {1660-4601}, mesh = {*Asbestos ; Dentistry ; Humans ; *Lung Neoplasms ; *Mesothelioma/etiology ; *Occupational Exposure/prevention &amp; control ; }, abstract = {Asbestos in all its forms is a Group 1 material agent with proven carcinogenic effects in the human being since 1977. Exposure to asbestos can be considered unsafe. The use of asbestos in the field of dentistry had a common use in the manufacture of dental prostheses in the 1960s and 1970s. Taking into account the long induction period of this agent and the plausibility for being a risk factor in dentistry, the objective of this study is to propose a plan for the prevention of occupational risks due to asbestos exposure in dentistry by means of the contribution of a panel of experts. An Expert Panel (EP) approach was used in which a group of nine experts identified and documented the use of asbestos in the dental profession. EP was created and followed the protocol in accordance with the EuropeAid Assessment Guidelines. As a result of this study, EP documented the common use and sources of asbestos in dentistry in prosthetic materials, dental dressings, and in the coating of casting cylinders. EP also created a consensus document on the priority measures for the Plan for the Prevention of Risks from Asbestos in Dentistry, based on previous reports from the European Commission Senior Labour Inspectors' Committee. The document concluded that obtainment of information, receiving specific training on the subject and performing epidemiological studies, and the proper risk assessments were the priority measures to adopt.}, }
@article {pmid35327475, year = {2022}, author = {Rovers, S and Janssens, A and Raskin, J and Pauwels, P and van Meerbeeck, JP and Smits, E and Marcq, E}, title = {Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma.}, journal = {Biomedicines}, volume = {10}, number = {3}, pages = {}, pmid = {35327475}, issn = {2227-9059}, support = {FFB210293//BOF research fund, University of Antwerp/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease. In this review, we describe the current preclinical and clinical evidence of various immune checkpoint inhibitors in MPM. We will consider the advantages of combined immune checkpoint blockade in comparison with single agent checkpoint inhibitor drugs. Furthermore, recent evidence suggests a role for T cell immunoglobulin and ITIM domain (TIGIT), an inhibitory immunoreceptor, as a novel target for immunotherapy. As this novel immune checkpoint remains largely unexplored in mesothelioma, we will discuss the potential of TIGIT blockade as an alternative therapeutic approach for MPM. This review will emphasize the necessity for new and improved treatments for MPM, while highlighting the recent advances and future perspectives of combined immune checkpoint blockade, particularly aimed at PD-L1 and TIGIT.}, }
@article {pmid35270479, year = {2022}, author = {Nishida, C and Yatera, K}, title = {The Impact of Ambient Environmental and Occupational Pollution on Respiratory Diseases.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {5}, pages = {}, pmid = {35270479}, issn = {1660-4601}, mesh = {*Air Pollutants, Occupational ; *Air Pollution/adverse effects ; *COVID-19/epidemiology ; Child ; Humans ; *Respiration Disorders ; SARS-CoV-2 ; }, abstract = {Ambient pollutants and occupational pollutants may cause and exacerbate various lung and respiratory diseases. This review describes lung and respiratory diseases in relation to ambient pollutants, particularly particulate matter (PM2.5), and occupational air pollutants, excluding communicable diseases and indoor pollutants, including tobacco smoke exposure. PM2.5 produced by combustion is an important ambient pollutant. PM2.5 can cause asthma attacks and exacerbations of chronic obstructive pulmonary disease in the short term. Further, it not only carries a risk of lung cancer and death, but also hinders the development of lung function in children in the long term. It has recently been suggested that air pollution, such as PM2.5, is a risk factor for severe coronavirus disease (COVID-19). Asbestos, which causes asbestosis, lung cancer, and malignant mesothelioma, and crystalline silica, which cause silicosis, are well-known traditional occupational pollutants leading to pneumoconiosis. While work-related asthma (WRA) is the most common occupational lung disease in recent years, many different agents cause WRA, including natural and synthetic chemicals and irritant gases. Primary preventive interventions that increase awareness of pollutants and reduce the development and exacerbation of diseases caused by air pollutants are paramount to addressing ambient and occupational pollution.}, }
@article {pmid35269773, year = {2022}, author = {Serio, G and Pezzuto, F and Fortarezza, F and Marzullo, A and Delfino, MC and d'Amati, A and Romano, DE and Maniglio, S and Caporusso, C and Lettini, T and Cavone, D and Vimercati, L}, title = {Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation.}, journal = {International journal of molecular sciences}, volume = {23}, number = {5}, pages = {}, pmid = {35269773}, issn = {1422-0067}, mesh = {*Asbestos/toxicity ; *Colorectal Neoplasms/chemically induced/diagnosis/genetics ; Humans ; *Lung Neoplasms/etiology/genetics ; *Mesothelioma/chemically induced/diagnosis ; *Mesothelioma, Malignant ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.}, }
@article {pmid35264891, year = {2022}, author = {Davis, A and Ke, H and Kao, S and Pavlakis, N}, title = {An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {13}, number = {}, pages = {1-12}, pmid = {35264891}, issn = {1179-2728}, abstract = {The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM. No systemic therapy had been demonstrated to improve OS in the second line setting until 2020. The publication of the Checkmate 743 trial in 2021 demonstrated a survival benefit of combination immunotherapy over standard chemotherapy in newly diagnosed patients with MPM. This finding was shortly followed by the CONFIRM trial which demonstrates a modest but significant survival benefit of second line nivolumab versus placebo in patients having previously received standard chemotherapy. The results of these trials, recent biomarker directed therapy and chemotherapy adjuncts are discussed within this review. The integration of immunotherapy for the few patients in whom radical surgical therapy is intended is currently the subject of clinical trials and offers the prospect of improving outcomes in this rare but devastating disease.}, }
@article {pmid35251640, year = {2022}, author = {Rijavec, E and Biello, F and Barletta, G and Dellepiane, C and Genova, C}, title = {Novel approaches for the treatment of unresectable malignant pleural mesothelioma: A focus on immunotherapy and target therapy (Review).}, journal = {Molecular and clinical oncology}, volume = {16}, number = {4}, pages = {89}, pmid = {35251640}, issn = {2049-9469}, abstract = {Malignant pleural mesothelioma (MPM) is considered a relatively uncommon disease but its incidence is increasing worldwide. Patients affected by MPM have a very severe prognosis and have been often occupationally and environmentally exposed to asbestos. In recent years, checkpoint inhibitors have dramatically revolutionized the paradigm for the treatment of several malignancies. Several efforts have also been made to improve the survival outcomes of patients with MPM and after decades, the standard-of-care systemic treatment for unresectable MPM, based on first-line combination chemotherapy with cisplatin and pemetrexed, has changed. In addition to checkpoint inhibitors, other types of treatments, such as molecularly targeted therapy have been evaluated. However, to date, the results of these investigations are not very encouraging. The aim of the present review is to provide a comprehensive overview of the most relevant data of clinical trials regarding recent treatment strategies of MPM with a particular focus on immunotherapeutic and targeted approaches.}, }
@article {pmid35236019, year = {2022}, author = {Freemantle, GG and Chetty, D and Olifant, M and Masikhwa, S}, title = {Assessment of asbestos contamination in soils at rehabilitated and abandoned mine sites, Limpopo Province, South Africa.}, journal = {Journal of hazardous materials}, volume = {429}, number = {}, pages = {127588}, doi = {10.1016/j.jhazmat.2021.127588}, pmid = {35236019}, issn = {1873-3336}, mesh = {*Asbestos ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Humans ; *Mesothelioma ; Soil ; South Africa ; }, abstract = {Prior to its termination, asbestos mining in South Africa was centred on the large crocidolite fields of the present day Northern Cape, the amosite (grunerite)-crocidolite fields of Limpopo, and chrysotile fields of Mpumalanga provinces. The legacy of these activities continues to affect surrounding communities in contemporary South Africa. The asbestos fields of Limpopo host two important former mining areas at Penge and at the Bewaarkloof near Chuenespoort. A large abandoned site is located southeast of Penge at Weltevreden, where there is no evidence of any rehabilitation. Two former mines, Lagerdraai and Uitkyk, are rehabilitated sites in an extensive string of closed mines that operated in the southern Bewaarkloof. Samples from the abandoned and rehabilitated mine sites were studied using semi-quantitative X-ray powder diffraction (XRD) to determine asbestos contamination levels in soils, and to assess distribution patterns of asbestos mineral species in the surrounding soils. Only where below detection (typically 1-3 mass%) from XRD, samples were assessed optically. The Weltevreden site, with no observable rehabilitation efforts, contrasts with the rehabilitated sites at Lagerdraai and Uitkyk. The predominant asbestiform mineral species at each site were successfully identified, with underlying geological asbestos mineral distribution trends recognised in the soils at the Bewaarkloof. Trace amounts of asbestiform minerals were identified in soils downstream of the Weltevreden mine, as well as in surrounding hillsides. The results indicate that XRD is a potentially useful tool for benchmarking sites yet to be rehabilitated as well as monitoring the effectiveness of previous rehabilitation efforts. The method is also a suitable first-pass for target areas that may require more detailed, time-consuming, and costly analysis.}, }
@article {pmid35223506, year = {2022}, author = {Fortarezza, F and Pezzuto, F and Marzullo, A and Cavone, D and Romano, DE and d'Amati, A and Serio, G and Vimercati, L}, title = {Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {823839}, pmid = {35223506}, issn = {2234-943X}, abstract = {Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.}, }
@article {pmid35216091, year = {2022}, author = {Štrbac, D and Dolžan, V}, title = {Novel and Future Treatment Options in Mesothelioma: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {23}, number = {4}, pages = {}, pmid = {35216091}, issn = {1422-0067}, support = {P1-170, L3-8203, and L3-2622.//Slovenian Research Agency/ ; }, mesh = {Animals ; Cell- and Tissue-Based Therapy/methods ; Clinical Trials as Topic ; Humans ; Immunotherapy/methods ; Mesothelioma/*drug therapy/immunology/*therapy ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; Tumor Microenvironment/drug effects ; }, abstract = {Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies.}, }
@article {pmid35211727, year = {2022}, author = {Spinazzè, A and Consonni, D and Borghi, F and Mazzucchelli, LA and Rovelli, S and Cattaneo, A and Zellino, C and Dallari, B and Pesatori, AC and Kromhout, H and Peters, S and Riboldi, L and Mensi, C and Cavallo, DM}, title = {Development of a Crosswalk to Translate Italian Occupation Codes to ISCO-68 Codes.}, journal = {Annals of work exposures and health}, volume = {66}, number = {6}, pages = {815-821}, doi = {10.1093/annweh/wxac009}, pmid = {35211727}, issn = {2398-7316}, mesh = {*Asbestos ; Female ; Humans ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; Occupations ; }, abstract = {In occupational epidemiology, job coding is an important-but time-consuming-step in assigning exposure. We implemented a tool (i.e. a crosswalk) to translate occupation codes from the Italian (ISTAT-CIP-91, n = 6319 five-digit job codes) to the International Standard Classification of Occupations (ISCO-68, n = 1881 five-digit job codes). The former is currently used in Italy for various purposes (e.g. in the National Mesothelioma Registry). The latter has been used in several studies on occupational cancers because it facilitates communication of results to the scientific community and, most importantly, because some job exposure matrices (JEMs) are based on international codes. Three authors created a table containing the crosswalk structure, providing an interpretation for each of the ISTAT-CIP-91 codes job descriptions and then manually recoding them according to ISCO-68. Two other authors independently revised it. The performance of the final version was assessed by comparison with results obtained by manual ISCO-68 coding performed in two previous case-control studies on asbestos and mesothelioma. More specifically, the automatically obtained ISCO-68 codes were merged with a JEM (DOM-JEM). The resulting individual asbestos exposure estimates (ever versus never exposed) were compared to those originally obtained (using the same DOM-JEM) from manual translation of ISTAT-CIP-91 to ISCO-68 (considered as the 'gold standard'). In the first study, among 159 peritoneal mesothelioma cases (400 job codes), Cohen's kappa was 0.91, sensitivity 0.95, and specificity 0.96. In the second study, among 716 pleural mesothelioma cases and controls (4400 job codes) kappa was 0.86, sensitivity 0.94, and specificity 0.91. Performance was better among in women. For men, performance was lower among cases than among controls (kappa 0.70, sensitivity 0.95, specificity 0.72 versus kappa 0.87, sensitivity 0.97, and specificity 0.92). In conclusion, the proposed tool allowed a rapid translation of thousands of job codes with good to excellent accuracy. The table containing ISTAT-CIP-91 codes and job descriptions and the corresponding ISCO-68 codes and job descriptions is made publicly available and can be freely used for epidemiological analyses in Italy and international collaborations.}, }
@article {pmid35207583, year = {2022}, author = {Caraballo-Arias, Y and Caffaro, P and Boffetta, P and Violante, FS}, title = {Quantitative Assessment of Asbestos Fibers in Normal and Pathological Pleural Tissue-A Scoping Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207583}, issn = {2075-1729}, abstract = {BACKGROUND: pleural mesothelioma is a rare cancer in the general population, but it is more common in subjects occupationally exposed to asbestos. Studies with asbestos fiber quantification in pleural tissue are scarce: for this reason, we aimed at undertaking a scoping review to summarize the evidence provided by studies in which asbestos fibers were determined by electron microscopy (SEM or TEM) in human pleural tissues, whether normal or pathologic.<br><br>MATERIALS AND METHODS: A scoping review of articles that quantified asbestos fibers in human pleural tissue (normal or pathologic) by electron microscopy (SEM or TEM), in subjects with asbestos exposure (if any) was performed.<br><br>RESULTS: The 12 studies selected comprised 137 cases, out of which 142 samples were analyzed. Asbestos fibers were detected in 111 samples (78%) and were below the detectable limit in 31 samples (22%). The concentration of asbestos fibers detected in the positive samples was distributed from as low as 0.01 mfgdt (millions of fibers per gram of dry tissue) up to 240 mfgdt. However, the minimum concentration of fibers overlaps in the three types of tissues (normal pleura, pleural plaque, mesothelioma) in terms of magnitude; therefore, it is not possible to distinguish a definite pattern which differentiates one tissue from the other.<br><br>CONCLUSIONS: The studies included were heterogeneous as to the representativeness of the samples and analytical techniques; the possibility of false negatives must be considered. It would be desirable to systematically search for asbestos fibers to fill the knowledge gap about the presence of asbestos fibers in normal or pathological pleural tissue in order to better understand the development of the different pleural diseases induced by this mineral.}, }
@article {pmid35206274, year = {2022}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, &#xd8;}, title = {A Cohort Study on Cancer Incidence among Women Exposed to Environmental Asbestos in Childhood with a Focus on Female Cancers, including Breast Cancer.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {4}, pages = {}, pmid = {35206274}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; *Breast Neoplasms/complications ; Child ; Cohort Studies ; Environmental Exposure/adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; *Lung Neoplasms/chemically induced/etiology ; *Mesothelioma/epidemiology ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: To examine the risk of cancer in former school children exposed to environmental asbestos in childhood with a focus on female cancers, including breast cancer.<br><br>METHODS: We retrieved a cohort of females (n = 6024) attending four schools located in the neighborhood of a large asbestos cement plant in Denmark. A reference cohort was frequency-matched 1:9 (n = 54,200) in sex and five-year age intervals. Using Danish registries, we linked information on historical employments, relatives' employments, cancer, and vital status. We calculated standardized incidence rates (SIRs) for all and specific cancers, comparing these rates with the reference cohort. Hazard ratios were calculated for selected cancers adjusted for occupational and familial asbestos exposure.<br><br>RESULTS: For cancer of the corpus uteri (SIR 1.29, 95% CI 1.01-1.66) and malignant mesothelioma (SIR 7.26, 95% CI 3.26-16.15), we observed significantly increased incidences. Occupationally, asbestos exposure had a significantly increased hazard ratio for cancer in the cervix, however, a significantly lower risk of ovarian cancer. The overall cancer incidence was similar to that of the reference cohort (SIR 1.02, 95% CI 0.96-1.07). The risk of cancer of the lung was increased for those exposed to occupational asbestos, those with family members occupationally exposed to asbestos and for tobacco smokers.<br><br>CONCLUSIONS: In our study, environmental asbestos exposure in childhood is associated with an increased risk of cancer of the corpus uteri and malignant mesothelioma in women.}, }
@article {pmid35205798, year = {2022}, author = {Shah, R and Klotz, LV and Glade, J}, title = {Current Management and Future Perspective in Pleural Mesothelioma.}, journal = {Cancers}, volume = {14}, number = {4}, pages = {}, pmid = {35205798}, issn = {2072-6694}, abstract = {Pleural mesothelioma is an aggressive malignancy arising from pleural mesothelial cell lining, predominantly associated with prior exposure to asbestos. The ban on asbestos use has led to its lower incidence in many countries, but globally the disease burden is expected to rise. Therefore, well-planned research is needed to develop more effective, tolerable and affordable drugs. The development of novel treatment has been too slow, with only two regimens of systemic therapy with robust phase 3 data approved formally to date. The treatment scenario for resectable disease remains controversial. However, recent developments in the understanding of disease and clinical trials have been encouraging, and may add better treatment options in the coming years. In this review, we discuss the current treatment options for pleural mesothelioma and shed light on some recent studies and ongoing trials.}, }
@article {pmid35204402, year = {2022}, author = {Foddis, R and Franzini, M and Bonotti, A and Marino, R and Silvestri, R and Fallahi, P and Chiappino, D and Emdin, M and Paolicchi, A and Cristaudo, A}, title = {Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35204402}, issn = {2075-4418}, support = {PRA 2017//University of Pisa/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582-0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807-0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis.}, }
@article {pmid35201802, year = {2022}, author = {Lond, B and Quincey, K and Apps, L and Darlison, L and Williamson, I}, title = {The experience of living with mesothelioma: A meta-ethnographic review and synthesis of the qualitative literature.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {41}, number = {5}, pages = {343-355}, doi = {10.1037/hea0001166}, pmid = {35201802}, issn = {1930-7810}, mesh = {*Adaptation, Psychological ; Europe ; Humans ; *Mesothelioma/ethnology/psychology/therapy ; }, abstract = {OBJECTIVE: Mesothelioma is a life limiting cancer caused by previous exposure to asbestos. Due to the continued use of asbestos products internationally, the condition presents an increasing risk to global health with case numbers peaking in industrially developed nations. With the cancer reducing patient well-being, this study aimed to synthesizes the qualitative findings of studies exploring the experiences of patients living with mesothelioma to generate new conceptual insights and guide therapeutic care.<br><br>METHOD: Thirteen databases were systematically searched: Academic Search Premier, BioMed Central, British Nursing Database, CINAHL Plus, Cochrane Library, Europe PubMed Central, MEDLINE, PsycARTICLES, PsycINFO, Science Direct, Scopus, Social Care Online, and Web of Science, between August and September 2020. Included articles were subject to quality appraisal using CASP checklists, and their respective findings analyzed using a metaethnographic form of qualitative data synthesis.<br><br>RESULTS: Twenty-two articles met the inclusion criteria, and the data synthesis produced three themes: (1) "complex trauma"; (2) "psycho-behavioral coping strategies"; and (3) "external sources of support." Combined, these themes form a novel conceptual framework and awareness of the patient experience that presents the lived trauma of disease alongside a patients coping processes and support pathways.<br><br>CONCLUSION: Robust therapeutic support is needed to address the psychosocial and existential burden shouldered by people with mesothelioma. Therapies that promote sentiments of acceptance, hope, and benefit finding are proposed alongside initiatives that foster patient empowerment and meaning, and further promote patient choice in deciding end-of-life care. Recommendations for future research are also made. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, }
@article {pmid35149582, year = {2022}, author = {van Kooten, JP and Belderbos, RA and von der Thüsen, JH and Aarts, MJ and Verhoef, C and Burgers, JA and Baas, P and Aalbers, AGJ and Maat, APWM and Aerts, JGJV and Cornelissen, R and Madsen, EVE}, title = {Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study.}, journal = {Thorax}, volume = {77}, number = {12}, pages = {1260-1267}, pmid = {35149582}, issn = {1468-3296}, mesh = {Humans ; Male ; Female ; Aged, 80 and over ; *Mesothelioma, Malignant ; Incidence ; *Pleural Neoplasms/epidemiology/therapy ; Pleura/pathology ; *Lung Neoplasms/epidemiology/therapy ; *Mesothelioma/epidemiology/therapy/diagnosis ; *Asbestos ; *Peritoneal Neoplasms/epidemiology/therapy/etiology ; }, abstract = {INTRODUCTION: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993.<br><br>MATERIALS AND METHODS: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed.<br><br>RESULTS: In total, 12&#x2009;168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001).<br><br>CONCLUSION: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.}, }
@article {pmid35143119, year = {2022}, author = {Louw, A and van Vliet, C and Peverall, J and Colkers, S and Acott, N and Creaney, J and Lee, YCG and Chai, SM}, title = {Analysis of early pleural fluid samples in patients with mesothelioma: A case series exploration of morphology, BAP1, and CDKN2A status with implications for the concept of mesothelioma in situ in cytology.}, journal = {Cancer cytopathology}, volume = {130}, number = {5}, pages = {352-362}, doi = {10.1002/cncy.22548}, pmid = {35143119}, issn = {1934-6638}, mesh = {Biomarkers, Tumor/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Homozygote ; Humans ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/diagnosis/genetics ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/genetics ; Retrospective Studies ; Sequence Deletion ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {BACKGROUND: The concept of mesothelioma in situ has been revisited and is a new World Health Organization diagnostic entity. The definition centers on ancillary techniques used in pleural mesothelioma (PM) assessment. At the authors' institution, most PM diagnoses are made on cytologic specimens. Effusion samples obtained before definitive PM diagnosis were interrogated using BRCA1-associated protein 1 gene (BAP1), cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and cytologic evaluation to assess whether early or possible in situ disease could be characterized.<br><br>METHODS: All cases of PM diagnosed between January 2008 and December 2019 were identified at a tertiary referral center. Patients who had a pleural fluid sample collected 24 months before the diagnosis were selected, numbering 8 in total. The cytomorphology of each sample was reviewed; and, retrospectively, BAP1 immunohistochemistry (IHC) and CDKN2A fluorescence in situ hybridization (FISH) were performed on initial and diagnostic samples.<br><br>RESULTS: The initial samples were deemed benign in 5 cases and atypical mesothelial proliferations in 3 cases. A spectrum of apparently normal to atypical cytomorphologic changes was identified. BAP1 loss was present in 6 of 8 initial cases, whereas CDKN2A homozygous deletion was identified in 1 of 7 initial cases. Either abnormality was identified in 7 of 8 initial samples.<br><br>CONCLUSIONS: Detectable abnormalities of BAP1 IHC and CDKN2A FISH were present in pleural fluid specimens before the development of cytomorphologic features diagnostic of PM. This is the largest series to date describing cytology samples early in the course of PM development, thereby highlighting a possible cytological equivalent for mesothelioma in situ.}, }
@article {pmid35127504, year = {2021}, author = {Endo, I and Amatya, VJ and Kushitani, K and Kambara, T and Nakagiri, T and Fujii, Y and Takeshima, Y}, title = {Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Promotes Cell Proliferation of Malignant Mesothelioma Cells by Downregulating p27[Kip1].}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {795467}, pmid = {35127504}, issn = {2234-943X}, abstract = {Malignant mesothelioma is a tumor with a poor prognosis, mainly caused by asbestos exposure and with no adequate treatment yet. To develop future therapeutic targets, we analyzed the microarray dataset GSE 29370 of malignant mesothelioma and reactive mesothelial hyperplasia, downloaded from the Gene Expression Omnibus (GEO) database. We identified insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) as one of the significantly upregulated genes in malignant mesothelioma. IGF2BP3 functions as an oncoprotein in many human cancers; however, to our knowledge, this is the first study on the biological function of IGF2BP3 in malignant mesothelioma cells. The knockdown of IGF2BP3 in malignant mesothelioma cells resulted in the suppression of cell proliferation with an increase in the proportion of cells in the G1 phase of the cell cycle. Furthermore, knockdown of IGF2BP3 inhibited cell migration and invasion. We focused on the cell cycle assay to investigate the role of IGF2BP3 in cell proliferation in malignant mesothelioma. Among the various proteins involved in cell cycle regulation, the expression of p27 Kip1 (p27) increased significantly upon IGF2BP3 knockdown. Next, p27 siRNA was added to suppress the increased expression of p27. The results showed that p27 knockdown attenuated the effects of IGF2BP3 knockdown on cell proliferation and G1 phase arrest. In conclusion, we found that IGF2BP3 promotes cell proliferation, a critical step in tumorigenesis, by suppressing the expression of p27 in malignant mesothelioma.}, }
@article {pmid35114507, year = {2022}, author = {Repo, P and Staskiewicz, A and Sutinen, E and Rönty, M and Tero T Kivelä,  and Myllärniemi, M and Turunen, JA}, title = {BAP1 germline variants in Finnish patients with malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {165}, number = {}, pages = {102-107}, doi = {10.1016/j.lungcan.2022.01.017}, pmid = {35114507}, issn = {1872-8332}, abstract = {OBJECTIVES: Although asbestos exposure is the most common cause of malignant mesothelioma (MM), an aggressive cancer of the pleura or peritoneum, up to 7% of patients harbor a genetic predisposition to MM. Pathogenic germline variants in the BRCA1-associated protein 1 (BAP1) gene cause a dominantly inherited tumor predisposition syndrome, BAP1-TPDS, in which MM is the second most common associated cancer. Other frequent cancers in BAP1-TPDS are uveal melanoma (UM), cutaneous melanoma and renal cell carcinoma. Additionally patients can exhibit benign skin lesions, BAP1-inactivated nevi (BIN). Most BINs arise sporadically, but patients with BAP1-TPDS may harbor multiple BINs before other tumors or as the only indication of the syndrome. Our objective was to establish the frequency of pathogenic germline BAP1 variants in Finnish patients with MM.<br><br>MATERIALS AND METHODS: 56 DNA samples archived in the Helsinki Biobank from Finnish patients with MM were sequenced for germline BAP1 variations. Formalin fixed paraffin embedded nevi from a pathogenic variant carrier were subjected to immunohistochemistry and exome sequencing.<br><br>RESULTS: Sanger sequencing identified one patient with Finnish founder mutation c.1780_1781insT, p.(G549Vfs*49) in BAP1. The carrier was diagnosed with MM over fifteen years before the cohorts mean onset age (mean 68, range 27 to 82) although the patient had no asbestos exposure or family history of BAP1-TPDS. However, the patient had three BINs removed prior to the MM. The c.1780_1781insT is now found from five Finnish BAP1-TPDS families with unknown common ancestor.<br><br>CONCLUSION: The frequency of pathogenic germline BAP1 variants in Finnish patients with MM is 1.8&#xa0;% (95&#xa0;% CI, 0.04 to 9.2), comparable to the frequency in Finnish patients with UM (1.9&#xa0;%). The frequency of recurring BINs in patients with BAP1-TPDS should be studied further and genetic testing for BAP1 variants considered if the patient has&#xa0;&#x2265;&#xa0;2 BAP1-TPDS core tumors, including BINs.}, }
@article {pmid35102573, year = {2022}, author = {LeMasters, G and Lockey, JE and Hilbert, TJ and Burkle, JW and Rice, CH}, title = {Mortality of workers employed in refractory ceramic fiber manufacturing: An update.}, journal = {Journal of applied toxicology : JAT}, volume = {42}, number = {7}, pages = {1287-1293}, doi = {10.1002/jat.4295}, pmid = {35102573}, issn = {1099-1263}, support = {//High Temperature Insulation Wool Coalition to the University of Cincinnati, College of Medicine/ ; }, mesh = {Ceramics ; Cohort Studies ; Humans ; *Lung Neoplasms/mortality ; *Mesothelioma/mortality ; *Neoplasms/mortality ; *Occupational Diseases/complications/mortality ; *Occupational Exposure/adverse effects ; }, abstract = {This study evaluates the possible association between refractory ceramic fiber (RCF) exposure and all causes of death. Current and former employees (n = 1,119) hired from 1952 to 1999 at manufacturing facilities in New York (NY) state and Indiana were included. Work histories and quarterly plant-wide sampling from 1987 to 2015 provided cumulative fiber exposure (CFE) estimates. The full cohort was evaluated as well as individuals with lower and higher exposure, <45 and ≥45 fiber-months/cc. The Life-Table-Analysis-System was used for all standardized mortality rates (SMRs). Person-years at risk were accumulated from start of employment until 12/31/2019 or date of death. There was no significant association with all causes, all cancers, or lung cancer in any group. In the higher exposed, there was a significant elevation in both malignancies of the "urinary organs" (SMR = 3.59, 95% confidence interval [CI] 1.44, 7.40) and "bladder or other urinary site" (SMR = 4.04, 95% CI 1.10, 10.36), which persisted in comparison to regional mortality rates from NY state and Niagara County. However, six of the nine workers with urinary cancers were known smokers. In the lower exposed, there was a significant elevation in malignancies of the lymphatic and hematopoietic system (SMR = 2.54, 95% CI 1.27, 4.55) and leukemia (SMR = 4.21, 95% CI 1.69, 8.67). There was one pathologically unconfirmed mesothelioma death. A second employee currently living with a pathologically confirmed mesothelioma was identified, but the SMR was non-significant when both were included in the analyses. The association of these two mesothelioma cases with RCF exposure alone is unclear because of potential past exposure to asbestos.}, }
@article {pmid35100476, year = {2022}, author = {Hyland, RA and Chrzanowska, A and Hannaford-Turner, K and Davis, A and Ke, H and Bradbury, L and Nagrial, A and McCaughan, B and Hui, R and van Zandwijk, N and Takahashi, K and Kao, SC}, title = {Asbestos-related lung cancer: Clinical characteristics and survival outcomes in an Australian cohort seeking workers compensation.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {18}, number = {5}, pages = {e448-e455}, doi = {10.1111/ajco.13664}, pmid = {35100476}, issn = {1743-7563}, mesh = {*Asbestos/analysis/toxicity ; Australia ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma ; *Occupational Exposure/adverse effects ; Workers' Compensation ; }, abstract = {BACKGROUND AND OBJECTIVES: Due to difficulties in identifying sufficient-sized cohorts there remains uncertainty about prognostic and clinical differences that may be unique to asbestos-related lung cancer (ARLC). In this study, we use the Helsinki Criteria to define a group of ex-workers with lung cancer attributable to asbestos exposure and investigate differences that may exist.<br><br>METHODS: A total of 529 patients seeking workers' compensation for their lung cancer were assigned to either ARLC or the non-ARLC based on parameters defined in the Helsinki Criteria. Clinical and survival details were collected and analyzed.<br><br>RESULTS: In our study population, ARLC patients were on average older (72.1 &#xb1;&#xa0;7.8) than non-ARLC patients (66.5&#xa0;&#xb1;&#xa0;10.2, P&#xa0;<&#xa0;0.001) and were more likely to be diagnosed as a result of incidental findings or screening program (P&#xa0;<&#xa0;0.001). The groups were similar in terms of clinical characteristics with the only difference being that plaques were more prevalent among ARLC patients (P&#xa0;<&#xa0;0.001). Differences were observed for median overall survival (OS), ARLC (9 months) and non-ARLC (13 months, P&#xa0;=&#xa0;0.005), as well for treatment (P&#xa0;=&#xa0;0.01). After adjusting for age, however, these differences disappeared.<br><br>CONCLUSIONS: Age at diagnosis, pleural plaques, and asymptomatic presentation were the attributes that we identified as significantly different between asbestos-related cancer and other lung cancers. In this cohort, ARLC patients were older diagnosis and with worse overall survival.}, }
@article {pmid35098897, year = {2023}, author = {Le, HT and Dinh, HT and Ngo, TT}, title = {Asbestos dust concentrations and health conditions of workers at asbestos-cement corrugated sheet production manufacturers in Vietnam: a nationwide assessment.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {29}, number = {1}, pages = {263-267}, doi = {10.1080/10803548.2022.2035510}, pmid = {35098897}, issn = {2376-9130}, mesh = {Humans ; *Occupational Exposure/analysis ; Vietnam ; *Asbestos ; *Mesothelioma ; Dust/analysis ; }, abstract = {This study examined contemporary concentrations of asbestos dust during production and the health conditions of workers at asbestos-cement corrugated sheet production manufacturers in Vietnam. A nationwide survey was conducted on 28 factories (with 206 air samples) and 2459 workers. Asbestos fiber dust and the health status of workers were assessed. Results showed that 108/206 (52.4%) samples had asbestos fiber dust. The average concentration of asbestos fibers was 0.19 ± 0.14 fibers/ml. The percentage of workers with thickened pleural lesions/pleural calcification nodules was low. More studies are needed to evaluate the effectiveness of biomarkers in preventing the onset of lung cancer and mesothelioma in workers.}, }
@article {pmid35098108, year = {2021}, author = {Zolondick, AA and Gaudino, G and Xue, J and Pass, HI and Carbone, M and Yang, H}, title = {Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review.}, journal = {Precision cancer medicine}, volume = {4}, number = {}, pages = {}, pmid = {35098108}, issn = {2617-2216}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVE: The aim of this review is addressing the mechanisms of asbestos carcinogenesis, including chronic inflammation and autophagy-mediated cell survival, and propose potential innovative therapeutic targets to prevent mesothelioma development or improve drug efficacy by reducing inflammation and autophagy.<br><br>BACKGROUND: Diffuse malignant pleural mesothelioma is an aggressive cancer predominantly related to chronic inflammation caused by asbestos exposure. Millions of individuals have been exposed to asbestos or to other carcinogenic mineral fibers occupationally or environmentally, resulting in an increased risk of developing mesothelioma. Overall patient survival rates are notably low (about 8-14 months from the time of diagnosis) and mesothelioma is resistant to existing therapies. Additionally, individuals carrying inactivating germline mutations in the BRCA-associated protein 1 (BAP1) gene and other genes are predisposed to developing cancers, prevalently mesothelioma. Their risk of developing mesothelioma further increases upon exposure to asbestos. Recent studies have revealed the mechanisms and the role of inflammation in asbestos carcinogenesis. Biomarkers for asbestos exposure and malignant mesothelioma have also been identified. These findings are leading to the development of novel therapeutic approaches to prevent or delay the growth of mesothelioma.<br><br>METHODS: Review of full length manuscripts published in English from January 1980 to February 2021 gathered from PubMed.gov from the National Center of Biotechnology Information and the National Library of Medicine were used to inform this review.<br><br>CONCLUSION: Key regulators of chronic inflammation mediate asbestos-driven mesothelial cell transformation and survival through autophagic pathways. Recent studies have elucidated some of the key mechanisms involved in asbestos-induced chronic inflammation, which are largely driven by extracellular high mobility group box 1 (HMGB1). Upon asbestos exposure, mesothelial cells release HMGB1 from the nucleus to the cytoplasm and extracellular space, where HMGB1 initiates an inflammatory response. HMGB1 translocation and release also activates autophagy and other pro-survival mechanisms, which promotes mesothelioma development. HMGB1 is currently being investigated as a biomarker to detect asbestos exposure and to detect mesothelioma development in its early stage when therapy is more effective. In parallel, several approaches inhibiting HMGB1 activities have been studied and have shown promising results. Moreover, additional cytokines, such as IL-1&#x3b2; and TNF-&#x3b1; are being targeted to interfere with the inflammatory process that drives mesothelioma growth. Developing early detection methods and novel therapeutic strategies is crucial to prolong overall survival of patients with mesothelioma. Novel therapies targeting regulators of asbestos-induced inflammation to reduce mesothelioma growth may lead to clinical advancements to benefit patients with mesothelioma.}, }
@article {pmid35089637, year = {2022}, author = {Yue, L and Luo, Y and Jiang, L and Sekido, Y and Toyokuni, S}, title = {PCBP2 knockdown promotes ferroptosis in malignant mesothelioma.}, journal = {Pathology international}, volume = {72}, number = {4}, pages = {242-251}, doi = {10.1111/pin.13209}, pmid = {35089637}, issn = {1440-1827}, support = {19-251//Princess Takamatsu Cancer Research Fund/ ; JPMJCR19H4//Core Research for Evolutional Science and Technology/ ; JP19H05462 and JP20H05502//Japan Society for the Promotion of Science/ ; //JST CREST/ ; //JSPS Kakenhi/ ; //Research Grant of the Princess Takamatsu Cancer Research Fund/ ; }, mesh = {Animals ; *Ferroptosis ; Ferrous Compounds/metabolism ; Gene Knockdown Techniques ; Humans ; Iron/metabolism ; *Mesothelioma, Malignant/genetics/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; Rats ; }, abstract = {Malignant mesothelioma (MM) is still increasing worldwide. The pathogenesis depends on asbestos-induced iron accumulation, which eventually leads to ferroptosis-resistance of mesothelial cells via somatic mutations. Poly (rC)-binding proteins 1 and 2 (PCBP1/2) are recently recognized cytosolic Fe(II) chaperones. Here we studied the role of PCBP1/2 in rat/human mesothelial and MM cells as well as rat/human MM specimens. Normal peritoneal mesothelial cells in rats exhibited PCBP1 but not PCBP2 immunopositivity whereas primary/immortalized mesothelial cells showed PCBP1/2 immunopositivity. Rat MM specimens induced by intraperitoneal injection of chrysotile, including in situ lesion, revealed PCBP1/2 immunopositivity (90% for both) in the nucleus and cytoplasm with a tendency of higher expression in epithelioid subtype. Knockdown of PCBP2 but not PCBP1 significantly decreased both TfR1 and FTH expression in MM cells with inhibition of proliferation, indicating stagnation of intracellular iron transport. Erastin, a cysteine-deprivation type ferroptosis inducer, decreased the expression of both PCBP1/2 in MM cells. Furthermore, PCBP2 knockdown significantly increased the sensitivity of MM cells to erastin-induced ferroptosis with increased catalytic Fe(II). In conclusion, PCBP2 works for ferroptosis-resistance not only during mesothelial carcinogenesis but also in MM, which warrants further investigation as a novel therapeutic target.}, }
@article {pmid35089066, year = {2022}, author = {Kelsey, K}, title = {Epigenetics, environment and epidemiology: an interview with Karl Kelsey.}, journal = {Epigenomics}, volume = {14}, number = {6}, pages = {323-326}, doi = {10.2217/epi-2022-0008}, pmid = {35089066}, issn = {1750-192X}, mesh = {*Arsenic ; Biomarkers ; Case-Control Studies ; Epigenesis, Genetic ; Epigenomics ; Female ; Humans ; Male ; *Urinary Bladder Neoplasms ; }, abstract = {In this interview, Professor Karl Kelsey speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of environmental epigenomics and epidemiology. Dr Karl Kelsey, MD, MOH is a Professor of Epidemiology and Pathology and Laboratory Medicine at Brown University. He is the Founding Director of the Center for Environmental Health and Technology and Head of the Environmental Health Section at the Department of Epidemiology. Dr Kelsey is interested in the application of laboratory-based biomarkers in environmental disease, with experience in chronic disease epidemiology and tumor biology. The goals of his work include a mechanistic understanding of individual susceptibility to exposure-related cancers. In addition, his laboratory is interested in tumor biology, investigating somatic alterations in tumor tissue from the patients who have developed exposure-related cancers. This work involves the use of an epidemiologic approach to characterize epigenetic and genetic alteration of genes in the causal pathway for malignancy. Active work includes several studies of individual susceptibility to cancer. Dr Kelsey's laboratory mainly investigates susceptibility to smoking-related lung cancer and studies multi-racial and ethnic populations. In addition, the laboratory is also involved with the study of inherited susceptibility to brain tumors and pancreatic cancer. Major case control studies that are ongoing in the laboratory include studies designed to understand inherited and acquired susceptibility in head and neck cancers. The laboratory is also involved in a case control study of asbestos-associated mesothelioma, arsenic exposure, cigarette smoking and bladder cancer. Considerable work is being devoted to understanding the mechanisms of action of both asbestos and arsenic including their ability to affect promoter methylation and gene silencing in carcinogenesis. Recent laboratory studies includes an interest in using newly developed DNA methylation biomarkers to probe immune profiles from archived blood. Dr Kelsey received his MD from the University of Minnesota and Masters of Occupational Health from Harvard University.}, }
@article {pmid35081587, year = {2022}, author = {Tao, XG and Curriero, FC and Chee, EM and Mahesh, M}, title = {Updated Standardized Mortality Ratio Evaluation of Disease Risks of Shipyard Workers Exposed to Low Dose Ionizing Radiation.}, journal = {Journal of occupational and environmental medicine}, volume = {64}, number = {4}, pages = {e224-e230}, doi = {10.1097/JOM.0000000000002491}, pmid = {35081587}, issn = {1536-5948}, mesh = {*Asbestos ; *Asbestosis ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma ; *Occupational Diseases/etiology ; *Occupational Exposure/adverse effects ; Radiation, Ionizing ; }, abstract = {OBJECTIVE: To examine the risk of diseases among industrial workers with low and fractionated radiation exposures.<br><br>METHOD: The 372,047 US male shipyard radiation and non-radiation workers were followed for 54&#x200a;years and compared with US men using standardized mortality ratio (SMR) method.<br><br>RESULTS: SMRs for both radiation and non-radiation workers had lower risks of death from all causes (0.74; 95% confidence interval [CI] 0.74 to 0.75 and 0.77; 95% Cl 0.77 to 0.78, respectively) and from all cancers (0.92; 95% CI 0.91 to 0.93 and 0.90; 95% CI 0.89 to 0.91, respectively) compared with US men. Asbestos-related diseases including pleural cancers, mesothelioma, and asbestosis, but not lung cancers, were statistically higher in both radiation and non-radiation workers compared with the US men.<br><br>CONCLUSION: US shipyard male radiation and non-radiation workers did not show any elevated mortality risks that might be associated with radiation exposure.}, }
@article {pmid35078853, year = {2022}, author = {Kok, PS and Forde, PM and Hughes, B and Sun, Z and Brown, C and Ramalingam, S and Cook, A and Lesterhuis, WJ and Yip, S and O'Byrne, K and Pavlakis, N and Brahmer, J and Anagnostou, V and Ford, K and Fitzpatrick, K and Bricker, A and Cummins, MM and Stockler, M and Nowak, AK and , }, title = {Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e057663}, pmid = {35078853}, issn = {2044-6055}, mesh = {Adolescent ; Adult ; Aged ; Antibodies, Monoclonal ; Antineoplastic Combined Chemotherapy Protocols ; Clinical Trials, Phase III as Topic ; Humans ; *Lung Neoplasms/drug therapy ; *Mesothelioma/drug therapy/pathology ; *Mesothelioma, Malignant ; Middle Aged ; Multicenter Studies as Topic ; Quality of Life ; Randomized Controlled Trials as Topic ; Young Adult ; }, abstract = {INTRODUCTION: There is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers. Two recent single-arm, phase 2 trials [DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (PrE0505)] combining the programmed death ligand-1 (PD-L1) inhibitor durvalumab with standard first-line chemotherapy exceeded prespecified safety and activity criteria to proceed to a phase 3 confirmatory trial to assess this combination. We present the protocol of the DREAM3R trial.<br><br>METHODS AND ANALYSIS: This multicentre open-label randomised trial will recruit 480 treatment-na&#xef;ve adults with advanced pleural mesothelioma, randomised (2:1) to either 3-weekly durvalumab 1500&#x2009;mg plus 3-weekly doublet chemotherapy (cisplatin 75&#x2009;mg/m[2] or carboplatin, Area Under the Curve,AUC 5 and pemetrexed 500&#x2009;mg/m[2]) 4-6 cycles, followed by 4-weekly durvalumab 1500&#x2009;mg until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target accrual time is 27 months, with follow-up for an additional 24 months. This provides over 85% power if the true HR for overall survival (OS) is 0.70, with two-sided alpha of 0.05, assuming a median OS of 15 months in the control group. Randomisation is stratified by age (18-70 years vs >70), sex, histology (epithelioid vs non-epithelioid), platinum agent (cisplatin vs carboplatin) and region (USA vs Australia/New Zealand vs Other). The primary endpoint is OS. Secondary endpoints include progression-free survival, objective tumour response (by mRECIST V.1.1 and iRECIST), adverse events, health-related quality of life and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and PrE0505 studies, PD-L1 expression, tumour mutational burden, genomic characteristics and human leukocyte antigen subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma.<br><br>ETHICS AND DISSEMINATION: The protocol was approved by human research ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.<br><br>DRUG SUPPLY: AstraZeneca.<br><br>PROTOCOL VERSION: CTC 0231 / TOGA 18/001 / PrE0506 3.0, 29 July 2021.<br><br>TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04334759 ACTRN 12620001199909.}, }
@article {pmid35073065, year = {2022}, author = {Voloaca, OM and Clench, MR and Koellensperger, G and Cole, LM and Haywood-Small, SL and Theiner, S}, title = {Elemental Mapping of Human Malignant Mesothelioma Tissue Samples Using High-Speed LA-ICP-TOFMS Imaging.}, journal = {Analytical chemistry}, volume = {94}, number = {5}, pages = {2597-2606}, pmid = {35073065}, issn = {1520-6882}, mesh = {*Asbestos/toxicity ; Humans ; *Laser Therapy ; Mass Spectrometry/methods ; *Mesothelioma, Malignant ; Spectrum Analysis ; }, abstract = {This is the first report of the use of laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) to analyze human malignant pleural mesothelioma (MPM) samples at the cellular level. MPM is an aggressive, incurable cancer associated with asbestos exposure, with a long latency and poor overall survival. Following careful optimization of the laser fluence, the simultaneous ablation of soft biological tissue and hard mineral fibers was possible, allowing the spatial detection of elements such as Si, Mg, Ca, and Fe, which are also present in the glass substrate. A low-dispersion LA setup was employed, which provided the high spatial resolution necessary to identify the asbestos fibers and fiber fragments in the tissue and to characterize the metallome at the cellular level (a pixel size of 2 μm), with a high speed (at 250 Hz). The multielement LA-ICP-TOFMS imaging approach enabled (i) the detection of asbestos fibers/mineral impurities within the MPM tissue samples of patients, (ii) the visualization of the tissue structure with the endogenous elemental pattern at high spatial resolution, and (iii) obtaining insights into the metallome of MPM patients with different pathologies in a single analysis run. Asbestos and other mineral fibers were detected in the lung and pleura tissue of MPM patients, respectively, based on their multielement pattern (Si, Mg, Ca, Fe, and Sr). Interestingly, strontium was detected in asbestos fibers, suggesting a link between this potential toxic element and MPM pathogenesis. Furthermore, monitoring the metallome around the talc deposit regions (characterized by elevated levels of Al, Mg, and Si) revealed significant tissue damage and inflammation caused by talc pleurodesis. LA-ICP-TOFMS results correlated to Perls' Prussian blue and histological staining of the corresponding serial sections. Ultimately, the ultra-high-speed and high-spatial-resolution capabilities of this novel LA-ICP-TOFMS setup may become an important clinical tool for simultaneous asbestos detection, metallome monitoring, and biomarker identification.}, }
@article {pmid35058235, year = {2022}, author = {Senek, M and Robertson, S and Darlison, L and Creech, L and Tod, A}, title = {Malignant pleural mesothelioma patients' experience by gender: findings from a cross-sectional UK-national questionnaire.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35058235}, issn = {2052-4439}, mesh = {Cross-Sectional Studies ; Female ; Humans ; Male ; *Mesothelioma, Malignant ; Quality of Life ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {OBJECTIVES: Malignant mesothelioma is an aggressive malignancy of mesothelial surfaces, most commonly those of the pleura. The aim of this study was to understand, using a national questionnaire, the gendered care experiences of patients with malignant pleural mesothelioma (MPM).Patients were asked about their experience of the diagnostic process, about information clarity, health care professionals' knowledge, general practitioner support and overall satisfaction with care received.<br><br>SETTING: Recruitment of patients was carried out in three UK countries (England, Wales and Scotland) via mesothelioma clinical nurse specialists.<br><br>PARTICIPANTS: In total, 503 patients completed the questionnaire. 460 had MPM, the remainder had other types of mesothelioma. In accord with the study protocol, only the MPM patients were included in this study.Primary and secondary measures were: (1) time from symptom to diagnosis, (2) satisfaction with the diagnosis and treatment, and (3) quality of life and well-being.<br><br>RESULTS: There were gender differences in time from symptom to diagnosis. The time from symptom to diagnosis was significantly longer for women than men (median=152 days vs men=92&#x2009;days, p=0.01). Lack of a verified source of exposure to asbestos was a hindrance to private treatment access for women (95% of those that access private treatment are men). Patients were five times more likely to be satisfied if they thought that the doctors knew enough about their condition (OR=4.4, p=0.001) and nearly three times more likely to be satisfied if information was presented in a sensitive way (OR=2.8,p=0.01).<br><br>CONCLUSIONS: This study has several implications for clinical practice. Our findings suggest that the diagnostic time in women might be reduced by reviewing diagnostic processes including occupational history taking, and by revising the occupational risk of mesothelioma categorisation.}, }
@article {pmid35042132, year = {2022}, author = {Armato, SG and Nowak, AK and Francis, RJ and Katz, SI and Kholmatov, M and Blyth, KG and Gudmundsson, E and Kidd, AC and Gill, RR}, title = {Imaging in pleural mesothelioma: A review of the 15th International Conference of the International Mesothelioma Interest Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {164}, number = {}, pages = {76-83}, doi = {10.1016/j.lungcan.2021.12.008}, pmid = {35042132}, issn = {1872-8332}, support = {R25 CA240134/CA/NCI NIH HHS/United States ; S10 RR021039/RR/NCRR NIH HHS/United States ; }, mesh = {Humans ; *Lung Neoplasms/pathology ; Magnetic Resonance Imaging ; *Mesothelioma/diagnostic imaging/pathology ; Neoplasm Staging ; *Pleural Neoplasms/diagnosis/pathology ; Public Opinion ; }, abstract = {Imaging of mesothelioma plays a role in all aspects of patient management, including disease detection, staging, evaluation of treatment options, response assessment, pre-surgical evaluation, and surveillance. Imaging in this disease impacts a wide range of disciplines throughout the healthcare enterprise. Researchers and clinician-scientists are developing state-of-the-art techniques to extract more of the information contained within these medical images and to utilize it for more sophisticated tasks; moreover, image-acquisition technology is advancing the inherent capabilities of these images. This paper summarizes the imaging-based topics presented orally at the 2021 International Conference of the International Mesothelioma Interest Group (iMig), which was held virtually from May 7-9, 2021. These topics include an update on the mesothelioma staging system, novel molecular targets to guide therapy in mesothelioma, special considerations and potential pitfalls in imaging mesothelioma in the immunotherapy setting, tumor measurement strategies and their correlation with patient survival, tumor volume measurement in MRI and CT, CT-based texture analysis for differentiation of histologic subtype, diffusion-weighted MRI for the assessment of biphasic mesothelioma, and the prognostic significance of skeletal muscle loss with chemotherapy.}, }
@article {pmid35032816, year = {2022}, author = {Sculco, M and La Vecchia, M and Aspesi, A and Pinton, G and Clavenna, MG and Casalone, E and Allione, A and Grosso, F and Libener, R and Muzio, A and Rena, O and Baietto, G and Parini, S and Boldorini, R and Giachino, D and Papotti, M and Scagliotti, GV and Migliore, E and Mirabelli, D and Moro, L and Magnani, C and Ferrante, D and Matullo, G and Dianzani, I}, title = {Malignant pleural mesothelioma: Germline variants in DNA repair genes may steer tailored treatment.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {163}, number = {}, pages = {44-54}, doi = {10.1016/j.ejca.2021.12.023}, pmid = {35032816}, issn = {1879-0852}, mesh = {DNA Repair/genetics ; Germ Cells/pathology ; Humans ; *Lung Neoplasms/drug therapy/genetics/pathology ; *Mesothelioma/drug therapy/genetics/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/genetics/pathology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a tumour associated with asbestos exposure. Approximately, 10% of patients with MPM carry a germline pathogenic variant (PV), mostly in DNA repair genes, suggesting the occurrence of inherited predispositions.<br><br>AIM: This article aimed to&#xa0;1) search for new predisposing genes and assess the prevalence of PVs in DNA repair genes, by next-generation sequencing (NGS) analysis of germline DNA from 113 unselected patients with MPM and 2) evaluate whether these patients could be sensitive to tailored treatments.<br><br>METHODS: NGS was performed using a custom panel of 107 cancer-predisposing genes. To investigate the response to selected drugs in conditions of DNA repair insufficiency, we created a three-dimensional-MPM cell model that had a defect in ataxia telangiectasia mutated (ATM), the master regulator of DNA repair.<br><br>RESULTS: We identified PVs in approximately 7% of patients with MPM&#xa0;(8/113) and a new PV in BAP1 in a further patient with familial MPM. Most of these PVs were in genes involved or supposedly involved in DNA repair (BRCA1, BRIP1, CHEK2, SLX4, FLCN&#xa0;and BAP1). In&#xa0;vitro studies showed apoptosis induction in ATM-silenced/inhibited MPM spheroids treated with an enhancer of zeste homologue 2 inhibitor (tazemetostat).<br><br>CONCLUSIONS: Overall these data suggest that patients with MPM&#xa0;and DNA repair insufficiency may benefit from this treatment, which induces synthetic lethality.}, }
@article {pmid35010531, year = {2021}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, &#xd8;}, title = {Cancer Incidence and Risk of Multiple Cancers after Environmental Asbestos Exposure in Childhood-A Long-Term Register-Based Cohort Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {1}, pages = {}, pmid = {35010531}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Child ; Cohort Studies ; Environmental Exposure/statistics &amp; numerical data ; Humans ; Incidence ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases ; *Occupational Exposure/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: To examine the asbestos-associated cancer incidence and the risk of multiple cancers in former school children exposed to environmental asbestos in childhood.<br><br>METHODS: A cohort of 12,111 former school children, born 1940-1970, was established using 7th grade school records from four schools located at a distance of 100-750 m in the prevailing wind direction from a large asbestos-cement plant that operated from 1928 to 1984 in Aalborg, Denmark. Using the unique Danish personal identification number, we linked information on employments, relatives' employments, date of cancer diagnosis, and type of cancer and vital status to data on cohortees extracted from the Supplementary Pension Fund Register (employment history), the Danish Cancer Registry, and the Danish Civil Registration System. We calculated standardized incidence rates (SIRs) for asbestos-associated cancers, all cancers, and multiple cancers using rates for a gender and five-year frequency-matched reference cohort.<br><br>RESULTS: The overall incidence of cancer was modestly increased for the school cohort (SIR 1.07, 95% confidence interval (CI) 1.02-1.12) compared with the reference cohort. This excess was driven primarily by a significantly increased SIR for malignant mesothelioma (SIR 8.77, 95% CI 6.38-12.05). Former school children who had combined childhood environmental and subsequent occupational exposure to asbestos had a significantly increased risk of lung cancer. Within this group, those with additional household exposure by a relative had a significantly increased SIR for cancer of the pharynx (SIR 4.24, 95% CI 1.59-11.29). We found no significant difference in the number of subjects diagnosed with multiple cancers between the two cohorts.<br><br>CONCLUSIONS: Our study confirms the strong association between environmental asbestos exposure and malignant mesothelioma and suggests that environmental asbestos exposure in childhood may increase the overall cancer risk later in life.}, }
@article {pmid35010496, year = {2021}, author = {Binazzi, A and Di Marzio, D and Verardo, M and Migliore, E and Benfatto, L and Malacarne, D and Mensi, C and Consonni, D and Eccher, S and Mazzoleni, G and Comiati, V and Negro, C and Romanelli, A and Chellini, E and Angelini, A and Grappasonni, I and Madeo, G and Romeo, E and Di Giammarco, A and Carrozza, F and Angelillo, IF and Cavone, D and Vimercati, L and Labianca, M and Tallarigo, F and Tumino, R and Melis, M and Bonafede, M and Scarselli, A and Marinaccio, A and On Behalf Of The ReNaM Working Group, }, title = {Asbestos Exposure and Malignant Mesothelioma in Construction Workers-Epidemiological Remarks by the Italian National Mesothelioma Registry (ReNaM).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {1}, pages = {}, pmid = {35010496}, issn = {1660-4601}, mesh = {*Asbestos ; *Construction Industry ; Humans ; Italy/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Registries ; }, abstract = {Notwithstanding the ban in 1992, asbestos exposure for workers in the construction sector in Italy remains a concern. The purpose of this study is to describe the characteristics of malignant mesothelioma (MM) cases recorded by the Italian registry (ReNaM) among construction workers. Incident mesothelioma cases with a definite asbestos exposure have been analyzed. Characteristics of cases and territorial clusters of crude rates of MM in construction workers have been described, as well as the relation between asbestos use before the ban and the historical trend of workforce in the construction sector in Italy. ReNaM has collected 31,572 incident MM cases in the period from 1993 to 2018 and asbestos exposure has been assessed for 24,864 (78.2%) cases. An occupational exposure has been reported for 17,191 MM cases (69.1% of subjects with a definite asbestos exposure). Among them, 3574 had worked in the construction sector, with an increasing trend from 15.8% in the 1993-98 period to 23.9% in 2014-2018 and a ubiquitous territorial distribution. The large use of asbestos in construction sector before the ban makes probability of exposure for workers a real concern still today, particularly for those working in maintenance and removal of old buildings. There is a clear need to assess, inform, and prevent asbestos exposure in this sector.}, }
@article {pmid35004305, year = {2021}, author = {Crovella, S and Revelant, A and Muraro, E and Moura, RR and Brandão, L and Trovò, M and Steffan, A and Zacchi, P and Zabucchi, G and Minatel, E and Borelli, V}, title = {Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {784081}, pmid = {35004305}, issn = {2234-943X}, abstract = {Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.}, }
@article {pmid35001771, year = {2022}, author = {Korchevskiy, AA and Wylie, AG}, title = {Dimensional characteristics of the major types of amphibole mineral particles and the implications for carcinogenic risk assessment.}, journal = {Inhalation toxicology}, volume = {34}, number = {1-2}, pages = {24-38}, doi = {10.1080/08958378.2021.2024304}, pmid = {35001771}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/analysis/toxicity ; Carcinogenesis ; Carcinogens/toxicity ; Humans ; *Lung Neoplasms/chemically induced ; *Mesothelioma/chemically induced ; Minerals/toxicity ; Risk Assessment ; }, abstract = {Context: Though some significant advances have been made in recent decades to evaluate the importance of size and morphology (habit) of elongate mineral particles (EMPs), further research is needed to better understand the role of each dimensional metric in determining the levels of cancer potency.Objective: To determine dimensional parameters most relevant for predicting cancer potency of durable elongate particles, specifically amphibole and durable silicate minerals generally.Methods: A database on dimensional and other relevant characteristics of elongate amphibole mineral particles was created, containing particle-by-particle information for 128 099 particles. Integral statistical characteristics on dimensionality of various amphibole types and morphological habits of EMPs were calculated, compared, and correlated with published mesothelioma and lung cancer potency factors.Results: The highest absolute Pearson correlation (r = 0.97, r[2] = 0.94, p < 0.05) was achieved between mesothelioma potency (RM) and specific surface area. The highest correlation with adjusted lung cancer potency was found with particle aspect ratio (AR) (r = 0.80, r[2] = 0.64, p < 0.05). Cluster analysis demonstrates that fractions of thin fibers (width less than 0.15 and 0.25 µm) also closely relate both to lung cancer and RM. Asbestiform and non-asbestiform populations of amphiboles significantly differ by dimensionality and carcinogenic potency.Conclusions: Dimensional parameters and morphological habits of EMPs are the main drivers for the observable difference in cancer potency among amphibole populations.}, }
@article {pmid34992464, year = {2021}, author = {Tai, SY and Wu, J and Lee, LJ and Lu, TH}, title = {How Malignant Mesothelioma Was Coded in Mortality Data in Taiwan During Years When the Specific ICD Code Was Not Available?.}, journal = {Clinical epidemiology}, volume = {13}, number = {}, pages = {1135-1140}, pmid = {34992464}, issn = {1179-1349}, abstract = {PURPOSE: Malignant mesothelioma (MM) is associated with past exposure to asbestos and the latency period ranged from 20 to 40 years. Asbestos consumption reached a peak in the 1980s in Taiwan, and the MM mortality is expected to increase since 2000s. However, no specific code for MM was available before the International Classification of Disease, Tenth Revision (ICD-10), which was launched in 2008 in Taiwan. We examined how MM was coded in mortality data in Taiwan during the years when the ICD, Ninth Revision (ICD-9) was used.<br><br>PATIENTS AND METHODS: Double-coded mortality data (each death coded according to both ICD-10 and ICD-9 codes) for the period 2002-2008 were obtained for analysis. Detection rates (similar to sensitivity) and confirmation rates (similar to positive predictive value) for various potential proxy ICD-9 codes for MM were calculated.<br><br>RESULTS: For 113 deaths, for which the underlying cause of death was ICD-10 code C45 (MM), 14 corresponding ICD-9 codes were used. Four ICD-9 codes constituted 77% (87/113) of all MM deaths. The detection rate for code 199 (malignant neoplasm [MN] without specification of site) was 37% (42/113), that for code 163 (MN of pleura) was 18% (20/113), that for code 162 (MN of trachea, bronchus, and lung) was 12% (14/113), and that for code 173 (other MN of skin) was 10% (11/113). The confirmation rates for codes 199, 163, 162, and 173 were 0.9% (42/4759), 14.3% (20/140), 0.03% (14/51,778), and 1.5% (11/717), respectively.<br><br>CONCLUSION: ICD-9 codes 199, 163, 162, and 173 were most commonly used for MM deaths in Taiwan during the years before the ICD-10 introduction. However, when we used only ICD-9 code 163, which was most commonly used as a surrogate measure of MM in mortality studies during the ICD-9 era, we could detect only one-fifth of MM deaths in Taiwan.}, }
@article {pmid34984327, year = {2022}, author = {Orozco Morales, ML and Rinaldi, CA and de Jong, E and Lansley, SM and Gummer, JPA and Olasz, B and Nambiar, S and Hope, DE and Casey, TH and Lee, YCG and Leslie, C and Nealon, G and Shackleford, DM and Powell, AK and Grimaldi, M and Balaguer, P and Zemek, RM and Bosco, A and Piggott, MJ and Vrielink, A and Lake, RA and Lesterhuis, WJ}, title = {PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective.}, journal = {iScience}, volume = {25}, number = {1}, pages = {103571}, pmid = {34984327}, issn = {2589-0042}, abstract = {Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro anti-tumor effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma.}, }
@article {pmid34967848, year = {2022}, author = {,  and Kocarnik, JM and Compton, K and Dean, FE and Fu, W and Gaw, BL and Harvey, JD and Henrikson, HJ and Lu, D and Pennini, A and Xu, R and Ababneh, E and Abbasi-Kangevari, M and Abbastabar, H and Abd-Elsalam, SM and Abdoli, A and Abedi, A and Abidi, H and Abolhassani, H and Adedeji, IA and Adnani, QES and Advani, SM and Afzal, MS and Aghaali, M and Ahinkorah, BO and Ahmad, S and Ahmad, T and Ahmadi, A and Ahmadi, S and Ahmed Rashid, T and Ahmed Salih, Y and Akalu, GT and Aklilu, A and Akram, T and Akunna, CJ and Al Hamad, H and Alahdab, F and Al-Aly, Z and Ali, S and Alimohamadi, Y and Alipour, V and Aljunid, SM and Alkhayyat, M and Almasi-Hashiani, A and Almasri, NA and Al-Maweri, SAA and Almustanyir, S and Alonso, N and Alvis-Guzman, N and Amu, H and Anbesu, EW and Ancuceanu, R and Ansari, F and Ansari-Moghaddam, A and Antwi, MH and Anvari, D and Anyasodor, AE and Aqeel, M and Arabloo, J and Arab-Zozani, M and Aremu, O and Ariffin, H and Aripov, T and Arshad, M and Artaman, A and Arulappan, J and Asemi, Z and Asghari Jafarabadi, M and Ashraf, T and Atorkey, P and Aujayeb, A and Ausloos, M and Awedew, AF and Ayala Quintanilla, BP and Ayenew, T and Azab, MA and Azadnajafabad, S and Azari Jafari, A and Azarian, G and Azzam, AY and Badiye, AD and Bahadory, S and Baig, AA and Baker, JL and Balakrishnan, S and Banach, M and Bärnighausen, TW and Barone-Adesi, F and Barra, F and Barrow, A and Behzadifar, M and Belgaumi, UI and Bezabhe, WMM and Bezabih, YM and Bhagat, DS and Bhagavathula, AS and Bhardwaj, N and Bhardwaj, P and Bhaskar, S and Bhattacharyya, K and Bhojaraja, VS and Bibi, S and Bijani, A and Biondi, A and Bisignano, C and Bjørge, T and Bleyer, A and Blyuss, O and Bolarinwa, OA and Bolla, SR and Braithwaite, D and Brar, A and Brenner, H and Bustamante-Teixeira, MT and Butt, NS and Butt, ZA and Caetano Dos Santos, FL and Cao, Y and Carreras, G and Catalá-López, F and Cembranel, F and Cerin, E and Cernigliaro, A and Chakinala, RC and Chattu, SK and Chattu, VK and Chaturvedi, P and Chimed-Ochir, O and Cho, DY and Christopher, DJ and Chu, DT and Chung, MT and Conde, J and Cortés, S and Cortesi, PA and Costa, VM and Cunha, AR and Dadras, O and Dagnew, AB and Dahlawi, SMA and Dai, X and Dandona, L and Dandona, R and Darwesh, AM and das Neves, J and De la Hoz, FP and Demis, AB and Denova-Gutiérrez, E and Dhamnetiya, D and Dhimal, ML and Dhimal, M and Dianatinasab, M and Diaz, D and Djalalinia, S and Do, HP and Doaei, S and Dorostkar, F and Dos Santos Figueiredo, FW and Driscoll, TR and Ebrahimi, H and Eftekharzadeh, S and El Tantawi, M and El-Abid, H and Elbarazi, I and Elhabashy, HR and Elhadi, M and El-Jaafary, SI and Eshrati, B and Eskandarieh, S and Esmaeilzadeh, F and Etemadi, A and Ezzikouri, S and Faisaluddin, M and Faraon, EJA and Fares, J and Farzadfar, F and Feroze, AH and Ferrero, S and Ferro Desideri, L and Filip, I and Fischer, F and Fisher, JL and Foroutan, M and Fukumoto, T and Gaal, PA and Gad, MM and Gadanya, MA and Gallus, S and Gaspar Fonseca, M and Getachew Obsa, A and Ghafourifard, M and Ghashghaee, A and Ghith, N and Gholamalizadeh, M and Gilani, SA and Ginindza, TG and Gizaw, ATT and Glasbey, JC and Golechha, M and Goleij, P and Gomez, RS and Gopalani, SV and Gorini, G and Goudarzi, H and Grosso, G and Gubari, MIM and Guerra, MR and Guha, A and Gunasekera, DS and Gupta, B and Gupta, VB and Gupta, VK and Gutiérrez, RA and Hafezi-Nejad, N and Haider, MR and Haj-Mirzaian, A and Halwani, R and Hamadeh, RR and Hameed, S and Hamidi, S and Hanif, A and Haque, S and Harlianto, NI and Haro, JM and Hasaballah, AI and Hassanipour, S and Hay, RJ and Hay, SI and Hayat, K and Heidari, G and Heidari, M and Herrera-Serna, BY and Herteliu, C and Hezam, K and Holla, R and Hossain, MM and Hossain, MBH and Hosseini, MS and Hosseini, M and Hosseinzadeh, M and Hostiuc, M and Hostiuc, S and Househ, M and Hsairi, M and Huang, J and Hugo, FN and Hussain, R and Hussein, NR and Hwang, BF and Iavicoli, I and Ibitoye, SE and Ida, F and Ikuta, KS and Ilesanmi, OS and Ilic, IM and Ilic, MD and Irham, LM and Islam, JY and Islam, RM and Islam, SMS and Ismail, NE and Isola, G and Iwagami, M and Jacob, L and Jain, V and Jakovljevic, MB and Javaheri, T and Jayaram, S and Jazayeri, SB and Jha, RP and Jonas, JB and Joo, T and Joseph, N and Joukar, F and Jürisson, M and Kabir, A and Kahrizi, D and Kalankesh, LR and Kalhor, R and Kaliyadan, F and Kalkonde, Y and Kamath, A and Kameran Al-Salihi, N and Kandel, H and Kapoor, N and Karch, A and Kasa, AS and Katikireddi, SV and Kauppila, JH and Kavetskyy, T and Kebede, SA and Keshavarz, P and Keykhaei, M and Khader, YS and Khalilov, R and Khan, G and Khan, M and Khan, MN and Khan, MAB and Khang, YH and Khater, AM and Khayamzadeh, M and Kim, GR and Kim, YJ and Kisa, A and Kisa, S and Kissimova-Skarbek, K and Kopec, JA and Koteeswaran, R and Koul, PA and Koulmane Laxminarayana, SL and Koyanagi, A and Kucuk Bicer, B and Kugbey, N and Kumar, GA and Kumar, N and Kumar, N and Kurmi, OP and Kutluk, T and La Vecchia, C and Lami, FH and Landires, I and Lauriola, P and Lee, SW and Lee, SWH and Lee, WC and Lee, YH and Leigh, J and Leong, E and Li, J and Li, MC and Liu, X and Loureiro, JA and Lunevicius, R and Magdy Abd El Razek, M and Majeed, A and Makki, A and Male, S and Malik, AA and Mansournia, MA and Martini, S and Masoumi, SZ and Mathur, P and McKee, M and Mehrotra, R and Mendoza, W and Menezes, RG and Mengesha, EW and Mesregah, MK and Mestrovic, T and Miao Jonasson, J and Miazgowski, B and Miazgowski, T and Michalek, IM and Miller, TR and Mirzaei, H and Mirzaei, HR and Misra, S and Mithra, P and Moghadaszadeh, M and Mohammad, KA and Mohammad, Y and Mohammadi, M and Mohammadi, SM and Mohammadian-Hafshejani, A and Mohammed, S and Moka, N and Mokdad, AH and Molokhia, M and Monasta, L and Moni, MA and Moosavi, MA and Moradi, Y and Moraga, P and Morgado-da-Costa, J and Morrison, SD and Mosapour, A and Mubarik, S and Mwanri, L and Nagarajan, AJ and Nagaraju, SP and Nagata, C and Naimzada, MD and Nangia, V and Naqvi, AA and Narasimha Swamy, S and Ndejjo, R and Nduaguba, SO and Negoi, I and Negru, SM and Neupane Kandel, S and Nguyen, CT and Nguyen, HLT and Niazi, RK and Nnaji, CA and Noor, NM and Nuñez-Samudio, V and Nzoputam, CI and Oancea, B and Ochir, C and Odukoya, OO and Ogbo, FA and Olagunju, AT and Olakunde, BO and Omar, E and Omar Bali, A and Omonisi, AEE and Ong, S and Onwujekwe, OE and Orru, H and Ortega-Altamirano, DV and Otstavnov, N and Otstavnov, SS and Owolabi, MO and P A, M and Padubidri, JR and Pakshir, K and Pana, A and Panagiotakos, D and Panda-Jonas, S and Pardhan, S and Park, EC and Park, EK and Pashazadeh Kan, F and Patel, HK and Patel, JR and Pati, S and Pattanshetty, SM and Paudel, U and Pereira, DM and Pereira, RB and Perianayagam, A and Pillay, JD and Pirouzpanah, S and Pishgar, F and Podder, I and Postma, MJ and Pourjafar, H and Prashant, A and Preotescu, L and Rabiee, M and Rabiee, N and Radfar, A and Radhakrishnan, RA and Radhakrishnan, V and Rafiee, A and Rahim, F and Rahimzadeh, S and Rahman, M and Rahman, MA and Rahmani, AM and Rajai, N and Rajesh, A and Rakovac, I and Ram, P and Ramezanzadeh, K and Ranabhat, K and Ranasinghe, P and Rao, CR and Rao, SJ and Rawassizadeh, R and Razeghinia, MS and Renzaho, AMN and Rezaei, N and Rezaei, N and Rezapour, A and Roberts, TJ and Rodriguez, JAB and Rohloff, P and Romoli, M and Ronfani, L and Roshandel, G and Rwegerera, GM and S, M and Sabour, S and Saddik, B and Saeed, U and Sahebkar, A and Sahoo, H and Salehi, S and Salem, MR and Salimzadeh, H and Samaei, M and Samy, AM and Sanabria, J and Sankararaman, S and Santric-Milicevic, MM and Sardiwalla, Y and Sarveazad, A and Sathian, B and Sawhney, M and Saylan, M and Schneider, IJC and Sekerija, M and Seylani, A and Shafaat, O and Shaghaghi, Z and Shaikh, MA and Shamsoddin, E and Shannawaz, M and Sharma, R and Sheikh, A and Sheikhbahaei, S and Shetty, A and Shetty, JK and Shetty, PH and Shibuya, K and Shirkoohi, R and Shivakumar, KM and Shivarov, V and Siabani, S and Siddappa Malleshappa, SK and Silva, DAS and Singh, JA and Sintayehu, Y and Skryabin, VY and Skryabina, AA and Soeberg, MJ and Sofi-Mahmudi, A and Sotoudeh, H and Steiropoulos, P and Straif, K and Subedi, R and Sufiyan, MB and Sultan, I and Sultana, S and Sur, D and Szerencsés, V and Szócska, M and Tabarés-Seisdedos, R and Tabuchi, T and Tadbiri, H and Taherkhani, A and Takahashi, K and Talaat, IM and Tan, KK and Tat, VY and Tedla, BAA and Tefera, YG and Tehrani-Banihashemi, A and Temsah, MH and Tesfay, FH and Tessema, GA and Thapar, R and Thavamani, A and Thoguluva Chandrasekar, V and Thomas, N and Tohidinik, HR and Touvier, M and Tovani-Palone, MR and Traini, E and Tran, BX and Tran, KB and Tran, MTN and Tripathy, JP and Tusa, BS and Ullah, I and Ullah, S and Umapathi, KK and Unnikrishnan, B and Upadhyay, E and Vacante, M and Vaezi, M and Valadan Tahbaz, S and Velazquez, DZ and Veroux, M and Violante, FS and Vlassov, V and Vo, B and Volovici, V and Vu, GT and Waheed, Y and Wamai, RG and Ward, P and Wen, YF and Westerman, R and Winkler, AS and Yadav, L and Yahyazadeh Jabbari, SH and Yang, L and Yaya, S and Yazie, TSY and Yeshaw, Y and Yonemoto, N and Younis, MZ and Yousefi, Z and Yu, C and Yuce, D and Yunusa, I and Zadnik, V and Zare, F and Zastrozhin, MS and Zastrozhina, A and Zhang, J and Zhong, C and Zhou, L and Zhu, C and Ziapour, A and Zimmermann, IR and Fitzmaurice, C and Murray, CJL and Force, LM}, title = {Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.}, journal = {JAMA oncology}, volume = {8}, number = {3}, pages = {420-444}, pmid = {34967848}, issn = {2374-2445}, support = {001/WHO_/World Health Organization/International ; SCAF/15/02/CSO_/Chief Scientist Office/United Kingdom ; SPHSU17/CSO_/Chief Scientist Office/United Kingdom ; MC_UU_00022/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Disability-Adjusted Life Years ; *Global Burden of Disease ; Global Health ; Humans ; Incidence ; *Neoplasms/epidemiology ; Prevalence ; Quality-Adjusted Life Years ; Risk Factors ; }, abstract = {IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.<br><br>OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.<br><br>EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).<br><br>FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.<br><br>CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.}, }
@article {pmid34965001, year = {2022}, author = {Okazaki, Y}, title = {Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species.}, journal = {Pathology international}, volume = {72}, number = {2}, pages = {83-95}, doi = {10.1111/pin.13196}, pmid = {34965001}, issn = {1440-1827}, support = {JSPS KAKENHI 21K06968//Japan Society for the Promotion of Science/ ; //JSPS KAKENHI/ ; }, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Carcinogenesis ; Cation Transport Proteins/genetics/metabolism ; Deferasirox/administration &amp; dosage ; Humans ; Iron/*metabolism ; Iron Chelating Agents/administration &amp; dosage ; Mesothelioma, Malignant/chemically induced/*pathology ; Mice ; Mice, Transgenic ; Mineral Fibers/*adverse effects ; Nanotubes, Carbon/*adverse effects ; Oxidative Stress ; Reactive Oxygen Species/*metabolism ; }, abstract = {Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos-induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30-40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator-induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA-199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high-grade SM. Moreover, phlebotomy delayed MM development in crocidolite-induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod-like shapes in addition to the molecular mechanisms of MM development.}, }
@article {pmid34962302, year = {2022}, author = {Kottek, M and Yuen, ML}, title = {Public health risks from asbestos cement roofing.}, journal = {American journal of industrial medicine}, volume = {65}, number = {3}, pages = {157-161}, pmid = {34962302}, issn = {1097-0274}, mesh = {*Asbestos/toxicity ; Construction Materials/toxicity ; Humans ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; Public Health ; Weather ; }, abstract = {There is no identified risk-free threshold exposure to asbestos. Based on epidemiology and toxicology, asbestos fiber dimensions have been implicated in causing asbestos-related diseases. Phase-contrast microscopy provides only a limited index of exposure to fiber dimensions implicated in mesothelioma induction. Installed asbestos-containing materials (ACMs) create an ongoing risk of intense exposure during natural disasters and remodeling, along with low-level exposure arising from the continual emission of airborne asbestos into the environment arising from weathering of installed ACM. Epidemiological studies have demonstrated a risk of disease associated with proximity to asbestos cement roofing (ACR), while ongoing environmental emissions of asbestos from installed ACR have also been demonstrated. Owing to the limitations of the available data, a precautionary approach is warranted; asbestos-free roofing materials should be used in new construction and existing ACR should be removed at the earliest opportunity.}, }
@article {pmid34960727, year = {2021}, author = {Forte, IM and Indovina, P and Montagnaro, S and Costa, A and Iannuzzi, CA and Capone, F and Camerlingo, R and Malfitano, AM and Pentimalli, F and Ferrara, G and Quintiliani, M and Portella, G and Giordano, A and Ciarcia, R}, title = {The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach.}, journal = {Viruses}, volume = {13}, number = {12}, pages = {}, pmid = {34960727}, issn = {1999-4915}, mesh = {Antineoplastic Agents/*pharmacology ; *Apoptosis/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Cisplatin/*pharmacology ; Combined Modality Therapy ; Humans ; Mesothelioma, Malignant/drug therapy/physiopathology/*therapy/virology ; *Oncolytic Virotherapy ; Oncolytic Viruses/genetics/*physiology ; Varicellovirus/genetics/*physiology ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.}, }
@article {pmid34948918, year = {2021}, author = {Klebe, S and Hocking, AJ and Soeberg, M and Leigh, J}, title = {The Significance of Short Latency in Mesothelioma for Attribution of Causation: Report of a Case with Predisposing Germline Mutations and Review of the Literature.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948918}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Germ-Line Mutation ; Humans ; *Lung Neoplasms/genetics ; Male ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/genetics ; }, abstract = {Malignant mesothelioma is a tumour of the serosal membranes, related to asbestos exposure. Median latency is in the order of 40 years in various registries, but small numbers of cases with shorter latencies have long been reported and often dismissed as unrelated to asbestos exposure. However, emerging data regarding the significance of inherited mutations leading to a predisposition to mesothelioma suggest that the causative effect of asbestos may be associated with shorter latencies in a subset of patients. Here, we describe a male patient with germline mutations in RAD51 and p53 who developed peritoneal mesothelioma 8.5 years after well-documented asbestos exposure and discuss the current literature on the subject. Mesothelioma in situ is now a WHO-accepted diagnosis, but preliminary data reveal a potential lead time of 5 or more years to invasive disease, and this is also a factor which may affect the recording of latency (and potentially survival) in the future.}, }
@article {pmid34948906, year = {2021}, author = {Lysaniuk, B and Cely-García, MF and Giraldo, M and Larrahondo, JM and Serrano-Calderón, LM and Guerrero-Bernal, JC and Briceno-Ayala, L and Cruz Rodriguez, E and Ramos-Bonilla, JP}, title = {Using GIS to Estimate Population at Risk Because of Residence Proximity to Asbestos Processing Facilities in Colombia.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948906}, issn = {1660-4601}, mesh = {*Asbestos ; Asbestos, Serpentine ; Colombia/epidemiology ; Geographic Information Systems ; Humans ; *Mesothelioma ; Risk Factors ; }, abstract = {The recent enactment of the law banning asbestos in Colombia raises a significant number of challenges. The largest factories that have historically processed asbestos include five asbestos-cement facilities located in the cities of Sibaté (Cundinamarca), Cali (Valle del Cauca), and Barranquilla (Atlántico), and Manizales (Caldas), which has two, as well as a friction products facility in Bogotá D.C. An asbestos chrysotile mine has also operated in Colombia since 1980 in Campamento (Antioquia). In the framework of developing the National Asbestos Profile for Colombia, in this study, we estimated the population residing in the vicinity of asbestos processing plants or the mine and, therefore, potentially at risk of disease. Using a geographic information system, demographic data obtained from the last two general population censuses were processed to determine the number of people living within the concentric circles surrounding the asbestos facilities and the mine. In previous studies conducted in different countries of the world, an increased risk of asbestos-related diseases has been reported for people living at different distance bands from asbestos processing facilities. Based on these studies, circles of 500, 1000, 2000, 5000, and 10,000 m radii, centered on the asbestos processing facilities and the mine that operated in Colombia, were combined with the census data to estimate the number of people living within these radii. Large numbers of people were identified. It is estimated that in 2005, at the country level, 10,489 people lived within 500 m of an asbestos processing facility or mine. In 2018, and within a distance of 10,000 m, the number of people was 6,724,677. This information can aid public health surveillance strategies.}, }
@article {pmid34944051, year = {2021}, author = {Abukar, A and Wipplinger, M and Hariharan, A and Sun, S and Ronner, M and Sculco, M and Okonska, A and Kresoja-Rakic, J and Rehrauer, H and Qi, W and Beusechem, VWV and Felley-Bosco, E}, title = {Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34944051}, issn = {2073-4409}, support = {320030_182690/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {3' Untranslated Regions/genetics ; Adenosine Deaminase/metabolism ; Animals ; Cell Line, Tumor ; Epithelium/metabolism ; Genes, Reporter ; Humans ; Mesothelioma/genetics/metabolism/pathology ; Mice ; Models, Biological ; Protein Binding ; *Protein Biosynthesis ; *RNA Editing ; RNA, Double-Stranded/*chemistry ; *RNA-Binding Motifs ; RNA-Binding Proteins/*metabolism ; }, abstract = {Mesothelioma is an aggressive cancer associated with asbestos exposure. RNA-binding motif protein 8a (RBM8A) mRNA editing increases in mouse tissues upon asbestos exposure. The aim of this study was to further characterize the role of RBM8A in mesothelioma and the consequences of its mRNA editing. RBM8A protein expression was higher in mesothelioma compared to mesothelial cells. Silencing RBM8A changed splicing patterns in mesothelial and mesothelioma cells but drastically reduced viability only in mesothelioma cells. In the tissues of asbestos-exposed mice, editing of Rbm8a mRNA was associated with increased protein immunoreactivity, with no change in mRNA levels. Increased adenosine deaminase acting on dsRNA (ADAR)-dependent editing of Alu elements in the RBM8A 3'UTR was observed in mesothelioma cells compared to mesothelial cells. Editing stabilized protein expression. The unedited RBM8A 3'UTR had a stronger interaction with Musashi (MSI) compared to the edited form. The silencing of MSI2 in mesothelioma or overexpression of Adar2 in mesothelial cells resulted in increased RBM8A protein levels. Therefore, ADAR-dependent editing contributes to maintaining elevated RBM8A protein levels in mesothelioma by counteracting MSI2-driven downregulation. A wider implication of this mechanism for the translational control of protein expression is suggested by the editing of similarly structured Alu elements in several other transcripts.}, }
@article {pmid34943522, year = {2021}, author = {Gharib, AF and Alaa Eldeen, M and Khalifa, AS and Elsawy, WH and Eed, EM and Askary, AE and Eid, RA and Soltan, MA and Raafat, N}, title = {Assessment of Glutathione Peroxidase-1 (GPX1) Gene Expression as a Specific Diagnostic and Prognostic Biomarker in Malignant Pleural Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {12}, pages = {}, pmid = {34943522}, issn = {2075-4418}, support = {TURSP-2020/157//Taif University/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of MPM are considered the cornerstone success factors for the management of early MPM. Glutathione peroxidase-1 (GPX1) is an intracellular protein found to be extensively distributed in all cells, and it belongs to the GPX group. In the current study, we included ninety-eight patients with MPM that underwent surgery at the Zagazig University Hospital in Egypt. We assessed GPX1 gene expression level as it was thought to be related to pathogenicity of cancer in a variety of malignant tumors. We observed a significant elevation in GPX1-mRNA levels in MPM relative to the nearby normal pleural tissues. It was found to be of important diagnostic specificity in the differentiation of MPM from normal tissues. Moreover, we studied the survival of patients in correlation to the GPX1 expression levels and we reported that median overall survival was about 16 months in patients with high GPX1 expression levels, while it was found to be about 40 months in low GPX1 levels.}, }
@article {pmid34909922, year = {2021}, author = {Hajj, GNM and Cavarson, CH and Pinto, CAL and Venturi, G and Navarro, JR and Lima, VCC}, title = {Malignant pleural mesothelioma: an update.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {47}, number = {6}, pages = {e20210129}, pmid = {34909922}, issn = {1806-3756}, mesh = {*Asbestos/toxicity ; Humans ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Pleura ; *Pleural Neoplasms/diagnosis/therapy ; }, abstract = {Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure, but due to a latency period of more than 30 years and difficult diagnosis, most cases are not detected until they reach advanced stages. Treatment options for this tumor type are very limited and survival ranges from 12 to 36 months. This review discusses the molecular physiopathology, current diagnosis, and latest therapeutic options for this disease.}, }
@article {pmid34907223, year = {2021}, author = {Frontini, F and Bononi, I and Torreggiani, E and Di Mauro, G and Mazzoni, E and Stendardo, M and Boschetto, P and Libener, R and Guaschino, R and Grosso, F and Guerra, G and Martini, F and Tognon, M}, title = {Circulating microRNA-197-3p as a potential biomarker for asbestos exposure.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {23955}, pmid = {34907223}, issn = {2045-2322}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers/blood ; Circulating MicroRNA/*blood/genetics ; Female ; Humans ; Male ; MicroRNAs/*blood/genetics ; Middle Aged ; Occupational Exposure/*adverse effects ; }, abstract = {Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.}, }
@article {pmid34900693, year = {2021}, author = {Johnson, BW and Takahashi, K and Cheng, YY}, title = {Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {748444}, pmid = {34900693}, issn = {2234-943X}, abstract = {Malignant mesothelioma is an aggressive cancer with poor prognosis, predominantly caused by human occupational exposure to asbestos. The global incidence of mesothelioma is predicted to increase as a consequence of continued exposure to asbestos from a variety of sources, including construction material produced in the past in developed countries, as well as those currently being produced in developing countries. Mesothelioma typically develops after a long latency period and consequently it is often diagnosed in the clinic at an advanced stage, at which point standard care of treatment, such as chemo- and radio-therapy, are largely ineffective. Much of our current understanding of mesothelioma biology, particularly in relation to disease pathogenesis, diagnosis and treatment, can be attributed to decades of preclinical basic science research. Given the postulated rising incidence in mesothelioma cases and the limitations of current diagnostic and treatment options, continued preclinical research into mesothelioma is urgently needed. The ever-evolving landscape of preclinical models and laboratory technology available to researchers have made it possible to study human disease with greater precision and at an accelerated rate. In this review article we provide an overview of the various resources that can be exploited to facilitate an enhanced understanding of mesothelioma biology and their applications to research aimed to improve the diagnosis and treatment of mesothelioma. These resources include cell lines, animal models, mesothelioma-specific biobanks and modern laboratory techniques/technologies. Given that different preclinical models and laboratory technologies have varying limitations and applications, they must be selected carefully with respect to the intended objectives of the experiments. This review therefore aims to provide a comprehensive overview of the various preclinical models and technologies with respect to their advantages and limitations. Finally, we will detail about a highly valuable preclinical laboratory resource to curate high quality mesothelioma biospecimens for research; the biobank. Collectively, these resources are essential to the continued advancement of precision medicine to curtail the increasing health burden caused by malignant mesothelioma.}, }
@article {pmid34898002, year = {2022}, author = {Marazioti, A and Krontira, AC and Behrend, SJ and Giotopoulou, GA and Ntaliarda, G and Blanquart, C and Bayram, H and Iliopoulou, M and Vreka, M and Trassl, L and Pepe, MAA and Hackl, CM and Klotz, LV and Weiss, SAI and Koch, I and Lindner, M and Hatz, RA and Behr, J and Wagner, DE and Papadaki, H and Antimisiaris, SG and Jean, D and Deshayes, S and Grégoire, M and Kayalar, &#xd6; and Mortazavi, D and Dilege, &#x15e; and Tanju, S and Erus, S and Yavuz, &#xd6; and Bulutay, P and Fırat, P and Psallidas, I and Spella, M and Giopanou, I and Lilis, I and Lamort, AS and Stathopoulos, GT}, title = {KRAS signaling in malignant pleural mesothelioma.}, journal = {EMBO molecular medicine}, volume = {14}, number = {2}, pages = {e13631}, pmid = {34898002}, issn = {1757-4684}, mesh = {Animals ; Humans ; *Lung Neoplasms/genetics/pathology ; *Mesothelioma/genetics/pathology ; *Mesothelioma, Malignant/genetics/pathology ; Mice ; *Pleural Neoplasms/genetics/pathology ; *Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Signal Transduction ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRAS[G12D] in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRAS[G12D] lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.}, }
@article {pmid34874752, year = {2021}, author = {Sohn, EJ}, title = {Bioinformatic Analysis of Potential Biomarker for hsa-miR-196b-5p in Mesothelioma.}, journal = {Genetic testing and molecular biomarkers}, volume = {25}, number = {12}, pages = {772-780}, doi = {10.1089/gtmb.2021.0147}, pmid = {34874752}, issn = {1945-0257}, mesh = {Biomarkers ; Cell Line, Tumor ; Computational Biology ; Humans ; *Mesothelioma/drug therapy/genetics ; *Mesothelioma, Malignant/genetics ; MicroRNAs/genetics/metabolism/*supply &amp; distribution ; }, abstract = {Purpose: Malignant pleural mesothelioma is a rare neoplasia with a poor prognosis, and the majority of patients have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Materials and Methods: To determine the cytotoxicity of geldanamycin in mesothelioma H28 cells, the MTT assay was used. To determine changes in microRNA (miRNA) expression in geldanamycin-treated H28 cells, miRNA microarray analysis was performed. To determine the function of miR-196b-5p, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of miR-196b-5p targets predicted by miRwalk. Results: Our data showed that geldanamycin treatment reduced H28 cell viability in a dose-dependent manner. MicroRNA array analyses showed that expression of hsa-miR-196b-5p was downregulated in geldanamycin-treated H28 cells. Geldanamycin regulated miRNAs with roles in processes such as aging, angiogenesis, apoptosis, cell cycle, cell differentiation, cell proliferation, DNA repair, and secretion. Survival analysis showed that decreased expression of hsa-miR-196b-5p was significantly associated with a better outcome in mesothelioma patients. Expression of miR-196b-5p was also significantly associated with the developmental stages of mesothelioma. To narrow down the target genes of miR-196b-5p, we determined the overlap between the predicted target genes of miR-196b-5p and downregulated mRNAs in ovarian cancer based on the Gene Expression Omnibus dataset GSE12345. PDE1A, LAMA4, and PAPPA were identified as both miR-196b-5p targets and downregulated genes in GSE12345 and were thus considered targets of miR-196b-5p. Gene-miRNA expression correlation analysis showed that PDE1A, LAMA4, and PAPPA expression was negatively correlated with miR-196b-5p expression. Conclusions: We suggest that geldanamycin has potential for the treatment of mesothelioma via regulating miR-196b-5p. Furthermore, miR-196b-5p may be a potential biomarker for mesothelioma.}, }
@article {pmid34861373, year = {2022}, author = {Popat, S and Baas, P and Faivre-Finn, C and Girard, N and Nicholson, AG and Nowak, AK and Opitz, I and Scherpereel, A and Reck, M and , }, title = {Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[☆].}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {33}, number = {2}, pages = {129-142}, doi = {10.1016/j.annonc.2021.11.005}, pmid = {34861373}, issn = {1569-8041}, mesh = {Diagnosis, Differential ; Follow-Up Studies ; Humans ; *Lung Neoplasms/diagnosis/pathology/therapy ; *Mesothelioma/diagnosis/pathology/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/pathology/therapy ; }, }
@article {pmid34843704, year = {2022}, author = {Chen, Z and Song, S and Yang, C and Dai, Z and Gao, Y and Li, N and Zhu, J and Mao, W and Liu, J}, title = {Lipid profiling in malignant mesothelioma reveals promising signatures for diagnosis and prognosis: A plasma-based LC-MS lipidomics study.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {524}, number = {}, pages = {34-42}, doi = {10.1016/j.cca.2021.11.024}, pmid = {34843704}, issn = {1873-3492}, mesh = {Chromatography, Liquid ; Female ; Humans ; *Lipidomics ; Lipids ; Male ; *Mesothelioma, Malignant ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND AND AIM: Malignant mesothelioma (MM), being a rare and aggressive carcinoma, can barely be cured. Incidence of this cancer will keep climbing up in the next few decades since its major carcinogen, asbestos, is still in use in many countries. Unfortunately, prognosis of MM is unsatisfactory principally due to poor early diagnosis as a result of its long latency period and ambiguous symptoms. Lipids are known to contribute to cellular structure, signaling, and energy storage, and are widely reported to be related with tumorigenesis. Therefore, we aim to discover novel lipid biomarkers by plasma-based lipidomics that may improve MM diagnosis.<br><br>METHODS: Plasma samples from 25 MM patients and 32 healthy controls (HCs) were collected and analysed using a high-throughput liquid chromatography-mass spectrometry (LC-MS). Univariate and multivariate analyses were subsequently performed to visualize the separation trend between two groups and to screen for differential feature ions. Ions were annotated using LipidSearch 4.2 and their enriched pathways were detected on LIPEA. Receiver operating characteristic (ROC) curves were used for analysing each annotated lipid's diagnostic value. Survival analyses were performed to investigate each lipid's prognostic value.<br><br>RESULTS: In supervised partial least squares discriminant analysis (PLS-DA), clear separation between MM and HC groups was observed. A total of 34 differential lipids were annotated, among which 5 upregulated and 29 downregulated. Levels of plasma triacylglycerols (TGs) were higher in smoking versus non-smoking patients, and lower in female versus male patients. The top six lipids possessing highest diagnostic value included two phosphatidylethanolamines (PEs), two phosphatidylcholines (PCs) and two ceramides. Moreover, elevated circulating TG levels were associated with poorer survival, whereas increased monohexosylceramide (Hex1Cer) might be beneficial.<br><br>CONCLUSIONS: Our study revealed differentially expressed lipid patterns in MM compared to HC. PC, PE, and ceramides showed outstanding diagnostic performance, while TG and Hex1Cer exhibited significant prognostic values. Nevertheless, more studies should verify these trends as well as further investigating on underlying mechanisms.}, }
@article {pmid34841838, year = {2021}, author = {De Sario, M and Bauleo, L and Magnani, C and Ferrante, D and Marinaccio, A and Michelozzi, P and Romeo, E}, title = {L'impatto dell'esposizione occupazionale ad amianto sul tumore del polmone in Italia.}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {5}, pages = {353-367}, doi = {10.19191/EP21.5.P353.102}, pmid = {34841838}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms ; Male ; *Mesothelioma/etiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {OBJECTIVES: to perform a meta-analysis of cohort studies on lung cancer mortality in occupational sectors exposed to asbestos, particularly in the construction sector, and to use data from Italian cohorts exposed to asbestos to estimate the number of lung cancer cases attributable to asbestos in Italy.<br><br>METHODS: systematic literature review and estimation of lung cancer deaths and cases attributable to asbestos in Italian cohorts and from the Italian National Register of Malignant Mesothelioma (ReNaM).<br><br>SETTING AND PARTICIPANTS: the literature search was conducted in Medline and Embase (Ovid), including papers published from 1999 to May 2019. The following sectors were considered most exposed to asbestos: asbestos-cement, rolling-stock, shipyards, dockyards, glass workers, insulators, asphalt roll production workers, industrial ovens, miners. Moreover, the construction sector was included.<br><br>MAIN OUTCOME MEASURES: the standardized mortality ratio (SMR) was estimated from the meta-analysis of the literature review. The ratio lung cancer to mesothelioma attributable cases was estimated by occupational sector from the Italian cohorts. For the construction sector, the ratio lung cancer to mesothelioma cases was estimated within the exposed workers estimated by CAREX (1990-1993). The ratios were applied to the mesothelioma cases registered at the ReNaM for the 2010-2015 period, to obtain a national estimate of lung cancer cases attributable to occupational exposure to asbestos.<br><br>RESULTS: the meta-analytical SMR for lung cancer in men varied between 1.05 (asphalt roll) and 2.36 (insulation). The mean risk for all sectors was 1.37 in men and 1.60 in women. It increased in cohorts with latency higher than 20 years. Significant risks were observed in asbestos-cement (both genders), construction, and mining sectors. There was a mean of 1.1, 2.7, and 2.8 lung cancer deaths per mesothelioma death in the cement-asbestos, harbour, and construction sectors, respectively. The impact in terms of lung cancer cases estimated at the national level was equal to 3,814 cases between 2010 and 2015.<br><br>CONCLUSIONS: to provide an overall assessment of the impact of the occupational asbestos exposure, it is important to consider lung cancer cases, in addition to malignant mesotheliomas. This study was able to estimate the impact of asbestos on lung cancer in Italy 25 years after the ban of this occupational carcinogen, with the largest contribution in terms of attributable cases coming from the construction sector. It is urgent to implement adequate information and prevention strategies, health surveillance of workers, and the appropriate legal framework for insurance purposes.}, }
@article {pmid34840219, year = {2023}, author = {Kawamoto, Y and Kure, S and Katayama, H and Kawahara, K and Teduka, K and Kunugi, S and Onda, M and Motoda, N and Ohashi, R}, title = {Cytological Assessment of Desmoplastic Malignant Pleural Mesothelioma in an Autopsy Case.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {89}, number = {6}, pages = {616-622}, doi = {10.1272/jnms.JNMS.2022_89-605}, pmid = {34840219}, issn = {1347-3409}, mesh = {Humans ; Male ; Autopsy ; In Situ Hybridization, Fluorescence ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant/complications ; *Pleural Effusion/complications/pathology ; *Pleural Effusion, Malignant/complications/pathology ; *Pleural Neoplasms/diagnosis ; Middle Aged ; }, abstract = {INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma-type mesothelioma, comprising approximately 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, it may not be useful for DMPM because of the presence of desmoplasia and bland cellular atypia. We report a case, and previously undescribed cytological features, of DMPM that was diagnosed during autopsy.<br><br>CASE PRESENTATION: A man in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. A chest CT scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. During autopsy, scrape-imprint smears were prepared and cytology of pleural effusions was performed. The scrape-imprint smear samples showed spindle cells with mild nuclear atypia and grooves with fibrous stroma. Pleural effusion cytology revealed spindle cells with mild nuclear atypia, as well as grooves with loose epithelial connections. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in the cytological samples, thus indicating a diagnosis of DMPM, which was confirmed by fluorescence in situ hybridization.<br><br>CONCLUSION: Cytological procedures such as pleural effusion cytology and scrape-imprinting cytology may help in diagnosing rare tumors such as DMPM.}, }
@article {pmid34836499, year = {2021}, author = {Kelarji, AB and Alshutaihi, MS and Ghazal, A and Mahli, N and Agha, S}, title = {Correction to: A rare case of benign multicystic peritoneal mesothelioma misdiagnosed as hydatid cyst found in the liver parenchyma and abdomen cavity of a male with asbestos exposure.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {447}, pmid = {34836499}, issn = {1471-230X}, }
@article {pmid34834557, year = {2021}, author = {Filetti, V and Loreto, C and Falzone, L and Lombardo, C and Cannizzaro, E and Castorina, S and Ledda, C and Rapisarda, V}, title = {Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma.}, journal = {Journal of personalized medicine}, volume = {11}, number = {11}, pages = {}, pmid = {34834557}, issn = {2075-4426}, abstract = {Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.}, }
@article {pmid34830817, year = {2021}, author = {Cersosimo, F and Barbarino, M and Lonardi, S and Vermi, W and Giordano, A and Bellan, C and Giurisato, E}, title = {Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms.}, journal = {Cancers}, volume = {13}, number = {22}, pages = {}, pmid = {34830817}, issn = {2072-6694}, abstract = {Several studies have reported that cellular and soluble components of the tumor microenvironment (TME) play a key role in cancer-initiation and progression. Considering the relevance and the complexity of TME in cancer biology, recent research has focused on the investigation of the TME content, in terms of players and informational exchange. Understanding the crosstalk between tumor and non-tumor cells is crucial to design more beneficial anti-cancer therapeutic strategies. Malignant pleural mesothelioma (MPM) is a complex and heterogenous tumor mainly caused by asbestos exposure with few treatment options and low life expectancy after standard therapy. MPM leukocyte infiltration is rich in macrophages. Given the failure of macrophages to eliminate asbestos fibers, these immune cells accumulate in pleural cavity leading to the establishment of a unique inflammatory environment and to the malignant transformation of mesothelial cells. In this inflammatory landscape, stromal and immune cells play a driven role to support tumor development and progression via a bidirectional communication with tumor cells. Characterization of the MPM microenvironment (MPM-ME) may be useful to understand the complexity of mesothelioma biology, such as to identify new molecular druggable targets, with the aim to improve the outcome of the disease. In this review, we summarize the known evidence about the MPM-ME network, including its prognostic and therapeutic relevance.}, }
@article {pmid34830097, year = {2021}, author = {Ramundo, V and Zanirato, G and Aldieri, E}, title = {The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830097}, issn = {1422-0067}, mesh = {Biomarkers, Tumor/metabolism ; *Epithelial-Mesenchymal Transition ; Humans ; Mesothelioma, Malignant/*metabolism/pathology/therapy ; MicroRNAs/metabolism ; Neoplasm Metastasis ; Neoplasm Proteins/metabolism ; Pleural Neoplasms/*metabolism/pathology/therapy ; RNA, Neoplasm/metabolism ; Transforming Growth Factor beta/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.}, }
@article {pmid34827604, year = {2021}, author = {Javadi, J and Görgens, A and Vanky, H and Gupta, D and Hjerpe, A and El-Andaloussi, S and Hagey, D and Dobra, K}, title = {Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion.}, journal = {Biomolecules}, volume = {11}, number = {11}, pages = {}, pmid = {34827604}, issn = {2218-273X}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; Prognosis ; Male ; Female ; *Pleural Effusion/metabolism/diagnosis/pathology ; Aged ; *Biomarkers, Tumor/metabolism ; Middle Aged ; Exosomes/metabolism ; Mesothelioma, Malignant/diagnosis/pathology/metabolism ; Lung Neoplasms/metabolism/diagnosis/pathology ; Mesothelioma/diagnosis/metabolism/pathology ; Pleural Effusion, Malignant/metabolism/diagnosis/pathology ; Aged, 80 and over ; }, abstract = {Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (n = 9), benign (n = 6), and AD (n = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.}, }
@article {pmid34823106, year = {2021}, author = {Nowak, AK and Chin, WL and Keam, S and Cook, A}, title = {Immune checkpoint inhibitor therapy for malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {162}, number = {}, pages = {162-168}, doi = {10.1016/j.lungcan.2021.11.006}, pmid = {34823106}, issn = {1872-8332}, mesh = {Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; *Lung Neoplasms/drug therapy ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy ; }, abstract = {Mesothelioma is a rare and universally fatal cancer linked to exposure to asbestos. Until recently, standard of care treatment was chemotherapy; a treatment resulting in a minimal survival extension, and not improved upon for almost twenty years. However, the advent of cancer immunotherapy - and in particular the immune checkpoint inhibitor class of drugs - has resulted in recently approved new treatment options, with more currently under investigation. Here, we review clinical trials of both single agent and combination checkpoint inhibitors in mesothelioma, plus studies investigating their combination with chemotherapy. We also describe current advances in biomarker identification regarding prediction of patient response to checkpoint inhibitors. Finally, we assess the probable future direction of the field; including where current and developing technologies are likely to lead - in terms of both biomarker discovery and treatment options.}, }
@article {pmid34815344, year = {2021}, author = {Novelli, F and Bononi, A and Wang, Q and Bai, F and Patergnani, S and Kricek, F and Haglund, E and Suarez, JS and Tanji, M and Xu, R and Takanishi, Y and Minaai, M and Pastorino, S and Morris, P and Sakamoto, G and Pass, HI and Barbour, H and Gaudino, G and Giorgi, C and Pinton, P and Onuchic, JN and Yang, H and Carbone, M}, title = {BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {48}, pages = {}, pmid = {34815344}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Asbestos ; Biomarkers, Tumor/metabolism ; Carcinogenesis ; Cell Nucleus/metabolism ; Female ; Gene-Environment Interaction ; Germ-Line Mutation ; HMGB1 Protein/*chemistry/genetics ; Heterozygote ; Histone Deacetylase 1/*chemistry/genetics ; Incidence ; Inflammation ; Male ; Mesothelioma/metabolism ; Mice ; Mutation ; Prognosis ; Protein Binding ; Tumor Suppressor Proteins/*chemistry/metabolism ; Ubiquitin/chemistry ; Ubiquitin Thiolesterase/*chemistry/metabolism ; }, abstract = {Carriers of heterozygous germline BAP1 mutations (BAP1[+/-]) are affected by the "BAP1 cancer syndrome." Although they can develop almost any cancer type, they are unusually susceptible to asbestos carcinogenesis and mesothelioma. Here we investigate why among all carcinogens, BAP1 mutations cooperate with asbestos. Asbestos carcinogenesis and mesothelioma have been linked to a chronic inflammatory process promoted by the extracellular release of the high-mobility group box 1 protein (HMGB1). We report that BAP1[+/-] cells secrete increased amounts of HMGB1, and that BAP1[+/-] carriers have detectable serum levels of acetylated HMGB1 that further increase when they develop mesothelioma. We linked these findings to our discovery that BAP1 forms a trimeric protein complex with HMGB1 and with histone deacetylase 1 (HDAC1) that modulates HMGB1 acetylation and its release. Reduced BAP1 levels caused increased ubiquitylation and degradation of HDAC1, leading to increased acetylation of HMGB1 and its active secretion that in turn promoted mesothelial cell transformation.}, }
@article {pmid34788178, year = {2021}, author = {Dodge, DG and Engel, AM and Prueitt, RL and Peterson, MK and Goodman, JE}, title = {US EPA's TSCA risk assessment approach: a case study of asbestos in automotive brakes.}, journal = {Inhalation toxicology}, volume = {33}, number = {9-14}, pages = {295-307}, doi = {10.1080/08958378.2021.1998258}, pmid = {34788178}, issn = {1091-7691}, mesh = {*Asbestos ; Asbestos, Serpentine/analysis ; *Occupational Exposure ; Risk Assessment ; United States ; }, abstract = {The United States Environmental Protection Agency (US EPA) is currently refining its approach for risk assessments conducted under the amended Toxic Substances Control Act (TSCA), largely based on recommendations from the National Academies of Sciences, Engineering, and Medicine (NASEM). We identified several issues with the current TSCA risk assessment approach that were not addressed by NASEM in its recommendations. Here, we demonstrate these issues with a case study of the 'Risk Evaluation for Asbestos, Part 1: Chrysotile Asbestos,' which US EPA released in December 2020. In this evaluation, US EPA found that occupational and some consumer uses of automotive brakes and clutches that contain asbestos result in unreasonable risks. These risks were calculated from estimated exposures during brake work and an inhalation unit risk (IUR) developed for chrysotile asbestos. We found that US EPA overestimated risk as a result of unrealistic inputs to both the exposure and toxicity components of the risk equation, and because the Agency did not fully consider relevant epidemiology and toxicity evidence in its systematic review. Our evaluation demonstrates areas in which the TSCA risk assessment approach could be improved to result in risk evaluations that are supported by the available scientific evidence.}, }
@article {pmid34774176, year = {2021}, author = {Sidhu, C and Louw, A and Gary Lee, YC}, title = {Malignant Pleural Mesothelioma: Updates for Respiratory Physicians.}, journal = {Clinics in chest medicine}, volume = {42}, number = {4}, pages = {697-710}, doi = {10.1016/j.ccm.2021.08.006}, pmid = {34774176}, issn = {1557-8216}, mesh = {*Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/therapy ; *Mesothelioma, Malignant ; *Physicians ; *Pleural Neoplasms/diagnosis/therapy ; }, }
@article {pmid34768883, year = {2021}, author = {Çakılkaya, P and Sørensen, RR and Jürgensen, HJ and Krigslund, O and Gårdsvoll, H and Nielsen, CF and Santoni-Rugiu, E and Behrendt, N and Engelholm, LH}, title = {The Collagen Receptor uPARAP in Malignant Mesothelioma: A Potential Diagnostic Marker and Therapeutic Target.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34768883}, issn = {1422-0067}, support = {No 801481//European Union/ ; NNF19OC0058603//Novo Nordisk Foundation/ ; R231-A13820//Danish Cancer Society/ ; R231-A13832//Danish Cancer Society/ ; N/A//Region Hovedstadens Forskningsfond/ ; N/A//Simon Fougner Hartmanns family foundation/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Female ; Gene Expression ; Humans ; Immunoconjugates/metabolism ; Male ; Mannose-Binding Lectins/*metabolism/physiology ; Membrane Glycoproteins/*metabolism/physiology ; Mesothelioma, Malignant/diagnosis/*metabolism/physiopathology ; Middle Aged ; Receptors, Cell Surface/*metabolism/physiology ; Receptors, Collagen/genetics/metabolism/physiology ; Receptors, Mitogen/genetics ; Transcriptome ; Up-Regulation ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive cancer with limited therapeutic options. We have previously shown that the endocytic collagen receptor, uPARAP, is upregulated in certain cancers and can be therapeutically targeted. Public RNA expression data display uPARAP overexpression in MM. Thus, to evaluate its potential use in diagnostics and therapy, we quantified uPARAP expression by immunohistochemical H-score in formalin-fixed paraffin-embedded bioptic/surgical human tissue samples and tissue microarrays. We detected pronounced upregulation of uPARAP in the three main MM subtypes compared to non-malignant reactive mesothelial proliferations, with higher expression in sarcomatoid and biphasic than in epithelioid MM. The upregulation appeared to be independent of patients' asbestos exposure and unaffected after chemotherapy. Using immunoblotting, we demonstrated high expression of uPARAP in MM cell lines and no expression in a non-malignant mesothelial cell line. Moreover, we showed the specific internalization of an anti-uPARAP monoclonal antibody by the MM cell lines using flow cytometry-based assays and confocal microscopy. Finally, we demonstrated the sensitivity of these cells towards sub-nanomolar concentrations of an antibody-drug conjugate formed with the uPARAP-directed antibody and a potent cytotoxin that led to efficient, uPARAP-specific eradication of the MM cells. Further studies on patient cohorts and functional preclinical models will fully reveal whether uPARAP could be exploited in diagnostics and therapeutic targeting of MM.}, }
@article {pmid34768395, year = {2021}, author = {Zupanc, C and Franko, A and Štrbac, D and Dodič Fikfak, M and Kovač, V and Dolžan, V and Goričar, K}, title = {Serum Calretinin as a Biomarker in Malignant Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {21}, pages = {}, pmid = {34768395}, issn = {2077-0383}, support = {P1-0170, L3-8203, and L3-2622//Slovenian Research Agency/ ; }, abstract = {The early diagnosis of malignant mesothelioma (MM) could improve the prognosis of MM patients. To confirm an MM diagnosis, an immunohistochemical analysis of several tumor tissue markers, including calretinin, is currently required. Our aim is to evaluate serum calretinin as a potential biomarker in asbestos-related diseases, especially in MM. Our study includes 549 subjects: 164 MM patients, 117 subjects with asbestosis, 195 subjects with pleural plaques and 73 occupationally asbestos-exposed subjects without asbestos-related diseases. The serum calretinin concentration was determined with a commercially available enzyme immunoassay. Data on the soluble mesothelin-related peptides (SMRP) concentration are available from previous studies. MM patients had a significantly higher calretinin concentration than subjects without disease, subjects with pleural plaques or subjects with asbestosis (all p < 0.001). The histological type was significantly associated with serum calretinin: patients with sarcomatoid MM had lower calretinin than patients with the epithelioid type (p = 0.001). In a ROC curve analysis, the area under the curve for calretinin concentration predicting MM was 0.826 (95% CI = 0.782-0.869; p < 0.001). At the cutoff value of 0.32 ng/mL, sensitivity was 0.683, while specificity was 0.886. The combination of calretinin and SMRP had the highest predictive value. Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.}, }
@article {pmid34766064, year = {2021}, author = {Ke, H and Gill, AJ and McKenzie, C and Kench, JG and Chan, RCF and Pavlakis, N and Fulham, M and Koh, C and Kao, S}, title = {Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report.}, journal = {JTO clinical and research reports}, volume = {2}, number = {11}, pages = {100236}, pmid = {34766064}, issn = {2666-3643}, abstract = {Malignant mesothelioma with EWSR1-ATF1 fusion is a rare malignancy described in young adults without asbestos exposure. To the best of our knowledge, outcomes to local and systemic therapies for this subtype of malignant mesothelioma have not been described. This case report describes the clinical course of a 19-year-old man diagnosed with malignant peritoneal mesothelioma with EWSR1-ATF1 fusion localized to the abdomen. His disease followed an aggressive course and resulted in limited survival (18 mo). There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma and biologically targeted MET inhibition with crizotinib. More research is required in this rare subtype of peritoneal mesothelioma.}, }
@article {pmid34761371, year = {2021}, author = {Rapisarda, V and Broggi, G and Caltabiano, R and Lombardo, C and Castorina, S and Trovato, A and Ledda, C and Filetti, V and Loreto, C}, title = {ATG7 immunohistochemical expression in malignant pleural mesothelioma. A preliminary report.}, journal = {Histology and histopathology}, volume = {36}, number = {12}, pages = {1301-1308}, pmid = {34761371}, issn = {1699-5848}, support = {20722142130//2020/2022 PIA.CE.RI., University of Catania, DIPREME project/ ; }, mesh = {Aged ; Asbestos, Amphibole/*adverse effects ; Autophagy-Related Protein 7/genetics/*metabolism ; Biomarkers, Tumor/metabolism ; Female ; Humans ; *Immunohistochemistry ; Italy/epidemiology ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma, Malignant/epidemiology/*metabolism ; }, abstract = {Literature evidence has demonstrated a high incidence of asbestos-related malignant pleural mesothelioma (MPM) in a Sicilian town (Biancavilla, Italy), where fluoro-edenite (FE) fibers were discovered some decades ago. As ATG7 immunohistochemical analysis has been ascribed as a prognostic tool of improved survival, we decided to investigate, in MPM patients, exposed and not exposed to FE fibers, the immunohistochemical expression of this autophagy-related protein named ATG7. We analyzed the correlation between ATG7 immunohistochemical level and clinicopathological parameters. Twenty MPM tissue samples, from patients with available clinical and follow-up data, were included in paraffin and processed for immunohistochemistry. The immunohistochemical results confirmed activation of the autophagic process in MPM. Densitometric and morphometric expressions of ATG7 were significantly increased in MPMs when compared to the control tissues. A significant association of a high level of ATG7 with increased survival was demonstrated, with a mean overall survival (OS) of 12.5 months for patients with high expression vs. a mean OS of 4.5 months for patients with low ATG7 expression. In addition, a significant correlation between ATG7 expression and the survival time of MPM patients was observed. This study represents a starting point to hypothesize the prognostic role of ATG7 which could be a reliable prognostic indicator in MPM.}, }
@article {pmid34754347, year = {2022}, author = {Touma, T and Taira, R and Makida, T and Oshiro, K and Miyara, T and Taba, Y}, title = {Marked ventilation impairment due to progression of diffuse pleural thickening after cardiac surgery.}, journal = {Radiology case reports}, volume = {17}, number = {1}, pages = {1-4}, pmid = {34754347}, issn = {1930-0433}, abstract = {A 64-year-old Japanese man presented with dyspnea and shortness of breath during exertion. Chest computed tomography revealed bilateral pleural effusion. He was drowsy because of CO2 storage and died due to ventilatory impairment. His past medical history included a thymectomy and adjuvant radiotherapy with thymoma. He had undergone cardiac surgery and permanent pacemaker implantation. The autopsy examination revealed extensive bilateral pleural adhesions and diffuse visceral pleural thickening. An inspection of multiple lung sections failed to detect any asbestos body formation or mesothelioma. The patient's pleural effusion and diffuse pleural thickening may have exacerbated after cardiac surgery. In this case, the progression and pathophysiology of the pleural thickening could be traced by imaging and an autopsy, and we were able to estimate the factors that exacerbated the pleural thickening and ventilation impairment.}, }
@article {pmid34749677, year = {2021}, author = {Hemminki, K and Försti, A and Chen, T and Hemminki, A}, title = {Incidence, mortality and survival in malignant pleural mesothelioma before and after asbestos in Denmark, Finland, Norway and Sweden.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {1189}, pmid = {34749677}, issn = {1471-2407}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/*standards ; Denmark/epidemiology ; Environmental Exposure/adverse effects/*standards ; Female ; Finland/epidemiology ; History, 20th Century ; History, 21st Century ; Humans ; Incidence ; Male ; Mesothelioma, Malignant/*epidemiology/etiology ; Middle Aged ; Mortality/history/trends ; Norway/epidemiology ; Pleural Neoplasms/*epidemiology/etiology ; Sex Factors ; Survival Analysis ; Sweden/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal cancer, which is largely caused by exposure to asbestos. Reliable information about the incidence of MPM prior the influence of asbestos is lacking. The nationwide regional incidence trends for MPM remain poorly characterized. We use nationwide MPM data for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) to assess incidence, mortality and survival trends for MPM in these countries.<br><br>METHODS: We use the NORDCAN database for the analyses: incidence data were available from 1943 in DK, 1953 in FI and NO and 1958 in SE, through 2016. Survival data were available from 1967 through 2016. World standard population was used in age standardization.<br><br>RESULTS: The lowest incidence that we recorded for MPM was 0.02/100,000 for NO women and 0.05/100,000 for FI men in 1953-57, marking the incidence before the influence of asbestos. The highest rate of 1.9/100,000 was recorded for DK in 1997. Female incidence was much lower than male incidence. In each country, the male incidence trend for MPM culminated, first in SE around 1990. The regional incidence trends matched with earlier asbestos-related industrial activity, shipbuilding in FI and SE, cement manufacturing and shipbuilding in DK and seafaring in NO. Relative 1-year survival increased from about 20 to 50% but 5-year survival remained at or below 10%.<br><br>CONCLUSION: In the Nordic countries, the male incidence trends for MPM climaxed and started to decrease, indicating that the prevention of exposure was beneficial. Survival in MPM has improved for both sexes but long-term survival remains dismal.}, }
@article {pmid34740982, year = {2022}, author = {Hessel, PA}, title = {Mesothelioma among vehicle mechanics: a controversy?.}, journal = {Thorax}, volume = {77}, number = {5}, pages = {426-427}, doi = {10.1136/thoraxjnl-2021-217880}, pmid = {34740982}, issn = {1468-3296}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases ; *Occupational Exposure ; }, }
@article {pmid34738103, year = {2022}, author = {Inamasu, E and Tsuchiya, T and Yamauchi, M and Nishi, K and Matsuda, K and Sugawara, F and Sakaguchi, K and Mori, R and Matsumoto, K and Miyazaki, T and Hatachi, G and Doi, R and Watanabe, H and Tomoshige, K and Matsuda, N and Higami, Y and Shimokawa, I and Nakashima, M and Nagayasu, T}, title = {Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models.}, journal = {Journal of radiation research}, volume = {63}, number = {1}, pages = {19-29}, pmid = {34738103}, issn = {1349-9157}, support = {//Nagasaki University/ ; }, mesh = {Animals ; *Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Humans ; Male ; *Mesothelioma/drug therapy/metabolism/radiotherapy ; *Mesothelioma, Malignant ; Mice ; Mice, Nude ; *Pleural Neoplasms/drug therapy/metabolism/radiotherapy ; Radiation Tolerance ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.}, }
@article {pmid34725624, year = {2021}, author = {Gupta, A and Vasileva, A and Manthri, S}, title = {The Rarest of the Rare: A Case of BAP1-Mutated Primary Peritoneal Mesothelioma.}, journal = {Cureus}, volume = {13}, number = {9}, pages = {e18380}, pmid = {34725624}, issn = {2168-8184}, abstract = {Malignant mesotheliomas (MM), as described are rare tumors that are mostly associated with occupational exposure to asbestos. They most commonly occur in the pleura. Other unfamiliar sites where they can occur are the peritoneum, pericardium, and tunica vaginalis. There is no significant correlation between the amount and duration of asbestos exposure to mesothelioma development as reported by various studies over the years. Apart from the environmental exposure, the development of malignant mesothelioma has been linked to a mutation in the BAP1 gene, which can predispose the patient to develop other malignancies associated with BAP1 mutation. We report a case of a 43-year-old man without any significant risk factors, who presented with a complaint of abdominal discomfort and was found to have malignant peritoneal mesothelioma (MPM). With a known familial history of mesothelioma and melanoma, our patient underwent genetic testing which revealed a mutation in BAP1, affirming the strong association with the development of MPM. Young patients who develop malignant mesothelioma without risk factors for MM should have germline testing for BAP1. This case report is unique and highlights a familial variant of mesothelioma, even rare with peritoneal mesothelioma in our patient.}, }
@article {pmid34698447, year = {2022}, author = {Danese, MD and Daumont, M and Nwokeji, E and Gleeson, M and Penrod, JR and Lubeck, D}, title = {Treatment patterns and outcomes in older patients with advanced malignant pleural mesothelioma: Analyses of Surveillance, Epidemiology, and End Results-Medicare data.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {5}, number = {9}, pages = {e1568}, pmid = {34698447}, issn = {2573-8348}, mesh = {Aged ; Female ; Humans ; Male ; Medicare ; *Mesothelioma/drug therapy/epidemiology ; *Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; Platinum/therapeutic use ; *Pleural Neoplasms/drug therapy/epidemiology ; Retrospective Studies ; United States/epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant pleural mesothelioma (MPM) is important to understand the unmet needs of this population.<br><br>AIM: To evaluate the demographic and clinical characteristics, treatment patterns, and outcomes among older patients diagnosed with advanced MPM in the United States between 2007 and 2013.<br><br>METHODS: This was a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims. We included patients who were age 66 or older at the time of their primary MPM diagnosis between 2007 and 2013 and followed them through 2014. Treated patients who received first-line chemotherapy with pemetrexed and platinum within 90&#x2009;days of diagnosis, second-line, or third-line therapy were identified for evaluation of outcomes.<br><br>RESULTS: There were 666 older patients with advanced MPM, of whom 82% were male, 87% White, 78% stage IV, and 70% had no mobility limitation indicators at diagnosis. There were 262 patients who received first-line chemotherapy for advanced MPM, most of whom (80%; n&#xa0;=&#xa0;209) received pemetrexed-platinum. Of these 209 patients, 41% (n&#xa0;=&#xa0;86) initiated second-line therapy, and 26% (n&#xa0;=&#xa0;22) initiated third-line therapy. Median overall survival for the cohort of 209 patients was 7.2&#xa0;months. Patients with epithelioid histology had better median overall survival (12.2&#xa0;months) compared with other histologies (4.4-5.6&#xa0;months). Within 90&#x2009;days of diagnosis of advanced MPM, 78% of patients were hospitalized, 52% visited an emergency department, and 21% had hospice care. The 2-year cost of care was over $100&#x2009;000 for all patients with advanced MPM treated with first-line pemetrexed-platinum.<br><br>CONCLUSIONS: Although first-line systemic anticancer treatment was generally consistent with guidelines (e.g., pemetrexed-platinum), poor patient outcomes highlight the need for effective treatment options for older patients with advanced MPM.}, }
@article {pmid34689163, year = {2021}, author = {Shrestha, S and Adhikary, G and Naselsky, W and Xu, W and Friedberg, JS and Eckert, RL}, title = {ACTL6A suppresses p21[Cip1] tumor suppressor expression to maintain an aggressive mesothelioma cancer cell phenotype.}, journal = {Oncogenesis}, volume = {10}, number = {10}, pages = {70}, pmid = {34689163}, issn = {2157-9024}, support = {R01 CA211909/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is a poor prognosis cancer of the mesothelial lining that develops in response to exposure to various agents including asbestos. Actin-Like Protein 6A (ACTL6A, BAF53a) is a SWI/SNF regulatory complex protein that is elevated in cancer cells and has been implicated as a driver of cancer cell survival and tumor formation. In the present study, we show that ACTL6A drives mesothelioma cancer cell proliferation, spheroid formation, invasion, and migration, and that these activities are markedly attenuated by ACTL6A knockdown. ACTL6A expression reduces the levels of the p21[Cip1] cyclin-dependent kinase inhibitor and tumor suppressor protein. DNA binding studies show that ACTL6A interacts with Sp1 and p53 binding DNA response elements in the p21[Cip1] gene promoter and that this is associated with reduced p21[Cip1] promoter activity and p21[Cip1] mRNA and protein levels. Moreover, ACTL6A suppression of p21[Cip1] expression is required for maintenance of the aggressive mesothelioma cancer cell phenotype suggesting that p21[Cip1] is a mediator of ACTL6A action. p53, a known inducer of p21[Cip1] expression, is involved ACTL6A in regulation of p21[Cip1] in some but not all mesothelioma cells. In addition, ACTL6A knockout markedly reduces tumor formation and this is associated with elevated tumor levels of p21[Cip1]. These findings suggest that ACTL6A suppresses p21[Cip1] promoter activity to reduce p21[Cip1] protein as a mechanism to maintain the aggressive mesothelioma cell phenotype.}, }
@article {pmid34682428, year = {2021}, author = {Kim, EA}, title = {Standardized Incidence Ratio and Standardized Mortality Ratio of Malignant Mesothelioma in a Worker Cohort Using Employment Insurance Database in Korea.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {20}, pages = {}, pmid = {34682428}, issn = {1660-4601}, mesh = {Employment ; Female ; Humans ; Incidence ; *Insurance ; Male ; *Mesothelioma, Malignant ; *Occupational Exposure ; Republic of Korea/epidemiology ; }, abstract = {Malignant mesothelioma is one of the appropriate indicators for assessing the carcinogenic effects of asbestos. This study compared the risk ratio of mesothelioma according to the industry in the worker cohort. A cohort was constructed using the Korean employment insurance system during 1995-2017, enrolling 13,285,895 men and 10,452,705 women. The standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were calculated using the indirect standardization method. There were 641 malignant mesotheliomas that occurred; the SIR was significantly higher than the general population (men 1.36, 95% confidence interval (CI) 1.24-1.48, women 1.44, 95% CI: 1.23-1.7). More than half (52.8%) of malignant mesothelioma cases occurred in the manufacturing (n = 240, 38.6%, SIR: men, 1.72, 95% CI: 1.37-2.15, women, 3.31, 95% CI: 1.71-5.79) and construction industries (n = 88, 14.2%, SIR: men, 1.54 95% CI: 1.33-1.78, women, 1.62 95% CI: 1.25-2.11). The accommodation and food service (men, 2.56 95% CI: 1.28-4.58, women 1.35, 95% CI: 0.65-2.48) and real estate (men 1.34, 95% CI: 0.98-1.83, women 1.95, 95% CI: 0.78-4.02) also showed a high SIR, indicating the risk of asbestos-containing materials in old buildings. The incidence of malignant mesothelioma is likely to increase in the future, given the long latency of this disease. Moreover, long-term follow-up studies will be needed.}, }
@article {pmid34681644, year = {2021}, author = {Badger, R and Park, K and Pietrofesa, RA and Christofidou-Solomidou, M and Serve, KM}, title = {Late Inflammation Induced by Asbestiform Fibers in Mice Is Ameliorated by a Small Molecule Synthetic Lignan.}, journal = {International journal of molecular sciences}, volume = {22}, number = {20}, pages = {}, pmid = {34681644}, issn = {1422-0067}, mesh = {Adaptive Immunity/drug effects ; Animals ; Asbestos, Amphibole/*toxicity ; B-Lymphocytes/cytology/immunology/metabolism ; Butylene Glycols/pharmacology/*therapeutic use ; Chemokine CCL2/metabolism ; Female ; Glucosides/pharmacology/*therapeutic use ; Immunity, Innate/drug effects ; Immunoglobulin Isotypes/metabolism ; Immunoglobulins/metabolism ; Inflammation/chemically induced/pathology/*prevention &amp; control ; Interleukin-6 ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects/genetics ; T-Lymphocytes/cytology/immunology/metabolism ; }, abstract = {Exposure to Libby amphibole (LA) asbestos-like fibers is associated with increased risk of asbestosis, mesothelioma, pulmonary disease, and systemic autoimmune disease. LGM2605 is a small molecule antioxidant and free radical scavenger, with anti-inflammatory effects in various disease models. The current study aimed to determine whether the protective effects of LGM2605 persist during the late inflammatory phase post-LA exposure. Male and female C57BL/6 mice were administered daily LGM2605 (100 mg/kg) via gel cups for 3 days before and 14 days after a 200 µg LA given via intraperitoneal (i.p.) injection. Control mice were given unsupplemented gel cups and an equivalent dose of i.p. saline. On day 14 post-LA treatment, peritoneal lavage was assessed for immune cell influx, cytokine concentrations, oxidative stress biomarkers, and immunoglobulins. During the late inflammatory phase post-LA exposure, we noted an alteration in trafficking of both innate and adaptive immune cells, increased pro-inflammatory cytokine concentrations, induction of immunoglobulin isotype switching, and increased oxidized guanine species. LGM2605 countered these changes similarly among male and female mice, ameliorating late inflammation and altering immune responses in late post-LA exposure. These data support possible efficacy of LGM2605 in the prolonged treatment of LA-associated disease and other inflammatory conditions.}, }
@article {pmid34679210, year = {2021}, author = {Hiraku, Y and Watanabe, J and Kaneko, A and Ichinose, T and Murata, M}, title = {MicroRNA expression in lung tissues of asbestos-exposed mice: Upregulation of miR-21 and downregulation of tumor suppressor genes Pdcd4 and Reck.}, journal = {Journal of occupational health}, volume = {63}, number = {1}, pages = {e12282}, pmid = {34679210}, issn = {1348-9585}, support = {23659328//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 24390153//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 15H04784//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 18H03038//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; //Grants-in-Aid for Scientific Research/ ; }, mesh = {Animals ; Apoptosis Regulatory Proteins/*genetics ; Asbestos/toxicity ; Asbestos, Crocidolite/*administration &amp; dosage ; Asbestos, Serpentine/*administration &amp; dosage ; Disease Models, Animal ; Down-Regulation ; GPI-Linked Proteins/*genetics ; Gene Expression/*drug effects ; Lung/pathology ; Male ; Mice ; Mice, Inbred ICR ; MicroRNAs/*genetics ; Microarray Analysis ; RNA-Binding Proteins/*genetics ; Up-Regulation ; }, abstract = {OBJECTIVES: Asbestos causes lung cancer and malignant mesothelioma in humans, but the precise mechanism has not been well understood. MicroRNA (miRNA) is a short non-coding RNA that suppresses gene expression and participates in human diseases including cancer. In this study, we examined the expression levels of miRNA and potential target genes in lung tissues of asbestos-exposed mice by microarray analysis.<br><br>METHODS: We intratracheally administered asbestos (chrysotile and crocidolite, 0.05 or 0.2&#xa0;mg/instillation) to 6-week-old ICR male mice four times weekly. We extracted total RNA from lung tissues and performed microarray analysis for miRNA and gene expression. We also carried out real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemistry to confirm the results of microarray analysis.<br><br>RESULTS: Microarray analysis revealed that the expression levels of 14&#xa0;miRNAs were significantly changed by chrysotile and/or crocidolite (>2-fold, P&#xa0;<&#xa0;.05). Especially, miR-21, an oncogenic miRNA, was significantly upregulated by both chrysotile and crocidolite. In database analysis, miR-21 was predicted to target tumor suppressor genes programmed cell death 4 (Pdcd4) and reversion-inducing-cysteine-rich protein with kazal motifs (Reck). Although real-time PCR showed that Pdcd4 was not significantly downregulated by asbestos exposure, Western blotting and immunohistochemistry revealed that PDCD4 expression was reduced especially by chrysotile. Reck was significantly downregulated by chrysotile in real-time PCR and immunohistochemistry.<br><br>CONCLUSIONS: This is the first study demonstrating that miR-21 was upregulated and corresponding tumor suppressor genes were downregulated in lung tissues of asbestos-exposed animals. These molecular events are considered to be an early response to asbestos exposure and may contribute to pulmonary toxicity and carcinogenesis.}, }
@article {pmid34676483, year = {2022}, author = {Sonobe, M and Kou, Y and Yamazaki, N and Sakaguchi, Y and Tanaka, H}, title = {Staged removal of artificial patches for thoracic empyema after extrapleural pneumonectomy for diffuse malignant pleural mesothelioma.}, journal = {General thoracic and cardiovascular surgery}, volume = {70}, number = {2}, pages = {193-196}, pmid = {34676483}, issn = {1863-6713}, mesh = {Aged ; *Empyema, Pleural/etiology/surgery ; Humans ; Male ; *Mesothelioma/surgery ; *Mesothelioma, Malignant ; *Pleural Neoplasms/surgery ; Pneumonectomy/adverse effects ; }, abstract = {A 69-year-old man with occupational exposure to asbestos was referred to our hospital with right diffuse malignant pleural mesothelioma. He underwent extrapleural pneumonectomy with reconstruction of the pericardium and diaphragm using elongated polytetrafluoroethylene patches, followed by postoperative chemotherapy and chest wall irradiation. One year later, he was hospitalized because of a right empyema caused by Escherichia coli infection. As chest drainage and systemic antibiotics did not eliminate the abscess around the artificial patches, a Clagett window was created. To avoid mediastinal and liver overshift into the right thoracic cavity, we only performed partial resection of the diaphragm patch and incision of the artificial pericardium. After 19 days of irrigation and dressing change, the artificial patches were completely removed. Two months later, the patient provided a culture-negative sample and had an improved nutritional status; we therefore performed closure of the Clagett window with thoracoplasty. He did not experience recurrence of empyema.}, }
@article {pmid34673618, year = {2021}, author = {Sunitha, S and Shah, AH and Gami, A and Trivedi, P}, title = {Thigh mass in a patient with malignant pleural mesothelioma: Metastasis at an unusual site.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {4}, pages = {834-836}, doi = {10.4103/IJPM.IJPM_463_20}, pmid = {34673618}, issn = {0974-5130}, mesh = {Asbestos/adverse effects ; Humans ; Male ; Medicine, Ayurvedic ; Mesothelioma, Malignant/*pathology ; Middle Aged ; Muscle Neoplasms/*secondary ; Occupational Exposure/adverse effects ; Pleural Cavity/pathology ; Soft Tissue Neoplasms/*pathology ; Thigh/*pathology ; }, abstract = {Soft tissue tumors are a highly heterogeneous group of lesions with varied clinical presentation. The majority is primary tumors and metastatic tumors are very rare. Malignant pleural mesothelioma presenting as a soft tissue mass at a distant site is even rarer and can cause diagnostic challenges both clinically and pathologically. We report a case of malignant pleural mesothelioma presenting as a soft tissue mass in the left thigh. A 59-year-old man, non-smoker, working in a cement factory since 30 years presented with complains of difficulty in walking since 1½ months. Review of his previous medical records revealed malignant pleural mesothelioma, which was diagnosed 9 months before. He had denied chemotherapy and was on Ayurvedic medication. The lesion involved the adjacent intercostal muscles. Few enlarged lymph nodes were noted in mediastinal and cervical regions. Biopsy of left supraclavicular and right cervical lymph nodes showed metastases. Metastasis from malignant pleural mesothelioma to the thigh was confirmed by immunohistochemistry. The tumor was positive for CK5/6, CK7, Calretinin and vimentin and immunonegative for CEA, Napsin A and TTF 1.}, }
@article {pmid34664557, year = {2021}, author = {Sánchez-Trujillo, L and Sanz-Anquela, JM and Ortega, MA}, title = {Use of the Minimum Basic Data Set as a tool for the epidemiological surveillance of mesothelioma.}, journal = {Anales del sistema sanitario de Navarra}, volume = {44}, number = {3}, pages = {405-415}, doi = {10.23938/ASSN.0969}, pmid = {34664557}, issn = {2340-3527}, mesh = {*Asbestos/adverse effects ; Humans ; Incidence ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Spain/epidemiology ; }, abstract = {BACKGROUND: Mesothelioma is a very aggressive tumor that appears after several decades of asbestos exposure. The Minimum Basic Data Set (MBDS) has been validated for the incidence of mesothelioma in Italy, but not in Spain. The objectives of this investigation are: to estimate the prevalence, incidence and mortality of mesothelioma in the Community of Madrid (CM); to evaluate the distribution of this risk within the territory; and to explore validity of the MBDS in the epidemiological surveillance of mesothelioma.<br><br>METHODS: Prevalence, incidence and mortality mesothelioma rates were calculated for the CM from data of the MBDS (2016 and 2017), and mortality data of the Spanish National Statistics Institute (INE) for the same period. The geographical distribution of cases and deaths, and its correlation at municipal level was studied. Statistical analysis with R and Excel tools was carried out.<br><br>RESULTS: The incidence of mesothelioma in the CM was higher than in previous years. Mortality estimated by the MBDS and calculated using INE data for 2016 were similar in the CM. The correlation between the geographical patterns of risk of mesothelioma obtained from the two sources was high (r = 0.86). The aggregation of cases continues in municipalities in the south, detecting the maximum risk in Aranjuez.<br><br>CONCLUSION: The MBDS and INE are good resources for monitoring the risk of mesothelioma. New studies that investigate the aggregation of cases in Aranjuez are required.}, }
@article {pmid34663305, year = {2021}, author = {Sato, T and Nakanishi, H and Akao, K and Okuda, M and Mukai, S and Kiyono, T and Sekido, Y}, title = {Three newly established immortalized mesothelial cell lines exhibit morphological phenotypes corresponding to malignant mesothelioma epithelioid, intermediate, and sarcomatoid types, respectively.}, journal = {Cancer cell international}, volume = {21}, number = {1}, pages = {546}, pmid = {34663305}, issn = {1475-2867}, support = {JP19H03527//japan society for the promotion of science/ ; JP18K07255//japan society for the promotion of science/ ; 20K16462//japan society for the promotion of science/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a very aggressive tumor that develops from mesothelial cells, mainly due to asbestos exposure. MM is categorized into three major histological subtypes: epithelioid, sarcomatoid, and biphasic, with the biphasic subtype containing both epithelioid and sarcomatoid components. Patients with sarcomatoid mesothelioma usually show a poorer prognosis than those with epithelioid mesothelioma, but it is not clear how these morphological phenotypes are determined or changed during the oncogenic transformation of mesothelial cells.<br><br>METHODS: We introduced the E6 and E7 genes of human papillomavirus type 16 and human telomerase reverse transcriptase gene in human peritoneal mesothelial cells and established three morphologically different types of immortalized mesothelial cell lines.<br><br>RESULTS: HOMC-B1 cells exhibited epithelioid morphology, HOMC-A4 cells were fibroblast-like, spindle-shaped, and HOMC-D4 cells had an intermediate morphology, indicating that these three cell lines closely mimicked the histological subtypes of MM. Gene expression profiling revealed increased expression of NOD-like receptor signaling-related genes in HOMC-A4 cells. Notably, the combination treatment of HOMC-D4 cells with TGF-&#x3b2; and IL-1&#x3b2; induced a morphological change from intermediate to sarcomatoid morphology.<br><br>CONCLUSIONS: Our established cell lines are useful for elucidating the fundamental mechanisms of mesothelial cell transformation and mesothelial-to-mesenchymal transition.}, }
@article {pmid34656224, year = {2021}, author = {Nowak, AK}, title = {CONFIRMing single-drug immune checkpoint blockade efficacy in mesothelioma.}, journal = {The Lancet. Oncology}, volume = {22}, number = {11}, pages = {1485-1487}, doi = {10.1016/S1470-2045(21)00516-7}, pmid = {34656224}, issn = {1474-5488}, mesh = {Clinical Trials as Topic ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunotherapy/*methods ; Mesothelioma/*drug therapy/immunology/pathology ; Pharmaceutical Preparations/*administration &amp; dosage ; }, }
@article {pmid34652478, year = {2022}, author = {Ebbinghaus-Mier, D and Ebbinghaus, R and Prager, HM and Schöps, W and Golka, K}, title = {[Mesothelioma of the tunica vaginalis of the testis-a histopathological finding with far-reaching consequences].}, journal = {Der Urologe. Ausg. A}, volume = {61}, number = {3}, pages = {292-296}, pmid = {34652478}, issn = {1433-0563}, mesh = {Humans ; Male ; *Mesothelioma/diagnosis/etiology/surgery ; *Mesothelioma, Malignant ; *Testicular Hydrocele/diagnosis/etiology/surgery ; *Testicular Neoplasms/diagnosis/pathology/surgery ; }, abstract = {Mesotheliomas are very aggressive tumors, almost exclusively caused by asbestos. Four of the 5 mesotheliomas assessed in the years 2014-2020 were recognized as occupational diseases, the 5th case was discontinued due to lack of the patient's cooperation. Surgical exposure of the testis was performed under the suspected diagnoses of hydrocele (n = 3), spermatocele (n = 1) as well as "unknown" (n = 1). This proves that a histopathological examination of removed tissue is the gold standard in scrotal interventions. Every mesothelioma must always be reported as an occupational disease.}, }
@article {pmid34651555, year = {2021}, author = {Paustenbach, D and Brew, D and Ligas, S and Heywood, J}, title = {A critical review of the 2020 EPA risk assessment for chrysotile and its many shortcomings.}, journal = {Critical reviews in toxicology}, volume = {51}, number = {6}, pages = {509-539}, doi = {10.1080/10408444.2021.1968337}, pmid = {34651555}, issn = {1547-6898}, mesh = {Aged ; *Asbestos ; Asbestos, Serpentine/toxicity ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; Risk Assessment ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; United States/epidemiology ; United States Environmental Protection Agency ; }, abstract = {From 2018 to 2020, the United States Environmental Protection Agency (EPA) performed a risk evaluation of chrysotile asbestos to evaluate the hazards of asbestos-containing products (e.g. encapsulated products), including brakes and gaskets, allegedly currently sold in the United States. During the public review period, the EPA received more than 100 letters commenting on the proposed risk evaluation. The Science Advisory Committee on Chemicals (SACC), which peer reviewed the document, asked approximately 100 questions of the EPA that they expected to be addressed prior to publication of the final version of the risk assessment on 30 December 2020. After careful analysis, the authors of this manuscript found many significant scientific shortcomings in both the EPA's draft and final versions of the chrysotile risk evaluation. First, the EPA provided insufficient evidence regarding the current number of chrysotile-containing brakes and gaskets being sold in the United States, which influences the need for regulatory oversight. Second, the Agency did not give adequate consideration to the more than 200 air samples detailed in the published literature of auto mechanics who changed brakes in the 1970-1989 era. Third, the Agency did not consider more than 15 epidemiology studies indicating that exposures to encapsulated chrysotile asbestos in brakes and gaskets, which were generally in commerce from approximately 1950-1985, did not increase the incidence of any asbestos-related disease. Fourth, the concern about chrysotile asbestos being a mesothelioma hazard was based on populations in two facilities where mixed exposure to chrysotile and commercial amphibole asbestos (amosite and crocidolite) occurred. All 8 cases of pleural cancer and mesothelioma in the examined populations arose in facilities where amphiboles were present. It was therefore inappropriate to rely on these cohorts to predict the health risks of exposure to short fiber chrysotile, especially of those fibers filled with phenolic resins. Fifth, the suggested inhalation unit risk (IUR) for chrysotile asbestos was far too high since it was not markedly different than for amosite, despite the fact that the amphiboles are a far more potent carcinogen. Sixth, the approach to low dose modeling was not the most appropriate one in several respects, but, without question, it should have accounted for the background rate of mesothelioma in the general population. Just one month after this assessment was published, the National Academies of Science notified the EPA that the Agency's systematic review process was flawed. The result of the EPA's chrysotile asbestos risk evaluation is that society can expect dozens of years of scientifically unwarranted litigation. Due to an aging population and because some fraction of the population is naturally predisposed to mesothelioma given the presence of various genetic mutations in DNA repair mechanisms (e.g. BAP1 and others), the vast majority of mesotheliomas in the post-2035 era are expected to be spontaneous and unrelated in any way to exposure to asbestos. Due to the EPA's analysis, it is our belief that those who handled brakes and gaskets in the post-1985 era may now believe that those exposures were the cause of their mesothelioma, when a risk assessment based on the scientific weight of evidence would indicate otherwise.}, }
@article {pmid34649858, year = {2021}, author = {Magnavita, N and Congedo, MT and Di Prinzio, RR and Iuliano, A}, title = {War journalism: an occupational exposure.}, journal = {BMJ case reports}, volume = {14}, number = {10}, pages = {}, pmid = {34649858}, issn = {1757-790X}, mesh = {*Asbestos/toxicity ; Dust ; Humans ; Male ; *Mesothelioma/chemically induced ; Middle Aged ; *Occupational Diseases/etiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; Silicon Dioxide ; }, abstract = {Apart from the risk of accidents, war theatres present a hazard related to numerous long-lasting toxic agents. For 10 years, a >60-year-old male journalist worked in war theatres in the Far and Near East where he was exposed to asbestos and other toxic substances (metals, silica, clays, polycyclic aromatic hydrocarbons and other organic substances) contained in dust and smoke of destroyed buildings. More than 15 years later, he developed a mucoepidermoid carcinoma of the soft palate and, subsequently, a pleural malignant mesothelioma. The safety of war journalists should focus not only on preventing the risk of being killed, but also on providing protection from toxic and carcinogenic agents. Exposure to substances released during the destruction of buildings can also pose a carcinogenic risk for survivors.}, }
@article {pmid34645127, year = {2021}, author = {Angelini, A and Chellini, E}, title = {[Inventory of occupational exposure to asbestos with particular reference to Tuscan workers].}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {5 Suppl 1}, pages = {1-120}, doi = {10.19191/EP21.5S1.073}, pmid = {34645127}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Italy/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {This Catalogue is a collection of information on the use of raw asbestos and asbestos-containing materials used in several industries and occupational activities, with particular attention to the situation of Tuscany, a region of Central Italy. The work was developed at the Institute for Cancer Research, Prevention and Clinical Network (ISPRO) of Florence, where epidemiologic research and surveillance activities have been developing since 1988 and where the coordination and evaluation of the regional health surveillance programme provided to past asbestos workers started in 2016 and is still ongoing. The Catalogue aims at being a working tool for all health professionals engaged in examining and classifying the occupational asbestos exposures of subjects both affected by diseases that could be associated to this carcinogen and examined within the regional health surveillance programme. It is necessary for the health personnel engaged in the above-mentioned activities to know or to have the possibility to find exact and detailed data on asbestos exposure by occupational sector. These data are briefly described in the 29 factsheets this Catalogue consists of. In each factsheet, the presence and every use of asbestos are described, with reference to a precise occupational sector. Several occupational sectors can be considered together because of analogies on asbestos exposure. Occupations are considered on the basis of existing evidence on the use of raw asbestos or asbestos-containing materials (as semi-finished or finished products or as auxiliary materials in production processes). Besides the presence and use of asbestos, a description of the possible exposures of workers is reported. Sources of information were scientific and grey literature as well as the 7,187 occupational histories of mesothelioma registered by the specific Tuscan registry. Some factsheets have been revised and enhanced by Italian experts on the asbestos exposure with a specific competence in the examined sectors. Each factsheet includes also questions to be addressed to workers in order to examine in depth their possible asbestos exposure. For those who would like to expand their knowledge on this topic, references are reported both at the end of each factsheet and at the end of the volume. In all industrialized countries, also in those which have not already banned asbestos use, a decrease in the use of this material and in the relative exposure have been observing since the end of the Seventies, few years after the general consensus within the scientific community on asbestos carcinogenicity. This decreasing trend has been becoming greater and greater since the end of the Eighties, when more restrictive regulations have been approved and applied, especially in occupational settings. Nevertheless, nowadays asbestos-related diseases are still diagnosed due to past exposures, although during next decade a decreasing incidence of malignant mesothelioma - the cancer most specifically related to this carcinogen and characterized by a very bad prognosis and the longest latency - could be observed. Particular attention will be paid to jobs regarding renovation of old buildings containing asbestos and to decontamination activities. In conclusion, this Catalogue is a working tool - although it is not exhaustive and could be upgraded with new information - for all professionals engaged in asbestos risk prevention activities as health personnel, personnel of insurance companies, employers, and employee representatives.}, }
@article {pmid34641979, year = {2021}, author = {Kuroda, A}, title = {Recent progress and perspectives on the mechanisms underlying Asbestos toxicity.}, journal = {Genes and environment : the official journal of the Japanese Environmental Mutagen Society}, volume = {43}, number = {1}, pages = {46}, pmid = {34641979}, issn = {1880-7046}, support = {JPMEERF201950001//environmental restoration and conservation agency/ ; 19H04291//japan society for the promotion of science/ ; }, abstract = {Most cases of mesothelioma are known to result from exposure to asbestos fibers in the environment or occupational ambient air. The following questions regarding asbestos toxicity remain partially unanswered: (i) why asbestos entering the alveoli during respiration exerts toxicity in the pleura; and (ii) how asbestos causes mesothelioma, even though human mesothelial cells are easily killed upon exposure to asbestos. As for the latter question, it is now thought that the frustrated phagocytosis of asbestos fibers by macrophages prolongs inflammatory responses and gives rise to a "mutagenic microenvironment" around mesothelial cells, resulting in their malignant transformation. Based on epidemiological and genetic studies, a carcinogenic model has been proposed in which BRCA1-associated protein 1 mutations are able to suppress cell death in mesothelial cells and increase genomic instability in the mutagenic microenvironment. This leads to additional mutations, such as CDKN2A [p16], NF2, TP53, LATS2, and SETD2, which are associated with mesothelioma carcinogenesis. Regarding the former question, the receptors involved in the intracellular uptake of asbestos and the mechanism of transfer of inhaled asbestos from the alveoli to the pleura are yet to be elucidated. Further studies using live-cell imaging techniques will be critical to fully understanding the mechanisms underlying asbestos toxicity.}, }
@article {pmid34641792, year = {2021}, author = {Kelarji, AB and Alshutaihi, MS and Ghazal, A and Mahli, N and Agha, S}, title = {A rare case of benign multicystic peritoneal mesothelioma misdiagnosed as hydatid cyst found in the liver parenchyma and abdomen cavity of a male with asbestos exposure.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {374}, pmid = {34641792}, issn = {1471-230X}, mesh = {Abdomen ; *Asbestos ; Diagnostic Errors ; *Echinococcosis ; Humans ; Liver ; Male ; *Mesothelioma, Cystic/diagnosis/surgery ; Middle Aged ; Neoplasm Recurrence, Local ; }, abstract = {BACKGROUND: Benign Multicystic Peritoneal Mesothelioma (BMPM) is one of the rarest diseases in medicine with only more than 200 cases worldwide. This paper aims to report a case of Benign Multicystic Peritoneal Mesothelioma that strangely arose from the liver and was long treated as Hydatid cyst. The case also had many risk factors including asbestos exposure that had not yet been linked with Benign Multicystic Peritoneal Mesothelioma.<br><br>CASE PRESENTATION: We report a case of a 62&#xa0;years old male with a history of a perforated peptic ulcer and a cystic mass in the liver that was misdiagnosed as hydatid cyst 7&#xa0;years ago. He presented with generalized abdominal pain and bloating. Image studies showed many cystic formations filled with clear fluid. An en bloc surgery was performed and a pathologic study showed a multiloculated mass lined by flat or cuboidal epithelium leading to the diagnosis of BMPM. A follow up was scheduled after 3&#xa0;months revealed total recurrence.<br><br>CONCLUSION: BMPM resembles many other cystic lesions in the abdomen and should be taken into consideration when dealing with nontypical cystic formations. Its diagnostic and treatment methods are still hazy making this disease difficult to approach.}, }
@article {pmid34639316, year = {2021}, author = {Fazzo, L and Binazzi, A and Ferrante, D and Minelli, G and Consonni, D and Bauleo, L and Bruno, C and Bugani, M and De Santis, M and Iavarone, I and Magnani, C and Romeo, E and Zona, A and Alessi, M and Comba, P and Marinaccio, A}, title = {Burden of Mortality from Asbestos-Related Diseases in Italy.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {19}, pages = {}, pmid = {34639316}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; *Asbestosis ; Humans ; Italy/epidemiology ; *Mesothelioma ; *Occupational Diseases ; }, abstract = {Asbestos is one of the major worldwide occupational carcinogens. The global burden of asbestos-related diseases (ARDs) was estimated around 231,000 cases/year. Italy was one of the main European asbestos producers until the 1992 ban. The WHO recommended national programs, including epidemiological surveillance, to eliminate ARDs. The present paper shows the estimate of the burden of mortality from ARDs in Italy, established for the first time. National standardized rates of mortality from mesothelioma and asbestosis and their temporal trends, based on the National Institute of Statistics database, were computed. Deaths from lung cancer attributable to asbestos exposure were estimated using population-based case-control studies. Asbestos-related lung and ovarian cancer deaths attributable to occupational exposure were estimated, considering the Italian occupational cohort studies. In the 2010-2016 period, 4400 deaths/year attributable to asbestos were estimated: 1515 from mesothelioma, 58 from asbestosis, 2830 from lung and 16 from ovarian cancers. The estimates based on occupational cohorts showed that each year 271 deaths from mesothelioma, 302 from lung cancer and 16 from ovarian cancer were attributable to occupational asbestos exposure in industrial sectors with high asbestos levels. The important health impact of asbestos in Italy, 10-25 years after the ban, was highlighted. These results suggest the need for appropriate interventions in terms of prevention, health care and social security at the local level and could contribute to the global estimate of ARDs.}, }
@article {pmid34639307, year = {2021}, author = {Kwon, SC and Lee, SS and Kang, MS and Huh, DA and Lee, YJ}, title = {The Epidemiologic Characteristics of Malignant Mesothelioma Cases in Korea: Findings of the Asbestos Injury Relief System from 2011-2015.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {19}, pages = {}, pmid = {34639307}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Incidence ; Italy ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Republic of Korea/epidemiology ; }, abstract = {(1) Background: The purpose of this study was to investigate the epidemiological characteristics of malignant mesothelioma in Korea by investigating cases compensated under the asbestos injury relief system. (2) Methods: A total of 407 compensated cases between 2011 and 2015 were reviewed using medical records and resident registrations in order to investigate the dates of diagnosis and death. Asbestos exposure and patients' general characteristics were investigated through face-to-face interviews. The standardized incidence ratio was calculated as the number of observations from 2005 to 2014 per exposure region in Korea, using the mid-annual population of each region in 2009 as the standard population. (3) Results: Among the 407 cases, 65.1% were male. The pleura and peritoneum were affected in 76.9% and 23.1% of cases, respectively. For peritoneal mesothelioma, the median survival duration was longer (p = 0.005), and the proportion of affected women was higher than that in pleural mesothelioma. The standardized incidence ratio (95% CI) by province of primary exposure was Chungnam 3.33 (2.51-4.35), Ulsan 1.85 (0.97-3.21), and Seoul 1.32 (1.06-1.63). (4) Conclusions: Although the representativeness of the data is limited, it is sufficient to assume the epidemiologic characteristics of malignant mesothelioma, help improve the compensation system, and contribute to future policies.}, }
@article {pmid34638565, year = {2021}, author = {Yuen, ML and Zhuang, L and Rath, EM and Yu, T and Johnson, B and Sarun, KH and Wang, Y and Kao, S and Linton, A and Clarke, CJ and McCaughan, BC and Takahashi, K and Lee, K and Cheng, YY}, title = {The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM).}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34638565}, issn = {1422-0067}, support = {2018//Regional Collaboration Program Grant/ ; }, mesh = {Aminopyridines/pharmacology ; Antigens, CD/*genetics/*metabolism ; Cadherins/*genetics/*metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; ErbB Receptors/metabolism ; Focal Adhesion Kinase 1/*antagonists &amp; inhibitors ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; MicroRNAs/genetics/metabolism/*physiology ; Protein Interaction Maps ; Protein Kinase Inhibitors/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM. The immunohistochemistry (IHC) results showed that the majority of MPM FFPE samples exhibited either the absence of, or very low, E-cadherin protein expression in MPM tissue. We showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. In summary, MPM cells that did not express CDH1 mRNA were sensitive to PND-1186, and MPM cells that retained CDH1 mRNA were resistant. A cell cycle analysis showed that PND-1186 induced cell cycle disruption by inducing the G2/M arrest of MPM cells. A protein-protein interaction study showed that EGFR is linked to the FAK pathway, and a target scan of the microRNAs revealed that microRNAs (miR-17, miR221, miR-222, miR137, and miR148) interact with EGFR 3'UTR. Transfection of MPM cells with these microRNAs sensitised the CHD1-expressing FAK-inhibitor-resistant MPM cells to the FAK inhibitor.}, }
@article {pmid34612763, year = {2021}, author = {Korchevskiy, AA and Wylie, AG}, title = {Dimensional determinants for the carcinogenic potency of elongate amphibole particles.}, journal = {Inhalation toxicology}, volume = {33}, number = {6-8}, pages = {244-259}, doi = {10.1080/08958378.2021.1971340}, pmid = {34612763}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*adverse effects/chemistry ; Environmental Pollutants/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; }, abstract = {CONTEXT: Carcinogenic properties of particulates depend, among other factors, on dimensional characteristics that affect their ability to reach sensitive tissue, to be removed or retained, and to interact with the cells.<br><br>OBJECTIVE: To model mesothelioma and lung cancer potency of amphibole particles based on their dimensional characteristics and mineral habit (asbestiform vs. nonasbestiform) utilizing epidemiological data and detailed size information.<br><br>METHODS: The datasets from recently created depository of dimensional information of elongate mineral particles were used to correlate mesothelioma and lung cancer potency with the fraction of particles in a specific size range and the ratio of length and width in different powers. In addition, the cancer potency factors were estimated and compared for 30 asbestiform, 15 nonasbestiform, and 10 mixed datasets.<br><br>RESULTS: For particles longer than 5&#x2009;&#xb5;m, the highest correlation with mesothelioma potency was achieved for width <0.22&#x2009;&#xb5;m, and with lung cancer <0.28&#x2009;&#xb5;m. The statistical power of the correlation was observed to lose significance at a maximum width of 0.6-0.7&#x2009;&#xb5;m. Mesothelioma potency correlated with length in the power of 1.9 divided by width in the power of 2.97, lung cancer potency with length in the power of 0.4 divided by width in the power of 1.17. The predicted cancer potencies of asbestiform, nonasbestiform, and mixed categories were significantly different.<br><br>CONCLUSION: While additional studies in this direction are warranted, this paper should serve as an additional confirmation for the role of fiber dimensions in the carcinogenicity of amphibole elongate mineral particles (EMPs).}, }
@article {pmid34602383, year = {2022}, author = {Gupta, N and Soni, A and Mahajan, R and Selhi, P and Tyagi, R and Garg, B and Kaur, H}, title = {Peritoneal malignant mesothelioma: Slippery like an eel to diagnose on cytology-case series of 3 cases.}, journal = {Journal of the American Society of Cytopathology}, volume = {11}, number = {1}, pages = {40-45}, doi = {10.1016/j.jasc.2021.08.007}, pmid = {34602383}, issn = {2213-2945}, mesh = {Ascitic Fluid/cytology/pathology ; Cytological Techniques ; Diagnosis, Differential ; Humans ; Liver/cytology/pathology ; Male ; Mesothelioma, Malignant/*diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/pathology ; Peritoneum/cytology/pathology ; }, abstract = {INTRODUCTION: Peritoneal malignant mesothelioma is an extremely rare tumor and is a difficult diagnosis to be made on cytology alone. We report 3 cases where the cytologic features were misdiagnosed as carcinoma/lymphoma but histopathology and immunohistochemistry (IHC) established the diagnosis of malignant mesothelioma.<br><br>CLINICAL DETAILS: Case 1 was a 60-year-old man with multiloculated ascites and omental caking. Peritoneal fluid was reported as malignant on cytology but was misclassified as adenocarcinoma. Case 2, a 45-year-old man with ascites and peritoneal nodularity, radiologically mimicking peritoneal carcinomatosis, was also reported positive for malignancy on ascitic fluid cytology. Fine-needle aspiration (FNAC) from omental fat revealed signet ring cells, thus misleading to cytologic diagnosis of adenocarcinoma. Case 3 was a 63-year-old man with perisplenic mass with extensive omental caking and peritoneal nodularity that was also suspected to be peritoneal carcinomatosis on radiology. FNAC smears from perisplenic mass showed sheets of plasmacytoid cells. On cytology, the differential diagnoses offered were neuroendocrine tumor or non-Hodgkin lymphoma. The diagnosis of malignant mesothelioma was established only after IHC on histopathologic sections in all these cases. None of our patients had history of prior asbestos exposure.<br><br>CONCLUSION: In such clinical scenarios, with radiology suggesting peritoneal carcinomatosis, the cytologic features need corroboration by IHC/fluorescence in situ hybridization on cell block or biopsy to correctly identify malignant mesothelioma and differentiate it from metastatic carcinomatous deposits and benign mesothelial proliferation.}, }
@article {pmid34590026, year = {2021}, author = {Nakagawa, K and Kijima, T and Okada, M and Morise, M and Kato, M and Hirano, K and Fujimoto, N and Takenoyama, M and Yokouchi, H and Ohe, Y and Hida, T and Aoe, K and Kishimoto, T and Hirokawa, M and Matsuki, H and Kaneko, Y and Yamada, T and Morimoto, C and Takeda, M}, title = {Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma.}, journal = {JTO clinical and research reports}, volume = {2}, number = {6}, pages = {100178}, pmid = {34590026}, issn = {2666-3643}, abstract = {INTRODUCTION: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study.<br><br>METHODS: The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5&#xa0;&#xd7; once-weekly infusions, followed by a 1-wk rest).<br><br>RESULTS: The study included 31 patients (median age&#xa0;= 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater&#xa0;than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The&#xa0;best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths.<br><br>CONCLUSIONS: The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.}, }
@article {pmid34575358, year = {2021}, author = {Musso, V and Diotti, C and Palleschi, A and Tosi, D and Aiolfi, A and Mendogni, P}, title = {Management of Pleural Effusion Secondary to Malignant Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {18}, pages = {}, pmid = {34575358}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive pleural tumour which has been epidemiologically linked to occupational exposure to asbestos. MPM is often associated with pleural effusion, which is a common cause of morbidity and whose management remains a clinical challenge. In this review, we analysed the literature regarding the diagnosis and therapeutic options of pleural effusion secondary to mesothelioma. Our aim was to provide a comprehensive view on this subject, and a new algorithm was proposed as a practical aid to clinicians dealing with patients suffering from pleural effusion.}, }
@article {pmid34572485, year = {2021}, author = {Štrbac, D and Dolžan, V}, title = {Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review.}, journal = {Biomolecules}, volume = {11}, number = {9}, pages = {}, pmid = {34572485}, issn = {2218-273X}, mesh = {Biomarkers, Tumor/*metabolism ; Body Fluids/metabolism ; Genetic Variation ; Humans ; Matrix Metalloproteinases/*metabolism ; Mesothelioma/*drug therapy/*enzymology/genetics ; *Molecular Targeted Therapy ; }, abstract = {Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.}, }
@article {pmid34566802, year = {2021}, author = {Di Basilio, D and Shigemura, J and Guglielmucci, F}, title = {Commentary: SARS-CoV-2 and Asbestos Exposure: Can Our Experience With Mesothelioma Patients Help Us Understand the Psychological Consequences of COVID-19 and Develop Interventions?.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {720160}, pmid = {34566802}, issn = {1664-1078}, }
@article {pmid34549571, year = {2021}, author = {Barbieri, PG and Calisti, R and Calabresi, C}, title = {[Pleural malignant mesotheliomas from environmental exposures to asbestos In Italy].}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {4}, pages = {289-295}, doi = {10.19191/EP21.4.P289.085}, pmid = {34549571}, issn = {1120-9763}, mesh = {*Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Humans ; Italy/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; Sicily ; }, abstract = {Pleural mesothelioma clusters from outdoor environmental exposure have been highlighted also in Italy and, on the basis of epidemiological surveillance coordinated by the Italian National Mesothelioma Register, their frequency has been estimated at about 4.5%. Epidemiological studies and evaluations of some regional mesothelioma registers have made it possible to highlight that the dispersion of asbestos fibers in the outdoor environment was the only ascertained cause of mesothelioma in subjects from asbestos-cement factories, from the Balangero mine (Piedmont Region), from some serpentine rock quarries with tremolite outcrops in the Southern Apennines and in Alta Val di Susa (Piedmont Region); from chrysotile and serpentine caves in Valmalenco (Lombardy Region). Furthermore, cases of pleural mesothelioma were clearly caused by environmental pollution from fluoroedenite fibers in Biancavilla (Sicily Region). On the other hand, regional mesothelioma registers have also reported other circumstances of environmental asbestos exposure, like in the case of steel industry, shipbuilding, chemical plants, railway lines, and repair/demolition of railway carriages. However, these reports have not found confirmation on the basis of ad-hoc studies and it is likely that there is a lack of homogeneity in the assessment of individual cases. Apart from the scenarios which have been the subject of ad-hoc studies, the assessment of the causal role of environmental exposure to "in place" asbestos in the onset of pleural mesothelioma is problematic without an effort to more carefully examine the circumstances of possible exposure, harmonization of the attribution criteria used in the individual regional registers, analytical assessment of the impact of such exposure on the risk of onset of mesothelioma.}, }
@article {pmid34540427, year = {2021}, author = {Khatib, S and Asad, O and Asad, H and Sabobeh, T}, title = {A Rare Case of Malignant Pleural Mesothelioma in a Young Healthy Male Without Asbestos Exposure.}, journal = {Cureus}, volume = {13}, number = {8}, pages = {e17199}, pmid = {34540427}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor that arises from mesothelial cells of pleural cavity. The main risk factor for MPM is asbestos exposure with most cases discovered in elderly males after a long latency period. However, here we report a rare case of MPM diagnosed in a healthy young male patient without significant asbestos exposure. We report the case of an otherwise healthy 47-year-old male who presented with one week of exertional dyspnea and chest pain. Chest X-ray showed unilateral large pleural effusion. Chest CT scan revealed confluent right hilar mass and pleural thickening. Pleural fluid analysis showed exudative features. Cytology was negative for malignant cells. Core tissue biopsy showed features of epithelioid mesothelioma. Although most cases of MPM have been reported in elderly male patients with significant asbestos exposure, more research is needed to explain the pathogenesis of MPM in young patients without asbestos exposure.}, }
@article {pmid34526026, year = {2021}, author = {Airoldi, C and Magnani, C and Lazzarato, F and Mirabelli, D and Tunesi, S and Ferrante, D}, title = {Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.}, journal = {Environmental health : a global access science source}, volume = {20}, number = {1}, pages = {103}, pmid = {34526026}, issn = {1476-069X}, mesh = {Aged ; Asbestos/*adverse effects ; Case-Control Studies ; Cluster Analysis ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Spatial Analysis ; }, abstract = {BACKGROUND: Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering.<br><br>METHODS: A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed.<br><br>RESULTS: One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5&#xa0;km and 5-10&#xa0;km, respectively (reference&#x2009;>&#x2009;15&#xa0;km). Finally, a significant (p&#x2009;<&#x2009;0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors.<br><br>CONCLUSIONS: In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.}, }
@article {pmid34519165, year = {2021}, author = {Torkki, P and Paajanen, J and Kytö, V and Laaksonen, S and Räsänen, J and Myllärniemi, M and Ilonen, I}, title = {Evidence for marked underutilization of insurance billing in malignant pleural mesothelioma in Finland.}, journal = {Thoracic cancer}, volume = {12}, number = {19}, pages = {2594-2600}, pmid = {34519165}, issn = {1759-7714}, mesh = {Finland ; Health Care Costs/*statistics &amp; numerical data ; Humans ; Insurance, Health/*statistics &amp; numerical data ; Mesothelioma, Malignant/*economics/*therapy ; Retrospective Studies ; }, abstract = {BACKGROUND: Substantial variation in health care costs for malignant pleural mesothelioma (MPM) has previously been identified.<br><br>MATERIALS AND METHODS: We analyzed the changes in health care costs in MPM in Finland during 2002-2012. Finland has low-threshold public health care and a mandatory Workers' Compensation scheme that covers all occupational-related disease expenses. The costs include treatment costs for inpatients, hospice care, medication costs, rehabilitation costs, and travel costs. All costs are expressed in 2012 prices, adjusted using the consumer price index.<br><br>RESULTS: A total of 907 MPM patients were included in the study. Mean duration of inpatient episodes increased 7% per year from 2002 to 2012, correlating with total costs (R[2] &#xa0;=&#xa0;0.861, p&#x2009;<&#x2009;0.05). The annual total costs for treatment increased from 1.7 to 4.3&#xa0;m&#x20ac; during the study period and the cost per patient from 27&#x2009;000 to 43&#x2009;000&#xa0;&#x20ac;. The overall costs increased progressively by the number of procedures performed. In patients who had been compensated for occupational cause by Workers' Compensation Center, only 36% of the overall care costs were billed from the insurance company. Billing of inpatient costs was 86% in these patients.<br><br>CONCLUSION: During the study period, we found that the costs of MPM increased more than the average health care costs. This may be because of advanced diagnostic workup or more costly treatment (e.g., pemetrexed). Moreover, only one-third of all health care costs are charged to Workers' Compensation Insurance.}, }
@article {pmid34511983, year = {2021}, author = {Xie, D and Hu, J and Wu, T and Cao, K and Luo, X}, title = {Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma.}, journal = {International journal of general medicine}, volume = {14}, number = {}, pages = {4987-5003}, pmid = {34511983}, issn = {1178-7074}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM.<br><br>METHODS: Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers.<br><br>RESULTS: WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (&#x2265;4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of >0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1).<br><br>CONCLUSION: These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.}, }
@article {pmid34491782, year = {2022}, author = {Nowak, AK and Jackson, A and Sidhu, C}, title = {Management of Advanced Pleural Mesothelioma-At the Crossroads.}, journal = {JCO oncology practice}, volume = {18}, number = {2}, pages = {116-124}, doi = {10.1200/OP.21.00426}, pmid = {34491782}, issn = {2688-1535}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; *Mesothelioma/drug therapy/etiology ; *Mesothelioma, Malignant ; Nivolumab/therapeutic use ; *Pleural Neoplasms/drug therapy/pathology ; }, abstract = {The management of pleural mesothelioma has changed with the demonstration that first-line checkpoint blockade therapy improves survival. This review covers issues of relevance to the practicing medical oncologist, with an emphasis on the palliative setting and on new information. Until recently, standard systemic therapy for mesothelioma was combination chemotherapy with platinum and pemetrexed. In 2020, combination immunotherapy with ipilimumab and nivolumab was approved as first-line systemic therapy for mesothelioma following release of the results from the CheckMate 743 trial. This trial showed improved overall survival for patients receiving ipilimumab and nivolumab over those treated with platinum and pemetrexed chemotherapy. When the survival results were examined by histologic subtype, the survival benefit was most significant in those with nonepithelioid mesothelioma, a group for which combination immunotherapy is now standard of care. The most important outstanding issue from CheckMate-743 is a better understanding, through translational studies, of which patients with epithelioid mesothelioma may benefit from combination immunotherapy. The next generation of first-line clinical trials in mesothelioma will report the results of first-line combination chemoimmunotherapy. For those patients who receive first-line dual checkpoint blockade, there is no evidence as to the efficacy of subsequent chemotherapy. However, given the known first-line efficacy of cisplatin or carboplatin and pemetrexed, combination chemotherapy is an appropriate subsequent choice for those who progress on or after dual immunotherapy. For those who previously received chemotherapy without immunotherapy, single-agent nivolumab provides benefit over best supportive care. In summary, both chemotherapy and immunotherapy should be considered for all patients during their disease course. Another topical issue is the growing appreciation that some individuals have an inherited predisposition to mesothelioma; referral to a clinical geneticist should be considered under some circumstances. The role of surgery and multimodality therapy is controversial, with results awaited from the fully recruited MARS-2 clinical trial. Patient selection, staging, and multidisciplinary review are critical to identify those who might benefit from a multimodality approach. Finally, a proactive, multidisciplinary approach to symptom management and the principles of management of pleural effusions are critical to manage the symptom burden of mesothelioma and optimize patient well-being.}, }
@article {pmid34487023, year = {2022}, author = {Dick, IM and Lee, YCG and Cheah, HM and Miranda, A and Robinson, BWS and Creaney, J}, title = {Profile of soluble factors in pleural effusions predict prognosis in mesothelioma.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {33}, number = {1}, pages = {159-169}, pmid = {34487023}, issn = {1875-8592}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; *Lung Neoplasms/metabolism ; *Mesothelioma/diagnosis/metabolism ; *Pleural Effusion/diagnosis ; *Pleural Effusion, Malignant/diagnosis ; *Pleural Neoplasms/diagnosis ; Prognosis ; }, abstract = {BACKGROUND: Pleural mesothelioma is a deadly asbestos induced cancer. Less than 10% of mesothelioma patients survive 5 years post diagnosis. However survival can range from a few months to a number of years. Accurate prediction of survival is important for patients to plan for their remaining life, and for clinicians to determine appropriate therapy. One unusual feature of mesothelioma is that patients frequently present with tumor-associated pleural effusions early in the course of the disease.<br><br>OBJECTIVE: To study whether cells and molecules present in pleural effusions provide prognostic information for mesothelioma.<br><br>METHODS: We profiled the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively "soluble factors") involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients.Associations with survival were evaluated by Cox proportional hazards regression methods. Results for the two soluble factors most significantly and independently associated with survival were validated in an independent set of samples (n= 51) using a separate assay system.<br><br>RESULTS: Survival analysis revealed that IL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. Lipocalin2 and IL4 were associated with better prognosis.<br><br>CONCLUSIONS: This study demonstrates that pleural effusions rich in a range of soluble factors are associated with poor prognosis. These findings will enhance our ability to prognosticate outcomes in mesothelioma patients.}, }
@article {pmid34445720, year = {2021}, author = {Lisini, D and Lettieri, S and Nava, S and Accordino, G and Frigerio, S and Bortolotto, C and Lancia, A and Filippi, AR and Agustoni, F and Pandolfi, L and Piloni, D and Comoli, P and Corsico, AG and Stella, GM}, title = {Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, pmid = {34445720}, issn = {1422-0067}, support = {#08050//IRCCS Policlinico San Mattteo/ ; }, mesh = {Combined Modality Therapy ; Drug Delivery Systems/methods ; Humans ; Immunotherapy/methods ; Mesothelioma/pathology/therapy ; Mesothelioma, Malignant/*pathology/*therapy ; Pleural Neoplasms/pathology/therapy ; Soft Tissue Neoplasms/pathology/therapy ; Tumor Microenvironment/drug effects/physiology ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.}, }
@article {pmid34444165, year = {2021}, author = {Lemen, RA and Landrigan, PJ}, title = {Sailors and the Risk of Asbestos-Related Cancer.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {16}, pages = {}, pmid = {34444165}, issn = {1660-4601}, mesh = {*Asbestos/analysis/toxicity ; Asbestos, Serpentine ; Humans ; *Mesothelioma/chemically induced/epidemiology ; *Military Personnel ; Ships ; }, abstract = {Sailors have long been known to experience high rates of injury, disease, and premature death. Many studies have shown asbestos-related diseases among shipyard workers, but few have examined the epidemiology of asbestos-related disease and death among asbestos-exposed sailors serving on ships at sea. Chrysotile and amphibole asbestos were used extensively in ship construction for insulation, joiner bulkhead systems, pipe coverings, boilers, machinery parts, bulkhead panels, and many other uses, and asbestos-containing ships are still in service. Sailors are at high risk of exposure to shipboard asbestos, because unlike shipyard workers and other occupationally exposed groups, sailors both work and live at their worksite, making asbestos standards and permissible exposure limits (PELs). based on an 8-h workday inadequate to protect their health elevated risks of mesothelioma and other asbestos-related cancers have been observed among sailors through epidemiologic studies. We review these studies here.}, }
@article {pmid34439349, year = {2021}, author = {Brims, F}, title = {Epidemiology and Clinical Aspects of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {16}, pages = {}, pmid = {34439349}, issn = {2072-6694}, abstract = {Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The incidence of mesothelioma in different countries reflect the historical patterns of commercial asbestos utilisation in the last century and predominant occupational exposures mean that mesothelioma is mostly seen in males. Modern imaging techniques and advances in immunohistochemical staining have contributed to an improved diagnosis of mesothelioma. There have also been recent advances in immune checkpoint inhibition, however, mesothelioma remains very challenging to manage, especially considering its limited response to conventional systemic anticancer therapy and that no cure exists. Palliative interventions and support remain paramount with a median survival of 9-12 months after diagnosis. The epidemiology and diagnosis of mesothelioma has been debated over previous decades, due to a number of factors, such as the long latent period following asbestos exposure and disease occurrence, the different potencies of the various forms of asbestos used commercially, the occurrence of mesothelioma in the peritoneal cavity and its heterogeneous pathological and cytological appearances. This review will describe the contemporary knowledge on the epidemiology of mesothelioma and provide an overview of the best clinical practice including diagnostic approaches and management.}, }
@article {pmid34439164, year = {2021}, author = {Carbotti, G and Dozin, B and Martini, S and Giordano, C and Scordamaglia, F and Croce, M and Filaci, G and Ferrini, S and Fabbi, M}, title = {IL-27 Mediates PD-L1 Expression and Release by Human Mesothelioma Cells.}, journal = {Cancers}, volume = {13}, number = {16}, pages = {}, pmid = {34439164}, issn = {2072-6694}, support = {GR-2013-02356568//Italian Ministry of Health/ ; 5 x 1000 Funds//Italian Ministry of Health/ ; Ricerca Corrente 2018-2021//Italian Ministry of Health/ ; }, abstract = {Malignant mesothelioma (MM) is a rare tumor with an unfavorable prognosis. MM genesis involves asbestos-mediated local inflammation, supported by several cytokines, including IL-6. Recent data showed that targeting PD-1/PD-L1 is an effective therapy in MM. Here, we investigated the effects of IL-6 trans-signaling and the IL-6-related cytokine IL-27 on human MM cells in vitro by Western blot analysis of STAT1/3 phosphorylation. The effects on PD-L1 expression were tested by qRT-PCR and flow-cytometry and the release of soluble (s)PD-L1 by ELISA. We also measured the concentrations of sPD-L1 and, by multiplexed immunoassay, IL-6 and IL-27 in pleural fluids obtained from 77 patients in relation to survival. IL-27 predominantly mediates STAT1 phosphorylation and increases PD-L1 gene and surface protein expression and sPD-L1 release by human MM cells in vitro. IL-6 has limited activity, whereas a sIL-6R/IL-6 chimeric protein mediates trans-signaling predominantly via STAT3 phosphorylation but has no effect on PD-L1 expression and release. IL-6, IL-27, and sPD-L1 are present in pleural fluids and show a negative correlation with overall survival, but only IL-27 shows a moderate albeit significant correlation with sPD-L1 levels. Altogether these data suggest a potential role of IL-27 in PD-L1-driven immune resistance in MM.}, }
@article {pmid34430345, year = {2021}, author = {Mathilakathu, A and Borchert, S and Wessolly, M and Mairinger, E and Beckert, H and Steinborn, J and Hager, T and Christoph, DC and Kollmeier, J and Wohlschlaeger, J and Mairinger, T and Schmid, KW and Walter, RFH and Brcic, L and Mairinger, FD}, title = {Mitogen signal-associated pathways, energy metabolism regulation, and mediation of tumor immunogenicity play essential roles in the cellular response of malignant pleural mesotheliomas to platinum-based treatment: a retrospective study.}, journal = {Translational lung cancer research}, volume = {10}, number = {7}, pages = {3030-3042}, pmid = {34430345}, issn = {2218-6751}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare malignant tumor associated with asbestos exposure, with infaust prognosis and overall survival below 20 months in treated patients. Platinum is still the backbone of the chemotherapy protocols, and the reasons for the rather poor efficacy of platinum compounds in MPM remain largely unknown. Therefore, we aimed to analyze differences in key signaling pathways and biological mechanisms in therapy-naïve samples and samples after chemotherapy in order to evaluate the effect of platinum-based chemotherapy.<br><br>METHODS: The study cohort comprised 24 MPM tumor specimens, 12 from therapy-na&#xef;ve and 12 from patients after platinum-based therapy. Tumor samples were screened using the NanoString nCounter platform for digital gene expression analysis with an appurtenant custom-designed panel comprising a total of 366 mRNAs covering the most important tumor signaling pathways. Significant pathway associations were identified by gene set enrichment analysis using the WEB-based GEne SeT AnaLysis Toolkit (WebGestalt).<br><br>RESULTS: We have found reduced activity of TNF (normalized enrichment score: 2.03), IL-17 (normalized enrichment score: 1.93), MAPK (normalized enrichment score: 1.51), and relaxin signaling pathways (normalized enrichment score: 1.42) in the samples obtained after platinum-based therapy. In contrast, AMPK (normalized enrichment score: -1.58), mTOR (normalized enrichment score: -1.50), Wnt (normalized enrichment score: -1.38), and longevity regulating pathway (normalized enrichment score: -1.31) showed significantly elevated expression in the same samples.<br><br>CONCLUSIONS: We could identify deregulated signaling pathways due to a directed cellular response to platinum-induced cell stress. Our results are paving the ground for a better understanding of cellular responses and escape mechanisms, carrying a high potential for improved clinical management of patients with MPM.}, }
@article {pmid34395196, year = {2021}, author = {Tran, T and Egilman, D and Rigler, M and Emory, T}, title = {A Critique of Helsinki Criteria for Using Lung Fiber Levels to Determine Causation in Mesothelioma Cases.}, journal = {Annals of global health}, volume = {87}, number = {1}, pages = {73}, pmid = {34395196}, issn = {2214-9996}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*toxicity ; Humans ; Lung/*pathology ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma, Malignant/*chemically induced/epidemiology ; Mineral Fibers/*analysis/toxicity ; Occupational Exposure/*adverse effects/analysis ; Particulate Matter/analysis/chemistry ; }, abstract = {Asbestos is a known human carcinogen and the chief known cause of mesothelioma. In 1997, a group of experts developed the Helsinki Criteria, which established criteria for attribution of mesothelioma to asbestos. The criteria include two methods for causation attribution: 1) a history of significant occupational, domestic, or environmental exposure and/or 2) pathologic evidence of exposure to asbestos. In 2014, the Helsinki Criteria were updated, and these attribution criteria were not changed. However, since the Helsinki Criteria were first released in 1997, some pathologists, cell biologists, and others have claimed that a history of exposure cannot establish causation unless the lung asbestos fiber burden exceeds "the background range for the laboratory in question to attribute mesothelioma cases to exposure to asbestos." This practice ignores the impact on fiber burden of clearance/translocation over time, which in part is why the Helsinki Criteria concluded that a history of exposure to asbestos was independently sufficient to attribute causation to asbestos. After reviewing the Helsinki Criteria, we conclude that their methodology is fatally flawed because a quantitative assessment of a background lung tissue fiber level cannot be established. The flaws of the Helsinki Criteria are both technical and substantive. The 1995 paper that served as the scientific basis for establishing background levels used inconsistent methods to determine exposures in controls and cases. In addition, historic controls cannot be used to establish background fiber levels for current cases because ambient exposures to asbestos have decreased over time and control cases pre-date current cases by decades. The use of scanning electron microscope (SEM) compounded the non-compatibility problem; the applied SEM cannot distinguish talc from anthophyllite because it cannot perform selected area electron diffraction, which is a crucial identifier in ATEM for distinguishing the difference between serpentine asbestos, amphibole asbestos, and talc.}, }
@article {pmid34390717, year = {2022}, author = {Ciocan, C and Pira, E and Coggiola, M and Franco, N and Godono, A and La Vecchia, C and Negri, E and Boffetta, P}, title = {Mortality in the cohort of talc miners and millers from Val Chisone, Northern Italy: 74 years of follow-up.}, journal = {Environmental research}, volume = {203}, number = {}, pages = {111865}, doi = {10.1016/j.envres.2021.111865}, pmid = {34390717}, issn = {1096-0953}, mesh = {Cause of Death ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Male ; *Occupational Exposure ; *Talc/toxicity ; }, abstract = {OBJECTIVE: To update the analysis of mortality of a cohort of talc miners and millers in Northern Italy.<br><br>METHODS: We analyzed overall mortality and mortality from specific causes of death during 1946-2020 of 1749 male workers in a talc mine where asbestos was not detected (1184 miners and 565 millers) employed during 1946-1995.<br><br>RESULTS: The overall standardized mortality ratio (SMR) was 1.21 (95&#xa0;% confidence interval [CI] 1.14-1.28); no deaths were observed from pleural cancer. Mortality from lung cancer was not increased (SMR&#xa0;=&#xa0;1.02 95&#xa0;% CI 0.82-1.27), while mortality from pneumoconiosis was (SMR 9.55; 95&#xa0;% CI 7.43-12.08), especially among miners (SMR 12.74; 95&#xa0;% CI 9.79-16.31). There was a trend in risk of pneumoconiosis with increasing duration of employment in the overall cohort, and the SMR for 25+ years of employment was 15.12 (95&#xa0;% CI 10.89-20.43).<br><br>CONCLUSIONS: This uniquely long-term follow up confirms the results of previous analyses, namely the lack of association between exposure to talc with no detectable level of asbestos and lung cancer and mesothelioma. Increased mortality from pneumoconiosis among miners is related to past exposure to silica.}, }
@article {pmid34389715, year = {2021}, author = {Grosso, S and Marini, A and Gyuraszova, K and Voorde, JV and Sfakianos, A and Garland, GD and Tenor, AR and Mordue, R and Chernova, T and Morone, N and Sereno, M and Smith, CP and Officer, L and Farahmand, P and Rooney, C and Sumpton, D and Das, M and Teodósio, A and Ficken, C and Martin, MG and Spriggs, RV and Sun, XM and Bushell, M and Sansom, OJ and Murphy, D and MacFarlane, M and Le Quesne, JPC and Willis, AE}, title = {The pathogenesis of mesothelioma is driven by a dysregulated translatome.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4920}, pmid = {34389715}, issn = {2041-1723}, support = {MC_UU_00025/6/MRC_/Medical Research Council/United Kingdom ; MR/K00252X/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/4/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom ; 5TR019/MRC_/Medical Research Council/United Kingdom ; 28879/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_1203/1/MRC_/Medical Research Council/United Kingdom ; A17196/CRUK_/Cancer Research UK/United Kingdom ; 5TR00/MRC_/Medical Research Council/United Kingdom ; MCA/600/MRC_/Medical Research Council/United Kingdom ; PCL/18/06/CSO_/Chief Scientist Office/United Kingdom ; MC_EX_G0902052/MRC_/Medical Research Council/United Kingdom ; 24388/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_A600_1024/MRC_/Medical Research Council/United Kingdom ; 29372/CRUK_/Cancer Research UK/United Kingdom ; 21139/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; A29252/CRUK_/Cancer Research UK/United Kingdom ; 30062/CRUK_/Cancer Research UK/United Kingdom ; A21139/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/7/MRC_/Medical Research Council/United Kingdom ; 29252/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Asbestos ; Humans ; Mechanistic Target of Rapamycin Complex 1/antagonists &amp; inhibitors/metabolism ; Mechanistic Target of Rapamycin Complex 2/antagonists &amp; inhibitors/metabolism ; Mesothelioma, Malignant/chemically induced/*genetics/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/genetics/metabolism ; Naphthyridines/pharmacology ; Oncogenes/*genetics ; Polyribosomes/drug effects/metabolism ; Protein Biosynthesis/drug effects/*genetics ; RNA, Messenger/*genetics/metabolism ; Tumor Cells, Cultured ; Mice ; }, abstract = {Malignant mesothelioma (MpM) is an aggressive, invariably fatal tumour that is causally linked with asbestos exposure. The disease primarily results from loss of tumour suppressor gene function and there are no 'druggable' driver oncogenes associated with MpM. To identify opportunities for management of this disease we have carried out polysome profiling to define the MpM translatome. We show that in MpM there is a selective increase in the translation of mRNAs encoding proteins required for ribosome assembly and mitochondrial biogenesis. This results in an enhanced rate of mRNA translation, abnormal mitochondrial morphology and oxygen consumption, and a reprogramming of metabolic outputs. These alterations delimit the cellular capacity for protein biosynthesis, accelerate growth and drive disease progression. Importantly, we show that inhibition of mRNA translation, particularly through combined pharmacological targeting of mTORC1 and 2, reverses these changes and inhibits malignant cell growth in vitro and in ex-vivo tumour tissue from patients with end-stage disease. Critically, we show that these pharmacological interventions prolong survival in animal models of asbestos-induced mesothelioma, providing the basis for a targeted, viable therapeutic option for patients with this incurable disease.}, }
@article {pmid34386422, year = {2021}, author = {Zhang, C and Wu, L and de Perrot, M and Zhao, X}, title = {Carbon Nanotubes: A Summary of Beneficial and Dangerous Aspects of an Increasingly Popular Group of Nanomaterials.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {693814}, pmid = {34386422}, issn = {2234-943X}, abstract = {Carbon nanotubes (CNTs) are nanomaterials with broad applications that are produced on a large scale. Animal experiments have shown that exposure to CNTs, especially one type of multi-walled carbon nanotube, MWCNT-7, can lead to malignant transformation. CNTs have characteristics similar to asbestos (size, shape, and biopersistence) and use the same molecular mechanisms and signaling pathways as those involved in asbestos tumorigenesis. Here, a comprehensive review of the characteristics of carbon nanotubes is provided, as well as insights that may assist in the design and production of safer nanomaterials to limit the hazards of currently used CNTs.}, }
@article {pmid34379126, year = {2021}, author = {Zhai, Z and Ruan, J and Zheng, Y and Xiang, D and Li, N and Hu, J and Shen, J and Deng, Y and Yao, J and Zhao, P and Wang, S and Yang, S and Zhou, L and Wu, Y and Xu, P and Lyu, L and Lyu, J and Bergan, R and Chen, T and Dai, Z}, title = {Assessment of Global Trends in the Diagnosis of Mesothelioma From 1990 to 2017.}, journal = {JAMA network open}, volume = {4}, number = {8}, pages = {e2120360}, pmid = {34379126}, issn = {2574-3805}, mesh = {Age Factors ; Cross-Sectional Studies ; Forecasting ; Geography ; Global Burden of Disease/*history/*trends ; Global Health/*statistics &amp; numerical data/*trends ; History, 20th Century ; History, 21st Century ; Humans ; Incidence ; Mesothelioma/*diagnosis/*epidemiology/*history ; Prevalence ; Sex Factors ; Socioeconomic Factors ; }, abstract = {IMPORTANCE: It is difficult for policy makers and clinicians to formulate targeted management strategies for mesothelioma because data on current epidemiological patterns worldwide are lacking.<br><br>OBJECTIVE: To evaluate the mesothelioma burden across the world and describe its epidemiological distribution over time and by sociodemographic index (SDI) level, geographic location, sex, and age.<br><br>Annual case data and age-standardized rates of incidence, death, and disability-adjusted life-years associated with mesothelioma among different age groups were obtained from the Global Burden of Disease 2017 database. The estimated annual percentage changes in age-standardized rates were calculated to evaluate temporal trends in incidence and mortality. The study population comprised individuals from 21 regions in 195 countries and territories who were diagnosed with mesothelioma between 1990 and 2017. Data were collected from May 23, 2019, to January 18, 2020.<br><br>MAIN OUTCOMES AND MEASURES: Primary outcomes were incident cases, deaths, and their age-standardized rates and estimated annual percentage changes. Secondary outcomes were disability-adjusted life-years and relative temporal trends.<br><br>RESULTS: Overall, 34&#x202f;615 new cases (95% uncertainty interval [UI], 33&#x202f;530-35&#x202f;697 cases) of mesothelioma and 29&#x202f;909 deaths (95% UI, 29&#x202f;134-30&#x202f;613 deaths) associated with mesothelioma were identified in 2017, and more than 70% of these cases and deaths were among male individuals. In 1990, the number of incident cases was 21&#x202f;224 (95% UI, 17&#x202f;503-25&#x202f;450), and the number of deaths associated with mesothelioma was 17 406 (95% UI, 14&#x202f;495-20&#x202f;660). These numbers increased worldwide from 1990 to 2017, with more than 50% of cases recorded in regions with high SDI levels, whereas the age-standardized incidence rate (from 0.52 [95% UI, 0.43-0.62] in 1990 to 0.44 [95% UI, 0.42-0.45] in 2017) and the age-standardized death rate (from 0.44 [95% UI, 0.37-0.52] in 1990 to 0.38 [95% UI, 0.37-0.39] in 2017) decreased, with estimated annual percentage changes of -0.61 (95% CI, -0.67 to -0.54) for age-standardized incidence rate and -0.44 (95% CI, -0.52 to -0.37) for age-standardized death rate. The proportion of incident cases among those 70 years or older continued to increase (from 36.49% in 1990 to 44.67% in 2017), but the proportion of patients younger than 50 years decreased (from 16.74% in 1990 to 13.75% in 2017) over time. In addition, mesothelioma incident cases and age-standardized incidence rates began to decrease after 20 years of a complete ban on asbestos use. For example, in Italy, a complete ban on asbestos went into effect in 1992; incident cases increased from 1409 individuals (95% UI, 1013-1733 individuals) in 1990, peaked in 2015 after 23 years of the asbestos ban, then decreased from 1820 individuals (95% UI, 1699-1981 individuals) in 2015 to 1746 individuals (95% UI, 1555-1955 individuals) in 2017.<br><br>CONCLUSIONS AND RELEVANCE: This cross-sectional study found that incident cases of mesothelioma and deaths associated with mesothelioma continuously increased worldwide, especially in resource-limited regions with low SDI levels. Based on these findings, global governments and medical institutions may consider formulating optimal policies and strategies for the targeted prevention and management of mesothelioma.}, }
@article {pmid34373297, year = {2021}, author = {Ferrante, P}, title = {Hospitalisation costs of malignant mesothelioma: results from the Italian hospital discharge registry (2001-2018).}, journal = {BMJ open}, volume = {11}, number = {8}, pages = {e046456}, pmid = {34373297}, issn = {2044-6055}, mesh = {*Asbestos/adverse effects ; Hospitalization ; Hospitals ; Humans ; Incidence ; Italy/epidemiology ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant ; *Occupational Exposure ; Patient Discharge ; *Pleural Neoplasms ; Registries ; Retrospective Studies ; }, abstract = {OBJECTIVES: This paper aims to establish hospitalisation costs of mesothelioma in Italy and to evaluate hospital-related trends associated with the 1992 asbestos ban.<br><br>DESIGN: This is a retrospective population-based study of Italian hospitalisations treating pleura, peritoneum and pericardium mesothelioma in the period 2001-2018.<br><br>SETTINGS: Public and private Italian hospitals reached by the Ministry of Health (coverage close to 100%).<br><br>PARTICIPANTS: 157&#x2009;221 admissions with primary or contributing diagnosis of pleural, peritoneal or hearth cancer discharged from 2001 to 2018.Primary and secondary outcome measures: number, length and cost of hospitalisations with related percentages.<br><br>RESULTS: Each year, Italian hospitals treated a mesothelioma in 6025 admissions on average. Mean annual costs by site were &#x20ac;20 293 733, &#x20ac;3183&#x2009;632 and &#x20ac;40 443 for pleura, peritoneum and pericardium, respectively. Pericardial mesothelioma showed the highest cost per admission (&#x20ac;6117), followed by peritoneal (&#x20ac;4549) and pleural cases (&#x20ac;3809). Percentage of hospitalisation costs attributable to mesothelioma was higher when it is located in pleura (53.4%) and pericardium (51.8%) with respect to peritoneum (41.2%). Overall annual hospitalisation cost, percentages of number and length of admissions showed an inverted U-shape, with maxima (of &#x20ac;25 850 276, 0.064% and 0.096%, respectively) reached in 2011-2013. Mean age at discharge and percentages of surgery and of urgent cases increased over time.<br><br>CONCLUSIONS: The highest impact of mesothelioma on the National Health System was recorded 20 years after the asbestos ban (2011-2013). Hospitals should expect soon fewer but more severe patients needing more cares. To study the disease prevalence could help assistance planning of next decade.}, }
@article {pmid34361048, year = {2021}, author = {Chmielewska-Kassassir, M and Wozniak, LA}, title = {Phytochemicals in Malignant Pleural Mesothelioma Treatment-Review on the Current Trends of Therapies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {15}, pages = {}, pmid = {34361048}, issn = {1422-0067}, support = {2015/19/N/NZ3/01497//Narodowym Centrum Nauki/ ; }, mesh = {Animals ; Antineoplastic Agents, Phytogenic/chemistry/*therapeutic use ; Biological Products/chemistry/*therapeutic use ; Humans ; Mesothelioma, Malignant/*drug therapy/metabolism ; Polyphenols/chemistry/*therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.}, }
@article {pmid34359365, year = {2021}, author = {Li, N and Yang, C and Zhou, S and Song, S and Jin, Y and Wang, D and Liu, J and Gao, Y and Yang, H and Mao, W and Chen, Z}, title = {Combination of Plasma-Based Metabolomics and Machine Learning Algorithm Provides a Novel Diagnostic Strategy for Malignant Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {34359365}, issn = {2075-4418}, support = {81672315//National Natural Science Foundation of China/ ; 81302840//National Natural Science Foundation of China/ ; 2017C04G1360498//Key R&amp;D Program Projects in Zhejiang Province/ ; LY20H280001//Zhejiang Provincial Natural Science Fund/ ; 2017KY256//Projects of Zhejiang Province Medical and Health Science and Technology Plan/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive and incurable carcinoma that is primarily caused by asbestos exposure. However, the current diagnostic tool for MM is still under-developed. Therefore, the aim of this study is to explore the diagnostic significance of a strategy that combined plasma-based metabolomics with machine learning algorithms for MM.<br><br>METHODS: Plasma samples collected from 25 MM patients and 32 healthy controls (HCs) were randomly divided into train set and test set, after which analyzation was performed by liquid chromatography-mass spectrometry-based metabolomics. Differential metabolites were screened out from the samples of the train set. Subsequently, metabolite-based diagnostic models, including receiver operating characteristic (ROC) curves and Random Forest model (RF), were established, and their prediction accuracies were calculated for the test set samples.<br><br>RESULTS: Twenty differential plasma metabolites were annotated in the train set; 10 of these metabolites were validated in the test set. The seven most prevalent diagnostic metabolites were taurocholic acid), 0.7142 (uracil), 0.7142 (biliverdin), 0.8571 (histidine), 0.5000 (tauroursodeoxycholic acid), 0.8571 (pyrroline hydroxycarboxylic acid), and 0.7857 (phenylalanine). Furthermore, RF based on 20 annotated metabolites showed a prediction accuracy of 0.9286, and its optimized version achieved 1.0000 in the test set. Moreover, the comparison between the samples of peritoneal MM (n = 8) and pleural MM (n = 17) illustrated a significant increase in levels of taurocholic acid and tauroursodeoxycholic acid, as well as an evident decrease in biliverdin.<br><br>CONCLUSIONS: Our results revealed the potential diagnostic value of plasma-based metabolomics combined with machine learning for MM. Further research with large sample size is worthy conducting. Moreover, our data demonstrated dysregulated metabolism pathways in MM, which aids in better understanding of molecular mechanisms related to the initiation and development of MM.}, }
@article {pmid34354974, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Colosio, C and Previderè, C and Belluso, E}, title = {Evaluation of Deposition and Clearance of Asbestos (Detected by SEM-EDS) in Lungs of Deceased Subjects Environmentally and/or Occupationally Exposed in Broni (Pavia, Northern Italy).}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {678040}, pmid = {34354974}, issn = {2296-2565}, mesh = {*Asbestos/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; Humans ; Lung ; *Lung Neoplasms/chemically induced ; }, abstract = {Biodurability is one of the main determinants of asbestos hazardousness for human health. Very little is known about the actual persistence of asbestos in lungs and its clearance, nor about differences in this regard between the different mineralogical types of asbestos. The aim of the present study was to evaluate the amount, the dimensional characteristics and the mineralogic kinds of asbestos in lungs (measured using SEM-EDS) of a series of 72 deceased subjects who were certainly exposed to asbestos (mainly crocidolite and chrysotile) during their life. Moreover, we investigated possible correlations between the lung burden of asbestos (in general and considering each asbestos type), as well as their dimension (length, width, and l/w ratio) and the duration of exposure, the latency- in case of malignant mesothelioma (MM), the survival and the time since the end of exposure. In 62.5% of subjects, asbestos burden in lungs was lower that the threshold considered demonstrative for occupational exposure. In 29.1% of cases no asbestos was found. Chrysotile was practically not detected. The mean length of asbestos fibers and the length to width ratio were significantly related to the duration of exposure to asbestos. No other statistically significant correlations were found between the amount and dimensional characteristics of asbestos (nor with the relative amount of each asbestos type) and the other chronological variables considered. In conclusion, it was pointed out that chrysotile can be completely removed from human lungs in <8 years and, instead, amphiboles persist much more time. The present results suggest, as well, that the finding of no asbestos in lungs cannot rule out the attribution of MM to asbestos (in particular, chrysotile) inhaled in an occupational setting. This point is of crucial importance from a legal point of view.}, }
@article {pmid34350658, year = {2021}, author = {Mensi, C and Zellino, C and Polonioli, M and Dallari, B and Pesatori, AC and Riboldi, L and Consonni, D}, title = {Pleural mesothelioma in a circus worker.}, journal = {Journal of occupational health}, volume = {63}, number = {1}, pages = {e12250}, pmid = {34350658}, issn = {1348-9585}, support = {acronym: PRIMATE-code ARL_2/2018//Fondazione Regionale per la Ricerca Biomedica/ ; BRiC P55 and//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; BRiC P59//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; }, mesh = {Aged, 80 and over ; Asbestos/*toxicity ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVES: To describe an unusual occupational asbestos exposure in a patient with mesothelioma.<br><br>METHODS: Since 2000, the Lombardy Mesothelioma Registry (LMR) collects cases of malignant mesothelioma (MM) occurring among people residing in the Lombardy Region, North-West Italy, with a population of 10&#xa0;million inhabitants. For each case, clinical records and asbestos exposure are collected. Each case is then classified in agreement with the guidelines of the National Mesothelioma Registry.<br><br>RESULTS: We identified a male (86&#xa0;years old), former smoker, who had been working for 53&#xa0;years as a circus truck driver and tamer of lions and tigers. The first circumstance of exposure was the use of an asbestos tape that wrapped around the hoop in the feline jumping show with a flaming hoop. The second one was the presence of insulating panels protecting the engine placed inside the trucks.<br><br>CONCLUSION: A new MM case with an occupational etiology has been found in the public entertainment, an occupational sector not usually considered at risk for the presence of asbestos.}, }
@article {pmid34349988, year = {2021}, author = {Iyoda, A and Azuma, Y and Sakai, T and Koezuka, S and Otsuka, H and Tochigi, N and Isobe, K and Sano, A}, title = {Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.}, journal = {Molecular and clinical oncology}, volume = {15}, number = {3}, pages = {188}, pmid = {34349988}, issn = {2049-9469}, abstract = {Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis. The present study assessed the effectiveness of argon plasma coagulation (APC) treatment in patients with MPM who underwent radical pleural decortication (PD). The clinical data from 11 patients who underwent radical PD treated with APC at Toho University Omori Medical Center from July 2015 to March 2020 were retrospectively analyzed. Clinical features, local recurrence, and clinical prognoses were evaluated. The median overall survival was 18.5 months, and the 1- and 2-year overall survival rates were 71.6 and 43.0%, respectively. One patient survived 5 years but had recurrent tumors. The median disease-free survival was 11.1 months. The 1- and 2-year disease-free survival rates were 49.9 and 12.5%, respectively. Three patients had no recurrences, two of whom were followed continuously (39.6 and 10.2 months). The present study revealed that APC treatment for MPM might be associated with good survival and prognosis. APC as an additional intraoperative treatment for patients with MPM may be further investigated with larger multi-center clinical trials to support its efficacy.}, }
@article {pmid34345849, year = {2021}, author = {Gualtieri, AF}, title = {Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre crystal-chemical and physical parameters to the key characteristics of cancer.}, journal = {Current research in toxicology}, volume = {2}, number = {}, pages = {42-52}, pmid = {34345849}, issn = {2666-027X}, abstract = {Airborne fibres and particularly asbestos represent hazards of great concern for human health because exposure to these peculiar particulates may cause malignancies such as lung cancer and mesothelioma. Currently, many researchers worldwide are focussed on fully understanding the patho-biological mechanisms leading to carcinogenesis prompted by pathogenic fibres. Along this line, the present work introduces a novel approach to correlate how and to what extent the physical/crystal-chemical and morphological parameters (including length, chemistry, biodurability, and surface properties) of mineral fibres cause major adverse effects with an emphasis on asbestos. The model described below conceptually attempts to bridge the gap between toxicity and carcinogenicity of mineral fibres and has several implications: 1) it provides a tool to measure the toxicity and pathogenic potential of asbestos minerals, allowing a quantitative rank of the different types (e.g. chrysotile vs. crocidolite); 2) it can predict the toxicity and pathogenicity of "unregulated" or unclassified fibres; 3) it reveals the parameters of a mineral fibre that are active in stimulating key characteristics of cancer, thus offering a strategy for developing specific cancer prevention strategies and therapies. Chrysotile, crocidolite and fibrous glaucophane are described here as mineral fibres of interest.}, }
@article {pmid34339095, year = {2021}, author = {Prusak, A and van der Zwan, JM and Aarts, MJ and Arber, A and Cornelissen, R and Burgers, S and Duijts, SFA}, title = {The psychosocial impact of living with mesothelioma: Experiences and needs of patients and their carers regarding supportive care.}, journal = {European journal of cancer care}, volume = {30}, number = {6}, pages = {e13498}, doi = {10.1111/ecc.13498}, pmid = {34339095}, issn = {1365-2354}, mesh = {Adaptation, Psychological ; Aged ; Caregivers ; Female ; Humans ; Male ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Qualitative Research ; }, abstract = {OBJECTIVE: Mesothelioma is a rare cancer with a poor prognosis caused by exposure to asbestos. Psychosocial support and care for mesothelioma patients and their carers is limited and not tailored to their specific needs. The aim of this study was to explore patients' and carers' needs and experiences regarding psychosocial support and their coping mechanisms dealing with psychosocial problems.<br><br>METHODS: A qualitative study was performed using semi-structured interviews with both mesothelioma patients and their carers. Participants were recruited through two specialised hospitals and two patient organisations. All interviews were transcribed verbatim and thematically analysed.<br><br>RESULTS: Ten patients (70% male, mean age 67.7) and five carers (20% male, mean age 65) participated in the study. The main themes identified for patients were active coping, limited needs and limited knowledge and awareness about psychosocial support. The main themes for carers were passive coping and 'it's all about the patient'.<br><br>CONCLUSION: Mesothelioma patients do not seem to have high needs for psychosocial support, whereas carers do. However, knowledge about and awareness of psychosocial support is low among mesothelioma patients. The findings from this study should be used to adjust guidelines for psychosocial support in mesothelioma patients and their carers.}, }
@article {pmid34333253, year = {2021}, author = {Onagi, H and Hayashi, T and Saito, T and Kishikawa, S and Takamochi, K and Suzuki, K}, title = {Malignant pleural mesothelioma showing rare morphology indistinguishable from myxofibrosarcoma concomitant with EGFR-mutated lung adenocarcinoma: A case report.}, journal = {International journal of surgery case reports}, volume = {85}, number = {}, pages = {106237}, pmid = {34333253}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Primary tumors of the pleura are rare, with malignant mesothelioma being the most common of these neoplasms. Pathological diagnosis of sarcomatoid mesothelioma can be more challenging than that of epithelioid malignant mesothelioma because of its similarities with true sarcomas and restricted or inconsistent expression of mesothelial markers in immunohistochemistry analysis.<br><br>PRESENTATION OF CASE: Here, we present an unusual case of malignant pleural mesothelioma concomitant with lung adenocarcinoma in a 72-year-old Japanese man, a smoker with no family history of cancer and asbestos exposure. Malignant pleural mesothelioma is composed of epithelial and spindle-shaped cells. Spindle-shaped cells with scant eosinophilic cytoplasm and hyperchromatic nuclei proliferated in abundant myxoid stroma containing thin-walled blood vessels, mimicking myxofibrosarcoma. The loss of BAP1 (BRCA1-associated protein 1) expression, as assessed by immunohistochemistry, and homozygous deletions of CDKN2A, detected using fluorescence in situ hybridization (FISH), were observed in both components. Targeted sequencing revealed that lung adenocarcinoma harbored EGFR mutations, whereas no mutations were detected in either component of biphasic mesothelioma.<br><br>DISCUSSION: Although alcian blue-stained mucins were detected in biphasic mesothelioma subsets, the clinicopathological significance of myxoid stroma in biphasic and sarcomatoid mesothelioma remains largely unknown.<br><br>CONCLUSION: Our case presented a unique morphology mimicking myxofibrosarcoma in a sarcomatoid component of biphasic mesothelioma; therefore, it raises a question on the clinicopathological significance of myxoid stroma in sarcomatous areas of biphasic and sarcomatoid mesothelioma.}, }
@article {pmid34322630, year = {2021}, author = {Scopa, P}, title = {Reconstruction of asbestos exposure in workers suffering from pleural neoplasms and employed in sectors not generally associated with high exposure levels: the importance of an accurate standardized assessment of occupational medicine.}, journal = {Journal of preventive medicine and hygiene}, volume = {62}, number = {1}, pages = {E148-E151}, pmid = {34322630}, issn = {2421-4248}, mesh = {*Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/etiology ; *Occupational Exposure/adverse effects/analysis ; *Occupational Medicine ; *Pleural Neoplasms/diagnosis/etiology ; Reproducibility of Results ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma onset in workers exposed to asbestos is well known with reference to multiple working sectors. In some cases, occurring among workers of sectors characterized by a presumed lower relevance of asbestos exposure, the absence of a well-defined correlation can prevent their emergence and compensation. To improve definition of these cases, this article underlines the importance of a standardized approach to occupational anamnesis.<br><br>METHODS: Thorough standardized occupational health assessment method application in a case of pleural malignant neoplasm occurred in a hauler, a job generally not associated with high levels of exposure to asbestos fibres.<br><br>RESULTS: Assessment of malignant pleural mesothelioma diagnosis and dual mode relevant occupational exposure to asbestos during both truck driving and loading and unloading operations of asbestos-containing goods.<br><br>CONCLUSIONS: Systematic occupational medicine assessment with accurate standardized approach is essential for reconstruction of asbestos exposure, in order to highlight every aspect useful to establish causal link between cases of pleural mesothelioma and possible occupational and non-occupational exposure to the mineral, even in cases where the first-level occupational history does not appear to be suggestive.}, }
@article {pmid34313510, year = {2021}, author = {Brustugun, OT and Nilssen, Y and Eide, IJZ}, title = {Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {60}, number = {10}, pages = {1250-1256}, doi = {10.1080/0284186X.2021.1955971}, pmid = {34313510}, issn = {1651-226X}, mesh = {Female ; Humans ; Male ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/epidemiology/therapy ; *Pleural Neoplasms/epidemiology/therapy ; Prognosis ; }, abstract = {BACKGROUND: Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy.<br><br>MATERIAL AND METHODS: Complete national data on 1509 pleural and peritoneal malignant mesothelioma from the Cancer Registry of Norway from 2000 to 2019 are presented. Age standardised incidence and median survival were calculated.<br><br>RESULTS: The age-standardised incidence of pleural mesothelioma among males has decreased from 1.7 per 100 000 in 2000-2004 to 1.1 in 2015-2019, whereas the incidence for females has been stable, lower than 0.3 per 100 000 throughout the period. Incidence of peritoneal mesotheliomas remained low, below 0.08 per 100 000. The female to male ratio among pleural mesotheliomas was 1:7 with no differences among morphological subtypes, whereas this ratio was 1:1.2 in peritoneal mesotheliomas. Median age at diagnosis for pleural mesothelioma was 73&#x2009;years and 76&#x2009;years for females and males respectively in the last 5-year period, and 67&#x2009;years for peritoneal mesotheliomas of both sexes. Median survival among pleural mesotheliomas has been stable, with significantly worse prognosis among sarcomatoid subtype (5.4&#x2009;months) compared to epithelioid subtype (15.8&#x2009;months). Peritoneal mesothelioma of the epithelioid subtype, representing 38% of cases, had a median survival of 43.3&#x2009;months, contrasting the non-epithelioid subtype of 5.1&#x2009;months.<br><br>DISCUSSION: Mesothelioma is still a significant disease with a dismal prognosis. Improvement in treatment is warranted.}, }
@article {pmid34299971, year = {2021}, author = {Fang, YJ and Chuang, HY and Pan, CH and Chang, YY and Cheng, Y and Lee, LJ and Wang, JD}, title = {Increased Risk of Gastric Cancer in Asbestos-Exposed Workers: A Retrospective Cohort Study Based on Taiwan Cancer Registry 1980-2015.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {14}, pages = {}, pmid = {34299971}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Cohort Studies ; Female ; Humans ; Incidence ; *Lung Neoplasms ; Male ; *Mesothelioma ; *Occupational Diseases/chemically induced/epidemiology ; *Occupational Exposure/adverse effects ; Registries ; Retrospective Studies ; *Stomach Neoplasms/chemically induced/epidemiology ; Taiwan/epidemiology ; }, abstract = {Asbestos has been recognized as a human carcinogen associated with malignant mesothelioma, cancers of lung, larynx, and ovary. However, a putative association between gastric cancer and asbestos exposure remains controversial. In this study, we aimed to explore gastric cancer risk of workers potentially exposed to asbestos in Taiwan. The asbestos occupational cohort was established from 1950 to 2015 based on the Taiwan Labor Insurance Database, and Taiwan Environmental Protection Agency regulatory datasets, followed by the Taiwan Cancer Registry for the period 1980-2015. Standardized incidence ratios (SIRs) for cancer were computed for the whole cohort using reference rates of the general population, and also reference labor population. Compared with the general population, SIR of the asbestos occupational cohort for the gastric cancer increased both in males (1.05, 95% confidence interval (CI): 1.02-1.09) and females (1.10, 95% CI: 1.01-1.18). A total of 123 worksites were identified to have cases of malignant mesothelioma, where increased risk for gastric cancer was found with a relative risk of 1.76 (95% CI: 1.63-1.90). This 35-year retrospective cohort study of asbestos-exposed workers in Taiwan may provide support for an association between occupational exposure to asbestos and gastric cancer.}, }
@article {pmid34299035, year = {2021}, author = {Yuan, L and Sun, B and Xu, L and Chen, L and Ou, W}, title = {The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {22}, number = {14}, pages = {}, pmid = {34299035}, issn = {1422-0067}, support = {2020Y002//the Fundamental Research Funds of Zhejiang Sci-Tech University/ ; 81728012//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Histone-Lysine N-Methyltransferase/*metabolism ; Humans ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma/metabolism/*pathology ; }, abstract = {SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase that exerts important effects on epigenetic gene regulation. SETDB1 complexes (SETDB1-KRAB-KAP1, SETDB1-DNMT3A, SETDB1-PML, SETDB1-ATF7IP-MBD1) play crucial roles in the processes of histone methylation, transcriptional suppression and chromatin remodelling. Therefore, aberrant trimethylation at H3K9 due to amplification, mutation or deletion of SETDB1 may lead to transcriptional repression of various tumour-suppressing genes and other related genes in cancer cells. Lung cancer is the most common type of cancer worldwide in which SETDB1 amplification and H3K9 hypermethylation have been indicated as potential tumourigenesis markers. In contrast, frequent inactivation mutations of SETDB1 have been revealed in mesothelioma, an asbestos-associated, locally aggressive, highly lethal, and notoriously chemotherapy-resistant cancer. Above all, the different statuses of SETDB1 indicate that it may have different biological functions and be a potential diagnostic biomarker and therapeutic target in lung cancer and mesothelioma.}, }
@article {pmid34298661, year = {2021}, author = {Pouliquen, DL and Kopecka, J}, title = {Malignant Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {14}, pages = {}, pmid = {34298661}, issn = {2072-6694}, abstract = {Malignant mesothelioma (MM) is a rare and aggressive cancer, related to chronic inflammation and oxidative stress caused mainly by exposure to asbestos [...].}, }
@article {pmid34295692, year = {2021}, author = {Menis, J and Pasello, G and Remon, J}, title = {Immunotherapy in malignant pleural mesothelioma: a review of literature data.}, journal = {Translational lung cancer research}, volume = {10}, number = {6}, pages = {2988-3000}, pmid = {34295692}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface, associated with asbestos exposure, whose incidence is still growing in some areas of the world. MPM is still considered a rare and an orphan disease with an unchanged median overall survival (OS) ranging from 8 to 14 months and no treatment advances in the last 15 years both in local and advanced disease. In the recent years, chronic inflammation of the mesothelium together with local tumor suppression plays a major role in the malignant transformation. Also, significant heterogeneity in both tumor and the microenvironment is at the basis of MPM biology. Preclinical data have demonstrated the immunogenicity and the lack of an effective antitumor response by the immune system in MPM thus paving the way to the development of immune therapeutics in this disease. Still there is no clear evidence of any predictive biomarker so that, given the close interaction between the immune infiltrate and mesothelial cells, a number of trials are ongoing to investigate the role and prognostic value of the immune microenvironment. In this review we summarize the rationale for immune therapeutics development in MPM, as well as, the relevant literature and ongoing trials of immune checkpoint inhibitors (ICIs) and vaccines used as both first-line treatment and beyond.}, }
@article {pmid34295165, year = {2021}, author = {Gu, R and Jiang, L and Duan, T and Chen, C and Wu, S and Mu, D}, title = {A Case of Pulmonary Embolism with Sarcomatoid Malignant Pleural Mesothelioma with Long-Term Pleural Effusion.}, journal = {OncoTargets and therapy}, volume = {14}, number = {}, pages = {4231-4237}, pmid = {34295165}, issn = {1178-6930}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that originates from pleural mesothelial cells. In recent years, with the development of asbestos-related industries and the increase in air pollution, its incidence has been increased. The incidence of pulmonary embolism combined with sarcomatoid MPM is very low and the prognosis is extremely poor. We here report a case of a patient with long term of pleural effusion and finally diagnosed as pulmonary embolism with sarcomatoid MPM.<br><br>CASE: A 75-year-old male with a 30-year history of asbestos exposure was admitted to our hospital due to chest pain and difficulty in breathing after exercise. Radiologic examination revealed pleural effusion, computed tomography pulmonary angiography (CTPA) suggests pulmonary embolism, and we consider pleural effusion caused by pulmonary embolism. After anticoagulant therapy for pulmonary embolism and pleural puncture to reduce pleural effusion, the patient's symptoms improved. However, after that, the patient was still admitted to the hospital several times because of recurrent chest pain and dyspnea symptoms, and radiologic examination always showed unexplained pleural effusion. Finally, pathological and immunohistochemical examinations of the pleural biopsy specimens were performed, and the diagnosis was confirmed as sarcomatoid MPM.<br><br>CONCLUSION: In summary, sarcomatoid MPM with pulmonary embolism is relatively rare, and the prognosis is poor. Clinicians need to be alert to its occurrence. When the first diagnosis is confirmed and the effect of targeted treatment is still not good, the possibility of other diseases should be considered. In clinical practice, pleural biopsy guided by PET-CT is a good choice for patients with sarcomatoid MPM who cannot tolerate open pleural biopsies or thoracoscopy. And patients should undergo pleural morphology and immunohistochemistry as soon as possible, which are helpful for timely diagnosis.}, }
@article {pmid34291807, year = {2021}, author = {Santana, VS and Salvi, L and Cavalcante, F and Campos, F and Algranti, E}, title = {Underreporting of mesothelioma, asbestosis and pleural plaques in Brazil.}, journal = {Occupational medicine (Oxford, England)}, volume = {71}, number = {4-5}, pages = {223-230}, doi = {10.1093/occmed/kqab073}, pmid = {34291807}, issn = {1471-8405}, mesh = {*Asbestos/adverse effects ; *Asbestosis ; Brazil/epidemiology ; Humans ; *Lung Neoplasms ; *Mesothelioma/etiology ; *Pleural Diseases/etiology ; *Pleural Neoplasms/etiology ; }, abstract = {BACKGROUND: Brazil has a long history of heavy asbestos consumption. However, the number of asbestos-related diseases (ARDs) falls far below the one expected compared with other asbestos consumer countries.<br><br>AIMS: To examine underreporting of ARDs, that is mesothelioma, asbestosis and pleural plaques, in Brazil's Mortality Information System (SIM).<br><br>METHODS: Health information systems (HIS) were mapped, datasets retrieved and records of ARD deaths extracted. Records were pair-matched using anonymous linkage to create a single database. ARD-reported cases missing in SIM were considered unreported. The study's period ranged from 2008 to 2014, when every HIS contributed to the ARD records pool.<br><br>RESULTS: A total of 1298 registered ARD deaths were found, 996 cases of mesothelioma (77%) and 302 (23%) of asbestosis and pleural plaques. SIM was the major single data source of ARD but 335 mesothelioma deaths were missing, an average underreporting of 33%, with no clear time trend. For asbestosis and pleural plaques, underreporting of ARD oscillated from 55% in 2010 to 25% in 2014, a declining trend. ARD underreporting was not associated with sex or age.<br><br>CONCLUSIONS: One-third of underreported ARD deaths in the universal SIM is unacceptably high and, apparently, it has not been improving substantially over time. After recoveries from multiple databases, the number of cases is still below, which could be expected based on asbestos consumption. Interoperability of multiple information systems could enhance case detection and improve the precision of mortality estimates, which are crucial for surveillance and for evaluation of remedial policies.}, }
@article {pmid34283067, year = {2021}, author = {Oddone, E and Bollon, J and Nava, CR and Consonni, D and Marinaccio, A and Magnani, C and Gasparrini, A and Barone-Adesi, F}, title = {Effect of Asbestos Consumption on Malignant Pleural Mesothelioma in Italy: Forecasts of Mortality up to 2040.}, journal = {Cancers}, volume = {13}, number = {13}, pages = {}, pmid = {34283067}, issn = {2072-6694}, support = {MR/R013349/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Statistical models used to forecast malignant pleural mesothelioma (MPM) trends often do not take into account historical asbestos consumption, possibly resulting in less accurate predictions of the future MPM death toll. We used the distributed lag non-linear model (DLNM) approach to predict future MPM cases in Italy until 2040, based on past asbestos consumption figures. Analyses were conducted using data on male MPM deaths (1970-2014) and annual asbestos consumption using data on domestic production, importation, and exportation. According to our model, the peak of MPM deaths is expected to occur in 2021 (1122 expected cases), with a subsequent decrease in mortality (344 MPM deaths in 2039). The exposure-response curve shows that relative risk (RR) of MPM increased almost linearly for lower levels of exposure but flattened at higher levels. The lag-specific RR grew until 30 years since exposure and decreased thereafter, suggesting that the most relevant contributions to the risk come from exposures which occurred 20-40 years before death. Our results show that the Italian MPM epidemic is approaching its peak and underline that the association between temporal trends of MPM and time since exposure to asbestos is not monotonic, suggesting a lesser role of remote exposures in the development of MPM than previously assumed.}, }
@article {pmid34281119, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Frontini, A and Colosio, C and Vigliaturo, R and Belluso, E}, title = {Reply to Mirabelli et al. Is Mesothelioma Unrelated to the Lung Asbestos Burden? Comment on "Visonà et al. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples. Int. J. Environ. Res. Public Health 2021, 18, 2053".}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34281119}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Italy/epidemiology ; Lung ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure/adverse effects ; Public Health ; }, abstract = {We appreciate very much the interest of Mirabelli et al. [...].}, }
@article {pmid34281114, year = {2021}, author = {Mirabelli, D and Angelini, A and Barbieri, PG and Calisti, R and Capacci, F and Girardi, P and Silvestri, S and Somigliana, AB}, title = {Is Mesothelioma Unrelated to the Lung Asbestos Burden? Comment on Visonà et al. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples. Int. J. Environ. Res. Public Health 2021, 18, 2053.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34281114}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Italy/epidemiology ; Lung ; *Lung Neoplasms/epidemiology ; *Mesothelioma/epidemiology ; Public Health ; }, abstract = {We read with interest the report by Visonà and coworkers on the lung asbestos fiber burden in an autopsy series of decedents from mesothelioma (MM: 59 cases) and individuals who "suffered from asbestosis and died of its complications" (13 cases) [...].}, }
@article {pmid34277071, year = {2021}, author = {Freudenberger, DC and Shah, RD}, title = {A narrative review of the health disparities associated with malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {13}, number = {6}, pages = {3809-3815}, pmid = {34277071}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer of the mesothelial lining of the pleura that has traditionally been associated with asbestos exposure in an industrial setting. Asbestos usage has fortunately been banned or phased out in most industrialized countries resulting in its decline in countries such as the United States. Despite this, MPM continues to place significant burden on its affected patients resulting in overall poor prognosis and survival. Questions arise as to what factors, especially what health disparities, contribute to the disease's dismal prognosis. This article will present a narrative review of recent literature that identifies the impact age, sex, race, access to medical centers, and economics have on the diagnosis, treatment, and prognosis of MPM. As will be discussed, research has shown that factors including younger age, female sex, non-white race, private insurance, Medicare, and higher income have been associated with better survival in MPM. Whereas older age, male sex, white race, lack of insurance, and lower income are associated with worse survival. The identification of these and other health disparities related to MPM may allow for future research, clinical guidelines, and policies to be implemented to decrease the burden health disparities create in the diagnosis, treatment, and prognosis of patients with MPM.}, }
@article {pmid34249695, year = {2021}, author = {Hiltbrunner, S and Mannarino, L and Kirschner, MB and Opitz, I and Rigutto, A and Laure, A and Lia, M and Nozza, P and Maconi, A and Marchini, S and D'Incalci, M and Curioni-Fontecedro, A and Grosso, F}, title = {Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {660039}, pmid = {34249695}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival improvements in the last years, mirroring very limited therapeutic advances. Platinum-based chemotherapy in combination with pemetrexed and surgery are the standard of care, but prognosis is still unacceptably poor with median overall survival of approximately 12 months. The genomic landscape of MPM has been widely characterized showing a low mutational burden and the impairment of tumor suppressor genes. Among them, BAP1 and BLM are present as a germline inactivation in a small subset of patients and increases predisposition to tumorigenesis. Other studies have demonstrated a high frequency of mutations in DNA repair genes. Many therapy approaches targeting these alterations have emerged and are under evaluation in the clinic. High-throughput technologies have allowed the detection of more complex molecular events, like chromotripsis and revealed different transcriptional programs for each histological subtype. Transcriptional analysis has also paved the way to the study of tumor-infiltrating cells, thus shedding lights on the crosstalk between tumor cells and the microenvironment. The tumor microenvironment of MPM is indeed crucial for the pathogenesis and outcome of this disease; it is characterized by an inflammatory response to asbestos exposure, involving a variety of chemokines and suppressive immune cells such as M2-like macrophages and regulatory T cells. Another important feature of MPM is the dysregulation of microRNA expression, being frequently linked to cancer development and drug resistance. This review will give a detailed overview of all the above mentioned features of MPM in order to improve the understanding of this disease and the development of new therapeutic strategies.}, }
@article {pmid34244457, year = {2022}, author = {Thomsen, RW and Riis, AH and Flachs, EM and Garabrant, DH and Bonde, JPE and Sørensen, HT}, title = {Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study.}, journal = {Thorax}, volume = {77}, number = {5}, pages = {477-485}, doi = {10.1136/thoraxjnl-2020-215041}, pmid = {34244457}, issn = {1468-3296}, mesh = {Adult ; *Asbestos/adverse effects/analysis ; *Asbestosis/epidemiology ; Cohort Studies ; Denmark/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; Male ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; Motor Vehicles ; *Occupational Diseases/epidemiology/etiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/complications ; Young Adult ; }, abstract = {INTRODUCTION: The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems.<br><br>METHODS: We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services).<br><br>RESULTS: Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes.<br><br>CONCLUSIONS: We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.}, }
@article {pmid34241641, year = {2021}, author = {Golka, K and Böthig, R and Jungmann, O and Forchert, M and Zellner, ME and Schöps, W}, title = {[Occupational cancers in urology].}, journal = {Der Urologe. Ausg. A}, volume = {60}, number = {8}, pages = {1061-1072}, pmid = {34241641}, issn = {1433-0563}, mesh = {Humans ; *Kidney Neoplasms ; Male ; *Occupational Diseases/diagnosis/epidemiology/etiology ; *Occupational Exposure/adverse effects ; *Urinary Bladder Neoplasms/chemically induced/epidemiology ; *Urology ; }, abstract = {Cancers can be triggered by occupational causes. In the field of urology, bladder cancer is by far the most frequent occupationally induced tumor disease. Causes are particularly carcinogenic aromatic amines and carcinogenic polycyclic aromatic hydrocarbons. The frequency of this disease has shifted over the last decades from the classical hazard in the chemical industry to the users. Among a variety of hazardous occupations, hairdressers and painters are the best known. Rarely, renal cell carcinoma can be triggered by high trichloroethylene exposure and mesothelioma of the tunica vaginalis testis by asbestos. If a disease that can be caused by occupational activities has been confirmed (e.g. urinary bladder cancer), the risk factors must be recorded by a complete occupational history from the first employment on in order to be able to report a suspected occupational disease. In addition, spinal cord injury due to occupational and commuting accidents can lead to urinary bladder cancer over the long term.}, }
@article {pmid34240508, year = {2021}, author = {Hiroshima, K and Wu, D and Koh, E and Sekine, Y and Ozaki, D and Yusa, T and Nakazawa, T and Tsuji, S and Miyagi, Y and Walts, AE and Marchevsky, AM and Husain, AN and Imai, K}, title = {Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas.}, journal = {Pathology international}, volume = {71}, number = {9}, pages = {604-613}, pmid = {34240508}, issn = {1440-1827}, support = {//Ministry of the Environment of Japan/ ; JP20cm0106406//Japan Agency for Medical Research and Development/ ; //Nichias Corporation, Tokyo, Japan/ ; }, mesh = {Carcinoma, Squamous Cell/*diagnosis/pathology ; Diagnosis, Differential ; Epithelium/pathology ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/pathology ; Membrane Proteins/genetics/*metabolism ; Mesothelioma, Malignant/*diagnosis/pathology ; Tissue Array Analysis ; }, abstract = {Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.}, }
@article {pmid34235080, year = {2021}, author = {Behrouzfar, K and Burton, K and Mutsaers, SE and Morahan, G and Lake, RA and Fisher, SA}, title = {How to Better Understand the Influence of Host Genetics on Developing an Effective Immune Response to Thoracic Cancers.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {679609}, pmid = {34235080}, issn = {2234-943X}, abstract = {Thoracic cancers pose a significant global health burden. Immune checkpoint blockade therapies have improved treatment outcomes, but durable responses remain limited. Understanding how the host immune system interacts with a developing tumor is essential for the rational development of improved treatments for thoracic malignancies. Recent technical advances have improved our understanding of the mutational burden of cancer cells and changes in cancer-specific gene expression, providing a detailed understanding of the complex biology underpinning tumor-host interactions. While there has been much focus on the genetic alterations associated with cancer cells and how they may impact treatment outcomes, how host genetics affects cancer development is also critical and will greatly determine treatment response. Genome-wide association studies (GWAS) have identified genetic variants associated with cancer predisposition. This approach has successfully identified host genetic risk factors associated with common thoracic cancers like lung cancer, but is less effective for rare cancers like malignant mesothelioma. To assess how host genetics impacts rare thoracic cancers, we used the Collaborative Cross (CC); a powerful murine genetic resource designed to maximize genetic diversity and rapidly identify genes associated with any biological trait. We are using the CC in conjunction with our asbestos-induced MexTAg mouse model, to identify host genes associated with mesothelioma development. Once genes that moderate tumor development and progression are known, human homologues can be identified and human datasets interrogated to validate their association with disease outcome. Furthermore, our CC-MexTAg animal model enables in-depth study of the tumor microenvironment, allowing the correlation of immune cell infiltration and gene expression signatures with disease development. This strategy provides a detailed picture of the underlying biological pathways associated with mesothelioma susceptibility and progression; knowledge that is crucial for the rational development of new diagnostic and therapeutic strategies. Here we discuss the influence of host genetics on developing an effective immune response to thoracic cancers. We highlight current knowledge gaps, and with a focus on mesothelioma, describe the development and application of the CC-MexTAg to overcome limitations and illustrate how the knowledge gained from this unique study will inform the rational design of future treatments of mesothelioma.}, }
@article {pmid34234080, year = {2021}, author = {Ken Takahashi, }, title = {Asbestos Diseases Research Institute - A New WHO Collaborating Center.}, journal = {Industrial health}, volume = {59}, number = {3}, pages = {143-145}, pmid = {34234080}, issn = {1880-8026}, mesh = {Academies and Institutes ; *Asbestos/adverse effects ; *Asbestosis/epidemiology ; Humans ; *Mesothelioma ; *Occupational Exposure ; World Health Organization ; }, }
@article {pmid34227091, year = {2021}, author = {Pagliuca, F and Zito Marino, F and Morgillo, F and Della Corte, C and Santini, M and Vicidomini, G and Guggino, G and De Dominicis, G and Campione, S and Accardo, M and Cozzolino, I and Franco, R}, title = {Inherited predisposition to malignant mesothelioma: germline BAP1 mutations and beyond.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {12}, pages = {4236-4246}, doi = {10.26355/eurrev_202106_26129}, pmid = {34227091}, issn = {2284-0729}, mesh = {Aged ; Female ; *Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Male ; Mesothelioma, Malignant/epidemiology/*genetics/pathology ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma (MM) is a rare aggressive neoplasm arising from mesothelial lining of body cavities, most commonly pleura and peritoneum. It is characterised by a poor prognosis and limited treatment options. A universally recognised risk factor for the development of MM is exposure to asbestos. However, evidence supporting a genetic susceptibility to the development of MM has been accumulating during the last decades. Intensive research for the identification of MM susceptibility genes has led to the discovery of BAP1 and to the definition of the so-called "BAP1-related tumour predisposition syndrome". Patients carrying germline BAP1 mutations have an increased risk for the early development of tumours, including MMs, uveal melanomas, cutaneous melanocytic lesions, clear cell renal cell carcinomas and basal cell carcinomas. Furthermore, pathogenic variants in tumour suppressor genes with a role in DNA repair have been recently described in families with clustered MM cases. These genetic alterations seem to confer exaggerate sensitivity to asbestos carcinogenic effect and, arguably, increased response to specific chemotherapeutic strategies. While the translational significance of BAP1 alterations is explored in the research field, the identification of families carrying germline BAP1 mutations is mandatory to start appropriate surveillance programs and guarantee the best clinical management to these patients.}, }
@article {pmid34226685, year = {2021}, author = {Obacz, J and Yung, H and Shamseddin, M and Linnane, E and Liu, X and Azad, AA and Rassl, DM and Fairen-Jimenez, D and Rintoul, RC and Nikolić, MZ and Marciniak, SJ}, title = {Biological basis for novel mesothelioma therapies.}, journal = {British journal of cancer}, volume = {125}, number = {8}, pages = {1039-1055}, pmid = {34226685}, issn = {1532-1827}, support = {G1002610/MRC_/Medical Research Council/United Kingdom ; MR/R009120/1/MRC_/Medical Research Council/United Kingdom ; MR/S005579/1/MRC_/Medical Research Council/United Kingdom ; MR/V028669/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Asbestos/*toxicity ; Combined Modality Therapy ; Epigenesis, Genetic ; *Gene Regulatory Networks ; Humans ; Mesothelioma/chemically induced/genetics/pathology/*therapy ; Prognosis ; }, abstract = {Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies.}, }
@article {pmid34211838, year = {2021}, author = {Faversani, A and Favero, C and Dioni, L and Pesatori, AC and Bollati, V and Montoli, M and Musso, V and Terrasi, A and Fusco, N and Nosotti, M and Vaira, V and Palleschi, A}, title = {An EBC/Plasma miRNA Signature Discriminates Lung Adenocarcinomas From Pleural Mesothelioma and Healthy Controls.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {643280}, pmid = {34211838}, issn = {2234-943X}, abstract = {BACKGROUND: Despite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis.<br><br>METHODS: We profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database.<br><br>RESULTS: miR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways.<br><br>CONCLUSIONS: Overall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.}, }
@article {pmid34210265, year = {2021}, author = {Saracino, L and Bortolotto, C and Tomaselli, S and Fraolini, E and Bosio, M and Accordino, G and Agustoni, F and Abbott, DM and Pozzi, E and Eleftheriou, D and Morbini, P and Rinaldi, P and Primiceri, C and Lancia, A and Comoli, P and Filippi, AR and Stella, GM}, title = {Integrating data from multidisciplinary Management of Malignant Pleural Mesothelioma: a cohort study.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {762}, pmid = {34210265}, issn = {1471-2407}, support = {Plagencell project//Fondazione Regionale per la Ricerca Biomedica/ ; }, mesh = {Cohort Studies ; Databases, Factual ; Female ; Humans ; Male ; Mesothelioma, Malignant/*epidemiology/mortality/*therapy ; Pleural Neoplasms/*epidemiology/mortality/*therapy ; Survival Analysis ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural layers. MPM has a strong association with asbestos, mainly caused by exposure to its biopersistent fibers in at least 80% of cases. Individuals with a chronic exposure to asbestos might develop disease with a 20-40-year latency with few or no symptoms. Such has been the case in the Italian regions of Piedmont and Lombardy, where industrial production of materials laden with asbestos, mainly cements, has been responsible for the onset of a large epidemic. Since 2018, a multidisciplinary team at San Matteo hospital in Pavia has been collecting data on over 100 patients with MPM. The main goal of this project is to define and describe an integrated profile for each MPM case at diagnosis by using data mining and partition analysis.<br><br>METHODS: Here we bring together exhaustive epidemiologic, histologic and radiologic data of 88 MPM patients that came to our observation and draw correlations with predictive and prognostic significance.<br><br>RESULTS: The median overall survival (OS) was 15.6&#x2009;months. Most patients presented with pleural effusion, irrespective of disease stage. Quite unexpectedly, no statistically significant association was demonstrated between OS and TNM disease stage at diagnosis. Although average OS is similar in male and female patients, partition analysis of data underlined a significant differential hierarchy of predictor categories based on patient gender. In females with no smoking history, full chemotherapeutic regimens are associated with better outcomes. Moreover, concerning second line treatments, vinorelbine emerged as the most advantageous choice for female patients, whereas in the male subgroup no statistically significant difference resulted between gemcitabine and vinorelbine.<br><br>CONCLUSION: A multidisciplinary approach to MPM is mandatory to define better therapeutic approaches, personalize the management and improve patient outcomes.}, }
@article {pmid34207798, year = {2021}, author = {Broggi, G and Angelico, G and Filetti, V and Ledda, C and Lombardo, C and Vitale, E and Rapisarda, V and Loreto, C and Caltabiano, R}, title = {Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {12}, pages = {}, pmid = {34207798}, issn = {1660-4601}, mesh = {Arginine ; Asbestos, Amphibole ; Biomarkers, Tumor/genetics ; Humans ; *Lung Neoplasms/chemically induced/genetics ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; RNA Splicing Factors ; Serine ; Serine-Arginine Splicing Factors/genetics ; }, abstract = {UNLABELLED: The Serine and Arginine-Rich Splicing Factor 1 (SRSF1) has a proto-oncogenic function, being associated with angiogenesis and frequently overexpressed in many human malignant neoplasms. Its immunohistochemical expression has never been investigated in malignant pleural mesothelioma (MPM). We evaluated SRSF1 immunoexpression and its possible relation to angiogenesis in a selected cohort of 10 fluoro-edenite(FE)-induced MPM cases.<br><br>METHODS: Immunohistochemical analyses with an anti-SRSF1 antibody were performed. We interpreted the cases as positive if tumor cell nuclei were stained; a semi-quantitative analysis of the cases was performed by evaluating the intensity of staining and the percentage of tumor positive cells. A microvessel density (MVD) count was also performed.<br><br>RESULTS: High and low immunoexpressions of SRSF1 were seen in six and four MPMs, respectively. A trend of shorter overall survival was found in FE-induced MPM patients with SRSF1 overexpression. In addition, a significant association between high-MVD and high SRSF1 immunoexpression (p = 0.0476) was found.<br><br>CONCLUSIONS: SRSF1 appears to be involved in MPM pathogenesis and its immunoexpression may represent a prognostic biomarker capable of identifying subgroups of patients with different prognosis. However, given the preliminary nature of the present study, further investigations on larger series, and additional in vitro studies, are required to validate our findings.}, }
@article {pmid34206956, year = {2021}, author = {Désage, AL and Karpathiou, G and Peoc'h, M and Froudarakis, ME}, title = {The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Cancers}, volume = {13}, number = {13}, pages = {}, pmid = {34206956}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.}, }
@article {pmid34205400, year = {2021}, author = {Kwak, K and Cho, SI and Paek, D}, title = {Future Incidence of Malignant Mesothelioma in South Korea: Updated Projection to 2038.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {12}, pages = {}, pmid = {34205400}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Incidence ; Male ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Republic of Korea/epidemiology ; }, abstract = {Malignant mesothelioma (MM) is a cancer that is largely caused by exposure to asbestos. Although asbestos is no longer used in South Korea, the incidence of MM continues to increase due to its long latent period. We aimed to update the previous prediction of MM incidence until 2038. We predicted the incidence of MM over the next 20 years (2019-2038) in South Korea using Møller's age-period-cohort (APC) model and a Poisson regression model based on asbestos consumption. The APC model predicted that the crude incidence rate would increase sharply in men and slowly in women. Despite the sex discrepancy in the rate of increase, the incidence rate for both sexes is expected to continue increasing until 2038. In the Poisson model, the crude incidence rate was predicted to increase continuously until 2038, and far more cases of MM were predicted to occur compared with the results of the APC model. When compared with actual incidence data, the APC model was deemed more suitable than the Poisson model. The APC model predicted a continuous increase over the next 20 years with no peak, suggesting that the incidence of MM will continue to rise far into the future.}, }
@article {pmid34201002, year = {2021}, author = {Coccè, V and La Monica, S and Bonelli, M and Alessandri, G and Alfieri, R and Lagrasta, CA and Madeddu, D and Frati, C and Flammini, L and Lisini, D and Marcianti, A and Parati, E and Paino, F and Giannì, A and Farronato, G and Falco, A and Spaggiari, L and Petrella, F and Pessina, A}, title = {Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34201002}, issn = {2073-4409}, mesh = {Adolescent ; Adult ; Aged ; Animals ; *Cell Cycle ; Cell Line, Tumor ; *Cell Proliferation ; *Cell Survival ; Female ; Humans ; Mesenchymal Stem Cells ; Mesothelioma, Malignant/*pathology ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM.<br><br>METHODS: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice.<br><br>RESULTS: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment.<br><br>CONCLUSIONS: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.}, }
@article {pmid34199722, year = {2021}, author = {Terenziani, R and Zoppi, S and Fumarola, C and Alfieri, R and Bonelli, M}, title = {Immunotherapeutic Approaches in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34199722}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerging immunotherapy treatments for MPM (ICIs, engineered T cells to express chimeric antigen receptors (CARs), dendritic cells (DCs) vaccines), focusing on the biological and immunological features of this tumor as well as on the issues surrounding clinical trial design.}, }
@article {pmid34199544, year = {2021}, author = {Lorenzini, E and Ciarrocchi, A and Torricelli, F}, title = {Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34199544}, issn = {2077-0383}, support = {//Italian Ministry of Health though Bando per la Valorizzazione della Ricerca in ambito Oncologico 2020-Fondi 5 per Mille/ ; //Italian Ministry of Health though Bando per la Valorizzazione della Ricerca in ambito Oncologico 2019-Fondi 5 per Mille/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.}, }
@article {pmid34172838, year = {2023}, author = {Marant Micallef, C and Charvat, H and Houot, MT and Vignat, J and Straif, K and Paul, A and El Yamani, M and Pilorget, C and Soerjomataram, I}, title = {Estimated number of cancers attributable to occupational exposures in France in 2017: an update using a new method for improved estimates.}, journal = {Journal of exposure science &amp; environmental epidemiology}, volume = {33}, number = {1}, pages = {125-131}, pmid = {34172838}, issn = {1559-064X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Female ; Humans ; Male ; *Asbestos ; Benzene ; Carcinogens ; Dust ; France/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; *Occupational Diseases/epidemiology/etiology ; *Occupational Exposure ; Rubber ; }, abstract = {BACKGROUND: Over the last 50 years, occupational exposure to carcinogenic agents has been widely regulated in France.<br><br>OBJECTIVE: Report population-attributable fraction (PAF) and number of attributable cancer cases linked to occupational exposure in France based on an updated method to estimate lifetime occupational exposure prevalence.<br><br>METHODS: Population-level prevalence of lifetime exposure to ten carcinogenic agents (asbestos, benzene, chromium VI, diesel engine exhaust, formaldehyde, nickel compounds, polycyclic aromatic hydrocarbons, silica dust, trichloroethylene, wood dust) and two occupational circumstances (painters and rubber industry workers) were estimated using the French Census linked with MATG&#xc9;N&#xc9; job-exposure matrices and French occupational surveys. PAF and number of attributable cancer cases were calculated using the estimated prevalence, relative risks from systematic review and national estimates of cancer incidence in 2017.<br><br>RESULTS: The lifetime occupational exposure prevalences were much higher in men than in women ranging from 0.2% (workers in the rubber industry) to 10.2% in men (silica), and from 0.10% (benzene, PAH and workers in the rubber industry) to 5.7% in women (formaldehyde). In total, 4,818 cancer cases (men: 4,223; women: 595) were attributable to the ten studied carcinogens and two occupational circumstances, representing 5.2% of cases among the studied cancer sites (M: 7.0%; W: 1.9%). In both sexes, mesothelioma (M: 689 cases; W: 160) and lung cancer (M: 3,032; W: 308) were the largest cancer sites impacted by the studied occupational agents and circumstances.<br><br>SIGNIFICANCE: A moderate proportion of the cancer cases in France is linked to carcinogens in occupational settings. Our method provides more precise estimates of attributable cancer taking into account evolution of exposure to occupational agents by sex, age and time. This methodology can be easily replicated using cross-sectional occupational data to aid priority making and implementation of prevention strategies in the workplace.}, }
@article {pmid34161674, year = {2022}, author = {Ke, H and Kao, S and Lee, K and Takahashi, K and Goh, HP and Linton, A}, title = {The minimum standard of care for managing malignant pleural mesothelioma in developing nations within the Asia-Pacific Region.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {18}, number = {3}, pages = {177-190}, doi = {10.1111/ajco.13611}, pmid = {34161674}, issn = {1743-7563}, mesh = {*Asbestos ; Developing Countries ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/therapy ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/epidemiology/therapy ; Standard of Care ; }, abstract = {Malignant pleural mesothelioma (MPM) is an incurable malignancy associated with high symptom burden and poor prognosis. The relationship between asbestos exposure and MPM incidence is well-established. The incidence rate of MPM in Australia and New Zealand is among the highest globally. Matching the experience of other nations with legal restrictions on asbestos, incidence is expected to fall. In contrast, the incidence of MPM is rising in the developing nations of the Asia-Pacific as consumption and mining (albeit to a lesser extent) of asbestos continues. The incidence of MPM in these nations is currently low or unknown, reflecting insufficient latency periods since industrial use of asbestos, deficient resources for accurate diagnosis, and lack of occupational disease or cancer registries. The landscape of treatment for MPM is rapidly changing with combination immunotherapy now demonstrating improved survival in the first-line setting. Considering vast global inequity in access to anticancer treatments, establishing minimum standard of care for MPM in developing nations is of greater significance. Here, we review the evidence that form the basis of our minimum-standard recommendations for diagnosis, systemic treatment, management of recurrent pleural effusions, and symptom management. We also briefly review evidence-based treatment that may be considered for those with access.}, }
@article {pmid34155270, year = {2021}, author = {Kishimoto, T and Kojima, Y and Fujimoto, N}, title = {Significance of secretory leukocyte peptidase inhibitor in pleural fluid for the diagnosis of benign asbestos pleural effusion.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12965}, pmid = {34155270}, issn = {2045-2322}, mesh = {Area Under Curve ; Asbestosis/complications/*diagnosis/*metabolism ; *Biomarkers ; Biomarkers, Tumor ; Diagnosis, Differential ; Humans ; Mesothelioma, Malignant/diagnosis/etiology/metabolism ; Pleural Effusion/*diagnosis/etiology/*metabolism ; Pleural Effusion, Malignant/diagnosis/metabolism ; ROC Curve ; Secretory Leukocyte Peptidase Inhibitor/*metabolism ; }, abstract = {Secretory leukocyte peptidase inhibitor (SLPI) is a biomarker present in the respiratory tract that protects against tissue destruction and aids in wound healing. We examined whether SLPI in pleural effusion can be used to distinguish benign asbestos pleural effusion (BAPE) from early-stage malignant pleural mesothelioma (MPM) and other diseases. We measured the levels of SLPI, hyaluronic acid (HA), soluble mesothelin-related peptides (SMRP), CCL2, galectin-3, and CYFRA21-1 in 51 patients with BAPE, 37 patients with early-stage MPM, 77 patients with pleural effusions due to non-small-cell lung cancer (LCa), and 74 patients with other pleural effusions. SLPI levels in the pleural fluid of patients with BAPE were significantly lower than those in patients with MPM, LCa, and other pleural effusions (p < 0.0001). The area under the curve (AUC) for SLPI's ability to distinguish BAPE from MPM was 0.902, with a sensitivity of 82.4% and a specificity of 86.5%. This AUC was not only favourable but was better than the AUC for the ability of CYFRA21-1 to distinguish BAPE (0.853). The combination of SLPI and CYFRA21-1 achieved an AUC of 0.965 for the differentiation between BAPE and MPM. Pleural fluid SLPI as well as CYFRA21-1 and HA is useful as a biomarker to diagnose BAPE, which needs to be distinguished from early-stage MPM.}, }
@article {pmid34120777, year = {2022}, author = {Ramada Rodilla, JM and Calvo Cerrada, B and Serra Pujadas, C and Delclos, GL and Benavides, FG}, title = {Fiber burden and asbestos-related diseases: an umbrella review.}, journal = {Gaceta sanitaria}, volume = {36}, number = {2}, pages = {173-183}, pmid = {34120777}, issn = {1578-1283}, support = {P30 ES030285/ES/NIEHS NIH HHS/United States ; T42 OH008421/OH/NIOSH CDC HHS/United States ; }, mesh = {*Asbestos/toxicity ; Asbestos, Amphibole ; Humans ; *Lung Neoplasms/chemically induced/epidemiology ; *Mesothelioma/chemically induced/etiology ; *Occupational Exposure/adverse effects ; Risk Assessment ; }, abstract = {OBJECTIVE: What are the levels of asbestos exposure that cause each type of health effect? The objective of this study was to review the available scientific evidence on exposure levels for asbestos and their relationship to health effects.<br><br>METHOD: An umbrella review of English-language reviews and meta-analyses, from 1980 to March 2021 was conducted. We included reviews involving quantified asbestos exposures and health outcomes. The review has been adapted to the indications of the PRISMA declaration. Methodological quality of the selected studies was assessed using the AMSTAR instrument.<br><br>RESULTS: We retrieved 196 references. After applying the search strategy and quality analysis, 10 reviews were selected for in-depth analysis. For lung cancer, the highest risk was observed with exposure to amphiboles. Longer, thinner fibers had the greatest capacity to cause lung cancer, especially those > 10 &#x3bc;m in length. For mesothelioma, longer and thinner fibers were also more pathogenic; amphiboles &#x2265; 5 &#x3bc;m are especially associated with increased mesothelioma risk. No studies observed an increased risk for lung cancer or mesothelioma at asbestos exposure levels <0.1 f/ml. No reviews provided information on exposure concentrations for pulmonary fibrosis. Currently, there is limited evidence in humans to establish the causal relationship between gastrointestinal cancer and asbestos exposure.<br><br>CONCLUSIONS: Banning all asbestos exposure remains the best measure to preventing its negative health effects. The highest quality reviews and meta-analyses support that there is little risk of lung cancer or mesothelioma at daily exposure levels below 0.1 f/ml.}, }
@article {pmid34116230, year = {2021}, author = {Tsim, S and Alexander, L and Kelly, C and Shaw, A and Hinsley, S and Clark, S and Evison, M and Holme, J and Cameron, EJ and Sharma, D and Wright, A and Grundy, S and Grieve, D and Ionescu, A and Breen, DP and Paramasivam, E and Psallidas, I and Mukherjee, D and Chetty, M and Cox, G and Hart-Thomas, A and Naseer, R and Edwards, J and Daneshvar, C and Panchal, R and Munavvar, M and Ostroff, R and Alexander, L and Hall, H and Neilson, M and Miller, C and McCormick, C and Thomson, F and Chalmers, AJ and Maskell, NA and Blyth, KG}, title = {Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {16}, number = {10}, pages = {1705-1717}, pmid = {34116230}, issn = {1556-1380}, support = {29801/CRUK_/Cancer Research UK/United Kingdom ; A29801/CRUK_/Cancer Research UK/United Kingdom ; A31287/CRUK_/Cancer Research UK/United Kingdom ; A17196/CRUK_/Cancer Research UK/United Kingdom ; 15960/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Asbestos ; Biomarkers, Tumor ; Calcium-Binding Proteins ; Extracellular Matrix Proteins ; GPI-Linked Proteins ; Humans ; *Lung Neoplasms/diagnosis ; *Mesothelioma/diagnosis/etiology ; *Pleural Neoplasms/diagnosis/etiology ; Proteomics ; Retrospective Studies ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory.<br><br>METHODS: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure.<br><br>RESULTS: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p&#xa0;= 0.0015) and 0.516 [0.443-0.589], p&#xa0;= 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume.<br><br>CONCLUSIONS: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.}, }
@article {pmid34082107, year = {2021}, author = {Vandenhoeck, J and van Meerbeeck, JP and Fransen, E and Raskin, J and Van Camp, G and Op de Beeck, K and Lamote, K}, title = {DNA Methylation as a Diagnostic Biomarker for Malignant Mesothelioma: A Systematic Review and Meta-Analysis.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {16}, number = {9}, pages = {1461-1478}, doi = {10.1016/j.jtho.2021.05.015}, pmid = {34082107}, issn = {1556-1380}, mesh = {*Asbestos/adverse effects ; Biomarkers, Tumor/genetics/metabolism ; DNA Methylation ; Humans ; *Lung Neoplasms/diagnosis/genetics ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; }, abstract = {Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Because of several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is a need for diagnostic biomarkers that may contribute to early detection. Recently, the epigenome of tumors is being extensively investigated to identify biomarkers. This manuscript is a systematic review summarizing the state-of-the-art research investigating DNA methylation in mesothelioma. Four literature databases (PubMed, Scopus, Web of Science, MEDLINE) were systematically searched for studies investigating DNA methylation in mesothelioma up to October 16, 2020. A meta-analysis was performed per gene investigated in at least two independent studies. A total of 53 studies investigated DNA methylation of 97 genes in mesothelioma and are described in a qualitative overview. Furthermore, ten studies investigating 13 genes (APC, CDH1, CDKN2A, DAPK, ESR1, MGMT, miR-34b/c, PGR, RARβ, RASSF1, SFRP1, SFRP4, WIF1) were included in the quantitative meta-analysis. In this meta-analysis, the APC gene is significantly hypomethylated in mesothelioma, whereas CDH1, ESR1, miR-34b/c, PGR, RARβ, SFRP1, and WIF1 are significantly hypermethylated in mesothelioma. The three genes that are the most appropriate candidate biomarkers from this meta-analysis are APC, miR-34b/c, and WIF1. Nevertheless, both study number and study objects comprised in this meta-analysis are too low to draw final conclusions on their clinical applications. The elucidation of the genome-wide DNA methylation profile of mesothelioma is desirable in the future, using a standardized genome-wide methylation analysis approach. The most informative CpG sites from this signature could then form the basis of a panel of highly sensitive and specific biomarkers that can be used for the diagnosis of mesothelioma and even for the screening of an at high-risk population of asbestos-exposed individuals.}, }
@article {pmid34073720, year = {2021}, author = {Napoli, F and Listì, A and Zambelli, V and Witel, G and Bironzo, P and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34073720}, issn = {2072-6694}, support = {IG 2019 - ID. 23760 project//Associazione Italiana per la Ricerca sul Cancro/ ; Ricerca Locale 2019//Universit&#xe0; degli Studi di Torino/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13-15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients' genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.}, }
@article {pmid34071989, year = {2021}, author = {Cugliari, G and Allione, A and Russo, A and Catalano, C and Casalone, E and Guarrera, S and Grosso, F and Ferrante, D and Sculco, M and La Vecchia, M and Pirazzini, C and Libener, R and Mirabelli, D and Magnani, C and Dianzani, I and Matullo, G}, title = {New DNA Methylation Signals for Malignant Pleural Mesothelioma Risk Assessment.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34071989}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. The evaluation of asbestos exposure was conducted considering the frequency, the duration and the intensity of occupational, environmental and domestic exposure. A genome-wide methylation array was performed to identify novel blood DNA methylation (DNAm) markers of MPM. Multiple regression analyses adjusting for potential confounding factors and interaction between asbestos exposure and DNAm on the MPM odds ratio were applied. Epigenome-wide analysis (EWAS) revealed 12 single-CpGs associated with the disease. Two of these showed high statistical power (99%) and effect size (>0.05) after false discovery rate (FDR) multiple comparison corrections: (i) cg03546163 in FKBP5, significantly hypomethylated in cases (Mean Difference in beta values (MD) = -0.09, 95% CI = -0.12|-0.06, p = 1.2 × 10[-7]), and (ii) cg06633438 in MLLT1, statistically hypermethylated in cases (MD = 0.07, 95% CI = 0.04|0.10, p = 1.0 × 10[-6]). Based on the interaction analysis, asbestos exposure and epigenetic profile together may improve MPM risk assessment. Above-median asbestos exposure and hypomethylation of cg03546163 in FKBP5 (OR = 20.84, 95% CI = 8.71|53.96, p = 5.5 × 10[-11]) and hypermethylation of cg06633438 in MLLT1 (OR = 11.71, 95% CI = 4.97|29.64, p = 5.9 × 10[-8]) genes compared to below-median asbestos exposure and hyper/hypomethylation of single-CpG DNAm, respectively. Receiver Operation Characteristics (ROC) for Case-Control Discrimination showed a significant increase in MPM discrimination when DNAm information was added in the model (baseline model, BM: asbestos exposure, age, gender and white blood cells); area under the curve, AUC = 0.75; BM + cg03546163 at FKBP5. AUC = 0.89, 2.1 × 10[-7]; BM + cg06633438 at MLLT1. AUC = 0.89, 6.3 × 10[-8]. Validation and replication procedures, considering independent sample size and a different DNAm analysis technique, confirmed the observed associations. Our results suggest the potential application of DNAm profiles in blood to develop noninvasive tests for MPM risk assessment in asbestos-exposed subjects.}, }
@article {pmid34070888, year = {2021}, author = {Rossi, G and Davoli, F and Poletti, V and Cavazza, A and Lococo, F}, title = {When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34070888}, issn = {2077-0383}, abstract = {The diagnosis of malignant mesothelioma (MPM) does not pose difficulties when presenting with usual clinico-radiologic features and morphology. Pathology textbooks and national/international guidelines generally describe the findings of classic MPM, underlining common clinical presentation, the gold standard of sampling techniques, usual morphologic variants, immunohistochemical results of several positive and negative primary antibodies in the differential diagnosis, and the role of novel molecular markers. Nevertheless, MPM often does not follow the golden rules in routine practice, while the literature generally does not sufficiently emphasize unusual features of its manifestation. This gap may potentially create problems for patients in sustaining a difficult diagnosis of MPM in clinical practice and during legal disputes. Indeed, the guidelines accidentally tend to favor the job of lawyers and pathologists defending asbestos-producing industries against patients suffering from MPM characterized by uncommon features. The current review is aimed at underlining the wide spectrum of clinical and radiological presentation of MPM, the possibility to consistently use cytology for diagnostic intent, the aberrant immunohistochemical expression using so-called specific negative and positive primary antibodies, and finally proposing some alternative and more unbiased approaches to the diagnosis of MPM.}, }
@article {pmid34069196, year = {2021}, author = {Lee, KM and Godderis, L and Furuya, S and Kim, YJ and Kang, D}, title = {Comparison of Asbestos Victim Relief Available Outside of Conventional Occupational Compensation Schemes.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34069196}, issn = {1660-4601}, mesh = {*Asbestos ; France ; Humans ; Japan ; *Lung Neoplasms ; *Mesothelioma/chemically induced ; Netherlands ; *Occupational Diseases ; *Occupational Exposure ; Republic of Korea ; United Kingdom ; Workers' Compensation ; }, abstract = {The asbestos victim relief schemes were introduced to resolve the issue of victims of asbestos-related diseases not receiving compensation through conventional legal orders. This article seeks to derive the differences and commonalities of various asbestos victim relief schemes available outside of the conventional occupational compensation system along with a systematic understanding and to propose plans for improvement through a comparative study. After the degree of asbestos exposure, the population, and the period of implementation were corrected, the recognized claims of the total of conventional occupational compensation schemes and the asbestos victim relief schemes could be ranked in the order of South Korea (KOR) (1867, total), France (FRA) (1571), Japan (JPN) (966), KOR (847, asbestosis grade 2,3 excluded), the United Kingdom (GBR) (670), and the Netherlands (NLD) (95). The average amount of compensation per person, in the case of mesothelioma, was higher in the order of FRA (4.60 times), KOR (1.46 times), GBR (1.03 times), and NLD (0.73 times) of the median income per year. The differences between countries were largely caused by the purpose of institutional design and influenced by the level of qualification, the existence of an expiration date, type of disease, type of benefit, level of judgment criteria, the existence of a procedure for appeals, and recognition rate (GBR: 102%, FRA: 84%, NLD: 81%, JPN: 76%, KOR: 73%, and BEL: 54%). Based on this analysis, suggestions could be made regarding the expansion of disease types, benefit types, and the overall review of judgment criteria.}, }
@article {pmid34068638, year = {2021}, author = {Vimercati, L and Cavone, D and Delfino, MC and Bruni, B and De Maria, L and Caputi, A and Sponselli, S and Rossi, R and Resta, L and Fortarezza, F and Pezzuto, F and Serio, G}, title = {Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature.}, journal = {Cancers}, volume = {13}, number = {9}, pages = {}, pmid = {34068638}, issn = {2072-6694}, abstract = {Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma "misclassification", "misdiagnosis", "diagnostic challenge" or "diagnostic pitfall" and on unsolved questions about its histogenesis and possible risk factors.}, }
@article {pmid34066159, year = {2021}, author = {Anobile, DP and Bironzo, P and Picca, F and Lingua, MF and Morena, D and Righi, L and Napoli, F and Papotti, MG and Pittaro, A and Di Nicolantonio, F and Gigliotti, C and Bussolino, F and Comunanza, V and Guerrera, F and Sandri, A and Leo, F and Libener, R and Aviles, P and Novello, S and Taulli, R and Scagliotti, GV and Riganti, C}, title = {Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {10}, pages = {}, pmid = {34066159}, issn = {2072-6694}, support = {23760//Associazione Italiana per la Ricerca sul Cancro/ ; 21408//Associazione Italiana per la Ricerca sul Cancro/ ; EX60% Funding 2019//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; TOPMESO JTC 2017//ERANet Transcan2/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy.<br><br>METHODS: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation.<br><br>RESULTS: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro.<br><br>CONCLUSION: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.}, }
@article {pmid34060417, year = {2021}, author = {Ierardi, AM and Mathis, C and Urban, A and Jacobs, N and Finley, B and Gaffney, S}, title = {Potential airborne asbestos exposures in dentistry: a comprehensive review and risk assessment.}, journal = {Critical reviews in toxicology}, volume = {51}, number = {4}, pages = {301-327}, doi = {10.1080/10408444.2021.1910624}, pmid = {34060417}, issn = {1547-6898}, mesh = {Air Pollutants, Occupational/*analysis ; *Asbestos ; Asbestos, Serpentine ; *Dentistry ; Environmental Monitoring ; Humans ; Lung Neoplasms ; Mesothelioma/chemically induced/epidemiology ; No-Observed-Adverse-Effect Level ; Occupational Exposure/*statistics &amp; numerical data ; Risk Assessment ; }, abstract = {Chrysotile was formerly used in the manufacture of casting ring liner (CRL) and periodontal dressing powder (PDP). The purpose of this study was to describe the potential for airborne asbestos exposure among dental professionals who may have used these products and to assess their risk of asbestos-related disease (ARD). Task-specific exposure data associated with CRL and PDP were identified and compared to regulatory standards for asbestos and health-based benchmarks. Personal airborne fiber concentrations ranged from 0.008-3.5 f/cc by PCM (duration: 3-420 minutes) for CRL (tearing, placement), and from <0.0044-<0.297 f/cc by PCM (duration: 5-28 minutes) for PDP (mixing). Eight-hour time-weighted average (TWA) exposures were calculated using the reported task-based airborne fiber concentrations and associated sampling durations. For CRL tasks, the upper-bound calculated 8-hour TWA of 0.022 f/cc (tearing, placement) did not exceed regulatory standards for asbestos (≥0.1 f/cc). All samples collected during the mixing of PDP resulted in non-measurable fiber concentrations. The greatest estimated cumulative asbestos exposure for dental professionals using CRL (tearing, placement) of 0.33 f/cc-years is well below "best estimate", published chrysotile no-observed-adverse-effect-levels (NOAEL) for ARD (lung cancer = 89-168 f/cc-years; pleural mesothelioma = 208-415 f/cc-years). As such, the use of asbestos-containing CRL and/or PDP is not expected to pose an increased risk of ARD among dental professionals. This conclusion is consistent with the lack of an increased risk of ARD reported in epidemiological studies of these occupations.}, }
@article {pmid34059094, year = {2021}, author = {Haakensen, VD and Nowak, AK and Ellingsen, EB and Farooqi, SJ and Bjaanæs, MM and Horndalsveen, H and Mcculloch, T and Grundberg, O and Cedres, SM and Helland, &#xc5;}, title = {NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {232}, pmid = {34059094}, issn = {1479-5876}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Humans ; Ipilimumab/therapeutic use ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; Nivolumab/therapeutic use ; Vaccination ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for. Telomerase is expressed in mesothelioma cells, but only sparsely in normal tissues and is therefore an attractive target for therapeutic vaccination. Vaccination against telomerase is tolerable and has shown to induce immune responses associated with increased survival in other cancer types. There is a well-founded scientific rationale for the combination of a telomerase vaccine and checkpoint inhibition to improve treatment response in MPM patients.<br><br>METHODS: NIPU is a randomized, multi-centre, open-label, phase II study comparing the efficacy and safety of nivolumab and ipilimumab with or without telomerase vaccine in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy. Participants (n&#xa0;=&#xa0;118) are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomised to the experimental arm receive 8 intradermal injections of UV1 vaccine during the first three months of treatment. Tumour tissue, blood, urine, faeces and imaging will be collected for biomarker analyses and exploration of mechanisms for response and resistance to therapy.<br><br>DISCUSSION: Checkpoint inhibition is used for treatment of mesothelioma, but many patients still do not respond. Increasing therapy response to immunotherapy is an important goal. Possible approaches include combination with chemotherapy, radiotherapy, targeted therapy and other immunotherapeutic agents. Predictive biomarkers are necessary to ensure optimal treatment for each patient and to prevent unnecessary side effects. This trial seeks to improve treatment response by combining checkpoint inhibition with a telomerase vaccine and also to explore mechanisms for treatment response and resistance. Knowledge gained in the NIPU study may be transferred to the first line setting and to other cancers with limited benefit from immunotherapy.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov: NCT04300244, registered March 8th, 2020, https://clinicaltrials.gov/ct2/show/NCT04300244?term=NIPU&amp;draw=2&amp;rank=1 .}, }
@article {pmid34052509, year = {2021}, author = {Scarselli, A and Marinaccio, A and Iavicoli, S}, title = {Ophiolitic outcrops, naturally occurring asbestos exposure and mortality risk from malignant mesothelioma in Calabria (Southern Italy).}, journal = {Public health}, volume = {195}, number = {}, pages = {57-60}, doi = {10.1016/j.puhe.2021.04.008}, pmid = {34052509}, issn = {1476-5616}, mesh = {*Asbestos/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/epidemiology ; Male ; *Mesothelioma, Malignant ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: Naturally occurring asbestos from ophiolitic outcrops can pose a health risk to the resident population. Some studies have documented this risk of exposure in many areas around the world. The aim of the study is to estimate the possible impact on health caused by asbestos outcrops present in some areas of Calabria, a region of southern Italy.<br><br>STUDY DESIGN: The design of the study is observational and uses routinely collected data on employment, compensations and mortality.<br><br>METHODS: Data from archives of mortality in the period 2005-2015 were selected. Standardized mortality ratio (SMR) for malignant mesothelioma (MM) by municipalities of residence with reference to the regional population was estimated assuming a Poisson distribution of the data. Administrative archives of companies' employment records and occupational disease compensation data were used to exclude occupational origin cases.<br><br>RESULTS: A total of 163 cases of MM were identified. Statistically significant excess risks (P-value <0.05) were observed for several municipalities, some of which were located in areas where asbestos outcrops had previously been identified. Significant SMRs vary between 44.0 and 5.2. The mean age at death in the areas at risk of ophiolitic outcrops ranges from 65.4 to 77.1 years, and the gender ratio (male/female) ranges from 0.66 to 1.3.<br><br>CONCLUSIONS: Monitoring of areas most involved in the risk of environmental contamination from ophiolitic outcrops is highly suggested. Full implementation of the local MM surveillance system is strongly encouraged. Further investigations are recommended to specifically identify the cause of exposure and confirm the hypothesis of a causal association with asbestos naturally occurring in these risk areas.}, }
@article {pmid34040906, year = {2021}, author = {Thomas, A and Karakattu, S and Cagle, J and Hoskere, G}, title = {Malignant Pleural Mesothelioma Epidemiology in the United States From 2000 to 2016.}, journal = {Cureus}, volume = {13}, number = {4}, pages = {e14605}, pmid = {34040906}, issn = {2168-8184}, abstract = {Introduction Pleural mesothelioma constitutes about 80% of all mesotheliomas. The peak incidence of malignant mesothelioma estimated using the cancer registries was in early 1990 to 2000 in the United States. The disease is primarily associated with asbestos exposure. The latency period between asbestos exposure and the development of malignant pleural mesothelioma (MPM) can range anywhere from 15 to 60 years. Asbestos exposure was peaked during the industrial revolution and World War II due to military and shipyard exposures. It is often difficult for the pathologist to distinguish different histological subtypes; due to the disease's rarity and the inadequate tissue sample obtained. There is no available data on the difference in epidemiology of different subtypes of MPM. Surveillance Epidemiology and End Results (SEER), cancer incidence data include population-based registries covering approximately 34.6% of the U.S. population. Here in our study, we analyze malignant pleural mesothelioma epidemiology in the United States, emphasizing different histological subtypes. Methods SEER data from 2000 to 2016 was used in our study. The primary site of cancer is selected as pleura, and malignant behavior only is selected as the filter. Data were analyzed using the SEER stat program. Overall epidemiology of MPM and epidemiology of epithelioid, fibrous, and biphasic histological subtypes were analyzed separately. We used annual percentage change (APC) to evaluate the trend in the epidemiology of MPM. Results summary A total of 11,857 cases of MPM were included in the primary cohort from the SEER 18 registry from 2000 to 2016. The total prevalence of MPM was highest in 2009 and was lowest in 2016. The APC in MPM incidence during this period is -2.0. After removing 5,989 cases with non-specified histology during the same period, the APC for each histological type is -0.7 for fibrous type, 1.8 for epithelioid type, and 2.9 for biphasic type. Out of 17 regional registries included in the study, the greatest statistically significant change in APC was seen in the Hawaiian registry -4.1. In contrast, the lowest statistically significant difference was seen in Seattle (Puget Sound) registry -1.7. The APC in the incidence of MPM among males during the study period was -2.4 while that of females was -0.9. The Iowa registry showed a statistically significant increase in APC of the epithelioid malignant mesothelioma with a statistically insignificant reduction in the overall MPM APC. Conclusion The overall incidence of MPM in the United States is declining, while the data showed an increase in the incidence of epithelioid and biphasic histological subtypes. The authors believe that these conflicting results can be attributed to improved histological diagnosis and improved biopsy techniques.}, }
@article {pmid34036634, year = {2021}, author = {Baur, X and Frank, AL and Soskolne, CL and Oliver, LC and Magnani, C}, title = {Malignant mesothelioma: Ongoing controversies about its etiology in females.}, journal = {American journal of industrial medicine}, volume = {64}, number = {7}, pages = {543-550}, doi = {10.1002/ajim.23257}, pmid = {34036634}, issn = {1097-0274}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Incidence ; Male ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; }, abstract = {Malignant mesothelioma (MM) is one of the most aggressive cancers with the poorest of outcomes. There is no doubt that mesothelioma in males is related to asbestos exposure, but some authors suggest that most of the cases diagnosed in females are "idiopathic." In our assessment of the science, the "low risk" of mesothelioma in females is because of the nonsystematic recording of exposure histories among females. Indeed, asbestos exposure is mentioned in only some of the studies that include females. We estimate the risk of MM among females to be close to that in males. The absence of detailed exposure histories should be rectified in future studies involving women. As a matter of social justice, the ongoing failure to recognize asbestos as the cause of a majority of cases of MM in females does them, and their kin, a profound disservice.}, }
@article {pmid34033161, year = {2022}, author = {Louw, A and Lee, YCG and Acott, N and Creaney, J and van Vliet, C and Chai, SM}, title = {Diagnostic utility of BAP1 for malignant pleural mesothelioma in pleural fluid specimens with atypical morphology.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {33}, number = {1}, pages = {84-92}, doi = {10.1111/cyt.13015}, pmid = {34033161}, issn = {1365-2303}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; *Lung Neoplasms/diagnosis/genetics/metabolism ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {OBJECTIVE: To assess the utility of BRCA1-associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in fluid samples with atypical cytology.<br><br>METHODS: Pleural fluid samples with an atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') received between January 2015 and March 2018 at a tertiary referral centre were identified. Results of routine IHC testing were recorded for each case. BAP1 by IHC was performed and a final diagnosis sought from subsequent pathology specimens, medical records, or consensus clinical diagnosis.<br><br>RESULTS: Of 50 cases identified, 41 were reported as atypical and 9 as suspicious. Seven (14%) demonstrated loss of BAP1 staining, 40 retained BAP1 staining, 1 had heterogeneous staining, and 2 had insufficient cells for analysis. All seven cases with BAP1 loss were diagnosed with MPM on follow-up. Of those with retained BAP1, 52.5% (21) were subsequently diagnosed with MPM, while 40% (16) had non-MPM diagnoses after a median follow-up of 24&#xa0;months. Three cases were not further investigated based on patient and clinician decision. The case with heterogeneous staining was diagnosed as mesothelioma by clinical consensus.<br><br>CONCLUSIONS: BAP1 IHC loss is highly specific for malignancy and has value as a rule-in test. Even in a tertiary centre with clinical interest in the cytological diagnosis of MPM this investigation was able to increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable, as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy.}, }
@article {pmid34012597, year = {2021}, author = {Schumann, SO and Kocher, G and Minervini, F}, title = {Epidemiology, diagnosis and treatment of the malignant pleural mesothelioma, a narrative review of literature.}, journal = {Journal of thoracic disease}, volume = {13}, number = {4}, pages = {2510-2523}, pmid = {34012597}, issn = {2072-1439}, abstract = {The malignant pleural mesothelioma is a very aggressive tumor which is arising from mesothelial cells and is associated with asbestos exposure. It is a heterogeneous cancer that shows a complex pattern of molecular changes, including genetic, chromosomic, and epigenetic abnormalities. The malignant pleural mesothelioma is characterized by a silent and slow clinical progression with an average period of 20-40 years from the asbestos exposure phase to the start of the symptoms. Unfortunately, to date, the therapeutic options are very limited, especially if the tumor is detected late. This narrative review provides an extended overview of the present evidence in the literature regarding the epidemiology, diagnostic pathways and treatment approaches of the malignant pleural mesothelioma. The treatment of mesothelioma has evolved slowly over the last 20 years not only from a surgical point of view but also radiotherapy, chemotherapy and immunotherapy play nowadays a key role. Several surgical strategies are available ranging from extrapleural pneumonectomy to cytoreductive surgery but a multidisciplinary approach seems to be mandatory because a single approach has not proved to date to be resolutive. New non-surgical treatment options appear to be promising but the results have to be taken in account with caution because clear evidence with high-quality studies is still lacking.}, }
@article {pmid34008015, year = {2021}, author = {Cheung, M and Kadariya, Y and Sementino, E and Hall, MJ and Cozzi, I and Ascoli, V and Ohar, JA and Testa, JR}, title = {Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors.}, journal = {Human molecular genetics}, volume = {30}, number = {18}, pages = {1750-1761}, pmid = {34008015}, issn = {1460-2083}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; *Genetic Predisposition to Disease ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*genetics ; Male ; Mesothelioma, Malignant/*genetics ; Risk Factors ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {There is irrefutable evidence that germline BRCA1-associated protein 1 gene (BAP1) mutations contribute to malignant mesothelioma (MM) susceptibility. However, BAP1 mutations are not found in all cases with evidence of familial MM or in other high-risk cancer families affected by various cancers, including MM. The goal of this study was to use whole genome sequencing (WGS) to determine the frequency and types of germline gene variants occurring in 12 MM patients who were selected from a series of 141 asbestos-exposed MM patients with a family history of cancer but without a germline BAP1 mutation. WGS was also performed on two MM cases, a proband and sibling, from a previously reported family with multiple cases of MM without the inheritance of a predisposing BAP1 mutation. Altogether, germline DNA sequencing variants were identified in 21 cancer-related genes in 10 of the 13 probands. Germline indel, splice site and missense mutations and two large deletions were identified. Among the 13 MM index cases, 6 (46%) exhibited one or more predicted pathogenic mutations. Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ and XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2 and SETD1B) or other cellular pathways: leucine-rich repeat kinase 2 gene (LRRK2) (two cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and the expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.}, }
@article {pmid34000787, year = {2021}, author = {Wilk, E and Krówczyńska, M}, title = {Malignant mesothelioma and asbestos exposure in Europe: Evidence of spatial clustering.}, journal = {Geospatial health}, volume = {16}, number = {1}, pages = {}, doi = {10.4081/gh.2021.951}, pmid = {34000787}, issn = {1970-7096}, mesh = {Aged ; *Asbestos ; Cluster Analysis ; Europe/epidemiology ; Female ; Humans ; *Lung Neoplasms/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Spatial Analysis ; Switzerland ; }, abstract = {Exposure to asbestos causes a wide range of diseases, such as asbestosis, malignant mesothelioma (MM) and other types of cancer. Many European countries have reduced production and use of asbestos and some have banned it altogether. Based on data derived from the World Health Organisation (WHO) Cancer Mortality Database, we investigated whether some regions in Europe could have a higher relative risk of MM incidence than others. The data were compared, including the number of MM deaths per million inhabitants and aged-standardized mortality rates. Applying Moran's I and Getis-Ord Gi statistic on the agedstandardized mortality rates of MM cases assisted the spatial analysis of the occurrence of health events leading to an assessment of the heterogeneity of distribution and cluster detection of MM. We found a statistically significant positive autocorrelation for the male population and also the general population, while there was no statistically significant positive one for the female population. Hotspots of relative risk of developing MM were found in northwestern Europe. For the general population, Great Britain and the Netherlands stood out with high levels at the 99% and 95% confidence levels, respectively. For the male population, the results were similar, but with addition of risk also in Belgium and Switzerland. However, in many European countries with high asbestos use per capita, the MM incidence was found to still be low. The reasons for this are not yet clear, but part of the problem is certainly due to incomplete data in registers and databases. The latency time can be longer than 40 years and is related to the intensity and time of exposure (occupational, para-occupational and environmental). In Europe, even though peak production occurred in the 1960s and 1970s, a significant decrease in production did not occur until 25 years later, which means that the impact will continue for as late as The mid 2030s.}, }
@article {pmid33998299, year = {2021}, author = {Tanrıverdi, Z and Meteroglu, F and Yüce, H and Şenyiğit, A and Işcan, M and Unüvar, S}, title = {The usefulness of biomarkers in diagnosis of asbestos-induced malignant pleural mesothelioma.}, journal = {Human &amp; experimental toxicology}, volume = {40}, number = {11}, pages = {1817-1824}, doi = {10.1177/09603271211017324}, pmid = {33998299}, issn = {1477-0903}, mesh = {Adult ; Asbestos/*toxicity ; Biomarkers, Tumor/blood ; Cell Adhesion Molecules/*blood ; Chitinase-3-Like Protein 1/*blood ; Cross-Sectional Studies ; Female ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*blood ; Male ; Mesothelioma, Malignant/blood/*chemically induced/*diagnosis/physiopathology ; Middle Aged ; Neopterin/*blood ; Pleural Neoplasms/chemically induced/diagnosis/physiopathology ; Prospective Studies ; Tenascin/*blood ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a malignant tumor that is associated mostly with asbestos exposure. The present study was to evaluates the diagnostic value of neopterin, periostin, YKL-40, Tenascin-C (TNC), and Indolamine 2,3-dioxygenase (IDO) as noninvasive markers of malign pleural mesothelioma.<br><br>METHODS: Included in the study were 30 patients diagnosed with malign pleural mesothelioma, and 25 people as a control group. Biomarker levels were determined using an enzyme immunoassay . A Mann-Whitney U test and Spearman correlation methods were used for the statistical analysis.<br><br>RESULTS: All evaluated biomarkers were found to be significantly higher in the MPM group than in the control group (p < 0.05). There was no effect of such variables as gender, age or MPMsubtype on the parameters (p > 0.05) in the patient group. All biomarkers were positively correlated with each other (p < 0.001).<br><br>CONCLUSIONS: The current non-invasive biomarkers that can be used in the diagnosis of MPM yielded significant results and can make important contributions to the early diagnosis of MPM.}, }
@article {pmid33971174, year = {2022}, author = {Zhou, N and Rice, DC and Tsao, AS and Lee, PP and Haymaker, CL and Corsini, EM and Antonoff, MB and Hofstetter, WL and Rajaram, R and Roth, JA and Swisher, SG and Vaporciyan, AA and Walsh, GL and Mehran, RJ and Sepesi, B}, title = {Extrapleural Pneumonectomy Versus Pleurectomy/Decortication for Malignant Pleural Mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {113}, number = {1}, pages = {200-208}, doi = {10.1016/j.athoracsur.2021.04.078}, pmid = {33971174}, issn = {1552-6259}, mesh = {Aged ; Female ; Humans ; Male ; Mesothelioma, Malignant/mortality/*surgery ; Middle Aged ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*methods ; Postoperative Complications/epidemiology ; Retrospective Studies ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP versus P/D.<br><br>METHODS: Patients with the diagnosis of malignant pleural mesothelioma who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis.<br><br>RESULTS: Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs 0%; P&#xa0;= .031); when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 versus 22 months, respectively (P&#xa0;= .276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P&#xa0;= .029), macroscopic complete resection (HR, 0.41; P&#xa0;= .004), adjuvant radiation therapy (HR, 0.57; P&#xa0;= .019), and more recent operative years (HR, 0.93; P&#xa0;= .011)-but not P/D-to be associated with better survival. Asbestos exposure (HR, 2.35; P&#xa0;= .003) and pathologic nodal disease (HR, 1.61; P&#xa0;= .048) were associated with worse survival.<br><br>CONCLUSIONS: In a multimodality treatment setting, P/D and EPP had comparable long-term oncologic outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate.}, }
@article {pmid33959504, year = {2021}, author = {Arrieta, O and Muñoz-Montaño, W and Muñiz-Hernández, S and Campos, S and Catalán, R and Soto-Molina, H and Guzmán Vázquez, S and Díaz-Álvarez, O and Martínez-Pacheco, V and Turcott, JG and Ramos-Ramírez, M and Cabrera-Miranda, L and Barrón, F and Cardona, AF}, title = {Efficacy, Safety, and Cost-Minimization Analysis of Continuous Infusion of Low-Dose Gemcitabine Plus Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {641975}, pmid = {33959504}, issn = {2234-943X}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is rare and aggressive neoplasia, with a poor prognosis; furthermore, the monetary cost of its treatment represents a major challenge for many patients. The economic burden this malignancy imposes is underscored by the fact that asbestos exposure, which is the most frequent risk factor, is much more prevalent in the lower socioeconomic population of developing countries. The aims of the present study were to evaluate the efficacy, safety, and cost of continuous infusion of low-dose Gemcitabine plus Cisplatin (CIGC) as a treatment strategy for patients with unresectable MPM.<br><br>METHODS: We performed a prospective cohort study to determine efficacy and safety of continuous infusion gemcitabine at a dose of 250 mg/m2 in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 of a 21-day cycle in patients with unresectable MPM. We also performed a cost-minimization analysis to determine if this chemotherapy regimen is less expensive than other currently used regimens.<br><br>RESULTS: The median number of chemotherapy cycles was six (range 1-11 cycles); objective response rate was documented in 46.2%, and disease control rate was seen in&#xa0;81.2%. Median PFS was 8.05 months (CI 95% 6.97-9.13); median OS was 16.16 months (CI 95% 12.5-19.9). The cost minimization analysis revealed savings of 66.4, 61.9, and 97.7% comparing CIGC with short-infusion gemcitabine plus cisplatin (SIGC), cisplatin plus pemetrexed (CP), and cisplatin plus pemetrexed and bevacizumab (CPB), respectively. Furthermore, this chemotherapy regimen proved to be safe at the administered dosage.<br><br>CONCLUSION: CIGC is an effective and safe treatment option for patients with unresectable MPM; besides, this combination is a cost-saving option when compared with other frequently used chemotherapy schemes. Therefore, this treatment scheme should be strongly considered for patients with unresectable MPM and limited economic resources.}, }
@article {pmid33952230, year = {2021}, author = {Gray, SG}, title = {Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma.}, journal = {BMC pulmonary medicine}, volume = {21}, number = {1}, pages = {148}, pmid = {33952230}, issn = {1471-2466}, mesh = {Antineoplastic Agents/*therapeutic use ; CTLA-4 Antigen/antagonists &amp; inhibitors ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Immunotherapy ; Lung Neoplasms/*therapy ; Mesothelioma, Malignant/*therapy ; Pleural Neoplasms/*therapy ; Programmed Cell Death 1 Ligand 2 Protein/antagonists &amp; inhibitors ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; }, abstract = {BACKGROUND: The role of immunotherapy in cancer is now well-established, and therapeutic options such as checkpoint inhibitors are increasingly being approved in many cancers such as non-small cell lung cancer (NSCLC). Malignant pleural mesothelioma (MPM) is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Evidence from clinical trials of checkpoint inhibitors in this rare disease, suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer.<br><br>MAIN TEXT: While the majority of studies currently focus on the established checkpoint inhibitors (CTLA4 and PD1/PDL1), there are many other potential checkpoints that could also be targeted. In this review I provide a synopsis of current clinical trials of immunotherapies in MPM, explore potential candidate new avenues that may become future targets for immunotherapy and discuss aspects of immunotherapy that may affect the clinical outcomes of such therapies in this cancer.<br><br>CONCLUSIONS: The current situation regarding checkpoint inhibitors in the management of MPM whilst encouraging, despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Additional studies are therefore required to further delineate and improve our understanding of both checkpoint inhibitors and the immune system in MPM. Moreover, many new potential checkpoints have yet to be studied for their therapeutic potential in MPM. All these plus the existing checkpoint inhibitors will require the development of new biomarkers for patient stratification, response and also for predicting or monitoring the emergence of resistance to these agents in MPM patients. Other potential therapeutic avenues such CAR-T therapy or treatments like oncolytic viruses or agents that target the interferon pathway designed to recruit more immune cells to the tumor also hold great promise in this hard to treat cancer.}, }
@article {pmid33946118, year = {2021}, author = {Aigner, C and Brüning, T and Eberhardt, WEE and Härter, M and Kaelberlah, HP and Metzenmacher, M and Shah, R and Taube, C and Thomas, M}, title = {[The Current Therapy of Asbestos-Associated Malignant Pleural Mesothelioma - An Expert Consensus Paper].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {75}, number = {10}, pages = {776-794}, pmid = {33946118}, issn = {1438-8790}, mesh = {*Asbestos/adverse effects ; Consensus ; Humans ; *Lung Neoplasms/diagnosis/therapy ; *Mesothelioma/diagnosis/therapy ; *Mesothelioma, Malignant ; *Occupational Exposure ; *Pleural Neoplasms/diagnosis/therapy ; }, abstract = {Asbestos-related mesotheliomas belong to the group of the most frequent occupational diseases in Germany, reaching about 1,000 new cases per year. The disease has a dismal prognosis because most tumors remain asymptomatic for a long time and therefore are diagnosed as incidental findings at later stages.During the last decade the German Social Accident Insurance (DGUV) has made considerable efforts to prepone the diagnosis in order to detect the disease at earliest possible stages. These efforts resulted in new findings showing that, in a high-risk group, a combination of the biomarkers calretinin and mesothelin was able to advance the diagnosis up to 12 months.Ideally, the diagnosis of a mesothelioma at an early stage has to be accompanied by the best possible individualized therapy. Standard therapeutic strategies are surgery and chemotherapy, added by radiotherapy and psycho-oncology. In recent years, several new therapeutic avenues are being explored. This review comprehensively presents both old and new therapeutic options in mesothelioma, based on international Leitlinien and new studies.}, }
@article {pmid33945895, year = {2021}, author = {Ejegi-Memeh, S and Robertson, S and Taylor, B and Darlison, L and Tod, A}, title = {Gender and the experiences of living with mesothelioma: A thematic analysis.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {52}, number = {}, pages = {101966}, doi = {10.1016/j.ejon.2021.101966}, pmid = {33945895}, issn = {1532-2122}, mesh = {Female ; Humans ; Male ; Men ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Qualitative Research ; }, abstract = {PURPOSE: Mesothelioma is a terminal cancer caused by exposure to asbestos. As a cancer with a higher rate in men than women, women's experiences of living with mesothelioma are often underexplored. Furthermore, men's experiences are often taken for granted and therefore have remained underexplored. This paper considers men's and women's experiences across the mesothelioma pathway.<br><br>METHODS: This qualitative study incorporated semi-structured interviews with 13 men and 11 women living with mesothelioma. Telephone interviews took place between July and December 2019, and were audio recorded, transcribed and anonymised. Thematic analysis was used to analyse the data.<br><br>RESULTS: Three themes were developed in relation to the gendered experience of mesothelioma: familial responsibility and social perceptions; support preferences; and treatment and trials. Analysis suggests that men and women's sense of familial responsibility varied. Differences in priorities and motivations influenced approaches to seeking support, compensation and, making decisions around treatments and clinical trials.<br><br>CONCLUSIONS: The current study reports on how gender can influence the experience of living with mesothelioma. The findings indicate how the patients' role in their families and society can more broadly influence their experiences, choices and preferences. Nurses caring for mesothelioma patients need high quality research on which to base their practice. Recognition and an understanding of the underlyingfactors influencing patients' decision-making will enable nurses and other professionals to support their patients better.}, }
@article {pmid33945357, year = {2021}, author = {Davis, AP and Kao, SC and Clarke, SJ and Boyer, M and Pavlakis, N}, title = {Emerging biological therapies for the treatment of malignant pleural mesothelioma.}, journal = {Expert opinion on emerging drugs}, volume = {26}, number = {2}, pages = {179-192}, doi = {10.1080/14728214.2021.1924670}, pmid = {33945357}, issn = {1744-7623}, mesh = {Biological Therapy/methods ; Biomarkers, Tumor/metabolism ; Humans ; Immunotherapy/*methods ; Mesothelioma, Malignant/immunology/*therapy ; Pleural Neoplasms/immunology/*therapy ; Precision Medicine ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.}, }
@article {pmid33927865, year = {2021}, author = {Muralidhar, V}, title = {An unusual presentation of acute abdomen: infarcted peritoneal cyst-a probable asbestos-related benign cystic mesothelioma.}, journal = {Journal of surgical case reports}, volume = {2021}, number = {4}, pages = {rjab129}, pmid = {33927865}, issn = {2042-8812}, abstract = {This is a report of a rare case of an infarcted pelvic intra-abdominal cyst, having no mesenteric connection presenting as an acute abdomen. The patient had significant asbestos exposure. The cyst was treated successfully by surgical excision. Histopathology showed an infarcted cyst; the lining was destroyed, precluding marker studies. A diagnosis of benign cystic peritoneal mesothelioma (BCPM) was made by excluding other causes of solitary pelvic intra-abdominal cysts. BCPM has been classified as an asbestos-related neoplasm and is usually seen in the pelvis adjunct to the urinary bladder. One-year post-surgery, there was no recurrence. The case report shows that infarcted pelvic mesothelial cysts can present as an acute abdomen and can be treated successfully by total excision with no recurrence.}, }
@article {pmid33917061, year = {2021}, author = {Brcic, L and Mathilakathu, A and Walter, RFH and Wessolly, M and Mairinger, E and Beckert, H and Kreidt, D and Steinborn, J and Hager, T and Christoph, DC and Kollmeier, J and Mairinger, T and Wohlschlaeger, J and Schmid, KW and Borchert, S and Mairinger, FD}, title = {Digital Gene Expression Analysis of Epithelioid and Sarcomatoid Mesothelioma Reveals Differences in Immunogenicity.}, journal = {Cancers}, volume = {13}, number = {8}, pages = {}, pmid = {33917061}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with asbestos exposure. Median survival ranges from 14 to 20 months after initial diagnosis. As of November 2020, the FDA approved a combination of immune checkpoint inhibitors after promising intermediate results. Nonetheless, responses remain unsatisfying. Adequate patient stratification to improve response rates is still lacking. This retrospective study analyzed formalin fixed paraffin embedded specimens from a cohort of 22 MPM. Twelve of those samples showed sarcomatoid, ten epithelioid differentiation. Complete follow-up, including radiological assessment of response by modRECIST and time to death, was available with reported deaths of all patients. RNA of all samples was isolated and subjected to digital gene expression pattern analysis. Our study revealed a notable difference between epithelioid and sarcomatoid mesothelioma, showing differential gene expression for 304/698 expressed genes. Whereas antigen processing and presentation to resident cytotoxic T cells as well as phagocytosis is highly affected in sarcomatoid mesothelioma, cell-cell interaction via cytokines seems to be of greater importance in epithelioid cases. Our work reveals the specific role of the immune system within the different histologic subtypes of MPM, providing a more detailed background of their immunogenic potential. This is of great interest regarding therapeutic strategies including immunotherapy in mesothelioma.}, }
@article {pmid33910295, year = {2021}, author = {Li, N and Wang, D and Chen, ZJ and Mao, WM}, title = {[Asbestos-induced malignant peritoneal mesothelioma complicated with lung cancer:a case report].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {4}, pages = {305-307}, doi = {10.3760/cma.j.cn121094-20200114-00029}, pmid = {33910295}, issn = {1001-9391}, support = {81672315//National Natural Science Foundation of China/ ; }, mesh = {*Asbestos/adverse effects ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Peritoneal Neoplasms ; }, abstract = {Asbestos is harmful to human, and populations with occupational and environmental exposure to respirable asbestos fibers have higher risk of cancers like malignant mesothelioma and lung cancer. At present, patient with asbestos-induced malignant peritoneal mesothelioma and lung cancer is rare. In this study, we analyzed the clinical data of a case of asbestos-induced malignant peritoneal mesothelioma complicated with lung cancer to investigate the diagnosis and treatment of this disease.}, }
@article {pmid33890321, year = {2021}, author = {Zhang, F and Yuan, X and Sun, H and Yin, X and Gao, Y and Zhang, M and Jia, Z and Yu, M and Ying, S and Xia, H and Ju, L and Xiao, Y and Tao, H and Lou, J and Zhu, L}, title = {A nontoxic dose of chrysotile can malignantly transform Met-5A cells, in which microRNA-28 has inhibitory effects.}, journal = {Journal of applied toxicology : JAT}, volume = {41}, number = {11}, pages = {1879-1892}, doi = {10.1002/jat.4174}, pmid = {33890321}, issn = {1099-1263}, mesh = {Asbestos, Serpentine/*toxicity ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; MicroRNAs/*metabolism ; }, abstract = {Chrysotile, which is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC), has extensive application in the industry and can lead to lung or other cancers. However, whether chrysotile causes malignant mesothelioma and its molecular mechanism remain debatable. Thus, this study aimed to demonstrate the mesothelioma-inducing potential of chrysotile at the mesothelial cellular level and the function of microRNA-28 in malignantly transformed mesothelial MeT-5A cells. MeT-5A cells malignantly transformed by a nontoxic dose of chrysotile were named Asb-T, and miR-28 expression was downregulated in Asb-T cells. Restoration of miR-28 expression inhibited the proliferation, migration and invasion of Asb-T cells. We verified that IMPDH is a putative target of miR-28. The expression of IMPDH was significantly higher in Asb-T MeT-5A cells than in control cells, whereas the opposite trend was observed with miR-28 overexpression. Additionally, inhibition of IMPDH had similar effects as miR-28 overexpression. After miR-28 was elevated or IMPDH was inhibited, Ras activation was reduced, and its downstream pathways (the Erk and Akt signalling pathways) were inhibited. Surprisingly, the content of miR-28 in the blood of mesothelioma patients was higher than that in control subjects. Overall, nontoxic doses of chrysotile can cause malignant transformation of MeT-5A cells. Moreover, miR-28 inhibits the proliferation, migration and invasion of Asb-T MeT-5A cells, negatively regulates the expression of IMPDH through the Ras signalling pathway and may be an important therapeutic target.}, }
@article {pmid33889258, year = {2021}, author = {Ouafki, I and Nouiakh, L and Boujarnija, R and Amarti, A and Amaadour, L and Oualla, K and Benbrahim, Z and Arifi, S and Mellas, N}, title = {[Malignant mesothelioma of the ovary: a case report].}, journal = {The Pan African medical journal}, volume = {38}, number = {}, pages = {92}, pmid = {33889258}, issn = {1937-8688}, mesh = {Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Mesothelioma, Malignant/*diagnosis/pathology/therapy ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/*diagnosis/pathology/therapy ; Tomography, X-Ray Computed ; }, abstract = {Primary malignant mesothelioma of the ovary (PMMO) is an extremely rare tumor which can develop from mesothelial cells. This neoplasia is caused predominantly by exposure to asbestos or other cancer-causing agents. Preoperative assessment, based on computed tomography (CT) scan, magnetic resonance imaging and positron emission tomography, is essential for cancer staging. Anatomopathological diagnosis is based on immunohistochemical findings. PMMO is an exceptional disease involving a multidisciplinary therapeutic strategy including the use of chemotherapy which improves the management and prognosis of patients. This study reports the case of a female patient undergoing suboptimal surgery complemented by adjuvant chemotherapy with complete radiological response and 1-year disease-free survival.}, }
@article {pmid33874885, year = {2021}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Ito, T and Otsuki, T}, title = {Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction.}, journal = {Environmental health and preventive medicine}, volume = {26}, number = {1}, pages = {50}, pmid = {33874885}, issn = {1347-4715}, support = {16K09114//Japan Society for the Promotion of Science/ ; 27B068//Kawasaki Medical School/ ; 28B008//Kawasaki Medical School/ ; }, mesh = {Asbestos/*adverse effects ; CD8-Positive T-Lymphocytes/cytology/drug effects/*immunology/metabolism ; Humans ; Interleukin-15/*pharmacology ; Lymphocyte Activation/*drug effects/immunology ; T-Lymphocytes, Cytotoxic/cytology/drug effects/*immunology/metabolism ; }, abstract = {BACKGROUND: Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8[+] T cells. Recently, we reported that asbestos-induced suppression of CTL induction is not due to insufficient levels of interleukin-2 (IL-2). In this study, we continue to investigate the mechanism responsible for the effect of asbestos fibers on the differentiation of CTLs and focus on interleukin-15 (IL-15) which is known to be a regulator of T lymphocyte proliferation.<br><br>METHODS: For MLR, human peripheral blood mononuclear cells (PBMCs) were cultured with irradiated allogenic PBMCs upon exposure to chrysotile B asbestos at 5 &#x3bc;g/ml for 7 days. After 2 days of culture, IL-15 was added at 1 ng/ml. After 7 days of MLR, PBMCs were collected and analyzed for phenotypic and functional markers of CD8[+] T cells with fluorescence-labeled anti-CD3, anti-CD8, anti-CD45RA, anti-CD45RO, anti-CD25, and anti-granzyme B antibodies using flow cytometry. To examine the effect of IL-15 on the expression level of intracellular granzyme B in proliferating and non-proliferating CD8[+] lymphocytes, PBMCs were stained using carboxyfluorescein diacetate succinimidyl ester (CFSE) and then washed and used for the MLR.<br><br>RESULTS: IL-15 addition partially reversed the decrease in CD3[+]CD8[+] cell numbers and facilitated complete recovery of granzyme B[+] cell percentages. IL-15 completely reversed the asbestos-induced decrease in percentage of granzyme B[+] cells in both non-proliferating CFSE-positive and proliferating CFSE-negative CD8[+] cells. The asbestos-induced decrease in the percentage of CD25[+] and CD45RO[+] cells in CD8[+] lymphocytes was not reversed by IL-15.<br><br>CONCLUSION: These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.}, }
@article {pmid33872411, year = {2021}, author = {Ezeka, G and Adhikary, G and Kandasamy, S and Friedberg, JS and Eckert, RL}, title = {Sulforaphane inhibits PRMT5 and MEP50 function to suppress the mesothelioma cancer cell phenotype.}, journal = {Molecular carcinogenesis}, volume = {60}, number = {7}, pages = {429-439}, pmid = {33872411}, issn = {1098-2744}, support = {R01 CA211909/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Animals ; Anticarcinogenic Agents/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Histones/metabolism ; Humans ; Isothiocyanates/*pharmacology ; Mesothelioma/*drug therapy/metabolism/*pathology ; Mice, Inbred NOD ; Phenotype ; Protein-Arginine N-Methyltransferases/genetics/*metabolism ; Signal Transduction/drug effects ; Sulfoxides/*pharmacology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; Mice ; }, abstract = {Mesothelioma is a highly aggressive cancer of the mesothelial lining that is caused by exposure to asbestos. Surgical resection followed by chemotherapy is the current treatment strategy, but this is marginally successful and leads to drug-resistant disease. We are interested in factors that maintain the aggressive mesothelioma cancer phenotype as therapy targets. Protein arginine methyltransferase 5 (PRMT5) functions in concert with the methylosome protein 50 (MEP50) cofactor to catalyze symmetric dimethylation of key arginine resides in histones 3 and 4 which modifies the chromatin environment to alter tumor suppressor and oncogene expression and enhance cancer cell survival. Our studies show that PRMT5 or MEP50 loss reduces H4R3me2s formation and that this is associated with reduced cancer cell spheroid formation, invasion, and migration. Treatment with sulforaphane (SFN), a diet-derived anticancer agent, reduces PRMT5/MEP50 level and H4R3me2s formation and suppresses the cancer phenotype. We further show that SFN treatment reduces PRMT5 and MEP50 levels and that this reduction is required for SFN suppression of the cancer phenotype. SFN treatment also reduces tumor formation which is associated with reduced PRMT5/MEP50 expression and activity. These findings suggest that SFN may be a useful mesothelioma treatment agent that operates, at least in part, via suppression of PRMT5/MEP50 function.}, }
@article {pmid33851620, year = {2021}, author = {Fujishima, F and Konosu-Fukaya, S and Nabeshima, K and McNamara, KM and Sakamoto, K and Sakurada, J and Sasano, H and Nakamura, Y}, title = {Histological and immunohistochemical characteristics and p16 status studied by FISH in six incidentally detected cases of well-differentiated papillary mesothelioma of the peritoneum.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {2}, pages = {277-281}, doi = {10.4103/IJPM.IJPM_111_20}, pmid = {33851620}, issn = {0974-5130}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence ; Male ; Mesothelioma/diagnosis/*pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*pathology/surgery ; Peritoneum/pathology ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/metabolism ; }, abstract = {Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial neoplasm, which is generally regarded as benign or indolent in terms of its clinical behavior. However, details about WDPM have remained relatively unknown. Therefore, in this study, we examined six incidentally detected cases of WDPM of the peritoneum. All six cases were surgically excised, without any additional therapeutic measures. None of the cases showed recurrence. All six cases presented single lesions and the tumor sizes ranged from 2 to 10 mm. Histologically, all six cases exhibited papillary proliferation of cytologically bland mesothelial cells with a fibroconnective tissue core. One of the cases (Case 6) presented small invasive foci in the stalk. The tumor cells were immunohistochemically positive for mesothelial markers and negative for GLUT-1, p53, and CD146. The Ki-67 labeling index of the tumor cells was lower than 5% at the hot spots. All samples were BAP1-positive. None of the samples presented p16 homozygous deletion, as assessed by fluorescence in situ hybridization (FISH). None of the patients deceased due to WDPM. However, in Case 3, death occurred due to pancreatic cancer. The results of this study indicate the importance of analyzing immunohistochemical markers and p16 status to diagnose WDPM accurately.}, }
@article {pmid33834530, year = {2021}, author = {DeBono, NL and Warden, H and Logar-Henderson, C and Shakik, S and Dakouo, M and MacLeod, J and Demers, PA}, title = {Incidence of mesothelioma and asbestosis by occupation in a diverse workforce.}, journal = {American journal of industrial medicine}, volume = {64}, number = {6}, pages = {476-487}, doi = {10.1002/ajim.23245}, pmid = {33834530}, issn = {1097-0274}, mesh = {Aged ; Asbestosis/*epidemiology ; Female ; Humans ; Incidence ; Industry/statistics &amp; numerical data ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupations/*statistics &amp; numerical data ; Ontario/epidemiology ; *Population Surveillance ; Proportional Hazards Models ; Registries ; Workers' Compensation/statistics &amp; numerical data ; Workforce/statistics &amp; numerical data ; }, abstract = {OBJECTIVE: We sought to characterize detailed patterns of mesothelioma and asbestosis incidence in the workforce as part of an occupational disease surveillance program in Ontario, Canada.<br><br>METHODS: The Occupational Disease Surveillance System (ODSS) cohort was established using workers' compensation claims data and includes 2.18 million workers employed from 1983 to 2014. Workers were followed for mesothelioma and asbestosis diagnoses in Ontario Cancer Registry, physician, hospital, and ambulatory care records through 2016. Trends in incidence rates were estimated over the study period. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>RESULTS: A total of 854 mesothelioma and 737 asbestosis cases were diagnosed during follow-up. Compared with all other workers in the ODSS, those employed in construction trades occupations had the greatest adjusted incidence rate of both mesothelioma (223 cases; HR, 2.38; 95% CI: 2.03-2.78) and asbestosis (261 cases; HR, 3.64; 95% CI: 3.11-4.25). Rates were particularly elevated for insulators, pipefitters and plumbers, and carpenters. Workers in welding and flame cutting, boiler making, and mechanic and machinery repair occupations, as well as those in industrial chemical and primary metal manufacturing industries, had strongly elevated rates of both diseases. Rates were greater than anticipated for workers in electrical utility occupations and education and related services.<br><br>CONCLUSIONS: Results substantiate the risk of mesothelioma and asbestosis in occupation and industry groups in the Ontario workforce with known or suspected asbestos exposure. Sustained efforts to prevent the occurrence of additional cases of disease in high-risk groups are warranted.}, }
@article {pmid33816102, year = {2021}, author = {Mizuhashi, K and Okamoto, K and Kishimoto, T}, title = {A patient with epithelioid pleural mesothelioma (Myxoid variant) who survived for a long period without treatment.}, journal = {Respiratory medicine case reports}, volume = {33}, number = {}, pages = {101381}, pmid = {33816102}, issn = {2213-0071}, abstract = {Pleural mesothelioma is a disease with a very poor prognosis. Here, we report a mesothelioma patient who survived for 5 years and a half. As a result of the autopsy, the tumor was diagnosed as a myxoid variant, which is internationally proposed as a histological subtype of epithelioid mesothelioma with a relatively favorable prognosis. Since patients with this disease are expected to survive for a long period even without treatment, careful determination of the therapeutic approach is considered necessary. This report is considered to be the first of a myxoid variant epithelioid pleural mesothelioma in Japan.}, }
@article {pmid33804168, year = {2021}, author = {Barbarino, M and Giordano, A}, title = {Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System.}, journal = {Cancers}, volume = {13}, number = {6}, pages = {}, pmid = {33804168}, issn = {2072-6694}, abstract = {In 2014, the International Agency for Research on Cancer (IARC) classified the first type of carbon nanotubes (CNTs) as possibly carcinogenic to humans, while in the case of other CNTs, it was not possible to ascertain their toxicity due to lack of evidence. Moreover, the physicochemical heterogeneity of this group of substances hamper any generalization on their toxicity. Here, we review the recent relevant toxicity studies produced after the IARC meeting in 2014 on an homogeneous group of CNTs, highlighting the molecular alterations that are relevant for the onset of mesothelioma. Methods: The literature was searched on PubMed and Web of Science for the period 2015-2020, using different combinations keywords. Only data on normal cells of the respiratory system after exposure to fully characterized CNTs for their physico-chemical characteristics were included. Recent studies indicate that CNTs induce a sustained inflammatory response, oxidative stress, fibrosis and histological alterations. The development of mesothelial hyperplasia, mesothelioma, and lungs tumors have been also described in vivo. The data support a strong inflammatory potential of CNTs, similar to that of asbestos, and provide evidence that CNTs exposure led to molecular alterations known to have a key role in mesothelioma onset. These evidences call for an urgent improvement of studies on exposed human populations and adequate systems for monitoring the health of workers exposed to this putative carcinogen.}, }
@article {pmid33802313, year = {2021}, author = {Lettieri, S and Bortolotto, C and Agustoni, F and Lococo, F and Lancia, A and Comoli, P and Corsico, AG and Stella, GM}, title = {The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {5}, pages = {}, pmid = {33802313}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and-in specific geographic regions-erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.}, }
@article {pmid33799965, year = {2021}, author = {Schiavello, M and Gazzano, E and Bergandi, L and Silvagno, F and Libener, R and Riganti, C and Aldieri, E}, title = {Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {5}, pages = {}, pmid = {33799965}, issn = {2072-6694}, abstract = {Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.}, }
@article {pmid33792699, year = {2021}, author = {Fujihira, H and Takakura, D and Matsuda, A and Abe, M and Miyazaki, M and Nakagawa, T and Kajino, K and Denda-Nagai, K and Noji, M and Hino, O and Irimura, T}, title = {Bisecting-GlcNAc on Asn388 is characteristic to ERC/mesothelin expressed on epithelioid mesothelioma cells.}, journal = {Journal of biochemistry}, volume = {170}, number = {3}, pages = {317-326}, pmid = {33792699}, issn = {1756-2651}, support = {JP19ae0101026//Japan Agency for Medical Research and Development/ ; 18K14655//Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research/ ; //Promotion and Mutual Aid Corporation for Private Schools of Japan/ ; }, mesh = {Acetylglucosamine/*metabolism ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Chromatography, Liquid/methods ; Epithelioid Cells/metabolism ; GPI-Linked Proteins/*metabolism ; Glycosylation ; Humans ; Lectins/*metabolism ; Mass Spectrometry/methods ; Mesothelin ; Mesothelioma/*metabolism ; Mesothelioma, Malignant/metabolism ; Protein Array Analysis/methods ; }, abstract = {Mesothelioma is a highly aggressive tumour associated with asbestos exposure and is histologically classified into three types: epithelioid-type, sarcomatoid-type and biphasic-type. The prognosis of mesothelioma patients is poor and there is no effective molecular-targeting therapy as yet. ERC/mesothelin is a glycoprotein that is highly expressed on several types of cancers including epithelioid mesothelioma, but also expressed on normal mesothelial cells. This is a predicted reason why there is no clinically approved therapeutic antibody targeting ERC/mesothelin. In the present study, we focussed on the differential glycosylation between ERC/mesothelin present on epithelioid mesothelioma and that on normal mesothelial cells and aimed to reveal a distinct feature of epithelioid mesothelioma cells. Lectin microarray analysis of ERC/mesothelin using cells and patient specimens showed significantly stronger binding of PHA-E4 lectin, which recognizes complex-type N-glycans having a so-called bisecting-GlcNAc structure, to ERC/mesothelin from epithelioid mesothelioma cells than that from normal mesothelial cells. Further, liquid chromatography/mass spectrometry analysis on ERC/mesothelin from epithelioid mesothelioma cells confirmed the presence of a bisecting-GlcNAc attached to Asn388 of ERC/mesothelin. These results suggest that this glycoproteome could serve as a potential target for the generation of a highly selective and safe therapeutic antibody for epithelioid mesothelioma.}, }
@article {pmid33781046, year = {2021}, author = {Huang, XY and Ye, Q}, title = {[Asbestos exposure and asbestos-related malignant diseases:an epidemiological review].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {3}, pages = {233-236}, doi = {10.3760/cma.j.cn121094-20200226-00089}, pmid = {33781046}, issn = {1001-9391}, support = {2019-XZ-70//Consutting Research Project of Chinese Academy of Engineering/ ; Z181100001718118//Capital Clinical Character1stic Application Research/ ; }, mesh = {*Asbestos/adverse effects ; Carcinogens/toxicity ; Humans ; *Lung Neoplasms/chemically induced/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Asbestos has high fire resistance, electrical insulation and thermal insulation. It is an important fire prevention, insulation and insulation material. It is widely used in industrial production and daily life. In 1987, the international agency for research on cancer (IARC) has listed asbestos as a class I carcinogen; in 2012, IARC confirmed that all types of asbestos have carcinogenic effect. By 2019, asbestos has been banned in 66 countries and regions around the world. Asbestos exposure increases the risk of human malignant tumor. Lung cancer and mesothelioma are known asbestos induced tumors. Epidemiological studies also support that asbestos exposure is related to the incidence of malignant tumors in reproductive system, digestive system, urinary system, nasopharynx head and neck. We summarized the epidemiological studies of asbestos induced tumors in order to provide reference for further research.}, }
@article {pmid33778549, year = {2020}, author = {Gill, RR and Murphy, DJ and Seethamraju, RT and Mazzola, E and Bueno, R and Richards, WG}, title = {Interobserver Variability of Quantitative and Qualitative Assessment Using MRI in Malignant Pleural Mesothelioma.}, journal = {Radiology. Cardiothoracic imaging}, volume = {2}, number = {2}, pages = {e190066}, pmid = {33778549}, issn = {2638-6135}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: To evaluate the interobserver variability associated with quantitative and qualitative MRI assessments of malignant pleural mesothelioma (MPM).<br><br>MATERIALS AND METHODS: Patients with MPM who underwent uniform-protocol preoperative MRI between 2009 and 2014 were included. The MRI-derived tumor volume was estimated. Unidimensional measurements of maximal pleural thickness (P max) and average pleural thickness (P avg) on axial MR images; maximal fissural thickness (F max); maximal diaphragmatic thickness (D max); and average diaphragmatic thickness (D avg) on sagittal reconstructed images were acquired. Interobserver agreement regarding the American Joint Committee on Cancer (AJCC) tumor stage at each criterion level was assessed by using Cohen &#x3ba; statistics. Agreement between quantitative measurements was assessed by using Bland-Altman plots and intraclass correlation coefficients (ICCs).<br><br>RESULTS: The study cohort included 349 patients (median age, 68 years [age range, 30-90 years), 273 (78%) of whom were men and 203 (58%) of whom had epithelioid-subtype tumors. Qualitative assessment performed by using the AJCC staging criteria (eighth edition) was concordant in 31% of cases and yielded considerable disagreement (&#x3ba; = 0.177). Inspection of the Bland-Altman plots led to decisive agreement between the two reviewers regarding MRI-derived tumor volume (ICC, 0.979). There was also a good degree of agreement between the two reviewers regarding unidimensional measurements of D max (ICC, 0.807), D avg (ICC, 0.823), P max (ICC, 0.787), P avg (ICC, 0.787), and F max (ICC, 0.659).<br><br>CONCLUSION: Quantitative assessment can enhance the clinical staging of MPM. Compared with qualitative assessment, quantitative assessment has low interobserver variability and could yield a tumor size criterion that is currently lacking in the AJCC clinical staging of MPM.Supplemental material is available for this article.&#xa9; RSNA, 2020.}, }
@article {pmid33775406, year = {2021}, author = {Klebe, S and Nakatani, Y and Dobra, K and Butnor, KJ and Roden, AC and Nicholson, AG and Marchevsky, AM and Husain, AN and Segal, A and Walts, AE and Weynand, B and Michael, CW and Dacic, S and Godbolt, D and Attanoos, R and Santoni-Rugiu, E and Galateau-Salle, F and Hiroshima, K and Moreira, AL and Burn, J and Nabeshima, K and Gibbs, AR and Churg, A and Litzky, LA and Brcic, L and Tsao, MS and Mino-Kenudson, M and Rørvig, SB and Tazelaar, HD and Krausz, T and Zhang, YZ and Chirieac, LR and Beasley, MB and Hjerpe, A}, title = {The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis.}, journal = {Pathology}, volume = {53}, number = {4}, pages = {446-453}, doi = {10.1016/j.pathol.2020.12.005}, pmid = {33775406}, issn = {1465-3931}, mesh = {Cytodiagnosis ; Early Diagnosis ; Humans ; Mesothelioma, Malignant/classification/*diagnosis/pathology/therapy ; Pathologists ; Serous Membrane/pathology ; Surveys and Questionnaires ; World Health Organization ; }, abstract = {Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS.}, }
@article {pmid37034512, year = {2023}, author = {Simsek, FS and Cakmak, M and Kuslu, D and Balci, TA and In, E and Ozercan, IH and Narin, Y}, title = {How can we use positron emission tomography/computed tomography more accurately for characterization of asbestos-related pleural thickening?.}, journal = {Archives of medical science : AMS}, volume = {19}, number = {2}, pages = {385-391}, pmid = {37034512}, issn = {1734-1922}, abstract = {INTRODUCTION: There is no consensus about the standardized uptake value maximum (SUVmax) cut-off value to characterize pleural thickening worldwide. Sometimes, this causes unnecessary invasive diagnostic procedures. Our first aim is to determine a cut-off value for SUVmax. Secondly, we try to answer the following question: If we use this cut-off value together with morphological parameters, can we differentiate benign thickening from malignant pleural mesothelioma (MPM) more accurately?<br><br>MATERIAL AND METHODS: Thirty-seven patients who underwent 2-deoxy-2-fluoro-D-glucose ([[18]F]FDG) positron emission tomography/computed tomography (PET/CT) before pleural biopsy were included the study. All of patients had histopathologically proven primary pleural disease. Their [18F]FDG-PET/CT imaging reports were re-assessed. If a patient's SUVmax or size of the thickening was not mentioned in the report, we calculated it with their [18F]FDG-PET/CT.<br><br>RESULTS: Age, pleural effusion, size, and SUVmax were found to have a relationship with MPM. We found the size > 14 mm, and SUVmax > 4.0 as cut-off values for MPM. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for size > 14 mm were found to be 86.4%, 85.2%, 82.6%, 88.5%, respectively. For SUVmax > 4.0, sensitivity, specificity, PPV, NPV were 90.9%, 87.0%, 85.1%, 92.2%, respectively.<br><br>CONCLUSIONS: If a patient has SUVmax > 4.0 and/or size > 14 mm, the risk of MPM is high. These patients should undergo biopsy. If a patient's SUVmax < 4.0, size < 14 mm and does not have pleural effusion, he/she has low risk for MPM. These patients can undergo the follow-up. If a patient's SUVmax < 4, size < 14, and has pleural effusion the MPM risk is approximately 4%. These patients can undergo biopsy/cytology/follow-up. Novel studies are needed for these patients.}, }
@article {pmid33749247, year = {2021}, author = {Reid, G and Klebe, S and van Zandwijk, N and George, AM}, title = {Asbestos and Zeolites: from A to Z via a Common Ion.}, journal = {Chemical research in toxicology}, volume = {34}, number = {4}, pages = {936-951}, doi = {10.1021/acs.chemrestox.0c00286}, pmid = {33749247}, issn = {1520-5010}, mesh = {Asbestos/*adverse effects/metabolism ; Humans ; Nanotubes, Carbon/adverse effects ; Zeolites/*adverse effects/metabolism ; }, abstract = {Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.}, }
@article {pmid33741915, year = {2021}, author = {Zhang, M and Luo, JL and Sun, Q and Harber, J and Dawson, AG and Nakas, A and Busacca, S and Sharkey, AJ and Waller, D and Sheaff, MT and Richards, C and Wells-Jordan, P and Gaba, A and Poile, C and Baitei, EY and Bzura, A and Dzialo, J and Jama, M and Le Quesne, J and Bajaj, A and Martinson, L and Shaw, JA and Pritchard, C and Kamata, T and Kuse, N and Brannan, L and De Philip Zhang, P and Yang, H and Griffiths, G and Wilson, G and Swanton, C and Dudbridge, F and Hollox, EJ and Fennell, DA}, title = {Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1751}, pmid = {33741915}, issn = {2041-1723}, support = {C61811/A24218/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; 25352/CRUK_/Cancer Research UK/United Kingdom ; 25253/CRUK_/Cancer Research UK/United Kingdom ; 20466/CRUK_/Cancer Research UK/United Kingdom ; 17786/CRUK_/Cancer Research UK/United Kingdom ; 30025/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Chromosome Deletion ; Clone Cells/metabolism/pathology ; Cluster Analysis ; Cohort Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; *Mutation ; Pleural Neoplasms/*genetics ; Prognosis ; Tumor Microenvironment/genetics ; Tumor Suppressor Proteins/classification/*genetics ; Exome Sequencing/methods ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.}, }
@article {pmid33718042, year = {2021}, author = {Schiopu, SRI and Käsmann, L and Schönermarck, U and Fischereder, M and Grabmaier, U and Manapov, F and Rauch, J and Orban, M}, title = {Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report.}, journal = {Translational lung cancer research}, volume = {10}, number = {2}, pages = {1039-1046}, pmid = {33718042}, issn = {2218-6751}, abstract = {Malignant mesothelioma is an aggressive cancer associated with prior exposure to asbestos and dismal prognosis. Immune checkpoint inhibitor therapy is currently approved by the Food and Drug Administration for pre-treated malignant pleural mesothelioma. We describe a 75-year-old patient with disseminated, progressive malignant mesothelioma receiving 2 cycles of pembrolizumab who presented with generalized muscle weakness, shortness of breath, double vision and ptosis. There was no previous history of cardiovascular disease. The clinical picture, supported by the detection of anti-titin autoantibodies suggested myasthenia gravis (MG). Also, cardiac biomarkers were elevated. Echocardiography showed new severely reduced ejection fraction. A 12-lead resting electrocardiogram (ECG) revealed ST segment elevation in the posterior leads with polymorphic ventricular extrasystoles. Because cardiac catheterization revealed no relevant coronary lesions, immune checkpoint inhibitor-associated myocarditis and MG were suspected. Management and Outcome: The patient was started on steroids. Within a few days of presentation respiratory failure set in and the patient was intubated. Recurrent arrhythmias followed, which were treated by repeated emergency electrical cardioversion. In order to relieve myasthenic symptoms, plasma exchange was initiated and 10 cycles were carried out. This consequently also led to an improvement of myocarditis. Upon discharge, the ejection fraction recovered. The patient recovered and was alive at 1-year follow-up, without relevant limitations to his quality of life. Discussion and Conclusion: The article further discusses the use of plasma exchange for immune checkpoint inhibitor-associated myocarditis based on a review of literature. We conclude that patients showing no improvement after steroid therapy for immune checkpoint inhibitor-related myocarditis should be evaluated for plasma exchange, which appears to be an effective treatment option.}, }
@article {pmid33713739, year = {2021}, author = {Sun, S and Frontini, F and Qi, W and Hariharan, A and Ronner, M and Wipplinger, M and Blanquart, C and Rehrauer, H and Fonteneau, JF and Felley-Bosco, E}, title = {Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development.}, journal = {Cancer letters}, volume = {507}, number = {}, pages = {26-38}, doi = {10.1016/j.canlet.2021.03.004}, pmid = {33713739}, issn = {1872-7980}, mesh = {Animals ; Asbestos, Crocidolite ; Asbestosis/complications ; Cell Line, Tumor ; DNA Methylation ; Disease Models, Animal ; Endogenous Retroviruses/genetics/metabolism/*pathogenicity ; Gene Expression Regulation, Neoplastic ; Host-Pathogen Interactions ; Interferon Regulatory Factors/genetics/metabolism ; Interferon Type I/genetics/*metabolism ; Mesothelioma/etiology/genetics/metabolism/*virology ; Mice ; Promoter Regions, Genetic ; *RNA Editing ; RNA, Double-Stranded/genetics/*metabolism ; Signal Transduction ; }, abstract = {Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.}, }
@article {pmid33692175, year = {2021}, author = {Shamseddin, M and Obacz, J and Garnett, MJ and Rintoul, RC and Francies, HE and Marciniak, SJ}, title = {Use of preclinical models for malignant pleural mesothelioma.}, journal = {Thorax}, volume = {76}, number = {11}, pages = {1154-1162}, pmid = {33692175}, issn = {1468-3296}, support = {BRC-1215-20014/DH_/Department of Health/United Kingdom ; G1002610/MRC_/Medical Research Council/United Kingdom ; MR/V028669/1/MRC_/Medical Research Council/United Kingdom ; MR/R009120/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; *Asbestos ; *Lung Neoplasms ; *Mesothelioma ; *Mesothelioma, Malignant ; Mice ; *Pleural Neoplasms ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations, spheroids and microfluidic chips have more recently been used to investigate the role of the three-dimensional environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice and patient-derived xenografts. Here, we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.}, }
@article {pmid33691361, year = {2021}, author = {Yu, M and Yu, M and Zhu, LJ and Yuan, XY and Zhang, X}, title = {[Expression and clinical significance of SETD2 in maligant pleural mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {2}, pages = {91-98}, doi = {10.3760/cma.j.cn121094-20200831-00505}, pmid = {33691361}, issn = {1001-9391}, support = {11-ZC02//The Key Program of Zhejiang Medical Science: Occupational Health Sciences/ ; 2019D002//The Funding of Zhejiang Academy of Medical Sciences/ ; }, mesh = {*Asbestos ; Histone-Lysine N-Methyltransferase ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Pleural Neoplasms/genetics ; Protein Serine-Threonine Kinases ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {Objective: To analyze the gene mutation profile in malignant pleural mesothelioma (MPM) and investigate the expression of high-frequency mutant genes and its relationship with clinicopathological parameters. To screen out key genes and clinicopathologic factors related to the prognosis of MPM patients. Methods: The second generation sequencing data, somatic mutation data and clinical pathological data of 86 MPM cases and gene chip expression data of 89 MPM cases were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) in March 2020. Summarize the gene mutation profile of tissue samples in the TCGA database and analyze the relationship between the expression level of high-frequency mutation genes and the clinicopathological characteristics, asbestos exposure history and prognosis of MPM patients. The genes significantly related to MPM prognosis were screened out for gene set enrichment analysis (GSEA) . Survival analysis and GSEA were performed for the selected key genes and clinicopathological features verification using the microarray expression data from the GEO database. Results: The top 10 genes with highest single nucleotide variations frequencies were BAP1, NF2, TP53, TTN, SETD2, LATS2, CCDC168, FAT4, PTCH1 and ZNF469. The high expression rates of NF2, TP53, SETD2 and CCDC168 genes in wild type were higher than those of mutated type, and the differences were statistically significant (P<0.05) . Cox multivariate analysis of TCGA data showed that MPM patients with epithelial type (HR=0.425, 95%CI: 0.235-0.767, P<0.01) and SETD2 low expression (HR=0.516, 95%CI: 0.307-0.868, P=0.011) had lower risk of death. The survival analysis of GEO data verified that patients with epithelial type MPM had longer survival time, while patients with sarcoma type MPM had shortest survival time (P<0.01) . GSEA showed that SETD2 was involved in G2M checkpoint, E2F targets, MYC signaling pathways, protein secretion, mitotic spindle, MTORC1 pathway, TGF-β pathway, androgen response and uv response. Conclusion: MPM is accompanied with higher frequency of gene mutations represented by BAP1, NF2, TP53, TTN, SETD2, LATS2 and so on. SETD2 expression level and epithelia type of MPM may be influential factors for MPM prognosis.}, }
@article {pmid33691360, year = {2021}, author = {Yu, M and Yu, M and Ying, SB and Yuan, XY and Jiang, ZQ and Lou, JL and Zhu, LJ and Zhang, X}, title = {[The impact of CD8 and CTLA-4 expression on histopathological character and survival in mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {2}, pages = {85-90}, doi = {10.3760/cma.j.cn121094-20200831-00506}, pmid = {33691360}, issn = {1001-9391}, support = {2017183851//The Project of Zhejiang Medical &amp; Health Science/ ; 2019D002//The Funding of Zhejiang Academy of Medical Sciences/ ; 11-ZC02//The Key Program of Zhejiang Medical Science: Occupational Health Sciences/ ; }, mesh = {CD8-Positive T-Lymphocytes ; CTLA-4 Antigen ; Humans ; Ki-67 Antigen ; *Mesothelioma ; *Mesothelioma, Malignant ; Retrospective Studies ; }, abstract = {Objective: To investigate the survival and death risk factors of mesothelioma cases stratified by the expression levels of CD8 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) , providing new clue to evaluate disease progression and clinical outcome. Methods: This was a retrospective case report, which included 47 clinically and pathologically confirmed mesothelioma cases on November 2016. Their clinical and pathological information, asbestos exposure history and survival data were collected. Infiltrated lymphocyte, 5-methylcytosine (5-mC) , CTLA-4, CD8 and Ki-67 antigen were detected using hematoxylin-eosin staining and immunohistochemistry. Survival time and death risk factors of mesothelioma patients with different CD8 and CTLA-4 protein expression characteristics were analyzed. And analyze the influence of Ki-67 expression on the survival of patients with different CD8 and CTLA-4 protein and gene expression characteristics. Results: Among the 47 cases, 63.8% (30/47) had low/medium level of infiltrated lymphocyte. The immunohistochemistry scores of CTLA-4, CD8, 5-mC and Ki-67 were 92.97 (54.95, 120.65) , 72.41 (36.62, 89.82) , 11.09 (3.40, 52.89) and 5.88 (2.41, 11.48) , respectively. Patients with CD8(high) CTLA-4(high) had higher 5-mC level than those with CD8(high) CTLA-4(low) (P<0.01) . The median survival time of 27 cases was 0.83±0.29 year. The median survival times of those with CD8(high) CTLA-4(high) and CD8(high) CTLA-4(low) were 0.58±0.51 year and 0.83±0.30 year, respectively (P=0.521) . The immunohistochemistry score of Ki-67 ≥5.88 was an independent death risk factor for patients with CD8(high) CTLA-4(low) (HR=8.40, P=0.01) . Under different CD8 and CTLA-4 protein expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 expression were 0.57±0.11 years and 2.31±0.46 years, respectively (P<0.01) . Under different CD8 and CTLA-4 mRNA expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 mRNA expression were 1.20±0.36 years and 3.38±0.43 years, respectively (P=0.018) . Conclusion: Mesothelioma case with high CD8 but low CTLA-4 content might coexist DNA hypomethylation. In the presence of high Ki-67 expression, their survival time appears to be shortened with increased death risk.}, }
@article {pmid33691359, year = {2021}, author = {Zhang, X}, title = {[Indispensable urgency for prevention and control of asbestos-related cancer].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {2}, pages = {81-84}, doi = {10.3760/cma.j.cn121094-20200831-00504}, pmid = {33691359}, issn = {1001-9391}, mesh = {*Asbestos ; *Asbestosis ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Neoplasms ; *Occupational Exposure ; }, }
@article {pmid33691040, year = {2021}, author = {García López, V}, title = {[Programs for Asbestos Abatement. Lessons from Poland].}, journal = {Archivos de prevencion de riesgos laborales}, volume = {24}, number = {1}, pages = {62-73}, doi = {10.12961/aprl.2021.24.01.06}, pmid = {33691040}, issn = {1578-2549}, mesh = {*Asbestos/adverse effects/analysis ; Europe ; Humans ; *Mesothelioma/epidemiology/etiology/prevention &amp; control ; *Occupational Exposure/prevention &amp; control ; Poland ; Spain ; }, abstract = {The commercialization of asbestos in Europe in the second half of the 20th century translated into consumption of millions of tons of this material. Occupational exposure to asbestos is controlled under the 2009 European Union Directive. Currently, through epidemiological surveillance and pathology registries (mainly mesotheliomas), it is possible to record past exposures. Despite prohibiting its use, large amounts of asbestos remain in buildings, infrastructures and vehicles, among others. The road to elimination of existing asbestos began with a 2013 European Parliament Resolution and the Opinion of the European Economic and Social Committee (2015 / C 251/03).To better understand barriers to implementing these plans, we reviewed the experience in Poland the only country that to date has implemented an action plan with great financial support, together with actions carried out in Spain generally, and Navarre specifically, given the latter's exhaustive registry of exposed workers.The enormous economic effort required to implement these plans, along with the environmental risks associated with asbestos abatement, require detailed planning, which should consider understanding why the objectives set by Poland, a benchmark country, have not been achieved to date.}, }
@article {pmid33678145, year = {2021}, author = {Carey, RN and Pfau, JC and Fritzler, MJ and Creaney, J and de Klerk, N and W Bill Musk, A and Franklin, P and Sodhi-Berry, N and Brims, F and Reid, A}, title = {Autoantibodies and cancer among asbestos-exposed cohorts in Western Australia.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {84}, number = {11}, pages = {475-483}, pmid = {33678145}, issn = {1528-7394}, support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Asbestos/*adverse effects ; Autoantibodies/*blood ; Female ; Humans ; Lung Neoplasms/chemically induced/*immunology ; Male ; Mesothelioma, Malignant/chemically induced/*immunology ; Middle Aged ; Mining ; Occupational Exposure/*adverse effects ; Western Australia ; }, abstract = {Asbestos exposure is associated with many adverse health conditions including malignant mesothelioma and lung cancer as well as production of autoantibodies. Autoantibodies may serve as biomarkers for asbestos exposure in patients with cancer, and autoimmune dysfunction has been linked to increased rates of various cancers. The aim of this study was to examine the hypothesis that autoantibodies are more frequent in asbestos-exposed individuals with either lung cancer or mesothelioma than those without these conditions. Asbestos-exposed individuals from Western Australia who had lung cancer (n = 24), malignant mesothelioma (n = 24), or no malignancy (n = 51) were tested for antinuclear autoantibodies (ANA) using indirect immunofluorescence and specific extractable nuclear autoantibodies (ENA) employing a multiplexed addressable laser bead immunoassay. Contrary to the hypothesis, data demonstrated that individuals without malignancy were more likely to be positive for ANA compared to those with cancer. However, autoantibodies to histone and Ro-60 were found to be associated with lung cancer. These results support a possible predictive value for specific autoantibodies in the early detection of lung cancer and/or in our understanding of the role of autoimmune processes in cancer. However, further studies are needed to identify specific target antigens for the antibodies.}, }
@article {pmid33673264, year = {2021}, author = {Arachi, D and Furuya, S and David, A and Mangwiro, A and Chimed-Ochir, O and Lee, K and Tighe, P and Takala, J and Driscoll, T and Takahashi, K}, title = {Development of the "National Asbestos Profile" to Eliminate Asbestos-Related Diseases in 195 Countries.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33673264}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Income ; *Mesothelioma ; World Health Organization ; }, abstract = {Worldwide, 230,000+ people die annually from asbestos-related diseases (ARDs). The World Health Organization (WHO) recommends that countries develop a National Asbestos Profile (NAP) to eliminate ARDs. For 195 countries, we assessed the global status of NAPs (A: bona fide NAP, B: proxy NAP, C: relevant published information, D: no relevant information) by national income (HI: high, UMI: upper-middle, LMI: lower-middle, LI: low), asbestos bans (banned, no-ban) and public data availability. Fourteen (7% of 195) countries were category A (having a bona fide NAP), while 98, 51 and 32 countries were categories B, C and D, respectively. Of the 14 category-A countries, 8, 3 and 3 were LMI, UMI and HI, respectively. Development of a bona fide NAP showed no gradient by national income. The proportions of countries having a bona fide NAP were similar between asbestos-banned and no-ban countries. Public databases useful for developing NAPs contained data for most countries. Irrespective of the status of national income or asbestos ban, most countries have not developed a NAP despite having the potential. The global status of NAP is suboptimal. Country-level data on asbestos and ARDs in public databases can be better utilized to develop NAPs for globally eliminating ARDs.}, }
@article {pmid33669843, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Frontini, A and Colosio, C and Belluso, E}, title = {Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33669843}, issn = {1660-4601}, mesh = {*Asbestos ; Environmental Exposure ; Humans ; Italy/epidemiology ; Lung ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure/adverse effects ; Tumor Microenvironment ; }, abstract = {Increased mortality due to malignant mesothelioma has been demonstrated by several epidemiologic studies in the area around Broni (a small town in Lombardy, northern Italy), where a factory producing asbestos cement was active between 1932 and 1993. Until now, the inorganic fiber burden in lungs has not been investigated in this population. The aim of this study is to assess the lung fiber burden in 72 individuals with previous occupational and/or anthropogenic environmental exposure to asbestos during the activity of an important asbestos cement factory. Inorganic fiber lung burden was assessed in autoptic samples taken from individuals deceased from asbestos-related diseases using a scanning electron microscope equipped with an energy-dispersive spectrometer. Significant differences in the detected amount of asbestos were pointed out among the three types of exposure. In most lung samples taken from patients who died of mesothelioma, very little asbestos (or, in some cases, no fibers) was found. Such subjects showed a significantly lower median amount of asbestos as compared to asbestosis. Almost no chrysotile was detected in the examined samples. Overall, crocidolite was the most represented asbestos, followed by amosite, tremolite/actinolite asbestos, and anthophyllite asbestos. There were significant differences in the amount of crocidolite and amosite fibers according to the kind of exposure. Overall, these findings provide novel insights into the link between asbestos exposure and mesothelioma, as well as the different impacts of the various types of asbestos on human health in relation to their different biopersistences in the lung microenvironment.}, }
@article {pmid33669318, year = {2021}, author = {Gariazzo, C and Binazzi, A and Alfò, M and Massari, S and Stafoggia, M and Marinaccio, A}, title = {Predictors of Lung Cancer Risk: An Ecological Study Using Mortality and Environmental Data by Municipalities in Italy.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33669318}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Cities ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/epidemiology/etiology ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; }, abstract = {Lung cancer (LC) mortality remains a consistent part of the total deaths occurring worldwide. Its etiology is complex as it involves multifactorial components. This work aims in providing an epidemiological assessment on occupational and environmental factors associated to LC risk by means of an ecological study involving the 8092 Italian municipalities for the period 2006-2015. We consider mortality data from mesothelioma as proxy of asbestos exposure, as well as PM2.5 and radon levels as a proxy of environmental origin. The compensated cases for occupational respiratory diseases, urbanization and deprivation were included as predictors. We used a negative binomial distribution for the response, with analysis stratified by gender. We estimated that asbestos is responsible for about 1.1% (95% CI: 0.8, 1.4) and 0.5% (95% CI: 0.2, 0.8) of LC mortality in males and females, respectively. The corresponding figures are 14.0% (95% CI: 12.5, 15.7) and 16.3% (95% CI: 16.2, 16.3) for PM2.5 exposure, and 3.9% (95% CI: 3.5, 4.2) and 1.6% (95% CI: 1.4, 1.7) for radon exposure. The assessment of determinants contribution to observed LC deaths is crucial for improving awareness of its origin, leading to increase the equity of the welfare system.}, }
@article {pmid33668103, year = {2021}, author = {Wortzel, JD and Wiebe, DJ and Elahi, S and Agawu, A and Barg, FK and Emmett, EA}, title = {Ascertainment Bias in a Historic Cohort Study of Residents in an Asbestos Manufacturing Community.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {5}, pages = {}, pmid = {33668103}, issn = {1660-4601}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/NH/NIH HHS/United States ; P30 ES013508/NH/NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Asbestos ; Cohort Studies ; Environmental Exposure ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Middle Aged ; *Occupational Exposure ; Young Adult ; }, abstract = {This paper describes follow-up for a cohort of 4530 residents living in the asbestos manufacturing community of Ambler, PA, U.S. in 1930. Using re-identified census data, cause and date of death data obtained from the genealogic website Ancestry.com, along with geospatial analysis, we explored relationships among demographic characteristics, occupational, paraoccupational and environmental asbestos exposures. We identified death data for 2430/4530 individuals. Exposure differed significantly according to race, gender, age, and recency of immigration to the U.S. Notably, there was a significant difference in the availability of year of death information for non-white vs. white individuals (odds ratio (OR) = 0.62 p-value < 0.001), females (OR = 0.53, p-value < 0.001), first-generation immigrants (OR = 0.67, p-value = 0.001), second-generation immigrants (OR = 0.31, p-value < 0.001) vs. non-immigrants, individuals aged less than 20 (OR = 0.31 p-value < 0.001) and individuals aged 20 to 59 (OR = 0.63, p-value < 0.001) vs. older individuals. Similarly, the cause of death was less often available for non-white individuals (OR = 0.42, p-value <0.001), first-generation immigrants and (OR = 0.71, p-value = 0.009), second-generation immigrants (OR = 0.49, p-value < 0.001), individuals aged less than 20 (OR = 0.028 p-value < 0.001), and individuals aged 20 to 59 (OR = 0.26, p-value < 0.001). These results identified ascertainment bias that is important to consider in analyses that investigate occupational, para-occupational and environmental asbestos exposure as risk factors for mortality in this historic cohort. While this study attempts to describe methods for assessing itemized asbestos exposure profiles for a community in 1930 using Ancestry.com and other publicly accessible databases, it also highlights how historic cohort studies likely underestimate the impact of asbestos exposure on vulnerable populations. Future work will aim to assess mortality patterns in this cohort.}, }
@article {pmid33662805, year = {2021}, author = {Kotsiou, OS and Gourgoulianis, KI and Zarogiannis, SG}, title = {The role of nitric oxide in pleural disease.}, journal = {Respiratory medicine}, volume = {179}, number = {}, pages = {106350}, doi = {10.1016/j.rmed.2021.106350}, pmid = {33662805}, issn = {1532-3064}, mesh = {Anti-Inflammatory Agents ; Asbestos/adverse effects ; Biomarkers/metabolism ; Humans ; Mesothelioma/diagnosis/etiology ; Nitric Oxide/metabolism/pharmacology/*physiology ; Nitric Oxide Donors/pharmacology ; Pleura/metabolism ; Pleural Diseases/diagnosis/*etiology/therapy ; Signal Transduction ; }, abstract = {Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.}, }
@article {pmid33660947, year = {2021}, author = {Guzmán-Casta, J and Carrasco-CaraChards, S and Guzmán-Huesca, J and Sánchez-Ríos, CP and Riera-Sala, R and Martínez-Herrera, JF and Peña-Mirabal, ES and Bonilla-Molina, D and Alatorre-Alexander, JA and Martínez-Barrera, LM and Rodríguez-Cid, JR}, title = {Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma.}, journal = {Thoracic cancer}, volume = {12}, number = {7}, pages = {1014-1022}, pmid = {33660947}, issn = {1759-7714}, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Mesothelioma, Malignant/*mortality ; Prognosis ; Progression-Free Survival ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years.<br><br>METHODS: This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression-free survival (PFS).<br><br>RESULTS: A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4-9.5 months) and median OS was 12&#x2009;months (95% CI: 11.3-12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment.<br><br>CONCLUSIONS: Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.}, }
@article {pmid33655329, year = {2021}, author = {Yamamoto, S and Lee, S and Ariyasu, T and Endo, S and Miyata, S and Yasuda, A and Harashima, A and Ohta, T and Kumagai-Τakei, N and Ito, T and Shimizu, Y and Srinivas, B and Sada, N and Nishimura, Y and Otsuki, T}, title = {Ingredients such as trehalose and hesperidin taken as supplements or foods reverse alterations in human T cells, reducing asbestos exposure-induced antitumor immunity.}, journal = {International journal of oncology}, volume = {58}, number = {4}, pages = {}, pmid = {33655329}, issn = {1791-2423}, mesh = {Asbestos/*adverse effects ; CD4-Positive T-Lymphocytes/drug effects/*immunology/metabolism ; Cells, Cultured ; *Dietary Supplements ; Hesperidin/*pharmacology ; Humans ; Interferon-gamma/immunology ; Interleukin-17/immunology ; Male ; Mesothelioma, Malignant/chemically induced/*immunology/prevention &amp; control ; Middle Aged ; Receptors, CXCR3/immunology ; Trehalose/*pharmacology ; }, abstract = {Exposure of human immune cells to asbestos causes a reduction in antitumor immunity. The present study aimed to investigate the recovery of reduced antitumor immunity by several ingredients taken as supplements or foods, including trehalose (Treh) and glycosylated hesperidin (gHesp). Peripheral blood CD4[+] cells were stimulated with IL‑2, anti‑CD3 and anti‑CD28 antibodies for 3 days, followed by further stimulation with IL‑2 for 7 days. Subsequently, cells were stimulated with IL‑2 for an additional 28 days. During the 28 days, cells were cultured in the absence or presence of 50 <em>µ</em>g/ml chrysotile asbestos fibers. In addition, cells were treated with 10 mM Treh or 10 <em>µ</em>M gHesp. Following culture for 28 days, reverse transcription‑quantitative PCR was performed to assess the expression levels of transcription factors, cytokines and specific genes, including matrix metalloproteinase‑7 (MMP‑7), nicotinamide nucleotide transhydrogenase (NNT) and C‑X‑C motif chemokine receptor 3, in unstimulated cells (fresh) and cells stimulated with PMA and ionomycin (stimuli). The results demonstrated that compared with the control group, chrysotile‑exposure induced alterations in MMP‑7, NNT and IL‑17A expression levels were not observed in the 'Treh' and 'gHesp' groups in stimulated cells. The results suggested that Treh and gHesp may reverse asbestos exposure‑induced reduced antitumor immunity in T helper cells. However, further investigation is required to confirm the efficacy of future trials involving the use of these compounds with high‑risk human populations exposed to asbestos, such as workers involved in asbestos‑handling activities.}, }
@article {pmid33652123, year = {2021}, author = {Sridharan, S and Taylor-Just, A and Bonner, JC}, title = {Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {73}, number = {}, pages = {105126}, pmid = {33652123}, issn = {1879-3177}, support = {P30 ES025128/ES/NIEHS NIH HHS/United States ; R01 ES020897/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Biomarkers ; Cell Line ; Cell Transformation, Neoplastic/*genetics ; Epithelial Cells/*drug effects/metabolism ; Male ; Mesothelioma/genetics ; Nanotubes, Carbon/*toxicity ; Osteopontin/*genetics ; Pleura/cytology ; RNA, Messenger ; Rats, Inbred F344 ; Rats ; }, abstract = {Mesothelioma is a cancer of the lung pleura primarily associated with inhalation of asbestos fibers. Multi-walled carbon nanotubes (MWCNTs) are engineered nanomaterials that pose a potential risk for mesothelioma due to properties that are similar to asbestos. Inhaled MWCNTs migrate to the pleura in rodents and some types cause mesothelioma. Like asbestos, there is a diversity of MWCNT types. We investigated the neoplastic potential of tangled (tMWCNT) versus rigid (rMWCNT) after chronic exposure using serial passages of rat mesothelial cells in vitro. Normal rat mesothelial (NRM2) cells were exposed to tMWCNTs or rMWCNTs for 45 weeks over 85 passages to determine if exposure resulted in transformation to a neoplastic phenotype. Rat mesothelioma (ME1) cells were used as a positive control. Osteopontin (OPN) mRNA was assayed as a biomarker of transformation by real time quantitative polymerase chain reaction (qPCR) and transformation was determined by a cell invasion assay. Exposure to rMWCNTs, but not tMWCNTs, resulted in transformation of NRM2 cells into an invasive phenotype that was similar to ME1 cells. Moreover, exposure of NRM2 cells to rMWCNTs increased OPN mRNA that correlated with cellular transformation. These data suggest that OPN is a potential biomarker that should be further investigated to screen the carcinogenicity of MWCNTs in vitro.}, }
@article {pmid33640705, year = {2021}, author = {Niu, X and Zhou, C and Hu, A and Su, L and Lin, D and Han, H and Lu, Y}, title = {Malignant mesothelioma without asbestos exposure diagnosed during EGFR-TKI treatment of lung adenocarcinoma: A case report.}, journal = {Cancer treatment and research communications}, volume = {27}, number = {}, pages = {100345}, doi = {10.1016/j.ctarc.2021.100345}, pmid = {33640705}, issn = {2468-2942}, mesh = {Adenocarcinoma of Lung/diagnosis/*drug therapy/genetics ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; ErbB Receptors/antagonists &amp; inhibitors/genetics ; Fatal Outcome ; Humans ; Lung Neoplasms/diagnosis/*drug therapy/genetics ; Male ; Mesothelioma, Malignant/*diagnosis/drug therapy/genetics/secondary ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/drug therapy/genetics/pathology ; Pleural Neoplasms/*diagnosis/drug therapy/genetics/pathology ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; }, abstract = {Synchronous malignant mesothelioma (MM) and lung carcinoma are extremely rare in patients without a history of asbestos exposure and poses tremendous difficulties in clinical management. We report a patient without asbestos exposure diagnosed with MM during EGFR-TKI treatment of lung adenocarcinoma (LUAD), who responded to first-line chemotherapy with pemetrexed plus carboplatin and failed to subsequent systemic therapy. Clinicians should be careful about the possibility of MM comorbidity in LUAD patients whose lesions respond differently to EGFR-TKI, even in those without a history of asbestos exposure.}, }
@article {pmid33635114, year = {2021}, author = {Hoton, D and Luyckx, M and Galant, C and Dano, H}, title = {Hibernoma-like Changes and TFE3 Expression in Mesothelioma Mimicking TFE3-Translocation Renal Cell Carcinoma: A Diagnostic Pitfall.}, journal = {International journal of surgical pathology}, volume = {29}, number = {6}, pages = {627-630}, doi = {10.1177/1066896921998000}, pmid = {33635114}, issn = {1940-2465}, mesh = {Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/analysis/genetics/*metabolism ; Biomarkers, Tumor/analysis/genetics/*metabolism ; Carcinoma, Renal Cell/diagnosis/pathology ; Female ; Humans ; Kidney Neoplasms/diagnosis/pathology ; Lipoma/diagnosis/pathology ; Mesothelioma/*diagnosis/genetics/secondary ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/genetics/secondary ; Peritoneum/pathology ; Translocation, Genetic ; }, abstract = {The long delay between asbestos exposure and the development of mesothelioma will likely result in an increased incidence of mesothelioma in our industrialized societies. Radiation therapy is another factor known to induce these tumors. We describe a rare case of foamy looking mesothelioma in a 63-year-old patient with a long oncology history of a supposed peritoneal carcinomatosis. The pathologist was faced with a diagnostic pitfall as this peritoneal clear cell tumor expressed transcription factor binding to immunoglobulin heavy constant mu enhancer 3 (TFE3) at the nuclear level. Fortunately, the pathologist performed an extensive panel of immunomarkers, leading to a final diagnosis of epithelioid mesothelioma. Thus, we describe the first case of mesothelioma expressing TFE3. Note that there was no rearrangement of TFE3 in fluorescence in situ hybridization.}, }
@article {pmid33624546, year = {2021}, author = {Rossi, G and Caroli, G and Caruso, D and Stella, F and Davoli, F}, title = {Pseudocarcinomatous Mesothelioma: A Hitherto Unreported Presentation closely simulating primary lung cancer.}, journal = {International journal of surgical pathology}, volume = {29}, number = {7}, pages = {775-779}, doi = {10.1177/1066896921997559}, pmid = {33624546}, issn = {1940-2465}, mesh = {Adenocarcinoma of Lung/*diagnosis ; Aged ; Diagnosis, Differential ; Humans ; Lung/diagnostic imaging ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma, Malignant/*diagnosis/pathology ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {Malignant mesothelioma (MM) has a wide range of clinical, radiologic, and pathologic presentations, mimicking lung cancer or interstitial lung diseases when predominantly involving the lung parenchyma. The case herein refers to a 79-year-old man, active smoker without asbestos exposure, incidentally discovered to have a pulmonary nodule in the right upper lobe (1.5 cm). The lesion was misinterpreted as primary lung adenocarcinoma at the frozen section in light of the predominant lepidic growth pattern. Definitive examination confirmed neoplastic proliferation along alveolar structures. However, the unusual globous shape of tumor cells along the alveoli abruptly merging with normal pneumocytes prompted us to perform some immunostains that surprisingly revealed a mesothelial differentiation (positive staining with calretinin, cytokeratins (CK5/6), D2-40, and negativity with BRCA-associated protein 1 (BAP1), Thyroid Transcription Factor 1 [TTF-1], claudin-4, carcinoembryonic antigen [CEA], and napsin). MM represents the pathologic counterpart of so-called pseudomesotheliomatous carcinoma, since it appears as a localized pulmonary neoplastic nodule displaying a predominant lepidic growth pattern (pseudocarcinomatous mesothelioma). The challenging diagnostic features of this unique case and a review of similar cases in the literature are discussed.}, }
@article {pmid33622366, year = {2021}, author = {Baur, X and Frank, AL}, title = {Ongoing downplaying of the carcinogenicity of chrysotile asbestos by vested interests.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {16}, number = {1}, pages = {6}, pmid = {33622366}, issn = {1745-6673}, abstract = {Industries that mine, manufacture and sell asbestos or asbestos-containing products have a long tradition of promoting the use of asbestos, while placing the burden of economic and health costs on workers and society. This has been successfully done in recent years and decades in spite of the overwhelming evidence that all asbestos types are carcinogenic and cause asbestosis. In doing so, the asbestos industry has undermined the WHO campaign to reach a worldwide ban of asbestos and to eliminate asbestos-related diseases. Even worse, in recent years they succeeded in continuing asbestos mining and consuming in the range of about 1.3 million tons annually. Nowadays, production takes place predominantly in Russia, Kazakhstan and China. Chrysotile is the only asbestos type still sold and represents 95% of asbestos traded over the last century.The asbestos industry, especially its PR agency, the International Chrysotile Association, ICA, financed by asbestos mining companies in Russia, Kazakhstan and Zimbabwe and asbestos industrialists in India and Mexico, continues to be extremely active by using slogans such as chrysotile can be used safely.Another approach of the asbestos industry and of some of its insurance agencies is to broadly defeat liability claims of asbestos victims.In doing so they systematically use inappropriate science produced by their own and/or by industry-affiliated researchers. Some of the latter were also engaged in producing defense material for other industries including the tobacco industry. Frequent examples of distributing such disinformation include questioning or denying established scientific knowledge about adverse health effects of asbestos. False evidence continues to be published in scientific journals and books.The persisting strong influence of vested asbestos-related interests in workers and public health issues including regulations and compensation necessitate ongoing alertness, corrections and appropriate reactions in scientific as well as public media and policy advisory bodies.}, }
@article {pmid33617892, year = {2021}, author = {Ierardi, AM and Urban, A and Marsh, GM}, title = {A quantitative weight of evidence assessment of Hill's guidelines for causal inference for cosmetic talc as a cause of mesothelioma.}, journal = {Toxicology and applied pharmacology}, volume = {417}, number = {}, pages = {115461}, doi = {10.1016/j.taap.2021.115461}, pmid = {33617892}, issn = {1096-0333}, mesh = {Animals ; Causality ; Humans ; Mesothelioma/*chemically induced/diagnosis/epidemiology ; Pleural Neoplasms/*chemically induced/diagnosis/epidemiology ; Probability ; Risk Assessment ; Risk Factors ; Talc/*adverse effects ; Time Factors ; Toxicity Tests ; }, abstract = {Cosmetic talc has been suggested to cause mesothelioma. To assess a potential causal relationship between cosmetic talc and mesothelioma, a quantitative weight of evidence analysis was performed in accordance with Hill's nine original guidelines for causal inference using a published empirical model to weight each respective guideline. Various epidemiological, toxicological, and exposure studies related to cosmetic talc and risk of mesothelioma were included in an evaluation of each of Hill's guidelines. Probabilities that the guidelines were true were assigned based on expert judgment. We applied a sensitivity analysis to evaluate the variability of our probability estimates. The overall probability of causality for cosmetic talc and mesothelioma was approximately 1.29% (range: 0.73%-3.96%). This low probability of causality supports the conclusion that cosmetic talc is not related to the development of mesothelioma.}, }
@article {pmid33614517, year = {2021}, author = {Cheng, YY and Yuen, ML and Jin, H}, title = {Editorial: Epigenetic Modifications in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {650136}, doi = {10.3389/fonc.2021.650136}, pmid = {33614517}, issn = {2234-943X}, }
@article {pmid33614198, year = {2021}, author = {Pestak, CR and Boyce, TW and Myers, OB and Hopkins', LO and Wiggins, CL and Wissore, BR and Sood, A and Cook, LS}, title = {A Population-Based Feasibility Study of Occupation and Thoracic Malignancies in New Mexico.}, journal = {Southwest journal of pulmonary &amp; critical care}, volume = {22}, number = {1}, pages = {23-25}, pmid = {33614198}, issn = {2160-6773}, support = {KL2 RR031976/RR/NCRR NIH HHS/United States ; P30 CA118100/CA/NCI NIH HHS/United States ; UL1 TR000041/TR/NCATS NIH HHS/United States ; HHSN261201800014I/CA/NCI NIH HHS/United States ; U01 GM132175/GM/NIGMS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; HHSN261201800014C/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Occupational exposures in mining and oil/gas extraction are known risk factors for thoracic malignancies (TMs). Given the relatively high proportion of these industries in New Mexico (NM), we conducted a feasibility study of adult lifetime occupational history among TM cases. We hypothesized a higher proportion of occupational TM in NM relative to the estimated national average of 10-14%.<br><br>METHODS: We identified incident TM cases through the population-based New Mexico Tumor Registry (NMTR), from 2017-2018. Cases completed a telephone interview. An adjudication panel reviewed case histories and classified cancers as probable, possible, or non-occupational related, taking into account the presence, duration, and latency of exposures. We characterized recruitment and describe job titles and exposures among those with occupational TMs. We also compared the distributions of industry between those with and without occupational TM.<br><br>RESULTS: The NMTR identified 400 eligible TM cases, 290 of which were available to be recruited (n=285 lung/bronchial cancer; n=5 mesotheliomas). Of the latter, 60% refused and 18% were deceased, 9% had invalid addresses, 11% were unable to be reached by telephone, and 3% were too ill to participate. The 43 cases who completed an interview held 236 jobs. A total of 33% of cases were classified as probable occupational TM and 5% as possible occupational TM.<br><br>CONCLUSIONS: High rates of early mortality and refusals were significant barriers to study participation. Nonetheless, the proportion of probable occupational TMs greatly exceeded the estimated national average, highlighting the need for further study of occupational TM in the state.}, }
@article {pmid33577225, year = {2022}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Miranda, RN and Fournier, KF and Raghav, KP and Ramalingam, P}, title = {Malignant Peritoneal Mesothelioma Associated With Endometriosis: A Clinicopathologic Study of 15 Cases.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {41}, number = {1}, pages = {59-67}, doi = {10.1097/PGP.0000000000000762}, pmid = {33577225}, issn = {1538-7151}, mesh = {Adolescent ; Adult ; Aged ; Cohort Studies ; Cytoreduction Surgical Procedures ; Endometriosis/complications/*pathology/surgery ; Female ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Mesothelioma, Malignant/complications/*pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/complications/*pathology/surgery ; Peritoneum/pathology/surgery ; Young Adult ; }, abstract = {Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including "adhesion-like" appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.}, }
@article {pmid33574130, year = {2021}, author = {Sato, T and Mukai, S and Ikeda, H and Mishiro-Sato, E and Akao, K and Kobayashi, T and Hino, O and Shimono, W and Shibagaki, Y and Hattori, S and Sekido, Y}, title = {Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {5}, pages = {921-931}, doi = {10.1158/1541-7786.MCR-20-0637}, pmid = {33574130}, issn = {1557-3125}, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; Cell Proliferation/physiology ; Cytoskeletal Proteins/*metabolism ; Female ; Guanine Nucleotide Exchange Factors/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Mechanistic Target of Rapamycin Complex 1/*metabolism ; Mesothelioma, Malignant/*genetics/pathology ; Mice ; Mice, Nude ; Ras Homolog Enriched in Brain Protein/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor that typically develops after a long latency following asbestos exposure. Although mechanistic target of rapamycin complex 1 (mTORC1) activation enhances MM cell growth, the mTORC1 inhibitor everolimus has shown limited efficacy in clinical trials of MM patients. We explored the mechanism underlying mTORC1 activation in MM cells and its effects on cell proliferation and progression. Analysis of the expression profiles of 87 MMs from The Cancer Genome Atlas revealed that 40 samples (46%) displayed altered expression of RPTOR (mTORC1 component) and genes immediately upstream that activate mTORC1. Among them, we focused on RHEB and RHEBL1, which encode direct activators of mTORC1. Exogenous RHEBL1 expression enhanced MM cell growth, indicating that RHEB-mTORC1 signaling acts as a pro-oncogenic cascade. We investigated molecules that directly activate RHEBs, identifying SmgGDS as a novel RHEB-binding protein. SmgGDS knockdown reduced mTORC1 activation and inhibited the proliferation of MM cells with mTORC1 activation. Interestingly, SmgGDS displayed high binding affinity with inactive GDP-bound RHEBL1, and its knockdown reduced cytosolic RHEBL1 without affecting its activation. These findings suggest that SmgGDS retains GDP-bound RHEBs in the cytosol, whereas GTP-bound RHEBs are localized on intracellular membranes to promote mTORC1 activation. We revealed a novel role for SmgGDS in the RHEB-mTORC1 pathway and its potential as a therapeutic target in MM with aberrant mTORC1 activation. IMPLICATIONS: Our data showing that SmgGDS regulates RHEB localization to activate mTORC1 indicate that SmgGDS can be used as a new therapeutic target for MM exhibiting mTORC1 activation.}, }
@article {pmid33567673, year = {2021}, author = {Keller, M and Reis, K and Hjerpe, A and Dobra, K and Aspenström, P}, title = {Cytoskeletal Organization Correlates to Motility and Invasiveness of Malignant Mesothelioma Cells.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33567673}, issn = {2072-6694}, support = {CAN 2017/527//Cancerfonden/ ; CAN 2015/479//Cancerfonden/ ; Beslut 2017/160(180)//Stiftelsen Olle Engkvist Byggm&#xe4;stare/ ; }, abstract = {Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link between asbestos exposure and progression of MM. Direct invasion of the surrounding tissues is the main feature of MM, which is dependent on dysregulated communication between the mesothelium and the microenvironment. This communication is dependent on the dynamic organization of the cytoskeleton. We have analyzed the organization and function of key cytoskeletal components in MM cell lines of increasing malignancies measured as migratory and invasive properties, and we show that highly malignant and invasive MM cells have an organization of the actin filament and vimentin systems that is distinct from the less malignant MM cell lines. In addition, the Hippo tumor suppressor pathway was inactivated in the invasive MM cells, which was seen as increased YAP nuclear localization.}, }
@article {pmid33567623, year = {2021}, author = {Lococo, F}, title = {Malignant Pleural Mesothelioma: Time Is Running Out.}, journal = {Journal of clinical medicine}, volume = {10}, number = {4}, pages = {}, pmid = {33567623}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare but highly malignant disease of the pleura usually related to asbestos exposure [...].}, }
@article {pmid33562413, year = {2021}, author = {Emmett, EA}, title = {Asbestos in High-Risk Communities: Public Health Implications.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33562413}, issn = {1660-4601}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos/toxicity ; Female ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma/epidemiology/etiology ; Montana ; *Occupational Exposure ; Pennsylvania ; Public Health ; Turkey ; Western Australia/epidemiology ; }, abstract = {Asbestos-related diseases (ARDs)-mesothelioma, lung cancer, and asbestosis-are well known as occupational diseases. As industrial asbestos use is eliminated, ARDs within the general community from para-occupational, environmental, and natural exposures are more prominent. ARD clusters have been studied in communities including Broni, Italy; Libby, Montana; Wittenoom, Western Australia; Karain, Turkey; Ambler, Pennsylvania; and elsewhere. Community ARDs pose specific public health issues and challenges. Community exposure results in higher proportions of mesothelioma in women and a younger age distribution than occupational exposures. Exposure amount, age at exposure, fiber type, and genetic predisposition influence ARD expression; vulnerable groups include those with social and behavioral risk, exposure to extreme events, and genetic predispositions. To address community exposure, regulations should address all carcinogenic elongated mineral fibers. Banning asbestos mining, use, and importation will not reduce risks from asbestos already in place. Residents of high-risk communities are characteristically exposed through several pathways differing among communities. Administrative responsibility for controlling environmental exposures is more diffuse than for workplaces, complicated by diverse community attitudes to risk and prevention and legal complexity. The National Mesothelioma Registries help track the identification of communities at risk. High-risk communities need enhanced services for screening, diagnosis, treatment, and social and psychological support, including for retired asbestos workers. Legal settlements could help fund community programs. A focus on prevention, public health programs, particularization to specific community needs, and participation is recommended.}, }
@article {pmid33562138, year = {2021}, author = {Vogl, M and Rosenmayr, A and Bohanes, T and Scheed, A and Brndiar, M and Stubenberger, E and Ghanim, B}, title = {Biomarkers for Malignant Pleural Mesothelioma-A Novel View on Inflammation.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33562138}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient's outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.}, }
@article {pmid33555117, year = {2021}, author = {Miyagawa, C and Takaya, H and Sakai, K and Nishio, K and Konishi, M and Minamiguchi, S and Shimada, T and Matsumura, N}, title = {A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review.}, journal = {The oncologist}, volume = {26}, number = {5}, pages = {356-361}, pmid = {33555117}, issn = {1549-490X}, mesh = {Adolescent ; Anaplastic Lymphoma Kinase/genetics ; Calmodulin-Binding Proteins/genetics ; Exons/genetics ; Female ; Gene Rearrangement ; Humans ; Membrane Proteins/genetics ; *Mesothelioma, Malignant ; Nerve Tissue Proteins/genetics ; Oncogene Proteins, Fusion/genetics ; *Peritoneal Neoplasms/drug therapy/genetics ; }, abstract = {Recently, several malignant peritoneal mesotheliomas (MPMs), occurring in young women without asbestos exposure and with fusion genes such as anaplastic lymphoma kinase (ALK) and Ewing sarcoma breakpoint region 1, have been reported. In the present case, we encountered MPM with STRN-ALK fusion in a 17-year-old female adolescent. The case did not respond to chemotherapy and is currently in a clinical trial of alectinib. This is the fourth reported case of MPM with STRN-ALK fusion. Of the 45 cancer cases with STRN-ALK fusion in which the fusion partners were examined, all cases except for the current case showed fusion of exon 3 of STRN and exon 20 of ALK. This is the first case with fusion of exon 2 of STRN and exon 20 of ALK. Further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion. KEY POINTS: Malignant peritoneal mesotheliomas (MPMs) can occur in young women without asbestos exposure and show fusion genes that activate anaplastic lymphoma kinase (ALK) by gene rearrangement. ALK rearrangement and the fusion partner can be detected by companion diagnostics and by next generation sequencing. Patients with MPMs with ALK rearrangement may benefit from target therapy.}, }
@article {pmid33544514, year = {2021}, author = {Franko, A and Goricar, K and Dodic Fikfak, M and Kovac, V and Dolzan, V}, title = {The role of polymorphisms in glutathione-related genes in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {55}, number = {2}, pages = {179-186}, pmid = {33544514}, issn = {1581-3207}, mesh = {Aged ; Asbestos/toxicity ; Asbestosis/*genetics ; Cross-Sectional Studies ; Female ; Genotype ; Glutamate-Cysteine Ligase/genetics ; Glutathione/*genetics ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Humans ; Male ; Mesothelioma, Malignant/*genetics ; Middle Aged ; Pleural Diseases/*genetics ; *Polymorphism, Genetic ; Regression Analysis ; Smoking/epidemiology ; }, abstract = {BACKGROUND: The study investigated the influence of GCLC, GCLM, GSTM1, GSTT1 and GSTP1 polymorphisms, as well as the influence of interactions between polymorphism and interactions between polymorphisms and asbestos exposure, on the risk of developing pleural plaques, asbestosis and malignant mesothelioma (MM).<br><br>SUBJECTS AND METHODS: The cross sectional study included 940 asbestos-exposed subjects, among them 390 subjects with pleural plaques, 147 subjects with asbestosis, 225 subjects with MM and 178 subjects with no asbestos-related disease. GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272 genotypes were determined using PCR based methods. In statistical analysis, logistic regression was used.<br><br>RESULTS: GSTT1 null genotype was associated with the decreased risk for pleural plaques (OR = 0.63; 95% CI = 0.40-0.98; p = 0.026) and asbestosis (OR = 0.51; 95% CI = 0.28-0.93; p = 0.028), but not for MM. A positive association was found between GSTP1 rs1695 AG + GG vs. AA genotypes for MM when compared to pleural plaques (OR = 1.39; 95% CI = 1.00-1.94; p = 0.049). The interactions between different polymorphisms showed no significant influence on the risk of investigated asbestos-related diseases. The interaction between GSTT1 null polymorphism and asbestos exposure decreased the MM risk (OR = 0.17; 95% CI = 0.03-0.85; p = 0.031).<br><br>CONCLUSIONS: Our findings suggest that GSTT1 null genotype may be associated with a decreased risk for pleural plaques and asbestosis, may modify the association between asbestos exposure and MM and may consequently act protectively on MM risk. This study also revealed a protective effect of the interaction between GSTP1 rs1695 polymorphism and asbestos exposure on MM risk.}, }
@article {pmid33540554, year = {2021}, author = {De Rienzo, A and Coleman, MH and Yeap, BY and Severson, DT and Wadowski, B and Gustafson, CE and Jensen, RV and Chirieac, LR and Richards, WG and Bueno, R}, title = {Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {3}, pages = {}, pmid = {33540554}, issn = {2072-6694}, support = {P30 CA006516/CA/NCI NIH HHS/United States ; RO1CA120528//National Cancer Research Institute/ ; }, abstract = {Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.}, }
@article {pmid33538989, year = {2021}, author = {Nadal, E and Bosch-Barrera, J and Cedrés, S and Coves, J and García-Campelo, R and Guirado, M and López-Castro, R and Ortega, AL and Vicente, D and de Castro-Carpeño, J}, title = {SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020).}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {23}, number = {5}, pages = {980-987}, pmid = {33538989}, issn = {1699-3055}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/toxicity ; Carcinogens/toxicity ; Combined Modality Therapy/methods ; Cytoreduction Surgical Procedures ; Deoxycytidine/analogs &amp; derivatives/therapeutic use ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Immunotherapy/methods ; Medical Oncology ; Mesothelioma, Malignant/*diagnosis/etiology/pathology/*therapy ; Neoplasm Staging ; Pemetrexed/therapeutic use ; Platinum Compounds/therapeutic use ; Pleural Neoplasms/*diagnosis/etiology/pathology/*therapy ; Radiotherapy/methods ; Societies, Medical ; Spain ; Vinorelbine/therapeutic use ; Gemcitabine ; }, abstract = {Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.}, }
@article {pmid33537296, year = {2020}, author = {Rossini, M and Martini, F and Torreggiani, E and Fortini, F and Aquila, G and Sega, FVD and Patergnani, S and Pinton, P and Maniscalco, P and Cavallesco, G and Rizzo, P and Tognon, M}, title = {Metformin Induces Apoptosis and Inhibits Notch1 in Malignant Pleural Mesothelioma Cells.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {534499}, pmid = {33537296}, issn = {2296-634X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related cancer arising from the mesothelial cells lining the pleural cavity. MPM is characterized by a silent clinical progression and a highly resistance to conventional chemo/radio-therapies. MPM patients die in a few months/years from diagnosis. Notch signaling is a well-conserved cell communication system, which regulates many biological processes. In humans, the dysregulation of Notch pathway potentially contributes to cancer onset/progression, including MPM. Metformin is the first-line drug used to treat type 2 diabetes mellitus. Metformin is proven to be an effective antitumor drug in preclinical models of different types of cancer. To date, clinical efficacy is being studied in many clinical trials. In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated. MPM cells showed high levels of Notch1 activation compared to normal pleural mesothelial cells. Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.}, }
@article {pmid33533198, year = {2021}, author = {Fukui, T and Okubo, T and Tanimoto, N and Okuma, H and Shiina, Y and Kohama, M and Yamada, J and Funada, Y and Ikura, Y}, title = {Malignant pleural mesothelioma in a patient with pneumothorax: A cumbersome subtype both clinically and pathologically.}, journal = {Thoracic cancer}, volume = {12}, number = {6}, pages = {974-977}, pmid = {33533198}, issn = {1759-7714}, mesh = {Female ; Humans ; Mesothelioma, Malignant/*complications/pathology ; Middle Aged ; Pleural Neoplasms/*complications/pathology ; Pneumothorax/*etiology/physiopathology ; }, abstract = {Here, we report a case of malignant pleural mesothelioma (MPM) that was very difficult to diagnose. A 62-year-old woman with a surgical history of recurrent bilateral pneumothorax was admitted to our hospital with severe dysphagia. Computed tomography (CT) detected stenosis in the lower esophagus. Immunohistochemical examination of a biopsy sample from the stenotic region was suggestive of MPM. Chemotherapy was initiated, but the patient soon weakened and died. Autopsy revealed atypical cells, identical to those seen in the biopsy sample which had spread into the stenotic esophagus and entire thoracic cavity. Although neither pleural thickening/nodules nor asbestos bodies were observed, we finally diagnosed the tumor as a biphasic-type MPM. We re-examined previous surgical specimens of pneumothorax and acknowledged foci of bland mesothelial cell proliferation which had the same pathological findings as tumor cells at autopsy. The lack of asbestos exposure and pleural thickening, an initial manifestation of pneumothorax, and faint cytological atypia prevented an early diagnosis. In cases of recurrent pneumothorax in elderly patients, MPM should be included in the differential diagnosis.}, }
@article {pmid33533181, year = {2021}, author = {Piro, R and Fontana, M and Livrieri, F and Menzella, F and Casalini, E and Taddei, S and De Giorgi, F and Facciolongo, N}, title = {Pleural mesothelioma: When echo-endoscopy (EUS-B-FNA) leads to diagnosis in a minimally invasive way.}, journal = {Thoracic cancer}, volume = {12}, number = {6}, pages = {981-984}, pmid = {33533181}, issn = {1759-7714}, mesh = {Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Female ; Humans ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Pleural Neoplasms/*diagnostic imaging ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related and locally invasive tumor with poor prognosis. The acquisition of histological material is mandatory in order to establish a diagnosis. In this situation, the sampling of tissue is generally performed via a thoracoscopic pleural biopsy, either medically or surgically. The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or transesophageal fine needle aspiration with an EBUS scope (EUS-B-FNA) of pleural lesions have only rarely been reported due to the theoretical limitations of tissue acquisition in such cases. We herein report a rare case of MPM successfully diagnosed via EUS-B-FNA in a 49-year-old woman with an unusual presentation characterized by solid thickening in the right mediastinal pleura.}, }
@article {pmid33533080, year = {2021}, author = {Dell, LD and Gallagher, AE and Yost, LJ and Mundt, KA}, title = {Integration of Evidence on Community Cancer Risks from Elongate Mineral Particles in Silver Bay, Minnesota.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {41}, number = {9}, pages = {1674-1692}, pmid = {33533080}, issn = {1539-6924}, mesh = {*Environmental Exposure ; Humans ; Minerals/*toxicity ; Minnesota ; Neoplasms/*chemically induced ; Risk Factors ; }, abstract = {The potential for cancer-related risks to community members from ambient exposure to elongate mineral particles (EMPs) in taconite processing has not been formally evaluated. We evaluated 926 ambient air samples including 12,928 EMPs (particle structures with length-to-width ratio ≥3:1) collected over 26 years near a taconite processing facility in Silver Bay, Minnesota. Eighty-two percent of EMPs were ≤3 μm in length and 97% of EMPs had an average aspect ratio <20:1. A total of 935 (7.3%) EMPs had length >5 μm and AR ≥3:1. Average ambient concentration of NIOSH countable amphibole EMPs over all years was 0.000387 EMPs per cubic centimeter (EMP/cm[3]). Of 12,765 nonchrysotile EMPs, the number of amphiboles with length and width dimensions that correlate best with asbestos-related carcinogenicity ranged from four (0.03%) to 13 (0.1%) and the associated ambient amphibole air concentrations ranged from 0.000003 to 0.000007 EMP/cm[3] . After 65 years of taconite processing in Silver Bay, evidence of an increased risk of mesothelioma and lung cancer in community members who did not work in the taconite industry is lacking. The absence of an increased risk of asbestos-related cancer in the Silver Bay community is coherent with supporting evidence from epidemiological and toxicological studies, as well as ambient exposure data and lake sediment data collected in Minnesota Iron Range communities. Collectively, the data provide consistent evidence that nonasbestiform amphibole minerals lack the carcinogenic potential exhibited by amphibole asbestos.}, }
@article {pmid33515502, year = {2021}, author = {Nowak, AK}, title = {New and old treatments for malignant mesothelioma: not just immunotherapy.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {6}, pages = {547-549}, doi = {10.1016/S2213-2600(20)30516-6}, pmid = {33515502}, issn = {2213-2619}, mesh = {Deoxycytidine/analogs &amp; derivatives ; Humans ; Immunotherapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy ; Gemcitabine ; }, }
@article {pmid33509005, year = {2021}, author = {Cook, AM and McDonnell, A and Millward, MJ and Creaney, J and Hasani, A and McMullen, M and Meniawy, T and Robinson, BWS and Lake, RA and Nowak, AK}, title = {A phase 1b clinical trial optimizing regulatory T cell depletion in combination with platinum-based chemotherapy in thoracic cancers.}, journal = {Expert review of anticancer therapy}, volume = {21}, number = {5}, pages = {465-474}, doi = {10.1080/14737140.2021.1882308}, pmid = {33509005}, issn = {1744-8328}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; *Carcinoma, Non-Small-Cell Lung/drug therapy ; Cisplatin ; Cyclophosphamide/administration &amp; dosage/toxicity ; Humans ; *Lung Neoplasms/drug therapy ; Pemetrexed ; Platinum/therapeutic use ; T-Lymphocytes, Regulatory ; }, abstract = {Background: Single-agent cyclophosphamide can deplete regulatory T-cells (Treg). We aimed to determine optimal dosing and scheduling of oral cyclophosphamide, alongside pemetrexed-based chemotherapy, to deplete Treg in mesothelioma or non-small-cell lung cancer patients.Methods: 31 Patients received pemetrexed ± cisplatin or carboplatin on day 1 of a 21-day cycle (maximum 6 cycles). From cycle two, patients received cyclophosphamide, 50 mg/day, with intrapatient escalation to maximum 100/150 mg/day alternately. Immunological changes were examined by flow cytometry. Primary endpoint was Treg proportion of CD4[+] T-cells, with doses tailored to target Treg nadir <4%.Results: Reduction in Treg proportion was observed on day 8 of all cycles, and was not augmented by cyclophosphamide. Few patients achieved the <4% Treg target. Treg proliferation reached nadir one week after chemotherapy, and peaked on day 1 of the subsequent cycle. Efficacy parameters were similar to chemotherapy alone. Seventeen percent of patients ceased cyclophosphamide due to toxicity.Conclusions: Specific Treg depletion to the degree seen with single-agent cyclophosphamide was not observed during pemetrexed-based chemotherapy. This study highlights the poor evidence basis for use of cyclophosphamide as an immunotherapeutic in combination with chemotherapy, and the importance of detailed flow cytometry studies.Trial registration: Clinical trial registration: www.anzctr.org.au identifier is ACTRN12609000260224.}, }
@article {pmid33506658, year = {2020}, author = {Barone Adesi, F and Bruno, C and Calisti, R and Chellini, E and Comba, P and Consonni, D and Fazzo, L and Fedeli, U and Forastiere, F and Magnani, C and Marinaccio, A and Merler, E and Mirabelli, D and Ricci, P and Terracini, B}, title = {[Effects of Asbestos on Human Health. Document of the Italian Epidemiological Association (AIE)].}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {5-6}, pages = {327-338}, doi = {10.19191/EP20.5-6.A001.064}, pmid = {33506658}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; *Asbestosis/epidemiology/etiology ; Carcinogens/toxicity ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Exposure/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: the Italian Epidemiological Association (AIE) intends to formulate assessments and recommendations on the most relevant and critical aspects in the preparation, conduct, and interpretation of epidemiological investigations on the health effects of exposure to asbestos and asbestos-like fibres.<br><br>the document was prepared by a working group of AIE associates, with a broad curriculum of epidemiological investigations, starting from the evaluation of scientific evidence, and was subsequently evaluated by the AIE governing body.<br><br>RESULTS: the topics covered included: &#x2022; consumption and presence of asbestos; &#x2022; association between asbestos exposure and disease; &#x2022; epidemiological surveillance of asbestos related diseases in Italy; &#x2022; risk function for asbestos related diseases; &#x2022; increased risk and anticipation of the disease; &#x2022; interaction between asbestos and other carcinogens; &#x2022; diagnosis in epidemiological studies; &#x2022; assessment of exposure to asbestos; &#x2022; epidemiological evidence on asbestos related diseases.<br><br>CONCLUSIONS: the document ends with a summary of the conclusions of scientific research shared by AIE, with reflection on the methodology to be followed for the application at individual level of the results of epidemiological studies, and the proposal of themes on which to direct research.}, }
@article {pmid33502280, year = {2021}, author = {Ringgaard Petersen, T and Panou, V and Meristoudis, C and Weinreich, UM and Røe, OD}, title = {Clinical prognostic factors in pleural mesothelioma: best supportive care and anti-tumor treatments in a real-life setting.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {60}, number = {4}, pages = {521-527}, doi = {10.1080/0284186X.2021.1876246}, pmid = {33502280}, issn = {1651-226X}, mesh = {Female ; Humans ; *Lung Neoplasms/therapy ; *Mesothelioma/therapy ; *Pleural Neoplasms/drug therapy ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: This study aims to investigate patient- and disease characteristics associated with survival in malignant pleural mesothelioma (MPM) patients with anti-tumor treatment or with best supportive care (BSC).<br><br>MATERIALS AND METHODS: Consecutive MPM cases diagnosed in North Denmark Region from 1972 to 2015 were reevaluated and verified by two pathologists using modern immunohistochemical techniques. Danish registries and hospital records were used to gather patient-, asbestos exposure-, and disease information.<br><br>RESULTS: Of the 279 patients, anti-tumor treatment was administered to 184 patients (66.0%). All of those received chemotherapy alone or as part of a multimodal treatment, where pemetrexed was given to 126 (68.5%) patients. Asbestos exposure was documented in 92.5% of all patients. In the treated group, mean age was lower (66&#x2009;years versus 74&#x2009;years, p&#x2009;<&#x2009;0.01), rate of occupational asbestos exposure was higher (74.5 versus 54.7%, p&#x2009;<&#x2009;0.01), more patients had better performance score (98.4 versus 60%, p&#x2009;<&#x2009;0.01) and stage was lower (81 versus 63.2%, p&#x2009;<&#x2009;0.01) compared to the BSC group. Multivariate analysis showed that epithelioid subtype was the only common prognostic factor for OS in both groups. In BSC patients, good PS and female gender was associated with improved OS. Median overall survival (OS) was 17 versus 4&#x2009;months (p&#x2009;<&#x2009;0.01), and independently of the histopathological subtype, the median and 2-year survival was higher in the treated versus the BSC group (p&#x2009;<&#x2009;0.02).<br><br>CONCLUSIONS: This retrospective study showed that epithelioid subtype is the only independent positive prognostic factor of survival in treated patients with MPM. For BSC patients, the epithelioid subtype, good PS, and female gender were positive prognostic factors, while age and comorbidities were not significant. This study with long-term follow-up of treated and BSC MPM patients can contribute to the clinical stratification of patients. Further validation is appropriate to verify these findings.}, }
@article {pmid33498425, year = {2021}, author = {Kwak, K and Zoh, KE and Paek, D}, title = {Incidence of Cancer and Asbestos-Related Diseases among Residents Living near Abandoned Asbestos Mines in South Korea: A Retrospective Cohort Study Using National Health Insurance Database.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {3}, pages = {}, pmid = {33498425}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Incidence ; Male ; *Mesothelioma ; National Health Programs ; *Occupational Exposure ; Republic of Korea/epidemiology ; Retrospective Studies ; }, abstract = {The use of asbestos has been banned since 2009 in South Korea. However, there is still a risk of exposure to environmental asbestos originating from abandoned asbestos mines. We constructed a retrospective dynamic cohort using the National Health Insurance Database of South Korea. We determined the risk of developing asbestos-related diseases (ARDs) among residents living near asbestos mines compared with those living in the control area and the general population. The risks of asbestosis (adjusted hazards ratio [HR] 65.40, 95% CI = 35.02-122.12) and pleural plaques (adjusted HR 3.55, 95% CI = 1.96-6.41) were significantly increased among residents living near the asbestos mines compared with the control area. The risk of malignant mesothelioma was increased near asbestos mines compared with the control area; however, it was not significant (adjusted HR 1.83, 95% CI = 0.61-5.47). When a separate analysis according to sex was conducted, the risk of mesothelioma among male residents was statistically significant (adjusted HR 8.30, 95% CI = 1.04-66.63), and the standardized incidence ratio (SIR) was significantly increased (SIR 3.48, 95% CI = 1.50-6.85). The risk of ARDs was increased due to environmental asbestos exposure near abandoned asbestos mines in South Korea.}, }
@article {pmid33472960, year = {2021}, author = {Asciak, R and George, V and Rahman, NM}, title = {Update on biology and management of mesothelioma.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {30}, number = {159}, pages = {}, pmid = {33472960}, issn = {1600-0617}, support = {MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; }, mesh = {*Asbestos/adverse effects ; Biology ; Humans ; *Mesothelioma/diagnosis/genetics/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/epidemiology/etiology ; }, abstract = {Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread prohibition of asbestos production and supply, its incidence continues to increase. It is heterogeneous in its presentation and behaviour, and diagnosis can be notoriously difficult. Identification of actionable gene mutations has proven challenging and current treatment options are largely ineffective, with a median survival of 10-12 months.However, the past few years have witnessed major advances in our understanding of the biology and pathogenesis of mesothelioma. This has also revealed the limitations of existing diagnostic algorithms and identified new treatment targets.Recent clinical trials have re-examined the role of surgery, provided new options for the management of associated pleural effusions and heralded the addition of targeted therapies. The increasing complexity of mesothelioma management, along with a desperate need for further research, means that a multidisciplinary team framework is essential for the delivery of contemporary mesothelioma care.This review provides a synthesised overview of the current state of knowledge and an update on the latest research in the field.}, }
@article {pmid33466653, year = {2021}, author = {Marcq, E and Van Audenaerde, JRM and De Waele, J and Merlin, C and Pauwels, P and van Meerbeeck, JP and Fisher, SA and Smits, ELJ}, title = {The Search for an Interesting Partner to Combine with PD-L1 Blockade in Mesothelioma: Focus on TIM-3 and LAG-3.}, journal = {Cancers}, volume = {13}, number = {2}, pages = {}, pmid = {33466653}, issn = {2072-6694}, support = {141433//Agentschap voor Innovatie door Wetenschap en Technologie/ ; 11455//Kom op tegen Kanker/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9-12 months, due to the limited effectiveness of any conventional anti-cancer treatment. New therapeutic strategies are needed to complement the limited armamentarium against MPM. We decided to focus on the combination of different immune checkpoint (IC) blocking antibodies (Abs). Programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), and lymphocyte activation gene-3 (LAG-3) blocking Abs were tested as monotherapies, and as part of a combination strategy with a second IC inhibitor. We investigated their effect in vitro by examining the changes in the immune-related cytokine secretion profile of supernatant collected from treated allogeneic MPM-peripheral blood mononuclear cell (PBMC) co-cultures. Based on our in vitro results of cytokine secretion, and flow cytometry data that showed a significant upregulation of PD-L1 on PBMC after co-culture, we chose to further investigate the combinations of anti PD-L1 + anti TIM-3 versus anti PD-L1 + anti LAG-3 therapies in vivo in the AB1-HA BALB/cJ mesothelioma mouse model. PD-L1 monotherapy, as well as its combination with LAG-3 blockade, resulted in in-vivo delayed tumor growth and significant survival benefit.}, }
@article {pmid33466544, year = {2021}, author = {Mensi, C and Dallari, B and Polonioli, M and Riboldi, L and Consonni, D and Pesatori, AC}, title = {Mesothelioma in Agriculture in Lombardy, Italy: An Unrecognized Risk.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {1}, pages = {}, pmid = {33466544}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; *Agriculture ; *Asbestos/toxicity ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; Middle Aged ; *Occupational Exposure ; }, abstract = {Cohort studies showed consistently low risks for malignant mesothelioma (MM) among agricultural workers, however the investigated exposures did not include asbestos. Our aim is to describe sources of asbestos exposure of MM in agriculture. Twenty-six MM cases in agricultural or seed trades workers were identified through the MM registry of the Lombardy region, Italy in 2000-2016. Asbestos exposures were investigated through a standardized questionnaire. The most frequent exposure circumstances were recycled jute bags previously containing asbestos (11 cases) and maintenance and repair of asbestos roofs (12 subjects). Three subjects performed maintenance and repair of tractor asbestos brakes and two used asbestos filters for wine production. Our data suggest asbestos exposure opportunities in the agricultural setting, underlining the need to look for this exposure in subjects affected with mesothelioma.}, }
@article {pmid33465294, year = {2021}, author = {Eccher, A and Girolami, I and Lucenteforte, E and Troncone, G and Scarpa, A and Pantanowitz, L}, title = {Diagnostic mesothelioma biomarkers in effusion cytology.}, journal = {Cancer cytopathology}, volume = {129}, number = {7}, pages = {506-516}, doi = {10.1002/cncy.22398}, pmid = {33465294}, issn = {1934-6638}, mesh = {Biomarkers, Tumor/*analysis ; Homozygote ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mesothelioma, Malignant/*diagnosis/genetics/*metabolism/pathology ; Pleural Effusion/genetics/*metabolism/*pathology ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1-associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.}, }
@article {pmid36034504, year = {2021}, author = {Noda, R and Yanagisawa, S and Inoue, M and Hara, T}, title = {A case of brain metastasis with pathological transformation of long-surviving malignant pleural mesothelioma: illustrative case.}, journal = {Journal of neurosurgery. Case lessons}, volume = {1}, number = {3}, pages = {CASE2099}, pmid = {36034504}, issn = {2694-1902}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer, and in 80% of cases the cause is asbestos exposure. In 1972, the World Health Organization (WHO) declared asbestos is a carcinogenic substance. Since then, every developed country has restricted and banned the product. Because of its high heat resistance, asbestos had been widely used as building material for decades. The WHO estimated that approximately 125 million people are exposed to asbestos, and more than 107,000 die from asbestos-related diseases annually. Because of its long incubation period, the number of patients is estimated to keep increasing in the near future.<br><br>OBSERVATIONS: The authors report a case of long-surviving MPM with a rushed clinical course after brain metastasis. A 69-year-old woman diagnosed with MPM (epithelial type) 6 years earlier presented with a brain metastasis. The pathological result of the brain metastasis was the sarcomatoid type. This case showed the possibility of subtype transition after long survival.<br><br>LESSONS: This article aids in understanding the long-term natural history of MPM and the possibility of epithelial-mesenchymal transition. Neurosurgeons have to be aware of its the natural history and the possibility of brain metastasis.}, }
@article {pmid33438079, year = {2021}, author = {Borrelli, EP and McGladrigan, CG}, title = {A Review of Pharmacologic Management in the Treatment of Mesothelioma.}, journal = {Current treatment options in oncology}, volume = {22}, number = {2}, pages = {14}, pmid = {33438079}, issn = {1534-6277}, mesh = {Antineoplastic Agents/administration &amp; dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Biomarkers, Tumor ; Clinical Decision-Making ; Combined Modality Therapy ; Disease Management ; Disease Susceptibility ; Drug Development ; Humans ; Mesothelioma/diagnosis/*drug therapy/epidemiology/etiology ; Standard of Care ; Treatment Outcome ; }, abstract = {Mesothelioma is a rare and severe form of cancer that is associated with asbestos exposure. Approximately 2500 Americans die annually from this condition with a median survival of 1 year. The latency period of this disease ranges anywhere from 20 to 70 years, with shorter latency periods associated with a higher exposure intensity to asbestos. Therefore, cases of mesothelioma are expected in the coming decades. This highlights the need for clinicians to understand the pharmacologic regimens available for treating this rare, yet serious malignancy. With multiple treatment regimens available in the treatment of this condition, clinicians should take an evidence-based approach and consider the totality of evidence and safety information while considering the best patient-centered approach for treatment. This article provides a review of current pharmacologic treatment options available for mesothelioma and goes into detail about the recommended medication regimens and dosages and the available evidence of efficacy, effectiveness, and/or safety and estimates the annual cost of treatment for these medications on the U.S. healthcare system per patient. A brief introduction is provided for several promising agents currently under investigation for mesothelioma as well.}, }
@article {pmid33435788, year = {2022}, author = {Germine, M and Puffer, JH}, title = {Anthophyllite asbestos from Staten Island, New York: Longitudinal fiber splitting.}, journal = {Archives of environmental &amp; occupational health}, volume = {77}, number = {4}, pages = {268-275}, doi = {10.1080/19338244.2021.1873095}, pmid = {33435788}, issn = {2154-4700}, mesh = {*Asbestos ; Asbestos, Amphibole/analysis ; Humans ; *Mesothelioma/chemically induced/epidemiology ; New York ; }, abstract = {Asbestos ore was sampled from a historical anthophyllite mine in Staten Island, New York. High-resolution transmission electron microscopy (HRTEM) was used to image the structure of nineteen fibers of the anthophyllite asbestos. The anthophyllite was characterized by a high level of chain width disorder, involving wide chain multiplicity faults (CMFs) that were frequent in fibers, randomly spaced, and ranged from one to eight chains in width. This chain width disorder was manifest by streaking of electron diffraction rows of chain width. The anthophyllite asbestos fibers were found to be produced by longitudinal splitting rather than crystal growth. Such splitting is a function of cleavage along CMFs rather than crystal boundaries. The morphology of the fibers is consistent with anthophyllite asbestos mined in Finland associated with lung cancer and mesothelioma. These findings may have regulatory implications.}, }
@article {pmid33422732, year = {2021}, author = {Ejegi-Memeh, S and Darlison, L and Moylan, A and Tod, A and Sherborne, V and Warnock, C and Taylor, BH}, title = {Living with mesothelioma: A qualitative study of the experiences of male military veterans in the UK.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {50}, number = {}, pages = {101889}, doi = {10.1016/j.ejon.2020.101889}, pmid = {33422732}, issn = {1532-2122}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Family/psychology ; Female ; Humans ; Life Change Events ; Male ; Mesothelioma/nursing/*psychology ; Middle Aged ; Military Personnel/psychology ; Qualitative Research ; Self-Help Groups ; United Kingdom ; Veterans/*psychology ; }, abstract = {PURPOSE: The UK has the highest incidence of mesothelioma in the world. Evidence in the United States suggests that mesothelioma may disproportionately affect military veterans. However, there has been no investigation of the experience of UK veterans living with mesothelioma. The Military Mesothelioma Experience Study (MiMES) aimed to understand the experience and health/support needs of British Armed Forces personnel/veterans with mesothelioma.<br><br>METHODS: Semi-structured interviews were conducted with 13 veterans living with mesothelioma, and nine family members of veterans living with mesothelioma. Participants were recruited via charities and asbestos support groups. Data were analysed using thematic analysis.<br><br>RESULTS: Participants' experiences are presented using three themes, i) exposure to asbestos and awareness of asbestos related diseases, ii) using military strategies to cope with mesothelioma and iii) preferences for information and support. MiMES indicates that the nature and range of UK military veterans' asbestos exposure is varied and not limited to high risk occupations. Participants' knowledge of asbestos and experience of mesothelioma influenced their experiences of diagnosis. Participants had coping strategies influenced by their military experiences. Assistance in navigating health and military systems was considered beneficial, especially if support was provided by professionals with knowledge or experience of the military. Attributes which may inhibit veterans from seeking professional support are discussed.<br><br>CONCLUSION: MiMES provides insight into how UK military veterans experience and cope with mesothelioma. Key implications focus on the role that Mesothelioma Nurse Specialists, Asbestos Support Groups and veterans groups play in providing acceptable support for UK veterans.}, }
@article {pmid33419364, year = {2020}, author = {Affatato, R and Mendogni, P and Del Gobbo, A and Ferrero, S and Ricci, F and Broggini, M and Rosso, L}, title = {Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients.}, journal = {Cancers}, volume = {12}, number = {12}, pages = {}, pmid = {33419364}, issn = {2072-6694}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a very aggressive tumor originating from mesothelial cells. Although several etiological factors were reported to contribute to MPM onset, environmental exposure to asbestos is certainly a major risk factor. The latency between asbestos (or asbestos-like fibers) exposure and MPM onset is very long. MPM continues to be a tumor with poor prognosis despite the introduction of new therapies including immunotherapy. One of the major problems is the low number of preclinical models able to recapitulate the features of human tumors. This impacts the possible discovery of new treatments and combinations.<br><br>METHODS: In this work, we aimed to generate patient-derived xenografts (PDXs) from MPM patients covering the three major histotypes (epithelioid, sarcomatoid, and mixed) occurring in the clinic. To do this, we obtained fresh tumors from biopsies or pleurectomies, and samples were subcutaneously implanted in immunodeficient mice within 24 h.<br><br>RESULTS: We successfully isolated different PDXs and particularly concentrated our efforts on three covering the three histotypes. The tumors that grew in mice compared well histologically with the tumors of origin, and showed stable growth in mice and a low response to cisplatin, as was observed in the clinic.<br><br>CONCLUSIONS: These models are helpful in testing new drugs and combinations that, if successful, could rapidly translate to the clinical setting.}, }
@article {pmid33414743, year = {2020}, author = {Granieri, A and Bonafede, M and Marinaccio, A and Iavarone, I and Marsili, D and Franzoi, IG}, title = {SARS-CoV-2 and Asbestos Exposure: Can Our Experience With Mesothelioma Patients Help Us Understand the Psychological Consequences of COVID-19 and Develop Interventions?.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {584320}, pmid = {33414743}, issn = {1664-1078}, abstract = {Since its emergence, the novel coronavirus disease of 2019 (COVID-19) has had enormous physical, social, and psychological impacts worldwide. The aim of this article was to identify elements of our knowledge on asbestos exposure and malignant mesothelioma (MM) that can provide insight into the psychological impact of the COVID-19 pandemic and be used to develop adequate interventions. Although the etiology of Covid-19 and MM differs, their psychological impacts have common characteristics: in both diseases, there is a feeling of being exposed through aerial contagion to an "invisible killer" without boundaries that can strike even the strongest individuals. In both cases, affected persons can experience personality dysfunction, anxiety, depression, and posttraumatic symptoms; helplessness, hopelessness, and projection of destructive thoughts onto external forces often emerge, while defense mechanisms such as denial, splitting, repression, and reduced emotional expression are used by individuals to contain their overwhelming anxieties. We believe that in both diseases, an integrated multidimensional intervention offered by hospitals and other public health services is the most effective approach to alleviating patients' and caregivers' psychological distress. In particular, we emphasize that in the context of both MM and COVID-19, Brief Psychoanalytic Group therapy can help patients and caregivers attribute meaning to the significant changes in their lives related to the experience of the disease and identify adaptive strategies and more realistic relational modalities to deal with what has happened to them. We also highlight the importance of developing a surveillance system that includes individual anamnestic evaluation of occupational risk factors for COVID-19 disease.}, }
@article {pmid33414260, year = {2021}, author = {Gunatilake, S and Lodge, D and Neville, D and Jones, T and Fogg, C and Bassett, P and Begum, S and Kerley, S and Marshall, L and Glaysher, S and Elliott, S and Stores, R and Bishop, L and Chauhan, A}, title = {Predicting survival in malignant pleural mesothelioma using routine clinical and laboratory characteristics.}, journal = {BMJ open respiratory research}, volume = {8}, number = {1}, pages = {}, pmid = {33414260}, issn = {2052-4439}, mesh = {Humans ; Laboratories ; *Lung Neoplasms/diagnosis ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis ; Retrospective Studies ; }, abstract = {INTRODUCTION: The prognosis of malignant pleural mesothelioma (MPM) is poor, with a median survival of 8-12 months. The ability to predict prognosis in MPM would help clinicians to make informed decisions regarding treatment and identify appropriate research opportunities for patients. The aims of this study were to examine associations between clinical and pathological information gathered during routine care, and prognosis of patients with MPM, and to develop a 6-month mortality risk prediction model.<br><br>METHODS: A retrospective cohort study of patients diagnosed with MPM at Queen Alexandra Hospital, Portsmouth, UK between December 2009 and September 2013. Multivariate analysis was performed on routinely available histological, clinical and laboratory data to assess the association between different factors and 6-month survival, with significant associations used to create a model to predict the risk of death within 6 months of diagnosis with MPM.<br><br>RESULTS: 100 patients were included in the analysis. Variables significantly associated with patient survival in multivariate analysis were age (HR 1.31, 95%&#x2009;CI 1.09 to 1.56), smoking status (current smoker HR 3.42, 95%&#x2009;CI 1.11 to 4.20), chest pain (HR 2.14, 95%&#x2009;CI 1.23 to 3.72), weight loss (HR 2.13, 95%&#x2009;CI 1.18 to 3.72), platelet count (HR 1.05, 95%&#x2009;CI 1.00 to 1.10), urea (HR 2.73, 95%&#x2009;CI 1.31 to 5.69) and adjusted calcium (HR 1.47, 95%&#x2009;CI 1.10 to 1.94). The resulting risk model had a c-statistic value of 0.76. A Hosmer-Lemeshow test confirmed good calibration of the model against the original dataset.<br><br>CONCLUSION: Risk of death at 6 months in patients with a confirmed diagnosis of MPM can be predicted using variables readily available in clinical practice. The risk prediction model we have developed may be used to influence treatment decisions in patients with MPM. Further validation of the model requires evaluation of its performance on a separate dataset.}, }
@article {pmid33400741, year = {2020}, author = {Reis, K and Arbiser, JL and Hjerpe, A and Dobra, K and Aspenström, P}, title = {Inhibitors of cytoskeletal dynamics in malignant mesothelioma.}, journal = {Oncotarget}, volume = {11}, number = {50}, pages = {4637-4647}, pmid = {33400741}, issn = {1949-2553}, abstract = {Malignant mesotheliomas (MMs) are highly aggressive mesenchymal tumors that originate from mesothelial cells lining serosal cavities; i.e., the pleura, peritoneum, and pericardium. Classically, there is a well-established link between asbestos exposure, oxidative stress, release of reactive oxygen species, and chronic inflammatory mediators that leads to progression of MMs. MMs have an intermediate phenotype, with co-expression of mesenchymal and epithelial markers and dysregulated communication between the mesothelium and the microenvironment. We have previously shown that the organization and function of key cytoskeletal components can distinguish highly invasive cell lines from those more indolent. Here, we used these tools to study three different types of small-molecule inhibitors, where their common feature is their influence on production of reactive oxygen species. One of these, imipramine blue, was particularly effective in counteracting some key malignant properties of highly invasive MM cells. This opens a new possibility for targeted inhibition of MMs based on well-established molecular mechanisms.}, }
@article {pmid33399341, year = {2021}, author = {Argani, P and Lian, DWQ and Agaimy, A and Metzler, M and Wobker, SE and Matoso, A and Epstein, JI and Sung, YS and Zhang, L and Antonescu, CR}, title = {Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {5}, pages = {653-661}, pmid = {33399341}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; P50 CA217694/CA/NCI NIH HHS/United States ; }, mesh = {Abdominal Neoplasms/enzymology/*genetics/pathology ; Adolescent ; Anaplastic Lymphoma Kinase/*genetics ; Biomarkers, Tumor/analysis/*genetics ; Child ; Female ; *Gene Fusion ; *Gene Rearrangement ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/enzymology/*genetics/pathology ; Molecular Diagnostic Techniques ; Testicular Neoplasms/enzymology/*genetics/pathology ; }, abstract = {Pediatric mesotheliomas are rare and their pathogenesis remains undefined. In this study, we report 5 cases of malignant mesothelioma in children, characterized by fusions involving the anaplastic lymphoma kinase (ALK) gene. Four cases occurred in females involving the abdominal cavity and were characterized by a pure epithelioid morphology. The fifth arose in the tunica vaginalis of a 15-year-old male and displayed a biphasic epithelioid-sarcomatoid phenotype. All cases demonstrated the classic morphologic and immunohistochemical features of malignant mesothelioma, including tubulopapillary architecture and cuboidal epithelioid cells with eosinophilic cytoplasm and uniform nuclei with vesicular chromatin. Immunohistochemically, all cases showed labeling for ALK, cytokeratins, WT1, and calretinin, while lacking expression of adenocarcinoma immunomarkers. Four cases demonstrated weak-moderate labeling for PAX8 protein, which resulted in diagnostic challenges with primary peritoneal serous carcinoma. The ALK genetic abnormalities were investigated by a combination of molecular methods. Archer FusionPlex was performed in 2 cases, showing fusions between ALK with either STRN or TPM1 genes, resulting in a transcript that retained the ALK kinase domain. One case was further studied by DNA targeted sequencing, but no additional genetic alterations were observed. In 1 case, cytogenetic analysis showed the presence of a t(2;15)(p23;q22) and fluorescence in situ hybridization confirmed the ALK gene break-apart. In the remaining 2 cases, ALK gene rearrangements were demonstrated by fluorescence in situ hybridization. Unlike adult mesotheliomas, which are tightly linked to asbestos exposure, often show loss of BAP1 expression and have complex karyotypes, ALK-rearranged mesothelioma appears to be similar to other fusion-positive mesotheliomas, such as those harboring EWSR1/FUS-ATF1 fusions, sharing significant morphologic overlap, occurring in young patients and displaying a simple, translocation-driven genetic profile.}, }
@article {pmid33388783, year = {2021}, author = {Marinaccio, A and Consonni, D and Mensi, C and Mirabelli, D and Migliore, E and Magnani, C and Di Marzio, D and Gennaro, V and Mazzoleni, G and Girardi, P and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Madeo, G and Romeo, E and Ascoli, V and Carrozza, F and Angelillo, IF and Cavone, D and Tumino, R and Melis, M and Curti, S and Brandi, G and Mattioli, S and Iavicoli, S and , }, title = {Authors' response: Mezei et al's "Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis".}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {47}, number = {1}, pages = {87-89}, pmid = {33388783}, issn = {1795-990X}, mesh = {*Asbestos/adverse effects ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Pericardium ; Testis ; }, abstract = {Mezei et al's letter (1) is an opportunity to provide more details about our study on pericardial and tunica vaginalis testis (TVT) mesothelioma (2), which is based on the Italian national mesothelioma registry (ReNaM): a surveillance system on mesothelioma, with individual asbestos exposure assessment. Incidence of pericardial mesothelioma has been estimated around 0.5 and 0.2 cases per 10 million person-years in men and women, respectively, and around 1 case for TVT mesothelioma. ReNaM collected 138 cases thanks to its long period of observation (1993-2015) and national coverage. Conducting a population-based case-control study with incidence-density sampling of controls across Italy and over a 23 year time-span should have been planned in 1993 and would have been beyond feasibility and ReNaM scope. We rather exploited two existing series of controls (3). The resulting incomplete time- and spatial matching of cases and controls is a limitation of our study and has been acknowledged in our article. The analysis of case-control studies can nevertheless be accomplished in logistic models accounting for the variables of interest, in both individually and frequency matched studies (4). Furthermore, analyses restricted to (i) regions with enrolled controls, (ii) cases with definite diagnosis, (iii) incidence period 2000-2015, and (iv) subjects born before 1950 have been provided in the manuscript, confirming the strength of the association with asbestos exposure (supplemental material tables S4-7). Following Mezei et al's suggestion, we performed further sensitivity analyses by restriction to regions with controls and fitting conditional regression models using risk-sets made of combinations of age and year of birth categories (5-year classes for both). We confirmed positive associations with occupational exposure to asbestos of pericardial mesothelioma, with odds ratios (OR) (adjusted for region) of 9.16 among women [95% confidence interval (CI) 0.56-150] and 5.63 (95% CI 1.02-31.0) among men; for TVT mesothelioma the OR was 7.70 (95% CI 2.89-20.5). Using risk sets of age categories and introducing year of birth (5-year categories) as a covariate (dummy variables) the OR were similar: OR (adjusted for region) of 9.17 among women (95% CI 0.56-150) and 5.76 (95% CI 1.07-31.0) among men; for TVT the OR was 9.86 (95% CI 3.46-28.1). Possible bias from incomplete geographical overlap between cases and controls has been addressed in the paper (table S4) and above. In spatially restricted analyses, OR were larger than in those including cases from the whole country, indicating that bias was towards the null. Mezei et al further noted that "the regional distribution of controls is different from that of person-time observed". This objection is not relevant because the above analyses were adjusted by region. Our controls were provided by a population-based study on pleural mesothelioma (called MISEM) and a hospital-based study on cholangiocarcinoma (called CARA). In MISEM, the response rate was 48.4%, a low but not unexpected rate as participation among population controls is usually lower and has been declining over time (5). It is important to underline that ReNaM applied the same questionnaire that was used for interviews and carried out the same exposure assessment as both MISEM and CARA. As repeatedly stated in ReNaM papers (6-7), each regional operating center assesses asbestos exposure based on the individual questionnaire, other available information, and knowledge of local industries. Occupational exposure to asbestos is classified as definite, probable or possible. Occupational exposure is (i) definite when the subject`s work was reported or otherwise known to have involved the use of asbestos or asbestos-containing materials (MCA); (ii) probable when subjects worked in factories where asbestos or MCA were used, but their personal exposure could not be documented; and (iii) possible when they were employed in industrial activities known to entail the use of asbestos or MCA. Hence, the definite and probable categories are closer to one another and were combined in our analyses. In any case, restricting analyses to subjects with definite occupational exposure and using each set of controls separately, as suggested by Mezei et al, yielded elevated OR for TVT and pericardial mesothelioma among men using both the above described modelling strategies; the OR could not be calculated for women. There were 70 (25 pericardial and 45 TVT) occupationally exposed mesothelioma cases. In population-based studies, analyses by occupation are limited by the low prevalence of most specific jobs. As briefly reported in our paper, for purely descriptive purposes, the industrial activity of exposure (cases may have multiple exposures), were construction (22 exposures, 7 and 15 for pericardial and TVT mesotheliomas, respectively), steel mills and other metal working industries (4 and 11), textile industries (2 and 3), and agriculture (2 and 5); other sectors had lower exposure frequencies. The absence of industries like asbestos-cement production, shipbuilding and railway carriages production/repair should not be surprising and had already been observed (7). In the Italian multicenter cohort study of asbestos workers (8), given the person-years of observation accrued by workers employed in these industries and gender- and site-specific crude incidence rates, approximately 0.1 case of pericardial and 0.2 of TVT mesothelioma would have been expected from 1970 to 2010. Even increasing ten-fold such figures to account for higher occupational risks among these workers would not change much. Asbestos exposure in agriculture has been repeatedly discussed in ReNaM reports (9: pages 70, 73, 128, 164 and 205). Exposure opportunities included the presence of asbestos in wine production, reuse of hessian bags previously containing asbestos, or construction and maintenance of rural buildings. Similarly, mesothelioma cases and agricultural workers exposed to asbestos have been noted in France (10). In conclusion, the additional analyses we performed according to Mezei et al's suggestions confirm the association between asbestos exposure and pericardial and TVT mesothelioma, supporting the causal role of asbestos for all mesotheliomas. ReNaM`s continuing surveillance system with national coverage is a precious platform for launching analytical studies on pleural and extra pleural mesothelioma. References 1. Mezei G, Chang ET, Mowat FS, Moolgavkar SH. Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis Scand J Work Environ Health. 2021;47(1):85-86. https://doi.org/10.5271/3909 2. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 3. Greenland S. Control-initiated case-control studies. Int J Epidemiol 1985 Mar;14(1):130-4. https://doi.org/10.1093/ije/14.1.130. 4. Pearce N. Analysis of matched case-control studies. BMJ 2016 Feb;352:i969. https://doi.org/10.1136/bmj.i969. 5. Bigert C, Gustavsson P, Straif K, Pesch B, Brüning T, Kendzia B et al. Lung cancer risk among cooks when accounting for tobacco smoking: a pooled analysis of case-control studies from Europe, Canada, New Zealand, and China. J Occup Environ Med 2015 Feb;57(2):202-9. https://doi.org/10.1097/JOM.0000000000000337. 6. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 7. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 8. Ferrante D, Chellini E, Merler E, Pavone V, Silvestri S, Miligi L et al.; the working group. Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure. Occup Environ Med 2017 Dec;74(12):887-98. https://doi.org/10.1136/oemed-2016-104100. 9. ReNaM VI Report. Available from: https://www.inail.it/cs/internet/docs/alg-pubbl-registro-nazionale-mesoteliomi-6-rapporto.pdf. Italian 10. Marant Micallef C, Shield KD, Vignat J, Baldi I, Charbotel B, Fervers B et al. Cancers in France in 2015 attributable to occupational exposures. Int J Hyg Environ Health 2019 Jan;222(1):22-9. https://doi.org/10.1016/j.ijheh.2018.07.015.}, }
@article {pmid33381446, year = {2020}, author = {Yoshikawa, Y and Kuribayashi, K and Minami, T and Ohmuraya, M and Kijima, T}, title = {Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {554570}, pmid = {33381446}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is strongly associated with occupational or environmental asbestos exposure and arises from neoplastic transformation of mesothelial cells in the pleural cavity. The only standard initial treatment for unresectable MPM is combination chemotherapy with cisplatin (CDDP) and pemetrexed (PEM). Further, CDDP/PEM is the only approved regimen with evidence of prolonged overall survival (OS), although the median OS for patients treated with this regimen is only 12 months after diagnosis. Thus, the development of new therapeutic strategies has been investigated for approximately 20 years. In contrast to recent advances in personalized lung cancer therapies, diagnostic and prognostic biomarker research has just started in mesothelioma. Epigenetic alterations include DNA methylation, histone modifications, and other chromatin-remodeling events. These processes are involved in numerous cellular processes including differentiation, development, and tumorigenesis. Epigenetic modifications play an important role in gene expression and regulation related to malignant MPM phenotypes and histological subtypes. An immune checkpoint PD-1 inhibitor, nivolumab, was approved as second-line therapy for patients who had failed initial chemotherapy, based on the results of the MERIT study. Various clinical immunotherapy trials are ongoing in patients with advanced MPM. In this review, we describe recent knowledge on epigenetic alterations, which might identify candidate therapeutic targets and immunotherapeutic regimens under development for MPM.}, }
@article {pmid33380218, year = {2021}, author = {Seastedt, KP and Pruett, N and Hoang, CD}, title = {Mouse models for mesothelioma drug discovery and development.}, journal = {Expert opinion on drug discovery}, volume = {16}, number = {6}, pages = {697-708}, pmid = {33380218}, issn = {1746-045X}, support = {ZIA BC011657/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; *Asbestos ; Carcinogenesis ; Drug Discovery ; *Lung Neoplasms ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; Mice ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Mesothelioma is an aggressive mesothelial lining tumor. Available drug therapies include chemotherapeutic agents, targeted molecular therapies, and immune system modulators. Mouse models were instrumental in the discovery and evaluation of such therapies, but there is need for improved understanding of the role of inflammation, tumor heterogeneity, mechanisms of carcinogenesis, and the tumor microenvironment. Novel mouse models may provide new insights and drive drug therapy discovery that improves efficacy.<br><br>AREAS COVERED: This review concerns available mouse models for mesothelioma drug discovery and development including the advantages and disadvantages of each. Gaps in current knowledge of mesothelioma are highlighted, and future directions for mouse model research are considered.<br><br>EXPERT OPINION: Soon, CRISPR-Cas gene-editing will improve understanding of mesothelioma mechanisms foundational to the discovery and testing of efficacious therapeutic targets. There are at least two likely areas of upcoming methodology development. One is concerned with precise modeling of inflammation - is it a causal process whereby inflammatory signals contribute to tumor initiation, or is it a secondary passenger process driven by asbestos exposure effects? The other area of methods improvement regards the availability of humanized immunocompromised mice harboring patient-derived xenografts. Combining human tumors in an environment with human immune cells will enable rapid innovation in immuno-oncology therapeutics.}, }
@article {pmid33379304, year = {2020}, author = {Oddone, E and Bollon, J and Nava, CR and Minelli, G and Imbriani, M and Consonni, D and Marinaccio, A and Magnani, C and Barone-Adesi, F}, title = {Forecast of Malignant Peritoneal Mesothelioma Mortality in Italy up to 2040.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {1}, pages = {}, pmid = {33379304}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; Female ; Forecasting ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Peritoneal Neoplasms/*mortality ; }, abstract = {Despite their differences, pleural and peritoneal mesothelioma are frequently lumped together to describe epidemic curves and to forecast future mesothelioma trends. This study aims to describe the malignant peritoneal mesothelioma (MPeM) epidemic in Italy (1996-2016) and to forecast future trends up to 2040 in order to contribute to the assessment of MPeM future burden. All MPeM deaths in Italy from 1996-2016 were collected (as provided by the Italian National Statistical Institute (ISTAT)) in order to estimate MPeM mortality rates for each 3-year period from 1996 to 2016. Poisson age-period-cohort (APC) models were then used to forecast MPeM future trends. Between 2017 and 2040, 1333 MPeM deaths are expected. The number of MPeM deaths, as well as mortality rates, are expected to constantly decrease throughout the considered period. Based on considering the information from this study, it can be concluded that the MPeM epidemic has probably already reached its peak in Italy.}, }
@article {pmid33363966, year = {2020}, author = {Brahim, D and Mechergui, N and Ben Said, H and Cherif, D and Ladhari, N and Youssef, I}, title = {Peritoneal mesothelioma associated with bladder cancer and occupational exposure to asbestos: A case report.}, journal = {Clinical case reports}, volume = {8}, number = {12}, pages = {3529-3532}, pmid = {33363966}, issn = {2050-0904}, abstract = {Mesothelioma is a rare tumor usually located on the pleura. In this typical location, it is closely linked to asbestos exposure. However, in other locations such as in peritoneal mesothelioma, the association to asbestos remains unusual.}, }
@article {pmid33347735, year = {2021}, author = {Re, A and Shersher, D and Allen, A and Schwarting, R and Ren, S}, title = {Malignant pleural neoplasm with both differentiation of epithelioid mesothelioma and squamous-cell carcinoma, a rare phenomena.}, journal = {Diagnostic cytopathology}, volume = {49}, number = {6}, pages = {E234-E237}, doi = {10.1002/dc.24686}, pmid = {33347735}, issn = {1097-0339}, mesh = {Aged ; Asbestos/toxicity ; Carcinoma, Squamous Cell/etiology/*pathology ; Cell Differentiation ; Humans ; Male ; Mesothelioma, Malignant/*pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*pathology ; }, abstract = {Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely to asbestos exposure. We present a case of 72-year-old male with a 27 year work-related history of asbestos exposure who presented with dyspnea. Chest computed tomography scan showed a large, right pleural effusion with compressive right lung atelectasis. Biopsies, subsequent pleurectomy and lung wedge resections revealed epithelioid malignant mesothelioma with associated focal non-keratinizing squamous-cell carcinoma, supported by extensive immunohistochemical stains and molecular studies. The patient was treated with 6 cycles of carboplatin/pemetrexed, showing no new metastases. Seven months post-treatment, the patient presented with progressive dyspnea and large pleural effusions. Bilateral pleural fluid was collected and showed malignant epithelioid cells, morphologically similar to the patient's pleural neoplastic cells. However, the tumor was positive for squamous cells markers and showed BAP1 loss, while negative for mesothelial markers. The findings support the diagnosis of squamous-cell carcinoma and were consistent with the patient's previously diagnosed pleural neoplastic origin. A malignant mesothelioma associated with squamous-cell carcinoma is a rare phenonmenon. To our knowledge, only two case reports are available in current literature. This unique case shows a single pleura tumor differentiating as both malignant mesothelioma and squamous-cell carcinoma. Squamous-cell carcinoma is the predominating malignancy seen within the bilateral pleural effusions, a potential pitfall for cytology specimen diagnosis.}, }
@article {pmid33346174, year = {2020}, author = {Fazzo, L and Minelli, G and Bruno, C and Comba, P and Conti, S and De Santis, M and Zona, A and Binazzi, A and Magnani, C and Marinaccio, A and Iavarone, I}, title = {Early mortality from malignant mesothelioma in Italy as a proxy of environmental exposure to asbestos in children.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {56}, number = {4}, pages = {478-486}, doi = {10.4415/ANN_20_04_10}, pmid = {33346174}, issn = {2384-8553}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Child ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*etiology/*mortality ; Middle Aged ; Time Factors ; }, abstract = {Malignant mesothelioma (MM) is a rare neoplasm caused by asbestos. Mortality from MM in ≤50 years old people, considering the long latency, is likely related to asbestos exposure in childhood. Mortality from MM (C45, ICD10 code) is described among ≤50 years (ys) old people in Italy, in 2003-2016. National and regional Standardized Rates (SRs) were computed by age-class. The North-South trend of regional SRs, increasing in >50ys age-class, showed a flat cline in ≤50ys old people. Municipal Standardized Mortality Ratios (SMRs) were computed, with respect to regional figures, for ≤50 ys old population. In Italy, 487 people ≤50 ys old died from MM, in 2003-2016 (2.5% of all MM deaths), corresponding to 35/year. The highest SMRs were observed in Northern Regions, the most industrialized areas. Exceeding SMRs were found in 10 municipalities where former asbestos-cement plants, shipyards, and a quarry contaminated by fluoro-edenite fibres were present. Early mortality from MM, proxy of childhood environmental asbestos exposure, deserves particular concern.}, }
@article {pmid33344293, year = {2020}, author = {Chand, MT and Edens, J and Lin, T and Anderson, I and Berri, R}, title = {Benign multicystic peritoneal mesothelioma: literature review and update.}, journal = {Autopsy &amp; case reports}, volume = {10}, number = {3}, pages = {e2020159}, pmid = {33344293}, issn = {2236-1960}, abstract = {Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor diagnosed predominantly in pre-menopausal women. Associated risk factors include endometriosis and pelvic inflammatory disease in women, and prior abdominal surgery in both genders. To date, the pathogenesis of this disease remains controversial with possible etiologies, including a neoplastic versus a reactive process. Given the risk factors, some authors believe that this disease is secondary to a reactive process. However, because some studies describe cases where there is no prior surgical history or inflammatory milieu present, and because of this entity's predilection for recurrence, some authors believe the origin to be neoplastic. Some genetic and familial associations have also been reported. Malignant transformation is extremely rare, with only two cases reported in the literature, despite the recurrence potential. Like the etiology, the name of this entity is also controversial. Some authors prefer the term "peritoneal inclusion cyst (PCM)" instead of "benign cystic mesothelioma" and argue that the term mesothelioma should only be used when there is evidence of atypia. Most cases of BMPM are discovered incidentally. Others reflect sequela of tumor mass effect. It appears intra-operatively as large, multi-focal, cystic lesions in the peritoneal and pelvic cavity. Diagnosis is achieved through surgical sampling with histopathological examination. Immunobiologically, BMPM exhibits multiple small cystic spaces with flattened lining containing calretinin positive cells without atypical features, mitotic figures, or tissue invasion. Treatment includes cytoreductive surgery. Here we present a case of BMPM in a 60-year-old male - a rare disease in an uncommon patient population.}, }
@article {pmid33336248, year = {2021}, author = {Bartkowiak, K and Casjens, S and Andreas, A and Ačkar, L and Joosse, SA and Raiko, I and Brüning, T and Geffken, M and Peine, S and Johnen, G and Weber, DG and Pantel, K}, title = {Sensitive Blood-Based Detection of Asbestos-Associated Diseases Using Cysteine-Rich Angiogenic Inducer 61 as Circulating Protein Biomarker.}, journal = {Clinical chemistry}, volume = {67}, number = {2}, pages = {363-373}, doi = {10.1093/clinchem/hvaa232}, pmid = {33336248}, issn = {1530-8561}, mesh = {Aged ; Aged, 80 and over ; Asbestosis/blood/*diagnosis ; Biomarkers/blood ; Case-Control Studies ; Cysteine-Rich Protein 61/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mesothelioma/blood/*diagnosis ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Detection of asbestos-associated diseases like asbestosis or mesothelioma is still challenging. We sought to improve the diagnosis of benign asbestos-associated disease (BAAD) by detection of the protein cysteine-rich angiogenic inducer 61 (Cyr61) in human plasma.<br><br>METHODS: Plasma Cyr61 was quantified using an enzyme-linked immunosorbent assay. Plasma samples from males diagnosed with BAAD, but without a malignant disease (n&#x2009;=&#x2009;101), and malignant mesothelioma (n&#x2009;=&#x2009;21; 15 males, 6 females), as well as nonasbestos-exposed healthy control participants (n&#x2009;=&#x2009;150; 58 males, 92 females) were analyzed. Clinical sensitivity and specificity of Cyr61 were determined by receiver operating characteristic analysis.<br><br>RESULTS: The median plasma Cyr61 concentration for healthy control participants was 0.27&#x2009;ng/mL. Cytoplasmic Cyr61 in peripheral blood mononuclear cells from healthy control participants was evenly distributed, as detected by immunofluorescent staining. The increase in plasma Cyr61 concentrations in the BAAD study group was statistically significant compared to the healthy control participants (P&#x2009;<&#x2009;0.0001). For the detection of BAAD vs male healthy control participants, clinical sensitivity was 88% and clinical specificity 95% with an area under the curve of 0.924 at maximal Youden Index. For a predefined clinical specificity of 100%, the clinical sensitivity was 76%. For male mesothelioma patients vs male healthy control participants, the clinical sensitivity at maximal Youden Index was 95% with a clinical specificity of 100% (area under the curve, 0.997) and for a predefined clinical specificity of 100%, the clinical sensitivity was 93%.<br><br>CONCLUSIONS: In our study, plasma Cyr61 protein concentrations showed to be a new biomarker for asbestos-associated diseases like BAAD and mesothelioma in men, which deserves further investigation in large-scale cohort studies.}, }
@article {pmid33329908, year = {2020}, author = {Park, EK and Johnson, AR and Wilson, D and Thomas, PS and Yates, DH}, title = {Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders.}, journal = {Safety and health at work}, volume = {11}, number = {4}, pages = {425-430}, pmid = {33329908}, issn = {2093-7911}, abstract = {BACKGROUND: Asbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM.<br><br>METHODS: This study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months.<br><br>RESULTS: Mean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p&#xa0;=&#xa0;0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy.<br><br>CONCLUSION: Monitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.}, }
@article {pmid33319489, year = {2021}, author = {Sakai, K and Inoue, M and Mikami, S and Nishimura, H and Kuwabara, Y and Kojima, A and Toda, M and Ogawa-Kobayashi, Y and Kikuchi, S and Hirata, Y and Mikami-Saito, Y and Kyoyama, H and Moriyama, G and Shiibashi, M and Seike, M and Gemma, A and Uematsu, K}, title = {Functional inhibition of heat shock protein 70 by VER-155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism.}, journal = {Thoracic cancer}, volume = {12}, number = {4}, pages = {491-503}, pmid = {33319489}, issn = {1759-7714}, support = {16-B-1-22//Saitama Medical University/ ; 18-B-1-19//Saitama Medical University/ ; }, mesh = {Autophagy ; Cell Line, Tumor ; Cell Proliferation ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Mesothelioma/*drug therapy/pathology ; Pleural Neoplasms/*drug therapy/pathology ; Purine Nucleosides/pharmacology/*therapeutic use ; Transfection ; }, abstract = {BACKGROUND: Pleural mesothelioma, a devastating asbestos-associated malignancy, urgently requires a novel effective therapy. Heat shock protein 70 (HSP70), which is synthesized in the cell response to protein damage, is expected to be a new target for antitumor treatment. In addition to its well-known protein refolding function, HSP70 regulates cell proliferation through different pathways, including PI3K/AKT/mTOR, and autophagy in malignant cells. In this study, we attempted to clarify the effects of VER-155008, an HSP70 inhibitor, on pleural mesothelioma.<br><br>METHODS: Human pleural mesothelioma cell lines 211H, H2452 and H28 were cultured with VER-155008, and protein expression, cell proliferation, colony formation, cell cycle, synergistic effect with cisplatin, and autophagy induction were analyzed.<br><br>RESULTS: In mesothelioma cell lines, VER-155008 (5.0 &#x3bc;M or more) inhibited cell growth and colony formation, accompanied by G1 cell cycle arrest. According to western blot analysis, VER-155008 reduced p-AKT expression. However, VER-155008 failed to show a synergistic effect with cisplatin on cell growth. Mesothelioma cells transfected with the novel plasmid pMRX-IP-GFP-LC3-RFP-LC3&#x394;G, which was developed for the quantitative and statistical estimation of macroautophagy, showed enhanced macroautophagy upon treatment with VER-155008 and gefitinib which is an EGFR-tyrosine kinase inhibitor. In addition, fetal bovine serum deprivation induced macroautophagy was further enhanced by VER-155008.<br><br>CONCLUSIONS: On the basis of these results, functional HSP70 inhibition by VER-155008 suppressed cell growth in pleural mesothelioma cells, accompanied by enhanced macroautophagy. HSP70 inhibition is thus expected to become a new strategy for treating mesothelioma.<br><br>KEY POINTS: Significant findings of the study In pleural mesothelioma cells, inhibition of HSP70 function by VER-155008 suppressed cell proliferation accompanied by induction of autophagy which was synergistically enhanced under the starvation condition, whereas gefitinib, an EGFR-TKI, did not show the same synergistic effect in autophagy. What this study adds The inhibition of HSP70 induced autophagy and suppressed cell proliferation in mesothelioma cells.}, }
@article {pmid33318203, year = {2020}, author = {Bononi, A and Goto, K and Ak, G and Yoshikawa, Y and Emi, M and Pastorino, S and Carparelli, L and Ferro, A and Nasu, M and Kim, JH and Suarez, JS and Xu, R and Tanji, M and Takinishi, Y and Minaai, M and Novelli, F and Pagano, I and Gaudino, G and Pass, HI and Groden, J and Grzymski, JJ and Metintas, M and Akarsu, M and Morrow, B and Hassan, R and Yang, H and Carbone, M}, title = {Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {52}, pages = {33466-33473}, pmid = {33318203}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; Z01 BC010816/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Asbestos, Crocidolite ; Asbestosis/*genetics ; Family ; Female ; *Genetic Predisposition to Disease ; Genomic Instability ; Germ-Line Mutation/*genetics ; Heterozygote ; Humans ; Incidence ; Inflammation/pathology ; Male ; Mesothelioma/*genetics ; Mice ; Middle Aged ; RecQ Helicases/*genetics ; }, abstract = {Rare biallelic BLM gene mutations cause Bloom syndrome. Whether BLM heterozygous germline mutations (BLM[+/-]) cause human cancer remains unclear. We sequenced the germline DNA of 155 mesothelioma patients (33 familial and 122 sporadic). We found 2 deleterious germline BLM[+/-] mutations within 2 of 33 families with multiple cases of mesothelioma, one from Turkey (c.569_570del; p.R191Kfs*4) and one from the United States (c.968A>G; p.K323R). Some of the relatives who inherited these mutations developed mesothelioma, while none with nonmutated BLM were affected. Furthermore, among 122 patients with sporadic mesothelioma treated at the US National Cancer Institute, 5 carried pathogenic germline BLM[+/-] mutations. Therefore, 7 of 155 apparently unrelated mesothelioma patients carried BLM[+/-] mutations, significantly higher (P = 6.7E-10) than the expected frequency in a general, unrelated population from the gnomAD database, and 2 of 7 carried the same missense pathogenic mutation c.968A>G (P = 0.0017 given a 0.00039 allele frequency). Experiments in primary mesothelial cells from Blm[+/-] mice and in primary human mesothelial cells in which we silenced BLM revealed that reduced BLM levels promote genomic instability while protecting from cell death and promoted TNF-α release. Blm[+/-] mice injected intraperitoneally with asbestos had higher levels of proinflammatory M1 macrophages and of TNF-α, IL-1β, IL-3, IL-10, and IL-12 in the peritoneal lavage, findings linked to asbestos carcinogenesis. Blm[+/-] mice exposed to asbestos had a significantly shorter survival and higher incidence of mesothelioma compared to controls. We propose that germline BLM[+/-] mutations increase the susceptibility to asbestos carcinogenesis, enhancing the risk of developing mesothelioma.}, }
@article {pmid33314519, year = {2020}, author = {Kishimoto, T and Fujimoto, N and Mizuhashi, K and Kozawa, S and Miura, M}, title = {Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist.}, journal = {Journal of occupational health}, volume = {62}, number = {1}, pages = {e12182}, pmid = {33314519}, issn = {1348-9585}, support = {//The research and development, and the dissemination project/ ; //Japan Organization of Occupational Health and Safety/ ; }, mesh = {Aged ; Aged, 80 and over ; Asbestosis/*diagnosis ; Checklist/*standards ; Diagnosis, Differential ; Humans ; Male ; Middle Aged ; Occupational Diseases/*diagnosis ; Occupational Exposure/analysis ; Pleural Effusion/*diagnosis ; Radiography ; Reproducibility of Results ; Retrospective Studies ; Thoracentesis ; Thoracoscopy ; }, abstract = {OBJECTIVES: In Japan, benign asbestos pleural effusion (BAPE) has been eligible for industrial accident compensation since 2003 as an asbestos-related disease despite the lack of good criteria. We compiled a criteria into a checklist of essential items and for excluding other diseases inducing pleural effusion as a diagnosis process.<br><br>METHOD: Thoracentesis was performed in order to confirm the presence of pleural effusion at the initial diagnosis, and 105 suspected BAPE patients were retrospectively examined. We complied a checklist comprising the following diagnostic items: (a) occupational asbestos exposure; (b) confirmation of exudate of pleural effusion; (c) exclusion of pleural effusion with malignant tumors based on negative results of CEA and hyaluronic acid, and cytology of pleural effusion; (d) exclusion of rheumatic, bacterial, and tuberculous pleuritis; (d) radiological findings for exclusion of malignancies; and (e) histopathological findings based on thoracoscopy that exclude malignancies (when thoracoscopy was not performed, there was confirmation that no malignancies were present during 3-month follow-up observation). Cases that satisfied all items were defined as BAPE.<br><br>RESULTS: Among the 105 suspected cases, there were five cases that had no occupational asbestos exposure; six cases in which transudate of on pleural effusion; one case each of rheumatoid pleuritis and tuberculous pleuritis; and five cases of pleural mesothelioma based on chest radiography and histopathological findings within 3&#xa0;months after initial diagnosis. Therefore, we excluded 18 cases from the 105 candidates and determined 87 cases of BAPE.<br><br>CONCLUSION: We consider that six items described above are suitable for diagnosing BAPE.}, }
@article {pmid33312638, year = {2020}, author = {Moteallemi, A and Minaei, M and Tahmasbizadeh, M and Fadaei, S and Masroor, K and Fanaei, F}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Mashhad City, Iran: levels, spatial distribution and seasonal variations.}, journal = {Journal of environmental health science &amp; engineering}, volume = {18}, number = {2}, pages = {1239-1246}, pmid = {33312638}, issn = {2052-336X}, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. The objectives of this study were to monitor the levels of asbestos fibers in ambient air of Mashhad, Iran during 2018, and to draw its Geographic Information System (GIS) distribution map for the city. In this descriptive study, 13 sampling points in Mashhad city were chosen. Sampling of asbestos was carried out for 3 hour during summer and winter at 2018. Sampling of asbestos was performed using MCE (Mixed Cellulose Ester) membrane filters (pour size 0.45 µm; diameter: 25 mm) and cassette holder and peripheral pump. The samples were the analyzed by the phase contrast microscopy (PCM) method (NIOSH7400). Also, to investigate the type of asbestos and for more accurate counting of fibers, Scanning Electron Microscopy (SEM) analysis was utilized. Meteorological parameter were recorded through portable devices. To draw the graphs, Excel, R and Arc GIS software were used. Results showed that the mean asbestos fiber concentrations were equal to 11.40 ± 2.14 and 14.38 ± 2.52 f/L in summer and winter, respectively. The maximum level of asbestos fiber was detected in the station of Baitolmoghaddas square by 26.64 ± 2.14 and 19.3 SEM f/L in winter and summer, respectively. High concentration of asbestos fiber observed in this study can be attributed to the heavy traffic, the presence of prominent industries in the vicinity of the study area, and topographic features. The results from this research recommends that suitable controlling policies should be regulated to reduce both ambient air asbestos and its adverse health endpoints in Mashhad.}, }
@article {pmid33304846, year = {2020}, author = {Cheng, YY and Yuen, ML and Rath, EM and Johnson, B and Zhuang, L and Yu, TK and Aleksova, V and Linton, A and Kao, S and Clarke, CJ and McCaughan, BC and Takahashi, K and Lee, K}, title = {CDKN2A and MTAP Are Useful Biomarkers Detectable by Droplet Digital PCR in Malignant Pleural Mesothelioma: A Potential Alternative Method in Diagnosis Compared to Fluorescence In Situ Hybridisation.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {579327}, pmid = {33304846}, issn = {2234-943X}, abstract = {BACKGROUND: The diagnosis of malignant pleural mesothelioma (MPM) can be difficult, in part due to the difficulty in distinguishing between MPM and reactive mesothelial hyperplasia (RMH). The tumor suppressor gene, CDKN2A, is frequently silenced by epigenetic mechanisms in many cancers; in the case of MPM it is mostly silenced via genomic deletion. Co-deletion of the CDKN2A and methylthioadenosine phosphorylase (MTAP) genes has been researched extensively and discovered to be a highly specific characteristic of MPM. Most studies have used FISH to detect the deletion of CDKN2A and IHC for MTAP as a surrogate for this. In this study, we aim to investigate and validate droplet digital PCR (ddPCR) as an emerging alternative and efficient testing method in diagnosing MPM, by particularly emphasizing on the loss of MTAP and CDKN2A.<br><br>METHODS: This study included 75 formalin fixed paraffin embedded (FFPE) MPM tissue, and 12 normal pleural tissue and 10 RMH as control. Additionally, primary MPM cell lines and normal pleural samples were used as biomarker detection controls, as established in our previous publication. All FFPE specimens were processed to isolate the DNA, that was subsequently used for ddPCR detection of CDKN2A and MTAP. FFPE samples were also analyzed by fluorescence in situ hybridization (FISH) for CDKN2A and MTAP deletion, and for MTAP IHC expression. Concordance of IHC and ddPCR with FISH were studied in these samples.<br><br>RESULTS: 95% and 82% of cases showed co-deletion of both MTAP and CDKN2A when determined by FISH and ddPCR respectively. ddPCR has a sensitivity of 72% and specificity of 100% in detecting CDKN2A homozygous loss in MPM. ddPCR also has a concordance rate of 92% with FISH in detecting homozygous loss of CDKN2A. MTAP IHC was 68% sensitive and 100% specific for detecting CDKN2A homozygous loss in MPM when these losses were determined by ddPCR.<br><br>CONCLUSION: Our study confirms that MTAP is often co-deleted with CDKN2A in MPM. Our in-house designed ddPCR assays for MTAP and CDKN2A are useful in differentiating MPM from RMH, and is highly concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.}, }
@article {pmid33304592, year = {2021}, author = {Cheah, HM and Fitzgerald, D and Louw, A and Creaney, J and Lee, YCG}, title = {Hyaluronic acid in viscous malignant mesothelioma pleural effusion.}, journal = {Respirology case reports}, volume = {9}, number = {1}, pages = {e00694}, pmid = {33304592}, issn = {2051-3380}, abstract = {Malignant pleural effusion (MPE) is common with mesothelioma. We report two cases of extraordinarily viscous MPEs associated with mesothelioma. The viscosity prohibited spontaneous gravity-dependent drainage via indwelling pleural catheters. Our ex vivo experiments found very high hyaluronic acid (HA) content within the fluid. Treatment of the fluid with hyaluronidase, but not with deoxyribonucleases, significantly reduced fluid viscosity. The results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. Research into strategies of counteracting HA properties in the management of MPEs may provide further insight.}, }
@article {pmid33300108, year = {2021}, author = {Dell'Anno, I and Martin, SA and Barbarino, M and Melani, A and Silvestri, R and Bottaro, M and Paolicchi, E and Corrado, A and Cipollini, M and Melaiu, O and Giordano, A and Luzzi, L and Gemignani, F and Landi, S}, title = {Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma.}, journal = {Investigational new drugs}, volume = {39}, number = {3}, pages = {644-657}, pmid = {33300108}, issn = {1573-0646}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Repositioning ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mesothelioma/*drug therapy/genetics/metabolism ; Pleural Neoplasms/*drug therapy/genetics/metabolism ; Risedronic Acid/*pharmacology ; STAT1 Transcription Factor/*antagonists &amp; inhibitors/metabolism ; Vidarabine/*analogs &amp; derivatives/pharmacology ; }, abstract = {Objectives Malignant pleural mesothelioma (MPM) is an occupational disease mainly due to asbestos exposure. Effective therapies for MPM are lacking, making this tumour type a fatal disease. Materials and Methods In order to meet this need and in view of a future "drug repositioning" approach, here we screened five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model, with a library of 1170 FDA-approved drugs. Results Among several potential compounds, we found that fludarabine (F-araA) and, to a lesser extent, risedronic acid (RIS) were cytotoxic in MPM cells, in comparison to the non-malignant Met-5A cells. In particular, F-araA reduced the proliferation and the colony formation ability of the MPM malignant cells, in comparison to the non-malignant control cells, as demonstrated by proliferation and colony formation assays, in addition to measurement of the phospho-ERK/total-ERK ratio. We have shown that the response to F-araA was not dependent upon the expression of DCK and NT5E enzymes, nor upon their functional polymorphisms (rs11544786 and rs2295890, respectively). Conclusion This drug repositioning screening approach has identified that F-araA could be therapeutically active against MPM cells, in addition to other tumour types, by inhibiting STAT1 expression and nucleic acids synthesis. Further experiments are required to fully investigate this.}, }
@article {pmid33257382, year = {2020}, author = {Tanaka, T and Miyamoto, Y and Sakai, A and Fujimoto, N}, title = {Nivolumab for malignant peritoneal mesothelioma.}, journal = {BMJ case reports}, volume = {13}, number = {11}, pages = {}, pmid = {33257382}, issn = {1757-790X}, mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Male ; Mesothelioma, Malignant/diagnostic imaging/*drug therapy ; Nivolumab/*therapeutic use ; Peritoneal Neoplasms/diagnostic imaging/*drug therapy ; Radiography, Abdominal ; Tomography, X-Ray Computed ; }, abstract = {Malignant peritoneal mesothelioma (MPeM) is a highly malignant neoplasm of the peritoneum, which carries a poor prognosis. A 70-year-old man, who was employed in the shipbuilding industry and exposed to asbestos for 50 years, was found to have a low-density lesion in the peritoneum around the liver and spleen, associated with multiple mediastinal and parasternal lymphadenopathy. Laparoscopic exploration was performed, and biopsy specimen analysis led to a diagnosis of MPeM. Initial systemic chemotherapy comprising cisplatin and pemetrexed yielded a modest cytoreductive effect. However, 4 months later, the patient presented with abdominal distension and anorexia. CT images revealed massive ascites, bowel obstruction and an enlarged intra-abdominal tumour, which was considered progression of the MPeM. The patient was treated with nivolumab. Bowel obstruction was improved after the first administration, and his sense of abdomen distension completely disappeared after the third administration. This case supports the utility of immunotherapy in MPeM.}, }
@article {pmid33238762, year = {2021}, author = {Arulananda, S and Lee, EF and Fairlie, WD and John, T}, title = {The role of BCL-2 family proteins and therapeutic potential of BH3-mimetics in malignant pleural mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {21}, number = {4}, pages = {413-424}, doi = {10.1080/14737140.2021.1856660}, pmid = {33238762}, issn = {1744-8328}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Biomimetic Materials/pharmacology ; Cell Survival ; Humans ; Mesothelioma/*drug therapy/pathology ; Molecular Targeted Therapy ; Pleural Neoplasms/*drug therapy/pathology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Survival Rate ; }, abstract = {Introduction: With limited recent therapeutic changes, malignant pleural mesothelioma (MPM) is associated with poor survival and death within 12 months, making it one of the most lethal malignancies. Due to unregulated asbestos use in developing countries and home renovation exposures, cases of MPM are likely to present for decades. As MPM is largely driven by dysregulation of tumor suppressor genes, researchers have examined other mechanisms of subverting tumor proliferation and spread. Over-expression of pro-survival BCL-2 family proteins impairs cells from undergoing apoptosis, and BH3-mimetics targeting them are a novel treatment option across various cancers, though have not been widely investigated in MPM.Areas covered: This review provides an overview of MPM and its current treatment landscape. It summarizes the role of BCL-2 family proteins in tumorigenesis and the therapeutic potential of BH3-mimetics . Finally, it discusses the role of BCL-2 proteins in MPM and the pre-clinical rationale for investigating BH3-mimetics as a therapeutic strategy.Expert opinion: As a disease without readily actionable oncogene driver mutations and with modest benefit from immune checkpoint inhibition, novel therapeutic options are urgently needed for MPM. Hence, BH3-mimetics provide a promising treatment option, with evidence supporting dependence on pro-survival BCL-2 proteins for MPM cell survival.}, }
@article {pmid33233407, year = {2020}, author = {Cugliari, G and Catalano, C and Guarrera, S and Allione, A and Casalone, E and Russo, A and Grosso, F and Ferrante, D and Viberti, C and Aspesi, A and Sculco, M and Pirazzini, C and Libener, R and Mirabelli, D and Magnani, C and Dianzani, I and Matullo, G}, title = {DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, pmid = {33233407}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10[-9]) OS-related differential methylation of a single-CpG (cg03546163), located in the 5'UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.}, }
@article {pmid33230247, year = {2020}, author = {Jiang, Z and Shen, W and Ying, S and Gao, Z and He, X and Chen, R and Xia, H and Guo, X and Fang, Y and Zhang, Y and Miao, J and Zhou, J and Zhang, X and Chen, J and Lou, J}, title = {Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {20373}, pmid = {33230247}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/*genetics/metabolism ; Extracellular Matrix Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; HMGB1 Protein/*genetics/metabolism ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/chemically induced/diagnosis/*genetics/mortality ; Male ; Mesothelioma, Malignant/chemically induced/diagnosis/*genetics/mortality ; Microarray Analysis ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {Fibulin-3 is an extracellular matrix glycoprotein widely expressed in various tissues. Tissue fibulin-3 expression have never been reported in association with prognosis of mesothelioma. Hence, we sought to determine the association between fibulin-3 expression and mesothelioma survival. We made a tissue microarray, which was comprised of cancer and normal tissue from mesothelioma patients (n = 82) during the period 1998-2017 in China. Fibulin-3 and HGMB1 expression were analyzed by immunohistochemistry method. Kaplan-Meier method and Cox proportional hazard models were used for analyzing survival data. Overall, 61 cases (74.4%) were female; 90.2% were of epithelioid type; the median overall survival time was 12.5 months. Fibulin-3 and HMGB1 were highly expressed in tumor tissue rather than adjacent tissue. The expression of fibulin-3 in tissue was correlated with that of HMGB1 (r = 0.32, P = 0.003). High expression of fibulin-3 in tumor tissue could predict poor survival in patients with mesothelioma (P = 0.02). This remained true in a multivariate model, with a significant hazard ratio of 1.91. We demonstrated that fibulin-3 in tumor tissue was a novel biomarker of poor survival of mesothelioma, suggesting it may be a relevant target for therapeutic intervention.}, }
@article {pmid33197421, year = {2021}, author = {Xia, H and Feng, L and Lin, L and Jiang, Z and Chen, J and Shi, W and Ying, S and Yu, M and Ju, L and Zhu, L and Shi, L and Zhang, X and Lou, J}, title = {Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS.}, journal = {Environmental research}, volume = {193}, number = {}, pages = {110467}, doi = {10.1016/j.envres.2020.110467}, pmid = {33197421}, issn = {1096-0953}, mesh = {Biomarkers ; Biomarkers, Tumor ; Chromatography, Liquid ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms ; ROC Curve ; Tandem Mass Spectrometry ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.}, }
@article {pmid33149905, year = {2020}, author = {Filetti, V and Vitale, E and Broggi, G and Hagnäs, MP and Candido, S and Spina, A and Lombardo, C}, title = {Update of in vitro, in vivo and ex vivo fluoro-edenite effects on malignant mesothelioma: A systematic review (Review).}, journal = {Biomedical reports}, volume = {13}, number = {6}, pages = {60}, pmid = {33149905}, issn = {2049-9434}, abstract = {Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous phases tremolite and actinolite. Indeed, epidemiological studies have shown that FE fibers have similar effects to those of asbestos fibers. Such studies have reported a high incidence of malignant mesothelioma (MM), an aggressive neoplasm of the serosal membranes lining the pleural cavity, in individuals residing there due to FE exposure in Biancavilla related to environmental contamination. Evidence has led to the classification of FE as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). The aim of this systematic review is to compare the results achieved in in vitro, in vivo and ex vivo experimental studies involving FE in order to update the current knowledge on the pathogenesis and molecular mechanisms responsible for FE-mediated MM development as well as the availability of effective biomarkers for MM prevention and diagnosis. This review is focused on the pathophysiological mechanisms mediated by inflammation induced by FE fiber exposure and which are responsible for MM development. This review also discusses the discovery of new diagnostic and prognostic biomarkers for the management of this pathology. It is known that the risk of cancer development increases with chronic inflammation, arising from enhanced reactive oxygen species (ROS) and NO[•] production stimulated by the body to remove exogenous agents, causing DNA damage and enhanced signal transduction that may lead to activation of oncogenes. Studies concerning MM biomarker discovery indicate that several biomarkers have been proposed for MM, but mesothelin is the only Food and Drug Administration (FDA)-approved biomarker for MM, with limitations. In recent studies, in silico analysis to identify selected miRNAs highly deregulated in cancer samples when compared with normal control have been developed. This in silico approach could represent an effort in the field of biomarker discovery for MM.}, }
@article {pmid33149886, year = {2020}, author = {Notue, YA and Mbessoh, UI and Nganwa, G and Pambe, JN and Mefire, AC and Moifo, B and Sando, Z}, title = {Sarcomatoid malignant peritoneal mesothelioma presenting as a localized mesenteric tumor with no previous asbestos exposure.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {10}, pages = {rjaa419}, pmid = {33149886}, issn = {2042-8812}, abstract = {Sarcomatoid malignant peritoneal mesothelioma is the rarest and most lethal form of peritoneal mesothelioma. We present the case of a sarcomatoid malignant peritoneal mesothelioma presenting as a localized mesenteric tumor in a 54-year-old female with no previous asbestos exposure. This clinical presentation is extremely rare and is the first documented in Cameroon.}, }
@article {pmid33148505, year = {2020}, author = {Khaliullin, TO and Kisin, ER and Guppi, S and Yanamala, N and Zhernovkov, V and Shvedova, AA}, title = {Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes.}, journal = {Toxicology and applied pharmacology}, volume = {409}, number = {}, pages = {115302}, doi = {10.1016/j.taap.2020.115302}, pmid = {33148505}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/adverse effects ; Animals ; Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Autoimmune Diseases/chemically induced/metabolism ; Bodily Secretions/*drug effects ; Cells, Cultured ; Cytokines/*metabolism ; Lung Neoplasms/chemically induced/metabolism ; Macrophages, Alveolar/*drug effects/metabolism ; Mesothelioma, Malignant/chemically induced/metabolism ; Mice ; Mice, Inbred C57BL ; Mineral Fibers/adverse effects ; Minerals/*adverse effects ; Occupational Exposure/adverse effects ; Particle Size ; Particulate Matter/adverse effects ; Transcription, Genetic/*drug effects ; }, abstract = {Human exposures to asbestiform elongate mineral particles (EMP) may lead to diffuse fibrosis, lung cancer, malignant mesothelioma and autoimmune diseases. Cleavage fragments (CF) are chemically identical to asbestiform varieties (or habits) of the parent mineral, but no consensus exists on whether to treat them as asbestos from toxicological and regulatory standpoints. Alveolar macrophages (AM) are the first responders to inhaled particulates, participating in clearance and activating other resident and recruited immunocompetent cells, impacting the long-term outcomes. In this study we address how EMP of asbestiform versus non-asbestiform habit affect AM responses. Max Planck Institute (MPI) cells, a non-transformed mouse line that has an AM phenotype and genotype, were treated with mass-, surface area- (s.a.), and particle number- (p.n.) equivalent concentrations of respirable asbestiform and non-asbestiform riebeckite/tremolite EMP for 24 h. Cytotoxicity, cytokines secretion and transcriptional changes were evaluated. At the equal mass, asbestiform EMP were more cytotoxic, however EMP of both habits induced similar LDH leakage and decrease in viability at s.a. and p.n. equivalent doses. DNA damage assessment and cell cycle analysis revealed differences in the modes of cell death between asbestos and respective CF. There was an increase in chemokines, but not pro-inflammatory cytokines after all EMP treatments. Principal component analysis of the cytokine secretion showed close clustering for the s.a. and p.n. equivalent treatments. There were mineral- and habit-specific patterns of gene expression dysregulation at s.a. equivalent doses. Our study reveals the critical nature of EMP morphometric parameters for exposure assessment and dosing approaches used in toxicity studies.}, }
@article {pmid33143837, year = {2020}, author = {Liu, Y and Tong, J and Ling, X and Cao, W and Fang, L}, title = {A Case of Systemic Lupus Erythematosus with Malignant Pleural Mesothelioma in a 42-year Woman.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {30}, number = {10}, pages = {1099-1101}, doi = {10.29271/jcpsp.2020.10.1099}, pmid = {33143837}, issn = {1681-7168}, mesh = {Female ; Humans ; *Lupus Erythematosus, Systemic/complications/diagnosis/drug therapy ; *Mesothelioma/diagnosis/drug therapy ; *Mesothelioma, Malignant ; *Pleural Effusion/etiology ; *Pleural Neoplasms/diagnosis/drug therapy ; }, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterised by inflammation. Malignant pleural mesothelioma (MPM) is a highly invasive malignant tumor derived from pleural mesothelial cells. Here, we report a case of SLE with MPM. A 42-year woman with no exposure to asbestos presented with severe left chest pain. Initially, we diagnosed her with SLE because of the clinical manifestations and high antinuclear antibody titer. Finally, a diagnosis of MPM was made, based on pleural biopsy. Her condition was under control after one cycle of chemotherapy and oral methotrexate. However, three years later, she was admitted with dyspnea, mild orthopnea, and tachycardia, and died one month later after discontinuing treatment. MPM is rare, and MPM with SLE is even rarer. We should pay attention to pleural effusion when diagnosing SLE. If possible, a pleural biopsy should be performed to reduce misdiagnosis and missed diagnosis. Key Words: Pleural effusion, Systemic lupus erythematosus (SLE), Mesothelioma.}, }
@article {pmid33133607, year = {2020}, author = {MacMillan, M and Roy, B and McLaren, S and Nowak, AK and Thomas, R and Lee, YCG}, title = {Widespread pulmonary invasion by malignant pleural mesothelioma: an important diagnostic consideration.}, journal = {Respirology case reports}, volume = {8}, number = {9}, pages = {e00675}, pmid = {33133607}, issn = {2051-3380}, abstract = {We report a rare case of early and extensive pulmonary invasion of malignant pleural mesothelioma (MPM) in a 70-year-old woman. She first presented with a hydropneumothorax and subsequent workup, including video-assisted thoracoscopy (VAT), confirmed MPM. After VAT, she developed dyspnoea, cough, and widespread pulmonary infiltrates of uncertain aetiology. These infiltrates progressed over the following months, failed to respond to antibiotics, and were strongly fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET). Bronchoalveolar lavage (BAL) yielded extremely viscous fluid containing mesothelioma cells. These cells were also found in the sputum when nebulized deoxyribonuclease (DNase) was trialled to enhance clearance of the pulmonary fluid. The patient deteriorated rapidly with progressive mediastinal and contralateral MPM involvement and died one month later. This case highlights the importance of including tumour invasion as a differential diagnosis of non-resolving pulmonary infiltrates in patients with MPM.}, }
@article {pmid33133014, year = {2020}, author = {Gesmundo, I and Silvagno, F and Banfi, D and Monica, V and Fanciulli, A and Gamba, G and Congiusta, N and Libener, R and Riganti, C and Ghigo, E and Granata, R}, title = {Calcitriol Inhibits Viability and Proliferation in Human Malignant Pleural Mesothelioma Cells.}, journal = {Frontiers in endocrinology}, volume = {11}, number = {}, pages = {559586}, pmid = {33133014}, issn = {1664-2392}, mesh = {Calcitriol/*pharmacology/therapeutic use ; Cell Cycle Checkpoints/drug effects/physiology ; Cell Line, Tumor ; Cell Proliferation/*drug effects/physiology ; Cell Survival/*drug effects/physiology ; Humans ; Mesothelioma, Malignant/drug therapy/*pathology ; Tumor Cells, Cultured ; Vitamins/*pharmacology/therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, often associated with exposure to asbestos and characterized by poor prognosis and limited treatment options. The biologically active form of vitamin D, calcitriol, exerts anticancer effects in many cell types, both alone and in combination with chemotherapy drugs, through binding to vitamin D receptor (VDR); however, the role of calcitriol in MPM is still unknown. This study aimed to determine the potential antitumor role of calcitriol in MPM. The results showed that calcitriol reduces cell viability and proliferation in human MPM cells lines, which express both cytoplasmic and nuclear VDR; furthermore, calcitriol potentiated the inhibitory activity of the chemotherapy drug PEM. These effects were paralleled by cell cycle arrest and inhibition in expression of c-Myc and cyclins involved in cell cycle progression. Exposure of MPM cells to calcitriol also produced an alteration in mitochondrial function and inhibition in the expression of respiratory chain complex subunits. Finally, the inhibitory effects of calcitriol were also observed on viability of human primary MPM cells. Collectively, these results indicate a novel anticancer role for calcitriol in MPM, suggesting potential for vitamin D derivatives, alone or in combination with chemotherapy, in the treatment of this malignancy.}, }
@article {pmid33119974, year = {2020}, author = {Barbieri, PG and Mirabelli, D and Madeo, E and Somigliana, A}, title = {[Asbestos exposure and related diseases among friction products workers (1971-2016)].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {42}, number = {3}, pages = {145-152}, pmid = {33119974}, issn = {1592-7830}, mesh = {Aged ; Air Pollutants, Occupational/analysis ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis/*toxicity ; Asbestosis/*epidemiology ; Automobiles ; Female ; Friction ; Humans ; Italy ; *Lung ; Lung Neoplasms/*epidemiology/etiology ; Male ; *Manufacturing Industry ; Mesothelioma/epidemiology ; Middle Aged ; Mineral Fibers/analysis ; Occupational Exposure/*adverse effects/analysis/statistics &amp; numerical data ; Preliminary Data ; Talc/toxicity ; Time Factors ; }, abstract = {Worldwide studies have been published on the mortality of workers employed in asbestos-based materials for the production of clutches and brakes. However no one of these studies is related to Italian cases. Furthermore, not even surveys have been conducted in Italy to characterize the correlation between asbestos exposures and the possible occurring of asbestos-related disease. Our objectives are the following: i) to assess and quantify the asbestos exposure cases, ii) to describe the nature and the frequency of asbestos-related diseases among blue collar employees of an important factory producing brakes and clutches with chrysotile asbestos content from 1971 to 1993 and iii) to provide preliminary data on cumulative asbestos exposure estimated using lung fibre burden analysis. Critical appraisal of airborne asbestos fibre measurements and identification of cases of asbestos-related diseases between the blue collar employees, either notified to the local health authority or recovered from the Italian national Mesothelioma registry was investigated. Lung fibre burden analysis using the lung tissue samples from two deceased blue collar employees was also performed. Airborne asbestos fibre measurements (carried out in 1982) suggested asbestos fibres average concentrations of about 0.3 f/ml, while all 1992 measurements showed results below 0.1 f/ml. Furthermore, since 1988, we identified four cases of pleural plaques, three cases of asbestosis and seven cases of lung cancer. No case of malignant mesothelioma was found. In both lung cancer cases, analysed to measure the lung fibre burden, commercial amphiboles were absent or in limited concentration but chrysotile and, especially, tremolite asbestos were present in noticeable amount. In conclusion, since 1971 and up to early 1980s, exposure to chrysotile asbestos and talc, likely contaminated by tremolite, had been significant and comparable to levels causing asbestosis long-term risk. No case of malignant mesothelioma was found, that is consistent with the absence of amphiboles and with the lower risk of mesothelioma associated with the chrysotile asbestos. However a subset of the blue collar employees, the ones employed later on, could still have not reached the full risk condition, and so being still at risk of developing malignant mesothelioma. In the two lung cancer cases studied, the lung fibre burden was essentially made of chrysotile and tremolite. Lastly, lung cancer occurrence in the population of blue collar employees has been likely underestimated and the correct determination of lung cancer risk should be done through the mortality analysis of this population.}, }
@article {pmid33093002, year = {2020}, author = {Brandi, G and Deserti, M and Palloni, A and Turchetti, D and Zuntini, R and Pedica, F and Frega, G and De Lorenzo, S and Abbati, F and Rizzo, A and Di Marco, M and Massari, F and Tavolari, S}, title = {Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos.}, journal = {Cancer genetics}, volume = {248-249}, number = {}, pages = {57-62}, doi = {10.1016/j.cancergen.2020.10.001}, pmid = {33093002}, issn = {2210-7762}, mesh = {Asbestos/*adverse effects ; Bile Duct Neoplasms/etiology/*pathology ; *Carcinogens ; Cholangiocarcinoma/etiology/*pathology ; Female ; *Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations.}, }
@article {pmid33087407, year = {2020}, author = {Wong, JYY and Rice, C and Blair, A and Silverman, DT}, title = {Mesothelioma risk among those exposed to chrysotile asbestos only and mixtures that include amphibole: a case-control study in the USA, 1975-1980.}, journal = {Occupational and environmental medicine}, volume = {}, number = {}, pages = {}, pmid = {33087407}, issn = {1470-7926}, support = {Z01 CP010136/ImNIH/Intramural NIH HHS/United States ; ZIA CP010120/ImNIH/Intramural NIH HHS/United States ; }, abstract = {OBJECTIVES: Occupational asbestos exposure is causally linked to mesothelioma. However, whether exposure to only chrysotile asbestos is associated with mesothelioma risk, and the heterogeneity in risk by different fibre types/lengths remains unclear. We investigated whether mesothelioma risk differs among workers exposed to only chrysotile asbestos compared with chrysotile and ≥1 amphibole (ie, amosite, tremolite, anthophyllite and crocidolite) over the working lifetime.<br><br>METHODS: We analysed next-of-kin interview data including occupational histories for 580 white men (176 cases and 404 controls) from a case-control study of mesothelioma conducted in the USA in 1975-1980. Asbestos exposure was determined by an occupational hygienist using a job-exposure matrix and exposure categories included chrysotile only and nine chrysotile-amphibole mixtures. Logistic regression models were used to estimate the ORs and 95% CIs of mesothelioma, comparing each asbestos category to the unexposed group, adjusted for age at death and data source. Analysis of contrasts was used to assess overall heterogeneity and pair-wise differences in risk.<br><br>RESULTS: Exposure to long and short chrysotile only was associated with increased mesothelioma risk compared with the unexposed (OR=3.8 (95% CI 1.3 to 11.2)). The complex mixture of extra-long amosite, short and long chrysotile, tremolite and anthophyllite was associated with the highest risk (OR=12.8 (95% CI 4.1 to 40.2)). There was evidence for overall heterogeneity among the asbestos exposure categories (p heterogeneity=0.02). However, the lower risk observed for exposure to chrysotile only compared with the complex mixture was not significant (p difference=0.10).<br><br>CONCLUSIONS: Our findings suggest that policies aimed at regulating asbestos should target both pure chrysotile and mixtures that include amphibole.}, }
@article {pmid33085641, year = {2020}, author = {Piber, P and Vavpetic, N and Goricar, K and Dolzan, V and Kovac, V and Franko, A}, title = {The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {54}, number = {4}, pages = {429-436}, pmid = {33085641}, issn = {1581-3207}, mesh = {Aged ; Alleles ; Case-Control Studies ; Female ; Genetic Variation ; Genotype ; Humans ; Inflammation Mediators/metabolism ; Interleukin-1beta/*genetics ; Male ; Mesothelioma, Malignant/diagnostic imaging/*genetics ; MicroRNAs/*genetics ; Middle Aged ; Pleural Diseases/diagnostic imaging/*genetics ; Pleural Neoplasms/diagnostic imaging/*genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {Background Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13-0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14-0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28-0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions Our findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.}, }
@article {pmid33069179, year = {2020}, author = {Janošíková, M and Nakládalová, M and Štěpánek, L and Boriková, A and Vildová, H and Fošum, M}, title = {Occurrence of asbestos-related occupational diseases in the Czech Republic in the last 20 years.}, journal = {Central European journal of public health}, volume = {28 Suppl}, number = {}, pages = {S37-S42}, doi = {10.21101/cejph.a6297}, pmid = {33069179}, issn = {1210-7778}, mesh = {*Asbestos/toxicity ; Czech Republic/epidemiology ; Humans ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Asbestos-related diseases are still a current problem worldwide. What is their occurrence in the Czech Republic? The answer is the subject of this study, which aims to provide a general and regional overview of the situation over the last 20 years with a more detailed focus on mesothelioma, the development of which is highly associated with asbestos exposure and the issue of their recognition as an occupational disease.<br><br>METHODS: In its retrospective reviews, the study is based on analyses of data from the Institute of Health Information and Statistics of the Czech Republic and data from the Czech National Cancer Registry, which also interconnects.<br><br>RESULTS: In the last 20 years, 512 new cases of occupational diseases from asbestos have been reported, namely 228 cases of pleural thickening, 133 mesotheliomas, 92 asbestoses, and 59 cases of lung cancer. In the last 5 years, mesotheliomas (n = 39) predominated among the reported diseases with a 45% proportion in the total number of 86 cases. The trend in their incidence, as the only one among asbestos-related diseases, is not declining. There was a significant difference in the overall incidence of mesothelioma in a general population and the incidence of occupational mesotheliomas. At the national level, occupational aetiology was acknowledged in only 11.3% of cases of mesothelioma on average. The highest proportion of occupational mesotheliomas and the highest incidence of all asbestos-related diseases were found in regions where the largest asbestos processing plants were located.<br><br>CONCLUSION: The authors emphasize the importance of work history for the diagnostic process of asbestos-related diseases and also the need to perform follow-up examinations for their early detection.}, }
@article {pmid33065463, year = {2020}, author = {Fusco, N and Vaira, V and Righi, I and Sajjadi, E and Venetis, K and Lopez, G and Cattaneo, M and Castellani, M and Rosso, L and Nosotti, M and Clerici, M and Ferrero, S}, title = {Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {150}, number = {}, pages = {53-61}, doi = {10.1016/j.lungcan.2020.09.026}, pmid = {33065463}, issn = {1872-8332}, mesh = {B7-H1 Antigen ; Humans ; *Lung Neoplasms ; Lymphocytes, Tumor-Infiltrating ; *Mesothelioma, Malignant ; Prognosis ; Tumor Microenvironment ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare tumor with an extremely poor prognosis. Its pathogenesis is related to an immune response against asbestos fibers. The T-lymphocytes, including CD8[POS] and CD4[POS] cells, are an important part of the MPM immune microenvironment, and likely contribute to the therapy resistance observed in these tumors. Here, we sought to characterize the MPM-specific lymphocytes subpopulations within the tumor immune microenvironment to identify novel clinically relevant immunologic subtypes of tumors. Representative formalin-fixed, paraffin-embedded (FFPE) tissue blocks of 88 MPMs were included in tissue microarrays and subjected to tumor-infiltrating lymphocytes (TILs) quantification and subtyping by immunohistochemistry (IHC) with antibodies specific for CD4, CD8, and CD19. Further, PD-L1 (clone 22C3) expression was assessed by IHC as a combined positive score (CPS). Our data show that PD-L1 expression by tumor cells or the presence of a sarcomatoid component is related to increased stromal TILs presence in MPM. Survival analyses showed that low CD4[POS] and high CD8[POS] stromal TILs are associated with poor patients' survival. In MPMs with PD-L1 CPS > 1, stromal CD8[HIGH] was a poor prognostic factor, akin stromal CD4[POS] peritumoral TILs correlated with a worse prognosis. Furthermore, we demonstrated that a high CD4[POS]/CD8[POS] ratio in the tumor immune microenvironment is an independent prognostic factor for survival. Finally, we provided evidence that the characterization of the stromal immune landscape of MPM predicts responses to chemotherapy in subgroups of MPM. The results of this study provide novel insights into the clinical scenario of immune-related biomarkers in MPM.}, }
@article {pmid33055488, year = {2021}, author = {Sekine, I and Yamamoto, Y and Suzuki, T and Suzuki, H}, title = {Malignant Pleural Mesothelioma in Patients Who Previously Received Radiotherapy for Their First Malignant Tumor.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {60}, number = {5}, pages = {663-665}, pmid = {33055488}, issn = {1349-7235}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms/radiotherapy ; *Mesothelioma/radiotherapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/radiotherapy ; }, }
@article {pmid33055477, year = {2021}, author = {Nakashima, K and Demura, Y and Oi, M and Tabata, M and Tada, T and Shiozaki, K and Akai, M and Ishizuka, T}, title = {The Association between Malignant Pleural Mesothelioma and Thoracic Radiation Therapy for Hodgkin's Lymphoma: The First Case Report in Japan.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {60}, number = {5}, pages = {771-775}, pmid = {33055477}, issn = {1349-7235}, mesh = {*Asbestos ; Europe ; Female ; *Hodgkin Disease/radiotherapy ; Humans ; Japan/epidemiology ; *Mesothelioma/diagnosis/etiology ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/etiology/radiotherapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is mostly observed in patients with a history of asbestos exposure. Although other causes are rare, there are several reports of MPM induced by therapeutic radiation, mainly in Europe and North America. However, no such case has been reported in Japan. We herein report a 50-year-old Japanese woman who developed MPM 25 years after thoracic radiation therapy for Hodgkin's lymphoma. The patient had no history of exposure to asbestos; therefore, her history of radiation therapy was considered to be the cause of MPM. Clinicians should consider secondary MPM in patients with a history of thoracic radiation therapy.}, }
@article {pmid33054855, year = {2020}, author = {Saleh, DM and Alexander, WT and Numano, T and Ahmed, OHM and Gunasekaran, S and Alexander, DB and Abdelgied, M and El-Gazzar, AM and Takase, H and Xu, J and Naiki-Ito, A and Takahashi, S and Hirose, A and Ohnishi, M and Kanno, J and Tsuda, H}, title = {Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat.}, journal = {Particle and fibre toxicology}, volume = {17}, number = {1}, pages = {48}, pmid = {33054855}, issn = {1743-8977}, mesh = {Air Pollutants/*toxicity ; Animals ; Asbestos, Crocidolite ; Carcinogenicity Tests ; Inhalation Exposure ; Lung ; Lung Neoplasms ; Mesothelioma ; Nanotubes, Carbon/*toxicity ; Rats ; Trachea/drug effects ; }, abstract = {BACKGROUND: Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80-90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos.<br><br>RESULTS: There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5&#x2009;mg MWCNT-B, and 1.0&#x2009;mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5&#x2009;mg MWCNT-B, and 1.0&#x2009;mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups.<br><br>CONCLUSIONS: The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.}, }
@article {pmid33050791, year = {2020}, author = {Hariharan, A and Sun, S and Wipplinger, M and Felley-Bosco, E}, title = {RNA editing in mesothelioma: a look forward.}, journal = {Open biology}, volume = {10}, number = {10}, pages = {200112}, pmid = {33050791}, issn = {2046-2441}, mesh = {Adenosine Deaminase/metabolism ; Animals ; Cell Proliferation ; Disease Progression ; *Gene Expression Regulation, Neoplastic ; Genomic Instability ; Humans ; Interferon Type I/metabolism ; Mesothelioma/*genetics/metabolism/pathology/therapy ; Protein Binding ; *RNA Editing ; RNA Processing, Post-Transcriptional ; RNA-Binding Proteins/metabolism ; }, abstract = {RNA editing is a post-transcriptional process increasing transcript diversity, thereby regulating different biological processes. We recently observed that mutations resulting from RNA editing due to hydrolytic deamination of adenosine increase during the development of mesothelioma, a rare cancer linked to chronic exposure to asbestos. This review gathers information from the published literature and public data mining to explore several aspects of RNA editing and their possible implications for cancer growth and therapy. We address possible links between RNA editing and particular types of mesothelioma genetic and epigenetic alterations and discuss the relevance of an edited substrate in the context of current chemotherapy or immunotherapy.}, }
@article {pmid33049597, year = {2020}, author = {Orbach, D and André, N and Brecht, IB and López Almaraz, R and Ben-Ami, T and Vermersch, S and Carton, M and Virgone, C and Bisogno, G and Schneider, DT and Bajciova, V and Reguerre, Y and Galateau-Salle, F and Stachowicz-Stencel, T and Dvir, R and Rees, H and Bien, E and Ferrari, A and Ben Arush, M}, title = {Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {140}, number = {}, pages = {63-70}, doi = {10.1016/j.ejca.2020.09.011}, pmid = {33049597}, issn = {1879-0852}, mesh = {Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Chemotherapy, Adjuvant/methods ; Child ; Child, Preschool ; Cisplatin/therapeutic use ; Cytoreduction Surgical Procedures/methods ; Europe ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Mesothelioma, Malignant/*drug therapy ; Neoadjuvant Therapy/methods ; Peritoneal Neoplasms/drug therapy ; Retrospective Studies ; Young Adult ; }, abstract = {INTRODUCTION: Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon.<br><br>MATERIAL AND METHODS: The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents&#xa0;and young adults (&#x2264;21 year) diagnosed with mesothelial tumours treated between 1987 and 2018.<br><br>RESULTS: Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases)&#xa0;or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient).<br><br>CONCLUSIONS: Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC.}, }
@article {pmid33045471, year = {2020}, author = {Duong, BTV and Wu, L and Green, BJ and Bavaghar-Zaeimi, F and Wang, Z and Labib, M and Zhou, Y and Cantu, FJP and Jeganathan, T and Popescu, S and Pantea, J and de Perrot, M and Kelley, SO}, title = {A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103031}, pmid = {33045471}, issn = {2352-3964}, support = {R33 CA204574/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Asbestos/adverse effects ; *Biomarkers, Tumor ; Cell Line ; Disease Models, Animal ; Female ; Gene Expression Profiling/methods ; Humans ; *Liquid Biopsy/methods/standards ; Male ; Mesothelin ; Mesothelioma/*diagnosis/etiology ; Mice ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplastic Cells, Circulating/*pathology ; Occupational Exposure/adverse effects ; Prognosis ; Reproducibility of Results ; Transcriptome ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer related to asbestos exposure. Early diagnosis is challenging due to generic symptoms and a lack of biomarkers. We previously demonstrated that mesothelial precursor cells (MPC) characterized by mesothelin (MSLN)+CD90+CD34+ could be implicated in the development of mesothelioma after asbestos exposure. Here, we aimed to determine the clinical significance of detecting MPC in blood for early-stage diagnosis and prognosis of mesothelioma.<br><br>METHODS: Due to the rarity of MPC in blood, it is challenging to identify this cell population using conventional techniques. Hence, we have developed a microfluidic liquid biopsy platform called MesoFind that utilizes an immunomagnetic, mesothelin capture strategy coupled with immunofluorescence to identify rare populations of cells at high sensitivity and precision. To validate our technique, we compared this approach to flow cytometry for the detection of MPC in murine blood and lavage samples. Upon successful validation of the murine samples, we then proceeded to examine circulating MPC in 23 patients with MPM, 23 asbestos-exposed individuals (ASB), and 10 healthy donors (HD) to evaluate their prognostic and diagnostic value.<br><br>FINDING: MPC were successfully detected in the blood of murine samples using MesoFind but were undetectable with flow cytometry. Circulating MPC were significantly higher in patients with epithelioid MPM compared to HD and ASB. The MPC subpopulation, MSLN+ and CD90+, were upregulated in ASB compared to HD suggesting an early role in pleural damage from asbestos. The MPC subpopulation, MSLN+ and CD34+, in contrast, were detected in advanced MPM and associated with markers of poor prognosis, suggesting a predominant role during cancer progression.<br><br>INTERPRETATION: The identification of circulating MPC presents an attractive solution for screening and early diagnosis of epithelioid mesothelioma. The presence of different subtypes of MPC have a prognostic value that could be of assistance with clinical decisions in patients with MPM.<br><br>FUNDING: Princess Margaret Hospital Foundation Mesothelioma Research Fund, Toronto General &amp; Western Hospital Foundation.}, }
@article {pmid33040390, year = {2021}, author = {Korchevskiy, A}, title = {Using benchmark dose modeling for the quantitative risk assessment: Carbon nanotubes, asbestos, glyphosate.}, journal = {Journal of applied toxicology : JAT}, volume = {41}, number = {1}, pages = {148-160}, doi = {10.1002/jat.4063}, pmid = {33040390}, issn = {1099-1263}, mesh = {Adult ; Asbestos/*toxicity ; Benchmarking ; *Dose-Response Relationship, Drug ; Female ; Glycine/*analogs &amp; derivatives/*toxicity ; Humans ; Male ; Middle Aged ; Nanotubes, Carbon/*toxicity ; Nervous System Diseases/*chemically induced ; Occupational Exposure/adverse effects ; Risk Assessment/*methods ; }, abstract = {Benchmark dose method is one of the most famous quantitative approaches available for toxicological risks prediction. However, it is not fully clear how occupational health professionals can use it for specific workplace scenarios requiring carcinogen risk assessment. The paper explores the hypothesis that benchmark dose method allows to effectively approximate dose-response data on carcinogenic response, providing reasonable estimations of risks in the situations when a choice between more complex models is not warranted for practical purposes. Three case studies were analyzed for the agents with different levels of scientific confidence in human carcinogenicity: carbon nanotubes, amosite asbestos, and glyphosate. For each agent, a critical study was determined, and a dose-response slope factor was quantified, based on the weighted average lower bound benchmark dose. The linear slope factors of 0.111 lifetime excess cases of lung carcinoma per mg/m[3] of MWCNT-7 (in rats exposure equivalent), 0.009 cases of mesothelioma per f/cc-years of cumulative exposure to amosite asbestos, and 0.000094 cases of malignant lymphoma per mg/kg/day of glyphosate (in mice equivalent) were determined. The correlations between the proposed linear predictive models and observed data points were R = 0.96 (R[2] = 0.92) for carbon nanotubes, R = 0.97 (R[2] = 0.95) for amosite asbestos, and R = 0.89 (R[2] = 0.79) for glyphosate. In all three cases, the linear extrapolation yielded comparable level of risk estimations with the "best fit" nonlinear model; for nanoparticles and amosite asbestos, linear estimations were more conservative. By performing a simulation study, it was demonstrated that a weighted average benchmark dose expressed the highest correlation with multistage and quantal-linear models.}, }
@article {pmid33037108, year = {2021}, author = {Slomovitz, B and de Haydu, C and Taub, M and Coleman, RL and Monk, BJ}, title = {Asbestos and ovarian cancer: examining the historical evidence.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {31}, number = {1}, pages = {122-128}, doi = {10.1136/ijgc-2020-001672}, pmid = {33037108}, issn = {1525-1438}, mesh = {Asbestos/adverse effects/chemistry/*history ; Biomedical Research/*history/standards ; Causality ; Diagnostic Errors ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Mesothelioma, Malignant/diagnosis ; Observational Studies as Topic ; Ovarian Neoplasms/*diagnosis ; Peritoneal Neoplasms/diagnosis ; Retrospective Studies ; Talc ; }, abstract = {Asbestos recently returned to the spotlight when Johnson &amp; Johnson halted sales of baby powder due to lawsuits claiming that the talc in baby powder may have been contaminated with asbestos, which has been linked to the risk of ovarian cancer development. Although talc and asbestos have some structural similarities, only asbestos is considered causally associated with ovarian cancer by the WHO's International Agency for Research on Cancer. While it is useful to understand the types and properties of asbestos and its oncologic biology, the history of its association with ovarian cancer is largely based on retrospective observational studies in women working in high asbestos exposure environments. In reviewing the literature, it is critical to understand the distinction between associative risk and causality, and to examine the strength of association in the context of how the diagnosis of ovarian cancer is made and how the disease should be distinguished from a similar appearing but unrelated neoplasm, malignant mesothelioma. Based on contextual misinterpretation of these factors, it is imperative to question the International Agency for Research on Cancer's assertion that asbestos has a clear causal inference to ovarian cancer. This has important clinical implications in the way patients are conceivably counseled and provides motivation to continue research to improve the understanding of the association between asbestos and ovarian cancer.}, }
@article {pmid33036536, year = {2020}, author = {Song, PP and Sun, XW and Zhang, SQ and Gao, Y and Zhang, H and Chen, YX}, title = {[Clinical analysis of 30 cases with asbestos-related occupational tumors].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {38}, number = {9}, pages = {693-695}, doi = {10.3760/cma.j.cn121094-20190930-00460}, pmid = {33036536}, issn = {1001-9391}, support = {2018-WJZD058//Medical Research Guidance Plan for Qingdao in 2018/ ; }, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; Tomography, X-Ray Computed ; }, abstract = {Asbestos is classified as a Class 1 carcinogen by the International Cancer Organization (IARC) , and almost all types of asbestos are carcinogenic. The clinical data of 30 asbestos-induced occupational tumor patients in Qingdao city from January 2002 to May 2019 were analyzed, including 24 cases of asbestos-induced lung cancer and 6 cases of asbestos-induced malignant mesothelioma. Mesothelioma was significantly worse than lung cancer in terms of malignancy, the survival time of patients is shorter, and the mortality rate was higher. Both its diagnostic methods and treatment methods should be improved. The high incidence of asbestos-caused tumors is coming. It is recommended that workers exposed to asbestos dust should undergo regular chest CT examinations for early detection, early diagnosis and early treatment.}, }
@article {pmid33036531, year = {2020}, author = {Jiang, ZQ and Shao, DC and Cheng, YR and Miao, C and Chai, JR and Xu, CM and Yu, M and Wang, J and Li, T and Chen, JQ}, title = {[Detection and comparison of fiber count concentration in processing environment of asbestos and man-made mineral fiber].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {38}, number = {9}, pages = {675-678}, doi = {10.3760/cma.j.cn121094-20191128-00546}, pmid = {33036531}, issn = {1001-9391}, mesh = {*Asbestos/analysis ; China ; Dust/analysis ; Humans ; *Mesothelioma ; Mineral Fibers/analysis ; }, abstract = {Objective: To connect with the measurement data of asbestos dust fiber concentration in foreign countries, improve the accuracy of asbestos fiber detection in China, and understand the dust exposure in the working environment of asbestos and man-made mineral fiber production and processing sites in Zhejiang Province. The fiber count concentrations of working environment in glass fiber, ceramic fiber and asbestos processing plants were measured and compared. Methods: The dust concentration in the working environment of two glass fiber factories, one ceramic fiber factory and eight asbestos products processing factories was measured. The total dust mass concentration was measured according to GBZ/T 192.1-2007, and the fiber count concentration was measured by phase contrast microscope. Kruskal Wallis was used to test and compare the dust concentration in the working environment of each post. The correlation between asbestos mass concentration and fiber count concentration was analyzed by Spearman correlation. Results: Under the phase contrast microscope, there were many short and fine asbestos fibers in the field of vision, and there were many impurities around. The average dust concentration of asbestos processing plant was 3.2 f/ml, and the dust concentration of cotton ginning was the highest (6.68 f/ml) . There was a significantly positive correlation between asbestos fiber count concentration and mass concentration (r=0.535, P=0.033) . The average fiber count concentration of glass fiber factory was 0.001 f/ml, and the highest was 0.005 f/ml. The average fiber count concentration of ceramic fiber factory was 0.001 f/ml, and the highest was 0.006 f/ml. Conclusion: The fiber count concentration in the working environment of asbestos factory in Zhejiang Province is obviously over the standard, which is one of the important reasons for the high incidence of mesothelioma in this area. Short and small asbestos fibers are easy to be ignored when counting. It is necessary to improve the actual operation process of fiber counting to form a laboratory standard in China.}, }
@article {pmid33032525, year = {2020}, author = {Kumagai-Takei, N and Nishimura, Y and Maeda, M and Hayashi, H and Matsuzaki, H and Lee, S and Yoshitome, K and Ito, T and Otsuki, T}, title = {Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes.}, journal = {Environmental health and preventive medicine}, volume = {25}, number = {1}, pages = {59}, pmid = {33032525}, issn = {1347-4715}, support = {H18-1-3-3-1//Japan Science and Technology Agency/ ; 19659153//Japan Society for the Promotion of Science/ ; 20390178//Japan Society for the Promotion of Science/ ; 20890270//Japan Society for the Promotion of Science/ ; 21659161//Japan Society for the Promotion of Science/ ; 23790679//Japan Society for the Promotion of Science/ ; 25860470//Japan Society for the Promotion of Science/ ; 16K09114//Japan Society for the Promotion of Science/ ; Tokutei Kenkyu Josei I, 2008//Takeda Science Foundation/ ; 21-107//Kawasaki Medical School/ ; 21-401//Kawasaki Medical School/ ; 20-411I//Kawasaki Medical School/ ; 22-A29//Kawasaki Medical School/ ; 23B66//Kawasaki Medical School/ ; 23P3//Kawasaki Medical School/ ; 26B39//Kawasaki Medical School/ ; 29B051//Kawasaki Medical School/ ; Kyoiku Kenkyu Josei, 2009//The Kawasaki Foundation for Medical Science and Medical Welfare/ ; Kenkyu Josei, 2009//The Ryobi Teien Memory Foundation/ ; Tokubetsu Dengen Syozai Ken Kagaku Gijyutsu Sinkou Jigyou Kenkyu Itaku, 2010-2012//Okayama prefecture/ ; }, mesh = {Asbestos/*toxicity ; Asbestos, Serpentine/toxicity ; Cell Differentiation/*drug effects ; Cell Proliferation/*drug effects ; Humans ; Lung Neoplasms/*immunology ; Mesothelioma/*immunology ; Mesothelioma, Malignant ; T-Lymphocytes, Cytotoxic/*drug effects/immunology ; }, abstract = {Asbestos exposure is known to cause malignant mesothelioma, which is associated with poor prognosis. We focused on and examined the effect of asbestos exposure on the differentiation and function of cytotoxic T lymphocytes (CTLs). CTLs have the ability to specifically attack tumor cells after being differentiated from naïve CD8[+] T cells following antigen stimulation. Exposure to chrysotile B asbestos suppressed the differentiation of CTLs during the mixed lymphocyte reaction (MLR) and was associated with a decrease in proliferation of CD8[+] T cells. Additionally, in an effort to investigate the mechanism associated with suppressed CTL differentiation upon exposure to asbestos, we focused on IL-2, a cytokine involved in T cell proliferation. Our findings indicated that insufficient levels of IL-2 are not the main cause for the suppressed induction of CTLs by asbestos exposure, although they suggest potential improvement in the suppressed CTL function. Furthermore, the functional properties of peripheral blood CD8[+] lymphocytes from asbestos-exposed individuals with pleural plaque (PP) and patients with malignant mesothelioma (MM) were examined. MM patients showed lower perforin levels in CD8[+] lymphocytes following stimulation compared with PP-positive individuals. The production capacity of IFN-γ in the MM group tended to be lower compared with healthy volunteers or PP-positive individuals. In an effort to determine whether chronic and direct asbestos exposure affected the function of CD8[+] T cells, cultured human CD8[+] T cells were employed as an in vitro model and subjected to long-term exposure to chrysotile (CH) asbestos. This resulted in decreased levels of intracellular perforin and secreted IFN-γ. Those findings underlie the possibility that impaired CD8[+] lymphocyte function is caused by asbestos exposure, which fail to suppress the development of MM. Our studies therefore reveal novel effects of asbestos exposure on CTLs, which might contribute towards the development and implementation of an effective strategy for the prevention and cure of malignant mesothelioma.}, }
@article {pmid33032291, year = {2020}, author = {Zhang, X and Yang, L and Chen, W and Kong, M}, title = {Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis.}, journal = {Oncology research and treatment}, volume = {43}, number = {12}, pages = {656-671}, doi = {10.1159/000510534}, pmid = {33032291}, issn = {2296-5262}, mesh = {Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; Computational Biology/*methods ; Databases, Genetic ; Down-Regulation ; Drug Discovery/*methods ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Genes, Neoplasm ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; Microarray Analysis ; Molecular Targeted Therapy/methods ; Peroxisome Proliferator-Activated Receptors/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Protein Interaction Maps/genetics ; Up-Regulation ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is closely linked to asbestos exposure and is an extremely aggressive tumor with poor prognosis.<br><br>OBJECTIVE: Our study aimed to elucidate hub genes and potential drugs in MPM by integrated bioinformatics analysis.<br><br>METHODS: GSE42977 was download from the Gene Expression Omnibus (GEO) database; the differentially expressed genes (DEGs) with adj.p value <0.05 and |logFC| &#x2265;2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by DAVID database. The STRING database was used to construct a protein-protein interaction network, and modules analysis and hub genes acquisition were performed by Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to assess the impact of hub genes on the prognosis of MPM patients. The Drug-Gene Interaction database (DGIdb) was used to select the related drugs.<br><br>RESULTS: A total of 169 upregulated and 70 downregulated DEGs were identified. These DEGs are enriched in the pathway of extracellular matrix-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and PPAR signaling pathway. Finally, 10 hub genes (CDC20, CDK1, UBE2C, TOP2A, CCNB2, NUSAP1, KIF20A, AURKA, CEP55, and ASPM) were identified, which are considered to be closely related to the poor prognosis of MPM. In addition, 119 related drugs that may have a therapeutic effect on MPM were filtered out.<br><br>CONCLUSION: These discovered genes and small-molecule drugs provide some new ideas for further research on MPM.}, }
@article {pmid33020398, year = {2020}, author = {Iannuzzi, CA and Indovina, P and Forte, IM and Di Somma, S and Malfitano, AM and Bruno, M and Portella, G and Pentimalli, F and Giordano, A}, title = {Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines.}, journal = {International journal of molecular sciences}, volume = {21}, number = {19}, pages = {}, pmid = {33020398}, issn = {1422-0067}, mesh = {Adenoviridae/genetics ; Apoptosis/drug effects ; Asbestos/toxicity ; Cell Cycle Proteins/*antagonists &amp; inhibitors/genetics/pharmacology ; Cell Line, Tumor ; Cell Survival/*drug effects ; DNA Damage/drug effects ; Humans ; Mesothelioma, Malignant/chemically induced/*drug therapy/genetics/virology ; Oncolytic Virotherapy ; Oncolytic Viruses/genetics ; Phosphorylation/drug effects ; Protein Kinase Inhibitors ; Protein-Tyrosine Kinases/*antagonists &amp; inhibitors/genetics ; Pyrazoles/*pharmacology ; Pyrimidinones/*pharmacology ; }, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, for which no therapy proves to be effective. We have recently shown that the oncolytic adenovirus dl922-947 had antitumor effects in MM cell lines and murine xenografts. Previous studies demonstrated that dl922-947-induced host cell cycle checkpoint deregulation and consequent DNA lesions associated with the virus efficacy. However, the cellular DNA damage response (DDR) can counteract this virus action. Therefore, we assessed whether AZD1775, an inhibitor of the G2/M DNA damage checkpoint kinase WEE1, could enhance MM cell sensitivity to dl922-947. Through cell viability assays, we found that AZD1775 synergized with dl922-947 selectively in MM cell lines and increased dl922-947-induced cell death, which showed hallmarks of apoptosis (annexinV-positivity, caspase-dependency, BCL-XL decrease, chromatin condensation). Predictably, dl922-947 and/or AZD1775 activated the DDR, as indicated by increased levels of three main DDR players: phosphorylated histone H2AX (γ-H2AX), phospho-replication protein A (RPA)32, phospho-checkpoint kinase 1 (CHK1). Dl922-947 also increased inactive Tyr-15-phosphorylated cyclin-dependent kinase 1 (CDK1), a key WEE1 substrate, which is indicative of G2/M checkpoint activation. This increase in phospho-CDK1 was effectively suppressed by AZD1775, thus suggesting that this compound could, indeed, abrogate the dl922-947-induced DNA damage checkpoint in MM cells. Overall, our data suggest that the dl922-947-AZD1775 combination could be a feasible strategy against MM.}, }
@article {pmid33014860, year = {2020}, author = {Rozitis, E and Johnson, B and Cheng, YY and Lee, K}, title = {The Use of Immunohistochemistry, Fluorescence in situ Hybridization, and Emerging Epigenetic Markers in the Diagnosis of Malignant Pleural Mesothelioma (MPM): A Review.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {1742}, pmid = {33014860}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos related disease that is generally considered to be difficult to diagnose, stage and treat. The diagnostic process is continuing to evolve and requires highly skilled pathology input, and generally an extensive list of biomarkers for definitive diagnosis. Diagnosis of MPM requires histological evidence of invasion by malignant mesothelial cells often confirmed by various immunohistochemical biomarkers in order to separate it from pleural metastatic carcinoma. Often when invasion of neoplastic mesothelial cells into adjacent tissue is not apparent, further immunohistochemical testing - namely BAP1 and MTAP, as well as FISH testing for loss of p16 (CDKN2A) are used to separate reactive mesothelial proliferation due to benign processes, from MPM. Various combinations of these markers, such as BAP1 and/or MTAP immunohistochemistry alongside FISH testing for loss of p16, have shown excellent sensitivity and specificity in the diagnosis of MPM. Additionally, over the recent years, research into epigenetic marker use in the diagnosis of MPM has gained momentum. Although still in their research stages, various markers in DNA methylation, long non-coding RNA, micro RNA, circular RNA, and histone modifications have all been found to support diagnosis of MPM with generally good sensitivity and specificity. Many of these studies are however, limited by small sample sizes or other study limitations and further research into the area would be beneficial. Epigenetic markers show promise for use in the future to facilitate the diagnosis of MPM.}, }
@article {pmid33012432, year = {2020}, author = {Ripley, RT}, title = {Extended Pleurectomy and Decortication for Malignant Pleural Mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {451-460}, doi = {10.1016/j.thorsurg.2020.07.002}, pmid = {33012432}, issn = {1558-5069}, mesh = {Humans ; Mesothelioma, Malignant/*surgery ; Pleura/*surgery ; Pleural Neoplasms/surgery ; Thoracic Surgical Procedures/*methods ; Treatment Outcome ; }, abstract = {Extended pleurectomy and decortication (ePD) is a difficult operation performed for the surgical resection of malignant pleural mesothelioma that can achieve a macroscopic complete resection with preservation of the lung. With lower perioperative mortality, similar long-term survival, and better tolerance in patients with lower performance status, ePD has become the preferred operation rather than extrapleural pneumonectomy despite lack of a direct comparison. As ePD has become more popular, international collaboration is underway to create surgical guidelines based on collection of operative data. These efforts will improve the safety and standardization of this operation.}, }
@article {pmid33012429, year = {2020}, author = {Pass, HI and Alimi, M and Carbone, M and Yang, H and Goparaju, CM}, title = {Mesothelioma Biomarkers: Discovery in Search of Validation.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {395-423}, doi = {10.1016/j.thorsurg.2020.08.001}, pmid = {33012429}, issn = {1558-5069}, mesh = {Asbestos/adverse effects ; *Biomarkers, Tumor/analysis/blood/genetics/metabolism ; Calbindin 2/analysis/blood/genetics/metabolism ; Extracellular Matrix Proteins/analysis/blood/genetics/metabolism ; HMGB1 Protein/analysis/blood/genetics/metabolism ; Humans ; Mesothelioma, Malignant/*blood/chemistry/genetics/metabolism ; Multidrug Resistance-Associated Proteins/analysis/*blood/genetics/metabolism ; Pleural Neoplasms/blood/chemistry/genetics/metabolism ; Prognosis ; Proteomics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that can only be treated successfully when correctly diagnosed and treated early. The asbestos-exposed population is a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. We review recent work with biomarker development in MPM and literature of the last 20 years on the most promising blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms are covered. SMRP is the only validated blood-based biomarker with diagnostic, monitoring and prognostic value. To strengthen development and testing of MPM biomarkers, cohorts for validation must be established by enlisting worldwide collaborations.}, }
@article {pmid33012428, year = {2020}, author = {Wadowski, B and De Rienzo, A and Bueno, R}, title = {The Molecular Basis of Malignant Pleural Mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {383-393}, pmid = {33012428}, issn = {1558-5069}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Computational Biology/methods ; Epigenesis, Genetic ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Mesothelioma, Malignant/etiology/*genetics ; Pleural Neoplasms/etiology/genetics ; Transcriptome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural lining associated with asbestos exposure in greater than 80% of cases. It is characterized by molecular heterogeneity both between patients and within individual tumors. Next-generation sequencing technology and novel computational techniques have resulted in a greater understanding of the epigenetic, genetic, and transcriptomic hallmarks of MPM. This article reviews these features and discusses the implications of advances in MPM molecular biology in clinical practice.}, }
@article {pmid32999071, year = {2020}, author = {Xue, J and Patergnani, S and Giorgi, C and Suarez, J and Goto, K and Bononi, A and Tanji, M and Novelli, F and Pastorino, S and Xu, R and Caroccia, N and Dogan, AU and Pass, HI and Tognon, M and Pinton, P and Gaudino, G and Mak, TW and Carbone, M and Yang, H}, title = {Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {41}, pages = {25543-25552}, pmid = {32999071}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Asbestos/*adverse effects ; Autophagy/*drug effects ; Cell Transformation, Neoplastic/*chemically induced ; Cells, Cultured ; Epithelial Cells/cytology/metabolism ; HMGB1 Protein/*metabolism ; Humans ; Male ; Mesothelioma/*metabolism ; Mice ; Mice, Knockout ; Middle Aged ; Occupational Exposure ; }, abstract = {Asbestos causes malignant transformation of primary human mesothelial cells (HM), leading to mesothelioma. The mechanisms of asbestos carcinogenesis remain enigmatic, as exposure to asbestos induces HM death. However, some asbestos-exposed HM escape cell death, accumulate DNA damage, and may become transformed. We previously demonstrated that, upon asbestos exposure, HM and reactive macrophages releases the high mobility group box 1 (HMGB1) protein that becomes detectable in the tissues near asbestos deposits where HMGB1 triggers chronic inflammation. HMGB1 is also detectable in the sera of asbestos-exposed individuals and mice. Searching for additional biomarkers, we found higher levels of the autophagy marker ATG5 in sera from asbestos-exposed individuals compared to unexposed controls. As we investigated the mechanisms underlying this finding, we discovered that the release of HMGB1 upon asbestos exposure promoted autophagy, allowing a higher fraction of HM to survive asbestos exposure. HMGB1 silencing inhibited autophagy and increased asbestos-induced HM death, thereby decreasing asbestos-induced HM transformation. We demonstrate that autophagy was induced by the cytoplasmic and extracellular fractions of HMGB1 via the engagement of the RAGE receptor and Beclin 1 pathway, while nuclear HMGB1 did not participate in this process. We validated our findings in a novel unique mesothelial conditional HMGB1-knockout (HMGB1-cKO) mouse model. Compared to HMGB1 wild-type mice, mesothelial cells from HMGB1-cKO mice showed significantly reduced autophagy and increased cell death. Autophagy inhibitors chloroquine and desmethylclomipramine increased cell death and reduced asbestos-driven foci formation. In summary, HMGB1 released upon asbestos exposure induces autophagy, promoting HM survival and malignant transformation.}, }
@article {pmid32988786, year = {2020}, author = {Cattaneo, M and Mendogni, P and Damarco, F and Tosi, D}, title = {Spontaneous diaphragmatic rupture following neoadjuvant chemotherapy and cytoreductive surgery in malignant pleural mesothelioma: A case report and review of the literature.}, journal = {International journal of surgery case reports}, volume = {77S}, number = {Suppl}, pages = {S85-S87}, pmid = {32988786}, issn = {2210-2612}, abstract = {INTRODUCTION: Diaphragmatic rupture (DR) is an acquired diaphragmatic defect that can cause herniation of abdominal organs into the chest. It is usually a trauma-related lesion, but rarely it can occur spontaneously. Every DR with abdominal herniation should be considered a surgical emergency.<br><br>PRESENTATION OF CASE: A 61-year-old male patient, with previous exposure to asbestos, was diagnosed of Stage Ib malignant pleural mesothelioma (MPM). He underwent neo-adjuvant chemotherapy (three cycle of cisplatin-pemetrexed combination) and a cytoreductive surgery with pleurectomy/decortication. Post-operative course was characterized by prolonged air-leakage (PAL). After three months, during a follow-up CT-scan, a spontaneous diaphragmatic rupture (SDR) with gastric herniation was detected and treated by a laparascopic diaphragmatic repair and suture.<br><br>DISCUSSION: Spontaneous diaphragmatic rupture (SDR) is an extremely rare injury of the diaphragm (less than 1% of all DR). In this case, potential predisposing factors for SDR could be: presence of diaphragmatic "locus minoris resistentiae" due to thinning of the diaphragm and increase tissue fragility after neo-adjuvant chemotherapy and diaphragmatic pleural stripping; increased thoraco-abdominal pressure gradient due to PAL and residual pleural space. Thus, we confirmed the feasibility and safety of the laparoscopic approach.<br><br>CONCLUSION: We highlight the multifactor etiopathology, the challenging diagnosis and the importance of a prompt treatment of SDR.}, }
@article {pmid32977478, year = {2020}, author = {Kumagai-Takei, N and Lee, S and Srinivas, B and Shimizu, Y and Sada, N and Yoshitome, K and Ito, T and Nishimura, Y and Otsuki, T}, title = {The Effects of Asbestos Fibers on Human T Cells.}, journal = {International journal of molecular sciences}, volume = {21}, number = {19}, pages = {}, pmid = {32977478}, issn = {1422-0067}, mesh = {Asbestos/*toxicity ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Humans ; *Immunity, Cellular ; Mesothelioma, Malignant/chemically induced/*immunology/pathology ; T-Lymphocytes, Regulatory/*immunology/pathology ; }, abstract = {Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos fibers on immunocompetent cells, however, have not been well studied. Asbestos physically comprises a fibrous substance, which differs from silica particles which are a particulate substance, although chemically it is a mineral silicate. Since silicosis patients previously exposed to silica particles often suffer from lung and autoimmune diseases, it is clear that silica exposure impairs immune tolerance. Similarly, asbestos may alter the immune system in asbestos-exposed individuals. Given that malignant tumors can result following exposure to asbestos, the attenuation of anti-tumor immunity in cases of asbestos exposure is an important area of investigation. We observed the effect of asbestos fibers on T lymphocytes, such as CD8+ cytotoxic T lymphocytes (CTLs), CD4+ helper T (Th), and regulatory T (Treg) cells, and showed that anti-tumor immunity was attenuated, as demonstrated in a system that stimulates fresh cells isolated from peripheral blood in vitro and a system that is continuously exposed to a cell line. In this manuscript, we introduce the experiments and results of studies on CTLs, as well as Th and Treg cells, and discuss how future changes in immunocompetent cells induced by asbestos fibers can be clinically linked.}, }
@article {pmid32971078, year = {2020}, author = {Lysaniuk, B and Cely-García, MF and Mazzeo, A and Marsili, D and Pasetto, R and Comba, P and Ramos-Bonilla, JP}, title = {Where are the landfilled zones? Use of historical geographic information and local spatial knowledge to determine the location of underground asbestos contamination in Sibaté (Colombia).}, journal = {Environmental research}, volume = {191}, number = {}, pages = {110182}, doi = {10.1016/j.envres.2020.110182}, pmid = {32971078}, issn = {1096-0953}, mesh = {*Asbestos ; Cities ; Colombia ; Environmental Exposure ; *Occupational Exposure ; Waste Disposal Facilities ; }, abstract = {INTRODUCTION: Sibaté is a municipality located in the central region of Colombia, where the first asbestos-cement facility of the country has been in operation since 1942. Both a malignant pleural mesothelioma cluster and landfilled zones with the presence of an underground friable asbestos layer have been identified in Sibaté. There is still limited knowledge regarding the history of the construction of landfilled zones, and what kinds of materials were deposited. The current study aims to improve our understanding of the history and characteristics of the landfilled zones present in Sibaté.<br><br>METHODS: Two participatory workshops with inhabitants of Sibat&#xe9; were conducted to determine when the landfilled zones were built and their location. Information collected in participatory workshops was crossed with both topographic maps and aerial photographs, giving special attention to zones within the urban area of the municipality that in the past were inundated with water from El Mu&#xf1;a Reservoir. An opportunistic soil sampling campaign was conducted in suspected landfilled zones that had not been previously sampled, during the replacement of pipelines of the drainage system ordered by the municipality.<br><br>RESULTS: The analysis of historical topographic maps, combined with the interpretation of aerial photographs, confirmed the disposal of residues in areas that were previously inundated with water from El Mu&#xf1;a Reservoir, creating landfilled zones in the urban area of Sibat&#xe9;. On top of these landfilled zones, a football stadium and a football field with an athletic track were built. The location of landfilled zones identified using geographic analysis was similar to the location identified analyzing maps constructed by inhabitants of Sibat&#xe9; in participatory workshops. The four soil samples collected during an opportunistic sampling campaign confirmed the presence in new locations of the underground friable asbestos layer discovered in previous studies.<br><br>DISCUSSION: Based on the extension of the landfilled zones, the presence of friable asbestos in these areas, and the close proximity to a school and residential dwellings, there could have been major dispersion events of asbestos fibers in the urban area of Sibat&#xe9; during the disposal of residue materials and the construction of the landfilled zones. Thus, important asbestos exposures may have occurred among residents of Sibat&#xe9;, which is aggravated by the fact that during those years, more than 50% of the population of Sibat&#xe9; was 25 years old or younger. Although the results of the current study improved our understanding of the processes and chronology associated with the landfilled zones, the uncertainty regarding their exact location remains significant. It is important to continue investigating the adverse health effects resulting from this potential asbestos exposure source.}, }
@article {pmid32967259, year = {2020}, author = {Chimed-Ochir, O and Arachi, D and Driscoll, T and Lin, RT and Takala, J and Takahashi, K}, title = {Burden of Mesothelioma Deaths by National Income Category: Current Status and Future Implications.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {18}, pages = {}, pmid = {32967259}, issn = {1660-4601}, mesh = {Asbestos/toxicity ; Global Health ; Humans ; *Income ; *Mesothelioma/economics/mortality ; Reproducibility of Results ; }, abstract = {Background: This study compares estimates of the global-level mesothelioma burden with a focus on how existing national mortality data were utilized and further assesses the interrelationship of country-level mesothelioma burden and asbestos use with national income status. Methods: Country-level mesothelioma deaths in the WHO Mortality Database as of December 2019 were analyzed by national income category of countries in terms of data availability and reliability. Numbers of mesothelioma deaths from the study of Odgerel et al. were reanalyzed to assess country-level mesothelioma death burdens by national income status. Results: Among 80 high-income countries, 54 (68%) reported mesothelioma to the WHO and 26 (32%) did not, and among 60 upper middle-income countries, the respective numbers (proportions) were 39 (65%) countries and 21 (35%) countries, respectively. In contrast, among 78 low- and lower middle-income countries, only 11 (14%) reported mesothelioma deaths while 67 (86%) did not. Of the mesothelioma deaths, 29,854 (78%) were attributed to high- and upper middle-income countries, and 8534 (22%) were attributed to low- and lower middle- income countries. Conclusions: The global mesothelioma burden, based on reported numbers, is currently shouldered predominantly by high-income countries; however, mesothelioma burdens will likely manifest soon in upper middle-income and eventually in low and lower middle-income countries.}, }
@article {pmid32966235, year = {2021}, author = {Cheng, TJ and More, SL and Maddaloni, MA and Fung, ES}, title = {Evaluation of potential gastrointestinal carcinogenicity associated with the ingestion of asbestos.}, journal = {Reviews on environmental health}, volume = {36}, number = {1}, pages = {15-26}, doi = {10.1515/reveh-2020-0061}, pmid = {32966235}, issn = {2191-0308}, mesh = {Animals ; Asbestos/*toxicity ; Gastrointestinal Neoplasms/chemically induced/*epidemiology/pathology ; Humans ; Mesothelioma/chemically induced/epidemiology/pathology ; }, abstract = {The inhalation of asbestos, depending on the fiber type and dose, may be associated with the development of mesothelioma and other asbestos-related diseases. However, little is known about the potential adverse effects associated with the ingestion of asbestos. Evidence of asbestos fibers released from asbestos-cement pipes used in water distribution systems has led to concerns of potentially contaminated drinking water. The purpose of this study is to determine whether ingestion of asbestos fibers may lead to cancerous effects on the gastrointestinal (GI) tract. Data from animal and human studies were analyzed using a weight-of-evidence approach to evaluate the potential risk of GI cancers associated with asbestos ingestion. Seventeen human and 23 animal studies were identified and evaluated in this study. Animal studies were conducted in multiple species with inconsistent dosing protocols. Overall, animal studies reported that the asbestos fibers, irrespective of fiber type and dose, failed to produce any definitive GI carcinogenic effect. The 17 identified human epidemiological studies reported the ingestion of asbestos-contaminated water with concentrations from 1 to 71,350 million fibers per liter (MFL). A majority of the epidemiology studies reported statistically significant increases in multiple GI-specific cancers. However, these findings are confounded due to several critical study limitations including flawed study design, small sample size, selection bias, lack of individual exposure history, lack of adequate latency, and the inability to account for confounders including occupational history, diet, and smoking history. Based on our weight-of-evidence assessment, there is insufficient evidence of causality between the ingestion of asbestos and an increased incidence of GI cancers.}, }
@article {pmid32963780, year = {2020}, author = {Ohnishi, Y and Fujii, T and Sakamoto, T and Watanabe, M and Motohashi, T and Kubo, H and Nakajima, M}, title = {Malignant mesothelioma metastatic to the oral region and latest topics (Review).}, journal = {Molecular and clinical oncology}, volume = {13}, number = {5}, pages = {61}, pmid = {32963780}, issn = {2049-9450}, abstract = {Malignant mesothelioma (MM) is a rare neoplasm with poor prognosis that usually develops after exposure to asbestos, and is characterised by aggressive local invasion and metastatic spread. While metastasis to the oral cavity is very rare, a total of 23 cases of MM metastasising to the oral cavity were identifed. Among those, the tongue was the most common site of metastasis (39.1%), and frequently involved the epithelioid MM cell type. Recent studies have elucidated the mechanisms underlying the development of MM. Chronic inflammation has been implicated in promoting MM growth and was shown to play a key role by driving the release of high mobility group box protein 1 following asbestos deposition. Inherited heterozygous germline mutations in the deubiquitylase BRCA-associated protein 1 were shown to increase the incidence of MM in some families. Infection by the simian virus 40 was also found to be associated with the occurrence of MM. Moreover, the increasing incidence rates of MM, together with its propensity to metastasise to the oral cavity, indicate that clinicians and pathologists should be highly aware of this disease. Furthermore, identification of novel serum biomarkers would enable better screening and treatment of MM, and improve the survival outcomes.}, }
@article {pmid32959879, year = {2021}, author = {Giles Murphy, T and Bornstein, S and Oudyk, J and Demers, PA}, title = {A Quantitative Retrospective Exposure Assessment for Former Chrysotile Asbestos Miners and Millers from Baie Verte, NL, Canada.}, journal = {Annals of work exposures and health}, volume = {65}, number = {1}, pages = {113-126}, pmid = {32959879}, issn = {2398-7316}, support = {//CIHR/Canada ; }, mesh = {*Asbestos/adverse effects ; Asbestos, Serpentine ; Canada ; Humans ; Italy ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/chemically induced/epidemiology ; *Occupational Exposure ; Quebec ; Retrospective Studies ; }, abstract = {Despite numerous studies of asbestos workers in the epidemiologic literature, there are very few cohort studies of chrysotile asbestos miners/millers that include high-quality retrospective exposure assessments. As part of the creation of the Baie Verte Miners' Registry in 2008, a two-dimensional job exposure matrix (JEM) was developed for estimating asbestos exposures for former chrysotile asbestos miners/millers. Industrial hygiene data collected between 1963 and 1994 were analysed to assess validity for use in a retrospective exposure assessment and epidemiologic study. Registered former employees were divided into 52 exposure groups (EGs) based on job title and department and mean asbestos concentrations were calculated for each EG. The resulting exposure estimates were linked to individual registrants' work histories allowing for the calculation of cumulative asbestos exposure for each registrant. The distribution of exposure for most EGs (82.6%) could be described as fitting a log-normal distribution, although variability within some EGs (55%) exceeded a geometric standard deviation (GSD) of 2.5. Overall, the data used to create EGs in the development of the JEM were deemed to be of adequate quality for estimating cumulative asbestos exposures for the former employees of the Baie Verte asbestos mine/mill. The variability between workers in the same job was often high and is an important factor to be considered when using estimates of cumulative asbestos exposure to adjudicate compensation claims. The exposures experienced in this cohort were comparable to those of other chrysotile asbestos miners/millers cohorts, specifically Italian and Québec cohorts.}, }
@article {pmid32944078, year = {2020}, author = {Wahlbuhl, E and Liehr, T and Rincic, M and Azawi, S}, title = {Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines.}, journal = {Molecular cytogenetics}, volume = {13}, number = {}, pages = {43}, pmid = {32944078}, issn = {1755-8166}, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare aggressive cancer primary located in pleura and lung. MMs can be divided into biphasic, epithelioid and sarcomatoid subtypes. In majority of cases MMs are induced by asbestos fiber exposure. As latency period after asbestos exposure ranges between ~ 10 and 60 years MMs are mainly observed in elder people. Human MM, being a rare tumor type, lacks detailed cytogenetic data, while molecular genetic studies have been undertaken more frequently. However, murine MM cell lines are also regularly applied to get more insight into MM biology and to test new therapy strategies.<br><br>RESULTS: Here the murine MM cell lines AB1, AB22 and AC29 were studied by molecular cytogenetics and molecular karyotyping. Interestingly, yet there were no genetic or genomic studies undertaken for these already in 1992 established cell lines. The obtained data on genomic imbalances in these murine cell lines was translated into the human genome as previously reported based on human and murine genomic browsers.<br><br>CONCLUSIONS: It turned out that all three cell lines showed high similarities in copy number variants as observed typically in human MM. Also, all three cell lines were most similar to human epithelioid MMs, and should be used as models therefore.}, }
@article {pmid32933580, year = {2020}, author = {Fisher, SA and Peddle-McIntyre, CJ and Burton, K and Newton, RU and Marcq, E and Lake, RA and Nowak, AK}, title = {Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model.}, journal = {BMC research notes}, volume = {13}, number = {1}, pages = {435}, pmid = {32933580}, issn = {1756-0500}, support = {CRE APP1107043//National Health and Medical Research Council/ ; Health Research Fund//Slater &amp; Gordon/ ; KotK_UA/2018/11519/1//Kom Op Tegen Kanker (Stand Up to Cancer)/ ; hShort-Term Research Fellowship April 2019//European Respiratory Society-ERS/ ; }, mesh = {Animals ; *Asbestos/toxicity ; Disease Models, Animal ; *Mesothelioma/chemically induced/therapy ; *Mesothelioma, Malignant ; Mice ; *Occupational Exposure ; }, abstract = {OBJECTIVE: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen-induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma.<br><br>RESULTS: Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non-asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre-clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.}, }
@article {pmid32929059, year = {2020}, author = {Costa, C and Indovina, P and Mattioli, E and Forte, IM and Iannuzzi, CA and Luzzi, L and Bellan, C and De Summa, S and Bucci, E and Di Marzo, D and De Feo, M and Mutti, L and Pentimalli, F and Giordano, A}, title = {P53-regulated miR-320a targets PDL1 and is downregulated in malignant mesothelioma.}, journal = {Cell death &amp; disease}, volume = {11}, number = {9}, pages = {748}, pmid = {32929059}, issn = {2041-4889}, mesh = {B7-H1 Antigen/*genetics/*metabolism ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Down-Regulation ; HEK293 Cells ; Humans ; Mesothelioma, Malignant/genetics/*metabolism/pathology ; MicroRNAs/genetics/*metabolism ; Transfection ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer, related to asbestos exposure, which has a dismal prognosis. MPM diagnosis is late and often challenging, suggesting the need to identify more reliable molecular biomarkers. Here, we set out to identify differentially expressed miRNAs in epithelioid, biphasic, and sarcomatoid MPMs versus normal mesothelium and explored specific miRNA contribution to mesothelial tumorigenesis. We screened an LNA™-based miRNA-microrray with 14 formalin-fixed paraffin-embedded (FFPE) MPMs and 6 normal controls. Through real-time qRT-PCR we extended the analysis of a miRNA subset and further investigated miR-320a role through state-of-the-art techniques. We identified 16 upregulated and 32 downregulated miRNAs in MPMs versus normal tissue, including the previously identified potential biomarkers miR-21, miR-126, miR-143, miR-145. We showed in an extended series that miR-145, miR-10b, and miR-320a levels can discriminate tumor versus controls with high specificity and sensitivity. We focused on miR-320a because other family members were found downregulated in MPMs. However, stable miR-320a ectopic expression induced higher proliferation and migration ability, whereas miR-320a silencing reduced these processes, not supporting a classic tumor-suppressor role in MPM cell lines. Among putative targets, we found that miR-320a binds the 3'-UTR of the immune inhibitory receptor ligand PDL1 and, consistently, miR-320a modulation affects PDL1 levels in MPM cells. Finally, we showed that p53 over-expression induces the upregulation of miR-320a, along with miR-200a and miR-34a, both known to target PDL1, and reduces PDL1 levels in MPM cells. Our data suggest that PDL1 expression might be due to a defective p53-regulated miRNA response, which could contribute to MPM immune evasion or tumorigenesis through tumor-intrinsic roles.}, }
@article {pmid32927122, year = {2021}, author = {Reardon, ES and Shukla, V and Xi, S and Gara, SK and Liu, Y and Straughan, D and Zhang, M and Hong, JA and Payabyab, EC and Kumari, A and Richards, WG and De Rienzo, A and Hassan, R and Miettinen, M and Xi, L and Raffeld, M and Uechi, LT and Li, X and Wang, R and Chen, H and Hoang, CD and Bueno, R and Schrump, DS}, title = {UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {16}, number = {1}, pages = {89-103}, pmid = {32927122}, issn = {1556-1380}, support = {P30 CA016042/CA/NCI NIH HHS/United States ; R01 CA120528/CA/NCI NIH HHS/United States ; ZIA BC011115/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; CCAAT-Enhancer-Binding Proteins/genetics ; Cell Line, Tumor ; Cell Proliferation ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/drug therapy/genetics ; *Mesothelioma, Malignant ; Mice ; *Pleural Neoplasms/drug therapy/genetics ; Ubiquitin-Protein Ligases ; }, abstract = {INTRODUCTION: Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in malignant pleural mesothelioma (MPM). This study was undertaken to explore the therapeutic potential of targeting UHRF1 in MPM.<br><br>METHODS: Microarray, real-time quantitative reverse transcription-polymerase chain reaction, immunoblot, and immunohistochemistry techniques were used to evaluate UHRF1 expression in normal mesothelial cells (NMCs) cultured with or without asbestos, MPM lines, normal pleura, and primary MPM specimens. The impact of UHRF1 expression on MPM patient survival was evaluated using two independent databases. RNA-sequencing, proliferation, invasion, and colony formation assays, and murine xenograft experiments were performed to evaluate gene expression and growth of MPM cells after biochemical or pharmacologic inhibition of UHRF1 expression.<br><br>RESULTS: UHRF1 expression was significantly higher in MPM lines and specimens relative to NMC and normal pleura. Asbestos induced UHRF1 expression in NMC. The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM. UHRF1 knockdown reversed genomewide DNA hypomethylation, and inhibited proliferation, invasion, and clonogenicity of MPM cells, and growth of MPM xenografts. These effects were phenocopied by the repurposed chemotherapeutic agent, mithramycin. Biochemical or pharmacologic up-regulation of p53 significantly reduced UHRF1 expression in MPM cells. RNA-sequencing experiments exhibited the pleiotropic effects of UHRF1 down-regulation and identified novel, clinically relevant biomarkers of UHRF1 expression in MPM.<br><br>CONCLUSIONS: UHRF1 is an epigenetic driver in MPM. These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy.}, }
@article {pmid32922794, year = {2020}, author = {Tada, Y and Tagawa, M and Yusa, T and Yatomi, M and Shimomura, I and Suzuki, T and Takeshita, Y and Sato, T and Shimada, H and Hiroshima, K}, title = {Diffuse pleural thickening and thoracic contraction: An indistinguishable case from malignant pleural mesothelioma.}, journal = {SAGE open medical case reports}, volume = {8}, number = {}, pages = {2050313X20948716}, pmid = {32922794}, issn = {2050-313X}, abstract = {The differential diagnosis of reactive mesothelial hyperplasia and mesothelioma is difficult. We present a rare case of diffuse pleural thickening with thoracic contraction that was indistinguishable from mesothelioma. A 66-year-old woman with no history of asbestos exposure visited our hospital with a complaint of dyspnea. The clinical findings included circumferential pleural thickening on chest computed tomography image and a high concentration of hyaluronic acid in the pleural fluid. Pleural biopsies obtained by thoracoscopy under local anesthesia were pathologically consistent with mesothelioma, but the patient refused to take any kind of mesothelioma treatments. Four months later, she consented to a surgical pleural biopsy under general anesthesia to obtain larger tissue samples, which included typical proliferating polygonal cells positive for CAM5.2, calretinin, WT-1, D2-40, CK5/6, epithelial membrane antigen, and glucose transporter-1 and negative for carcinoembryonic antigen, BerEP4, and MOC31. The analysis was consistent with diagnosis of epithelioid mesothelioma. Fluorescence in situ hybridization, however, showed the presence of p16 gene, and the expression of BRCA1-associated protein-1 was detected by immunohistochemistry. Our final diagnosis was diffuse pleural thickening unrelated to asbestos exposure. Differential diagnosis of diffuse pleural thickening and malignant mesothelioma is thus difficult and routine immunohistochemical examinations are often insufficient for accurate diagnosis. Multiple diagnostic methods are required for correct diagnosis in a clinically marginal case.}, }
@article {pmid32911426, year = {2020}, author = {Lam, SK and Yan, S and Xu, S and Ho, JC}, title = {Targeting polyamine as a novel therapy in xenograft models of malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {148}, number = {}, pages = {138-148}, doi = {10.1016/j.lungcan.2020.08.016}, pmid = {32911426}, issn = {1872-8332}, mesh = {Animals ; Eflornithine ; Heterografts ; *Lung Neoplasms/drug therapy ; *Mesothelioma, Malignant ; Mice ; Mice, Nude ; Polyamines ; }, abstract = {INTRODUCTION: Inhalation of asbestos fibers is the key culprit in malignant pleural mesothelioma (MPM). Although the import and use of asbestos have been restricted, the incidence of MPM continues to increase globally due to the prolonged lag time in malignant transformation. The development of a novel adjuvant therapy for the minority of individuals with resectable early-stage disease and effective treatment for those with unresectable MPM are urgently needed. Our preliminary data revealed that ornithine decarboxylase (ODC) is highly expressed in MPM xenografts. This study aimed to determine the treatment effects of α-difluoromethylornithine (DFMO), a specific ODC inhibitor, in MPM xenografts.<br><br>RESULTS: In an "extended adjuvant DFMO treatment" setting, nude mice were fed with DFMO for 7 days prior to inoculation of 200,000 cells. DFMO suppressed tumor growth and increased median survival in both xenografts. In H226 xenograft, 43 % of treated mice had not reached the humane endpoint by day 132, mimicking long-term survival. DFMO decreased spermidine, increased nitrotyrosine and activated apoptosis in both xenografts. Furthermore, increase in nitrosocysteine, intratumoral IL-6, keratinocyte chemoattractant and TNF&#x3b1;, DNA lesion and inhibition of the Akt/mTOR pathway were induced by DFMO in H226 xenograft. In "DFMO treatment" setting, 10[7] cells were inoculated into nude mice and DFMO treatment commenced when tumor size reached &#x223c;50-100&#x2009;mm[3]. DFMO also suppressed tumor growth by similar mechanisms. Supplementation with spermidine reversed the therapeutic effect of DFMO. DFMO increased actin nitration at tyrosine 53 and inhibited actin polymerization.<br><br>CONCLUSION: DFMO is preclinically effective in treating MPM.}, }
@article {pmid32892058, year = {2020}, author = {Fuso Nerini, I and Roca, E and Mannarino, L and Grosso, F and Frapolli, R and D'Incalci, M}, title = {Is DNA repair a potential target for effective therapies against malignant mesothelioma?.}, journal = {Cancer treatment reviews}, volume = {90}, number = {}, pages = {102101}, doi = {10.1016/j.ctrv.2020.102101}, pmid = {32892058}, issn = {1532-1967}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Clinical Trials, Phase II as Topic ; DNA Damage ; *DNA Repair ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; Mutation ; Poly(ADP-ribose) Polymerase Inhibitors/administration &amp; dosage/*pharmacology/therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Germinal and acquired mutations in genes of DNA repair pathways, in particular of homologous recombination repair, are frequent in MPM. Here we overview the available experimental data suggesting that an impaired DNA repair system affects MPM pathogenesis by leaving lesions through the genome unresolved. DNA repair defects represent a vulnerability of MPM, and it seems plausible to propose that leveraging these deficiencies could have therapeutic potential for patients with MPM, for whom there is an urgent need of more effective therapies.}, }
@article {pmid32888937, year = {2020}, author = {Prabhakaran, S and Hocking, A and Kim, C and Hussey, M and Klebe, S}, title = {The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas.}, journal = {Human pathology}, volume = {105}, number = {}, pages = {1-8}, doi = {10.1016/j.humpath.2020.08.005}, pmid = {32888937}, issn = {1532-8392}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Female ; GATA3 Transcription Factor/*analysis ; Humans ; *Immunohistochemistry ; Ki-67 Antigen/analysis ; Male ; Mesothelioma, Malignant/*chemistry/mortality/pathology/therapy ; Middle Aged ; Pleural Neoplasms/*chemistry/mortality/pathology/therapy ; Predictive Value of Tests ; Prognosis ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {Malignant pleural mesothelioma is associated with asbestos exposure and poor outcomes. The usefulness of immunohistochemistry for diagnosis of sarcomatoid mesothelioma, especially the desmoplastic type, is limited, and more effective markers are required. GATA binding protein 3 (GATA3) has been suggested as a diagnostic marker for sarcomatoid mesothelioma. The potential usefulness of GATA3 for prognostication and its clinical and pathological correlations in different subtypes of mesothelioma have not been evaluated. We investigated the immunohistochemical labeling and associations for GATA3, BRCA1-associated protein 1 (BAP1), and Ki67 labeling in three major histological types of pleural malignant mesotheliomas. We examined 149 clinically annotated malignant mesotheliomas and assessed associations of GATA3 expression with clinical variables and prognosis. In addition, we labeled 10 cases of fibrous pleuritis with GATA3, all of which were negative. GATA3 was positive in 75 of 149 (50%) mesotheliomas, with the highest incidence of labeling seen in the sarcomatoid subtype (73%), compared with the biphasic (50%) and epithelioid (40%), mesotheliomas. A total of eight desmoplastic mesotheliomas showed labeling with GATA3. Patients whose tumors had sarcomatoid histology showed poorer survival than those with the other subtypes (p < 0.001), but overall GATA3 labeling did not have a statistically significant association with survival (p = 0.602). There was no association of GATA3 labeling and BAP1 status or Ki67 index. Our study includes the largest cohort of mesotheliomas that has been labeled for GATA3 to date. GATA3 is a useful marker for sarcomatoid mesothelioma, including the desmoplastic subtype. Discordance in GATA3 and BAP1 labeling of epithelioid and sarcomatoid components in the biphasic subtype is not uncommon.}, }
@article {pmid32888453, year = {2020}, author = {Nowak, AK and Lesterhuis, WJ and Kok, PS and Brown, C and Hughes, BG and Karikios, DJ and John, T and Kao, SC and Leslie, C and Cook, AM and Pavlakis, N and Briscoe, K and O'Byrne, KJ and Karapetis, CS and Lam, WS and Langford, A and Yip, S and Stockler, MR}, title = {Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in.}, journal = {The Lancet. Oncology}, volume = {21}, number = {9}, pages = {1213-1223}, doi = {10.1016/S1470-2045(20)30462-9}, pmid = {32888453}, issn = {1474-5488}, mesh = {Adolescent ; Adult ; Aged ; Antibodies, Anti-Idiotypic/administration &amp; dosage/adverse effects ; Antibodies, Monoclonal/*administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/adverse effects ; Australia/epidemiology ; B7-H1 Antigen/antagonists &amp; inhibitors/genetics ; Cisplatin/*administration &amp; dosage/adverse effects ; Female ; Humans ; Lung Neoplasms/*drug therapy/genetics/immunology/pathology ; Male ; Mesothelioma/*drug therapy/genetics/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration &amp; dosage/adverse effects ; Pleural Neoplasms/*drug therapy/genetics/immunology/pathology ; Progression-Free Survival ; }, abstract = {BACKGROUND: There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma.<br><br>METHODS: DREAM was a multicentre, single-arm, open-label, phase 2 trial done in nine hospitals in Australia. Eligible patients were aged 18 years or older and had histologically confirmed malignant pleural mesothelioma considered unsuitable for cancer-directed surgery, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease as per the modified Response Evaluation Criteria in Solid Tumors version 1.0 (mRECIST) for mesothelioma that was previously untreated with systemic therapy. All histological subtypes were eligible. The first six participants were treated for two cycles in a safety run-in. All participants received cisplatin 75 mg/m[2], pemetrexed 500 mg/m[2], and durvalumab 1125 mg intravenously on day 1 of a 3-weekly schedule for a maximum of six cycles. Change from cisplatin to carboplatin with an area under the curve of 5 was permitted. Durvalumab was continued for a maximum of 12 months. The primary endpoint was progression-free survival at 6 months, measured according to mRECIST for malignant pleural mesothelioma and analysed in the intention-to-treat population. Safety analyses included all participants who receive at least one dose of any study drug. This study is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12616001170415.<br><br>FINDINGS: Between Dec 28, 2016, and Sept 27, 2017, 55 participants were enrolled. 54 patients were eligible and were followed up for a median of 28&#xb7;2 months (IQR 26&#xb7;5-30&#xb7;2). 31 (57%; 95% CI 44-70) of 54 patients were alive and progression-free at 6 months. The most common grade 3-4 adverse events were neutropenia (seven [13%] patients), nausea (six [11%]), and anaemia (four [7%]). A total of 60 serious adverse events occurred in 29 participants, five of which were considered possibly related to durvalumab. Five patients died during the study treatment; none of these five deaths were attributed to study treatment.<br><br>INTERPRETATION: The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomised phase 3 trial.<br><br>FUNDING: AstraZeneca.}, }
@article {pmid32887638, year = {2020}, author = {Dell'Anno, I and Barone, E and Mutti, L and Rassl, DM and Marciniak, SJ and Silvestri, R and Landi, S and Gemignani, F}, title = {Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report).}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {341}, pmid = {32887638}, issn = {1479-5876}, support = {G0601840/MRC_/Medical Research Council/United Kingdom ; G1002610/MRC_/Medical Research Council/United Kingdom ; MR/R009120/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Basigin/metabolism ; Humans ; *Mesothelioma, Malignant ; Monocarboxylic Acid Transporters ; Muscle Proteins/metabolism ; Prognosis ; *Symporters ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease.<br><br>METHODS: We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan-Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients' overall survival (OS).<br><br>RESULTS: We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS.<br><br>CONCLUSION: In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker.}, }
@article {pmid32882916, year = {2020}, author = {Cakiroglu, E and Senturk, S}, title = {Genomics and Functional Genomics of Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32882916}, issn = {1422-0067}, mesh = {Animals ; Biomarkers, Tumor/genetics/*metabolism ; Genomics/*methods ; Humans ; Mesothelioma, Malignant/genetics/metabolism/*pathology ; Phenomics/*methods ; Pleural Neoplasms/genetics/metabolism/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.}, }
@article {pmid32881200, year = {2020}, author = {Mori, D and Kido, S and Hiraki, M and Sumi, K and Ureshino, N and Masuda, M and Nabeshima, K and Akashi, M}, title = {Peritoneal adenomatoid (microcystic) mesothelioma.}, journal = {Pathology international}, volume = {70}, number = {11}, pages = {876-880}, doi = {10.1111/pin.13006}, pmid = {32881200}, issn = {1440-1827}, mesh = {Adenomatoid Tumor/*pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Mesothelioma/*pathology ; Mesothelioma, Malignant/diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*pathology ; Peritoneum/*pathology ; Prognosis ; }, abstract = {There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.}, }
@article {pmid32875620, year = {2020}, author = {Petrof, O and Neyens, T and Nuyts, V and Nackaerts, K and Nemery, B and Faes, C}, title = {On the impact of residential history in the spatial analysis of diseases with a long latency period: A study of mesothelioma in Belgium.}, journal = {Statistics in medicine}, volume = {39}, number = {26}, pages = {3840-3866}, doi = {10.1002/sim.8697}, pmid = {32875620}, issn = {1097-0258}, mesh = {*Asbestos/toxicity ; Belgium/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Spatial Analysis ; }, abstract = {Mesothelioma is a rare cancer caused by exposure to asbestos. Belgium has a known long history of asbestos production, resulting in one of the highest mesothelioma mortality rates worldwide. While the production of asbestos has stopped completely, the long latency period of mesothelioma, which can fluctuate between 20 and 40 years after exposure, causes incidences still to be frequent. Mesothelioma's long incubation time affects our assessment of its geographical distribution as well. Since patients' residential locations are likely to change a number of times throughout their lives, the location where the patients develop the disease is often far from the location where they were exposed to asbestos. Using the residential history of patients, we propose the use of a convolution multiple membership model (MMM), which includes both a spatial conditional autoregressive and an unstructured random effect. Pancreatic cancer patients are used as a control population, reflecting the population at risk for mesothelioma. Results show the impact of the residential mobility on the geographical risk estimation, as well as the importance of acknowledging the latency period of a disease. A simulation study was conducted to investigate the properties of the convolution MMM. The robustness of the results for the convolution MMM is assessed via a sensitivity analysis.}, }
@article {pmid32869268, year = {2020}, author = {Sayan, M and Mamidanna, S and Fuat Eren, M and Daliparty, V and Zoto Mustafayev, T and Nelson, C and Ohri, N and Jabbour, SK and Guven Mert, A and Atalar, B}, title = {New horizons from novel therapies in malignant pleural mesothelioma.}, journal = {Advances in respiratory medicine}, volume = {88}, number = {4}, pages = {343-351}, pmid = {32869268}, issn = {2543-6031}, support = {R50 CA275877/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/*adverse effects ; Clinical Trials as Topic ; Humans ; Mesothelioma, Malignant/chemically induced/*therapy ; Neoplasm Staging ; Pleural Neoplasms/chemically induced/*therapy ; Radiotherapy, Adjuvant ; }, abstract = {Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.}, }
@article {pmid36238033, year = {2020}, author = {Bae, JY and Kim, Y and Kang, HJ and Kwon, H and Shim, SS}, title = {Imaging Features of Various Benign and Malignant Tumors and Tumorlike Conditions of the Pleura: A Pictorial Review.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {81}, number = {5}, pages = {1109-1120}, pmid = {36238033}, issn = {2288-2928}, abstract = {Pleural masses may be caused by various conditions, including benign and malignant neoplasms and non-neoplastic tumorlike conditions. Primary pleural neoplasms include solitary fibrous tumor, malignant mesothelioma, and primary pleural non-Hodgkin's lymphoma. Metastatic disease is the most common neoplasm of the pleura and may uncommonly occur in patients with hematologic malignancy, including lymphoma, leukemia, and multiple myeloma. Pleural effusion is usually associated with pleural malignancy. Rarely, pleural malignancy may arise from chronic empyema, and the most common cell type is non-Hodgkin's lymphoma (pyothorax-associated lymphoma). Non-neoplastic pleural masses may be observed in several benign conditions, including tuberculosis, pleural plaques caused by asbestos exposure, and pleural loose body. Herein, we present a review of benign and malignant pleural neoplasms and tumorlike conditions with illustrations of their computed tomographic images.}, }
@article {pmid32863225, year = {2020}, author = {Ito, F and Yanatori, I and Maeda, Y and Nimura, K and Ito, S and Hirayama, T and Nagasawa, H and Kohyama, N and Okazaki, Y and Akatsuka, S and Toyokuni, S}, title = {Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium.}, journal = {Redox biology}, volume = {36}, number = {}, pages = {101616}, pmid = {32863225}, issn = {2213-2317}, mesh = {Animals ; *Asbestos ; Epithelium ; *Ferroptosis ; Ferrous Compounds ; Hydrogen Peroxide ; Macrophages ; *Mesothelioma ; Mutagens ; Rats ; beta Catenin/genetics ; }, abstract = {Asbestos is still a social burden worldwide as a carcinogen causing malignant mesothelioma. Whereas recent studies suggest that local iron reduction is a preventive strategy against carcinogenesis, little is known regarding the cellular and molecular mechanisms surrounding excess iron. Here by differentially using high-risk and low-risk asbestos fibers (crocidolite and anthophyllite, respectively), we identified asbestos-induced mutagenic milieu for mesothelial cells. Rat and cell experiments revealed that phagocytosis of asbestos by macrophages results in their distinctive necrotic death; initially lysosome-depenent cell death and later ferroptosis, which increase intra- and extra-cellular catalytic Fe(II). DNA damage in mesothelial cells, as assessed by 8-hydroxy-2'-deoxyguanosine and γ-H2AX, increased after crocidolite exposure during regeneration accompanied by β-catenin activation. Conversely, β-catenin overexpression in mesothelial cells induced higher intracellular catalytic Fe(II) with increased G2/M cell-cycle fraction, when p16[INK4A] genomic loci localized more peripherally in the nucleus. Mesothelial cells after challenge of H2O2 under β-catenin overexpression presented low p16[INK4A] expression with a high incidence of deletion in p16[INK4A] locus. Thus, crocidolite generated catalytic Fe(II)-rich mutagenic environment for mesothelial cells by necrotizing macrophages with lysosomal cell death and ferroptosis. These results suggest novel molecular strategies to prevent mesothelial carcinogenesis after asbestos exposure.}, }
@article {pmid32849853, year = {2020}, author = {Bai, Y and Wang, X and Hou, J and Geng, L and Liang, X and Ruan, Z and Guo, H and Nan, K and Jiang, L}, title = {Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {899}, pmid = {32849853}, issn = {1664-8021}, abstract = {Malignant pleural mesothelioma (MPM), predominantly caused by asbestos exposure, is a highly aggressive cancer with poor prognosis. The staging systems currently used in clinics is inadequate in evaluating the prognosis of MPM. In this study, a five-gene signature was developed and enrolled into a prognostic risk score model by LASSO Cox regression analysis based on two expression profiling datasets (GSE2549 and GSE51024) from Gene Expression Omnibus (GEO). The five-gene signature was further validated using the Cancer Genome Atlas (TCGA) MPM dataset. Univariate and multivariate Cox analyses proved that the five-gene signature was an independent prognostic factor for MPM. The signature remained statistically significant upon stratification by Brigham stage, AJCC stage, gender, tumor size, and lymph node status. Time-dependent receiver operating characteristic (ROC) curve indicated good performance of our model in predicting 1- and 2-years overall survival in MPM patients. The C-index was 0.784 for GSE2549 and 0.753 for the TCGA dataset showing moderate predictive accuracy of our model. Furthermore, Gene Set Enrichment Analysis suggested that the five-gene signature was related to pathways resulting in MPM tumor progression. Together, we have established a five-gene signature significantly associated with prognosis in MPM patients. Hence, the five-genes signature may serve as a potentially useful prognostic tool for MPM patients.}, }
@article {pmid32847019, year = {2020}, author = {Airoldi, C and Ferrante, D and Mirabelli, D and Azzolina, D and Magnani, C}, title = {Evaluation of Nonresponse Bias in a Case-Control Study of Pleural Mesothelioma.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {17}, pages = {}, pmid = {32847019}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Bias ; Case-Control Studies ; Female ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Occupational Exposure ; *Pleural Neoplasms ; }, abstract = {Nonparticipation limits the power of epidemiological studies, and can cause bias. In a case-control study on pleural malignant mesothelioma (MM), we found low participation in interviews (63%) among controls. Our goal was to characterize nonresponder controls and assess nonresponse bias in our study. We selected all nonresponder controls (204) and a random sample of responder controls (174). Data were obtained linking hospital admissions and town registrars, and concordance between sources was assessed. Nonresponse bias was evaluated using a logistic regression model applying the inverse probability weighting approach. The odds ratio (OR) for the status of the respondents was 0.61 (95% confidence interval (CI): 0.33-1.16) for controls aged 61-70, 0.37 (CI: 0.20-0.66) for those aged 71-80, and 0.40 (CI: 0.20-0.80) for those aged above 80 (reference group: ≤60 years). Controls with low education level had lower OR (0.47; CI: 0.26-0.84). After adjustment, the ORs for MM by categories of cumulative exposure to asbestos were similar to the unadjusted results, ranging from 4.6 (CI: 1.8-11.7) for cumulative exposures between 0.1 and 1 f/mL-y to 57.5 (CI: 20.2-163.9) above 10 f/mL-y. Responder controls were younger and had higher education level. Nevertheless, there was little evidence of bias from nonresponse in the risk estimates of MM.}, }
@article {pmid32826527, year = {2021}, author = {Mujahed, T and Tazelaar, HD and Sukov, WR and Halling, KC and Davila, JI and Glass, C and Pavlisko, EN and Strickland, KC and Roggli, V and Haque, M and Mneimneh, W and Carter, E and Galateau-Salle, F and Glidden, D and Garcia-Kennedy, R and Larsen, BT}, title = {Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {2}, pages = {255-262}, doi = {10.1097/PAS.0000000000001574}, pmid = {32826527}, issn = {1532-0979}, mesh = {Adolescent ; Adult ; Catheters, Indwelling/*adverse effects ; Female ; Humans ; Male ; Mesothelioma, Malignant/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*etiology/pathology ; Portasystemic Shunt, Surgical/*adverse effects ; Ventriculoperitoneal Shunt/*adverse effects ; Young Adult ; }, abstract = {Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.}, }
@article {pmid32823952, year = {2020}, author = {Johnson, TG and Schelch, K and Lai, K and Marzec, KA and Kennerson, M and Grusch, M and Reid, G and Burgess, A}, title = {YB-1 Knockdown Inhibits the Proliferation of Mesothelioma Cells through Multiple Mechanisms.}, journal = {Cancers}, volume = {12}, number = {8}, pages = {}, pmid = {32823952}, issn = {2072-6694}, support = {IIRS-18-103//National Breast Cancer Foundation/ ; T 1062 Firnberg Program//Austrian Science Fund/ ; }, abstract = {Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein that has been shown to regulate proliferation, invasion and metastasis in a variety of cancer types. We previously demonstrated that YB-1 is overexpressed in mesothelioma cells and its knockdown significantly reduces tumour cell proliferation, migration, and invasion. However, the mechanisms driving these effects are unclear. Here, we utilised an unbiased RNA-seq approach to characterise the changes to gene expression caused by loss of YB-1 knockdown in three mesothelioma cell lines (MSTO-211H, VMC23 and REN cells). Bioinformatic analysis showed that YB-1 knockdown regulated 150 common genes that were enriched for regulators of mitosis, integrins and extracellular matrix organisation. However, each cell line also displayed unique gene expression signatures, that were differentially enriched for cell death or cell cycle control. Interestingly, deregulation of STAT3 and p53-pathways were a key differential between each cell line. Using flow cytometry, apoptosis assays and single-cell time-lapse imaging, we confirmed that MSTO-211H, VMC23 and REN cells underwent either increased cell death, G1 arrest or aberrant mitotic division, respectively. In conclusion, this data indicates that YB-1 knockdown affects a core set of genes in mesothelioma cells. Loss of YB-1 causes a cascade of events that leads to reduced mesothelioma proliferation, dependent on the underlying functionality of the STAT3/p53-pathways and the genetic landscape of the cell.}, }
@article {pmid32823056, year = {2020}, author = {Torres-Roman, JS and Gomez-Rubio, V and Sanchez-Trujillo, L and Delgado-Rosas, E and Puche-Vergara, F and Sanz-Anquela, JM and Ortega, MA}, title = {Geographic study of mortality due to mesothelioma in Peru and its evolution.}, journal = {Cancer epidemiology}, volume = {68}, number = {}, pages = {101791}, doi = {10.1016/j.canep.2020.101791}, pmid = {32823056}, issn = {1877-783X}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Carcinogens/*toxicity ; Child ; Child, Preschool ; Female ; Geography ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/epidemiology/etiology/*mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Peru/epidemiology ; Prognosis ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Peru has a public health problem because of asbestos imports. We analyzed the mortality trends for mesothelioma in Peru and its provinces from 2005 to 2014 and estimated their relationship with the amount of asbestos imported previously.<br><br>METHODS: We computed age-standardized mortality rates (ASMRs) per 100,000 population (direct method and SEGI world standard population reference), and the standardized mortality ratio (SMR). The relationship between the amount of asbestos imported annually along the period 1965-2010 and the number of mesothelioma deaths per year from 2005 to 2014 was estimated by log-linear Poisson regression models and Pearson correlation calculations.<br><br>RESULTS: After correcting the number of deaths, Peru registered 428 cases (or 430 when corrected cases are rounded by sex) between 2005 and 2014. The highest ASMRs were in Arequipa and Callao (range: 0.40-0.41/100,000 population), followed by Huancavelica (0.36/100,000 population). This translates into approximately one death per each 68-111 of asbestos tons imported. The latency period for the higher level of positive correlation found was 8 years (r&#x202f;=&#x202f;0.8). Male female sex ratio was lower in provinces such as Junin and Hunacavelica with geological asbestos risk.<br><br>CONCLUSIONS: Two patterns of mesothelioma risk have been detected, occupational and environmental. During the 2002-2006 years, Peru increased the asbestos use. If crocidolite imports were also increased, this could be behind the 8 years latency period detected. Peru should boost strategies towards the total ban of all forms of asbestos.}, }
@article {pmid32816595, year = {2021}, author = {Johnson, NF}, title = {Inhalation Toxicity of Talc.}, journal = {Journal of aerosol medicine and pulmonary drug delivery}, volume = {34}, number = {2}, pages = {79-107}, doi = {10.1089/jamp.2020.1609}, pmid = {32816595}, issn = {1941-2703}, mesh = {Administration, Inhalation ; Animals ; Carcinogens ; Humans ; Lung ; *Lung Neoplasms ; *Talc/toxicity ; }, abstract = {Respirable talc powder (RTP) is a complex mineral mixture of talc along with accessory minerals, including tremolite, anthophyllite, quartz, magnesite, dolomite, antigorite, lizardite, and chlorite. The industrial mining, milling, and processing of talc ore is associated with elevated incidences of fibrotic and neoplastic diseases, which are also seen among workers exposed to RTP in secondary industries and individuals using processed cosmetic talc for personal use. There is controversial evidence of a link between the talc-induced lung diseases and a potential contamination with asbestos fibers. This controversy is fueled by inadequate exposure data and the complex mineralogy and terminology of the accessory minerals. Talc aerosols exhibit a wide range of mineral habits, including particulates and fibrous structures that have dimensional and compositional characteristics related to the development of asbestos-related lung disease. The inhalation toxicology of RTP is based on the analysis of occupational hygiene and animal inhalation studies conducted between the 1940s and the 1990s and more recent mechanistic studies conducted both in vivo and in vitro. The review of talc toxicity studies reveals that the occupational studies provide only equivocal links between any of the components of the aerosols and the development of pulmonary cancer; however, there is substantial evidence of an association between the aerosols and pleural and pulmonary fibrosis and the development of nonmalignant respiratory disease. The animal inhalation and implantation studies appear to be less than optimal, which also appears to be true for the in vivo and in vitro studies. The mechanistic studies have identified the key pathogenic characteristics of asbestos to be long and thin fibers that are durable in lung tissues and fluids. Talc toxicity studies show that talc particles and fibers are durable and can remain in the lung for up to 40 years after the end of exposure. This extended tissue residence is considered to constitute a continuing tissue exposure that is capable of inducing the documented inflammatory and proliferative response. There is less consensus as to whether there is a threshold fiber length effect, as long, thin fibers (>5 μm) form only a small fraction of talc aerosols and the possible role of fibers >5 μm in the translocation from the lung to the pleura and their association with pleural fibrotic and carcinogenic lesions. Long, thin fibers are preferentially deposited in hot spots in the lung, such as airway bifurcations, areas typically associated with the development of lung cancer. The platy structures typical of talc can form oblate structures behaving more as fibers in the air stream, and these have also been shown to deposit preferentially in such locations. The review of the inhalation toxicity of talc provides a plausible explanation for the carcinogenic potential of RTP.}, }
@article {pmid32815857, year = {2020}, author = {Alpert, N and van Gerwen, M and Flores, R and Taioli, E}, title = {Gender Differences in Outcomes of Patients With Mesothelioma.}, journal = {American journal of clinical oncology}, volume = {43}, number = {11}, pages = {792-797}, pmid = {32815857}, issn = {1537-453X}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; *Sex Characteristics ; Survival Rate ; Treatment Outcome ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Mesothelioma is a rare and deadly form of cancer, linked to asbestos exposure. Although the United Kingdom has banned asbestos, the incidence rate remains high. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the United Kingdom.<br><br>MATERIALS AND METHODS: Pleural mesothelioma cases from 2005 to 2014 were extracted from the United Kingdom Lung Cancer Dataset. Multivariable logistic regression was used to assess the clinical and demographic factors associated with gender. A multivariable Cox proportional hazards model and propensity matching methods were used to assess gender differences in overall survival while accounting for potential confounders.<br><br>RESULTS: There were 8479 (87.8%) male and 1765 (17.2%) female individuals included in the analysis. Female individuals were significantly younger, with more epithelial histology than male individuals. Female individuals had significantly better overall survival (adjusted hazard ratio, 0.85, 95% confidence interval, 0.81-0.90). Results remained similar when stratifying by age and performance status, and when limiting to patients with epithelial histology.<br><br>CONCLUSIONS: The study increases knowledge about gender differences in mesothelioma survival and is the first to directly examine this in the United Kingdom. It further disentangles the effects of age, histology, and health status. Increased estrogen may improve survival and could provide a potential target for future therapies.}, }
@article {pmid32811344, year = {2021}, author = {Barbieri, PG and Mirabelli, D}, title = {Diagnosis of lung cancer: a necropsy-based study of 128 cases (1997-2016).}, journal = {Tumori}, volume = {107}, number = {3}, pages = {226-230}, doi = {10.1177/0300891620949665}, pmid = {32811344}, issn = {2038-2529}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/diagnosis ; Autopsy/methods ; Female ; Humans ; Lung Neoplasms/chemically induced/*diagnosis ; Male ; Mesothelioma/chemically induced/diagnosis ; Mesothelioma, Malignant/chemically induced/diagnosis ; Middle Aged ; Pleural Diseases/chemically induced/diagnosis ; Pleural Neoplasms/chemically induced/diagnosis ; Prevalence ; }, abstract = {BACKGROUND: The diagnosis of lung cancer (LC) may be difficult to make in the elderly. We report on the diagnostic elements available in life in an LC necropsy case series of asbestos-exposed workers and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices.<br><br>METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1997-2016) in patients with LC employed in the Monfalcone shipyards. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings.<br><br>RESULTS: Data on 128 autopsy-confirmed LC cases were available; in life, 119 had been diagnosed as LC. Among these, 49 had histologic confirmation of diagnosis (17 with immunophenotyping); histology had been negative in 4. Cytology had been the main positive finding and the basis for diagnosis in 24 cases, but had been negative in 13. Chest computed tomography had been the basis for diagnosis in 45; in 18 cases, it had been negative. Nine patients had received a diagnosis different from LC, among whom 4 had been suspected to have malignant pleural mesothelioma by chest computed tomography. Pleural plaques were found in 124 and histologic asbestosis in 46 cases.<br><br>CONCLUSIONS: Autopsies confirmed all LC diagnoses received in life, including 46 that would have been considered only possible LC based on clinical workup. The overall survival in this case series was poor. The high prevalence of pleural plaques and asbestosis suggest severity of asbestos exposures.}, }
@article {pmid32787452, year = {2020}, author = {Uhlenhopp, DJ and Saliares, A and Gaduputi, V and Sunkara, T}, title = {An Unpleasant Surprise: Abdominal Presentation of Malignant Mesothelioma.}, journal = {Journal of investigative medicine high impact case reports}, volume = {8}, number = {}, pages = {2324709620950121}, pmid = {32787452}, issn = {2324-7096}, mesh = {Abdominal Pain/etiology ; Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma, Malignant/*chemically induced/*pathology ; Retroperitoneal Neoplasms/*chemically induced/*pathology ; }, abstract = {Malignant mesothelioma is an aggressive cancer associated with asbestos exposure with median survival time of 8 to 14 months following diagnosis. Given that mesothelial cells also line the peritoneum and pericardium, malignant mesothelioma can present in unusual sites and in patients with nonrespiratory complaints. A 73-year-old male presented to the emergency department for worsening intermittent diffuse abdominal pain for the past 3 months with associated unintentional 40-pound weight loss, early satiety, and diarrhea. He denied exposure to asbestos. Computed tomography imaging revealed multiple masses concerning for malignancy including the primary retroperitoneal mass, a mass involving the terminal ileum, and a mass in the right upper lung. Esophagogastroduodenoscopy demonstrated significant mass effect within the stomach without signs of endoluminal infiltration. Computed tomography-guided biopsy of the retroperitoneal abdominal and intramuscular paraspinal masses was performed. Stage IV epithelioid mesothelioma was confirmed when hematoxylin and eosin staining revealed pleomorphic malignancy nuclei containing a vesicular chromatin pattern and prominent nucleoli and immunohistochemical staining was positive for CK Oscar, cytokeratin 7, GATA3, calretinin, EMA, and CK5/6. He was started on cisplatin, pemetrexed, and bevacizumab but developed severe abdominal pain with pneumoperitoneum and bowel perforation 1 month later and expired shortly thereafter. To our knowledge, this represents a highly atypical presentation of malignant mesothelioma considering the involvement of the retroperitoneum with diffuse lesions in the abdominopelvic cavity and thorax (sparing the lung pleurae). This case also calls attention to the occurrence of malignant mesothelioma in patients without known asbestos exposure and the crucial role of pathology in diagnosing atypical presentations.}, }
@article {pmid32783735, year = {2020}, author = {Rosner, D and Markowitz, G}, title = {Baby Powders and the Precautionary Principle.}, journal = {American journal of public health}, volume = {110}, number = {9}, pages = {1378-1379}, pmid = {32783735}, issn = {1541-0048}, mesh = {Asbestos/*adverse effects ; Consumer Product Safety ; Female ; Humans ; Mesothelioma/chemically induced/prevention &amp; control ; Ovarian Neoplasms/chemically induced/prevention &amp; control ; Powders/adverse effects/chemistry ; Risk Factors ; Talc/*adverse effects/chemistry ; }, }
@article {pmid32777272, year = {2020}, author = {Manangama, G and Gramond, C and Audignon-Durand, S and Baldi, I and Fabro-Peray, P and Gilg Soit Ilg, A and Guénel, P and Lebailly, P and Luce, D and Stücker, I and Brochard, P and Lacourt, A}, title = {Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system - Results from three French case-control studies.}, journal = {Environmental research}, volume = {191}, number = {}, pages = {110024}, doi = {10.1016/j.envres.2020.110024}, pmid = {32777272}, issn = {1096-0953}, mesh = {Adult ; *Asbestos ; Case-Control Studies ; Central Nervous System ; Humans ; Lung ; *Lung Neoplasms/chemically induced/epidemiology ; Male ; *Occupational Diseases ; *Occupational Exposure/adverse effects ; Retrospective Studies ; }, abstract = {OBJECTIVES: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults.<br><br>METHODS: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2029 lung cancer cases and 2591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure.<br><br>RESULTS: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR&#xa0;=&#xa0;1.51; 95% CI: 1.22-1.86 and brain tumors (OR&#xa0;=&#xa0;1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR&#xa0;=&#xa0;0.78; 95% CI: 0.46-1.33).<br><br>CONCLUSION: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.}, }
@article {pmid32769428, year = {2021}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Ferrufino-Schmidt, MC and Miranda, RN and Sams, R and Royal, RE and Raghav, KPS and Fournier, KF and Ramalingam, P}, title = {Malignant Mesothelioma of the Peritoneum in Women: A Clinicopathologic Study of 164 Cases.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {1}, pages = {45-58}, doi = {10.1097/PAS.0000000000001545}, pmid = {32769428}, issn = {1532-0979}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Mesothelioma, Malignant/mortality/*pathology/therapy ; Middle Aged ; Peritoneal Neoplasms/mortality/*pathology/therapy ; Young Adult ; }, abstract = {Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.}, }
@article {pmid32769345, year = {2020}, author = {Kazaz, IO and Teoman, AS and Mungan, S}, title = {Mesothelioma of the tunica vaginalis testis: A case report.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {3}, pages = {475-477}, doi = {10.4103/IJPM.IJPM_780_18}, pmid = {32769345}, issn = {0974-5130}, mesh = {Aged ; Biomarkers, Tumor ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Orchiectomy ; Testicular Hydrocele/diagnosis ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Testis/*pathology/surgery ; }, abstract = {Primary mesotheliomas of the tunica vaginalis testis are very rare malignant tumors. They are generally associated with exposure to asbestos. They may manifest as hydrocele, testis tumor, inguinal hernia, or epididymitis. After differential diagnosis, treatment is primarily surgical. Adjuvant therapeutic methods for mesotheliomas of the tunica vaginalis testis, with their high mortality, are controversial. Here, we present a mesothelioma case derived from tunica vaginalis testis acting as long-term pyocele with no known asbestos exposure.}, }
@article {pmid32764839, year = {2020}, author = {Wang, Q and Wang, Q and Zhao, Z and Alexander, DB and Zhao, D and Xu, J and Tsuda, H}, title = {Pleural translocation and lesions by pulmonary exposed multi-walled carbon nanotubes.}, journal = {Journal of toxicologic pathology}, volume = {33}, number = {3}, pages = {145-151}, pmid = {32764839}, issn = {0914-9198}, abstract = {Carbon nanotubes (CNTs) are recently developed tubular nanomaterials, with diameters ranging from a few nanometers to tens of nanometers, and the length reaching up to several micrometers. They can be either single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Due to their nano-scaled structure, CNTs have a unique set of mechanical, electrical, and chemical properties that make them useful in information technologies, optoelectronics, energy technologies, material sciences, medical technologies, and other fields. However, with the wide application and increasing production of CNTs, their potential risks have led to concerns regarding their impact on environment and health. The shape of some types of CNTs is similar to asbestos fibers, which suggests that these CNTs may cause characteristic pleural diseases similar to those found in asbestos-exposed humans, such as pleural plaques and malignant mesothelioma. Experimental data indicate that CNTs can induce lung and pleural lesions, inflammation, pleural fibrosis, lung tumors, and malignant mesothelioma upon inhalation in the experimental animals. In this review, we focus on the potential of MWCNTs to induce diseases similar to those by asbestos, molecular and cellular mechanisms associated with these diseases, and we discuss a method for evaluating the pleural toxicity of MWCNTs.}, }
@article {pmid32760782, year = {2020}, author = {Plesker, R and Köhler, K and von Gerlach, S and Boller, K and Vogt, M and Feder, IS}, title = {Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (Chlorocebus aethiops).}, journal = {Primate biology}, volume = {7}, number = {1}, pages = {5-12}, pmid = {32760782}, issn = {2363-4715}, abstract = {A spontaneous reactive mesothelial hyperplasia occurred in a female, 15.7-year-old African green monkey (grivet; Chlorocebus aethiops). At necropsy, massive effusions were found in the abdomen, the thorax, and the pericardium. Additionally, multiple small, beige-gray nodules were detected on the serosal surfaces of the abdominal organs. Histopathologically, the mesothelial cells resembled the epithelioid subtype of a mesothelioma, but no infiltrative or invasive growth could be demonstrated. The mesothelial cells on the thoracis, liver, and intestinal serosa were accompanied by chronic serositis. Mesothelial cells expressed cytokeratin, vimentin, calretinin, desmin, Wilms Tumor 1 (WT-1) protein, and epithelial membrane antigen (EMA). Cells were negative for carcinoembryonic antigen (CEA), cluster of differentiation 15 (CD15), and podoplanin. Ultrastructurally, cells revealed a moderate amount of microvilli of medium length, perinuclear tonofilament bundles, and long desmosomes. In fluorescence in situ hybridization (FISH) for the detection of characteristic gene loss (p16; CDKN2A), NF2, and MTAP, no deletions were detected. No asbestos fibers and no presence of Simian virus 40 antigen (SV40) could be demonstrated.}, }
@article {pmid32759747, year = {2020}, author = {Marzullo, A and Serio, G and Pezzuto, F and Fortarezza, F and Cazzato, G and Caporusso, C and Lettini, T and Cavone, D and Delfino, MC and Vimercati, L}, title = {A Single Liver Metastasis from Pleural Biphasic Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {8}, pages = {}, pmid = {32759747}, issn = {2075-4418}, abstract = {Virtually any malignancy can metastasize to the liver. Large solitary metastases are rare and can be difficult to distinguish from primary tumors. Malignant mesothelioma is often considered as a locally invasive cancer but tumor dissemination to extra-thoracic sites is possible, and the liver can be involved. Herein, we present a rare case of pleural mesothelioma with a solitary large liver metastasis diagnosed postmortem in a ninety-two-year-old man with 35 years of exposure to asbestos. Results of immunohistochemical staining of the pleural and liver tumor were similar, both positive for low-molecular weight keratins, calretinin, vimentin, and podoplanin, and negative for Claudin-4, TTF1, CEA, BerEP4, CK7, CK19, CK20, BAP1, Hep Par1, p40, and WT1. Fluorescent in-situ hybridization (FISH) for p16/CDKN2A was also performed and a homozygous deletion was detected in both tumors, supporting the diagnosis of mesothelioma. Reporting this case, we would like to point out that extra-thoracic dissemination from pleural mesothelioma, even if exceptional, can occur. In cases where differential diagnoses are challenging, the value of ancillary techniques and a practical approach to diagnostic work-up is of primary importance.}, }
@article {pmid32755622, year = {2020}, author = {Luo, Y and Deng, J and Cui, Y and Li, T and Bai, J and Huang, L and Sun, Y and Dong, F and Zhang, Q}, title = {Long-term instillation to four natural representative chrysotile of China induce the inactivation of P53 and P16 and the activation of C-JUN and C-FOS in the lung tissues of Wistar rats.}, journal = {Toxicology letters}, volume = {333}, number = {}, pages = {140-149}, doi = {10.1016/j.toxlet.2020.07.033}, pmid = {32755622}, issn = {1879-3169}, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; Bronchoalveolar Lavage Fluid/cytology ; China ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Cytokines/metabolism ; Environmental Pollutants/chemistry/*toxicity ; Gene Expression/drug effects ; Inhalation Exposure/adverse effects ; JNK Mitogen-Activated Protein Kinases/genetics/*metabolism ; Leukocyte Count ; Leukocytes/cytology/drug effects ; Lung/*drug effects/immunology/metabolism/pathology ; Male ; Mineral Fibers/toxicity ; Proto-Oncogene Proteins c-fos/genetics/*metabolism ; Rats, Wistar ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Chrysotile is the only type of asbestos still widely exploited, and all kinds of asbestos including chrysotile was classified as a group I carcinogen by the IARC. There is a wealth of evidence that chrysotile can cause a range of cancers, including cancer of the lung, larynx, ovary, and mesothelioma. As the second largest chrysotile producer, China is at great risk of occupational exposure. Moreover, our previous experiment and some other studies have shown that the toxicity of mineral fibre from various mining areas may be different. To explore the oncogenic potential of chrysotile from different mining areas of China, Wistar rats were administered 0.5 mL chrysotile asbestos suspension of 2.0 mg/mL (from Akesai, Gansu; Mangnai, Qinghai; XinKang, Sichuan; and Shannan, Shaanxi) dissolved in saline by intratracheal instillation once-monthly and were sacrificed at 1 mo, 6 mo, and 12 mo. Our results found that chrysotile caused lung inflammation and lung tissue damage. Moreover, prolonged exposure of chrysotile can induce inactivation of the tumor suppressor gene P53 and P16 and activation of the protooncogene C-JUN and C-FOS both in the messenger RNA and protein level. In addition, chrysotile from Shannan and XinKang has a stronger effect which may link to cancer than that from Akesai and Mangnai.}, }
@article {pmid32732250, year = {2020}, author = {Cerciello, F and Choi, M and Sinicropi-Yao, SL and Lomeo, K and Amann, JM and Felley-Bosco, E and Stahel, RA and Robinson, BWS and Creaney, J and Pass, HI and Vitek, O and Carbone, DP}, title = {Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {10}, pages = {1973-1982}, pmid = {32732250}, issn = {1538-7755}, support = {U01 CA111295/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Mass Spectrometry/*methods ; Mesothelioma, Malignant/*genetics ; Middle Aged ; Pleural Neoplasms/*genetics ; Proteomics/*methods ; }, abstract = {BACKGROUND: We have verified a mass spectrometry (MS)-based targeted proteomics signature for the detection of malignant pleural mesothelioma (MPM) from the blood.<br><br>METHODS: A seven-peptide biomarker MPM signature by targeted proteomics in serum was identified in a previous independent study. Here, we have verified the predictive accuracy of a reduced version of that signature, now composed of six-peptide biomarkers. We have applied liquid chromatography-selected reaction monitoring (LC-SRM), also known as multiple-reaction monitoring (MRM), for the investigation of 402 serum samples from 213 patients with MPM and 189 cancer-free asbestos-exposed donors from the United States, Australia, and Europe.<br><br>RESULTS: Each of the biomarkers composing the signature was independently informative, with no apparent functional or physical relation to each other. The multiplexing possibility offered by MS proteomics allowed their integration into a single signature with a higher discriminating capacity than that of the single biomarkers alone. The strategy allowed in this way to increase their potential utility for clinical decisions. The signature discriminated patients with MPM and asbestos-exposed donors with AUC of 0.738. For early-stage MPM, AUC was 0.765. This signature was also prognostic, and Kaplan-Meier analysis showed a significant difference between high- and low-risk groups with an HR of 1.659 (95% CI, 1.075-2.562; P = 0.021).<br><br>CONCLUSIONS: Targeted proteomics allowed the development of a multianalyte signature with diagnostic and prognostic potential for MPM from the blood.<br><br>IMPACT: The proteomic signature represents an additional diagnostic approach for informing clinical decisions for patients at risk for MPM.}, }
@article {pmid32731396, year = {2020}, author = {Javadi, J and Dobra, K and Hjerpe, A}, title = {Multiplex Soluble Biomarker Analysis from Pleural Effusion.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32731396}, issn = {2218-273X}, support = {CAN 2018/653//Cancerfonden/International ; }, mesh = {Adenocarcinoma/diagnosis/*pathology ; Biomarkers, Tumor/analysis ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Mesothelioma, Malignant/diagnosis/*pathology ; Pleural Effusion/diagnosis/*pathology ; Prognosis ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.}, }
@article {pmid32727552, year = {2020}, author = {Lehnert, M and Weber, DG and Taeger, D and Raiko, I and Kollmeier, J and Stephan-Falkenau, S and Brüning, T and Johnen, G and , }, title = {Determinants of plasma calretinin in patients with malignant pleural mesothelioma.}, journal = {BMC research notes}, volume = {13}, number = {1}, pages = {359}, pmid = {32727552}, issn = {1756-0500}, support = {IN-1214264//Ruhr-Universit&#xe4;t Bochum/ ; }, mesh = {Calbindin 2 ; Cross-Sectional Studies ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: Calretinin is a well-known immunohistochemical tissue marker in the diagnosis of malignant mesothelioma. Promising results also indicate the use in early detection. In the present cross-sectional survey, correlations of calretinin plasma levels with clinical features were investigated. Plasma samples of 60 patients with malignant pleural mesothelioma (MPM) and 111 cancer-free controls formerly exposed to asbestos were compared. Calretinin concentrations were determined in plasma using an enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: The median concentration was higher in MPM patients than in controls (0.79 vs. 0.23&#xa0;ng/ml; p&#x2009;<&#x2009;0.0001). Patients with epithelioid MPM or biphasic MPM had higher calretinin plasma levels than patients with sarcomatoid MPM. Strong expression of calretinin in the tumor tissue was associated with higher plasma levels. Preoperative patients showed higher levels of calretinin than patients after thoracic surgery (1.20 vs. 0.67&#xa0;ng/ml; p&#x2009;=&#x2009;0.096). The suitability of plasma calretinin has been confirmed as a tumor marker in the differential diagnosis of epithelioid MPM. The value of plasma calretinin for therapy monitoring or as a prognostic marker should be further investigated.}, }
@article {pmid32726334, year = {2020}, author = {Schüz, J and Bukhtiyarov, I and Olsson, A and Moissonnier, M and Ostroumova, E and Feletto, E and Schonfeld, SJ and Byrnes, G and Tskhomariia, I and McCormack, V and Straif, K and Kashanskiy, S and Morozova, T and Kromhout, H and Kovalevskiy, E}, title = {Occupational cohort study of current and former workers exposed to chrysotile in mine and processing facilities in Asbest, the Russian Federation: Cohort profile of the Asbest Chrysotile Cohort study.}, journal = {PloS one}, volume = {15}, number = {7}, pages = {e0236475}, pmid = {32726334}, issn = {1932-6203}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adult ; Asbestos/adverse effects ; Asbestos, Serpentine/*adverse effects ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/chemically induced/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology/pathology ; Occupational Exposure/*adverse effects ; Russia/epidemiology ; }, abstract = {A historical cohort study in workers occupationally exposed to chrysotile was set up in the town of Asbest, the Russian Federation, to study their cause-specific mortality, with a focus on cancer. Chrysotile has different chemical and physical properties compared with other asbestos fibres; therefore it is important to conduct studies specifically of chrysotile and in different geographical regions to improve the knowledge about its carcinogenicity. Setting was the town of Asbest, Sverdlovsk oblast, the Russian Federation. Participants were all current and former employees with at least one year of employment between 1/1/1975 and 31/12/2010 in the mine, enrichment factories, auto-transport and external rail transportation departments, the central laboratory, and the explosives unit of the company. Of the 35,837 cohort members, 12,729 (35.5%) had died (2,373 of them of cancer, including 10 of mesothelioma), 18,799 (52.5%) were known to be alive at the end of the observation period (2015), and 4,309 (12.0%) were censored before the end of 2015. Mean follow-up duration was 21.7 years in men and 25.9 years in women. The mean age at death was 59.4 years in men and 66.5 years in women. This is the largest occupational cohort of chrysotile workers to date, and the only one with a large proportion of exposed female workers.}, }
@article {pmid32723839, year = {2020}, author = {Kwak, K and Paek, D and Zoh, KE}, title = {Author's response to 'Re: Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis by Kwak et al'.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {9}, pages = {656-657}, doi = {10.1136/oemed-2020-106737}, pmid = {32723839}, issn = {1470-7926}, mesh = {*Asbestos/adverse effects ; *Colonic Neoplasms ; *Colorectal Neoplasms ; Humans ; *Mesothelioma ; }, }
@article {pmid32710945, year = {2020}, author = {Gandhi, M and Nair, S}, title = {New vistas in malignant mesothelioma: MicroRNA architecture and NRF2/MAPK signal transduction.}, journal = {Life sciences}, volume = {257}, number = {}, pages = {118123}, doi = {10.1016/j.lfs.2020.118123}, pmid = {32710945}, issn = {1879-0631}, mesh = {Animals ; Biomarkers, Tumor ; Humans ; Lung Neoplasms/*metabolism ; *MAP Kinase Signaling System ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; MicroRNAs/*metabolism ; NF-E2-Related Factor 2/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is a cancer of the mesothelial lining of the pleura, peritoneum, pericardium and testes. The most common form is asbestos-linked MM that is etiologically linked to repeated asbestos exposure with a long latency period, although non-asbestos MM has also been reported. Late diagnosis, poor survival rates, lack of diagnostic and prognostic markers act as major impediments in the clinical management of MM. Despite advances in immune checkpoint inhibition and CAR T-cell-based therapies, MM which is of different histologic subtypes remains challenging to treat. We review microRNAs (miRNAs) and the miRNA interactome implicated in MM which can be useful as circulating miRNA biomarkers for early diagnosis of MM and as biomarkers for prognostication in MM. Further, we underscore the relevance of the NRF2/MAPK signal transduction pathway that has been implicated in MM which may be useful as druggable targets or as biomarkers of predictive response. In addition, since MM is driven partly by inflammation, we elucidate chemopreventive phytochemicals that are beneficial in MM, either via crosstalk with the NRF2/MAPK pathway or via concerted anticancer mechanisms, and may be of benefit as adjuvants in chemotherapy. Taken together, a multifactorial approach comprising identification of miRNA target hubs and NRF2/MAPK biomarkers along with appropriately designed clinical trials may enable early detection and faster intervention in MM translating into better patient outcomes for this aggressive cancer.}, }
@article {pmid32709739, year = {2020}, author = {Boffetta, P}, title = {Re: Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis by Kwak et al.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {9}, pages = {655}, doi = {10.1136/oemed-2020-106588}, pmid = {32709739}, issn = {1470-7926}, mesh = {*Asbestos/adverse effects ; *Colonic Neoplasms ; *Colorectal Neoplasms/etiology ; Humans ; *Mesothelioma ; }, }
@article {pmid32708306, year = {2020}, author = {Bonelli, M and Terenziani, R and Zoppi, S and Fumarola, C and La Monica, S and Cretella, D and Alfieri, R and Cavazzoni, A and Digiacomo, G and Galetti, M and Petronini, PG}, title = {Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {21}, number = {14}, pages = {}, pmid = {32708306}, issn = {1422-0067}, support = {N/A//Associazione Augusto per la Vita (Novellara, RE)/ ; N/A//CHIESI Farmaceutici S.p.A. (Parma)/ ; N/A//Transfer Oil S.p.A. (Colorno, PR)/ ; N/A//Famiglia Gigetto Furlotti (Parma)/ ; N/A//A.VO.PRO.RI.T. (Parma)/ ; N/A//Ing. Marco Nocivelli, EPTA S.p.A (Milano)/ ; 2018.0184//Fondazione CARIPARMA/ ; }, mesh = {Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cyclin-Dependent Kinase 4/*antagonists &amp; inhibitors ; Cyclin-Dependent Kinase 6/*antagonists &amp; inhibitors ; Energy Metabolism/*drug effects ; Glycolysis/drug effects ; Humans ; Mesothelioma, Malignant/drug therapy/*metabolism ; Mitochondria/drug effects/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Piperazines/pharmacology ; Pleural Neoplasms/drug therapy/*metabolism ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/antagonists &amp; inhibitors/metabolism ; Pyridines/pharmacology ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/*antagonists &amp; inhibitors/metabolism ; }, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients is CDKN2A/ARF loss, leading to aberrant activation of the Rb pathway. In MPM cells, we previously demonstrated the therapeutic efficacy of targeting this signaling with the CDK4/6 inhibitor palbociclib in combination with PI3K/mTOR inhibitors. Here, we investigated whether such combination may have an impact on cell energy metabolism. Methods: The study was performed in MPM cells of different histotypes; metabolic analyses were conducted by measuring GLUT-1 expression and glucose uptake/consumption, and by SeaHorse technologies. Results: MPM cell models differed for their ability to adapt to metabolic stress conditions, such as glucose starvation and hypoxia. Independently of these differences, combined treatments with palbociclib and PI3K/mTOR inhibitors inhibited cell proliferation more efficaciously than single agents. The drugs alone reduced glucose uptake/consumption as well as glycolysis, and their combination further enhanced these effects under both normoxic and hypoxic conditions. Moreover, the drug combinations significantly impaired mitochondrial respiration as compared with individual treatments. These metabolic effects were mediated by the concomitant inhibition of Rb/E2F/c-myc and PI3K/AKT/mTOR signaling. Conclusions: Dual blockade of glycolysis and respiration contributes to the anti-tumor efficacy of palbociclib-PI3K/mTOR inhibitors combination.}, }
@article {pmid32700418, year = {2020}, author = {Voloaca, OM and Greenhalgh, CJ and Cole, LM and Clench, MR and Managh, AJ and Haywood-Small, SL}, title = {Laser ablation inductively coupled plasma mass spectrometry as a novel clinical imaging tool to detect asbestos fibres in malignant mesothelioma.}, journal = {Rapid communications in mass spectrometry : RCM}, volume = {34}, number = {21}, pages = {e8906}, doi = {10.1002/rcm.8906}, pmid = {32700418}, issn = {1097-0231}, mesh = {*Asbestos/analysis/chemistry ; Cell Line, Tumor ; Humans ; Lasers ; *Lung Neoplasms/diagnostic imaging/pathology ; Mass Spectrometry/*methods ; *Mesothelioma, Malignant/diagnostic imaging/pathology ; Microscopy/*methods ; }, abstract = {RATIONALE: Malignant pleural mesothelioma is an extremely aggressive and incurable malignancy associated with prior exposure to asbestos fibres. Difficulties remain in relation to early diagnosis, notably due to impeded identification of asbestos in lung tissue. This study describes a novel laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging approach to identify asbestos within mesothelioma models with clinical significance.<br><br>METHODS: Human mesothelioma cells were exposed to different types of asbestos fibres and prepared on plastic slides for LA-ICP-MS analysis. No further sample preparation was required prior to analysis, which was performed using an NWR Image 266&#x2009;nm laser ablation system coupled to an Element XR sector-field ICP mass spectrometer, with a lateral resolution of 2&#x2009;&#x3bc;m. Data was processed using LA-ICP-MS ImageTool v1.7 with the final graphic production made using DPlot software.<br><br>RESULTS: Four different mineral fibres were successfully identified within the mesothelioma samples based on some of the most abundant elements that make up these fibres (Si, Mg and Fe). Using LA-ICP-MS as an imaging tool provided information on the spatial distribution of the fibres at cellular level, which is essential in asbestos detection within tissue samples. Based on the metal counts generated by the different types of asbestos, different fibres can be identified based on shape, size, and elemental composition. Detection of Ca was attempted but requires further optimisation.<br><br>CONCLUSIONS: Detection of asbestos fibres in lung tissues is very useful, if not necessary, to complete the pathological dt9iagnosis of asbestos-related malignancies in the medicolegal field. For the first time, this study demonstrates the successful application of LA-ICP-MS imaging to identify asbestos fibres and other mineral fibres within mesothelioma samples. Ultimately, high-resolution, fast-speed LA-ICP-MS analysis has the potential to be integrated into clinical workflow to aid earlier detection and stratification of mesothelioma patient samples.}, }
@article {pmid32699075, year = {2020}, author = {Pass, HI and Alimi, M and Carbone, M and Yang, H and Goparaju, CM}, title = {Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {12}, pages = {2524-2540}, doi = {10.1158/1055-9965.EPI-20-0083}, pmid = {32699075}, issn = {1538-7755}, support = {U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*metabolism ; Early Detection of Cancer/*methods ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm, which can be treated successfully only if correctly diagnosed and treated in early stages. The asbestos-exposed population serves as a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. This review details the recent work with biomarker development in MPM and the contributions of the NCI Early Detection Research Network Biomarker Developmental Laboratory of NYU Langone Medical Center. The literature of the last 20 years was reviewed to comment on the most promising of the blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms as well as novel studies such as "breath testing" are covered. Soluble mesothelin-related proteins (SMRP) have been characterized extensively and constitute an FDA-approved biomarker in plasma with diagnostic, monitoring, and prognostic value in MPM. Osteopontin is found to be a valuable prognostic biomarker for MPM, while its utility in diagnosis is slightly lower. Other biomarkers, such as calretinin, fibulin 3, and High-Mobility Group Box 1 (HMGB1), remain under study and need international validation trials with large cohorts of cases and controls to demonstrate any utility. The EDRN has played a key role in the development and testing of MPM biomarkers by enlisting collaborations all over the world. A comprehensive understanding of previously investigated biomarkers and their utility in screening and early diagnosis of MPM will provide guidance for further future research.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."}, }
@article {pmid32691574, year = {2020}, author = {Loreto, C and Ledda, C and Tumino, R and Lombardo, C and Vitale, E and Filetti, V and Caltabiano, R and Rapisarda, V}, title = {Activation of caspase-3 in malignant mesothelioma induced by asbestiform fiber: an in vivo study.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {34}, number = {3}, pages = {1163-1166}, doi = {10.23812/19-441-L-50}, pmid = {32691574}, issn = {0393-974X}, mesh = {Caspase 3/genetics ; Humans ; Italy ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; }, }
@article {pmid32690542, year = {2020}, author = {Carbone, M and Harbour, JW and Brugarolas, J and Bononi, A and Pagano, I and Dey, A and Krausz, T and Pass, HI and Yang, H and Gaudino, G}, title = {Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer.}, journal = {Cancer discovery}, volume = {10}, number = {8}, pages = {1103-1120}, pmid = {32690542}, issn = {2159-8290}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 CA125970/CA/NCI NIH HHS/United States ; P50 CA196516/CA/NCI NIH HHS/United States ; P30 CA240139/CA/NCI NIH HHS/United States ; U01 CA111295/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; R01 CA175754/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Kidney Neoplasms ; *Melanoma ; Mutation ; *Skin Neoplasms ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; *Uveal Neoplasms ; }, abstract = {Among more than 200 BAP1-mutant families affected by the "BAP1 cancer syndrome," nearly all individuals inheriting a BAP1 mutant allele developed one or more malignancies during their lifetime, mostly uveal and cutaneous melanoma, mesothelioma, and clear-cell renal cell carcinoma. These cancer types are also those that, when they occur sporadically, are more likely to carry somatic biallelic BAP1 mutations. Mechanistic studies revealed that the tumor suppressor function of BAP1 is linked to its dual activity in the nucleus, where it is implicated in a variety of processes including DNA repair and transcription, and in the cytoplasm, where it regulates cell death and mitochondrial metabolism. BAP1 activity in tumor suppression is cell type- and context-dependent. BAP1 has emerged as a critical tumor suppressor across multiple cancer types, predisposing to tumor development when mutated in the germline as well as somatically. Moreover, BAP1 has emerged as a key regulator of gene-environment interaction.This article is highlighted in the In This Issue feature, p. 1079.}, }
@article {pmid32683434, year = {2020}, author = {Brook, MS and Black, PM and Salmond, J and Dirks, KN and Berry, TA and Steinhorn, G}, title = {Erionite in Auckland bedrock and malignant mesothelioma: an emerging public and occupational health hazard?.}, journal = {The New Zealand medical journal}, volume = {133}, number = {1518}, pages = {73-78}, pmid = {32683434}, issn = {1175-8716}, mesh = {Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Mesothelioma, Malignant ; New Zealand/epidemiology ; Occupational Exposure/*adverse effects ; *Occupational Health ; *Public Health ; Zeolites/*adverse effects ; }, abstract = {Overseas, emerging research has shown that where erionite is present in bedrock as a zeolite, and then subsequently disturbed and blown into the atmosphere, resulting exposure is associated with health effects similar to those caused by asbestos, including malignant mesothelioma (MM). Erionite-induced MM is thought to be particularly prevalent in the construction and quarrying industries, in regions where rock containing erionite is disturbed. In 2015, the then Government Chief Scientist, Sir Peter Gluckman, reported that erionite was a more potent carcinogen than asbestos, and more recent studies have established its presence in the Auckland Region. However, globally at present, there are no established occupational exposure limits for erionite, standard sampling and analytical methods or exposure mitigation guidelines. Given the many major construction projects being carried out in Auckland at the present time, which involve the removal of large quantities of bedrock containing erionite, an assessment of the health risks such activities pose to the public is needed.}, }
@article {pmid32682370, year = {2020}, author = {Cheng, L and Li, N and Xu, XL and Mao, WM}, title = {Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma.}, journal = {Current drug targets}, volume = {21}, number = {15}, pages = {1606-1612}, doi = {10.2174/1389450121666200719011234}, pmid = {32682370}, issn = {1873-5592}, support = {81802995//National Natural Science Foundation of China/ ; 2018RC020, 2018KY024//Medical Science and Technology Project of Zhejiang Province/ ; }, mesh = {Animals ; B7-H1 Antigen/metabolism ; Cancer-Associated Fibroblasts/immunology ; Dendritic Cells/immunology ; Humans ; *Immunotherapy ; Killer Cells, Natural/immunology ; Mesothelioma, Malignant/*immunology/*therapy ; Myeloid-Derived Suppressor Cells/immunology ; T-Lymphocytes/immunology ; Tumor Microenvironment/*immunology ; Tumor-Associated Macrophages/immunology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without chemotherapy, and/or radiation therapy. The mechanism of carcinogenesis has not been fully elucidated, although approximately 80% of cases can still be linked to asbestos exposure. The tumor immune microenvironment (TME) has been proven to play an important role in MPM pathogenesis and treatment outcomes. Several molecular pathways have been implicated in the MPM tumor microenvironment, such as angiogenesis, apoptosis, cell cycle regulation, and stromal processes. Immunotherapy has already shown promising results in other thoracic solid tumors, such as non-small-cell lung cancer (NSCLC). However, immunotherapy has shown less convincing results in MPM than in melanoma and NSCLC. A multicenter, randomized trial (DETERMINE) proved that immune checkpoint inhibition using tremelimumab, an anti-cytotoxic T lymphocyteassociated protein 4 (CTLA-4) antibody, failed to improve median overall survival. Therefore, it is important to explore the relationship between the characteristics of the tumor microenvironment and immunotherapy. Here, we review the heterogeneity of the TME and the progress in the understanding of the immune microenvironment and immunotherapy in MPM to explore the mechanisms of resistance to immunotherapy.}, }
@article {pmid32682189, year = {2020}, author = {Remon, J and Nadal, E and Dómine, M and Ruffinelli, J and García, Y and Pardo, JC and López, R and Cilleruelo, A and García-Campelo, R and Martín, P and Juan, O and González-Larriba, JL and Provencio, M and Olmedo, E and Ponce, S and Cumplido, D and Barenys, C and Majem, M and Massutti, B and Rodriguez-Abreu, D and Porta, R and Sala, MA and Martinez-Kareaga, M and Lianes, P and Reguart, N}, title = {Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {147}, number = {}, pages = {83-90}, doi = {10.1016/j.lungcan.2020.06.034}, pmid = {32682189}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms/diagnosis/epidemiology/therapy ; *Mesothelioma/diagnosis/epidemiology/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/epidemiology/therapy ; Spain/epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain.<br><br>MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments.<br><br>RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N&#x202f;=&#x202f;315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy.<br><br>CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.}, }
@article {pmid32676359, year = {2020}, author = {Hjerpe, A and Abd Own, S and Dobra, K}, title = {Integrative approach to cytologic and molecular diagnosis of malignant pleural mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {3}, pages = {934-943}, pmid = {32676359}, issn = {2218-6751}, abstract = {The global incidence of malignant mesothelioma (MM) causes considerable disease burden, suffering and health care costs. Beside preventive measures and ban the use of asbestos, early diagnosis would largely improve the chance of curative treatment. Current histologic criteria, however, requiring presence of invasion in the surrounding fatty tissue fail to identify MM in sufficiently early stage. Unilateral accumulation of pleural effusion is one of the earliest clinical manifestations of MM that occurs in approximately 90% of the patients. Therapeutic thoracocenthesis is necessary to remove the fluid and to relieve patients' symptoms. This effusion is easily accessible and offers early and minimally invasive diagnosis by combining cytology with immunologic, molecular- and biomarker analyses. Typically, the fluid is rich in malignant cells and cell groups, but incipient stages of the disease may be difficult to recognize as the malignant cells can be masked by presence of inflammatory or reactive mesothelial cells. Recurrent, hemorrhagic and cell rich effusion should always be suspicious for MM and adequately prepared and analyzed to provide necessary information for subsequent therapy. Importantly, early detection of MM by integrating cytology and molecular approaches has high sensitivity and positive predictive value and has a major impact on patient survival. Thus, a conclusive positive MM cytology should lead to treatment without delay. This review summarizes molecular and diagnostic criteria of MM diagnosis.}, }
@article {pmid34589956, year = {2020}, author = {Ahmadzada, T and Cooper, WA and Holmes, M and Mahar, A and Westman, H and Gill, AJ and Nordman, I and Yip, PY and Pal, A and Zielinski, R and Pavlakis, N and Nagrial, A and Daneshvar, D and Brungs, D and Karikios, D and Aleksova, V and Burn, J and Asher, R and Grau, GE and Hosseini-Beheshti, E and Reid, G and Clarke, S and Kao, S}, title = {Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population.}, journal = {JTO clinical and research reports}, volume = {1}, number = {4}, pages = {100075}, pmid = {34589956}, issn = {2666-3643}, abstract = {INTRODUCTION: We investigated the efficacy and toxicity of pembrolizumab in patients with mesothelioma from a real-world Australian population. We aimed to determine clinical factors and predictive biomarkers that could help select patients who are likely to benefit from pembrolizumab.<br><br>METHOD: Patients with mesothelioma who were treated with pembrolizumab as part of the Insurance and Care New South Wales compensation scheme were included. Clinical information was collected retrospectively. Tumor biomarkers such as programmed death-ligand 1 (PD-L1), BAP1, and CD3-positive (CD3+) tumor-infiltrating lymphocytes (TILs) were examined using archival formalin-fixed paraffin-embedded tumor samples.<br><br>RESULTS: A total of 98 patients were included with a median age of 70 years (range, 46-91 y); 92% were men; 76% had epithelioid subtype; 21% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Pembrolizumab was used as second-line or subsequent-line treatment in 94 patients and as first-line treatment in four patients. The overall response rate was 18%, and the disease control rate was 56%. The median progression-free survival (PFS) was 4.8 months (95% confidence interval: 3.6-6.2), and the median overall survival (OS) was 9.5 months (95% confidence interval: 6.6-13.7). Immune-related adverse events occurred in 27% of patients, of which nine (9%) were of grade 3 or higher. In the multivariable analysis, factors independently associated with longer PFS included baseline ECOG status of 0 (median PFS: 12 mo versus 4 mo, p < 0.01) and PD-L1 tumor proportion score of greater than or equal to 1% (median PFS: 6 mo versus 4 mo, p < 0.01). Baseline platelet count of less than or equal to 400&#xa0;&#xd7; 10[9]/liter was independently associated with longer PFS and OS (median PFS: 6 mo versus 2 mo, p&#xa0;= 0.05; median OS: 10 mo versus 4 mo, p&#xa0;= 0.01), whereas lack of pretreatment dexamethasone was independently associated with OS but not PFS (median OS: 10 mo versus 3 mo, p&#xa0;= 0.01). The odds of response were higher for patients with baseline ECOG status of 0 (p&#xa0;= 0.02) and with greater than or equal to 5% CD3+ TILs in the tumor (p < 0.01). PD-L1 expression, BAP1 loss, and CD3+ TILs in the stroma were not significantly associated with the overall response rate.<br><br>CONCLUSIONS: Immunotherapy is a reasonable treatment option for patients with mesothelioma. Our results are comparable to other clinical trials investigating pembrolizumab in mesothelioma in terms of response. Good performance status assessment remains the most robust predictor for patient outcomes. CD3+ TILs in the tumor may help select patients that are likely to respond to pembrolizumab, whereas factors such as PD-L1 expression, baseline platelet count, and lack of pretreatment dexamethasone may help predict survival outcomes from pembrolizumab treatment.}, }
@article {pmid32667289, year = {2020}, author = {Świątkowska, B}, title = {[The Amiantus Program in Poland - 20 years of implementation].}, journal = {Medycyna pracy}, volume = {71}, number = {5}, pages = {595-601}, doi = {10.13075/mp.5893.00997}, pmid = {32667289}, issn = {2353-1339}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*diagnosis/epidemiology/*history/*prevention &amp; control ; Female ; History, 21st Century ; Humans ; Male ; Mass Screening/history/methods/statistics &amp; numerical data ; Middle Aged ; National Health Programs/*history ; Occupational Diseases/history/*prevention &amp; control ; Occupational Exposure/history/*prevention &amp; control ; Poland ; Population Surveillance/methods ; }, abstract = {BACKGROUND: Despite the ban on the production of asbestos-containing materials, introduced in Poland over 20 years ago, new cases of asbestos-related diseases are still being recorded. Systematic control of respiratory function in people exposed to asbestos dust is, therefore, extremely important due to the biological properties of this mineral.<br><br>MATERIAL AND METHODS: The Amiantus preventive medical examination program was undertaken in 2000 to implement the legal rights of former employees of asbestos processing plants for this type of examinations. People who have ever been employed in such factories have been authorized to use preventive medical examinations for the rest of their lives. The research is continuous, spread over time and focused, in particular, on the assessment of the respiratory system.<br><br>RESULTS: Since the beginning of the program, throughout 20 years of its implementation, 8329 people have been examined, including 5199 (62.4%) men for whom a total of 34 454 medical examinations have been carried out. During the program period, the percentage of diagnosed pathologies increased from 8% in 2000 to 25% in 2019. Overall, 2078 asbestos-related diseases were diagnosed among former employees of asbestos processing plants under the Amiantus Program, which accounted for 25% of this group. Among all diseases caused by exposure to asbestos, the most common were: asbestosis (1880 cases - 90.5%), lung cancer (121 cases - 5.8%) and pleural mesothelioma (77 cases - 3.7%). Diseases of pleura in the form of plaques and diffuse pleural thickening were diagnosed in 40% of the examined patients, while radiological pulmonary shadows affected over 65% of former employees of asbestos processing plants.<br><br>CONCLUSIONS: The Amiantus Program, thanks to the long observation period, enabled monitoring the health of former employees exposed to asbestos, and created a unique opportunity to carry out epidemiological analyzes. These studies allowed the authors to expand their knowledge of the natural history of asbestos-related diseases. Med Pr. 2020;71(5):595-601.}, }
@article {pmid32664483, year = {2020}, author = {Indovina, P and Forte, IM and Pentimalli, F and Giordano, A}, title = {Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade.}, journal = {Cancers}, volume = {12}, number = {7}, pages = {}, pmid = {32664483}, issn = {2072-6694}, support = {ID 483418//Mesothelioma Applied Research Foundation/ ; Ricerca Corrente (M4/7)//Italian Ministry of Health/ ; }, abstract = {Abstract: Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.}, }
@article {pmid32649346, year = {2020}, author = {Louw, A and Creaney, J and Thomas, A and Van Vliet, C and Harvey, NT and Wood, BA and Mesbah Ardakani, N}, title = {Histologically Diverse BAP1-Deficient Melanocytic Tumors in a Patient With BAP1 Tumor Predisposition Syndrome.}, journal = {The American Journal of dermatopathology}, volume = {42}, number = {11}, pages = {872-875}, doi = {10.1097/DAD.0000000000001719}, pmid = {32649346}, issn = {1533-0311}, mesh = {Female ; Germ-Line Mutation ; Humans ; Melanoma/genetics/*pathology ; Mesothelioma/genetics ; Middle Aged ; Neoplastic Syndromes, Hereditary/*genetics/*pathology ; Pleural Neoplasms/genetics ; Skin Neoplasms/genetics/*pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BRCA1-associated protein-1 (BAP1)-deficient cutaneous tumors are common in patients with BAP1 tumor predisposition syndrome, frequently presenting before other associated neoplasms, and can serve as an early marker to identify individuals with this disease. The typical lesions are dermal based and composed of a combination of larger epithelioid melanocytes with abundant glassy cytoplasm and smaller cells resembling those of a conventional nevus. There is often a component of interspersed lymphocytes. However, BAP1-deficient melanocytic tumors can show a spectrum of histologic appearances, ranging from lesions with pure epithelioid, pure conventional nevus, or rhabdoid cells and tumors with an intraepidermal component. To demonstrate such morphologic variation, we present a case of a 50-year-old woman with multiple histologically diverse BAP1-deficient melanocytic tumors and germline BAP1 mutation, identified after a diagnosis of pleural mesothelioma. We also discuss the pathogenesis and potential histopathological and clinical indications of germline versus sporadic etiology in the assessment of BAP1-deficient melanocytic tumors.}, }
@article {pmid32648970, year = {2020}, author = {Schüz, J and Kromhout, H}, title = {Re Ferrante et al (2020). Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {834-835}, doi = {10.1002/ajim.23154}, pmid = {32648970}, issn = {1097-0274}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Asbestos, Serpentine ; Cohort Studies ; Humans ; Incidence ; Italy ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid32648944, year = {2020}, author = {Ferrante, D and Mirabelli, D and Silvestri, S and Azzolina, D and Giovannini, A and Tribaudino, P and Magnani, C}, title = {Ferrante et al respond.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {836-837}, doi = {10.1002/ajim.23153}, pmid = {32648944}, issn = {1097-0274}, mesh = {*Asbestos, Serpentine ; Cohort Studies ; Humans ; Incidence ; Italy ; *Mesothelioma ; }, }
@article {pmid32633902, year = {2020}, author = {Maat, A and Abdullah, S and Schouten, G and Cornelissen, R and Bogers, A and Mahtab, E}, title = {Video-assisted biopsy and talc pleurodesis for malignant pleural mesothelioma.}, journal = {Multimedia manual of cardiothoracic surgery : MMCTS}, volume = {2020}, number = {}, pages = {}, doi = {10.1510/mmcts.2020.038}, pmid = {32633902}, issn = {1813-9175}, mesh = {Aged ; Humans ; Image-Guided Biopsy/*methods ; *Lung Neoplasms/pathology/physiopathology/therapy ; Male ; *Mesothelioma/pathology/physiopathology/therapy ; Mesothelioma, Malignant ; Pleural Effusion, Malignant/etiology/prevention &amp; control ; Pleurodesis/*methods ; Thoracic Surgery, Video-Assisted/*methods ; }, abstract = {Malignant pleural mesothelioma is a disease of the pleural cavity that is strongly associated with asbestos exposure. In most cases it carries a poor prognosis. Patients often present with respiratory symptoms, caused by pleural effusion. Treatment, preferably in a multimodal setting, cannot provide cure, but can prolong survival and improve quality of life in selected cases. Prior to eventual cytoreductive surgery, surgical intervention can provide histopathological proof of disease, and symptoms can be controlled with talc pleurodesis. We present the case of a 67-year-old patient with malignant pleural mesothelioma who underwent video-assisted thoracoscopic biopsy and talc pleurodesis, and demonstrate our technique with a video tutorial showing how we performed the procedure.}, }
@article {pmid32631013, year = {2020}, author = {Fazzo, L and Cernigliaro, A and De Santis, M and Quattrone, G and Bruno, C and Zona, A and Tumino, R and Cascone, G and Scondotto, S and Comba, P}, title = {Occupational cohort study of asbestos-cement workers in a contaminated site in Sicily (Italy).}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {2-3}, pages = {137-144}, doi = {10.19191/EP20.2-3.P137.036}, pmid = {32631013}, issn = {1120-9763}, mesh = {Asbestos ; Asbestosis/*epidemiology ; Cohort Studies ; Construction Materials ; Female ; Humans ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; Sicily/epidemiology ; }, abstract = {OBJECTIVES: to analyse the asbestos-related diseases risk among the former workers of Sacelit asbestos-cement plant, operating in San Filippo del Mela (Sicily: 1958- 1993).<br><br>DESIGN: cohort study.<br><br>SETTING AND PARTICIPANTS: 228 subjects were employed in Sacelit from 1958 to 1993. Due to the available observation periods, the analyses of the different outcomes were performed for the subjects alive at the beginning of the respective follow up periods: mortality (1986-2018) was analysed for 204 subjects (177 men, 27 women), hospitalization (2001-2016) for 164 workers (139 men, 25 women) and the incidence of mesothelioma (1998-2016) was estimated for 178 subjects (153 men, 25 women).<br><br>MAIN OUTCOMES MEASURES: mortality (Standardized Mortality Ratio: SMR) and hospitalization (Standardized Hospitalization Ratio: SHR) from specific diseases were analysed. Incidence (Standardized Incidence Ratio: SIR) of mesothelioma cases was detected, also. SMR (1986-2014), SHR (2001-2016) and SIR (1998-2016), with 95% Confidence Intervals, were computed with respect to the regional rates, with STATA11.<br><br>RESULTS: in the men cohort, mortality from lung (17 cases, SMR 2.83) and pleural cancers (5 cases, SMR 30) and from asbestosis (15 cases, SMR 1,930) was in excess. The risk of hospitalization was in excess, in both genders, from lung cancer (men: 6 cases, SHR 4.1; women: 2 cases, SHR 8.6) and asbestosis (men: 17 cases, SHR 1,304; women: 6 cases, SHR 2,455). The incidence of mesothelioma was in excess in men (5 cases, SIR 23.9); no female cases of mesothelioma were observed.<br><br>CONCLUSIONS: a high occurrence of asbestos-related diseases in the cohort, particularly among men, was observed. The excess of hospitalization from asbestosis and lung cancer was highlighted also in women. The prosecution of the on-going health surveillance plan is particularly appropriated.}, }
@article {pmid32626907, year = {2021}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {47}, number = {1}, pages = {85-86}, pmid = {32626907}, issn = {1795-990X}, mesh = {*Asbestos/adverse effects ; Case-Control Studies ; Female ; Humans ; Italy ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Middle Aged ; *Occupational Exposure ; Pericardium ; Testis ; }, abstract = {As the first case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis (mTVT), the paper by Marinaccio et al (1) is potentially an important epidemiologic contribution. A careful review of the paper, however, raises a number of methodological issues. Any case-control study can be viewed as being nested within a conceptual cohort, with controls being sampled from the at-risk cohort as cases arise over time. This view of case-control studies leads to the concept of incidence-density sampling of controls (eg, 2, 3). For Marinaccio et al (1) this would mean that, as cases were registered over the study period, each would be matched to an individual control or set of controls of the same gender, age, and region of the country (since asbestos exposure varies by time and region [4]). For example, if a case were 50 years old in 1995, then any matched control should be close to age 50 in 1995 and of the same gender and from the same region as the case. Matching for age in this fashion automatically results in matching for year of birth, which is essential in this context because birth-cohort effects are determinants of asbestos exposure and mesothelioma incidence (eg, 5-8). If Marinaccio et al (1) used this scheme for age-matching, one would expect to see similar distributions of cases (table 1) and controls (table S3 in the supplemental material) by period of birth. Among males, however, the distributions of mesothelioma cases (whether pericardial or mTVT) and controls by period of birth are clearly different (P<0.001). Among females, the distributions of cases of pericardial mesothelioma and controls by birth year are less dissimilar (P≈0.05). Thus, the female cases of pericardial mesothelioma are better matched to controls on year of birth than are male cases of either mTVT or pericardial mesothelioma. We note also that the distributions of male and female controls by year of birth are distinctly different (P<0.002), whereas the birth-year distributions of cases of mesothelioma by site and gender are not (P≈0.8). In the Marinaccio et al (1) sensitivity analysis restricted to subjects born before 1950, the distributions of cases and controls by period of birth remain significantly different. Therefore, based on the reported evidence, cases and controls were not matched on birth cohort, thereby possibly biasing the results. Similarly, bias may result from the lack of matching on geographic region; while cases were registered from across Italy, controls were selected from only six regions. Although a sensitivity analysis restricted cases and controls to those from only the six regions, a comparison of tables S1 and S3 indicates that the regional distribution of controls is different from that of person-time observed; that is, the controls do not appear to be representative of the underlying population at risk by region. The second major issue of concern has to do with ascertainment of asbestos exposure. Information on exposure for the cases was presumably obtained at the time of registration. The two sets of controls, obtained from previously unpublished case-control studies, were interviewed during 2014-2015 and 2014-2016; that is, many years after the exposure for most cases was ascertained (1993-2015). Few other details of the control groups are provided, except that participation by one set of controls was <50%, raising additional concerns about selection bias. For details on the second set of controls, Marinaccio et al (1) reference a paper by Brandi et al (9). On review of that paper, however, we found no description of the control group, only references to three earlier papers. Marinaccio et al (1) present analyses only with both sets of controls combined; to evaluate potential sources of bias from the use of different sets of controls, they should also report results using each set of controls separately. The authors also did not detail their methods of exposure classification. For example, what does probable or possible exposure mean? The authors should at least present separate analyses of definite occupational exposure. Eighty cases of mTVT were registered, but only 68 were included in the analyses. Information on the 12 omitted cases (eg, age, year of birth, and region) would be helpful. Marinaccio et al (1) did not provide clear information on what occupations and/or industries they considered as exposed to asbestos. In an earlier study, Marinaccio et al (10) remarked on the absence of pericardial mesothelioma and mTVT in industries with the highest exposures to asbestos, saying, "[t]he absence of exposures in the shipbuilding, railway and asbestos-cement industries … for all the 67 pericardial and testicular cases is noteworthy but not easy to interpret." By contrast, Marinaccio et al (1) stated, "[t]he economic sectors more frequently associated with asbestos exposure were construction, steel mills, metal-working industry, textile industry and agriculture." The possibility of exposure in the "agriculture economic sector" was not mentioned in Marinaccio et al (10) and appears not to have been considered in previous epidemiologic studies in Italy. In general, epidemiologic studies indicate that farmers and agricultural workers are not at increased risk of developing mesothelioma (eg, 11-17). The fact that few, if any, cases of mTVT and pericardial mesothelioma occurred in industries traditionally associated with high asbestos exposure raises the possibility that the results of Marinaccio et al (1) are attributable to deficiencies in study design, very possibly bias in the selection of controls, and deficiencies in exposure assessment and classification as described above, leading to a spurious association of occupational exposure with mTVT and male pericardial mesothelioma. Conflict of interest This research has received no outside funding. All authors are employees of Exponent, Inc., an international scientific and engineering consulting company. All authors have worked as both consulting and testifying experts in litigation matters related to asbestos exposure and asbestos-related disease. References 1. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 2. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 2008; Philadelphia: Wolters Kluwer/Lippincott Williams &amp; Wilkins. 3. Richardson DB. An incidence density sampling program for nested case-control analyses. Occup Environ Med 2004 Dec;61(12):e59. https://doi.org/10.1136/oem.2004.014472. 4. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 5. La Vecchia C, Decarli A, Peto J, Levi F, Tomei F, Negri E. An age, period and cohort analysis of pleural cancer mortality in Europe. Eur J Cancer Prev 2000 Jun;9(3):179-84. https://doi.org/10.1097/00008469-200006000-00005. 6. Price B, Ware A. Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003. Am J Epidemiol 2004 Jan;159(2):107-12. https://doi.org/10.1093/aje/kwh025. 7. Moolgavkar SH, Meza R, Turim J. Pleural and peritoneal mesotheliomas in SEER: age effects and temporal trends, 1973-2005. Cancer Causes Control 2009 Aug;20(6):935-44. https://doi.org/10.1007/s10552-009-9328-9. 8. Moolgavkar SH, Chang ET, Mezei G, Mowat FS. Chapter 3. Epidemiology of mesothelioma. In Testa JR. Asbestos and mesothelioma; 2017. pp. 43-72. Cham, Switzerland: Springer International Publishing. 9. Brandi G, Di Girolamo S, Farioli A, de Rosa F, Curti S, Pinna AD et al. Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis. Cancer Causes Control 2013 May;24(5):911-8. https://doi.org/10.1007/s10552-013-0167-3. 10. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 11. Teschke K, Morgan MS, Checkoway H, Franklin G, Spinelli JJ, van Belle G et al. Mesothelioma surveillance to locate sources of exposure to asbestos. Can J Public Health 1997 May-Jun;88(3):163-8. https://doi.org/10.1007/BF03403881. 12. Bouchardy C, Schüler G, Minder C, Hotz P, Bousquet A, Levi F et al. Cancer risk by occupation and socioeconomic group among men--a study by the Association of Swiss Cancer Registries. Scand J Work Environ Health 2002;28(1 Suppl 1):1-88. 13. Hemminki K, Li X. Time trends and occupational risk factors for pleural mesothelioma in Sweden. J Occup Environ Med 2003a Apr;45(4):456-61. https://doi.org/10.1097/01.jom.0000058341.05741.7e. 14. Hemminki K, Li X. Time trends and occupational risk factors for peritoneal mesothelioma in Sweden. J Occup Environ Med 2003b Apr;45(4):451-5. https://doi.org/10.1097/01.jom.0000052960.59271.d4. 15. Pukkala E, Martinsen JI, Lynge E, Gunnarsdottir HK, Sparén P, Tryggvadottir L et al. Occupation and cancer - follow-up of 15 million people in five Nordic countries. Acta Oncol 2009;48(5):646-790. https://doi.org/10.1080/02841860902913546. 16. Rolland P, Gramond C, Berron H, Ducamp S, Imbernon E, Goldberg M et al. Mesotheliome pleural: Professions et secteurs d'activite a risque chez les hommes [Pleural mesothelioma: Professions and occupational areas at risk among humans]. 2005; Institut de Veille Sanitaire, Departement Sante Travai, Saint-Maurice, France. 17. Rolland P, Gramond C, Lacourt A, Astoul P, Chamming's S, Ducamp S et al. PNSM Study Group. Occupations and industries in France at high risk for pleural mesothelioma: A population-based case-control study (1998-2002). Am J Ind Med 2010 Dec;53(12):1207-19. https://doi.org/10.1002/ajim.20895.}, }
@article {pmid32624414, year = {2020}, author = {Paajanen, J and Laaksonen, S and Ilonen, I and Vehmas, T and Mäyränpää, MI and Sutinen, E and Kettunen, E and Salo, JA and Räsänen, J and Wolff, H and Myllärniemi, M}, title = {Clinical Features in Patients With Malignant Pleural Mesothelioma With 5-Year Survival and Evaluation of Original Diagnoses.}, journal = {Clinical lung cancer}, volume = {21}, number = {6}, pages = {e633-e639}, doi = {10.1016/j.cllc.2020.05.020}, pmid = {32624414}, issn = {1938-0690}, mesh = {Aged ; Case-Control Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma, Malignant/*mortality/pathology/therapy ; Middle Aged ; Pleural Neoplasms/*mortality/pathology/therapy ; Prognosis ; Registries/*statistics &amp; numerical data ; Retrospective Studies ; Survival Rate ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival.<br><br>MATERIALS AND METHODS: Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists.<br><br>RESULTS: Our study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time.<br><br>CONCLUSION: We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors.}, }
@article {pmid32604114, year = {2020}, author = {Xu, T and Hu, J and Zhang, X and Cao, J and Chen, Y}, title = {A Case of Localized Malignant Peritoneal Mesothelioma Evaluated by 18F-FDG PET/CT.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {11}, pages = {890-891}, doi = {10.1097/RLU.0000000000003158}, pmid = {32604114}, issn = {1536-0229}, mesh = {Aged ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*diagnostic imaging/pathology ; Mesothelioma/*diagnostic imaging/pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging/pathology ; *Positron Emission Tomography Computed Tomography ; Prognosis ; }, abstract = {Localized malignant mesothelioma is rare. The prognosis is generally more favorable for this condition than for diffuse malignant mesothelioma. An elderly woman recently complained of abdominal pain, fever, and weight loss. She had no history of asbestos exposure. Her serum CEA level was elevated. Plain CT revealed a mass under the left diaphragm, with liquefaction and necrosis. A contrast-enhanced scan showed circular enhancement of the mass. A subsequent biopsy of the mass revealed a poorly differentiated carcinoma. PET/CT showed a significant FDG-avid subphrenic mass without any indications of metastasis. Postoperative pathological and immunohistochemical examination confirmed a case of malignant mesothelioma.}, }
@article {pmid32602389, year = {2022}, author = {Boice, JD and Cohen, SS and Mumma, MT and Chen, H and Golden, AP and Beck, HL and Till, JE}, title = {Mortality among U.S. military participants at eight aboveground nuclear weapons test series.}, journal = {International journal of radiation biology}, volume = {98}, number = {4}, pages = {679-700}, doi = {10.1080/09553002.2020.1787543}, pmid = {32602389}, issn = {1362-3095}, support = {U01 CA137026/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; *Mesothelioma ; *Myocardial Ischemia ; *Nuclear Weapons ; Radiometry ; }, abstract = {BACKGROUND: Approximately 235,000 military personnel participated at one of 230 U.S. atmospheric nuclear weapons tests from 1945 through 1962. At the Nevada Test Site (NTS), the atomic veterans participated in military maneuvers, observed nuclear weapons tests, or provided technical support. At the Pacific Proving Ground (PPG), they served aboard ships or were stationed on islands during or after nuclear weapons tests.<br><br>MATERIAL AND METHODS: Participants at seven test series, previously studied with high-quality dosimetry and personnel records, and the first test at TRINITY formed the cohort of 114,270 male military participants traced for vital status from 1945 through 2010. Dose reconstructions were based on Nuclear Test Personnel Review records, Department of Defense. Standardized mortality ratios (SMR) and Cox and Poisson regression models were used in the analysis.<br><br>RESULTS: Most atomic veterans were enlisted men, served in the Navy at the PPG, and were born before 1930. Vital status was determined for 96.8% of the veterans; 60% had died. Enlisted men had significantly high all-causes mortality SMR (1.06); officers had significantly low all-causes mortality SMR (0.71). The pattern of risk over time showed a diminution of the 'healthy soldier effect': the all-causes mortality SMR after 50 years of follow-up was 1.00. The healthy soldier effect for all cancers also diminished over time. The all-cancer SMR was significantly high after 50&#x2009;years (SMR 1.10) primarily from smoking-related cancers, attributed in part to the availability of cigarettes in military rations. The highest SMR was for mesothelioma (SMR 1.56) which was correlated with asbestos exposure in naval ships. Prostate cancer was significantly high (SMR 1.13). Ischemic heart disease was significantly low (SMR 0.84). Estimated mean doses varied by organ were low; e.g., the mean red bone marrow dose was 6 mGy (maximum 108 mGy). Internal cohort dose-response analyses provided no evidence for increasing trends with radiation dose for leukemia (excluding chronic lymphocytic leukemia (CLL)) [ERR (95% CI) per 100 mGy -0.37 (-1.08, 0.33); n&#x2009;=&#x2009;710], CLL, myelodysplastic syndrome, multiple myeloma, ischemic heart disease, or cancers of the lung, prostate, breast, and brain.<br><br>CONCLUSION: No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65&#x2009;years. The 95% confidence limits were narrow and excluded mortality risks per unit dose that are two to four times higher than those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.}, }
@article {pmid32600665, year = {2020}, author = {Marinaccio, A and Gariazzo, C and Di Marzio, D and Iavicoli, S and , }, title = {Predictors of filing claims and receiving compensation in malignant mesothelioma patients.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {124}, number = {9}, pages = {1032-1040}, doi = {10.1016/j.healthpol.2020.06.005}, pmid = {32600665}, issn = {1872-6054}, mesh = {*Asbestos/toxicity ; Filing ; Humans ; Italy ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Although the predominant occupation origin of mesothelioma is well known, determinant factors involved in filing compensation are scarcely investigated. A linkage between incident mesothelioma cases collected by Italian mesothelioma register (ReNaM) and compensation claims and assignment by Italian national insurance Institute (INAIL) has been conducted for cases diagnosed in the period 2010-2015 and occupational exposure to asbestos. Logistic regression models and decision tree models have been used to identify demographic, diagnostic and anamnestic factors significant for filing and receiving compensation. We have included in the analyses 5019 mesothelioma cases, and among them, 3321 (66.2 %) were found in INAIL archives as mesothelioma cases who fil claims for compensation. The modalities of asbestos exposure, sector of working activities and job type are crucial factors. Furthermore, gender, age at diagnosis, area of residence have been found to be significant predictors of probability to fil claims. Relative risks to fil claims were obtained for the above determinants and conditions to maximize the probability to obtain compensation identified. Our findings demonstrate that there is a need to enforce policies for improving awareness of the occupational origin for mesothelioma cases. Stakeholders, occupational health and safety institutions can play an important role for improving the sensitization regarding the rights of compensation benefits, ensuring the equity and the effectiveness of insurance, welfare and public health systems.}, }
@article {pmid32596966, year = {2020}, author = {Sherborne, V and Seymour, J and Taylor, B and Tod, A}, title = {What are the psychological effects of mesothelioma on patients and their carers? A scoping review.}, journal = {Psycho-oncology}, volume = {29}, number = {10}, pages = {1464-1473}, doi = {10.1002/pon.5454}, pmid = {32596966}, issn = {1099-1611}, mesh = {*Adaptation, Psychological ; Caregivers/*psychology ; Emotions ; Female ; Humans ; Male ; Mental Health ; Mesothelioma, Malignant/*psychology ; Palliative Care ; *Psychological Distress ; Quality of Life/*psychology ; Stress, Psychological ; Uncertainty ; }, abstract = {OBJECTIVE: Despite recent advances in research, malignant mesothelioma remains an incurable and devastating disease, typically bringing shock and emotional distress to patients and carers. Little research has addressed the psychological impact on either group. This scoping review examines the current state of evidence on the psychological effects of mesothelioma on patients and carers, and identifies areas for further research.<br><br>METHODS: We searched PubMed, PsychINFO, CINAHL, the Cochrane Library and Web of Science for English-language peer-reviewed research articles published 1981 to 2019 reporting studies focussing on the psychological effects of mesothelioma on patients and carers. Following data extraction and quality appraisal, reflexive thematic analysis was used to identify themes.<br><br>RESULTS: Seventeen articles met the inclusion criteria. Carers' experiences were generally amalgamated with patients'. Three themes were developed. The Passing of Time included the importance of timing of interventions; delays in the medical journey; awareness of different time-phases in mesothelioma; and uncertainty/certainty. Dealing with Difficult Feelings reflected ubiquitous negative emotions, feelings about identity and states of being and associated coping strategies. Craving Good Communication covered issues related to sharing of information and to positive/negative aspects of communication.<br><br>CONCLUSIONS: Though limited, the evidence indicates that mesothelioma, with its high symptom-burden, incurability, rarity and asbestos-related causation, leads to complex and inter-relating psychological effects on patients and carers. These effects are both negative and positive. The sparse literature gives a partial picture and demonstrates an urgent need for more nuanced research. Studies exploring the experiences of specific groups are recommended, with particular attention required to carers.}, }
@article {pmid32583627, year = {2020}, author = {Shinozaki-Ushiku, A and Kohsaka, S and Kage, H and Oda, K and Miyagawa, K and Nakajima, J and Aburatani, H and Mano, H and Ushiku, T}, title = {Genomic profiling of multiple primary cancers including synchronous lung adenocarcinoma and bilateral malignant mesotheliomas: Identification of a novel BAP1 germline variant.}, journal = {Pathology international}, volume = {70}, number = {10}, pages = {775-780}, doi = {10.1111/pin.12977}, pmid = {32583627}, issn = {1440-1827}, support = {JP19kk0205016//Japan Agency for Medical Research and Development/ ; //Sysmex Corporation/ ; }, mesh = {Adenocarcinoma of Lung/complications/*diagnosis/genetics/pathology ; Aged ; Genetic Predisposition to Disease ; Genomics ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Lung Neoplasms/complications/*diagnosis/genetics/pathology ; Male ; Mesothelioma, Malignant/complications/*diagnosis/genetics/pathology ; Neoplasms, Multiple Primary ; Peritoneal Neoplasms/complications/*diagnosis/genetics/pathology ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; Urinary Bladder Neoplasms/complications/*diagnosis/genetics/pathology ; }, abstract = {We report a case with a rare combination of synchronous lung adenocarcinoma and bilateral malignant pleural mesotheliomas in a 70-year-old male without asbestos exposure. He metachronously developed peritoneal malignant mesothelioma, intrahepatic cholangiocarcinoma, urothelial carcinoma of the bladder and prostatic adenocarcinoma. Immunohistochemistry revealed complete loss of BAP1 expression in all seven lesions. Targeted next generation sequencing using Todai OncoPanel identified a novel germline variant (c.1565_1566del, p.P522Rfs*14) of BAP1. Additionally, different nonsynonymous somatic mutations of BAP1 were identified in four lesions including lung adenocarcinoma, malignant pleural and peritoneal mesotheliomas, and bladder cancer. The remaining two lesions had different somatic mutations in genes other than BAP1. Multiple BAP1-deficient cancers that developed in a single patient suggest the newly identified germline variant of BAP1 gene to be pathogenic and this case expands the clinical spectrum of BAP1-tumor predisposition syndrome. Screening for BAP1 status is highly recommended in cases with a similar combination of cancers.}, }
@article {pmid32581164, year = {2020}, author = {Ide, Y and Yuki, T and Taooka, Y and Higashi, Y and Tachiyama, Y}, title = {Malignant Peritoneal Mesothelioma Presenting with Polymyalgia Rheumatica-like Syndrome.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {59}, number = {20}, pages = {2629-2632}, pmid = {32581164}, issn = {1349-7235}, mesh = {Adult ; Diagnosis, Differential ; Giant Cell Arteritis/diagnosis ; Glucocorticoids/therapeutic use ; Humans ; Male ; Mesothelioma, Malignant/*complications ; Paraneoplastic Syndromes/*complications/*diagnosis ; Peritoneal Neoplasms/*complications ; Polymyalgia Rheumatica/diagnosis ; }, abstract = {A 30-year-old man was admitted to our hospital because of pain in his proximal extremities. The pain mimicked polymyalgia rheumatica (PMR) and it temporarily improved by a low dose of glucocorticoids, but his symptoms relapsed many times. After six years of glucocorticoid treatment, he developed abdominal pain and ascites, for which he was diagnosed with malignant peritoneal mesothelioma (MPM). His PMR-like symptoms improved with cytoreductive surgery and chemotherapy for MPM. Finally, we diagnosed this PMR-like syndrome to be paraneoplastic syndrome with MPM. Although cases of MPM complicated by PMR-like syndrome are rare, MPM should be taken into account in the differential diagnosis.}, }
@article {pmid32581053, year = {2020}, author = {Blondy, T and d'Almeida, SM and Briolay, T and Tabiasco, J and Meiller, C and Chéné, AL and Cellerin, L and Deshayes, S and Delneste, Y and Fonteneau, JF and Boisgerault, N and Bennouna, J and Grégoire, M and Jean, D and Blanquart, C}, title = {Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma.}, journal = {Journal for immunotherapy of cancer}, volume = {8}, number = {1}, pages = {}, pmid = {32581053}, issn = {2051-1426}, mesh = {Aged ; Biomarkers, Tumor/genetics/*metabolism ; CD8-Positive T-Lymphocytes/immunology/metabolism/pathology ; Cytokines/metabolism ; Female ; Follow-Up Studies ; Humans ; Interleukins/genetics/*metabolism ; Macrophage Colony-Stimulating Factor/genetics/*metabolism ; Macrophages/immunology/metabolism/pathology ; Male ; Mesothelioma, Malignant/genetics/immunology/metabolism/*pathology ; Monocytes/immunology/metabolism/pathology ; Pleural Effusion/immunology/metabolism/*pathology ; Pleural Neoplasms/genetics/immunology/metabolism/*pathology ; Prognosis ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics/*metabolism ; Survival Rate ; T-Lymphocytes, Cytotoxic/immunology ; Tumor Microenvironment/immunology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The tumor microenvironment content, particularly the presence of macrophages, was described as crucial for the development of the disease. This work aimed at studying the involvement of the M-CSF (CSF-1)/IL-34/CSF-1R pathway in the formation of macrophages in MPM, using samples from patients.<br><br>METHODS: Pleural effusions (PEs), frozen tumors, primary MPM cells and MPM cell lines used in this study belong to biocollections associated with clinical databases. Cytokine expressions were studied using real-time PCR and ELISA. The Cancer Genome Atlas database was used to confirm our results on an independent cohort. An original three-dimensional (3D) coculture model including MPM cells, monocytes from healthy donors and a tumor antigen-specific cytotoxic CD8 T cell clone was used.<br><br>RESULTS: We observed that high interleukin (IL)-34 levels in PE were significantly associated with a shorter survival of patients. In tumors, expression of CSF1 was correlated with 'M2-like macrophages' markers, whereas this was not the case with IL34 expression, suggesting two distinct modes of action of these cytokines. Expression of IL34 was higher in MPM cells compared with primary mesothelial cells. Particularly, high expression of IL34 was observed in MPM cells with an alteration of CDKN2A. Finally, using 3D coculture model, we demonstrated the direct involvement of MPM cells in the formation of immunosuppressive macrophages, through activation of the colony stimulating factor-1 receptor (CSF1-R) pathway, causing the inhibition of cytotoxicity of tumor antigen-specific CD8[+] T cells.<br><br>CONCLUSIONS: The M-CSF/IL-34/CSF-1R pathway seems strongly implicated in MPM and could constitute a therapeutic target to act on immunosuppression and to support immunotherapeutic strategies.}, }
@article {pmid32571118, year = {2020}, author = {Ierardi, AM and Marsh, GM}, title = {Absence of mesothelioma risk maintained in an expanded international cohort of cosmetic talc miners and millers.}, journal = {Inhalation toxicology}, volume = {32}, number = {6}, pages = {257-264}, doi = {10.1080/08958378.2020.1781304}, pmid = {32571118}, issn = {1091-7691}, mesh = {Cohort Studies ; Cosmetics ; Europe/epidemiology ; Extraction and Processing Industry ; Humans ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Risk Factors ; *Talc ; Vermont/epidemiology ; }, abstract = {Objectives: Based on novel information for the Vermont cosmetic talc miner/miller cohort, including a reported case of mesothelioma, we sought to update our prior pooled statistical power analyses of mesothelioma incidence among European cosmetic talc miners/millers. With the inclusion of the Vermont cohort, we expanded our pooled analysis by 17,170 person-years of observation.Methods: Cosmetic talc miner/miller cohort studies conducted in Italy, Norway, France, Austria, and Vermont were pooled. The expected numbers of mesothelioma cases for each cohort as reported in these studies were used. Our statistical power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities.Results: A total of 130,514 person-years of observation was generated across the five cohorts. One case of mesothelioma was observed (in the Vermont cohort), while approximately 3.34 cases (a mid-value estimate) were expected overall. Thus, we found that the pooled cohorts had 59% and 78% power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. The work history characteristics of the one mesothelioma case, which included mention of prior asbestos exposure on the case's death certificate, do not support a causal link with cosmetic talc exposure.Conclusions: Despite the recent finding of one case of mesothelioma in the Vermont cohort (a case unlikely related to talc exposure), we continue to conclude that the epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that cosmetic talc exposures are associated with an increased risk of pleural mesothelioma.}, }
@article {pmid32560575, year = {2020}, author = {Panou, V and Røe, OD}, title = {Inherited Genetic Mutations and Polymorphisms in Malignant Mesothelioma: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32560575}, issn = {1422-0067}, mesh = {Alleles ; Animals ; DNA Repair ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; Genetic Variation ; *Germ-Line Mutation ; Humans ; Mesothelioma, Malignant/*genetics ; Pedigree ; *Polymorphism, Single Nucleotide ; }, abstract = {Malignant mesothelioma (MM) is mainly caused by air-born asbestos but genetic susceptibility is also suspected to be a risk factor. Recent studies suggest an increasing number of candidate genes that may predispose to MM besides the well-characterized BRCA1-associated protein-1 gene. The aim of this review is to summarize the most important studies on germline mutations for MM. A total of 860 publications were retrieved from Scopus, PubMed and Web of Science, of which 81 met the inclusion criteria and were consider for this review. More than 50% of the genes that are reported to predispose to MM are involved in DNA repair mechanisms, and the majority of them have a role in the homologous recombination pathway. Genetic alterations in tumor suppressor genes involved in chromatin, transcription and hypoxia regulation have also been described. Furthermore, we identified several single nucleotide polymorphisms (SNPs) that may promote MM tumorigenesis as a result of an asbestos-gene interaction, including SNPs in DNA repair, carcinogen detoxification and other genes previously associated with other malignancies. The identification of inherited mutations for MM and an understanding of the underlying pathways may allow early detection and prevention of malignancies in high-risk individuals and pave the way for targeted therapies.}, }
@article {pmid32560553, year = {2020}, author = {Bonafede, M and Granieri, A and Binazzi, A and Mensi, C and Grosso, F and Santoro, G and Franzoi, IG and Marinaccio, A and Guglielmucci, F}, title = {Psychological Distress after a Diagnosis of Malignant Mesothelioma in a Group of Patients and Caregivers at the National Priority Contaminated Site of Casale Monferrato.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {12}, pages = {}, pmid = {32560553}, issn = {1660-4601}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/diagnosis/epidemiology/etiology/psychology ; Carcinogens ; Caregivers/*psychology/statistics &amp; numerical data ; Cross-Sectional Studies ; Depression/epidemiology/etiology/psychology ; Environmental Exposure/statistics &amp; numerical data ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology/*psychology ; Middle Aged ; Occupational Diseases/diagnosis/*epidemiology/etiology/*psychology ; *Psychological Distress ; Registries/statistics &amp; numerical data ; Risk Factors ; Stress Disorders, Post-Traumatic/epidemiology/etiology/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Patients of malignant mesothelioma (MM) and their caregivers face significant physical and psychological challenges. The purpose of the present study is to examine the emotional impact after the diagnosis of MM in a group of patients and familial caregivers in a National Priority Contaminated Site (NPCS).<br><br>METHODS: A sample of 108 patients and 94 caregivers received a sociodemographic/clinical questionnaire, the Beck Depression Inventory II, the Davidson Trauma Scale, the Coping Orientation to the Problems Experienced-New Italian Version, and the Defense style questionnaire. The risk of depressive and post-traumatic stress disorder (PTSD) symptoms in relation to the strategies of coping and defense mechanisms was estimated in patients and caregivers separately by logistic regression models.<br><br>RESULTS: For patients, a high risk of depression was associated with high usage of Defense Style Questionnaire (DSQ) Isolation (OR: 53.33; 95% CI: 3.22-882.30; p = 0.01) and DSQ Somatization (OR: 16.97; 95% CI: 1.04-275.90; p = 0.05). Other significant risks emerged for some coping strategies and some defenses regarding both depression and trauma in patients and caregivers.<br><br>CONCLUSIONS: This research suggests that for both patients and caregivers unconscious adaptive processes have a central role in dealing with overwhelming feelings related to the disease.}, }
@article {pmid32553000, year = {2020}, author = {Musk, AW and de Klerk, N and Reid, A and Hui, J and Franklin, P and Brims, F}, title = {Asbestos-related diseases.}, journal = {The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease}, volume = {24}, number = {6}, pages = {562-567}, doi = {10.5588/ijtld.19.0645}, pmid = {32553000}, issn = {1815-7920}, mesh = {*Asbestos/toxicity ; *Asbestosis/diagnostic imaging/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology/therapy ; Pleura ; }, abstract = {Knowledge of asbestos-related diseases has been accumulating for over one hundred years as the industrial value of asbestos was recognised for the strength of its fibres and their resistance to destruction, resulting in increasing production and use until the multiple health effects have become apparent. Deposition in the lung parenchyma results in an inflammatory/progressively fibrotic response, with impaired gas exchange and reduced lung compliance ('asbestosis'), causing progressive dyspnoea and respiratory failure for which only palliation is indicated, although anti-fibrotic agents used for idiopathic usual interstitial pneumonitis remain to be evaluated. Benign pleural effusion, diffuse pleural fibrosis (occasionally with associated rolled atelectasis) and pleural plaques are the non-malignant pleural diseases that result from fibres reaching the pleura. But the main issues that led to the ban on asbestos in industry are those of malignancy: lung cancer, malignant mesothelioma (MM) of the pleura and MM of the peritoneum. Bronchogenic carcinoma risk from asbestos exposure is dose-dependent and multiplies the risk attributable to tobacco smoking. The principles of treatment are as for all cases of lung cancer. Low-dose computed tomography screening of exposed people can detect early-stage, non-small cell cancers, with improved survival. The amphibole varieties of asbestos are much more potent causes of MM than chrysotile, and the risk increases exponentially for 40-50 years following first exposure. As MM is non-resectable and poorly responsive to chemotherapy and radiotherapy, curative treatment is not possible and screening not justified.}, }
@article {pmid32549902, year = {2020}, author = {Frank, AL}, title = {Global use of asbestos - legitimate and illegitimate issues.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {15}, number = {}, pages = {16}, pmid = {32549902}, issn = {1745-6673}, abstract = {BACKGROUND: Exposure to asbestos causes non-malignant and malignant diseases including asbestosis, lung cancer, and mesothelioma. The modern history of such diseases goes back more than a century.<br><br>MAIN TEXT: While much is known about the ability of asbestos to cause disease, the carcinogenic mechanism is not yet understood. Continuing legitimate scientific questions include such issues as potential differential toxicity and carcinogenicity of different fiber types. Illegitimate issues include the supposed "safe" use of asbestos, and the chrysotile hypothesis.<br><br>CONCLUSION: Asbestos disease issues are highly politicized and vested economic interests perpetuate false issues regarding the hazards of asbestos.}, }
@article {pmid32549782, year = {2020}, author = {Franko, A and Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V}, title = {NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases.}, journal = {Journal of medical biochemistry}, volume = {39}, number = {1}, pages = {91-99}, pmid = {32549782}, issn = {1452-8258}, abstract = {BACKGROUND: This study aimed to investigate the association between NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms and the risk of developing pleural plaques, asbestosis, and malignant mesothelioma (MM), and to study the influence of the interactions between polymorphisms and asbestos exposure on the risk of developing these diseases.<br><br>METHODS: The case-control study included 416 subjects with pleural plaques, 160 patients with asbestosis, 154 subjects with MM and 149 subjects with no asbestos disease. The NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms were determined using real-time PCR-based methods. In the statistical analysis, standard descriptive statistics was followed by univariate and multivariate logistic regression modelling.<br><br>RESULTS: Asbestos exposure (medium and high vs low) was associated with the risk for each studied asbestos-related disease. An increased risk of pleural plaques was found for CARD8 rs2043211 at + TT genotypes (OR = 1.48, 95% CI 1.01-2.16, p = 0.042). When the analysis was performed for MM patients as cases, and pleural plaques patients as controls, a decreased MM risk was observed for carriers of CARD8 rs2043211 TT genotype (OR = 0.52, 95% CI 0.27-1.00, p = 0.049). The interactions between NLRP3 rs35829419 and CARD8 rs2043211 genotypes did not influence the risk of any asbestos-related disease. However, when testing interactions with asbestos exposure, a decreased risk of asbestosis was found for NLRP3 CA+AA genotypes (OR = 0.09, 95% CI 0.01-0.60, p = 0.014).<br><br>CONCLUSIONS: The results of our study suggest that NLRP3 and CARD8 polymorphisms could affect the risk of asbestos-related diseases.}, }
@article {pmid32535843, year = {2020}, author = {Shibata, R and Ozaki, T and Tada, K and Aoyama, T and Watanabe, M and Himuro, N and Takahashi, K and Ito, K and Yasuno, T and Miyake, K and Masutani, K and Uesugi, N and Nabeshima, K and Nakashima, H}, title = {Secondary renal amyloidosis associated with asbestos-related pleuropulmonary diseases.}, journal = {CEN case reports}, volume = {9}, number = {4}, pages = {385-391}, pmid = {32535843}, issn = {2192-4449}, mesh = {Adult ; Aged ; Amyloidosis/*complications/pathology ; Angiotensin Receptor Antagonists/therapeutic use ; Asbestos/*adverse effects ; Asian People/ethnology ; Biopsy ; Female ; Humans ; Kidney/diagnostic imaging/pathology ; Male ; Middle Aged ; Nephrotic Syndrome/*diagnosis/drug therapy/etiology ; Occupational Exposure ; Pleura/pathology ; Pleural Diseases/complications/pathology ; Pleural Effusion/diagnosis/etiology ; Tomography, X-Ray Computed/methods ; }, abstract = {Here, we present a 67-year-old Japanese man who developed insidious-onset nephrotic syndrome. He had a history of occupational asbestos exposure for about 8 years during his 30s, and was found to have pleural effusion 3 years before his present illness. At that time, repeated cytology testing of his pleural effusion found no malignant cells, and pleural biopsy found fibrous pleuritis without evidence of malignant mesothelioma. Percutaneous kidney biopsy found massive deposits of AA-type amyloid in the glomeruli, small arteries, and medulla. Computed tomography showed a calcified mass in the right lower lung that was positive for [67]Ga uptake, but transbronchial lung biopsy and bronchoalveolar lavage found no evidence of malignancy. He was diagnosed with rounded atelectasis and diffuse pleural thickening. As these benign asbestos-related diseases have no standard treatment, we administered low-dose angiotensin II receptor blocker to preserve kidney function. Unfortunately, his nephrotic syndrome persists, with progressive chronic kidney failure. Kidney involvement in patients with asbestos-related disease is rare. To our knowledge, this is the first case to present with secondary amyloidosis. Kidney biopsy should be considered for patients with existing asbestos-related pleuropulmonary diseases who have urinary abnormalities or renal dysfunction, to clarify the incidence and pathophysiology of renal manifestations.}, }
@article {pmid32530527, year = {2020}, author = {Horio, D and Minami, T and Kitai, H and Ishigaki, H and Higashiguchi, Y and Kondo, N and Hirota, S and Kitajima, K and Nakajima, Y and Koda, Y and Fujimoto, E and Negi, Y and Niki, M and Kanemura, S and Shibata, E and Mikami, K and Takahashi, R and Yokoi, T and Kuribayashi, K and Kijima, T}, title = {Tumor-associated macrophage-derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma.}, journal = {Cancer science}, volume = {111}, number = {8}, pages = {2895-2906}, pmid = {32530527}, issn = {1349-7006}, support = {18K08161//Japan Society for the Promotion of Science/ ; 18K15962//Japan Society for the Promotion of Science/ ; 18K15963//Japan Society for the Promotion of Science/ ; 20K08555//Japan Society for the Promotion of Science/ ; }, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Asbestos/toxicity ; Biopsy ; Cell Line, Tumor ; Cisplatin/pharmacology/therapeutic use ; Female ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/*metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mesothelioma, Malignant/chemically induced/drug therapy/mortality/*pathology ; Middle Aged ; Pemetrexed/pharmacology/therapeutic use ; Pleura/*pathology ; Receptors, Interleukin-1 Type I/*metabolism ; Spheroids, Cellular ; Tumor Microenvironment/drug effects ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive malignant neoplasm. Due to the difficulty of achieving curative surgical resection in most patients with MPM, a combination chemotherapy of cisplatin and pemetrexed has been the only approved regimen proven to improve the prognosis of MPM. However, the median overall survival time is at most 12 mo even with this regimen. There has been therefore a pressing need to develop a novel chemotherapeutic strategy to bring about a better outcome for MPM. We found that expression of interleukin-1 receptor (IL-1R) was upregulated in MPM cells compared with normal mesothelial cells. We also investigated the biological significance of the interaction between pro-inflammatory cytokine IL-1β and the IL-1R in MPM cells. Stimulation by IL-1β promoted MPM cells to form spheroids along with upregulating a cancer stem cell marker CD26. We also identified tumor-associated macrophages (TAMs) as the major source of IL-1β in the MPM microenvironment. Both high mobility group box 1 derived from MPM cells and the asbestos-activated inflammasome in TAMs induced the production of IL-1β, which resulted in enhancement of the malignant potential of MPM. We further performed immunohistochemical analysis using clinical MPM samples obtained from patients who were treated with the combination of platinum plus pemetrexed, and found that the overexpression of IL-1R tended to correlate with poor overall survival. In conclusion, the interaction between MPM cells and TAMs through a IL-1β/IL-1R signal could be a promising candidate as the target for novel treatment of MPM (Hyogo College of Medicine clinical trial registration number: 2973).}, }
@article {pmid32528683, year = {2020}, author = {Amore, D and Massa, S and Caterino, U and Casazza, D and Palma, A and Curcio, C}, title = {Mediastinal malignant mesothelioma discovered in a patient with dysphagia.}, journal = {Respirology case reports}, volume = {8}, number = {6}, pages = {e00592}, pmid = {32528683}, issn = {2051-3380}, abstract = {A mediastinal mass in patients with a history of asbestos exposure should raise the suspicion of malignant mesothelioma.}, }
@article {pmid32526494, year = {2020}, author = {Catelan, D and Consonni, D and Biggeri, A and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Estimate of environmental and occupational components in the spatial distribution of malignant mesothelioma incidence in Lombardy (Italy).}, journal = {Environmental research}, volume = {188}, number = {}, pages = {109691}, doi = {10.1016/j.envres.2020.109691}, pmid = {32526494}, issn = {1096-0953}, mesh = {*Asbestos/toxicity ; Bayes Theorem ; Environmental Exposure ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure ; Registries ; }, abstract = {INTRODUCTION: Measuring and mapping the occurrence of malignant mesothelioma (MM) is a useful means to monitor the impact of past asbestos exposure and possibly identify previously unknown sources of asbestos exposure.<br><br>OBJECTIVE: Our goal is to decompose the observed spatial pattern of incidence of MM in the Lombardy region (Italy) in gender-specific components linked to occupational exposure and a shared component linked to environmental exposure.<br><br>MATERIALS AND METHODS: We selected from the Lombardy Region Mesothelioma Registry (RML) all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in the period 2000-2016. We mapped at municipality level crude incidence rates and smoothed rates using the Besag York and Molli&#xe9; model separately for men and women. We then decomposed the spatial pattern of MM in gender-specific occupational components and a shared environmental component using a multivariate hierarchical Bayesian model.<br><br>RESULTS: We globally analyzed 6226&#xa0;MM cases, 4048 (2897 classified as occupational asbestos exposure at interview) in men and 2178 (780 classified as occupational asbestos exposure at interview) in women. The geographical analysis showed a strong spatial pattern in the distribution of incidence rates in both genders. The multivariate hierarchical Bayesian model decomposed the spatial pattern in occupational and environmental components and consistently identified some known occupational and environmental hot spots. Other areas at high risk for MM occurrence were highlighted, contributing to better characterize environmental exposures from industrial sources and suggesting a role of natural sources in the Alpine region.<br><br>CONCLUSION: The spatial pattern highlights areas at higher risk which are characterized by the presence of industrial sources - asbestos-cement, metallurgic, engineering, textile industries - and of natural sources in the Alpine region. The multivariate hierarchical Bayesian model was able to disentangle the geographical distribution of MM cases in two components interpreted as occupational and environmental.}, }
@article {pmid32520630, year = {2020}, author = {Tran, T and Egilman, D and Rigler, M}, title = {Response to Roggli et al. (2020) "Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation".}, journal = {Ultrastructural pathology}, volume = {44}, number = {3}, pages = {314-315}, doi = {10.1080/01913123.2020.1778148}, pmid = {32520630}, issn = {1521-0758}, mesh = {Asbestos, Amphibole ; Humans ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; Mineral Fibers ; Talc ; }, }
@article {pmid32517259, year = {2020}, author = {Staumont, B and Jamakhani, M and Costa, C and Vandermeers, F and Sriramareddy, SN and Redouté, G and Mascaux, C and Delvenne, P and Hubert, P and Safari, R and Willems, L}, title = {TGFα Promotes Chemoresistance of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {12}, number = {6}, pages = {}, pmid = {32517259}, issn = {2072-6694}, support = {CDR//Fonds De La Recherche Scientifique - FNRS/ ; T&#xe9;l&#xe9;vie//Fonds De La Recherche Scientifique - FNRS/ ; Asbestos grants//Belgian Foundation against Cancer/ ; }, abstract = {Background: There is no standard chemotherapy for refractory or relapsing malignant pleural mesothelioma (MPM). Our previous reports nevertheless indicated that a combination of an anthracycline (doxorubicin) and a lysine deacetylase inhibitor (valproic acid, VPA) synergize to induce the apoptosis of MPM cells and reduce tumor growth in mouse models. A Phase I/II clinical trial indicated that this regimen is a promising therapeutic option for a proportion of MPM patients. Methods: The transcriptomes of mesothelioma cells were compared after Illumina HiSeq 4000 sequencing. The expression of differentially expressed genes was inhibited by RNA interference. Apoptosis was determined by cell cycle analysis and Annexin V/7-AAD labeling. Protein expression was assessed by immunoblotting. Preclinical efficacy was evaluated in BALB/c and NOD-SCID mice. Results: To understand the mechanisms involved in chemoresistance, the transcriptomes of two MPM cell lines displaying different responses to VPA-doxorubicin were compared. Among the differentially expressed genes, transforming growth factor alpha (TGFα) was associated with resistance to this regimen. The silencing of TGFα by RNA interference correlated with a significant increase in apoptosis, whereas the overexpression of TGFα desensitized MPM cells to the apoptosis induced by VPA and doxorubicin. The multi-targeted inhibition of histone deacetylase (HDAC), HER2 and TGFα receptor (epidermal growth factor receptor/EGFR) improved treatment efficacy in vitro and reduced tumor growth in two MPM mouse models. Finally, TGFα expression but not EGFR correlated with patient survival. Conclusions: Our data show that TGFα but not its receptor EGFR is a key factor in resistance to MPM chemotherapy. This observation may contribute to casting light on the promising but still controversial role of EGFR signaling in MPM therapy.}, }
@article {pmid32515059, year = {2020}, author = {Orriols, R and Tarrés, J and Albertí-Casas, C and Rosell-Murphy, M and Abós-Herràndiz, R and Canela-Soler, J}, title = {Malignant asbestos-related disease in a population exposed to asbestos.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {796-802}, doi = {10.1002/ajim.23141}, pmid = {32515059}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*toxicity ; Cities/epidemiology ; Construction Materials/*toxicity ; Environmental Exposure/*adverse effects/analysis ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects/analysis ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Sex Distribution ; Spain/epidemiology ; }, abstract = {OBJECTIVES: The first asbestos fiber cement plant in Spain operated in Cerdanyola, in the Barcelona metropolitan area, between 1907 and 1997. We describe clinical and epidemiological characteristics of patients diagnosed with the malignant asbestos-related disease (ARD) in the area of the plant between 2007 and 2016.<br><br>METHODS: A prospective, descriptive study was undertaken in the 12 municipalities of the county of Barcelona most proximate to the plant. We describe malignant ARD cases by time of diagnosis, source of exposure, periods of exposure and latency, and distribution by sex. Cumulative incidence and age-standardized incidence rates (ASIR) are calculated.<br><br>RESULTS: Of 477 patients diagnosed with ARD between 2007 and 2016, 128 (26%) presented with asbestos-associated malignancy. Pleural mesothelioma was noted in 105 patients (82.0%) with a linear trend Z-score of -0.2 (NS) in men and 2.7 (P&#x2009;<&#x2009;.01) in women. The highest ASIRs for malignant ARD (6.1/100&#x2009;000 residents/year; 95% confidence interval [CI], 2.2-13.3) and pleural mesothelioma&#xa0;(4.8/100&#x2009;000 residents/year; 95% CI, 1.5-11.6) occurred in municipalities closest to the focal point of contamination. The origin of malignant ARD was nonoccupational in 32.2% of men and 81.6% of women (P&#x2009;<&#x2009;.001).<br><br>CONCLUSIONS: More than 20 years after the closure of the fiber cement plant, the grave consequences of exposure to asbestos remain. The detection of cases of pleural mesothelioma in men seems to have plateaued whereas in women an ascending trend continues, which principally has its origin in nonoccupational exposures.}, }
@article {pmid32509926, year = {2020}, author = {Marques de Sousa, S and Pereira, F and Duarte, M and Marques, M and Vázquez, D and Marques, C}, title = {Malignant Peritoneal Mesothelioma as a Rare Cause of Dyspeptic Complaints and Ascites: A Diagnostic Challenge.}, journal = {GE Portuguese journal of gastroenterology}, volume = {27}, number = {3}, pages = {197-202}, pmid = {32509926}, issn = {2341-4545}, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is a rare malignancy of the mesothelial cells in the peritoneum. The best-defined risk factor is asbestos exposure, but germline mutations in BAP1 also increase susceptibility to this tumor. The diagnosis of MPM is challenging since clinical manifestations are often nonspecific.<br><br>CASE PRESENTATION: We describe a case of MPM in a 53-year-old former construction worker with prior asbestos exposure. The clinical presentation was a 3-month history of dyspeptic complaints. As initial workup, abdominal ultrasound and upper gastrointestinal endoscopy were performed. Chronic gastritis due to Helicobacter pylori was detected, which was promptly treated but without symptom relief. Abdominal ultrasound showed small volume ascites with hyperechogenic foci, which was later confirmed on computed tomography scan showing the presence of peritoneal nodules in the greater omentum and mesentery. A thorough investigation was conducted based on the suspicion of peritoneal carcinomatosis. A non-peritoneal primary tumor was not found. Ascitic cytology and immunocytochemical studies were suggestive of mesothelioma. He underwent exploratory laparotomy and inoperable peritoneal disease was observed. Peritoneal biopsy confirmed epithelioid-type MPM. Systemic therapy was initiated with platinum plus pemetrexed with good response. The last follow-up was 38 months after the diagnosis.<br><br>DISCUSSION/CONCLUSION: The diagnosis of MPM is challenging since it requires a high degree of suspicion. MPM has a poor prognosis. The standard of treatment recommended is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. For those who are inoperable, systemic therapy with pemetrexed-cisplatin combination is the alternative. Given the infrequency of disease, it is imperative to ensure patient participation in clinical trials with the purpose of treatment standardization.}, }
@article {pmid32492522, year = {2020}, author = {Marsh, GM and Ierardi, AM}, title = {Confidence interval function analysis to evaluate the risk of mesothelioma among an expanded international cohort of cosmetic talc miners and millers.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {115}, number = {}, pages = {104696}, doi = {10.1016/j.yrtph.2020.104696}, pmid = {32492522}, issn = {1096-0295}, mesh = {Confidence Intervals ; Cosmetics ; Data Interpretation, Statistical ; Humans ; Mesothelioma/*epidemiology ; Mining ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; Risk ; Talc/*adverse effects ; }, abstract = {We used pooled data from international cosmetic talc miner/miller cohorts to determine whether hypothesized increased mesothelioma risks are consistent with the observed data. We evaluated the confidence interval function for the observed pooled mesothelioma SMRs (observed = 1; expected = 3.17, 3.34, or 3.60), and calculated the value of α for the upper 100(1 - 2α)% confidence limit that equals various SMRs of interest (1.5, 2.0, 2.5, 3.0). Using the mid-value estimate of expected number of cases (3.34), the probability (α) that the true mesothelioma SMR is at or above 2.0, or at or above 3.0 is 0.0096 and 0.0005, respectively. Thus, a mesothelioma SMR ≥2.0 is not compatible with the observed pooled data, providing further support for our conclusion that cosmetic talc exposure is not associated with an elevated risk of mesothelioma.}, }
@article {pmid32489446, year = {2020}, author = {Alghamdi, ZM and Othman, SA and Al-Yousef, MJ and AlFadel, BZ}, title = {Intrapulmonary location of benign solitary fibrous tumor.}, journal = {Annals of thoracic medicine}, volume = {15}, number = {2}, pages = {98-101}, pmid = {32489446}, issn = {1817-1737}, abstract = {Intrapulmonary solitary fibrous tumors (SFTs) are sporadic mesenchymal neoplasms that typically arise from visceral or parietal pleura. While accounting for <5% of all pleural tumors, SFTs are known to occur in nearly all bodily organs, including nasopharynx, bladder, prostate, soft tissue of neck, buttocks, extremities, and abdominal wall. Such tumors have been previously designated localized fibrous mesothelioma or pleural fibroma. SFTs have no genetic basis and are unrelated to environmental factors such as tobacco smoking or asbestos exposure. Herein, we describe a 24-year-old woman whose clinical presentation mimicked atypical carcinoid tumor. A diagnosis of intrapulmonary SFT was achieved by surgical resection.}, }
@article {pmid32475501, year = {2020}, author = {Severson, DT and De Rienzo, A and Bueno, R}, title = {Mesothelioma in the age of "Omics": Before and after The Cancer Genome Atlas.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {160}, number = {4}, pages = {1078-1083.e2}, pmid = {32475501}, issn = {1097-685X}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly fatal cancer of the pleura that has been defeating standard and investigational therapies since its first description. The efficacies of chemotherapy, radiotherapy, and surgical therapy are limited, and we have been writing for decades that improved therapies are needed. MPM is born of inflammation, and approximately 80% of cases are associated with the smoldering tissue inflammatory responses against the carcinogenic fibers of asbestos. Emerging data on the use of programmed cell death protein 1 immune checkpoint inhibitors were initially exciting, but response is less than 20% and these agents are finding their place on the list of approaches with narrow efficacy. Molecular targeted therapies have revolutionized the treatment of other cancers, commonly result in striking antitumor responses, and directly embody precision medicine. For an example, we prescribe drugs for some lung adenocarcinomas that target the secondary mutations that develop as a resistance mechanism to their initial targeted therapy. The discovery of molecular therapeutics for any tumor begins with identification of a target through investigation of the genomic, epigenomic, and transcriptomic drivers of its carcinogenesis. Such an advance could revolutionize the treatment of mesothelioma. A comprehensive dissection of MPM’s molecular structure was recently published by 2 groups, the first from the Brigham and Women’s Hospital and then from The Cancer Genome Atlas. In the Invited Expert Opinion article that follows, a practical account of the molecular underpinnings of MPM is eloquently presented by the Brigham group and will inspire the discovery and translation of novel molecular targets by mesothelioma investigators and practitioners.}, }
@article {pmid32475021, year = {2020}, author = {Korša, L and Lukač, A and Kovačević, L and Bilić, I and Prutki, M and Marušić, Z}, title = {Breast metastasis as the initial presentation of malignant pleural mesothelioma.}, journal = {The breast journal}, volume = {26}, number = {10}, pages = {2063-2064}, doi = {10.1111/tbj.13898}, pmid = {32475021}, issn = {1524-4741}, mesh = {*Breast Neoplasms ; Female ; Humans ; *Lung Neoplasms/diagnostic imaging ; Male ; *Mesothelioma/diagnostic imaging ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/diagnostic imaging ; }, abstract = {Metastatic involvement of the breast is far less common than primary breast carcinoma, comprising 0.5%-6.6% of all breast malignancies. Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with higher incidence among men, particularly smokers, strongly associated with asbestos exposure. The epithelioid type of MPM can represent a diagnostic pitfall in this setting, as it shows similar histologic features to primary breast carcinoma as well as other metastatic epithelioid malignancies. We report a rare case of breast metastasis of malignant pleural mesothelioma in a 61-year-old female.}, }
@article {pmid32472158, year = {2020}, author = {Greimelmaier, K and Wohlschläger, J and Probst, A and Hager, T and Wardelmann, E and Werlein, C and Jonigk, D and Müller, KM}, title = {[Mesothelial proliferation of the tunica vaginalis testis].}, journal = {Der Pathologe}, volume = {41}, number = {4}, pages = {406-410}, doi = {10.1007/s00292-020-00797-6}, pmid = {32472158}, issn = {1432-1963}, mesh = {Cell Proliferation ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; *Lung Neoplasms/diagnosis ; Male ; *Mesothelioma/diagnosis ; *Testicular Neoplasms/pathology ; Testis ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {Proliferative changes seen in reactive mesothelial hyperplasia of a hydrocele sac may mimic malignant mesothelioma. There is no immunohistochemical staining that reliably separates benign from malignant mesothelial proliferations. However, the combined analysis of BAP1 by immunohistochemistry and CDKN2A by FISH has been reported to yield both a high specificity and sensitivity in this differential diagnosis. In addition, the evaluation of risk factors such as asbestos exposure or prior traumata may be helpful for the correct diagnosis. Exclusion of stromal invasion, which is diagnostic for malign mesothelioma, is of utmost importance. Therefore, extended histological workup is essential.}, }
@article {pmid32435497, year = {2020}, author = {Weber, DG and Casjens, S and Brik, A and Raiko, I and Lehnert, M and Taeger, D and Gleichenhagen, J and Kollmeier, J and Bauer, TT and Brüning, T and Johnen, G and , }, title = {Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies.}, journal = {Biomarker research}, volume = {8}, number = {}, pages = {15}, pmid = {32435497}, issn = {2050-7771}, abstract = {BACKGROUND: For the detection of malignant mesothelioma additional markers are needed besides the established panel consisting of calretinin and mesothelin. The aim of this study was the identification and verification of long non-coding RNAs (lncRNAs) as complementing circulating markers.<br><br>METHODS: Candidate lncRNAs were identified in silico using previously published RNA expression profiles and verified using quantitative PCR (qPCR) in mesothelioma cell lines as well as human plasma samples from mesothelioma patients and asbestos-exposed controls.<br><br>RESULTS: GAS5 (growth arrest-specific transcript&#xa0;5) as a single marker is marked by a low sensitivity of 14%, but the combination of GAS5 with calretinin and mesothelin increased the panel's sensitivity from 64 to 73% at a predefined specificity of 97%. Circulating GAS5 is not affected by pleurectomy before blood collection, age, or smoking status.<br><br>CONCLUSIONS: GAS5 is verified as an appropriate circulating marker for the supplement of calretinin and mesothelin to detect malignant mesothelioma. Although the sensitivity of GAS5 is too low for the use as a single marker, the addition of GAS5 as a third marker improves the performance of the established marker panel. The benefit of GAS5 for the detection of malignant mesothelioma at early stages needs to be validated in a prospective study.}, }
@article {pmid32429446, year = {2020}, author = {Di Gilio, A and Catino, A and Lombardi, A and Palmisani, J and Facchini, L and Mongelli, T and Varesano, N and Bellotti, R and Galetta, D and de Gennaro, G and Tangaro, S}, title = {Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32429446}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanced stage of the disease. Breath analysis, aimed at the identification of diagnostic Volatile Organic Compounds (VOCs) pattern in exhaled breath, is believed to improve early detection of MPM. Therefore, in this study, breath samples from 14 MPM patients and 20 healthy controls (HC) were collected and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC/MS). Nonparametric test allowed to identify the most weighting variables to discriminate between MPM and HC breath samples and multivariate statistics were applied. Considering that MPM is an aggressive neoplasm leading to a late diagnosis and thus the recruitment of patients is very difficult, a promising data mining approach was developed and validated in order to discriminate between MPM patients and healthy controls, even if no large population data are available. Three different machine learning algorithms were applied to perform the classification task with a leave-one-out cross-validation approach, leading to remarkable results (Area Under Curve AUC = 93%). Ten VOCs, such as ketones, alkanes and methylate derivates, as well as hydrocarbons, were able to discriminate between MPM patients and healthy controls and for each compound which resulted diagnostic for MPM, the metabolic pathway was studied in order to identify the link between VOC and the neoplasm. Moreover, five breath samples from asymptomatic asbestos-exposed persons (AEx) were exploratively analyzed, processed and tested by the validated statistical method as blinded samples in order to evaluate the performance for the early recognition of patients affected by MPM among asbestos-exposed persons. Good agreement was found between the information obtained by gold-standard diagnostic methods such as computed tomography CT and model output.}, }
@article {pmid32392897, year = {2020}, author = {Abbott, DM and Bortolotto, C and Benvenuti, S and Lancia, A and Filippi, AR and Stella, GM}, title = {Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32392897}, issn = {2072-6694}, abstract = {Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets. Here we recapitulate current knowledge on MPM with focus on the emerging network between genetic asset and inflammatory microenvironment which characterize the disease as amenable target for novel therapeutic approaches.}, }
@article {pmid32383566, year = {2020}, author = {Kilitci, A and Uygun, N and Emir, ML}, title = {Sarcomatoid Type of Paratesticular Malignant Mesothelioma in a Dry-Cleaning Worker Exposed to Asbestos and Diagnostic Value of WT-1.}, journal = {Puerto Rico health sciences journal}, volume = {39}, number = {1}, pages = {39-44}, pmid = {32383566}, issn = {2373-6011}, mesh = {Asbestos/toxicity ; Humans ; Male ; Mesothelioma, Malignant/*diagnosis/pathology ; Middle Aged ; Occupational Exposure/adverse effects ; Sarcoma/*diagnosis/pathology ; Testicular Neoplasms/*diagnosis/pathology ; WT1 Proteins/analysis ; }, abstract = {Of the 3 major histologic types of malignant paratesticular mesothelioma (MPM) (epithelial, sarcomatoid, and biphasic), many cases of epithelial and biphasic mesothelioma have been reported in the literature. Pure sarcomatoid MPM is the least common but the most aggressive of the 3 major histologic types of mesothelioma cells. It is limited to only 2 cases in the literature The sarcomatoid type of MPM can be confused clinically and histologically with true sarcomas because it is rarely seen. We present a case who had been exposed to asbestos for years due to his involvement in the dry-cleaning industry and who was diagnosed with the sarcomatoid type of MPM but had a relatively prolonged survival not usually seen with this tumor. This report also emphasizes the significance of an immunohistochemical examination, focusing especially on the diagnostic role of WT-1.}, }
@article {pmid32382335, year = {2020}, author = {Zhang, G and Yang, DL and Zheng, G and Liang, Y}, title = {Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma.}, journal = {Oncology letters}, volume = {19}, number = {6}, pages = {3871-3880}, pmid = {32382335}, issn = {1792-1074}, abstract = {Malignant peritoneal mesothelioma (MPeM) is an incurable cancer strongly associated with asbestos exposure and characterised by poor prognosis. The aim of the present study was to elucidate the prognostic and predictive value of CD146 and survivin expression in MPeM. Diagnostic biopsies from 60 patients with MPeM were collected and analysed for CD146, survivin and Ki-67 expression using immunohistochemistry. Complete clinical and follow-up information was obtained from patients' records. CD146 was expressed in 31/60 MPeM specimens and survivin in 34/60 specimens, with both expression levels being significantly associated with the Ki-67 labelling index (Ki-67LI). Kaplan-Meier and univariate Cox regression analyses revealed that a lower peritoneal cancer index (PCI), tumour-directed treatment, stage I, lower Ki-67LI and lower CD146 and survivin expression had a statistically positive effect on overall survival (OS). Cox regression analysis revealed that PCI [hazard ratio (HR)=1.99; 95% CI, 1.04-3.83; P=0.038], survivin (HR=1.47; 95% CI, 1.03-2.10; P=0.034) and treatment protocol including intraperitoneal chemotherapy (HR=0.28; 95% CI, 0.14-0.57; P=0.013) and systemic chemotherapy (HR=0.13; 95% CI, 0.04-0.42; P=0.013) retained independent prognostic significance for OS. All of these were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted and observed survival. The C-index of the nomogram for predicting OS was 0.77. A lower PCI, intraperitoneal chemotherapy, systemic chemotherapy and a lower level of survivin were powerful prognostic markers in patients with MPeM. The proposed nomogram provides individual survival prediction for patients with MPeM.}, }
@article {pmid32374117, year = {2020}, author = {Barbieri, PG and Calisti, R and Silvestri, S and Calabresi, C and Consonni, D and Angelini, A and Carnevale, F and Cavariani, F and Sala, O}, title = {[About the asbestos and the Position Paper on asbestos of the Italian Society of Occupational Medicine].}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {1}, pages = {73-83}, doi = {10.19191/EP20.1.P073.019}, pmid = {32374117}, issn = {1120-9763}, mesh = {*Asbestos ; Asbestosis/epidemiology ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; }, abstract = {The SIML Position Paper dedicated to asbestos (PPA) is addressed (mainly) to competent practitioners (CP) for the purposes to provide a guidance about a set of items classified as markedly interesting: the actuality of asbestos exposure and the evaluation of the related risk; the diagnosis of the asbestos related diseases; the shape of the risk functions (namely about mesotheliomas); the causal relationship between exposure and disease; the medical surveillance of the workers currently and previously exposed. The scientific literature doesn't acknowledge the idea that nowadays in Italy the frequency of pleural mesotheliomas deriving from environmental asbestos from outdoor sources exposures is really a relevant item. Inside the SIML PPA the chapter concerning industrial hygiene and environmental monitoring themes shows inaccuracies and deficiencies, so resulting of scarce utility for the CPs that should be called for a more cooperative role in front of the employers. The arguments of the diagnosis of the asbestos related diseases is developed with an undue emphasis upon the differential histological diagnosis of asbestosis and, especially, of pleural mesothelioma: nosographic aspects that hardly are posed to the attention of the CP. A similar emphasis is posed towards the shape of the risk function for pleural mesothelioma, a theme absent from the current practice of the CP such as of other occupational practitioners. In conclusion, next to themes of undoubted interest for the PC, the SIML PPA dwells on the scrutiny of some topics representing critical elements of the current contrast between consultants and valuers in the context of criminal prosecutions: subjects having forensic relevance but far from the "application actuality" for the CP invoked in the PPA. A greater transparency, last but not least, was to have been posed, inside the SIML PPA, in the disclosure of the conflict of interests (COIs) of some Authors, declaring their consultancy in favour of companies.}, }
@article {pmid32374111, year = {2020}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Bonafede, M and Verardo, M and Migliore, E and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Fedeli, U and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Pascucci, C and Madeo, G and Romeo, E and Trafficante, L and Carrozza, F and Angelillo, IF and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and , }, title = {The epidemiological surveillance of malignant mesothelioma in Italy (1993-2015): methods, findings, and research perspectives.}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {1}, pages = {23-30}, doi = {10.19191/EP20.1.P023.014}, pmid = {32374111}, issn = {1120-9763}, mesh = {Adult ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Occupational Diseases/epidemiology ; Occupational Exposure/statistics &amp; numerical data ; Population Surveillance ; Registries ; }, abstract = {BACKGROUND: as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures.<br><br>OBJECTIVES: to describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer.<br><br>DESIGN: analysis of data by malignant mesothelioma incident cases surveillance system.<br><br>SETTING AND PARTICIPANTS: Italy, network of regional surveillance system, all Italian regions.<br><br>MAIN OUTCOME MEASURES: a Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epidemiological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated.<br><br>RESULTS: at December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818).<br><br>CONCLUSIONS: the Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitoring the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.}, }
@article {pmid32369821, year = {2020}, author = {Campanella, NC and Silva, EC and Dix, G and de Lima Vazquez, F and Escremim de Paula, F and Berardinelli, GN and Balancin, M and Chammas, R and Mendoza Lopez, RV and Silveira, HCS and Capelozzi, VL and Reis, RM}, title = {Mutational Profiling of Driver Tumor Suppressor and Oncogenic Genes in Brazilian Malignant Pleural Mesotheliomas.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {87}, number = {3}, pages = {208-216}, doi = {10.1159/000507373}, pmid = {32369821}, issn = {1423-0291}, mesh = {Carcinogenesis ; Cohort Studies ; Female ; *Genes, Tumor Suppressor ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma, Malignant/*genetics ; Middle Aged ; *Mutation ; *Oncogenes ; Paraffin Embedding ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60% of cases) and sarcomatous (∼20%). Its identification depends upon pathological investigation supported by clinical and radiological evidence and more recently ancillary molecular testing. Treatment options are currently limited, with no known targeted therapies available.<br><br>OBJECTIVES: To elucidate the mutation profile of driver tumor suppressor and oncogenic genes in a cohort of Brazilian patients.<br><br>METHODS: We sequenced 16 driver genes in a series of 43 Brazilian malignant mesothelioma (MM) patients from 3 distinct Brazilian centers. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue blocks, and the TERT promoter region was amplified by PCR followed by direct capillary sequencing. The Illumina TruSight Tumor 15 was used to evaluate 250 amplicons from 15 genes associated with solid tumors (AKT1, GNA11, NRAS, BRAF, GNAQ, PDGFRA, EGFR, KIT, PIK3CA, ERBB2, KRAS, RET, FOXL2, MET,and TP53). Library preparation with the TruSight Tumor 15 was performed before sequencing at the MiSeq platform. Data analysis was performed using Sophia DDM software.<br><br>RESULTS: Out of 43 MPM patients, 38 (88.4%) were epithelioid subtype and 5 (11.6%) were sarcomatoid histotype. Asbestos exposure was present in 15 (39.5%) patients with epithelioid MPM and 3 (60%) patients with sarcomatoid MPM. We found a TERT promoter mutation in 11.6% of MM, and the c.-146C>T mutation was the most common event. The next-generation sequencing was successful in 33 cases. A total of 18 samples showed at least 1 pathogenic, with a median of 1.8 variants, ranging from 1 to 6. The most mutated genes were TP53 and ERBB2 with 7 variants each, followed by NRAS BRAF, PI3KCA, EGFR and PDGFRA with 2 variants each. KIT, AKT1, and FOXL2 genes exhibited 1 variant each. Interestingly, 2 variants observed in the PDGFRA gene are classic imatinib-sensitive therapy.<br><br>CONCLUSIONS: We concluded that Brazilian MPM harbor mutation in classic tumor suppressor and oncogenic genes, which might help in the guidance of personalized treatment of MPM.}, }
@article {pmid32367143, year = {2020}, author = {Fadel, M and Evanoff, BA and Andersen, JH and d'Errico, A and Dale, AM and Leclerc, A and Descatha, A}, title = {Not just a research method: If used with caution, can job-exposure matrices be a useful tool in the practice of occupational medicine and public health?.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {46}, number = {5}, pages = {552-553}, pmid = {32367143}, issn = {1795-990X}, mesh = {*Asbestos ; France ; Humans ; Occupational Exposure/*analysis ; *Occupational Medicine ; Occupations ; Public Health ; }, abstract = {The recent editorial by Dr Susan Peters "Although a valuable method in occupational epidemiology, job-exposure matrices are no magic fix" ably describes the strengths and limitations of job-exposure matrix (JEM) approaches in occupational epidemiology research (1). In addition to their use in research, we would like to add that JEM may also be of use in compensation and surveillance efforts in occupational health. JEM could assist the compensation process by supporting the assessment of relevant exposures related to specific health conditions (2). The potential usefulness of a JEM as a decision tool for compensation of work-related musculoskeletal disorders has been examined (3). Because occupational diseases are often under-recognized, another practical application is using a JEM to screen for occupational exposures as part of health surveillance. Use of JEM to screen for asbestos and wood dust exposure in the clinical setting has shown promising results (4-6). By summarizing multiple exposures at a job level (7), JEM may also assist policy-makers in setting priorities for hazards and controls at work, as well as occupational practitioners to target prevention efforts and direct the conduct of more precise exposure measures to particular jobs. Sharing JEM across different countries may be useful in providing estimates of exposures across larger populations to calculate global burden of disease related to occupational exposure. The JEMINI (JEM InterNatIonal) initiative was launched to explore the possibility of developing international JEM that could be used across countries (8). Beginning with physical (biomechanical) exposures, this open group has started homogenizing job coding systems and comparing some available JEM. Estimating differences in the level of exposure between countries will require much more work, without guaranteed success. As Peters mentioned, many limitations exist in the use of JEM. Users of JEM must consider the source of exposure data - expert assessments, data collected from individual workers, or environmental sampling. The coding of occupations is time consuming and can introduce error (9), and more testing of and comparison with automated job coding systems is needed (10). JEM reflect an "average" level of exposure within a job at the expense of individual variation. At population level, JEM can offer a useful estimate of exposures. If used at an individual level in a clinical or compensation setting, JEM cannot replace the professionals involved in exposure assessment but may help them focus their action more effectively on complex situations that require their expertise. In conclusion, these JEM developed for research might also be used as a public health tool, provided that their limitations are properly taken into account. References 1. Peters S. Although a valuable method in occupational epidemiology, job-exposure matrices are no magic fix. Scand J Work Environ Health 2020;46:2314. https://doi.org/10.5271/sjweh.3894 2. Kerbrat J, Descatha A. (The recognition of health consequences of difficult working conditions in France and its evaluation with the use of a job-exposure matrix). Arch Mal Prof Environ. 2018;79:493500. https://doi.org/10.1016/j.admp.2017.12.001 3. Fadel M, Valter R, Quignette A, Descatha A. Usefulness of a job-exposure matrix « MADE » as a decision tool for compensation of work-related musculoskeletal disorders. Eur J Public Health 2019;29:86870. https://doi.org/10.1093/eurpub/cky274 4. Lorentz E, Despreaux T, Quignette A, Chinet T, Descatha A. (Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma). Rev Mal Respir. 2019;36:108895. https://doi.org/10.1016/j.rmr.2019.08.006 5. Imbernon E, Goldberg M, Spyckerell Y, Steinmetz J, Bonenfant S, Fournier B. (Use of a job-exposure matrix for the screening of occupational exposure to asbestos). Rev Epidemiol Sante Publique 2004;52:717. https://doi.org/10.1016/S0398-7620(04)99018-9 6. Carton M, Bonnaud S, Nachtigal M, Serrano A, Carole C, Bonenfant S, et al. Post-retirement surveillance of workers exposed to asbestos or wood dust: first results of the French national SPIRALE Program. Epidemiol Prev. 2011;35:31523. 7. Guéguen A, Goldberg M, Bonenfant S, Martin JC. Using a representative sample of workers for constructing the SUMEX French general population based job-exposure matrix. Occup Environ Med. 2004;61:58693. https://doi.org/10.1136/oem.2003.010660 8. Descatha A, Evanoff BA, Andersen JH, Fadel M, Ngabirano L, Leclerc A, et al. JEMINI (Job Exposure Matrix InterNatIonal) Initiative: a Utopian Possibility for Helping Occupational Exposure Assessment All Around the World? J Occup Environ Med. 2019;61:e3201. https://doi.org/10.1097/JOM.0000000000001631 9. Petersen SB, Flachs EM, Svendsen SW, Marott JL, Budtz-Jørgensen E, Hansen J, et al. Influence of errors in job codes on job exposure matrix-based exposure assessment in the register-based occupational cohort DOC*X. Scand J Work Environ Health 2020;46:25967. https://doi.org/10.5271/sjweh.3857 10. Buckner-Petty S, Dale AM, Evanoff BA. Efficiency of autocoding programs for converting job descriptors into standard occupational classification (SOC) codes. Am J Ind Med. 2019;62:5968. https://doi.org/10.1002/ajim.22928.}, }
@article {pmid32364316, year = {2020}, author = {Trama, A and Proto, C and Signorelli, D and Garassino, MC and Lo Russo, G and Ganzinelli, M and Prelaj, A and Mensi, C and Gangemi, M and Gennaro, V and Chellini, E and Caldarella, A and Angelillo, IF and Ascoli, V and Pascucci, C and Tagliabue, G and Cusimano, R and Bella, F and Falcini, F and Merler, E and Masanotti, G and Ziino, A and Michiara, M and Gola, G and Storchi, C and Mangone, L and Vitale, MF and Cirilli, C and Tumino, R and Scuderi, T and Fanetti, AC and Piffer, S and Tiseo, M and Gatta, G and Botta, L and , }, title = {Treatment patterns among patients with malignant pleural mesothelioma: An Italian, population-based nationwide study.}, journal = {Thoracic cancer}, volume = {11}, number = {6}, pages = {1661-1669}, pmid = {32364316}, issn = {1759-7714}, support = {NA//Associazione Italiana Esposti Amianto (Italian Association of Asbestos Expositions AIEA)/International ; Investigator Grant - IG 2012 number 13534, year 20//Associazione Italiana per la Ricerca sul Cancro (Italian Association for cancer research-AIRC)/International ; RF-INT- 201241451, year 2008//Italian Ministry of Health/International ; }, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/epidemiology/pathology/*therapy ; Middle Aged ; Pleural Neoplasms/epidemiology/pathology/*therapy ; Pneumonectomy/*mortality ; Prognosis ; Radiotherapy/*mortality ; Registries/*statistics &amp; numerical data ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions.<br><br>METHODS: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department.<br><br>RESULTS: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department.<br><br>CONCLUSIONS: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services.<br><br>KEY POINTS: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions.<br><br>WHAT THIS STUDY ADDS: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.}, }
@article {pmid32354783, year = {2020}, author = {Dyer, C}, title = {Doctor with mesothelioma wins settlement for asbestos exposure in late 1990s.}, journal = {BMJ (Clinical research ed.)}, volume = {369}, number = {}, pages = {m1783}, doi = {10.1136/bmj.m1783}, pmid = {32354783}, issn = {1756-1833}, }
@article {pmid34594644, year = {2020}, author = {Chen, M and Wang, H and Zhang, J and Yu, C and Liu, W and Xu, Y}, title = {Distribution of Asbestos Enterprises and Asbestosis Cases - China, 1997-2019.}, journal = {China CDC weekly}, volume = {2}, number = {18}, pages = {305-309}, pmid = {34594644}, issn = {2096-7071}, abstract = {Asbestos is classified as a Class I Carcinogen by the International Agency for Research on Cancer (IARC) because exposure causes mesothelioma and lung cancer in addition to asbestosis and plaques. So far, asbestos has been banned in 67 countries, but chrysotile, a commonly encountered form of asbestos, is still widely used in China and most developing countries. Most asbestos-caused cancers are not reported, recorded, and compensated in many countries.<br><br>WHAT IS ADDED BY THIS REPORT?: Enterprises manufacturing asbestos products have been migrating from economically developed Eastern China to relatively underdeveloped central and western regions between 2010 and 2019. Asbestosis cases reported in Tianjin, Beijing, Shandong, Xinjiang, Gansu, Qinghai, and Sichuan accounted for a large proportion of the total cases in China, which was inconsistent with the distribution of asbestos-related enterprises (AREs). The reported asbestosis cases versus total pneumoconiosis cases declined from 2.81% to 0.39% from 2006-2017, and this proportion reached 0.69% in 2018.<br><br>Robust occupational and environmental health assessments and reporting are needed to define the epidemiology of asbestos-related lung diseases, and management of using asbestos and existing products containing asbestos need strengthening and follow-up. Enterprises should be encouraged to use safer substitutes and gradually ban asbestos materials in China.}, }
@article {pmid32352426, year = {2020}, author = {Angelini, A and Chellini, E and Parducci, D and Puccetti, M and Mauro, L}, title = {[Not Available].}, journal = {La Medicina del lavoro}, volume = {111}, number = {2}, pages = {126-132}, pmid = {32352426}, issn = {0025-7818}, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mesothelioma/epidemiology ; Occupational Diseases ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology ; }, abstract = {UNLABELLED: «Reconstruction of the asbestos exposure in a textile company producing sewing threads through the use of an unusual information source».<br><br>BACKGROUND:: The Tuscan Regional Operating Center (ROC) of Malignant Mesotheliomas has identified a cluster of 11 cases of malignant mesothelioma occurred in a textile plant manufacturing sewing thread. Using the common research method, the ROC had not previously been able to identify the specific sources of asbestos exposure causing such a large cluster.<br><br>OBJECTIVES:: The ROC&#x2019;s objective was to review all cases of the cluster and to better identify their occupational asbestos exposures.<br><br>METHODS:: The cases&#x2019; occupational histories of asbestos exposure have been reviewed, using information deriving from the annual reports sent to the Tuscany Region since 1988 by all the asbestos removal companies according to the Law no. 257/1992, article 9, and from interviews to former employees of the plant.<br><br>RESULTS:: The work cycle has been reconstructed and enriched with the new information about the asbestos presence and its uses in the plant. The eleven cases were all reclassified as &#x201c;certainly occupational exposed&#x201d; given that the new collected information depicted a widespread asbestos pollution of the workplace during the period of employment of all cases.<br><br>CONCLUSIONS:: Using different sources of information, in addition to those traditionally collected through questionnaires, to reconstruct past asbestos exposuresallowed us to clarify the existence of the cluster of mesothelioma cases and the highest level of occupational asbestos exposure was attributed to all cases with consequent activation of the medico-legal procedure.}, }
@article {pmid32345664, year = {2020}, author = {Lacerenza, S and Ciregia, F and Giusti, L and Bonotti, A and Greco, V and Giannaccini, G and D'Antongiovanni, V and Fallahi, P and Pieroni, L and Cristaudo, A and Lucacchini, A and Mazzoni, MR and Foddis, R}, title = {Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome.}, journal = {Cancer genomics &amp; proteomics}, volume = {17}, number = {3}, pages = {225-236}, pmid = {32345664}, issn = {1790-6245}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Cell Line, Tumor ; Female ; GPI-Linked Proteins/blood ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelin ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Oxidoreductases Acting on Sulfur Group Donors/blood ; Pleural Neoplasms/*blood/pathology ; Proteome/*metabolism ; ROC Curve ; Saposins/blood ; Secretory Pathway ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) a rare neoplasm linked to asbestos exposure is characterized by a poor prognosis. Soluble mesothelin is currently considered the most specific diagnostic biomarker. The aim of the study was to identify novel biomarkers by proteomic analysis of two MPM cell lines secretome.<br><br>MATERIALS AND METHODS: The protein patterns of MPM cells secretome were examined and compared to a non-malignant mesothelial cell line using two-dimensional gel electrophoresis coupled to mass spectrometry. Serum levels of candidate biomarkers were determined in MPM patients and control subjects.<br><br>RESULTS: Two up-regulated proteins involved in cancer biology, prosaposin and quiescin Q6 sulfhydryl oxidase 1, were considered candidate biomarkers. Serum levels of both proteins were significantly higher in MPM patients than control subjects. Combining the data of each receiver-operating characteristic analysis predicted a good diagnostic accuracy.<br><br>CONCLUSION: A panel of the putative biomarkers represents a promising tool for MPM diagnosis.}, }
@article {pmid32330840, year = {2020}, author = {Ahmadzada, T and Kao, S and Reid, G and Clarke, S and Grau, GE and Hosseini-Beheshti, E}, title = {Extracellular vesicles as biomarkers in malignant pleural mesothelioma: A review.}, journal = {Critical reviews in oncology/hematology}, volume = {150}, number = {}, pages = {102949}, doi = {10.1016/j.critrevonc.2020.102949}, pmid = {32330840}, issn = {1879-0461}, mesh = {Biomarkers ; *Cell-Derived Microparticles ; *Exosomes ; *Extracellular Vesicles ; Humans ; *Mesothelioma ; }, abstract = {Extracellular vesicles (EV) are secreted by all cells, including cancer cells, as a mode of intercellular transport and communication. The main types of EV known to date include exosomes, microvesicles and apoptotic bodies, as well as oncosomes and large oncosomes, which are specific to cancer cells. These different EV populations carry specific cargo from one cell to another to stimulate a specific response. They can be found in all body fluids and can be detected in liquid biopsies. EV released from mesothelioma cells can reveal important information about the molecules and signalling pathways involved in the development and progression of the tumour. The presence of tumour-derived EV in circulating body fluids makes them potential novel biomarkers for early diagnosis, prognostication and surveillance of cancer. In this review, we explore the characteristics and functional roles of EV reported in the literature, with a focus on their role in malignant pleural mesothelioma.}, }
@article {pmid32330788, year = {2020}, author = {Filetti, V and Falzone, L and Rapisarda, V and Caltabiano, R and Eleonora Graziano, AC and Ledda, C and Loreto, C}, title = {Modulation of microRNA expression levels after naturally occurring asbestiform fibers exposure as a diagnostic biomarker of mesothelial neoplastic transformation.}, journal = {Ecotoxicology and environmental safety}, volume = {198}, number = {}, pages = {110640}, doi = {10.1016/j.ecoenv.2020.110640}, pmid = {32330788}, issn = {1090-2414}, mesh = {Adult ; Asbestos/*toxicity ; Asbestos, Amphibole/*toxicity ; Biomarkers/analysis ; Cell Line ; Cell Transformation, Neoplastic/*chemically induced ; *Environmental Exposure ; Epithelium/*drug effects ; Female ; Gene Expression Profiling ; Humans ; Male ; MicroRNAs/*genetics ; Middle Aged ; Neoplasms, Mesothelial/*chemically induced/diagnosis ; Sicily ; }, abstract = {Fluoro-edenite (FE) is a silicate mineral identified in the lava products of Monte Calvario from stone quarries located in the southeast of Biancavilla, a small city of the Etnean volcanic complex (Sicily, Italy). Inhalation of FE fibers has been associated with a higher incidence of Malignant Mesothelioma (MM), a highly aggressive neoplasm of the serosal membranes lining the pleural cavity. Only 5% of MM patients are diagnosed at an early stage and the median survival is approximate 6-12 months. Many diagnostic biomarkers have been proposed for MM. Several studies demonstrated that microRNAs (miRNAs) may be used as good non-invasive diagnostics, as well as prognostic biomarkers for various human diseases, including cancer. On these bases, the aim of the present study was to identify a set of miRNAs involved in the development and progression of MM and potentially used as diagnostic biomarkers. For these purposes, in silico analyses were performed on healthy/exposed to asbestos fibers subjects vs. patients with MM. These analyses revealed a set of miRNAs strictly involved in MM by merging the lists of miRNAs found differentially expressed in the three miRNA expression datasets analyzed. The result of these computational evaluations allowed the execution of functional in vitro experiments performed on normal pleural mesothelial cell line (MeT-5A) and MM cell line (JU77) in order to test the carcinogenetic effects and epigenetic modulation induced by FE exposure. The in vitro results showed that the expression levels of hsa-miR-323a-3p vary significantly in both supernatant- and cell-derived miRNAs derived from treated and untreated cells. Secreted and cellular hsa-miR-101-3p in MeT-5A treated with FE fibers and JU77 cells showed different trends of expression. As regard hsa-miR-20b-5p, there was no differential expression between secreted and cellular hsa-miR-20b-5p. This miRNA has been shown a significant up-regulation in JU77 cells vs. control and treated MeT-5A. As a future plan, translational analyses will be performed on a subset of patients chronically exposed to FE fibers to further verify the clinical role of such miRNAs in high-risk individuals and their possible use as biomarkers of FE exposure or MM early onset.}, }
@article {pmid32328661, year = {2020}, author = {Girardi, P and Merler, E and Ferrante, D and Silvestri, S and Chellini, E and Angelini, A and Luberto, F and Fedeli, U and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mirabelli, D and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Azzolina, D and Tunesi, S and Miligi, L and Perticaroli, P and Pettinari, A and Cuccaro, F and Nannavecchia, AM and Bisceglia, L and Marinaccio, A and Pavone, VLM and Magnani, C}, title = {Factors Affecting Asbestosis Mortality Among Asbestos-Cement Workers in Italy.}, journal = {Annals of work exposures and health}, volume = {64}, number = {6}, pages = {622-635}, doi = {10.1093/annweh/wxaa037}, pmid = {32328661}, issn = {2398-7316}, mesh = {*Asbestos/adverse effects ; Asbestos, Serpentine ; *Asbestosis ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres.<br><br>METHODS: Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied.<br><br>RESULTS: Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446-563; females 1027, 95% CI: 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos.<br><br>CONCLUSIONS: Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.}, }
@article {pmid32326213, year = {2020}, author = {Cellai, F and Bonassi, S and Cristaudo, A and Bonotti, A and Neri, M and Ceppi, M and Bruzzone, M and Milić, M and Munnia, A and Peluso, M}, title = {Chromatographic Detection of 8-Hydroxy-2'-Deoxyguanosine in Leukocytes of Asbestos Exposed Workers for Assessing Past and Recent Carcinogen Exposures.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {32326213}, issn = {2075-4418}, support = {NA//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; NA//Regione Toscana/ ; }, abstract = {Asbestos fibers include a group of silicate minerals that occur in the environment and are widely employed in occupational settings. Asbestos exposure has been associated to various chronic diseases; such as pulmonary fibrosis; mesothelioma; and lung cancer; often characterized by a long period of latency. Underlying mechanisms that are behind the carcinogenic effect of asbestos have not been fully clarified. Therefore; we have conducted an epidemiological study to evaluate the relationship between 8-hydroxy-2'-deoxyguanosine (8-oxodG), one of the most reliable biomarkers of oxidative stress and oxidative DNA damage; and asbestos exposure in the peripheral blood of residents in Tuscany and Liguria regions; Italy; stratified by occupational exposure to this carcinogen. Levels of 8-oxodG were expressed such as relative adduct labeling (RAL); the frequency of 8-oxodG per 10[5] deoxyguanosine was significantly higher among exposed workers with respect to the controls; i.e., 3.0 ± 0.2 Standard Error (SE) in asbestos workers versus a value of 1.3 ± 0.1 (SE) in unexposed controls (p < 0.001). When the relationship with occupational history was investigated; significant higher levels of 8-oxodG were measured in current and former asbestos workers vs. healthy controls; 3.1 ± 0.3 (SE) and 2.9 ± 0.2 (SE), respectively. After stratification for occupational history; a significant 194% excess of adducts was found in workers with 10 or more years of past asbestos exposure (p < 0.001). 8-oxodG can be used for medical surveillance programs of cohorts of workers with past and recent exposures to carcinogens for the identification of subjects requiring a more intense clinical surveillance.}, }
@article {pmid32318342, year = {2020}, author = {Ferrari, L and Carugno, M and Mensi, C and Pesatori, AC}, title = {Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {445}, pmid = {32318342}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer, which originates from the mesothelial cells of the pleura and is associated with asbestos exposure. In light of its aggressive nature, late diagnosis and dismal prognosis, there is an urgent need for identification of biomarkers in easily accessible samples (such as blood) for early diagnosis of MPM. In the last 10 years, epigenetic markers, such as DNA methylation and microRNAs (miRNAs), have gained popularity as possible early diagnostic and prognostic biomarkers in cancer research. The aim of this review is to provide a critical analysis of the current evidences on circulating epigenetic biomarkers for MPM and on their translational potential to the clinical practice for early diagnosis and for prognosis.}, }
@article {pmid32312030, year = {2020}, author = {Loreto, C and Caltabiano, R and Graziano, ACE and Castorina, S and Lombardo, C and Filetti, V and Vitale, E and Rapisarda, G and Cardile, V and Ledda, C and Rapisarda, V}, title = {Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1.}, journal = {European journal of histochemistry : EJH}, volume = {64}, number = {2}, pages = {}, pmid = {32312030}, issn = {2038-8306}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Asbestosis/*physiopathology ; Female ; Fibroblasts/drug effects ; Heme Oxygenase-1/*metabolism ; Humans ; Immunohistochemistry ; Inflammation/physiopathology ; Lung/*drug effects/pathology ; Macrophage Migration-Inhibitory Factors/*metabolism ; Male ; Sheep ; }, abstract = {Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.}, }
@article {pmid32308151, year = {2020}, author = {Sturchio, E and Berardinelli, MG and Boccia, P and Zanellato, M and Gioiosa, S}, title = {MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma.}, journal = {Archives of environmental &amp; occupational health}, volume = {75}, number = {8}, pages = {471-482}, doi = {10.1080/19338244.2020.1747966}, pmid = {32308151}, issn = {2154-4700}, mesh = {Animals ; Asbestos/toxicity ; Biomarkers, Tumor/analysis ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; MicroRNAs/*analysis ; Occupational Exposure/adverse effects ; Predictive Value of Tests ; Prognosis ; }, abstract = {Malignant mesothelioma is an aggressive tumor resistant to current therapies with a latency period ranging between 20 and 60 years, caused by inhalation of asbestos fibers, that continues to represent a social and healthcare issue. The high percentage of people exposed to asbestos for professional or environmental reasons is associated with the high biopersistence of its fibers and with its widespread use in the last century. Approximately 20-40% of men report an occupational history that might have caused the workplace exposure (criteria Helsinki, 1997). Some authors are evaluating the possible use of bioindicators as a screening and early diagnosis tool. In this regard, the use of microRNAs has been proposed as powerful diagnostic and prognostic biomarkers for many tumors and human diseases. This review focuses on the current state of knowledge on the key role of microRNAs expression as new malignant mesothelioma biomarkers, in early clinical diagnostic applications.}, }
@article {pmid32301278, year = {2020}, author = {Barbarino, M and Cesari, D and Bottaro, M and Luzzi, L and Namagerdi, A and Bertolino, FM and Bellan, C and Proietti, F and Somma, P and Micheli, M and de Santi, MM and Guazzo, R and Mutti, L and Pirtoli, L and Paladini, P and Indovina, P and Giordano, A}, title = {PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.}, journal = {Journal of cellular and molecular medicine}, volume = {24}, number = {10}, pages = {5565-5577}, pmid = {32301278}, issn = {1582-4934}, mesh = {Cell Line, Tumor ; Chromatography, Liquid ; Epithelial-Mesenchymal Transition/genetics ; *Gene Deletion ; *Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; *Gene Silencing ; Humans ; Immunohistochemistry ; Mesothelioma/*genetics/metabolism/pathology ; Protein-Arginine N-Methyltransferases/*genetics ; Purine-Nucleoside Phosphorylase/*genetics ; Tandem Mass Spectrometry ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.}, }
@article {pmid32290761, year = {2020}, author = {Laubenthal, TG}, title = {Regulated Asbestos Analysis: EPA Polarized Light Microscopy Method and the Implications for Reported Fiber Sizes.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {30}, number = {2}, pages = {83-85}, doi = {10.1177/1048291120917952}, pmid = {32290761}, issn = {1541-3772}, mesh = {*Asbestos ; Asbestos, Serpentine ; Humans ; *Mesothelioma ; Microscopy, Polarization ; }, }
@article {pmid32290540, year = {2020}, author = {Vimercati, L and Cavone, D and Delfino, MC and Caputi, A and De Maria, L and Sponselli, S and Corrado, V and Ferri, GM and Serio, G}, title = {Asbestos Air Pollution: Description of a Mesothelioma Cluster Due to Residential Exposure from an Asbestos Cement Factory.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {8}, pages = {}, pmid = {32290540}, issn = {1660-4601}, mesh = {Aged ; *Air Pollution ; *Asbestos/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; Middle Aged ; *Occupational Exposure/adverse effects ; }, abstract = {The study describes a cluster of 71 malignant mesothelioma cases among Bari residents without asbestos exposure other than residential exposure. This small cohort, as expected, was composed of a majority of females (56.34%) with a M/F ratio of 0.8, ages ≤ 65 years old (52.11%) and the epithelioid morphological type (78.87%). Sixty-four subjects (90.14%) lived between 10 m and 1000 m from the asbestos cement factory (Fibronit), and the latency length was longer than 55 years for 25 subjects (35.21%). The adjusted risk (adjusted OR) of observing the epithelial form of mesothelioma among subjects living at small distances from Fibronit was high (OR = 1.870 (0.353-9.905)) for people living 550-1000 m from the site and for those living less than 550 m from the site (OR = 1.470 (0.262-8.248)). Additionally, the subjects with a high length of exposure showed a relevant risk of epithelioid mesothelioma both for 21-40 years of exposure (OR = 2.027 (0.521-7.890)) and more than 40 years of exposure (OR = 2.879 (0.651-12.736)). All of the estimates were high but not significant because this transitional study has a typically low power. The adjustment for latency showed the same trend. Using detailed information collected by the regional mesothelioma registry, this study provided evidence of a continuing health impact of the Fibronit asbestos cement factory in Bari on the resident population.}, }
@article {pmid32282287, year = {2020}, author = {Metintas, S and Ak, G and Metintas, M}, title = {Potential years of life and productivity loss due to malignant mesothelioma in Turkey.}, journal = {Archives of environmental &amp; occupational health}, volume = {75}, number = {8}, pages = {464-470}, doi = {10.1080/19338244.2020.1747380}, pmid = {32282287}, issn = {2154-4700}, mesh = {Adult ; *Efficiency ; Female ; Humans ; *Life Expectancy ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Mortality/*trends ; Population Surveillance ; Risk Assessment ; Risk Factors ; Turkey/epidemiology ; }, abstract = {The study aimed to calculate years of life lost (YLL) and years of potential life lost (YPLL) due to malignant mesothelioma (MM) in Turkey. YLL was computed by estimating the difference between age at death due to MM and the expected death age. To calculate YPLL, all deaths above 65 years (retirement age) were disregarded. Of the 5,617 deaths due to MM in the study period, 3,241 (57.70%) were male and 2,376 (42.30%) were female. The median YLL and YPLL were 16.58 and 25.13 for males and 19.83 and 28.50 years for females. YLL and YPLL were shorter in males than females (p < 0.001). Premature mortality cost per death was $ 45,963.57 (2.23 times higher for males). MM is associated with high YLL, YPLL and economic burden in a country with environmental asbestos exposure in the rural areas.}, }
@article {pmid32253443, year = {2020}, author = {Marinaccio, A and Consonni, D and Mensi, C and Mirabelli, D and Migliore, E and Magnani, C and Di Marzio, D and Gennaro, V and Mazzoleni, G and Girardi, P and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Madeo, G and Romeo, E and Ascoli, V and Carrozza, F and Angelillo, IF and Cavone, D and Tumino, R and Melis, M and Curti, S and Brandi, G and Mattioli, S and Iavicoli, S and , }, title = {Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {46}, number = {6}, pages = {609-617}, pmid = {32253443}, issn = {1795-990X}, mesh = {Adolescent ; Adult ; Aged ; *Asbestos ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Pericardium/*pathology ; Registries ; Testicular Neoplasms/*epidemiology ; Young Adult ; }, abstract = {Objectives The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. Methods Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993-2015, incidence rates, survival median period and prognostic factors have been evaluated. A case-control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. Results Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85-7.31 and OR 3.42, 95% CI 1.93-6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. Conclusions For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.}, }
@article {pmid32249197, year = {2020}, author = {Lau, B and Boyer, M and Lee, JH and Kao, S}, title = {Clinical Trials Eligibility of Patients With Malignant Pleural Mesothelioma: Use of Novel Therapies and Outcomes.}, journal = {Clinical lung cancer}, volume = {21}, number = {4}, pages = {378-383.e1}, doi = {10.1016/j.cllc.2020.01.007}, pmid = {32249197}, issn = {1938-0690}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/administration &amp; dosage ; Cisplatin/administration &amp; dosage ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase III as Topic ; *Eligibility Determination ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma, Malignant/*drug therapy/pathology ; Middle Aged ; *Patient Selection ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Survival Rate ; }, abstract = {INTRODUCTION: Studies of bevacizumab and pembrolizumab in the treatment of malignant pleural mesothelioma suggest anticancer efficacy; clinical trial populations are not reflective of real-world patients. We aimed to determine the proportion of real-world patients who would be eligible for trials, identify patients who participated in clinical trials, and examine treatment and outcome data.<br><br>PATIENTS AND METHODS: Consecutive patients with unresectable malignant pleural mesothelioma seen at our center from January 2012 to July 2018 were assessed with regards to their eligibility for Mesothelioma Avastin Cisplatin Study (MAPS) and KEYNOTE-028 clinical trials. Prognostic information, treatment use, and overall survival (OS) data were also collected.<br><br>RESULTS: A total of 133 patients were included: 50% and 37%, respectively, did not meet trial eligibility for MAPS or KEYNOTE-028, most commonly owing to age&#xa0;&#x2265;75 (23%), Eastern Cooperative Oncology Group performance status of&#xa0;&#x2265;2 (21%), concomitant medication (21%), or comorbidity (12%). MAPS eligibility did not correlate with use of bevacizumab (P&#xa0;= .30) or improved OS (P&#xa0;= .87). Eligibility for KEYNOTE-028 correlated with pembrolizumab use (P&#xa0;< .001), but not improved OS (P&#xa0;= .21). Patients who received an investigational anticancer therapy on any clinical trial had improved OS: 32.4 (95% CI, 23.9-40.9) months versus 20.5 (95% CI, 15.8-25.3) months (P&#xa0;= .01).<br><br>CONCLUSION: Only&#xa0;&#x2264;63% of our patients were eligible for these trials, highlighting the differences between real-world patients and the highly select trial population. Our patients who participated in clinical trials had superior OS, further emphasizing the selection bias in the trial population.}, }
@article {pmid32248600, year = {2020}, author = {Okazaki, Y and Chew, SH and Nagai, H and Yamashita, Y and Ohara, H and Jiang, L and Akatsuka, S and Takahashi, T and Toyokuni, S}, title = {Overexpression of miR-199/214 is a distinctive feature of iron-induced and asbestos-induced sarcomatoid mesothelioma in rats.}, journal = {Cancer science}, volume = {111}, number = {6}, pages = {2016-2027}, pmid = {32248600}, issn = {1349-7006}, support = {//Ministry of Education, Culture, Sports, Science and Technology/ ; Young Scientist (B)(23790440)//Japan Society for the Promotion of Science/ ; Young Scientist (B)(25860292)//Japan Society for the Promotion of Science/ ; JP17H04064//JSPS Kakenhi/ ; JP19H05462//JSPS Kakenhi/ ; JPMJCR19H4//JST CREST/ ; }, mesh = {Animals ; Asbestos/toxicity ; Cell Line ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Iron/toxicity ; Lung Neoplasms/genetics/metabolism/*pathology ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; MicroRNAs/*biosynthesis ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Rats ; Twist-Related Protein 1/*biosynthesis ; }, abstract = {Malignant mesothelioma (MM) is one of the most lethal tumors in humans. The onset of MM is linked to exposure to asbestos, which generates reactive oxygen species (ROS). ROS are believed to be derived from the frustrated phagocytosis and the iron in asbestos. To explore the pathogenesis of MM, peritoneal MM was induced in rats by the repeated intraperitoneal injection of iron saccharate and nitrilotriacetate. In the present study, we used microarray techniques to screen the microRNA (miR) expression profiles of these MM. We observed that the histological subtype impacted the hierarchical clustering of miR expression profiles and determined that miR-199/214 is a distinctive feature of iron saccharate-induced sarcomatoid mesothelioma (SM). Twist1, a transcriptional regulator of the epithelial-mesenchymal transition, has been shown to activate miR-199/214 transcription; thus, the expression level of Twist1 was examined in iron-induced and asbestos-induced mesotheliomas in rats. Twist1 was exclusively expressed in iron saccharate-induced SM but not in the epithelioid subtype. The Twist1-miR-199/214 axis is activated in iron saccharate-induced and asbestos-induced SM. The expression levels of miR-214 and Twist1 were correlated in an asbestos-induced MM cell line, suggesting that the Twist1-miR-199/214 axis is preserved. MeT5A, an immortalized human mesothelial cell line, was used for the functional analysis of miR. The overexpression of miR-199/214 promoted cellular proliferation, mobility and phosphorylation of Akt and ERK in MeT5A cells. These results indicate that miR-199/214 may affect the aggressive biological behavior of SM.}, }
@article {pmid32242530, year = {2020}, author = {Ramos-Bonilla, JP and Marsili, D and Comba, P}, title = {Epidemiological research as a driver of prevention: the Sibaté study. Commentary.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {56}, number = {1}, pages = {6-9}, doi = {10.4415/ANN_20_01_03}, pmid = {32242530}, issn = {2384-8553}, mesh = {Academies and Institutes ; Asbestos/analysis/*toxicity ; Colombia/epidemiology ; Conservation of Natural Resources/*legislation &amp; jurisprudence ; Construction Materials ; Environmental Exposure ; *Epidemiologic Studies ; Female ; Humans ; Intersectoral Collaboration ; Male ; *Manufacturing and Industrial Facilities ; Mesothelioma/epidemiology/etiology/*prevention &amp; control ; Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology/*prevention &amp; control ; Soil Pollutants/analysis ; Universities ; Urban Health ; Waste Disposal Facilities ; }, abstract = {Although asbestos exposure and risks can be prevented, only five countries in Latin America have banned asbestos, including Colombia. Beginning in 2011, a collaboration between the Istituto Superiore di Sanità in Italy and Universidad de los Andes in Colombia was established, bringing together relevant expertise aiming to improve our understanding of the asbestos problem. An important result of this collaboration was a recently published study conducted in Sibaté, Colombia, a municipality where an asbestos-cement facility has operated since 1942. The evidence collected suggests the presence of a mesothelioma cluster in Sibaté. Landfilled zones with an underground layer of friable asbestos were also discovered in the urban area of the municipality. The importance of this type of collaboration can go beyond understanding the impact of asbestos at the local level, which is crucial, and may also contribute in solving unanswered questions of the problem in countries that banned asbestos decades ago.}, }
@article {pmid32223452, year = {2020}, author = {van Zandwijk, N and Reid, G and Frank, AL}, title = {Asbestos-related cancers: the 'Hidden Killer' remains a global threat.}, journal = {Expert review of anticancer therapy}, volume = {20}, number = {4}, pages = {271-278}, doi = {10.1080/14737140.2020.1745067}, pmid = {32223452}, issn = {1744-8328}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {Introduction: Asbestos, the most frequent cause of occupational cancer, continues to be consumed on a massive scale, with millions of people exposed on a daily basis. This review explains why we have failed in curtailing the silent epidemic of asbestos-related disease and why the numbers of asbestos victims are likely to remain high. Emerging and developed countries have to be reminded that asbestos exposure has yet to become a problem of the past. The worldwide spread of asbestos, followed by the surge of asbestos-related cancers, resembles the lung cancer epidemic caused by smoking and stimulated by manufacturers.Areas covered: Underreporting of malignant mesothelioma and asbestos-induced lung cancer, frequently-used arguments in the amphibole/chrysotile debate and the conclusion from bona-fide research organizations, that all forms of asbestos are carcinogenic, are reviewed. Special attention is paid to the consequences of ubiquitous environmental asbestos and the 'changing face' of malignant mesothelioma in countries with heavy asbestos use in the past.Expert opinion: Experts in oncology, respiratory medicine, occupational and public health, and basic researchers must take responsibility and acknowledge the ongoing silent epidemic of asbestos-related diseases. The call for a world-wide asbestos ban is more urgent than ever.}, }
@article {pmid32213537, year = {2020}, author = {Hoon, SN and Fyfe, K and Peddle-McIntyre, CJ and Bowyer, S and Hawkins, F and Jeffery, E and Chih, HJ and Creaney, J and Nowak, A and Brims, F}, title = {Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): rationale and protocol.}, journal = {BMJ open respiratory research}, volume = {7}, number = {1}, pages = {}, pmid = {32213537}, issn = {2052-4439}, mesh = {Absorptiometry, Photon ; Appetite Stimulants/adverse effects/*therapeutic use ; Australia ; Body Composition/drug effects ; Cachexia/*complications/*drug therapy/etiology/physiopathology ; Clinical Trials, Phase II as Topic ; Cross-Over Studies ; Double-Blind Method ; Humans ; Hydrazines/adverse effects/*therapeutic use ; Linear Models ; Mesothelioma, Malignant/*complications ; Muscle Strength/drug effects ; Oligopeptides/adverse effects/*therapeutic use ; Pilot Projects ; Quality of Life ; Randomized Controlled Trials as Topic ; Weight Gain/drug effects ; }, abstract = {INTRODUCTION: Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia.<br><br>METHODS AND ANALYSIS: A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival >3 months and cachexia (defined as >5%&#x2009;weight loss in 6 months or body mass index <20&#x2009;kg/m[2] with weight loss >2%).<br><br>ETHICS AND DISSEMINATION: Ethical approval has been granted. Results will be reported in peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (U1111-1240-6828).}, }
@article {pmid32208261, year = {2020}, author = {Neitzel, RL and Sayler, SK and Demond, AH and d'Arcy, H and Garabrant, DH and Franzblau, A}, title = {Measurement of asbestos emissions associated with demolition of abandoned residential dwellings.}, journal = {The Science of the total environment}, volume = {722}, number = {}, pages = {137891}, pmid = {32208261}, issn = {1879-1026}, support = {P30 ES017885/ES/NIEHS NIH HHS/United States ; }, abstract = {Many cities are revitalizing their urban cores through the demolition of abandoned residential dwellings (ARDs). However, data regarding the emissions of asbestos during such an operation are sparse. We measured airborne asbestos emissions from emergency demolitions (demolitions on structures deemed too dangerous to enter and remove asbestos) of ARDs in Detroit. High-flow air sampling was conducted during ARD demolitions. Air samples were analyzed using Phased Contrast Microscopy (PCM), and a subset using Transmission Electron Microscopy (TEM). One hundred and one air samples were collected on 25 emergency demolitions. Fifty-four of the 101 PCM samples (53%) exceeded the limit of detection (LOD). However, only 2 of 46 TEM samples (4%) exceeded the LOD for asbestos; these latter samples were from two different demolitions and each contained a single chrysotile asbestos fiber. Using conservative exposure assumptions and commonly-accepted risk estimation formulae, we estimated the lifetime risk of mesothelioma and lung cancer combined to be less than one case per one million people. Emissions of airborne asbestos during emergency (unabated) ARD demolition operations appear to be negligible. As a result, the associated health risk for asbestos-related disease is also negligible. Reconsideration of current regulatory mandates for asbestos abatement in ARDs may be warranted.}, }
@article {pmid32206576, year = {2020}, author = {Gray, SG and Mutti, L}, title = {Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S100-S119}, pmid = {32206576}, issn = {2218-6751}, abstract = {At the clinical level the role of immunotherapy in cancer is currently at a pivotal point. Therapies such as checkpoint inhibitors are being approved at many levels in cancers such as non-small cell lung cancer (NSCLC). Mesothelioma is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Various clinical trials for checkpoint inhibitors have been conducted in this rare disease, and suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer. Most recently approved as a salvage therapy in mesothelioma was granted in Japan, regulatory approval for their use in the clinic elsewhere lags. In this article we review the current pertinent clinical trials of immunotherapies in malignant mesothelioma, discuss the current issues that may affect the clinical outcomes of such therapies and further evaluate potential candidate new avenues that may become future targets for immunotherapy in this cancer.}, }
@article {pmid32206572, year = {2020}, author = {Yoshikawa, Y and Emi, M and Nakano, T and Gaudino, G}, title = {Mesothelioma developing in carriers of inherited genetic mutations.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S67-S76}, pmid = {32206572}, issn = {2218-6751}, abstract = {Malignant mesothelioma is associated with the exposure to asbestos fibers. Recent discovery of the BAP1 cancer syndrome, a Mendelian disorder with high-penetrance autosomal dominant inheritance fostered the genotyping for nucleotide-level or larger structural alteration of germline DNA. Inherited heterozygous mutations of the BAP1 gene increase the susceptibility to carcinogenic fibers, leading to a concept of gene x environment interaction (GxE) as a pathogenetic mechanism of mesothelioma. Several studies on cohorts of unselected patients with mesothelioma or on familial/early-onset cohorts of mesothelioma cases converged on BAP1 as the more frequent germline mutated gene, followed by other genes involved in DNA repair and homologous recombination. Evidence has been emerging that patients with mesothelioma carrying germline mutations of BAP1 and of other genes, such as those involved in DNA repair and tumor suppressor genes, have better prognosis and higher chemosensitivity when compared with patients with germline wildtype Bap1. We report here a germline genomic analysis targeted 22 genes in a cohort of 101 Japanese patients irrespective of asbestos exposure, age at diagnosis, or personal or family history of cancer. By comparing the results with the Human Genetic Variation Database (HGVD) and the Genome Aggregation Database (gnomAD) we selected rare germline variants with a Combined Annotation Dependent Depletion (CADD) >20. We show here that 31 of 101 subjects were carrying 25 rare variants in 14 genes, neither reported in the HGVD nor in the gnomAD database for 14/25 variants. Besides pathogenic variants of BAP1, rare missense variants were found in genes encoding lysine-specific histone methyltransferase SETD2 and SETDB1 and genes encoding subunits of the mSWI/SNF chromatin remodeling complex. The complete scenario of the genetic background consisting of pathogenic germline variants required for the predisposition and GxE for pathogenesis of mesothelioma appears complex, and further large-scale studies are warranted.}, }
@article {pmid32206570, year = {2020}, author = {Carbone, M and Gazdar, A and Butel, JS}, title = {SV40 and human mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S47-S59}, pmid = {32206570}, issn = {2218-6751}, abstract = {Simian virus 40 (SV40) is a DNA tumor virus capable of infecting and transforming human mesothelial (HM) cells in vitro. Hamsters injected intracardially to expose most tissue types to SV40 preferentially develop mesotheliomas. In humans, asbestos is the main cause of mesothelioma, and asbestos and SV40 are co-carcinogens in transforming HM cells in tissue culture and in causing mesothelioma in hamsters. Laser microdissection experiments conducted in the laboratory of Adi Gazdar demonstrated that SV40 was present specifically in the malignant mesothelioma cells and not in nearby stromal cells. Further experiments demonstrated that SV40 remains episomal in HM cells and astrocytes because of the production of a long antisense RNA that represses viral capsid protein production. Thus, the potent SV40 oncoprotein, T-antigen (Tag), is expressed, but because the capsid proteins are not produced, the cells are not lysed and, instead, become transformed. Together this evidence suggests that SV40 may contribute to the development of mesotheliomas in humans. However, epidemiological evidence to support this hypothesis is lacking. This chapter also summarizes the introduction of SV40, a monkey virus, into the human population as an unrecognized contaminant of early poliovaccines. In addition to mesotheliomas, SV40 now is linked with brain cancers, osteosarcomas, and lymphomas in humans. Explanations are provided for the apparent geographic variations in SV40 prevalence and for controversies about the role of SV40 in human cancer.}, }
@article {pmid32206569, year = {2020}, author = {Gaudino, G and Xue, J and Yang, H}, title = {How asbestos and other fibers cause mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S39-S46}, pmid = {32206569}, issn = {2218-6751}, abstract = {Mesothelioma has long been associated with the exposure to asbestos, which was largely used in manufacturing activities. Toxicology studies in vitro and in vivo demonstrated that asbestos fibers were carcinogenic, and epidemiology studies revealed that asbestos exposure was paralleled by the increase in the incidence of mesothelioma and related mortality rates. More recently, the role of chronic inflammation and the molecular mechanisms involved in carcinogenesis by mineral fibers were elucidated following the discovery of the roles of HMGB1 and inflammasome. A change of paradigm was the discovery of a prevalence of mesotheliomas attributable to inherited mutations of cancer susceptibility genes. The discovery of BAP1 as a predisposition gene for the development of familial mesothelioma and other cancers implemented genome studies in patients with mesothelioma and routine clinical surveys in individuals at risk to identify germline mutations associated with cancers included in the BAP1 syndrome. A further progress in the approach to asbestos-related malignancy was the adoption of combined genetics and environmental analyses according to the model of gene-environment (GxE) interactions. This review aims at updating on the most recently discovered mechanisms of tumorigenesis and the pivotal role of GxE interactions.}, }
@article {pmid32206568, year = {2020}, author = {Alpert, N and van Gerwen, M and Taioli, E}, title = {Epidemiology of mesothelioma in the 21[st] century in Europe and the United States, 40 years after restricted/banned asbestos use.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S28-S38}, pmid = {32206568}, issn = {2218-6751}, abstract = {Research has established a strong association between asbestos exposure and malignant mesothelioma, a deadly form of cancer. Since the early 1980's many countries have restricted or banned the production of asbestos, leading to a decline of occupational asbestos exposure in many industrialized countries. However, some countries continue to use asbestos, and worldwide rates of mesothelioma are still increasing. Because of the long latency between exposure and mesothelioma occurrence and the persistence of environmental exposure, incidence rates (IR) may decrease very slowly for several years ahead. In this review, we examine estimates of asbestos consumption before widespread asbestos regulations and the trends in incidence and mortality rates, as well as changes over time for the United States and Europe. In some countries with earlier asbestos restrictions, mesothelioma incidence has been in a modest decline over time. However, asbestos exposure is still a burden worldwide and legislative action is needed to obtain a full ban. The pattern of mesothelioma is shifting from a mostly male disease to a disease that affects females as well in substantial numbers. Studies on unknown sources of asbestos exposure, of other sources of natural exposure to asbestos and asbestos-like fibers, as well as of individual genetic susceptibility to asbestos fibers are needed.}, }
@article {pmid32206566, year = {2020}, author = {Carbone, M}, title = {This special volume of mesothelioma is dedicated to my friend Adi Gazdar.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S1-S2}, doi = {10.21037/tlcr.2020.01.15}, pmid = {32206566}, issn = {2218-6751}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, }
@article {pmid32187018, year = {2020}, author = {Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V and Franko, A}, title = {Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {54}, number = {1}, pages = {86-95}, pmid = {32187018}, issn = {1581-3207}, mesh = {Aged ; Alleles ; Asbestos ; Asbestosis/*blood ; Carcinogens ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; GPI-Linked Proteins/*blood/chemistry/*genetics ; Genetic Variation ; Genotype ; Humans ; Male ; Mesothelin ; Mesothelioma, Malignant/*blood/etiology/mortality ; Middle Aged ; Peptides/blood/genetics ; Peritoneal Neoplasms/blood/etiology/mortality ; Polymorphism, Genetic ; Protein Isoforms/blood/genetics ; Protein Kinases ; Statistics, Nonparametric ; }, abstract = {Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.}, }
@article {pmid32183600, year = {2020}, author = {Funahashi, S and Okazaki, Y and Akatsuka, S and Takahashi, T and Sakumi, K and Nakabeppu, Y and Toyokuni, S}, title = {Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice.}, journal = {Free radical research}, volume = {54}, number = {2-3}, pages = {195-205}, doi = {10.1080/10715762.2020.1743285}, pmid = {32183600}, issn = {1029-2470}, mesh = {Animals ; Asbestos, Crocidolite/*adverse effects/*metabolism ; DNA Repair Enzymes/*deficiency ; Female ; Injections, Intraperitoneal/*methods ; Mice ; Phosphoric Monoester Hydrolases/*deficiency ; }, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis. Recent sequencing studies on human and rodent malignant mesothelioma (MM) revealed frequently mutated genes, including CDKN2A, BAP1 and NF2. Crocidolite directly or indirectly catalyses the generation of hydroxyl radicals, which appears to be the major driving force for mesothelial mutations. DNA base modification is an oxidative DNA damage mechanism, where 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most abundant modification both physiologically and pathologically. Multiple distinct mechanisms work together to decrease the genomic level of 8-OHdG through the enzymatic activities of Mutyh, Ogg1 and Mth1. Knockout of one or multiple enzymes is not lethal but increases the incidence of tumors. Here, we used single knockout (KO) mice to test whether the deficiency of these three genes affects the incidence and prognosis of asbestos-induced MM. Intraperitoneal injection of 3 mg crocidolite induced MM at a fraction of 14.8% (4/27) in Mth1 KO, 41.4% (12/29) in Mutyh KO and 24.0% (6/25) in Ogg1 KO mice, whereas 31.7% (20/63) induction was observed in C57BL/6 wild-type (Wt) mice. The lifespan of female Mth1 KO mice was longer than that of female Wt mice (p = 0.0468). Whole genome scanning of MM with array-based comparative genomic hybridization revealed rare genomic alterations compared to MM in rats and humans. These results indicate that neither Mutyh deficiency nor Ogg1 deficiency promotes crocidolite-induced MM in mice, but the sanitizing nucleotide pool with Mth1 is advantageous in crocidolite-induced mesothelial carcinogenesis.}, }
@article {pmid32183579, year = {2020}, author = {Roggli, VL and Carney, JM and Sporn, TA and Pavlisko, EN}, title = {Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation.}, journal = {Ultrastructural pathology}, volume = {44}, number = {2}, pages = {211-218}, doi = {10.1080/01913123.2020.1737286}, pmid = {32183579}, issn = {1521-0758}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/analysis ; Female ; Humans ; Male ; Mesothelioma, Malignant/*chemistry ; Middle Aged ; Mineral Fibers/adverse effects/*analysis ; Peritoneal Neoplasms/*chemistry ; Pleural Neoplasms/*chemistry ; Talc/adverse effects/*analysis ; }, abstract = {Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.}, }
@article {pmid32175619, year = {2020}, author = {Emory, TS and Maddox, JC and Kradin, RL}, title = {Malignant mesothelioma following repeated exposures to cosmetic talc: A case series of 75 patients.}, journal = {American journal of industrial medicine}, volume = {63}, number = {6}, pages = {484-489}, pmid = {32175619}, issn = {1097-0274}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects/analysis ; Asbestos, Amphibole/adverse effects/analysis ; Barbering ; Beauty Culture ; Female ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma, Malignant/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/epidemiology/etiology ; Talc/*adverse effects/analysis ; Time Factors ; }, abstract = {BACKGROUND: Asbestos is the primary known cause of malignant mesothelioma. Some cosmetic talc products have been shown to contain asbestos. Recently, repeated exposures to cosmetic talc have been implicated as a cause of mesothelioma.<br><br>METHODS: Seventy-five individuals (64 females; 11 males) with malignant mesothelioma, whose only known exposure to asbestos was repeated exposures to cosmetic talcum powders, were reviewed in medical-legal consultation. Out of the 75 cases, 11 were examined for asbestiform fibers.<br><br>RESULTS: All subjects had pathologically confirmed malignant mesothelioma. The mean age at diagnosis was 61&#x2009;&#xb1;&#x2009;17 years. The mean latency from exposure to diagnosis was 50 &#xb1;&#x2009;13 years. The mean exposure duration was 33&#x2009;&#xb1;&#x2009;16 years. Four mesotheliomas (5%) occurred in individuals working as barbers/cosmetologists, or in a family member who swept the barber shop. Twelve (16%) occurred in individuals less than 45 years old (10 females; 2 males). Forty-eight mesotheliomas were pleural (40 females; 8 males), 23 were peritoneal (21 females; 2 males). Two presented with concomitant pleural and peritoneal disease. There was one pericardial, and one testicular mesothelioma. The majority (51) were of the epithelioid histological subtype, followed by 13 biphasic, 8 sarcomatoid, 2 lymphohistiocytoid, and 1 poorly differentiated. Of the 11 individuals whose nontumorous tissues were analyzed for the presence of asbestiform fibers, all showed the presence of anthophyllite and/or tremolite asbestos.<br><br>CONCLUSIONS: Mesotheliomas can develop following exposures to cosmetic talcum powders. These appear to be attributable to the presence of anthophyllite and tremolite contaminants in cosmetic talcum powder.}, }
@article {pmid32169964, year = {2020}, author = {Napolitano, A and Antoine, DJ and Pellegrini, L and Baumann, F and Pagano, I and Pastorino, S and Goparaju, CM and Prokrym, K and Canino, C and Pass, HI and Carbone, M and Yang, H}, title = {Expression of Concern: HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {6}, pages = {1529}, doi = {10.1158/1078-0432.CCR-20-0338}, pmid = {32169964}, issn = {1557-3265}, }
@article {pmid32156681, year = {2020}, author = {Viscardi, G and Di Liello, R and Morgillo, F}, title = {How I treat malignant pleural mesothelioma.}, journal = {ESMO open}, volume = {4}, number = {Suppl 2}, pages = {e000669}, pmid = {32156681}, issn = {2059-7029}, mesh = {Humans ; Lung Neoplasms/*pathology/*therapy ; Mesothelioma/*pathology/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; }, abstract = {Malignant pleural mesothelioma is a rare and aggressive malignancy mostly associated with occupational asbestos exposure. Prognosis is poor and only highly selected patients may benefit from aggressive surgical management, also as part of a multimodal approach. In advanced disease, the combination of pemetrexed and platinum remains the only established treatment, while efficacy evidence of second line chemotherapy is lacking. Thus, a deeper knowledge of biology of the disease and more effective treatments are urgently needed. Refer to specialised centres with multidisciplinary expertise is mandatory, as well as inclusion of patients in clinical trials is advisable whenever possible. In all stages of disease focus on symptoms control is paramount.}, }
@article {pmid32142836, year = {2020}, author = {Paajanen, J and Laaksonen, S and Kettunen, E and Ilonen, I and Vehmas, T and Salo, J and Räsänen, J and Sutinen, E and Ollila, H and Mäyränpää, MI and Myllärniemi, M and Wolff, H}, title = {Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival.}, journal = {Human pathology}, volume = {98}, number = {}, pages = {110-119}, doi = {10.1016/j.humpath.2020.02.007}, pmid = {32142836}, issn = {1532-8392}, mesh = {Epithelioid Cells/*pathology ; Female ; Humans ; Lung Neoplasms/mortality/*pathology/surgery ; Male ; Mesothelioma/mortality/*pathology/surgery ; Mesothelioma, Malignant ; Necrosis ; Neoplasm Grading ; Pleural Neoplasms/mortality/*pathology/surgery ; Time Factors ; Treatment Outcome ; }, abstract = {Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34, 90%) and a tubulopapillary growth pattern (n = 30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49, 61%) and solid growth pattern (n = 59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P < 0.001) and the presence of necrosis (P = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P < 0.001) and presence of exophytic polypoid growth (P = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.}, }
@article {pmid32133285, year = {2020}, author = {Nowak, AK and Brosseau, S and Cook, A and Zalcman, G}, title = {Antiangiogeneic Strategies in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {126}, pmid = {32133285}, issn = {2234-943X}, abstract = {There is a strong rationale for inhibiting angiogenesis in mesothelioma. Vascular endothelial growth factor (VEGF) is an autocrine growth factor in mesothelioma and a potent mitogen for mesothelial cells. Further, the abnormal tumor vasculature promotes raised interstitial pressure and hypoxia, which may be detrimental to both penetration and efficacy of anticancer agents. Antiangiogenic agents have been trialed in mesothelioma for close to two decades, with early phase clinical trials testing vascular targeting agents, the VEGF-A targeting monoclonal antibody bevacizumab, and numerous tyrosine kinase inhibitors, many with multiple targets. None of these have shown efficacy which has warranted further development as single agents in any line of therapy. Whilst a randomized phase II trial combining the multitargeted tyrosine kinase inhibitor nintedanib with platinum/pemetrexed chemotherapy was positive, these results were not confirmed in a subsequent phase III study. The combination of cisplatin and pemetrexed with bevacizumab, in appropriately selected patients, remains the only anti-angiogenic combination showing efficacy in mesothelioma. Extensive efforts to identify biomarkers of response have not yet been successful.}, }
@article {pmid32123850, year = {2019}, author = {Fan, X and McLaughlin, C and Robinson, C and Ravasini, J and Schelch, K and Johnson, T and van Zandwijk, N and Reid, G and George, AM}, title = {Zeolites ameliorate asbestos toxicity in a transgenic model of malignant mesothelioma.}, journal = {FASEB bioAdvances}, volume = {1}, number = {9}, pages = {550-560}, pmid = {32123850}, issn = {2573-9832}, abstract = {Malignant mesothelioma (MM) is an almost invariably fatal cancer caused by asbestos exposure. The toxicity of asbestos fibers is related to their physicochemical properties and the generation of free radicals. We set up a pilot study to investigate the potential of the zeolite clinoptilolite to counteract the asbestos carcinogenesis by preventing the generation of reactive nitrogen and oxygen radicals. In cell culture experiments, clinoptilolite prevented asbestos-induced cell death, reactive oxygen species production, DNA degradation, and overexpression of genes known to be up-regulated by asbestos. In an asbestos-induced transgenic mouse model of MM, mice were injected intraperitoneal injections with blue asbestos, with or without clinoptilolite, and monitored for 30 weeks. By the end of the trial all 13 mice injected with asbestos alone had reached humane end points, whereas only 7 of 29 mice receiving crocidolite and clinoptilolite reached a similar stage of disease. Post-mortem examination revealed pinpoint mesothelioma-like tumors in affected mice, and the absence of tumor formation in surviving mice. Interestingly, the macrophage clearance system, which was largely suppressed in asbestos-treated mice, exhibited evidence of increased phagocytosis in mice treated with asbestos and clinoptilolite. Our study suggests that inhibiting the asbestos-induced generation of reactive oxygen species and stimulating the macrophage system may represent a pathway to amelioration of asbestos-induced toxicity. Additional studies are warranted to explore the underlying mechanisms responsible for our observations.}, }
@article {pmid32117755, year = {2020}, author = {Reid, G and Johnson, TG and van Zandwijk, N}, title = {Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {105}, pmid = {32117755}, issn = {2234-943X}, abstract = {microRNAs (miRNAs) are an important class of non-coding RNA that post-transcriptionally regulate the expression of most protein-coding genes. Their aberrant expression in tumors contributes to each of the hallmarks of cancer. In malignant pleural mesothelioma (MPM), in common with other tumor types, changes in miRNA expression are characterized by a global downregulation, although elevated levels of some miRNAs are also found. While an increasing number of miRNAs exhibit altered expression in MPM, relatively few have been functionally characterized. Of a growing number with tumor suppressor activity in vitro, miR-16, miR-193a, and miR-215 were also shown to have tumor suppressor activity in vivo. In the case of miR-16, the significant inhibitory effects on tumor growth following targeted delivery of miR-16-based mimics in a xenograft model was the basis for a successful phase I clinical trial. More recently overexpressed miRNAs with oncogenic activity have been described. Many of these changes in miRNA expression are related to the characteristic loss of tumor suppressor pathways in MPM tumors. In this review we will highlight the studies providing evidence for therapeutic effects of modulating microRNA levels in MPM, and discuss these results in the context of emerging approaches to miRNA-based therapy.}, }
@article {pmid32117751, year = {2020}, author = {Testa, JR and Berns, A}, title = {Preclinical Models of Malignant Mesothelioma.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {101}, pmid = {32117751}, issn = {2234-943X}, abstract = {Rodent models of malignant mesothelioma help facilitate the understanding of the biology of this highly lethal cancer and to develop and test new interventions. Introducing the same genetic lesions as found in human mesothelioma in mice results in tumors that show close resemblance with the human disease counterpart. This includes the extensive inflammatory responses that characterize human malignant mesothelioma. The relatively fast development of mesothelioma in mice when the appropriate combination of lesions is introduced, with or without exposure to asbestos, make the autochthonous models particularly useful for testing new treatment strategies in an immunocompetent setting, whereas Patient-Derived Xenograft models are particularly useful to assess effects of inter- and intra-tumor heterogeneity and human-specific features of mesothelioma. It is to be expected that new insights obtained by studying these experimental systems will lead to new more effective treatments for this devastating disease.}, }
@article {pmid32114955, year = {2020}, author = {Kim, K and Ko, Y and Oh, H and Ha, M and Kang, J and Kwon, EJ and Kang, JW and Kim, Y and Heo, HJ and Kim, G and Kim, JW and Kim, YH}, title = {MicroRNA-98 is a prognostic factor for asbestos-induced mesothelioma.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {83}, number = {3}, pages = {126-134}, doi = {10.1080/15287394.2020.1734891}, pmid = {32114955}, issn = {1528-7394}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor ; Carcinogens/*toxicity ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Mesothelioma/chemically induced/*diagnosis ; MicroRNAs/genetics/*metabolism ; Middle Aged ; }, abstract = {Malignant pleural mesothelioma (MPM) is a type of cancer characterized by a short survival time and poor prognosis. Malignant pleural mesothelioma is most frequently associated with exposure to asbestos and other elongated mineral fibers. The aim of this study was to examine molecular differences between asbestos-exposed and non-exposed MPM patients and assess prognostic significances of molecular factors. Clinical and genetic data were downloaded from Cancer Genome Atlas. To identify the molecular differences, Significant Analysis of Microarray method was used. Prognostic significances of differentially expressed genes were confirmed by using Kaplan-Meier curve with the Log-Rank test. Although mRNAs did not exhibit any significant differences between the two patient groups, nine miRNAs were found to be down-regulated in the asbestos-exposed group. The top five pathways most relevant to the selected miRNAs were extracted through pathway enrichment analysis. Survival analysis revealed that high expression of only hsa-miR-98 was significantly associated with poor prognosis in patients with asbestos-exposed MPM. Evidence suggests that management of the aggressiveness and progression of asbestos-induced MPM may require high levels of hsa-miR-98 due to its tumor-suppressive role. This study might be helpful in enhancing our understanding of the biological mechanisms underlying asbestos-induced MPM and for acquiring greater insights into targeted therapy.Abbreviations: FDR: false discovery rate; MM: malignant mesothelioma; MPM: malignant pleural mesothelioma; mRNA: messenger RNA; miRNA: microRNA; SAM: significance analysis of microarrays; TCGA: the cancer genome atlas.}, }
@article {pmid32106829, year = {2020}, author = {Drevinskaite, M and Patasius, A and Kevlicius, L and Mickys, U and Smailyte, G}, title = {Malignant mesothelioma of the tunica vaginalis testis: a rare case and review of literature.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {162}, pmid = {32106829}, issn = {1471-2407}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Biopsy ; Cisplatin/therapeutic use ; Deoxycytidine/analogs &amp; derivatives/therapeutic use ; Disease Progression ; Fatal Outcome ; Humans ; Lung Neoplasms/complications/*diagnosis/therapy ; Lymphadenopathy ; Male ; Mesothelioma/complications/*diagnosis/therapy ; Mesothelioma, Malignant ; Orchiectomy ; Pemetrexed/therapeutic use ; Prognosis ; Testicular Hydrocele/etiology/*surgery ; Testicular Neoplasms/complications/*diagnosis/therapy ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant mesothelioma of the tunica vaginalis is a rare tumour which comprises less than 1% of all mesotheliomas.<br><br>CASE PRESENTATION: 69-years old patient with painful hard mass and hydrocele in the right scrotum to whom a right hydrocelectomy was performed. Any history of scrotal trauma or exposure to asbestos was not present. Excisional biopsy revealed a multinodular tumour with focal areas of necrosis and infiltrative growth. According to morphological and immunohistochemical findings, diagnosis of malignant biphasic mesothelioma of the tunica vaginalis testis was made. Two months after hydrocelectomy, right inguinal orchidectomy was performed. Post-surgical whole body CT scan revealed paraaortic and pararenal lymphadenopathy, likely to be metastatic. Adjuvant treatment with 6&#x2009;cycles of cisplatin and pemetrexed was applied. After 3&#x2009;cycles of chemotherapy, CT scan showed progression and the treatment was changed to gemcitabine 1 month after.<br><br>CONCLUSIONS: Although malignant mesothelioma of the tunica vaginalis is a rare malignancy, it poses a diagnostic challenge which can mimic common inguinal or scrotal diseases such as hydrocele. Despite aggressive surgical procedures or adjuvant therapies, the prognosis remains poor.}, }
@article {pmid32083805, year = {2020}, author = {Quetel, L and Meiller, C and Assié, JB and Blum, Y and Imbeaud, S and Montagne, F and Tranchant, R and de Wolf, J and Caruso, S and Copin, MC and Hofman, V and Gibault, L and Badoual, C and Pintilie, E and Hofman, P and Monnet, I and Scherpereel, A and Le Pimpec-Barthes, F and Zucman-Rossi, J and Jaurand, MC and Jean, D}, title = {Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival.}, journal = {Molecular oncology}, volume = {14}, number = {6}, pages = {1207-1223}, pmid = {32083805}, issn = {1878-0261}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; Female ; *Genetic Heterogeneity ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma, Malignant/epidemiology/*genetics/pathology ; Middle Aged ; Mutation/genetics ; Pleural Neoplasms/epidemiology/*genetics/pathology ; Survival Analysis ; Young Adult ; }, abstract = {Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo-molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well annotated with histologic, molecular and clinical data of patients. Targeted next-generation sequencing was performed focusing on the major MPM mutated genes and the TERT promoter. Molecular heterogeneity was characterized using predictors allowing classification of each tumor into the previously described molecular subtypes and the determination of the proportion of epithelioid-like and sarcomatoid-like components (E/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that TERT promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in TERT promoter, NF2, and LATS2 were more frequent in nonepithelioid MPM and positively associated with the S.score. BAP1, NF2, TERT promoter, TP53, and SETD2 mutations were enriched in some molecular subtypes. NF2 mutation rate was higher in asbestos unexposed patient. TERT promoter, NF2, and TP53 mutations were associated with a poorer overall survival. Our findings lead to a better characterization of MPM heterogeneity by identifying new significant associations between mutational status and histologic and molecular heterogeneity. Strikingly, we highlight the strong association between new mutations and overall survival.}, }
@article {pmid32082887, year = {2019}, author = {Döngel, &#x130; and Akbaş, A and Benli, &#x130; and Bayram, M}, title = {Comparison of serum biochemical markers in patients with mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.}, journal = {Turk gogus kalp damar cerrahisi dergisi}, volume = {27}, number = {3}, pages = {374-380}, pmid = {32082887}, issn = {1301-5680}, abstract = {BACKGROUND: In this study, we aimed to compare serum biochemical markers in patients with malignant pleural mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.<br><br>METHODS: Between September 01, 2010 and March 31, 2011, a total of 540 participants (354 males, 186 females; mean age 61.4 years; range, 35 to 89 years) were included in the study. The participants were divided into four groups as follows: (1) patients with pleural plaques (n=277); (2) healthy individuals with normal chest X-rays who were exposed to environmental asbestos (n=121); (3) healthy individuals with normal chest X-rays who were not exposed to environmental asbestos (n=118); and (4) patients with malignant pleural mesothelioma (n=24). Serum levels of carcinoembryonic antigen, cancer antigen 125, 15-3, 19-9, free T3, free T4, thyroidstimulating hormone, vitamin B12, folate, and ferritin were measured.<br><br>RESULTS: Serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels were higher with lower free T3 levels in Group 4 than the other groups. The areas under the curve for cancer antigen 125 and 15-3 were 0.78 and 0.67, respectively in the differential diagnosis of mesothelioma from other pathologies (p<0.001 for both). Optimal limits of these biomarkers were 13.63 and 18.43 ng/mL, respectively with 83% and 75% sensitivity and 69% and 48% specificity, respectively.<br><br>CONCLUSION: The combination or individual use of serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels may be helpful for early diagnosis and treatment of malignant pleural mesothelioma.}, }
@article {pmid32081346, year = {2020}, author = {Sinha, S and Swift, AJ and Kamil, MA and Matthews, S and Bull, MJ and Fisher, P and De Fonseka, D and Saha, S and Edwards, JG and Johns, CS}, title = {The role of imaging in malignant pleural mesothelioma: an update after the 2018 BTS guidelines.}, journal = {Clinical radiology}, volume = {75}, number = {6}, pages = {423-432}, doi = {10.1016/j.crad.2019.12.001}, pmid = {32081346}, issn = {1365-229X}, support = {205188/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Diagnostic Imaging/*standards ; Early Detection of Cancer ; Humans ; Mesothelioma, Malignant/*diagnostic imaging/pathology ; Neoplasm Staging ; Pleural Neoplasms/*diagnostic imaging/pathology ; *Practice Guidelines as Topic ; Societies, Medical ; }, abstract = {Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.}, }
@article {pmid32080953, year = {2020}, author = {Okazaki, Y and Misawa, N and Akatsuka, S and Kohyama, N and Sekido, Y and Takahashi, T and Toyokuni, S}, title = {Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats.}, journal = {Cancer science}, volume = {111}, number = {4}, pages = {1180-1192}, pmid = {32080953}, issn = {1349-7006}, support = {JP17H04064 and JP19H05462//Japan Society for the Promotion of Science/ ; JP25860292//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p15/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; Homozygote ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Rats ; Risk Factors ; Sequence Deletion/genetics ; }, abstract = {The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers. Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite, and actinolite types. Although few studies have been undertaken, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7), and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, whereas the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a 2-day time-lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, but anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, whereas anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Furthermore, the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5/8] and loss of heterozygosity [3/8]) by array-based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter/length are discussed.}, }
@article {pmid32077824, year = {2020}, author = {Loreto, C and Lombardo, C and Caltabiano, R and Ledda, C and Hagnas, M and Filetti, V and Rapisarda, V}, title = {An In vivo Immunohistochemical Study on MacroH2A.1 in Lung and Lymph-Node Tissues Exposed to an Asbestiform Fiber.}, journal = {Current molecular medicine}, volume = {20}, number = {8}, pages = {653-660}, doi = {10.2174/1566524020666200220130023}, pmid = {32077824}, issn = {1875-5666}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Histones/*metabolism ; Immunohistochemistry/*methods ; Lung/drug effects/*metabolism/pathology ; Lymph Nodes/drug effects/*metabolism/pathology ; Sheep ; }, abstract = {AIMS: The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE.<br><br>BACKGROUND: The correlation between asbestiform fibers, lung cancer, pleural mesothelioma, and other lung diseases is already well established as the pathophisiological pathophysiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing the release of growth factors, cytokines, and reactive oxygen and nitrite species, with DNA damage that causes chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivo as it results upregulated in senescent cells determining a permanent growth-arrest.<br><br>OBJECTIVE: Evaluate the possible role of the histone variant in the organism in response to deep insight understanding the mechanisms of toxicity and the cellular response to FE.<br><br>METHODS: Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical immunohistochemical evaluations. Densitometric, morphometric, and statistical analysis analyses were conducted.<br><br>RESULTS: Tissue sections of FE exposed sheep demonstrated overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these this molecule in the cellular response triggered by FE directed exposure.<br><br>CONCLUSION: In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.}, }
@article {pmid32065212, year = {2020}, author = {Barbieri, PG and Somigliana, A and Chen, Y and Consonni, D and Vignola, R and Finotto, L}, title = {Lung Asbestos Fibre Burden and Pleural Mesothelioma in Women with Non-occupational Exposure.}, journal = {Annals of work exposures and health}, volume = {64}, number = {3}, pages = {297-310}, doi = {10.1093/annweh/wxaa009}, pmid = {32065212}, issn = {2398-7316}, mesh = {*Asbestos/adverse effects ; Autopsy ; Female ; Humans ; Lung ; *Mesothelioma/etiology ; Occupational Exposure ; *Pleural Neoplasms/etiology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) due to environmental and familial (domestic) asbestos exposure is well recognized. However, information on cumulative asbestos dose in subjects affected by MPM is limited.<br><br>OBJECTIVES: To evaluate the residual lung asbestos fibre and asbestos body burden in women with MPM with past environmental and/or familial asbestos exposure.<br><br>METHODS: We collected lung samples from autopsies regarding 15 non-occupationally asbestos-exposed MPM cases, divided in three groups: (i) familial exposure from the Fincantieri shipyards in Monfalcone (No. 7), (ii) environmental and familial asbestos exposure from the asbestos-cement plant Fibronit in Broni (No. 6), and (iii) environmental exposure from the Fibronit plant (No. 2). Asbestos body (AB) and fibres (AF) per gram of dry lung tissue were counted by optical and scanning electron microscopy, respectively, and expressed as geometric means and standard deviations (GM, GSD).<br><br>RESULTS: GM/GSD of AB counts were 6123/9.6 (Group 1), 13 800/10.4 (Group 2), and 8400/1.1 (Group 3); GM/GSD of AF were 0.6/2.1 (Group 1), 7.9/2.1 (Group 2), and 6.0/2.3 (Group 3) million. Pleural plaques were observed in 12 cases.<br><br>CONCLUSIONS: Exclusive familial exposure to asbestos determined cumulative doses close to those observed in moderate occupational exposure circumstances. Our results also suggest that combined environmental and familial exposures may cause unexpectedly high cumulative fibre doses.}, }
@article {pmid32054819, year = {2020}, author = {, }, title = {Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {3}, pages = {151-159}, pmid = {32054819}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Carcinogens ; Disabled Persons/statistics &amp; numerical data ; Female ; Global Burden of Disease/*statistics &amp; numerical data/*trends ; Global Health/statistics &amp; numerical data/trends ; Humans ; *Life Expectancy ; Lung Neoplasms/mortality ; Male ; Mesothelioma ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/*epidemiology/mortality ; Occupational Diseases/epidemiology ; Occupational Exposure/adverse effects/*statistics &amp; numerical data ; Quality-Adjusted Life Years ; Risk Assessment ; Risk Factors ; Sex Distribution ; Socioeconomic Factors ; Young Adult ; }, abstract = {OBJECTIVES: This study provides a detailed analysis of the global and regional burden of cancer due to occupational carcinogens from the Global Burden of Disease 2016 study.<br><br>METHODS: The burden of cancer due to 14 International Agency for Research on Cancer Group 1 occupational carcinogens was estimated using the population attributable fraction, based on past population exposure prevalence and relative risks from the literature. The results were used to calculate attributable deaths and disability-adjusted life years (DALYs).<br><br>RESULTS: There were an estimated 349&#x2009;000 (95% Uncertainty Interval 269&#x2009;000 to 427&#x2009;000) deaths and 7.2 (5.8 to 8.6)&#x2009;million DALYs in 2016 due to exposure to the included occupational carcinogens-3.9% (3.2% to 4.6%) of all cancer deaths and 3.4% (2.7% to 4.0%) of all cancer DALYs; 79% of deaths were of males and 88% were of people aged 55 -79 years. Lung cancer accounted for 86% of the deaths, mesothelioma for 7.9% and laryngeal cancer for 2.1%. Asbestos was responsible for the largest number of deaths due to occupational carcinogens (63%); other important risk factors were secondhand smoke (14%), silica (14%) and diesel engine exhaust (5%). The highest mortality rates were in high-income regions, largely due to asbestos-related cancers, whereas in other regions cancer deaths from secondhand smoke, silica and diesel engine exhaust were more prominent. From 1990 to 2016, there was a decrease in the rate for deaths (-10%) and DALYs (-15%) due to exposure to occupational carcinogens.<br><br>CONCLUSIONS: Work-related carcinogens are responsible for considerable disease burden worldwide. The results provide guidance for prevention and control initiatives.}, }
@article {pmid32050546, year = {2020}, author = {Töreyin, ZN and Ghosh, M and Göksel, &#xd6; and Göksel, T and Godderis, L}, title = {Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, pmid = {32050546}, issn = {1660-4601}, mesh = {*Asbestos ; *Biomarkers, Tumor/analysis ; *Breath Tests ; Exhalation ; Humans ; *Mesothelioma/diagnosis ; Prospective Studies ; *Volatile Organic Compounds ; }, abstract = {Malignant pleural mesothelioma (MPM) is mainly related to previous asbestos exposure. There is still dearth of information on non-invasive biomarkers to detect MPM at early stages. Human studies on exhaled breath biomarkers of cancer and asbestos-related diseases show encouraging results. The aim of this systematic review was to provide an overview on the current knowledge about exhaled breath analysis in MPM diagnosis. A systematic review was conducted on MEDLINE (PubMed), EMBASE and Web of Science databases to identify relevant studies. Quality assessment was done by the Newcastle-Ottawa Scale. Six studies were identified, all of which showed fair quality and explored volatile organic compounds (VOC) based breath profile using Gas Chromatography Coupled to Mass Spectrometry (GC-MS), Ion Mobility Spectrometry Coupled to Multi-capillary Columns (IMS-MCC) or pattern-recognition technologies. Sample sizes varied between 39 and 330. Some compounds (i.e, cyclohexane, P3, P5, P50, P71, diethyl ether, limonene, nonanal, VOC IK 1287) that can be indicative of MPM development in asbestos exposed population were identified with high diagnostic accuracy rates. E-nose studies reported breathprints being able to distinguish MPM from asbestos exposed individuals with high sensitivity and a negative predictive value. Small sample sizes and methodological diversities among studies limit the translation of results into clinical practice. More prospective studies with standardized methodologies should be conducted on larger populations.}, }
@article {pmid32050285, year = {2020}, author = {Habbel, VSA and Mahler, EA and Feyerabend, B and Oldhafer, KJ and Lipp, MJ}, title = {[Diffuse malignant peritoneal mesothelioma (DMPM) - a rare diagnosis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {58}, number = {2}, pages = {146-151}, doi = {10.1055/a-1083-6962}, pmid = {32050285}, issn = {1439-7803}, mesh = {Antineoplastic Agents/*administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols ; Combined Modality Therapy ; *Cytoreduction Surgical Procedures/methods ; Female ; Humans ; Hyperthermia, Induced/*methods ; Male ; Mesothelioma/drug therapy/mortality/surgery/*therapy ; Peritoneal Neoplasms/drug therapy/mortality/surgery/*therapy ; Prognosis ; Survival Rate ; }, abstract = {Diffuse malignant peritoneal mesothelioma (DMPM) is a rare diagnosis, found more frequently in men than in women. Symptoms are unspecific abdominal disorders making that diagnosis difficult to set. Causes of DMPM are yet to be discovered in entirety. Asbestos exposure is the reason for approximately 7 % of all peritoneal mesotheliomas. Until the evaluation of systematic cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) DMPM was a fatal diagnosis with a median overall survival (OS) of 4-13 months. The prognosis of DMPM dramatically improved with implementation of CRS and HIPEC to an OS of 30-92 month nowadys. CRS and HIPEC were performed in this case.}, }
@article {pmid32050148, year = {2020}, author = {Singh, R and Cherrie, JW and Rao, B and Asolekar, SR}, title = {Assessment of the future mesothelioma disease burden from past exposure to asbestos in ship recycling yards in India.}, journal = {International journal of hygiene and environmental health}, volume = {225}, number = {}, pages = {113478}, doi = {10.1016/j.ijheh.2020.113478}, pmid = {32050148}, issn = {1618-131X}, mesh = {Adult ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Humans ; India ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Recycling ; *Ships ; Young Adult ; }, abstract = {The recycling of end-of-life vessels is a complex activity that generates an enormous amount of hazardous waste, including asbestos-containing materials (ACM). Efforts by the Government of India to comply with national and international regulations and improved standard operating procedures are expected to lower the exposure risk of the workforce to hazardous substances, including asbestos. The current workers are likely to face lesser risks than did those exposed in the past. The present study assesses the health risks from past exposure of asbestos for those workers engaged in handling and removing ACM in ship recycling yards before environmentally sound recycling of obsolete ships was introduced in the early 2000s. Estimates were made of the number of workers exposed, and the intensity of exposure and these data were used to estimate the likely number of mesothelioma deaths in the future. It was estimated that nearly 15% of the total workforce engaged in ship recycling will suffer from mesothelioma which translates to about 4,513 mesothelioma deaths among the total of 31,000 workers estimated to be ever employed in the yards from 1994 till 2002. Recommendations are made for a practical approach to the safe handling of ACMs in Indian ship recycling yards.}, }
@article {pmid32041759, year = {2020}, author = {Ahmed, ST and Barvo, M and Kamath, N and Alweis, R}, title = {Acute popliteal thrombus workup leads to discovery of primary peritoneal mesothelioma in the absence of any known asbestos exposure.}, journal = {BMJ case reports}, volume = {13}, number = {2}, pages = {}, pmid = {32041759}, issn = {1757-790X}, mesh = {Abdomen/diagnostic imaging ; Aged ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos ; Ascites/diagnostic imaging ; Biopsy, Large-Core Needle ; Carboplatin/therapeutic use ; Diagnosis, Differential ; Emergency Service, Hospital ; Humans ; Lung Neoplasms/*diagnosis/drug therapy ; Male ; Mesothelioma/*diagnosis/drug therapy ; Mesothelioma, Malignant ; Pelvis/diagnostic imaging ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/drug therapy ; Popliteal Artery/surgery ; Positron Emission Tomography Computed Tomography ; Thrombosis/surgery ; }, abstract = {A 75-year-old man presented to the emergency department with 1-day history of right lower limb pain and 3-month history of vague abdominal pain. In the emergency department a thrombus was discovered in the right popliteal artery. CT scan of the abdomen and pelvis revealed high-density material in the pelvis, multiple hypodensities on the liver, ascites with omental nodularity, and high-density material along the stomach wall. He underwent thrombectomy and was started on anticoagulation therapy. The core needle biopsy revealed primary omental mesothelioma. There was no history of any known asbestos exposure. He also had to undergo therapeutic paracentesis twice due to abdominal distension. Mesothelioma treatment of carboplatin and pemetrexed was started, and the patient is currently receiving this chemotherapy treatment regimen.}, }
@article {pmid32041124, year = {2020}, author = {Airoldi, C and Ferrante, D and Miligi, L and Piro, S and Stoppa, G and Migliore, E and Chellini, E and Romanelli, A and Sciacchitano, C and Mensi, C and Cavone, D and Romeo, E and Massari, S and Marinaccio, A and Magnani, C}, title = {Estimation of Occupational Exposure to Asbestos in Italy by the Linkage of Mesothelioma Registry (ReNaM) and National Insurance Archives. Methodology and Results.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, pmid = {32041124}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; Humans ; Industry ; Italy ; Mesothelioma/*chemically induced ; National Health Programs ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.}, }
@article {pmid32040984, year = {2020}, author = {Wylie, AG and Korchevskiy, A and Segrave, AM and Duane, A}, title = {Modeling mesothelioma risk factors from amphibole fiber dimensionality: mineralogical and epidemiological perspective.}, journal = {Journal of applied toxicology : JAT}, volume = {40}, number = {4}, pages = {515-524}, doi = {10.1002/jat.3923}, pmid = {32040984}, issn = {1099-1263}, mesh = {Aerosols ; Asbestos, Amphibole/*adverse effects/analysis ; Construction Materials/*adverse effects/analysis ; Humans ; Linear Models ; Mesothelioma/diagnosis/*epidemiology ; *Models, Theoretical ; Nonlinear Dynamics ; Occupational Exposure/*adverse effects ; Particle Size ; Risk Assessment ; Risk Factors ; }, abstract = {Amphiboles are common rock-forming minerals but when they form asbestos, they are known carcinogens. Mesothelioma mortality among miners and millers per the unit of asbestiform amphibole exposure varies significantly across cohorts when asbestos exposure measurements are based on the membrane filter method. Because the cohorts were exposed to different occurrences of asbestiform amphibole, variance in mesothelioma potency (RM) among cohorts is likely due to differences in exposure characteristics not reflected by the membrane filter method. In this paper using both linear and nonlinear models we correlate RM from four mining and milling cohorts with two-dimensional parameters of the exposure. The parameters are based on the proportion of elongated minerals that are >5 μm in length from each occurrence that also have either (a) width ≤ 0.15 μm, or (b) width ≤ 0.25 μm. Based on the models we derived, it was possible to quantify RM for the occurrences of asbestiform amphibole associated with mesothelioma excess but for which epidemiologically based RM has not been published. It was demonstrated that modeled RM for amphibole occurrences in nonasbestiform habits are lower (fibrous glaucophane) or not significant (cleavage fragments). The results of the study can be used in a risk assessment of elongated mineral particles and have implications for public policy and regulations.}, }
@article {pmid32039010, year = {2019}, author = {Nicolini, F and Bocchini, M and Bronte, G and Delmonte, A and Guidoboni, M and Crinò, L and Mazza, M}, title = {Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1519}, pmid = {32039010}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CAR-T cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and on-going clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.}, }
@article {pmid32035500, year = {2020}, author = {Pais, A and Pinto, N and Cardoso, J and Fernandes, M and Coutinho, AI and Oliveira, AS and Carvalho, L and Bárbara, C}, title = {[Diffuse Intraparenchymal Mesothelioma: An Atypical Presentation].}, journal = {Acta medica portuguesa}, volume = {33}, number = {2}, pages = {143-146}, doi = {10.20344/amp.11406}, pmid = {32035500}, issn = {1646-0758}, mesh = {Asbestosis/*diagnosis ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma, Malignant/*diagnosis ; Middle Aged ; Occupational Diseases/*diagnosis ; Pleural Neoplasms/*diagnosis ; }, abstract = {Pleural mesothelioma is a disease associated with exposure to asbestos. Although rare, it is the most common malignant pleural neoplasm. It is difficult to diagnose and it has a poor prognosis. We report the case of a 62-year-old male patient with a history of prolonged occupational exposure to asbestos, with dyspnea for minor exertion and productive cough, for several months. Imaging studies revealed extensive interstitial involvement with marked thickening of the interlobular and centrilobular septa and tenuous pleural involvement. Several differential diagnoses were considered such as, asbestosis, cryptogenic organizing pneumonia, desquamative interstitial pneumonia, pleuropulmonary metastases, and/or bronchopulmonary infection, but the histological and immunohistochemical results were compatible with pleural mesothelioma - a rare malignant neoplasm, with pleural origin, with a high mortality rate.}, }
@article {pmid32033249, year = {2020}, author = {Aoki, K and Saito, N}, title = {Biocompatibility and Carcinogenicity of Carbon Nanotubes as Biomaterials.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {32033249}, issn = {2079-4991}, abstract = {With the development of nanotechnology in recent years, there have been concerns about the health effects of nanoparticles. Carbon nanotubes (CNTs) are fibrous nanoparticles with a micro-sized length and nano-sized diameter, which exhibit excellent physical properties and are widely studied for their potential application in medicine. However, asbestos has been historically shown to cause pleural malignant mesothelioma and lung cancer by inhalation exposure. Because carbon nanotubes are also fibrous nanotubes, some have raised concerns about its possible carcinogenicity. We have reported that there is no clear evidence of carcinogenicity by local and intravenous administration of multi-walled CNTs to cancer mice models. We firmly believe that CNTs can be a safe, new, and high-performance biomaterials by controlling its type, site of administration, and dosage.}, }
@article {pmid32021524, year = {2020}, author = {Cheng, YY and Rath, EM and Linton, A and Yuen, ML and Takahashi, K and Lee, K}, title = {The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {11}, number = {}, pages = {1-11}, pmid = {32021524}, issn = {1179-2728}, abstract = {Asbestos is a naturally occurring mineral consisting of extremely fine fibres that can become trapped in the lungs after inhalation. Occupational and environmental exposures to asbestos are linked to development of lung cancer and malignant mesothelioma, a cancer of the lining surrounding the lung. This review discusses the factors that are making asbestos-induced lung cancer a continuing problem, including the extensive historic use of asbestos and decades long latency between exposure and disease development. Genomic mutations of DNA nucleotides and gene rearrangements driving lung cancer are well-studied, with biomarkers and targeted therapies already in clinical use for some of these mutations. The genes involved in these mutation biomarkers and targeted therapies are also involved in epigenetic mechanisms and are discussed in this review as it is hoped that identification of epigenetic aberrations in these genes will enable the same gene biomarkers and targeted therapies to be used. Currently, understanding of how asbestos fibres trapped in the lungs leads to epigenetic changes and lung cancer is incomplete. It has been shown that oxidoreduction reactions on fibre surfaces generate reactive oxygen species (ROS) which in turn damage DNA, leading to genetic and epigenetic alterations that reduce the activity of tumour suppressor genes. Epigenetic DNA methylation changes associated with lung cancer are summarised in this review, and some of these changes will be due to asbestos exposure. So far, little research has been carried out to separate the asbestos driven epigenetic changes from those due to non-asbestos causes of lung cancer. Asbestos-associated lung cancers exhibit less methylation variability than lung cancers in general, and in a large proportion of samples variability has been found to be restricted to promoter regions. Epigenetic aberrations in cancer are proving to be promising biomarkers for diagnosing cancers. It is hoped that further understanding of epigenetic changes in lung cancer can result in useful asbestos-associated lung cancer biomarkers to guide treatment. Research is ongoing into the detection of lung cancer epigenetic alterations using non-invasive samples of blood and sputum. These efforts hold the promise of non-invasive cancer diagnosis in the future. Efforts to reverse epigenetic aberrations in lung cancer by epigenetic therapies are ongoing but have not yet yielded success.}, }
@article {pmid32006662, year = {2020}, author = {Gaetani, S and Monaco, F and Alessandrini, F and Tagliabracci, A and Sabbatini, A and Bracci, M and Valentino, M and Neuzil, J and Amati, M and Santarelli, L and Tomasetti, M}, title = {Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {121}, number = {}, pages = {105700}, doi = {10.1016/j.biocel.2020.105700}, pmid = {32006662}, issn = {1878-5875}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinogens/*chemistry ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/*metabolism ; }, abstract = {MiR-222 and miR-126 are associated with asbestos exposure and the ensuing malignancy, but the mechanism(s) of their regulation remain unclear. We evaluated the mechanism by which asbestos regulates miR-222 and miR-126 expression in the context of cancer etiology. An 'in vitro' model of carcinogen-induced cell transformation was used based on exposing bronchial epithelium BEAS-2B cells to three different carcinogens including asbestos. Involvement of the EGFR pathway and the role of epigenetics have been investigated in carcinogen-transformed cells and in malignant mesothelioma, a neoplastic disease associated with asbestos exposure. Increased expression of miR-222 and miR-126 were found in asbestos-transformed cells, but not in cells exposed to arsenic and chrome. Asbestos-mediated activation of the EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation, which was reversed by EGFR inhibition. Conversely, asbestos-induced miR-126 expression was affected neither by EGFR modulation nor inflammation. Rather than methylation of the miR-126 host gene EGFL7, epigenetic mechanism involving DNMT1- and PARP1-mediated chromatin remodeling was found to upregulate of miR-126 in asbestos-exposed cells, while miR-126 was downregulated in malignant cells. Analysis of MM tissue supported the role of PARP1 in miR-126 regulation. Therefore, activation of the EGFR pathway and the PARP1-mediated epigenetic regulation both play a role in asbestos-induced miRNA expression, associated with in asbestos-induced carcinogenesis and tumor progression.}, }
@article {pmid32005436, year = {2020}, author = {Fels Elliott, DR and Jones, KD}, title = {Diagnosis of Mesothelioma.}, journal = {Surgical pathology clinics}, volume = {13}, number = {1}, pages = {73-89}, doi = {10.1016/j.path.2019.10.001}, pmid = {32005436}, issn = {1875-9157}, mesh = {Biopsy ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/*diagnosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Mesothelioma/*diagnosis/diagnostic imaging/pathology ; Radiography ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma is a rare neoplasm that arises from mesothelial cells lining body cavities including the pleura, pericardium, peritoneum, and tunica vaginalis. Most malignant mesotheliomas occur in the chest and are frequently associated with a history of asbestos exposure. The diagnosis of malignant mesothelioma is challenging and fraught with pitfalls, particularly in small biopsies. This article highlights what the pathologist needs to know regarding the clinical and radiographic presentation of mesothelioma, histologic features including subtypes and variants, and recent advances in immunohistochemical markers and molecular testing.}, }
@article {pmid32002299, year = {2020}, author = {Ma, S and Chee, J and Fear, VS and Forbes, CA and Boon, L and Dick, IM and Robinson, BWS and Creaney, J}, title = {Pre-treatment tumor neo-antigen responses in draining lymph nodes are infrequent but predict checkpoint blockade therapy outcome.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684714}, pmid = {32002299}, issn = {2162-4011}, mesh = {Animals ; Antigens, Neoplasm/genetics ; *Cancer Vaccines ; Humans ; Immune Checkpoint Inhibitors/*pharmacology ; Intracellular Signaling Peptides and Proteins/genetics ; Lymph Nodes ; Mice ; *Neoplasms/genetics/therapy ; T-Lymphocytes, Cytotoxic ; }, abstract = {Immune checkpoint blockade (ICPB) is a powerfully effective cancer therapy in some patients. Tumor neo-antigens are likely main targets for attack but it is not clear which and how many tumor mutations in individual cancers are actually antigenic, with or without ICPB therapy and their role as neo-antigen vaccines or as predictors of ICPB responses. To examine this, we interrogated the immune response to tumor neo-antigens in a murine model in which the tumor is induced by a natural human carcinogen (i.e. asbestos) and mimics its human counterpart (i.e. mesothelioma). We identified and screened 33 candidate neo-antigens, and found T cell responses against one candidate in tumor-bearing animals, mutant UQCRC2. Interestingly, we found a high degree of inter-animal variation in the magnitude of neo-antigen responses in otherwise identical mice. ICPB therapy with Cytotoxic T-lymphocyte-associated protein (CTLA-4) and α-glucocorticoid-induced TNFR family related gene (GITR) in doses that induced tumor regression, increased the magnitude of responses and unmasked functional T cell responses against another neo-antigen, UNC45a. Importantly, the magnitude of the pre-treatment draining lymph node (dLN) response to UNC45a closely corresponded to ICPB therapy outcomes. Surprisingly however, boosting pre-treatment UNC45a-specific T cell numbers did not improve response rates to ICPB. These observations suggest a novel biomarker approach to the clinical prediction of ICPB response and have important implications for the development of neo-antigen vaccines.}, }
@article {pmid32002298, year = {2020}, author = {Sneddon, S and Rive, CM and Ma, S and Dick, IM and Allcock, RJN and Brown, SD and Holt, RA and Watson, M and Leary, S and Lee, YCG and Robinson, BWS and Creaney, J}, title = {Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684713}, pmid = {32002298}, issn = {2162-4011}, mesh = {Antigens, Neoplasm/genetics ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Immunotherapy ; *Mesothelioma, Malignant/immunology ; Receptors, Cell Surface ; }, abstract = {Neoantigens present unique and specific targets for personalized cancer immunotherapy strategies. Given the low mutational burden yet immunotherapy responsiveness of malignant mesothelioma (MM) when compared to other carcinogen-induced malignancies, identifying candidate neoantigens and T cells that recognize them has been a challenge. We used pleural effusions to gain access to MM tumor cells as well as immune cells in order to characterize the tumor-immune interface in MM. We characterized the landscape of potential neoantigens from SNVs identified in 27 MM patients and performed whole transcriptome sequencing of cell populations from 18 patient-matched pleural effusions. IFNγ ELISpot was performed to detect a CD8+ T cell responses to predicted neoantigens in one patient. We detected a median of 68 (range 7-258) predicted neoantigens across the samples. Wild-type non-binding to mutant binding predicted neoantigens increased risk of death in a model adjusting for age, sex, smoking status, histology and treatment (HR: 33.22, CI: 2.55-433.02, p = .007). Gene expression analysis indicated a dynamic immune environment within the pleural effusions. TCR clonotypes increased with predicted neoantigen burden. A strong activated CD8+ T-cell response was identified for a predicted neoantigen produced by a spontaneous mutation in the ROBO3 gene. Despite the challenges associated with the identification of bonafide neoantigens, there is growing evidence that these molecular changes can provide an actionable target for personalized therapeutics in difficult to treat cancers. Our findings support the existence of candidate neoantigens in MM despite the low mutation burden of the tumor, and may present improved treatment opportunities for patients.}, }
@article {pmid31977466, year = {2020}, author = {Fernández-Rodríguez, P and Martín-Marcuartu, JJ and Acevedo Báñez, I and Masero Carretero, JM and Jiménez-Hoyuela García, JM}, title = {99mTc-HDP Bone Scintigraphy, SPECT/CT, and 18F-FDG PET/CT Diagnosis Imaging of Incidental Pleural Mesothelioma in a Patient With Biochemical Recurrences of Prostate Cancer: Is it Really a Coincidence?.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {3}, pages = {e148-e150}, doi = {10.1097/RLU.0000000000002908}, pmid = {31977466}, issn = {1536-0229}, mesh = {Aged ; Diphosphonates ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/complications/*diagnostic imaging ; Male ; Mesothelioma/complications/*diagnostic imaging ; Mesothelioma, Malignant ; Organotechnetium Compounds ; Pleural Neoplasms/complications/*diagnostic imaging ; *Positron Emission Tomography Computed Tomography ; Prostatic Neoplasms/blood/*complications ; Radiopharmaceuticals ; *Single Photon Emission Computed Tomography Computed Tomography ; }, abstract = {We present the case of a 69-year-old man with history of prostate carcinoma treated with prostatectomy and subsequently with external beam radiotherapy and hormone therapy because of biochemical recurrences. More than 10 years after the diagnosis, follow-up Tc-HDP bone scans and SPECT/CT images demonstrated an incidental diagnosis of osteoblastic pleural plaques that quickly evolve to mesothelioma. PET/CT achieved the definitive diagnosis by guiding the biopsy to the highest and most accessible focus of glucidic hypermetabolism. Our case report raises the association between prostate cancer patients treated with external beam radiotherapy and the development of pleural mesothelioma despite having no history of exposure to asbestos.}, }
@article {pmid31967100, year = {2019}, author = {Vimercati, L and Cavone, D and Mansi, F and Cannone, ESS and DE Maria, L and Caputi, A and Delfino, MC and Serio, G}, title = {Health impact of exposure to asbestos in polluted area of Southern Italy.}, journal = {Journal of preventive medicine and hygiene}, volume = {60}, number = {4}, pages = {E407-E418}, pmid = {31967100}, issn = {2421-4248}, mesh = {*Asbestos ; Asbestosis/epidemiology/*mortality ; Cardiovascular Diseases/mortality ; Cause of Death ; *Environmental Exposure ; *Environmental Pollution ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/mortality ; Mesothelioma/epidemiology/*mortality ; Neoplasms/epidemiology/mortality ; *Occupational Exposure ; Peritoneal Neoplasms/epidemiology/mortality ; Personal Protective Equipment ; Pleural Neoplasms/epidemiology/*mortality ; }, abstract = {The three main sources of asbestos pollution in the city of Bari, Puglia, the former Fibronit asbestos factory, the Torre Quetta beach, the former Rossani barracks and the history of their reclamation are described. The results of cohort studies on factory workers and case-control studies on asbestos exposure to the resident population and the onset of mesothelioma are also reported. Finally, the data of the regional register of mesothelioma related to residents in the city of Bari and four new cases with environmental exposure due to the former Rossani barracks are presented.}, }
@article {pmid31965908, year = {2019}, author = {Peterson, MK and Mohar, I and Lam, T and Cook, TJ and Engel, AM and Lynch, H}, title = {Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {7}, pages = {597-613}, doi = {10.1080/10408444.2019.1692190}, pmid = {31965908}, issn = {1547-6898}, mesh = {Animals ; *Asbestos ; Environmental Exposure/*statistics &amp; numerical data ; Esophageal Neoplasms/*epidemiology ; *Hazardous Substances ; Humans ; }, abstract = {Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.}, }
@article {pmid31963601, year = {2020}, author = {Oddone, E and Bollon, J and Nava, CR and Bugani, M and Consonni, D and Marinaccio, A and Magnani, C and Barone-Adesi, F}, title = {Predictions of Mortality from Pleural Mesothelioma in Italy After the Ban of Asbestos Use.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {2}, pages = {}, pmid = {31963601}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Epidemics/*statistics &amp; numerical data ; Female ; Forecasting ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; }, abstract = {Even if the epidemic of malignant pleural mesothelioma (MPM) is still far from being over worldwide, the health effects of regulations banning asbestos can be evaluated in the countries that implemented them early. Estimates of MPM future burden can be useful to inform and support the implementation of anti-asbestos health policies all around the world. With this aim we described the trends of MPM deaths in Italy (1970-2014) and predicted the future number of cases in both sexes (2015-2039), with consideration of the national asbestos ban that was issued in 1992. The Italian National Statistical Institute (ISTAT) provided MPM mortality figures. Cases ranging from 25 to 89 years of age were included in the analysis. For each five-year period from 1970 to 2014, mortality rates were calculated and age-period-cohort Poisson models were used to predict future burden of MPM cases until 2039. During the period 1970-2014 a total number of 28,907 MPM deaths were observed. MPM deaths increased constantly over the study period, ranging from 1356 cases in 1970-1974 to 5844 cases in 2010-2014. The peak of MPM cases is expected to be reached in the period 2020-2024 (about 7000 cases). The decrease will be slow: about 26,000 MPM cases are expected to occur in Italy during the next 20 years (2020-2039). The MPM epidemic in Italy is far from being concluded despite the national ban implemented in 1992, and the peak is expected in 2020-2024, in both sexes. Our results are consistent with international literature.}, }
@article {pmid31929796, year = {2019}, author = {Borchert, S and Suckrau, PM and Wessolly, M and Mairinger, E and Hegedus, B and Hager, T and Herold, T and Eberhardt, WEE and Wohlschlaeger, J and Aigner, C and Bankfalvi, A and Schmid, KW and Walter, RFH and Mairinger, FD}, title = {Screening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy.}, journal = {Journal of oncology}, volume = {2019}, number = {}, pages = {2902985}, pmid = {31929796}, issn = {1687-8450}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor associated with a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons underlying the rather poor efficacy of platinum compounds remain largely unknown. Kinase activity might influence cellular response to these regimens.<br><br>MATERIALS AND METHODS: For this exploratory study, we screened MPM cell lines (NCI-H2452, NCI-H2052, and MSTO-211H) differing in response to cisplatin and benign control fibroblasts (MRC-5) for overall phosphorylation patterns as well as kinase activity with respect to cellular response to cisplatin-based therapeutics. We analysed the cell lines for cellular kinases in a high-throughput manner using the highly innovative technique PamGene. Cell state analysis including apoptosis, necrosis, and cell viability was performed by using enzyme activity and fluorescent-based assays.<br><br>RESULTS: Cisplatin alters cellular phosphorylation patterns affecting cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis. In cisplatin-responsive cell lines, phosphorylation of AKT1 and GSK3B was decreased but could not be influenced in cisplatin-resistant NCI-H2452 cells. Cisplatin-responsive cell lines showed increased phosphorylation levels of JNK1/2/3 but decreased phosphorylation in cisplatin-resistant NCI-H2452 cells.<br><br>CONCLUSION: Kinase phosphorylation and activity might play a crucial role in cellular response to cytostatic agents. Cisplatin influences phosphorylation patterns with distinct features in cisplatin-resistant cells. These alterations exert a significant impact on cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis of the respective tumor cells. Based on our results, the induction of p38 or JNK1/3, or inhibition of AKT1 by, for example, BIA-6, might offer a positive synergistic effect by induction of an apoptotic response to cisplatin-based treatment, thus potentially enhancing the clinical outcome of MPM patients.}, }
@article {pmid31927297, year = {2020}, author = {Cox, LA}, title = {Nonlinear dose-time-response functions and health-protective exposure limits for inflammation-mediated diseases.}, journal = {Environmental research}, volume = {182}, number = {}, pages = {109026}, doi = {10.1016/j.envres.2019.109026}, pmid = {31927297}, issn = {1096-0953}, mesh = {*Asbestos/toxicity ; Humans ; Inflammation ; Inhalation Exposure ; *Mesothelioma ; *Occupational Exposure ; *Occupational Health ; *Silicon Dioxide/toxicity ; Threshold Limit Values ; United States ; }, abstract = {Why have occupational safety regulations in the United States not been more successful in protecting worker health from mesothelioma risks, while apparently succeeding relatively well in reducing silicosis risks? This paper briefly discusses biological bases for thresholds and nonlinearities in exposure-response functions for respirable crystalline silica (RCS) and asbestos, based on modeling a chronic inflammation mode of action (mediated by activation of the NLRP3 inflammasome, for both RCS and asbestos). It applies previously published physiologically based pharmacokinetic (PBPK) models to perform computational experiments illuminating how different time courses of exposure with the same time-weighted average (TWA) concentration affect internal doses in target tissues (lung for RCS and mesothelium for asbestos). Key conclusions are that (i) For RCS, but not asbestos, limiting average (TWA) exposure concentrations also tightly constrains internal doses and ability to trigger chronic inflammation and resulting increases in disease risks (ii) For asbestos, excursions (i.e., spikes in concentrations); and especially the times between them are crucial drivers of internal doses and time until chronic inflammation; and hence (iii) These dynamic aspects of exposure, which are not addressed by current occupational safety regulations, should be constrained to better protect worker health. Adjusting permissible average exposure concentration limits (PELs) and daily excursion limits (ELs) is predicted to have little impact on reducing mesothelioma risks, but increasing the number of days between successive excursions is predicted to be relatively effective in reducing worker risks, even if it has little or no impact on TWA average concentrations.}, }
@article {pmid31921422, year = {2020}, author = {Kim, MK and Kim, HW and Jang, M and Oh, SS and Yong, SJ and Jeong, Y and Jung, SH and Choi, JW}, title = {LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma.}, journal = {Biomarker research}, volume = {8}, number = {}, pages = {1}, pmid = {31921422}, issn = {2050-7771}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database.<br><br>METHODS: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction.<br><br>RESULTS: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&amp;2 (LOXL1&amp; LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11).<br><br>CONCLUSIONS: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.}, }
@article {pmid31917456, year = {2020}, author = {Ugelvig Petersen, K and Pukkala, E and Martinsen, JI and Lynge, E and Tryggvadottir, L and Weiderpass, E and Kjærheim, K and Heikkinen, S and Hansen, J}, title = {Cancer incidence among seafarers and fishermen in the Nordic countries.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {46}, number = {5}, pages = {461-468}, pmid = {31917456}, issn = {1795-990X}, mesh = {Adult ; Aged ; Humans ; Incidence ; Male ; Middle Aged ; Naval Medicine/*statistics &amp; numerical data ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Scandinavian and Nordic Countries/epidemiology ; }, abstract = {Objectives Maritime workers may be exposed to several occupational hazards at sea. The aim of this study was to assess cancer incidence among seafarers and fishermen in the Nordic countries and identify patterns in morbidity in the context of existing studies in this field. Methods A cohort of 81 740 male seafarers and 66 926 male fishermen was established from census data on 15 million citizens in the five Nordic countries. Using personal identity codes, information on vital status and cancer was linked to members of the cohort from the national population and cancer registries for the follow-up period 1961-2005. Standardized incidence ratios (SIR) were calculated applying national cancer incidence rates for each country and pooling results. Results The overall incidence of cancer was increased among the male seafarers [SIR 1.22, 95% confidence interval (CI) 1.19-1.23]. Significant excesses were observed for multiple cancer sites among the seafarers, while results for the fishermen were mixed. Lip cancer incidence was increased among both maritime populations. For mesothelioma (SIR 2.17, 95% CI 1.83-2.56 seafarers) and non-melanoma skin cancer (SIR 1.23, 95% CI 1.14-1.32 seafarers), incidence was increased among the seafarers. Conclusion In our cohort, seafaring was associated with a higher overall incidence of cancer compared to the general population. While the majority of cancers could not be linked to specific occupational factors, increases in mesothelioma, lip and non-melanoma-skin cancer indicate previous exposure to asbestos, ultraviolet radiation and potentially also chemicals with dermal carcinogenic properties at sea.}, }
@article {pmid31916469, year = {2020}, author = {Dodson, RF and Poye, LW}, title = {Tissue burden evaluation of elongated mineral particles in two individuals with mesothelioma and whose work history included manufacturing tile.}, journal = {Ultrastructural pathology}, volume = {44}, number = {1}, pages = {17-31}, doi = {10.1080/01913123.2019.1709935}, pmid = {31916469}, issn = {1521-0758}, mesh = {Asbestos, Amphibole/adverse effects/*analysis ; Humans ; Male ; Mesothelioma, Malignant/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; Talc/adverse effects/*agonists ; }, abstract = {Two cases with diagnosis of mesothelioma were referred to our laboratories with a request for tissue burden analysis in order to determine the presence of ferruginous bodies and uncoated elongated mineral particles in tissue samples. The individuals shared in common a past background of working in tile manufacturing facilities where industrial talc was used in the production of the products. Both were found to have ferruginous bodies in their lung tissues as well as elongated talc fibers/ribbons and elevated numbers of noncommercial amphiboles in their tissues. To our knowledge, this is the first report of tissue assessment for the presence of elongated mineral particles in individuals whose exposures to talc occurred were while working in the manufacture of tile products and who developed the fiber-related cancer - mesothelioma.}, }
@article {pmid31905913, year = {2019}, author = {Klebe, S and Leigh, J and Henderson, DW and Nurminen, M}, title = {Asbestos, Smoking and Lung Cancer: An Update.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {1}, pages = {}, pmid = {31905913}, issn = {1660-4601}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure ; Tobacco Smoking/*adverse effects ; }, abstract = {This review updates the scientific literature concerning asbestos and lung cancer, emphasizing cumulative exposure and synergism between asbestos exposure and tobacco smoke, and proposes an evidence-based and equitable approach to compensation for asbestos-related lung cancer cases. This update is based on several earlier reviews written by the second and third authors on asbestos and lung cancer since 1995. We reevaluated the peer-reviewed epidemiologic studies. In addition, selected in vivo and in vitro animal studies and molecular and cellular studies in humans were included. We conclude that the mechanism of lung cancer causation induced by the interdependent coaction of asbestos fibers and tobacco smoke at a biological level is a multistage stochastic process with both agents acting conjointly at all times. The new knowledge gained through this review provides the evidence for synergism between asbestos exposure and tobacco smoke in lung cancer causation at a biological level. The evaluated statistical data conform best to a multiplicative model for the interaction effects of asbestos and smoking on the lung cancer risk, with no requirement for asbestosis. Any asbestos exposure, even in a heavy smoker, contributes to causation. Based on this information, we propose criteria for the attribution of lung cancer to asbestos in smokers and non-smokers.}, }
@article {pmid31905042, year = {2019}, author = {Cox, LA}, title = {Dose-response modeling of NLRP3 inflammasome-mediated diseases: asbestos, lung cancer, and malignant mesothelioma as examples.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {7}, pages = {614-635}, doi = {10.1080/10408444.2019.1692779}, pmid = {31905042}, issn = {1547-6898}, mesh = {*Asbestos ; Carcinogens, Environmental ; *Dose-Response Relationship, Drug ; Environmental Exposure/*statistics &amp; numerical data ; Humans ; Inflammasomes ; Inflammation ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; Risk Assessment ; }, abstract = {Can a single fiber of amphibole asbestos increase the risk of lung cancer or malignant mesothelioma (MM)? Traditional linear no-threshold (LNT) risk assessment assumptions imply that the answer is yes: there is no safe exposure level. This paper draws on recent scientific progress in inflammation biology, especially elucidation of the activation thresholds for NLRP3 inflammasomes and resulting chronic inflammation, to model dose-response relationships for malignant mesothelioma and lung cancer risks caused by asbestos exposures. The modeling integrates a physiologically based pharmacokinetics (PBPK) front end with inflammation-driven two-stage clonal expansion (I-TSCE) models of carcinogenesis to describe how exposure leads to chronic inflammation, which in turn promotes carcinogenesis. Together, the combined PBPK and I-TSCE modeling predict that there are practical thresholds for exposure concentration below which asbestos exposure does not cause chronic inflammation in less than a lifetime, and therefore does not increase chronic inflammation-dependent cancer risks. Quantitative examples using model parameter estimates drawn from the literature suggest that practical thresholds may be within about a factor of 2 of some past exposure levels for some workers. The I-TSCE modeling framework explains previous puzzling aspects of asbestos epidemiology, such as why age at first exposure is a better predictor of lifetime MM risk than exposure duration. It may be a valuable tool for risk analysts when LNT assumptions are not justified due to inflammation response thresholds mediating dose-response relationships.}, }
@article {pmid31904012, year = {2019}, author = {Colin, DJ and Bejuy, O and Germain, S and Triponez, F and Serre-Beinier, V}, title = {Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {154}, pages = {}, doi = {10.3791/60272}, pmid = {31904012}, issn = {1940-087X}, mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Fluorodeoxyglucose F18/chemistry ; Humans ; Lung Neoplasms/*diagnostic imaging/metabolism/pathology ; Mesothelioma/*diagnostic imaging/metabolism/pathology ; Mesothelioma, Malignant ; Mice, Nude ; Organ Size ; Pleural Neoplasms/*diagnostic imaging/metabolism/pathology ; *Positron Emission Tomography Computed Tomography ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor arising in the mesothelium that covers the lungs, the heart, and the thoracic cavity. MPM development is mainly associated with asbestos. Treatments provide only modest survival since the median survival average is 9-18 months from the time of diagnosis. Therefore, more effective treatments must be identified. Most data describing new therapeutic targets were obtained from in vitro experiments and need to be validated in reliable in vivo preclinical models. This article describes one such reliable MPM orthotopic model obtained after injection of a human MPM cell line H2052/484 into the pleural cavity of immunodeficient athymic mice. Transplantation in the orthotopic site allows studying the progression of tumor in the natural in vivo environment. Positron emission tomography/computed tomography (PET/CT) molecular imaging using the clinical [[18]F]-2-fluoro-2-deoxy-D-glucose ([[18]F]FDG) radiotracer is the diagnosis method of choice for examining patients with MPM. Accordingly, [[18]F]FDG-PET/CT was used to longitudinally monitor the disease progression of the H2052/484 orthotopic model. This technique has a high 3R potential (Reduce the number of animals, Refine to lessen pain and discomfort, and Replace animal experimentation with alternatives) since the tumor development can be monitored non-invasively and the number of animals required could be significantly reduced. This model displays a high development rate, a rapid tumor growth, is cost-efficient and allows for rapid clinical translation. By using this orthotopic xenograft MPM model, researchers can assess biological responses of a reliable MPM model following therapeutic interventions.}, }
@article {pmid31901768, year = {2020}, author = {Lam, WS and Creaney, J and Chen, FK and Chin, WL and Muruganandan, S and Arunachalam, S and Attia, MS and Read, C and Murray, K and Millward, M and Spiro, J and Chakera, A and Gary Lee, YC and Nowak, AK}, title = {A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {140}, number = {}, pages = {87-92}, doi = {10.1016/j.lungcan.2019.12.018}, pmid = {31901768}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Benzamides/*therapeutic use ; Female ; Fibroblast Growth Factors/*antagonists &amp; inhibitors ; Follow-Up Studies ; Humans ; Male ; Mesothelioma, Malignant/*drug therapy/metabolism/pathology ; Middle Aged ; Piperazines/*therapeutic use ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; Prognosis ; Pyrazoles/*therapeutic use ; *Salvage Therapy ; Survival Rate ; }, abstract = {OBJECTIVES: Currently, there is no optimal salvage therapy for patients with malignant pleural mesothelioma (MPM) who relapse after treatment with first-line chemotherapy. In line with the strong preclinical rationale for targeting fibroblast growth factor receptor (FGFR) signalling in malignant mesothelioma, we conducted a phase II study assessing the efficacy of AZD4547, an oral tyrosine multi-kinase FGFR 1-3 inhibitor, as a second or third-line treatment.<br><br>MATERIALS AND METHODS: We conducted a single-center, open-label, single-arm phase II study of AZD4547 in eligible patients with confirmed, measurable MPM and radiological progression after first or second-line systemic chemotherapy. Patients received continuous, twice-daily oral AZD4547 on a 3-weekly cycle. The primary end point was 6-month progression free survival (PFS6). Response was assessed with CT scan every 6 weeks according to the modified RECIST criteria for mesothelioma (mRECIST) and toxicities were also assessed. The study used a Simon's two-stage design: 26 patients would be recruited to the first stage and more than 7 (27 %) of 26 patients were required to achieve PFS6 to continue to stage two, for a potential total cohort of 55 patients.<br><br>RESULTS: 3 of 24 patients (12 %) were progression-free at 6 months. Hence, the study fulfilled stopping criteria regardless of further recruitment and warranted discontinuation. The most common toxicities (across all grades) were hyperphosphatemia, xerostomia, mucositis, retinopathy, dysgeusia, and fatigue. Maximum toxicities were grade 2 or below for all patients across all cycles. There was no association between tumour BAP1 protein loss and clinical outcomes.<br><br>CONCLUSIONS: The FGFR 1-3 inhibitor AZD4547 did not demonstrate efficacy in patients with MPM who had progressed after first line treatment with platinum-based chemotherapy.}, }
@article {pmid31900296, year = {2020}, author = {Hinkamp, CA and Dalal, SN and Butt, Y and Cabo Chan, AV}, title = {Diffuse epithelioid malignant mesothelioma of the pleura presenting as a hydropneumothorax and vertebral body invasion.}, journal = {BMJ case reports}, volume = {13}, number = {1}, pages = {}, pmid = {31900296}, issn = {1757-790X}, mesh = {Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Humans ; Hydropneumothorax/*surgery ; Lung Neoplasms/*therapy ; Male ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Neoplasm Invasiveness ; Pleural Neoplasms/*therapy ; Thoracic Neoplasms/secondary/*therapy ; }, abstract = {Malignant mesothelioma is an uncommon form of neoplastic transformation of the mesothelial cells that line the serosal surfaces of the body. It most commonly affects the pleura and is often associated with pleural effusions and pleural-based masses. The annual incidence in the United States is only 3300 cases, representing less than 0.3% of all cancers worldwide, although this is likely underestimated. We present a case of diffuse epithelioid malignant pleural mesothelioma in a patient with remote, short-term asbestos exposure complicated by recurrent left-sided hydropneumothoraces and pleural-based invasion of the T12 vertebral body, which represent two rare coexisting complications. This case illustrates the importance of maintaining a broad differential for hydropneumothorax, particularly as the risk factors may be decades removed and the degree of asbestos exposure to induce a malignant mesothelioma may be smaller than has been traditionally thought.}, }
@article {pmid31895128, year = {2020}, author = {Walters, GI}, title = {Occupational exposures and idiopathic pulmonary fibrosis.}, journal = {Current opinion in allergy and clinical immunology}, volume = {20}, number = {2}, pages = {103-111}, pmid = {31895128}, issn = {1473-6322}, mesh = {*Cost of Illness ; Dust ; Humans ; Idiopathic Pulmonary Fibrosis/*epidemiology/etiology/prevention &amp; control ; Incidence ; Inhalation Exposure/adverse effects ; Meta-Analysis as Topic ; Occupational Diseases/*epidemiology/etiology/prevention &amp; control ; Occupational Exposure/*adverse effects/prevention &amp; control ; Prevalence ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: A recent meta-analysis of data from international case-control studies reports a population attributable fraction of 16% for occupational factors in the cause of idiopathic pulmonary fibrosis (IPF). Smoking, genetic factors and other prevalent diseases only partly explain IPF, and so this review aims to summarize recent progress in establishing which occupational exposures are important in cause.<br><br>RECENT FINDINGS: IPF is a rare disease, although it is the commonest idiopathic interstitial pneumonia. Epidemiological study suggests that incidence of IPF is increasing, particularly in older men. There are significant associations with IPF and occupational exposures to organic dust, including livestock, birds and animal feed, metal dust, wood dust and silica/minerals. Estimates of effect vary between studies, and are influenced by the distribution of employment, study design and case definition. Inhalation of asbestos fibres is a known cause of usual interstitial pneumonia (as seen histologically in IPF), though there are significant linear relationships between asbestos consumption, and mortality from both IPF and mesothelioma, leading to the hypothesis that low-level asbestos exposure may cause IPF.<br><br>SUMMARY: Research must focus on exposure-response relationships between asbestos and other occupational inhaled hazards, and IPF. Funding bodies and policy makers should acknowledge the significant occupational burden on IPF.}, }
@article {pmid36046389, year = {2020}, author = {Viscardi, G and Di Natale, D and Fasano, M and Brambilla, M and Lobefaro, R and De Toma, A and Galli, G}, title = {Circulating biomarkers in malignant pleural mesothelioma.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {1}, number = {6}, pages = {434-451}, pmid = {36046389}, issn = {2692-3114}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.}, }
@article {pmid31887736, year = {2019}, author = {Totaro, M and Giorgi, S and Filippetti, E and Gallo, A and Frendo, L and Privitera, G and Baggiani, A}, title = {[Asbestos in drinking water and hazards to human health: a narrative synthesis].}, journal = {Igiene e sanita pubblica}, volume = {75}, number = {4}, pages = {303-312}, pmid = {31887736}, issn = {0019-1639}, mesh = {Asbestos/*adverse effects/toxicity ; Carcinogens ; Drinking Water/*analysis ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/etiology/prevention &amp; control ; Mesothelioma/etiology/prevention &amp; control ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The term asbestos refers to six unique fibrous minerals mostly used in the production of asbestos cement sheets and pipes. According to the World Health Organization and the International Agency for Research on Cancer (IARC), there exists at least "sufficient evidence" that all types of asbestos may cause cancer in humans (mesothelioma, lung cancer, laryngeal tumor and ovarian cancer). The only asbestos limit in drinking water is 7 million fiber/liter. This study is a narrative synthesis about the possible hazards to human health related to the presence of asbestos in drinking water. The various scientific studies and epidemiological reports examined highlight that there is an ongoing debate on the possible carcinogenic risk associated with asbestos exposure through ingestion. Nevertheless, considering the latency with which diseases caused by asbestos may emerge, control measures should be adopted.}, }
@article {pmid31878930, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Response to the "Letter to the Editor" by Gabor Mezei et al., Comments on Vimercati et al., 2019, "Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (Southern Italy) mesothelioma register".}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {112}, pmid = {31878930}, issn = {1476-069X}, }
@article {pmid31878926, year = {2019}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Comments on Vimercati et al., 2019, "Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register".}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {111}, pmid = {31878926}, issn = {1476-069X}, }
@article {pmid31876833, year = {2020}, author = {Kodama, E and Kodama, T and Ichikawa, T and Ikoma, H and Hashimoto, J}, title = {18F-FDG Uptake of Localized Malignant Peritoneal Mesothelioma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {2}, pages = {161-163}, doi = {10.1097/RLU.0000000000002901}, pmid = {31876833}, issn = {1536-0229}, mesh = {Aged ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*diagnostic imaging ; Male ; Mesothelioma/*diagnostic imaging ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging ; *Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals ; }, abstract = {We present 2 cases of malignant peritoneal mesothelioma (MPM) characterized by a localized solid mass without ascites and showing F-FDG uptake. A 79-year-old man with a history of asbestos exposure suffered from an epithelioid MPM originating from the hepatoduodenal ligament with FDG uptake (SUVmax 16.8). Another 80-year-old man with esophageal cancer showed desmoplastic MPM of the small bowel mesentery with FDG uptake (SUVmax 4.0). Desmoplastic MPM is more aggressive and yields poorer prognosis compared with the epithelioid type. However, the present desmoplastic MPM case showed mild FDG uptake because of rich fibrosis.}, }
@article {pmid31876584, year = {2020}, author = {Pavlisko, EN and Liu, B and Green, C and Sporn, TA and Roggli, VL}, title = {Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases.}, journal = {The American journal of surgical pathology}, volume = {44}, number = {3}, pages = {293-304}, doi = {10.1097/PAS.0000000000001418}, pmid = {31876584}, issn = {1532-0979}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Carcinogens/toxicity ; Databases, Factual ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/chemically induced/diagnosis/mortality/*pathology ; Mesothelioma/chemically induced/diagnosis/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Prognosis ; Survival Analysis ; United States/epidemiology ; }, abstract = {We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant. The peritoneal tumors consisted of 82% epithelioid, 13% biphasic, and 5% sarcomatoid. The immunohistochemical profile was typical of what is well-accepted and previously described for MM. When examining tumor subtype and location, there was a trend toward epithelioid subtype and peritoneal location; however, this did not reach statistical significance. Age at the time of diagnosis ranged from 19 to 93 years with a mean of 60 years. The median age at time of diagnosis for pleural MM was 65 years and for peritoneal MM was 52 years. A further look at age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for epithelioid variant, and this was magnified in the peritoneum. A majority of our cases were exposed to asbestos through a household contact. Asbestosis and parietal pleural plaque were present in 5% and 50% of cases with data, respectively. Fiber analysis data was available in 67 cases; 38 cases had elevated asbestos fiber burden, and tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.}, }
@article {pmid31868762, year = {2020}, author = {Steffen, JE and Tran, T and Yimam, M and Clancy, KM and Bird, TB and Rigler, M and Longo, W and Egilman, DS}, title = {Serous Ovarian Cancer Caused by Exposure to Asbestos and Fibrous Talc in Cosmetic Talc Powders-A Case Series.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {2}, pages = {e65-e77}, doi = {10.1097/JOM.0000000000001800}, pmid = {31868762}, issn = {1536-5948}, mesh = {*Asbestos ; Asbestos, Amphibole ; *Cosmetics ; Environmental Exposure/*analysis ; Female ; Humans ; Mesothelioma ; Middle Aged ; Ovarian Neoplasms/*chemically induced ; Powders ; *Talc ; }, abstract = {OBJECTIVE: Asbestos is a known cause of ovarian cancer. We report 10 cases of serous ovarian cancer among users of Johnson &amp; Johnson (J&amp;J) asbestos-containing "cosmetic" talc products.<br><br>METHODS: We conducted an asbestos exposure assessment during talc application and analyzed surgical tissues and talc containers for asbestos and talc.<br><br>RESULTS: Talc was found in all cases and tremolite and/or anthophyllite asbestos was found in 8/10 cases. The asbestos fibers found in the "cosmetic" talc containers matched those found in tissues. We estimated inhaled asbestos dose ranged from 0.38 to 5.18 fiber years.<br><br>CONCLUSION: We provide evidence that the inhaled dose of asbestos/fibrous talc from "cosmetic" talc use causes ovarian cancer. The unique combination of the types of asbestiform minerals detected in cancerous tissue and "cosmetic" talc is a fingerprint for exposure to asbestos-containing talc.}, }
@article {pmid31867277, year = {2019}, author = {Chu, GJ and van Zandwijk, N and Rasko, JEJ}, title = {The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1366}, pmid = {31867277}, issn = {2234-943X}, abstract = {Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make connection with the outcome of immunotherapy trials.}, }
@article {pmid35582270, year = {2019}, author = {Williams, M and Cheng, YY and Phimmachanh, M and Winata, P and van Zandwijk, N and Reid, G}, title = {Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways.}, journal = {Cancer drug resistance (Alhambra, Calif.)}, volume = {2}, number = {4}, pages = {1193-1206}, pmid = {35582270}, issn = {2578-532X}, abstract = {Aim: Aberrant microRNA expression is a common event in cancer drug resistance, however its involvement in malignant pleural mesothelioma (MPM) drug resistance is largely unexplored. We aimed to investigate the contribution of microRNAs to the resistance to drugs commonly used in the treatment of MPM. Methods: Drug resistant MPM cell lines were generated by treatment with cisplatin, gemcitabine or vinorelbine. Expression of microRNAs was quantified using RT-qPCR. Apoptosis and drug sensitivity assays were carried out following transfection with microRNA mimics or BCL2 siRNAs combined with drugs. Results: Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only. Similarly, in parental cell lines, miR-15a or miR-16 mimics sensitised cells to all drugs, whereas miR-34a increased response to cisplatin and vinorelbine. Increased microRNA expression increased drug-induced apoptosis and caused BCL2 mRNA and protein reduction. RNAi-mediated knockdown of BCL2 partly recapitulated the increase in drug sensitivity in cisplatin and vinorelbine treated cells. Conclusion: Drug-resistant MPM cell lines exhibited reduced expression of tumour suppressor microRNAs. Increasing tumour suppressor of microRNA expression sensitised both drug resistant and parental cell lines to chemotherapeutic agents, in part through targeting of BCL2. Taken together, these data suggest that miR-15a, miR-16 and miR-34a are involved in the acquired and intrinsic drug resistance phenotype of MPM cells.}, }
@article {pmid31850200, year = {2019}, author = {Tomasetti, M and Gaetani, S and Monaco, F and Neuzil, J and Santarelli, L}, title = {Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1293}, pmid = {31850200}, issn = {2234-943X}, abstract = {Asbestos exposure leads to epigenetic and epigenomic modifications that, in association with ROS-induced DNA damage, contribute to cancer onset. Few miRNAs epigenetically regulated in MM have been described in literature; miR-126, however, is one of them, and its expression is regulated by epigenetic mechanisms. Asbestos exposure induces early changes in the miRNAs, which are reversibly expressed as protective species, and their inability to reverse reflects the inability of the cells to restore the physiological miRNA levels despite the cessation of carcinogen exposure. Changes in miRNA expression, which results from genetic/epigenetic changes during tumor formation and evolution, can be detected in fluids and used as cancer biomarkers. This article has reviewed the epigenetic mechanisms involved in miRNA expression in MM, focusing on their role as biomarkers of early diagnosis and therapeutic effects.}, }
@article {pmid31846450, year = {2019}, author = {Apostoli, P and Boffetta, P and Bovenzi, M and Cocco, PL and Consonni, D and Cristaudo, A and Discalzi, G and Farioli, A and Manno, M and Mattioli, S and Pira, E and Soleo, L and Taino, G and Violante, FS and Zocchetti, C}, title = {Position Paper on Asbestos of the Italian Society of Occupational Medicine.}, journal = {La Medicina del lavoro}, volume = {110}, number = {6}, pages = {459-485}, pmid = {31846450}, issn = {0025-7818}, mesh = {*Asbestos ; *Asbestosis ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; *Occupational Medicine ; *Pleural Neoplasms ; Retrospective Studies ; }, abstract = {The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.}, }
@article {pmid31842309, year = {2019}, author = {Vernez, D and Duperrex, O and Herrera, H and Perret, V and Rossi, I and Regamey, F and Guillemin, M}, title = {Exposure to Amosite-Containing Ceiling Boards in a Public School in Switzerland: A Case Study.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {24}, pages = {}, pmid = {31842309}, issn = {1660-4601}, mesh = {Adolescent ; Air Pollutants/*analysis ; Air Pollution, Indoor/*analysis ; Asbestos, Amosite/*analysis ; Child ; *Construction Materials ; Dose-Response Relationship, Drug ; Environmental Monitoring ; Female ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma ; Mesothelioma, Malignant ; Risk Assessment ; Schools ; Switzerland ; }, abstract = {The measurement of an airborne concentration in Amosite fibers above 5035 F/m[3] in a school prompted a retrospective quantitative health risk assessment. Dose estimates were built using air measurements, laboratory experiments, previous exposure data, and interviews. A dose response model was adapted for amosite-only exposure and adjusted for the life expectancy and lung cancer incidence in the Swiss population. The average yearly concentrations found were 52-320 F/m[3]. The high concentration previously observed was not representative of the average exposure in the building. Overall, the risk estimates for the different populations of the school were low and in the range of 2 × 10[-6] to 3 × 10[-5] for mesothelioma and 4 × 10[-7] to 8 × 10[-6] for lung cancer. The results evidenced however that children have to be considered at higher risk when exposed to asbestos, and that the current reference method and target values are of limited use for amphibole-only exposures. This study confirmed that quantitative health risk assessments and participatory approaches are powerful tools to support public decisions and build constructive communication between exposed people, experts, and policy-makers.}, }
@article {pmid31833271, year = {2019}, author = {Pellegrini, I and Sibille, A and Paulus, A and Vaillant, F and Radermecker, MA and Corhay, JL and Louis, R and Duysinx, B}, title = {[How I manage... Malignant pleural mesothelioma in 2019].}, journal = {Revue medicale de Liege}, volume = {74}, number = {12}, pages = {627-632}, pmid = {31833271}, issn = {0370-629X}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Combined Modality Therapy ; Humans ; *Mesothelioma/drug therapy ; Pemetrexed ; *Pleural Neoplasms/drug therapy ; }, abstract = {Malignant pleural mesothelioma is a rare disease originating from mesothelial cells of the pleura and is related to asbestos exposure. The tumor is generally extended at the time of diagnosis and the treatment consists of a systemic palliative therapy. Radical approach is limited to very selected patients and is performed in expert centers but without validated schema. Radiotherapy alone is mainly used in palliative intent. Platinum-based chemotherapy in association with pemetrexed is the frontline standard of care and provides a 12-month overall survival. The addition of bevacizumab, an antiangiogenic drug, shows an improvement in median survival. To date, there is no second-line treatment approved for this disease and therefore inclusion in trials is recommended. Currently, various studies are investigating target therapy, immunotherapy and intrapleural perioperative treatment.}, }
@article {pmid31823764, year = {2019}, author = {Kishimoto, T and Fujimoto, N and Ebara, T and Omori, T and Oguri, T and Niimi, A and Yokoyama, T and Kato, M and Usami, I and Nishio, M and Yoshikawa, K and Tokuyama, T and Tamura, M and Yokoyama, Y and Tsuboi, K and Matsuo, Y and Xu, J and Takahashi, S and Abdelgied, M and Alexander, WT and Alexander, DB and Tsuda, H}, title = {Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1204}, pmid = {31823764}, issn = {1471-2407}, support = {14030101-01//Ministry of Health, Labour and Welfare/ ; 13801370//Ministry of Health, Labour and Welfare/ ; 16768893//Ministry of Health, Labour and Welfare/ ; H24//Princess Takamatsu Cancer Research Fund/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/blood ; Biomarkers, Tumor/blood ; Chemokine CCL2/*blood ; Disease Progression ; Female ; Healthy Volunteers ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*blood ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients.<br><br>METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA.<br><br>RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM.<br><br>CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.}, }
@article {pmid31821579, year = {2020}, author = {Ferrante, D and Mirabelli, D and Silvestri, S and Azzolina, D and Giovannini, A and Tribaudino, P and Magnani, C}, title = {Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {135-145}, doi = {10.1002/ajim.23071}, pmid = {31821579}, issn = {1097-0274}, support = {//This study was partially supported by Istituto Superiore di Sanit&#xe0; - Progetto Amianto (to C.M)/International ; }, mesh = {Adult ; Asbestos, Serpentine/*toxicity ; Asbestosis/*mortality ; Cause of Death ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Mining ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Risk Factors ; }, abstract = {BACKGROUND: We studied cancer mortality and mesothelioma incidence in 974 male workers employed at least 6 months at the Balangero mine (Italy), the largest chrysotile mine in Western Europe, active from 1917 to 1985.<br><br>METHODS: Vital status as of 31 May 2013, causes of deaths and mesothelioma incidence from 1990 were ascertained. Past exposure to asbestos by working area and calendar period was estimated, based on historical data of fibers concentrations. Individual cumulative exposure was assessed by applying estimates to the job history of cohort members. Standardized mortality ratios (SMRs) for selected causes and standardized incidence ratios for malignant mesothelioma (MM) were calculated based on regional reference rates. Poisson regression analysis was used to study MM and lung cancer risk by latency, duration, and cumulative exposure.<br><br>RESULTS: Mortality was increased for all causes (SMR&#x2009;=&#x2009;1.28; 95% confidence interval [CI]&#x2009;=&#x2009;1.17-1.40), pleural cancer (SMR&#x2009;=&#x2009;4.30; 95% CI&#x2009;=&#x2009;1.58-9.37), asbestosis (SMR&#x2009;=&#x2009;375.06; 95% CI&#x2009;=&#x2009;262.68-519.23). An increase was also found for lung cancer (SMR&#x2009;=&#x2009;1.14; 95% CI&#x2009;= &#x2009;0.81-1.55) and peritoneal cancer (SMR&#x2009;=&#x2009;3.25; 95% CI&#x2009;=&#x2009;0.39-11.75). The risk of both pleural and peritoneal cancer mortality and of mesothelioma incidence increased with increasing cumulative exposure, duration, and latency. Poisson regression analyses showed an increase in mesothelioma risk with cumulative asbestos exposure and suggest a similar trend for lung cancer. Asbestosis mortality also increased with cumulative exposure.<br><br>CONCLUSIONS: Among Balangero chrysotile miners and millers, the occurrence of malignant and nonmalignant asbestos-related diseases was increased by exposure, with dose-response relation. The study confirms the carcinogenicity of chrysotile asbestos, in particular for pleural mesothelioma.}, }
@article {pmid31819191, year = {2020}, author = {Urso, L and Cavallari, I and Sharova, E and Ciccarese, F and Pasello, G and Ciminale, V}, title = {Metabolic rewiring and redox alterations in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {122}, number = {1}, pages = {52-61}, pmid = {31819191}, issn = {1532-1827}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Cell Transformation, Neoplastic/metabolism ; Cisplatin/therapeutic use ; Humans ; Loss of Function Mutation ; Lung Neoplasms/drug therapy/etiology/*genetics/*metabolism ; Mesothelioma/drug therapy/etiology/*genetics/*metabolism ; Mesothelioma, Malignant ; Oxidation-Reduction ; Pleural Neoplasms/drug therapy/etiology/*genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta ; Transforming Growth Factor beta1/metabolism ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in [18]F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.}, }
@article {pmid31814459, year = {2019}, author = {Pfau, JC and McNew, T and Hanley, K and Swan, L and Black, B}, title = {Autoimmune markers for progression of Libby amphibole lamellar pleural thickening.}, journal = {Inhalation toxicology}, volume = {31}, number = {11-12}, pages = {409-419}, pmid = {31814459}, issn = {1091-7691}, support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; }, mesh = {Antibodies, Antinuclear/metabolism ; Asbestos, Amphibole/*toxicity ; Autoantibodies/*metabolism ; Biomarkers ; Cell Line ; Collagen ; Cytokines/genetics/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Pleura/*drug effects/*pathology ; Sensitivity and Specificity ; }, abstract = {Exposure to Libby Asbestiform Amphibole (LAA) is associated with asbestos-related diseases, including mesothelioma, pulmonary carcinoma, pleural fibrosis, and systemic autoimmune diseases. The pleural fibrosis can manifest as a rapidly progressing lamellar pleural thickening (LPT), which causes thoracic pain, dyspnea, and worsening pulmonary function tests (PFT). It is refractory to treatment and frequently fatal.Objective: Because of the immune dysfunction that has been described in the LAA-exposed population and the association of pleural manifestations with the presence of autoantibodies, this study tested whether specific immunological factors were associated with progressive LPT and whether they could be used as markers of progressive disease.Methods: Subjects were placed into three study groups defined as (1) progressive LPT, (2) stable LPT, (3) no LPT. Serum samples were tested for antinuclear autoantibodies, mesothelial cell autoantibodies, anti-plasminogen antibodies, IL1 beta, and IL17; which have all been shown to be elevated in mice and/or humans exposed to LAA.Results: Group 1 had significantly higher mean values for all of the autoantibodies, but not IL1 or IL-17, compared to the control Group 3. All three autoantibody tests had high specificity but low sensitivity, but ROC area-under-the-curve values for all three antibodies were over 0.7, statistically higher than a test with no value. When all LPT subjects were combined (Progressive plus Stable), no marker had predictive value for disease.Conclusion: The data support the hypothesis that progressive LPT is associated with immunological findings that may serve as an initial screen for progressive LPT.}, }
@article {pmid31812249, year = {2020}, author = {Consonni, D and De Matteis, S and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Impact of an asbestos cement factory on mesothelioma incidence in a community in Italy.}, journal = {Environmental research}, volume = {183}, number = {}, pages = {108968}, doi = {10.1016/j.envres.2019.108968}, pmid = {31812249}, issn = {1096-0953}, mesh = {Adult ; *Asbestos/toxicity ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology ; }, abstract = {BACKGROUND: Broni is a small town (9000 inhabitants) in the province of Pavia, Lombardy, north-west Italy, where the second largest Italian asbestos cement factory (Fibronit) was in operation between 1932 and 1993. Based on Lombardy Mesothelioma Registry (RML) data (2000-2011), we previously showed a high impact of asbestos exposure on malignant mesothelioma (MM) incidence among Fibronit workers, their families, and people living in Broni and in the nearby town of Stradella (11,000 residents). Given the great concern of the community, we have recently updated the data regarding 5 more years (2012-2016).<br><br>METHODS: From the RML database we extracted subjects who ever worked in Fibronit, their family members, ever residents in Broni, and subjects living in Stradella and nearby towns at the time of diagnosis. For each type of exposure we calculated standardized incidence ratios (SIR&#xa0;=&#xa0;observed/expected cases).<br><br>RESULTS: In the period 2000-2016 we registered 56 cases (2.52 expected, SIR&#xa0;=&#xa0;22.2), 49 men (41 pleural, 8 peritoneal MM), 7 women (5 pleural, 2 peritoneal MM) with past occupational exposure in Fibronit. Among subjects never occupationally exposed and never exposed to extra-occupational sources unrelated to Fibronit, we counted 39 cases (4.24 expected, SIR&#xa0;=&#xa0;9.2), 10 men (all pleural MM), 29 women (28 pleural, 1 peritoneal MM) in Fibronit workers' families, 91 pleural mesothelioma cases (7.43 expected, SIR&#xa0;=&#xa0;12.2, 31 men, 60 women), ever residents in Broni, and 25 pleural mesothelioma cases (3.05 expected, SIR&#xa0;=&#xa0;8.2, 6 men, 19 women) living in Stradella at the time of diagnosis. The overall number of excess cases was about 194 (211 against 17.24 expected). In the remaining adjacent (No. 8) and surrounding (No. 17) municipalities (32,000 people) there were 7 cases (1 men, 6 women, 8.85 expected).<br><br>CONCLUSION: The mesothelioma burden related to the asbestos cement factory is still high on factory workers, their families, and residents in Broni and Stradella towns.}, }
@article {pmid31812210, year = {2019}, author = {Sonnick, MA and Weisman, S and Borczuk, AC and Turetz, ML}, title = {A Man in His 20s With Cough, Unilateral Pleural Effusion, and Nodular Pleural Thickening.}, journal = {Chest}, volume = {156}, number = {6}, pages = {e121-e126}, doi = {10.1016/j.chest.2019.05.040}, pmid = {31812210}, issn = {1931-3543}, mesh = {Adenocarcinoma of Lung/diagnosis ; Adult ; Asbestos ; Bartonella Infections/diagnosis ; Biopsy ; Cough/etiology ; Diagnosis, Differential ; Dyspnea/etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology ; Lymph Nodes/diagnostic imaging ; Lymphoma, Non-Hodgkin/diagnosis ; Male ; Mesothelioma/complications/*diagnosis/pathology ; Mesothelioma, Malignant ; Palatine Tonsil/diagnostic imaging ; Pleural Effusion/diagnostic imaging/etiology ; Pleural Effusion, Malignant/*diagnostic imaging/etiology ; Pleural Neoplasms/complications/*diagnosis/pathology ; Positron-Emission Tomography ; Spleen/diagnostic imaging ; Sweating ; Talc ; Thoracic Surgery, Video-Assisted ; }, abstract = {A man in his 20s presented to the ED after several months of progressive dyspnea, dry cough, and night sweats. He had no chest pain, fevers, weight loss, or sick contacts. He was previously healthy and took no medications. Social history was notable for 5 pack-years of tobacco use. The patient was sexually active with male partners and had a recent partner infected with human T-lymphotropic virus. The patient worked in set design and window installations, and wore a respirator when working around solvents and resins. From ages 2 to 7 years, he frequently visited buildings at his parents' workplace that were undergoing asbestos abatement. From ages 7 to 24 years, he frequently visited pottery studios where talc-containing products were used. He frequently visited northern Massachusetts, and infections with Borrelia burgdorferi and Bartonella henselae were common in family members. His stepfather had recently been infected with Anaplasma. There was no family history of cancer.}, }
@article {pmid31807495, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Corrigendum: Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {293}, pmid = {31807495}, issn = {2296-634X}, abstract = {[This corrects the article DOI: 10.3389/fcell.2019.00221.].}, }
@article {pmid31783178, year = {2020}, author = {Mian, I and Abdullaev, Z and Morrow, B and Kaplan, RN and Gao, S and Miettinen, M and Schrump, DS and Zgonc, V and Wei, JS and Khan, J and Pack, S and Hassan, R}, title = {Anaplastic Lymphoma Kinase Gene Rearrangement in Children and Young Adults With Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {15}, number = {3}, pages = {457-461}, pmid = {31783178}, issn = {1556-1380}, support = {Z01 BC010816/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anaplastic Lymphoma Kinase/genetics ; Child ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/genetics ; Male ; *Mesothelioma/genetics ; Prospective Studies ; Receptor Protein-Tyrosine Kinases/genetics ; Young Adult ; }, abstract = {INTRODUCTION: Children and young adults diagnosed with malignant mesothelioma may have unique genetic characteristics. In this study, we evaluated for the presence of the anaplastic lymphoma kinase (ALK) translocations in these patients.<br><br>METHODS: In a prospective study of mesothelioma natural history (ClinicalTrials.gov number NCT01950572), we assessed for the presence of the ALK translocation in patients younger than 40 years, irrespective of the site of disease. The presence of this translocation was assessed by means of fluorescence in situ hybridization (FISH). If the patients tested positive for the ALK translocation, both immunohistochemistry and RNA sequencing were performed on the tumor specimen.<br><br>RESULTS: Between September 2013 and December 2018, 373 patients were enrolled in the mesothelioma natural&#xa0;history study, of which 32 patients were 40 years old or younger at the time of their mesothelioma diagnosis. There were 25 patients with peritoneal mesothelioma, five with pleural mesothelioma, one with pericardial mesothelioma, and one with bicompartmental mesothelioma. Presence of&#xa0;an ALK translocation by FISH was seen in two of the 32 patients (6%) with mesothelioma. Both patients, a 14-year-old female and a 27-year-old male, had peritoneal mesothelioma and had no history of asbestos exposure, prior radiation therapy, or predisposing germline mutations. Neither had detectable ALK expression by immunohistochemistry. RNA sequencing revealed the presence of an STRN fusion partner in the female patient&#xa0;but failed to identify any fusion protein in the male patient.<br><br>CONCLUSIONS: Young patients with peritoneal mesothelioma should be evaluated for the presence of ALK translocations. Presence of this translocation should be assessed by FISH and these patients could potentially benefit from tyrosine kinase inhibitors targeting ALK.}, }
@article {pmid31766522, year = {2019}, author = {Martinotti, S and Patrone, M and Moccia, F and Ranzato, E}, title = {Targeting Calcium Signalling in Malignant Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {12}, pages = {}, pmid = {31766522}, issn = {2072-6694}, abstract = {Calcium ions (Ca[2+]) are central in cancer development and growth, serving as a major signaling system determining the cell's fate. Therefore, the investigation of the functional roles of ion channels in cancer development may identify novel approaches for determining tumor prognosis. Malignant mesothelioma is an aggressive cancer that develops from the serosal surface of the body, strictly related to asbestos exposure. The treatment of malignant mesothelioma is complex and the survival outcomes, rather than the overall survival data are, to date, disappointedly daunting. Nevertheless, conventional chemotherapy is almost ineffective. The alteration in the expression and/or activity of Ca[2+] permeable ion channels seems to be characteristic of mesothelioma cells. In this review, we explore the involvement of the Ca[2+]toolkit in this disease. Moreover, the established sensitivity of some Ca[2+]channels to selective pharmacological modulators makes them interesting targets for mesothelioma cancer therapy.}, }
@article {pmid31755376, year = {2019}, author = {Celsi, F and Crovella, S and Moura, RR and Schneider, M and Vita, F and Finotto, L and Zabucchi, G and Zacchi, P and Borelli, V}, title = {Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {82}, number = {20}, pages = {1088-1102}, doi = {10.1080/15287394.2019.1694612}, pmid = {31755376}, issn = {1528-7394}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Female ; Humans ; Inflammasomes/*genetics ; Iron/*metabolism ; Italy ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Pleural Neoplasms/chemically induced/*epidemiology ; Prevalence ; Retrospective Studies ; Risk Factors ; }, abstract = {Two of the major cancerous diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (LC). In addition to asbestos exposure, genetic factors have been suggested to be associated with asbestos-related carcinogenesis and lung genotoxicity. While genetic factors involved in the susceptibility to MPM were reported, to date the influence of individual genetic variations on asbestos-related lung cancer risk is still poorly understood. Since inflammation and disruption of iron (Fe) homeostasis are hallmarks of asbestos exposure affecting the pulmonary tissue, this study aimed at investigating the association between Fe-metabolism and inflammasome gene variants and susceptibility to develop LC or MPM, by comparing an asbestos-exposed population affected by LC with an "asbestos-resistant exposed population". A retrospective approach similar to our previous autopsy-based pilot study was employed in a novel cohort of autoptic samples, thus giving us the possibility to corroborate previous findings obtained on MPM by repeating the analysis in a novel cohort of autoptic samples. The protective role of HEPH coding SNP was further confirmed. In addition, the two non-coding SNPs, either in FTH1 or in TF, emerged to exert a similar protective role in a new cohort of LC exposed individuals from the same geographic area of MPM subjects. No association was found between NLRP1 and NLRP3 polymorphisms with susceptibility to develop MPM and LC. Further research into a specific MPM and LC "genetic signature" may be needed to broaden our knowledge of the genetic landscape attributed to result in MPM and LC.}, }
@article {pmid31743489, year = {2020}, author = {Cummings, KJ and Becich, MJ and Blackley, DJ and Deapen, D and Harrison, R and Hassan, R and Henley, SJ and Hesdorffer, M and Horton, DK and Mazurek, JM and Pass, HI and Taioli, E and Wu, XC and Zauderer, MG and Weissman, DN}, title = {Workshop summary: Potential usefulness and feasibility of a US National Mesothelioma Registry.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {105-114}, pmid = {31743489}, issn = {1097-0274}, support = {U19 OH009077/OH/NIOSH CDC HHS/United States ; R13 OH009753/OH/NIOSH CDC HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; R25 OH008802/OH/NIOSH CDC HHS/United States ; }, mesh = {Feasibility Studies ; Humans ; Mesothelioma, Malignant/*epidemiology ; Occupational Diseases/*epidemiology ; Population Surveillance ; Prognosis ; *Registries ; United States/epidemiology ; }, abstract = {The burden and prognosis of malignant mesothelioma in the United States have remained largely unchanged for decades, with approximately 3200 new cases and 2400 deaths reported annually. To address care and research gaps contributing to poor outcomes, in March of 2019 the Mesothelioma Applied Research Foundation convened a workshop on the potential usefulness and feasibility of a national mesothelioma registry. The workshop included formal presentations by subject matter experts and a moderated group discussion. Workshop participants identified top priorities for a registry to be (a) connecting patients with high-quality care and clinical trials soon after diagnosis, and (b) making useful data and biospecimens available to researchers in a timely manner. Existing databases that capture mesothelioma cases are limited by factors such as delays in reporting, deidentification, and lack of exposure information critical to understanding as yet unrecognized causes of disease. National disease registries for amyotrophic lateral sclerosis (ALS) in the United States and for mesothelioma in other countries, provide examples of how a registry could be structured to meet the needs of patients and the scientific community. Small-scale pilot initiatives should be undertaken to validate methods for rapid case identification, develop procedures to facilitate patient access to guidelines-based standard care and investigational therapies, and explore approaches to data sharing with researchers. Ultimately, federal coordination and funding will be critical to the success of a National Mesothelioma Registry in improving mesothelioma outcomes and preventing future cases of this devastating disease.}, }
@article {pmid31732616, year = {2020}, author = {Kandasamy, S and Adhikary, G and Rorke, EA and Friedberg, JS and Mickle, MB and Alexander, HR and Eckert, RL}, title = {The YAP1 Signaling Inhibitors, Verteporfin and CA3, Suppress the Mesothelioma Cancer Stem Cell Phenotype.}, journal = {Molecular cancer research : MCR}, volume = {18}, number = {3}, pages = {343-351}, pmid = {31732616}, issn = {1557-3125}, support = {R01 CA184027/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*antagonists &amp; inhibitors ; Animals ; Humans ; Mesothelioma/*drug therapy ; Mice ; Neoplastic Stem Cells/*drug effects ; Phenotype ; Photosensitizing Agents/pharmacology/*therapeutic use ; Signal Transduction ; Transcription Factors/*antagonists &amp; inhibitors ; Transfection ; Verteporfin/pharmacology/*therapeutic use ; YAP-Signaling Proteins ; }, abstract = {Mesothelioma is an aggressive cancer that has a poor prognosis. Tumors develop in the mesothelial lining of the pleural and peritoneal cavities in response to asbestos exposure. Surgical debulking followed by chemotherapy is initially effective, but this treatment ultimately selects for resistant cells that form aggressive and therapy-resistant recurrent tumors. Mesothelioma cancer stem cells (MCS) are a highly aggressive subpopulation present in these tumors that are responsible for tumor maintenance and drug resistance. In this article, we examine the impact of targeting YAP1/TAZ/TEAD signaling in MCS cells. YAP1, TAZ, and TEADs are transcriptional mediators of the Hippo signaling cascade that activate gene expression to drive tumor formation. We show that two YAP1 signaling inhibitors, verteporfin and CA3, attenuate the MCS cell phenotype. Verteporfin or CA3 treatment reduces YAP1/TEAD level/activity to suppress MCS cell spheroid formation, Matrigel invasion, migration, and tumor formation. These agents also increase MCS cell apoptosis. Moreover, constitutively active YAP1 expression antagonizes inhibitor action, suggesting that loss of YAP1/TAZ/TEAD signaling is required for response to verteporfin and CA3. These agents are active against mesothelioma cells derived from peritoneal (epithelioid) and patient-derived pleural (sarcomatoid) mesothelioma, suggesting that targeting YAP1/TEAD signaling may be a useful treatment strategy. IMPLICATIONS: These studies suggest that inhibition of YAP1 signaling may be a viable approach to treating mesothelioma.}, }
@article {pmid31727556, year = {2019}, author = {Lorentz, E and Despreaux, T and Quignette, A and Chinet, T and Descatha, A}, title = {[Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {10}, pages = {1088-1095}, doi = {10.1016/j.rmr.2019.08.006}, pmid = {31727556}, issn = {1776-2588}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Asbestos/toxicity ; Asbestosis/complications/*diagnosis/epidemiology ; Carcinoma, Bronchogenic/diagnosis/*epidemiology/etiology ; Female ; France/epidemiology ; Humans ; Lung Neoplasms/diagnosis/*epidemiology/etiology ; Male ; Mass Screening/*methods ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/diagnosis ; Occupational Exposure/analysis ; Silicon Dioxide/toxicity ; Silicosis/complications/*diagnosis/epidemiology ; Surveys and Questionnaires ; Work/statistics &amp; numerical data ; }, abstract = {INTRODUCTION: In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology.<br><br>METHODS: Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied.<br><br>RESULTS: The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices.<br><br>CONCLUSIONS: The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.}, }
@article {pmid31714372, year = {2020}, author = {Larson, TC and Williamson, L and Antao, VC}, title = {Follow-Up of the Libby, Montana Screening Cohort: A 17-Year Mortality Study.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {1}, pages = {e1-e6}, pmid = {31714372}, issn = {1536-5948}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Aluminum Silicates ; Asbestos ; Asbestos, Amphibole ; Asbestosis/*epidemiology ; Biometry ; Cohort Studies ; Environmental Exposure/*statistics &amp; numerical data ; Female ; Follow-Up Studies ; Humans ; Lung ; Lung Neoplasms ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Montana/epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; }, abstract = {OBJECTIVE: To evaluate mortality patterns among participants in a community-based screening program for asbestos-related disease.<br><br>METHODS: We calculated standardized mortality ratios (SMRs) and stratified results by exposure group (three occupational exposure groups, household contacts and residents without occupational asbestos exposure) and by radiographic abnormality presence.<br><br>RESULTS: All-cause mortality (15.8%; 1,429/8,043) was statistically lower than expected. Asbestosis was statistically elevated in all exposure groups. Lung cancer was moderately associated with vermiculite miner/miller employment. Mesothelioma was elevated in that same exposure group and among residents. Systemic autoimmune disease mortality was also elevated. Radiographic parenchymal abnormalities were associated with lung cancer mortality.<br><br>CONCLUSION: In addition to asbestos-related mortality in occupational exposure groups, this initial follow-up of this cohort also shows elevated mortality for some asbestos-related causes in non-occupational exposure groups.}, }
@article {pmid31713586, year = {2020}, author = {Finkelstein, MM and Meisenkothen, C}, title = {Malignant Mesothelioma Among Employees of a Connecticut Factory That Manufactured Friction Materials Using Chrysotile Asbestos: An Update.}, journal = {Annals of work exposures and health}, volume = {64}, number = {1}, pages = {106-109}, doi = {10.1093/annweh/wxz082}, pmid = {31713586}, issn = {2398-7316}, mesh = {Aged ; Asbestos, Serpentine/*toxicity ; Connecticut ; Friction ; Humans ; *Lung Neoplasms/chemically induced ; Male ; Mesothelioma, Malignant/*chemically induced ; *Occupational Exposure/adverse effects ; }, abstract = {There is an ongoing argument about the potency of chrysotile asbestos to cause malignant mesothelioma. Authors of chrysotile risk assessments have relied upon the results of an epidemiologic study, published in 1984, to state that there were no mesotheliomas found among workers at a Connecticut friction products plant. McDonald reported the first two cases in 1986. In 2010, we reported the work histories and pathologic reports of five individuals from the Connecticut plant who were diagnosed with mesothelioma. Despite this, a review of the health effects of chrysotile published in 2018 continued to state that there were no cases of mesothelioma from this plant. We report here two new cases that were diagnosed after the publication of our previous report, bringing the current total to nine cases. We also discuss the results of previously unpublished air sampling data from the plant. Chrysotile, mainly from Canada, was the only asbestos fiber type used until 1957 when some anthophyllite was added in making paper discs and bands. Beyond this original description of the anthophyllite usage from McDonald, there is a dearth of information about the amount of anthophyllite used in the plant, the frequency of its use, and the specific departments where it was used. For over 30 years in the published literature, this factory has alternatively been described as a 'chrysotile' or 'predominantly chrysotile' factory. While it is clear that some anthophyllite was used in the factory (in addition to 400 pounds of crocidolite in the laboratory), given the volume, frequency, and processes using chrysotile, it still seems satisfactory to describe this cohort as a predominantly, but not exclusively, chrysotile-exposed cohort.}, }
@article {pmid31701555, year = {2020}, author = {van Gerwen, M and Alpert, N and Flores, R and Taioli, E}, title = {An overview of existing mesothelioma registries worldwide, and the need for a US Registry.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {115-120}, doi = {10.1002/ajim.23069}, pmid = {31701555}, issn = {1097-0274}, mesh = {Global Health ; Humans ; Mesothelioma, Malignant/*epidemiology ; Occupational Diseases/*epidemiology ; Population Surveillance ; *Registries ; United States/epidemiology ; }, abstract = {The association between asbestos exposure, mainly in occupational settings, and malignant mesothelioma has been well established; this has prompted several countries to establish mesothelioma epidemiologic surveillance programs often at the request of national agencies. This review compares currently existing mesothelioma registries worldwide to develop a concept model for a US real-time case capture mesothelioma registry. Five countries were identified with a mesothelioma specific registry, including Italy, France, UK, Australia, and South Korea. All, except the UK, used interviews to collect exposure data. Linkage with the national death index was available or was in future plans for all registries. The registries have limited information on treatment, quality of life, and other patient-centered outcomes such as symptoms and pain management. To thoroughly collect exposure data, "real-time" enrollment is preferable; to maximize the capture of mesothelioma cases, optimal coverage, and a simplified consent process are needed.}, }
@article {pmid31693951, year = {2020}, author = {Gwenzi, W}, title = {Occurrence, behaviour, and human exposure pathways and health risks of toxic geogenic contaminants in serpentinitic ultramafic geological environments (SUGEs): A medical geology perspective.}, journal = {The Science of the total environment}, volume = {700}, number = {}, pages = {134622}, doi = {10.1016/j.scitotenv.2019.134622}, pmid = {31693951}, issn = {1879-1026}, mesh = {Africa ; Animals ; Asbestos, Serpentine ; Asbestosis ; Environmental Exposure ; *Environmental Monitoring ; Geology ; Hazardous Substances/*analysis ; Humans ; Iron ; Lung Neoplasms ; Mesothelioma ; Mesothelioma, Malignant ; Metals, Heavy ; Metals, Rare Earth ; Mining ; *Risk Assessment ; }, abstract = {Serpentinitic ultramafic geological environments (SUGEs) contain toxic geogenic contaminants (TGCs). Yet comprehensive reviews on the medical geology of SUGEs are still lacking. The current paper posits that TGCs occur widely in SUGEs, and pose human health risks. The objectives of the review are to: (1) highlight the nature, occurrence and behaviour of TGCs associated with SUGEs; (2) discuss the human intake pathways and health risks of TGCs; (4) identify the key risk factors predisposing human health to TGCs particularly in Africa; and (5) highlight key knowledge gaps and future research directions. TGCs of human health concern in SUGEs include chrysotile asbestos, toxic metals (Fe, Cr, Ni, Mn, Zn, Co), and rare earth elements. Human intake of TGCs occur via inhalation, and ingestion of contaminated drinking water, wild foods, medicinal plants, animal foods, and geophagic earths. Occupational exposure may occur in the mining, milling, sculpturing, engraving, and carving industries. African populations are particularly at high risk due to: (1) widespread consumption of wild foods, medicinal plants, untreated drinking water, and geophagic earths; (2) weak and poorly enforced environmental, occupational, and public health regulations; and (3) lack of human health surveillance systems. Human health risks of chrysotile include asbestosis, cancers, and mesothelioma. Toxic metals are redox active, thus generate reactive oxygen species causing oxidative stress. Dietary intake of iron and geophagy may increase the iron overload among native Africans who are genetically predisposed to such health risks. Synergistic interactions among TGCs particularly chrysotile and toxic metals may have adverse human health effects. The occurrence of SUGEs, coupled with the several risk factors in Africa, provides a unique and ideal setting for investigating the relationships between TGCs and human health risks. A conceptual framework for human health risk assessment and mitigation, and future research direction are highlighted.}, }
@article {pmid31690138, year = {2019}, author = {Boyles, MSP and Poland, CA and Raftis, J and Duffin, R}, title = {Assessment of the physicochemical properties of chrysotile-containing brake debris pertaining to toxicity.}, journal = {Inhalation toxicology}, volume = {31}, number = {8}, pages = {325-342}, doi = {10.1080/08958378.2019.1683103}, pmid = {31690138}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*chemistry ; Asbestos, Serpentine/*chemistry ; Automobiles ; Humans ; Macrophages/*drug effects ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Reactive Oxygen Species/analysis ; THP-1 Cells ; }, abstract = {Grinding and drilling of chrysotile asbestos-containing brake pads during the 20[th] century led to release of chrysotile, resulting in varying levels of workplace exposures of mechanics. Despite exposures, excess risk of mesothelioma remains in doubt. Objectives: The toxicity of particulates is primarily derived through a combination of physicochemical properties and dose and as such this study aimed to determine properties of asbestos-containing brake debris (BD) which may influence pathogenicity and potential of mesothelioma. Materials and Methods: Chrysotile-containing brake pads were ground - to reflect occupational activities, aerosolized, and size-fractionated to isolate respirable fractions. Analysis of morphology, biodurability, surface charge, and interactions with macrophages were undertaken. Results: The respirable fraction of BD contained ∼15-17% free chrysotile fibers thereby constituting a small but relevant potential long fiber dose. Acellular biodurability studies showed rapid dissolution and fragmentation of chrysotile fibers that was consistent for pure chrysotile control and BD samples. Conclusions: The long, free, respirable chrysotile fibers were present in BD, yet were of low bio-durability; incubation in artificial lysosomal fluid led to destruction of free fibers.}, }
@article {pmid31684803, year = {2021}, author = {Waldron, T}, title = {ERA Merewether - And asbestos.}, journal = {Journal of medical biography}, volume = {29}, number = {4}, pages = {189-195}, doi = {10.1177/0967772019883550}, pmid = {31684803}, issn = {1758-1087}, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/chemically induced ; Male ; *Mesothelioma/chemically induced ; }, abstract = {After a succession of posts and studying for the Bar, Edward Merewether joined the Medical Inspectorate of Factories in 1927. Not long thereafter he was asked to undertake a study of the effects of asbestos exposure on the lungs. His results showed that asbestos workers had a significant risk of developing pulmonary fibrosis and this resulted in the promulgation of regulations to limit exposure. Some years later, Merewether showed that asbestos workers also had a higher than expected risk of developing lung cancer, but on this occasion there was no further protective legislation, and the association was not generally accepted until some years later. Merewether's name is inextricably linked with the risks of asbestos exposure but after his death the importance of his efforts was often played down by those who wished to show that the government had not acted quickly enough, or vigorously enough to control the hazard. The contention of this paper is that these criticisms are not justified and that Merewether acted to the best of his ability, given the conditions and knowledge current at the time he was working.}, }
@article {pmid31682242, year = {2019}, author = {Świątkowska, B}, title = {[The occurrence of asbestos-related diseases among former employees of asbestos processing plants in Poland].}, journal = {Medycyna pracy}, volume = {70}, number = {6}, pages = {723-731}, doi = {10.13075/mp.5893.00890}, pmid = {31682242}, issn = {2353-1339}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects/*statistics &amp; numerical data ; Poland/epidemiology ; Population Surveillance ; }, abstract = {BACKGROUND: Despite the fact that asbestos is no longer used in production in Poland, there are still new cases of asbestos-related diseases among workers previously exposed to asbestos dust. This situation is related to the specificity of the biological activity of this mineral; the health consequences of asbestos can manifest not only during the exposure but also many years after exposure cessation. The aim of the analysis was to assess the occurrence of occupational diseases among people exposed to asbestos dust, who were examined under the Amiantus program.<br><br>MATERIAL AND METHODS: The research material consisted of the program cards filled by the doctors conducting the examinations as well as radiological images stored on the International Labour Organization form. The analysis covered 8049 people, including 37% of women surveyed in the years 2000-2017.<br><br>RESULTS: In the group of former employees of asbestos processing plants, the occupational disease was diagnosed in 1993 people (25%), including 584 women (19%). The most common was asbestosis (76% of occupational diseases) and pleural disease (17%). Malignant neoplasms accounted for 7% of all cases in this group. The analysis showed an increase in the incidence of respiratory system diseases along with the age of the surveyed persons, their seniority at asbestos processing plants and an increase in cumulative exposure. The chest radiographs revealed radiological changes among 75% of the examined cases, whereas the changes entitling to diagnose asbestosis, according to the criteria applicable in Poland, occurred in 23% of the workers. The adoption of international criteria would increase the incidence of asbestosis as an occupational disease by 19% in the study group.<br><br>CONCLUSIONS: The increase in the percentage of people with a diagnosed occupational disease provides evidence for the worsening health status of the former workers as well as a good detection of asbestos-related diseases among employees exposed to asbestos dust in the past. The results of the analysis indicate the need for undertaking a discussion in Poland on the implementation of international criteria for the diagnosis of asbestosis. Med Pr. 2019;70(6):723-31.}, }
@article {pmid31671889, year = {2019}, author = {Wörthmüller, J and Salicio, V and Oberson, A and Blum, W and Schwaller, B}, title = {Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin.}, journal = {International journal of molecular sciences}, volume = {20}, number = {21}, pages = {}, pmid = {31671889}, issn = {1422-0067}, mesh = {Antineoplastic Agents/*pharmacology ; Calbindin 2/genetics/*metabolism ; Carcinogenesis ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cisplatin/*pharmacology ; Down-Regulation ; Drug Resistance, Neoplasm/*drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Wnt Signaling Pathway/*drug effects ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca[2+]-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells' growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.}, }
@article {pmid31670764, year = {2020}, author = {Musk, AWB and Reid, A and Olsen, N and Hobbs, M and Armstrong, B and Franklin, P and Hui, J and Layman, L and Merler, E and Brims, F and Alfonso, H and Shilkin, K and Sodhi-Berry, N and de Klerk, N}, title = {The Wittenoom legacy.}, journal = {International journal of epidemiology}, volume = {49}, number = {2}, pages = {467-476}, doi = {10.1093/ije/dyz204}, pmid = {31670764}, issn = {1464-3685}, mesh = {*Asbestos, Crocidolite/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mining ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; Western Australia/epidemiology ; }, abstract = {The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine.}, }
@article {pmid31670225, year = {2019}, author = {Cinausero, M and Rihawi, K and Cortiula, F and Follador, A and Fasola, G and Ardizzoni, A}, title = {Emerging therapies in malignant pleural mesothelioma.}, journal = {Critical reviews in oncology/hematology}, volume = {144}, number = {}, pages = {102815}, doi = {10.1016/j.critrevonc.2019.102815}, pmid = {31670225}, issn = {1879-0461}, mesh = {Combined Modality Therapy ; Humans ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer of the pleural surfaces frequently related to asbestos exposure. It is characterized by a poor prognosis even for patients treated with trimodality therapy, including surgery, chemotherapy and radiotherapy. Moreover, the majority of patients are not candidates for surgery due to disease advanced stage or medical comorbidities. For these patients, the survival rate is even lower and few therapeutic options are currently available. Nevertheless, many interesting novel approaches are under investigation, among which immunotherapy represents one of the most promising emerging strategies. In this review, we will discuss the role of new therapeutic options, particularly immunotherapy, and present the results of the most important and promising clinical trials.}, }
@article {pmid31667596, year = {2020}, author = {Minami, K and Jimbo, N and Tanaka, Y and Hokka, D and Miyamoto, Y and Itoh, T and Maniwa, Y}, title = {Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {476}, number = {3}, pages = {469-473}, pmid = {31667596}, issn = {1432-2307}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Cyclin-Dependent Kinase Inhibitor p16/analysis/genetics ; *Early Diagnosis ; Genes, p16 ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis ; Purine-Nucleoside Phosphorylase/analysis/biosynthesis ; Sequence Deletion ; }, abstract = {Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.}, }
@article {pmid31662422, year = {2019}, author = {Reynolds, CJ and Minelli, C and Darnton, A and Cullinan, P}, title = {Mesothelioma mortality in Great Britain: how much longer will dockyards dominate?.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {12}, pages = {908-912}, doi = {10.1136/oemed-2019-105878}, pmid = {31662422}, issn = {1470-7926}, support = {MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; 201291/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Occupational Diseases/*mortality ; *Ships ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: We aimed to investigate whether there has been a geographic shift in the distribution of mesothelioma deaths in Great Britain given the decline of shipbuilding and progressive exposure regulation.<br><br>METHODS: We calculated age-adjusted mesothelioma mortality rates and estimated rate ratios for areas with and without a dockyard. We compared spatial autocorrelation statistics (Moran's I) for age-adjusted rates at local authority district level for 2002-2008 and 2009-2015. We measured the mean distance of the deceased's postcode to the nearest dockyard at district level and calculated the association of average distance to dockyard and district mesothelioma mortality using simple linear regression for men, for 2002-2008 and 2009-2015.<br><br>RESULTS: District age-adjusted male mortality rates fell during 2002-2015 for 80 of 348 districts (23%), rose for 267 (77%) and were unchanged for one district; having one or more dockyards in a district was associated with rates falling (OR=2.43, 95%&#x2009;CI 1.22 to 4.82, p=0.02). The mortality rate ratio for men in districts with a dockyard, compared with those without a dockyard was 1.41 (95% CI 1.35 to 1.48, p<0.05) for 2002-2008 and 1.18 (95% CI 1.13 to 1.23, p<0.05) for 2009-2015. Spatial autocorrelation (measured by Moran's I) decreased from 0.317 (95% CI 0.316 to 0.319, p=0.001) to 0.312 (95% CI 0.310 to 0.314, p=0.001) for men and the coefficient of the association between distance to dockyard and district level age-adjusted male mortality (per million population) from -0.16 (95% CI -0.21 to -0.10, p<0.01) to -0.13 (95% CI -0.18 to -0.07, p<0.01) for men, when comparing 2002-2008 with 2009-2015.<br><br>CONCLUSION: For most districts age-adjusted mesothelioma mortality rates increased through 2002-2015 but the relative contribution from districts with a dockyard fell. Dockyards remain strongly spatially associated with mesothelioma mortality but the strength of this association appears to be falling and mesothelioma deaths are becoming more dispersed.}, }
@article {pmid31655816, year = {2020}, author = {Fortin, M and Cabon, E and Berbis, J and Laroumagne, S and Guinde, J and Elharrar, X and Dutau, H and Astoul, P}, title = {Diagnostic Value of Computed Tomography Imaging Features in Malignant Pleural Mesothelioma.}, journal = {Respiration; international review of thoracic diseases}, volume = {99}, number = {1}, pages = {28-34}, doi = {10.1159/000503239}, pmid = {31655816}, issn = {1423-0356}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Squamous Cell/diagnostic imaging/secondary ; Female ; Humans ; Lung Neoplasms/pathology ; Male ; Mesothelioma, Malignant/*diagnostic imaging/pathology ; Middle Aged ; Neoplasms, Unknown Primary/pathology ; Pleural Effusion, Malignant/*diagnostic imaging/pathology ; Pleural Neoplasms/*diagnostic imaging/pathology/secondary ; Retrospective Studies ; Thoracentesis ; Thoracoscopy ; *Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Medical history, thoracentesis, and imaging features are usually the first steps in the investigation of a possible malignant pleural effusion (MPE). Unfortunately, the diagnostic yield of thoracentesis in this situation is suboptimal even if the procedure is repeated, especially in the context of malignant pleural mesothelioma (MPM). The next step for confirming the diagnosis, if clinically appropriate, is thoracoscopy, but not all patients are fit to undergo this procedure, so the diagnosis is then based on the medical history and imaging features only.<br><br>OBJECTIVES: Our objective was to evaluate the diagnostic value of the medical history and imaging features in MPM.<br><br>METHODS: We reviewed the imaging and medical charts of 92 patients with a final diagnosis of MPE included in our prospective medical thoracoscopy database. The clinical characteristics and imaging features of patients with primary MPE were compared with those of patients with secondary MPE.<br><br>RESULTS: Male sex (82 vs. 59%, p = 0.02), asbestos exposure (58 vs. 10%, p < 0.001), and mediastinal (68 vs. 33%, p = 0.04), diaphragmatic (75 vs. 31%, p = 0.001) and circumferential pleural thickening (55 vs. 19% p = 0.001) were significantly more frequent in MPM patients. In a multivariate linear regression model, only asbestos exposure (OR 11.2; 95% CI 3.4-36.9) and circumferential pleural thickening (OR 4.7; 95% CI 1.6-13.9) were significantly associated with a diagnosis of MPM.<br><br>CONCLUSION: In situations where it is impossible to obtain adequate pleural samples to differentiate MPM from a secondary pleural malignancy, the combination of circumferential pleural thickening and a history of asbestos exposure may be sufficient to make a clinical diagnosis.}, }
@article {pmid31648983, year = {2019}, author = {Alcala, N and Mangiante, L and Le-Stang, N and Gustafson, CE and Boyault, S and Damiola, F and Alcala, K and Brevet, M and Thivolet-Bejui, F and Blanc-Fournier, C and Le Rochais, JP and Planchard, G and Rousseau, N and Damotte, D and Pairon, JC and Copin, MC and Scherpereel, A and Wasielewski, E and Wicquart, L and Lacomme, S and Vignaud, JM and Ancelin, G and Girard, C and Sagan, C and Bonnetaud, C and Hofman, V and Hofman, P and Mouroux, J and Thomas de Montpreville, V and Clermont-Taranchon, E and Mazieres, J and Rouquette, I and Begueret, H and Blay, JY and Lantuejoul, S and Bueno, R and Caux, C and Girard, N and McKay, JD and Foll, M and Galateau-Salle, F and Fernandez-Cuesta, L}, title = {Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {191-202}, pmid = {31648983}, issn = {2352-3964}, support = {001/WHO_/World Health Organization/International ; R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; *Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*etiology/pathology ; Male ; Mesothelioma/*diagnosis/*etiology/pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*immunology ; Pleural Neoplasms/*diagnosis/*etiology/pathology ; Transcriptome ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options.<br><br>METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples.<br><br>FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series.<br><br>INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.}, }
@article {pmid32704189, year = {2019}, author = {Berry, D and Januch, J and Woodbury, L and Kent, D}, title = {Detection of Erionite and Other Zeolite Fibers in Soil by the Fluidized Bed Preparation Methodology.}, journal = {Microscope (Carshalton Beeches (Surrey))}, volume = {67}, number = {4}, pages = {147-158}, pmid = {32704189}, issn = {0026-282X}, support = {EPA999999/ImEPA/Intramural EPA/United States ; }, abstract = {Erionite is a zeolite mineral that can occur as fibrous particles in soil. Inhalation exposure to erionite fibers may result in increased risk of diseases, such as mesothelioma. Low level detection of mineral fibers in soils has traditionally been accomplished using polarized light microscopy (PLM) methods to analyze bulk samples providing detection limits of around 0.25% by weight. This detection level may not be sufficiently low enough for protection of human health and is subject to large variability between laboratories. The fluidized bed asbestos segregator (FBAS) soil preparation method uses air elutriation to separate mineral fibers, such as erionite, from soil particles with higher aerodynamic diameter and deposits those mineral fibers onto filters that can be quantitatively analyzed by microscopic techniques, such as transmission electron microscopy (TEM). In this study, performance evaluation (PE) standards of erionite in soil with nominal concentrations ranging from 0.1% to 0.0001% by weight were prepared using the FBAS soil preparation method and the resulting filters were analyzed by TEM. The analytical results of this study illustrate a linear relationship between the nominal concentration of erionite (as % by weight) in the PE standard and the concentration estimated by TEM analysis expressed as erionite structures per gram of test material (s/g). A method detection limit of 0.003% by weight was achieved, which is approximately 100 times lower than typical detection limits for soils by PLM. The FBAS soil preparation method was also used to evaluate authentic field soil samples to better estimate the concentrations of erionite in soils on a weight percent basis. This study demonstrates the FBAS preparation method, which has already been shown to reliably detect low levels of asbestos in soil, can also be used to quantify low levels of erionite in soil.}, }
@article {pmid32464005, year = {2019}, author = {Bolognesi, C and Bruzzone, M and Fontana, V and Ugolini, D and Compalati, A and Stagnaro, L and Ceppi, M}, title = {The Role of Micronucleus Assay to Detect Genetic Instability in Respiratory Cancer Patients.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {38}, number = {4}, pages = {345-352}, doi = {10.1615/JEnvironPatholToxicolOncol.2019030907}, pmid = {32464005}, issn = {2162-6537}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/genetics ; Mesothelioma, Malignant ; *Micronucleus Tests ; Middle Aged ; }, abstract = {Asbestos represents the main risk factor for malignant pleural mesothelioma (PM) even if only a minority of exposed people develop this tumor, suggesting a significant role for genetic susceptibility. This study aims to evaluate micronuclei (MN) frequency as a biomarker of genome instability in peripheral blood lymphocytes of PM and lung cancer (LC) patients when compared with healthy controls (HCs) and patients with nonneoplastic respiratory diseases (RDs). Lymphocyte cytokinesis-block MN assay was carried out on 317 subjects. Mutagen sensitivity, measured by quantifying MN frequency after an in vitro challenge with ionizing radiation, was evaluated in 252 subjects. A significant increase in MN frequency was observed in cancer patients compared to HCs, with a mean ratio (MR) of 1.35 and 1.36 at baseline and 1.43 and 1.38 after irradiation in PM and LC patients, respectively. A positive (synergistic) interaction between asbestos exposure and disease status was observed for MN frequency after irradiation in PM patients with possible exposure to asbestos (MR = 1.62). The evidence of increased genetic damage in cancer cases confirms lymphocyte cytokinesis-block MN assay as a sensitive predictor of the role of genetic instability in carcinogenic processes.}, }
@article {pmid31632972, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {221}, pmid = {31632972}, issn = {2296-634X}, abstract = {Lung cancers and malignant pleural mesothelioma (MPM) have some of the worst 5-year survival rates of all cancer types, primarily due to a lack of effective treatment options for most patients. Targeted therapies have shown some promise in thoracic cancers, although efficacy is limited only to patients harboring specific mutations or target expression. Although a number of actionable mutations have now been identified, a large population of thoracic cancer patients have no therapeutic options outside of first-line chemotherapy. It is therefore crucial to identify alternative targets that might lead to the development of new ways of treating patients diagnosed with these diseases. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) could serve as one such target. Recent studies also link this protein to many inherent behaviors of thoracic cancer cells such as proliferation, invasion, metastasis and involvement in cancer stem-like cells. Here, we review the regulation of YB-1 at the transcriptional, translational, post-translational and sub-cellular levels in thoracic cancer and discuss its potential use as a biomarker and therapeutic target.}, }
@article {pmid31624358, year = {2019}, author = {Nowak, AK and Forde, PM}, title = {Immunotherapy trials in mesothelioma - promising results, but don't stop here.}, journal = {Nature reviews. Clinical oncology}, volume = {16}, number = {12}, pages = {726-728}, pmid = {31624358}, issn = {1759-4782}, mesh = {Humans ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid31619883, year = {2019}, author = {Munot, MN and Utpat, KV and Desai, UD and Joshi, JM}, title = {Malignant Mesothelioma - Report of Two Cases with Different Presentations.}, journal = {Indian journal of occupational and environmental medicine}, volume = {23}, number = {2}, pages = {93-96}, pmid = {31619883}, issn = {0973-2284}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm that stems from the mesothelial cells lining the visceral cavities, namely, the pleura, peritoneum, pericardium, and tunica vaginalis of the testes. MPM is the most common variant of these and constitutes up to 80% of all malignant mesotheliomas. It is usually associated with asbestos exposure and is a locally invasive neoplasm that spreads along pleura and can involve lungs with locoregional metastasis. Diagnosis remains challenging due to the latency between asbestos exposure and clinical presentation and the variable clinicoradiological manifestations. Meticulous history taking, high index of, suspicion and multimodality approach toward diagnosis are the keys to better prognosis. We hereby present two interesting cases of MPM with different presentations.}, }
@article {pmid31610664, year = {2019}, author = {Levý, M and Boublíková, L and Büchler, T and Šimša, J}, title = {Treatment of Malignant Peritoneal Mesothelioma.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {32}, number = {5}, pages = {333-337}, doi = {10.14735/amko2019333}, pmid = {31610664}, issn = {1802-5307}, mesh = {Combined Modality Therapy ; *Cytoreduction Surgical Procedures ; Humans ; *Hyperthermia, Induced ; Mesothelioma/diagnosis/epidemiology/*therapy ; Peritoneal Neoplasms/diagnosis/epidemiology/*therapy ; }, abstract = {Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.}, }
@article {pmid31609780, year = {2020}, author = {Moline, J and Bevilacqua, K and Alexandri, M and Gordon, RE}, title = {Mesothelioma Associated With the Use of Cosmetic Talc.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {1}, pages = {11-17}, doi = {10.1097/JOM.0000000000001723}, pmid = {31609780}, issn = {1536-5948}, mesh = {*Asbestos ; *Cosmetics ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; *Talc ; }, abstract = {OBJECTIVE: To describe 33 cases of malignant mesothelioma among individuals with no known asbestos exposure other than cosmetic talcum powder.<br><br>METHODS: Cases were referred for medico-legal evaluation, and tissue digestions were performed in some cases. Tissue digestion for the six cases described was done according to standard methodology.<br><br>RESULTS: Asbestos of the type found in talcum powder was found in all six cases evaluated. Talcum powder usage was the only source of asbestos for all 33 cases.<br><br>CONCLUSIONS: Exposure to asbestos-contaminated talcum powders can cause mesothelioma. Clinicians should elicit a history of talcum powder usage in all patients presenting with mesothelioma.}, }
@article {pmid31596154, year = {2019}, author = {Ceresoli, GL and Rossi, A}, title = {Approved and emerging treatments of malignant pleural mesothelioma in elderly patients.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {12}, pages = {1179-1188}, doi = {10.1080/17476348.2019.1678386}, pmid = {31596154}, issn = {1747-6356}, mesh = {Aged ; Combined Modality Therapy ; Humans ; *Immunotherapy ; Lung Neoplasms/*drug therapy/therapy ; Mesothelioma/*drug therapy/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy/therapy ; Treatment Outcome ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with asbestos exposure as the dominant etiologic agent. Owing to the long latent period following exposure, MPM is often diagnosed late in life. Despite this, elderly patients are under-represented in clinical trials. To date, data regarding the tolerability and efficacy of anticancer treatments for elderly patients affected by MPM are still lacking.Areas covered: The current state-of-the-art of approved treatments employed in the treatment of MPM elderly patients is reviewed and discussed, with a look to emerging therapies. A structured search of bibliographic databases for peer-reviewed research literature and of main meeting abstracts using a focused review question was undertaken.Expert opinion: Even though the median age of MPM patients enrolled in the most recent experimental trials is increasing, no specific analysis has been reported so far in the elderly. Moreover, no data are available for the 'oldest of the elderly' (>75 years). Treatment of elderly patients with MPM is one of the major challenges to the clinician. There is a clear need of large, well-conducted retrospective studies and above all of prospective investigations in this patient population, both in the first-and in the second-line setting.}, }
@article {pmid31594840, year = {2019}, author = {Kwak, K and Paek, D and Zoh, KE}, title = {Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {11}, pages = {861-871}, doi = {10.1136/oemed-2019-105735}, pmid = {31594840}, issn = {1470-7926}, mesh = {Asbestos/*toxicity ; Cohort Studies ; Colorectal Neoplasms/*epidemiology/*mortality ; Female ; Hazardous Substances/*toxicity ; Humans ; Lung Neoplasms/epidemiology ; Male ; Occupational Exposure/*statistics &amp; numerical data ; Risk Factors ; }, abstract = {Asbestos exposure is associated with mesothelioma and cancer of the lung, larynx and ovary. However, the association between asbestos exposure and colorectal cancer is controversial despite several systematic reviews of the literature, including a number of meta-analyses. We performed a systematic review and meta-analysis to evaluate quantitatively the association between exposure to asbestos and colorectal cancer. We searched for articles on occupational asbestos exposure and colorectal cancer in PubMed, EMBASE and Web of Science published before April 2018. In total, 44 articles were selected and 46 cohort studies were analysed. The overall pooled risk estimates and corresponding 95% CIs of the association between occupational asbestos exposure and colorectal cancer were calculated using a random-effects model. Subgroup analyses and sensitivity tests were also performed. There was a significantly increased risk of colorectal cancer mortality among workers exposed to asbestos occupationally, with an overall pooled SMR of 1.16 (95% CI: 1.05 to 1.29). The pooled SMR for colorectal cancer was elevated in studies in which the asbestos-associated risk of lung cancer was also elevated (1.43; 95% CI: 1.30 to 1.56). This implies that the risk of colorectal cancer mortality increases as the level of asbestos exposure rises. A sensitivity analysis showed robust results and there was no publication bias. Although the effect size was small and the heterogeneity among studies was large, our findings indicate that occupational exposure to asbestos is a risk factor for colorectal cancer.}, }
@article {pmid31564247, year = {2019}, author = {Vimercati, L and Cavone, D and Caputi, A and Delfino, MC and De Maria, L and Ferri, GM and Serio, G}, title = {Malignant mesothelioma in construction workers: the Apulia regional mesothelioma register, Southern Italy.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {636}, pmid = {31564247}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Construction Industry/instrumentation ; Environmental Exposure/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung/drug effects/pathology ; Lung Neoplasms/chemically induced/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/diagnosis/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; *Registries ; }, abstract = {OBJECTIVE: Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma.<br><br>RESULTS: For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7&#xa0;years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9&#xa0;years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3&#xa0;years. The age at the start of exposure in 68.5% of cases is between 8 and 20&#xa0;years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.}, }
@article {pmid31557561, year = {2019}, author = {Takeda, M and Ohe, Y and Horinouchi, H and Hida, T and Shimizu, J and Seto, T and Nosaki, K and Kishimoto, T and Miyashita, I and Yamada, M and Kaneko, Y and Morimoto, C and Nakagawa, K}, title = {Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {137}, number = {}, pages = {64-70}, doi = {10.1016/j.lungcan.2019.09.010}, pmid = {31557561}, issn = {1872-8332}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/pharmacokinetics/*therapeutic use ; Cohort Studies ; Dipeptidyl Peptidase 4/immunology ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*drug therapy/immunology/pathology ; Male ; Maximum Tolerated Dose ; Mesothelioma/*drug therapy/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/immunology/pathology ; Prognosis ; Response Evaluation Criteria in Solid Tumors ; Tissue Distribution ; Young Adult ; }, abstract = {OBJECTIVES: CD26 is a transmembrane glycoprotein with dipeptidyl peptidase IV activity that is overexpressed in malignant pleural mesothelioma (MPM). We performed a phase I study to determine the maximum tolerated dose, pharmacokinetics, and antitumor activity of YS110, a monoclonal antibody to CD26, in Japanese patients with MPM intolerant of or refractory to prior standard therapies.<br><br>MATERIAL AND METHODS: The study was designed as an open-label, 3&#x2009;+&#x2009;3 dose-escalation, phase I trial. Patients were sequentially assigned to three dosing cohorts (2, 4, or 6&#x2009;mg/kg). Each 6-week treatment cycle consisted of YS110 administration weekly for 5 weeks followed by a 1-week rest period. Treatment was continued until disease progression, death, or intolerable toxicity. Corticosteroid, antihistamine, and acetaminophen administration before each infusion was adopted to limit infusion-related reactions (IRRs).<br><br>RESULTS: Nine Japanese patients (seven men and two women, mean age of 62.2 years), three in each dosing cohort, were enrolled in the study. No patient developed a dose-limiting toxicity. Adverse events of grade 3 or 4 developed in seven patients, with the most common such event being a decreased lymphocyte count. Two patients had mild or moderate IRRs. The serum concentration of YS110 increased in a dose-dependent manner. Among seven patients evaluable for tumor response, four showed stable disease and one achieved a partial response.<br><br>CONCLUSIONS: YS110 showed promising antitumor efficacy and was generally well tolerated in Japanese patients with advanced MPM at doses of up to 6&#x2009;mg/kg. YS110 will be tested at 6&#x2009;mg/kg in a subsequent phase II study.}, }
@article {pmid31546009, year = {2020}, author = {Hinz, TK and Heasley, LE}, title = {Translating mesothelioma molecular genomics and dependencies into precision oncology-based therapies.}, journal = {Seminars in cancer biology}, volume = {61}, number = {}, pages = {11-22}, doi = {10.1016/j.semcancer.2019.09.014}, pmid = {31546009}, issn = {1096-3650}, mesh = {Animals ; Biomarkers, Tumor ; Combined Modality Therapy ; Gene Expression Profiling/methods ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Genomics/methods ; Humans ; Loss of Function Mutation ; Mesothelioma/diagnosis/*etiology/*therapy ; Mesothelioma, Malignant/diagnosis/etiology/therapy ; Mutation ; *Precision Medicine/methods ; Receptor, Fibroblast Growth Factor, Type 1/genetics ; *Translational Research, Biomedical/methods ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, yet lethal asbestos-induced cancer and despite marked efforts to reduce occupational exposure, the incidence has not yet significantly declined. Since 2003, combined treatment with a platinum-based agent and pemetrexed has been the first-line therapy and no effective or approved second-line treatments have emerged. The seemingly slow advance in developing new MPM treatments does not appear to be related to a low level of clinical and pre-clinical research activity. Rather, we suggest that a key hurdle in successfully translating basic discovery into novel MPM therapeutics is the underlying assumption that as a rare cancer, it will also be molecularly and genetically homogeneous. In fact, lung adenocarcinoma and melanoma only benefitted from precision oncology upon full appreciation of the high degree of molecular heterogeneity inherent in these cancers, especially regarding the diversity of oncogenic drivers. Herein, we consider the recent explosion of molecular and genetic information that has become available regarding MPM and suggest ways in which the unfolding landscape may guide identification of novel therapeutic vulnerabilities within subsets of MPM that can be targeted in a manner consistent with the tenets of precision oncology.}, }
@article {pmid31538797, year = {2019}, author = {Geyer, SJ}, title = {Malignant Mesothelioma and Its Nonasbestos Causes: Talcum Powder Does Not Create Occult Asbestos Exposure.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {143}, number = {12}, pages = {1439}, doi = {10.5858/arpa.2019-0388-LE}, pmid = {31538797}, issn = {1543-2165}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Talc ; }, }
@article {pmid31534051, year = {2019}, author = {Hamaidia, M and Gazon, H and Hoyos, C and Hoffmann, GB and Louis, R and Duysinx, B and Willems, L}, title = {Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1-dependent mechanism.}, journal = {JCI insight}, volume = {4}, number = {18}, pages = {}, pmid = {31534051}, issn = {2379-3708}, mesh = {Animals ; Antineoplastic Agents, Immunological/pharmacology/therapeutic use ; Cell Communication/*immunology ; Cell Culture Techniques ; Cell Line, Tumor/transplantation ; Coculture Techniques ; Disease Models, Animal ; Enhancer of Zeste Homolog 2 Protein/antagonists &amp; inhibitors/genetics/immunology/*metabolism ; Humans ; Immunogenic Cell Death/drug effects/genetics ; Lung Neoplasms/*immunology/therapy ; Macrophages/*immunology/metabolism/transplantation ; Male ; Mesothelioma/*immunology/therapy ; Mesothelioma, Malignant ; Mice ; Peroxynitrous Acid/metabolism ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/*immunology ; RAW 264.7 Cells/transplantation ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {The roles of macrophages in orchestrating innate immunity through phagocytosis and T lymphocyte activation have been extensively investigated. Much less understood is the unexpected role of macrophages in direct tumor regression. Tumoricidal macrophages can indeed manifest cancer immunoediting activity in the absence of adaptive immunity. We investigated direct macrophage cytotoxicity in malignant pleural mesothelioma, a lethal cancer that develops from mesothelial cells of the pleural cavity after occupational asbestos exposure. In particular, we analyzed the cytotoxic activity of mouse RAW264.7 macrophages upon cell-cell contact with autologous AB1/AB12 mesothelioma cells. We show that macrophages killed mesothelioma cells by oxeiptosis via a mechanism involving enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27-specific (H3K27-specific) methyltransferase of the polycomb repressive complex 2 (PRC2). A selective inhibitor of EZH2 indeed impaired RAW264.7-directed cytotoxicity and concomitantly stimulated the PD-1 immune checkpoint. In the immunocompetent BALB/c model, RAW264.7 macrophages pretreated with the EZH2 inhibitor failed to control tumor growth of AB1 and AB12 mesothelioma cells. Blockade of PD-1 engagement restored macrophage-dependent antitumor activity. We conclude that macrophages can be directly cytotoxic for mesothelioma cells independent of phagocytosis. Inhibition of the PRC2 EZH2 methyltransferase reduces this activity because of PD-1 overexpression. Combination of PD-1 blockade and EZH2 inhibition restores macrophage cytotoxicity.}, }
@article {pmid31525810, year = {2019}, author = {Kim, RY and Sterman, DH and Haas, AR}, title = {Malignant Mesothelioma: Has Anything Changed?.}, journal = {Seminars in respiratory and critical care medicine}, volume = {40}, number = {3}, pages = {347-360}, doi = {10.1055/s-0039-1693406}, pmid = {31525810}, issn = {1098-9048}, mesh = {Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Biomarkers, Tumor ; Biopsy ; CTLA-4 Antigen/antagonists &amp; inhibitors ; Catheters, Indwelling ; Combined Modality Therapy ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis/pathology/*therapy ; Mesothelioma/diagnosis/pathology/*therapy ; Mesothelioma, Malignant ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/pathology/*therapy ; Pneumonectomy/methods ; Prognosis ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Radiotherapy, Adjuvant ; Thoracoscopy ; }, abstract = {Malignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.}, }
@article {pmid31511437, year = {2020}, author = {Huang, Q and Lan, YJ}, title = {Colorectal cancer and asbestos exposure-an overview.}, journal = {Industrial health}, volume = {58}, number = {3}, pages = {200-211}, pmid = {31511437}, issn = {1880-8026}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Colorectal Neoplasms/*mortality ; Construction Materials/adverse effects ; Humans ; Incidence ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; Occupational Exposure/*adverse effects ; Textile Industry/statistics &amp; numerical data ; }, abstract = {The relationship between colorectal cancer and asbestos exposure has not been fully clarified. This study aimed to determine the associations between asbestos exposure and colorectal cancer. We performed a meta-analysis to quantitatively evaluate this association. A fixed effects model was used to summarize the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We analyzed the dose-effect relationship using lung cancer standardized mortality ratio (SMR) and the risk of mesothelioma as a percent (%) as exposure surrogates. A total of 47 cohort studies were included. We identified 28 incidence cohort studies from 17 separate papers and extracted colorectal cancer standardized incidence ratio (SIR). Cancer mortality data were extracted from 19 separate cohorts among 13 papers. The overall colorectal cancer SMR for synthesis cohort was 1.07 (95% CI 1.02-1.12). Statistically significant excesses were observed in exposure to mixed asbestos (SMR/SIR=1.07), exposure to production (SMR/SIR=1.11), among asbestos cement workers (SMR/SIR=1.18) and asbestos textile workers (SMR/SIR=1.11). Additionally, we determined that the SMR for lung cancer increased with increased exposure to asbestos, as did the risk for colorectal cancer. This study confirms that colorectal cancer has a positive weak associations with asbestos exposure.}, }
@article {pmid31485011, year = {2020}, author = {Marchevsky, AM and Khoor, A and Walts, AE and Nicholson, AG and Zhang, YZ and Roggli, V and Carney, J and Roden, AC and Tazelaar, HD and Larsen, BT and LeStang, N and Chirieac, LR and Klebe, S and Tsao, MS and De Perrot, M and Pierre, A and Hwang, DM and Hung, YP and Mino-Kenudson, M and Travis, W and Sauter, J and Beasley, MB and Galateau-Sallé, F}, title = {Localized malignant mesothelioma, an unusual and poorly characterized neoplasm of serosal origin: best current evidence from the literature and the International Mesothelioma Panel.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {281-296}, pmid = {31485011}, issn = {1530-0285}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Child ; Diagnosis, Differential ; Evidence-Based Medicine ; Female ; Humans ; Male ; Mesothelioma, Malignant/diagnostic imaging/mortality/*pathology/therapy ; Middle Aged ; Pleural Neoplasms/diagnostic imaging/mortality/*pathology/therapy ; Predictive Value of Tests ; Prognosis ; Solitary Fibrous Tumor, Pleural/diagnostic imaging/mortality/*pathology/therapy ; Tumor Burden ; Young Adult ; }, abstract = {Localized malignant mesotheliomas (LMM) is an uncommon and poorly recognized neoplasm. Its pathologic diagnosis is often surprising in patients with serosal/subserosal based localized tumors that are clinically suspicious for metastatic lesions or primary sarcomas. Once a tumor is diagnosed as "mesothelioma", LMM is often mistaken for diffuse malignant mesothelioma (DMM). Best currently available evidence about LMM was collected from the literature and cases diagnosed by members of the International Mesothelioma Panel (IMP). One hundred and one (101) LMM have been reported in the English literature. Patients had localized tumors with identical histopathologic features to DMM. Patients ranged in age from 6 to 82 years; 75% were men. Most (82%) of the tumors were intrathoracic. Others presented as intrahepatic, mesenteric, gastric, pancreatic, umbilical, splenic, and abdominal wall lesions. Tumors varied in size from 0.6 to 15 cm. Most patients underwent surgical resection and/or chemotherapy or radiation therapy. Median survival in a subset of patients was 29 months. Seventy two additional LMM from IMP institutions ranged in age from 28 to 95 years; 58.3% were men. Sixty tumors (83.3%) were intrathoracic, others presented in intraabdominal sites. Tumors varied in size from 1.2 to 19 cm. Median survival for 51 cases was 134 months. Best evidence was used to formulate guidelines for the diagnosis of LMM. It is important to distinguish LMM from DMM as their treatment and prognosis is different. A multidisciplinary approach is needed for the diagnosis of LMM as it shows identical histopathology and immunophenotype to DMM.}, }
@article {pmid31477126, year = {2019}, author = {Abdelgied, M and El-Gazzar, AM and Alexander, WT and Numano, T and Iigou, M and Naiki-Ito, A and Takase, H and Hirose, A and Taquahashi, Y and Kanno, J and Abdelhamid, M and Abdou, KA and Takahashi, S and Alexander, DB and Tsuda, H}, title = {Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration.}, journal = {Particle and fibre toxicology}, volume = {16}, number = {1}, pages = {34}, pmid = {31477126}, issn = {1743-8977}, mesh = {Animals ; Carcinogens/chemistry/pharmacokinetics/*toxicity ; Inhalation Exposure ; Lung/*drug effects/pathology ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Mineral Fibers ; Pleura/*drug effects/pathology ; Rats, Inbred F344 ; Surface Properties ; Tissue Distribution ; Titanium/chemistry/pharmacokinetics/*toxicity ; }, abstract = {BACKGROUND: Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years.<br><br>RESULTS: There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50&#x2009;mg POT and 0.50&#x2009;mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25&#x2009;mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25&#x2009;mg POT, 0.5&#x2009;mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant.<br><br>CONCLUSION: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.}, }
@article {pmid31475103, year = {2019}, author = {Cavallari, I and Urso, L and Sharova, E and Pasello, G and Ciminale, V}, title = {Liquid Biopsy in Malignant Pleural Mesothelioma: State of the Art, Pitfalls, and Perspectives.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {740}, pmid = {31475103}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to asbestos exposure. Although the risk factors for MPM are well-known, the majority of MPM patients are diagnosed at an advanced stage and have a very poor prognosis. Circulating biomarkers for early diagnosis remain to be identified, and the current standard for MPM diagnosis relies on pleural biopsies. Robust non-invasive tests for the screening of asbestos-exposed subjects are therefore an important unmet clinical need. This review provides a critical summary of recent liquid biopsy-based studies aimed at discovering novel blood-based circulating biomarkers for the early diagnosis and prognostic stratification of MPM patients.}, }
@article {pmid31470859, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {78}, pmid = {31470859}, issn = {1476-069X}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Registries/*statistics &amp; numerical data ; Testicular Neoplasms/chemically induced/*epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare disease with a poor prognosis. The diagnosis and management of these lesions are often difficult for pathologists, surgeons, oncologists and occupational physicians. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy except orchidectomy.<br><br>METHODS: A systematic literature review was conducted among the articles published in the English literature on primary MMTVT. Moreover four cases from the Apulia mesothelioma register are reported here.<br><br>RESULTS: Two hundred eighty-nine cases of MMTVT have been reported from 1943 to 2018. Overall asbestos exposure has been investigated only for 58% of all cases reported in this review, while in 41.8% this data are not available. Noteworthy is the fact that in many reports there is not an anamnestic reconstruction of any asbestos exposure. A history of direct occupational, environmental or familial asbestos exposure is found in 27.6% of the cases. The four cases from the Apulia mesothelioma register are all with ascertained occupational exposure to asbestos.<br><br>CONCLUSIONS: The true incidence of asbestos exposure in MMTVT is underestimated because of insufficient information reported in older literature. To establish a broad consensus on the causal relationship between asbestos and MMTVT in the scientific community its necessary to analyze the same variables in the epidemiological studies. In general it should be recommended that a positive history of exposure to asbestos or to asbestos-containing materials are at risk for the development of a MMTVT and should be monitored.}, }
@article {pmid31467759, year = {2019}, author = {Hassan, D and Ligato, S}, title = {Localized Biphasic Malignant Peritoneal Mesothelioma with Rhabdoid Features Involving the Liver: Case Report and Review of the Literature.}, journal = {Case reports in pathology}, volume = {2019}, number = {}, pages = {2732674}, pmid = {31467759}, issn = {2090-6781}, abstract = {INTRODUCTION: Localized malignant mesotheliomas, defined as sharply circumscribed tumors of the serosal membrane with the microscopic appearance of diffuse malignant mesothelioma, are rare tumors; their behavior and prognosis are uncertain. Intrahepatic mesotheliomas are postulated to arise from mesothelial cells of Glisson's capsule.<br><br>CASE PRESENTATION: A 69-year-old female with no history of asbestos exposure presented with a one-month history of increasing abdominal pain associated with constitutional symptoms. Computerized Tomography (CT) scan of the abdomen and pelvis revealed a sizable soft tissue mass within the right paracolic gutter, abutting the inferior hepatic margin, the lateral abdominal wall, and descending colon. Ultrasound-guided biopsy of the mass suggested a poorly differentiated hepatocellular carcinoma. There was no disease elsewhere on PET scan. Surgical resection of the mass was performed. Pathological assessment suggested the tumor to be arising from the liver with invasion of the liver, abdominal wall musculature, and the adventitial surface of the ascending colon. A final diagnosis of localized biphasic malignant peritoneal mesothelioma with rhabdoid features was rendered based on morphology and the result of immunohistochemical studies. The abdominal wall margin was positive. The patient progressed over the course of 6 months despite receiving adjuvant chemotherapy and immunotherapy with metastases and a decline in performance status and was transitioned to hospice.<br><br>CONCLUSION: Localized malignant peritoneal mesotheliomas are rare tumors that may present clinically as a liver mass and simulate primary hepatic or secondary tumors. Definitive diagnosis is obtained by surgical resection in most cases. The clinical outcome is variable with most cases having a poor outcome.}, }
@article {pmid31442913, year = {2019}, author = {Li, Z and Jiang, L and Chew, SH and Hirayama, T and Sekido, Y and Toyokuni, S}, title = {Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia.}, journal = {Redox biology}, volume = {26}, number = {}, pages = {101297}, pmid = {31442913}, issn = {2213-2317}, mesh = {Antigens, Neoplasm/*genetics/*metabolism ; Apoptosis/*genetics ; Biomarkers ; Carbonic Anhydrase IX/*genetics/*metabolism ; Cell Line, Tumor ; Ferroptosis/*genetics ; Humans ; Hypoxia/*metabolism ; Lung Neoplasms/*genetics/*metabolism ; Mesothelioma/*genetics/*metabolism ; Mesothelioma, Malignant ; Mitochondria/genetics/metabolism ; Models, Biological ; Reactive Oxygen Species/metabolism ; }, abstract = {Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO2, bicarbonate and H[+]. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O2) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O2[-] and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.}, }
@article {pmid31428834, year = {2019}, author = {Keshava, HB and Tang, A and Siddiqui, HU and Raja, S and Raymond, DP and Bribriesco, A and Stevenson, J and Murthy, SC and Ahmad, U}, title = {Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.}, journal = {World journal of surgery}, volume = {43}, number = {12}, pages = {3239-3247}, pmid = {31428834}, issn = {1432-2323}, support = {U01 HL088955/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/mortality ; United States/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Projections based on regulations curtailing asbestos use in the USA suggest that peak incidence of pleural mesothelioma would occur between 2000 and 2005 and then decline. We analyzed the National Cancer Database (NCDB) to assess current trends in disease incidence, patient demographics, cancer treatment, and survival.<br><br>METHODS: The NCDB was queried to identify patients diagnosed with pleural mesothelioma from 2004 through 2014. Clinical and pathologic characteristics, treatments, and survival were analyzed. Risk factors for death were identified by multivariable Cox regression.<br><br>RESULTS: A total of 20,988 patients with pleural mesothelioma were reported to the NCDB. The number of cases per year increased from 1783 to 1961, accounting for roughly 0.3% of all reported cancers each year. The proportion of elderly patients increased from 75 to 80%, but distribution by sex remained constant (20% female). The proportion of patients undergoing treatment increased from 34 to 54%. One-year survival increased from 37 to 47% and 3-year survival from 9 to 15% (p&#x2009;<&#x2009;0.001). Factors associated with improved survival included younger age, female sex, epithelioid histology, treatment in an academic center, health insurance, higher income, and multimodality therapy.<br><br>CONCLUSIONS: The annual incidence of mesothelioma has not declined this century and remains stable. Reporting of histologic and clinical staging has improved. National trends suggest that survival is slowly increasing despite an aging cohort. Multimodal therapy and treatment at academic centers are modifiable risk factors associated with improved survival.}, }
@article {pmid31428586, year = {2019}, author = {Hoffmann, PR and Hoffmann, FW and Premeaux, TA and Fujita, T and Soprana, E and Panigada, M and Chew, GM and Richard, G and Hindocha, P and Menor, M and Khadka, VS and Deng, Y and Moise, L and Ndhlovu, LC and Siccardi, A and Weinberg, AD and De Groot, AS and Bertino, P}, title = {Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {720}, pmid = {31428586}, issn = {2234-943X}, support = {G12 MD007601/MD/NIMHD NIH HHS/United States ; R01 AI089999/AI/NIAID NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; R13 CA150300/CA/NCI NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; P30 GM103341/GM/NIGMS NIH HHS/United States ; G12 RR003061/RR/NCRR NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, abstract = {Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8[+] and CD4[+] T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4[+] T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8[+] and CD4[+] T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment.}, }
@article {pmid31420427, year = {2019}, author = {Bousema, JE and van de Luijtgaarden, KM and Wilhelmus, S and Poelman, MM}, title = {Acute severe abdominal pain in a young woman caused by a well-differentiated papillary mesothelioma of the peritoneum.}, journal = {BMJ case reports}, volume = {12}, number = {8}, pages = {}, pmid = {31420427}, issn = {1757-790X}, mesh = {Abdominal Pain/*diagnosis/etiology ; Acute Pain/*diagnosis/etiology ; Adult ; Female ; Humans ; Mesothelioma/complications/*diagnosis ; Peritoneal Neoplasms/complications/*diagnosis ; }, abstract = {Acute abdominal pain is a common symptom in young women. We describe a patient with acute illness and severe lower abdominal pain. Laboratory tests were normal except for mildly deranged inflammatory markers. No abnormalities were reported on abdominal ultrasonography and MRI, whereas diagnostic laparoscopy revealed a tumour located dorsally from the uterus. We resected the tumour and pathology results showed a well-differentiated papillary mesothelioma of the peritoneum (WDPMP). Microscopy showed evidence of acute ischaemia in the resected lesion, which was likely the cause of the acute abdominal pain. WDPMP is a rare disease that arises from the serous membranes which does not seem to have a relation to asbestos exposure. Generally, WDPMP has a mild clinical course and good long-term prognosis.}, }
@article {pmid31419715, year = {2019}, author = {Consonni, D and Migliore, E and Barone-Adesi, F and Dallari, B and De Matteis, S and Oddone, E and Pesatori, AC and Riboldi, L and Mirabelli, D and Mensi, C}, title = {Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy.}, journal = {Environmental research}, volume = {177}, number = {}, pages = {108636}, doi = {10.1016/j.envres.2019.108636}, pmid = {31419715}, issn = {1096-0953}, mesh = {*Asbestos ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/*statistics &amp; numerical data ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Factors ; }, abstract = {BACKGROUND: Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions.<br><br>METHODS: We used data from the Lombardy and Piedmont mesothelioma registries (period 2000-2016, age 45-74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP).<br><br>RESULTS: Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61-3.03) in Lombardy and 2.39 (2.17-2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively).<br><br>CONCLUSION: Men showed more than twofold increased PM rates and reached the same incidence as women 7-10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.}, }
@article {pmid31416570, year = {2019}, author = {Betti, M and Aspesi, A and Sculco, M and Matullo, G and Magnani, C and Dianzani, I}, title = {Genetic predisposition for malignant mesothelioma: A concise review.}, journal = {Mutation research. Reviews in mutation research}, volume = {781}, number = {}, pages = {1-10}, doi = {10.1016/j.mrrev.2019.03.001}, pmid = {31416570}, issn = {1388-2139}, mesh = {Animals ; Asbestos/toxicity ; DNA Repair/drug effects/genetics ; Environmental Exposure/adverse effects ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/drug effects/genetics ; Humans ; Lung Neoplasms/chemically induced/*etiology ; Mesothelioma/chemically induced/*etiology ; Mesothelioma, Malignant ; Risk Factors ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.}, }
@article {pmid31413184, year = {2019}, author = {Barone-Adesi, F and Ferrante, D and Chellini, E and Merler, E and Pavone, V and Silvestri, S and Miligi, L and Gorini, G and Bressan, V and Girardi, P and Ancona, L and Romeo, E and Luberto, F and Sala, O and Scarnato, C and Menegozzo, S and Oddone, E and Tunesi, S and Perticaroli, P and Pettinari, A and Cuccaro, F and Curti, S and Baldassarre, A and Cena, T and Angelini, A and Marinaccio, A and Mirabelli, D and Musti, M and Pirastu, R and Ranucci, A and Magnani, C and , }, title = {Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {9}, pages = {611-616}, doi = {10.1136/oemed-2019-105779}, pmid = {31413184}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Models, Theoretical ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.<br><br>METHODS: We used data from a pool of 43 Italian asbestos cohorts (51&#x2009;801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.<br><br>RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.<br><br>CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.}, }
@article {pmid31411568, year = {2019}, author = {Gudmundsson, G and Tomasson, K}, title = {[Asbestos and its effects on health of Icelanders - review].}, journal = {Laeknabladid}, volume = {105}, number = {7}, pages = {327-334}, doi = {10.17992/lbl.2019.0708.241}, pmid = {31411568}, issn = {1670-4959}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*epidemiology/pathology ; Construction Materials/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Iceland/epidemiology ; Incidence ; Lung Neoplasms/diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Risk Assessment ; Risk Factors ; Sex Distribution ; Time Factors ; }, abstract = {Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.}, }
@article {pmid31411522, year = {2019}, author = {Jiang, Y and Mei, Z and Cao, H and Li, S and Xu, H and Qiu, H and Liu, Y}, title = {Meningeal metastasis of a malignant peritoneal mesothelioma: A case report and literature review.}, journal = {Cancer biology &amp; therapy}, volume = {20}, number = {12}, pages = {1409-1415}, pmid = {31411522}, issn = {1555-8576}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor ; Biopsy ; Disease Progression ; Fatal Outcome ; Female ; Genetic Testing ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnostic imaging/etiology/*pathology ; Meningeal Neoplasms/*diagnosis/*secondary/therapy ; Mesothelioma/diagnostic imaging/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Multimodal Imaging/methods ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/diagnostic imaging/etiology/*pathology ; Radiotherapy, Intensity-Modulated ; }, abstract = {Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.}, }
@article {pmid31406977, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {11}, pages = {1844}, doi = {10.1093/annonc/mdz217}, pmid = {31406977}, issn = {1569-8041}, }
@article {pmid31406207, year = {2019}, author = {Munson, PB and Hall, EM and Farina, NH and Pass, HI and Shukla, A}, title = {Exosomal miR-16-5p as a target for malignant mesothelioma.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {11688}, pmid = {31406207}, issn = {2045-2322}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; R21 ES028857/ES/NIEHS NIH HHS/United States ; S10 OD025030/OD/NIH HHS/United States ; }, mesh = {Aniline Compounds/pharmacology ; Antineoplastic Agents/*pharmacology ; Benzylidene Compounds/pharmacology ; Cell Death ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin D1/*genetics/metabolism ; Exosomes/*chemistry/metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Indoles/pharmacology ; Lung Neoplasms/genetics/metabolism/pathology ; Maleimides/pharmacology ; Mesothelioma/genetics/metabolism/pathology ; Mesothelioma, Malignant ; MicroRNAs/*genetics/metabolism ; Molecular Targeted Therapy/methods ; Ornithine/analogs &amp; derivatives/pharmacology ; Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism ; Signal Transduction ; Small Molecule Libraries/pharmacology ; Transfection ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.}, }
@article {pmid31391078, year = {2019}, author = {Luberto, F and Ferrante, D and Silvestri, S and Angelini, A and Cuccaro, F and Nannavecchia, AM and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mirabelli, D and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Azzolina, D and Tunesi, S and Chellini, E and Miligi, L and Perticaroli, P and Pettinari, A and Bressan, V and Merler, E and Girardi, P and Bisceglia, L and Marinaccio, A and Massari, S and Magnani, C and , }, title = {Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {71}, pmid = {31391078}, issn = {1476-069X}, support = {Current research 2012: asbestos project. Operative Unit 2//Istituto Superiore Sanit&#xe0;/International ; Piano Ricerca 2016-2018, "Programma Speciale Amianto", Ricerca BRIC id 55//INAIL/International ; Piano Ricerca 2016-2018, "Programma Speciale Amianto", Ricerca BRIC id 59//INAIL/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Neoplasms/chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Sex Factors ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos.<br><br>METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40&#x2009;years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution.<br><br>RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40&#x2009;years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40&#x2009;years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%.<br><br>CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.}, }
@article {pmid31388672, year = {2020}, author = {Corti, A and Bonetti, J and Dominici, S and Piaggi, S and Fierabracci, V and Foddis, R and Pompella, A}, title = {Induction of Gamma-Glutamyltransferase Activity and Consequent Pro-oxidant Reactions in Human Macrophages Exposed to Crocidolite Asbestos.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {177}, number = {2}, pages = {476-482}, doi = {10.1093/toxsci/kfz175}, pmid = {31388672}, issn = {1096-0929}, mesh = {*Asbestos ; *Asbestos, Crocidolite/toxicity ; Humans ; Macrophages ; Reactive Oxygen Species ; gamma-Glutamyltransferase ; }, abstract = {Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiol, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at subtoxic concentrations (50-250 ng/1000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent pro-oxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.}, }
@article {pmid31383968, year = {2020}, author = {Wronkiewicz, SK and Roggli, VL and Hinrichs, BH and Kendler, A and Butler, RA and Christensen, BC and Marsit, CJ and Nelson, HH and McClean, MD and Kelsey, KT and Langevin, SM}, title = {Chrysotile fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {228-234}, pmid = {31383968}, issn = {1530-0285}, support = {R21 DE027227/DE/NIDCR NIH HHS/United States ; P30 ES006096/ES/NIEHS NIH HHS/United States ; R01 CA100679/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Asbestos, Serpentine/*adverse effects/analysis ; Case-Control Studies ; Epithelial Cells/chemistry/ultrastructure ; Humans ; Laryngeal Neoplasms/chemistry/*etiology/ultrastructure ; Larynx/chemistry/ultrastructure ; Male ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; Squamous Cell Carcinoma of Head and Neck/chemistry/*etiology/ultrastructure ; }, abstract = {Asbestos describes a group of naturally occurring fibrous silicate mineral compounds that have been associated with a number of respiratory maladies, including mesothelioma and lung cancer. In addition, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The main objective of this work was to strengthen existing evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding laryngeal and pharyngeal SCC, thus providing a more definitive biological link between exposure and disease. Six human papillomavirus (HPV)-negative laryngeal (n = 4) and pharyngeal (n = 2) SCC cases with a history working in an asbestos-exposed occupation were selected from a large population-based case-control study of head and neck cancer. A laryngeal SCC case with no history of occupational asbestos exposure was included as a control. Tissue cores were obtained from adjacent nonneoplastic tissue in tumor blocks from the initial primary tumor resection, and mineral fiber analysis was performed using a scanning electron microscope equipped with an energy dispersive X-ray analyzer (EDXA). Chrysotile asbestos fiber bundles were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure. All three cases had tumors originating in the larynx. In addition, a wollastonite fiber of unclear significance was identified one of the HPV-negative pharyngeal SCC cases. No mineral fibers were identified in adjacent tissue of the case without occupational exposure. The presence of asbestos fibers in the epithelial tissue surrounding laryngeal SCC in cases with a history of occupational asbestos exposure adds a key line of physical evidence implicating asbestos as an etiologic factor.}, }
@article {pmid31380709, year = {2019}, author = {Jacobs, NFB and Towle, KM and Finley, BL and Gaffney, SH}, title = {An updated evaluation of potential health hazards associated with exposures to asbestos-containing drywall accessory products.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {5}, pages = {430-444}, doi = {10.1080/10408444.2019.1639612}, pmid = {31380709}, issn = {1547-6898}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; *Construction Materials ; Environmental Exposure/*analysis/standards/statistics &amp; numerical data ; Humans ; Lung Neoplasms/epidemiology ; No-Observed-Adverse-Effect Level ; Risk Assessment ; }, abstract = {Following a previously published (2012) evaluation of the potential health hazards related to the use of asbestos-containing drywall accessory products, additional information regarding asbestos exposures during the use of accessory products, as well as studies of chrysotile asbestos risk as a function of exposure, have been published in the peer-reviewed literature. The purpose of this analysis is to update the original evaluation with this new information. It was previously estimated that a professional drywaller performing joint compound-associated tasks could have a lifetime cumulative chrysotile exposure of 12-26 f/cc-year. Using conservative assumptions regarding airborne asbestos levels during different drywalling tasks, task duration, and job tenure, we found that a range of 4.3-36.3 f/cc-year is a plausible estimate of a career drywaller's cumulative asbestos exposure from historical joint compound use. The estimated range for bystander exposures would be below (sometimes significantly below) this range depending on the frequency and duration of work near drywallers. Further, the estimated drywaller and bystander total fiber exposures were well below a recently published "no-observed adverse effect level, best estimate" for predominately chrysotile exposures of 89-168 f/cc-year for lung cancer and 208-415 f/cc-year for mesothelioma. We also determined that, even if the chrysotile or possibly talc ingredients in the drywall products had contained asbestiform tremolite, the cumulative tremolite exposures would have been well below a recently published tremolite no-effect level of 0.5-2.6 f/cc-year. Based on our calculations, typical drywall work using asbestos-containing drywall accessory products is not expected to increase the risk of asbestos-related lung cancer or mesothelioma. These conclusions are consistent with the lack of epidemiological evidence that drywall work resulted in an increased incidence of asbestos-related disease in the drywall trades.}, }
@article {pmid31380702, year = {2019}, author = {Marsh, GM and Ierardi, AM and Benson, SM and Finley, BL}, title = {Occupational exposures to cosmetic talc and risk of mesothelioma: an updated pooled cohort and statistical power analysis with consideration of latency period.}, journal = {Inhalation toxicology}, volume = {31}, number = {6}, pages = {213-223}, doi = {10.1080/08958378.2019.1645768}, pmid = {31380702}, issn = {1091-7691}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Cohort Studies ; Europe/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; Talc/*adverse effects ; Young Adult ; }, abstract = {Objectives: We previously published a pooled statistical power analysis of mesothelioma incidence in the Italian, Norwegian, Austrian, and French cosmetic talc miner and miller cohorts. Soon thereafter, updates to the Italian and Norwegian cohorts were published, providing an additional 14,322 person-years of observation. In this study, we provide an updated power analysis using the newly available information. Methods: We pooled the current results regarding pleural cancer/mesothelioma mortality or incidence in four cosmetic talc miner and miller cohorts in Italy, Norway, Austria, and France. We used the expected numbers of cases as reported by the authors and the power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities. Results: There was a pooled total of 113,344 person-years in the cohorts. Although 3.0 pleural cancers/mesotheliomas were expected, there were no reported pleural cancer or mesothelioma cases in any cohort. Our pooled analysis was associated with 79 and 62% power to detect a 3.0-fold and 2.5-fold or greater increase in pleural cancer/mesothelioma, respectively. These favorable power characteristics were effectively maintained when restricting the pooled cohort to workers with a latency period of 30 or more years (observation time from first employment). Conclusions: The epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that exposure to cosmetic talc is associated with the development of pleural cancer/mesothelioma.}, }
@article {pmid31376434, year = {2019}, author = {Butnor, KJ and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Mesothelioma of the tunica vaginalis testis.}, journal = {Human pathology}, volume = {92}, number = {}, pages = {48-58}, doi = {10.1016/j.humpath.2019.07.009}, pmid = {31376434}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Orchiectomy ; Retrospective Studies ; Testicular Neoplasms/*pathology/surgery ; Testis/*pathology/surgery ; Treatment Outcome ; }, abstract = {Malignant mesothelioma (MM) arising from the serosal membranes of the tunica vaginalis testis (TVT) is rare. Most examples in the published medical literature are individual case reports. This study presents the clinicopathological findings of mesothelioma of the TVT in one of the largest series to date. Individuals with mesothelioma of the TVT were identified from a database of more than 4000 mesothelioma cases, and their clinicopathological features were recorded. Eighteen men with MM and 2 with well-differentiated papillary mesothelioma of the TVT were identified, which represented 0.6% of males with mesothelioma in study population. The median age at diagnosis was 72 years (range, 32-85 years). A neoplasm was not suspected preoperatively in 12 of the 17 (71%) men whose clinical presentation was known, 7 of whom presented with hydrocele and 5 with inguinal hernia. The other 5 had a clinically recognized mass. Seven of the men underwent herniorrhaphy; 7, radical orchiectomy; 3, hydrocelectomy; and 3, paratesticular mass biopsy or excision as the initial diagnostic procedure. Twelve of the MM cases were epithelioid and 6 were biphasic. Among the 6 men with MM who had ≥6 months of follow-up, 1 was alive with no evidence of disease at 6 months, and 5 were known to have died of disease 8-74 months (median = 31.5 months) following diagnosis. Three men with MM had received either chemotherapy or radiation therapy. Of the 2 men initially diagnosed with well-differentiated papillary mesothelioma, 1 was alive without evidence of disease 5 years after diagnosis, while the other had findings more compatible with MM with peritoneal involvement 2 years following initial diagnosis. In 15 of the 18 cases of MM (83%), there was documented occupational or paraoccupational exposure to asbestos, the average duration of which was 33 years (range, 2-46 years). Information regarding the presence or absence of pleural plaques was available in 5 of the MM cases, and pleural plaques had been found in 4. Lung tissue was not available for fiber analysis in any of the cases. One additional case originally diagnosed at another institution as MM of the TVT was reclassified as adenocarcinoma following performance of additional immunohistochemical testing. TVT is a rare site of MM, the diagnosis of which is often unsuspected preoperatively. Like its counterparts at other serosal sites, MM of the TVT is an aggressive tumor with a poor prognosis that evidence would suggest is etiologically associated with asbestos in at least some cases.}, }
@article {pmid31375830, year = {2019}, author = {Sorahan, TM}, title = {Cancer incidence in UK electricity generation and transmission workers, 1973-2015.}, journal = {Occupational medicine (Oxford, England)}, volume = {69}, number = {5}, pages = {342-351}, pmid = {31375830}, issn = {1471-8405}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/etiology ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects/statistics &amp; numerical data ; *Power Plants ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Long-term health outcomes in cohorts of workers from the electricity supply industry have been studied.<br><br>AIMS: The aim of the study was to examine updated cancer incidence findings among a cohort of UK electricity generation and transmission workers.<br><br>METHODS: Cancer morbidity experienced by 81 616 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2015. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated based on national rates.<br><br>RESULTS: Overall cancer morbidity was slightly below expectation in males. Significant excesses were found in male workers for mesothelioma (observed [Obs] 763, SRR 326), skin cancer (non-melanoma) (Obs 5616, SRR 106), and prostate cancer (Obs 4298, SRR 106), and in female workers for cancer of the small intestine (Obs 13, SRR 220), nasal cancer (Obs 11, SRR 407), and breast cancer (Obs 758, SRR 110). More detailed analyses showed important contrasts, particularly for mesothelioma, lung cancer, skin cancer, prostate cancer and breast cancer.<br><br>CONCLUSIONS: A clear occupational excess of mesothelioma was not matched by a corresponding excess of asbestos-induced lung cancer. Confident interpretation of the excesses of cancers of the nasal cavities and small intestine is not possible, although occupational exposures received in this industry may well not be involved. An excess of skin cancer in transmission workers may be associated with outdoor working.}, }
@article {pmid31375770, year = {2020}, author = {Churg, A and Galateau-Salle, F and Roden, AC and Attanoos, R and von der Thusen, JH and Tsao, MS and Chang, N and De Perrot, M and Dacic, S}, title = {Malignant mesothelioma in situ: morphologic features and clinical outcome.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {297-302}, pmid = {31375770}, issn = {1530-0285}, mesh = {Aged ; Biomarkers, Tumor/analysis/genetics ; Biopsy ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Disease Progression ; Female ; Humans ; Male ; Mesothelioma, Malignant/enzymology/genetics/*pathology/therapy ; Middle Aged ; Neoplasm Invasiveness ; Peritoneal Neoplasms/enzymology/genetics/*pathology/therapy ; Pleural Neoplasms/enzymology/genetics/*pathology/therapy ; Purine-Nucleoside Phosphorylase/analysis ; Time Factors ; Treatment Outcome ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {The existence of an in situ phase of malignant mesothelioma has long been postulated but until recently has been impossible to prove. Here we describe ten patients with mesothelioma in situ, defined by a single layer of surface mesothelial cells showing loss of BAP1 nuclear immunostaining, no evidence of tumor by imaging and/or by direct examination of the pleura/peritoneum, and no invasive mesothelioma developing for at least 1 year. Nine cases were pleural and one peritoneal. Most patients were biopsied for repeated effusions of unknown etiology; in two patients mesothelioma in situ was found incidentally in lung cancer resections. In addition to surface mesothelium with BAP1 loss, one case had a surface papillary proliferation with BAP1 loss, and two cases had a small (few millimeter) nodule with BAP1 loss. CDKN2A was deleted by FISH in one of eight cases. Methylthioadenosine phosphorylase showed partial loss in the surface mesothelium by immunohistochemistry in three cases. Invasive malignant mesothelioma developed in seven patients with time between biopsy and invasive disease from 12 to 92 (median 60) months. Invasive mesothelioma has not developed in the other three patients at 12, 57, and 120 months, but the latter patient, who has pleural plaques, still has repeated pleural effusions, probably representing a so-called "benign asbestos effusion." We conclude that mesothelioma in situ, as diagnosed using the criteria outlined above, is associated with a high risk of developing invasive mesothelioma, but typically over a relatively protracted time, so that curable interventions maybe possible.}, }
@article {pmid31372931, year = {2020}, author = {Itano, H and Takeda, T and Yamada, T and Koide, M and Kobayashi, T}, title = {Heterologous sarcomatoid pleural mesothelioma with osteosarcomatous differentiation: a report of autopsy case that accomplished trimodality therapy and review of the literature.}, journal = {General thoracic and cardiovascular surgery}, volume = {68}, number = {8}, pages = {871-879}, doi = {10.1007/s11748-019-01182-8}, pmid = {31372931}, issn = {1863-6713}, mesh = {Aged ; Asbestos/adverse effects ; Autopsy ; Biopsy ; Cell Differentiation ; Fatal Outcome ; Humans ; Lung/pathology ; Male ; Mesothelioma/chemically induced/diagnostic imaging/*surgery ; Mesothelioma, Malignant/*surgery ; Neoplasm Recurrence, Local/mortality/*surgery ; Osteosarcoma/*surgery ; Pericardium/surgery ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*surgery ; Pneumonectomy ; Thoracic Wall/pathology ; }, abstract = {Heterologous mesothelioma is a very rare subtype of sarcomatoid mesothelioma characterized by the presence of malignant heterologous elements. A 69-year-old man with a strong history of asbestos exposure presented with a 5-cm mass in his chest wall, destroying the right 5th rib and spreading along the parietal pleura, on a CT. Biopsy revealed heterologous mesothelioma with osteosarcomatous elements, following which left extrapleural pneumonectomy was performed with combined resection of pericardium, hemidiaphragm, and 4th, 5th, and 6th costal segments. A small cytokeratin-positive epithelioid component in the resected tumor definitively confirmed the diagnosis. Post-operative chemotherapy and intensity-modulated radiotherapy were undertaken. After 12-month disease-free period post treatment, rapid intraperitoneal recurrence resulted in death. Autopsy revealed no tumors in the left thorax. We present here a case of heterologous osteosarcomatous pleural mesothelioma that followed a unique clinical course after trimodality therapy. In addition, literature of 54 cases of the similar heterologous mesothelioma was reviewed.}, }
@article {pmid31366157, year = {2019}, author = {Gogou, E and Hatzoglou, C and Zarogiannis, SG and Malli, F and Jagirdar, RM and Gourgoulianis, KI}, title = {Mesothelioma Mortality Rates in Greece for the Period 2005-2015 Is Increased Compared to Previous Decades.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {55}, number = {8}, pages = {}, pmid = {31366157}, issn = {1648-9144}, mesh = {Aged ; Aged, 80 and over ; Cause of Death/*trends ; Female ; Geographic Mapping ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/*mortality ; Middle Aged ; Occupational Diseases/epidemiology/mortality ; }, abstract = {Background and Objective: To present summary statistics regarding malignant mesothelioma (MM) mortality in Greece during the period 2005-2015 and compare it with previous decades, along with gender, age and geographical area analysis. Materials and Methods: The Hellenic Statistical Authority provided the data, which included all deaths for the period 1983 to 2015 that mentioned MM as the death cause in the corresponding death certificate. MM mortality rates have been calculated with respect to gender, age, and geographical location in Greece. Furthermore, a comparison analysis was made among three eleven consecutive year periods, in order to assess potential changes in the mortality rates. Results: The MM mortality rate has significantly increased during the period 2005-2015 both in males and females compared to earlier decades. The maximum number of MM deaths has shifted to an older age group of 70-80 years during the 2005-2015 period as compared to that of 1983-2004 in both genders. Additionally, MM mortality rates have significantly increased in all geographical areas except for the Epirus Prefecture. Conclusions: Our results demonstrate an increased MM mortality rate in Greece for the decade 2005-2015 as compared to the two previous decades. This increase is possibly due to the fact that the peak in asbestos production and use in Greece was in mid 1990s, while the asbestos ban came in effect in 2005. Based on these findings the MM epidemic in Greece has not yet peaked, therefore it is important to implement screening strategies for early MM detection.}, }
@article {pmid31364588, year = {2019}, author = {The Lancet Oncology, }, title = {Asbestos exposure: the dust cloud lingers.}, journal = {The Lancet. Oncology}, volume = {20}, number = {8}, pages = {1035}, doi = {10.1016/S1470-2045(19)30462-0}, pmid = {31364588}, issn = {1474-5488}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; }, }
@article {pmid31360386, year = {2019}, author = {Borrelli, E and Babcock, Z and Kogut, S}, title = {Costs of medical care for mesothelioma.}, journal = {Rare tumors}, volume = {11}, number = {}, pages = {2036361319863498}, pmid = {31360386}, issn = {2036-3605}, abstract = {Malignant mesothelioma is a rare and devastating form of cancer with an increasing economic burden. We sought to describe the direct cost burden of mesothelioma to the US health system. A systematic literature review was performed to locate published estimates of the medical cost of mesothelioma. In addition, we performed an analysis of hospital discharge data from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We also reviewed publicly available legal settlements. We found that published estimates of the cost of medical care for mesothelioma are sparse, and differ with respect to nation, timeframe, and types of cost included. For the year 2014 in the United States, we estimated a mean cost per mesothelioma hospitalization of US$24,124 (95% confidence interval: US$20,819-US$28,983) and a total cost for hospital care of US$44,214,835. In conclusion, we found that reports describing the direct medical cost of care for mesothelioma in the United States are lacking, yet the per-patient cost of care is substantial, as evidenced by analyses of inpatient care and legal settlements.}, }
@article {pmid31355511, year = {2019}, author = {Lee, MJ and Kuehne, N and Hueniken, K and Liang, S and Rai, S and Sorotsky, H and Herman, M and Shepshelovich, D and Bruce, J and Liang, M and Patel, D and Cheng, D and Chen, Z and Eng, L and Brown, MC and Cho, J and Leighl, NB and de Perrot, M and Reisman, D and Xu, W and Bradbury, PA and Liu, G}, title = {Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.}, journal = {Molecular carcinogenesis}, volume = {58}, number = {11}, pages = {1960-1973}, doi = {10.1002/mc.23088}, pmid = {31355511}, issn = {1098-2744}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*genetics/pathology ; Polymorphism, Single Nucleotide/genetics ; Prognosis ; Promoter Regions, Genetic ; Risk Factors ; Smoking/*adverse effects/genetics ; Transcription Factors/*genetics ; }, abstract = {Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.}, }
@article {pmid31355131, year = {2019}, author = {Di Somma, S and Iannuzzi, CA and Passaro, C and Forte, IM and Iannone, R and Gigantino, V and Indovina, P and Botti, G and Giordano, A and Formisano, P and Portella, G and Malfitano, AM and Pentimalli, F}, title = {The Oncolytic Virus dl922-947 Triggers Immunogenic Cell Death in Mesothelioma and Reduces Xenograft Growth.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {564}, pmid = {31355131}, issn = {2234-943X}, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure that urgently requires effective therapeutic strategies. Current treatments are unable to increase significantly patient survival, which is often limited to <1 year from diagnosis. Virotherapy, based on the use of oncolytic viruses that exert anti-cancer effects by direct cell lysis and through the induction of anti-tumor immune response, represents an alternative therapeutic option for rare tumors with limited life expectancy. In this study, we propose the use of the adenovirus dl922-947, engineered to allow selective replication in cancer cells, to counteract MPM. Methods: We performed a thorough preclinical assessment of dl922-947 effects in a set of MPM cell lines and xenografts. Cytotoxicity of dl922-947 alone and in combination assays was evaluated by sulforhodamine B assay. Cell cycle, calreticulin expression, and high mobility group box protein 1 (HMGB1) secretion were determined by flow cytometry, whereas ATP content was determined by a luminescence-based bioassay. The modulation of angiogenic factors in MPM-infected cells was evaluated through ELISA. Results: We found that dl922-947 infection exhibits cytotoxic effects in MPM cell lines, affecting cell viability, cell cycle progression, and regulating main hallmarks of immunogenic cell death inducing calreticulin surface exposure, HMGB1 and ATP release. Our results also suggest that dl922-947 may affect angiogenic signals by regulation of VEGF-A and IL-8 secretion. Furthermore, dl922-947 shows anti-tumor efficacy in murine xenograft models reducing tumor growth and enhancing survival. Finally, the combination with cisplatin potentiated the cytotoxic effect of dl922-947. Conclusions: Overall our data identify virotherapy, based on the use of dl922-947, as a new possible therapeutic strategy against MPM, which could be used alone, in combination with standard chemotherapy drugs, as shown here, or other approaches also aimed at enhancing the antitumoral immune response elicited by the virus.}, }
@article {pmid31336692, year = {2019}, author = {Krówczyńska, M and Wilk, E}, title = {Environmental and Occupational Exposure to Asbestos as a Result of Consumption and Use in Poland.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {14}, pages = {}, pmid = {31336692}, issn = {1660-4601}, mesh = {Asbestos/*analysis ; Construction Materials ; Environmental Exposure/*analysis ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Poland/epidemiology ; }, abstract = {UNLABELLED: Asbestos is harmful to human health; exposure to asbestos causes a wide range of asbestos-related diseases.<br><br>AIM: Malignant mesothelioma (MM) is unique to occupational and environmental asbestos exposure.<br><br>METHODS: Environmental asbestos exposure was examined in relation to asbestos use and manufacturing, the quantity of the asbestos-containing products still in use, the concentrations of asbestos fibres in the air and the number of MM cases diagnosed each year per county.<br><br>RESULTS: The correlation coefficient of the measurements of the asbestos fibre concentrations in the air and the quantity of asbestos-cement products in use is high and amounts to 0.68. Meanwhile, the correlation coefficient of the measurements of asbestos fibre concentrations in air and MM morbidity rate resulting from environmental exposure calculated for particular counties in provinces is low and amounts to 0.37. The highest MM morbidity rate was observed for Ma&#x142;opolskie and &#x15a;l&#x105;skie, a typical industrial area of Poland.<br><br>CONCLUSIONS: There are MM cases which are still attributable to occupational asbestos exposure, although MM cases resulting from environmental exposure to asbestos have an increased MM risk. Poland is among those countries with a low MM incidence rate, which seems to be an underestimation of environmental asbestos exposure. As long as asbestos-cement products are used in the environment, actions should be undertaken to protect public health.}, }
@article {pmid31328588, year = {2019}, author = {Korchevskiy, A and Rasmuson, JO and Rasmuson, EJ}, title = {Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality.}, journal = {Inhalation toxicology}, volume = {31}, number = {5}, pages = {180-191}, doi = {10.1080/08958378.2019.1640320}, pmid = {31328588}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Mineral Fibers/*toxicity ; *Models, Biological ; }, abstract = {Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. Objective: To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Methods: Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Results: Mesothelioma potency factors (RM) for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO2, total Fe oxides or total equivalent Fe[3+] as Fe2O3, and MgO. Modeled potency factors increase as the aspect ratio, SiO2, and total Fe oxide (or Fe2O3) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999, p < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. Conclusion: In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.}, }
@article {pmid31314677, year = {2020}, author = {Henley, SJ and Peipins, LA and Rim, SH and Larson, TC and Miller, JW}, title = {Geographic Co-Occurrence of Mesothelioma and Ovarian Cancer Incidence.}, journal = {Journal of women's health (2002)}, volume = {29}, number = {1}, pages = {111-118}, pmid = {31314677}, issn = {1931-843X}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Carcinoma, Ovarian Epithelial/*epidemiology ; Female ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Ovarian Neoplasms/*epidemiology ; Registries ; United States/epidemiology ; }, abstract = {Background: Asbestos is an established cause of several cancers, including mesothelioma and ovarian cancer. Incidence of mesothelioma, the sentinel asbestos-associated cancer, varies by state, likely reflecting different levels of asbestos exposure. We hypothesized that states with high mesothelioma incidence may also have high ovarian cancer incidence. Materials and Methods: Using data from the Centers for Disease Control and Prevention National Program for Cancer Registries and the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we examined the geographic co-occurrence of mesothelioma and ovarian cancer incidence rates by U.S. state for 2003-2015. Results: By state, mesothelioma incidence ranged from 0.5 to 1.3 cases per 100,000 persons and ovarian cancer incidence ranged from 9 to 12 cases per 100,000 females. When states were grouped by quartile of mesothelioma incidence, the average ovarian cancer incidence rate was 10% higher in states with the highest mesothelioma incidence than in states with the lowest mesothelioma incidence. Ovarian cancer incidence tended to be higher in states with high mesothelioma incidence (Pearson correlation r = 0.54; p < 0.0001). Conclusions: Data from state cancer registries show ovarian cancer incidence was positively correlated with mesothelioma incidence, suggesting asbestos may be a common exposure. The potential for asbestos exposure has declined since the 1970s because fewer products contain asbestos; however, some products, materials, and buildings may still release asbestos and thousands of workers may be exposed. Ensuring that people are protected from exposure to asbestos in their workplaces, homes, schools, and communities may reduce the risk of several cancers.}, }
@article {pmid31295974, year = {2019}, author = {Zona, A and Iavarone, I and Buzzoni, C and Conti, S and Santoro, M and Fazzo, L and Pasetto, R and Pirastu, R and Bruno, C and Ancona, C and Bianchi, F and Forastiere, F and Manno, V and Minelli, G and Minerba, A and Minichilli, F and Stoppa, G and Pierini, A and Ricci, P and Scondotto, S and Bisceglia, L and Cernigliaro, A and Ranzi, A and Comba, P and ,  and ,  and , }, title = {[SENTIERI: Epidemiological Study of Residents in National Priority Contaminated Sites. Fifth Report].}, journal = {Epidemiologia e prevenzione}, volume = {43}, number = {2-3 Suppl 1}, pages = {1-208}, doi = {10.19191/EP19.2-3.S1.032}, pmid = {31295974}, issn = {1120-9763}, mesh = {Adolescent ; Adult ; Aged ; Cause of Death ; Child ; Child, Preschool ; Congenital Abnormalities/epidemiology/etiology ; Endocrine Disruptors/toxicity ; Environmental Exposure/adverse effects ; Environmental Pollution/*adverse effects ; Environmental Restoration and Remediation ; Female ; Humans ; Incidence ; Industrial Waste/adverse effects ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Middle Aged ; Neoplasms/epidemiology/etiology ; Pregnancy ; Young Adult ; }, abstract = {INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program "Environment and Health". The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings.<br><br>METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs.<br><br>RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system.<br><br>CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.}, }
@article {pmid31290725, year = {2022}, author = {Mumma, MT and Sirko, JL and Boice, JD and Blot, WJ}, title = {Mesothelioma mortality within two radiation monitored occupational cohorts.}, journal = {International journal of radiation biology}, volume = {98}, number = {4}, pages = {786-794}, doi = {10.1080/09553002.2019.1642540}, pmid = {31290725}, issn = {1362-3095}, mesh = {*Asbestosis ; Humans ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; Nuclear Power Plants ; *Occupational Diseases ; *Occupational Exposure/adverse effects ; *Radiation Exposure/adverse effects ; Thorax ; }, abstract = {PURPOSE: The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation.<br><br>METHODS AND MATERIALS: Mortality was assessed among 253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung.<br><br>RESULTS: The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50-11.63) and for NPP workers (SMR 5.55; 95% CI 4.88-6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53-2.19). Likewise, deaths from asbestosis (n&#x2009;=&#x2009;189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n&#x2009;=&#x2009;1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96-1.27; p&#x2009;=&#x2009;.18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos.<br><br>CONCLUSIONS: An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.}, }
@article {pmid31289611, year = {2019}, author = {Williams, M and Cheng, YY and Kirschner, MB and Sarun, KH and Schelch, K and Winata, P and McCaughan, B and Kao, S and Van Zandwijk, N and Reid, G}, title = {Transcriptional suppression of the miR-15/16 family by c-Myc in malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {10}, number = {41}, pages = {4125-4138}, pmid = {31289611}, issn = {1949-2553}, abstract = {MicroRNA downregulation is frequent in malignant pleural mesothelioma (MPM), but the mechanisms responsible for loss of miR-15/16 and miR-193a are yet to be elucidated and were investigated in this study. Copy Number Variation (CNV) of microRNA-coding genes was analyzed in MPM cells by digital droplet PCR (ddPCR) and revealed heterozygous loss of miR-193a and miR-15a/16-1, but no change in miR-15b/16-2. Epigenetic control of microRNA expression was inferred following decitabine and Trichostatin A (TSA) treatment which did not substantially affect microRNA expression. Knockdown of c-Myc expression led to upregulation of SMC4, miR-15b and 16, and to a lesser extent DLEU2 and miR-15a, whereas c-Myc overexpression repressed microRNA expression. Chromatin immunoprecipitation (ChIP) assays confirmed the interaction of c-Myc with the DLEU2 and SMC4 promoters. Tumor microRNA expression was determined in samples from MPM patients, with samples of pleura from cardiac surgery patients used as controls. In tumor samples, a strong correlation was observed between the expression of miR-15b and 16 (R[2]=0.793), but not miR-15a and 16. Our data suggest that in MPM, the downregulation of miR-15/16 is due to transcriptional repression by c-Myc, primarily via control of the miR-15b/16-2 locus, while miR-193a-3p loss is due to genomic deletion.}, }
@article {pmid31289169, year = {2019}, author = {Taylor, L and Cooper, D and Aujayeb, A}, title = {Malignant deciduoid mesothelioma: a rare variant of epithelioid mesothelioma.}, journal = {BMJ case reports}, volume = {12}, number = {7}, pages = {}, pmid = {31289169}, issn = {1757-790X}, mesh = {Aged ; Asbestos/*adverse effects ; Deciduoma/*pathology ; Environmental Exposure ; Humans ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Mesothelioma, Malignant ; Palliative Care/methods ; Pleural Neoplasms/diagnostic imaging/pathology ; Prognosis ; Thoracoscopy/methods ; Tomography, X-Ray Computed/methods ; }, abstract = {We describe a case of a deciduoid mesothelioma, a rare variant of epithelioid mesothelioma, which is associated with a very poor prognosis. A review of the relevant literature is also included. The patient was a man with probable asbestos exposure and presented with classic features of pleural malignancy. Diagnosis was reached with close correlation between clinical, radiological and pathological findings.}, }
@article {pmid31285358, year = {2019}, author = {Consonni, D and Calvi, C and De Matteis, S and Mirabelli, D and Landi, MT and Caporaso, NE and Peters, S and Vermeulen, R and Kromhout, H and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Peritoneal mesothelioma and asbestos exposure: a population-based case-control study in Lombardy, Italy.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {8}, pages = {545-553}, pmid = {31285358}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; }, abstract = {OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy.<br><br>METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education.<br><br>RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency.<br><br>CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.}, }
@article {pmid31283845, year = {2019}, author = {Carbone, M and Adusumilli, PS and Alexander, HR and Baas, P and Bardelli, F and Bononi, A and Bueno, R and Felley-Bosco, E and Galateau-Salle, F and Jablons, D and Mansfield, AS and Minaai, M and de Perrot, M and Pesavento, P and Rusch, V and Severson, DT and Taioli, E and Tsao, A and Woodard, G and Yang, H and Zauderer, MG and Pass, HI}, title = {Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.}, journal = {CA: a cancer journal for clinicians}, volume = {69}, number = {5}, pages = {402-429}, pmid = {31283845}, issn = {1542-4863}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents, Immunological/*therapeutic use ; Asbestos/adverse effects ; Australia/epidemiology ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Carcinogenesis/chemically induced/genetics/pathology ; Combined Modality Therapy/methods ; Diagnostic Errors ; Europe/epidemiology ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Global Burden of Disease ; Humans ; Incidence ; Inhalation Exposure/adverse effects ; International Cooperation ; Mesothelioma/diagnosis/epidemiology/etiology/*therapy ; Molecular Targeted Therapy/methods ; Occupational Exposure/adverse effects ; Pleura/drug effects/pathology/surgery ; Pleural Neoplasms/diagnosis/epidemiology/etiology/*therapy ; Pneumonectomy/*methods ; Prognosis ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; United States/epidemiology ; }, abstract = {Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.}, }
@article {pmid31280996, year = {2019}, author = {Tsao, A and Nakano, T and Nowak, AK and Popat, S and Scagliotti, GV and Heymach, J}, title = {Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma.}, journal = {Seminars in oncology}, volume = {46}, number = {2}, pages = {145-154}, doi = {10.1053/j.seminoncol.2019.06.001}, pmid = {31280996}, issn = {1532-8708}, mesh = {Asbestos/toxicity ; Bevacizumab/therapeutic use ; Carcinogenesis/*drug effects/genetics ; Humans ; Indoles/therapeutic use ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mesothelioma/*drug therapy/genetics/pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*drug therapy/genetics/pathology ; Pleural Neoplasms/*drug therapy/genetics/pathology ; Quinazolines/therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a global health issue, the principal cause of which is exposure to asbestos. The prevalence is anticipated to rise over the next 2 decades, particularly in developing countries, due to the 30-50-year latency period between exposure to asbestos and carcinogenic development. Unresectable MPM has a poor prognosis and limited treatment options and, as such, there is a broad range of therapeutic targets of interest, including angiogenesis, immune checkpoints, mesothelin, as well as chemotherapeutic agents. Recently, the results of several randomized trials in the first-line setting combining antiangiogenic agents with chemotherapy have been reported. This review examines the scientific rationale for targeting angiogenesis in the treatment of unresectable MPM and analyzes recent clinical results with antiangiogenic agents in development (bevacizumab, nintedanib, and cediranib) for the management of MPM.}, }
@article {pmid31273181, year = {2019}, author = {Terakawa, H and Gabata, R and Haba, Y and Takada, S and Sakamoto, K and Sasaki, M}, title = {[A Case of Peritoneal Mesothelioma Diagnosed by Ileus].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {6}, pages = {1081-1083}, pmid = {31273181}, issn = {0385-0684}, mesh = {Aged ; *Asbestos ; Humans ; *Ileus/etiology ; Male ; *Mesothelioma/complications ; *Peritoneal Neoplasms/complications ; }, abstract = {The present case involved a man aged about 70 years. He visited our hospital with the main complaint of abdominal pain. We diagnosed him with intestinal obstruction, and we decided to perform surgery. White knot sections were spread inside the abdominal cavity, and the small intestine appeared as a single block. This block was resected and examined for peritoneal mesothelioma. Peritoneal mesothelioma is thought to have incubation period of 20-25 years after exposure to asbestos, and the number of affected patients will increase in the future. In some cases, peritoneal mesothelioma occurs only in the peritoneum; therefore, diagnosis often becomes difficult. Once intestinal obstruction occurs, administering chemotherapy is difficult. Therefore, early diagnosis is thought to be very important.}, }
@article {pmid31269586, year = {2019}, author = {Liu, XH and Wu, H and Huang, YF and Zhang, GY and Xu, MH}, title = {[Clinical characteristics of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis: a report of 6 cases].}, journal = {Zhonghua yi xue za zhi}, volume = {99}, number = {24}, pages = {1893-1897}, doi = {10.3760/cma.j.issn.0376-2491.2019.24.011}, pmid = {31269586}, issn = {0376-2491}, mesh = {Adult ; Aged ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Peritoneal Neoplasms ; *Peritonitis, Tuberculous ; Retrospective Studies ; }, abstract = {Objective: To reduce the misdiagnosis rate of ascites and improve the diagnosis rate of malignant peritoneal mesothelioma. Methods: From May 2008 to May 2018, in Xiangya Hospital of Central South University,the clinical data of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis were retrospectively analyzed. Results: (1) Among the 6 patients, they were male; the age of onset was 42-70 (52±9.57) years old, and there was no history of asbestos exposure. (2) All cases with abdominal pain or abdominal distension were there and the course of disease was more than 1 month to more than 2 years. (3) In all patients,the nature of ascites was exudate; ADA was higher than normal value and below 45 U/L; LDH value in ascites was higher than 200 U/L (83.3%); mesothelioma was considered in ascites cytology in 1 case. (4) Laparoscopic biopsy was performed in 2 cases and B-ultrasound guided biopsy in 4 cases; Among them, malignant peritoneal mesothelioma diagnosed by pathology. (5) In Immunohistochemical positive markers, MC was the most sensitive (100%), followed by CR (67%), CK-Pan (67%), Ki-67 (67%) and EMA (67%). (6) Two patients received treatment with operation, abdominal hyperthermic perfusion and postoperative systemic chemotherapy. Conclusions: (1) Malignant peritoneal mesothelioma should be considered in middle-aged and aged male patients with unexplained ascites and early laparoscopy or laparotomy for diagnosis. (2) ADA and LDH level in ascites are significant in differentiating tuberculous peritonitis from malignant peritoneal mesothelioma. (3) Immunohistochemical positive marker MC may be a potential specific marker for malignant mesothelioma. (4) The survival time of patients is improved by comprehensive treatment such as operation and chemotherapy.}, }
@article {pmid31267149, year = {2019}, author = {Jiménez-Ramírez, C and Casjens, S and Juárez-Pérez, CA and Raiko, I and Del Razo, LM and Taeger, D and Calderón-Aranda, ES and Rihs, HP and Acosta-Saavedra, LC and Weber, DG and Cabello-López, A and Pesch, B and Ochoa-Vázquez, MD and Burek, K and Torre-Bouscoulet, L and Pérez-Padilla, JR and García-Bazan, EM and Brüning, T and Johnen, G and Aguilar-Madrid, G}, title = {Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {5}, pages = {641-649}, pmid = {31267149}, issn = {1432-1750}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Calbindin 2/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/diagnosis/epidemiology ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis/epidemiology ; Mesothelioma, Malignant ; Mexico/epidemiology ; Middle Aged ; Pleural Neoplasms/*blood/diagnosis/epidemiology ; Predictive Value of Tests ; Prognosis ; Risk Assessment ; Risk Factors ; Sex Factors ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.<br><br>METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.<br><br>RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively.<br><br>CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.}, }
@article {pmid31265162, year = {2019}, author = {Numano, T and Higuchi, H and Alexander, DB and Alexander, WT and Abdelgied, M and El-Gazzar, AM and Saleh, D and Takase, H and Hirose, A and Naiki-Ito, A and Suzuki, S and Takahashi, S and Tsuda, H}, title = {MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats.}, journal = {Cancer science}, volume = {110}, number = {8}, pages = {2485-2492}, pmid = {31265162}, issn = {1349-7006}, support = {//5th Term Long-Range Research Initiative (2017) by Japan Chemical Industry Association/ ; H22-kagaku-ippan-005//Ministry of Health, Labour and Welfare/ ; H22-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H25-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; H27-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H28-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; //Egyptian Cultural Affairs and Missions Sector/ ; }, mesh = {Animals ; Asbestos, Crocidolite/adverse effects ; Injections, Intraperitoneal/methods ; Lung/*drug effects ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/*adverse effects ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Rats, Inbred F344 ; Trachea/drug effects/pathology ; }, abstract = {Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.}, }
@article {pmid31262194, year = {2019}, author = {Guazzelli, A and Meysami, P and Bakker, E and Bonanni, E and Demonacos, C and Krstic-Demonacos, M and Mutti, L}, title = {What can independent research for mesothelioma achieve to treat this orphan disease?.}, journal = {Expert opinion on investigational drugs}, volume = {28}, number = {8}, pages = {719-732}, doi = {10.1080/13543784.2019.1638363}, pmid = {31262194}, issn = {1744-7658}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage/pharmacology ; Drug Repositioning ; Humans ; Immunotherapy/methods ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Molecular Docking Simulation ; Molecular Targeted Therapy ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Rare Diseases/drug therapy/pathology ; Survival Rate ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival. Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy. Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment.}, }
@article {pmid31260913, year = {2019}, author = {Pyana Kitenge, J and Kapinga Kayembe, D and Tshibangu Muamba, M and Kachil Rubing, H and De Vos, B and Van Bouwel, J and Nemery, B}, title = {Malignant mesothelioma in Sub-Saharan Africa: A case report from Lubumbashi, DR Congo.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108556}, doi = {10.1016/j.envres.2019.108556}, pmid = {31260913}, issn = {1096-0953}, mesh = {Adult ; *Asbestos ; Congo ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; South Africa ; }, abstract = {Although asbestos has been used throughout Africa in the past decades, no reports of asbestos-related malignant mesothelioma are available from sub-Saharan Africa, except from South Africa and Zimbabwe. We present a case of a 39-year-old man who died from a histologically proven malignant mesothelioma of the peritoneum in Lubumbashi, DR Congo. No occupational exposure to asbestos could be found in his history. In view of his young age, we speculated that he had been exposed to asbestos as a child, which was highly plausible because he had grown up in one of the numerous mining estates of the region. The houses of these estates were often built with asbestos-containing materials, notably roofs made of corrugated asbestos-cement. The possibility of past domestic or environmental exposure to asbestos was substantiated by the identification of chrysotile and crocidolite fibres in samples of asbestos-cement collected from the home where the patient had lived as a child. To our knowledge, this is the first report of malignant mesothelioma from a country in the Central African region. We expect that heightened awareness and improved diagnosis will lead to the detection of more asbestos-related diseases in Africa.}, }
@article {pmid31260832, year = {2019}, author = {Tsao, MS and Carbone, M and Galateau-Salle, F and Moreira, AL and Nicholson, AG and Roden, AC and Adjei, AA and Aubry, MC and Fennell, DA and Gomez, D and Harpole, D and Hesdorffer, M and Hirsch, FR and Liu, G and Malik, S and Nowak, A and Peikert, T and Salgia, R and Szlosarek, P and Taioli, E and Yang, H and Tsao, A and Mansfield, AS}, title = {Pathologic Considerations and Standardization in Mesothelioma Clinical Trials.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {10}, pages = {1704-1717}, doi = {10.1016/j.jtho.2019.06.020}, pmid = {31260832}, issn = {1556-1380}, mesh = {Biological Specimen Banks ; Biomarkers, Tumor/*genetics ; Clinical Trials as Topic/*standards ; Diagnosis, Differential ; Humans ; Mesothelioma/*classification/genetics/*pathology ; Pleural Neoplasms/*classification/genetics/*pathology ; }, abstract = {The accurate diagnosis of mesothelioma is critical for the appropriate clinical management of this cancer. Many issues complicate making the diagnosis of mesothelioma including the presence of reactive mesothelial cells in benign pleural effusions, the heterogeneity of mesothelioma histopathology, the relatively high incidence of other epithelial malignancies that metastasize to the pleura, and primary sarcomas that arise within the pleura. Given the rapidly evolving field of molecular profiling and the need for translational correlates in mesothelioma clinical trials, the National Cancer Institute (NCI)-International Association for the Study of Lung Cancer-Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting was convened in March 2017 to develop a consensus on standard pathology guidelines for future NCI-sponsored clinical trials in mesothelioma. This consensus statement covers recommendations for specimen handling, pathologic classification and diagnosis, biobanking, and tissue correlative studies.}, }
@article {pmid31239765, year = {2019}, author = {Ospina, D and Villegas, VE and Rodríguez-Leguizamón, G and Rondón-Lagos, M}, title = {Analyzing biological and molecular characteristics and genomic damage induced by exposure to asbestos.}, journal = {Cancer management and research}, volume = {11}, number = {}, pages = {4997-5012}, pmid = {31239765}, issn = {1179-1322}, abstract = {Asbestos is one of the most important occupational carcinogens. Currently, about 125 million people worldwide are exposed to asbestos in the workplace. According to global estimates, at least 107,000 people die each year from lung cancer, mesothelioma, and asbestosis as a result of occupational exposure to asbestos. The high pathogenicity of this material is currently known, being associated with the development of pulmonary diseases, of which lung cancer is the main cause of death due to exposure to this mineral. Pulmonary diseases related to asbestos are a common clinical problem and a major health concern worldwide. Extensive research has identified many important pathogenic mechanisms; however, the precise molecular mechanisms involved, and the generated genomic damage that lead to the development of these diseases, are not completely understood. The modes of action that underlie this type of disease seem to differ depending on the type of fiber, lung clearance, and genetics. This evidences the need to increase our knowledge about these effects on human health. This review focuses on the characteristics of asbestos and the cellular and genomic damage generated in humans via exposure.}, }
@article {pmid31237454, year = {2019}, author = {Ledda, C and Caltabiano, R and Vella, F and Matera, S and Marconi, A and Loreto, C and Rapisarda, V}, title = {Fibulin-3 as biomarker of malignant mesothelioma.}, journal = {Biomarkers in medicine}, volume = {13}, number = {10}, pages = {875-886}, doi = {10.2217/bmm-2018-0285}, pmid = {31237454}, issn = {1752-0371}, mesh = {Asbestos/toxicity ; Biomarkers, Tumor/blood/*metabolism ; Databases, Factual ; ErbB Receptors/metabolism ; Extracellular Matrix Proteins/blood/*metabolism ; Humans ; Lung Neoplasms/chemically induced/mortality/*pathology ; Mesothelioma/chemically induced/mortality/*pathology ; Mesothelioma, Malignant ; Survival Rate ; }, abstract = {Many malignant diseases are associated with past asbestos exposure; the most lethal and strictly related to previous fiber exposure being malignant mesothelioma (MM). Effective preventive protocols may include sensitive and specific biomarkers. The role of Fb-3 has been recently investigated for MM early detection, but its role is still under debate. After an independent search for scientific literature, nine studies were included for a systematic review. Human Fb-3 levels seem to be able to separate healthy people with previous exposure to asbestiform fibers from MM patients. Fb-3 blood levels can distinguish MM effusions from other malignant and benign effusions. Furthers investigations on more significant groups of patients are desirable to validate and assess the validity of combining Fb-3 with other biomarkers.}, }
@article {pmid31229775, year = {2019}, author = {Ramos-Bonilla, JP and Cely-García, MF and Giraldo, M and Comba, P and Terracini, B and Pasetto, R and Marsili, D and Ascoli, V and Lysaniuk, B and Rodríguez, MC and Mazzeo, A and Panqueva, RDPL and Baldión, M and Cañón, D and García-Herreros, LG and Pinzón, B and Hernández, LJ and Silva, YA}, title = {An asbestos contaminated town in the vicinity of an asbestos-cement facility: The case study of Sibaté, Colombia.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108464}, doi = {10.1016/j.envres.2019.04.031}, pmid = {31229775}, issn = {1096-0953}, mesh = {Adult ; *Asbestos/toxicity ; Cities ; Colombia ; Environmental Exposure ; Female ; Humans ; Incidence ; Male ; *Mesothelioma/epidemiology ; Middle Aged ; *Occupational Exposure ; }, abstract = {INTRODUCTION: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town.<br><br>METHODS: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibat&#xe9;. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas.<br><br>RESULTS: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibat&#xe9;. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibat&#xe9; was 3.1&#x202f;&#xd7;&#x202f;10[5] persons-year for males and 1.6&#x202f;&#xd7;&#x202f;10[5] persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibat&#xe9; were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos.<br><br>CONCLUSION: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibat&#xe9;.}, }
@article {pmid31225962, year = {2019}, author = {Marsili, D and Canepa, A and Mossone, N and Comba, P}, title = {Environmental Health Education for Asbestos-Contaminated Communities in Italy: The Casale Monferrato Case Study.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, pmid = {31225962}, issn = {2214-9996}, mesh = {Adolescent ; Adult ; Asbestos/*toxicity ; Construction Materials/*toxicity ; Curriculum ; Environmental Exposure/adverse effects ; Environmental Health/*education ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Peer Group ; Pleural Neoplasms/epidemiology ; *Schools ; }, abstract = {BACKGROUND: Environmental health education contributes towards increasing awareness of communities to prevent exposure to hazardous substances. Casale Monferrato, the operating site for the Eternit asbestos-cement factory from 1907 to 1986, is a prioritized asbestos-contaminated site for remediation in Italy. The area is prone to severe asbestos-related diseases. About 50 cases of mesothelioma are diagnosed in Casale Monferrato annually; mesothelioma has been shown to be caused by occupational, environmental and domestic asbestos exposure.<br><br>OBJECTIVES: The goal of this paper is to analyze the Casale Monferrato case study in terms of youth engagement in environmental health education initiatives on asbestos risk and health impact. The paper aims at underlining the lessons learned in order to share the success of this initiative with other communities living in asbestos-contaminated sites in different countries.<br><br>METHODS: Peer education methodology has been used through the Asbestos Classroom to involve teachers, students and other local stakeholders in training activities, in selection of the contents for educational materials and interactive tools, as well as in choosing the presentation process for the aforementioned knowledge sharing instruments.<br><br>FINDINGS: From November 2014 to June 2018, 185 high school students and teachers were trained through the Asbestos Classroom. Through December 2018, they trained 3,241 classroom visitors. The Classroom relies on an inclusive participative process in which young people play a key role in the network of relationships within their community.<br><br>CONCLUSIONS: The paper corroborates the importance of engaging the educational system in communication&#xa0;efforts aimed at fostering collective awareness on environmental risk and health-related impacts for communities living in industrially contaminated sites. Considering the global dimension of the asbestos contamination and disease burden, this experience might be of relevance both in countries that banned asbestos and in those where asbestos is not yet prohibited.}, }
@article {pmid31211722, year = {2019}, author = {Metintas, M and Ak, G and Metintas, S and Yildirim, H and Dündar, E and Rahman, N}, title = {Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases.}, journal = {Journal of bronchology &amp; interventional pulmonology}, volume = {26}, number = {3}, pages = {210-218}, doi = {10.1097/LBR.0000000000000559}, pmid = {31211722}, issn = {1948-8270}, support = {MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Female ; Humans ; *Image-Guided Biopsy/adverse effects/methods ; Male ; Mesothelioma/complications/*diagnostic imaging/pathology ; Middle Aged ; Patient Selection ; Pleura/diagnostic imaging/pathology ; Pleural Effusion/*diagnostic imaging/etiology ; Pleural Neoplasms/complications/*diagnostic imaging/pathology/secondary ; Predictive Value of Tests ; Prospective Studies ; Thoracoscopy ; *Tomography, X-Ray Computed ; Triage ; Tuberculosis, Pleural/complications/*diagnostic imaging/pathology ; Young Adult ; }, abstract = {BACKGROUND: This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases.<br><br>METHODS: Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan-guided Abrams' needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan-guided Abrams' needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure.<br><br>RESULTS: A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable.<br><br>CONCLUSION: Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.}, }
@article {pmid31207975, year = {2019}, author = {Catino, A and de Gennaro, G and Di Gilio, A and Facchini, L and Galetta, D and Palmisani, J and Porcelli, F and Varesano, N}, title = {Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {6}, pages = {}, pmid = {31207975}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case-control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response.}, }
@article {pmid31205069, year = {2020}, author = {Alchami, FS and Attanoos, RL and Gibbs, A and Morgan, F and Jasani, B}, title = {Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {28}, number = {6}, pages = {444-447}, doi = {10.1097/PAI.0000000000000779}, pmid = {31205069}, issn = {1533-4058}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Polyomavirus Transforming/genetics/*metabolism ; Asbestos/*adverse effects ; Cell Transformation, Neoplastic/genetics ; Correlation of Data ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Mesothelioma, Malignant/etiology/genetics/*metabolism ; Middle Aged ; Pleural Neoplasms/etiology/genetics/*metabolism/pathology ; Poliovirus Vaccines/*adverse effects ; Retrospective Studies ; Simian virus 40/genetics/*metabolism ; United Kingdom ; }, abstract = {BACKGROUND: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.<br><br>MATERIALS AND METHODS: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.<br><br>RESULTS: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.<br><br>CONCLUSION: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.}, }
@article {pmid31200818, year = {2019}, author = {Tsim, S and Paterson, S and Cartwright, D and Fong, CJ and Alexander, L and Kelly, C and Holme, J and Evison, M and Blyth, KG}, title = {Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {133}, number = {}, pages = {123-129}, doi = {10.1016/j.lungcan.2019.05.017}, pmid = {31200818}, issn = {1872-8332}, support = {25355/CRUK_/Cancer Research UK/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Pleura/*pathology ; Pleural Effusion, Malignant/*diagnosis/pathology ; Pleural Neoplasms/*diagnosis/pathology ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVES: Negative effusion cytology is more common in certain forms of Malignant Pleural Effusion (MPE) and results in pathway delay. Local Anaesthetic Thoracoscopy (LAT) is extremely sensitive and safe but cannot be offered to all. A stratified pathway, including 'Direct to LAT' in selected cases could enhance patient experience but requires reliable baseline predictors of unhelpful cytology, including both negative (no malignant cells) and incomplete results (malignant cells identified but predictive markers failed), since pleural biopsies will be required in the latter for optimal management. This retrospective analysis of a prospective multi-centre study, sought to identify baseline features for pathway rationalization.<br><br>MATERIALS AND METHODS: 363/638 (57%) of patients recruited to the DIAPHRAGM study (ISRCTN10079972) were included. Prospective data, including final diagnoses, asbestos exposure and fluid cytology results were supplemented by retrospective Computed Tomography (CT) and predictive marker reports. Independent predictors of negative and incomplete cytology were determined by multivariable logistic regression. Contingency tables were used to assess diagnostic value of cytology in associated phenotypes.<br><br>RESULTS: 238/363 (66%) patients were diagnosed with MPE (18 tumour types). Fluid cytology was negative in 151/238 (63%) and independently associated with asbestos-exposure (Odds Ratio (OR) 5.34) and a malignant CT (OR 2.25). When both features were recorded the sensitivity and negative predictive value of fluid cytology were 19% (95% CI 11-30%) and 9% (95% CI 4-20%)), respectively. Cytology was incomplete in 34/238 (14%), i.e. 47% of positive cytology cases) but was not associated with any baseline feature. ORs for incomplete cytology in Ovarian, Breast, Renal and Lung Cancer were 83, 22, 21 and 9, respectively.<br><br>CONCLUSION: Negative cytology is extremely likely in patients with asbestos exposure and a malignant CT report. A 'Direct-to-LAT' approach may be appropriate in this setting. No baseline predictors of incomplete cytology were identified.}, }
@article {pmid31192957, year = {2019}, author = {Zan, X and Wang, Y and Shi, J and Zhao, L and Zhao, Y and Liu, R and Zhou, Y and Wan, Y and , }, title = {Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.}, journal = {Medicine}, volume = {98}, number = {24}, pages = {e16028}, pmid = {31192957}, issn = {1536-5964}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; *Meta-Analysis as Topic ; Pleural Neoplasms/*metabolism ; *Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM.<br><br>METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers.<br><br>RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication.<br><br>CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM.<br><br>ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.<br><br>PROSPERO REGISTRATION NUMBER: CRD42019125880.}, }
@article {pmid31179006, year = {2019}, author = {Taylor, BH and Warnock, C and Tod, A}, title = {Communication of a mesothelioma diagnosis: developing recommendations to improve the patient experience.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000413}, pmid = {31179006}, issn = {2052-4439}, mesh = {Asbestos/adverse effects ; Caregivers/*psychology ; *Communication ; Female ; Health Personnel/*psychology ; Humans ; Lung Neoplasms/*diagnosis/etiology/mortality/psychology ; Male ; Mesothelioma/*diagnosis/etiology/mortality/psychology ; Mesothelioma, Malignant ; *Professional-Patient Relations ; Prognosis ; Qualitative Research ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer linked to asbestos exposure and inhalation. As with other cancers, receiving a diagnosis of MPM is challenging and distressing. Particular challenges are associated with communicating a diagnosis of MPM, including explaining the disease and its prognosis, treatment options and legal and financial implications. Receiving A Diagnosis Of Mesothelioma (RADIO Meso) aimed to understand the experience of communicating a diagnosis of MPM from the perspective of patients, family carers and health professionals.<br><br>METHODS: This qualitative study comprised 31 individual interviews with patients, family carers and health professionals. This was followed by two group interviews (n=42) and an electronic consultation exercise (n=39).<br><br>RESULTS: This study provides unique insight into the mesothelioma diagnostic experience of patients, family carers and health professionals. Key findings include the importance of regarding diagnosis as a process, and provision of continuity and consistency. The clinical nurse specialist and effective multidisciplinary team working provided vital contributions to successful mesothelioma diagnostic communication. Facilitators to diagnostic communication included honesty and timeliness in communication, partnership working and maintaining a patient-centred approach. Challenges to enhancing mesothelioma diagnosis communication included accessing ongoing training, ensuring a suitable clinical environment and being able to allocate appropriate time.<br><br>CONCLUSION: The RADIO Meso study highlights factors that influence the communication of a diagnosis of MPM from the perspectives of individual patients and family carers. These findings provide the basis for a set of recommendations that can be used by health professionals to improve the MPM diagnostic experience.}, }
@article {pmid31171576, year = {2019}, author = {Takada, K and Fujimoto, N and Ozeki, T and Nishimura, J and Miyamoto, Y and Asano, M and Fuchimoto, Y and Wada, S and Ozaki, S and Igawa, T and Sonobe, H and Kishimoto, T}, title = {Small intestinal intussusception in an adult.}, journal = {Journal of clinical pathology}, volume = {72}, number = {7}, pages = {510}, doi = {10.1136/jclinpath-2017-204973}, pmid = {31171576}, issn = {1472-4146}, mesh = {Aged ; Autopsy ; Cell Proliferation ; Fatal Outcome ; Humans ; Intestine, Small/diagnostic imaging/pathology ; Intussusception/*diagnostic imaging/pathology ; Male ; Mesothelioma/*diagnostic imaging/pathology ; }, }
@article {pmid31169558, year = {2019}, author = {Louw, A and Badiei, A and Creaney, J and Chai, MS and Lee, YCG}, title = {Advances in pathological diagnosis of mesothelioma: what pulmonologists should know.}, journal = {Current opinion in pulmonary medicine}, volume = {25}, number = {4}, pages = {354-361}, doi = {10.1097/MCP.0000000000000578}, pmid = {31169558}, issn = {1531-6971}, mesh = {Cyclin-Dependent Kinase Inhibitor p16/analysis ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/diagnosis/pathology ; *Mesothelioma/diagnosis/pathology ; Mesothelioma, Malignant ; Pleural Effusion/*diagnosis/metabolism ; *Pleural Neoplasms/diagnosis/pathology ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {PURPOSE OF REVIEW: Malignant pleural mesothelioma (MPM) is a universally fatal illness with a rising incidence, particularly in developing countries. The diagnosis can be challenging and require repeated investigations with implications for the patient and healthcare system.<br><br>RECENT FINDINGS: Distinguishing between benign/reactive and malignant mesothelial proliferations can be challenging. Cytological diagnosis of MPM from pleural fluid is as reliable as histological analysis of tissue biopsies in epithelioid MPM - an approach endorsed by the International Academy of Cytology. Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway. The prognostic values of these molecules are being investigated. Clinicians should be aware of the recently described BAP1 tumor predisposition syndrome and offer genetic investigations in potential patients. Routine use of prophylactic radiotherapy in MPM patients after pleural interventions has been disproved in a randomized trial.<br><br>SUMMARY: Diagnosis of epithelioid MPM can be established on pleural fluid analysis in most patients. The use of BAP1 immunostaining and CDKN2A/p16 fluorescence in-situ hybridization are particularly useful in distinguishing benign from malignant mesothelial proliferations. Clinicians should ensure these investigations are available in the pathological assessment of cases to minimize invasive investigations and the associated risks.}, }
@article {pmid31166112, year = {2019}, author = {Santos Seoane, SM and Yano Escudero, R and Arenas García, V}, title = {An unexpected cause of dysphagia: pleural mesothelioma.}, journal = {Revista espanola de enfermedades digestivas}, volume = {111}, number = {6}, pages = {494-495}, doi = {10.17235/reed.2019.6024/2018}, pmid = {31166112}, issn = {1130-0108}, mesh = {Aged ; Deglutition Disorders/*etiology ; Humans ; Male ; Mesothelioma/*complications ; Pleural Neoplasms/*complications ; }, abstract = {Malignant mesothelioma usually originates from the pleura or peritoneum, and has a poor prognosis. The incidence of this type of tumor is increasing worldwide, which is probably a result of occupational or environmental exposure to asbestos. In 90% dyspnea, chest pain or a combination of both are usually the initial symptoms. Dysphagia only occurs in 1.4% and is very rare as the initial symptom. We present the case of a middle-aged patient, in whom the initial symptom was dysphagia, so an endoscopy was performed. This showed extrinsic compression of the esophagus that was demonstrated when performing the chest X-ray, in which it was revealed a posterior mediastinal mass surrounding the esophagus concentrically without mucosal invasion.}, }
@article {pmid31158563, year = {2019}, author = {Konen, T and Johnson, JE and Lindgren, P and Williams, A}, title = {Cancer incidence and mortality associated with non-occupational and low dose exposure to Libby vermiculite in Minnesota.}, journal = {Environmental research}, volume = {175}, number = {}, pages = {449-456}, doi = {10.1016/j.envres.2019.04.004}, pmid = {31158563}, issn = {1096-0953}, mesh = {*Aluminum Silicates ; *Asbestos ; Asbestos, Amphibole ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Minnesota/epidemiology ; Montana ; Occupational Exposure/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: A vermiculite processing plant in a Minneapolis, Minnesota neighborhood utilized asbestos-containing ore from Libby, Montana from the late 1930's until 1989. Multiple pathways of exposure to Libby asbestos were characterized in a cohort of over 6000 plant workers and residents living near the plant.<br><br>OBJECTIVE: We conducted a cohort linkage study to assess the impact of cumulative low dose exposure and the role of occupational history on asbestos-related mortality and cancer morbidity among cohort members residing near a vermiculite plant.<br><br>METHODS: Cohort members alive in 1988 (n&#x202f;=&#x202f;5848) were linked to the Minnesota Cancer Surveillance System to identify incident cases of mesothelioma, lung cancer, and all-cancer diagnosed from 1988 to 2010. Proportional incidence ratios (PIRs) were calculated for mesothelioma and lung cancer. Vital status and cause of death were ascertained from Minnesota vital records and the National Death Index (1988-2011). Mortality rates of the cohort (2001-2011) for asbestos-related outcomes were compared to the Minnesota population to estimate standardized mortality ratios (SMRs) and stratified by gender, exposure, and occupational history categories.<br><br>RESULTS: We identified seven cases of mesothelioma, with elevated incidence only in females (PIR&#x202f;=&#x202f;11.76, 95% CI: 3.17, 30.12). Lung cancer was elevated in both genders: PIR&#x202f;=&#x202f;1.54 (95% CI: 1.19, 2.0) in males and 1.62 (95% CI: 1.21, 2.12) in females. We found elevated mortality from COPD, lung cancer, and mesothelioma among females (SMR for mesothelioma in females&#x202f;=&#x202f;18.97, CI: 3.91, 55.45), among the 546 deaths identified. All four deaths from mesothelioma occurred in the >75th percentile of exposure (>0.0156 fiber/cc x months). The SMR for lung cancer and all respiratory cancer was elevated even after controlling for occupation.<br><br>CONCLUSIONS: Community exposure to Libby amphibole asbestos from a vermiculite processing plant is associated with increased risk of COPD, lung cancer and mesothelioma incidence and mortality, most notably among females, and is likely to remain a public health issue for years to come.}, }
@article {pmid31138176, year = {2019}, author = {Kettunen, E and Savukoski, S and Salmenkivi, K and Böhling, T and Vanhala, E and Kuosma, E and Anttila, S and Wolff, H}, title = {CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {507}, pmid = {31138176}, issn = {1471-2407}, support = {115372//Terveyden Tutkimuksen Toimikunta/ ; 109003//Ty&#xf6;suojelurahasto/ ; }, mesh = {Aged ; Asbestos/*adverse effects ; Chromosomes, Human/genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/*metabolism ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/chemically induced/genetics/*metabolism ; Male ; Mesothelioma/chemically induced/genetics/*metabolism ; Mesothelioma, Malignant ; Middle Aged ; Stromal Cells/metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.<br><br>METHODS: We studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.<br><br>RESULTS: We were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (>&#x2009;1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure (&#x2264; 0.5 million f/g) (51.4% vs 16.7%; p&#x2009;=&#x2009;0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p&#x2009;=&#x2009;0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.<br><br>CONCLUSIONS: We found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.}, }
@article {pmid31132706, year = {2019}, author = {Colombino, E and Capella, S and Casalinuovo, F and Racco, R and Pruiti, F and Volante, M and Di Marco Lo Presti, V and Belluso, E and Capucchio, MT}, title = {Malignant peritoneal mesothelioma in a boar who lived in Calabria (Italy): Wild animal as sentinel system of human health.}, journal = {The Science of the total environment}, volume = {683}, number = {}, pages = {267-274}, doi = {10.1016/j.scitotenv.2019.05.254}, pmid = {31132706}, issn = {1879-1026}, mesh = {Animals ; Asbestos/analysis ; Asbestosis/epidemiology/veterinary ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Monitoring/*methods ; Environmental Pollutants/analysis ; Humans ; Italy ; Lung Neoplasms/epidemiology/*veterinary ; Mesothelioma/epidemiology/*veterinary ; Mesothelioma, Malignant ; Swine ; }, abstract = {Mesothelioma is a tumor of the serosal membranes described both in human and veterinary medicine. While in humans the relationship between mesothelioma and exposure to asbestos and some other asbestiform minerals is well known, in animals it is still difficult to establish. In this paper a case of malignant peritoneal mesothelioma probably related to asbestos exposure in a wild boar is described. At post-mortem evaluation the peritoneum, diaphragm and serosal surface of liver and kidneys showed isolated to coalescent multiple nodular lesions. Samples from diaphragm, liver and lung were collected to perform microbiological and histological investigations. To assess the presence of asbestos and/or other asbestiform minerals, SEM-EDS investigations were performed on organs and soil samples collected from the area where the wild boar lived. Microbiological investigations were negative for Mycobacterium species. Gross and histological examination were compatible with a biphasic mesothelioma, with nodules composed of epithelioid and sarcomatoid elements with high pleomorphism. Immunohistochemistry revealed only multifocal scattered positivity for WT-1 and D2-40. Asbestos fibres were detected in all samples (organs and soil) by SEM-EDS, demonstrating a potential relationship between the neoplasia and the exposure to naturally occurring asbestos (NOA). In conclusion, the results of the present study are further confirmation that wild animals, such as the boar, are suitable sentinels to indicate the risk of environmental exposure to asbestos for human populations.}, }
@article {pmid31120531, year = {2019}, author = {Chen, T and Sun, XM and Wu, L}, title = {High Time for Complete Ban on Asbestos Use in Developing Countries.}, journal = {JAMA oncology}, volume = {5}, number = {6}, pages = {779-780}, doi = {10.1001/jamaoncol.2019.0446}, pmid = {31120531}, issn = {2374-2445}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; China ; Developing Countries ; Humans ; Mesothelioma/etiology/*prevention &amp; control ; Occupational Diseases/etiology/*prevention &amp; control ; Occupational Exposure/adverse effects/*prevention &amp; control ; Pleural Neoplasms/etiology/*prevention &amp; control ; }, }
@article {pmid31120100, year = {2019}, author = {Kamiya, H and Peters, S and Sodhi-Berry, N and Reid, A and Gordon, L and de Klerk, N and Brims, F and Musk, AW and Franklin, P}, title = {Validation of an Asbestos Job-Exposure Matrix (AsbJEM) in Australia: Exposure-Response Relationships for Malignant Mesothelioma.}, journal = {Annals of work exposures and health}, volume = {63}, number = {7}, pages = {719-728}, doi = {10.1093/annweh/wxz038}, pmid = {31120100}, issn = {2398-7316}, mesh = {Adult ; Asbestos/*adverse effects ; Australia/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*analysis ; Occupations/statistics &amp; numerical data ; Proportional Hazards Models ; Young Adult ; }, abstract = {OBJECTIVES: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates.<br><br>METHODS: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates.<br><br>RESULTS: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively.<br><br>CONCLUSION: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates.}, }
@article {pmid31119375, year = {2019}, author = {Galani, V and Varouktsi, A and Papadatos, SS and Mitselou, A and Sainis, I and Constantopoulos, S and Dalavanga, Y}, title = {The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment.}, journal = {Cancer chemotherapy and pharmacology}, volume = {84}, number = {2}, pages = {241-253}, doi = {10.1007/s00280-019-03878-3}, pmid = {31119375}, issn = {1432-0843}, mesh = {Apoptosis/*immunology ; Humans ; Lung Neoplasms/pathology/*therapy ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Prognosis ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies.}, }
@article {pmid31110054, year = {2019}, author = {Waqar, AB and Menzies, D and Casey, M and Doran, M}, title = {Paraneoplastic phenomenon in mesothelioma.}, journal = {Thorax}, volume = {74}, number = {7}, pages = {719-720}, doi = {10.1136/thoraxjnl-2019-213176}, pmid = {31110054}, issn = {1468-3296}, mesh = {Aged ; Biopsy ; Humans ; Lung Neoplasms/*complications/diagnostic imaging/pathology ; Male ; Mesothelioma/*complications/diagnostic imaging/pathology ; Mesothelioma, Malignant ; Ophthalmoplegia/*etiology ; Paraneoplastic Syndromes, Ocular/*etiology ; Pleural Effusion, Malignant/etiology ; Tomography, X-Ray Computed ; }, abstract = {A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.}, }
@article {pmid31107974, year = {2020}, author = {Milosevic, V and Kopecka, J and Salaroglio, IC and Libener, R and Napoli, F and Izzo, S and Orecchia, S and Ananthanarayanan, P and Bironzo, P and Grosso, F and Tabbò, F and Comunanza, V and Alexa-Stratulat, T and Bussolino, F and Righi, L and Novello, S and Scagliotti, GV and Riganti, C}, title = {Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.}, journal = {International journal of cancer}, volume = {146}, number = {1}, pages = {192-207}, doi = {10.1002/ijc.32419}, pmid = {31107974}, issn = {1097-0215}, mesh = {ATP Binding Cassette Transporter, Subfamily B/*genetics ; Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; Female ; Humans ; Interleukin-1beta/*metabolism ; Interleukin-8/*metabolism ; Mesothelioma/*drug therapy/metabolism/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; *Wnt Signaling Pathway ; }, abstract = {Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness-related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5-knocked-out (KO) IC clones were resensitized to the drugs in vitro and in patient-derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β-catenin/c-myc axis that also increased IL-8 and IL-1β production. IL-8 and IL-1β-KO IC clones reduced the c-myc-driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5-KO clones had lower IL-8 and IL-1β secretion, and c-myc transcriptional activity, suggesting that either Wnt/GSK3β/β-catenin and IL-8/IL-1β signaling drive c-myc-mediated transcription of ABCB5. ABCB5 correlated with lower time-to-progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients.}, }
@article {pmid31103412, year = {2019}, author = {Scagliotti, GV and Gaafar, R and Nowak, AK and Nakano, T and van Meerbeeck, J and Popat, S and Vogelzang, NJ and Grosso, F and Aboelhassan, R and Jakopovic, M and Ceresoli, GL and Taylor, P and Orlandi, F and Fennell, DA and Novello, S and Scherpereel, A and Kuribayashi, K and Cedres, S and Sørensen, JB and Pavlakis, N and Reck, M and Velema, D and von Wangenheim, U and Kim, M and Barrueco, J and Tsao, AS}, title = {Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.}, journal = {The Lancet. Respiratory medicine}, volume = {7}, number = {7}, pages = {569-580}, doi = {10.1016/S2213-2600(19)30139-0}, pmid = {31103412}, issn = {2213-2619}, mesh = {Aged ; Antineoplastic Agents/*administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols ; Cisplatin/*administration &amp; dosage ; Double-Blind Method ; Female ; Humans ; Indoles/*administration &amp; dosage ; Lung Neoplasms/*drug therapy/mortality/pathology ; Male ; Mesothelioma/*drug therapy/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration &amp; dosage ; Pleural Neoplasms/*drug therapy/mortality/pathology ; Progression-Free Survival ; }, abstract = {BACKGROUND: Nintedanib targets VEGF receptors 1-3, PDGF receptors α and β, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma.<br><br>METHODS: This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged &#x2265;18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m[2]) plus cisplatin (75 mg/m[2]) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100.<br><br>FINDINGS: Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5&#xb7;3 months (IQR 2&#xb7;8-7&#xb7;3) in the nintedanib group and 5&#xb7;1 months (2&#xb7;7-7&#xb7;8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6&#xb7;8 months [95% CI 6&#xb7;1-7&#xb7;0]) and the placebo group (7&#xb7;0 months [6&#xb7;7-7&#xb7;2]; HR 1&#xb7;01 [95% CI 0&#xb7;79-1&#xb7;30], p=0&#xb7;91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]).<br><br>INTERPRETATION: The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported.<br><br>FUNDING: Boehringer Ingelheim.}, }
@article {pmid31097089, year = {2019}, author = {MacRae, RM and Ashton, M and Lauk, O and Wilson, W and O'Rourke, N and Simone, CB and Rimner, A}, title = {The role of radiation treatment in pleural mesothelioma: Highlights of the 14th International Conference of the International mesothelioma interest group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {132}, number = {}, pages = {24-27}, doi = {10.1016/j.lungcan.2019.03.023}, pmid = {31097089}, issn = {1872-8332}, mesh = {Animals ; Combined Modality Therapy ; Congresses as Topic ; Humans ; International Cooperation ; Mesothelioma/*radiotherapy ; Pleural Neoplasms/*radiotherapy ; Public Opinion ; Radiation Oncology/*trends ; Radiotherapy/*methods ; }, abstract = {Radiation remains an important component of mesothelioma treatment in 2018. Its use as a treatment modality continues to evolve as the technology for planning and delivery continues to improve. Use of radiation to improve local control in the involved hemithorax has been a common adjuvant treatment post extrapleural pneumonectomy for many years. Modern treatment options with advanced planning techniques including protons and intensity modulated radiation therapy lead to new potential options for treatment post lung-sparing surgery or in the unresectable setting. Presentations and discussions on the implementation of these strategies for palliation, treatment of oligometastatic recurrence or unresectable disease were the focus of a session dedicated to the role of radiation therapy at the 14[th] International Conference of the International Mesothelioma Interest Group and are reviewed in this article. Preclinical data to better understand how to integrate radiation and the delivery of novel systemic therapy approached like check point inhibitors are also presented.}, }
@article {pmid31095409, year = {2019}, author = {Rosner, D and Markowitz, G and Chowkwanyun, M}, title = {"Nondetected": The Politics of Measurement of Asbestos in Talc, 1971-1976.}, journal = {American journal of public health}, volume = {109}, number = {7}, pages = {969-974}, pmid = {31095409}, issn = {1541-0048}, mesh = {Asbestos/*toxicity ; Carcinogens, Environmental/*adverse effects ; Cosmetics/*toxicity ; Humans ; Mesothelioma/chemically induced ; Mineral Fibers/adverse effects ; Particulate Matter/analysis ; Talc/*toxicity ; }, abstract = {The recent lawsuits against Johnson &amp; Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson &amp; Johnson has claimed that there was "no detectable asbestos" in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does "nondetected" mean? Here, we examine the historical development of the argument that asbestos in talcum powder was "nondetected." We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term "nondetected" rather than "asbestos-free" as a term of art.}, }
@article {pmid31092657, year = {2019}, author = {de Boer, NL and van Kooten, JP and Burger, JWA and Verhoef, C and Aerts, JGJV and Madsen, EVE}, title = {Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial.}, journal = {BMJ open}, volume = {9}, number = {5}, pages = {e026779}, pmid = {31092657}, issn = {2044-6055}, mesh = {Adjuvants, Immunologic/*therapeutic use ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Cancer Vaccines/*administration &amp; dosage/*therapeutic use ; *Clinical Trials, Phase II as Topic ; *Cytoreduction Surgical Procedures ; Dendritic Cells/*immunology ; Feasibility Studies ; Female ; Humans ; *Hyperthermia, Induced ; Immunotherapy ; Lung Neoplasms/pathology/*therapy ; Male ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/pathology/*therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.<br><br>METHODS AND ANALYSIS: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.<br><br>INTERVENTION: 4 to 6&#x2009;weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6&#x2009;months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.<br><br>ETHICS AND DISSEMINATION: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.<br><br>TRIAL REGISTRATION NUMBER: NTR7060. EudraCT: 2017-000897-12; Pre-Results.}, }
@article {pmid31087402, year = {2019}, author = {Loomis, D and Richardson, DB and Elliott, L}, title = {Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {471-477}, pmid = {31087402}, issn = {1097-0274}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 OH007803/OH/NIOSH CDC HHS/United States ; R01-OH007803/OH/NIOSH CDC HHS/United States ; }, mesh = {Adult ; Age Factors ; Asbestos, Serpentine/*adverse effects/analysis ; Cohort Studies ; Confidence Intervals ; Environmental Monitoring/methods ; Evaluation Studies as Topic ; Female ; Humans ; Lung Neoplasms/*chemically induced/*mortality/physiopathology ; Male ; Maximum Allowable Concentration ; Mesothelioma/*chemically induced/*mortality/physiopathology ; Mesothelioma, Malignant ; Middle Aged ; North Carolina/epidemiology ; Occupational Diseases/etiology/mortality ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/*chemically induced/*mortality/physiopathology ; Retrospective Studies ; Risk Assessment ; Sex Factors ; Survival Analysis ; Textile Industry ; }, abstract = {BACKGROUND: While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse.<br><br>METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression.<br><br>RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100&#x2009;f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations.<br><br>CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.}, }
@article {pmid31078776, year = {2019}, author = {Salaroglio, IC and Kopecka, J and Napoli, F and Pradotto, M and Maletta, F and Costardi, L and Gagliasso, M and Milosevic, V and Ananthanarayanan, P and Bironzo, P and Tabbò, F and Cartia, CF and Passone, E and Comunanza, V and Ardissone, F and Ruffini, E and Bussolino, F and Righi, L and Novello, S and Di Maio, M and Papotti, M and Scagliotti, GV and Riganti, C}, title = {Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {8}, pages = {1458-1471}, doi = {10.1016/j.jtho.2019.03.029}, pmid = {31078776}, issn = {1556-1380}, mesh = {Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Prognosis ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified.<br><br>METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome.<br><br>RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and&#xa0;4.2%, respectively), CD4 molecule-positive (CD4[+]) programmed&#xa0;death 1-positive (PD-1[+]) (>5.2%) and CD8[+]PD-1[+] (6.4%) cells, CD4[+] lymphocyte activating 3-positive (LAG-3[+]) (>2.8%) and CD8[+]LAG-3[+] (>2.8%) cells, CD4[+] T cell immunoglobulin and mucin domain 3-positive&#xa0;(TIM-3[+]) (>2.5%), and CD8[+]TIM-3[+] (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1[+]/LAG-3[+]/TIM-3[+] CD4[+] tumor-infiltrating lymphocytes correlated with overall survival.<br><br>CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.}, }
@article {pmid31078166, year = {2019}, author = {Labrèche, F and Kim, J and Song, C and Pahwa, M and Ge, CB and Arrandale, VH and McLeod, CB and Peters, CE and Lavoué, J and Davies, HW and Nicol, AM and Demers, PA}, title = {The current burden of cancer attributable to occupational exposures in Canada.}, journal = {Preventive medicine}, volume = {122}, number = {}, pages = {128-139}, doi = {10.1016/j.ypmed.2019.03.016}, pmid = {31078166}, issn = {1096-0260}, support = {//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Asbestos/toxicity ; Breast Neoplasms ; Canada/epidemiology ; Carcinogens/*toxicity ; Censuses ; Female ; Humans ; Lung Neoplasms ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology/prevention &amp; control ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; Prevalence ; Silicon Dioxide/toxicity ; Skin Neoplasms ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. Population attributable risks were estimated using Levin's equation and applied to the 2011 cancer statistics from the Canadian Cancer Registry. It is estimated that 15.5 million Canadians alive in 2011 were exposed, during at least one year between 1961 and 2001, to at least one carcinogen in the workplace. Overall, we estimated that in 2011, between 3.9% (95% CI: 3.1%-8.1%) and 4.2% (95% CI: 3.3%-8.7%) of all incident cases of cancer were due to occupational exposure, corresponding to lower and upper numbers of 7700-21,800 cases. Five of the cancer sites - mesothelioma, non-melanoma skin cancer, lung, female breast, and urinary bladder - account for a total of 7600 to 21,200 cancers attributable to occupational exposures such as solar radiation, asbestos, diesel engine exhaust, crystalline silica, and night shift work. Our study highlights cancer sites and occupational exposures that need recognition and efforts by all stakeholders to avoid preventable cancers in the future.}, }
@article {pmid31068670, year = {2019}, author = {Fitzgerald, RC and Rhodes, JM}, title = {Ingested asbestos in filtered beer, in addition to occupational exposure, as a causative factor in oesophageal adenocarcinoma.}, journal = {British journal of cancer}, volume = {120}, number = {12}, pages = {1099-1104}, pmid = {31068670}, issn = {1532-1827}, mesh = {Adenocarcinoma/*epidemiology/etiology ; Alcohol Drinking/*epidemiology ; Asbestos/*poisoning ; *Beer ; Esophageal Neoplasms/*epidemiology/etiology ; Food Contamination ; Humans ; Incidence ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/statistics &amp; numerical data ; }, abstract = {Oesophageal adenocarcinoma has become much more common over the past 50 years, particularly in Britain, with an unexplained male to female ratio of > 4:1. Given the use of asbestos filtration in commercial brewing and reports of its unregulated use in British public houses in the 1970's to clear draught beer "slops", we have assessed the hypothesis that ingested asbestos could be a causative factor for this increased incidence. Importantly, occupational asbestos exposure increases the risk of adenocarcinoma but not squamous cell carcinoma of the oesophagus. The presence of asbestos fibres was consistently reported in filtered beverages including beers in the 1970s and asbestos bodies have been found in gastrointestinal tissue, particularly oesophageal tissue, at autopsy. There is no reported association between the intake of alcohol and oesophageal adenocarcinoma but studies would mostly have missed exposure from draught beer before 1980. Oesophageal adenocarcinoma has some molecular similarities to pleural mesothelioma, a condition that is largely due to inhalation of asbestos fibres, including predominant loss of tumour suppressor genes rather than an increase of classical oncogenic drivers. Trends in incidence of oesophageal adenocarcinoma and mesothelioma are similar, rising rapidly over the past 50 years but now plateauing. Asbestos ingestion, either from beer consumed before around 1980, or from occupational exposure, seems a plausible causative factor for oesophageal adenocarcinoma. If this is indeed the case, its incidence should fall back to a low baseline by around 2050.}, }
@article {pmid31057996, year = {2019}, author = {Barsky, AR and Cengel, KA and Katz, SI and Sterman, DH and Simone, CB}, title = {First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4102}, pmid = {31057996}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive disease, with few, if any, curative interventions. While there is growing interest in using immunotherapy and immuno-gene therapy to treat MPM, very limited data currently exist for combining these modalities with radiotherapy. Preclinical data suggest that radiotherapy may be combined with immunotherapy to produce disease regression, with abscopal effects in mice with MPM. We report the first-ever case of abscopal effect in a patient with MPM, following radiotherapy and immuno-gene therapy. The patient was a 67-year-old male with prior asbestos exposure who presented with progressive dyspnea and thoracic pain. He underwent partial right pleurectomy, pleural biopsy, and talc pleurodesis, with pathology revealing epithelioid MPM. A subsequent chest computed tomography (CT) scan and fluoro-deoxyglucose positron-emission tomography (FDG-PET) CT scan showed extensive, right-sided, fluoro-deoxyglucose (FDG) avid mass-like pleural thickening encasing the right lung, with likely mediastinal extension, nodal metastases, and vascular compression. He enrolled in a clinical trial in which he received intrapleural interferon-alpha gene therapy but needed to discontinue therapy due to supraventricular tachycardia and superior vena cava syndrome induced from tumor burden. He was emergently treated with palliative radiotherapy to 30 Gy in 10 fractions. He was then started on pemetrexed and cisplatin chemotherapy. His subsequent chest CT scan two months after radiotherapy completion showed a dramatic treatment response within, as well as outside of, the irradiated field. After completion of radiotherapy, he did experience radiation esophagitis requiring nasogastric tube placement. Herein, we highlight the feasibility and efficacy of combining immuno-gene therapy with palliative radiotherapy to produce a substantial treatment response and an abscopal effect in a patient with unresectable MPM.}, }
@article {pmid31055741, year = {2019}, author = {Cui, Y and Zha, Y and Li, T and Bai, J and Tang, L and Deng, J and He, R and Dong, F and Zhang, Q}, title = {Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile.}, journal = {Environmental science and pollution research international}, volume = {26}, number = {18}, pages = {18708-18718}, doi = {10.1007/s11356-019-04978-6}, pmid = {31055741}, issn = {1614-7499}, support = {No. 41472046//National Natural Fund Project of China/ ; No. 41602033//National Natural Youth Fund Project of China/ ; No. YF17-Y12//the Fund&#xa0;Project of Sichuan Medical Law Research Center/ ; No. 2017LZXNYD-J24//Collaborative Fund of Luzhou Government and Southwest Medical University/ ; }, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; China ; Heme Oxygenase-1/metabolism ; Lipid Peroxidation/drug effects ; Lung/*drug effects/metabolism ; Lung Injury/*chemically induced/metabolism ; Male ; Oxidative Stress/*drug effects ; Particle Size ; Rats ; Rats, Wistar ; }, abstract = {Chrysotile accounts for some 90% to 95% of all the asbestos used worldwide. Scientific evidences have shown that asbestos (including chrysotile) exposure is associated with increased rates of lung cancer, asbestosis, and mesothelioma. However, molecular mechanisms underlying the toxicity effects of chrysotile are not clear. This study evaluated the oxidative stress in chronic lung toxicity caused by the intratracheal instillation (IT) of four kinds China representative chrysotile once a month for 12 months in Wistar rats. These results indicated that chrysotile exposure led to an obvious increase in lung mass and slowed the growth of body mass. Inflammation and fibrosis were observed by hematoxylin-eosin (HE) staining. Exposure to chrysotile significantly increased the accumulation of reactive oxygen species (ROS) and the level of lipid peroxidation and decreased antioxidant capacity in lung tissues. Furthermore, 1-6-month chrysotile exposure activated heme oxygenase-1 (HO-1) and heat shock protein 70 (HSP70) expression, whereas 12-month exposure caused significant decreases of two-factor expression levels in XK and MN groups when compared to negative control group. Therefore, our results suggested that chronic chrysotile pulmonary injury in Wistar rats is triggered by oxidative damage. Meanwhile, the oxidative damage of MN and XK was stronger than that of SSX and AKS, and the difference of oxidative damage in four chrysotile could have been brought by its properties, morphology, chemical composition, and particle size. With all the above mentioned in view, we hope that the revealed data in the experiment could contribute to the progress of further researches on the toxicity and mechanism of chrysotile.}, }
@article {pmid31046484, year = {2019}, author = {Nowak, AK and McDonnell, A and Cook, A}, title = {Immune checkpoint inhibition for the treatment of mesothelioma.}, journal = {Expert opinion on biological therapy}, volume = {19}, number = {7}, pages = {697-706}, doi = {10.1080/14712598.2019.1606209}, pmid = {31046484}, issn = {1744-7682}, mesh = {Antibodies, Monoclonal/*therapeutic use ; B7-H1 Antigen/immunology/metabolism ; Biomarkers, Tumor/metabolism ; CTLA-4 Antigen/immunology/metabolism ; Drug Therapy, Combination ; Humans ; Immunotherapy ; Mesothelioma/*drug therapy/pathology ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.<br><br>AREAS COVERED: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.<br><br>EXPERT OPINION: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.}, }
@article {pmid31046142, year = {2019}, author = {Macedo, RF and Cerqueira, EMFP and Algranti, E and Silva, D and De Capitani, EM}, title = {High frequency and severity of pleural changes in former workers exposed to anthophyllite associated with other contaminating amphibole asbestos in Brazil.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {503-510}, doi = {10.1002/ajim.22977}, pmid = {31046142}, issn = {1097-0274}, mesh = {Aged ; Asbestos, Amphibole/*adverse effects/analysis ; Asbestosis/*epidemiology/etiology ; Brazil/epidemiology ; Cohort Studies ; Databases, Factual ; Environmental Monitoring/methods ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*diagnosis/epidemiology ; Male ; Maximum Allowable Concentration ; Mesothelioma/chemically induced/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Mining ; Occupational Exposure/*adverse effects ; Occupational Health ; Pleural Neoplasms/chemically induced/*epidemiology/physiopathology ; Retrospective Studies ; Risk Assessment ; Spirometry/methods ; Time Factors ; Vital Capacity ; }, abstract = {OBJECTIVE: To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, São Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995.<br><br>METHODS: Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS).<br><br>RESULTS: XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum&#x2009;=&#x2009;1; maximum&#x2009;&#x2009;=&#x2009;18; interquartile interval&#x2009;=&#x2009;1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6&#x2009;&#xb1;&#x2009;7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85&#x2009;mL and 150&#x2009;mL, respectively.<br><br>CONCLUSION: This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.}, }
@article {pmid31038674, year = {2019}, author = {Oey, H and Daniels, M and Relan, V and Chee, TM and Davidson, MR and Yang, IA and Ellis, JJ and Fong, KM and Krause, L and Bowman, RV}, title = {Whole-genome sequencing of human malignant mesothelioma tumours and cell lines.}, journal = {Carcinogenesis}, volume = {40}, number = {6}, pages = {724-734}, doi = {10.1093/carcin/bgz066}, pmid = {31038674}, issn = {1460-2180}, mesh = {Cell Line, Tumor ; Humans ; Mesothelioma/*genetics/pathology ; Mutation ; Pleural Neoplasms/*genetics/pathology ; *Whole Genome Sequencing ; }, abstract = {Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.}, }
@article {pmid31033031, year = {2019}, author = {Shih, AR and Kradin, RL}, title = {Malignant mesothelioma in Lynch syndrome: A report of two cases and a review of the literature.}, journal = {American journal of industrial medicine}, volume = {62}, number = {5}, pages = {448-452}, doi = {10.1002/ajim.22968}, pmid = {31033031}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics ; Female ; *Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; }, abstract = {Malignant mesothelioma is a rare and aggressive cancer most typically associated with prior asbestos exposure. The nature of the relationship between asbestos exposure and hereditary familial syndromes predisposing to malignancy has not been determined. We report two Lynch syndrome patients with paraoccupational asbestos exposure who developed diffuse malignant mesothelioma of the pleura or peritoneum. Interestingly, one showed a separate focus of pleural well-differentiated papillary mesothelioma. It is likely that Lynch syndrome patients are at increased risk for the development of mesothelioma in the setting of exposure to asbestos, even at what is generally considered to be low levels. In the presence of a documented history of low-level asbestos exposure, patients with genetic predisposition disorders (including Lynch syndrome) should be considered to have an independent risk factor modifying the effects of asbestos exposure.}, }
@article {pmid31032152, year = {2019}, author = {Rakhra, A and Munir, A and Chilukuri, RS and Nahas, J}, title = {A Rare Case of Malignant Mesothelioma Presenting with Systemic Lupus Erythematosus Seropositivity: A Case Report and Review of Literature.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4092}, pmid = {31032152}, issn = {2168-8184}, abstract = {While malignant mesothelioma may initially present in a variety of ways, it is uncommon to present with systemic lupus erythematosus (SLE) seropositivity and thus obscuring its diagnosis. Our case involves a 75-year-old Caucasian male with a past medical history of essential hypertension, remote prostate cancer status post prostatectomy, and lifetime nontobacco use presenting with progressive shortness of breath over one month. After a negative cardiac assessment, a postcardiac catheterization chest X-ray (CXR) revealed a right-sided moderate-to-large pleural effusion that, on further workup, was found to be exudative. Effusion studies were negative for malignancy and bacterial growth. Recurrent accumulation of fluid after a thoracentesis one week prior prompted an autoimmune work up. Positive markers included antinuclear antibodies, anti-double stranded DNA antibodies, and anti-histone antibodies, while anti-Smith antibodies were negative. Although SLE was initially suspected based on serologies, no clinical signs or symptoms were present to fulfill the diagnosis criteria. A trial of oral prednisone resulted in decreased pleural effusion size with no further recurrence. Additional studies included a CT scan of the chest that showed pleural masses confirmed with biopsy to be epithelioid mesothelioma. Given the patient's age and new diagnosis of malignant mesothelioma, we hypothesized that the presence of autoantibodies was likely false positives due to acquired autoantibodies with age, hyperactivity of the immune system from malignancy, and possible prior asbestos exposure.}, }
@article {pmid31030080, year = {2019}, author = {Zona, A and Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Conti, S and Comba, P}, title = {Peritoneal mesothelioma mortality in Italy: Spatial analysis and search for asbestos exposure sources.}, journal = {Cancer epidemiology}, volume = {60}, number = {}, pages = {162-167}, doi = {10.1016/j.canep.2019.04.001}, pmid = {31030080}, issn = {1877-783X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Italy ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality ; Spatial Analysis ; }, abstract = {BACKGROUND: This study is part of a national plan of epidemiological surveillance of malignant mesothelioma (MM) mortality in Italy. The paper shows the results of malignant peritoneal mesothelioma (MPeM) mortality study in Italian Regions and municipalities.<br><br>METHODS: National Bureau of Statistics data for MPeM municipal mortality (ICD-10, Code C45.1) were analyzed in the time-window 2003-2014: mortality standardized rates (reference Italian population, census 2011), temporal trends of the annual national rates, Standardized Mortality Ratios and a municipal clustering analysis were performed.<br><br>RESULTS: 747 deaths for MPeM were recorded (0.10/100,000): 464 in men (0.14/100,000) and in 283 women (0.07/100,000). No significant MPeM mortality temporal trend was found. Seventeen municipalities showed excesses of mortality for MPeM in at least one gender and/or overall population. Four clusters in male population, and one in women were identified.<br><br>CONCLUSIONS: The study identifies some areas where remediation activities and/or health care actions may be warranted.}, }
@article {pmid31023248, year = {2019}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Physician requests by patients with malignant pleural mesothelioma in Japan.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {383}, pmid = {31023248}, issn = {1471-2407}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care ; Physicians ; Pleural Neoplasms/chemically induced/*epidemiology/pathology ; Quality of Life ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.<br><br>METHODS: This cross-sectional survey was part of a larger study (N&#x2009;=&#x2009;133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.<br><br>RESULTS: Responses (N&#x2009;=&#x2009;217) from MPM patients (N&#x2009;=&#x2009;73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.<br><br>CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.}, }
@article {pmid31022494, year = {2019}, author = {Christofidou-Solomidou, M and Pietrofesa, RA and Park, K and Albelda, SM and Serve, KM and Keil, DE and Pfau, JC}, title = {Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.}, journal = {Toxicology and applied pharmacology}, volume = {375}, number = {}, pages = {81-93}, pmid = {31022494}, issn = {1096-0333}, support = {R21 CA178654/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Butylene Glycols/*pharmacology ; Female ; Glucosides/*pharmacology ; Inflammation/*chemically induced/*prevention &amp; control ; Male ; Mice ; Mice, Inbred C57BL ; Organ Size ; Peritoneum/drug effects/pathology ; Spleen/drug effects/pathology ; }, abstract = {BACKGROUND: Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.<br><br>METHODS: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3&#x202f;days prior to and continued for 3&#x202f;days after a single intraperitoneal dose of LA fibers (200&#x202f;&#x3bc;g) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.<br><br>RESULTS: LA exposure induced a significant increase (p&#x202f;<&#x202f;0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p&#x202f;<&#x202f;0.0001) elevated post LA exposure, and were significantly (p&#x202f;<&#x202f;0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.<br><br>CONCLUSIONS: LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases.<br><br>SUMMARY: Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.}, }
@article {pmid30993422, year = {2019}, author = {Boffetta, P and Donato, F and Pira, E and Luu, HN and La Vecchia, C}, title = {Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.}, journal = {International archives of occupational and environmental health}, volume = {92}, number = {7}, pages = {949-957}, pmid = {30993422}, issn = {1432-1246}, mesh = {Asbestos/*toxicity ; Carcinogens, Environmental/adverse effects ; Female ; Humans ; Lung Neoplasms/epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/epidemiology/mortality ; Pleural Neoplasms/epidemiology/mortality ; Risk Factors ; *Time Factors ; }, abstract = {PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma.<br><br>METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies.<br><br>RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98).<br><br>CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.}, }
@article {pmid30968843, year = {2019}, author = {Fedrigotti, A and Riccadonna, A and Riccadonna, D}, title = {"Candido's List": the workers of Collotta Cis &amp; Figli at Molina di Ledro in Trento Province, Italy. A tale of magnesia, asbestos and work.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {90-93}, doi = {10.4415/ANN_19_01_16}, pmid = {30968843}, issn = {2384-8553}, mesh = {Asbestos, Amosite/*adverse effects/history ; Environmental Restoration and Remediation ; Female ; History, 19th Century ; Humans ; Italy ; Magnesium/adverse effects ; Magnesium Oxide/adverse effects ; Male ; Mesothelioma/*epidemiology/etiology/history ; Occupational Diseases/etiology/history ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology/history ; }, abstract = {The study entitled "Candido's List" (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to "virtually' enter the remaining worksites and listen to these spaces "tell" their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.}, }
@article {pmid30968842, year = {2019}, author = {Parolari, G}, title = {An outbreak of cancer and asbestosis among former amosite-exposed subjects in Ledro Valley, Italy. From discovery to environmental cleanup.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {80-89}, doi = {10.4415/ANN_19_01_15}, pmid = {30968842}, issn = {2384-8553}, mesh = {Adolescent ; Adult ; Aged ; Asbestos ; Asbestos, Amosite/*adverse effects ; Asbestosis/*epidemiology/mortality ; Child ; Disease Outbreaks ; Environmental Restoration and Remediation/*methods ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; Mesothelioma/epidemiology/etiology/mortality ; Middle Aged ; Neoplasms/chemically induced/*epidemiology/mortality ; Occupational Exposure/statistics &amp; numerical data ; Young Adult ; }, abstract = {Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.}, }
@article {pmid30968841, year = {2019}, author = {Marsili, D and Magnani, C and Canepa, A and Bruno, C and Luberto, F and Caputo, A and Fazzo, L and Zona, A and Comba, P}, title = {Communication and health education in communities experiencing asbestos risk and health impacts in Italy.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {70-79}, doi = {10.4415/ANN_19_01_14}, pmid = {30968841}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/prevention &amp; control ; Communication ; Environmental Exposure ; Health Education/*statistics &amp; numerical data ; Humans ; Incidence ; Italy/epidemiology ; Neoplasms/epidemiology/etiology ; Occupational Exposure ; Public Health Surveillance ; }, abstract = {INTRODUCTION: Numerous municipalities in Italy currently experience asbestos health impact, in particular excesses of pleural mesothelioma incidence and mortality. This paper presents an integrated analysis of epidemiological studies and communication actions in affected municipalities to highlight how communication has been implemented depending on health impact evidence and involvement of local stakeholders.<br><br>METHODOLOGY: Four case studies are identified concerning industrial and natural sources of asbestos exposure having different diseases burden. This integrated analysis benefited from multidisciplinary skills.<br><br>DISCUSSION: Evidence of different stakeholders engagement is presented to emphasize their role in the communication process. Similarities and differences among case studies allowed us to identify lessons-learned to be transferred in other asbestos contaminated sites.<br><br>CONCLUSIONS: The adoption of communication strategies and practices, since the very early evidence of asbestos health impact, represents a relevant contribution for epidemiological and health surveillance, particularly for those communities where asbestos health impact has only been recently reported.}, }
@article {pmid30946862, year = {2019}, author = {Finkelstein, MM}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {371}, number = {}, pages = {1-2}, doi = {10.1016/j.taap.2019.03.023}, pmid = {30946862}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*adverse effects ; Animals ; Asbestos/*adverse effects ; Mesothelioma/*chemically induced/diagnosis/epidemiology ; Mineral Fibers/adverse effects ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; }, abstract = {Dr. Garabrant presented a paper concerning a comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans at the Elongate Mineral Particles Conference in Charlottesville, Virginia in 2017. I was a participant at the Conference. Following Dr. Garabrant's talk, I rose in question period to point out that he had not considered information about the occurrence of mesothelioma in several cohorts that was published after the studies that he cited. These additional data were still not addressed in the paper published in your Journal. I believe that your readers would be interested in these, so this letter is written to draw the additional data to their attention.}, }
@article {pmid30944991, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {A survey of patient and caregiver experience with malignant pleural mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {12}, pages = {4675-4686}, pmid = {30944991}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Caregivers/*psychology ; Decision Making ; Female ; Grief ; Health Personnel/*psychology ; Humans ; Lung Neoplasms/*psychology/*therapy ; Male ; Mesothelioma/*psychology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care/methods ; Physician-Patient Relations ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As there is little information on the lived experience of MPM, our aim was to document the experience of MPM patients and their caregivers.<br><br>METHODS: Surveys for MPM patients and caregivers were developed from previous interviews with patients, caregivers, and health professionals, about treatments and decision-making. Participants were recruited from two hospitals, government compensation body, and support groups.<br><br>RESULTS: Survey responses were received from 78 MPM patients and 106 caregivers from January to September 2014.<br><br>PATIENTS: 85% male, median age 69&#xa0;years, median time since diagnosis 15&#xa0;months. Caregivers: median age 68, 91% female, 90% spouse of MPM patient, 95% bereaved. Most participants felt informed about treatment options but only 69% thought all treatment options were discussed. Chemotherapy was discussed most frequently (92-95%); ~80% had sufficient information for decision-making. Decision regarding chemotherapy was made by patient considering doctor's opinion (24%), doctor and patient equally (18%), and doctor (17%). Participants 'agreed'/'strongly agreed' that they made the right decision about chemotherapy (patients 81%, caregivers 60%), but 5% and 16%, respectively, regretted the decision. Most participants received 'sufficient' support (71%). A quarter reported seeing cancer nurse specialists. Palliative care referral: 31% patients, 85% caregivers. Caregivers would have liked to talk to someone by themselves (41%), more time with doctors (30%), psychological support (29%), and clearer information (31%). Bereaved caregivers requested grief counselling (39%) and post-death consultation with specialists (23-25%).<br><br>CONCLUSIONS: Satisfaction with treatment was high, but participants identified need for improved communication and quality information, discussion about all treatments, end-of-life assistance, and caregiver support after the patient's death.}, }
@article {pmid30941506, year = {2019}, author = {Lococo, F and Di Stefano, T and Rapicetta, C and Piro, R and Gelli, MC and Muratore, F and Ricchetti, T and Taddei, S and Zizzo, M and Cesario, A and Facciolongo, N and Paci, M}, title = {Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {3}, pages = {387-390}, pmid = {30941506}, issn = {1432-1750}, mesh = {Aged ; Bronchoscopy ; Diagnosis, Differential ; Endosonography ; Glucocorticoids/therapeutic use ; Humans ; Immunoglobulin G4-Related Disease/complications/*diagnosis/drug therapy/pathology ; Lung Neoplasms/*diagnosis ; Lymphadenopathy/diagnosis/etiology/pathology ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Diseases/complications/*diagnosis/drug therapy/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/*diagnosis ; Positron Emission Tomography Computed Tomography ; Prednisone/therapeutic use ; }, abstract = {We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a [18F]-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.}, }
@article {pmid30937282, year = {2019}, author = {Haygarth, M and Zaw, KK and Yachmenikova, V and Pokorny, AMJ and Kwong, KK and Heraganahally, SS}, title = {Bilateral diffuse pulmonary infiltrates secondary to malignant peritoneal mesothelioma - A rare clinical presentation.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {326-327}, pmid = {30937282}, issn = {2213-0071}, abstract = {Diffuse pulmonary metastasis secondary to primary peritoneal malignant mesothelioma is rarely reported in the literature. In this report we describe a 59-year-old Caucasian women with no known previous asbestos exposure presenting with bilateral diffuse pulmonary opacities in association with primary malignant peritoneal mesothelioma. The diagnosis was confirmed by ultrasound guided abdominal and bronchoscopy, trans-bronchial lung biopsy. The biopsy demonstrated positive staining with AE1/3, CK7, CK5/6, WT1, calretinin and D2 40. The cells were negative for BerEP4, PAX8, CA125, ER, CD34, ERG, P63, P40, Melan A, Gata3 and mammaglobin. The morphology and immunohistochemical profile supported a diagnosis of epithelioid malignant mesothelioma.}, }
@article {pmid30936339, year = {2019}, author = {Muralidhar, V and Raghav, P and Das, P and Goel, A}, title = {A case from India of pleural malignant mesothelioma probably due to domestic and environmental asbestos exposure: a posthumous report.}, journal = {BMJ case reports}, volume = {12}, number = {3}, pages = {}, pmid = {30936339}, issn = {1757-790X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Compensation and Redress/legislation &amp; jurisprudence ; Environmental Exposure/*adverse effects/legislation &amp; jurisprudence ; Fatal Outcome ; Humans ; India ; Lung Neoplasms/chemically induced/*diagnosis/mortality ; Male ; Mesothelioma/chemically induced/*diagnosis/mortality ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects/legislation &amp; jurisprudence ; Pleural Neoplasms/chemically induced/*diagnosis/mortality ; Workers' Compensation/legislation &amp; jurisprudence ; }, abstract = {India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.}, }
@article {pmid30928905, year = {2019}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Response to letter by Farioli et al.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {5}, pages = {356}, doi = {10.1136/oemed-2019-105740}, pmid = {30928905}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30927363, year = {2019}, author = {Koutros, S and Lubin, JH and Graubard, BI and Blair, A and Stewart, PA and Beane Freeman, LE and Silverman, DT}, title = {Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.}, journal = {American journal of epidemiology}, volume = {188}, number = {8}, pages = {1484-1492}, pmid = {30927363}, issn = {1476-6256}, support = {Z01 CP010120/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Acrylonitrile/*toxicity ; Aged ; Aged, 80 and over ; Cause of Death ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Mortality/*trends ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; United States/epidemiology ; }, abstract = {We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.}, }
@article {pmid30927189, year = {2019}, author = {Kennedy, JM}, title = {The forensic significance of pseudomesotheliomatous adenocarcinoma of the lung.}, journal = {Forensic science, medicine, and pathology}, volume = {15}, number = {3}, pages = {458-462}, pmid = {30927189}, issn = {1556-2891}, mesh = {Adenocarcinoma/metabolism/*pathology ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung/*pathology ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma ; Mesothelioma, Malignant ; }, abstract = {Pseudomesotheliomatous carcinomas (PMC) are rare tumors that clinically, macroscopically, and sometimes histologically resemble malignant pleural mesotheliomas. We report a case of a 91 year woman who was found to have diffuse nodular pleural thickening and a lung mass during a workup for persistent cough. She declined rapidly and died before a histologic diagnosis could be made. Postmortem examination revealed a tumor that diffusely involved the pleural surface with local extension into the chest wall, pericardium, and diaphragm along with a concurrent lung mass. Histologic examination showed poorly-differentiated cells predominantly arranged in sheets, cords, and nests with focal glandular differentiation. An immunohistochemical panel of calretinin, WT1, BEREP4, MOC31, and TTF1 confirmed the diagnosis of primary lung adenocarcinoma. The macroscopic, histologic, and immunohistochemical features used to distinguish metastatic and primary lung adenocarcinoma from epithelioid malignant mesothelioma are discussed. The distinction of malignant mesothelioma from pseudomesotheliomatous carcinoma is important for medicolegal reasons regarding asbestos related compensation claims.}, }
@article {pmid30924615, year = {2019}, author = {Algranti, E and Ramos-Bonilla, JP and Terracini, B and Santana, VS and Comba, P and Pasetto, R and Mazzeo, A and Cavariani, F and Trotta, A and Marsili, D}, title = {Prevention of Asbestos Exposure in Latin America within a Global Public Health Perspective.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, pmid = {30924615}, issn = {2214-9996}, mesh = {Asbestos, Serpentine/*economics/*toxicity ; Carcinogenesis ; Environmental Exposure/adverse effects/analysis/prevention &amp; control ; Humans ; Latin America/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Mesothelioma/*epidemiology ; Mining ; Occupational Exposure/adverse effects/analysis/*prevention &amp; control ; Public Health ; }, abstract = {BACKGROUND: Asbestos consumption in Latin America (LA) amounts to 10% of yearly global production. Little is known about the impact of asbestos exposure in the region.<br><br>OBJECTIVE: To discuss scientific and socio-economic issues and conflicts of interest and to summarize epidemiological data of asbestos health effects in LA.<br><br>DISCUSSION: Recent data on chrysotile strengthened the evidence of its carcinogenicity and showed an excessive risk of lung cancer at cumulative exposure levels as low as 1.5 fibre-years/ml. Technology for substitution is available for all asbestos-containing products and ceasing asbestos production and manufacturing will not result in unemployment and loss of income, except for the mining industry. The flawed arguments used by the industry to maintain its market, both to the public and in courtrooms, strongly relies on the lack of local evidence of the ill effects and on the invisibility of asbestos-related diseases in LA, due to the limited number of studies and the exposed workers' difficulty accessing health services. The few epidemiological studies available show clear evidence of clusters of mesothelioma in municipalities with a history of asbestos consumption and a forecasted rise in its incidence in Argentina and Brazil for the next decade. In Brazil, non-governmental organizations of asbestos workers were pivotal to counterbalance misinformation and inequities, ending recently in a Supreme Court decision backing an asbestos ban. In parallel, continuous efforts should be made to stimulate the growth of competent and ethical researchers to convey adequate information to the scientific community and to the general public.}, }
@article {pmid30917938, year = {2019}, author = {Linton, A and Blinman, P and Kao, S and van Zandwijk, N}, title = {Patterns of care and survival of older patients with malignant pleural mesothelioma.}, journal = {Journal of geriatric oncology}, volume = {10}, number = {4}, pages = {573-576}, doi = {10.1016/j.jgo.2019.02.013}, pmid = {30917938}, issn = {1879-4076}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*therapy ; Male ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; New South Wales ; Palliative Care/*statistics &amp; numerical data ; Pleural Neoplasms/mortality/*therapy ; Pneumonectomy/*statistics &amp; numerical data ; Radiotherapy/*statistics &amp; numerical data ; Radiotherapy, Adjuvant ; Survival Rate ; Thoracic Surgical Procedures/statistics &amp; numerical data ; }, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a cancer that primarily affects older adults. However this patient population is frequently under-represented in clinical studies. Therefore, we studied the impact of advancing age on treatment utilisation and clinical outcomes in an extensive series of minimally selected MPM patients.<br><br>MATERIALS AND METHODS: Patients with MPM receiving compensation from the New South Wales (NSW) Dust Diseases Authority (2002-2009) were assessed. They were categorised by age (<70&#x202f;years, 70-80&#x202f;years or&#x202f;>&#x202f;80&#x202f;years) and chi-square testing was used to assess the relationship between clinical and demographic variables, age, treatment and overall survival (OS).<br><br>RESULTS: We identified 910 patients; 41% were aged <70&#x202f;years, 40% were aged 70-80&#x202f;years, and 19% were aged >80&#x202f;years old. Median OS decreased with increasing age: 13.5&#x202f;months in <70&#x202f;years, 9.5&#x202f;months in 70-80&#x202f;years and 7.1&#x202f;months in >80&#x202f;years as did chemotherapy use (66%, 35% and 8% respectively). Radical surgical intervention, adjuvant, and palliative radiotherapy were less frequently used with advanced age. A Kaplan Meier analysis revealed that there was a significant survival advantage (p&#x202f;<&#x202f;.001) for patients <70 and 70-80&#x202f;years receiving chemotherapy (16.8 vs 7.0&#x202f;months; 13.9 vs 5.8&#x202f;months respectively), but not for patients >80&#x202f;years.<br><br>CONCLUSION: Advancing age group of NSW patients with MPM was associated with reduced treatment utilisation and a decline in OS. Prospective studies are warranted to verify if current treatment guidelines are relevant for the older adults with MPM.}, }
@article {pmid30915902, year = {2019}, author = {Grosso, F and Croce, A and Libener, R and Mariani, N and Pastormerlo, M and Maconi, A and Rinaudo, C}, title = {Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study.}, journal = {Tumori}, volume = {105}, number = {5}, pages = {404-410}, doi = {10.1177/0300891619839305}, pmid = {30915902}, issn = {2038-2529}, mesh = {Asbestos/isolation &amp; purification/*toxicity ; Bile Duct Neoplasms/chemically induced/*diagnostic imaging/pathology ; Cholangiocarcinoma/chemically induced/*diagnostic imaging/pathology ; Environmental Pollutants/isolation &amp; purification/toxicity ; Female ; Humans ; Italy ; Liver/*diagnostic imaging/drug effects/pathology ; Male ; Mesothelioma/chemically induced ; Microscopy, Electron, Scanning ; Occupational Exposure ; }, abstract = {PURPOSE: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure.<br><br>METHODS: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients' clinical features.<br><br>RESULTS: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation.<br><br>CONCLUSIONS: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.}, }
@article {pmid30915265, year = {2019}, author = {Robalino Gonzaga, ES and Guzman Rojas, P and Vanar, V}, title = {Malignant Peritoneal Mesothelioma Mimicking Recurrent Diverticulitis.}, journal = {Cureus}, volume = {11}, number = {1}, pages = {e3906}, pmid = {30915265}, issn = {2168-8184}, abstract = {Mesothelioma is an uncommon type of cancer arising from the mesothelial cells that form the lining of several cavities in the body. Exposure to asbestos is the leading known cause of mesothelioma. We present a 73-year-old male with a significant asbestos exposure and a recent history of recurrent diverticulitis who reported persistent left lower quadrant (LLQ) pain despite several courses of empiric antibiotic therapy. A recent computed tomography (CT) performed due to nonresolving symptoms showed possible nodularity of the mesentery and subsequent positron emission tomography (PET) scan demonstrated multiple hypermetabolic mesenteric lesions, notably in the left paracolic gutter. A colonoscopy was subsequently performed which demonstrated severe diverticulosis, but no obvious luminal lesions. The patient underwent an exploratory laparoscopy showing extensive peritoneal carcinomatosis involving all mesenteric surfaces and partial involvement of the right diaphragm. Final pathology revealed malignant epithelial mesothelioma with peritoneal seeding. The patient was referred to oncology and was started on hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS). Our case highlights a challenging presentation of malignant peritoneal mesothelioma (MPM), which is often initially misdiagnosed due to vague symptoms. Physicians should consider further diagnostic workup for unrelenting LLQ abdominal pain after diverticulitis has been treated.}, }
@article {pmid30900641, year = {2019}, author = {Punatar, CB and Jadhav, KK and Kumar, V and Sagade, SN}, title = {Malignant mesothelioma of tunica vaginalis without any risk factors: An uncommon case.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {Supplement}, pages = {S167-S169}, doi = {10.4103/jcrt.JCRT_1403_16}, pmid = {30900641}, issn = {1998-4138}, mesh = {Adult ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Mesothelioma, Malignant ; Orchiectomy ; Positron Emission Tomography Computed Tomography ; Scrotum/diagnostic imaging/*pathology/surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Testis/diagnostic imaging/*pathology/surgery ; Treatment Outcome ; Ultrasonography ; }, abstract = {Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare tumor. It is seen in elderly patients, with painless scrotal swelling being the most common presentation. The exact etiology is unknown; a few risk factors have been suggested. Here, we present an uncommon case of MM of TV without any known predisposing factors. We also discuss the possible risk factors, clinical presentation, pathological features and the difficulties in diagnosis, and management of this rare malignancy.}, }
@article {pmid30893058, year = {2019}, author = {Levpuscek, K and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {53}, number = {2}, pages = {206-212}, pmid = {30893058}, issn = {1581-3207}, mesh = {Aged ; Asbestos/toxicity ; Carcinogens/toxicity ; Case-Control Studies ; *DNA Repair ; DNA-Binding Proteins/*genetics ; Endonucleases/*genetics ; Female ; *Genetic Variation ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Genetic ; Retrospective Studies ; Risk ; X-ray Repair Cross Complementing Protein 1/*genetics ; }, abstract = {Background Malignant mesothelioma (MM) is a rare aggressive tumour of mesothelium caused by asbestos exposure. It has been suggested that the genetic variability of proteins involved in DNA repair mechanisms affects the risk of MM. This study investigated the influence of functional polymorphisms in ERCC1 and XRCC1 genes, the interactions between these polymorphisms as well as the interactions between these polymorphisms and asbestos exposure on MM risk. Patients and methods In total, 237 cases with MM and 193 controls with no asbestos-related disease were genotyped for ERCC1 and XRCC1 polymorphisms. Results ERCC1 rs3212986 polymorphism was significantly associated with a decreased risk of MM (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.41-0.91; p = 0.014). No associations were observed between other genetic polymorphisms and MM risk. Interactions between polymorphisms did not significantly influence MM risk. Interaction between ERCC1 rs11615 and asbestos exposure significantly influenced MM risk (OR = 3.61; 95% CI = 1.12-11.66; p = 0.032). Carriers of polymorphic ERCC1 rs11615 allele who were exposed to low level of asbestos had a decreased risk of MM (OR = 0.40; 95% CI = 0.19-0.84; p = 0.016). Interactions between other polymorphisms and asbestos exposure did not significantly influence MM risk. Conclusions Our findings suggest that the genetic variability of DNA repair mechanisms could contribute to the risk of developing MM.}, }
@article {pmid30892588, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Corrigendum: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {492}, doi = {10.1093/carcin/bgz037}, pmid = {30892588}, issn = {1460-2180}, }
@article {pmid30891101, year = {2019}, author = {Wang, Y and Jiang, Z and Yan, J and Ying, S}, title = {HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {4183157}, pmid = {30891101}, issn = {1875-8630}, mesh = {Animals ; Biomarkers, Tumor/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; HMGB1 Protein/*genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism/pathology ; Mesothelioma/drug therapy/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; }, abstract = {Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on in vivo and in vitro experimental evidence and outline the clinical findings of epidemiological investigations regarding the possible roles of HMGB1 as a biomarker for MM. We conclude that novel strategies targeting HMGB1 may suppress MM cells and interfere with asbestos-induced inflammation.}, }
@article {pmid30888083, year = {2019}, author = {Hino, O and Abe, M and Han, B and Yan, Y}, title = {In commemoration of the 2018 Mataro Nagayo Prize: A road to early diagnosis and monitoring of asbestos-related mesothelioma.}, journal = {Cancer science}, volume = {110}, number = {5}, pages = {1518-1524}, pmid = {30888083}, issn = {1349-7006}, support = {S1311011//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; S1511008L//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; //Institute for Environmental and Gender-Specific Medicine of Juntendo University Urayasu Hospital/ ; //Shizuoka Medical Research Center for Disaster of Juntendo University Shizuoka Hospital/ ; 221S0001//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Animals ; Asbestos/*adverse effects ; Awards and Prizes ; Biomarkers, Tumor/blood ; Disease Management ; Early Detection of Cancer/*methods ; Humans ; Japan ; Lung Neoplasms/blood/chemically induced/*diagnosis/*surgery ; Mesothelin ; Mesothelioma/blood/chemically induced/*diagnosis/*surgery ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/diagnosis/surgery ; Oncogene Proteins/*blood ; }, abstract = {Primarily caused by exposure to asbestos, mesothelioma is a typical occupational disease. The latency of mesothelioma is as long as 20-40 years, and the cancer initially progresses mainly along the surfaces of pleura or peritoneum without forming masses. As symptoms do not develop until late stages, it has been challenging to diagnose this disease in its early stages and to carry out complete surgical removal. In responding to Japan's asbestos crisis in the mid-2000s, we have developed and improved ERC/MSLN-based serum and radiological markers and pioneered the use of an N-ERC ELISA kit for screening populations at risk for asbestos exposure. In the present article, we review our research toward early diagnosis of asbestos-related mesothelioma before symptoms develop and share our clinical experience of screening, diagnosing and monitoring of this disease. This paper is dedicated to the author (Dr Okio Hino) to commemorate the honor bestowed upon him as the recipient of the Mataro Nagayo Prize in 2018.}, }
@article {pmid30886321, year = {2019}, author = {Jeffery, E and Lee, YCG and Newton, RU and Lyons-Wall, P and McVeigh, J and Nowak, AK and Cheah, HM and Nguyen, B and Fitzgerald, DB and Creaney, J and Straker, L and Peddle-McIntyre, CJ}, title = {Body composition and nutritional status in malignant pleural mesothelioma: implications for activity levels and quality of life.}, journal = {European journal of clinical nutrition}, volume = {73}, number = {10}, pages = {1412-1421}, doi = {10.1038/s41430-019-0418-9}, pmid = {30886321}, issn = {1476-5640}, mesh = {Aged ; Australia/epidemiology ; *Body Composition ; Cross-Sectional Studies ; Diet ; Exercise/*physiology ; Female ; Humans ; Lung Neoplasms/*physiopathology ; Male ; Malnutrition/epidemiology ; Mesothelioma/*physiopathology ; Mesothelioma, Malignant ; Middle Aged ; *Nutritional Status ; Pleural Neoplasms/*physiopathology ; Prospective Studies ; *Quality of Life ; Sarcopenia/epidemiology ; }, abstract = {BACKGROUND/OBJECTIVES: Malignant pleural mesothelioma (MPM) is an incurable cancer and optimizing daily physical activity and quality of life are key goals of patient management. Little is known about the prevalence of pre-sarcopenia and malnutrition in MPM or their associations with patient outcomes. This study aimed to determine the prevalence of pre-sarcopenia and malnutrition in MPM and investigate if activity levels and quality of life differed according to body composition and nutritional status.<br><br>SUBJECTS/METHODS: Patients with a diagnosis of MPM were recruited. Pre-sarcopenia was defined as low appendicular skeletal muscle mass (&#x2264;&#x2009;7.26&#x2009;kg/m[2] for men and &#x2264;&#x2009;5.45&#x2009;kg/m[2] for women), measured by dual energy X-ray absorptiometry. Malnutrition was defined as a rating of B or C on the Patient-Generated Subjective Global Assessment. Outcome measures included objective activity levels (Actigraph GT3X) and health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy General).<br><br>RESULTS: Sixty-one people participated (79% male, median age 69 [IQR 62-74] years and median BMI 25.8 [IQR 24.3-28.4] kg/m[2]). Fifty-four percent were pre-sarcopenic and 38% were malnourished. Percent of time spent in light activity/day was lower in participants with pre-sarcopenia compared with non-sarcopenic participants (median 25.4 [IQR 19.8-32.1]% vs. 32.3 [27.1-35.6]%; p&#x2009;=&#x2009;0.008). Participants with malnutrition had poorer HRQoL than well-nourished participants (mean 69.0 (16.3) vs. 84.4 (13.3); p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Participants with MPM had high rates of pre-sarcopenia and malnutrition. Pre-sarcopenia was associated with poorer activity levels, whilst malnutrition was associated with poorer quality of life. Interventions that aim to address reduced muscle mass and weight loss, should be tested in MPM to assess their impact on patient outcomes.}, }
@article {pmid30885349, year = {2019}, author = {Ahmadzada, T and Lee, K and Clarke, C and Cooper, WA and Linton, A and McCaughan, B and Asher, R and Clarke, S and Reid, G and Kao, S}, title = {High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {130}, number = {}, pages = {35-41}, doi = {10.1016/j.lungcan.2019.02.005}, pmid = {30885349}, issn = {1872-8332}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism ; Lung Neoplasms/*genetics/immunology/mortality ; Lymphocytes, Tumor-Infiltrating/*immunology ; Male ; Mesothelioma/*genetics/immunology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Nuclear Proteins/genetics/*metabolism ; Pleural Neoplasms/*genetics/immunology/mortality ; Prognosis ; Survival Analysis ; Tumor Suppressor Proteins/genetics/*metabolism ; Up-Regulation ; }, abstract = {OBJECTIVES: A number of key immune regulators show prognostic value in malignant pleural mesothelioma (MPM), but the association between Bridging integrator 1 (BIN1), indoleamine 2,3 dioxygenase 1 (IDO1) and patient outcome has not been investigated. We aimed to determine the expression of BIN1 and IDO1, their association with other markers and impact on overall survival (OS) in MPM.<br><br>MATERIALS AND METHODS: The expression of BIN1, IDO1, CD3, CD20 and CD68 were evaluated by immunohistochemistry in 67 patients who underwent pleurectomy/decortication. Survival analyses were performed using the Kaplan Meier method and significant biomarkers were entered into a Cox Regression multivariate model, accounting for known prognostic factors such as age, gender, histological subtype, PD-L1 expression and neutrophil-to-lymphocyte ratio.<br><br>RESULTS: Immune markers were variably expressed in tumor cells, ranging from 0% to 100% for BIN1 (median: 89%), and 0% to 77.5% for IDO1 (median: 0%). Expression of markers of tumor-infiltrating lymphocytes (TILs) and macrophages ranged from 0% to more than 50%. BIN1 expression was high in 35 patients (51%) and was associated with increased OS (median: 12 vs 6 months for high and low BIN1 respectively,p&#x2009;=&#x2009;0.03). Multivariate analysis showed BIN1 remained an independent prognostic indicator (HR 0.39; 95% CI: 0.18-0.82, p&#x2009;=&#x2009;0.01). The majority of patients had immune inflamed tumors (77%) and there was a significant association between TILs and BIN1 (p&#x2009;=&#x2009;0&#x2009;<&#x2009;0.01), PD-L1 (p=0.04) and CD68+ macrophages in the tumor (p&#x2009;<&#x2009;0.01). There were no significant associations between PD-L1 and BIN1 or IDO1.<br><br>CONCLUSION: High BIN1 expression is a favorable prognostic biomarker and is associated with TILs in MPM.}, }
@article {pmid30882147, year = {2019}, author = {Nakai, T and Matsumoto, Y and Sasada, S and Tanaka, M and Tsuchida, T and Ohe, Y and Motoi, N}, title = {Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {6}, pages = {559-566}, doi = {10.1093/jjco/hyz032}, pmid = {30882147}, issn = {1465-3621}, mesh = {Aged ; Biopsy/instrumentation/methods ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*diagnosis ; Thoracoscopy/*instrumentation/*methods ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is rarely an asbestos-related cancer with a poor prognosis that is difficult to distinguish from some benign conditions by using conventional biopsy techniques. The purpose of this study was to evaluate the utility of a novel biopsy technique using a cryoprobe during flex-rigid pleuroscopy for diagnosing MPM.<br><br>METHODS: Consecutive patients who underwent pleural cryobiopsy during flex-rigid pleuroscopy from June through November 2017 to diagnose the cause of pleural effusion were collected. From these, cases ultimately diagnosed as MPM were selected. Pleural biopsies were performed by using conventional instruments followed by a cryoprobe. The obtained samples were histologically examined and compared with regard to the quality (sample size, tissue depth, and crush rate), immunohistochemical (IHC) staining, and p16 by fluorescence in situ hybridization (FISH).<br><br>RESULTS: In total, five patients ultimately diagnosed as MPM were enrolled. The sample collected was significantly larger for cryobiopsy than conventional biopsy (18.9 mm2 vs. 6.7 mm2, P < 0.001). Full-thickness biopsies were achieved in four cases by using cryobiopsy compared with one case by conventional biopsy. Moreover, the crush rate was significantly less for cryobiopsy than conventional biopsy (9% vs. 35%, P < 0.001). The results of IHC staining and p16 by FISH were similar between biopsy techniques. Cryobiopsy successfully led to accurate diagnosis of MPM in all cases, whereas conventional biopsy was diagnostic in one case. No severe complications developed after either biopsy technique.<br><br>CONCLUSION: Cryobiopsy during flex-rigid pleuroscopy is a feasible and convenient biopsy technique that supports precise diagnosis of MPM.}, }
@article {pmid30879467, year = {2019}, author = {Miyata, T and Fujiwara, Y and Nishijima, K and Futagami, F and Nakamura, T and Takamura, H}, title = {Localized multiple malignant epithelioid peritoneal mesotheliomas arising from the hepatoduodenal ligament and diaphragm: a case report.}, journal = {Journal of medical case reports}, volume = {13}, number = {1}, pages = {66}, pmid = {30879467}, issn = {1752-1947}, mesh = {Female ; Humans ; Liver Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Lung Neoplasms/diagnostic imaging/*pathology/surgery ; Mesothelioma/diagnostic imaging/*pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Muscle Neoplasms/*pathology ; Neoplasm Invasiveness ; Peritoneal Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum. We report a rare case of resection of multiple localized malignant peritoneal mesotheliomas.<br><br>CASE PRESENTATION: A 55-year-old Japanese woman was admitted to our hospital because liver tumors were detected by abdominal ultrasonography during a screening examination. Blood examination findings, including tumor makers, were within normal ranges. She had no evidence of exposure to asbestos. Computed tomography showed four hypervascular, round liver tumors, one in the lateral liver segment adjacent to the hepatic hilus, and the other three on the liver surface. Computed tomography angiography revealed that the tumor in the lateral segment had strong enhancement and was fed from the left gastric artery. In contrast, the other tumors showed no enhancement, and were fed from the right inferior phrenic artery. Abnormal accumulation was identified in the four tumors only with [18]F-fluorodeoxyglucose positron emission tomography. It was very difficult to obtain a definitive preoperative diagnosis, but surgical resection was performed because we considered potential malignancy. Laparotomy revealed the principal site of the tumor in the lateral segment was on the hepatoduodenal ligament, and all other tumors were on the diaphragm. A left lobectomy and partial diaphragmatic resection were performed. The final pathological diagnosis was multiple malignant epithelioid mesotheliomas. Our patient has had no recurrence for 20&#x2009;months postoperatively.<br><br>CONCLUSIONS: In general, malignant peritoneal mesotheliomas are classified as diffuse tumors, which are often unresectable and have a poor prognosis. However, early diagnosis and treatment, particularly with the localized type, as in our patient, could lead to long-term survival of the patient. We recommend that multiple malignant epithelioid mesotheliomas be included in the differential diagnosis for patients with subcapsular hepatic tumors.}, }
@article {pmid30874891, year = {2019}, author = {Hutter, HP and Waldhoer, T and Müller, K and Hackl, M and Weitensfelder, L and Heinzl, H}, title = {Cancer incidence in an Austrian alpine valley 1983-2012 : A descriptive study.}, journal = {Wiener klinische Wochenschrift}, volume = {131}, number = {9-10}, pages = {200-204}, pmid = {30874891}, issn = {1613-7671}, mesh = {Asbestos/adverse effects ; Austria/epidemiology ; Hexachlorobenzene/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Neoplasms/*epidemiology ; }, abstract = {After one of Austria's largest environmental scandals in 2014, which involved the release of hexachlorobenzene (HCB) in the Carinthian valley Görtschitztal, concerns about increased cancer rates have arísen in the affected local population. A descriptive study was conducted to examine the cancer incidence rates between 1983 and 2012. Data from the affected area (Görtschitztal, district St. Veit) were compared to data from the neighboring area within the same district and Carinthia excluding St. Veit, considering incidence rates of liver, lung, kidney, thyroid cancer and mesothelioma. Prostate cancer and carcinoma in situ were both included and excluded from overall cancer incidents in order to prevent potential bias due to screening programs. Considering the observed variability at an overall level, no conspicuous differences in cancer incidences could be found (Carinthia: 495, St. Veit West: 408, St. Veit East: 572 cases per 100,000 person-years in 2012). For some cancer types, e. g. liver, thyroid cancer and mesothelioma, the affected region showed a higher increase in rates than the neighboring area or Carinthia overall; however, these increased rates date back to a time prior to the HCB exposure, suggesting other carcinogenic influences, such as asbestos exposure from antecedent years.}, }
@article {pmid30873891, year = {2019}, author = {Poland, CA and Duffin, R}, title = {The toxicology of chrysotile-containing brake debris: implications for mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {1}, pages = {11-35}, doi = {10.1080/10408444.2019.1568385}, pmid = {30873891}, issn = {1547-6898}, mesh = {Asbestos, Serpentine/*toxicity ; *Automobiles ; *Environmental Exposure ; Humans ; Mesothelioma/chemically induced/*epidemiology ; }, abstract = {The global use of "asbestos" in various commercial products has led to a wide range and pervasive legacy of disease. One such use of chrysotile asbestos was brake pads and was utilized commonly in automobiles and heavy vehicles. The result of incorporation of chrysotile into brake pads is associated with the exposure of mechanics fitting and servicing vehicles to liberated chrysotile fibers. Despite the proven exposure, the relative risk of malignant mesothelioma (MM) in this occupational population is broadly seen as low. The toxicity of particulates, including fibers such as chrysotile, is driven by a combination of dose and physicochemical properties. As such, it is plausible that chrysotile released from brake pads may have undergone modification, thereby altering the pathogenicity profile. The impact of high sheer stress causing shortening of long fibers, heat modification, binding of resin matrix to the fiber surface on the relative toxicity of brake debris with regards to MM is considered. It is apparent that released chrysotile can undergo significant modification, reducing the long fiber dose although not all modifications may lead to reduced toxicity.}, }
@article {pmid30873867, year = {2019}, author = {Baqui, AA and Boire, NA and Baqui, TT and Etwaru, DJ}, title = {Malignant Mesothelioma of the Tunica Vaginalis Testis-A Malignancy Associated With Asbestos Exposure and Trauma: A Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {7}, number = {}, pages = {2324709619827335}, pmid = {30873867}, issn = {2324-7096}, mesh = {Asbestos/*adverse effects ; Humans ; Immunohistochemistry ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Orchiectomy ; Testicular Hydrocele/etiology/*pathology ; Testicular Neoplasms/etiology/*pathology ; Testis/*injuries/*pathology ; }, abstract = {In this article, we report an unusual case of a malignant mesothelioma of the testis, presenting as hydrocele. The patient has a known medical history of trauma and occupational exposure to asbestos. The clinical features of this injury are discussed together with its immunohistochemistry. Surgical intervention is discussed due to the nature of this pathology.}, }
@article {pmid30870398, year = {2019}, author = {Cuccaro, F and Nannavecchia, AM and Silvestri, S and Angelini, A and Coviello, V and Bisceglia, L and Magnani, C}, title = {Mortality for Mesothelioma and Lung Cancer in a Cohort of Asbestos Cement Workers in BARI (Italy): Time Related Aspects of Exposure.}, journal = {Journal of occupational and environmental medicine}, volume = {61}, number = {5}, pages = {410-416}, doi = {10.1097/JOM.0000000000001580}, pmid = {30870398}, issn = {1536-5948}, mesh = {Asbestos/*adverse effects ; *Construction Industry ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; Time Factors ; }, abstract = {OBJECTIVE: In this cohort mortality study we used an exposure index to evaluate individual cumulative exposure as proxy of asbestos dose and we evaluated change in cancer mortality pattern after long time since the end of exposure.<br><br>METHODS: We calculated standardized mortality ratios (SMRs) for several causes of death stratified by latency, cumulative exposure, and time since last exposure (TSLE).<br><br>RESULTS: Latency: we observed a peak and then a decrease in SMR for lung, pleural, and peritoneal cancer. Cumulative Exposure: We observed a peak and then a decrease in SMR for lung and pleural cancer, not for peritoneal cancer. TSLE: Pleural cancer SMR peaked at 20 to 29 years, then decreased, peritoneal cancer SMR reached a plateau after 20 years and lung cancer mortality was in excess in each class.<br><br>CONCLUSIONS: We found different patterns in mortality in the main asbestos-related tumors.}, }
@article {pmid30863440, year = {2019}, author = {Liang, Y and Zheng, G and Yin, W and Song, H and Li, C and Tian, L and Yang, D}, title = {Significance of EGFR and PTEN Expression and PLR and NLR for Predicting the Prognosis of Epithelioid Malignant Peritoneal Mesothelioma.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {7103915}, pmid = {30863440}, issn = {1687-6121}, abstract = {OBJECTIVE: The aim of our study was to investigate the expression of EGFR and PTEN in tissues and measure the serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to evaluate the prognostic factors of patients with epithelioid malignant peritoneal mesothelioma (MPeM).<br><br>METHODS: 33 patients of pathologically diagnosed epithelioid MPeM tissues were analyzed using immunohistochemistry to detect EGFR and PTEN; the PLR and NLR were determined by using a routine blood test. We analyzed the relationships of these markers to age, sex, asbestos exposure, elevated platelet count, ascites, and clinical stage.<br><br>RESULTS: EGFR and PTEN expressions were positive in 22 (66.67%) and 7 (21.21%) epithelioid MPeM patients, respectively. However, these two markers as well as PLR and NLR were not significantly associated with age, sex, asbestos exposure, elevated platelet counts, ascites, and clinical stage (P > 0.05). The correlation between EGFR and PTEN was negative (r = -0.577, P < 0.001), but the correlation between NLR and PLR was positive (r = 0.456, P = 0.008). The median survival of all patients was 6 months. In univariate analysis, PTEN (P < 0.001), PLR (P = 0.014), and NLR (P = 0.015) affected the overall survival. Multivariate analysis revealed that PTEN and PLR were validated as predictive for overall survival of epithelioid MPeM (HR = 0.070, P = 0.001, and HR = 3.379, P = 0.007, respectively).<br><br>CONCLUSION: On the basis of these results, it is suggested that PTEN and PLR are risk factors for the prognosis of epithelioid MPeM, which may be targets for selective therapies and improve the outcomes of patients with epithelioid MPeM.}, }
@article {pmid30863365, year = {2019}, author = {Baird, AM and Easty, D and Jarzabek, M and Shiels, L and Soltermann, A and Klebe, S and Raeppel, S and MacDonagh, L and Wu, C and Griggs, K and Kirschner, MB and Stanfill, B and Nonaka, D and Goparaju, CM and Murer, B and Fennell, DA and O'Donnell, DM and Barr, MP and Mutti, L and Reid, G and Finn, S and Cuffe, S and Pass, HI and Opitz, I and Byrne, AT and O'Byrne, KJ and Gray, SG}, title = {When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {89}, pmid = {30863365}, issn = {1664-2392}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.}, }
@article {pmid30859065, year = {2019}, author = {Wallen, T and Jagan, N and Krishnan, M and Depew, Z}, title = {A 75 year old male with recurrent unilateral pleural effusion and positive ANA.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {301-303}, pmid = {30859065}, issn = {2213-0071}, abstract = {This case report describes the clinical course and diagnostic challenges arising in a 75 year old man who initially presented with progressive shortness of breath. Imaging revealed a pleural effusion, which was recurrent following thoracentesis. While his initial workup suggested an autoimmune etiology, further diagnostic testing revealed a diagnosis of malignant pleural mesothelioma. Curiously, the patient had no known asbestos exposure, which is classically associated with acquired mesothelioma. There are a small number of similar cases with a possible overlap between positive autoimmune serologies and mesothelioma; however, the underlying pathophysiology remains elusive. It is the authors' goal to contribute this case to the few cases describing such overlap syndromes.}, }
@article {pmid30851279, year = {2019}, author = {Mandel, JH and Odo, NU and Alexander, BH}, title = {Potential Problems with Determining Elongate Mineral Particle (EMP) Potency (Comments on article entitled, "A Comparison of Asbestos Fiber Potency and Elongate Mineral Particle (EMP) Potency for Mesothelioma in Humans").}, journal = {Toxicology and applied pharmacology}, volume = {370}, number = {}, pages = {131-132}, doi = {10.1016/j.taap.2019.03.002}, pmid = {30851279}, issn = {1096-0333}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30840592, year = {2019}, author = {Senk, B and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment.}, journal = {Radiology and oncology}, volume = {53}, number = {1}, pages = {96-104}, pmid = {30840592}, issn = {1581-3207}, mesh = {Age Factors ; Aged ; Alopecia/chemically induced ; Anemia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Aquaporin 1/*genetics ; Case-Control Studies ; Cisplatin/adverse effects/*therapeutic use ; Female ; Humans ; Leukopenia/chemically induced ; Logistic Models ; Lung Neoplasms/*drug therapy/*genetics/mortality ; Male ; Mesothelioma/*drug therapy/*genetics/mortality ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk Assessment ; Sex Factors ; Thrombocytopenia/chemically induced ; }, abstract = {Background Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment. Patients and methods The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis. Results AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37-0.96, Padj = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27-0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27-0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00-4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01-9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00-8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00-13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13-19.05, P = 0.034) in additive model. Conclusions AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.}, }
@article {pmid30834036, year = {2019}, author = {Abbas, H and Rodriguez, JC and Tariq, H and Niazi, M and Alemam, A and Nayudu, SK}, title = {Malignant Peritoneal Mesothelioma Without Asbestos Exposure.}, journal = {Gastroenterology research}, volume = {12}, number = {1}, pages = {48-51}, pmid = {30834036}, issn = {1918-2805}, abstract = {Malignant mesothelioma is a rare neoplasm of the serosal linings. Mesothelioma has been linked to asbestos exposure, with prior asbestos exposure linked to 33-50% of malignant peritoneal mesotheliomas. We describe a case of malignant peritoneal mesothelioma (MPM) without any prior exposure to asbestos in a 40-year-old Hispanic female who presented to the emergency department with worsening abdominal pain and distension. She had a history of beta thalassemia trait and iron deficiency anemia. Examination revealed a distended abdomen with protruding umbilicus and positive shifting dullness. Laboratory tests showed anemia. Computed tomography (CT) of the abdomen revealed massive complex ascites suspicious of a malignant process. Ascitic fluid analysis showed serum ascites albumin gradient (SAAG) of 1.1 g/dL with a total protein of 5.2 g/dL. She underwent laparoscopic peritoneal biopsy which yielded epithelioid type malignant mesothelioma. She was started on chemotherapy with cisplatin and pemetrexed. The last follow-up was 27 months after the diagnosis. MPM is a rare and life-threatening malignancy. Frequently, the symptoms are non-specific. This poses a diagnostic challenge for physicians and probably the reason why the diagnosis is often delayed, especially in the absence of risk factors.}, }
@article {pmid30815702, year = {2019}, author = {Pasetto, R and Zona, A and Fazzo, L and Binazzi, A and Bruno, C and Pirastu, R and Comba, P and Marinaccio, A}, title = {Proportion of mesothelioma attributable to living in industrially contaminated areas in Italy.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {45}, number = {5}, pages = {444-449}, doi = {10.5271/sjweh.3809}, pmid = {30815702}, issn = {1795-990X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Environmental Exposure/*statistics &amp; numerical data ; Female ; Humans ; Industry/*statistics &amp; numerical data ; Infant ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Risk Factors ; Sex Factors ; Spatial Analysis ; Young Adult ; }, abstract = {Objectives The aim of this study was to estimate the attributable proportion (AP) of mesothelioma resulting from living in or close to major Italian industrially contaminated areas. Methods For populations living close to 39 sites of "national priority for remediation", incident mesothelioma cases were extracted from the Italian National Mesothelioma Registry (ReNaM) in the period 2000‒2011. Each site was classified in one of seven asbestos risk groups (RG) on the basis of the type of industrial plants. RG were ranked by the a priori evidence on asbestos risk. The AP for each RG was calculated as the meta-analytic estimate of AP of sites of the same group by gender and age class (0-64, 65-74, ≥75 years). The sex ratio (men/women) was computed for each RG. Results Among men, the AP by age class had the same gradient in each RG, with the highest values in the age class 0-64 years and the lowest in the ≥75 class; in the age class 0-64 years, the AP was positive in each RG, >90% in the presence of asbestos cement factories and harbors with shipyards. Among women, the overall AP decreased by RG, with negative values in the last two ranked RG; the AP by age class was variable without a definite gradient. The sex ratio was close to one only in the RG "only asbestos-cement factories"; the highest value (9.6) was observed in the age class 0-64 years in the RG "harbors with shipyard". Conclusions The integration of a geographic- and case-based approach provides valuable insights into occupational and environmental determinants of mesothelioma risk in industrially contaminated sites.}, }
@article {pmid30809599, year = {2018}, author = {Biersack, B}, title = {Relations between approved platinum drugs and non-coding RNAs in mesothelioma.}, journal = {Non-coding RNA research}, volume = {3}, number = {4}, pages = {161-173}, pmid = {30809599}, issn = {2468-0540}, abstract = {Malignant mesothelioma diseases feature an increasing risk due to their severe forms and their association with asbestos exposure. Platinum(II) complexes such as cisplatin and carboplatin are clinically approved for the therapy of mesothelioma often in combination with antimetabolites such as pemetrexed or gemcitabine. It was observed that pathogenic properties of mesothelioma cells and the response of mesothelioma tumors towards platinum-based drugs are strongly influenced by non-coding RNAs, in particular, by small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These non-coding RNAs controlled drug sensitivity and the development of tumor resistance towards platinum drugs. An overview of the interactions between platinum drugs and non-coding RNAs is given and the influence of non-coding RNAs on platinum drug efficacy in mesothelioma is discussed. Suitable non-coding RNA-modulating agents with potentially beneficial effects on cisplatin treatment of mesothelioma diseases are mentioned. The understanding of mesothelioma diseases concerning the interactions of non-coding RNAs and platinum drugs will optimize existing therapy schemes and pave the way to new treatment options in future.}, }
@article {pmid30804167, year = {2019}, author = {Farioli, A and Boffetta, P and Curti, S and Garzaro, G and La Vecchia, C and Mattioli, S and Spatari, G and Violante, FS}, title = {Response to: 'Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom' by Reid et al.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {5}, pages = {355}, doi = {10.1136/oemed-2018-105637}, pmid = {30804167}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30804166, year = {2019}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, &#xd8;}, title = {Environmental asbestos exposure in childhood and risk of mesothelioma later in life: a long-term follow-up register-based cohort study.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {6}, pages = {407-413}, doi = {10.1136/oemed-2018-105392}, pmid = {30804166}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; Cohort Studies ; Denmark/epidemiology ; Environmental Exposure/adverse effects/statistics &amp; numerical data ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Metallurgy/statistics &amp; numerical data ; Middle Aged ; Registries/statistics &amp; numerical data ; Risk Assessment/*methods ; }, abstract = {OBJECTIVE: To examine the risk of malignant mesothelioma (MM) in former pupils who attended primary school near an asbestos cement plant.<br><br>METHODS: A cohort of 12&#x2009;111 former pupils, born 1940-1970, was established from individual historical records from four primary schools located at a distance of 100-750 m in the prevailing wind direction from an asbestos cement plant operating from 1928 to 1984 in Aalborg, Denmark. The school cohort and a comparison cohort consisting of 108&#x2009;987 gender and 5-year frequency-matched subjects were followed up (2015) for MM in the Danish Cancer Registry. Using Cox regression, HRs were estimated for the incidence of MM. Adjustments for occupational and familial asbestos exposure were made with a job exposure matrix. An SIR analysis including latency periods testing the cancer incidence rate was performed with the comparison cohort as the reference rate.<br><br>RESULTS: The median person-years of follow-up were 62.5 years in the school cohort and 62.2 years in the comparison cohort. There were 32 males and 6 females of the former pupils who developed MM during the follow-up: HRmale 7.01 (95% CI 4.24 to 11.57), HRfemale 7.43 (95% CI 2.50 to 22.13). Those who attended school 250 m north of the plant had the highest HR for MM, 10.65 (95% Cl 5.82 to 19.48). No significant trend between school distance and risk of MM was established (p=0.35).<br><br>CONCLUSION: Our results suggest that boys and girls who attended schools and lived in the neighbourhood of an asbestos cement plant later in life have a significantly increased risk of MM.}, }
@article {pmid30804152, year = {2019}, author = {Kim, M and Kim, HS}, title = {Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases.}, journal = {In vivo (Athens, Greece)}, volume = {33}, number = {2}, pages = {633-642}, pmid = {30804152}, issn = {1791-7549}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*pathology ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*pathology ; Patient Selection ; Peritoneal Neoplasms/epidemiology/*pathology ; Peritoneum/pathology ; Pleural Neoplasms/epidemiology/*pathology ; }, abstract = {BACKGROUND/AIM: Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases.<br><br>MATERIALS AND METHODS: The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining.<br><br>RESULTS: The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1.<br><br>CONCLUSION: We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.}, }
@article {pmid30776941, year = {2019}, author = {Wang, F and Chen, Y and Wang, Y and Yin, Y and Qu, G and Song, M and Wang, H}, title = {Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells.}, journal = {Nanotoxicology}, volume = {13}, number = {4}, pages = {543-557}, doi = {10.1080/17435390.2019.1571645}, pmid = {30776941}, issn = {1743-5404}, mesh = {A549 Cells ; Cell Culture Techniques ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; Cytokinesis/*drug effects ; Epithelial Cells/*drug effects/pathology ; Humans ; Mitosis/*drug effects ; Nanowires/chemistry/*toxicity ; Particle Size ; Silver/chemistry/*toxicity ; Surface Properties ; }, abstract = {Asbestos fiber has been associated with mesothelioma and lung cancer. However, the carcinogenic risks of other fiber nanomaterials with morphological similarities to asbestos have not been fully studied. Ultra-long silver nanowires (AgNWs) are increasingly used fiber-shaped nanomaterials with a high aspect ratio, but very few studies have investigated their health risks. Here, proliferation abnormalities of lung epithelial cells induced by ultra-long AgNWs were investigated. Ultra-long AgNW treatment induced dose- and diameter-dependent increase in the ratio of multinucleated cells. Further, proteins involved in mitosis and cytokinesis, including Aurora A, p-Histone 3 (ser10), RhoA, p-MLC, and myosin IIb, were significantly upregulated after an ultra-long AgNW treatment, leading to mitotic abnormalities and cytokinetic failure. Meanwhile, exposure to ultra-long AgNWs induced cell cycle arrest. Interestingly, a series of experiments demonstrated that ROS generation and Ag[+] release were not responsible for the multinucleation induced by ultra-long AgNWs, but ultra-long AgNWs in the intercellular bridge might obstruct the contractile ring and inhibit abscission of the cytokinetic furrow by direct physical contact. Altogether, our findings indicate that ultra-long AgNWs can induce chromosomal instability, which has important consequences for the safety of ultra-long AgNWs to human health.}, }
@article {pmid30774332, year = {2019}, author = {Cova, E and Pandolfi, L and Colombo, M and Frangipane, V and Inghilleri, S and Morosini, M and Mrakic-Sposta, S and Moretti, S and Monti, M and Pignochino, Y and Benvenuti, S and Prosperi, D and Stella, G and Morbini, P and Meloni, F}, title = {Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study.}, journal = {International journal of nanomedicine}, volume = {14}, number = {}, pages = {773-785}, pmid = {30774332}, issn = {1178-2013}, mesh = {Apoptosis/drug effects ; Biopsy ; CD146 Antigen/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Endocytosis/drug effects ; Gold/chemistry ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Metal Nanoparticles/*chemistry ; Pemetrexed/pharmacology/*therapeutic use ; Pleural Neoplasms/*drug therapy/pathology ; Reactive Oxygen Species/metabolism ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.<br><br>METHODS: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).<br><br>RESULTS: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.<br><br>CONCLUSION: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.}, }
@article {pmid30773744, year = {2019}, author = {Yoshida, GJ}, title = {Beyond Stanton and Pott hypothesis; carbon nanotubes-induced malignant mesothelioma as a disease of gene loss.}, journal = {Journal of occupational health}, volume = {61}, number = {2}, pages = {203-205}, pmid = {30773744}, issn = {1348-9585}, mesh = {Animals ; Asbestos/adverse effects ; Genes, p16 ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Mice ; Nanotubes, Carbon/*adverse effects ; Occupational Exposure/adverse effects ; }, }
@article {pmid30770142, year = {2019}, author = {Douglas, T and Van den Borre, L}, title = {Asbestos neglect: Why asbestos exposure deserves greater policy attention.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {123}, number = {5}, pages = {516-519}, doi = {10.1016/j.healthpol.2019.02.001}, pmid = {30770142}, issn = {1872-6054}, mesh = {*Asbestos ; *Carcinogens, Environmental ; Developing Countries ; Environmental Exposure/*adverse effects ; Health Policy ; Humans ; Lung Neoplasms/chemically induced/prevention &amp; control ; Mesothelioma/chemically induced/prevention &amp; control ; Occupational Exposure/adverse effects ; }, abstract = {While many public health threats are now widely appreciated by the public, the risks from asbestos exposure remain poorly understood, even in high-risk groups. This article makes the case that asbestos exposure is an important, ongoing global health threat, and argues for greater policy efforts to raise awareness of this threat. It also proposes the extension of asbestos bans to developing countries and increased public subsidies for asbestos testing and abatement.}, }
@article {pmid30759891, year = {2019}, author = {Bertrand, P and Blanquart, C and Héroguez, V}, title = {The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy.}, journal = {Biomolecules}, volume = {9}, number = {2}, pages = {}, pmid = {30759891}, issn = {2218-273X}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Proliferation/drug effects ; Drug Carriers/chemistry ; Drug Delivery Systems ; Histone Deacetylase Inhibitors/chemistry/*pharmacology ; Humans ; Hydrogen-Ion Concentration ; Nanoparticles/*chemistry ; Neoplasms/*drug therapy/pathology ; Polymerization ; }, abstract = {Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.}, }
@article {pmid30754975, year = {2018}, author = {Pelclová, D}, title = {Diagnostics and acknowledgement of occupational diseases - topics and challenges in the Czech Republic.}, journal = {Casopis lekaru ceskych}, volume = {157}, number = {8}, pages = {396-399}, pmid = {30754975}, issn = {0008-7335}, mesh = {*Asbestos/adverse effects ; *Asthma/diagnosis/etiology ; Czech Republic ; Humans ; *Mesothelioma/diagnosis/etiology ; *Occupational Diseases/diagnosis/therapy ; }, abstract = {The causes of occupational diseases are changing, thats why a regular update of Czech List of Occupational Diseases is needed. New compensable occupational diseases, such as cancer of the larynx and ovarian cancer due to asbestos, and chronic obstructive pulmonary diseases due to black coal dust were included in the last two updates of the Czech List. The need of an early examination at the Centers of Occupational Diseases is stressed in this article, especially before a surgery or other treatment of epicondylitis and carpal tunnel syndrome. These treatments may suppress the diagnostic hallmarks requested for acknowledgements of these disorders. Extrinsic allergic alveolitis, allergic rhinitis and bronchial asthma are underdiagnosed, and isocyanates belong among the key factors. Only about 10 % patients with mesotheliomas due to asbestos are compensated. The latency in cancers due to asbestos may reach more than 50 years.}, }
@article {pmid30744695, year = {2019}, author = {Weber, DG and Brik, A and Casjens, S and Burek, K and Lehnert, M and Pesch, B and Taeger, D and Brüning, T and Johnen, G and , }, title = {Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {77}, pmid = {30744695}, issn = {1756-0500}, mesh = {Adult ; Asbestosis/blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Circulating MicroRNA/*blood ; Early Detection of Cancer/*standards ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Middle Aged ; Prodromal Symptoms ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease.<br><br>RESULTS: Using prediagnostic plasma samples collected in median 8.9&#xa0;months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.}, }
@article {pmid30741658, year = {2019}, author = {García-Ibáñez, J and Cayuelas-Rubio, C and Durán-Rivera, A and Mitjana-Biosca, S and Monzó-Cataluña, A and Sánchez Ballester, F and Ramos de Campos, M and Ramos de Campos, M and López-Alcina, E}, title = {[Report of two cases of malignant mesothelioma of the tunica vaginalis.].}, journal = {Archivos espanoles de urologia}, volume = {72}, number = {1}, pages = {85-88}, pmid = {30741658}, issn = {0004-0614}, mesh = {Aged ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma/diagnosis ; *Testicular Hydrocele ; *Testicular Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: Paratesticular mesothelioma isan infrequent tumor and only 250 cases have been published.It originates in the scrotal tunica vaginalis. It represents0.3-1.4% of mesotheliomas and it predominates inpatients with history of asbestos exposure and old age. Itsdiagnosis is usually casual. Our objective is to present thecases that occurred in our service with malignant paratesticularmesothelioma and to carry out a review of the currentliterature on this pathology.<br><br>METHODS: We report two cases diagnosed with malignantparatesticular mesothelioma that happened in the lasttwo years.<br><br>RESULT: The first case was a 73-year-old male with asymptomatichydrocele. The second was a 57-year-oldmale who had testicular pain and hydrocele. Both werediagnosed of mesothelioma after hydrocelectomy. The firsttreatment was radical orchiectomy in both cases. The firstpatient did not need more treatments. The second patientpresented pulmonary nodules, lymphadenopathy and localrelapse, which was treated with chemotherapy and localresection.<br><br>CONCLUSION: Paratesticular mesothelioma is an infrequenttumor. Scrotal mass associated with hydrocele is thetypical form of presentation. Surgical treatment consists ofradical orchiectomy. They have poor prognosis because inmost cases there is rapid local and dissemination.}, }
@article {pmid30719319, year = {2019}, author = {Guo, X and Watanabe, J and Takahashi, K and Hayashi, T and Kurose, N and Sasaguri, Y and Uramoto, H and Iwagaki, H and Nabeshima, K and Yamada, S}, title = {Localized malignant pleural mesothelioma arising in the interlobar fissure: a unique surgical case masquerading clinicopathologically as primary lung adenocarcinoma.}, journal = {SAGE open medical case reports}, volume = {7}, number = {}, pages = {2050313X18824802}, pmid = {30719319}, issn = {2050-313X}, abstract = {An 80-year-old male with previous workplace exposure to asbestos presented with a history of an increase in the pulmonary-to-hilar mass, measuring more than 50 mm in diameter, likely in the right lower lobe. We first interpreted it as suspicious of primary lung adenocarcinoma with direct invasion to the right hilar lymph node. A right middle and lower lobectomy with partial resection of upper lobe was performed, and gross examination showed a hilar tumor lesion, involving the middle/lower lobe to hilar lymph node and looking whitish to yellow-grayish, partly adjacent to the right pulmonary artery. On microscopic examination, the tumor was located on the extrapulmonary, interlobar pleural fissure, predominantly composed of a proliferation of atypical epithelioid cells, often arranged in an irregular and fused tubular growth pattern with an involvement of pulmonary artery. Immunohistochemically, these atypical cells are positive for several mesothelial markers, including calretinin, cytokeratin 5/6, and WT-1, whereas negative for thyroid transcription factor 1. Furthermore, p16 deletions were specifically detected by fluorescence in situ hybridization, and electron microscopy showed numerous, significantly elongated microvilli. Taken together, we finally made a diagnosis of localized malignant pleural mesothelioma, epithelioid-type, arising in the right interlobar fissure between lower and middle lobes. We should be aware that, owing to its characteristic features, clinicians and pathologists might be able to raise interlobar fissure localized malignant pleural mesothelioma as one of the differential diagnoses, based on careful clinicopathological examinations.}, }
@article {pmid30711965, year = {2019}, author = {Salo, SAS and Ilonen, I and Laaksonen, S and Myllärniemi, M and Salo, JA and Rantanen, T}, title = {Malignant Peritoneal Mesothelioma: Treatment Options and Survival.}, journal = {Anticancer research}, volume = {39}, number = {2}, pages = {839-845}, doi = {10.21873/anticanres.13183}, pmid = {30711965}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Cytoreduction Surgical Procedures/mortality ; Female ; Finland ; Humans ; Hyperthermia, Induced ; Lung Neoplasms/*drug therapy/mortality/*surgery ; Male ; Mesothelioma/*drug therapy/mortality/*surgery ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/mortality/*surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.<br><br>MATERIALS AND METHODS: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.<br><br>RESULTS: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).<br><br>CONCLUSION: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.}, }
@article {pmid30706690, year = {2019}, author = {Rojas, L and Cardona, AF and Trejo-Rosales, R and Zatarain-Barrón, ZL and Ramírez-Tirado, LA and Ruiz-Patiño, A and Campos Gómez, S and Corrales, L and Oblitas, G and Bacon, L and Martín, C and de Lima, VCC and Freitas, HC and Mas, L and Vargas, C and Carranza, H and Otero, J and Pérez, MA and González, L and Chirinos, L and Granados, ST and Rodriguez, J and Báez, R and Remolina Bonilla, YA and Núñez Cerrillo, G and Archila, P and Cuello, M and Karachaliou, N and Rosell, R and Arrieta, O and , }, title = {Characteristics and long-term outcomes of advanced pleural mesothelioma in Latin America (MeSO-CLICaP).}, journal = {Thoracic cancer}, volume = {10}, number = {3}, pages = {508-518}, pmid = {30706690}, issn = {1759-7714}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/therapeutic use ; Female ; Humans ; Latin America/epidemiology ; Lung Neoplasms/drug therapy/*epidemiology/pathology/surgery ; Male ; Mesothelioma/drug therapy/*epidemiology/pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/therapeutic use ; Platinum/*therapeutic use ; Pleural Neoplasms/drug therapy/*epidemiology/pathology/surgery ; Progression-Free Survival ; Thoracic Surgical Procedures/methods ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population.<br><br>METHODS: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients.<br><br>RESULTS: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage&#x2009;III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P&#x2009;=&#x2009;0.013), and pleurodesis (P&#x2009;=&#x2009;0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders.<br><br>CONCLUSION: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.}, }
@article {pmid30706505, year = {2019}, author = {Sun, H}, title = {North-south gradient of mesothelioma and asbestos consumption-production in the United States-Progresses since the 1st asbestos partial ban in 1973.}, journal = {American journal of industrial medicine}, volume = {62}, number = {4}, pages = {337-346}, doi = {10.1002/ajim.22955}, pmid = {30706505}, issn = {1097-0274}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; Female ; Geography ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Mining/*statistics &amp; numerical data ; United States/epidemiology ; }, abstract = {BACKGROUND: Temporal trends and broad geographical distributions of asbestos use and the incidence of malignant mesothelioma (MM) in the US still need to be studied.<br><br>METHODS: Data on asbestos consumption and production between 1900 and 2015 and MM mortality and incidence rates between 1975 and 2015 in the US were examined. Spatial distributions of MM mortality and incidence rates and their association with climate zone were analyzed.<br><br>RESULTS: Decline of MM incidence and mortality rates in the US occurred about 20 years after the peak of asbestos consumption-production in 1973. There are apparent north-south (N-S) gradients in MM mortality and incidence rates in the US.<br><br>CONCLUSION: Recent decline of MM incidence and mortality rates in the US may be associated with reduced US asbestos consumption. N-S MM gradients between 1999 and 2015 were likely related to larger asbestos requirements in building materials in the northern states.}, }
@article {pmid30702033, year = {2020}, author = {Germine, M and Puffer, JH}, title = {Analytical transmission electron microscopy of amosite asbestos from South Africa.}, journal = {Archives of environmental &amp; occupational health}, volume = {75}, number = {1}, pages = {36-44}, doi = {10.1080/19338244.2018.1556201}, pmid = {30702033}, issn = {2154-4700}, mesh = {Asbestos, Amosite/*chemistry ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Molecular Structure ; South Africa ; }, abstract = {Using the recognized amosite standard, we have performed transmission electron microscopy (TEM), scanning electron microscopy (SEM), and chemical analyses. We use high-resolution transmission electron microscopy (HRTEM) and zone-axis selected area electron diffraction (SAED) to describe the molecular structure of the fibers. We find that both microscopic observational evidence and statistical dimensional characteristics indicate that the amosite fibers are formed by longitudinal splitting, with surfaces produced by fine twinning and lateral boundaries formed by parting parallel to the planes of double and triple sheets of amphibole chain structures. Our findings indicate that amosite would not be regulated under current asbestos regulations, which define amphibole asbestos as whole crystals that are not split and that form fibril bundles, not found in our standard. However, it is fully documented that amosite causes mesothelioma, lung cancer, and asbestosis.}, }
@article {pmid30687679, year = {2018}, author = {Visonà, SD and Villani, S and Manzoni, F and Chen, Y and Ardissino, G and Russo, F and Moretti, M and Javan, GT and Osculati, A}, title = {Impact of asbestos on public health: a retrospective study on a series of subjects with occupational and non-occupational exposure to asbestos during the activity of Fibronit plant (Broni, Italy).}, journal = {Journal of public health research}, volume = {7}, number = {3}, pages = {1519}, pmid = {30687679}, issn = {2279-9028}, abstract = {The goal of this study is to understand more about the role of asbestos in causing human diseases, first of all mesothelioma, by investigating a large series of deaths due to asbestos-related diseases (ARDs). The main aim is to clarify if even very low amounts of asbestos can cause mesothelioma and other ARDs, as well as to find out if a different individual vulnerability can be important. This retrospective study included 188 subjects who died from asbestos related diseases in 2000-2017 in the area around Broni, Italy, where an important asbestos cement factory had been active from 1932 until 1993. In each case, a forensic autopsy has been performed. In order to perform the present study, the records were retrieved, including the clinical files, the autopsy, and the histological report. The statistical analysis performed showed that there was a significant relation between the cause of death (mesothelioma, lung cancer or asbestosis) and the kind of exposure (occupational, neighborhood or household), showing that all the subjects not exposed occupationally (and, therefore, exposed to lower amounts of asbestos) died from mesothelioma, whereas the individuals who used to work at the plant died also from other caused (asbestosis, lung cancer). Significant differences were highlighted examining the distribution of the causes of death according to the smoking habits. Moreover, among the mesothelioma patients, the survival time was shorter in the subjects with a neighborhood or household exposure than in the occupationally exposed individuals. The study provided meaningful data about the role of asbestos in causing human pathologies. In particular, the present data appear to support the hypothesis that even an exposure to a very little amount of asbestos can cause mesothelioma in hypersusceptible subjects (probably, on a genetic basis).}, }
@article {pmid30687504, year = {2019}, author = {Matthews, C and Freeman, C and Sharples, LD and Fox-Rushby, J and Tod, A and Maskell, NA and Edwards, JG and Coonar, AS and Sivasothy, P and Hughes, V and Rahman, NM and Waller, DA and Rintoul, RC}, title = {MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000368}, pmid = {30687504}, issn = {2052-4439}, support = {G0600475/MRC_/Medical Research Council/United Kingdom ; PB-PG-1014-35050/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Catheters, Indwelling ; Clinical Trials, Phase III as Topic ; England/epidemiology ; Feasibility Studies ; Female ; Humans ; Lung Neoplasms/complications/mortality/*surgery ; Male ; Mesothelioma/complications/mortality/*surgery ; Mesothelioma, Malignant ; Multicenter Studies as Topic ; Observational Studies as Topic ; Pilot Projects ; Pleural Effusion, Malignant/etiology/mortality/*surgery ; Pleural Neoplasms/complications/mortality/*surgery ; Pleurodesis/adverse effects/instrumentation/*methods ; Randomized Controlled Trials as Topic ; Sample Size ; Survival Analysis ; Thoracic Surgery, Video-Assisted/adverse effects/instrumentation/*methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.<br><br>METHODS AND ANALYSIS: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.<br><br>ETHICS AND DISSEMINATION: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.<br><br>TRIAL REGISTRATION: NCT03412357.}, }
@article {pmid30686559, year = {2019}, author = {Neviere, Z and Berthet, P and Polycarpe, F and Dubos-Arvis, C and Dô, P and Gervais, R}, title = {[Malignant mesothelioma and constitutional BAP1 gene mutations].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {2}, pages = {241-248}, doi = {10.1016/j.rmr.2017.11.014}, pmid = {30686559}, issn = {1776-2588}, mesh = {Aftercare/methods ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*genetics/*therapy ; Medical Oncology/methods ; Mesothelioma/diagnosis/epidemiology/*genetics/*therapy ; Mesothelioma, Malignant ; *Mutation ; Referral and Consultation ; Tumor Suppressor Proteins/*genetics/physiology ; Ubiquitin Thiolesterase/*genetics/physiology ; }, abstract = {Malignant mesothelioma is a rare tumour, usually the result of asbestos exposure. Several cases of familial aggregation have been reported and recently shown to be associated with constitutional mutations of the BAP1 gene. BAP1 is a deubiquitinating enzyme implicated in several different cellular mechanisms such as the repair or differentiation of DNA. About a half of malignant mesotheliomas present a somatic, bi-allelic inactivation of BAP1, demonstrated by nuclear extinction on histochemistry. Constitutional alterations of BAP1 are extremely rare. Present in the heterozygous state they are transmitted as an autosomal dominant. They are associated with a risk of developing other tumours such as uveal and cutaneous melanomas, benign melanocytic tumours (melanocytic BAP1-mutated atypical intradermal tumour or MBAITS) and clear cell renal carcinomas. The causal link between mesothelioma and germinal mutations of BAP1 has still not been clearly identified. At present there is, in France, no consensus on recommendations for the management of patients with these mutations. This article is a synthesis of the literature on the functions of the BAP1 gene, the tumour risks related to its alteration and the follow up of patients bearing a constitutional mutation.}, }
@article {pmid30685089, year = {2019}, author = {Abayasiriwardana, KS and Wood, MK and Prêle, CM and Birnie, KA and Robinson, BW and Laurent, GJ and McAnulty, RJ and Mutsaers, SE}, title = {Inhibition of collagen production delays malignant mesothelioma tumor growth in a murine model.}, journal = {Biochemical and biophysical research communications}, volume = {510}, number = {2}, pages = {198-204}, doi = {10.1016/j.bbrc.2019.01.057}, pmid = {30685089}, issn = {1090-2104}, support = {/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Collagen/antagonists &amp; inhibitors/*biosynthesis ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Female ; Humans ; Inflammation ; Lung Neoplasms/*metabolism/pathology ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred CBA ; Pleural Neoplasms/*metabolism/pathology ; Thiazolidines/pharmacology ; Transforming Growth Factor beta/metabolism ; }, abstract = {Malignant mesothelioma is an aggressive fibrous tumor, predominantly of the pleura, with a very poor prognosis. Cell-matrix interactions are recognized important determinants of tumor growth and invasiveness but the role of the extracellular matrix in mesothelioma is unknown. Mesothelioma cells synthesize collagen as well as transforming growth factor-beta (TGF-β), a key regulator of collagen production. This study examined the effect of inhibiting collagen production on mesothelioma cell proliferation in vitro and tumor growth in vivo. Collagen production by mesothelioma cells was inhibited by incubating cells in vitro with the proline analogue thiaproline (thiazolidine-4-carboxylic acid) or by oral administration of thiaproline in a murine tumor model. Cell cytotoxicity was measured using neutral red uptake and lactate dehydrogenase assays. Proliferation was measured by tritiated thymidine incorporation, and inflammatory cell influx, proliferation, apoptosis and angiogenesis in tumors examined by immunohistochemical labelling. Tumor size was determined by tumor weight and collagen production was measured by HPLC. Thiaproline at non-toxic doses significantly reduced basal and TGF-β-induced collagen production by over 50% and cell proliferation by over 65%. In vivo thiaproline administration inhibited tumor growth at 10 days, decreasing the median tumor weight by 80%. The mean concentration of collagen was 50% lower in the thiaproline-treated tumors compared with the controls. There were no significant differences in vasculature or inflammatory cell infiltration but apoptosis was increased in thiaproline treated tumors at day 10. In conclusion, these observations strongly support a role for collagen in mesothelioma growth and establish the potential for inhibitors of collagen synthesis in mesothelioma treatment.}, }
@article {pmid30684047, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {Managing malignant pleural mesothelioma: experience and perceptions of health care professionals caring for people with mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {9}, pages = {3509-3519}, pmid = {30684047}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; *Attitude of Health Personnel ; Caregivers/*psychology ; Communication ; Female ; Humans ; Lung Neoplasms/pathology/*therapy ; Male ; Medical Oncology ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care/methods ; Pleural Neoplasms/pathology/*therapy ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; Referral and Consultation ; Refusal to Treat/*statistics &amp; numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor prognosis and heavy symptom burden. Here, we investigate health professionals' attitudes to management and decision-making in people with MPM.<br><br>METHODS: Survey questions were based on previous interviews with health professionals, MPM patients, and caregivers. Surveys were sent to specialist doctors and nurses who treat MPM.<br><br>RESULTS: Surveys were completed by 107 doctors and 19 nurses from January-September 2014. Most doctors were respiratory physicians (50%) or medical oncologists (35%). Overall, 90% of doctors estimated >&#x2009;10% of eligible MPM patients did not receive chemotherapy; 43% estimated the rate was >&#x2009;20%. Doctors believed clinical barriers to chemotherapy were clinician nihilism (70%); non-referral to medical oncology (49%); and lack of specialists in rural/regional areas (44%). Nurses perceived barriers as follows: delayed diagnosis (74%); non-referral to medical oncology (63%); lack of clinician knowledge (58%). Patient-related barriers were negative perception of chemotherapy (83%) and belief survival benefit not worthwhile (63%). Doctors' preference in decision-making was for the patient to make the decision while strongly considering the doctor's opinion (33%); equally with the doctor (29%); and using knowledge gained (23%). Nurses described their roles as providing patient support (100%); information (95%); intermediary (74%); and link to palliative care (74%). Overall, 95% believed they enabled better resource allocation and provided patients with holistic care (95%); clearer communication (89%); more time (89%); additional information (89%); timely referrals (89%).<br><br>CONCLUSIONS: Caring for patients with MPM is challenging and complex. Health care professionals believe under-utilisation of chemotherapy is occurring, primarily due to clinician nihilism and lack of medical oncology referral.}, }
@article {pmid30663400, year = {2018}, author = {Wang, QQ and Zheng, GQ and Yang, DL and Liang, YF and Yin, WJ and Su, SS}, title = {Pretreatment Controlling Nutritional Status Score and Lactate Dehydrogenase as Predictive Markers of Survival in Patients with Malignant Peritoneal Mesothelioma.}, journal = {Nutrition and cancer}, volume = {70}, number = {8}, pages = {1264-1274}, doi = {10.1080/01635581.2018.1560481}, pmid = {30663400}, issn = {1532-7914}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/therapeutic use ; Asbestos/toxicity ; Biomarkers, Tumor/blood ; Female ; Humans ; L-Lactate Dehydrogenase/*blood ; Male ; Mesothelioma/drug therapy/*mortality/surgery ; Middle Aged ; Nutritional Status/*physiology ; Peritoneal Neoplasms/drug therapy/*mortality/surgery ; Prognosis ; ROC Curve ; }, abstract = {OBJECTIVE: To investigate the relationships between the Controlling Nutritional Status (CONUT) score and ascites fluid lactate dehydrogenase (LDH) level, and prognosis in patients with malignant peritoneal mesothelioma (MPeM).<br><br>METHODS: A total of 125 patients with MPeM were selected for the study using a pathological screening method. Once the diagnosis is established, before the treatment their clinical characteristics and nutritional evaluations were recorded including CONUT score and ascites LDH level. The associations between CONUT, ascites LDH, and other clinicopathological features including body mass index, asbestos exposure, pathological type, and treatment method were analyzed. Prognostic parameters predicting overall survival (OS) were analyzed by Cox regression.<br><br>RESULTS: High CONUT score, high ascites LDH level were positively associated with poor prognosis in patients with MPeM according to univariate analyses (P&#x2009;<&#x2009;0.001, P&#x2009;<&#x2009;0.001, respectively), and CONUT score and ascites LDH were independent predictors of a poor prognosis according to multivariate analysis. When the CONUT score is greater than 3 and the ascites LHD is greater than 474&#x2009;IU/l, it indicates a poor prognosis.<br><br>CONCLUSIONS: CONUT score and ascites LDH are important factors influencing the prognosis of MPeM patients and should thus be considered in clinical applications.}, }
@article {pmid30659154, year = {2019}, author = {Villanova, T and Gesmundo, I and Audrito, V and Vitale, N and Silvagno, F and Musuraca, C and Righi, L and Libener, R and Riganti, C and Bironzo, P and Deaglio, S and Papotti, M and Cai, R and Sha, W and Ghigo, E and Schally, AV and Granata, R}, title = {Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {6}, pages = {2226-2231}, pmid = {30659154}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Disease Models, Animal ; Gene Expression ; Growth Hormone-Releasing Hormone/*antagonists &amp; inhibitors/genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*metabolism/*pathology ; Mesothelioma/drug therapy/*metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mitochondria/drug effects/metabolism ; Pleural Neoplasms/drug therapy/*metabolism/*pathology ; Receptors, Neuropeptide/genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with exposure to asbestos, with poor prognosis and no effective therapies. The strong inhibitory activities of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different experimental human cancers, including lung cancer; however, their role in MPM remains unknown. We assessed the effects of the GHRH antagonists MIA-602 and MIA-690 in vitro in MPM cell lines and in primary MPM cells, and in vivo in MPM xenografts. GHRH, GHRH receptor, and its main splice variant SV1 were found in all the MPM cell types examined. In vitro, MIA-602 and MIA-690 reduced survival and proliferation in both MPM cell lines and primary cells and showed synergistic inhibitory activity with the chemotherapy drug pemetrexed. In MPM cells, GHRH antagonists also regulated activity and expression of apoptotic molecules, inhibited cell migration, and reduced the expression of matrix metalloproteinases. These effects were accompanied by impairment of mitochondrial activity and increased production of reactive oxygen species. In vivo, s.c. administration of MIA-602 and MIA-690 at the dose of 5 μg/d for 4 wk strongly inhibited the growth of MPM xenografts in mice, along with reduction of tumor insulin-like growth factor-I and vascular endothelial growth factor. Overall, these results suggest that treatment with GHRH antagonists, alone or in association with chemotherapy, may offer an approach for the treatment of MPM.}, }
@article {pmid30651596, year = {2019}, author = {Sépult, C and Bellefroid, M and Rocks, N and Donati, K and Gérard, C and Gilles, C and Ludwig, A and Duysinx, B and Noël, A and Cataldo, D}, title = {ADAM10 mediates malignant pleural mesothelioma invasiveness.}, journal = {Oncogene}, volume = {38}, number = {18}, pages = {3521-3534}, pmid = {30651596}, issn = {1476-5594}, mesh = {ADAM10 Protein/*genetics ; Amyloid Precursor Protein Secretases/*genetics ; Animals ; Cadherins/genetics ; Cell Line, Tumor ; Cell Movement/*genetics ; Disease Progression ; Down-Regulation/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Lung Neoplasms/*genetics/*pathology ; Male ; Membrane Proteins/*genetics ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Pleural Neoplasms/*genetics/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and mesothelioma development is very long, the local invasion of mesothelioma is very rapid leading to a mean survival of one year after diagnosis. ADAM10 (A Disintegrin And Metalloprotease) sheddase targets membrane-bound substrates and its overexpression is associated with progression in several cancers. However, nothing is known about ADAM10 implication in MPM. In this study, we demonstrated higher ADAM10 expression levels in human MPM as compared to control pleural samples and in human MPM cell line. This ADAM10 overexpression was also observed in murine MPM samples. Two mouse mesothelioma cell lines were used in this study including one primary cell line obtained by repeated asbestos fibre injections. We show, in vitro, that ADAM10 targeting through shRNA and pharmacological (GI254023X) approaches reduced drastically mesothelioma cell migration and invasion, as well as for human mesothelioma cells treated with siRNA targeting ADAM10. Moreover, ADAM10 downregulation in murine mesothelioma cells significantly impairs MPM progression in vivo after intrapleural cell injection. We also demonstrate that ADAM10 sheddase downregulation decreases the production of a soluble N-cadherin fragment through membrane N-cadherin, which stimulated mesothelioma cell migration. Taken together, we demonstrate that ADAM10 is overexpressed in MPM and takes part to MPM progression through the generation of N-cadherin fragment that stimulates mesothelioma cell migration. ADAM10 inhibition is worth considering as a therapeutic perspective in mesothelioma context.}, }
@article {pmid30648431, year = {2019}, author = {Harris, EJA and Musk, A and de Klerk, N and Reid, A and Franklin, P and Brims, FJH}, title = {Diagnosis of asbestos-related lung diseases.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {3}, pages = {241-249}, doi = {10.1080/17476348.2019.1568875}, pmid = {30648431}, issn = {1747-6356}, mesh = {Asbestos/*toxicity ; Asbestosis/diagnosis/diagnostic imaging ; Humans ; Lung Diseases/chemically induced/*diagnosis/diagnostic imaging ; Lung Neoplasms/chemically induced/diagnosis/diagnostic imaging ; Occupational Exposure ; Risk Assessment ; }, abstract = {The diagnosis of lung disease in asbestos-exposed individuals is a process that not only requires a detailed occupational and tobacco smoking history, but the correlation with physical signs, appropriate imaging, detailed lung function assessment and histology/cytology when required. Worldwide, the total quantity of asbestos mined is static, having decreased dramatically in developed countries but increased in countries where there is no restriction on mining: for example, Russia, China, Brazil, and Kazakhstan. The predominant diagnostic challenge in most cases of possible asbestos-related disease is the significant interval between exposure and development of the disease. Also challenging is the estimation of an individual's risk of disease, not least because asbestos-induced malignancy can be rapidly fatal, and, in the case of lung cancer, early detection can lead to treatment with curative intent. Areas covered: Discussion of quantitative asbestos exposure estimation and risk assessment, selection of the most appropriate imaging modality and frequency of imaging. Expert commentary: Consideration of the future for asbestos-related lung disease includes screening those at highest risk particularly in relation to ongoing mining operations and the management of in-situ asbestos. In the future, screening programs designed with estimation of risk of malignancy, based on quantitative estimates of asbestos exposure, and smoking history are indicated.}, }
@article {pmid30642542, year = {2019}, author = {Wu, L and Dell'Anno, I and Lapidot, M and Sekido, Y and Chan, ML and Kohno, M and Serre-Beinier, V and Felley-Bosco, E and de Perrot, M}, title = {Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018).}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {127}, number = {}, pages = {138-145}, doi = {10.1016/j.lungcan.2018.11.034}, pmid = {30642542}, issn = {1872-8332}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Congresses as Topic ; Humans ; *International Cooperation ; Lung Neoplasms/*metabolism/pathology/therapy ; Mesothelioma/*metabolism/pathology/therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Pleural Neoplasms/*metabolism/pathology/therapy ; Public Opinion ; *Research ; Tumor Microenvironment ; }, abstract = {Here we summarize the most recent update of mesothelioma research in basic science presented at the 14[th] iMig2018 international conference. The symposium of basic science track mainly focused on the drivers of mesothelioma initiation and progression, molecular pathogenesis, and perspectives on potential therapeutic approaches. This review covers several promising fields including strategies efficiently inhibiting YAP/TAZ functions or their critical downstream targets, heparanase inhibitors, RAN depletion, and MIF/CD74 inhibitors that may be developed as novel therapeutic approaches. In addition, targeting mesothelioma stem cells by depleting M2-polarized macrophages in tumor microenvironment or blocking Tnfsf18 (GITRL)-GITR signalling might be translated into therapeutic modalities in mesothelioma treatment.}, }
@article {pmid30629589, year = {2019}, author = {Chicco, D and Rovelli, C}, title = {Computational prediction of diagnosis and feature selection on mesothelioma patient health records.}, journal = {PloS one}, volume = {14}, number = {1}, pages = {e0208737}, pmid = {30629589}, issn = {1932-6203}, mesh = {Computational Biology/methods ; Female ; Health Records, Personal ; Humans ; *Machine Learning ; Male ; Mesothelioma/*diagnosis ; Regression Analysis ; }, abstract = {BACKGROUND: Mesothelioma is a lung cancer that kills thousands of people worldwide annually, especially those with exposure to asbestos. Diagnosis of mesothelioma in patients often requires time-consuming imaging techniques and biopsies. Machine learning can provide for a more effective, cheaper, and faster patient diagnosis and feature selection from clinical data in patient records.<br><br>METHODS AND FINDINGS: We analyzed a dataset of health records of 324 patients having mesothelioma symptoms from Turkey. The patients had prior asbestos exposure and displayed symptoms consistent with mesothelioma. We compared probabilistic neural network, perceptron-based neural network, random forest, one rule, and decision tree classifiers to predict diagnosis of the patient records. We measured classifiers' performance through standard confusion matrix scores such as Matthews correlation coefficient (MCC). Random forest outperformed all models tried, obtaining MCC = +0.37 on the complete imbalanced dataset and MCC = +0.64 on the under-sampled balanced dataset. We then employed random forest feature selection to identify the two most relevant dataset traits associated with mesothelioma: lung side and platelet count. These two risk factors resulted so predictive, that decision tree focusing on them achieved the second top accuracy on the complete dataset diagnosis prediction (MCC = +0.28), outperforming all other methods and even decision tree itself applied to all features.<br><br>CONCLUSIONS: Our results show that machine learning can predict diagnoses of patients having mesothelioma symptoms with high accuracy, sensitivity, and specificity, in few minutes. Additionally, random forest can efficiently select the most important features of this clinical dataset (lung side and platelet count) in few seconds. The importance of pleural plaques in lung sides and blood platelets in mesothelioma diagnosis indicates that physicians should focus on these two features when reading records of patients with mesothelioma symptoms. Moreover, doctors can exploit our machinery to predict patient diagnosis when only lung side and platelet data are available.}, }
@article {pmid30623323, year = {2019}, author = {Taghizadeh, F and Jafari, AJ and Gholami, M and Kermani, M and Arfaeinia, H and Mohammadi, S and Dowlati, M and Shahsavani, A}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Shahryar City, Iran: levels, spatial distribution, seasonal variations, and health risk assessment.}, journal = {Environmental science and pollution research international}, volume = {26}, number = {7}, pages = {6450-6459}, pmid = {30623323}, issn = {1614-7499}, support = {31563//Environmental and occupational health center/ ; }, mesh = {Air Pollutants/*analysis ; Air Pollution/statistics &amp; numerical data ; Asbestos/*analysis ; Cities ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Monitoring ; Humans ; Iran/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Microscopy, Phase-Contrast ; Risk Assessment ; Seasons ; }, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. This study was designed and conducted within the time period of August 2017 and June 2018 to determine the concentration of asbestos fiber in the ambient air of Shahryar City and to evaluate their health effects for the general population of the city. For this purpose, samples were taken from four points, and overall 32 air samples were taken along the year. The samples were then analyzed by the phase contrast microscopy (PCM) method. Also, to investigate the type of asbestos and for more accurate counting of fibers, SEM analysis was utilized. Finally, based on the EPA IRIS method, the health effects resulting from asbestos risks were also evaluated. The results of this study indicated that the mean annual concentration of asbestos fiber in the ambient air of Shahryar City was obtained as 0.0019 f/ml PCM and 0.0072 f/ml SEM. Furthermore, the most polluted point was S1 point (0.0119 -0.0026 f/ml, PCM), while the lowest concentration was related to S4 point (0.001 f/ml PCM-0.0021 f/ml SEM). The mean annual risk resulting from airborne asbestos fiber in the ambient air of Shahryar City for all samples was obtained as 1.72 × 10[-6] to 2.2 × 10[-4], which was higher than the recommended risk range in some points.}, }
@article {pmid30622932, year = {2018}, author = {Lo Russo, G and Tessari, A and Capece, M and Galli, G and de Braud, F and Garassino, MC and Palmieri, D}, title = {MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {650}, pmid = {30622932}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis per se is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.}, }
@article {pmid30618090, year = {2019}, author = {Zha, L and Kitamura, Y and Kitamura, T and Liu, R and Shima, M and Kurumatani, N and Nakaya, T and Goji, J and Sobue, T}, title = {Population-based cohort study on health effects of asbestos exposure in Japan.}, journal = {Cancer science}, volume = {110}, number = {3}, pages = {1076-1084}, pmid = {30618090}, issn = {1349-7006}, support = {15H04774//Japan Society for the Promotion of Science KAKENHI/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Cohort Studies ; Humans ; Japan/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology ; }, abstract = {Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause-specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos-related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow-up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long-term residents' cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10-1.13) in men and 1.07 (95% CI, 1.06-1.09) in women; lung cancer, 1.28 (95% CI, 1.23-1.34) in men and 1.23 (95% CI, 1.14-1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83-7.78) in men and 14.99 (95% CI, 12.34-18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long-term residents' cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades.}, }
@article {pmid30609805, year = {2019}, author = {Turini, S and Bergandi, L and Gazzano, E and Prato, M and Aldieri, E}, title = {Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, pmid = {30609805}, issn = {1422-0067}, mesh = {Antibodies/immunology ; Asbestos, Serpentine/*toxicity ; Cadherins/genetics/metabolism ; Cell Line ; Down-Regulation/drug effects ; Epithelial Cells/cytology/drug effects/metabolism ; Epithelial-Mesenchymal Transition/*drug effects ; Fibronectins/genetics/metabolism ; Humans ; Lung Neoplasms/chemically induced/pathology ; Matrix Metalloproteinase 2/genetics/metabolism ; Mesothelioma/chemically induced/pathology ; Mesothelioma, Malignant ; Smad Proteins/genetics/metabolism ; Snail Family Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta/immunology/*metabolism ; Up-Regulation/drug effects ; Vimentin/genetics/metabolism ; Zinc Finger E-box-Binding Homeobox 1/genetics/metabolism ; beta Catenin/genetics/metabolism ; }, abstract = {Asbestos exposure increases the risk of asbestosis and malignant mesothelioma (MM). Both fibrosis and cancer have been correlated with the Epithelial to Mesenchymal Transition (EMT)-an event involved in fibrotic development and cancer progression. During EMT, epithelial cells acquire a mesenchymal phenotype by modulating some proteins. Different factors can induce EMT, but Transforming Growth Factor β (TGF-β) plays a crucial role in promoting EMT. In this work, we verified if EMT could be associated with MM development. We explored EMT in human mesothelial cells (MeT-5A) exposed to chrysotile asbestos: we demonstrated that asbestos induces EMT in MeT-5A cells by downregulating epithelial markers E-cadherin, β-catenin, and occludin, and contemporarily, by upregulating mesenchymal markers fibronectin, α-SMA, and vimentin, thus promoting EMT. In these cells, this mechanism is mediated by increased TGF-β secretion, which in turn downregulates E-cadherin and increases fibronectin. These events are reverted in the presence of TGF-β antibody, via a Small Mother Against Decapentaplegic (SMAD)-dependent pathway and its downstream effectors, such as Zinc finger protein SNAI1 (SNAIL-1), Twist-related protein (Twist), and Zinc Finger E-Box Binding Homeobox 1 (ZEB-1), which downregulate the E-cadherin gene. Since SNAIL-1, Twist, and ZEB-1 have been shown to be overexpressed in MM, these genes could be considered possible predictive or diagnostic markers of MM development.}, }
@article {pmid30603603, year = {2019}, author = {Shehata, M and Zaid, F and Ottaviano, P and Shweihat, Y and Munn, N}, title = {Case report: Steroid responsive mesothelioma-related pleural effusion.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {131-135}, pmid = {30603603}, issn = {2213-0071}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related tumor arising in the pleural cavity. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. The most common radiologic presentation is ipsilateral pleural effusion with or without pleural thickening or a mass. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Despite advancement in diagnostic procedures and biomolecular research, this tumor nevertheless has poor prognosis. Mesothelioma remains a diagnostic and therapeutic challenge and is likely to remain one in the years to come. Here we present the first reported case of steroid treatment responsive pleural effusion in a 72 year-old-male that initially was misdiagnosed as rheumatoid related effusion. However, Pleuroscopy with biopsy revealed mesothelioma.}, }
@article {pmid30596292, year = {2019}, author = {Ye, L and Ma, S and Robinson, BW and Creaney, J}, title = {Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {2}, pages = {181-192}, doi = {10.1080/17476348.2019.1563488}, pmid = {30596292}, issn = {1747-6356}, mesh = {*Cancer Vaccines ; Humans ; Immunologic Factors/*therapeutic use ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Precision Medicine/methods ; }, abstract = {Immunotherapy has long been considered a potential therapy for malignant mesothelioma and is currently being pursued as such. Some of the early phase clinical trials involving immunomodulators have demonstrated encouraging results and numerous clinical trials are underway to further investigate this treatment approach in various treatment settings and larger patient cohorts. Areas covered: This review summarizes the current and emerging clinical evidence for checkpoint blockade and other immunotherapeutic strategies in mesothelioma. The mesothelioma tumor immune microenvironment and mutational landscape are also discussed, including their impact on treatment strategies. We also provide an evaluation of the current evidence for neoantigen targeted personalized immunotherapy. Expert opinion: Immune checkpoint inhibitors work by unleashing the host immune response against probable neoantigens. Despite impressive activity in a small subset of patients and the potential for prolonged responses, most patients experience treatment failure. Neoantigen vaccines provide a potential complementary therapeutic strategy by increasing the immunogenic antigen load, which can lead to an increased tumor specific immune response. Further research is needed explore this treatment option in mesothelioma and technological advances are required to translate this concept into clinical practice.}, }
@article {pmid30594459, year = {2019}, author = {McGehee, E and Gerber, DE and Reisch, J and Dowell, JE}, title = {Treatment and Outcomes of Primary Pericardial Mesothelioma: A Contemporary Review of 103 Published Cases.}, journal = {Clinical lung cancer}, volume = {20}, number = {2}, pages = {e152-e157}, doi = {10.1016/j.cllc.2018.11.008}, pmid = {30594459}, issn = {1938-0690}, support = {K24 CA201543/CA/NCI NIH HHS/United States ; UL1 TR001105/TR/NCATS NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Heart Neoplasms/mortality/*therapy ; Humans ; Neoplasms, Mesothelial/mortality/*therapy ; Pemetrexed/*therapeutic use ; Pericardium ; Platinum/*therapeutic use ; Risk Factors ; Survival Analysis ; Treatment Outcome ; }, abstract = {Primary pericardial mesothelioma (PPM) is a rare cancer for which there is no consensus on treatment. We evaluated and summarized a large contemporary population of published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Using Ovid and PubMed, literature published from 2000 through 2016 was searched using the terms "primary pericardial mesothelioma," "pericardial mesothelioma," and "malignant pericardial mesothelioma." We identified 6 case series and 84 case reports for a total of 103 PPM cases published from 2000 through 2016. The median age at diagnosis was 55 years, and the median overall survival was 6 months. In univariate analyses of clinical characteristics including gender, asbestos exposure, tobacco use, prior radiation exposure, histologic subtype, and metastasis and/or mediastinal spread, only the presence of metastasis and/or mediastinal spread was a significant predictor of decreased survival (P = .015). Surgery did not provide a statistically significant survival benefit (P = .12). A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months, P = .002), specifically chemotherapy with a platinum agent with or without pemetrexed. In multivariate analysis, only the receipt of chemotherapy was associated with improved survival. PPM remains a rare and poorly understood malignancy with unclear etiology and a poor prognosis. In this retrospective systematic review, a survival benefit was seen in patients who received chemotherapy.}, }
@article {pmid30594195, year = {2018}, author = {Merlo, DF and Bruzzone, M and Bruzzi, P and Garrone, E and Puntoni, R and Maiorana, L and Ceppi, M}, title = {Mortality among workers exposed to asbestos at the shipyard of Genoa, Italy: a 55 years follow-up.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {94}, pmid = {30594195}, issn = {1476-069X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/*mortality ; *Ships ; Young Adult ; }, abstract = {BACKGROUND: Exposure to asbestos remains a global issue due to its massive use in the twentieth century and its long environmental persistence. Exposure to asbestos still occurs during dismantling of ships and vessels, buildings renovation, mining operations, and is reported in developing countries. Current estimate report exposure of hundreds of million people in occupational settings in countries where its use remains unregulated.<br><br>METHODS: We conducted a historical prospective cohort mortality study aimed at estimating mortality from specific causes, the temporal changes of pleural and lung cancer mortality, and the attributable fraction (AF) of lung cancer deaths following asbestos exposure. The study included 3984 shipyard workers employed at the shipyard of Genoa, Italy, between 1960 and 1981 and followed up to December 2014. Standardized Mortality Ratios (SMR) and their 95% confidence intervals (95%CI) were computed.<br><br>RESULTS: Overall deaths recorded were 3331 (83.6%). Excess mortality was observed for all cancers (SMR&#x2009;=&#x2009;127, 95%CI:120-134), pleural mesothelioma (575, 469-697), cancers of the larynx (183, 134-244) and of the lung (154, 139-170), and for respiratory tract diseases (127, 114-141), including asbestosis (2277, 1525-3270). Ninety out of 399 deaths (22.6%) from lung cancer were attributed to asbestos exposure. The estimated lung cancer AF was 49.3% in workers with the highest SMR for pleural cancer. Median latency times for pleural and lung cancer were 42.8&#x2009;years (minimum latency: 9.3&#x2009;years) and 38.7&#x2009;years (minimum latency: 6&#x2009;years). The peak of mesothelioma incidence, expected in Italy in the period 2015-2024, was confirmed.<br><br>CONCLUSIONS: The long follow-up period of our study allowed the detection of a substantial disease burden following asbestos exposure. These findings support the urgent need for the prevention of asbestos related diseases through the implementation of asbestos ban worldwide, including those countries where asbestos is still mined, manufactured and used.}, }
@article {pmid30567579, year = {2018}, author = {Xu, R and Barg, FK and Emmett, EA and Wiebe, DJ and Hwang, WT}, title = {Association between mesothelioma and non-occupational asbestos exposure: systematic review and meta-analysis.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {90}, pmid = {30567579}, issn = {1476-069X}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Cohort Studies ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: The risk of mesothelioma has been shown to be associated with exposure to asbestos fibers. Most of the existing literature focuses on occupational exposure; however, non-occupational asbestos exposure has also been identified as an important risk factor.<br><br>OBJECTIVE: To estimate the association between mesothelioma and non-occupational asbestos exposure, and evaluate control recruitment and exposure measurement methods.<br><br>METHODS: A systematic literature review was conducted to identify case-control (CC) and cohort studies that examined the association between mesothelioma and non-occupational exposure to asbestos, including neighborhood, domestic, and household exposure. Meta-analysis was performed to estimate a summary relative risk estimate (SRRE) and 95% confidence interval using random-effects models. Subgroup analyses were also conducted by exposure type, gender, region, and fiber type.<br><br>RESULTS: Twenty CC and 7 cohort studies were selected. Controls in CC studies were selected from the general population (55%), hospital records (18%), cancer registry (23%) and a combination of population and hospital records (5%). Multiple methods were used to measure neighborhood exposure (e.g., linear distance and direction of residence from an asbestos factory), domestic (e.g., whether living with an asbestos worker) and household exposure (e.g., whether involved in asbestos-containing home improvement projects). Primary meta-analyses suggested a SRRE of mesothelioma of 5.33 (95%CI: 2.53, 11.23) from neighborhood exposure, 4.31 (95%CI, 2.58, 7.20) from domestic exposure, and 2.41 (95%CI, 1.30, 4.48) from household exposure with large I[2] statistics ranging from 83-99%.<br><br>CONCLUSIONS: Non-occupational asbestos exposure is significantly associated with an elevated risk of mesothelioma. Funnel plots indicated a potential of publication bias. Some SRREs should be interpreted with cautions because of high between-studies heterogeneity.}, }
@article {pmid30563645, year = {2018}, author = {Rogers, AJ}, title = {Exposures estimates of the Wittenoom mining workforce and town residents - Implications associated with risk estimation for persons exposed to asbestiform riebeckite.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {168-170}, doi = {10.1016/j.taap.2018.06.032}, pmid = {30563645}, issn = {1096-0333}, mesh = {Adult ; Asbestos/analysis ; Asbestos, Crocidolite/analysis/*toxicity ; Australia/epidemiology ; Child ; Dust/analysis ; Environmental Exposure/*statistics &amp; numerical data ; Female ; Humans ; Industry ; Inhalation Exposure/*analysis ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; *Mining ; Occupational Exposure/*statistics &amp; numerical data ; Risk Assessment ; Workforce ; }, abstract = {The mining of crocidolite at Wittenoom from 1943 to 1966 is infamous due to the adverse health outcomes in the mining and milling workforce and the non-mining residents and families. Proportional latency risk analysis provided estimates that 6% of the mine workforce along with 1.9% of women and 1.1% of children residents who were environmentally exposed, have or will die from mesothelioma. The absence of environmental exposure data relevant to the period restricts the extrapolation of these historical risk outcomes being applied to the low level exposures from natural contaminant crocidolite and other amphibole fibres experienced in contemporary mining practices in the Pilbara region.}, }
@article {pmid30561515, year = {2019}, author = {Oddone, E and Terracini, B and Mirabelli, D and Mensi, C and Consonni, D and Barone-Adesi, F}, title = {Comment on: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {488-489}, doi = {10.1093/carcin/bgy179}, pmid = {30561515}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30558734, year = {2019}, author = {Kai, Y and Tsutani, Y and Ito, M and Mimura, T and Miyata, Y and Okada, M}, title = {Metachronous Lung Cancer After Pleurectomy/Decortication.}, journal = {The Annals of thoracic surgery}, volume = {107}, number = {1}, pages = {e1-e3}, doi = {10.1016/j.athoracsur.2018.05.087}, pmid = {30558734}, issn = {1552-6259}, abstract = {Pleurectomy/decortication is a surgical procedure for malignant pleural mesothelioma (MPM) and has been proposed as an alternative to extrapleural pneumonectomy. We report a second primary lung cancer developing after pleurectomy/decortication for MPM. A 59-year-old man was diagnosed with MPM on the right side and underwent pleurectomy/decortication. Follow-up computed tomography detected a nodule in the right upper lobe that was diagnosed as adenocarcinoma by wedge resection. Lung cancer and MPM are associated with asbestos exposure. However, predicting lung cancer after treatment for MPM is difficult. Careful follow-up of the spared lung is necessary for detecting second primary lung cancer or MPM recurrence.}, }
@article {pmid30557225, year = {2019}, author = {Schnatter, AR and Wojcik, NC and Jorgensen, G}, title = {Mortality Update of a Cohort of Canadian Petroleum Workers.}, journal = {Journal of occupational and environmental medicine}, volume = {61}, number = {3}, pages = {225-238}, pmid = {30557225}, issn = {1536-5948}, mesh = {Adult ; Canada/epidemiology ; Cause of Death ; *Extraction and Processing Industry ; Female ; Humans ; Lung Neoplasms/*epidemiology/*mortality ; Male ; Mesothelioma/*epidemiology/*mortality ; Mesothelioma, Malignant ; Occupational Diseases/*epidemiology/*mortality ; *Occupational Exposure ; *Petroleum ; }, abstract = {OBJECTIVE: This study updates the mortality experience of over 25,000 workers in a large Canadian petroleum company through December 31, 2006.<br><br>METHODS: Standardized mortality ratios were generated for all-cause and specific cause mortality.<br><br>RESULTS: All cause and all cancer mortality were favorable compared with the general Canadian population. Cancers of previous interest were largely consistent with expectation. There is a continuing excess of mesothelioma, which is of similar magnitude as the previous update, although based on larger numbers. This excess is mostly attributable to men who died in their 50s and 60s and who worked in the refining sector.<br><br>CONCLUSION: Most causes of death show mortality rates lower than the Canadian general population. Given the excess of mesothelioma observed, this study supports ongoing vigilance in asbestos exposure control programs, as refineries continue to remove asbestos from their facilities.}, }
@article {pmid30545133, year = {2018}, author = {Wörthmüller, J and Oberson, A and Salicio, V and Blum, W and Schwaller, B}, title = {Calretinin Functions in Malignant Mesothelioma Cells Cannot Be Replaced by the Closely Related Ca[2+]-Binding Proteins Calbindin-D28k and Parvalbumin.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30545133}, issn = {1422-0067}, support = {130680, 139226, 147697/1//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; }, mesh = {Calbindin 1/*metabolism ; Calbindin 2/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Clone Cells ; Down-Regulation ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Focal Adhesions/metabolism ; Green Fluorescent Proteins/metabolism ; Humans ; Lentivirus/metabolism ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Parvalbumins/*metabolism ; Phenotype ; }, abstract = {Calretinin (CR; CALB2) belonging to the family of EF-hand Ca[2+]-binding proteins (CaBP) is widely used as a positive marker for the identification of human malignant mesothelioma (MM) and functionally was suggested to play a critical role during carcinogenesis of this highly aggressive asbestos-associated neoplasm. Increasing evidence suggests that CR not only acts as a prototypical Ca[2+] buffer protein, i.e., limiting the amplitude of Ca[2+] signals but also as a Ca[2+] sensor. No studies have yet investigated whether other closely related CaBPs might serve as substitutes for CR's functions(s) in MM cells. Genetically modified MM cell lines with medium (MSTO-211H and ZL5) or low (SPC111) endogenous CR expression levels were generated that overexpress either CR's closest homologue calbindin-D28k (CB) or parvalbumin (PV), the latter considered as a "pure" Ca[2+] buffer protein. After lentiviral shCALB2-mediated CR downregulation, in both MSTO-211H and ZL5 cells expressing CB or PV, the CR deficiency-mediated increase in cell death was not prevented by CB or PV. With respect to proliferation and cell morphology of SPC111 cells, CB was able to substitute for CR, but not for CR's other functions to promote cell migration or invasion. In conclusion, CR has a likely unique role in MM that cannot be substituted by "similar" CaBPs.}, }
@article {pmid30534997, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Reply to letters to the editor by Brentisci et al. and Consonni and Mensi.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {341}, doi = {10.1093/annonc/mdy523}, pmid = {30534997}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30533375, year = {2019}, author = {Yamazoe, M and Tomioka, H and Kamada, T and Kaneko, M and Katsuyama, E}, title = {Simultaneous presence of lung adenocarcinoma and malignant pleural mesothelioma: A case report.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {45-49}, pmid = {30533375}, issn = {2213-0071}, abstract = {The co-presence of malignant pleural mesothelioma (MPM) and lung cancer is rare. We report a 70-year-old male with exposure to asbestos. Chest computed tomography revealed a right mediastinal mass combined with an enlarged ipsilateral lymph node and left pleural effusion. Transbronchial lung biopsy revealed lung adenocarcinoma. Thoracoscopic examination revealed multiple left pleural nodules, leading to the diagnosis of MPM. Despite aggressive anticancer drug therapy, he expired due to disease progression 2.5 years after diagnosis. Autopsy confirmed an epithelioid MPM in the left pleura. MPM comorbidity in patients diagnosed with lung cancer should be considered, especially in those exposed to asbestos.}, }
@article {pmid30530573, year = {2018}, author = {Lee, LJ and Lin, CK and Pan, CH and Cheng, Y and Chang, YY and Liou, SH and Wang, JD}, title = {Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.}, journal = {BMJ open}, volume = {8}, number = {12}, pages = {e021063}, pmid = {30530573}, issn = {2044-6055}, mesh = {Asbestos/*adverse effects ; Cluster Analysis ; Cohort Studies ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Manufacturing and Industrial Facilities/*statistics &amp; numerical data ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; Risk ; Taiwan ; }, abstract = {OBJECTIVE: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.<br><br>METHODS: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years.<br><br>RESULTS: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency &#x2265;30 years, and the shipbuilding industry presented a significant eRR given a latency &#x2265;40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed.<br><br>CONCLUSIONS: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.}, }
@article {pmid30527173, year = {2018}, author = {Serio, G and Vimercati, L and Pennella, A and Gentile, M and Cavone, D and Buonadonna, AL and Scattone, A and Fortarezza, F and De Palma, A and Marzullo, A}, title = {Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {126}, number = {}, pages = {106-111}, doi = {10.1016/j.lungcan.2018.10.012}, pmid = {30527173}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Comparative Genomic Hybridization ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; *Mutation ; Ubiquitin-Conjugating Enzymes/genetics ; }, abstract = {INTRODUCTION: Malignant mesothelioma is an aggressive malignancy of the thoracic cavity caused by prior asbestos exposure. In the peritoneum the mesothelioma is an extremely rare condition. In the present preliminary study, high-resolution array-comparative genomic hybridization (a-CGH) was performed to identify genetic imbalances in a series of malignant peritoneal mesothelioma cases.<br><br>MATERIALS AND METHODS: Between 1990 and 2008, among the cases recorded in the Apulia Mesothelioma Register, we found 22 peritoneal mesothelioma cases. CGH-array was performed on samples from all patients.<br><br>RESULTS: The CGH-array analysis revealed multiple chromosomal imbalances. Interestingly, deletion at 8p23.1 was observed in 12 cases. Furthermore, another novel deletion at 1q21 was present in 11. Often, 1q21 and 8p23.1 losses were present in the same patient (7 cases). Losses of BAP1 and CDKN2A loci were not detected.<br><br>DISCUSSION: The region at 8p23.1 contains the beta-defensin gene cluster (DEF) and 1q21 contains ubiquitin conjugating enzyme E2 (UBE2Q1). We hypotesized that the loss of function of ubiquitination, as well as of the defensins, could play an important role in the initial development and subsequent progression of mesothelioma.}, }
@article {pmid30518402, year = {2018}, author = {Chee, J and Watson, MW and Chopra, A and Nguyen, B and Cook, AM and Creaney, J and Lesterhuis, WJ and Robinson, BW and Lee, YCG and Nowak, AK and Lake, RA and McDonnell, AM}, title = {Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {864}, pmid = {30518402}, issn = {1756-0500}, support = {CA150787//U.S. Department of Defense/ ; }, mesh = {Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/blood/*immunology ; Mesothelioma/blood/*immunology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Effusion/blood/*immunology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Cell Surface/*metabolism ; T-Lymphocytes/*immunology ; }, abstract = {OBJECTIVE: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.<br><br>RESULTS: Both CD8[+] and CD4[+] T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1[+]) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.}, }
@article {pmid30506035, year = {2018}, author = {Okita, R and Nojima, Y and Saisho, S and Shimizu, K and Shirai, R and Kanomata, N and Oka, M and Nakata, M}, title = {Deciduoid type malignant pleural mesothelioma: a case report.}, journal = {AME case reports}, volume = {2}, number = {}, pages = {43}, pmid = {30506035}, issn = {2523-1995}, abstract = {Here, we report a patient with deciduoid type malignant pleural mesothelioma (MPM), which rapidly progressed. A 55-year-old man who might have been exposed to asbestos a few decades ago had severe back pain. The chest X-ray scanning and computed tomography (CT) revealed pleural thickness on his right thoracic space, without the presence of a lung mass. A pleural biopsy was performed and the patient was histologically diagnosed with deciduoid type MPM. Although he received two cycles of chemotherapy, his disease rapidly progressed and he died within two months of the diagnosis of deciduoid type MPM.}, }
@article {pmid30501113, year = {2018}, author = {Izquierdo-Sánchez, V and Muñiz-Hernández, S and Vázquez-Becerra, H and Pacheco-Yepez, J and Romero-Piña, ME and Arrieta, O and Medina, LA}, title = {Biodistribution and Tumor Uptake of [67]Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {12}, pages = {}, pmid = {30501113}, issn = {1420-3049}, support = {PAPIIT IN-225014, IN209916//Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; 154557//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; (017/027/IBI)(CEI/1147/17)//Instituto Nacional de Cancerolog&#xed;a/ ; }, mesh = {Animals ; Antibodies, Monoclonal, Humanized/*pharmacokinetics ; Cell Line, Tumor ; Fluorodeoxyglucose F18/chemistry ; Gallium Radioisotopes/*pharmacokinetics ; Humans ; Imaging, Three-Dimensional ; Liver/metabolism ; Lung Neoplasms/diagnostic imaging/*metabolism ; Male ; Mesothelioma/diagnostic imaging/*metabolism ; Mesothelioma, Malignant ; Mice, Nude ; Pleural Neoplasms/diagnostic imaging/*metabolism ; Positron Emission Tomography Computed Tomography ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with [67]Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.}, }
@article {pmid30513236, year = {2022}, author = {Till, JE and Beck, HL and Boice, JD and Mohler, HJ and Mumma, MT and Aanenson, JW and Grogan, HA}, title = {Asbestos exposure and mesothelioma mortality among atomic veterans.}, journal = {International journal of radiation biology}, volume = {98}, number = {4}, pages = {781-785}, doi = {10.1080/09553002.2018.1551641}, pmid = {30513236}, issn = {1362-3095}, support = {U01 CA137026/CA/NCI NIH HHS/United States ; }, mesh = {*Asbestos/adverse effects ; Cohort Studies ; Humans ; *Lung Neoplasms/etiology ; Male ; *Mesothelioma/complications ; *Occupational Diseases/etiology ; *Occupational Exposure/adverse effects ; *Veterans ; }, abstract = {BACKGROUND: The United States (U.S.) conducted 230 above-ground atmospheric nuclear weapons tests between 1945 and 1962 involving over 250,000 military personnel. This is the first quantitative assessment of asbestos-related mesothelioma, including cancers of the pleura and peritoneum, among military personnel who participated in above-ground nuclear weapons testing.<br><br>METHODS: Approximately 114,000 atomic veterans were selected for an epidemiological study because they were in one of eight series of weapons tests that were associated with somewhat higher personnel exposures than the other tests and because they have been previously studied. We were able to categorize specific jobs into potential for asbestos exposure based on a detailed database of the military activities of the atomic veterans. Standardized mortality ratios (SMR) were calculated by service, rank (officer/enlisted) and ratings (occupation code and work location aboard ship) after 65 years of follow-up.<br><br>RESULTS: Mesothelioma deaths were significantly increased overall (SMR 1.56; 95% CI 1.32-1.82; n&#x2009;=&#x2009;153). This increase was seen only among those serving in the PPG (SMR 1.97; 95% CI 1.65-2.34; n&#x2009;=&#x2009;134), enlisted men (SMR 1.81; 95% CI 1.53-2.13; n&#x2009;=&#x2009;145), and the 70,309 navy personnel (SMR 2.15; 95% CI 1.80-2.56; n&#x2009;=&#x2009;130). No increased mortality rates were seen among the other services: army (SMR 0.45), air force (SMR 0.85), or marines (SMR 0.75). Job categories with the highest potential for asbestos exposure (machinist's mates, boiler technicians, water tender, pipe fitters, and fireman) had an of SMR 6.47. Job categories with lower potential (SMR =1.35) or no potential (SMR =1.28) for asbestos exposure had non-significantly elevated mesothelioma mortality.<br><br>CONCLUSIONS: The large excess of mesothelioma deaths seen among atomic veterans was explained by asbestos exposure among enlisted naval personnel. The sources of exposure were determined to be on navy ships in areas (or with materials) with known asbestos content. No excess of mesothelioma was observed in other services or among naval personnel with minimal exposure to asbestos in this low-dose radiation exposed cohort.}, }
@article {pmid30500290, year = {2019}, author = {Regragui, M and Guebessi, NB}, title = {Primary Malignant Deciduoid Mesothelioma: A Challenging Diagnosis.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {143}, number = {4}, pages = {531-533}, doi = {10.5858/arpa.2017-0461-RS}, pmid = {30500290}, issn = {1543-2165}, mesh = {Decidua/*pathology ; Female ; Humans ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*pathology ; }, abstract = {Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.}, }
@article {pmid30489434, year = {2019}, author = {Dournes, G and Dubois, A and Benlala, I and Lacourt, A and Paris, C and Gislard, A and Clin, B and Pairon, JC and Baldacci, F and Laurent, F}, title = {3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography: A Validation Study.}, journal = {Journal of thoracic imaging}, volume = {34}, number = {5}, pages = {320-325}, doi = {10.1097/RTI.0000000000000377}, pmid = {30489434}, issn = {1536-0237}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Imaging, Three-Dimensional/*methods ; Male ; Plaque, Atherosclerotic/*diagnostic imaging ; Pleural Diseases/*chemically induced/*diagnostic imaging ; Reproducibility of Results ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {RATIONALE: As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos.<br><br>MATERIAL AND METHODS: A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the &#x3ba; test.<br><br>RESULTS: Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7&#x2009;cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with &#x3ba; values ranging from 0.30 to 0.60.<br><br>CONCLUSIONS: 3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.}, }
@article {pmid30479777, year = {2018}, author = {Park, S and Park, J and Lee, E and Eom, H and Shin, MY and Kim, J and Kang, D and Lee, S}, title = {Ovarian cancer in a former asbestos textile factory worker: a case report.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {65}, pmid = {30479777}, issn = {2052-4374}, abstract = {BACKGROUND: The International Agency for Research on Cancer (IARC) defined that asbestos is a group 1 substance that causes lung cancer, mesothelioma (pleura and peritoneum), laryngeal cancer, and ovarian cancer in humans. Many studies on lung cancer, and mesothelioma caused by asbestos exposure have been conducted, but there was no case report of ovarian cancer due to asbestos exposure in Korea. We describe a case of ovarian cancer caused by asbestos exposure in a worker who worked at an asbestos textile factory for 3 years and 7 months in the late 1970s.<br><br>CASE PRESENTATION: A 57-year-old woman visited the hospital because she had difficulty urinating. Ovarian cancer was suspected in radiologic examination, and exploratory laparotomy was performed. She was diagnosed with epithelial ovarian cancer. The patient did not undergo postoperative chemotherapy and recovered. She joined the asbestos factory in March 1976 and engaged in asbestos textile twisting and spinning for 1&#xa0;year, 2&#xa0;years and 7&#xa0;months respectively. In addition, she lived near the asbestos factory for more than 20&#xa0;years. There was no other specificity or family history.<br><br>CONCLUSION: Considering the patient's occupational and environmental history, it is estimated that she had been exposed to asbestos significantly, so we determined that ovarian cancer in the patient is highly correlated with the occupational exposure of asbestos and environmental exposure is a possible cause as well. Social devices are needed to prevent further exposure to asbestos. It is also necessary to recognize that ovarian cancer can occur in workers who have previously been exposed to asbestos, and the education and social compensation for those workers are needed.}, }
@article {pmid30479770, year = {2019}, author = {Tlotleng, N and Sidwell Wilson, K and Naicker, N and Koegelenberg, CF and Rees, D and Phillips, JI}, title = {The significance of non-occupational asbestos exposure in women with mesothelioma.}, journal = {Respirology case reports}, volume = {7}, number = {1}, pages = {e00386}, pmid = {30479770}, issn = {2051-3380}, abstract = {Malignant mesothelioma is a rare and aggressive pleural or peritoneal tumour almost always caused by exposure to asbestos fibres. Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure. A description of sources of exposure is important for prevention and possible financial compensation. Three women with cases of histologically confirmed malignant mesothelioma diagnosed from non-occupational asbestos exposure are described. Patients were contacted for an interview to assess their exposure history to asbestos. All three cases had mixed exposure histories related to secondary, environmental contamination, and domestic exposure. This case series highlight how ubiquitous asbestos is in the environment and how diverse the exposures may be. It is anticipated that a significant number of cases of non-occupational mesothelioma will be seen in many countries for several decades given the extent of asbestos containing materials.}, }
@article {pmid30475941, year = {2019}, author = {Consonni, D and Mensi, C}, title = {Comment on the paper 'Boffetta et al. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy. Ann Oncol 2018; 29(2): 484-489'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {340-341}, doi = {10.1093/annonc/mdy521}, pmid = {30475941}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30455474, year = {2018}, author = {Affar, EB and Carbone, M}, title = {BAP1 regulates different mechanisms of cell death.}, journal = {Cell death &amp; disease}, volume = {9}, number = {12}, pages = {1151}, pmid = {30455474}, issn = {2041-4889}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; 399244//CIHR/Canada ; }, mesh = {*Apoptosis ; Cell Death ; Humans ; *Neoplasms ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30451473, year = {2018}, author = {Krówczyńska, M and Wilk, E and Pabjanek, P and Olędzka, G}, title = {Pleural mesothelioma in Poland: Spatial analysis of malignant mesothelioma prevalence in the period 1999-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.667}, pmid = {30451473}, issn = {1970-7096}, mesh = {Air Pollutants/analysis ; Asbestos/*analysis ; Female ; Humans ; Incidence ; Inhalation Exposure/analysis ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Pleural Neoplasms/*chemically induced/*epidemiology ; Poland/epidemiology ; Prevalence ; Spatial Analysis ; }, abstract = {Malignant mesothelioma (MM), a rare and very deadly tumour, can be due to asbestos exposure. To better understand the cause of incidence of MM, spatial autocorrelation analysis with reference to the quantity of asbestos-cement products in use and the localisation of former asbestos manufacturing plants was applied. Geostatistical analysis shows that strong spatial clustering of MM incidence (referring to the general population as well as females and males separately) during the period 1999-2013 in the administrative units of Poland (provinces and counties). Incidence hotspots were found to be concentrated primarily in southern Poland but also seen in the county of Szczecin, which stands out in local autocorrelation analysis in north-western Poland. High incidence rates were discovered, in particular with reference to counties around former plants manufacturing asbestos-containing products, mainly asbestos-cement manufacturers. The highest frequency of MM incidence rate was found in within a 55 km radius of plants in or near the towns Trzebinia, Ogrodzieniec and Szczucin in the South, where asbestos-cement products had been manufactured for close to 40 years. Areas with significantly high incidence rates were also discovered in the provinces of Śląskie, Małopolskie and Świętokrzyskie in southern Poland.}, }
@article {pmid30451463, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Spatial analysis of asbestos exposure and occupational health care in Poland during the period 2004-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.689}, pmid = {30451463}, issn = {1970-7096}, mesh = {Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/*adverse effects/analysis ; Asbestosis/epidemiology ; Humans ; Inhalation Exposure/adverse effects/*analysis ; Lung Neoplasms/chemically induced/epidemiology ; Manufacturing Industry ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers ; Occupational Exposure/adverse effects/*analysis ; Occupational Health/*statistics &amp; numerical data ; Poland/epidemiology ; Smoking/epidemiology ; *Spatial Analysis ; Time Factors ; }, abstract = {Asbestos is carcinogenic to humans and exposure to this substance can cause a wide range of diseases. In Poland 1997, a statutory ban was introduced on the production, use and marketing of products containing asbestos. The National Programme for Asbestos Abatement for 2009-2032 includes scheduled activities considering asbestos exposure assessment and health protection. As there are several data sources for asbestos exposure in Poland, which are not linked, the aim of this study was to gather and order them developing a PostgreSQL database, an open-source, objectrelational system. The data gathered combines the following information: the quantity of asbestos-cement products in use, details of asbestos manufacturing plants, the results of the measurements of asbestos fibre concentrations in the air and cases of asbestos-related diseases. The relational database was then used to develop a spatial analysis of asbestos monitoring and exposure in Poland to demonstrate the current state of realisation of the National Asbestos Abatement Programme in the country for 2009-2032 with the use of geoinformation techniques. The use of a database on health aspects of occupational and environmental asbestos exposure was also proposed in Asbestos, Asbestosis, and Cancer: Helsinki Criteria update 2014.}, }
@article {pmid30450291, year = {2018}, author = {Broeckx, G and Pauwels, P}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {537-542}, pmid = {30450291}, issn = {2218-6751}, abstract = {Malignant peritoneal mesothelioma (MPM) is a very rare malignancy of the peritoneum and has a poor prognosis. Of all mesotheliomas, pleural mesothelioma is more common than MPM. In comparison to pleural mesothelioma, the link with asbestos exposure is weaker (33-50% vs. >80%), but it is still the best-defined risk factor. MPM spreads predominantly expansive rather than infiltrative and symptoms are related to tumor spread within the abdominal cavity. Often, MPM is encountered incidentally by diagnostic imaging or by surgery. Computed tomography scan is widely accepted as a first line modality in diagnostic imaging. In diagnostic histopathology, MPM presents some challenges. Firstly, adequate clinical information is of utmost importance to consider the possibility of the diagnosis of MPM. Furthermore, a few morphological subtypes and variants exist. The most sensitive immunohistochemical markers are calretinin (100%), WT1 (94%) and CK5/6 (89%). The malignant character of immunohistochemically demonstrated mesothelial cells is not always obvious. This paradigm somewhat changed with the advent of immunohistochemical demonstration of BAP1 (BRCA-1 associated protein 1). Loss of BAP1 expression supports a diagnosis of malignancy. The gold standard in treatment remains cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Targetable molecular pathways in MPM are being identified. An exciting finding was the demonstration of ALK rearrangements in a small subset of patients with MPM and it is hoped for that at least this small subgroup of patients could benefit from treatment with ALK inhibitors. First-generation tyrosine kinase inhibitors against epidermal growth factor receptor (EGFR) did not show any significant activity in MPM. In contrast, nintedanib, an angiokinase inhibitor, improved progression-free survival and bevacizumab, a humanized anti-VEGF antibody increased overall survival in patients with MPM, when administered in combination with cisplatin and pemetrexed. Ongoing immunotherapy trials will offer a possible new treatment.}, }
@article {pmid30450290, year = {2018}, author = {Brusselmans, L and Arnouts, L and Millevert, C and Vandersnickt, J and van Meerbeeck, JP and Lamote, K}, title = {Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {520-536}, pmid = {30450290}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour related to a historical exposure to asbestos fibres. Currently, the definite diagnosis is made only by the histological examination of a biopsy obtained through an invasive thoracoscopy. However, diagnosis is made too late for curative treatment because of non-specific symptoms mainly appearing at advanced stage disease. Hence, due to its biologic aggressiveness and the late diagnosis, survival rate is low and the patients' outcome poor. In addition, radiological imaging, like computed tomographic scans, and blood biomarkers are found not to be sensitive enough to be used as an early diagnostic tool. Detection in an early stage is assumed to improve the patients' outcome but is hampered due to non-specific and late symptomology. Hence, there is a need for a new screening and diagnostic test which could improve the patients' outcome. Despite extensive research has focused on blood biomarkers, not a single has been shown clinically useful, and therefore research recently shifted to "breathomics" techniques to recognize specific volatile organic compounds (VOCs) in the breath of the patient as potential non-invasive biomarkers for disease. In this review, we summarize the acquired knowledge about using breath analysis for diagnosing and monitoring MPM and asbestos-related disorders (ARD). Gas chromatography-mass spectrometry (GC-MS), the gold standard of breath analysis, appears to be the method with the highest accuracy (97%) to differentiate MPM patients from at risk asbestos-exposed subjects. There have already been found some interesting biomarkers that are significantly elevated in asbestosis (NO, 8-isoprostane, leukotriene B4, α-Pinene…) and MPM (cyclohexane) patients. Regrettably, the different techniques and the plethora of studies suffer some limitations. Most studies are pilot studies with the inclusion of a limited number of patients. Nevertheless, given the promising results and easy sampling methods, we can conclude that breath analysis may become a useful tool in the future to screen for MPM, but further research is warranted.}, }
@article {pmid30450289, year = {2018}, author = {Nuyts, V and Nawrot, T and Nemery, B and Nackaerts, K}, title = {Hotspots of malignant pleural mesothelioma in Western Europe.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {516-519}, pmid = {30450289}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma, a highly invasive tumour, has been epidemiologically linked to an occupational or environmental exposure to asbestos. Although asbestos has been widely used in diverse industrial applications and in construction, some industrial sectors have been affected much more than others. The objective of this review was to describe the existence of clusters of malignant pleural mesothelioma in Western European countries, based on epidemiological studies published between 2000 and 2015. MEDLINE (PubMed) and Embase were searched for relevant studies on spatial clustering of mesothelioma in Western European countries. Eventually, 16 different studies published between 2000 and 2015 were selected for a comprehensive analysis. Relevant studies on spatial clustering of mesothelioma were found for Belgium, the Netherlands, the United Kingdom, Germany, France, Spain, Italy and Denmark. Clustering of pleural mesothelioma was found mainly around shipyards (16 studies) and asbestos cement industries (10 studies). Although malignant pleural mesothelioma may be found throughout Western Europe, the present study indicates specific areas with higher past and also probable future incidence.}, }
@article {pmid30446780, year = {2018}, author = {Feder, IS and Jülich, M and Tannapfel, A and Tischoff, I}, title = {[The German Mesothelioma Register : Current pathological diagnostics and services].}, journal = {Der Pathologe}, volume = {39}, number = {Suppl 2}, pages = {241-246}, pmid = {30446780}, issn = {1432-1963}, mesh = {*Asbestos ; Germany ; Humans ; Lung ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {BACKGROUND: In Germany, asbestos-related diseases (asbestosis, lung cancer, mesothelioma) are recognised and compensated occupational diseases. The histologic diagnosis of mesothelioma is sometimes a challenge; additional immunohistochemical and molecular methods are needed. With lung dust analysis, the current asbestos fibre burden of the lung is measured (biomonitoring). Identification of grade I asbestosis (minimal asbestosis) requires directed histological examinations with up to 400-fold magnification, additional iron staining and possibly in connection with a lung dust analysis.<br><br>OBJECTIVES: Demonstration of current pathologic diagnostics in association with mesothelioma and lung dust analysis.<br><br>MATERIALS AND METHODS: Analysis of routine data from the German Mesothelioma Register.<br><br>RESULTS: Contrary to reactive mesothelial hyperplasia, malignant mesotheliomas have a&#xa0;nuclear BAP1 loss-of-expression in up to 66% of cases. For differential diagnosis between reactive versus malignant, a&#xa0;p16-FISH test may be helpful. BAP1 loss-of-expression and p16-deletion are independent markers. Evaluation of the dataset of the German Mesothelioma Register of patients with repeated tissue sampling proves the detection of asbestos fibres at the same level even after 40&#xa0;years. The asbestos fibre burden in the human lung remains stable over this long period of time. In the electron microscopic analysis, white asbestos was predominantly found.<br><br>CONCLUSIONS: The well-known and industrially appreciated characteristics of asbestos fibres (in ancient &#x1f04;&#x3c3;&#x3b2;&#x3b5;&#x3c3;&#x3c4;&#x3bf;&#x3c2; asbestos "imperishable") as biopersistent have also been experimentally confirmed in human lungs.}, }
@article {pmid30426024, year = {2018}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Otsuki, T}, title = {Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8[+] T Cell Line following Long-Term Exposure to Asbestos Fibers.}, journal = {Journal of immunology research}, volume = {2018}, number = {}, pages = {4391731}, pmid = {30426024}, issn = {2314-7156}, mesh = {Asbestos/adverse effects ; Asbestos, Serpentine/adverse effects ; CD8-Positive T-Lymphocytes/*immunology ; Cell Degranulation ; Cell Line ; Environmental Exposure/adverse effects ; Granzymes/metabolism ; Humans ; Interferon-gamma/*metabolism ; Lung Neoplasms/immunology/*metabolism ; Lymphocyte Activation ; Mesothelioma/immunology/*metabolism ; Mesothelioma, Malignant ; Perforin/*metabolism ; }, abstract = {Although the tumorigenicity of asbestos, which is thought to cause mesothelioma, has been clarified, its effect on antitumor immunity requires further investigation. We previously reported a decrease in the percentage of perforin[+] cells of stimulated CD8[+] lymphocytes derived from patients with malignant mesothelioma. Therefore, we examined the effects of long-term exposure to asbestos on CD8[+] T cell functions by comparing long-term cultures of the human CD8[+] T cell line EBT-8 with and without exposure to chrysotile (CH) asbestos as an in vitro model. Exposure to CH asbestos at 5 μg/ml or 30 μg/ml did not result in a decrease in intracellular granzyme B in EBT-8 cells. In contrast, the percentage of perforin[+] cells decreased at both doses of CH exposure. CH exposure at 30 μg/ml did not suppress degranulation following stimulation with antibodies to CD3. Secreted production of IFN-γ stimulated via CD3 decreased by CH exposure at 30 μg/ml, although the percentage of IFN-γ [+] cells induced by PMA/ionomycin did not decrease. These results indicate that long-term exposure to asbestos can potentially suppress perforin levels and the production of IFN-γ in human CD8[+] T cells.}, }
@article {pmid30417819, year = {2018}, author = {Røe, OD}, title = {[Asbestos and mesothelioma in Denmark 2017: status of a man-made cancer epidemic].}, journal = {Ugeskrift for laeger}, volume = {180}, number = {46}, pages = {}, pmid = {30417819}, issn = {1603-6824}, mesh = {*Asbestos/adverse effects ; Denmark/epidemiology ; Humans ; *Lung Neoplasms ; *Mesothelioma/epidemiology ; *Pleural Neoplasms/epidemiology ; Risk Factors ; }, abstract = {Asbestos-induced cancer is an increasing problem in Denmark, and 32 years after the closure of the Danish Eternit Factory in Aalborg there are > 140 new mesothelioma cases diagnosed yearly, numbers rapidly increasing. Asbestos-induced lung cancer may be six times this number. The non-occupational exposure and even neighborhood exposure as a risk factor suggests, that compensation for mesothelioma should be universal. At the Aalborg University Hospital a multidisciplinary research team has been formed to do epidemiological, translational and clinical studies through national and international collaborations. Transformative research on asbestos cancer should be stimulated.}, }
@article {pmid30410726, year = {2018}, author = {Berzenji, L and Van Schil, P}, title = {Multimodality treatment of malignant pleural mesothelioma.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {}, pmid = {30410726}, issn = {2046-1402}, mesh = {Animals ; Combined Modality Therapy/*methods/standards/trends ; Humans ; Lung Neoplasms/mortality/*therapy ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; Pleura/pathology ; Rare Diseases/therapy ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.}, }
@article {pmid30408567, year = {2019}, author = {Guarrera, S and Viberti, C and Cugliari, G and Allione, A and Casalone, E and Betti, M and Ferrante, D and Aspesi, A and Casadio, C and Grosso, F and Libener, R and Piccolini, E and Mirabelli, D and Dianzani, I and Magnani, C and Matullo, G}, title = {Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {3}, pages = {527-539}, doi = {10.1016/j.jtho.2018.10.163}, pmid = {30408567}, issn = {1556-1380}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/blood/*genetics ; Carcinogens/toxicity ; Case-Control Studies ; DNA/*blood/chemistry/genetics ; *DNA Methylation ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/blood/*diagnosis/etiology/pathology ; Male ; Mesothelioma/blood/*diagnosis/etiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/blood/*diagnosis/etiology/pathology ; Prognosis ; ROC Curve ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people.<br><br>METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas.<br><br>RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or&#xa0;excluding methylation, showed a significant increase in&#xa0;case/control discrimination when considering DNA methylation together with asbestos exposure (AUC&#xa0;= 0.81 versus AUC&#xa0;= 0.89, DeLong's test p&#xa0;= 0.0013).<br><br>CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the&#xa0;rationale to&#xa0;further investigate, in prospective studies, the potential use&#xa0;of blood DNA methylation profiles for the identification of&#xa0;early changes related to the MPM carcinogenic process.}, }
@article {pmid30401981, year = {2019}, author = {Matsushita, A and Sato, T and Mukai, S and Fujishita, T and Mishiro-Sato, E and Okuda, M and Aoki, M and Hasegawa, Y and Sekido, Y}, title = {TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.}, journal = {Oncogene}, volume = {38}, number = {11}, pages = {1966-1978}, pmid = {30401981}, issn = {1476-5594}, support = {25090053//Japan Society for the Promotion of Science (JSPS)/International ; 16H04706//Japan Society for the Promotion of Science (JSPS)/International ; 17K19628//Japan Society for the Promotion of Science (JSPS)/International ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; Cytokines/*genetics/metabolism ; Epithelium/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Hippo Signaling Pathway ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics/metabolism ; Lung Neoplasms/*genetics/metabolism/pathology ; Mesothelioma/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; Protein Serine-Threonine Kinases/*genetics/metabolism ; Signal Transduction/genetics ; Trans-Activators ; Transcription Factors/*genetics/metabolism ; Transcriptional Activation ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; }, abstract = {Malignant mesothelioma (MM) constitutes a very aggressive tumor that is caused by asbestos exposure after long latency. The NF2 tumor suppressor gene is mutated in 40-50% of MM; moreover, one of its downstream signaling cascades, the Hippo signaling pathway, is also frequently inactivated in MM cells. Although the YAP transcriptional coactivator, which is regulated by the Hippo pathway, can function as a pro-oncogenic protein, the role of TAZ, a paralog of YAP, in MM cells has not yet been clarified. Here, we show that TAZ is expressed and underphosphorylated (activated) in the majority of MM cells compared to immortalized mesothelial cells. ShRNA-mediated TAZ knockdown highly suppressed cell proliferation, anchorage-independent growth, cell motility, and invasion in MM cells harboring activated TAZ. Conversely, transduction of an activated form of TAZ in immortalized mesothelial cells enhanced these in vitro phenotypes and conferred tumorigenicity in vivo. Microarray analysis determined that activated TAZ most significantly enhanced the transcription of genes related to "cytokine-cytokine receptor interaction." Among selected cytokines, we found that IL-1 signaling activation plays a major role in proliferation in TAZ-activated MM cells. Both IL1B knockdown and an IL-1 receptor antagonist significantly suppressed malignant phenotypes of immortalized mesothelial cells and MM cells with activated TAZ. Overall, these results indicate an oncogenic role for TAZ in MMs via transcriptional induction of distinct pro-oncogenic genes including cytokines. Among these, IL-1 signaling appears as one of the most important cascades, thus potentially serving as a target pathway in MM cells harboring Hippo pathway inactivation.}, }
@article {pmid30376426, year = {2018}, author = {Pastorino, S and Yoshikawa, Y and Pass, HI and Emi, M and Nasu, M and Pagano, I and Takinishi, Y and Yamamoto, R and Minaai, M and Hashimoto-Tamaoki, T and Ohmuraya, M and Goto, K and Goparaju, C and Sarin, KY and Tanji, M and Bononi, A and Napolitano, A and Gaudino, G and Hesdorffer, M and Yang, H and Carbone, M}, title = {A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {36}, number = {35}, pages = {JCO2018790352}, pmid = {30376426}, issn = {1527-7755}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA111295/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: We hypothesized that four criteria could help identify malignant mesotheliomas (MMs) most likely linked to germline mutations of BAP1 or of other genes: family history of MM, BAP1-associated cancers, or multiple malignancies; or age younger than 50 years.<br><br>PATIENTS AND METHODS: Over the course of 7 years, 79 patients with MM met the four criteria; 22 of the 79 (28%) reported possible asbestos exposure. They were screened for germline BAP1 mutations by Sanger sequencing and by targeted next-generation sequencing (tNGS) for germline mutations in 55 additional cancer-linked genes. Deleterious mutations detected by tNGS were validated by Sanger sequencing.<br><br>RESULTS: Of the 79 patients, 43 (16 probands and 27 relatives) had deleterious germline BAP1 mutations. The median age at diagnosis was 54 years and median survival was 5 years. Among the remaining 36 patients with no BAP1 mutation, median age at diagnosis was 45 years, median survival was 9 years, and 12 had deleterious mutations of additional genes linked to cancer. When compared with patients with MMs in the SEER cohort, median age at diagnosis (72 years), median survival for all MM stages (8 months), and stage I (11 months) were significantly different from the 79 patients with MM in the current study (P < .0001).<br><br>CONCLUSION: We provide criteria that help identify a subset of patients with MM who had significantly improved survival. Most of these patients were not aware of asbestos exposure and carried either pathogenic germline mutations of BAP1 or of additional genes linked to cancer, some of which may have targeted-therapy options. These patients and their relatives are susceptible to development of additional cancers; therefore, genetic counseling and cancer screening should be considered.}, }
@article {pmid30375909, year = {2019}, author = {Laaksonen, S and Ilonen, I and Kuosma, E and Sutinen, E and Wolff, H and Vehmas, T and Husgafvel-Pursiainen, K and Salo, JA and Koli, K and Räsänen, J and Myllärniemi, M}, title = {Malignant pleural mesothelioma in Finland: regional and gender variation.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {58}, number = {1}, pages = {38-44}, doi = {10.1080/0284186X.2018.1532599}, pmid = {30375909}, issn = {1651-226X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Finland/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Distribution ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare occupational cancer with a poor prognosis. Even with a multimodality treatment approach, the treatment outcomes remain unsatisfactory. The use of asbestos has been banned in most developed countries, but MPM continues to be a significant occupational disease also in these countries. Aim of this study is to identify modern epidemiology and assess equality in care.<br><br>METHODS: Our study cohort consists of 1010 patients diagnosed with MPM in Finland during 2000-2012. The data were collected from the Finnish Cancer Registry, the National Workers' Compensation Center Registry and the National Registry of Causes of Death, Statistics Finland.<br><br>RESULTS: Women were diagnosed a mean of 4.5 years later than males (p&#x2009;=&#x2009;.001), but survival did not differ (overall median survival 9.7 months). A workers' compensation claim was more common in males (OR 11.0 [95% CI 7.5-16.2]) and in regions with a major asbestos industry (OR 1.7 [95% CI 1.3-2.2]). One-year and three-year survivals did not differ regionally. Patients without chemotherapy treatment had an inferior survival (RR 1.8 [95% CI 1.5-2.0]). The initial survival benefit gained with pemetrexed was diluted at 51 months.<br><br>CONCLUSIONS: MPM is a disease with a poor prognosis, although chemotherapy appears to improve survival time. Significant gender and regional variation exists among patients, with notable differences in diagnostic and treatment practices. Long-term outcomes with pemetrexed remain indeterminate.<br><br>IMPACT: Emphasize centralized consult services for the diagnosis, treatment and support that patients receive for MPM, facilitating equal outcomes and compensation.}, }
@article {pmid30370748, year = {2018}, author = {Algranti, E and Giannasi, F and Sousa Santana, V}, title = {[The fight for the asbestos ban in Brazil and the 2nd International seminar "Brazil without asbestos"].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {5-6}, pages = {388-390}, doi = {10.19191/EP18.5-6.P388.115}, pmid = {30370748}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Asbestosis/*prevention &amp; control ; Brazil ; Congresses as Topic ; Construction Materials/standards/statistics &amp; numerical data ; Environmental Policy/*legislation &amp; jurisprudence ; *Environmental Pollutants/toxicity ; Environmental Pollution/legislation &amp; jurisprudence/*prevention &amp; control ; Flame Retardants/toxicity ; Humans ; Mesothelioma/etiology/prevention &amp; control ; Occupational Health/legislation &amp; jurisprudence ; Pleural Neoplasms/etiology/prevention &amp; control ; }, }
@article {pmid30370160, year = {2018}, author = {Plato, N and Martinsen, JI and Kjaerheim, K and Kyyronen, P and Sparen, P and Weiderpass, E}, title = {Mesothelioma in Sweden: Dose-Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents.}, journal = {Safety and health at work}, volume = {9}, number = {3}, pages = {290-295}, pmid = {30370160}, issn = {2093-7911}, abstract = {BACKGROUND: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma.<br><br>METHODS: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios&#xa0;and 95% confidence intervals.<br><br>RESULTS: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0&#xa0;fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix.<br><br>CONCLUSION: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.}, }
@article {pmid30366103, year = {2019}, author = {Harris, EJA and Kao, S and McCaughan, B and Nakano, T and Kondo, N and Hyland, R and Nowak, AK and de Klerk, NH and Brims, FJH}, title = {Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {288-293}, doi = {10.1016/j.jtho.2018.10.005}, pmid = {30366103}, issn = {1556-1380}, mesh = {Aged ; Anemia/blood ; Chest Pain/etiology ; Cytoreduction Surgical Procedures ; Dyspnea/etiology ; Female ; Health Status Indicators ; Hemoglobins/metabolism ; Humans ; Male ; Mesothelioma/blood/complications/pathology/*surgery ; Middle Aged ; *Models, Statistical ; Pleural Neoplasms/blood/complications/pathology/*surgery ; Risk Assessment/methods ; Risk Factors ; Serum Albumin/metabolism ; Survival Rate ; Weight Loss ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.<br><br>METHODS: Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hy&#xf5;go, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1&#xa0;through 4); survival characteristics were then compared.<br><br>RESULTS: Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5-56.1) months; median age was 63.0 (interquartile range: 57.0-67.8) years, and 83.0% (n&#xa0;= 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p&#xa0;<&#xa0;0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57-0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center.<br><br>CONCLUSIONS: Using routinely available clinical variables, the CART model was able to stratify surgical patients into&#xa0;risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM.}, }
@article {pmid30362690, year = {2018}, author = {Trenti, E and Palermo, SM and D'Elia, C and Comploj, E and Pycha, A and Carella, R and Pycha, A}, title = {Malignant mesothelioma of tunica vaginalis testis: Report of a very rare case with review of the literature.}, journal = {Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica}, volume = {90}, number = {3}, pages = {212-214}, doi = {10.4081/aiua.2018.3.212}, pmid = {30362690}, issn = {1124-3562}, mesh = {Adult ; Follow-Up Studies ; Frozen Sections ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Lymph Node Excision ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Mesothelioma, Malignant ; Prognosis ; Testicular Hydrocele/*surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Mesothelioma of the tunica vaginalis testis is a extremely rare tumor and represents 0.3 to 0.5% of all malignant mesotheliomas. Exposure to asbestos often precedes illness. Because of its low incidence and nonspecific clinical presentation, it is mostly diagnosed accidentally during surgery for other reasons and the prognosis is usually poor. We present a case of a patient with a mesothelioma of tunica vaginalis testis, diagnosed secondarily during hydrocele surgery, with long-term survival after radical surgery.<br><br>MATERIALS AND METHODS: a 40 years old patient was admitted to our department for routine surgery of a left hydrocele. During the operation a frozen section analysis was requested because of the unusual nodular thickening of the tunica vaginalis: the examination revealed a diffuse malignant mesothelioma with epithelioid structure and tubular-papillary proliferation. Therefore a left hemi-scrotectomy with left inguinal lymph node dissection was performed.<br><br>RESULTS: The definitive histology confirmed the previous report of diffuse malignant mesothelioma with angio-invasion but normal testicle findings and negative lymph nodes. No metastases were found on the CT-scan. For the first 2 years a CT was repeated every 4 months, for other 3 years every 6 months and then yearly. Six years after surgery the patient is classified as no evidence of disease.<br><br>CONCLUSIONS: malignant mesothelioma of the tunica vaginalis testis is a rare entity, often initially thought to be a hydrocele or an epididymal cyst. An aggressive approach with hemiscrotectomy with or without inguinal and retroperitoneal lymphadenectomy can reduce the risk of recurrence.}, }
@article {pmid30362153, year = {2019}, author = {Matboli, M and Shafei, AE and Ali, MA and Gaber, AI and Galal, A and Tarek, O and Marei, M and Khairy, E and El-Khazragy, N and Anber, N and Abdel-Rahman, O}, title = {Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.}, journal = {Journal of cellular biochemistry}, volume = {120}, number = {3}, pages = {3203-3211}, doi = {10.1002/jcb.27586}, pmid = {30362153}, issn = {1097-4644}, mesh = {Cerebroside-Sulfatase/*blood ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Linear Models ; Lung Neoplasms/*blood ; Male ; Membrane Proteins/*blood ; Mesothelioma/*blood ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Pleural Neoplasms/*blood ; RNA, Long Noncoding/*blood ; Real-Time Polymerase Chain Reaction ; }, abstract = {AIM AND BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM.<br><br>METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A (ARSA) gene expression with their epigenetic regulators microRNA (miR-2053) and long noncoding RNA (lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.<br><br>RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM.<br><br>CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.}, }
@article {pmid30357666, year = {2018}, author = {Pascotto, E and Gianoncelli, A and Calligaro, C and Marcuzzo, T and Melato, M and Rizzardi, C and Pascolo, L}, title = {Ferruginous bodies resolved by synchrotron XRF in a dog with peritoneal malignant mesothelioma.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {35}, pages = {35707-35714}, pmid = {30357666}, issn = {1614-7499}, mesh = {Animals ; Asbestos/toxicity ; Dogs ; Environmental Exposure/*adverse effects ; Immunohistochemistry ; Iron/analysis ; Lung/pathology ; Lung Neoplasms/diagnostic imaging/*pathology ; Male ; Mesothelioma/diagnostic imaging/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/diagnostic imaging/*pathology ; Silicon/analysis ; Spectrometry, X-Ray Emission ; Synchrotrons ; }, abstract = {Mesothelioma is a malignant tumor mainly correlated to occupational asbestos exposure. Rare reports describe its occurrence also in animals, mainly linked to asbestos in the environment. Asbestos exposure is demonstrated by the appearance of characteristic histological hallmarks: asbestos containing ferruginous bodies that are iron-based structures forming around fibers and also other dust particles. Here we present a clinical case of a suspect of mesothelioma in the peritoneum of a dog with parallel histological observation of ferruginous bodies. To possibly correlate the dog tumor to environmental exposure, we performed X-ray fluorescence (XRF) analyses at two different synchrotrons to resolve the ferruginous bodies' composition. While the histological examination diagnoses a tubulo-papillary mesothelioma, the XRF analyses show that ferruginous bodies contain Si particles, resembling formations of exogenous origin; however, the morphology is unlikely that of asbestos fibers. We speculate that the peritoneal mesothelioma of this dog could be related to environmental exposure to non-asbestos material.}, }
@article {pmid30357324, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Response to comments on 'Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure' by Farioli et al. and Oddone et al.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {490-491}, doi = {10.1093/carcin/bgy145}, pmid = {30357324}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30349836, year = {2018}, author = {Ibrahim, AM and Al-Akchar, M and Obaidi, Z and Al-Johany, H}, title = {Malignant Peritoneal Mesothelioma: A Rare Cause of Ascites.}, journal = {Journal of investigative medicine high impact case reports}, volume = {6}, number = {}, pages = {2324709618807506}, pmid = {30349836}, issn = {2324-7096}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare diagnosis that presents with difficulties in diagnosis and management. This article reports a case of an 88-year-old male who presented with a 2-week history of abdominal distention and bloating. He worked at an insulation production factory between the ages of 23 and 25 years with presumed asbestos exposure. On the computed tomography scan of the abdomen/pelvis, the patient was found to have diffuse omental, peritoneal, and mesenteric nodularity with moderate to large ascites. Omental biopsy revealed MPM. The overall prognosis of MPM remains poor, with a median survival time of 12 months at the time of diagnosis. Treatment modalities offered in the United States include chemotherapy alone, cytoreductive surgery alone, or cytoreductive surgery/chemotherapy combination.}, }
@article {pmid30349716, year = {2018}, author = {Grosso, F and Roveta, A and Gallizzi, G and Belletti, M}, title = {Management of recurrent pleural mesothelioma: Successful rechallenge with nintedanib in combination with chemotherapy.}, journal = {Clinical case reports}, volume = {6}, number = {10}, pages = {2000-2004}, pmid = {30349716}, issn = {2050-0904}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, generally caused by asbestos exposure. This case details how a patient treated with nintedanib during the LUME-Meso study was rechallenged with nintedanib. The findings highlight the benefit of nintedanib rechallenge and the potential use of continuous anti-angiogenic therapy in MPM treatment.}, }
@article {pmid30349644, year = {2018}, author = {Adhikary, G and Grun, D and Alexander, HR and Friedberg, JS and Xu, W and Keillor, JW and Kandasamy, S and Eckert, RL}, title = {Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.}, journal = {Oncotarget}, volume = {9}, number = {77}, pages = {34495-34505}, pmid = {30349644}, issn = {1949-2553}, support = {R01 CA184027/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.}, }
@article {pmid30338612, year = {2018}, author = {Betti, M and Aspesi, A and Ferrante, D and Sculco, M and Righi, L and Mirabelli, D and Napoli, F and Rondón-Lagos, M and Casalone, E and Vignolo Lutati, F and Ogliara, P and Bironzo, P and Gironi, CL and Savoia, P and Maffè, A and Ungari, S and Grosso, F and Libener, R and Boldorini, R and Valiante, M and Pasini, B and Matullo, G and Scagliotti, G and Magnani, C and Dianzani, I}, title = {Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.}, journal = {Genes, chromosomes &amp; cancer}, volume = {57}, number = {11}, pages = {573-583}, doi = {10.1002/gcc.22670}, pmid = {30338612}, issn = {1098-2264}, support = {IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; 2015 IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; //Istituto Superiore di Sanit&#xe0; (Progetto Amianto)/International ; //Italian Institute for Genomic Medicine/International ; //Ministry of Health - Italy/International ; //Regione Piemonte/International ; GR-2011-02348356//Young Researcher/International ; 2011-02348356//Young Researcher/International ; //INAIL Bric program 2016-2018/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; DNA Repair/genetics ; Environmental Exposure/*analysis ; Female ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Italy ; Male ; Mesothelioma/epidemiology/*genetics ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.}, }
@article {pmid30321262, year = {2018}, author = {Brentisci, C and Gangemi, M and Migliore, E and Mirabelli, D and Stura, A}, title = {Comment on 'Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {12}, pages = {2395-2396}, doi = {10.1093/annonc/mdy463}, pmid = {30321262}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30319235, year = {2018}, author = {Jargin, SV}, title = {Asbestos and Mesothelioma: A Comment.}, journal = {Indian journal of occupational and environmental medicine}, volume = {22}, number = {2}, pages = {113-114}, pmid = {30319235}, issn = {0973-2284}, }
@article {pmid30317900, year = {2018}, author = {Duke, KS and Thompson, EA and Ihrie, MD and Taylor-Just, AJ and Ash, EA and Shipkowski, KA and Hall, JR and Tokarz, DA and Cesta, MF and Hubbs, AF and Porter, DW and Sargent, LM and Bonner, JC}, title = {Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes.}, journal = {Nanotoxicology}, volume = {12}, number = {9}, pages = {975-991}, pmid = {30317900}, issn = {1743-5404}, support = {CC999999//Intramural CDC HHS/United States ; P30 ES025128/ES/NIEHS NIH HHS/United States ; R01 ES020897/ES/NIEHS NIH HHS/United States ; T32 ES007046/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Dose-Response Relationship, Drug ; Granuloma, Respiratory Tract/*chemically induced/genetics/immunology ; Inhalation Exposure ; Lung/*drug effects/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nanotubes, Carbon/*chemistry/*toxicity ; Surface Properties ; Tertiary Lymphoid Structures/*chemically induced/genetics/immunology ; Tumor Suppressor Protein p53/genetics/*physiology ; }, abstract = {The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53[+/-]) mice has not been investigated. We hypothesized that p53[+/-] mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53[+/+]) or p53[+/-] mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53[+/+] or p53[+/-] mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53[+/-] and p53[+/+] mice. A constitutively larger area of CD45R[+]/CD3[+] lymphoid tissue was observed in p53[+/-] mice compared to p53[+/+] mice. Importantly, p53[+/-] mice had larger granulomas induced by rMWCNTs as compared to p53[+/+] mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation.}, }
@article {pmid30316650, year = {2018}, author = {Fournel, L and Janet-Vendroux, A and Canny-Hamelin, E and Mansuet-Lupo, A and Guinet, C and Bobbio, A and Damotte, D and Alifano, M}, title = {[Malignant pleural mesothelioma: The role of surgery].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {5}, pages = {351-358}, doi = {10.1016/j.pneumo.2018.09.006}, pmid = {30316650}, issn = {1776-2561}, mesh = {Chemotherapy, Adjuvant ; Combined Modality Therapy ; Humans ; Lung Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Pneumonectomy ; Radiotherapy, Adjuvant ; Thoracic Surgical Procedures/*methods ; Thoracoscopy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease, whose incidence is increasing. Asbestos is the primary causal agent.<br><br>STATE OF KNOWLEDGE: Knowledge about MPM has evolved. Thoracoscopy is essential for diagnosis of MPM. It allows performing pleural biopsies, to study the extent of the disease and to relieve dyspnea. The pathological diagnosis is also better codified with immunohistochemistry and with analysis by expert of Mesopath group. Curative surgical treatments are pleurectomy decortication and extended pneumonectomy in combination with chemotherapy and/or radiotherapy. Those heavy treatments improve survival in highly selected patients. For the other patients, supportive measures will be considered to reduce pain and dyspnea.<br><br>PROSPECT: Radical surgical treatment is only offered in therapeutic trials or multimodal treatment. Its place is not formally established. New therapies associated to surgical treatment are being studied.<br><br>CONCLUSIONS: Surgical management of MPM has to be operated in specialized teams where the survival benefit and quality of life is discussed case by case.}, }
@article {pmid30316012, year = {2019}, author = {Mansfield, AS and Peikert, T and Smadbeck, JB and Udell, JBM and Garcia-Rivera, E and Elsbernd, L and Erskine, CL and Van Keulen, VP and Kosari, F and Murphy, SJ and Ren, H and Serla, VV and Schaefer Klein, JL and Karagouga, G and Harris, FR and Sosa, C and Johnson, SH and Nevala, W and Markovic, SN and Bungum, AO and Edell, ES and Dong, H and Cheville, JC and Aubry, MC and Jen, J and Vasmatzis, G}, title = {Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {276-287}, pmid = {30316012}, issn = {1556-1380}, support = {K12 CA090628/CA/NCI NIH HHS/United States ; }, mesh = {Antigens/*genetics ; *Chromothripsis ; Clonal Selection, Antigen-Mediated ; Computer Simulation ; DNA, Neoplasm/analysis ; Gene Dosage ; Gene Rearrangement ; Genomics ; HLA-A Antigens/genetics ; HLA-B Antigens/genetics ; Humans ; Lymphocytes, Tumor-Infiltrating ; Mesothelioma/*genetics/pathology ; Peptides/genetics/immunology ; Pleural Neoplasms/*genetics/pathology ; Receptors, Antigen, T-Cell/genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; Survival Rate ; T-Lymphocytes/immunology ; Transcriptome/*genetics ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy.<br><br>METHODS: We used mate-pair (n&#xa0;= 22), RNA (n&#xa0;= 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome.<br><br>RESULTS: We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival.<br><br>CONCLUSIONS: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.}, }
@article {pmid30312759, year = {2019}, author = {Toyokuni, S}, title = {Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention.}, journal = {Free radical biology &amp; medicine}, volume = {133}, number = {}, pages = {206-215}, doi = {10.1016/j.freeradbiomed.2018.10.401}, pmid = {30312759}, issn = {1873-4596}, mesh = {Animals ; Asbestos/toxicity ; Carcinogenesis/chemically induced/*genetics/pathology ; Ferroptosis/*genetics ; Humans ; Iron/*metabolism ; Iron Overload/chemically induced/genetics/metabolism/pathology ; Lung Neoplasms/chemically induced/*metabolism/pathology ; Mesothelioma/chemically induced/*metabolism/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/toxicity ; Rats ; Transferrin/metabolism ; }, abstract = {Cancer is the primary cause of human mortality in most countries. This tendency has increased as various medical therapeutics have advanced, which suggests that we cannot escape carcinogenesis, although the final outcome may be modified by exposomes and statistics. Cancer is classified by its cellular differentiation. Mesothelial cells are distinct in that they line somatic cavities, facilitating the smooth movement of organs, but are not exposed to the external environment. Malignant mesothelioma, or simply mesothelioma, develops either in the pleural, peritoneal or pericardial cavities, or in the tunica vaginalis testes. Mesothelioma has been a relatively rare cancer but is socially important due to its association with asbestos exposure, caused by modern industrial development. The major pathogenic mechanisms include oxidative stress either via catalytic reactions against the asbestos surface or frustrated phagocytosis of macrophages, and specific adsorption of hemoglobin and histones by asbestos fibers in the presence of phagocytic activity of mesothelial cells. Multiwall carbon nanotubes of ~50 nm-diameter, additionally adsorbing transferrin, are similarly carcinogenic to mesothelial cells in rodents and were thus classified as Group 2B carcinogens. Genetic alterations found in human and rat mesothelioma notably contain changes found in other excess iron-induced carcinogenesis models. Phlebotomy and iron chelation therapies have been successful in the prevention of mesothelioma in rats. Alternatively, loading of oxidative stress by non-thermal plasma to mesothelioma cells causes ferroptosis. Therefore, carcinogenesis by foreign fibrous inorganic materials may overlap the uncovered molecular mechanisms of birth of life and its evolution.}, }
@article {pmid30309369, year = {2018}, author = {Smeele, P and d'Almeida, SM and Meiller, C and Chéné, AL and Liddell, C and Cellerin, L and Montagne, F and Deshayes, S and Benziane, S and Copin, MC and Hofman, P and Le Pimpec-Barthes, F and Porte, H and Scherpereel, A and Grégoire, M and Jean, D and Blanquart, C}, title = {Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.}, journal = {Molecular cancer}, volume = {17}, number = {1}, pages = {148}, pmid = {30309369}, issn = {1476-4598}, mesh = {Biomarkers, Tumor ; Brain-Derived Neurotrophic Factor/*blood/genetics ; Gene Expression ; Humans ; Lung Neoplasms/*blood/genetics/mortality/*pathology ; Mesothelioma/*blood/genetics/mortality/*pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*blood ; Pleural Effusion, Malignant/genetics/metabolism ; Pleural Neoplasms/*blood/genetics/mortality/*pathology ; Prognosis ; RNA, Messenger/genetics ; ROC Curve ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.}, }
@article {pmid30309285, year = {2018}, author = {Funahashi, S and Okazaki, Y and Nishiyama, T and Ohyoshi, H and Yasui, H and Nishida, K and Matsui, S and Toyokuni, S}, title = {Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice.}, journal = {Free radical research}, volume = {52}, number = {9}, pages = {1030-1039}, doi = {10.1080/10715762.2018.1514604}, pmid = {30309285}, issn = {1029-2470}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Carcinogenesis/drug effects/*genetics ; Cation Transport Proteins/*genetics ; Epithelial Cells ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Iron ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Transgenic ; }, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.}, }
@article {pmid30301262, year = {2018}, author = {Sarun, KH and Lee, K and Williams, M and Wright, CM and Clarke, CJ and Cheng, NC and Takahashi, K and Cheng, YY}, title = {Genomic Deletion of BAP1 and CDKN2A Are Useful Markers for Quality Control of Malignant Pleural Mesothelioma (MPM) Primary Cultures.}, journal = {International journal of molecular sciences}, volume = {19}, number = {10}, pages = {}, pmid = {30301262}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*standards ; Cell Line, Tumor ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Gene Deletion ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Primary Cell Culture/methods/*standards ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a deadly cancer that is caused by asbestos exposure and that has limited treatment options. The current standard of MPM diagnosis requires the testing of multiple immunohistochemical (IHC) markers on formalin-fixed paraffin-embedded tissue to differentiate MPM from other lung malignancies. To date, no single biomarker exists for definitive diagnosis of MPM due to the lack of specificity and sensitivity; therefore, there is ongoing research and development in order to identify alternative biomarkers for this purpose. In this study, we utilized primary MPM cell lines and tested the expression of clinically used biomarker panels, including CK8/18, Calretinin, CK 5/6, CD141, HBME-1, WT-1, D2-40, EMA, CEA, TAG72, BG8, CD15, TTF-1, BAP1, and Ber-Ep4. The genomic alteration of CDNK2A and BAP1 is common in MPM and has potential diagnostic value. Changes in CDKN2A and BAP1 genomic expression were confirmed in MPM samples in the current study using Fluorescence In situ Hybridization (FISH) analysis or copy number variation (CNV) analysis with digital droplet PCR (ddPCR). To determine whether MPM tissue and cell lines were comparable in terms of molecular alterations, IHC marker expression was analyzed in both sample types. The percentage of MPM biomarker levels showed variation between original tissue and matched cells established in culture. Genomic deletions of BAP1 and CDKN2A, however, showed consistent levels between the two. The data from this study suggest that genomic deletion analysis may provide more accurate biomarker options for MPM diagnosis.}, }
@article {pmid30300743, year = {2019}, author = {White, R and Pulford, E and Elliot, DJ and Thurgood, LA and Klebe, S}, title = {Quantitative mass spectrometry to identify protein markers for diagnosis of malignant pleural mesothelioma.}, journal = {Journal of proteomics}, volume = {192}, number = {}, pages = {374-382}, doi = {10.1016/j.jprot.2018.09.018}, pmid = {30300743}, issn = {1876-7737}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Disease-Free Survival ; Female ; Humans ; Male ; Mass Spectrometry ; *Mesothelioma/metabolism/mortality ; Middle Aged ; Neoplasm Proteins/*metabolism ; *Pleural Effusion, Malignant/metabolism/mortality ; Survival Rate ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is a devastating malignancy with a prognosis of <12 months. Even with bans on the use of asbestos in most Western countries, the incidence is still increasing due to the long latency periods between exposure and development of the disease. Diagnosis is often delayed due to invasive biopsies and lack of distinguishable markers. Patients frequently present with pleural effusions months to years before a radiologically detectable mass appears. This study aimed to investigate the proteome of pleural effusions taken from patients with MPM, adenocarcinoma and benign conditions in an attempt to identify a biomarker for early diagnosis. We identified several proteins that may be possible targets and warrant further investigation. Due to the predominance of up regulated proteins involved in VEGF signalling in MPM, we analysed VEGFA levels in effusions and found a strong correlation between VEGFA levels and survival in MPM.}, }
@article {pmid30296019, year = {2018}, author = {Behrens, MA}, title = {Asbestos Trust Transparency.}, journal = {Fordham law review}, volume = {87}, number = {1}, pages = {107-124}, pmid = {30296019}, issn = {0015-704X}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Asbestosis/etiology ; Bankruptcy ; Humans ; Liability, Legal/*economics ; Mesothelioma/etiology ; Occupational Exposure/*legislation &amp; jurisprudence ; *Truth Disclosure ; United States ; }, }
@article {pmid30293912, year = {2018}, author = {Mlika, M and Lamzirbi, O and Limam, M and Mejri, N and Ben Saad, S and Chaouch, N and Ben Miled, K and Marghli, A and Mezni, F}, title = {[Clinical and pathological profile of the pleural malignant mesothelioma: A retrospective study about 30 cases].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {6}, pages = {427-435}, doi = {10.1016/j.pneumo.2018.06.004}, pmid = {30293912}, issn = {1776-2561}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Tunisia/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: The malignant pleural mesothelioma (MPM) is a rare tumour usually associated to asbestos exposure. The delay between the exposure and the occurrence of the cancer can reach 40 years. This caused the pick of incidence described in many countries including Tunisia. The diagnosis is suspected based on clinical features but positive diagnosis is microscopic. Our aim was to describe the clinical and microscopic features of MPM through a single institution experience.<br><br>PATIENTS AND METHODS: We conducted a retrospective study about 30&#xa0;MPM diagnosed over a 20-year-period (1995-2015). We included only patients with complete records including clinical, radiologic and microscopic features. All the microscopic diagnoses were reviewed by 2&#xa0;pathologists. A mean of 12&#xa0;slides per case was reviewed. The diagnosis was based on the 2015&#xa0;WHO classification.<br><br>RESULTS: The mean age of the patients was 61&#xa0;years, average 22&#xa0;to 80&#xa0;years. The sex ratio was 6,5. An asbetose exposition was reported in 21&#xa0;cases. The most frequent symptoms was chest pain reported in 25&#xa0;cases. Physical exam was normal in 9&#xa0;cases. It revealed pleural syndorm in most patients (60&#xa0;%). Imaging findings consisted mainly in diffuse pleural thickening in 17&#xa0;cases. Twelve tumours were classified as stage I, 3&#xa0;stage II, 14&#xa0;stage III et 1&#xa0;stage IV. Pleural biopsy was performed using needle in 18&#xa0;cases, through thoracoscopy in 16&#xa0;cases, thoracotomy in 3&#xa0;cases and allowed the diagnosis in respectively 7&#xa0;cases/18, 16&#xa0;cases/16&#xa0;and 3&#xa0;cases/3. A lymph node biopsy was performed through mediastinoscopy in one case and yelded the diagnosis. The diagnosis was performed on surgical specimen in 2&#xa0;patients: one bullectomy and one right upper lobectomy. The microscopic exam concluded to an EM in 17&#xa0;cases, sarcomatoid mesothelioma (SM) in 4&#xa0;cases and biphasic mesothelioma (BM) in 9&#xa0;cases. Pan-cytokeratin antibody was used in all cases in association with 2&#xa0;antibodies with positive diagnostic value and 2&#xa0;antibodies with negative diagnostic value. It was repeated in 15&#xa0;cases and the most used antibodies were the anti-calretinin and the TTF1. This was due to the lack of fixation in one case and in order to reach a quality criteria in the other cases. Surgical resection was possible in 2&#xa0;patients. 15&#xa0;patients were lost of view after a mean follow-up period of 3&#xa0;months. Thirteen patients died before or during the follow-up.<br><br>CONCLUSION: This work was about a Tunisian experience in the diagnosis and management of MPM. The major limits faced were the incomplete databases, the small number of patients included. Microsocpic positive diagnosis necessitates a degree of expertise and every laboratory has to determine the most valuable antibodies through its experience in order to optimize the diagnosis and to reduce the delay of diagnosis.}, }
@article {pmid30293239, year = {2018}, author = {van Gerwen, M and Wolf, A and Liu, B and Flores, R and Taioli, E}, title = {Short-term outcomes of pleurectomy decortication and extrapleural pneumonectomy in mesothelioma.}, journal = {Journal of surgical oncology}, volume = {118}, number = {7}, pages = {1178-1187}, doi = {10.1002/jso.25260}, pmid = {30293239}, issn = {1096-9098}, support = {NCI CCSG P30 CA196521//National Cancer Institute/ ; }, mesh = {Aged ; Arrhythmias, Cardiac/epidemiology ; Databases, Factual ; Female ; *Hospital Mortality ; Humans ; Male ; Mesothelioma/mortality/*surgery ; Middle Aged ; New York/epidemiology ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*adverse effects ; Postoperative Complications ; Propensity Score ; }, abstract = {BACKGROUND/OBJECTIVES: We evaluated postoperative mortality and complications after extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) to better understand their effectiveness in malignant pleural mesothelioma (MPM).<br><br>METHODS: A meta-analysis was done to evaluate 30-day mortality and postoperative complications. In addition, in-patients data of 500 eligible patients with MPM who underwent EPP or P/D was extracted from the New York Statewide Planning and Research Cooperative System (SPARCS). Multivariate analyses and propensity matching were used to compare in-hospital mortality and postoperative complications in EPP vs P/D.<br><br>RESULTS: The meta-analysis showed a statistically significant difference in 30-day mortality (5% [95% CI: 4-6] vs P/D 2% [95% CI: 1-3]), proportion of complications (46% [95% CI: 36-56] vs 24% [95% CI: 15-34]) and postoperative arrhythmias (20% [95% CI: 12-31] vs 5% [95% CI: 2-8]) for EPP vs P/D. In-hospital mortality (OR adj : 2.6; 95% CI: 0.86-7.75) and postoperative complications (OR adj : 1.1; 95% CI: 0.68-1.86) were not different in EPP compared with P/D while supraventricular arrhythmia was significantly more frequent after EPP vs P/D (OR adj : 5.2; 95% CI: 2.34-11.33).<br><br>CONCLUSIONS: Postoperative mortality, postoperative complications, and particularly supraventricular arrhythmia are less frequent after P/D vs EPP. P/D, a less invasive surgery, may provide a better option when technically feasible for patients with MPM.}, }
@article {pmid30288361, year = {2018}, author = {Fear, VS and Tilsed, C and Chee, J and Forbes, CA and Casey, T and Solin, JN and Lansley, SM and Lesterhuis, WJ and Dick, IM and Nowak, AK and Robinson, BW and Lake, RA and Fisher, SA}, title = {Combination immune checkpoint blockade as an effective therapy for mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {10}, pages = {e1494111}, pmid = {30288361}, issn = {2162-4011}, abstract = {Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the best therapeutic option for mesothelioma have yet to be fully elucidated. Here, we used our well characterised mesothelioma tumour model to investigate the efficacy of different ICBP treatments to generate effective therapy for mesothelioma. We show that tumour resident regulatory T cell co-express high levels of CTLA-4, OX40 and GITR relative to T effector subsets and that these receptors are co-expressed on a large proportion of cells. Targeting any of CTLA-4, OX40 or GITR individually generated effective responses against mesothelioma. Furthermore, the combination of αCTLA-4 and αOX40 was synergistic, with an increase in complete tumour regressions from 20% to 80%. Other combinations did not synergise to enhance treatment outcomes. Finally, an early pattern in T cell response was predictive of response, with activation status and ICP receptor expression profile of T effector cells harvested from tumour and dLN correlating with response to immunotherapy. Taken together, these data demonstrate that combination ICPB can work synergistically to induce strong, durable immunity against mesothelioma in an animal model.}, }
@article {pmid30281709, year = {2018}, author = {Kalinke, LP and Kalinke, MA and Sarquis, LMM and Marcondes, L and Halfeld, T and Mensi, C and Consonni, D}, title = {[A proposal for the creation of a system to monitor cases of malignant mesothelioma in Curitiba, Paraná, Brazil].}, journal = {Cadernos de saude publica}, volume = {34}, number = {9}, pages = {e00171917}, doi = {10.1590/0102-311X00171917}, pmid = {30281709}, issn = {1678-4464}, mesh = {Asbestos/*toxicity ; Brazil/epidemiology ; Carcinogens/*toxicity ; Disease Notification/*methods ; Environmental Exposure/*adverse effects ; *Hospital Records ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; }, abstract = {The study proposes the creation of a system to monitor cases of malignant mesothelioma in the municipality of Curitiba, Paraná State, Brazil, based on the Italian model. This diagnosis-type action-research project featured exploratory and planning phases conducted from July 2015 to May 2017. The following search tools were used: Hospital-Based Cancer Registries Integrator with specific morphologies for mesothelioma; Hospital-Based Cancer Registry with codes C38.4 and C45 of the International Classification of Diseases, 10th revision, and/or records coded by the ICD-O with topographies C38 and C48; Population-Based Cancer Registry of the Curitiba Municipal Health Department, with the same codes. The study also identified, analyzed, and adapted to the Brazilian reality the model, questionnaires, and registry software for mesothelioma from Lombardy, Italy. Fifteen cases of mesothelioma were recorded in the Hospital-Based Cancer Registries Integrator. Two cases were recorded in the University Hospital-Based Cancer Registry and 16 in the Cancer Hospital. There were 317 cases recorded in the Population-Based Cancer Registry during the same period. Although some information was complete, data were lacking on patients' occupational history, thereby preventing the determination of a causal nexus. Given a predicted increase in cases of mesothelioma in the coming decades and the response to court cases, the implementation of registries has become essential to facilitate knowledge and follow-up on the determination of the causal link and specific sources of asbestos exposure in the country.}, }
@article {pmid30272283, year = {2018}, author = {Zhang, C and Hao, Y and Wu, L and Dong, X and Jiang, N and Cong, B and Liu, J and Zhang, W and Tang, D and De Perrot, M and Zhao, X}, title = {Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma.}, journal = {International journal of oncology}, volume = {53}, number = {6}, pages = {2531-2541}, pmid = {30272283}, issn = {1791-2423}, mesh = {Angiogenesis Inhibitors/*administration &amp; dosage/pharmacology ; Animals ; Antineoplastic Agents/*administration &amp; dosage/pharmacology ; Apoptosis Inducing Factor/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Curcumin/*administration &amp; dosage/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/blood supply/*drug therapy/metabolism ; Mesothelioma/blood supply/*drug therapy/metabolism ; Mesothelioma, Malignant ; Mice ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin‑induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)‑mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase‑independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM.}, }
@article {pmid30266660, year = {2018}, author = {Tsao, AS and Lindwasser, OW and Adjei, AA and Adusumilli, PS and Beyers, ML and Blumenthal, GM and Bueno, R and Burt, BM and Carbone, M and Dahlberg, SE and de Perrot, M and Fennell, DA and Friedberg, J and Gill, RR and Gomez, DR and Harpole, DH and Hassan, R and Hesdorffer, M and Hirsch, FR and Hmeljak, J and Kindler, HL and Korn, EL and Liu, G and Mansfield, AS and Nowak, AK and Pass, HI and Peikert, T and Rimner, A and Robinson, BWS and Rosenzweig, KE and Rusch, VW and Salgia, R and Sepesi, B and Simone, CB and Sridhara, R and Szlosarek, P and Taioli, E and Tsao, MS and Yang, H and Zauderer, MG and Malik, SM}, title = {Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {11}, pages = {1655-1667}, doi = {10.1016/j.jtho.2018.08.2036}, pmid = {30266660}, issn = {1556-1380}, mesh = {Consensus ; Humans ; Lung Neoplasms/pathology/*therapy ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; National Cancer Institute (U.S.) ; United States ; }, abstract = {On March 28- 29, 2017, the National Cancer Institute (NCI) Thoracic Malignacy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation convened the NCI-International Association for the Study of Lung Cancer- Mesothelioma Applied Research Foundation Mesothelioma Clinical Trials Planning Meeting in Bethesda, Maryland. The goal of the meeting was to bring together lead academicians, clinicians, scientists, and the U.S. Food and Drug Administration to focus on the development of clinical trials for patients in whom malignant pleural mesothelioma has been diagnosed. In light of the discovery of new cancer targets affecting the clinical development of novel agents and immunotherapies in malignant mesothelioma, the objective of this meeting was to assemble a consensus on at least two or three practice-changing multimodality clinical trials to be conducted through NCI's National Clinical Trials Network.}, }
@article {pmid30262573, year = {2018}, author = {Arnold, DT and De Fonseka, D and Perry, S and Morley, A and Harvey, JE and Medford, A and Brett, M and Maskell, NA}, title = {Investigating unilateral pleural effusions: the role of cytology.}, journal = {The European respiratory journal}, volume = {52}, number = {5}, pages = {}, doi = {10.1183/13993003.01254-2018}, pmid = {30262573}, issn = {1399-3003}, mesh = {Adenocarcinoma/complications/*diagnosis/epidemiology ; Aged ; Aged, 80 and over ; *Cytodiagnosis ; Female ; Humans ; Lung Neoplasms/complications/*diagnosis/epidemiology ; Male ; Mesothelioma/complications/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/complications/*diagnosis/epidemiology ; Pleural Effusion, Malignant/*diagnosis/epidemiology/etiology ; Prospective Studies ; Sensitivity and Specificity ; Thoracentesis ; United Kingdom/epidemiology ; }, abstract = {The vast majority of undiagnosed unilateral pleural effusions have fluid sent for cytological analysis. Despite widespread use, there is uncertainty about its sensitivity to diagnose malignant pleural effusions (MPEs). Our aim was to ascertain the utility of cytology using a large prospective cohort.Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited to this UK-based study. All had pleural fluid sent for cytological analysis. Cytological sensitivity was based on the final diagnosis at 12 months, confirmed by two consultants.Over 8 years, 921 patients were recruited, of which 515 had a MPE. Overall sensitivity of fluid cytology to diagnose malignancy was 46% (95% CI 42-58%). There was variation in sensitivity depending on cancer primary, with mesothelioma (6%) and haematological malignancies (40%) being significantly lower than adenocarcinomas (79%). MPEs secondary to ovarian cancer had high pick-up rates (95%). In asbestos-exposed males with exudative effusions, the risk of MPE was 60%, but cytological sensitivity was 11%.This is the largest prospective study of pleural fluid cytology and informs discussions with patients about the likely requirement for investigations following thoracentesis. In patients presenting with a clinical suspicion of mesothelioma, cytological sensitivity is low, so more definitive investigations could be performed sooner.}, }
@article {pmid30259910, year = {2018}, author = {Ascoli, V and Murer, B and Nottegar, A and Luchini, C and Carella, R and Calabrese, F and Lunardi, F and Cozzi, I and Righi, L}, title = {What's new in mesothelioma.}, journal = {Pathologica}, volume = {110}, number = {1}, pages = {12-28}, pmid = {30259910}, issn = {0031-2983}, mesh = {Biomarkers, Tumor/*analysis ; Biopsy ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/pathology ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Neoplasm Grading ; Pleural Neoplasms/*diagnosis/pathology ; Prognosis ; }, abstract = {Malignant pleural mesothelioma is a neoplasm characterized by a very poor prognosis and medico-legal implications. Diagnosis, prognosis and therapy are often challenging and include several issues. Cytological diagnosis is frequently the first step of the diagnostic process, and although its sensitivity may be somewhat lower, diagnostic criteria should be taken into account. When effusion cytology is inconclusive for the diagnosis, tissue biopsies should be taken. Even if the morphologic criteria for deciding whether a mesothelial proliferation is a benign or a malignant process have been defined, the separation of benign from malignant mesothelial proliferation is often a difficult problem for the pathologist, particularly on small biopsies. Thirdly, when the diagnosis is made, despite many efforts have been made to identify possible new biomarkers for early diagnosis, prognostic stratification and also predictive tools should be defined. Nowadays, the main prognostic parameter is still represented by the histological subtype, having the epithelioid MPM a better outcome than the sarcomatoid or biphasic MPM. A nuclear grading system have been also proposed to stratify patient outcome. Reliable predictive biomarkers are still lacking in MPM and a personalized therapeutic concept is eagerly needed. Mesothelioma occurs mostly as sporadic cancer and the main risk factor is asbestos exposure, but it also occurs among blood relatives suggesting possible increased genetic susceptibility besides shared exposures. Recently the study of genetic predisposition syndrome raised new aspect in the occurrence of mesothelioma cases. This review summarize these most important issues.}, }
@article {pmid30257964, year = {2019}, author = {Santarelli, L and Gaetani, S and Monaco, F and Bracci, M and Valentino, M and Amati, M and Rubini, C and Sabbatini, A and Pasquini, E and Zanotta, N and Comar, M and Neuzil, J and Tomasetti, M and Bovenzi, M}, title = {Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {28}, number = {1}, pages = {119-126}, doi = {10.1158/1055-9965.EPI-18-0453}, pmid = {30257964}, issn = {1538-7755}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/blood ; Carcinogens/toxicity ; Carcinoma, Non-Small-Cell Lung/*chemically induced ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; MicroRNAs/*blood/genetics ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies.<br><br>METHODS: Four groups of patients were included in the study, including patients with asbestos-related (NSCLC[Asb]) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population.<br><br>RESULTS: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion.<br><br>CONCLUSIONS: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis.<br><br>IMPACT: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.}, }
@article {pmid30256306, year = {2018}, author = {Tomasallo, CD and Christensen, KY and Raymond, M and Creswell, PD and Anderson, HA and Meiman, JG}, title = {An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {12}, pages = {1143-1149}, doi = {10.1097/JOM.0000000000001461}, pmid = {30256306}, issn = {1536-5948}, support = {U60 OH010898/OH/NIOSH CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos ; Case-Control Studies ; Construction Industry/statistics &amp; numerical data ; Death Certificates ; Extraction and Processing Industry/statistics &amp; numerical data ; Female ; Humans ; Incidence ; Industry/*statistics &amp; numerical data ; Lung Neoplasms/*epidemiology/mortality ; Male ; Manufacturing Industry/statistics &amp; numerical data ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/mortality ; Occupational Exposure/*statistics &amp; numerical data ; Peritoneal Neoplasms/*epidemiology/mortality ; Pleural Neoplasms/*epidemiology/mortality ; Registries ; Schools ; Teaching/statistics &amp; numerical data ; Wisconsin/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: The aim of the study was to describe mesothelioma occurrence in Wisconsin from 1997 to 2013 by usual industry and occupation (I&amp;O), including occupations generally considered low risk.<br><br>METHODS: Population-based rates and standardized incidence and mortality ratios were calculated. Two case-control analyses were designed to compare mesothelioma incidence and mortality in specific I&amp;O groups with occurrence of (1) brain and central nervous system cancers and (2) other causes of death, using logistic regression.<br><br>RESULTS: Mesothelioma incidence and mortality were elevated in Wisconsin (SIRadj = 1.20 [1.13 to 1.28]; SMRadj = 1.30 [1.22 to 1.38]). Certain industry (construction, manufacturing) and occupation (construction and extraction) groups were associated with increased odds of mesothelioma, with some evidence of increased risk among teachers.<br><br>CONCLUSIONS: Forty years after the Occupational and Safety Health Act, mesothelioma incidence and mortality remain elevated in Wisconsin, with increased risk continuing for certain I&amp;O groups.}, }
@article {pmid30254313, year = {2018}, author = {Johnen, G and Burek, K and Raiko, I and Wichert, K and Pesch, B and Weber, DG and Lehnert, M and Casjens, S and Hagemeyer, O and Taeger, D and Brüning, T and , }, title = {Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14321}, pmid = {30254313}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Calbindin 2/*blood ; Case-Control Studies ; Cohort Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/chemically induced/diagnosis ; Male ; Mesothelin ; Mesothelioma/*blood/chemically induced/diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Prognosis ; Prospective Studies ; }, abstract = {Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools - like minimally-invasive biomarkers - are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.}, }
@article {pmid30241199, year = {2018}, author = {Boffetta, P and Malvezzi, M and Pira, E and Negri, E and La Vecchia, C}, title = {International Analysis of Age-Specific Mortality Rates From Mesothelioma on the Basis of the International Classification of Diseases, 10th Revision.}, journal = {Journal of global oncology}, volume = {4}, number = {}, pages = {1-15}, pmid = {30241199}, issn = {2378-9506}, support = {P30 ES023515/ES/NIEHS NIH HHS/United States ; }, mesh = {Age Factors ; Female ; Humans ; International Classification of Diseases/*standards ; Mesothelioma/*mortality ; Mortality ; }, abstract = {Past analyses of mortality data from mesothelioma relied on unspecific codes, such as pleural neoplasms. We calculated temporal trends in age-specific mortality rates in Canada, the United States, Japan, France, Germany, Italy, the Netherlands, Poland, the United Kingdom, and Australia on the basis of the 10th version of the International Classification of Diseases, which includes a specific code for mesothelioma. Older age groups showed an increase (in the United States, a weaker decrease) during the study period, whereas in young age groups, there was a decrease (in Poland, a weaker increase, starting, however, from low rates). Results were consistent between men and women and between pleural and peritoneal mesothelioma, although a smaller number of events in women and for peritoneal mesothelioma resulted in less precise results. The results show the heterogeneous effect of the reduction of asbestos exposure on different age groups; decreasing mortality in young people reflects reduced exposure opportunity, and increasing mortality in the elderly shows the long-term effect of early exposures.}, }
@article {pmid30240694, year = {2018}, author = {Boffetta, P and Mundt, KA and Thompson, WJ}, title = {The epidemiologic evidence for elongate mineral particle (EMP)-related human cancer risk.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {100-106}, doi = {10.1016/j.taap.2018.09.021}, pmid = {30240694}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Minerals/*toxicity ; Neoplasms/*chemically induced/*epidemiology ; Occupational Exposure ; Particulate Matter/*toxicity ; Risk Assessment ; }, abstract = {Epidemiologic research on the role of fibers and other elongate mineral particles (EMP) and human diseases including cancers has generated a large body of literature over the last decades: nevertheless, there remain some questions for which the scientific community appears unable to reach consensus. Reasons for genuine differences in opinion include (i) ways in which exposures have been classified; (ii) methodological limitations of the available studies, (iii) criteria for the interpretation of study results, including potential underlying biological mechanisms, and (iv) methodology for integrating the evidence. Various approaches have been proposed in recent years to address these issues, which will be illustrated using examples from asbestos, talc, taconite, synthetic mineral fibers and silicon carbide, with emphasis on potential carcinogenic effects. Potential solutions include improved exposure and outcome assessment - including use of biomarkers and other molecular approaches, consideration of potential confounding and other sources of bias, implementation of guidelines for study quality assessment and evidence evaluation and integration.}, }
@article {pmid30209210, year = {2018}, author = {Finkelstein, MM}, title = {Response to: 'The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure' by Marinaccio et al.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {11}, pages = {844}, doi = {10.1136/oemed-2018-105129}, pmid = {30209210}, issn = {1470-7926}, mesh = {*Asbestos ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30209209, year = {2018}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Scarselli, A and Ferrante, P and Bonafede, M and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Merler, E and Girardi, P and Negro, C and D'Agostin, F and Romanelli, A and Chellini, E and Silvestri, S and Pascucci, C and Calisti, R and Stracci, F and Romeo, E and Ascoli, V and Trafficante, L and Carrozza, F and Angelillo, I and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and Iavicoli, S and , }, title = {Letter concerning: 'Response to: 'The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure' by Marinaccio et al'.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {11}, pages = {844-845}, doi = {10.1136/oemed-2018-105362}, pmid = {30209209}, issn = {1470-7926}, mesh = {*Asbestos ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30196105, year = {2018}, author = {Kharazmi, E and Chen, T and Fallah, M and Sundquist, K and Sundquist, J and Albin, M and Weiderpass, E and Hemminki, K}, title = {Familial risk of pleural mesothelioma increased drastically in certain occupations: A nationwide prospective cohort study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {103}, number = {}, pages = {1-6}, doi = {10.1016/j.ejca.2018.07.139}, pmid = {30196105}, issn = {1879-0852}, mesh = {Adolescent ; Adult ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology/pathology ; Prospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: We aimed to explore the effect of occupation on familial risk of pleural mesothelioma in a nationwide cohort study design.<br><br>METHOD: The nationwide Swedish Family-Cancer Database includes all Swedes born after 1931 and their biological parents, totalling 16.1 million individuals with about 2.3 million cancer patients. Hazards ratios (HRs) were calculated adjusting for age, sex&#xa0;and region of residence.<br><br>RESULTS: Having asbestos-related occupation in the absence of family history of mesothelioma increased risk of mesothelioma more than threefold (adjusted HR&#xa0;=&#xa0;3.2, 95% confidence interval [CI]: 3.0-3.5). In those who had a history of mesothelioma in their first-degree relatives and an asbestos-related occupation, risk of mesothelioma dramatically increased compared with individuals without such occupations and family history (without chronic obstructive pulmonary disease [COPD] HR&#xa0;=&#xa0;24, 95% CI: 15-39; with COPD 45, 95% CI: 15-141). In those who had a family history of mesothelioma and no history of an asbestos-related occupation, risk of mesothelioma did not show significant increase compared with those who had no family history of mesothelioma and no asbestos-related occupation (HR&#xa0;=&#xa0;1.6; 95% CI: 0.7-3.8).<br><br>CONCLUSION: First-degree relatives of patients with pleural mesothelioma had a drastic risk of developing this malignancy in case of certain occupations, which shows a gene-environment interaction is probable in risk of mesothelioma.}, }
@article {pmid30174219, year = {2019}, author = {Marant Micallef, C and Shield, KD and Vignat, J and Baldi, I and Charbotel, B and Fervers, B and Gilg Soit Ilg, A and Guénel, P and Olsson, A and Rushton, L and Hutchings, SJ and Cléro, E and Laurier, D and Scanff, P and Bray, F and Straif, K and Soerjomataram, I}, title = {Cancers in France in 2015 attributable to occupational exposures.}, journal = {International journal of hygiene and environmental health}, volume = {222}, number = {1}, pages = {22-29}, doi = {10.1016/j.ijheh.2018.07.015}, pmid = {30174219}, issn = {1618-131X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Carcinogens/*toxicity ; Female ; France/epidemiology ; Humans ; Male ; Neoplasms/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking.<br><br>OBJECTIVES: To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015.<br><br>METHODS: Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network.<br><br>RESULTS: In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%).<br><br>CONCLUSIONS: Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.}, }
@article {pmid30169798, year = {2018}, author = {Terracini, B}, title = {Commentary: Past and current asbestos exposure and future mesothelioma risks in Britain.}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1756-1757}, doi = {10.1093/ije/dyy175}, pmid = {30169798}, issn = {1464-3685}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; United Kingdom ; }, }
@article {pmid30158318, year = {2018}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {12}, pages = {898-903}, doi = {10.1136/oemed-2018-105108}, pmid = {30158318}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Age Distribution ; Asbestos, Crocidolite/*toxicity ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Infant ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Proportional Hazards Models ; Sex Distribution ; Western Australia/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: The presence of asbestos in public buildings is a legacy of past asbestos use in many developed countries. Of particular concern is the amount and current condition in schools and the vulnerability of children to mesothelioma. Our aim was to compare the risk of mesothelioma between those exposed to blue asbestos as children and as adults at Wittenoom.<br><br>METHODS: Public sources were used to establish the Wittenoom residents' cohort. Mesothelioma incidence rates per 100&#x2009;000 person-years at risk were derived for those first exposed to asbestos at Wittenoom as children (<15 years) or adults separately. Proportional hazards survival models examined the slope of the exposure-response relationship between asbestos exposure and incidence of mesothelioma in different sex and age groups.<br><br>RESULTS: The mesothelioma rate was lower among those first exposed as children (76.8 per 100 000) than those first exposed as adults (121.3 per 100 000). Adjusting for cumulative exposure to asbestos and sex, those exposed as adults had a greater risk of mesothelioma (adjusted HR 2.5, 95%&#x2009;CI 1.7 to 3.7). The slope of the exposure-response relationship did not differ between those exposed as children and those exposed as adults.<br><br>CONCLUSION: We found no greater susceptibility to mesothelioma among those first exposed to asbestos as children than those first exposed as adults. However, given the long latency of mesothelioma, and the greater years of life yet to be lived by the Wittenoom children, it is likely that there will be more cases of mesothelioma in the future among those first exposed as children.}, }
@article {pmid30157247, year = {2018}, author = {Rath, EM and Cheng, YY and Pinese, M and Sarun, KH and Hudson, AL and Weir, C and Wang, YD and Håkansson, AP and Howell, VM and Liu, GJ and Reid, G and Knott, RB and Duff, AP and Church, WB}, title = {BAMLET kills chemotherapy-resistant mesothelioma cells, holding oleic acid in an activated cytotoxic state.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0203003}, pmid = {30157247}, issn = {1932-6203}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Membrane/drug effects/metabolism ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/*drug effects ; Humans ; Hydrogen-Ion Concentration ; Lactalbumin/chemistry/*pharmacology ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Mitochondrial Proton-Translocating ATPases/metabolism ; Models, Molecular ; Molecular Conformation ; Oleic Acid/chemistry/*pharmacology ; }, abstract = {Malignant pleural mesothelioma is an aggressive cancer with poor prognosis. Here we have investigated in vitro efficacy of BAMLET and BLAGLET complexes (anti-cancer complexes consisting of oleic acid and bovine α-lactalbumin or β-lactoglobulin respectively) in killing mesothelioma cells, determined BAMLET and BLAGLET structures, and investigated possible biological mechanisms. We performed cell viability assays on 16 mesothelioma cell lines. BAMLET and BLAGLET having increasing oleic acid content inhibited human and rat mesothelioma cell line proliferation at decreasing doses. Most of the non-cancer primary human fibroblasts were more resistant to BAMLET than were human mesothelioma cells. BAMLET showed similar cytotoxicity to cisplatin-resistant, pemetrexed-resistant, vinorelbine-resistant, and parental rat mesothelioma cells, indicating the BAMLET anti-cancer mechanism may be different to drugs currently used to treat mesothelioma. Cisplatin, pemetrexed, gemcitabine, vinorelbine, and BAMLET, did not demonstrate a therapeutic window for mesothelioma compared with immortalised non-cancer mesothelial cells. We demonstrated by quantitative PCR that ATP synthase is downregulated in mesothelioma cells in response to regular dosing with BAMLET. We sought structural insight for BAMLET and BLAGLET activity by performing small angle X-ray scattering, circular dichroism, and scanning electron microscopy. Our results indicate the structural mechanism by which BAMLET and BLAGLET achieve increased cytotoxicity by holding increasing amounts of oleic acid in an active cytotoxic state encapsulated in increasingly unfolded protein. Our structural studies revealed similarity in the molecular structure of the protein components of these two complexes and in their encapsulation of the fatty acid, and differences in the microscopic structure and structural stability. BAMLET forms rounded aggregates and BLAGLET forms long fibre-like aggregates whose aggregation is more stable than that of BAMLET due to intermolecular disulphide bonds. The results reported here indicate that BAMLET and BLAGLET may be effective second-line treatment options for mesothelioma.}, }
@article {pmid30156102, year = {2018}, author = {Felley-Bosco, E and MacFarlane, M}, title = {Asbestos: Modern Insights for Toxicology in the Era of Engineered Nanomaterials.}, journal = {Chemical research in toxicology}, volume = {31}, number = {10}, pages = {994-1008}, doi = {10.1021/acs.chemrestox.8b00146}, pmid = {30156102}, issn = {1520-5010}, support = {MC_U132685863/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/4/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Air Pollutants/toxicity ; Asbestos/*toxicity ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Female ; Humans ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Mutation ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; Nanostructures/*chemistry ; Survival Rate ; Tumor Suppressor Protein p53/genetics/metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {Asbestos fibers are naturally occurring silicates that have been extensively used in the past, including house construction, but because of their toxicity, their use has been banned in 63 countries. Despite this, more than one million metric tons of asbestos are still consumed annually in countries where asbestos use has not been banned. Asbestos-related disease incidence is still increasing in several countries, including those countries that banned the use of asbestos more than 30 years ago. We highlight here recent knowledge obtained in experimental models about the mechanisms leading to tumor development following asbestos exposure, including genetic and epigenetic changes. Importantly, the landscape of alterations observed experimentally in tumor samples is consistent with alterations observed in clinical tumor samples; therefore, studies performed on early/precancer stages should help inform secondary prevention, which remains crucial in the absence of an efficient primary prevention. Knowledge gathered on asbestos should also help address future challenges, especially in view of the increased production of new materials that may behave similarly to asbestos fibers.}, }
@article {pmid30144378, year = {2019}, author = {Muscella, A and Cossa, LG and Vetrugno, C and Antonaci, G and Marsigliante, S}, title = {ADP sensitizes ZL55 cells to the activity of cisplatin.}, journal = {Journal of cellular physiology}, volume = {234}, number = {4}, pages = {4409-4417}, doi = {10.1002/jcp.27224}, pmid = {30144378}, issn = {1097-4652}, mesh = {Adenosine Triphosphate/*pharmacology ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Apoptosis/drug effects ; Caspases/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cisplatin/*pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms/*drug therapy/genetics/metabolism/pathology ; Mesothelioma/*drug therapy/genetics/metabolism/pathology ; Mesothelioma, Malignant ; Phosphorylation ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Ribosomal Protein S6 Kinases/metabolism ; Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists &amp; inhibitors/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor in which cisplatin therapy is commonly used, although its effectiveness is limited. It follows that research efforts dedicated to identify promising combinations that can synergistically kill cancer cells are needed. Because we recently demonstrated that ADP inhibits the proliferation of ZL55 cells, an MPM-derived cell line obtained from bioptic samples of asbestos-exposed patients. Our objective in this study was to investigate the hypothesis that ADP also potentiates the cytotoxic activity of cisplatin. Results show that in ZL55 cells ADP enhanced (a) the cytotoxicity of cisplatin by 12-fold, (b) the restraint of cell clonogenic potential cisplatin-mediated, and (c) the number of apoptotic cells. Cisplatin, but not ADP, caused caspases activation; nevertheless, poly(ADP-ribose) polymerase-1 was not only cleaved in cisplatin-treated cells but also in cells treated with ADP alone. Furthermore, ADP, but not cisplatin, decreased mTOR and 6SK phosphorylations. Both ADP and cisplatin increased p53 protein, but ADP was also able to enhance p53 messenger RNA. P53 silencing resulted in a very large decrement of cell death induced by ADP or by cisplatin and reverted ADP effects on mTOR/S6K phosphorylation, suggesting that activated p53 may act as a negative regulator of mTOR. Consistently, the inhibition of mTOR by rapamycin also sensitized cells to cisplatin, and the effects of cisplatin plus rapamycin were identical to those obtained with cisplatin plus ADP. These findings suggest that the combination of ADP and cisplatin may be a promising strategy for the clinical treatment of cisplatin-resistant MPM.}, }
@article {pmid30140191, year = {2018}, author = {Kang, DM and Kim, JE and Kim, YK and Lee, HH and Kim, SY}, title = {Occupational Burden of Asbestos-Related Diseases in Korea, 1998-2013: Asbestosis, Mesothelioma, Lung Cancer, Laryngeal Cancer, and Ovarian Cancer.}, journal = {Journal of Korean medical science}, volume = {33}, number = {35}, pages = {e226}, pmid = {30140191}, issn = {1598-6357}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis ; Europe ; Female ; Humans ; Laryngeal Neoplasms ; Lung Neoplasms ; Male ; Mesothelioma ; Middle Aged ; Occupational Diseases/*chemically induced ; Occupational Exposure ; Ovarian Neoplasms ; Republic of Korea ; }, abstract = {BACKGROUND: Asbestos exposure causes asbestos-related diseases (ARDs) including asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer. Although Korea used substantial amounts of asbestos in the past, no study has focused on its occupational burden of disease (OBD). Therefore, this study aimed to determine the OBDs of ARDs in Korea.<br><br>METHODS: The CARcinogen Exposure (CAREX) database was used to determine the proportion of exposed population. Relative risks for lung cancer, laryngeal cancer, and ovarian cancer were used to determine the population-attributable fraction. Data for deaths caused by ARDs during 1998-2013 were obtained from the World Health Organization mortality database. The potential years of life lost (PYLL) and annual average PYLL (APYLL) indicated OBDs.<br><br>RESULTS: In Korea, the number of ARD-attributable deaths and PYLL due to all ARDs during 1998-2013 were 4,492 and 71,763.7, respectively. The number of attributable deaths and PYLL due to asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer were 37 and 554.2, 808 and 15,877.0, 3,256 and 47,375.9, 120 and 1,605.5, and 271 and 6,331.1, respectively; additionally, the APYLL were 15.0, 19.7, 14.6, 13.4, and 23.4, respectively, and the average age at death was 70.4, 62.6, 69.1, 69.9, and 61.8, respectively. Our study showed that although the use of asbestos has ceased in Korea, the incidence of ARDs tends to increase.<br><br>CONCLUSION: Therefore, efforts to reduce future OBDs of ARDs, including early detection and proper management of ARDs, are needed in Korea.}, }
@article {pmid30137349, year = {2018}, author = {Krupoves, A}, title = {Commentary: Asbestos exposure and mesothelioma risk.}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1758-1759}, doi = {10.1093/ije/dyy176}, pmid = {30137349}, issn = {1464-3685}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; United Kingdom ; }, }
@article {pmid30137211, year = {2019}, author = {Farioli, A and Mattioli, S and Curti, S and Spatari, G and Violante, FS}, title = {Letter to the editor re: Dragani et al. (2018), 'Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure'.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {487}, doi = {10.1093/carcin/bgy111}, pmid = {30137211}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30134140, year = {2018}, author = {Chatfield, EJ}, title = {Measurement of elongate mineral particles: What we should measure and how do we do it?.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {36-46}, doi = {10.1016/j.taap.2018.08.010}, pmid = {30134140}, issn = {1096-0333}, mesh = {Animals ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis/toxicity ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Mesothelioma, Malignant ; Microscopy, Electron, Transmission ; Mineral Fibers/*analysis/toxicity ; Minerals/*analysis/toxicity ; Occupational Exposure ; Particle Size ; Particulate Matter/*analysis/toxicity ; }, abstract = {The length distributions of single fibrils of Coalinga, UICC-B and wet dispersed chrysotile were measured by transmission electron microscopy (TEM). It was found that the distributions significantly diverged above approximately 10 μm (μm) in length, corresponding to differences in published results of animal experiments. This result is in contrast to published data in which counting of an insufficient number of fibers resulted in an erroneous conclusion that the length distribution of Coalinga chrysotile fibrils was indistinguishable from those of other sources of chrysotile. The size distributions of the respirable particle size fractions from acknowledged tremolite asbestos samples were found to be dominated by elongate particles longer than 5 μm that are within the dimensional range of non-asbestiform amphiboles. Prior studies have shown that these elongate particles obscure a correlation between a specific size range of particles and results of animal implantation studies that used tremolite of various morphologies. In the prior studies, a reference protocol was developed from four crushed non-asbestiform amphiboles to differentiate the size range of amphibole particles that correlates with the mesothelioma frequencies observed in the animal studies. In the work reported here, this correlation was tested with TEM analyses of amphiboles from Libby, MT, Sparta, NJ and Homestake mine, Lead, SD, which represent known environmental/occupational situations. Further TEM analyses of the tremolite samples used in the original animal implantation studies have also shown that the numbers of elongate tremolite particles with lengths ≤5 μm implanted into the animals are not correlated with the observed mesothelioma frequencies.}, }
@article {pmid30133855, year = {2018}, author = {Finkelstein, MM}, title = {Letter Concerning: Glynn ME, Keeton KA, Gaffney SH, Sahmel J. Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence Between Urban and Rural Areas in the United States (1973-2012). Risk Analysis 2018;38(3):454-471.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {8}, pages = {1521-1523}, doi = {10.1111/risa.13124}, pmid = {30133855}, issn = {1539-6924}, mesh = {*Asbestos ; Humans ; Incidence ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; United States ; }, }
@article {pmid30133854, year = {2018}, author = {Keeton, KA and Glynn, ME and Gaffney, SH and Sahmel, J}, title = {Response to Letter to the Editor Regarding "Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence Between Urban and Rural Areas in the United States (1973-2012)" by Finkelstein.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {8}, pages = {1524-1528}, doi = {10.1111/risa.13169}, pmid = {30133854}, issn = {1539-6924}, mesh = {*Asbestos ; Humans ; Incidence ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; United States ; }, }
@article {pmid30126335, year = {2018}, author = {Egilman, D and Bird, T and Wilson, R}, title = {Use of Anti-Warnings to Falsely Reassure Downstream Users: An Asbestos Example.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {28}, number = {3}, pages = {515-538}, doi = {10.1177/1048291118794198}, pmid = {30126335}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; *Communication ; Humans ; Industry/*organization &amp; administration ; Mesothelioma/chemically induced ; Occupational Exposure/*adverse effects ; Safety ; Uncertainty ; }, abstract = {Product warnings are theoretically designed to reduce injuries associated with occupational, environmental, or consumer product exposures. Unfortunately, in an effort to protect sales, some companies have produced media and information to falsely reassure their customers about the risks associated with their products. These tactics have been termed "anti-warnings." We reviewed corporate documents uncovered in litigation alongside other historical publications to ascertain the types of anti-warnings used by Union Carbide Corporation (UCC) regarding their asbestos products. Our review finds that UCC went to great lengths to confuse their customers and make their particular asbestos product-which contained short-fiber, chrysotile asbestos-look safe. We discuss three primary communications methods UCC used: industry-produced publications, sales force direct communication with customers, and public speeches. These examples provide further insight into how corporations encourage uncertainty about the risks associated with their products. Understanding anti-warning methods is critical for the implementation of future policies that protect consumer, worker, and environmental health.}, }
@article {pmid30123503, year = {2018}, author = {Bosio, M and Salvaterra, E and Datturi, F and Morbini, P and Zorzetto, M and Inghilleri, S and Tomaselli, S and Mangiarotti, P and Meloni, F and Cerveri, I and Stella, GM}, title = {5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin.}, journal = {Multidisciplinary respiratory medicine}, volume = {13}, number = {}, pages = {27}, pmid = {30123503}, issn = {1828-695X}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM's molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic lesions that usually characterize solid epithelial-derived tumors. On this basis, our study aims at investigating MPM epigenetic profile.<br><br>METHODS: We here assessed through immunohistochemistry, FISH and methylation specific PCR, the expression of 5-hydroxymethylcytosine (5- hmC) - an epigenetic marker and an important regulator of embryonic development and carcinogenesis - and the methylation status of the promoter of the MTAP gene - encoding for an enzyme involved in the rescue process of methionine and adenine - in two relevant series of FF-PE MPM samples derived from MPM thoracoscopic biopsies. Tissue sampling was performed at diagnosis.<br><br>RESULTS: Within the limitations of the study cohort, the 5-hmC immunophenotype was different among the histological MPM types analysed. In fact, 18% of the epithelial MPMs were negative, 47% weakly positive, and 35% of the cases showed an intense expression of 5-hmC. Sarcomatoid and biphasic MPMs showed intense 5-hmC expression pattern (positive and weakly positive in more than 80% of cases). Among MPM featuring epithelial lineage, none showed methylation of MTAP promoter.<br><br>CONCLUSIONS: Mesothelial sarcomatoid tumors featured a methylation profile characterized by a permanent gene silencing. Epithelial MPM methylation profile was in-between that of sarcomatoid MPM and the one of epithelial-derived tumors. MTAP promoter methylation level cannot be considered a suitable biomarker of epithelial MPM arousal.}, }
@article {pmid30118736, year = {2019}, author = {Smith-Hannah, A and Naous, R}, title = {Primary peritoneal epithelioid mesothelioma of clear cell type with a novel VHL gene mutation: a case report.}, journal = {Human pathology}, volume = {83}, number = {}, pages = {199-203}, doi = {10.1016/j.humpath.2018.07.033}, pmid = {30118736}, issn = {1532-8392}, mesh = {Female ; Humans ; Mesothelioma/*genetics/*pathology ; Middle Aged ; Mutation ; Peritoneal Neoplasms/*genetics/*pathology ; Von Hippel-Lindau Tumor Suppressor Protein/*genetics ; }, abstract = {Clear cell variant of epithelioid mesothelioma is an extremely rare tumor with only isolated cases reported so far in the peritoneum. Here, we report a case of peritoneal epithelioid mesothelioma, clear cell variant, in a 63-year-old female patient with a novel VHL gene mutation and an unusual indolent clinical course. The patient, who has no clinical history of asbestos exposure, presented with a 27.2-cm upper abdominal mass and a 5.5-cm liver lesion. Retrospective review of the patient's abdominal computed tomographic scan 4 years ago showed 2 small abdominal lesions that were felt clinically to represent hemangiomas. These were retrospectively considered to have grown in size and represented the current abdominal mass. Both masses were subsequently biopsied and showed a proliferation of monomorphic epithelioid cells with distinct cell membranes, fine chromatin, and clear to finely vacuolated pale eosinophilic cytoplasm arranged in nests and solid sheets. Immunohistochemical staining confirmed it to be malignant mesothelioma. Clear cell variant of peritoneal epithelioid mesothelioma should always be considered in patients with an abdominal or pelvic mass with clear cell features. Given the rarity of such entity, its clinical course and prognosis remains unclear.}, }
@article {pmid30113886, year = {2018}, author = {Panou, V and Gadiraju, M and Wolin, A and Weipert, CM and Skarda, E and Husain, AN and Patel, JD and Rose, B and Zhang, SR and Weatherly, M and Nelakuditi, V and Knight Johnson, A and Helgeson, M and Fischer, D and Desai, A and Sulai, N and Ritterhouse, L and Røe, OD and Turaga, KK and Huo, D and Segal, J and Kadri, S and Li, Z and Kindler, HL and Churpek, JE}, title = {Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {36}, number = {28}, pages = {2863-2871}, pmid = {30113886}, issn = {1527-7755}, support = {T35 DK062719/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Genetic Predisposition to Disease/genetics ; Germ-Line Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Young Adult ; }, abstract = {PURPOSE: The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM).<br><br>METHODS: We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.<br><br>RESULTS: Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54).<br><br>CONCLUSION: A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.}, }
@article {pmid30111295, year = {2018}, author = {Löffler, MW and Steinhilber, J and Hilke, FJ and Haen, SP and Bösmüller, H and Montes-Mojarro, IA and Bonzheim, I and Stäbler, A and Faust, U and Grasshoff, U and Königsrainer, I and Rammensee, HG and Kanz, L and Königsrainer, A and Beckert, S and Riess, O and Schroeder, C}, title = {First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications.}, journal = {BMC medical genetics}, volume = {19}, number = {1}, pages = {144}, pmid = {30111295}, issn = {1471-2350}, mesh = {Carcinoma, Verrucous/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Mouth Neoplasms/*genetics ; PTEN Phosphohydrolase/*genetics ; Rare Diseases ; }, abstract = {BACKGROUND: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported.<br><br>CASE PRESENTATION: We here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36&#xa0;years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing.<br><br>DISCUSSION AND CONCLUSIONS: We here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.}, }
@article {pmid30109162, year = {2018}, author = {Salazar, C and Kanter Md, N and Abboud, A}, title = {Malignant Pleural Mesothelioma, Biphasic Type: An Unusual and Insidious Case of Rapidly Progressive Small Blue Cell Tumor.}, journal = {Cureus}, volume = {10}, number = {6}, pages = {e2749}, pmid = {30109162}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm. It predominantly affects elderly individuals aged over 70 years presenting with a unilateral pleural tumor usually associated with previous asbestos exposure. The respiratory symptoms are associated with ipsilateral pleural involvement with concomitant pleural effusions. The diagnosis of MPM is established by the morphologic and immunohistochemical features of a cytologic specimen. MPM can present as three histologic subtypes: epithelioid, sarcomatoid, or biphasic. We present a case of an 85-year-old Caucasian female with a history of occupational asbestos exposure. She complained of 1-week history of progressive sharp right flank and scapular pain with mild shortness of breath, dry cough and pleuritic chest pain. CT of the chest showed a large loculated right pleural effusion with adjacent pleural thickening. CT abdomen and pelvis was negative for other neoplastic findings. CT-guided core biopsy of the right pleural-based mass was positive for a spindle to plasmacytoid small blue cell tumor. An extensive immunohistochemical panel was non-specific. A focal OSCAR keratin and WT-1 expression in the absence of carcinoma markers, a malignant mesothelioma, biphasic type was diagnosed. Further workup with PET-CT and cytotoxic chemotherapy combined with immunotherapy or tyrosine kinase inhibitors was recommended by oncology. The patient refused further imaging and treatment, and palliative care was consulted.}, }
@article {pmid30104558, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Asbestos Exposure and the Mesothelioma Incidence in Poland.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, pmid = {30104558}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*statistics &amp; numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mesothelioma, Malignant ; Poland/epidemiology ; Risk Factors ; }, abstract = {UNLABELLED: Asbestos is carcinogenic to humans; the exposure to asbestos causes a wide range of diseases.<br><br>AIM: Malignant mesothelioma (MM) is unique for asbestos exposure.<br><br>METHODS: Based on the physical inventory of asbestos-cement roofing, the social-economic situation of communes, the proximity of asbestos manufacturing plants, the land use data referring to the surface of the built-up area, and the historical data on the annexations, the amount of asbestos-containing products in use was estimated by computing best Random Forest models. Per capita asbestos use is an indicator to compare the state of asbestos use among countries. MM cases in the local administrative units (provinces) were tested by the application of Moran's I and Getis and Ord statistic.<br><br>RESULTS: The total amount of asbestos roofing in Poland was estimated at 738,068,000 m&#xb2; (8.2 million tons). In total there were 28 plants in Poland located in 11 provinces throughout the country. The amount of asbestos-cement roofing in use is correlated primarily with the measurements of asbestos concentration fibers (rs = 0.597). MM raw morbidity rate was calculated, stratified by province, and classified into five groups with respect to incidence. Hotspots of MM cases are in the southern part of Poland.<br><br>CONCLUSIONS: MM cases are concentrated in the same geographical areas, which may indicate an increasing impact of environmental exposure. The results of the local and global autocorrelation clearly indicate a statistically significant relationship between incidences of MM in provinces. Poland and other Eastern European countries are among countries with low MM incidence rate. Detailed investigation is desirable since the current MM morbidity rate in Poland seems to be underestimated.}, }
@article {pmid30101018, year = {2018}, author = {Negi, Y and Kuribayashi, K and Doi, H and Funaguchi, N and Koda, Y and Fujimoto, E and Mikami, K and Minami, T and Yokoi, T and Kijima, T}, title = {Double cancer comprising malignant pleural mesothelioma and squamous cell carcinoma of the lung treated with radiotherapy: A case report.}, journal = {Molecular and clinical oncology}, volume = {9}, number = {2}, pages = {181-186}, pmid = {30101018}, issn = {2049-9450}, abstract = {Pleurectomy/decortication (P/D) is the surgical treatment of choice for early malignant mesothelioma, but it remains unclear whether radiotherapy along with P/D should be used as multimodal treatment for this disease. We herein present the case of a 76-year-old man with a history of asbestos exposure who was diagnosed with left-sided malignant pleural mesothelioma in February 2010. The patient underwent chemotherapy with a combination of cisplatin and pemetrexed and achieved stable disease, after which time he was kept under observation. A positron emission tomography/computed tomography scan performed in February 2011 revealed nodular shadows with fluorodeoxyglucose uptake in S3 of the left lung; using bronchoscopy, the patient was diagnosed with stage IIB (cT3N0M0) primary squamous cell carcinoma. Chemoradiotherapy with vinorelbine and 60 Gy/20 fr radiotherapy was performed, and a partial response was obtained, suggesting that the radiotherapy used to treat the carcinoma of the lung may have also helped control the disease activity of the pre-existing mesothelioma. The present case indicates the value of radiotherapy in the treatment of malignant mesothelioma. The aim of the present study was to examine the possibility of new multimodal treatments for mesothelioma, along with a discussion of the relevant literature.}, }
@article {pmid30098092, year = {2018}, author = {Aida, S and Aida, J and Naoi, M and Kato, M and Tsuura, Y and Natsume, I and Takubo, K}, title = {Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells.}, journal = {Pathology international}, volume = {68}, number = {9}, pages = {503-508}, doi = {10.1111/pin.12710}, pmid = {30098092}, issn = {1440-1827}, support = {JP C26460457//JSPS KAKENHI/ ; }, mesh = {Adenocarcinoma of Lung/pathology ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Effusion/pathology ; Pleural Effusion, Malignant/*pathology ; Telomere/*pathology ; }, abstract = {We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial cells and examined their correlation with asbestos exposure and the expression of markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from 35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM) and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-). Telomere length was measured using the tissue quantitative fluorescence in situ hybridization method, and expressed as normalized telomere-to-centromere ratio. NN cases had significantly longer telomeres than MM (P < 0.001) and LA (P < 0.001) cases. Telomeres in NNpp+ cases were slightly shorter than those of NNpp- cases (P = 0.047). MM and LA showed almost the same telomere length. NN cases with shorter telomeres tended to show aberrant expression of epithelial membrane antigen (EMA), CD146, glucose transporter 1 (GLUT1) and IGF-II messenger RNA-binding protein 3 (IMP3). These results suggest that telomere shortening and subsequent genetic instability play an important role in the development of MM. Measurement of telomere length of cells in pleural effusion might be helpful for earlier detection of MM.}, }
@article {pmid30084369, year = {2018}, author = {Lucas, C}, title = {Miracle mineral or mesothelioma: cancer and asbestos in the USA.}, journal = {The Lancet. Oncology}, volume = {19}, number = {7}, pages = {868}, doi = {10.1016/S1470-2045(18)30352-8}, pmid = {30084369}, issn = {1474-5488}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology/physiopathology ; *Medicine in the Arts ; Mesothelioma/epidemiology/etiology/physiopathology ; Mesothelioma, Malignant ; *Motion Pictures ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology/physiopathology ; United States/epidemiology ; }, }
@article {pmid30077661, year = {2018}, author = {Garabrant, DH and Pastula, ST}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {127-136}, doi = {10.1016/j.taap.2018.07.003}, pmid = {30077661}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*toxicity ; Aluminum Silicates/toxicity ; Asbestos/*toxicity ; Asbestos, Amosite/toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Carcinogens/*toxicity ; Cohort Studies ; Humans ; Iron/toxicity ; Lung Neoplasms/etiology/*mortality ; Mesothelioma/etiology/*mortality ; Minerals/*toxicity ; Mining ; Occupational Exposure ; Particle Size ; Particulate Matter/*toxicity ; Silicates/toxicity ; Talc/toxicity ; }, abstract = {We analyzed the mesothelioma mortality in cohorts of workers exposed to crocidolite, amosite, and chrysotile to estimate asbestos fiber potency for mesothelioma, using the method of Hodgson and Darnton (2000). We relied on the original 17 cohort studies in their analysis, along with 3 updates of those studies and 3 new asbestos cohort studies published since 2000. We extended the analyses to examine the mesothelioma potency of tremolite in vermiculite from Libby, Montana, and for non-asbestiform elongate mineral particles (EMPs) in taconite iron ore, talc, and South Dakota gold mining. Mesothelioma potency (RMeso) was calculated as the percent of all expected deaths that were due to mesothelioma per fiber/cc-year of exposure.The RMeso was 0.0012 for chrysotile, 0.099 for amosite, and 0.451 for crocidolite: thus, the relative potency of chrysotile:amosite:crocidolite was 1:83:376, which was not appreciably different from the estimates by Hodgson and Darnton in 2000. The RMeso for taconite mining fibers was 0.069 which was slightly smaller than that for amosite. The RMeso for Libby fibers was 0.028 which was greater than that for chrysotile and less than that for amosite. Talc and gold mining EMPs were non-potent for mesothelioma. Although there are a number of methods for estimating fiber potency of asbestos and non-asbestiform EMPs, the method of Hodgson and Darnton provides a uniform method by which fiber potency can be compared across many fiber types. Our estimates of RMeso provide a useful addition to our knowledge of mesothelioma potency for different asbestos and non-asbestiform EMP fibers.}, }
@article {pmid30072200, year = {2019}, author = {Lin, RT and Chang, YY and Wang, JD and Lee, LJ}, title = {Upcoming epidemic of asbestos-related malignant pleural mesothelioma in Taiwan: A prediction of incidence in the next 30 years.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {1 Pt 3}, pages = {463-470}, doi = {10.1016/j.jfma.2018.07.013}, pmid = {30072200}, issn = {0929-6646}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Female ; *Forecasting ; Humans ; Incidence ; Infant ; Infant, Newborn ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/chemically induced/*epidemiology ; Regression Analysis ; Sex Distribution ; Taiwan/epidemiology ; Young Adult ; }, abstract = {BACKGROUND/PURPOSE: Globally, asbestos-related diseases (ARDs) keep rising over the coming decades. The epidemic of ARDs will be a burden on public health. We aimed to predict the malignant pleural mesothelioma (MPM) incidence in the next 30 years for Taiwan based on historical asbestos consumption.<br><br>METHODS: We collected annual data on local asbestos consumption during 1939-2015 and sex-specific incidence of pleural cancer as a proxy for MPM during 1979-2013. We applied Poisson log-linear models to predict future MPM numbers under the assumption that latency periods between asbestos exposure and MPM incidence were between 25 and 45 years.<br><br>RESULTS: Asbestos consumption reached a peak in the 1980s, with a total of 668 thousand metric tons during 1939-2015. The observed number of MPM incidence increased by 9- and 6-fold in males and females during 1979-2013, with a cumulative number of 907. Given a latency period of 31 years, MPM incidences were expected to peak around 2012-2016 for males and 2016-2020 for females. In 2017-2046, the predicted total number of new MPM might reach 659 cases (95% confidence interval&#xa0;=&#xa0;579-749); and the male to female ratios ranged from 1.8 to 2.8.<br><br>CONCLUSION: The MPM epidemic in Taiwan will likely peak in 2012-2020 as a result of local asbestos consumption. Approximately 659 new MPM cases in the next 30 years warrant an urgent need to implement a total asbestos ban and put more resources on a comprehensive surveillance, diagnosis, and follow-up health care system for ARDs.}, }
@article {pmid30060501, year = {2018}, author = {Sage, AP and Martinez, VD and Minatel, BC and Pewarchuk, ME and Marshall, EA and MacAulay, GM and Hubaux, R and Pearson, DD and Goodarzi, AA and Dellaire, G and Lam, WL}, title = {Genomics and Epigenetics of Malignant Mesothelioma.}, journal = {High-throughput}, volume = {7}, number = {3}, pages = {}, pmid = {30060501}, issn = {2571-5135}, abstract = {Malignant mesothelioma is an aggressive and lethal asbestos-related disease. Diagnosis of malignant mesothelioma is particularly challenging and is further complicated by the lack of disease subtype-specific markers. As a result, it is especially difficult to distinguish malignant mesothelioma from benign reactive mesothelial proliferations or reactive fibrosis. Additionally, mesothelioma diagnoses can be confounded by other anatomically related tumors that can invade the pleural or peritoneal cavities, collectively resulting in delayed diagnoses and greatly affecting patient management. High-throughput analyses have uncovered key genomic and epigenomic alterations driving malignant mesothelioma. These molecular features have the potential to better our understanding of malignant mesothelioma biology as well as to improve disease diagnosis and patient prognosis. Genomic approaches have been instrumental in identifying molecular events frequently occurring in mesothelioma. As such, we review the discoveries made using high-throughput technologies, including novel insights obtained from the analysis of the non-coding transcriptome, and the clinical potential of these genetic and epigenetic findings in mesothelioma. Furthermore, we aim to highlight the potential of these technologies in the future clinical applications of the novel molecular features in malignant mesothelioma.}, }
@article {pmid30060470, year = {2018}, author = {Jean, D and Jaurand, MC}, title = {Mesotheliomas in Genetically Engineered Mice Unravel Mechanism of Mesothelial Carcinogenesis.}, journal = {International journal of molecular sciences}, volume = {19}, number = {8}, pages = {}, pmid = {30060470}, issn = {1422-0067}, mesh = {Animals ; *Animals, Genetically Modified ; Carcinogenesis/*genetics ; Epithelium/pathology ; Humans ; Lung/pathology ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; *Mice ; Mutation ; Neoplasms, Experimental/*genetics ; Rats ; }, abstract = {Malignant mesothelioma (MM), a rare and severe cancer, mainly caused as a result of past-asbestos exposure, is presently a public health concern. Current molecular studies aim to improve the outcome of the disease, providing efficient therapies based on the principles of precision medicine. To model the molecular profile of human malignant mesothelioma, animal models have been developed in rodents, wild type animals and genetically engineered mice harbouring mutations in tumour suppressor genes, especially selecting genes known to be inactivated in human malignant mesothelioma. Animals were either exposed or not exposed to asbestos or to other carcinogenic fibres, to understand the mechanism of action of fibres at the molecular level, and the role of the selected genes in mesothelial carcinogenesis. The aim of the manuscript was to compare mesothelioma models to human malignant mesothelioma and to specify the clue genes playing a role in mesothelial carcinogenesis. Collectively, MM models recapitulate the clinical features of human MM. At least two altered genes are needed to induce malignant mesothelioma in mice. Two pathways regulated by Cdkn2a and Trp53 seem independent key players in mesothelial carcinogenesis. Other genes and pathways appear as bona fide modulators of the neoplastic transformation.}, }
@article {pmid30049702, year = {2018}, author = {Lin, RT and Soeberg, MJ and Chien, LC and Fisher, S and Takala, J and Lemen, R and Driscoll, T and Takahashi, K}, title = {Bibliometric analysis of gaps in research on asbestos-related diseases: declining emphasis on public health over 26 years.}, journal = {BMJ open}, volume = {8}, number = {7}, pages = {e022806}, pmid = {30049702}, issn = {2044-6055}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Bibliometrics ; Biomedical Research/*trends ; China ; Finland ; Humans ; Italy ; Mesothelioma/*etiology ; Netherlands ; Public Health/trends ; }, abstract = {OBJECTIVES: The global burden of asbestos-related diseases (ARDs) is significant, and most of the world's population live in countries where asbestos use continues. We examined the gaps between ARD research and suggestions of WHO and the International Labour Organization on prevention.<br><br>METHODS: From the Web of Science, we collected data on all articles published during 1991-2016 and identified a subset of ARD-related articles. We classified articles into three research areas-laboratory, clinical and public health-and examined their time trends. For all and the top 11 countries publishing ARD-related articles, we calculated the proportions of all ARD-related articles that were in each of the three areas, the average rates of ARD-related articles over all articles, and the average annual per cent changes of rates.<br><br>RESULTS: ARD-related articles (n=14&#x2009;284) accounted for 1.3&#x2030; of all articles in 1991, but this had declined to 0.8&#x2030; by 2016. Among the three research areas, the clinical area accounted for the largest proportion (65.0%), followed by laboratory (26.5%) and public health (24.9%). The public health area declined faster than the other areas, at -5.7% per year. Discrepancies were also observed among the top 11 countries regarding emphasis on public health research, with Finland and Italy having higher, and China and the Netherlands lower, emphases.<br><br>CONCLUSIONS: There is declining emphasis on the public health area in the ARD-related literature. Under the ongoing global situation of ARD, primary prevention will remain key for some time, warranting efforts to rectify the current trend in ARD-related research.}, }
@article {pmid30032843, year = {2018}, author = {Rosskamp, M and De Schutter, H and Henau, K and Nackaerts, K and Van Meerbeeck, JP and Praet, M and Van Eycken, L}, title = {Assessing the completeness and correctness of the registration of malignant mesothelioma in Belgium.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {122}, number = {}, pages = {38-43}, doi = {10.1016/j.lungcan.2018.05.018}, pmid = {30032843}, issn = {1872-8332}, mesh = {Aged ; Asbestos/*adverse effects ; Belgium/epidemiology ; Cohort Studies ; *Databases, Factual ; Female ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Registries/*statistics &amp; numerical data ; Survival Analysis ; Survivors ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a rare and aggressive cancer mostly caused by asbestos exposure, and for which the diagnosis is difficult. This study aimed to assess the completeness and correctness of MM registration using 3 independent national databases: the Belgian Cancer Registry (BCR), the population-based mortality statistics (certificates of death, COD), and the Belgian Mesothelioma Registry (BMR).<br><br>METHODS: The study cohort included all MM reported to the BCR and diagnosed between 2004 and 2012 (n&#x202f;=&#x202f;2292), all patients reviewed by the pathology commission of the BMR (2004-2012; n&#x202f;=&#x202f;2019), and COD data for all Belgian citizens (2004-2013). Available data were compared in terms of registered cases, histological diagnosis, performed immunohistochemical (IHC) tests, and IHC test results.<br><br>RESULTS: Comparison of BCR with BMR registrations showed 94.8% concordant cases. The proportion of MM diagnoses originally reported to BCR with unspecified MM morphology was reduced from 25.8% to less than 1%.<br><br>RESULTS: from IHC tests were available for 95.3% of concordant MM cases. Different IHC patterns could be distinguished by MM histology. MM cases registered at BCR for which COD mentioned an MM as underlying cause of death represented 76.4% of deceased cases. MM long-term survivors (survival >3&#x202f;years; 10.9%) were characterised by distinct clinical and biological characteristics.<br><br>CONCLUSIONS: A comparison of independent Belgian MM registration databases elucidated under-registration and misclassification and revealed possible reasons for observed discordances. Combining all the available information resulted in enhanced completeness and correctness of MM registration in Belgium and allowed for the identification and characterisation of MM long-term survivors.}, }
@article {pmid30030099, year = {2018}, author = {Sonvico, F and Barbieri, S and Colombo, P and Barocelli, E and Mucchino, C and Cantoni, AM and Petronini, PG and Rusca, M and Carbognani, P and Ampollini, L}, title = {Combined hyaluronate-based films loaded with pemetrexed and cisplatin for the treatment of malignant pleural mesothelioma: Preliminary evaluation in an orthotopic tumor recurrence model.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {123}, number = {}, pages = {89-97}, doi = {10.1016/j.ejps.2018.07.035}, pmid = {30030099}, issn = {1879-0720}, mesh = {Animals ; *Antineoplastic Agents/administration &amp; dosage/therapeutic use ; Cell Line, Tumor ; *Cisplatin/administration &amp; dosage/therapeutic use ; *Drug Carriers ; *Hyaluronic Acid ; Lung Neoplasms/*drug therapy ; Male ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Neoplasm Recurrence, Local/drug therapy ; *Pemetrexed/administration &amp; dosage/therapeutic use ; Pleural Neoplasms/*drug therapy ; Rats ; Rats, Inbred F344 ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by a long latency period of 20-50 years after exposure to the main aetiology agent that is asbestos. MPM treatments include surgery, chemotherapy, and radiation therapy, with the combination pemetrexed and cisplatin being the standard chemotherapy approach. Despite this multimodality therapy one of the major issues after surgery is the high rate of local recurrence of the tumor. One possible approach would be the intrapleural application of implants loaded with anticancer drug to be applied during surgery to prevent local tumor recurrence. The implant proposed in the present work is a polymeric film of hyaluronic acid loaded with pemetrexed. The film developed is a hydrophilic, thin and flexible film sufficiently resistant to be applied intrapleurally adhering to the mesothelial surface. The release of pemetrexed from the film was found to be complete within2 h in phosphate buffered saline. In an orthotopic model of mesothelioma recurrence in rats, pemetrexed loaded films showed the same antitumor efficacy of pemetrexed disodium solutions administered intravenously or intrapleurally, while when administered in combination with cisplatin-loaded hyaluronate film, the implants almost completely prevented tumor recurrence. The local administration of drug-loaded polymer implants appears an ideal chemotherapy strategy especially for patients in which surgery is already selected as a viable therapeutic option.}, }
@article {pmid30030095, year = {2018}, author = {Mossman, BT}, title = {Mechanistic in vitro studies: What they have told us about carcinogenic properties of elongated mineral particles (EMPs).}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {62-67}, doi = {10.1016/j.taap.2018.07.018}, pmid = {30030095}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Asbestos/toxicity ; Carcinogenesis ; Carcinogens/*toxicity ; Cell Transformation, Neoplastic/drug effects ; Chromosomes/drug effects ; DNA/drug effects ; Humans ; Minerals/*toxicity ; }, abstract = {In vitro studies using target and effecter cells of mineral-induced cancers have been critical in determining the mechanisms of pathogenesis as well as the properties of elongated mineral particles (EMPs) important in eliciting these responses. Historically, in vitro models of 'mutagenesis' and immortalized cell lines were first used to test the theory that EMPs were mutagenic to cells, and 'genotoxicity', as defined as damage to DNA often culminating in cell death, was observed in a dose-dependent fashion as responses of many cell types to a number of EMPs. As two-stage and multi-step models of cancer development emerged in the 1970s and 1980s, differentiated 3D organ cultures and monolayers of lung epithelial and mesothelial cells were used to probe the mechanisms of cancer development. These studies demonstrated a spectrum of pre-neoplastic changes, including hyperplasia and squamous metaplasia, in response to long (>5 μm in length) needlelike EMPs whereas long, curly chrysotile fibers caused acute cytotoxicity. Shorter fibers of many types were taken up by cells and encompassed in phagolysosomes. Comparative studies using chemical carcinogens showed that chemical agents interacted directly with DNA whereas long EMPs appeared to be promoters of cancers via a number of mechanisms such as inflammation, generation of oxidants, and instigation of cell division. The multitude of these signaling cascades and epigenetic mechanisms of both lung cancers and mesotheliomas have been most recently studied in normal or telomerase immortalized human cells. Importantly, many of these pathways are elicited by long, straight amphibole asbestos fibers or carbon nanotubes in rodents and not by short (<5 μm) EMPs, fragments, or nonfibrous particles. However, the chemistry and surface properties of long fibers are also critical in cell responses to minerals.}, }
@article {pmid30030093, year = {2018}, author = {Abello, A and Steinkeler, J and Das, AK}, title = {A Bilateral Metachronous Mesothelioma of the Tunica Vaginalis.}, journal = {Urology}, volume = {120}, number = {}, pages = {e1-e2}, doi = {10.1016/j.urology.2018.07.003}, pmid = {30030093}, issn = {1527-9995}, abstract = {This is a unique case of bilateral metachronous testicular mesothelioma of the tunica vaginalis. Testicular mesothelioma is a rare entity found in patients with or without asbestos occupational exposure. The tumor most commonly presents as a unilateral testicular mass. More rare presentations include bilateral synchronous or metachronous tumors. Treatment is with surgical resection and prognosis is not generally favorable. The benefits of adjuvant therapy with radiation or chemotherapy remain unknown and further studies are needed.}, }
@article {pmid30025147, year = {2019}, author = {Panou, V and Vyberg, M and Meristoudis, C and Hansen, J and Bøgsted, M and Omland, &#xd8; and Weinreich, UM and Røe, OD}, title = {Non-occupational exposure to asbestos is the main cause of malignant mesothelioma in women in North Jutland, Denmark.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {45}, number = {1}, pages = {82-89}, doi = {10.5271/sjweh.3756}, pmid = {30025147}, issn = {1795-990X}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Denmark/epidemiology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Registries ; Risk Assessment ; }, abstract = {Objectives Diffuse malignant mesothelioma (MM) is mainly caused by asbestos inhalation. The malignancy is rare among women and studies of the prevalence and causative role of non-occupational asbestos exposure among women with MM are scarce. This observational study aimed to elucidate the asbestos exposure patterns among women with MM. Methods All histological and cytological specimens from women diagnosed with MM between 1974-2015 at the Institute of Pathology, Aalborg University Hospital in Denmark, were re-evaluated. Occupational and habitation information were obtained from Danish registries and medical journals based on record linkage via the unique person ID. The number of MM cases in each parish in the region of North Jutland was determined and the incidence density in parishes was used to calculate the spatial relative risk (RR) of MM among women. Results Diagnosis of MM was confirmed in 91 women. Exposure types were classified as occupational (9%), domestic (10%), environmental (22%), combination of domestic and environmental (34%) and unknown (25%). Twenty continuous parishes formed a MM "hotspot" around the asbestos-consuming industries in the city of Aalborg. Of these, the maximum RR was found in a parish housing an asbestos factory [RR 10.5, 95% confidence interval (CI) 5.5-19.4, environmental exposure in particular RR 2.9, 95% CI 0.7-6.1]. Conclusion Non-occupational asbestos exposure is the main cause of MM and may account for up to 66% of MM cases among women in North Jutland, Denmark.}, }
@article {pmid30022998, year = {2018}, author = {Nabavi, N and Wei, J and Lin, D and Collins, CC and Gout, PW and Wang, Y}, title = {Pre-clinical Models for Malignant Mesothelioma Research: From Chemical-Induced to Patient-Derived Cancer Xenografts.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {232}, pmid = {30022998}, issn = {1664-8021}, abstract = {Malignant mesothelioma (MM) is a rare disease often associated with environmental exposure to asbestos and other erionite fibers. MM has a long latency period prior to manifestation and a poor prognosis. The survival post-diagnosis is often less than a year. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. Occupational exposure to asbestos, mining, and migration are reasons that we expect to continue to see growing incidence of mesothelioma in the coming decades. Despite improvements in survival achieved with multimodal therapies and cytoreductive surgeries, less morbid, more effective interventions are needed. Thus, identifying prognostic and predictive biomarkers for MM, and developing novel agents for targeted therapy, are key unmet needs in mesothelioma research and treatment. In this review, we discuss the evolution of pre-clinical model systems developed to study MM and emphasize the remarkable capability of patient-derived xenograft (PDX) MM models in expediting the pre-clinical development of novel therapeutic approaches. PDX disease model systems retain major characteristics of original malignancies with high fidelity, including molecular, histopathological and functional heterogeneities, and as such play major roles in translational research, drug development, and precision medicine.}, }
@article {pmid30018519, year = {2018}, author = {Strbac, D and Goricar, K and Dolzan, V and Kovac, V}, title = {Matrix Metalloproteinases Polymorphisms as Baseline Risk Predictors in Malignant Pleural Mesothelioma.}, journal = {Radiology and oncology}, volume = {52}, number = {2}, pages = {160-166}, pmid = {30018519}, issn = {1318-2099}, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure.<br><br>PATIENTS AND METHODS: The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%-75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).<br><br>RESULTS: Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44-1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35-0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma.<br><br>CONCLUSIONS: The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.}, }
@article {pmid30009035, year = {2018}, author = {An, YS and Kim, HD and Kim, HC and Jeong, KS and Ahn, YS}, title = {The characteristics of asbestos-related disease claims made to the Korea Workers' Compensation and Welfare Service (KCOMWEL) from 2011 to 2015.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {45}, pmid = {30009035}, issn = {2052-4374}, abstract = {BACKGROUND: This study aimed to enhance understanding of the epidemiologic characteristics of asbestos-related diseases, and to provide information that could inform policy-making aimed at prevention and compensation for occupational asbestos exposure, through analyzing asbestos-related occupational disease claims to Korea Workers' Compensation and Welfare Service from 2011 to 2015.<br><br>METHODS: We analyzed 113 workers who filed medical care claims or survivor benefits for asbestos exposure and occupational-related disease from 2011 to 2015. Among these claims, we selected approved workers' compensation claims relating to malignant mesothelioma and lung cancer, and analyzed the general characteristics, exposure characteristics, pathological characteristics, and occupation and industry distribution.<br><br>RESULTS: Malignant mesothelioma and lung cancer occurred predominantly in males at 89.7 and 94%, respectively. The mean age at the time of diagnosis for malignant mesothelioma and lung cancer was 59.5 and 59.7&#xa0;years, respectively, while the latency period for malignant mesothelioma and lung cancer was 34.1 and 33.1&#xa0;years, respectively. The companies involving exposed workers were most commonly situated within the Busan-Ulsan-Gyeongnam region. Histology results for lung cancer indicated adenocarcinoma as the most common form, accounting for approximately one half of all claims, followed by squamous cell carcinoma, and small cell lung cancer. The most common occupation type was construction in respect of malignant mesothelioma, and shipbuilding in respect of lung cancer.<br><br>CONCLUSIONS: Considering the long latency period of asbestos and that the peak period of asbestos use in Korea was throughout the mid-1990s, damage due to asbestos-related diseases is expected to show a continued long-term increase. Few studies providing an epidemiologic analysis of asbestos-related diseases are available; therefore, this study may provide baseline data to assist in predicting and preparing for future harm due to asbestos exposure.<br><br>TRIAL REGISTRATION: DUIH 2018-02-004-001. Registered 28 Februrary 2018.}, }
@article {pmid30008600, year = {2018}, author = {Aguilar-Madrid, G and Pesch, B and Calderón-Aranda, ES and Burek, K and Jiménez-Ramírez, C and Juárez-Pérez, CA and Ochoa-Vázquez, MD and Torre-Bouscoulet, L and Acosta-Saavedra, LC and Sada-Ovalle, I and García-Figueroa, J and Alvarado-Cabrero, I and Castillo-González, P and Báez-Saldaña, AR and Pérez-Padilla, JR and Osnaya-Juárez, J and Rivera-Rosales, RM and García-Bazán, EM and Bautista-Aragón, YL and Lazcano-Hernandez, E and Munguía-Canales, DA and Argote-Greene, LM and Taeger, D and Weber, DG and Casjens, S and Raiko, I and Brüning, T and Johnen, G}, title = {Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.}, journal = {International journal of medical sciences}, volume = {15}, number = {9}, pages = {883-891}, pmid = {30008600}, issn = {1449-1907}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Calbindin 2/*blood ; Case-Control Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mexico ; Middle Aged ; Pleural Neoplasms/blood/*diagnosis ; }, abstract = {Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.}, }
@article {pmid30001711, year = {2018}, author = {Kittaneh, M and Berkelhammer, C}, title = {Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefits to patient and family members.}, journal = {Journal of translational medicine}, volume = {16}, number = {1}, pages = {194}, pmid = {30001711}, issn = {1479-5876}, mesh = {Female ; Germ-Line Mutation/*genetics ; Humans ; Laparoscopy ; Lung Neoplasms/diagnostic imaging/*genetics/pathology ; Male ; Mesothelioma/diagnostic imaging/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pedigree ; Peritoneal Neoplasms/diagnostic imaging/*genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Germline mutations in the BRCA-1 associated tumor protein 1 (BAP1) increase susceptibility to mesothelioma and other cancers. We describe a patient with a family history of peritoneal mesothelioma, who developed malignant peritoneal mesothelioma at age 45 in the absence of known asbestos exposure. These findings lead us to hypothesize that the mesothelioma occurred in the setting of germline a BAP1 mutation. This was confirmed by genetic testing. The subsequent therapeutic choices for the patient and testing of at-risk family members highlight the importance of recognizing this genetic syndrome and screening for individuals at high risk.}, }
@article {pmid29990795, year = {2018}, author = {Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Zona, A and Conti, S and Comba, P}, title = {Epidemiological surveillance of mesothelioma mortality in Italy.}, journal = {Cancer epidemiology}, volume = {55}, number = {}, pages = {184-191}, doi = {10.1016/j.canep.2018.06.010}, pmid = {29990795}, issn = {1877-783X}, mesh = {Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*mortality ; Male ; Mesothelioma/*epidemiology/*mortality ; Mesothelioma, Malignant ; Pleural Neoplasms/*epidemiology/*mortality ; *Population Surveillance ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is causally linked to asbestos exposure with an estimated etiological fraction of 80% or more.<br><br>METHODS: Standardized rates of all mesothelioma (C45, ICD-10) and malignant pleural mesothelioma (C45.0, ICD-10) mortality in Italy were computed at national and regional levels, for the period 2003-2014. Standardized Mortality Ratios (SMRs, with 95% Confidence Intervals) were calculated for each of the 8047 Italian municipalities, for both diseases, with respect to Regional figures. A geographical clustering analysis at municipal level was performed, applying SatScan methods.<br><br>RESULTS: In Italy, 16,086 persons (about 1,340/year) died for MM, in analysed period. National Standardized rates of MM mortality are 3.65/100,000 in men and 1.09/100,000 in women, with an increasing annual trend, among male population. The highest rates were found in men from Northern Regions. Significant clusters (p&#x202f;<&#x202f;0.10) were found corresponding to areas that hosted major asbestos-cement plants, naval shipyards, petrochemical plants and refineries. Furthermore, excesses were found corresponding to chemical and textile industries; the latter involving, particularly, female population. Excesses were found also in areas near the chrysotile mine of Balangero, and in Biancavilla, a town with a stone quarry contaminated by fluoro-edenitic fibres; an excess of MM mortality was observed among male population living in a minor island where a Navy shipyard is located.<br><br>CONCLUSIONS: Mortality for mesothelioma in Italy is still increasing, twenty-six years after the asbestos ban. Epidemiological surveillance of mesothelioma mortality allows to detect the temporal trend of the disease and highlights previously unknown or underestimated sources of asbestos exposure.}, }
@article {pmid29982378, year = {2018}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {39}, number = {9}, pages = {1151-1156}, doi = {10.1093/carcin/bgy089}, pmid = {29982378}, issn = {1460-2180}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*analysis/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced/*diagnosis ; Male ; Mesothelioma/*chemically induced/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; }, abstract = {Asbestos exposure is the main etiology of malignant mesothelioma, but there are conflicting data on whether the intensity of exposure modulates the development of this disease. This study considered 594 patients with malignant mesothelioma for whom count data on asbestos bodies and fibers (per gram of wet lung tissue) were available. The relationships between age at diagnosis (a time-to-event outcome variable) and these two measures of internal asbestos exposure, along with other possible modulating factors (sex, tumor location, histological subtype and childhood exposure), were assessed on multivariable Cox proportional hazard models, stratifying by decade of birth year. For both measures of asbestos in lung tissue, younger age at diagnosis was associated with higher internal measures of exposure to asbestos. Stratified Cox analyses showed that for each doubling in asbestos body count patients were 1.07 times more likely to be diagnosed at a younger age [hazard ratio (HR) = 1.07; 95% confidence interval (CI), 1.04-1.09; P = 2.2 × 10-7] and for each doubling in asbestos fiber count patients were 1.13 times more likely to be diagnosed at a younger age (HR = 1.13; 95% CI, 1.09-1.17; P = 8.6 × 10-11). None of the other variables considered were associated with age at diagnosis. Our finding that tumors become clinically apparent at a younger age in heavily exposed subjects suggests that asbestos is involved not only in the malignant mesothelioma tumor initiation but, somehow, also in the progression of the disease.}, }
@article {pmid29977434, year = {2018}, author = {Pranay, P and Serafimov, V and Hall, J and Goel, A and Mushtaq, M}, title = {Metastatic biphasic pleural mesothelioma presenting with cauda equina syndrome.}, journal = {Radiology case reports}, volume = {13}, number = {3}, pages = {736-739}, pmid = {29977434}, issn = {1930-0433}, abstract = {Patient with previous asbestos exposure on a watchful wait and watch regime presents acutely with cauda equina syndrome. Radiological imaging confirmed a mass with direct invasion of the spinal cord. Histology confirmed metastatic pleural mesothelioma.}, }
@article {pmid29970876, year = {2018}, author = {Jones, RG and Karthik, F and Dugar, A and Kanagarajan, K and Desai, K and Bhandari, M}, title = {Nivolumab Immunotherapy in Malignant Mesothelioma: A Case Report Highlighting a New Opportunity for Exceptional Outcomes.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {783-789}, pmid = {29970876}, issn = {1941-5923}, mesh = {Aged ; Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Immunotherapy ; Male ; Mesothelioma/*drug therapy ; Nivolumab ; Pleural Neoplasms/*drug therapy ; Treatment Outcome ; }, abstract = {BACKGROUND Malignant pleural mesothelioma (MPM) is a highly lethal cancer with a median survival of ~12 months even with aggressive intervention. Frontline therapy relies on systemic cisplatin and pemetrexed chemotherapy and has a response rate of ~35-41%; currently, there are no US Food and Drug Administration approved second-line therapies for MPM. Herein, we present a patient with MPM who experienced rapid disease progression after standard therapy but who had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. CASE REPORT A 68-year-old male with a history of work-related asbestos exposure was diagnosed with MPM. He was treated with primary resection followed by systemic chemotherapy with cisplatin and pemetrexed. When chemotherapy failed, he was switched to immunotherapy with nivolumab and achieved an exceptional response. CONCLUSIONS We report the first case of a patient with MPM who experienced rapid disease progression after standard therapy but had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. As outcomes with traditional chemotherapy regimens remain disappointing, there is a substantial need for new approaches to MPM; our case highlights a new therapeutic opportunity even in the face of aggressive disease. Indeed, a new era of investigation utilizing immunotherapy for mesothelioma is beginning, with much anticipation.}, }
@article {pmid29966799, year = {2018}, author = {Mutti, L and Peikert, T and Robinson, BWS and Scherpereel, A and Tsao, AS and de Perrot, M and Woodard, GA and Jablons, DM and Wiens, J and Hirsch, FR and Yang, H and Carbone, M and Thomas, A and Hassan, R}, title = {Scientific Advances and New Frontiers in Mesothelioma Therapeutics.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {9}, pages = {1269-1283}, pmid = {29966799}, issn = {1556-1380}, support = {Z01 BC010816-01//Intramural NIH HHS/United States ; }, mesh = {Humans ; *Lung Neoplasms ; *Mesothelioma ; Mesothelioma, Malignant ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium, and rarely, the tunica vaginalis. The incidence of MPM is expected to increase worldwide in the next two decades. However, even with the use of multimodality treatment, MPM remains challenging to treat, with a 5-year survival rate of less than 5%. The International Association for the Study of Lung Cancer has gathered experts in different areas of mesothelioma research and management to summarize the most significant scientific advances and new frontiers related to mesothelioma therapeutics.}, }
@article {pmid29961174, year = {2018}, author = {Hylebos, M and Op de Beeck, K and van den Ende, J and Pauwels, P and Lammens, M and van Meerbeeck, JP and Van Camp, G}, title = {Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma.}, journal = {Familial cancer}, volume = {17}, number = {4}, pages = {569-576}, pmid = {29961174}, issn = {1573-7292}, mesh = {Asbestos/*toxicity ; Belgium ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology/*genetics ; Male ; Mesothelioma/chemically induced/epidemiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation ; Prevalence ; RNA-Binding Proteins/genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Familial clustering of malignant mesothelioma (MM) has been linked to the presence of germline mutations in BAP1. However, families with multiple MM patients, without segregating BAP1 mutation were described, suggesting the existence of other predisposing genetic factors. In this study, we report a previously undescribed Belgian family, in which BAP1 was found to be absent in the epithelial malignant mesothelial cells of the index patient. Whole exome analysis did not reveal a germline or somatic BAP1 variant. Also, no germline or somatic copy number changes in the BAP1 region could be identified. However, germline variants, predicted to be damaging, were detected in 11 other 'Cancer census genes' (i.e. MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1 and MYO5A). Of these, the one in RBM15 seems to be the most interesting given its low minor allele frequency and absence in the germline DNA of the index patient's mother. The importance of this 'Cancer census gene' in familial MM clustering needs to be evaluated further. Nevertheless, this study strengthens the suspicion that, next to germline BAP1 alterations, other genetic factors might predispose families to the development of MM.}, }
@article {pmid29960000, year = {2018}, author = {Kane, AB and Hurt, RH and Gao, H}, title = {The asbestos-carbon nanotube analogy: An update.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {68-80}, pmid = {29960000}, issn = {1096-0333}, support = {P42 ES013660/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Disease Models, Animal ; Humans ; Lung Diseases/chemically induced ; Nanostructures/toxicity ; Nanotechnology ; Nanotubes, Carbon/*toxicity ; Occupational Exposure/adverse effects ; }, abstract = {Nanotechnology is an emerging industry based on commercialization of materials with one or more dimensions of 100 nm or less. Engineered nanomaterials are currently incorporated into thin films, porous materials, liquid suspensions, or filler/matrix nanocomposites with future applications predicted in energy and catalysis, microelectronics, environmental sensing and remediation, and nanomedicine. Carbon nanotubes are one-dimensional fibrous nanomaterials that physically resemble asbestos fibers. Toxicologic studies in rodents demonstrated that some types of carbon nanotubes can induce mesothelioma, and the World Health Organization evaluated long, rigid multiwall carbon nanotubes as possibly carcinogenic for humans in 2014. This review summarizes key physicochemical similarities and differences between asbestos fibers and carbon nanotubes. The "fiber pathogenicity paradigm" has been extended to include carbon nanotubes as well as other high-aspect-ratio fibrous nanomaterials including metallic nanowires. This paradigm identifies width, length, and biopersistence of high-aspect-ratio fibrous nanomaterials as critical determinants of lung disease, including mesothelioma, following inhalation. Based on recent theoretical modeling studies, a fourth factor, mechanical bending stiffness, will be considered as predictive of potential carcinogenicity. Novel three-dimensional lung tissue platforms provide an opportunity for in vitro screening of a wide range of high aspect ratio fibrous nanomaterials for potential lung toxicity prior to commercialization.}, }
@article {pmid29959999, year = {2018}, author = {Roggli, VL}, title = {Measuring EMPs in the lung what can be measured in the lung: Asbestiform minerals and cleavage fragments.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {14-17}, doi = {10.1016/j.taap.2018.06.026}, pmid = {29959999}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational ; Asbestos/*analysis ; Humans ; Lung/*chemistry ; Lung Neoplasms ; Mesothelioma ; Mesothelioma, Malignant ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mineral Fibers/analysis ; Minerals/*analysis ; Particle Size ; Particulate Matter/*analysis ; }, abstract = {Asbestos mineral fibers have been associated with the development of a variety of diseases in humans and experimental animals, including asbestosis, lung cancer, and mesothelioma. Asbestos includes several mineral types divided into two mineral groups, serpentine and amphibole forms. Chrysotile is the serpentine mineral classified as asbestos, whereas the amphiboles include amosite, crocidolite, tremolite, actinolite and anthophyllite. There are a number of mineral fibers that occur with asbestiform morphology and that have been associated with various asbestos-induced diseases. These include the Libby amphiboles (associated with a vermiculite mine northwest of Libby, MT), erionite (in Turkey and North America), fluoro-edenite (in Sicily), and perhaps balangeroite (in Italy). In addition, each of the asbestos minerals occurs in a non-fibrous form, and these may occur as cleavage fragments that satisfy the definition for a fiber, i.e., particles with an aspect ratio of at least 3:1 and roughly parallel sides. Cleavage fragments of non-asbestiform minerals have not been associated with asbestos-induced diseases nor are these minerals regulated by the Occupational Safety and Health Administration. Finally, there are a number of other mineral species which can occur in human lung samples that satisfy the definition for a fiber as given above. These similarly have not been associated with asbestos-induced diseases. All of these various minerals satisfying the definition for a fiber can be referred to as elongated mineral particles (EMP). It is the purpose of this presentation to discuss the role of scanning electron microscopy (SEM) equipped with an energy dispersive x-ray analyzer (EDXA) in the detection and classification of EMP in human lung samples.}, }
@article {pmid29949929, year = {2018}, author = {Colin, DJ and Cottet-Dumoulin, D and Faivre, A and Germain, S and Triponez, F and Serre-Beinier, V}, title = {Experimental Model of Human Malignant Mesothelioma in Athymic Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {7}, pages = {}, pmid = {29949929}, issn = {1422-0067}, mesh = {Animals ; Body Fluids/metabolism ; Carcinogenesis/pathology ; Cell Count ; Cell Line, Tumor ; Cell Survival ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics/immunology/*pathology ; Macrophages/metabolism ; Mesothelioma/genetics/immunology/*pathology ; Mesothelioma, Malignant ; Mice, Nude ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a thoracic aggressive cancer caused by asbestos exposure, which is difficult to diagnose and treat. Here, we characterized an in vivo orthotopic xenograft model consisting of human mesothelioma cells (designed as H2052/484) derived from a pleural NCI-H2052 tumor injected in partially immunodeficient athymic mice. We assessed tumor formation and tumor-dependent patterns of inflammation. H2052/484 cells conserved their mesothelioma phenotype and most characteristics from the parental NCI-H2052 cells. After intra-thoracic injection of H2052/484 cells, thoracic tumors developed in nearly all mice (86%) within 14 days, faster than from parental NCI-H2052 cells. When the mice were euthanized, the pleural lavage fluid was examined for immune cell profiles. The pleural immune cell population increased with tumor development. Interestingly, the proportion of myeloid-derived suppressor cell and macrophage (especially CD206[+] M2 macrophages) populations increased in the pleural fluid of mice with large mesothelioma development, as previously observed in immunocompetent mice. This reliable orthotopic model recapitulates human mesothelioma and may be used for the study of new treatment strategies.}, }
@article {pmid29946373, year = {2018}, author = {Bensaid, D and Blondy, T and Deshayes, S and Dehame, V and Bertrand, P and Grégoire, M and Errami, M and Blanquart, C}, title = {Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma.}, journal = {Clinical epigenetics}, volume = {10}, number = {}, pages = {79}, pmid = {29946373}, issn = {1868-7083}, mesh = {B7-H1 Antigen/*genetics/metabolism ; Benzamides/pharmacology/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; DNA Methylation/drug effects ; Decitabine/*pharmacology/therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Epigenesis, Genetic/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase Inhibitors/*pharmacology/therapeutic use ; Humans ; Hydroxamic Acids/pharmacology/therapeutic use ; Immunotherapy ; Killer Cells, Natural/cytology/drug effects ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Male ; Mesothelioma/drug therapy/*genetics/metabolism ; Mesothelioma, Malignant ; T-Lymphocytes, Regulatory/cytology/drug effects ; Valproic Acid/*pharmacology/therapeutic use ; Vorinostat/*pharmacology/therapeutic use ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a very rare and highly aggressive cancer of the pleura associated in most cases with asbestos exposure. To date, no really efficient treatments are available for this pathology. Recently, it has been shown that epigenetic drugs, particularly DNA methylation or histone acetylation modulating agents, could be very efficient in terms of cytotoxicity for several types of cancer cells. We previously showed that a hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi) (valproic acid (VPA)) combination was immunogenic and led to the induction of an anti-tumor immune response in a mice model of mesothelioma. However, VPA is not very specific, is active at millimolar concentrations and is responsible for side effects in clinic. To improve this approach, we studied four newly synthetized HDACi, two hydroxamates (ODH and NODH) and two benzamides (ODB and NODB), in comparison with VPA and SAHA. We evaluated their toxicity on immune cells and their immunogenicity on MPM cells in combination with decitabine.<br><br>RESULTS: All the tested HDACi were toxic for immune cells at high concentrations. Combination with decitabine increased toxicity of HDACi only towards T-cell clone. A decrease in the proportion of regulatory T cells and natural killer cells was observed in particular with VPA and ODH. In MPM cells, all HDACi combinations induced NY-ESO-1 cancer testis antigen (CTA) expression and the recognition of the treated cells by a NY-ESO-1 specific T-CD8 clone. However, for MAGE-A1, MAGE-A3 and XAGE-1b mRNA expression, the results obtained depended on the HDACi used and on the CTA studied. Depending on the MPM cell line studied, molecules alone increased moderately PD-L1 expression. When combined, a higher stimulation of this immune check point inhibitor expression was observed. Decitabine-induced anti-viral response seemed to be inhibited in the presence of HDACi.<br><br>CONCLUSIONS: This work shows that the combination of decitabine and HDACi could be of interest for MPM immunotherapy. However, this combination induced PD-L1 expression which suggests that an association with anti-PD-L1 therapy should be performed to induce an efficient anti-tumor immune response.}, }
@article {pmid29932955, year = {2018}, author = {Cox, LAT}, title = {Biological mechanisms of non-linear dose-response for respirable mineral fibers.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {137-144}, doi = {10.1016/j.taap.2018.06.016}, pmid = {29932955}, issn = {1096-0333}, mesh = {Animals ; Cytokines ; Dose-Response Relationship, Drug ; Humans ; Inflammasomes/*drug effects ; Inhalation Exposure/*adverse effects ; Mineral Fibers/*toxicity ; NLR Family, Pyrin Domain-Containing 3 Protein/*genetics ; Particulate Matter/*toxicity ; Risk Assessment ; }, abstract = {Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds.}, }
@article {pmid29928505, year = {2018}, author = {Blum, W and Henzi, T and Châtel-Soulet, HE and Pecze, L and Rodriguez, JW and Vrugt, B and Schwaller, B}, title = {Absence of calretinin protein expression in malignant mesotheliomas from asbestos-exposed NF2[+/-] mice and mouse mesothelioma cell lines from various mouse strains.}, journal = {Biomarker research}, volume = {6}, number = {}, pages = {19}, pmid = {29928505}, issn = {2050-7771}, abstract = {BACKGROUND: Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; Calb2) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2[+/-] mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model. Additionally, we sought to ascertain the presence of calretinin in MM cell lines from other mouse strains. We also intended to investigate the role of calretinin in mesotheliomagenesis by comparing the survival of asbestos-exposed NF2[+/-] and NF2[+/-]CR[-/-] mice.<br><br>METHODS: NF2[+/-] and NF2[+/-]CR[-/-] mice, both lines on a C57Bl/6J background, were exposed to asbestos following an established protocol. Tumor histology and asbestos-induced mortality were&#xa0;assessed. MM and granuloma from NF2[+/-] mice were analyzed with immunohistochemical methods for calretinin expression. Levels of Calb2 mRNA and calretinin expression in tumors and MM cell lines of various mouse strains were determined by RT-qPCR and Western blot analysis, respectively.<br><br>RESULTS: No expression of calretinin at the protein level was detected, neither in MM from NF2[+/-] mice, NF2[+/-] MM-derived cell lines nor immortalized mesothelial cells of mouse origin. At the mRNA level we detected Calb2 expression in MM cell lines from different mouse strains. Survival of NF2[+/-] and NF2[+/-]CR[-/-] mice exposed to asbestos showed no significant difference in a log-rank (Kaplan-Meier) comparison.<br><br>CONCLUSIONS: The concomitant determination of calretinin and mesothelin blood levels has been proposed for early detection of human MM. Mouse MM models based on asbestos exposure are assumed to yield helpful information on the time course of appearance of mesothelin and calretinin in the blood of asbestos-treated mice determining the earliest time point for interventions. However, the observed absence of calretinin in MM from NF2[+/-] mice and derived cell lines, as well as from MM cells from Balb/c and C3H mice likely precludes the use of calretinin as a biomarker for mouse MM. The results also indicate possible species differences with respect to an involvement of calretinin in the formation of MM.}, }
@article {pmid29916421, year = {2018}, author = {Granieri, A and Borgogno, FV and Franzoi, IG and Gonella, M and Guglielmucci, F}, title = {Development of a Brief Psychoanalytic Group therapy (BPG) and its application in an asbestos national priority contaminated site.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {54}, number = {2}, pages = {160-166}, doi = {10.4415/ANN_18_02_12}, pmid = {29916421}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Lung Neoplasms/*psychology ; Mesothelioma/*psychology ; Mesothelioma, Malignant ; Occupational Exposure ; Psychoanalytic Therapy/*methods ; Psychotherapy, Group/*methods ; }, abstract = {The aim of the present paper is to describe the development of a Brief Psychoanalytic Group therapy for contaminated sites and its application in the National Priority Contaminated Site of Casale Monferrato. Before presenting the core of the clinical intervention, a brief examination of some clinical features encountered working with malignant mesothelioma patients and their caregivers is offered. These aspects have been pivotal elements in the construction of a psychoanalytically oriented time-limited (i.e., 12 sessions) group therapy. This model of intervention was designed by one of the Authors (AG) and is aimed at reducing the impact of living in a threatening place where both physical well-being and health are put to the test. At a psychological level, in fact, living in contaminated sites arouses death anxieties, which can deeply compromise the quality of time remaining to live together with loved ones after a fatal cancer diagnosis.}, }
@article {pmid29916419, year = {2018}, author = {Comba, P and D'Angelo, M and Fazzo, L and Magnani, C and Marinaccio, A and Mirabelli, D and Terracini, B}, title = {Mesothelioma in Italy: the Casale Monferrato model to a national epidemiological surveillance system.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {54}, number = {2}, pages = {139-148}, doi = {10.4415/ANN_18_02_10}, pmid = {29916419}, issn = {2384-8553}, mesh = {Case-Control Studies ; Cohort Studies ; Environmental Exposure ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/epidemiology ; Occupational Exposure ; Pleural Neoplasms/epidemiology ; Population Surveillance ; }, abstract = {The purpose of the present paper is to review the origin and development of the epidemiology of mesothelioma in Italy, starting with the detection and investigation of the major outbreak of the disease observed in Casale Monferrato, Piedmont Region. Over the last four decades, mortality among the cohort of ex-Eternit workers has been measured at three points in time. More recently, population based case-control studies in the area of Casale Monferrato have provided new light on the dose-response curve of the relationship between asbestos exposure and mesotheliomas. The publication of the first Casale Monferrato study had a major impact in the country and contributed to the decision of the Italian Parliament to ban the use of asbestos. The experience of Casale Monferrato represents a lesson in several terms, from the epidemiological surveillance to the health care of the victims and the relationship between epidemiologists, victims, their relatives and residents in contaminated areas.}, }
@article {pmid29915796, year = {2018}, author = {Losi, L and Botticelli, L and Taccagni, G and Longinotti, E and Lancellotti, C and Scurani, L and Zannoni, GF}, title = {Malignant peritoneal mesothelioma in a woman with bilateral ovarian serous borderline tumour: Potential interactions between the two diseases.}, journal = {Gynecologic oncology reports}, volume = {24}, number = {}, pages = {39-42}, pmid = {29915796}, issn = {2352-5789}, abstract = {We report a case of a 59-year-old woman with peritoneal malignant mesothelioma and no previous exposure to asbestos with a diagnosis of bilateral ovarian serous borderline tumour with peritoneal implants one year before. We discuss the histopathological and immunohistochemical findings to explain possible and potential interactions between the two diseases. To our knowledge, the association of both serous borderline ovarian tumour and malignant peritoneal mesothelioma has never been described before in the same woman and in such a tight temporal connection. This finding raises numerous issues about the origin of the two tumours and further biomolecular studies are needed to fully understand the carcinogenetic process. From a clinical point of view, this case report can be useful to gynaecologists because it leads to recommend a careful examination of the peritoneal cavity during a surgical resection of borderline serous tumour. Moreover, it may suggest performing a close follow-up associated with a careful surveillance of the patient, especially in the case of micropapillary pattern, to oncologists. A complete clinical approach could help to detect sooner possible relapses or other metachronous malignancies.}, }
@article {pmid29914087, year = {2018}, author = {Ledda, C and Senia, P and Rapisarda, V}, title = {Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on.}, journal = {Cancers}, volume = {10}, number = {6}, pages = {}, pmid = {29914087}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MM) is a highly aggressive tumor characterized by a poor prognosis. Although its carcinogenesis mechanism has not been strictly understood, about 80% of MM can be attributed to occupational and/or environmental exposure to asbestos fibers. The identification of non-invasive molecular markers for an early diagnosis of MM has been the subject of several studies aimed at diagnosing the disease at an early stage. The most studied biomarker is mesothelin, characterized by a good specificity, but it has low sensitivity, especially for non-epithelioid MM. Other protein markers are Fibulin-3 and osteopontin which have not, however, showed a superior diagnostic performance. Recently, interesting results have been reported for the HMGB1 protein in a small but limited series. An increase in channel proteins involved in water transport, aquaporins, have been identified as positive prognostic factors in MM, high levels of expression of aquaporins in tumor cells predict an increase in survival. MicroRNAs and protein panels are among the new indicators of interest. None of the markers available today are sufficiently reliable to be used in the surveillance of subjects exposed to asbestos or in the early detection of MM. Our aim is to give a detailed account of biomarkers available for MM.}, }
@article {pmid29908246, year = {2018}, author = {Utell, MJ and Maxim, LD}, title = {Refractory ceramic fibers: Fiber characteristics, potential health effects and clinical observations.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {113-117}, doi = {10.1016/j.taap.2018.06.011}, pmid = {29908246}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational ; Ceramics/*toxicity ; Humans ; Inhalation Exposure ; Mineral Fibers/*toxicity ; Occupational Diseases ; Occupational Exposure ; Respiratory Tract Diseases/chemically induced/pathology ; }, abstract = {Refractory ceramic fibers (RCFs) are amorphous fibers that belong to a class of materials termed synthetic vitreous fibers (SVFs), also called man-made mineral fibers (MMMFs), which includes alkaline earth silicate wool, glass wool, rock (stone) wool, slag wool, and special-purpose glass fibers. RCFs are more durable and biopersistent than several other SVFs, although very much less biopersistent than either amosite or crocidolite asbestos. Chronic inhalation studies indicated that rats and hamsters exposed to RCF fibers developed fibrosis and tumors. Epidemiological studies at the University of Cincinnati funded by the Industry indicated that exposed workers; (1) exhibited symptoms (e.g., dyspnea) similar to those reported in other dust-exposed populations, (2) developed statistically, but not clinically, significant deficits in certain measures of pulmonary function in a cross sectional study, but no excessive decline in a longitudinal study, and (3) a dose related increase in pleural plaques, but no interstitial fibrosis. The 2003 mortality study indicated no incremental lung cancer and no cases of mesothelioma. RCF producers developed a comprehensive industry wide product stewardship program (PSP) beginning in the late 1980s. In conjunction with the PSP, there has been a progressive decrease in the TWA concentration of fibers by manufacturers and end-users. The research program has successfully produced more soluble fibers and undertaken efforts to develop larger diameter fibers. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer.}, }
@article {pmid29895204, year = {2018}, author = {Tweedale, G and Castleman, B}, title = {Jock McCulloch (1945-2018): A Tribute.}, journal = {International journal of health services : planning, administration, evaluation}, volume = {48}, number = {3}, pages = {586-591}, doi = {10.1177/0020731418780607}, pmid = {29895204}, issn = {1541-4469}, mesh = {Agent Orange/history/toxicity ; Asbestosis/history ; Australia ; History, 20th Century ; History, 21st Century ; Humans ; Occupational Diseases/history ; Occupational Health/*history ; South Africa ; }, abstract = {Jock William McCulloch, who died at Melbourne, Australia, in January 2018, was one of the foremost historians of occupational health of his generation. This tribute reviews his career and oeuvre, which was tragically ended by his death from mesothelioma.}, }
@article {pmid29873855, year = {2018}, author = {Angelico, G and Ieni, A and Caltabiano, R and Zeppa, P and Tuccari, G}, title = {Aquaporin-1 expression in fluoro-edenite-induced mesothelioma effusions: An approach by cell-block procedure.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {29}, number = {5}, pages = {455-460}, doi = {10.1111/cyt.12583}, pmid = {29873855}, issn = {1365-2303}, mesh = {Aged ; Aged, 80 and over ; Aquaporin 1/*metabolism ; Asbestos, Amphibole/*toxicity ; Biomarkers, Tumor/*metabolism ; Cohort Studies ; Cytodiagnosis ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/*diagnosis/mortality ; Male ; Mesothelioma/*chemically induced/*diagnosis/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Effusion, Malignant/*chemically induced/*diagnosis/mortality ; Prognosis ; }, abstract = {OBJECTIVE: Aquaporin 1 (AQP-1) is a water channel protein found in cell membranes, whose expression has been considered an independent favourable prognostic factor in pleural malignant mesothelioma (MM). The aim of this study was to evaluate the expression of AQP-1 and its prognostic value in a series of pleural MM effusions, from a geographical area with high concentrations of fluoro-edenite (FE).<br><br>METHODS: We selected 25 MM cases from Biancavilla (Italy), an area with high environmental concentrations of FE. Cytological samples, cell-blocks (CB), clinical and follow-up data were available for all cases. Immunohistochemistry for calretinin, CK5/6, WT1, CK7 and TTF1 was used on CB sections to confirm the cytological diagnosis of MM. Immunohistochemistry for AQP-1 was performed and high expression was defined when &#x2265;50% of tumour cells showed linear and circumferential membranous staining.<br><br>RESULTS: The cohort included 16 men and nine women (median age: 67.5&#xa0;years; range: 49-88&#xa0;years). The median survival was 14&#xa0;months (range 1.5-60&#xa0;months), with a significant value (P = 0.006). All cases have been histologically confirmed and classified as epithelioid (16 cases), biphasic (seven cases) and sarcomatoid (two cases). AQP-1 high expression has been observed in 16 cases. Comparing AQP-1 high expression to the survival of corresponding patients, a significant association with a slight increased overall survival of 12&#xa0;months has been demonstrated. Nine patients with a AQP-1 score less than 50% showed a shorter median overall survival (7&#xa0;months).<br><br>CONCLUSIONS: AQP-1 high expression is detectable on cytological samples of FE-induced MM with a prognostic value.}, }
@article {pmid29869702, year = {2018}, author = {Barbiero, F and Zanin, T and Pisa, FE and Casetta, A and Rosolen, V and Giangreco, M and Negro, C and Bovenzi, M and Barbone, F}, title = {Cancer incidence in a cohort of asbestos-exposed workers undergoing health surveillance.}, journal = {International archives of occupational and environmental health}, volume = {91}, number = {7}, pages = {831-841}, pmid = {29869702}, issn = {1432-1246}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Cohort Studies ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Population Surveillance ; }, abstract = {OBJECTIVES: To compare a local cohort of 2488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995-2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study.<br><br>METHODS: Standardized incidence ratios (SIRs), with 95% confidence interval (95% CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974 and 1994. For internal comparisons, we calculated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up.<br><br>RESULTS: Among cohort members the SIR was 8.82 (95% CI 5.95-12.61) for mesothelioma and 1.61 (95% CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974 and 1984 was 2.09 (95% CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR&#x2009;=&#x2009;1.53 95% CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost threefold for lung cancer (IRR&#x2009;=&#x2009;2.94 95% CI 1.01-8.57).<br><br>CONCLUSIONS: This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974 and 1984.}, }
@article {pmid29853412, year = {2018}, author = {Fujimoto, N and Aoe, K and Kozuki, T and Oze, I and Kato, K and Kishimoto, T and Hotta, K}, title = {A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol.}, journal = {Clinical lung cancer}, volume = {19}, number = {5}, pages = {e705-e707}, doi = {10.1016/j.cllc.2018.05.001}, pmid = {29853412}, issn = {1938-0690}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration &amp; dosage ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Male ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Nivolumab/administration &amp; dosage ; Pemetrexed/administration &amp; dosage ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Prospective Studies ; *Research Design ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: The purpose of this study is to assess the efficacy and safety of combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma (MPM).<br><br>PATIENTS AND METHODS: Patients with untreated, advanced, or metastatic MPM who meet the inclusion and exclusion criteria will be included. A total of 18 patients will be enrolled from 4 Japanese institutions within 1 year. Combination chemotherapy with cisplatin (75 mg/m[2]), pemetrexed (500 mg/m[2]), and nivolumab (360 mg/person) is administered every 3 weeks for a total of 4 to 6 cycles. Then, maintenance therapy with nivolumab will be administered until disease progression, unacceptable toxicities, or the patient's condition meets the withdrawal criteria. The primary end point is the centrally reviewed overall response rate. The secondary end points include the disease control rate, overall survival, progression-free survival, and adverse events.<br><br>CONCLUSION: This phase II trial evaluating first-line combination chemotherapy for unresectable MPM commenced in January 2018. This is the first prospective trial to evaluate the effect of an anti-programmed death-1 antibody combined with cisplatin and pemetrexed for unresectable MPM.}, }
@article {pmid29850181, year = {2018}, author = {Ahmadzada, T and Reid, G and Kao, S}, title = {Biomarkers in malignant pleural mesothelioma: current status and future directions.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 9}, pages = {S1003-S1007}, pmid = {29850181}, issn = {2072-1439}, }
@article {pmid29845703, year = {2018}, author = {Saji, T and Nishita, M and Ogawa, H and Doi, T and Sakai, Y and Maniwa, Y and Minami, Y}, title = {Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells.}, journal = {Genes to cells : devoted to molecular &amp; cellular mechanisms}, volume = {23}, number = {7}, pages = {606-613}, doi = {10.1111/gtc.12599}, pmid = {29845703}, issn = {1365-2443}, mesh = {Cell Line, Tumor ; Cell Proliferation ; Humans ; Lung Neoplasms/genetics/*metabolism ; Mesothelioma/genetics/*metabolism ; Mesothelioma, Malignant ; Receptor Tyrosine Kinase-like Orphan Receptors/genetics/*metabolism/physiology ; Signal Transduction ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis and closely related to exposure to asbestos. MPM is a heterogeneous tumor with three main histological subtypes, epithelioid, sarcomatoid, and biphasic types, among which sarcomatoid type shows the poorest prognosis. The Ror-family of receptor tyrosine kinases, Ror1 and Ror2, is expressed in various types of tumor cells at higher levels and affects their aggressiveness. However, it is currently unknown whether they are expressed in and involved in aggressiveness of MPM. Here, we show that Ror1 and Ror2 are expressed in clinical specimens and cell lines of MPM with different histological features. Studies using MPM cell lines indicate that expression of Ror2 is associated tightly with high invasiveness of MPM cells, whereas Ror1 can contribute to their invasion in the absence of Ror2. However, both Ror1 and Ror2 promote proliferation of MPM cells. We also show that promoted invasion and proliferation of MPM cells by Ror signaling can be mediated by the Rho-family of small GTPases, Rac1, and Cdc42. These findings elucidate the critical role of Ror signaling in promoting invasion and proliferation of MPM cells.}, }
@article {pmid29845408, year = {2018}, author = {Tartarone, A and Lerose, R and Aieta, M}, title = {Is there a role for immunotherapy in malignant pleural mesothelioma?.}, journal = {Medical oncology (Northwood, London, England)}, volume = {35}, number = {7}, pages = {98}, pmid = {29845408}, issn = {1559-131X}, mesh = {Antineoplastic Agents/*therapeutic use ; CTLA-4 Antigen/antagonists &amp; inhibitors ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; *Immunotherapy ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; Programmed Cell Death 1 Ligand 2 Protein/antagonists &amp; inhibitors ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; }, abstract = {Malignant pleural mesothelioma (MPM) is a very aggressive malignancy, mainly caused by asbestos exposure. Patients with MPM have a poor prognosis that remained substantially unchanged in the last few years and limited effective therapeutic options with no recognized second or further-line therapy. In this context, also in view of the positive results observed in other tumor types, immunotherapy could play a relevant role. This review focuses on the most promising immunotherapies being investigated in MPM.}, }
@article {pmid29794065, year = {2018}, author = {Butnor, KJ and Rueckert, J and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Malignant peritoneal mesothelioma in patients with endometriosis.}, journal = {Journal of clinical pathology}, volume = {71}, number = {11}, pages = {971-974}, doi = {10.1136/jclinpath-2018-205099}, pmid = {29794065}, issn = {1472-4146}, mesh = {Adult ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Biopsy ; Endometriosis/etiology/*pathology ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/chemistry/etiology/*pathology ; Mesothelioma/chemistry/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/chemistry/etiology/*pathology ; Peritoneum/chemistry/*pathology ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; }, abstract = {AIMS: Florid mesothelial hyperplasia is known to result from endometriosis. Well-differentiated papillary mesothelioma and multiloculated peritoneal inclusion cysts have also been described in women with endometriosis. To our knowledge, peritoneal diffuse malignant mesothelioma (MM) arising in the setting of endometriosis has not been reported. The purpose of this study is to report the clinicopathological characteristics of women with MM and endometriosis.<br><br>METHODS: The surgical pathology files of a tertiary academic medical centre and the consultation files of one of the study authors were reviewed for cases of MM in females with and without endometriosis.<br><br>RESULTS: Six women with MM and endometriosis ranging in age from 29 to 55 years (median=45 years) were identified. All had peritoneal MM and endometriosis involving the peritoneum and/or adnexa. Five had epithelioid MM and one had biphasic MM. Two had paraoccupational exposure to asbestos. The median age of women with MM and endometriosis (44.5 years) was significantly less than the median age of cases without endometriosis (58.0 years) (p value=0.01).<br><br>CONCLUSIONS: To our knowledge, this is the first report of MM in women with endometriosis. Interestingly, MM in the setting of endometriosis has only been observed in the peritoneum and not in other serosal cavities. The findings in the present study suggest that chronic serosal inflammation secondary to endometriosis may be an inducing factor in rare cases of MM of the peritoneum.}, }
@article {pmid29792222, year = {2018}, author = {Kerger, BD}, title = {Longevity and pleural mesothelioma: age-period-cohort analysis of incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-2013.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {337}, pmid = {29792222}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Aging ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Infant ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries/*statistics &amp; numerical data ; United States/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years with an age-related elevation in risk. An age-period-cohort analysis of the SEER 9 cancer registries (1973-2013) was conducted using 5-year intervals of age, calendar period, and birth cohort after stratification into four gender-age groups (male and female; 0-74 and 75+ years).<br><br>RESULTS: Gender-specific time trends in age-adjusted PM incidence by age groups were observed. After adjusting for cohort effects, males in the 0-74-year age group experienced rapidly declining PM incidence rates following the observed peak in 1978-1982, whereas continuously increasing incidence rates were observed among older males. A significant cohort effect was also observed among males in both age groups, with peak incidence rates in the 1926-1930/1928-1932 birth cohorts and thereafter. The distinct period and cohort effects among males age 0-74&#xa0;years may be driven by declining age-adjusted PM incidence rates corresponding to the decline in occupational asbestos exposures post-World War II, whereas the increasing time trend seen in both genders at age 75+ may reflect an increasing proportion due to longevity-related factors.}, }
@article {pmid29779004, year = {2018}, author = {Ugelvig Petersen, K and Volk, J and Kaerlev, L and Lyngbeck Hansen, H and Hansen, J}, title = {Cancer incidence among merchant seafarers: an extended follow-up of a Danish cohort.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {8}, pages = {582-585}, doi = {10.1136/oemed-2018-105037}, pmid = {29779004}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Cohort Studies ; Denmark/epidemiology ; Employment ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/epidemiology/etiology ; Humans ; Incidence ; Lip Neoplasms/epidemiology/etiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; *Occupations ; Respiratory Tract Neoplasms/epidemiology/etiology ; Sex Factors ; *Ships ; Ultraviolet Rays/adverse effects ; Urogenital Neoplasms/epidemiology/etiology ; }, abstract = {OBJECTIVES: While maritime safety generally has improved dramatically over the last century, modern seafarers are still faced with numerous occupational hazards potentially affecting their risk of chronic diseases such as cancer. The aim of this study is to offer updated information on the incidence of specific cancers among both male and female seafarers.<br><br>METHODS: Using records from the Danish Seafarer Registry, all seafarers employed on Danish ships during 1986-1999 were identified, resulting in a cohort of 33&#x2009;084 men and 11&#x2009;209 women. Information on vital status and cancer was linked to each member of the cohort from the Danish Civil Registration System and the Danish Cancer Registry using the unique Danish personal identification number. SIRs were estimated for specific cancers using national rates.<br><br>RESULTS: The overall incidence of cancer was increased for both male and female seafarers (SIR 1.19, 95%&#x2009;CI 1.15 to 1.23, and SIR 1.14, 95%&#x2009;CI 1.07 to 1.22) compared with the general population. This excess was primarily driven by increases in gastrointestinal, respiratory and genitourinary cancers. In addition, male seafarers working in areas with asbestos exposure showed significantly increased risk of mesothelioma. Finally, the male seafarers had an increased risk of lip cancer.<br><br>CONCLUSIONS: The majority of cancers among seafarers continue to be lifestyle-related. However, occupational exposure to asbestos and ultraviolet radiation seems to affect the cancer pattern among the male seafarers as well.}, }
@article {pmid29774715, year = {2018}, author = {Chellini, E and Battisti, F and Pellegri, M and Baldacci, M and Sallese, D and Cristaudo, A and Sartorelli, P and Arcangeli, G and Paoli, M and Fani, S and Festa, G and Calà, P}, title = {[Health surveillance programme for workers with past asbestos exposure in Tuscany Region (Central Italy)].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {171-177}, doi = {10.19191/EP18.2.P171.047}, pmid = {29774715}, issn = {1120-9763}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Asbestosis/complications/diagnosis/*epidemiology ; Diagnostic Screening Programs ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; *Population Surveillance ; Program Evaluation ; Stakeholder Participation ; }, abstract = {Asbestos-related diseases are characterized by a long latency time since exposure. This accounts for a health surveillance programme addressed to asbestos workers to be performed for decades after the cessation of occupational exposure. We describe the health surveillance programme for former asbestos-exposed workers in Tuscany Region (Central Italy), with particular attention to organization and related critical issues. The Deliberation of the Regional Administration of Tuscany (No. 396/2016) supports the programme, defined by a regional group of experts, and defines the public health services where the programme has to be implemented. The programme activities are classified in two levels: a first level for a basic health evaluation and a second level for in-depth analyses. The former asbestos workers, aged less than 80 years and with cessation of occupational asbestos exposure in the last 30 years, that might be included free of charge in the programme are about 5.600. The funds assigned to develop the programme from 2016 to 2024 were 2,044,808 euros. The Regional Administration of Tuscany decided to offer and guarantee a homogeneous programme in the whole region. The identification of a specific public health programme and the cooperation of social stakeholders, defined with specific regional agreements, might facilitate to overcome the problems which are still open, such as a broaden invitation to adhere to the programme, an extended knowledge on the service, and the application of a similar health programme for still-working former asbestos workers.}, }
@article {pmid29774711, year = {2018}, author = {Caputo, A and De Santis, M and Manno, V and Cauzillo, G and Bruni, BM and Palumbo, L and Conti, S and Comba, P}, title = {[Health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy)].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {142-150}, doi = {10.19191/EP18.2.P142.043}, pmid = {29774711}, issn = {1120-9763}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/*etiology/mortality ; Environmental Exposure ; Environmental Monitoring ; Environmental Pollutants/*toxicity ; Female ; Geography, Medical ; Geological Phenomena ; Hospitalization/statistics &amp; numerical data ; Humans ; Incidence ; Italy ; Male ; Mesothelioma/etiology/mortality ; Mineral Fibers/toxicity ; Ovarian Neoplasms/mortality ; Population Surveillance ; Respiratory Tract Neoplasms/etiology/mortality ; }, abstract = {OBJECTIVES: to estimate the health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy).<br><br>DESIGN: geographic mortality, hospitalization, and incidence study. Setting and participant s: population resident in 12 Municipalities of Mount Pollino area with naturally occurring asbestos fibres.<br><br>MAIN OUTCOME MEASURES: standardized mortality ratio (SMR) and standardized hospitalization rate (SHR) for asbestos-related diseases; standardized incidence ratio (SIR) for mesotheliomas. Result s: in the area of Mount Pollino, where asbestos fibres naturally occur, especially in the sub-area in which fibres are close to dwellings and settlements, it was observed: &#x2022; a significant excess of mesothelioma incidence (SIR: 208; CI95% 111-355; 13 observed); &#x2022; a non-significant excess of hospitalization for malignant pleural neoplasms (SHR: 176; CI95% 93-335; 9 observed); &#x2022; a significant excess for mortality and hospitalization for pneumoconiosis (SMR: 534; CI95% 345-824; 20 observed - SHR: 245; CI95% 149-405; 15 observed); &#x2022; a significant excess for hospitalization (SHR: 852; CI95% 290-2,506; 3 observed) for asbestosis.<br><br>CONCLUSION: it is necessary to continue environmental monitoring and environmental remediation in the area with higher asbestos exposure. It is suggested to implement a permanent process of epidemiological surveillance in this same area. A communication plan with local administrators, general practitioners, school teachers, media, and the resident population at large should be realized.}, }
@article {pmid29774705, year = {2018}, author = {Terracini, B}, title = {[Parliamentary committee of inquiry about health of Italian soldiers exposed to uranium, asbestos, and vaccines].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {114-115}, doi = {10.19191/EP18.2.P114.037}, pmid = {29774705}, issn = {1120-9763}, mesh = {*Advisory Committees ; Asbestos/*adverse effects ; Forecasting ; Government Agencies ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology ; *Military Personnel ; Occupational Diseases/*epidemiology/etiology ; *Occupational Exposure ; Uranium/*adverse effects ; Vaccines/*adverse effects ; }, }
@article {pmid29772681, year = {2018}, author = {Furuya, S and Chimed-Ochir, O and Takahashi, K and David, A and Takala, J}, title = {Global Asbestos Disaster.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {5}, pages = {}, pmid = {29772681}, issn = {1660-4601}, mesh = {Asbestosis/diagnosis/*epidemiology/etiology/prevention &amp; control ; Cost of Illness ; Global Health/*statistics &amp; numerical data ; Humans ; Mesothelioma/diagnosis/*epidemiology/etiology/prevention &amp; control ; }, abstract = {Introduction: Asbestos has been used for thousands of years but only at a large industrial scale for about 100[-]150 years. The first identified disease was asbestosis, a type of incurable pneumoconiosis caused by asbestos dust and fibres. The latest estimate of global number of asbestosis deaths from the Global Burden of Disease estimate 2016 is 3495. Asbestos-caused cancer was identified in the late 1930's but despite today's overwhelming evidence of the strong carcinogenicity of all asbestos types, including chrysotile, it is still widely used globally. Various estimates have been made over time including those of World Health Organization and International Labour Organization: 107,000[-]112,000 deaths. Present estimates are much higher. Objective: This article summarizes the special edition of this Journal related to asbestos and key aspects of the past and present of the asbestos problem globally. The objective is to collect and provide the latest evidence of the magnitude of asbestos-related diseases and to provide the present best data for revitalizing the International Labor Organization/World Health Organization Joint Program on Asbestos-related Diseases. Methods: Documentation on asbestos-related diseases, their recognition, reporting, compensation and prevention efforts were examined, in particular from the regulatory and prevention point of view. Estimated global numbers of incidence and mortality of asbestos-related diseases were examined. Results: Asbestos causes an estimated 255,000 deaths (243,223[-]260,029) annually according to latest knowledge, of which work-related exposures are responsible for 233,000 deaths (222,322[-]242,802). In the European Union, United States of America and in other high income economies (World Health Organization regional classification) the direct costs for sickness, early retirement and death, including production losses, have been estimated to be very high; in the Western European countries and European Union, and equivalent of 0.70% of the Gross Domestic Product or 114 × 10[8] United States Dollars. Intangible costs could be much higher. When applying the Value of Statistical Life of 4 million EUR per cancer death used by the European Commission, we arrived at 410 × 10[8] United States Dollars loss related to occupational cancer and 340 × 10[8] related to asbestos exposure at work, while the human suffering and loss of life is impossible to quantify. The numbers and costs are increasing practically in every country and region in the world. Asbestos has been banned in 55 countries but is used widely today; some 2,030,000 tons consumed annually according to the latest available consumption data. Every 20 tons of asbestos produced and consumed kills a person somewhere in the world. Buying 1 kg of asbestos powder, e.g., in Asia, costs 0.38 United States Dollars, and 20 tons would cost in such retail market 7600 United States Dollars. Conclusions: Present efforts to eliminate this man-made problem, in fact an epidemiological disaster, and preventing exposures leading to it are insufficient in most countries in the world. Applying programs and policies, such as those for the elimination of all kind of asbestos use-that is banning of new asbestos use and tight control and management of existing structures containing asbestos-need revision and resources. The International Labor Organization/World Health Organization Joint Program for the Elimination of Asbestos-Related Diseases needs to be revitalized. Exposure limits do not protect properly against cancer but for asbestos removal and equivalent exposure elimination work, we propose a limit value of 1000 fibres/m[3].}, }
@article {pmid29753121, year = {2018}, author = {Armato, SG and Nowak, AK}, title = {Revised Modified Response Evaluation Criteria in Solid Tumors for Assessment of Response in Malignant Pleural Mesothelioma (Version 1.1).}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {7}, pages = {1012-1021}, doi = {10.1016/j.jtho.2018.04.034}, pmid = {29753121}, issn = {1556-1380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Humans ; Lung Neoplasms/diagnostic imaging/drug therapy/*pathology ; Mesothelioma/diagnostic imaging/drug therapy/*pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnostic imaging/drug therapy/*pathology ; *Response Evaluation Criteria in Solid Tumors ; Survival Rate ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma poses unique difficulties in tumor measurement and response assessment; however, robust and reproducible assessment of response is critically important in the conduct, interpretation, and reporting of clinical trials.<br><br>METHODS: The current de facto standard for the assessment of mesothelioma tumor response, "modified RECIST" (Response Evaluation Criteria in Solid Tumors), was published in 2004 as a research paper. Practical application of the modified RECIST guidelines has suffered from varied interpretations, resulting in inaccuracies and inconsistencies in tumor response assessment across and within mesothelioma clinical trials. The presented "modified RECIST 1.1 for mesothelioma" response assessment guidelines provide a much-needed update that incorporates recommendations from RECIST 1.1 and approaches to other practical issues, including: (1) definition of minimally measurable disease; (2) definition of measurable lesions; (3) acceptable measurement location; (4) non-pleural disease considerations; (5) characterization of non-measurable pleural disease; (6) assessment of pathological lymph nodes; (7) establishing progressive disease; and (8) accommodations for bilateral pleural disease.<br><br>RESULTS: These modified RECIST 1.1 guidelines for mesothelioma tumor response collate and apply research published since the development of modified RECIST, align modified RECIST with RECIST 1.1, address those aspects of tumor measurement that were neglected or not well characterized in the modified RECIST paper, and clarify ambiguous or difficult measurement issues that have been highlighted through the subsequent decade of clinical trials research.<br><br>CONCLUSION: Adoption of the modified RECIST 1.1 guidelines for mesothelioma is recommended to harmonize the&#xa0;application of tumor measurement and response assessment across the next generation of clinical trials in this disease.}, }
@article {pmid29742950, year = {2018}, author = {Arnoldussen, YJ and Skaug, V and Aleksandersen, M and Ropstad, E and Anmarkrud, KH and Einarsdottir, E and Chin-Lin, F and Granum Bjørklund, C and Kasem, M and Eilertsen, E and Apte, RN and Zienolddiny, S}, title = {Inflammation in the pleural cavity following injection of multi-walled carbon nanotubes is dependent on their characteristics and the presence of IL-1 genes.}, journal = {Nanotoxicology}, volume = {12}, number = {6}, pages = {522-538}, doi = {10.1080/17435390.2018.1465139}, pmid = {29742950}, issn = {1743-5404}, mesh = {Animals ; Asbestos, Crocidolite/toxicity ; Fibrosis ; Inflammation/*chemically induced ; Interleukin-1/*genetics ; Mice ; Mice, Inbred C57BL ; Nanotubes, Carbon/*toxicity ; Pleural Cavity/*drug effects/pathology ; }, abstract = {Upon inhalation, multi-walled carbon nanotubes (MWCNTs) may reach the subpleura and pleural spaces, and induce pleural inflammation and/or mesothelioma in humans. However, the mechanisms of MWCNT-induced pathology after direct intrapleural injections are still only partly elucidated. In particular, a role of the proinflammatory interleukin-1 (IL-1) cytokines in pleural inflammation has so far not been published. We examined the MWCNT-induced pleural inflammation, gene expression abnormalities, and the modifying role of IL-1α and β cytokines following intrapleural injection of two types of MWCNTs (CNT-1 and CNT-2) compared with crocidolite asbestos in IL-1 wild-type (WT) and IL-1α/β KO (IL1-KO) mice. Histopathological examination of the pleura 28 days post-exposure revealed mesothelial cell hyperplasia, leukocyte infiltration, and fibrosis occurring in the CNT-1 (Mitsui-7)-exposed group. The pleura of these mice also showed the greatest changes in mRNA and miRNA expression levels, closely followed by CNT-2. In addition, the CNT-1-exposed group also presented the greatest infiltrations of leukocytes and proliferation of fibrous tissue. WT mice were more prone to development of sustained inflammation and fibrosis than IL1-KO mice. Prominent differences in genetic and epigenetic changes were also observed between the two genotypes. In conclusion, the fibrotic response to MWCNTs in the pleura depends on the particles' physico-chemical properties and on the presence or absence of the IL-1 genes. Furthermore, we found that CNT-1 was the most potent inducer of inflammatory responses, followed by CNT-2 and crocidolite asbestos.}, }
@article {pmid29738812, year = {2018}, author = {Asgharian, B and Owen, TP and Kuempel, ED and Jarabek, AM}, title = {Dosimetry of inhaled elongate mineral particles in the respiratory tract: The impact of shape factor.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {27-35}, pmid = {29738812}, issn = {1096-0333}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {Asbestos/toxicity ; Computer Simulation ; Humans ; Inhalation Exposure/*adverse effects ; Minerals/*toxicity ; Occupational Exposure ; Particle Size ; Particulate Matter/*toxicity ; Respiratory Tract Diseases/*chemically induced ; Risk Assessment ; }, abstract = {Inhalation exposure to some types of fibers (e.g., asbestos) is well known to be associated with respiratory diseases and conditions such as pleural plaques, fibrosis, asbestosis, lung cancer, and mesothelioma. In recent years, attention has expanded to other types of elongate mineral particles (EMPs) that may share similar geometry with asbestos fibers but which may differ in mineralogy. Inhalability, dimensions and orientation, and density are major determinants of the aerodynamic behavior for fibers and other EMPs; and the resultant internal dose is recognized as being the critical link between exposure and pathogenesis. Insufficient data are available to fully understand the role of specific physicochemical properties on the potential toxicity across various types of fiber materials. While additional information is required to assess the potential health hazards of EMPs, dosimetry models are currently available to estimate the initially deposited internal dose, which is an essential step in linking airborne exposures to potential health risks. Based on dosimetry model simulations, the inhalability and internal dose of EMPs were found to be greater than that of spherical particles having the same mass or volume. However, the complexity of the dependence of internal dose on EMPs dimensions prevented a straightforward formulation of the deposition-dimension (length or diameter) relationship. Because health outcome is generally related to internal dose, consideration of the factors that influence internal dose is important in assessing the potential health hazards of airborne EMPs.}, }
@article {pmid29737238, year = {2017}, author = {Metintas, S and Ak, G and Bogar, F and Yilmaz, S and Metintas, M}, title = {Asbestos knowledge and awareness level in central part of Anatolia.}, journal = {International journal of occupational and environmental health}, volume = {23}, number = {3}, pages = {243-249}, pmid = {29737238}, issn = {2049-3967}, mesh = {Adult ; Aged ; *Asbestos ; *Environmental Exposure ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; *Rural Population/statistics &amp; numerical data ; Turkey ; Young Adult ; }, abstract = {Background Asbestos-contaminated soil has been used by people for many years in the rural part of Anatolia. However, there is no program to control usage of asbestos in this region. Objective To determine the knowledge and awareness level about asbestos in a region where asbestos-related diseases are endemic due to environmental exposure to asbestos in the rural setting. Methods This study included 760 participants, recruited using non-probability sampling, who were classified into four groups according to residence and asbestos exposure type (urban, rural; asbestos-exposed, asbestos-unexposed). Asbestos knowledge and awareness was measured via the Asbestos Knowledge and Awareness Questionnaire (AKAQ). The cut-off value of questionnaire was determined by the K-means cluster analysis for sufficient and insufficient knowledge and awareness level. A multiple logistic regression analysis was performed to determine independent factors affecting sufficient knowledge and awareness of participants about asbestos. Results The median and mean score of the AKAQ in study group were 30 and 33.9, respectively. The urban asbestos-exposed group had a higher score than the urban asbestos-unexposed and both rural groups (p < 0.001). Factors affecting asbestos knowledge and awareness were education status (p = 0.035), asbestos exposure (p = 0.003) and living in the rural area (p = 0.005). Sufficient knowledge and awareness (score > 45) was higher among participants who had graduated from university and had asbestos exposure. Insufficient knowledge and awareness level was higher among participants living in rural areas. Conclusion In this region of Anatolia, knowledge and awareness level of asbestos was low among people at risk for environmental asbestos exposure. People should be aware of asbestos and its hazards by a well-designed training program and be monitored for asbestos-related diseases.}, }
@article {pmid29733442, year = {2018}, author = {Baur, X}, title = {Review on the adverse health effects of asbestiform antigorite, a non-regulated asbestiform serpentine mineral.}, journal = {American journal of industrial medicine}, volume = {61}, number = {7}, pages = {625-630}, doi = {10.1002/ajim.22857}, pmid = {29733442}, issn = {1097-0274}, mesh = {Animals ; Asbestos, Serpentine/*adverse effects/chemistry/toxicity ; Asbestosis/epidemiology/*etiology ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; *Mining ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Although antigorite is generally described as platy, its fibrous (asbestiform) variant is present widespread in serpentinite rocks. In addition to its primarily fibrous occurrence, asbestiform antigorite may also be formed from serpentinite with massive appearance during tunneling and mining. It is not of commercial interest, but exposure may occur in the certain environments.<br><br>METHODS AND RESULTS: Detailed studies of the structural features of this antigorite type revealed characteristics closely related to those of chrysotile. Therefore, it is plausible that this serpentine mineral may present a similar health risk for exposed subjects. This is in agreement with results from clinical and animal studies, as well as in vitro experiments showing the cytotoxic, fibrogenic, and carcinogenic potential of antigorite, similar to that of chrysotile and amphibole asbestos.<br><br>CONCLUSIONS: Current evidence supports a need for an update to existing regulations to include unregulated asbestiform antigorite, similar to regulatory measures taken for asbestos.}, }
@article {pmid29723687, year = {2018}, author = {Galateau Salle, F and Le Stang, N and Nicholson, AG and Pissaloux, D and Churg, A and Klebe, S and Roggli, VL and Tazelaar, HD and Vignaud, JM and Attanoos, R and Beasley, MB and Begueret, H and Capron, F and Chirieac, L and Copin, MC and Dacic, S and Danel, C and Foulet-Roge, A and Gibbs, A and Giusiano-Courcambeck, S and Hiroshima, K and Hofman, V and Husain, AN and Kerr, K and Marchevsky, A and Nabeshima, K and Picquenot, JM and Rouquette, I and Sagan, C and Sauter, JL and Thivolet, F and Travis, WD and Tsao, MS and Weynand, B and Damiola, F and Scherpereel, A and Pairon, JC and Lantuejoul, S and Rusch, V and Girard, N}, title = {New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {8}, pages = {1189-1203}, pmid = {29723687}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Biopsy ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Reproducibility of Results ; }, abstract = {INTRODUCTION: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components.<br><br>METHODS: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis.<br><br>RESULTS: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa&#xa0;= 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p&#xa0;= 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio&#xa0;= 3.2; 95% confidence interval: 1.6 - 8.0; and p&#xa0;= 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio&#xa0;= 4.5; 95% confidence interval: 1.2 - 16.3, p&#xa0;= 0.02).<br><br>CONCLUSIONS: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.}, }
@article {pmid29723551, year = {2018}, author = {Garcia, E and Newfang, D and Coyle, JP and Blake, CL and Spencer, JW and Burrelli, LG and Johnson, GT and Harbison, RD}, title = {Evaluation of airborne asbestos exposure from routine handling of asbestos-containing wire gauze pads in the research laboratory.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {96}, number = {}, pages = {135-141}, doi = {10.1016/j.yrtph.2018.04.020}, pmid = {29723551}, issn = {1096-0295}, mesh = {*Absorbent Pads ; Air Pollution, Indoor/*analysis ; Asbestos/administration &amp; dosage/*analysis ; *Environmental Monitoring ; Humans ; *Laboratories ; *Research ; }, abstract = {Three independently conducted asbestos exposure evaluations were conducted using wire gauze pads similar to standard practice in the laboratory setting. All testing occurred in a controlled atmosphere inside an enclosed chamber simulating a laboratory setting. Separate teams consisting of a laboratory technician, or technician and assistant simulated common tasks involving wire gauze pads, including heating and direct wire gauze manipulation. Area and personal air samples were collected and evaluated for asbestos consistent with the National Institute of Occupational Safety Health method 7400 and 7402, and the Asbestos Hazard Emergency Response Act (AHERA) method. Bulk gauze pad samples were analyzed by Polarized Light Microscopy and Transmission Electron Microscopy to determine asbestos content. Among air samples, chrysotile asbestos was the only fiber found in the first and third experiments, and tremolite asbestos for the second experiment. None of the air samples contained asbestos in concentrations above the current permissible regulatory levels promulgated by OSHA. These findings indicate that the level of asbestos exposure when working with wire gauze pads in the laboratory setting is much lower than levels associated with asbestosis or asbestos-related lung cancer and mesothelioma.}, }
@article {pmid29719805, year = {2018}, author = {Sattar, N and Durrance, R and Khan, A and Patel, N and Mora, M and Shalonov, A}, title = {Malignant mesothelioma presenting as recurrent hydro-pneumothorax: An atypical case presentation and literature review.}, journal = {Respiratory medicine case reports}, volume = {23}, number = {}, pages = {152-155}, pmid = {29719805}, issn = {2213-0071}, abstract = {Malignant Pleural Mesothelioma (MPM) is a rare pleural malignancy, with a vague presentation complicated by a decades-long latency period between environmental exposure and clinical manifestations. Spontaneous hydro-pneumothorax is a rare presentation of MPM, most often requiring invasive tissue biopsy to confirm the etiologic diagnosis. We present the case of 79-year-old male smoker with no documented history of asbestos exposure, who was found to have MPM after presenting with dyspnea and subsequently found to have recurrent hydro-pneumothorax. On Literature review of the limited documented cases of MPM with hydro-pneumothorax, we found an exclusively male population with a significant smoking history, a marked right sided pathology predominance, and a generally poor prognosis. While this corresponds with the examined case, and suggests that the presence of hydro-pneumothorax implies a high-grade tumor and significant tissue invasion, and therefore poor prognosis similar to that of stage 4 disease, it differs from more generalized case reviews of MPM, most importantly in their anatomical descriptions, prognostic indicators, and epidemiologic tendencies.}, }
@article {pmid29714657, year = {2019}, author = {Barbieri, PG and Mirabelli, D and Magnani, C and Brollo, A}, title = {On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997-2016).}, journal = {Tumori}, volume = {105}, number = {4}, pages = {304-311}, doi = {10.1177/0300891618765538}, pmid = {29714657}, issn = {2038-2529}, mesh = {Asbestos/adverse effects ; Autopsy/methods ; Humans ; Immunohistochemistry/methods ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Diseases/*diagnosis ; Pleural Effusion/diagnosis ; Pleural Neoplasms/*diagnosis ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices.<br><br>METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1977-2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping.<br><br>RESULTS: Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases.<br><br>CONCLUSIONS: Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.}, }
@article {pmid29709339, year = {2019}, author = {Wu, TH and Lee, LJ and Yuan, CT and Chen, TW and Yang, JC}, title = {Prognostic factors and treatment outcomes of malignant pleural mesothelioma in Eastern Asian patients - A Taiwanese study.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {1 Pt 2}, pages = {230-236}, doi = {10.1016/j.jfma.2018.04.001}, pmid = {29709339}, issn = {0929-6646}, mesh = {Aged ; Databases, Factual ; Female ; Hospitals, University ; Humans ; Lung Neoplasms/diagnosis/*mortality/*therapy ; Male ; Mesothelioma/diagnosis/*mortality/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/*mortality/*therapy ; Prognosis ; Survival Analysis ; Taiwan/epidemiology ; }, abstract = {BACKGROUND/PURPOSE: There are scarce reports on the prognostic factors and treatment outcomes of patients with malignant pleural mesothelioma (MPM) in Asia. This study aimed to address these matters in a real-world setting.<br><br>METHODS: Medical records of patients with histologically proven MPM diagnosed between 1977 and 2016 at the National Taiwan University Hospital were reviewed. Variables including age, gender, performance status, asbestos exposure, smoking history, histology subtype, staging, and treatment received were recorded. All patients were followed until death or March 1st, 2017. Survival and prognostic factors were analyzed by the Kaplan-Meir method and the Cox proportional hazard model.<br><br>RESULTS: A total of 93 patients was identified, including 65 men and 28 women. An increasing trend of MPM cases diagnosed was observed in the past 40 years. Stage I/II disease (HR 0.24, 95% CI 0.13-0.46) and epithelioid histology (HR 0.42, 95% CI 0.23-0.75) were associated with favorable prognosis, whereas age &#x2265;70 years (HR 2.66, 95% CI 1.36-5.22) and ECOG &#x2265;2 (HR 5.03, 95% CI 2.69-9.4) were poor prognostic factors. After adjustment for prognostic factors, surgery in stage I-III MPM (HR 0.36, 95% CI 0.15-0.83) and systemic therapy in stage III/IV disease (HR 0.42, 95% CI 0.19-0.94) conferred a survival benefit.<br><br>CONCLUSION: This is one of the largest case series of MPM reported in Asia outside of Japan. Prognostic factors in the study population included age, performance status, stage, and histology subtype. Surgery in potentially resectable disease and systemic therapy in advanced MPM confer a survival benefit in Asian patients.}, }
@article {pmid29701625, year = {2018}, author = {Barbiero, F and Zanin, T and Pisa, FE and Casetta, A and Rosolen, V and Giangreco, M and Negro, C and Bovenzi, M and Barbone, F}, title = {Mortality in a cohort of asbestos-exposed workers undergoing health surveillance.}, journal = {La Medicina del lavoro}, volume = {109}, number = {2}, pages = {83-86}, pmid = {29701625}, issn = {0025-7818}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/complications/*mortality ; Carcinogens ; Child ; Child, Preschool ; Cohort Studies ; Construction Materials/adverse effects ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/etiology/*mortality ; Population Surveillance ; }, abstract = {BACKGROUND: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health surveillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality.<br><br>OBJECTIVES: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy.<br><br>METHODS: Standardized Mortality Ratios (SMR), with 95% Confidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994).<br><br>RESULTS: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60).<br><br>CONCLUSIONS: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure.}, }
@article {pmid29699512, year = {2018}, author = {Blum, W and Pecze, L and Rodriguez, JW and Steinauer, M and Schwaller, B}, title = {Regulation of calretinin in malignant mesothelioma is mediated by septin 7 binding to the CALB2 promoter.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {475}, pmid = {29699512}, issn = {1471-2407}, support = {130680//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/International ; 139226//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (CH)/International ; }, mesh = {Animals ; Base Sequence ; Butyrates/pharmacology ; Calbindin 2/chemistry/*genetics/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line, Tumor ; Cytokines/metabolism ; Enhancer Elements, Genetic ; *Gene Expression Regulation, Neoplastic/drug effects ; Genes, Reporter ; Humans ; Lung Neoplasms/*genetics/*metabolism/pathology ; Mesothelioma/*genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; *Promoter Regions, Genetic ; Protein Binding ; Protein Transport ; Proteolysis ; Response Elements ; Septins/*metabolism ; }, abstract = {BACKGROUND: The calcium-binding protein calretinin (gene name: CALB2) is currently considered as the most sensitive and specific marker for the diagnosis of malignant mesothelioma (MM). MM is a very aggressive tumor strongly linked to asbestos exposure and with no existing cure so far. The mechanisms of calretinin regulation, as well as its distinct function in MM are still poorly understood.<br><br>METHODS: We searched for transcription factors binding to the CALB2 promoter and modulating calretinin expression. For this, DNA-binding assays followed by peptide shotgun-mass spectroscopy analyses were used. CALB2 promoter activity was assessed by dual-luciferase reporter assays. Furthermore, we analyzed the effects of CALB2 promoter-binding proteins by lentiviral-mediated overexpression or down-regulation of identified proteins in MM cells. The modulation of expression of such proteins by butyrate was determined by subsequent Western blot analysis. Immunohistochemical analysis of embryonic mouse lung tissue served to verify the simultaneous co-expression of calretinin and proteins interacting with the CALB2 promoter during early development. Finally, direct interactions of calretinin with target proteins were evidenced by co-immunoprecipitation experiments.<br><br>RESULTS: Septin 7 was identified as a butyrate-dependent transcription factor binding to a CALB2 promoter region containing butyrate-responsive elements (BRE) resulting in decreased calretinin expression. Accordingly, septin 7 overexpression decreased calretinin expression levels in MM cells. The regulation was found to operate bi-directionally, i.e. calretinin overexpression also decreased septin 7 levels. During murine embryonic development calretinin and septin 7 were found to be co-expressed in embryonic mesenchyme and undifferentiated mesothelial cells. In MM cells, calretinin and septin 7 colocalized during cytokinesis in distinct regions of the cleavage furrow and in the midbody region of mitotic cells. Co-immunoprecipitation experiments revealed this co-localization to be the result of a direct interaction between calretinin and septin 7.<br><br>CONCLUSIONS: Our results demonstrate septin 7 not only serving as a "cytoskeletal" protein, but also as a transcription factor repressing calretinin expression. The negative regulation of calretinin by septin 7 and vice versa sheds new light on mechanisms possibly implicated in MM formation and identifies these proteins as transcriptional regulators and putative targets for MM therapy.}, }
@article {pmid29698884, year = {2018}, author = {Ismael, H and Cox, S}, title = {Primary intrahepatic mesotheliomas: A case presentation and literature review.}, journal = {International journal of surgery case reports}, volume = {47}, number = {}, pages = {1-6}, pmid = {29698884}, issn = {2210-2612}, abstract = {INTRODUCTION: Primary Intrahepatic mesotheliomas are malignant tumors arising from the mesothelial cell layer covering Glisson's capsule of the liver. They are exceedingly rare with only fourteen cases reported in the literature. They have nonspecific signs and symptoms and need a high index of suspicion and an extensive workup prior to surgery. Surgery remains the mainstay of treatment.<br><br>PRESENTATION OF CASE: 48&#x202f;year old male presented with a 3 months history of abdominal pain, productive cough, anemia and weight loss. He had no history of asbestos exposure. A computed tomography scan and magnetic resonance study demonstrated a heterogeneous subscapular mass within the dome of the right hepatic lobe measuring 11.3&#x202f;&#xd7;&#x202f;6.1&#x202f;cm involving the diaphragm. Combined resection of the liver and diaphragm was performed to achieve negative margins. Pathology demonstrated an epithelioid necrotic intrahepatic mesothelioma that stained positive for calretinin, CK AE1/AE3, WT-1, D2-40 and CK7.<br><br>DISCUSSION: Primary intrahepatic mesotheliomas originate from the mesothelial cells lining Glisson's capsule of the liver. They predominantly invade the liver but may also abut or involve the diaphragm. Surgery should include a diagnostic laparoscopy to rule out occult disease or diffuse peritoneal mesothelioma. Complete resection with negative margins should be attempted while maintaining an adequate future liver remnant. Attempts at dissecting the tumor off the involved diaphragm will result in excessive bleeding and may leave residual disease behind.<br><br>CONCLUSION: Intrahepatic mesotheliomas are rare peripherally-located malignant tumors of the liver. They require a high index of suspicion and a comprehensive workup prior to operative intervention.}, }
@article {pmid29692597, year = {2018}, author = {Saha, A and Mandal, PK and Manna, A and Khan, K and Pal, S}, title = {Well differentiated papillary mesothelioma of abdomen- a rare case with diagnostic dilemma.}, journal = {Journal of laboratory physicians}, volume = {10}, number = {2}, pages = {248-250}, pmid = {29692597}, issn = {0974-2727}, abstract = {Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.}, }
@article {pmid29690982, year = {2018}, author = {Sritharan, SS and Frandsen, JL and Omland, &#xd8; and Bruun, JM}, title = {[Malignant pleural mesothelioma].}, journal = {Ugeskrift for laeger}, volume = {180}, number = {15}, pages = {}, pmid = {29690982}, issn = {1603-6824}, mesh = {Asbestos/adverse effects ; Denmark/epidemiology ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/etiology/therapy ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/therapy ; Prognosis ; Workers' Compensation ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. The disease is of importance, since the incidence in Denmark is increasing despite cessation of the use of asbestos in the 1980s. MPM has a long latency period, and the first symptom is often dyspnoea, typically caused by pleural effusion. The diagnosis is a challenge, because cytology often is non-conclusive, and thoracoscopy is needed to obtain biopsies for immunohistochemistry. The occupational history is important, since the patients are entitled to compensation. The treatment is often limited to palliation.}, }
@article {pmid29685095, year = {2018}, author = {Takemura, Y and Satoh, M and Hatanaka, K and Kubota, S}, title = {Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells.}, journal = {Bioscience, biotechnology, and biochemistry}, volume = {82}, number = {7}, pages = {1159-1164}, doi = {10.1080/09168451.2018.1459466}, pmid = {29685095}, issn = {1347-6947}, mesh = {Apoptosis/*drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cytidine/*analogs &amp; derivatives/pharmacology ; DNA (Cytosine-5-)-Methyltransferase 1/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Fibroblasts/cytology/drug effects ; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism ; Humans ; Mesothelioma/enzymology/metabolism/*pathology ; S Phase/*drug effects ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Malignant mesothelioma is an asbestos-related aggressive tumor and current therapy remains ineffective. Zebularine as a DNA methyltransferase (DNMT) inhibitor has an anti-tumor effect in several human cancer cells. The aim of the present study was to investigate whether zebularine could induce antiproliferative effect in human malignant mesothelioma cells. Zebularine induced cell growth inhibition in a dose-dependent manner. In addition, zebularine dose-dependently decreased expression of DNMT1 in all malignant mesothelioma cells tested. Cell cycle analysis indicated that zebularine induced S phase delay. Zebularine also induced cell death in malignant mesothelioma cells. In contrast, zebularine did not induce cell growth inhibition and cell death in human normal fibroblast cells. These results suggest that zebularine has a potential for the treatment of malignant mesothelioma by inhibiting cell growth and inducing cell death.}, }
@article {pmid29677456, year = {2019}, author = {Metintas, S and Ak, G and Metintas, M}, title = {A review of the cohorts with environmental and occupational mineral fiber exposure.}, journal = {Archives of environmental &amp; occupational health}, volume = {74}, number = {1-2}, pages = {76-84}, doi = {10.1080/19338244.2018.1467873}, pmid = {29677456}, issn = {2154-4700}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Mesothelioma, Malignant ; Mineral Fibers/*toxicity ; *Occupational Exposure ; Rural Population ; Zeolites/*toxicity ; }, abstract = {The aim of the study was to examine factors associated with Malignant Mesothelioma (MM) incidence rate of the groups with occupational asbestos and environmental asbestos or erionite exposure in rural area. In this ecological study, a total of 21 cohort datasets (8 environmental and 13 occupational) were evaluated. Data were analyzed using a multiple linear regression analysis model. In environmental cohorts, the risk of MM incidence was higher in women and people exposed to erionite. In this cohort, the incidence rate of MM increased as the median exposure time increased, while the incidence decreased as the median cumulative exposure dose increased. In occupational cohorts, the incidence rate of MM was positively correlated with the median cumulative exposure dose. The risk of mesothelioma was lower in those exposed to tremolite than others. Environmental asbestos exposure is as important as occupational exposure to develop MM, and it has its own unique exposure features on the risk of MM.}, }
@article {pmid29669604, year = {2018}, author = {Fennell, DA and Kirkpatrick, E and Cozens, K and Nye, M and Lester, J and Hanna, G and Steele, N and Szlosarek, P and Danson, S and Lord, J and Ottensmeier, C and Barnes, D and Hill, S and Kalevras, M and Maishman, T and Griffiths, G}, title = {CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial.}, journal = {Trials}, volume = {19}, number = {1}, pages = {233}, pmid = {29669604}, issn = {1745-6215}, support = {25352/CRUK_/Cancer Research UK/United Kingdom ; C16728/A21400/CRUK_/Cancer Research UK/United Kingdom ; 15956/CRUK_/Cancer Research UK/United Kingdom ; 21400/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Antineoplastic Agents, Immunological/adverse effects/economics/*therapeutic use ; Clinical Trials, Phase III as Topic ; Cost-Benefit Analysis ; Double-Blind Method ; Drug Costs ; Female ; Humans ; Male ; Mesothelioma/*drug therapy/economics/immunology/pathology ; Multicenter Studies as Topic ; *Neoplasm Recurrence, Local ; Nivolumab/adverse effects/economics/*therapeutic use ; Peritoneal Neoplasms/*drug therapy/economics/immunology/pathology ; Pleural Neoplasms/*drug therapy/economics/immunology/pathology ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; Progression-Free Survival ; Quality of Life ; Randomized Controlled Trials as Topic ; Time Factors ; Treatment Outcome ; United Kingdom ; }, abstract = {BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.<br><br>METHODS: The addition of 12&#xa0;months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240&#xa0;mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12&#xa0;months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints).<br><br>DISCUSSION: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK.<br><br>TRIAL REGISTRATION: EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.}, }
@article {pmid29666782, year = {2018}, author = {Rossini, M and Rizzo, P and Bononi, I and Clementz, A and Ferrari, R and Martini, F and Tognon, MG}, title = {New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {91}, pmid = {29666782}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.}, }
@article {pmid29664355, year = {2018}, author = {Caltabiano, R and Loreto, C and Vitale, E and Matera, S and Miozzi, E and Migliore, M and Angelico, G and Tumino, R and Ledda, C and Rapisarda, V}, title = {Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report.}, journal = {Future oncology (London, England)}, volume = {14}, number = {6s}, pages = {53-57}, doi = {10.2217/fon-2017-0386}, pmid = {29664355}, issn = {1744-8301}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/*toxicity ; Biomarkers, Tumor/metabolism ; Biopsy ; Environmental Exposure/*adverse effects ; Extracellular Matrix Proteins/*metabolism ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lung/pathology ; Lung Neoplasms/chemically induced/epidemiology/*pathology ; Male ; Mesothelioma/chemically induced/epidemiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Prognosis ; Retrospective Studies ; Sicily/epidemiology ; }, abstract = {An increased standardized incidence and mortality rate were reported due to malignant mesothelioma (MM) in Biancavilla. Environmental investigations showed the presence of an asbestiform fiber: fluoro-edenite (FE). MM develops with a latency of 20-60 years from exposure and specific and sensitive biomarkers are urgently needed. For this purpose, we evaluated Fibulin-3 (Fb-3) immunoexpression in human cases of MM related to FE exposure and its prognostic role. Immunohistochemical analysis of Fb-3 was carried out in eight MM patients resident in Biancavilla and the analysis showed evidence of environmental exposure to FE fibers. Six MM cases (3 epithelioid and 3 biphasic) showed a high immunoexpression of Fb-3 in neoplastic cells with nuclear and cytoplasmic localization. One epithelioid and one biphasic subtype did not show Fb-3 immunostaining. The results demonstrate the implication of Fb-3 in MM due to FE exposure and may possibly suggest its potential role as a diagnostic and prognostic marker.}, }
@article {pmid29664352, year = {2018}, author = {Rapisarda, V and Loreto, C and Castorina, S and Romano, G and Garozzo, SF and Musumeci, A and Migliore, M and Avola, R and Cinà, D and Pomara, C and Ledda, C}, title = {Occupational exposure to fluoro-edenite and prevalence of anti-nuclear autoantibodies.}, journal = {Future oncology (London, England)}, volume = {14}, number = {6s}, pages = {59-62}, doi = {10.2217/fon-2017-0389}, pmid = {29664352}, issn = {1744-8301}, mesh = {Adult ; Antibodies, Antinuclear/*blood/immunology ; Asbestos, Amphibole/*toxicity ; Humans ; Lung/pathology ; Lung Neoplasms/blood/chemically induced/*immunology/mortality ; Male ; Mesothelioma/blood/chemically induced/*immunology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Sicily/epidemiology ; Survival Rate ; }, abstract = {An environmental contamination due to an asbestiform mineral fiber, fluoro-edenite (FE), caused a significantly increased mortality rate for malignant mesothelioma in Biancavilla, Italy. Exposure to fluoro-edenite has been associated with inflammatory processes as an early response to inhaled fibers. The aim was to explore prevalence of anti-nuclear autoantibodies (ANA) in a group of construction workers residing and working in the contaminated area. Prevalences for samples positive to ANA were 60% (n = 9) and 13% (n = 2), for exposed and nonexposed, respectively (p-value <0.05), the odds ratio was 9.75 (95% CI: 1.59-59.69). The significance of elevated ANAs in subjects exposed to fibers is unknown; additional studies may provide a better opportunity to establish a correlation between autoimmunity and environmental exposure.}, }
@article {pmid29663493, year = {2018}, author = {Munson, P and Lam, YW and MacPherson, M and Beuschel, S and Shukla, A}, title = {Mouse serum exosomal proteomic signature in response to asbestos exposure.}, journal = {Journal of cellular biochemistry}, volume = {119}, number = {7}, pages = {6266-6273}, pmid = {29663493}, issn = {1097-4644}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Asbestos/administration &amp; dosage/*toxicity ; Blood Proteins/drug effects/*metabolism ; Carcinogens/administration &amp; dosage/*toxicity ; Exosomes/drug effects/*metabolism ; Mice ; Mice, Inbred C57BL ; Proteomics ; Respiratory Aspiration ; }, abstract = {Asbestos-induced diseases like fibrosis and mesothelioma are very aggressive, without any treatment options. These diseases are diagnosed only at the terminal stages due to lack of early stage biomarkers. The recent discovery of exosomes as circulating biomarkers led us to look for exosomal biomarkers of asbestos exposure in mouse blood. In our model, mice were exposed to asbestos as a single bolus dose by oropharyngeal aspiration. Fifty-six days later blood was collected, exosomes were isolated from plasma and characterized and subjected to proteomic analysis using Tandem Mass Tag labeling. We identified many proteins, some of which were more abundant in asbestos exposed mouse serum exosomes, and three selected proteins were validated by immunoblotting. Our study is the first to show that serum exosomal proteomic signatures can reveal some important proteins relevant to asbestos exposure that have the potential to be validated as candidate biomarkers. We hope to extrapolate the positive findings of this study to humans in future studies.}, }
@article {pmid29659015, year = {2018}, author = {Barbarino, M and Cesari, D and Intruglio, R and Indovina, P and Namagerdi, A and Bertolino, FM and Bottaro, M and Rahmani, D and Bellan, C and Giordano, A}, title = {Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre-clinical assessment.}, journal = {Journal of cellular physiology}, volume = {233}, number = {9}, pages = {7391-7401}, doi = {10.1002/jcp.26579}, pmid = {29659015}, issn = {1097-4652}, mesh = {Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Down-Regulation/drug effects ; *Drug Repositioning ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inhibitory Concentration 50 ; Mesothelioma/*drug therapy/genetics/pathology ; Pyrvinium Compounds/pharmacology/*therapeutic use ; RNA, Messenger/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Time Factors ; Wnt Signaling Pathway/drug effects/genetics ; beta Catenin/metabolism ; }, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, whose incidence is increasing worldwide. Unfortunately, no effective therapies are currently available and the prognosis is extremely poor. Recently, the anti-helminthic drug pyrvinium pamoate has attracted a strong interest for its anti-cancer activity, which has been demonstrated in many cancer models. Considering the previously established inhibitory effect of pyrvinium pamoate on the Wnt/β-catenin pathway and given the important role of this pathway in MM, we investigated the potential anti-tumor activity of this drug in MM cell lines. We observed that pyrvinium pamoate significantly impairs MM cell proliferation, cloning efficiency, migration, and tumor spheroid formation. At the molecular level, our data show that pyrvinium pamoate down-regulates the expression of β-catenin and Wnt-regulates genes. Overall, our study suggests that the repurposing of pyrvinium pamoate for MM treatment could represent a new promising therapeutic approach.}, }
@article {pmid29656754, year = {2018}, author = {Sneddon, S and Dick, I and Lee, YCG and Musk, AWB and Patch, AM and Pearson, JV and Waddell, N and Allcock, RJN and Holt, RA and Robinson, BWS and Creaney, J}, title = {Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {119}, number = {}, pages = {64-70}, doi = {10.1016/j.lungcan.2018.03.009}, pmid = {29656754}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; DNA Copy Number Variations ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Mutation/*genetics ; Neurofibromin 2/*genetics ; Pleural Effusion, Malignant/*genetics/pathology ; Tumor Cells, Cultured ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.<br><br>MATERIALS AND METHODS: DNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model.<br><br>RESULTS: We identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66% and 59% respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32.<br><br>CONCLUSION: Short term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.}, }
@article {pmid29651248, year = {2018}, author = {Sinis, SI and Hatzoglou, C and Gourgoulianis, KI and Zarogiannis, SG}, title = {Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {295}, pmid = {29651248}, issn = {1664-042X}, abstract = {Nanoparticles have great potential for numerous applications due to their unique physicochemical properties. However, concerns have been raised that they may induce deleterious effects on biological systems. There is accumulating evidence that, like asbestos, inhaled nanomaterials of >5 μm and high aspect ratio (3:1), particularly rod-like carbon nanotubes, may inflict pleural disease including mesothelioma. Additionally, a recent set of case reports suggests that inhalation of polyacrylate/nanosilica could in part be associated with inflammation and fibrosis of the pleura of factory workers. However, the adverse outcomes of nanoparticle exposure to mesothelial tissues are still largely unexplored. In that context, the present review aims to provide an overview of the relevant pathophysiological implications involving toxicological studies describing effects of engineered nanoparticles on mesothelial cells and membranes. In vitro studies primarily emphasize on simulating cellular uptake and toxicity of nanotubes on benign or malignant cell lines. On the other hand, in vivo studies focus on illustrating endpoints of serosal pathology in rodent animal models. From a molecular aspect, some nanoparticle categories are shown to be cytotoxic and genotoxic after acute treatment, whereas chronic incubation may lead to malignant-like transformation. At an organism level, a number of fibrous shaped nanotubes are related with features of chronic inflammation and MWCNT-7 is the only type to consistently inflict mesothelioma.}, }
@article {pmid29641489, year = {2018}, author = {Felley-Bosco, E and Rehrauer, H}, title = {Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29641489}, issn = {1422-0067}, mesh = {Animals ; Asbestos/toxicity ; *Genetic Heterogeneity ; Mesothelioma/etiology/*genetics ; Mice ; RNA, Untranslated/*genetics ; Transcriptome ; }, abstract = {Mesothelioma is an aggressive, rapidly fatal cancer and a better understanding of its molecular heterogeneity may help with making more efficient therapeutic strategies. Non-coding RNAs represent a larger part of the transcriptome but their contribution to diseases is not fully understood yet. We used recently obtained RNA-seq data from asbestos-exposed mice and performed data mining of publicly available datasets in order to evaluate how non-coding RNA contribute to mesothelioma heterogeneity. Nine non-coding RNAs are specifically elevated in mesothelioma tumors and contribute to human mesothelioma heterogeneity. Because some of them have known oncogenic properties, this study supports the concept of non-coding RNAs as cancer progenitor genes.}, }
@article {pmid29635378, year = {2018}, author = {Schelch, K and Wagner, C and Hager, S and Pirker, C and Siess, K and Lang, E and Lin, R and Kirschner, MB and Mohr, T and Brcic, L and Marian, B and Holzmann, K and Grasl-Kraupp, B and Krupitza, G and Laszlo, V and Klikovits, T and Dome, B and Hegedus, B and Garay, T and Reid, G and van Zandwijk, N and Klepetko, W and Berger, W and Grusch, M and Hoda, MA}, title = {FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal.}, journal = {Carcinogenesis}, volume = {39}, number = {4}, pages = {534-545}, doi = {10.1093/carcin/bgy018}, pmid = {29635378}, issn = {1460-2180}, mesh = {Cell Line, Tumor ; Epidermal Growth Factor/*metabolism ; Epithelial-Mesenchymal Transition/*physiology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibroblast Growth Factor 2/*metabolism ; Humans ; Lung Neoplasms/metabolism/*pathology ; Matrix Metalloproteinase 1/metabolism ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/metabolism/*pathology ; Signal Transduction/physiology ; }, abstract = {Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting pleural surfaces, occurs in three main histological subtypes. The epithelioid and sarcomatoid subtypes are characterized by cuboid and fibroblastoid cells, respectively. The biphasic subtype contains a mixture of both. The sarcomatoid subtype expresses markers of epithelial-mesenchymal transition (EMT) and confers the worst prognosis, but the signals and pathways controlling EMT in MPM are not well understood. We demonstrate that treatment with FGF2 or EGF induced a fibroblastoid morphology in several cell lines from biphasic MPM, accompanied by scattering, decreased cell adhesion and increased invasiveness. This depended on the MAP-kinase pathway but was independent of TGFβ or PI3-kinase signaling. In addition to changes in known EMT markers, microarray analysis demonstrated differential expression of MMP1, ESM1, ETV4, PDL1 and BDKR2B in response to both growth factors and in epithelioid versus sarcomatoid MPM. Inhibition of MMP1 prevented FGF2-induced scattering and invasiveness. Moreover, in MPM cells with sarcomatoid morphology, inhibition of FGF/MAP-kinase signaling induced a more epithelioid morphology and gene expression pattern. Our findings suggest a critical role of the MAP-kinase axis in the morphological and behavioral plasticity of mesothelioma.}, }
@article {pmid29616141, year = {2018}, author = {de Fonseka, D and Underwood, W and Stadon, L and Rahman, N and Edey, A and Rogers, C and Maskell, NA}, title = {Randomised controlled trial to compare the diagnostic yield of positron emission tomography CT (PET-CT) TARGETed pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy (TARGET trial).}, journal = {BMJ open respiratory research}, volume = {5}, number = {1}, pages = {e000270}, pmid = {29616141}, issn = {2052-4439}, support = {PB-PG-0214-33095/DH_/Department of Health/United Kingdom ; }, abstract = {INTRODUCTION: Pleural malignancy, particularly malignant pleural mesothelioma (MPM) is increasing in incidence due to the long latency period from exposure to asbestos to development of the disease. MPM can be challenging to diagnose. For patients presenting without a pleural effusion, CT-guided biopsy remains the primary choice of biopsy, but the diagnostic sensitivity of this investigation is 70%-75%. Therefore, a proportion of patients will go on to require further biopsies. If the first biopsy is non-diagnostic, the chances of further non-diagnostic biopsies are high in MPM.<br><br>METHODS: Target is a multicentre randomised controlled trial, aiming to recruit 78 patients over a 30-month period, from 10 centres in the UK. Patients will be randomised to either the standard arm which is a second CT-guided biopsy, or the interventional arm, a positron emission tomography-CT scan followed by a targeted CT-guided biopsy. Patients will be followed up for 12 months (patients recruited in the last 6 months of recruitment will have 6 months of follow-up). MPM biomarker mesothelin will be checked at baseline, 6&#x2009;month and 12&#x2009;month follow-up appointments where patients are able to attend these appointments.<br><br>ETHICS AND DISSEMINATION: Ethical approval for this trial was granted by the South West-Exeter research and ethics committee (reference number 15/SW/0156). Results of the trial will be published in a peer-reviewed journal and presented at an international conference.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN 14024829; Pre-results.}, }
@article {pmid29608538, year = {2018}, author = {Liu, Y and Marsh, GM and Roggli, VL}, title = {Asbestos Fiber Concentrations in the Lungs of Brake Repair Workers: An Updated Analysis Using Several Regression Methods to Handle Nondetectable Measurements.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {7}, pages = {661-671}, doi = {10.1097/JOM.0000000000001320}, pmid = {29608538}, issn = {1536-5948}, mesh = {Adult ; Aged ; Asbestos, Amphibole/*analysis/toxicity ; *Automobiles ; Humans ; Limit of Detection ; Lung/*chemistry ; Maintenance ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects/analysis/*statistics &amp; numerical data ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Regression Analysis ; }, abstract = {OBJECTIVES: The aim of the study was to reanalyze an updated database of lung asbestos fiber levels for 21 brake repair workers who died of mesothelioma using robust maximum likelihood-based regression methods to address nondetectable measurements.<br><br>METHODS: We applied bivariate normal regression to address the doubly left-censored situation where both the lung fiber concentration of noncommercial (TAA) and commercial amphiboles (AC) were subject to detection limits. For the single left-censored situation, we applied censored normal regression to study the relationship between duration of employment (DOE) and TAA.<br><br>RESULTS: We found a statistically significant positive relationship between TAA and AC (&#x3b2;&#x200a;=&#x200a;0.49, 95% confidence interval [CI], 0.11 to 0.86) and a not statistically significant relationship between DOE and TAA (&#x3b2;&#x200a;=&#x200a;0.02, 95% CI, -0.03 to 0.06).<br><br>CONCLUSIONS: Our results provide additional support for the conclusion that exposure to commercial amphibole asbestos, and not chrysotile, is related to the occurrence of mesothelioma among some brake workers.}, }
@article {pmid29587685, year = {2018}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Quality of life of survivors of malignant pleural mesothelioma in Japan: a cross sectional study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {350}, pmid = {29587685}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/*epidemiology/therapy ; Male ; Mesothelioma/*epidemiology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care ; Pleural Neoplasms/*epidemiology/therapy ; *Quality of Life ; Surveys and Questionnaires ; *Survivors ; }, abstract = {BACKGROUND: Previous studies have indicated that people with malignant pleural mesothelioma (MPM) have a poor quality of life (QOL); however, information about the QOL of people with MPM in Japan is anecdotal. The aims of this study were to investigate the QOL of survivors of MPM in Japan and to determine the factors that correlate with their QOL.<br><br>METHODS: This was a cross sectional study. The included patients were those diagnosed with MPM in Japan. We created a self-administered questionnaire consisting of 64 questions. The questionnaires were sent to hospitals and patient advocacy groups, distributed to the patients, completed, and sent back to the researchers by postal mail. QOL was assessed with the European Organization for Research and Treatment of Cancer 16 questionnaire (QLQ) and the short version of the core domains of the Comprehensive Quality of Life Outcome questionnaire (CoQoLo).<br><br>RESULTS: In total, 133 questionnaires were collected. The QLQ assessments demonstrated that the survivors of MPM most frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The symptom scales were acceptable, but the functional scales were significantly poorer for the patients with poor performance statuses (PSs). The short CoQoLo assessment was very unfavorable for 'Being free from physical pain.' Being a long-term survivor and a survivor with a poor PS were significantly correlated with poor global health status.<br><br>CONCLUSIONS: Survivors of MPM have impaired function, a variety of symptoms, and lower QOL. Survivors of MPM, even those in good physical condition, need broad support.}, }
@article {pmid29587439, year = {2018}, author = {Sato, T and Sekido, Y}, title = {NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29587439}, issn = {1422-0067}, mesh = {Actins/metabolism ; Antineoplastic Agents/pharmacology/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; *Genetic Variation ; Hippo Signaling Pathway ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Mesothelioma/drug therapy/*genetics/metabolism ; Mesothelioma, Malignant ; Neurofibromin 2/*genetics/metabolism ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {The neurofibromatosis type 2 (NF2) gene encodes merlin, a tumor suppressor protein frequently inactivated in schwannoma, meningioma, and malignant mesothelioma (MM). The sequence of merlin is similar to that of ezrin/radixin/moesin (ERM) proteins which crosslink actin with the plasma membrane, suggesting that merlin plays a role in transducing extracellular signals to the actin cytoskeleton. Merlin adopts a distinct closed conformation defined by specific intramolecular interactions and regulates diverse cellular events such as transcription, translation, ubiquitination, and miRNA biosynthesis, many of which are mediated through Hippo and mTOR signaling, which are known to be closely involved in cancer development. MM is a very aggressive tumor associated with asbestos exposure, and genetic alterations in NF2 that abrogate merlin's functional activity are found in about 40% of MMs, indicating the importance of NF2 inactivation in MM development and progression. In this review, we summarize the current knowledge of molecular events triggered by NF2/merlin inactivation, which lead to the development of mesothelioma and other cancers, and discuss potential therapeutic targets in merlin-deficient mesotheliomas.}, }
@article {pmid29580185, year = {2018}, author = {Beaucham, C and King, B and Feldmann, K and Harper, M and Dozier, A}, title = {Assessing occupational erionite and respirable crystalline silica exposure among outdoor workers in Wyoming, South Dakota, and Montana.}, journal = {Journal of occupational and environmental hygiene}, volume = {15}, number = {6}, pages = {455-465}, doi = {10.1080/15459624.2018.1447116}, pmid = {29580185}, issn = {1545-9632}, mesh = {Construction Industry ; Forestry ; Humans ; Inhalation Exposure/analysis ; Montana ; National Institute for Occupational Safety and Health, U.S. ; Occupational Exposure/*analysis/prevention &amp; control ; Particulate Matter/analysis ; Silicon Dioxide/*analysis ; South Dakota ; United States ; Wyoming ; Zeolites/*analysis ; }, abstract = {Erionite is a naturally occurring fibrous mineral found in many parts of the world, including the western United States. Inhalational exposure to erionite fibers in some localities is associated with health effects similar to those caused by asbestos exposure, including malignant mesothelioma. Therefore, there is concern regarding occupational exposures in the western United States. Currently, there are no standard sampling and analytical methods for airborne erionite fibers, as well as no established occupational exposure limits. Due to the potential adverse health effects, characterizing and minimizing exposures is prudent. Crystalline silica also occurs naturally in areas where erionite is found, principally as the mineral quartz. Work activities involving rocks containing quartz and soils derived from those rocks can lead to exposure to respirable crystalline silica (RCS). The typically dry and dusty environment of the western United States can increase the likelihood of exposures to aerosolized rocks and soils, but inhalation exposure is also possible in more humid conditions. In this case study, we describe several outdoor occupational environments with potential exposures to erionite and RCS. We describe our method for evaluating those exposures and demonstrate: (1) the occurrence of occupational exposures to airborne erionite and RCS, (2) that the chemical make-up of the erionite mineral can be determined, and (3) that effective dust control practices are needed to reduce employee exposures to these minerals.}, }
@article {pmid29577057, year = {2018}, author = {Field, Z and Zori, A and Khullar, V and Mota, M and Feely, M and Firpi, RJ}, title = {Malignant Peritoneal Mesothelioma Presenting as Mucinous Ascites.}, journal = {ACG case reports journal}, volume = {5}, number = {}, pages = {e23}, pmid = {29577057}, issn = {2326-3253}, abstract = {We present a rare case of a 46-year-old man presenting with mucinous ascites secondary to malignant peritoneal mesothelioma (MPM) that was diagnosed via colonoscopy with biopsies. Both our findings and the clinical presentation were unique. While it is widely known that asbestos exposure is commonly associated with pleural mesothelioma, 6-10% of malignant mesotheliomas arise from the peritoneum. To date, only 4 cases of MPM with the primary tumor site in the colon have been described in the literature.}, }
@article {pmid29575036, year = {2018}, author = {Bonafede, M and Ghelli, M and Corfiati, M and Rosa, V and Guglielmucci, F and Granieri, A and Branchi, C and Iavicoli, S and Marinaccio, A}, title = {The psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects: A systematic review of published studies.}, journal = {American journal of industrial medicine}, volume = {61}, number = {5}, pages = {400-412}, doi = {10.1002/ajim.22831}, pmid = {29575036}, issn = {1097-0274}, mesh = {Adaptation, Psychological ; Asbestos/*adverse effects ; Depression/psychology ; Female ; Humans ; Lung Neoplasms/epidemiology/*psychology ; Male ; Mesothelioma/epidemiology/*psychology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Quality of Life ; Social Support ; *Stress, Psychological ; }, abstract = {BACKGROUND: The purpose of this study is to present the results of a systematic review of published research that focuses on psychological aspects of malignant mesothelioma patients and asbestos-exposed people.<br><br>METHODS: Our research includes primary studies published between 1980 and 2016, using information from the Cochrane Library, the Psychology Behavioral Sciences Collection, PsychINFO, PubMed, PubGet, PubPsych, and Scopus, in compliance with PRISMA guidelines.<br><br>RESULTS: We identified 12 papers that investigated the psychological distress and care needs of mesothelioma patients, and nine papers for asbestos-exposed subjects.<br><br>CONCLUSIONS: This paper highlights the paucity of studies on the psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects. It confirms that malignant mesothelioma is associated with the physical, emotional, and social functioning of patients, while also suggesting that the risk of developing asbestos-related diseases among asbestos-exposed subjects is associated with high levels of psychological distress, despair, and mental health difficulties.}, }
@article {pmid29574645, year = {2018}, author = {Vimercati, L and Cavone, D and Lovreglio, P and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Environmental asbestos exposure and mesothelioma cases in Bari, Apulia region, southern Italy: a national interest site for land reclamation.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {16}, pages = {15692-15701}, pmid = {29574645}, issn = {1614-7499}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Asbestos/*toxicity ; Carcinogens, Environmental/*toxicity ; Cities ; *Environmental Exposure ; Fatal Outcome ; Female ; Humans ; Italy ; Lung Neoplasms/chemically induced/diagnosis/*drug therapy/*surgery ; Male ; Mesothelioma/chemically induced/diagnosis/*drug therapy/*surgery ; Mesothelioma, Malignant ; Middle Aged ; Treatment Outcome ; }, abstract = {Asbestos is an environmental carcinogen, and asbestos-related diseases are a global-scale public health issue. We report three cases (one male and two females) of pleural malignant mesothelioma (PMM) caused by environmental asbestos exposure reported by the Apulia Regional Operating Centre (COR) to the National Mesothelioma Registry (ReNaM). The patients revealed no history of asbestos exposure even after detailed assessment. The environmental (neighborhood) asbestos exposure for each of the three cases was due to both the residential history of the subjects and their workplace, close to a military barracks, at a distance of between 45 and 100 m. Moreover, in addition to this new source of pollution, an asbestos cement factory was located in the urban area of Bari municipality, in the Apulia region, southern Italy. Environmental-residential/neighborhood asbestos exposure in the city of Bari, a contaminated area classified as a site of national concern for land reclamation, is discussed also with reference to the military barracks.}, }
@article {pmid29574404, year = {2018}, author = {Marsh, GM and Riordan, AS and Keeton, KA and Benson, SM}, title = {Response to: 'Reanalysis of non-occupational exposure to asbestos and the risk of pleural mesothelioma' by Finkelstein.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {6}, pages = {473-474}, doi = {10.1136/oemed-2018-105020}, pmid = {29574404}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, }
@article {pmid29572002, year = {2018}, author = {Tsim, S and Humphreys, CA and Cowell, GW and Stobo, DB and Noble, C and Woodward, R and Kelly, CA and Alexander, L and Foster, JE and Dick, C and Blyth, KG}, title = {Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {118}, number = {}, pages = {48-56}, pmid = {29572002}, issn = {1872-8332}, support = {25355/CRUK_/Cancer Research UK/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor ; Contrast Media ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening.<br><br>MATERIALS AND METHODS: 60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in at least one ROI at or before 4.5&#x202f;min) was compared with subjective MRI and Computed Tomography (CT) morphology results. MSIG was correlated against tumour MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma.<br><br>RESULTS: 71% (41/58) patients had PM. Pleural thickening was <10&#x202f;mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61-94%), specificity 83% (95% CI 68-91%), positive predictive value 68% (95% CI 47-84%), negative predictive value 92% (78-97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r&#x202f;=&#x202f;0.4258, p&#x202f;=&#x202f;.02).<br><br>DISCUSSION: ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted.}, }
@article {pmid29571785, year = {2018}, author = {Kato, K and Gemba, K and Ashizawa, K and Arakawa, H and Honda, S and Noguchi, N and Honda, S and Fujimoto, N and Kishimoto, T}, title = {Low-dose chest computed tomography screening of subjects exposed to asbestos.}, journal = {European journal of radiology}, volume = {101}, number = {}, pages = {124-128}, doi = {10.1016/j.ejrad.2018.02.017}, pmid = {29571785}, issn = {1872-7727}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Cross-Sectional Studies ; Female ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/*diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnostic imaging/epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Prevalence ; Prospective Studies ; *Radiation Dosage ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVES: The primary aim was to reveal the prevalence of lung cancer (LC) and malignant pleural mesothelioma (MPM) in subjects with past asbestos exposure (AE). We also examined pulmonary or pleural changes correlated with the development of LC.<br><br>MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional study. There were 2132 subjects enrolled between 2010 and 2012. They included 96.2% men and 3.8% women, with a mean age of 76.1 years; 78.8% former or current smokers; and 21.2% never smokers. We screened subjects using low-dose computed tomography (CT). The CT images were taken with a CT dose Index of 2.7&#x202f;mGy. The evaluated CT findings included subpleural curvilinear shadow/subpleural dots, ground glass opacity or interlobular reticular opacity, traction bronchiectasia, honeycombing change, parenchymal band, emphysema changes, pleural effusion, diffuse pleural thickening, rounded atelectasis, pleural plaques (PQs), and tumor formation.<br><br>RESULTS: The PQs were detected in most of subjects (89.4%) and emphysema changes were seen in 46.0%. Fibrotic changes were detected in 565 cases (26.5%). A pathological diagnosis of LC was confirmed in 45 cases (2.1%) and MPM was confirmed in 7 cases (0.3%). The prevalence of LC was 2.5% in patients with a smoking history, which was significantly higher than that in never smokers (0.7%, p&#x202f;=&#x202f;0.027). The prevalence of LC was 2.8% in subjects with emphysema changes, which was higher than that of subjects without those findings (1.6%); although, the difference was not statistically significant (p&#x202f;=&#x202f;0.056). The prevalence of LC in subjects with both fibrotic plus emphysema changes was 4.0%, which was significantly higher than that of subjects with neither of those findings (1.8%, p&#x202f;=&#x202f;0.011). Logistic regression analysis revealed smoking history, fibrotic plus emphysema changes, and pleural effusion as significant explanatory variables.<br><br>CONCLUSIONS: Smoking history, fibrotic plus emphysema changes, and pleural effusion were correlated with the prevalence of LC.}, }
@article {pmid29564943, year = {2018}, author = {Maxim, LD and Utell, MJ}, title = {Review of refractory ceramic fiber (RCF) toxicity, epidemiology and occupational exposure.}, journal = {Inhalation toxicology}, volume = {30}, number = {2}, pages = {49-71}, doi = {10.1080/08958378.2018.1448019}, pmid = {29564943}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Environmental Monitoring ; Humans ; Mineral Fibers/*toxicity ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects/analysis ; }, abstract = {This literature review on refractory ceramic fibers (RCF) summarizes relevant information on manufacturing, processing, applications, occupational exposure, toxicology and epidemiology studies. Rodent toxicology studies conducted in the 1980s showed that RCF caused fibrosis, lung cancer and mesothelioma. Interpretation of these studies was difficult for various reasons (e.g. overload in chronic inhalation bioassays), but spurred the development of a comprehensive product stewardship program under EPA and later OSHA oversight. Epidemiology studies (both morbidity and mortality) were undertaken to learn more about possible health effects resulting from occupational exposure. No chronic animal bioassay studies on RCF have been conducted since the 1980s. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer. Evidence supporting a finding that urinary tumors are associated with RCF exposure remains, but is weaker. One reported, but unconfirmed, mesothelioma was found in an individual with prior occupational asbestos exposure. An elevated SMR for leukemia was found, but was absent in the highly exposed group and has not been observed in studies of other mineral fibers. The industry will continue the product stewardship program including the mortality study.}, }
@article {pmid29553831, year = {2018}, author = {Munson, P and Lam, YW and Dragon, J and MacPherson, M and Shukla, A}, title = {Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {32}, number = {8}, pages = {4328-4342}, pmid = {29553831}, issn = {1530-6860}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; P20 RR021905/RR/NCRR NIH HHS/United States ; P30 GM118228/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Carcinogens/toxicity ; Cell Line ; Epithelial Cells/drug effects/*physiology ; Epithelial-Mesenchymal Transition/drug effects/physiology ; Epithelium/drug effects/*physiology ; Exosomes/*genetics ; Gene Expression/drug effects/*genetics ; Humans ; Inhalation Exposure/adverse effects ; Lung/drug effects/*physiology ; Macrophages/drug effects/physiology ; }, abstract = {Asbestos exposure is a determinate cause of many diseases, such as mesothelioma, fibrosis, and lung cancer, and poses a major human health hazard. At this time, there are no identified biomarkers to demarcate asbestos exposure before the presentation of disease and symptoms, and there is only limited understanding of the underlying biology that governs asbestos-induced disease. In our study, we used exosomes, 30-140 nm extracellular vesicles, to gain insight into these knowledge gaps. As inhaled asbestos is first encountered by lung epithelial cells and macrophages, we hypothesize that asbestos-exposed cells secrete exosomes with signature proteomic cargo that can alter the gene expression of mesothelial cells, contributing to disease outcomes like mesothelioma. In the present study using lung epithelial cells (BEAS2B) and macrophages (THP-1), we first show that asbestos exposure causes changes in abundance of some proteins in the exosomes secreted from these cells. Furthermore, exposure of human mesothelial cells (HPM3) to these exosomes resulted in gene expression changes related to epithelial-to-mesenchymal transition and other cancer-related genes. This is the first report to indicate that asbestos-exposed cells secrete exosomes with differentially abundant proteins and that those exosomes have a gene-altering effect on mesothelial cells.-Munson, P., Lam, Y.-W., Dragon, J. MacPherson, M., Shukla, A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.}, }
@article {pmid29547510, year = {2018}, author = {Allen, LP and Baez, J and Stern, MEC and Takahashi, K and George, F}, title = {Trends and the Economic Effect of Asbestos Bans and Decline in Asbestos Consumption and Production Worldwide.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {3}, pages = {}, pmid = {29547510}, issn = {1660-4601}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Asbestos/economics/toxicity ; Environmental Exposure/*prevention &amp; control ; Gross Domestic Product ; Humans ; }, abstract = {Although some countries have reduced asbestos consumption and instituted bans, other countries continue to produce and consume asbestos even as asbestos-related deaths mount and the associated societal costs are high. Asbestos production and consumption has declined globally; the number of bans has increased; and the speed at which countries have tapered off consumption has increased. Using country-level data, we study the economic impact of historical changes in the production and use of asbestos. We compare changes in gross domestic product (GDP) following the enactment of asbestos bans. We do not find any significant effect on GDP following an asbestos ban. In a regional case study, we compare changes in GDP and employment with changes in asbestos production. Regional-level data revealed a temporary employment decline at the local level that was then reversed.}, }
@article {pmid29545973, year = {2018}, author = {Naeini, YB and Arcega, R and Hirschowitz, S and Rao, N and Xu, H}, title = {Post-irradiation pericardial malignant mesothelioma with deletion of p16: a case report.}, journal = {Cancer biology &amp; medicine}, volume = {15}, number = {1}, pages = {97-102}, pmid = {29545973}, issn = {2095-3941}, abstract = {Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15-25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.}, }
@article {pmid29534192, year = {2018}, author = {Gilham, C and Rake, C and Hodgson, J and Darnton, A and Burdett, G and Peto Wild, J and Newton, M and Nicholson, AG and Davidson, L and Shires, M and Treasure, T and Peto, J and , }, title = {Past and current asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS).}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1745-1756}, pmid = {29534192}, issn = {1464-3685}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis ; Carcinogens, Environmental/*adverse effects ; Environmental Exposure/*standards ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Regression Analysis ; Risk Assessment ; Risk Factors ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Occupational and environmental airborne asbestos concentrations are too low and variable for lifetime exposures to be estimated reliably, and building workers and occupants may suffer higher exposure when asbestos in older buildings is disturbed or removed. Mesothelioma risks from current asbestos exposures are therefore not known.<br><br>METHODS: We interviewed and measured asbestos levels in lung samples from 257 patients treated for pneumothorax and 262 with resected lung cancer, recruited in England and Wales. Average lung burdens in British birth cohorts from 1940 to 1992 were estimated for asbestos-exposed workers and the general population.<br><br>RESULTS: Regression analysis of British mesothelioma death rates and average lung burdens in birth cohorts born before 1965 suggests a lifetime mesothelioma risk of approximately 0.01% per fibre/mg of amphiboles in the lung. In those born since 1965, the average lung burden is &#x223c;1 fibre/mg among those with no occupational exposure.<br><br>CONCLUSIONS: The average lifetime mesothelioma risk caused by recent environmental asbestos exposure in Britain will be about 1 in 10&#xa0;000. The risk is an order of magnitude higher in a subgroup of exposed workers and probably in occupants in the most contaminated buildings. Further data are needed to discover whether asbestos still present in buildings, particularly schools, is a persistent or decreasing hazard to workers who disturb it and to the general population, and whether environmental exposure occurs predominantly in childhood or after beginning work. Similar studies are needed in other countries to estimate continuing environmental and occupational mesothelioma hazards worldwide, including the contribution from chrysotile.}, }
@article {pmid29531907, year = {2018}, author = {van Zandwijk, N and McDiarmid, J and Brahmbhatt, H and Reid, G}, title = {Response to "An innovative mesothelioma treatment based on mir-16 mimic loaded EGFR targeted minicells (TargomiRs)".}, journal = {Translational lung cancer research}, volume = {7}, number = {Suppl 1}, pages = {S60-S61}, pmid = {29531907}, issn = {2218-6751}, }
@article {pmid29524617, year = {2018}, author = {McCambridge, AJ and Napolitano, A and Mansfield, AS and Fennell, DA and Sekido, Y and Nowak, AK and Reungwetwattana, T and Mao, W and Pass, HI and Carbone, M and Yang, H and Peikert, T}, title = {Progress in the Management of Malignant Pleural Mesothelioma in 2017.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {5}, pages = {606-623}, pmid = {29524617}, issn = {1556-1380}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; 15569/CRUK_/Cancer Research UK/United Kingdom ; 21400/CRUK_/Cancer Research UK/United Kingdom ; R01 CA160715/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Immunotherapy/*methods/trends ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication, and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. Whereas recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 and the expression programmed death receptor ligand 1, are highlighting new potential therapeutic strategies. Furthermore, there continues to be an ever-expanding number of clinical studies investigating systemic therapies for MPM. These trials are primarily focused on immunotherapy using immune checkpoint inhibitors alone or in combination with other immunotherapies and nonimmunotherapies. In addition, other promising targeted therapies, including pegylated adenosine deiminase (ADI-PEG20), which focuses on argininosuccinate synthase 1-deficient tumors, and tazemetostat, an enhancer of zeste 2 polycomb repressive complex 2 subunit inhibitor of BRCA1 associated protein 1 gene (BAP1)-deficient tumors, are currently being explored.}, }
@article {pmid29523930, year = {2018}, author = {Casalone, E and Allione, A and Viberti, C and Pardini, B and Guarrera, S and Betti, M and Dianzani, I and Aldieri, E and Matullo, G}, title = {DNA methylation profiling of asbestos-treated MeT5A cell line reveals novel pathways implicated in asbestos response.}, journal = {Archives of toxicology}, volume = {92}, number = {5}, pages = {1785-1795}, doi = {10.1007/s00204-018-2179-y}, pmid = {29523930}, issn = {1432-0738}, mesh = {Antigens, Neoplasm/genetics ; Asbestos/chemistry/*toxicity ; Asbestos, Crocidolite/administration &amp; dosage/toxicity ; Asbestos, Serpentine/administration &amp; dosage/toxicity ; Carbonic Anhydrase IX/genetics ; Cell Line ; DNA Methylation/*drug effects ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects ; Humans ; Lung Neoplasms/chemically induced/genetics ; Mesothelioma/chemically induced/genetics ; Mesothelioma, Malignant ; Real-Time Polymerase Chain Reaction ; Transcriptome/*drug effects ; }, abstract = {Occupational and environmental asbestos exposure is the main determinant of malignant pleural mesothelioma (MPM), however, the mechanisms by which its fibres contribute to cell toxicity and transformation are not completely clear. Aberrant DNA methylation is a common event in cancer but epigenetic modifications involved specifically in MPM carcinogenesis need to be better clarified. To investigate asbestos-induced DNA methylation and gene expression changes, we treated Met5A mesothelial cells with different concentrations of crocidolite and chrysotile asbestos (0.5 ÷ 5.0 µg/cm[2], 72 h incubation). Overall, we observed 243 and 302 differentially methylated CpGs (≥ 10%) between the asbestos dose at 5 µg/cm[2] and untreated control, in chrysotile and crocidolite treatment, respectively. To examine the dose-response effect, Spearman's correlation test was performed and significant CpGs located in genes involved in migration/cell adhesion processes were identified in both treatments. Moreover, we found that both crocidolite and chrysotile exposure induced a significant up-regulation of CA9 and SRGN (log2 fold change > 1.5), previously reported as associated with a more aggressive MPM phenotype. However, we found no correlation between methylation and gene expression changes, except for a moderate significant inverse correlation at the promoter region of DKK1 (Spearman rho = - 1, P value = 0.02) after chrysotile exposure. These results describe for the first time the relationship between DNA methylation modifications and asbestos exposure. Our findings provide a basis to further explore and validate asbestos-induced DNA methylation changes, that could influence MPM carcinogenesis and possibly identifying new chemopreventive target.}, }
@article {pmid29520212, year = {2018}, author = {Franko, A and Kotnik, N and Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V}, title = {The Influence of Genetic Variability on the Risk of Developing Malignant Mesothelioma.}, journal = {Radiology and oncology}, volume = {52}, number = {1}, pages = {105-111}, pmid = {29520212}, issn = {1318-2099}, abstract = {BACKGROUND: Malignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in the mechanism of carcinogenesis; therefore, genetic variability in antioxidative defence may modify an individual's susceptibility to this cancer. This study investigated the influence of functional polymorphisms of NQO1, CAT, SOD2 and hOGG1 genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk.<br><br>PATIENTS AND METHODS: In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms.<br><br>RESULTS: The risk of malignant mesothelioma increased with smoking, odds ratio (OR) 9.30 [95% confidence interval (CI): 4.83-17.98] and slightly with age, OR 1.10 (95% CI: 1.08-1.14). Medium and high asbestos exposures represented 7-times higher risk of malignant mesothelioma compared to low exposure, OR 7.05 (95% CI 3.59-13.83). NQO1 rs1800566 was significantly associated with increased malignant mesothelioma risk, OR 1.73 (95% CI 1.02-2.96). Although there was no independent association between either CAT rs1001179 or hOGG1 rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, ORint 0.27 (95% CI 0.10-0.77).<br><br>CONCLUSIONS: Our findings suggest a role of both genetic variability in antioxidative defence and repair as well as the impact of gene-gene interactions in the development of malignant mesothelioma. The results of this study could add to our understanding of pathogenesis of malignant mesothelioma and contribute to prevention and earlier diagnosis of this aggressive cancer.}, }
@article {pmid29508763, year = {2018}, author = {Scherpereel, A and Wallyn, F and Albelda, SM and Munck, C}, title = {Novel therapies for malignant pleural mesothelioma.}, journal = {The Lancet. Oncology}, volume = {19}, number = {3}, pages = {e161-e172}, doi = {10.1016/S1470-2045(18)30100-1}, pmid = {29508763}, issn = {1474-5488}, support = {P01 CA066726/CA/NCI NIH HHS/United States ; R01 CA172921/CA/NCI NIH HHS/United States ; }, mesh = {Angiogenesis Inhibitors/adverse effects/*therapeutic use ; Animals ; Antineoplastic Agents, Immunological/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Humans ; Lung Neoplasms/*drug therapy/immunology/metabolism/pathology ; Mesothelioma/*drug therapy/immunology/metabolism/pathology ; Mesothelioma, Malignant ; Molecular Targeted Therapy/adverse effects/*methods ; Pleural Neoplasms/*drug therapy/immunology/metabolism/pathology ; Signal Transduction/drug effects ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments.}, }
@article {pmid29507806, year = {2018}, author = {Foddis, R and Bonotti, A and Landi, S and Fallahi, P and Guglielmi, G and Cristaudo, A}, title = {Biomarkers in the prevention and follow-up of workers exposed to asbestos.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S360-S368}, pmid = {29507806}, issn = {2072-1439}, abstract = {Although in most developed countries the use of asbestos is banned, there is still a consistent portion of the world where asbestos extraction, trading and manufacturing of asbestos-made products is largely diffuse. Worldwide, hundreds of millions of people are at risk of developing an asbestos caused disease because of occupational, environmental or domestic exposure. The WHO estimates that asbestos is responsible for more than 100,000 deaths yearly. This scenario has prompted the research on biomarkers potentially useful for early diagnosis, prognosis and preventive programs on exposed population as well. Here we reviewed the up-to-date literature on this field of research highlighting that along with mesothelin and osteopontin (OPN), some more recently investigated molecules, such as high mobility group box 1 (HMGB1) protein, fibulin-3 and some miRNAs showed very promising. Most of the carried-out studies showed an interesting diagnostic and prognostic performance of some biomarkers, but since they usually lack adequate either specificity or sensitivity, their use in screening or in preventive programs is still not recommended on a routine basis. However, this review suggests the need for more reliable experimental design involving larger population and preferring longitudinal screening of asbestos exposed individuals rather than a single baseline assessment investigation. In addition, given their better diagnostic accuracy, the use of panels including several biomarkers is highly recommended.}, }
@article {pmid29507805, year = {2018}, author = {Cristaudo, A and Bonotti, A and Guglielmi, G and Fallahi, P and Foddis, R}, title = {Serum mesothelin and other biomarkers: what have we learned in the last decade?.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S353-S359}, pmid = {29507805}, issn = {2072-1439}, abstract = {In the last decade there is been much interest in noninvasive, economic and well-accepted diagnostic tests for screening of subjects exposed to asbestos, and in patients with malignant pleuric mesothelioma (MPM) for diagnosis or monitoring response to treatment. Several biomarkers have been suggested as tools for screening and early diagnosis of MPM. Currently, in patients with MPM, have been reported high levels of soluble mesothelin-related peptides (SMRP), plasmatic osteopontin (pOPN), vimentin, fibulin-3 and many others as promising marker for diagnosis, even their use in prevention monitoring is still discussed. In this type of disease, a key role could be played by miRNAs, which expression has been investigated in a large series of MPM to examine new pathways useful in diagnosis, prognosis and therapy. An altered expression of some proteins has been reported, useful as biomarkers, in comparative proteomic analysis of malignant pleural mesothelioma. New promising markers are nowadays under study and alone or better in combination, they'll be very helpful in diagnosing, monitoring mesothelioma patients or for screening of risk groups.}, }
@article {pmid29507804, year = {2018}, author = {Bruno, R and Alì, G and Fontanini, G}, title = {Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S342-S352}, pmid = {29507804}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in clinical practice, a prospective validation is necessary, as these approaches could surely improve the differential diagnosis between malignant and benign pleural lesions.}, }
@article {pmid29507796, year = {2018}, author = {Alì, G and Bruno, R and Fontanini, G}, title = {The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S276-S284}, pmid = {29507796}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM), an asbestos-induced tumor, represents significant diagnostic challenges for pathologists. Its histological diagnosis is stepwise and should be based on morphological assessment, supported by clinical and radiological findings, and supplemented with immunohistochemistry (IHC) and, more recently, molecular tests. The main diagnostic dilemmas are the differential diagnoses with benign mesothelial proliferations and other pleural malignant tumors. The present review is an update regarding the morphological, immunohistochemical, and molecular features with respect to MPM diagnosis. Data sources include a survey of the biomedical literature from PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and textbooks focusing on the pathological diagnosis of MPM and associated immunohistochemical and molecular markers. The histological findings of MPM could facilitate its diagnosis and provide important prognostic information. The immunohistochemical approach should rest on the application of a panel including positive (mesothelial-related) and negative markers with greater than 80% sensitivity and specificity, which need to be selected based on morphology and clinical information. Moreover, in challenging cases, fluorescent in situ hybridization (FISH) testing for the p16 deletion and IHC to evaluate the loss of BRCA1-associated protein 1 (BAP1) expression could be useful in distinguishing benign from malignant pleural proliferations.}, }
@article {pmid29507795, year = {2018}, author = {Ceruti, P and Lonni, S and Baglivo, F and Marchetti, G}, title = {Endoscopic diagnosis and management of pleural effusion in malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S269-S275}, pmid = {29507795}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive tumor, that requires proper diagnosis and management. Symptoms are nonspecific and chest computed tomography (CT) and chest ultrasound (US) are important radiological tools in the initial workup to identify early pathological signs. Performing a medical thoracoscopy (MT) is essential for a definitive diagnosis of MPM. The procedure, integrated with a prior US, allows a global evaluation of the pleural cavity and the execution of multiple targeted biopsies, with low risk of complications. Some different endoscopic patterns are recognized. Thoracoscopic biopsies provide enough material to allow a thorough pathological and immunohistochemical characterization. The presence of extensive pleural adhesions and critical patient conditions are the only absolute contraindications. The clinical course of MPM is characterized by chronic symptoms such as chest pain and progressive dyspnea, the latter caused mainly by recurrent pleural effusion. Palliative interventions are required in order to relieve symptoms and improve the quality of life (QoL). These include thoracentesis, pleurodesis and the placement of an indwelling pleural catheter.}, }
@article {pmid29507794, year = {2018}, author = {Falaschi, F and Romei, C and Fiorini, S and Lucchi, M}, title = {Imaging of malignant pleural mesothelioma: it is possible a screening or early diagnosis program?-a systematic review about the use of screening programs in a population of asbestos exposed workers.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S262-S268}, pmid = {29507794}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) in an uncommon neoplasia with high mortality rate, mostly related to professional asbestos exposure. Clinical manifestations are not specific so that diagnosis is performed at advanced stage and screening protocols are not feasible now. On the other hand, asbestos-exposed workers have a high incidence of developing lung cancer. Low-dose computed tomography (LDCT) is a volumetric acquisition technique with high spatial resolution and a low dose exposure; it is used in many trials to detect lung tumours at an early stage in screening protocols, reducing mortality rate in smoker subjects. In recent papers, the possibly role of lung cancer screening was evaluated and recommended also in subjects exposed to asbestos. This article summarizes previous and present clinical trials validated for lung cancer screening, to discuss the possibility of early diagnosis or screening programs in a population of asbestos exposed workers by LDCT.}, }
@article {pmid29507793, year = {2018}, author = {Bianco, A and Valente, T and De Rimini, ML and Sica, G and Fiorelli, A}, title = {Clinical diagnosis of malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S253-S261}, pmid = {29507793}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour which, despite progress in diagnostic procedures and biomolecular research, has poor prognosis. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. MPM diagnosis requires imaging procedures X-ray and computed tomography (CT) scans; magnetic resonance imaging (MRI) better defines the extension of the tumor while PET scanning provides additional information on metabolic activity, metastases, and response to treatment. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Multimodality treatment including surgery, chemotherapy and radiotherapy has been associated with a better survival in selected patients. Clinical translational research including new approaches targeting immune-checkpoints is opening new horizons which may lead to personalised treatments.}, }
@article {pmid29507792, year = {2018}, author = {Melaiu, O and Gemignani, F and Landi, S}, title = {The genetic susceptibility in the development of malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S246-S252}, pmid = {29507792}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity whose main risk factor is exposure to asbestos. However, it has been shown that only a minority of exposed people develops MPM. In fact, the incidence among professionally exposed workers was shown to vary between 0.5% and 18.0%. Various hints suggested that other important cofactors could play a role, in particular the genetic susceptibility. Impressive is the case of Cappadocians families exposed to erionite and affected by an "epidemic" of MPM with about half of the inhabitants dying for the disease. However, no results for a "Cappadocia" gene of susceptibility to MPM have been obtained yet and more studies are needed. Among asbestos-exposed workers, several studies reported familial cases of MPM, suggesting that heredity could be important in the tumor development. However, large studies on familial clusters showed only weak increased risks that could be attributable also to indirect exposures in a contaminated household. Moreover, the risk of developing MPM is increased of a limited extent among people exposed to asbestos with a positive history of familial cancers. A particular is represented by carriers of germline mutations within BAP1 gene. In families and in animal models, mutations within BAP1 are strongly predisposing to develop MPM. However, also other types of cancer (such as uveal melanoma) are present, thus BAP1 mutations are considered as responsible for a hereditary form of a multi-cancer syndrome. In any case, among sporadic MPM, the prevalence of germline BAP1 mutations is negligible. Finally, genetic studies highlighted the presence of low-risk susceptibility alleles, such as those within XRCC3, NAT2 or GSTM1. Two different genome-wide association studies could not find positive associations reaching the genome-wide statistical significance threshold, however, both were concordant in showing a weak signal within the SDK1 gene region. Overall, it could be concluded that, as for other types of sporadic cancers, the susceptibility to develop MPM following asbestos exposure is modulated moderately by the individual genetic background. Further studies on larger series could help in a better characterization of more genes predisposing to MPM, being this tumor a rare disease.}, }
@article {pmid29507791, year = {2018}, author = {Pira, E and Donato, F and Maida, L and Discalzi, G}, title = {Exposure to asbestos: past, present and future.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S237-S245}, pmid = {29507791}, issn = {2072-1439}, abstract = {This paper summarises the past, present and future of asbestos exposure. The future scenarios as to the mesothelioma incidence in countries, where asbestos has been banned, are discussed.}, }
@article {pmid29507789, year = {2018}, author = {Marinaccio, A and Binazzi, A and Bonafede, M and Di Marzio, D and Scarselli, A and , }, title = {Epidemiology of malignant mesothelioma in Italy: surveillance systems, territorial clusters and occupations involved.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S221-S227}, pmid = {29507789}, issn = {2072-1439}, abstract = {BACKGROUND: As a legacy of the large asbestos consumption until the definitive ban in 1992, Italy is currently suffering a severe epidemic of asbestos related diseases. The aim of this paper is to describe the surveillance system for mesothelioma incidence and to provide evidences regarding the occurrence of the disease in Italy and the circumstances of asbestos exposure.<br><br>METHODS: Italian National Register of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with Regional Operating Centres (CORs) active in each Italian region, identifying incident malignant mesothelioma (MM) cases from health care structures. Occupational history, lifestyle habits and residential history are obtained using a standardised questionnaire, administered by a trained interviewer, to the subject or to the next of kin. Descriptive epidemiological figures, occupations involved in exposures and territorial maps of MM cases have been produced.<br><br>RESULTS: At December 2016, ReNaM has collected 27,356 MM cases for the incidence period between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of interviewed cases (14,818). Non-occupational exposure is still relevant with 4.9% and 4.4% of cases for which respectively a familial exposure (due to the cohabitation with an occupational exposed subject) and an environmental exposure (due to the residence near a contaminated site) has been detected.<br><br>DISCUSSION: The epidemiological surveillance of MM incident cases, by the means of a national register for estimating the occurrence of the disease and identifying the circumstances of asbestos exposure, is a relevant tool for preventing asbestos exposure, for supporting the effectiveness of insurance system and for estimating reliable epidemiological figures.}, }
@article {pmid29507420, year = {2018}, author = {Rehrauer, H and Wu, L and Blum, W and Pecze, L and Henzi, T and Serre-Beinier, V and Aquino, C and Vrugt, B and de Perrot, M and Schwaller, B and Felley-Bosco, E}, title = {How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations.}, journal = {Oncogene}, volume = {37}, number = {20}, pages = {2645-2659}, pmid = {29507420}, issn = {1476-5594}, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Asbestos, Crocidolite/*adverse effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Lung Neoplasms/chemically induced/*genetics/metabolism ; Macrophage Activation ; Mesothelioma/chemically induced/*genetics/metabolism ; Mesothelioma, Malignant ; Mice ; Mutation ; Phosphoproteins ; Polymorphism, Single Nucleotide ; *RNA Editing ; Trans-Activators ; Transcription Factors ; *Transcriptional Activation ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; YAP-Signaling Proteins ; }, abstract = {Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with further activation in tumors, paralleled by increased levels of cells with nuclear YAP/TAZ. Arg1 was one of the highest upregulated genes in inflamed tissue and tumor. Inflamed tissue showed increased levels of single-nucleotide variations, with an RNA-editing signature, which were even higher in the tumor samples. Subcutaneous injection of asbestos-treated, but tumor-free mice with syngeneic mesothelioma tumor cells resulted in a significantly higher incidence of tumor growth when compared to naïve mice supporting the role of the environment in tumor progression.}, }
@article {pmid29506546, year = {2018}, author = {Yin, W and Zheng, G and Yang, K and Song, H and Liang, Y}, title = {Analysis of prognostic factors of patients with malignant peritoneal mesothelioma.}, journal = {World journal of surgical oncology}, volume = {16}, number = {1}, pages = {44}, pmid = {29506546}, issn = {1477-7819}, support = {1213018ZD//Cangzhou Science and Technology Research and Development Plan/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Cisplatin/administration &amp; dosage ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/drug therapy/*pathology ; Lymphocytes/*pathology ; Male ; Mesothelioma/drug therapy/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neutrophils/*pathology ; Pemetrexed/administration &amp; dosage ; Peritoneal Neoplasms/drug therapy/*pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: The study aims to find out independent prognostic factors for patients with malignant peritoneal mesothelioma (MPeM).<br><br>METHODS: Patients with pathologically proven MPeM were retrospectively reviewed. Potential prognostic factors were analyzed, including age, gender, asbestos exposure, body mass index (BMI), treatment, and laboratory results, such as blood routine examination and liver functions. The influences of various risk factors on the prognoses were analyzed by univariate analysis. A Cox regression model analysis established independent factors for the survival prognosis of the patients.<br><br>RESULTS: Seventy MPeM patients, including 33 patients who received intraperitoneal chemotherapy with cisplatin, 14 patients who received systemic chemotherapy with cisplatin&#x2009;+&#x2009;pemetrexed, and 21 untreated patients were included in this study. The 1-year survival was 32.9%, the 2-year survival was 10%, and the 3-year survival was 2.9%. The median age of MPeM was 62&#xa0;years, and the female-to-male ratio was 1:0.56. The univariate and multivariate analyses showed that treatment, albumin (ALB), and blood neutrophil-to-lymphocyte ratio (NLR) were independent factors that affected the overall survival (OS) of MPeM patients.<br><br>CONCLUSION: High blood NLR and hypoalbuminemia are adverse prognostic factors for MPeM patients. Systemic chemotherapy and intraperitoneal chemotherapy can prolong the survival period.}, }
@article {pmid29498660, year = {2018}, author = {Pietrofesa, RA and Chatterjee, S and Park, K and Arguiri, E and Albelda, SM and Christofidou-Solomidou, M}, title = {Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {7}, number = {3}, pages = {}, pmid = {29498660}, issn = {2076-3921}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R21 AT008291/AT/NCCIH NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, abstract = {Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2[-]/[-]) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm[2]) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2[-/-] macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.}, }
@article {pmid29495596, year = {2018}, author = {Angelico, G and Caltabiano, R and Loreto, C and Ieni, A and Tuccari, G and Ledda, C and Rapisarda, V}, title = {Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report.}, journal = {International journal of molecular sciences}, volume = {19}, number = {3}, pages = {}, pmid = {29495596}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Aquaporin 1/genetics/*metabolism ; Asbestos, Amphibole/*adverse effects ; Biomarkers, Tumor ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*etiology/*metabolism/mortality/pathology ; Male ; Mesothelioma/*etiology/*metabolism/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*etiology/*metabolism/pathology ; Prognosis ; Proportional Hazards Models ; }, abstract = {BACKGROUND: The immunohistochemical expression of aquaporin-1 (AQP1) in asbestos-related malignant pleural mesothelioma (MPM) is emerging as a useful prognostic indicator of improved survival. A significantly increased incidence of MPM in a small town in southern Italy was ascribed to exposure to fluoro-edenite (FE), a naturally occurring asbestos fiber. We investigated the immunohistochemical expression of AQP1 in patients affected by FE-related MPM; taking into consideration its suggested independent prognostic role, its possible correlation with clinicopathological parameters and patient outcome was also evaluated.<br><br>METHODS: Ten patients were selected for this study, as neoplastic tissue blocks, clinical and follow-up data were available. The immunohistochemical overexpression of AQP1 was defined as &#x2265;50% of tumor cells showing membranous staining.<br><br>RESULTS: Six cases showed AQP1 expression in &#x2265;50% of tumor cells; in this group, a significant association of AQP1 overexpression with an increased median overall survival (OS) of 26.3 months was observed. By contrast, four patients exhibited an AQP1 score of <50% of stained cells, with a shorter median OS of 8.9 months.<br><br>CONCLUSIONS: The present study represents further confirmation of the hypothesized prognostic role of AQP1, which seems a reliable prognostic indicator.}, }
@article {pmid29480760, year = {2018}, author = {Attanoos, RL and Churg, A and Galateau-Salle, F and Gibbs, AR and Roggli, VL}, title = {Malignant Mesothelioma and Its Non-Asbestos Causes.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {142}, number = {6}, pages = {753-760}, doi = {10.5858/arpa.2017-0365-RA}, pmid = {29480760}, issn = {1543-2165}, mesh = {Asbestos, Serpentine/adverse effects ; Europe ; Female ; Germ-Line Mutation ; Humans ; Lung Neoplasms/chemically induced/*etiology/genetics/pathology ; Male ; Mesothelioma/chemically induced/*etiology/genetics/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/adverse effects ; North America ; Peritoneal Neoplasms/chemically induced/*etiology/genetics/pathology ; Pleural Neoplasms/chemically induced/*etiology/genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; Zeolites/adverse effects ; }, abstract = {CONTEXT: - Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma.<br><br>OBJECTIVE: - To provide a review of non-asbestos causes for malignant mesothelioma.<br><br>DATA SOURCES: - Review of relevant published literature via PubMed and other search engines.<br><br>CONCLUSIONS: - Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 (BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).}, }
@article {pmid29473898, year = {2018}, author = {Soeberg, M and Vallance, DA and Keena, V and Takahashi, K and Leigh, J}, title = {Australia's Ongoing Legacy of Asbestos: Significant Challenges Remain Even after the Complete Banning of Asbestos Almost Fifteen Years Ago.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {2}, pages = {}, pmid = {29473898}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/*etiology/prevention &amp; control ; Australia/epidemiology ; Female ; *Health Policy ; Humans ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects/*legislation &amp; jurisprudence ; }, abstract = {The most effective way of reducing the global burden of asbestos-related diseases is through the implementation of asbestos bans and minimising occupational and non-occupational exposure to respirable asbestos fibres. Australia's asbestos consumption peaked in the 1970s with Australia widely thought to have had among the highest per-capita asbestos consumption level of any country. Australia's discontinuation of all forms of asbestos and asbestos-containing products and materials did not occur at a single point of time. Crocidolite consumption ceased in the late 1960s, followed by amosite consumption stopping in the mid 1980s. Despite significant government reports being published in 1990 and 1999, it was not until the end of 2003 that a complete ban on all forms of asbestos (crocidolite, amosite, and chrysotile) was introduced in Australia. The sustained efforts of trade unions and non-governmental organisations were essential in forcing the Australian government to finally implement the 2003 asbestos ban. Trade unions and non-government organisations continue to play a key role today in monitoring the government's response to Australian asbestos-related disease epidemic. There are significant challenges that remain in Australia, despite a complete asbestos ban being implemented almost fifteen years ago. The Australian epidemic of asbestos-related disease has only now reached its peak. A total of 16,679 people were newly diagnosed with malignant mesothelioma between 1982 and 2016, with 84% of cases occurring in men. There has been a stabilisation of the age-standardised malignant mesothelioma incidence rate in the last 10 years. In 2016, the incidence rate per 100,000 was 2.5 using the Australian standard population and 1.3 using the Segi world standard population. Despite Australia's complete asbestos ban being in place since 2003, public health efforts must continue to focus on preventing the devastating effects of avoidable asbestos-related diseases, including occupational and non-occupational groups who are potentially at risk from exposure to respirable asbestos fibres.}, }
@article {pmid29458304, year = {2017}, author = {Barlow, CA and Grespin, M and Best, EA}, title = {Asbestos fiber length and its relation to disease risk.}, journal = {Inhalation toxicology}, volume = {29}, number = {12-14}, pages = {541-554}, doi = {10.1080/08958378.2018.1435756}, pmid = {29458304}, issn = {1091-7691}, mesh = {Animals ; Asbestos/metabolism/*toxicity ; Carcinogens/metabolism/*toxicity ; Cells, Cultured ; Environmental Exposure/adverse effects ; Humans ; Lung/*drug effects/metabolism/pathology ; Mineral Fibers/*toxicity ; Occupational Exposure/adverse effects ; Pulmonary Fibrosis/chemically induced/metabolism/pathology ; Risk Factors ; }, abstract = {Differences in chemical and crystalline composition, fiber dimension, aerodynamic characteristics and biodurability are among the critical factors that define the toxicological and pathological consequences of asbestos exposure. Specifically, fiber dimension can impact whether the fiber is respired, whether and how deeply it is deposited in the lung, and how efficiently and rapidly it may be cleared. This paper provides a current, comprehensive evaluation of the weight of evidence regarding the relationship between asbestos fiber length and disease potency (for malignant and nonmalignant endpoints). In vitro studies, animal exposure studies and epidemiology data were reviewed. We found that the data reported over the last several decades consistently support the conclusions that exposure to fibers longer than 10 µm and perhaps 20 µm are required to significantly increase the risk of developing asbestos-related disease in humans and that there is very little, if any, risk associated with exposure to fibers shorter than 5 µm. Fiber length as a predictor of potency has been evaluated by several federal agencies in the U.S. and could significantly influence future regulatory decisions for elongated mineral particles (EMPs) and high-aspect ratio nanoparticles (HARNs).}, }
@article {pmid29438360, year = {2018}, author = {Linton, A and Cheng, YY and Griggs, K and Schedlich, L and Kirschner, MB and Gattani, S and Srikaran, S and Chuan-Hao Kao, S and McCaughan, BC and Klebe, S and van Zandwijk, N and Reid, G}, title = {An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {118}, number = {6}, pages = {e13}, doi = {10.1038/bjc.2018.3}, pmid = {29438360}, issn = {1532-1827}, abstract = {This corrects the article DOI: 10.1038/bjc.2017.85.}, }
@article {pmid29435293, year = {2018}, author = {Yano, M and Ikeda, Y and Kato, T and Sakaki, M and Sato, S and Yabuno, A and Kozawa, E and Yasuda, M}, title = {A case of peritoneal malignant mesothelioma following radiation therapy for cervical cancer.}, journal = {Molecular and clinical oncology}, volume = {8}, number = {2}, pages = {302-305}, pmid = {29435293}, issn = {2049-9450}, abstract = {The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively. The patient underwent concurrent chemoradiotherapy (CCRT), and a complete response was achieved. After 54 months, ascites was found at the rectouterine pouch, but peritoneal cytology suggested reactive mesothelial cell. After 62 months of CCRT, magnetic resonance imaging revealed masses in both the salpinges. The serum levels of SCC and CA125 were 0.9 ng/ml and 506.1 U/ml, respectively. Following this, left salpingectomy and peritoneal biopsy were performed laparoscopically. Histologic examination revealed atypical mesothelial cells with no continuity of background tubal epithelium. Immunohistochemistry showed positive staining for calretinin, thrombomodulin, mesothelin and glucose transporter 1. Based on these findings, the patient was diagnosed with PMM epithelioid type and underwent systemic chemotherapy; stable disease status has been obtained for 3 months. This case demonstrates the possibility of PMM occurrence within 10 years after radiotherapy, and indicates the importance of histological and immunohistochemical examination, particularly in cases of an atypical tumorigenesis pattern from the primary cancer.}, }
@article {pmid29434985, year = {2018}, author = {Yoneda, K and Chikaishi, Y and Kuwata, T and Ohnaga, T and Tanaka, F}, title = {Capture of mesothelioma cells with 'universal' CTC-chip.}, journal = {Oncology letters}, volume = {15}, number = {2}, pages = {2635-2640}, pmid = {29434985}, issn = {1792-1074}, abstract = {Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.}, }
@article {pmid29430704, year = {2018}, author = {Tanaka, H and Akiyama, Y and Kitamura, A and Matsumoto, N and Tomita, M and Kataoka, H}, title = {Malignant mesothelioma with squamous differentiation.}, journal = {Histopathology}, volume = {72}, number = {7}, pages = {1216-1220}, doi = {10.1111/his.13482}, pmid = {29430704}, issn = {1365-2559}, mesh = {Carcinoma, Squamous Cell/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {AIMS: We report the autopsy findings of a 58-year-old man with malignant mesothelioma in the left pleural cavity.<br><br>METHODS AND RESULTS: The patient had a history of asbestos exposure, and the chest computed tomography scan on initial admission demonstrated an extrapleural sign, suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, he died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumour lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumour was composed of a mixture of mesothelioma and tumour cells with squamous differentiation mimicking squamous cell carcinoma.<br><br>CONCLUSIONS: To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English-language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.}, }
@article {pmid29424961, year = {2018}, author = {Abdel-Rahman, O}, title = {Global trends in mortality from malignant mesothelioma: Analysis of WHO mortality database (1994-2013).}, journal = {The clinical respiratory journal}, volume = {12}, number = {6}, pages = {2090-2100}, doi = {10.1111/crj.12778}, pmid = {29424961}, issn = {1752-699X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Databases, Factual ; Female ; Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; *Registries ; Retrospective Studies ; Sex Distribution ; Survival Rate/trends ; }, abstract = {BACKGROUND AND OBJECTIVE: Little is known about the extent to which asbestos use ban has affected global trends in malignant mesothelioma. This study investigated recent global mortality trends of malignant mesothelioma.<br><br>METHODS: Data were collected from International Agency for Research on Cancer/World Health Organization mortality database to examine age-standardized, gender-specific mortality rates for malignant mesothelioma (ICD10-C45). Cross-sectional mortality rates (2009-2013) as well as trends over time (1994-2013) were also reported. Gender-specific annual percent change (APC) was calculated to examine trends over time for each country.<br><br>RESULTS: Among the 30 countries with highest mesothelioma mortality in men, there is almost 10-fold variation in mortality rates during 2009-2013 ranging from 6.25 per 100&#xa0;000 for United Kingdom to 0.64 per 100&#xa0;000 in Portugal; whereas, among the 30 countries with highest mesothelioma mortality in women, there is a 4-fold variation in mortality rates during 2009-2013 ranging from 1.08 per 100&#xa0;000 for United Kingdom to 0.26 per 100&#xa0;000 in Ireland. Mortality rates were higher in men compared to women in 32 out of 35 evaluable countries. Among males and over the last 10 years of covered years, mesothelioma mortality was significantly declining in 9&#xa0;countries (United Kingdom, Sweden, France, Germany, Netherlands, Canada, United States, Australia, and New Zealand); whereas, it was significantly rising in 5&#xa0;countries (Poland, Spain, China-Hong Kong, Japan, and Republic of Korea). In the remaining countries, APC was stable. Among females and over the last 10 years of covered years, mesothelioma mortality was significantly declining in 1 country only (Italy); whereas, it was significantly rising in 3 countries (Poland, Argentina, and Republic of Korea). In the remaining countries, APC was stable.<br><br>CONCLUSIONS: There is a worldwide variability in the burden and trends of mesothelioma mortality; and despite the ban on asbestos in many countries, mesothelioma still represents an important cause of mortality.}, }
@article {pmid29421994, year = {2017}, author = {Fathi Fathabadi, MK and Abdolahnejad, A and Teiri, H and Hajizadeh, Y}, title = {Spatio-seasonal variation of airborne asbestos concentration in urban areas of Shiraz, Iran.}, journal = {International journal of occupational and environmental health}, volume = {23}, number = {2}, pages = {143-150}, pmid = {29421994}, issn = {2049-3967}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos/*analysis ; Cities ; *Construction Industry ; *Environmental Monitoring ; Geographic Information Systems ; Iran ; Microscopy, Electron, Scanning ; Microscopy, Phase-Contrast ; Seasons ; Spatial Analysis ; }, abstract = {Background Asbestos fiber is mainly released from friction product in brakes and clutch linings and from reinforcing agent in the asbestos-cement industry. It leads to serious health problem such as mesothelioma and lung cancer. The objectives of this study were to monitor the levels of asbestos fibers in ambient air of Shiraz, Iran during 2014, and to draw its GIS distribution map for the city. Methods Samples were collected by mixed cellulose ester filters mounted on an open-faced filter holder using a SKC sampling pump. Fiber counting was conducted using both phase contrast microscopy (PCM) method to determine total fibers, and scanning electron microscopy (SEM) method to identify non-asbestos from asbestos fibers. Results The average concentrations of asbestos fibers in ambient air of the city were 1.11 ± 0.25 PCM f/l and 12.21 ± 2.52 SEM f/l. The highest concentration of asbestos fibers was measured in Valiasr square amounting 1.96 ± 0.34 PCM f/l and 16.87 ± 2.14 SEM f/l. Conclusions The average of asbestos fibers in all sampling points was higher than the WHO guideline (0.05 PCM f/l, 2.2 SEM f/l). This may be attributed to the frequently occurrence of heavy traffic, the existence of relevant industries in and around the city, and the topographic characteristics of the city. Thus, product substitution, traffic smoothing and industrial sites relocating are suggested to eliminate the asbestos fibers emission.}, }
@article {pmid29419731, year = {2018}, author = {Kumagai-Takei, N and Yamamoto, S and Lee, S and Maeda, M and Masuzzaki, H and Sada, N and Yu, M and Yoshitome, K and Nishimura, Y and Otsuki, T}, title = {Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, pmid = {29419731}, issn = {1422-0067}, mesh = {Animals ; Apoptosis ; Asbestos/administration &amp; dosage/*adverse effects/metabolism ; Biomarkers ; Carcinogens ; Cytokines ; Environmental Exposure ; Humans ; Inflammation/*etiology/metabolism/pathology ; Inflammation Mediators ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Mesothelioma, Malignant ; T-Lymphocytes/*drug effects/immunology/metabolism ; }, abstract = {Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure.}, }
@article {pmid29416614, year = {2018}, author = {Thompson, JK and Shukla, A and Leggett, AL and Munson, PB and Miller, JM and MacPherson, MB and Beuschel, SL and Pass, HI and Shukla, A}, title = {Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma.}, journal = {Oncotarget}, volume = {9}, number = {1}, pages = {293-305}, pmid = {29416614}, issn = {1949-2553}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; S10 RR019246/RR/NCRR NIH HHS/United States ; }, abstract = {Malignant mesothelioma is an aggressive cancer in desperate need of treatment. We have previously shown that extracellular signaling regulated kinase 5 (ERK5) plays an important role in mesothelioma pathogenesis using ERK5 silenced human mesothelioma cells exhibiting significantly reduced tumor growth in immunocompromised mice. Here, we used a specific ERK 5 inhibitor, XMD8-92 in various in vitro and in vivo models to demonstrate that inhibition of ERK5 can slow down mesothelioma tumorigenesis. First, we show a dose dependent toxicity of XMD8-92 to 2 human mesothelioma cell lines growing as a monolayer. We also demonstrate the inhibition of ERK5 phosphorylation in various human mesothelioma cell lines by XMD8-92. We further confirmed the toxicity of XMD8-92 towards mesothelioma cell lines grown as spheroids in a 3-D model as well as in intraperitoneal (immune-competent) and intrapleural (immune-deficient) mouse models with and without chemotherapeutic drugs. To ascertain the mechanism, we explored the role of the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in the process. We found XMD8-92 attenuated naïve and chemotherapeutic-induced inflammasome priming and activation in mesothelioma cells. It can thus be concluded that ERK5 inhibition attenuates mesothelioma tumor growth and this phenomenon in part is regulated by the inflammasome.}, }
@article {pmid29415822, year = {2018}, author = {Scherpereel, A and Willemin, MC and Wasielewski, E and Dhalluin, X}, title = {[Anti-tumor immunotherapy in malignant pleural mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {35}, number = {4}, pages = {465-476}, doi = {10.1016/j.rmr.2017.07.025}, pmid = {29415822}, issn = {1776-2588}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/administration &amp; dosage/adverse effects ; Cisplatin/administration &amp; dosage/adverse effects ; Combined Modality Therapy ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Pemetrexed/administration &amp; dosage/adverse effects ; Pleural Neoplasms/*drug therapy ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a quite rare cancer, but with increasing incidence, that is usually induced by previous asbestos exposure. Its prognosis is poor and there is no validated curative therapy to date. Surgery of MPM, done only by few expert teams within a multimodal treatment is of limited and still disputed value. The standard treatment of MPM, relying on first-line chemotherapy by combined cisplatin-pemetrexed is often poorly effective, even if combination with bevacizumab anti-VEGF antibodies has slightly improved the results. Moreover, no second line treatment is recommended in case of failure of this chemotherapy. Therefore, the search of new therapies or strategies is crucial and the recruitment of patients in clinical trials is highly encouraged.<br><br>BACKGROUND: Among the treatments under investigation, various anti-tumour immunotherapies, in particular immune checkpoints inhibitors (ICI), currently exhibit the most promising preliminary results. First data from the phase II, randomized "IFCT MAPS-2", recently presented during the 2017 ASCO meeting, confirmed the value of ICI in MPM patients in cases of chemotherapy failure.<br><br>OUTLOOK AND CONCLUSIONS: However, several exciting immunotherapies other than ICI are presently being evaluated in MPM and are reported in this article. Moreover, many questions still need to be answered about immunotherapy: what is its potential value as first line treatment? How to target the best candidates for these treatments? Which combinations between immunotherapy and standard chemotherapy, targeted therapies, surgery or radiotherapy? Finally, it is now essential that every clinician has sufficient knowledge about the possible toxicities of immunotherapy.}, }
@article {pmid29413505, year = {2018}, author = {Blyth, KG and Murphy, DJ}, title = {Progress and challenges in Mesothelioma: From bench to bedside.}, journal = {Respiratory medicine}, volume = {134}, number = {}, pages = {31-41}, doi = {10.1016/j.rmed.2017.11.015}, pmid = {29413505}, issn = {1532-3064}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Biopsy ; Humans ; Lung Neoplasms/*diagnostic imaging/genetics/pathology/*therapy ; Magnetic Resonance Imaging ; Mesothelioma/*diagnostic imaging/genetics/pathology/*therapy ; Mesothelioma, Malignant ; Mutation ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography ; Translational Research, Biomedical/methods/*trends ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is currently an incurable cancer with a typical survival of 1 year from the time of diagnosis. The recent genomic and transcriptomic characterization of MPM presents new opportunities and challenges for MPM researchers. Recent advances in clinical and laboratory diagnostics, and proposals for an updated, data-driven, staging system, also present new challenges for clinicians and hospital services involved in MPM care. The aim of this review is first to introduce the reader to the topic of MPM, a disease that is causally linked to prior, typically occupational, exposure to asbestos fibres. Secondly, we will discuss MPM from the clinical and laboratory perspectives, including reviews of current and evolving therapies and our present understanding of the molecular basis of the disease. Finally, we will attempt to identify critical knowledge gaps that currently prevent more effective treatment, including the challenges involved in early detection and chemoprophylaxis.}, }
@article {pmid29395477, year = {2018}, author = {Soloukey Tbalvandany, SS and Maat, AAPWM and Cornelissen, RR and Nuyttens, JJJME and Takkenberg, JJJM}, title = {WWW mesothelioma information: Surfing on unreliable waters. A cross-sectional study into the content and quality of online informational resources for mesothelioma patients.}, journal = {Patient education and counseling}, volume = {101}, number = {6}, pages = {1088-1094}, doi = {10.1016/j.pec.2018.01.009}, pmid = {29395477}, issn = {1873-5134}, mesh = {Benchmarking ; Consumer Health Information ; Cross-Sectional Studies ; Decision Making ; Humans ; Information Services/*standards ; *Information Storage and Retrieval ; *Internet ; Mesothelioma/*diagnosis/*therapy ; Netherlands ; Patients/*psychology ; }, abstract = {OBJECTIVE: Malignant Mesothelioma (MM) is a rare asbestos related disease mostly diagnosed in low-skilled patients. The decision-making process for MM treatment is complicated, making an adequate provision of information necessary. The objective of this study is to assess the content and quality of online informational resources available for Dutch MM patients.<br><br>METHODS: The first 100 hits of a Google search were studied using the JAMA benchmarks, the Modified Information Score (MIS) and the International Patient Decision Aid Standard Scoring (IPDAS).<br><br>RESULTS: A total of 37 sources were included. Six of the 37 resources were published by hospitals. On average, the informational resources scored 37 points on the MIS (scale 0-100). The resources from a (bio)medical sources scored the best on this scale. However, on the domain of use of language, these resources scored the worst.<br><br>CONCLUSIONS: The current level of medical content and quality of online informational resources for patient with MM is below average and cannot be used as decision-aids for patients.<br><br>PRACTICE IMPLICATIONS: The criteria used in this article could be used for future improvements of online informational resources for patients, both online, offline and through health education in the care path.}, }
@article {pmid29387394, year = {2018}, author = {Tian, D and Wen, H and Brown, HE and Wang, X and Zhang, L and Fu, M}, title = {Multiple intracranial metastases from postoperative giant sarcomatoid malignant pleural mesothelioma: A case report and literature review.}, journal = {Molecular and clinical oncology}, volume = {8}, number = {1}, pages = {34-37}, pmid = {29387394}, issn = {2049-9450}, abstract = {Sarcomatoid malignant pleural mesothelioma (SMPM) is a rare tumor with poor response to treatment and a dismal prognosis. Distant metastases are not uncommon and usually appear at the late stages of the disease. However, cerebral metastases have rarely been documented. We herein report a case of a giant sarcomatoid carcinoma of the pleura in a 41-year-old male patient with no history of exposure to asbestos, who presented with a chief complaint of left-sided chest pain for 1 month. Extrapleural pneumonectomy and rib excision were performed. At 5 months after the surgery, the patient was diagnosed with multiple intracranial metastatic neoplasms and succumbed to the disease soon thereafter. The aim of the present case report was to emphasize this rare metastatic pattern and aggressive clinical course of SMPM, with a supplementary review of the previously published literature.}, }
@article {pmid29386699, year = {2017}, author = {Cheng, YY and Mok, E and Tan, S and Leygo, C and McLaughlin, C and George, AM and Reid, G}, title = {SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {2536187}, pmid = {29386699}, issn = {1875-8630}, mesh = {Adaptor Proteins, Signal Transducing ; Asbestos/*toxicity ; Biomarkers, Tumor/blood/*genetics/metabolism ; Carcinogens/*toxicity ; Cell Line, Tumor ; DNA Methylation/drug effects ; Epigenesis, Genetic ; Eye Proteins/blood/*genetics/metabolism ; Humans ; Lung Neoplasms/blood/*genetics ; Membrane Proteins/blood/*genetics/metabolism ; Mesothelioma/blood/*genetics ; Mesothelioma, Malignant ; }, abstract = {Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56%) and SFRP5 (70%) in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.}, }
@article {pmid29375946, year = {2017}, author = {Arda, E and Arıkan, MG and Cetin, G and Kuyumcuoğlu, U and Usta, U}, title = {Malignant Mesothelioma of Tunica Vaginalis Testis: Macroscopic and Microscopic Features of a Very Rare Malignancy.}, journal = {Cureus}, volume = {9}, number = {11}, pages = {e1860}, pmid = {29375946}, issn = {2168-8184}, abstract = {Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is an extremely rare tumour, usually mimicking benign pathologies of the scrotum. Our case is an 84-year-old male patient who appealed with a painless, left-sided scrotal swelling longer than 2 months. Although the level of tumour markers was normal, ultrasonographic examination results forced us to perform an inguinal scrotal exploration. Multiple small papillary tumours, both on tunica vaginalis and tunica albuginea, were detected intraoperatively. Due to these findings, radical orchiectomy was performed. A pathological evaluation showed malignant mesothelioma (MM) of the tunica vaginalis testis. Exposure to asbestos is a well-known risk factor. Furthermore, a history of trauma, herniorrhaphy and chronic hydroceles is blamed as a possible risk factor. Scrotal ultrasonography is the mainstay of primary diagnosis and, therefore, it should not be overlooked when dealing with benign scrotal cysts or hydroceles, which are very common pathologies at these decades, too. Radical inguinal orchiectomy is the primary treatment choice for localised MMTVT disease, whereas in signs of lymph node metastasis, inguinal lymph node dissection is required. Radical resection should be completed with chemotherapy and/or radiotherapy for an advanced or recurrent disease. This case, which is very rarely reported in the literature and detected during inguinal exploration, along with the pathological works that supported the diagnosis, was presented with this report.}, }
@article {pmid29375377, year = {2017}, author = {Oien, DB and Garay, T and Eckstein, S and Chien, J}, title = {Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy.}, journal = {Frontiers in pharmacology}, volume = {8}, number = {}, pages = {970}, pmid = {29375377}, issn = {1663-9812}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM103326/GM/NIGMS NIH HHS/United States ; }, abstract = {Reactive oxygen species (ROS) can promote or inhibit tumorigenesis. In mesothelioma, asbestos exposure to serous membranes induces ROS through iron content and chronic inflammation, and ROS promote cell survival signaling in mesothelioma. Moreover, a current chemotherapy regimen for mesothelioma consisting of a platinum and antifolate agent combination also induce ROS. Mesothelioma is notoriously chemotherapy-resistant, and we propose that ROS induced by cisplatin and pemetrexed may promote cell survival signaling pathways, which ultimately may contribute to chemotherapy resistance. In The Cancer Genome Atlas datasets, we found AXL kinase expression is relatively high in mesothelioma compared to other cancer samples. We showed that ROS induce the phosphorylation of AXL, which was blocked by the selective inhibitor BGB324 in VMC40 and P31 mesothelioma cells. We also showed that cisplatin and pemetrexed induce the phosphorylation of AXL and Akt, which was also blocked by BGB324 as well as by N-acetylcysteine antioxidant. AXL knockdown in these cells enhances sensitivity to cisplatin and pemetrexed. Similarly, AXL inhibitor BGB324 also enhances sensitivity to cisplatin and pemetrexed. Finally, higher synergy was observed when cells were pretreated with BGB324 before adding chemotherapy. These results demonstrate cisplatin and pemetrexed induce ROS that activate AXL, and blocking AXL activation enhances the efficacy of cisplatin and pemetrexed. These results suggest AXL inhibition combined with the current chemotherapy regimen may represent an effective strategy to enhance the efficacy of chemotherapy in mesothelioma. This is the first study, to our knowledge, on chemotherapy-induced activation of AXL and cell survival pathways associated with ROS signaling.}, }
@article {pmid29371938, year = {2017}, author = {Hylebos, M and Van Camp, G and Vandeweyer, G and Fransen, E and Beyens, M and Cornelissen, R and Suls, A and Pauwels, P and van Meerbeeck, JP and Op de Beeck, K}, title = {Large-scale copy number analysis reveals variations in genes not previously associated with malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {69}, pages = {113673-113686}, pmid = {29371938}, issn = {1949-2553}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor that is often causally associated with asbestos exposure. Comparative genomic hybridization techniques and arrays demonstrated a complex set of copy number variations (CNVs) in the MPM-genome. These techniques however have a limited resolution, throughput and flexibility compared to next-generation sequencing platforms. In this study, the presence of CNVs in the MPM-genome was investigated using an MPM-cohort (N = 85) for which genomic microarray data are available through 'The Cancer Genome Atlas' (TCGA). To validate these results, the genomes of MPMs and matched normal samples (N = 21) were analyzed using low-pass whole genome sequencing on an 'Illumina HiSeq' platform. CNVs were detected using in-house developed analysis pipelines and frequencies of copy number loss and gain were calculated. In both datasets, losses on chromosomes 1, 3, 4, 6, 9, 13 and 22 and gains on chromosomes 1, 5, 7 and 17 were found in at least 25% and 15% of MPMs, respectively. Besides the well-known MPM-associated genes, CDKN2A, NF2 and BAP1, other interesting cancer-associated genes were listed as frequently involved in a copy number loss (e.g. EP300, SETD2 and PBRM1). Moreover, four cancer-associated genes showed a high frequency of copy number gain in both datasets (i.e. TERT, FCGR2B, CD79B and PRKAR1A). A statistically significant association between overall survival and the presence of copy number loss in the CDKN2A-containing region was observed in the TCGA-set. In conclusion, recurrent CNVs were detected in both datasets, occurring in regions harboring known MPM-associated genes and genes not previously linked to MPM.}, }
@article {pmid29342862, year = {2018}, author = {Tolani, B and Acevedo, LA and Hoang, NT and He, B}, title = {Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications.}, journal = {International journal of molecular sciences}, volume = {19}, number = {1}, pages = {}, pmid = {29342862}, issn = {1422-0067}, mesh = {*Disease Progression ; Genes, Tumor Suppressor ; Genome ; Humans ; Lung Neoplasms/genetics/immunology/*pathology ; Mesothelioma/genetics/immunology/*pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/genetics/immunology/*pathology ; Tumor Microenvironment ; }, abstract = {Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several molecular pathways have been implicated in the MPM tumor microenvironment; such as angiogenesis; apoptosis; cell-cycle regulation and several growth factor-related pathways predicted to be amenable to therapeutic intervention. Furthermore, the availability of genomic data has improved our understanding of the pathobiology of MPM. The MPM genomic landscape is dominated by inactivating mutations in several tumor suppressor genes; such as CDKN2A; BAP1 and NF2. Given the complex heterogeneity of the tumor microenvironment in MPM; a better understanding of the interplay between stromal; endothelial and immune cells at the molecular level is required; to chaperone the development of improved personalized therapeutics. Many recent advances at the molecular level have been reported and several exciting new treatment options are under investigation. Here; we review the challenges and the most up-to-date biological advances in MPM pertaining to the molecular pathways implicated; progress at the genomic level; immunological progression of this fatal disease; and its link with developmental cell pathways; with an emphasis on prognostic and therapeutic treatment strategies.}, }
@article {pmid29338319, year = {2018}, author = {Matboli, M and Shafei, AE and Azazy, AE and Reda, M and El-Khazragy, N and Nagy, AA and Ali, MA and Sobhi, M and Abdel-Rahman, O}, title = {Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients.}, journal = {Biomarkers in medicine}, volume = {12}, number = {2}, pages = {129-139}, doi = {10.2217/bmm-2017-0224}, pmid = {29338319}, issn = {1752-0371}, mesh = {Adult ; Aged ; Area Under Curve ; Asbestos/toxicity ; Biomarkers, Tumor/blood ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*diagnosis/genetics/pathology ; Male ; Mesothelioma/*diagnosis/genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/*blood/genetics/metabolism ; Middle Aged ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Smoking ; }, abstract = {AIM: miRNAs may act as promising diagnostic and prognostic biomarkers of mesothelioma. This study integrates serum miR-548a-3p and miR-20a expression based on in silico data analysis followed by clinical validation in malignant mesothelioma patients (malignant pleural mesothelioma [MPM]).<br><br>PATIENTS &amp; METHODS: Serum miR-548a-3p and&#xa0;&#xa0;miR-20a level was assessed in the serum of patients with MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time PCR.<br><br>RESULTS: The expression of serum miR-548a-3p and&#xa0;&#xa0;miR-20a was positive in 91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate between cases and controls. The sensitivity of the combined chosen serum miRNAs reached 100% in the diagnosis of MPM.<br><br>CONCLUSION: The current work revealed that sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for MPM.}, }
@article {pmid29337930, year = {2018}, author = {Baur, X}, title = {Asbestos-Related Disorders in Germany: Background, Politics, Incidence, Diagnostics and Compensation.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {1}, pages = {}, pmid = {29337930}, issn = {1660-4601}, mesh = {Asbestos/*toxicity ; Compensation and Redress ; Germany/epidemiology ; Humans ; Incidence ; Occupational Diseases/*chemically induced/diagnosis/economics/epidemiology ; Occupational Exposure/*adverse effects/economics/legislation &amp; jurisprudence ; Politics ; }, abstract = {There was some limited use of asbestos at end of the 19th century in industrialized countries including Germany, but its consumption dramatically increased after World War II. The increase in use and exposure was followed by the discovery of high numbers of asbestos-related diseases with a mean latency period of about 38 years in Germany. The strong socio-political pressure from the asbestos industry, its affiliated scientists and physicians has successfully hindered regulatory measures and an asbestos ban for many years; a restrictive stance that is still being unravelled in compensation litigation. This national experience is compared with the situation in other industrialized countries and against the backdrop of the constant efforts of the WHO to eliminate asbestos-related diseases worldwide.}, }
@article {pmid29320538, year = {2018}, author = {Patch, AM and Nones, K and Kazakoff, SH and Newell, F and Wood, S and Leonard, C and Holmes, O and Xu, Q and Addala, V and Creaney, J and Robinson, BW and Fu, S and Geng, C and Li, T and Zhang, W and Liang, X and Rao, J and Wang, J and Tian, M and Zhao, Y and Teng, F and Gou, H and Yang, B and Jiang, H and Mu, F and Pearson, JV and Waddell, N}, title = {Germline and somatic variant identification using BGISEQ-500 and HiSeq X Ten whole genome sequencing.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190264}, pmid = {29320538}, issn = {1932-6203}, mesh = {*Genome, Human ; *Germ Cells ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; INDEL Mutation ; Polymorphism, Single Nucleotide ; }, abstract = {Technological innovation and increased affordability have contributed to the widespread adoption of genome sequencing technologies in biomedical research. In particular large cancer research consortia have embraced next generation sequencing, and have used the technology to define the somatic mutation landscape of multiple cancer types. These studies have primarily utilised the Illumina HiSeq platforms. In this study we performed whole genome sequencing of three malignant pleural mesothelioma and matched normal samples using a new platform, the BGISEQ-500, and compared the results obtained with Illumina HiSeq X Ten. Germline and somatic, single nucleotide variants and small insertions or deletions were independently identified from data aligned human genome reference. The BGISEQ-500 and HiSeq X Ten platforms showed high concordance for germline calls with genotypes from SNP arrays (>99%). The germline and somatic single nucleotide variants identified in both sequencing platforms were highly concordant (86% and 72% respectively). These results indicate the potential applicability of the BGISEQ-500 platform for the identification of somatic and germline single nucleotide variants by whole genome sequencing. The BGISEQ-500 datasets described here represent the first publicly-available cancer genome sequencing performed using this platform.}, }
@article {pmid29316066, year = {2018}, author = {Kimura, N and Hasegawa, M and Hiroshima, K}, title = {SMARCB1/INI1/BAF47- deficient pleural malignant mesothelioma with rhabdoid features.}, journal = {Pathology international}, volume = {68}, number = {2}, pages = {128-132}, doi = {10.1111/pin.12623}, pmid = {29316066}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Rhabdoid Tumor/metabolism/*pathology ; SMARCB1 Protein/*deficiency ; Tumor Suppressor Proteins/deficiency ; Ubiquitin Thiolesterase/deficiency ; }, abstract = {Malignant mesothelioma (MM) with rhabdoid features is an MM variant. Fifteen cases have been reported previously, all of which were combined with other types of MM. Herein, we report an autopsy case of pleural MM with monomorphic rhabdoid features. The patient was a 62-year-old male without a history of asbestos exposure. An autopsy revealed a soft, granular tumor that replaced the entire left pleura and had invaded to the diaphragm and lower lobe of the lung. The tumor cells, which had eosinophilic plump cytoplasm and eccentric nuclei, were loosely cohesive. Immunohistochemistry showed that the cells were diffusely positive for calretinin, D2-40, vimentin, CAM5.2, and AE1/AE3; and negative for WT-1, TTF-1, CK7, CEA, desmin, CD34, BCL-2, S100 protein, and p40. Neither homozygous deletion of p16 nor BAP-1 protein loss was observed. Loss of INI1/BAF47 protein, an indicator of malignant rhabdoid tumor, was observed. Therefore, MM with rhabdoid features was confirmed.}, }
@article {pmid29306869, year = {2018}, author = {Solbes, E and Harper, RW}, title = {Biological responses to asbestos inhalation and pathogenesis of asbestos-related benign and malignant disease.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {66}, number = {4}, pages = {721-727}, doi = {10.1136/jim-2017-000628}, pmid = {29306869}, issn = {1708-8267}, mesh = {Asbestos/*adverse effects ; Humans ; *Inhalation Exposure ; Lung Diseases/diagnosis/etiology ; Mass Screening ; Risk Factors ; }, abstract = {Asbestos comprises a group of fibrous minerals that are naturally occurring in the environment. Because of its natural properties, asbestos gained popularity for commercial applications in the late 19th century and was used throughout the majority of the 20th century, with predominant use in the construction, automotive, and shipbuilding industries. Asbestos has been linked to a spectrum of pulmonary diseases, such as pleural fibrosis and plaques, asbestosis, benign asbestos pleural effusion, small cell lung carcinoma, non-small cell lung carcinoma, and malignant mesothelioma. There are several mechanisms through which asbestos can lead to both benign and malignant disease, and they include alterations at the chromosomal level, activation of oncogenes, loss of tumor suppressor genes, alterations in cellular signal transduction pathways, generation of reactive oxygen and nitrogen species, and direct mechanical damage to cells from asbestos fibers. While known risk factors exist for the development of asbestos-related malignancies, there are currently no effective means to determine which asbestos-exposed patients will develop malignancy and which will not. There are also no established screening strategies to detect asbestos-related malignancies in patients who have a history of asbestos exposure. In this article, we present a case that highlights the different biological responses in human hosts to asbestos exposure.}, }
@article {pmid29303291, year = {2018}, author = {Kolek, V}, title = {[Malign pleural mesothelioma - so far an undefeated tumor].}, journal = {Vnitrni lekarstvi}, volume = {63}, number = {11}, pages = {884-888}, pmid = {29303291}, issn = {0042-773X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Humans ; Immunotherapy/methods ; *Lung Neoplasms/diagnosis/therapy ; *Mesothelioma/diagnosis/therapy ; Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/therapy ; Pneumonectomy/methods ; }, abstract = {Malign pleural mesothelioma is the most frequent primary tumor of the pleura of high aggressiveness. Its most frequent cause is contact with asbestos and, although working with asbestos is already prohibited in developed countries, its incidence is on the increase so far. Diagnostics primarily considers anamnesis, clinical symptoms and immunohistochemical examination of a tumor sample. The basic therapy used over the past 10 years is chemotherapy with cisplatin - pemetrexed combinations. Numerous studies are going on with a different biologically targeted therapy, immunotherapy and other drugs which may improve patients prognosis. The surgical approach is limited by a suitable choice of patients and sufficient experience of the medical center. Extrapleural pneumonectomy or extended pleurectomy are performed. However even the combined therapy with adjuvant or neoadjuvant chemotherapy or radiotherapy has not considerably extended survival.Key words: diagnostics - epidemiology - malign pleural mesothelioma - therapy.}, }
@article {pmid29298805, year = {2018}, author = {}, title = {Correction: Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {78}, number = {1}, pages = {309}, doi = {10.1158/0008-5472.CAN-17-3445}, pmid = {29298805}, issn = {1538-7445}, }
@article {pmid29298350, year = {2018}, author = {Tatsuta, T and Satoh, T and Sugawara, S and Hara, A and Hosono, M}, title = {Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190653}, pmid = {29298350}, issn = {1932-6203}, mesh = {Amphibian Proteins/isolation &amp; purification/*pharmacology ; Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Synergism ; Female ; Humans ; In Vitro Techniques ; Lectins/isolation &amp; purification/*pharmacology ; Male ; Mesothelioma/*pathology ; Mice, Inbred BALB C ; Mice, Nude ; Ovum/*chemistry ; Pemetrexed/administration &amp; dosage ; Rana catesbeiana ; Ribonucleases/isolation &amp; purification/*pharmacology ; Weight Loss/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma is an aggressive cancer that results from exposure to asbestos. The therapeutic options for this type of cancer are limited; therefore, the development of novel therapeutic agents is urgently required. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a novel therapeutic candidate for cancer, which exhibits antitumor activity mediated through RNA degradation. In the present study, we evaluated the effect of cSBL in vitro and in vivo. Xenograft-competent H2452 and MSTO human mesothelioma cell lines were treated with cSBL, and the pathway by which cSBL induces apoptosis was analyzed. In vivo studies were performed using nude mice inoculated with one of the two cell lines, and the effects of cSBL and pemetrexed were monitored simultaneously. Furthermore, the pharmacological interactions between the three agents (pemetrexed, cisplatin and cSBL) were statistically assessed. It was demonstrated that cSBL treatments caused morphological and biochemical apoptotic changes in both cell lines. Caspase cascade analysis revealed that an intrinsic pathway mediated cSBL-induced apoptosis. The administration of cSBL significantly inhibited tumor growth in two xenograft models, without any adverse effects. Furthermore, the combination index and dose reduction index values indicated that the cSBL + pemetrexed combination showed the highest synergism, and thus potential for reducing dosage of each drug, compared with the other combinations, including the existing pemetrexed + cisplatin regimen. cSBL exerted prominent antitumor effects on malignant mesothelioma cells in vitro and in vivo, and showed favorable effects when combined with pemetrexed. These results suggest that cSBL has potential as a novel drug for the treatment of malignant mesothelioma.}, }
@article {pmid29296529, year = {2017}, author = {Schürch, CM and Forster, S and Brühl, F and Yang, SH and Felley-Bosco, E and Hewer, E}, title = {The "don't eat me" signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {1}, pages = {e1373235}, pmid = {29296529}, issn = {2162-4011}, abstract = {Diffuse malignant mesothelioma (DMM) is one of the prognostically most discouraging cancers with median survivals of only 12-22 months. Due to its insidious onset and delayed detection, DMM is often at an advanced stage at diagnosis and is considered incurable. Combined chemo- and radiotherapy followed by surgery only marginally affect outcome at the cost of significant morbidity. Because of the long time period between exposure to asbestos and disease onset, the incidence of DMM is still rising and predicted to peak around 2020. Novel markers for the reliable diagnosis of DMM in body cavity effusion specimens as well as more effective, targeted therapies are urgently needed. Here, we show that the "don't eat me" signalling molecule CD47, which inhibits phagocytosis by binding to signal regulatory protein α on macrophages, is overexpressed in DMM cells. A two-marker panel of high CD47 expression and BRCA1-associated protein 1 (BAP-1) deficiency had a sensitivity of 78% and specificity of 100% in discriminating DMM tumour cells from reactive mesothelial cells in effusions, which is superior to the currently used four-marker combination of BAP-1, glucose transporter type 1, epithelial membrane antigen and desmin. In addition, blocking CD47 inhibited growth and promoted phagocytosis of DMM cell lines by macrophages in vitro. Furthermore, DMM tumours in surgical specimens from patients as well as in a mouse DMM model expressed high levels of CD47 and were heavily infiltrated by macrophages. Our study demonstrates that CD47 is an accurate novel diagnostic DMM biomarker and that blocking CD47 may represent a promising therapeutic strategy for DMM.}, }
@article {pmid29289945, year = {2018}, author = {Finkelstein, MM}, title = {Reanalysis of non-occupational exposure to asbestos and the risk of pleural mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {6}, pages = {472-473}, doi = {10.1136/oemed-2017-104783}, pmid = {29289945}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, }
@article {pmid29284684, year = {2017}, author = {Carder, M and Darnton, A and Gittins, M and Stocks, SJ and Ross, D and Barber, CM and Agius, RM}, title = {Chest physician-reported, work-related, long-latency respiratory disease in Great Britain.}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.00961-2017}, pmid = {29284684}, issn = {1399-3003}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Occupational Diseases/*chemically induced/*epidemiology ; *Occupational Exposure ; Physicians ; Respiration Disorders/*chemically induced/*epidemiology ; Sex Distribution ; Silicon Dioxide/toxicity ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent.LLRD incidence and incidence rate ratios by occupation were estimated (1996-2014). Mesothelioma cases by occupation were compared with proportional mortality ratios.Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0-8.2); mesothelioma, 5.4 (4.8-6.0); pneumoconiosis, 1.9 (1.7-2.2); lung cancer, 0.8 (0.6-1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2-0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation.Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.}, }
@article {pmid29279043, year = {2018}, author = {Yanamala, N and Kisin, ER and Gutkin, DW and Shurin, MR and Harper, M and Shvedova, AA}, title = {Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {81}, number = {4}, pages = {60-79}, doi = {10.1080/15287394.2017.1408201}, pmid = {29279043}, issn = {1528-7394}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Asbestos, Crocidolite/*toxicity ; Calcium Compounds/*toxicity ; Female ; Inflammation/chemically induced ; Lung/*drug effects/immunology/pathology ; Mice ; Mice, Inbred C57BL ; Silicates/*toxicity ; Transcriptome/*drug effects ; Zeolites/*toxicity ; }, abstract = {Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.}, }
@article {pmid29277245, year = {2018}, author = {Tranchant, R and Montagne, F and Jaurand, MC and Jean, D}, title = {[Molecular heterogeneity of malignant pleural mesotheliomas].}, journal = {Bulletin du cancer}, volume = {105}, number = {1}, pages = {35-45}, doi = {10.1016/j.bulcan.2017.11.007}, pmid = {29277245}, issn = {1769-6917}, mesh = {Asbestos/toxicity ; Carcinogens/toxicity ; Chromosome Aberrations ; Epigenesis, Genetic ; Humans ; Lung Neoplasms/classification/etiology/*genetics/therapy ; Mesothelioma/classification/etiology/*genetics/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/classification/etiology/*genetics/therapy ; Prognosis ; Transcription, Genetic ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2[LN] tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2[LN] subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma.}, }
@article {pmid29269588, year = {2017}, author = {Feder, IS and Tischoff, I and Theile, A and Schmitz, I and Merget, R and Tannapfel, A}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.02204-2017}, pmid = {29269588}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, }
@article {pmid29269586, year = {2017}, author = {Sartorelli, P}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.02188-2017}, pmid = {29269586}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, }
@article {pmid29269580, year = {2017}, author = {Oliver, LC and Belpoggi, F and Budnik, LT and Egilman, D and Frank, AL and Mandrioli, D and Soskolne, CL and Terracini, B and Welch, L and Baur, X}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.01644-2017}, pmid = {29269580}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, }
@article {pmid29269578, year = {2017}, author = {Lamote, K and Vynck, M and Thas, O and Van Cleemput, J and Nackaerts, K and van Meerbeeck, JP}, title = {Exhaled breath to screen for malignant pleural mesothelioma: a validation study.}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.00919-2017}, pmid = {29269578}, issn = {1399-3003}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Belgium ; *Breath Tests ; Case-Control Studies ; Cross-Sectional Studies ; Exhalation ; Female ; Humans ; Logistic Models ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pleural Neoplasms/*diagnosis ; ROC Curve ; Volatile Organic Compounds/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly caused by asbestos exposure and has a poor prognosis. Breath contains volatile organic compounds (VOCs) and can be explored as an early detection tool. Previously, we used multicapillary column/ion mobility spectrometry (MCC/IMS) to discriminate between patients with MPM and asymptomatic high-risk persons with a high rate of accuracy. Here, we aim to validate these findings in different control groups.Breath and background samples were obtained from 52 patients with MPM, 52 healthy controls without asbestos exposure (HC), 59 asymptomatic former asbestos workers (AEx), 41 patients with benign asbestos-related diseases (ARD), 70 patients with benign non-asbestos-related lung diseases (BLD) and 56 patients with lung cancer (LC).After background correction, logistic lasso regression and receiver operating characteristic (ROC) analysis, the MPM group was discriminated from the HC, AEx, ARD, BLD and LC groups with 65%, 88%, 82%, 80% and 72% accuracy, respectively. Combining AEx and ARD patients resulted in 94% sensitivity and 96% negative predictive value (NPV). The most important VOCs selected were P1, P3, P7, P9, P21 and P26.We discriminated MPM patients from at-risk subjects with great accuracy. The high sensitivity and NPV allow breath analysis to be used as a screening tool for ruling out MPM.}, }
@article {pmid29269563, year = {2018}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Scarselli, A and Ferrante, P and Bonafede, M and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Merler, E and Girardi, P and Negro, C and D'Agostin, F and Romanelli, A and Chellini, E and Silvestri, S and Pascucci, C and Calisti, R and Stracci, F and Romeo, E and Ascoli, V and Trafficante, L and Carrozza, F and Angelillo, IF and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and Iavicoli, S and , }, title = {The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {4}, pages = {254-262}, pmid = {29269563}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; Registries ; Risk Factors ; Sex Factors ; }, abstract = {INTRODUCTION: The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.<br><br>METHODS: Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated.<br><br>RESULTS: In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries.<br><br>CONCLUSIONS: The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.}, }
@article {pmid29265930, year = {2018}, author = {Crovella, S and Moura, RR and Cappellani, S and Celsi, F and Trevisan, E and Schneider, M and Brollo, A and Nicastro, EM and Vita, F and Finotto, L and Zabucchi, G and Borelli, V}, title = {A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {81}, number = {5}, pages = {98-105}, doi = {10.1080/15287394.2017.1416911}, pmid = {29265930}, issn = {1528-7394}, mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Aged ; Aged, 80 and over ; Apoptosis Regulatory Proteins/*genetics/metabolism ; Asbestos/*toxicity ; Body Burden ; Female ; Genetic Variation ; Humans ; Italy ; Lung/drug effects/*pathology ; Lung Neoplasms/*genetics/metabolism ; Male ; Mesothelioma/*genetics/metabolism ; Mesothelioma, Malignant ; Middle Aged ; NLR Proteins ; Occupational Exposure/*adverse effects ; }, abstract = {The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.}, }
@article {pmid29260910, year = {2018}, author = {Khella, MS and Salem, AM and Abdel-Rahman, O and Saad, AS}, title = {The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.}, journal = {Genetic testing and molecular biomarkers}, volume = {22}, number = {2}, pages = {79-84}, doi = {10.1089/gtmb.2017.0146}, pmid = {29260910}, issn = {1945-0257}, mesh = {Adult ; Aged ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics ; Case-Control Studies ; Female ; Humans ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Pleural Neoplasms/*genetics/pathology ; *Polymorphism, Genetic ; Risk ; Young Adult ; }, abstract = {AIMS: Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk.<br><br>MATERIALS AND METHODS: FTO rs9939609 (T >A) genotypes were screened using a TaqMan[&#xae;] Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design.<br><br>RESULTS: In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI]&#x2009;=&#x2009;1.04-5.92, p&#x2009;=&#x2009;0.04) and a 3.46-fold (95% CI&#x2009;=&#x2009;0.99-12.01, p&#x2009;=&#x2009;0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI&#x2009;=&#x2009;1.13-6.12, p&#x2009;=&#x2009;0.025).<br><br>CONCLUSIONS: The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.}, }
@article {pmid29260624, year = {2018}, author = {Brosseau, S and Dhalluin, X and Zalcman, G and Scherpereel, A}, title = {Immunotherapy in relapsed mesothelioma.}, journal = {Immunotherapy}, volume = {10}, number = {2}, pages = {77-80}, doi = {10.2217/imt-2017-0144}, pmid = {29260624}, issn = {1750-7448}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/*adverse effects ; Clinical Trials as Topic ; Costimulatory and Inhibitory T-Cell Receptors/immunology ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/mortality/*therapy ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; Occupational Diseases/immunology/*therapy ; Pleural Neoplasms/immunology/mortality/*therapy ; Recurrence ; Survival Analysis ; Vascular Endothelial Growth Factor A/immunology ; }, }
@article {pmid29253374, year = {2017}, author = {Korda, RJ and Clements, MS and Armstrong, BK and Law, HD and Guiver, T and Anderson, PR and Trevenar, SM and Kirk, MD}, title = {Risk of cancer associated with residential exposure to asbestos insulation: a whole-population cohort study.}, journal = {The Lancet. Public health}, volume = {2}, number = {11}, pages = {e522-e528}, doi = {10.1016/S2468-2667(17)30192-5}, pmid = {29253374}, issn = {2468-2667}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Australia/epidemiology ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Housing/*statistics &amp; numerical data ; Humans ; Male ; Middle Aged ; Neoplasms/*chemically induced/epidemiology ; Risk ; }, abstract = {BACKGROUND: The health risks associated with living in houses insulated with asbestos are unknown. Loose-fill asbestos was used to insulate some houses in the Australian Capital Territory (ACT). We compared the incidence of mesothelioma and other cancers in residents of the ACT who did and did not live in these houses.<br><br>METHODS: Our cohort study included all ACT residents identified using Medicare enrolment data. These data were linked to addresses of affected residential properties in the ACT to ascertain exposure. We followed up residents by linking data to the Australian Cancer Database and National Death Index. Outcomes were diagnosis of mesothelioma and selected other cancers. Effects were estimated for males and females separately using standardised incidence ratios (SIRs), adjusting for age and calendar time of diagnosis.<br><br>FINDINGS: Between Nov 1, 1983, and Dec 31, 2013, 1&#x2008;035&#x2008;578 ACT residents were identified from the Medicare database. Of these, 17&#x2008;248 (2%) had lived in an affected property, including seven (2%) of 285 people diagnosed with mesothelioma. The adjusted incidence of mesothelioma in males who had lived at an affected property was 2&#xb7;5 times that of unexposed males (SIR 2&#xb7;54, 95% CI 1&#xb7;02-5&#xb7;24). No mesotheliomas were reported among females who had lived at an affected property. Among individuals who had lived at an affected property, there was an elevated incidence of colorectal cancer in women (SIR 1&#xb7;73, 95% CI 1&#xb7;29-2&#xb7;26) and prostate cancer in men (1&#xb7;29, 1&#xb7;07-1&#xb7;54); colorectal cancer was increased, although not significantly, in males (SIR 1&#xb7;32, 95% CI 0&#xb7;99-1&#xb7;72), with no significant increase in the other cancers studied.<br><br>INTERPRETATION: Residential asbestos insulation is likely to be unsafe. Our findings have important health, social, financial, and legal implications for governments and communities in which asbestos has been used to insulate houses.<br><br>FUNDING: ACT Government.}, }
@article {pmid29253372, year = {2017}, author = {de Klerk, N and Reid, A}, title = {Hazards of residential exposure to household asbestos.}, journal = {The Lancet. Public health}, volume = {2}, number = {11}, pages = {e490-e491}, doi = {10.1016/S2468-2667(17)30200-1}, pmid = {29253372}, issn = {2468-2667}, mesh = {*Asbestos ; Housing ; Humans ; *Mesothelioma ; }, }
@article {pmid29248759, year = {2018}, author = {Croce, A and Capella, S and Belluso, E and Grosso, F and Mariani, N and Libener, R and Rinaudo, C}, title = {Asbestos fibre burden in gallbladder: A case study.}, journal = {Micron (Oxford, England : 1993)}, volume = {105}, number = {}, pages = {98-104}, doi = {10.1016/j.micron.2017.12.001}, pmid = {29248759}, issn = {1878-4291}, mesh = {Aged, 80 and over ; Asbestos, Crocidolite/isolation &amp; purification/*toxicity ; Asbestos, Serpentine/isolation &amp; purification/*toxicity ; Female ; Gallbladder/*chemistry/pathology ; Humans ; Lung Neoplasms/*mortality/pathology ; Mesothelioma/*mortality/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; }, abstract = {The methods conventionally used to determine the burden of asbestos fibres inhaled/incorporated in lung require chemical digestion of the biological matrix before counting/characterising the inorganic fibrous phases under scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS). Asbestos fibres can also be present in extra-pulmonary organs, and we set out to quantify the fibres in gallbladder. Although the standardised procedure requires approximately 5 × 10[-1] g of wet tissue, this amount of tissue is not always available. We applied the procedure on about 9 × 10[-4] g of gallbladder from a patient with known environmental and workplace exposure to asbestos. The patient died of malignant pleural mesothelioma and was also affected by severe bile-tract problems. The traditional procedure of digesting tissue samples in NaClO and filtering the resulting suspension was carried out. The filter was then examined under SEM/EDS using two methods 1. following the standardised procedure to assess the fibre burden in lung by investigating only 2 mm[2] of the filter (660 microscopic fields), and 2. analysing all the microscopic fields in one-quarter of the filter (about 82 mm[2]). In parallel, histological sections (prepared in the usual way for medical diagnosis) were analysed without digestion or manipulation of the sample using variable pressure SEM/EDS. The fibre counts obtained using the two methods were of the same order of magnitude, i.e., ∼10[5] fibres/g of wet tissue. We showed that the counting of fibres in human tissue may be successfully carried out even when a limited amount of tissue is available. We also found that, when exposure to asbestos is considerable, the number of asbestos fibres accumulating in the gallbladder may be significant.}, }
@article {pmid29247244, year = {2017}, author = {Cerruti, F and Jocollè, G and Salio, C and Oliva, L and Paglietti, L and Alessandria, B and Mioletti, S and Donati, G and Numico, G and Cenci, S and Cascio, P}, title = {Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {17626}, pmid = {29247244}, issn = {2045-2322}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Bortezomib/*pharmacology ; Cell Line, Tumor ; Epithelium/pathology ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Proteasome Endopeptidase Complex/*metabolism ; Proteasome Inhibitors/*pharmacology ; Ubiquitinated Proteins/metabolism ; }, abstract = {Based on promising results in preclinical models, clinical trials have been performed to evaluate the efficacy of the first-in-class proteasome inhibitor bortezomib towards malignant pleural mesothelioma (MPM), an aggressive cancer arising from the mesothelium of the serous cavities following exposure to asbestos. Unexpectedly, only minimal therapeutic benefits were observed, thus implicating that MPM harbors inherent resistance mechanisms. Identifying the molecular bases of this primary resistance is crucial to develop novel pharmacologic strategies aimed at increasing the vulnerability of MPM to bortezomib. Therefore, we assessed a panel of four human MPM lines with different sensitivity to bortezomib, for functional proteasome activity and levels of free and polymerized ubiquitin. We found that highly sensitive MPM lines display lower proteasome activity than more bortezomib-resistant clones, suggesting that reduced proteasomal capacity might contribute to the intrinsic susceptibility of mesothelioma cells to proteasome inhibitors-induced apoptosis. Moreover, MPM equipped with fewer active proteasomes accumulated polyubiquitinated proteins, at the expense of free ubiquitin, a condition known as proteasome stress, which lowers the cellular apoptotic threshold and sensitizes mesothelioma cells to bortezomib-induced toxicity as shown herein. Taken together, our data suggest that an unfavorable load-versus-capacity balance represents a critical determinant of primary apoptotic sensitivity to bortezomib in MPM.}, }
@article {pmid29244982, year = {2017}, author = {Qin, KR and Dua, D}, title = {Diagnostic Dilemma: Primary Peritoneal Mesothelioma With Para-Occupational Asbestos Exposure.}, journal = {Journal of global oncology}, volume = {3}, number = {6}, pages = {828-832}, pmid = {29244982}, issn = {2378-9506}, mesh = {Antineoplastic Agents/therapeutic use ; *Asbestos ; Carboplatin/therapeutic use ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*diagnosis/drug therapy/pathology ; Mesothelioma/*diagnosis/drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/drug therapy/pathology ; Tomography, X-Ray Computed ; }, }
@article {pmid29240325, year = {2017}, author = {}, title = {Tort Law--Expert Testimony in Asbestos Litigation--District of South Carolina Holds the Every Exposure Theory Insufficient to Demonstrate Specific Causation Even If Legal Conclusions are Scientifically Sound.--Haskins v. 3m Co., Nos. 2:15-cv-02086, 3:15-cv-02123, 2017 WL 3118017 (D.S.C. July 21, 2017).}, journal = {Harvard law review}, volume = {131}, number = {2}, pages = {658-665}, pmid = {29240325}, issn = {0017-811X}, mesh = {Asbestosis/*etiology ; *Causality ; Expert Testimony/*legislation &amp; jurisprudence ; Humans ; Mesothelioma/*etiology ; Science ; South Carolina ; }, }
@article {pmid29229551, year = {2018}, author = {Nuvoli, B and Camera, E and Mastrofrancesco, A and Briganti, S and Galati, R}, title = {Modulation of reactive oxygen species via ERK and STAT3 dependent signalling are involved in the response of mesothelioma cells to exemestane.}, journal = {Free radical biology &amp; medicine}, volume = {115}, number = {}, pages = {266-277}, doi = {10.1016/j.freeradbiomed.2017.12.008}, pmid = {29229551}, issn = {1873-4596}, mesh = {Acetylcysteine/pharmacology ; Androstadienes/*pharmacology ; Antineoplastic Agents/*pharmacology ; Aromatase Inhibitors/*pharmacology ; Asbestos/adverse effects ; Cell Death ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclic AMP/metabolism ; Environmental Exposure/adverse effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Mesothelioma/*drug therapy ; Oxidative Stress ; Pleural Neoplasms/*drug therapy ; Reactive Oxygen Species/metabolism ; Receptors, Estrogen ; Receptors, G-Protein-Coupled ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Treatment Outcome ; }, abstract = {Pleural mesothelioma is a deadly form of cancer. The prognosis is extremely poor due to the limited treatment modalities. Uptake of asbestos fibres, the leading cause of mesothelioma, lead to the accumulation of reactive-oxygen-species (ROS). Interestingly, increasing ROS production by using ROS-generating drugs may offer a strategy to selectively trigger cell death. Exemestane, an aromatase inhibitor, has previously shown anti-tumor properties in mesothelioma preclinical models suggesting a role of G protein-coupled receptor 30 (GPR30) in the drug response. As exemestane, in addition to blocking estrogen biosynthesis, generates ROS that are able to arrest the growth of breast cancer, we explored the role of ROS, antioxidant defense system, and ROS-induced signalling pathways in mesothelioma cells during exemestane response. Here we report that exemestane treatment reduced cell proliferation with an increase in ROS production and reduction of cyclic adenosine monophosphate (cAMP) levels in MSTO-H211, Ist-Mes1, Ist-Mes2 and MPP89 exemestane-sensitive mesothelioma cell lines, but not in NCI-H2452 exemestane-insensitive mesothelioma cells. Exemestane induced a significant antioxidant response in NCI-H2452 cells, as highlighted by an increase in γ-glutamylcysteine levels, catalase (Cat), superoxide-dismutase and (SOD) and glutathione-peroxidase (GSH-Px) activity and nuclear factor E2-related factor 2 (Nrf2) activation, responsible for drug insensitivity. Conversely, exemestane elevated ROS levels along with increased ERK phosphorylation and a reduction of p-STA3 in exemestane-sensitive mesothelioma cells. ROS generation was the crucial event of exemestane action because ROS inhibitor N-acetyl-L-cysteine (NAC) abrogated p-ERK and p-STAT3 modulation and cellular death. Exemestane also modulates ERK and STAT3 signalling via GPR30. Results indicate an essential role of ROS in the antiproliferative action of exemestane in mesothelioma cells. It is likely that the additional oxidative insults induced by exemestane results in the lethal effects of mesothelioma cells by increasing ROS production. As such, manipulating ROS levels with exemestane seems to be a feasible strategy to selectively kill mesothelioma cells with less toxicity to normal cells by regulating ERK and STAT3 activity.}, }
@article {pmid29209316, year = {2017}, author = {Agostinis, C and Vidergar, R and Belmonte, B and Mangogna, A and Amadio, L and Geri, P and Borelli, V and Zanconati, F and Tedesco, F and Confalonieri, M and Tripodo, C and Kishore, U and Bulla, R}, title = {Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {1559}, pmid = {29209316}, issn = {1664-3224}, abstract = {C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) via its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) via enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.}, }
@article {pmid29207669, year = {2017}, author = {Lamote, K and Brinkman, P and Vandermeersch, L and Vynck, M and Sterk, PJ and Van Langenhove, H and Thas, O and Van Cleemput, J and Nackaerts, K and van Meerbeeck, JP}, title = {Breath analysis by gas chromatography-mass spectrometry and electronic nose to screen for pleural mesothelioma: a cross-sectional case-control study.}, journal = {Oncotarget}, volume = {8}, number = {53}, pages = {91593-91602}, pmid = {29207669}, issn = {1949-2553}, abstract = {RATIONALE: Malignant pleural mesothelioma (MPM) is mainly caused by previous exposure to asbestos fibers and has a poor prognosis. Due to a long latency period between exposure and diagnosis, MPM incidence is expected to peak between 2020-2025. Screening of asbestos-exposed individuals is believed to improve early detection and hence, MPM management. Recent developments focus on breath analysis for screening since breath contains volatile organic compounds (VOCs) which reflect the cell's metabolism.<br><br>OBJECTIVES: The goal of this cross-sectional, case-control study is to identify VOCs in exhaled breath of MPM patients with gas chromatography-mass spectrometry (GC-MS) and to assess breath analysis to screen for MPM using an electronic nose (eNose).<br><br>METHODS: Breath and background samples were taken from 64 subjects: 16 healthy controls (HC), 19 asymptomatic former asbestos-exposed (AEx) individuals, 15 patients with benign asbestos-related diseases (ARD) and 14 MPM patients. Samples were analyzed with both GC-MS and eNose.<br><br>RESULTS: Using GC-MS, AEx individuals were discriminated from MPM patients with 97% accuracy, with diethyl ether, limonene, nonanal, methylcyclopentane and cyclohexane as important VOCs. This was validated by eNose analysis. MPM patients were discriminated from AEx+ARD participants by GC-MS and eNose with 94% and 74% accuracy, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 91%, 82%, 100% for GC-MS and 82%, 55%, 82%, 55% for eNose, respectively.<br><br>CONCLUSION: This study shows accurate discrimination of patients with MPM from asymptomatic asbestos-exposed persons at risk by GC-MS and eNose analysis of exhaled VOCs and provides proof-of-principle of breath analysis for MPM screening.}, }
@article {pmid29206890, year = {2018}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {2}, pages = {484-489}, doi = {10.1093/annonc/mdx762}, pmid = {29206890}, issn = {1569-8041}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/analysis ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Textile Industry ; Tumor Suppressor Proteins/*biosynthesis ; Ubiquitin Thiolesterase/*biosynthesis ; }, abstract = {BACKGROUND: Diagnosis of mesothelioma based on death certificate is subject to misclassification, which may bias the results of epidemiology studies. A high proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1 (BAP1) gene.<br><br>METHODS: We searched medical and pathology records and specimens for 127 workers from a textile-asbestos factory in Italy who died during 1963-2013 with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death certificate, to confirm the diagnosis with immunohistochemistry markers. We calculated the odds ratio of confirmation by selected characteristics and asbestos exposure variables. When sufficient pathology material was available, we analyzed BAP1 protein expression.<br><br>RESULTS: The diagnosis of mesothelioma was histologically confirmed for 35 cases (27.6%); 5 cases were classified as non-mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record but no sufficient material was available for revision (26.0%); no records were available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation was not associated with sex, location of the neoplasm, age, or duration of employment; however, there was a significant association with time since first employment (P for linear trend 0.04). An association between duration of employment and time since first employment was observed for confirmed cases but not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases (51.4%), without an association with sex, location, age, indices of asbestos exposure, or survival.<br><br>CONCLUSIONS: We were able to confirm by immunohistochemistry a small proportion of mesothelioma diagnoses on certificates of deceased asbestos workers, and confirmation correlated with latency of asbestos exposure but not other characteristics. BAP1 protein loss is a frequent event in mesothelioma of asbestos-exposed workers, but does not correlate with exposure.}, }
@article {pmid29200597, year = {2017}, author = {Jiang, Z and Ying, S and Shen, W and He, X and Chen, J and Xia, H and Yu, M and Xiao, Y and Feng, L and Zhu, L and Ju, L and Guo, X and Zhang, Y and Shen, JW and Tong, Y and Zhang, X and Lou, J}, title = {Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {1725354}, pmid = {29200597}, issn = {1875-8630}, mesh = {Aged ; Asbestos/adverse effects ; Asbestosis/*blood/epidemiology ; Biomarkers/blood ; Case-Control Studies ; China ; Extracellular Matrix Proteins/*blood ; Female ; Humans ; Lung Neoplasms/*blood/epidemiology ; Male ; Mesothelioma/*blood/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/statistics &amp; numerical data ; }, abstract = {Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.}, }
@article {pmid29197906, year = {2017}, author = {Glass, WI and Clayson, H}, title = {Asbestos-worker exposure, family disease.}, journal = {The New Zealand medical journal}, volume = {130}, number = {1466}, pages = {90-91}, pmid = {29197906}, issn = {1175-8716}, mesh = {Asbestos/*toxicity ; *Family Health/economics/legislation &amp; jurisprudence ; Humans ; *Inhalation Exposure ; Lung Neoplasms/chemically induced/economics ; Mesothelioma/chemically induced/economics ; *Occupational Exposure ; *Workers' Compensation/economics/legislation &amp; jurisprudence ; }, abstract = {Family members, mostly female, can be at risk of asbestos-related disease as a result of the transfer of asbestos from the workplace to the home on the hair, boots and clothes of the worker. It is argued that in these cases the home should be recognised as an extension of the workplace and that the employer has a duty of care to contain and control the asbestos. Given these circumstances, the family member with the disease should be entitled to cover under the Accidence Compensation Legislation.}, }
@article {pmid29197848, year = {2017}, author = {Gravito-Soares, M and Gravito-Soares, E and Almeida, J and Fraga, J and Tomé, L}, title = {Challenging and uncommon diagnosis of long-evolution ascites.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, pmid = {29197848}, issn = {1757-790X}, mesh = {Alcoholism/*complications ; Ascites/*complications/pathology ; Biopsy ; Humans ; Liver/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*etiology/pathology ; Peritoneum/pathology ; }, abstract = {This is a case report of a 45-year-old Caucasian man with chronic alcoholism. No history of liver disease or asbestos exposure. He complained of ascites during the last 3 years with worsening in the last year with severe ascites development. Diagnostic paracentesis showed SAAG 1.1 and high cellularity with neutrophil count >250 cells/µL. Ascitic fluid cytology revealed reactive mesothelial hyperplasia. Thoracoabdominopelvic ultrasonography/CT/MRI and fludeoxyglucose positron emission tomography/CT showed 'omental cake' pattern suggesting peritoneal carcinomatosis. An exploratory laparoscopy revealed moderate interloop adhesions and necrosis with whitish exudate in the right pelvic excavation. Biochemical/cytological/histological/microbiological study only revealed reactive mesothelial cells, necrosis and lymphohistiocytic inflammatory infiltrate. A second exploratory laparoscopy with liver and peritoneal biopsies and appendectomy/mesoappendix excision showed a well-differentiated tubulopapillary mesothelioma. The patient was referred for intraperitoneal chemotherapy and is undergoing monthly therapeutic paracentesis.}, }
@article {pmid29193587, year = {2018}, author = {Ohara, Y and Chew, SH and Shibata, T and Okazaki, Y and Yamashita, K and Toyokuni, S}, title = {Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats.}, journal = {Cancer science}, volume = {109}, number = {2}, pages = {330-339}, pmid = {29193587}, issn = {1349-7006}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Disease Models, Animal ; Iron/blood ; Lung Neoplasms/blood/*chemically induced/pathology/*prevention &amp; control ; Male ; Mesothelioma/blood/*chemically induced/pathology/*prevention &amp; control ; Mesothelioma, Malignant ; Phlebotomy/*methods ; Rats ; Survival Analysis ; Treatment Outcome ; Tumor Burden ; }, abstract = {Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. Malignant mesothelioma is difficult to diagnose at an early stage, yet there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses. Accordingly, as an effective strategy to prevent asbestos-induced MM, we undertook the use of an iron chelator, deferasirox, which decreased the epithelial-mesenchymal transition in a crocidolite-induced rat MM model. However, this agent may show adverse effects. Here, we studied the effects of iron removal by phlebotomy as a realistic measure on the same rat model. We injected a total of 5 mg crocidolite i.p. to F1 hybrid rats between the Fischer-344 and Brown-Norway strains at the age of 6 weeks. We repeated weekly or biweekly phlebotomy of 6-8 mL/kg/time from 10 to 60 weeks of age. The animals were observed until 120 weeks. In male rats, phlebotomy significantly decreased the weight and nuclear grade of MM, and modestly reduced the associated ascites and the fraction of more malignant sarcomatoid subtype. Weekly phlebotomy prolonged long-term survival. Our results indicate that appropriate phlebotomy may be a practical preventive measure to attenuate the initiation and promotion capacity of asbestos towards MM by reducing iron in individuals exposed to asbestos.}, }
@article {pmid29187476, year = {2017}, author = {Matsubara, T and Toyokawa, G and Yamada, Y and Nabeshima, K and Haratake, N and Kozuma, Y and Akamine, T and Takamori, S and Shoji, F and Okamoto, T and Maehara, Y}, title = {A Case of the Resected Lymphohistiocytoid Mesothelioma: BAP1 Is a Key of Accurate Diagnosis.}, journal = {Anticancer research}, volume = {37}, number = {12}, pages = {6937-6941}, doi = {10.21873/anticanres.12158}, pmid = {29187476}, issn = {1791-7530}, mesh = {Aged, 80 and over ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Fluorodeoxyglucose F18 ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis/diagnostic imaging/*surgery ; Male ; Mesothelioma/diagnosis/diagnostic imaging/*surgery ; Mesothelioma, Malignant ; Positron-Emission Tomography/methods ; Tomography, X-Ray Computed/methods ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a well-known malignant tumor that occurs in the pleura and is histopathologically classified into three subtypes. Lymphohistiocytoid mesothelioma (LHM) is considered a variant of epithelioid MM, and few cases have been reported. First case of LHM was reported by Henderson et al. in 1988. It is difficult to precisely diagnose LHM, and it is often misdiagnosed as reactive mesothelial cell proliferation.<br><br>CASE REPORT: An 82-year-old man, with the smoking history of nine pack-years, was referred to our Department due to an abnormal shadow and pleural effusion in the left lung field on the chest X-ray imaging. His occupation was a teacher through his life without any asbestos exposure. Computed tomography (CT) and [18]F-fluorodeoxyglucose-position emission tomography showed a tumor which was suggestive of malignancy on the left chest wall, with the possible invasion into the left 2nd to 4th ribs. He underwent a CT-guided biopsy and a thoracentesis, but the tumor was shown to be a benign tumor indicative of a reactive mesothelial cell proliferation. Then, he underwent a surgical resection and the tumor was suspected of liposarcoma macroscopically. Histological and immunohistochemical findings were suggestive of mesothelial lesion, such as nodular histiocytic or mesothelial hyperplasia. However, loss of BAP1 and no p16 homozygous deletion in the tumor cells led to the diagnosis of LHM, not a benign lesion.}, }
@article {pmid29182465, year = {2017}, author = {}, title = {Author's response to: "Letter to the Editor" regarding content of "Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States" by R. A. Lemen, Journal of Toxicology and Environmental Health, Part B 2016; 19: 250-265.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {20}, number = {8}, pages = {389}, doi = {10.1080/10937404.2017.1400769}, pmid = {29182465}, issn = {1521-6950}, mesh = {Asbestos/*analysis ; Environmental Health ; Lung Neoplasms ; *Mesothelioma ; Pleural Neoplasms ; United States ; }, }
@article {pmid29165392, year = {2017}, author = {Westerholm, P and Remaéus, B and Svartengren, M}, title = {The Tale of Asbestos in Sweden 1972-1986-The Pathway to a Near-Total Ban.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29165392}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/*epidemiology ; Environmental Exposure/*statistics &amp; numerical data ; Humans ; Incidence ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Mesothelioma, Malignant ; Occupational Exposure/statistics &amp; numerical data ; Sweden ; }, abstract = {This paper provides a narrative of the national intervention strategy in Sweden aimed to restrict the industrial use of asbestos. For many years, asbestos was imported for widespread industrial use, resulting in large amounts throughout Swedish society. In 1972, the whistle was blown in a Communist Party parliamentary motion describing asbestos as a health hazard and requesting action to prohibit its use. Although the motion was rejected, it initiated the extensive charting of asbestos sources on a tripartite basis, involving government agencies, and employer and trade-union organizations. Restrictive asbestos management practices were enforced from July 1982. The year 1985 saw the Government Asbestos Commission review, covering use-determining factors, international regulations, and assessments of cancer risks. The relative risks of chrysotile and amphibole were considered internationally (by the IARC), since chrysotile (a Canadian export) was regarded as unharmful in Canada at that time. Prohibiting asbestos use resulted in its virtual disappearance as an import to Sweden from the early 1980s. However, asbestos has undergone a transition from an occupational to a public-health hazard (although some work-related hazards, such as handling and disposal, remain). The transition reflects the public's exposure to existing stocks, in homes, workplaces, etc. Mesothelioma incidence has come to be regarded as an indicator of prevention effectiveness.}, }
@article {pmid29165150, year = {2017}, author = {Matsuzaki, H and Kumagai-Takei, N and Lee, S and Maeda, M and Sada, N and Hatayama, T and Yamamoto, S and Ikeda, M and Yoshitome, K and Min, Y and Nishimura, Y and Otsuki, T}, title = {Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos.}, journal = {Environmental health and preventive medicine}, volume = {22}, number = {1}, pages = {53}, pmid = {29165150}, issn = {1347-4715}, mesh = {Asbestos/*adverse effects/*immunology ; Asbestosis/immunology ; Biomarkers/*analysis/blood ; CD8-Positive T-Lymphocytes ; Humans ; Killer Cells, Natural/*immunology ; Lung Neoplasms/chemically induced/immunology ; Mesothelioma/chemically induced/immunology ; Mesothelioma, Malignant ; Mucosal-Associated Invariant T Cells/*immunology ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; }, abstract = {The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos exposure and asbestos-induced cancers and suggested the usefulness of serum/plasma IL-10 and TGF-β, surface CXCR3 expression in Tresp, the secreting potential of IFN-γ in Tresp, intracellular perforin level in CTL, and surface expression NKp46 in NK cells. Although other unexplored cytokines in serum/plasma and molecules in these immunological cells, including Th17, should be investigated by experimental procedures in addition to a comprehensive analysis of screening methods, biomarkers based on immunological alterations may be helpful in clinical situations to screen the high-risk population exposed to asbestos and susceptible to asbestos-related cancers such as mesothelioma.}, }
@article {pmid29149911, year = {2017}, author = {Winata, P and Williams, M and McGowan, E and Nassif, N and van Zandwijk, N and Reid, G}, title = {The analysis of novel microRNA mimic sequences in cancer cells reveals lack of specificity in stem-loop RT-qPCR-based microRNA detection.}, journal = {BMC research notes}, volume = {10}, number = {1}, pages = {600}, pmid = {29149911}, issn = {1756-0500}, support = {11/TPG/3-06//Cancer Institute NSW/ ; 11/TPG/3-06//Cancer Institute NSW/ ; PhD Scholarship//Sydney Catalyst/ ; RG14-17//Cancer Council NSW/ ; }, mesh = {Antineoplastic Agents/administration &amp; dosage/*analysis/therapeutic use ; Cell Line, Tumor ; *Drug Delivery Systems ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; MicroRNAs/administration &amp; dosage/*analysis/chemical synthesis/therapeutic use ; Molecular Mimicry ; *Molecular Probe Techniques ; Nucleic Acid Probes ; *Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR.<br><br>RESULTS: The custom assays efficiently and specifically amplified the consensus mimics. However, we found that these assays gave a signal when total RNA from untransfected and control mimic-transfected cells were used as templates. Further investigation revealed that the reverse transcription step using stem-loop primers appeared to introduce substantial non-specific amplification with either total RNA or synthetic RNA templates. This suggests that reverse transcription using stem-loop primers suffers from an intrinsic lack of specificity for the detection of highly similar microRNAs in the same family, especially when analysing total RNA. These results suggest that RT-qPCR is unlikely to be an effective means to detect delivery of microRNA mimic-based drugs to tumour cells in patients.}, }
@article {pmid29137208, year = {2017}, author = {Marsili, D and Angelini, A and Bruno, C and Corfiati, M and Marinaccio, A and Silvestri, S and Zona, A and Comba, P}, title = {Asbestos Ban in Italy: A Major Milestone, Not the Final Cut.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29137208}, issn = {1660-4601}, mesh = {*Air Pollutants, Occupational ; *Asbestos ; Environmental Health ; *Environmental Policy ; Humans ; Italy ; Occupational Exposure/*prevention &amp; control ; }, abstract = {Background and history: Italy was the main asbestos producer and one of the greatest consumers in 20th century Europe until the asbestos ban was introduced in 1992. Asbestos exposure affected the population in a wide range of working environments, namely mining and marketing of asbestos, asbestos cement production, shipyards and textile industries. This also determined a widespread environmental asbestos exposure affecting the surrounding communities. Methods: To investigate the drivers and difficulties of the process leading to the asbestos ban and its subsequent implementation, we focused on stakeholder involvement, environmental health policies, capacity building and communication. Results: In the past three decades, stakeholder involvement has been instrumental in advancing the industrial asbestos replacement process, prevention and remediation interventions. Furthermore, involvement also contributed to the integration of environmental and health policies at national, regional and local levels, including capacity building and communication. In a global public health perspective, international scientific cooperation has been established with countries using and producing asbestos. Discussion and Conclusions: Key factors and lessons learnt in Italy from both successful and ineffective asbestos policies are described to support the relevant stakeholders in countries still using asbestos contributing to the termination of its use.}, }
@article {pmid29131723, year = {2017}, author = {Magnani, C and Mirabelli, D and Terracini, B}, title = {Comment on "Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States" by R A Lemen, Journal of Toxicology and Environmental Health, Part B 2016;19:250-265.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {20}, number = {8}, pages = {387-388}, doi = {10.1080/10937404.2017.1400762}, pmid = {29131723}, issn = {1521-6950}, mesh = {*Asbestos ; Environmental Health ; Humans ; Lung Neoplasms ; *Mesothelioma ; United States ; }, }
@article {pmid29129162, year = {2017}, author = {Musk, ABW and de Klerk, N and Brims, FJ}, title = {Mesothelioma in Australia: a review.}, journal = {The Medical journal of Australia}, volume = {207}, number = {10}, pages = {449-452}, doi = {10.5694/mja17.00397}, pmid = {29129162}, issn = {1326-5377}, mesh = {Antineoplastic Agents/therapeutic use ; *Asbestos ; Australia/epidemiology ; Compensation and Redress ; Humans ; Incidence ; Mesothelioma/drug therapy/*epidemiology ; Occupational Diseases/drug therapy/*epidemiology ; Occupational Exposure/statistics &amp; numerical data ; Pleural Neoplasms/drug therapy/*epidemiology ; Prognosis ; }, abstract = {The incidence of malignant mesothelioma in Australia is among the highest in the world as a result of widespread use of asbestos by industry and in construction throughout the 20th century. The risk of developing malignant mesothelioma after asbestos exposure is dose-related; a transient, low dose exposure confers a correspondingly very low risk of disease. Malignant mesothelioma is a heterogeneous disease, partly explaining the limited role of biomarkers in screening and diagnosis. The prognosis remains poor, and early advice on medico-legal compensation and a collaborative team approach to managing malignant mesothelioma are both essential. Chemotherapy can have a modest treatment effect in some people. New therapies, such as immunotherapy, do not yet have a defined role in the treatment of malignant mesothelioma. As treatment options for malignant mesothelioma are limited and no cure is available, there is no established role for early detection or screening of at risk populations. A multidisciplinary approach to caring for patients with malignant mesothelioma and their carers is vital.}, }
@article {pmid29124998, year = {2017}, author = {Pierce, JS and Riordan, AS and Miller, EW and Gaffney, SH and Hollins, DM}, title = {Evaluation of the presence of asbestos in cosmetic talcum products.}, journal = {Inhalation toxicology}, volume = {29}, number = {10}, pages = {443-456}, doi = {10.1080/08958378.2017.1392656}, pmid = {29124998}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*analysis ; Cosmetics/*chemistry ; Humans ; Microscopy, Electron, Transmission ; Spectrometry, X-Ray Emission ; Talc/*chemistry ; X-Ray Diffraction ; }, abstract = {Talc has been used for over a century in a variety of cosmetic products. While pure cosmetic talc (free of asbestos) is not considered a risk factor for mesothelioma, it has been recently suggested that inhalation of cosmetic talc containing trace levels of asbestos is a risk factor for mesothelioma. Bulk analyses of cosmetic talcum products were performed in the 1960s and 1970s, however, the analytical methods used at that time were incapable of determining whether asbestos minerals were present in the asbestiform versus non-asbestiform habit. The distinction between these two mineral habits is critical, as non-asbestiform amphibole minerals do not present an asbestos-related cancer risk via inhalation. As such, we evaluated six historical talcum powders using modern-era analytical methods to determine if asbestos is present, and if so, to identify the mineral habit (asbestiform versus non-asbestiform) of the asbestos. Based on their labels, the products were produced by four manufacturers and sold between 1940 and 1977. The products were analyzed in duplicate by two laboratories using standard protocols. Laboratory A analyzed samples using X-ray diffraction (XRD) and polarized light microscopy (PLM), and Laboratory B analyzed samples using PLM and transmission electron microscopy (TEM) with energy dispersive X-ray analysis (EDX) and selected area electron diffraction (SAED). No asbestiform minerals were found in any of the products. Nonetheless, even if some historical cosmetic talcum products contained trace amounts (≤0.1%) of asbestiform minerals, any resulting asbestos exposure would be expected to be exceedingly low, and comparable to exposures from breathing ambient air.}, }
@article {pmid29124996, year = {2017}, author = {LeMasters, G and Lockey, JE and Hilbert, TJ and Levin, LS and Burkle, JW and Shipley, R and Perme, C and Meyer, CA and Rice, CH}, title = {A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers.}, journal = {Inhalation toxicology}, volume = {29}, number = {10}, pages = {462-470}, doi = {10.1080/08958378.2017.1394931}, pmid = {29124996}, issn = {1091-7691}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kaolin/*toxicity ; Male ; Middle Aged ; Mineral Fibers/*toxicity ; Neoplasms/etiology ; *Occupational Exposure ; Odds Ratio ; Respiratory Tract Diseases/*etiology/*mortality ; Risk Factors ; Young Adult ; }, abstract = {AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers.<br><br>METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes.<br><br>RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR&#x2009;=&#x2009;3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR&#x2009;=&#x2009;2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR&#x2009;=&#x2009;2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR)&#x2009;=&#x2009;6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR=&#x2009;9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (&#x2265;1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results.<br><br>CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.}, }
@article {pmid29113949, year = {2018}, author = {Johnson, TG and Schelch, K and Cheng, YY and Williams, M and Sarun, KH and Kirschner, MB and Kao, S and Linton, A and Klebe, S and McCaughan, BC and Lin, RCY and Pirker, C and Berger, W and Lasham, A and van Zandwijk, N and Reid, G}, title = {Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {2}, pages = {258-272}, doi = {10.1016/j.jtho.2017.10.016}, pmid = {29113949}, issn = {1556-1380}, mesh = {Animals ; Cell Movement/physiology ; DNA Methylation ; Gene Knockdown Techniques ; Heterografts ; Humans ; Lung Neoplasms/genetics/*metabolism/pathology ; Mesothelioma/genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs/antagonists &amp; inhibitors/biosynthesis/genetics/*metabolism ; Neoplasm Invasiveness ; Pleural Neoplasms/genetics/*metabolism/pathology ; Promoter Regions, Genetic ; Transfection ; Y-Box-Binding Protein 1/genetics/*metabolism ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterized by frequent chromosomal deletions of tumor suppressors, including microRNAs. MiR-137 plays a tumor suppressor role in other cancers, so the aim of this study was to characterize it and its target Y-box binding protein 1 (YBX1) in MPM.<br><br>METHODS: Expression, methylation, and copy number status of miR-137 and its host gene MIR137HG were assessed by polymerase chain reaction. Luciferase reporter assays confirmed a direct interaction between miR-137 and Y-box binding protein 1 gene (YBX1). Cells were transfected with a miR-137 inhibitor, miR-137 mimic, and/or YBX1 small interfering RNA, and growth, colony formation, migration and invasion assays were conducted.<br><br>RESULTS: MiR-137 expression varied among MPM cell lines and tissue specimens, which was associated with copy number variation and promoter hypermethylation. High miR-137 expression was linked to poor patient survival. The miR-137 inhibitor did not affect target levels or growth, but interestingly, it increased miR-137 levels by means of mimic transfection suppressed growth, migration, and invasion, which was linked to direct YBX1 downregulation. YBX1 was overexpressed in MPM cell lines and inversely correlated with miR-137. RNA interference-mediated YBX1 knockdown significantly reduced cell growth, migration, and invasion.<br><br>CONCLUSIONS: MiR-137 can exhibit a tumor-suppressive function in MPM by targeting YBX1. YBX1 knockdown significantly reduces tumor growth, migration, and invasion of MPM cells. Therefore, YBX1 represents a potential target for novel MPM treatment strategies.}, }
@article {pmid29112873, year = {2017}, author = {Port, J and Murphy, DJ}, title = {Mesothelioma: Identical Routes to Malignancy from Asbestos and Carbon Nanotubes.}, journal = {Current biology : CB}, volume = {27}, number = {21}, pages = {R1173-R1176}, doi = {10.1016/j.cub.2017.07.026}, pmid = {29112873}, issn = {1879-0445}, mesh = {Animals ; *Asbestos ; Humans ; Inflammation ; *Lung Neoplasms ; *Mesothelioma ; Mice ; *Nanotubes, Carbon ; }, abstract = {Exposure of laboratory mice to carbon nanotubes mimics exposure to asbestos, from initial and chronic inflammation, through loss of the same tumour-suppressor pathways and eventual sporadic development of malignant mesothelioma. Fibres of a similar nature may pose significant health risks to humans.}, }
@article {pmid29112861, year = {2017}, author = {Chernova, T and Murphy, FA and Galavotti, S and Sun, XM and Powley, IR and Grosso, S and Schinwald, A and Zacarias-Cabeza, J and Dudek, KM and Dinsdale, D and Le Quesne, J and Bennett, J and Nakas, A and Greaves, P and Poland, CA and Donaldson, K and Bushell, M and Willis, AE and MacFarlane, M}, title = {Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf).}, journal = {Current biology : CB}, volume = {27}, number = {21}, pages = {3302-3314.e6}, pmid = {29112861}, issn = {1879-0445}, support = {MC_U132685863/MRC_/Medical Research Council/United Kingdom ; MC_UP_1203/1/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1024/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Animals ; Asbestos/*toxicity ; Carcinogenesis/chemically induced/genetics ; Cell Proliferation/drug effects ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p19/genetics/*metabolism ; Female ; Humans ; Lung Neoplasms/*chemically induced/genetics/*pathology ; Male ; Mesothelioma/*chemically induced/genetics/*pathology ; Mesothelioma, Malignant ; Methylation/drug effects ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Nanotubes, Carbon/*toxicity ; }, abstract = {Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma. Manufactured carbon nanotubes (CNTs) are similar to asbestos in terms of their fibrous shape and biopersistent properties and thus may pose an asbestos-like inhalation hazard. Here we show that instillation of either long CNTs or long asbestos fibers into the pleural cavity of mice induces mesothelioma that exhibits common key pro-oncogenic molecular events throughout the latency period of disease progression. Sustained activation of pro-oncogenic signaling pathways, increased proliferation, and oxidative DNA damage form a common molecular signature of long-CNT- and long-asbestos-fiber-induced pathology. We show that hypermethylation of p16/Ink4a and p19/Arf in CNT- and asbestos-induced inflammatory lesions precedes mesothelioma; this results in silencing of Cdkn2a (Ink4a/Arf) and loss of p16 and p19 protein, consistent with epigenetic alterations playing a gatekeeper role in cancer. In end-stage mesothelioma, silencing of p16/Ink4a is sustained and deletion of p19/Arf is detected, recapitulating human disease. This study addresses the long-standing question of which early molecular changes drive carcinogenesis during the long latency period of mesothelioma development and shows that CNT and asbestos pose a similar health hazard.}, }
@article {pmid29111984, year = {2018}, author = {Ripabelli, G and Tamburro, M and Di Tella, D and Carrozza, F and Sammarco, ML}, title = {Asbestos Exposures, Mesothelioma Incidence and Mortality, and Awareness by General Practitioners in the Molise Region, Central Italy.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {2}, pages = {e90-e97}, doi = {10.1097/JOM.0000000000001211}, pmid = {29111984}, issn = {1536-5948}, mesh = {Adult ; Age Factors ; Aged ; Asbestosis/diagnosis/epidemiology ; Clinical Competence ; *Environmental Exposure ; Female ; *General Practitioners ; *Health Knowledge, Attitudes, Practice ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/diagnosis/*epidemiology/mortality ; Middle Aged ; Pleural Neoplasms/*epidemiology/mortality ; Registries ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate environmental asbestos sources, mesothelioma incidence and mortality, and awareness on asbestos-related diseases (ARDs) by general practitioners (GPs) in Molise Region.<br><br>METHODS: The contaminated sites in three towns were identified by census; mesothelioma incidence (2000 to 2012) and mortality (2003 to 2013) was achieved from local registries; GPs were interviewed on practiced population's exposures and ARDs diagnosis.<br><br>RESULTS: About 54.3% of visited sites were contaminated (71.2% by friable asbestos) and 38.8% was extremely damaged. Over above time-periods, 32 mesothelioma cases (62.5% males, 25% in people aged 70 to 75 years) and 27 deaths (90% males, 69&#x200a;&#xb1;&#x200a;10 years, 70.4% pleural mesothelioma) have been reported. A total of 122 GPs were interviewed who had diagnosed 40 mesothelioma and 28 asbestosis cases.<br><br>CONCLUSION: There is the need of remediation/removal interventions for contaminated sites and of strategies to increase GPs awareness on asbestos risks for better patients' management.}, }
@article {pmid29100460, year = {2017}, author = {Birnie, KA and Prêle, CM and Thompson, PJ and Badrian, B and Mutsaers, SE}, title = {Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {44}, pages = {78193-78207}, pmid = {29100460}, issn = {1949-2553}, abstract = {Malignant mesothelioma is an aggressive and often fatal cancer associated with asbestos exposure. The disease originates in the mesothelial lining of the serosal cavities, most commonly affecting the pleura. Survival rates are low as diagnosis often occurs at an advanced stage and current treatments are limited. Identifying new diagnostic and therapeutic targets for mesothelioma remains a priority, particularly for the new wave of victims exposed to asbestos through do-it-yourself renovations and in countries where asbestos is still mined and used. Recent advances have demonstrated a biological role for the small but powerful gene regulators microRNA (miRNA) in mesothelioma. A number of potential therapeutic targets have been identified. MiRNA have also become popular as potential biomarkers for mesothelioma due to their stable expression in bodily fluid and tissues. In this review, we highlight the current challenges associated with the diagnosis and treatment of mesothelioma and discuss how targeting miRNA may improve diagnostic, prognostic and therapeutic approaches.}, }
@article {pmid29099505, year = {2018}, author = {Feder, IS and Theile, A and Tannapfel, A}, title = {Histological findings and lung dust analysis as the basis for occupational disease compensation in asbestos-related lung cancer in Germany.}, journal = {International journal of occupational medicine and environmental health}, volume = {31}, number = {3}, pages = {293-305}, doi = {10.13075/ijomeh.1896.01148}, pmid = {29099505}, issn = {1896-494X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Asbestosis/*diagnosis/diagnostic imaging/pathology ; Dust/analysis ; Germany ; Histological Techniques ; Humans ; Lung Diseases/*diagnosis/pathology ; Middle Aged ; Occupational Diseases/*diagnosis/pathology ; Occupational Exposure/statistics &amp; numerical data ; Pleural Diseases/diagnosis/pathology ; Workers' Compensation ; }, abstract = {OBJECTIVES: This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease.<br><br>MATERIAL AND METHODS: For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings.<br><br>RESULTS: For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated.<br><br>CONCLUSIONS: Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305.}, }
@article {pmid29094504, year = {2018}, author = {Schelch, K and Kirschner, MB and Williams, M and Cheng, YY and van Zandwijk, N and Grusch, M and Reid, G}, title = {A link between the fibroblast growth factor axis and the miR-16 family reveals potential new treatment combinations in mesothelioma.}, journal = {Molecular oncology}, volume = {12}, number = {1}, pages = {58-73}, pmid = {29094504}, issn = {1878-0261}, mesh = {Cell Line, Tumor ; Down-Regulation ; Fibroblast Growth Factor 2/*therapeutic use ; Fibroblast Growth Factors/*metabolism ; Humans ; Lung Neoplasms/*drug therapy/*metabolism ; Mesothelioma/*drug therapy/*metabolism ; Mesothelioma, Malignant ; MicroRNAs/genetics/*metabolism ; Pleura/pathology ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Receptors, Fibroblast Growth Factor/genetics/metabolism ; Recombinant Proteins/*therapeutic use ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy with very limited therapeutic options. Fibroblast growth factor (FGF) signals play important roles in mesothelioma cell growth. Several FGFs and FGF receptors (FGFRs) are predicted targets of the miR-15/16 family, which is downregulated in MPM. The aim of this study was to explore the link between the miR-15/16 family and the FGF axis in MPM. Expression analyses via RT-qPCR showed downregulation of the FGF axis after transfection with miR-15/16 mimics. Direct interaction was confirmed by luciferase reporter assays. Restoration of miR-15/16 led to dose-dependent growth inhibition in MPM cell lines, which significantly correlated with their sensitivity to FGFR inhibition. Treatment with recombinant FGF2 prevented growth inhibition and further reduced the levels of FGF/R-targeting microRNAs, indicating a vicious cycle between miR-15/16 down- and FGF/FGFR signaling upregulation. Combined inhibition of two independent miR-15/16 targets, the FGF axis and Bcl-2, resulted in additive or synergistic activity. Our data indicate that post-transcriptional repression of FGF-mediated signals contributes to the tumor suppressor function of the microRNA-15/16 family. Inhibiting hyperactivated FGF signals and Bcl-2 might serve as a novel therapeutic combination strategy in MPM.}, }
@article {pmid29086761, year = {2017}, author = {Buresti, G and Colonna, F and Corfiati, M and Valenti, A and Persechino, B and Marinaccio, A and Rondinone, BM and Iavicoli, S}, title = {Economic impact of malignant mesothelioma in Italy: an estimate of the public and social costs.}, journal = {La Medicina del lavoro}, volume = {108}, number = {5}, pages = {358-366}, doi = {10.23749/mdl.v108i5.6505}, pmid = {29086761}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; *Cost of Illness ; Female ; *Health Care Costs ; Humans ; Italy ; Lung Neoplasms/*economics ; Male ; Mesothelioma/*economics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*economics ; Public Health/*economics ; }, abstract = {BACKGROUND: Despite their considerable interest for public health policies and for occupational disease management and assessment, the economic costs of asbestos-related diseases (ARDs) for society have not been fully estimated or even frequently discussed.<br><br>OBJECTIVES: The aim of this study was to estimate the economic burden of mesothelioma in Italy by assessing the overall societal cost of the disease, applying an econometric model.<br><br>METHODS: We analyzed two main cost groups, public and social. The first includes expenditure borne by the State and other public bodies (medical care costs, insurance, tax and benefits), while the latter uses the human capital approach to measure the loss of productivity suffered by the economy as a whole.<br><br>RESULTS: We provide an estimate of euro 33,000 per patient for medical care costs and euro 25,000 for insurance and compensation; tax and benefits seem to roughly compensate. We estimated a loss of more than euro 200,000 per patient, in terms of loss of production.<br><br>CONCLUSIONS: This study offers a practical approach for estimating the economic impact of mesothelioma, and provides empirical evidence of the huge economic burden linked to this disease, with its high etiologic fraction.}, }
@article {pmid29085453, year = {2017}, author = {Kim, YR and Song, MH and Lee, JW and Bae, JH and Kim, JE and Kang, DM and Lee, SY}, title = {Identification of tumor antigens in malignant mesothelioma.}, journal = {Oncology letters}, volume = {14}, number = {4}, pages = {4557-4562}, pmid = {29085453}, issn = {1792-1074}, abstract = {Serological analysis of recombinant tumor cDNA expression library (SEREX) is a powerful and widely used method to explore the cancer immune environment. In the present study, immunoscreening of normal testicular tissues and malignant mesothelioma (MM) cancer MSTO-211H cell line cDNA libraries with sera from 5 MM patients led to the isolation of 16 independent antigens, which were designated 'Korea Pusan-Malignant Mesothelioma' (KP-MM)-1 to -16. In total, 3/16 antigens were identified using the results of previous SEREX analyses, and 13 were newly identified. Of these, KP-MM-8, which was subsequently identified as amyotrophic lateral sclerosis 2 chromosome region candidate 11, was shown to be tissue-restricted. Reverse transcription-polymerase chain reaction demonstrated KP-MM-8 to be expressed strongly only in the normal testis, and weakly in the spleen, prostate, ovary, heart and skeletal muscle. In addition, KP-MM-8 mRNA was identified in MM cell lines, and in various other cancer cell lines, including MM (3/4), lung cancer (5/7), melanoma (5/7) and liver cancer (5/5) cell lines. Additionally, 2/16 antigens (KP-MM-2 and KP-MM-6) exclusively reacted with sera from cancer patients. However, KP-MM-8 reacted with 1 of 8 MM sera. Notably, 8/8 patients with MM and 8/8 normal individuals exhibited antibodies reactive to KP-MM-5, which was identified as cell division cycle 25B, a known oncogene. Overall, this data suggests that KP-MM-8 may be considered as a cancer/testis-like antigen and KP-MM-5 as an immunogenic tumor antigen in MM patients.}, }
@article {pmid29084128, year = {2017}, author = {Mangone, L and Di Felice, E and Storchi, C and Romanelli, A and Broccoli, S and Vicentini, M and Giorgi Rossi, P}, title = {The effects of improving the mesothelioma surveillance network on sensitivity, timeliness in reporting and asbestos exposure assessment.}, journal = {La Medicina del lavoro}, volume = {108}, number = {5}, pages = {367-376}, doi = {10.23749/mdl.v108i5.5929}, pmid = {29084128}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; *Epidemiological Monitoring ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*statistics &amp; numerical data ; Registries/*statistics &amp; numerical data ; Sensitivity and Specificity ; Time Factors ; }, abstract = {BACKGROUND: In Italy, Mesothelioma Registries (MRs) have been established by law for the epidemiological surveillance of occupational cancers. MRs collect information about asbestos exposure of incident cases, through interviews. In the Emilia-Romagna region, MR was implemented in 1996 and extended its network of health professionals who report suspected mesothelioma in 2001 and 2007.<br><br>OBJECTIVES: This study evaluated the impact of the extension of the network on MR sensitivity and timeliness.<br><br>METHODS: Mesothelioma cases were analysed in three subsequent periods: 1996-2001 (before any network extension), 2002-2007 (after first extension) and 2008-2014 (after second extension). Sensitivity was evaluated by the proportion of cases directly reported by the network out of the total number of incident cases; reporting and interview timeliness were assessed by median times between diagnosis and, respectively, reporting and interview. Pleural mesothelioma reporting timeliness was also evaluated by use of quantile regression models, stratified by diagnostic certainty and adjusted by sex and age.<br><br>RESULTS: Sensitivity increased from 79.4% (1996-2001), to 89.0% (2002-2007) and to 91.4% (2008-2013). For mesothelioma with diagnostic certainty, we recorded considerably reduced reporting times from the 50th percentile on, whereas for uncertain mesothelioma relevant reductions were observed also in the lower percentiles. A reduced time to interview was observed too, which was more significant for uncertain cases. The proportion of patients directly interviewed increased from 33.5% (1996-2001), to 39.1% (2002-2007), to 49.5% (2008-2014).<br><br>CONCLUSIONS: The extended network improved the MR sensitivity and allowed shorter reporting and interview times and more frequent patient interviews, thus improving accuracy of exposure definition.}, }
@article {pmid29083343, year = {2017}, author = {Chiesa, V and Odone, A and Signorelli, C}, title = {Forensic Epidemiology in Italy: principles and practice.}, journal = {Acta bio-medica : Atenei Parmensis}, volume = {88}, number = {3}, pages = {360-364}, pmid = {29083343}, issn = {2531-6745}, mesh = {*Epidemiology ; *Forensic Sciences ; Humans ; Italy ; }, abstract = {Forensic epidemiology (FE) implies the use of epidemiological data in the processes and the involvement of epidemiologists in judicial proceedings. FE is essential for the assessment of causal association between the exposure to specific agents and the occurrence of diseases. In this paper we describe FE principles and applications in the Italian context as in recent years FE emerged increasingly as well as the need of experienced and trained epidemiological experts able to navigate legal proceedings. In the literature, the principles of FE have been widely described by different authors, among them: Kennet Rothman who introduced the definition of cause, Sir Austin Bradford Hill who proposed an analytic framework to assess the causal association, and recently by Sana Loue who described the actual legislation and application of FE in the United States. Despite the legislation varies among different countries epidemiological methods and theories represent the foundation for the application of FE we illustrate in this paper. The association between environmental pollution and disease, mobile phones and cancer, vaccines and autism, asbestos and pleural mesothelioma are all situations that underscore the need for FE investigations in criminal acts. Causal association is a complex process: in real life only in limited cases causal associations are assessed by gathering robust scientific evidence, while cases with doubts and situations where different approaches to questions may lead to discordant arguments to questions may lead to discordant arguments are more frequent. Therefore, during the assessment of causation in civil and criminal matters the choice the epidemiological expert - with his knowledge and expertise - and the evidence from well-designed studies are crucial to fill the gaps between clinical and epidemiological data and the low.}, }
@article {pmid29080447, year = {2017}, author = {Salo, SAS and Ilonen, I and Laaksonen, S and Myllärniemi, M and Salo, JA and Rantanen, T}, title = {Epidemiology of malignant peritoneal mesothelioma: A population-based study.}, journal = {Cancer epidemiology}, volume = {51}, number = {}, pages = {81-86}, doi = {10.1016/j.canep.2017.10.008}, pmid = {29080447}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/mortality/pathology ; Male ; Mesothelioma/*epidemiology/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality/pathology ; Registries ; Retrospective Studies ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the mesothelial cells in the peritoneum with poor prognosis. Earlier reports from other countries indicate an incidence of 0.2-3 new cases per million per year. No previous studies have examined the national epidemiology of MPeM in Nordic countries. This study aimed to clarify the epidemiology of MPeM in Finland over a 12-year period.<br><br>METHODS: The data consisted of cancer notifications, laboratory notifications, and death certificate information in the Finnish Cancer Registry (FCR) and Statistics Finland (SF) of all MPeM patients from 2000 to 2012 in Finland. We also collected data on occupational disease compensations from the Workers' Compensation Center (WCC) of Finland. Any missing information was collected from the respective patient's file of every patient obtained from health institutions that had treated the patients.<br><br>RESULTS: Between January 1, 2000 and December 31, 2012, 90 new MPeM cases (56 males, 34 females) occurred in Finland. Median annual incidence was four new cases, which corresponded to 0.74 new cases per million per year. MPeM was deemed an occupational disease in 21 patients (23.3%). 71 patients (78.9%) of whom had a known cause of death, with a median survival of 4 months. The number of deaths linked to other disease than mesothelioma was 28/74 (37.8%).<br><br>CONCLUSIONS: Our study indicates that MPeM in Finland is rare and fatal, which is in accordance with previous reports from other countries. MPeM is also a fatal disease, since most of the patients died due to MPeM.}, }
@article {pmid29078648, year = {2017}, author = {Perikleous, P and Waller, DA}, title = {Video assisted thoracoscopic and open chest surgery in diagnosis and treatment of malignant pleural diseases.}, journal = {Journal of visualized surgery}, volume = {3}, number = {}, pages = {85}, pmid = {29078648}, issn = {2221-2965}, abstract = {Parenchymal cancers of lung, breast, gastrointestinal tract and ovaries as well as lymphomas and mesotheliomas are among the most common cancer types causing malignant effusions, though almost all tumour types have been reported to cause a malignant effusion. The prognosis heavily depends on patients' response to systemic therapy however, regardless of the causing pathology and histopathologic form, malignant pleural disease is normally associated with a poor prognosis. To date, there are not sufficient data to allow accurate predictions of survival that would facilitate decision making for managing patients with malignant pleural diseases. Interventions are directed towards drainage of the effusion and, when appropriate, concurrent or subsequent pleurodesis or establishing long-term drainage to prevent re-accumulation. The rate of re-accumulation of the pleural effusion, the patient's prognosis, and the severity of the patient's symptoms should guide the subsequent choice of therapy. In contemporary medicine, not many cancers have managed to generate as intense debates concerning treatment, as malignant pleural mesothelioma. The relative advantages of surgery, radiation, chemotherapy and any combination of the three are continuously reassessed and reconsidered, even though not always based on scientific evidence. The aim of surgery in mesothelioma may be prolongation of life, in addition to palliation of symptoms. Longer recovery periods from more extensive surgical procedures could be justified, in carefully selected patients. Surgical options include: Video assisted thoracoscopic (VATS) pleurodesis, VATS partial pleurectomy (VATS PP)-both parietal and visceral; open pleurectomy decortication (PD)-with an extended option (EPD) and extrapleural pneumonectomy (EPP). Current evidence implies that EPD can be performed reliably in specialised centres with good results, both in terms of mortality and survival; however, no operation has yet been shown to be beneficial in a prospective randomized controlled clinical trial.}, }
@article {pmid29073511, year = {2017}, author = {Mensi, C and Mendola, M and Dallari, B and Sokooti, M and Tabibi, R and Riboldi, L and Consonni, D}, title = {Differences between peritoneal and pleural mesothelioma in Lombardy, Italy.}, journal = {Cancer epidemiology}, volume = {51}, number = {}, pages = {68-73}, doi = {10.1016/j.canep.2017.10.003}, pmid = {29073511}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Registries ; }, abstract = {BACKGROUND: We examined characteristics of peritoneal (PEM) and pleural (PLM) mesothelioma in Lombardy, Italy.<br><br>METHODS: From the Lombardy Mesothelioma Registry we selected PEM (N=300) and PLM (N=5011) cases diagnosed in 2000-2014. We investigated asbestos exposure and presence of asbestosis or pleural plaques.<br><br>RESULTS: Incidence rates (per 1,000,000 person-years, world standardized) of PEM were 1.2 (men) and 0.9 (women), compared with 22.6 and 8.4 for PLM. Asbestosis (both genders) and pleural plaques (men) were more frequent among PEM cases. Occupational asbestos exposure was similar in PEM and PLM cases. We found higher proportions of PEMs employed in the asbestos cement production.<br><br>CONCLUSION: The higher frequency of pleural plaques in PEM cases confirm the association between asbestos and peritoneal mesothelioma. The higher proportions of asbestosis and of past employment in the asbestos-cement sector among PEM cases suggest a possible role of high exposures to asbestos in the peritoneal mesothelioma genesis.}, }
@article {pmid29072598, year = {2017}, author = {Lemen, RA and Landrigan, PJ}, title = {Toward an Asbestos Ban in the United States.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29072598}, issn = {1660-4601}, mesh = {Animals ; Asbestos/*history/toxicity ; Carcinogens/*history/toxicity ; Government Regulation ; History, 19th Century ; History, 20th Century ; Humans ; Occupational Exposure/*legislation &amp; jurisprudence/*prevention &amp; control ; United States ; }, abstract = {Many developed countries have banned the use of asbestos, but not the United States. There have, however, been multiple efforts in the US to establish strict exposure standards, to limit asbestos use, and to seek compensation through the courts for asbestos-injured workers' In consequence of these efforts, asbestos use has declined dramatically, despite the absence of a legally mandated ban. This manuscript presents a historical review of these efforts.}, }
@article {pmid29072053, year = {2017}, author = {Emami, H and Ilbeigi, A and Khodadad, K}, title = {An Overview of Asbestos and Malignant Pleural Mesothelioma: An Iranian Perspective.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {10}, pages = {2619-2623}, pmid = {29072053}, issn = {2476-762X}, abstract = {Asbestos refers to a group of minerals that appears naturally in the environment as bundles of fibers. The incidence rate of asbestos-related diseases has considerably increased as well as the amount of asbestos utilization in few countries. Malignant pleural mesothelioma (MPM) is a rare type of aggressive and life threatening neoplasm which arise from various serous surfaces: pleura, peritoneum, tunica vaginalis and pericardium. The first case of MPM was reported in 1947. MPM etiologically is associated to the exposure of asbestos fibers. This form of malignancy is difficult to diagnose in paraclinical work-ups because mesothelioma could occur within 10-20 years of the first-time exposure to asbestos. The burden of MPM is not yet to be wholly understood. The toxic side effects of asbestos on environment and people compelled the European countries to accept the French view upon this matter. However, this approach has not been accepted by some developing countries. This review provides a brief points and facts in relation to MPM and asbestos in Iran.}, }
@article {pmid29068368, year = {2017}, author = {Metintaş, S and Batırel, HF and Bayram, H and Yılmaz, &#xdc; and Karadağ, M and Ak, G and Metintaş, M}, title = {Turkey National Mesothelioma Surveillance and Environmental Asbestos Exposure Control Program.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29068368}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Environmental Exposure/*prevention &amp; control ; Environmental Monitoring ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; *Population Surveillance ; Risk ; Rural Population/statistics &amp; numerical data ; Turkey/epidemiology ; Young Adult ; }, abstract = {Malignant mesothelioma (MM) is an important health problem due to ongoing asbestos exposure. Environmental asbestos exposure leads to a high risk of MM in Turkey. The Turkish Mesothelioma Working Group and the Turkish Public Health Institute designed and performed the Turkey National Mesothelioma Surveillance and Environmental Asbestos Exposure Control Program (TUNMES-EAECP). The aim of this study was to analyze the results of the TUNMES-EAECP. Patients diagnosed with MM (code C45.0-C45.9) between 2008 and 2012 were identified. The "from case to the field" method was used to determine the villages with current or previous asbestos exposure. Special public health teams took soil samples from these villages, which were then examined using an X-ray diffractometer. Direct Standardized Average Annual Mesothelioma Incidence Rate (AMIR) and relative risk (RR) of MM were calculated. Finally, a projection on the incidence of MM between 2013 and 2033 was made. The number of confirmed MM cases was 5617 with a male to female ratio of 1.36. Mean age was 61.7 ± 13.4 (20-96) years. The median survival was eight (95% CI 7.6-8.4) months. Asbestos exposure continues in 379 villages, with 158,068 people still living in high risk areas. The standardized AMIR was 2.33/100,000 per year. The risk of MM was higher in males, in both sexes over the age of 40, in asbestos-containing provinces, and in those where the TUNMES was organized. Among the population with continuing asbestos exposure in rural areas, the number of MM cases between 2013 and 2033 was estimated as 2511. As such, the incidence of MM in Turkey is as high as in industrialized countries. Asbestos exposure in rural areas continues to be a serious problem in Turkey, which obviates the necessity for effective preventive measures.}, }
@article {pmid29061909, year = {2018}, author = {Lacourt, A and Leveque, E and Goldberg, M and Leffondre, K}, title = {Dose-time response association between occupational asbestos exposure and pleural mesothelioma: authors' response.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {2}, pages = {161-162}, doi = {10.1136/oemed-2017-104802}, pmid = {29061909}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, }
@article {pmid29059207, year = {2017}, author = {Alfaleh, MA and Howard, CB and Sedliarou, I and Jones, ML and Gudhka, R and Vanegas, N and Weiss, J and Suurbach, JH and de Bakker, CJ and Milne, MR and Rumballe, BA and MacDiarmid, JA and Brahmbhatt, H and Mahler, SM}, title = {Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.}, journal = {PloS one}, volume = {12}, number = {10}, pages = {e0186137}, pmid = {29059207}, issn = {1932-6203}, mesh = {Animals ; *Cell Proliferation ; Humans ; Mesothelin ; Mesothelioma/*pathology ; Mice ; Receptors, Cell Surface/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV) are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs) which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN). Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.}, }
@article {pmid29034666, year = {2017}, author = {Serrier, H and Sultan-Taïeb, H and Luce, D and Béjean, S}, title = {[Respiratory cancers attributable to occupational exposures: what is the cost to society in France].}, journal = {Sante publique (Vandoeuvre-les-Nancy, France)}, volume = {29}, number = {4}, pages = {509-524}, doi = {10.3917/spub.174.0509}, pmid = {29034666}, issn = {0995-3914}, mesh = {Female ; France/epidemiology ; Humans ; Male ; Occupational Diseases/*economics/epidemiology ; Occupational Exposure/*adverse effects/*economics ; Respiratory Tract Neoplasms/chemically induced/*economics/epidemiology ; Risk Factors ; }, abstract = {OBJECTIVE: To estimate the social cost of respiratory cancers attributable to occupational risk factors in France in 2010.<br><br>METHODS: We estimated the number of cases of respiratory cancers attributable to each identified occupational risk factor according to the attributable fractions method. We also estimated direct (costs of hospital stays, drugs, outpatient care) and indirect costs (production losses) related to morbidity (absenteeism and presenteeism) and mortality (years of lost production). Production losses for paid work and unpaid domestic activities were taken into account.<br><br>RESULTS: The social cost of respiratory cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons, painting occupations (unidentified carcinogen), crystalline silica, wood and leather dust in France in 2010 was estimated to be between &#x20ac;960 and 1,866 million. The cost of lung cancer represents between &#x20ac;804 and 1,617 million. The three risk factors with the greatest impact are asbestos (&#x20ac;530 to 890 million), diesel engine exhaust (&#x20ac;227 to 394 million), and crystalline silica (&#x20ac;116 to 268 million).<br><br>CONCLUSION: These results provide a conservative estimate of the public health and economic burden of respiratory cancers attributable to occupational risk factors from a societal perspective.}, }
@article {pmid29030093, year = {2018}, author = {Cherrie, JW and McElvenny, D and Blyth, KG}, title = {Estimating past inhalation exposure to asbestos: A tool for risk attribution and disease screening.}, journal = {International journal of hygiene and environmental health}, volume = {221}, number = {1}, pages = {27-32}, doi = {10.1016/j.ijheh.2017.09.013}, pmid = {29030093}, issn = {1618-131X}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Asbestos/*administration &amp; dosage ; Humans ; Inhalation Exposure/*analysis ; Risk Assessment ; }, abstract = {INTRODUCTION: Late presentation is common in mesothelioma. Reliable assessment of past exposure to asbestos is a necessary first step for risk attribution and for the development of a future screening programme. Such a programme could maximise access to trials of novel therapies and would pave the way for development of novel chemoprophylaxis strategies. This paper describes a method for individual exposure reconstruction along with data from a validation study.<br><br>METHODS: The exposure assessment method uses only descriptive information about the circumstances of the work that could be obtained from questioning the worker. The assessment is based on the tasks carried out and includes parameters for substance emission potential, activity emission potential, the effectiveness of any local control measures, passive emission, the fractional time the asbestos source is active and the efficiency of any respiratory protection worn.<br><br>RESULTS: There was a good association between the estimated and measured exposure levels. Pearson's correlation coefficient between the log-transformed measurements and estimates from the model was 0.86, and 95% of the estimated individual values were within about a factor of ten of the associated measured value. The method described would be suitable for pre-selecting individuals at high risk of malignant pleural mesothelioma for screening using appropriate tools and/or enrolment in clinical trials of chemo-prophylaxis.<br><br>DISCUSSION: This method is of potential clinical value in developing novel treatment approaches for mesothelioma. Pilot studies to test this approach are urgently needed.}, }
@article {pmid29020669, year = {2017}, author = {Gogali, A and Ntzani, EE and Manda-Stachouli, C and Peristeri, S and Tzarouchi, L and Laiou, E and Konstantinidis, A and Constantopoulos, SH and Dalavanga, Y}, title = {Evidence Suggesting the End of Universal Domestic Asbestos Exposure in Metsovo, NW Greece.}, journal = {Respiration; international review of thoracic diseases}, volume = {94}, number = {6}, pages = {510-517}, doi = {10.1159/000480151}, pmid = {29020669}, issn = {1423-0356}, mesh = {Adult ; Asbestos/adverse effects/*analysis ; Asbestosis/*diagnostic imaging ; Bronchoalveolar Lavage Fluid/chemistry ; Calcinosis/diagnostic imaging/*etiology ; Environmental Exposure/adverse effects/*analysis ; Female ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Inhabitants of Metsovo, NW Greece, had been domestically exposed to asbestos from a gradually abandoned whitewash ("luto") that resulted in a declining epidemic of malignant mesothelioma.<br><br>OBJECTIVES: We aimed to evaluate whether other sources of asbestos exposure exist following "luto" abandonment.<br><br>METHODS: Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were used to evaluate residual asbestos exposure in younger Metsovites through the identification of pleural calcifications and asbestos bodies, respectively. In order to provide a historical universally exposed group for comparison, we used the accumulated chest CTs and chest roentgenograms of our previous studies, performed in Metsovites with confirmed exposure but negative chest roentgenogram. As an additional external comparison group, we also assessed CT scans and chest roentgenograms of Metsovites being older than our target group obtained from the records of the Radiology Department between 2009 and 2011. In order to be able to compare our BAL findings, we sought historical controls among BAL studies performed in Metsovites with known exposure to "luto," in the 1980s-1990s, mainly to evaluate alveolitis. Those belonging to individuals of the same age range were used for further comparison.<br><br>RESULTS: Twenty-two Metsovites born between 1960 and 1980 consented to undergo a chest CT scan, while another 14 CTs were retrieved from the records of the Radiology Department (among 86 of all ages), thus increasing the number of individuals studied to 36. Five of the 36 Metsovites studied were former "luto" users for a short period of time. Minimal pleural calcifications were present in 2 of them, while all chest CTs of nonusers were negative. All 8 BAL studies were negative for asbestos bodies.<br><br>CONCLUSION: "Luto" use seems to have been the only source of considerable asbestos exposure in Metsovo.}, }
@article {pmid28986649, year = {2017}, author = {Tischoff, I and Tannapfel, A}, title = {[Mesothelioma].}, journal = {Der Pathologe}, volume = {38}, number = {6}, pages = {547-560}, pmid = {28986649}, issn = {1432-1963}, mesh = {Asbestos/adverse effects ; Female ; Germany ; Humans ; *Lung Neoplasms/etiology/pathology ; Male ; *Mesothelioma/etiology/pathology ; Middle Aged ; Risk Factors ; }, abstract = {Malignant mesotheliomas are rare and aggressive tumours arising from mesothelial cells of the pleura and peritoneum. Infrequent sites of origin are the pericardium and tunica vaginalis testis. More than 80% of mesotheliomas are localized in the pleura. Men are more frequently affected than women. The median age is >60 years. Asbestos exposure is the best known aetilogical risk factor and is reported in 54-90% of patients. In Germany, malignant mesotheliomas caused by occupational asbestos exposure are compensated as occupational disease since 1977. Several neoplastic and non-neoplastic lesions like metastasis, sarcomas, lymphomas or pleuritis with reactive mesothelial proliferation have to be distinguished from malignant mesotheliomas. Especially, the pathohistological differentiation between atypical reactive mesothelial proliferation from malignant mesothelioma is a diagnostic challenge.}, }
@article {pmid28985440, year = {2017}, author = {Binazzi, A and Marinaccio, A and Corfiati, M and Bruno, C and Fazzo, L and Pasetto, R and Pirastu, R and Biggeri, A and Catelan, D and Comba, P and Zona, A}, title = {Mesothelioma incidence and asbestos exposure in Italian national priority contaminated sites.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {43}, number = {6}, pages = {550-559}, doi = {10.5271/sjweh.3676}, pmid = {28985440}, issn = {1795-990X}, mesh = {Asbestos/*toxicity ; Bayes Theorem ; Environmental Exposure/statistics &amp; numerical data ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Occupational Exposure/*statistics &amp; numerical data ; Registries/*statistics &amp; numerical data ; }, abstract = {Objectives This study aimed to (i) describe mesothelioma incidence in the Italian national priority contaminated sites (NPCS) on the basis of data available from the Italian National Mesothelioma Registry (ReNaM) and (ii) profile NPCS using Bayesian rank analysis. Methods Incident cases of mesothelioma and standardized incidence ratios (SIR) were estimated for both genders in each of the 39 selected NPCS in the period 2000-2011. Age-standardized rates of Italian geographical macro areas were used to estimate expected cases. Rankings of areas were produced by a hierarchical Bayesian model. Asbestos exposure modalities were discussed for each site. Results In the study period, 2683 incident cases of mesothelioma (1998 men, 685 women) were recorded. An excess of mesothelioma incidence was confirmed in sites with a known past history of direct use of asbestos (among men) such as Balangero (SIR 197.1, 95% CI 82.0-473.6), Casale Monferrato (SIR 910.7, 95% CI 816.5-1012.8), and Broni (SIR 1288.5, 95% CI 981.9-1691.0), in sites with shipyards and harbors (eg, Trieste, La Spezia, Venice, and Leghorn), and in settings without documented direct use of asbestos. The analysis ranked the sites of Broni and Casale Monferrato (both genders) and Biancavilla (only for women) the highest. Conclusions The present study confirms that asbestos pollution is a risk for people living in polluted areas, due to not only occupational exposure in industrial settings with direct use of asbestos but also the presence of asbestos in the environment. Epidemiological surveillance of asbestos-related diseases is a fundamental tool for monitoring the health profile in NPCS.}, }
@article {pmid28984470, year = {2017}, author = {Sobhani, N and Corona, SP and Bonazza, D and Ianza, A and Pivetta, T and Roviello, G and Cortale, M and Guglielmi, A and Zanconati, F and Generali, D}, title = {Advances in systemic therapy for malignant mesothelioma: future perspectives.}, journal = {Future oncology (London, England)}, volume = {13}, number = {23}, pages = {2083-2101}, doi = {10.2217/fon-2017-0224}, pmid = {28984470}, issn = {1744-8301}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Immunotherapy ; Lung Neoplasms/mortality/pathology/*therapy ; Mesothelioma/mortality/pathology/*therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.}, }
@article {pmid28979837, year = {2017}, author = {Ju, L and Wu, W and Yin, X and Xiao, Y and Jia, Z and Lou, J and Yu, M and Ying, S and Chen, T and Jiang, Z and Li, W and Chen, J and Zhang, X and Zhu, L}, title = {miR-30d is related to asbestos exposure and inhibits migration and invasion in NCI-H2452 cells.}, journal = {FEBS open bio}, volume = {7}, number = {10}, pages = {1469-1479}, pmid = {28979837}, issn = {2211-5463}, abstract = {Pleural malignant mesothelioma (MM) is a highly aggressive tumor that is typically related to asbestos exposure and has a latency of 20-60 years. Several microRNA contribute to MM initiation and progression, but the mechanisms are not clear. Here, we found that miR-30d is downregulated in the pleural MM cell line NCI-H2452, in the plasma of asbestos-exposed individuals, and in asbestos-exposed mesothelial cells. Furthermore, we investigated the influence of the overexpression of miR-30d in pleural MM cells. We demonstrated that miR-30d overexpression could suppress pleural MM cell proliferation, migration, and invasion in vitro and could promote cell apoptosis but could not significantly influence cell cycle. The mRNA and protein expression of vimentin and TWIST1 decreased, and the mRNA expression of CDH1 increased in NCI-H2452 cells that overexpressed miR-30d. We therefore conclude that miR-30d is related to asbestos exposure and inhibits cell migration and invasion by regulating the epithelial-mesenchymal transition in NCI-H2452 cells.}, }
@article {pmid28960945, year = {2017}, author = {Yamaji, M and Ota, A and Wahiduzzaman, M and Karnan, S and Hyodo, T and Konishi, H and Tsuzuki, S and Hosokawa, Y and Haniuda, M}, title = {Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells.}, journal = {Cancer medicine}, volume = {6}, number = {11}, pages = {2646-2659}, pmid = {28960945}, issn = {2045-7634}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Benzylamines/pharmacology ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Forkhead Box Protein O1/metabolism ; G1 Phase Cell Cycle Checkpoints/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Glycogen Synthase Kinase 3 beta/metabolism ; Heterocyclic Compounds, 3-Ring/pharmacology ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Imidazoles ; Inhibitory Concentration 50 ; Mesothelioma/*drug therapy ; Oxadiazoles/pharmacology ; Phosphorylation/drug effects ; Phosphorylcholine/analogs &amp; derivatives/pharmacology ; Pleural Neoplasms/*drug therapy ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/*antagonists &amp; inhibitors/metabolism ; Pyrazoles/*pharmacology ; Pyridines ; Pyrimidines/pharmacology ; Pyrroles/pharmacology ; Quinoxalines/pharmacology ; Sulfonamides/pharmacology ; Thiadiazoles/pharmacology ; Thiophenes/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM), an asbestos-related occupational disease, is an aggressive and incurable tumor of the thoracic cavity. Despite recent advances in MPM treatment, overall survival of patients with MPM is very low. Recent studies have implicated that PI3K/Akt signaling is involved in MPM cell survival and development. To investigate the effects of Akt inhibitors on MPM cell survival, we examined the effects of nine selective Akt inhibitors, namely, afuresertib, Akti-1/2, AZD5363, GSK690693, ipatasertib, MK-2206, perifosine, PHT-427, and TIC10, on six MPM cell lines, namely, ACC-MESO-4, Y-MESO-8A, MSTO-211H, NCI-H28, NCI-H290, and NCI-H2052, and a normal mesothelial cell line MeT-5A. Comparison of IC50 values of the Akt inhibitors showed that afuresertib, an ATP-competitive specific Akt inhibitor, exerted tumor-specific effects on MPM cells. Afuresertib significantly increased caspase-3 and caspase-7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Moreover, afuresertib strongly arrested the cell cycle in the G1 phase. Western blotting analysis showed that afuresertib increased the expression of p21[WAF][1/][CIP][1] and decreased the phosphorylation of Akt substrates, including GSK-3β and FOXO family proteins. These results suggest that afuresertib-induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Furthermore, afuresertib significantly enhanced cisplatin-induced cytotoxicity. Interestingly, results of gene set enrichment analysis showed that afuresertib modulated the expression E2F1 and MYC, which are associated with fibroblast core serum response. Together, these results suggest that afuresertib is a useful anticancer drug for treating patients with MPM.}, }
@article {pmid28960045, year = {2017}, author = {Kim, JS and Lim, SY and Hwang, J and Kang, EJ and Choi, YJ}, title = {A Case Report of Primary Pericardial Malignant Mesothelioma Treated with Pemetrexed and Cisplatin.}, journal = {Journal of Korean medical science}, volume = {32}, number = {11}, pages = {1879-1884}, pmid = {28960045}, issn = {1598-6357}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Calbindin 2/metabolism ; Cardiac Tamponade/diagnosis ; Cisplatin/*therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Keratins/metabolism ; Lung Neoplasms/diagnosis/*drug therapy ; Mesothelioma/diagnosis/*drug therapy ; Mesothelioma, Malignant ; Pemetrexed/*therapeutic use ; Pleural Neoplasms/diagnosis/*drug therapy ; Thorax/diagnostic imaging ; Tomography, X-Ray Computed ; Treatment Outcome ; Ultrasonography ; Vimentin/metabolism ; }, abstract = {Primary pericardial malignant mesothelioma (PPM) is a very rare malignancy, with an incidence of less than 0.002% and represents less than 5% of all mesotheliomas. The cause of pericardial mesothelioma is uncertain that differ from pleural mesothelioma which is associated with asbestos exposure. This malignancy is terribly aggressive and has very poor prognosis with less than six months of overall survival. We present a case of a 71-year-old woman who was diagnosed with cardiac tamponade caused by PPM and received chemotherapy with pemetrexed and cisplatin for six months. During two years she was alive without disease progression. To better understand the clinical, pathologic features and treatment outcome of this entity, we reviewed 23 cases described in the English literature from 2009, together with our case, provided a total of 24 cases. Based on this review, we suggest that PPM must be considered in patients who have unexplained massive pericardial effusion and recommend chemotherapy with pemetrexed and cisplatin for the better outcome of PPM.}, }
@article {pmid28951802, year = {2017}, author = {MacLeod, JS and Harris, MA and Tjepkema, M and Peters, PA and Demers, PA}, title = {Cancer Risks among Welders and Occasional Welders in a National Population-Based Cohort Study: Canadian Census Health and Environmental Cohort.}, journal = {Safety and health at work}, volume = {8}, number = {3}, pages = {258-266}, pmid = {28951802}, issn = {2093-7911}, abstract = {BACKGROUND: Welders are exposed to many known and suspected carcinogens. An excess lung cancer risk among welders is well established, but whether this is attributable to welding fumes is unclear. Excess risks of other cancers have been suggested, but not established. We investigated welding cancer risks in the population-based Canadian Census Health and Environmental Cohort.<br><br>METHODS: Among 1.1 million male workers, 12,845 welders were identified using Standard Occupational Classification codes and followed through retrospective linkage of 1991 Canadian Long Form Census and Canadian Cancer Registry (1992-2010) records. Hazard ratios (HRs) were calculated using Cox proportional hazards models based on estimated risks of lung cancer, mesothelioma, and nasal, brain, stomach, kidney, and bladder cancers, and ocular melanoma. Lung cancer histological subtypes and risks by industry group and for occasional welders were examined. Some analyses restricted comparisons to blue-collar workers to minimize effects of potential confounders.<br><br>RESULTS: Among welders, elevated risks were observed for lung cancer [HR: 1.16, 95% confidence interval (CI): 1.03-1.31], mesothelioma (HR: 1.78, 95% CI: 1.01-3.18), bladder cancer (HR: 1.40, 95% CI: 1.15-1.70), and kidney cancer (HR: 1.30, 95% CI: 1.01-1.67). When restricted to blue-collar workers, lung cancer and mesothelioma risks were attenuated, while bladder and kidney cancer risks increased.<br><br>CONCLUSION: Excess risks of lung cancer and mesothelioma may be partly attributable to factors including smoking and asbestos. Welding-specific exposures may increase bladder and kidney cancer risks, and particular sources of exposure should be investigated. Studies that are able to disentangle welding effects from smoking and asbestos exposure are needed.}, }
@article {pmid28949000, year = {2018}, author = {Jiang, Z and Chen, T and Chen, J and Ying, S and Gao, Z and He, X and Miao, C and Yu, M and Feng, L and Xia, H and Wu, W and Chen, R and Morinaga, K and Lou, J and Zhang, X}, title = {Hand-spinning chrysotile exposure and risk of malignant mesothelioma: A case-control study in Southeastern China.}, journal = {International journal of cancer}, volume = {142}, number = {3}, pages = {514-523}, doi = {10.1002/ijc.31077}, pmid = {28949000}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/*poisoning ; Case-Control Studies ; China/epidemiology ; Female ; Humans ; Logistic Models ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*statistics &amp; numerical data ; Retrospective Studies ; Risk ; Textile Industry/statistics &amp; numerical data ; }, abstract = {While chrysotile has been commonly used by Chinese textile industry for many years, investigations on the association of chrysotile exposure with risk of mesothelioma in China are scarce. We conducted a case-control study in a county located at Southeastern China, including 46 cases and 230 individually matched controls. A semi-quantitative method based on experts' assessment was used for evaluating hand-spinning chrysotile exposure. Conditional logistic regression models were used to assess the association of asbestos exposure with risk of mesothelioma. We found that hand-spinning chrysotile exposure was associated with significantly elevated risk of mesothelioma, reaching OR =10 (95% CIs: 1.4-65) for possible exposure and 64 (12-328) for definite exposure. Our data suggested a dose-response relationship of chrysotile exposure duration with risk of mesothelioma, reaching 28 (6-134) for <6 years, 51 (11-247) for 7-17 years and 56 (9-351) for ≥18 years. A dose-response relationship of cumulative exposure index (CEI) with risk of mesothelioma was found, reaching 28 (6-137) for CEI at 0-0.5 fibers per milliliter years (f/mL-year), 36 (7-184) for CEI at 0.5-28.6 f/mL-years and 79 (14-451) for CEI > 28.6 f/mL-years. We found a dose-response relationship of chrysotile exposure duration and CEI with risk of mesothelioma in Southeastern China, adding valuable information on health hazards of chrysotile exposure in China where chrysotile is still used nationwide.}, }
@article {pmid28947868, year = {2017}, author = {Zhao, J and Zuo, T and Zheng, R and Zhang, S and Zeng, H and Xia, C and Yang, Z and Chen, W}, title = {Epidemiology and trend analysis on malignant mesothelioma in China.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {29}, number = {4}, pages = {361-368}, pmid = {28947868}, issn = {1000-9604}, abstract = {OBJECTIVE: Population-based cancer registration data were used to analyze the epidemiology and trend of malignant mesothelioma in China, and the result would provide basic data for its prevention and control.<br><br>METHODS: Malignant mesothelioma data in 2013 were retrieved from the database of National Cancer Registry. Malignant mesothelioma incidence and mortality were estimated using age-specific rate by urban/rural and gender according to the national population in 2013. Malignant mesothelioma data from 22 cancer registries were used for trend analysis during 2000-2013.<br><br>RESULTS: It is estimated that there were 2,041 new malignant mesothelioma cases and 1,659 malignant mesothelioma deaths occurred in 2013. The crude incidence rate in China were 1.50/10[6] (males 1.67/10[6], females 1.32/10[6]), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 1.03/10[6] and 1.02/10[6], respectively. The crude mortality rate in China was 1.22/10[6] (males 1.67/10[6], females 1.32/10[6]), age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 0.83/10[6] and 0.81/10[6], respectively. There was an increasing trend of incidence rate for malignant mesothelioma in registration areas of China during 2000-2013 with annual percentage change (APC) of 2.5% [95% confidence interval (95% CI): 0.6%-4.5%]. After age standardization, no significant differences were observed. No matter for crude mortality rates or age-standardized mortality rates, no significant differences were observed during 2000-2013.<br><br>CONCLUSIONS: Malignant mesothelioma is the major occupational and environmental neoplasm associated with asbestos exposure. The increasing incidence trend suggests that more attention should be paid on this disease.}, }
@article {pmid28947493, year = {2017}, author = {Landrigan, PJ}, title = {Data on mesothelioma mortality: a powerful tool for preventing asbestos-related disease.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {849-850}, doi = {10.1136/oemed-2017-104688}, pmid = {28947493}, issn = {1470-7926}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*mortality/*prevention &amp; control ; Occupational Exposure/adverse effects/statistics &amp; numerical data ; }, }
@article {pmid28940402, year = {2017}, author = {Kradin, RL and Eng, G and Christiani, DC}, title = {Diffuse peritoneal mesothelioma: A case series of 62 patients including paraoccupational exposures to chrysotile asbestos.}, journal = {American journal of industrial medicine}, volume = {60}, number = {11}, pages = {963-967}, doi = {10.1002/ajim.22768}, pmid = {28940402}, issn = {1097-0274}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*toxicity ; Carcinogens/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Exposure/*adverse effects/legislation &amp; jurisprudence ; Peritoneal Neoplasms/*etiology/pathology ; Time Factors ; }, abstract = {BACKGROUND: Diffuse peritoneal malignant mesothelioma (DPM) is caused by exposure to asbestos. The medical literature has linked DPM primarily to high levels of asbestos exposure, in particular amosite. Controversy persists as to whether chrysotile is capable of causing DPM, especially when exposures are paraoccupational.<br><br>METHODS: Sixty-two subjects (51 men, 11 women) with DPM were reviewed in medical-legal consultation with deposition and product identification evidence.<br><br>RESULTS: All had pathologically confirmed DPM. Most were exposed to both amphibole and chrysotile, but chrysotile alone was documented in 14/62 (26%) cases. A total of 7/14 (50%) cases of the paraoccupational exposures were to chrysotile alone. Women were younger than men as were those with paraoccupational versus those with occupational exposure. The mean duration of exposure for all cases was 17.9&#x2009;&#xb1;&#x2009;10 years and latency from time of first exposure was 45.9&#x2009;+&#x2009;11.6 years.<br><br>CONCLUSIONS: DPM occurs with both occupational and paraoccupational exposures to asbestos and may be seen in paraoccupational exposures to chrysotile asbestos.}, }
@article {pmid28937307, year = {2017}, author = {Møller, P and Jacobsen, NR}, title = {Weight of evidence analysis for assessing the genotoxic potential of carbon nanotubes.}, journal = {Critical reviews in toxicology}, volume = {47}, number = {10}, pages = {867-884}, doi = {10.1080/10408444.2017.1367755}, pmid = {28937307}, issn = {1547-6898}, mesh = {*DNA Damage ; Hazardous Substances/*toxicity ; Humans ; Mutagenicity Tests ; Nanotubes, Carbon/*toxicity ; }, abstract = {Carbon nanotube (CNT) is a nanomaterial that has received interest because of its high-tensile strength and low weight. Although CNTs differ substantially in physico-chemical properties, they share high aspect ratio which resembles that of asbestos and other fibers causing lung cancer and mesothelioma. One type of multi-walled CNTs (i.e. MWCNT-7) has been classified as possibly carcinogenic to humans by IARC (Group 2B) based on experimental animal data, whereas other types of MWCNTs and single-walled CNTs (SWCNT) could not be classified due to lack of data from epidemiologic studies and insufficient mechanistic evidence. Damage to DNA is considered to be a key mechanistic step in the development of fiber-induced cancer. Thus, the genotoxic potential can be a cornerstone in the evaluation of hazards of CNTs. The present study used a weight of evidence (WoE) analysis to evaluate the genotoxicity of different types of CNTs. Genotoxicity endpoints close to cancer (mutations and chromosome aberrations) and animal models had highest weight in the WoE analysis. Eight CNT materials out of 130, which had been assessed in several studies, were evaluated in the WoE analysis. The results demonstrated that MWCNT-7 has strongest WoE for a genotoxic hazard among the MWCNTs. Two types of SWCNTs have a similar WoE for genotoxicity as MWCNT-7. Several reference materials from the Joint Research Centre have less WoE for genotoxicity. The WoE analysis demonstrates a difference in genotoxicity for CNTs, but further research is required to unravel the physico-chemical characteristics that govern the differences in genotoxic hazard.}, }
@article {pmid28935666, year = {2017}, author = {Marsh, GM and Riordan, AS and Keeton, KA and Benson, SM}, title = {Non-occupational exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {11}, pages = {838-846}, doi = {10.1136/oemed-2017-104383}, pmid = {28935666}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Environmental Exposure/*adverse effects/analysis ; Female ; *Housing ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Occupational Exposure ; Pleural Neoplasms/*chemically induced ; *Residence Characteristics ; Risk Assessment ; }, abstract = {OBJECTIVE: To conduct an updated literature review and meta-analysis of studies of pleural malignant mesothelioma (PMM) risk among persons exposed to asbestos non-occupationally (household and neighbourhood).<br><br>METHODS: We performed a literature search for articles available in the National Center for Biotechnology Information's PubMed database published between 1967 and 2016. Meta-analyses were conducted to calculate pooled PMM risk estimates, stratifying for household or neighbourhood exposure to asbestos and/or predominant asbestos fibre type (chrysotile, amphibole or mixed).<br><br>RESULTS: Eighteen studies in 12 countries comprising 665 cases met the meta-analysis inclusion criteria. We identified 13 estimates of PMM risk from neighbourhood exposures, 10 from household and one from mixed exposure, and combined the estimates using random-effects models. The overall meta-relative risk (meta-RR) was 5.9 (95% CI 4.4 to 8.7). The meta-RRs for household and neighbourhood exposures were 5.4 (95% CI 2.6 to 11.2) and 6.9 (95% CI 4.2 to 11.4), respectively. We observed trends in risk in relation to fibre type for both household and neighbourhood studies. For chrysotile, mixed and amphibole fibres, respectively, meta-RRs for neighbourhood studies were 3.8 (95% CI 0.4 to 38.4), 8.4 (95% CI 4.7 to 14.9) and 21.1 (95% CI 5.3 to 84.5) and meta-RRs for household studies were 4.0 (95% CI 0.8 to 18.8), 5.3 (95% CI 1.9 to 15.0) and 21.1 (95% CI 2.8 to 156.0).<br><br>CONCLUSIONS: PMM risks from non-occupational asbestos exposure are consistent with the fibre-type potency response observed in occupational settings. By relating our findings to knowledge of exposure-response relationships in occupational settings, we can better evaluate PMM risks in communities with ambient asbestos exposures from industrial or other sources.}, }
@article {pmid28929108, year = {2017}, author = {Ju, L and Wu, W and Yu, M and Lou, J and Wu, H and Yin, X and Jia, Z and Xiao, Y and Zhu, L and Yang, J}, title = {Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure.}, journal = {BioMed research international}, volume = {2017}, number = {}, pages = {2747215}, pmid = {28929108}, issn = {2314-6141}, mesh = {Asbestos/*toxicity ; Carcinogens ; Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; DNA Damage/drug effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Nanotubes, Carbon/*toxicity ; Time Factors ; }, abstract = {Despite being a commercially important product, multiwalled carbon nanotubes (MWCNTs) continue to raise concerns over human health due to their structural similarity to asbestos. Indeed, exposure to MWCNT has been shown to induce lung cancer and even mesothelioma, but contradictory results also exist. To clarify the potentially carcinogenic effects of rigid and rod-like MWCNT and to elucidate the underlying mechanisms, the effects of MWCNT on human mesothelial cell MeT-5A were examined throughout 3 months of continuous exposure, including cytotoxicity, genotoxicity, and cell motility. It was found that MWCNT did not affect MeT-5A cell proliferation at 10 μg/cm[2] within 72 h treatment, but under the same condition, MWCNT induced genotoxicity and perturbed cell motility. In addition, MeT-5A cells demonstrated different cellular responses to MWCNT after short-term and long-term exposure. Taken together, our results indicated a possible carcinogenic potential for MWCNT after long-term treatment, in which Annexin family proteins might be involved.}, }
@article {pmid28925565, year = {2017}, author = {Egilman, D}, title = {Response to Hessel.}, journal = {American journal of industrial medicine}, volume = {60}, number = {10}, pages = {915-920}, doi = {10.1002/ajim.22773}, pmid = {28925565}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Australia ; *Automobiles ; Humans ; Industry/*legislation &amp; jurisprudence ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Research Support as Topic/*ethics ; }, }
@article {pmid28915695, year = {2017}, author = {Pouliquen, DL and Nawrocki-Raby, B and Nader, J and Blandin, S and Robard, M and Birembaut, P and Grégoire, M}, title = {Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {34}, pages = {57552-57573}, pmid = {28915695}, issn = {1949-2553}, abstract = {A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration. The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro. Secondly, the potential of intraperitoneal curcumin administration to kill tumor cells in vivo was evaluated in tumor-bearing rats, in comparison with a reference epigenetic drug, SAHA. Both agents administered at days 21 and 26 after tumor challenge produced necrosis within the solid tumors at day 28. However, tumor tissue necrosis induced with curcumin was much more extensive than with SAHA, and was characterized by infiltration with mononuclear phagocytic cells. In contrast, tumor tissue treated with SAHA contained foci of resistant cells and was infiltrated by many isolated CD8+ cells. The treatment of tumor-bearing rats with 1.5 mg/kg curcumin on days 7, 9, 11 and 14 after tumor challenge dramatically reduced the mean total tumor mass at day 16. Clusters of CD8+ T lymphocytes were observed at the periphery of small residual tumor masses in the peritoneal cavity, which presented a significant reduction in mitotic index, IL6 and vimentin expression compared with tumors in untreated rats. These data open up interesting new prospects for the therapy of sarcomatoid mesothelioma with curcumin and its derivatives.}, }
@article {pmid28914691, year = {2017}, author = {Zadnik, V and Primic Zakelj, M and Jarm, K and Zagar, T}, title = {Time trends and spatial patterns in the mesothelioma incidence in Slovenia, 1961-2014.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {26 Joining forces for better cancer registration in Europe}, number = {}, pages = {S191-S196}, doi = {10.1097/CEJ.0000000000000384}, pmid = {28914691}, issn = {1473-5709}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries/*statistics &amp; numerical data ; Slovenia/epidemiology ; Time Factors ; }, abstract = {We aimed to explore the temporal and spatial variations in mesothelioma incidence in Slovenia for the last 50 years and, among these, to evaluate the consequences of asbestos usage. The incidence data from the population-based Cancer Registry of Republic of Slovenia for the period 1961-2014 were analysed. The data of asbestos imported to Slovenia were used as a proxy for asbestos exposure in manufacturing areas. Log-linear joinpoint regression and age-period-cohort Poisson models were used in the time-trend analysis. The mesothelioma maps were produced according to the method of local standardized incidence ratio estimates and are presented together with the map of Slovenian major asbestos-exposed locations. The maximum value of the asbestos import curve corresponds to the peak of mesothelioma curve exactly 30 years later. Both increases before the peak are comparable in time interval and steepness. The highest mesothelioma risk was detected for the cohort born between 1940 and 1944. In maps, the mesothelioma clusters manifest around known asbestos sources predominantly in the years 1980-1990, but in the last few years, the geographical distribution is more dispersed. The data from our long-existing population-based cancer registry provide a good insight into the on-going mesothelioma epidemic in Slovenia. Our results imply that the mesothelioma peak has already been reached in Slovenia. In the future, new cases will emerge more randomly throughout the country.}, }
@article {pmid28913871, year = {2017}, author = {Greenberg, M}, title = {Experimental asbestos studies in the UK: 1912-1950.}, journal = {American journal of industrial medicine}, volume = {60}, number = {11}, pages = {956-962}, doi = {10.1002/ajim.22762}, pmid = {28913871}, issn = {1097-0274}, mesh = {Animals ; Asbestos/*history/toxicity ; Asbestosis/*history ; Biomedical Research/*history/methods ; Carcinogens/*history/toxicity ; Guinea Pigs ; History, 19th Century ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/*history ; *Mining ; Occupational Exposure/adverse effects/*history ; Pulmonary Fibrosis/etiology/history ; Rats ; Schools, Medical/history ; United Kingdom ; }, abstract = {The asbestos industry originated in the UK in the 1870s. By 1898, asbestos had many applications and was reported to be one of the four leading causes of severe occupational disease. In 1912, the UK government sponsored an experimental study that reported that exposure to asbestos produced no more than a modicum of pulmonary fibrosis in guinea pigs. In the 1930s, the newly established Medical Research Council, with assistance from industry, sponsored a study of the effects of exposing animals to asbestos by injection (intratracheal and subcutaneous) and by inhalation in the factory environment. Government reports, publications, and contemporary records obtained by legal discovery have been reviewed in the context of the stage of scientific development and the history of the times. Experimenters were engaged in a learning process during the 1912-1950 period, and their reports of the effects of asbestos were inconsistent. Pathologists who studied the effects of asbestos experimentally, at whole animal, tissue and cellular levels, advanced experimental methodology and mechanistic knowledge. In the hands of public relations experts, however, research was exploited to preserve an industry and perpetuate preventable diseases, a practice that continues to this day.}, }
@article {pmid28910456, year = {2018}, author = {Hung, YP and Dong, F and Watkins, JC and Nardi, V and Bueno, R and Dal Cin, P and Godleski, JJ and Crum, CP and Chirieac, LR}, title = {Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma.}, journal = {JAMA oncology}, volume = {4}, number = {2}, pages = {235-238}, pmid = {28910456}, issn = {2374-2445}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anaplastic Lymphoma Kinase/*genetics/metabolism ; DNA Mutational Analysis/methods ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*genetics/metabolism ; Male ; Mesothelioma/*genetics/metabolism ; Mesothelioma, Malignant ; Middle Aged ; *Mutation ; Oncogene Proteins, Fusion/genetics ; Peritoneal Neoplasms/*genetics/metabolism ; *Translocation, Genetic/genetics ; Young Adult ; }, abstract = {IMPORTANCE: Malignant peritoneal mesothelioma is a rare, aggressive tumor arising from the peritoneal lining, induced by asbestos, therapeutic radiation, or germline mutations. Nevertheless, the molecular features remain largely unknown.<br><br>OBJECTIVE: To investigate anaplastic lymphoma kinase (ALK) rearrangements in a large series of peritoneal mesothelioma and characterize the mutational landscape of these tumors.<br><br>We studied 88 consecutive patients (39 men, 49 women; median age 61, range 17-84 years) with peritoneal mesotheliomas diagnosed at a single institution between 2005 and 2015. We identified ALK-positive mesotheliomas by immunohistochemistry and confirmed ALK rearrangement by fluorescence in situ hybridization (FISH). In ALK-rearranged cases, we characterized the fusion partners using targeted next-generation sequencing of both tumor DNA and RNA. In select cases, we quantified asbestos fibers by combined scanning electron microscopy and x-ray spectroscopy. We also explored ALK rearrangement in a separate series of 205 patients with pleural mesothelioma.<br><br>MAIN OUTCOMES AND MEASURES: Identification and characterization of novel ALK rearrangements and correlations with clinicopathologic characteristics.<br><br>RESULTS: Anaplastic lymphoma kinase was positive by immunohistochemistry in 11 (13%) peritoneal mesotheliomas (focal weak in 8, diffuse strong in 3). In focal weak ALK-positive cases, no ALK rearrangement was detected by FISH or next-generation sequencing. In strong diffuse ALK-positive cases, FISH confirmed ALK rearrangements, and next-generation sequencing identified novel fusion partners ATG16L1, STRN, and TPM1. Patients with ALK-rearranged peritoneal mesotheliomas were women and younger than patients without ALK rearrangement (median age 36 vs 62; Mann-Whitney test, P&#x2009;=&#x2009;.02), but all other clinicopathologic characteristics (size of tumor nodules, histology, treatment, and survival) were not different. No asbestos fibers were detected in ALK-rearranged cases. Furthermore, loss of chromosomal region 9p or 22q or genetic alterations in BAP1, SETD2, or NF2 typically present in peritoneal mesothelioma were absent in the ALK-rearranged cases. All pleural mesotheliomas were ALK-negative by immunohistochemistry.<br><br>CONCLUSIONS AND RELEVANCE: We identified unique ALK rearrangements in a subset of patients with peritoneal mesothelioma, each lacking asbestos fibers, therapeutic radiation, and cytogenetic and molecular alterations typically found in these tumors. Identification of clinically actionable ALK rearrangements may represent a novel pathogenetic mechanism of malignant peritoneal mesothelioma with promise for targeted therapy.}, }
@article {pmid28884745, year = {2018}, author = {Vivero, M and Bueno, R and Chirieac, LR}, title = {Clinicopathologic and genetic characteristics of young patients with pleural diffuse malignant mesothelioma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {31}, number = {1}, pages = {122-131}, pmid = {28884745}, issn = {1530-0285}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/genetics ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/genetics/mortality/*pathology ; Male ; Mesothelioma/genetics/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/genetics/mortality/*pathology ; Proportional Hazards Models ; Young Adult ; }, abstract = {Pleural diffuse malignant mesothelioma typically presents during the seventh decade of life and has poor prognosis. Recent epidemiologic studies have shown differences between young and older mesothelioma patients, but the biology of pleural mesothelioma in young patients is poorly understood. We studied the clinicopathologic and genetic characteristics in pleural mesothelioma patients aged 35 years and younger. Thirty-six consecutive pleural mesothelioma patients aged 35 years and younger were compared with 48 older patients. We examined demographic and clinical characteristics, histologic type, growth patterns, mitotic index, and nuclear grade on hematoxylin and eosin-stained slides, BAP1 protein expression by immunohistochemistry, and CDKN2A and NF2 deletions by fluorescence in situ hybridization. Clinicopathologic and cytogenetic results were compared between young and older groups, and correlated with overall survival. Young patients were more frequently women, reported less asbestos exposure, and had a greater frequency of prior therapeutic radiation and family history of breast cancer than older patients (P<0.05 each). There were no histologic differences between young and older patients (all P>0.05). CDKN2A deletion was less prevalent in young patients (P=0.01), loss of BAP1 protein expression less frequent in young patients (P=0.06), and NF2 deletion rates similar between groups (P>0.05 each). Median overall survival was 40 vs 26 months (P=0.10) in young and older patients, respectively, and 47 vs 31 months (P=0.04) when comparing patients with epithelioid histology only. High mitotic index and non-epithelioid histology were the only characteristics associated with a poor overall survival in young patients. Young patients with pleural mesothelioma have an equal sex distribution and are more likely to have a history of mantle radiation, family history of breast cancer, and lower rates of CDKN2A deletion than older patients. Our results suggest that pleural mesothelioma in young patients has distinctive clinical and genetic characteristics, despite some similarities to pleural mesothelioma in older patients.}, }
@article {pmid28881848, year = {2017}, author = {Lagniau, S and Lamote, K and van Meerbeeck, JP and Vermaelen, KY}, title = {Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moonshot?.}, journal = {Oncotarget}, volume = {8}, number = {32}, pages = {53751-53762}, pmid = {28881848}, issn = {1949-2553}, abstract = {Early diagnosis of malignant pleural mesothelioma (MPM) is a challenge for clinicians. The disease is usually detected in an advanced stage which precludes curative treatment. We assume that only new and non-invasive biomarkers allowing earlier detection will result in better patient management and outcome. Many efforts have already been made to find suitable biomarkers in blood and pleural effusions, but have not yet resulted in a valid and reproducible diagnostic one. In this review, we will highlight the strengths and shortcomings of blood and fluid based biomarkers and highlight the potential of breath analysis as a non-invasive screening tool for MPM. This method seems very promising in the early detection of diverse malignancies, because exhaled breath contains valuable information on cell and tissue metabolism. Research that focuses on breath biomarkers in MPM is in its early days, but the few studies that have been performed show promising results. We believe a breathomics-based biomarker approach should be further explored to improve the follow-up and management of asbestos exposed individuals.}, }
@article {pmid28870611, year = {2017}, author = {van Zandwijk, N and Pavlakis, N and Kao, SC and Linton, A and Boyer, MJ and Clarke, S and Huynh, Y and Chrzanowska, A and Fulham, MJ and Bailey, DL and Cooper, WA and Kritharides, L and Ridley, L and Pattison, ST and MacDiarmid, J and Brahmbhatt, H and Reid, G}, title = {Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study.}, journal = {The Lancet. Oncology}, volume = {18}, number = {10}, pages = {1386-1396}, doi = {10.1016/S1470-2045(17)30621-6}, pmid = {28870611}, issn = {1474-5488}, mesh = {Adult ; Aged ; Australia ; Biopsy, Needle ; Cancer Care Facilities ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Infusions, Intravenous ; Kaplan-Meier Estimate ; Lung Neoplasms/diagnostic imaging/*drug therapy/mortality/pathology ; Male ; Maximum Tolerated Dose ; Mesothelioma/diagnostic imaging/*drug therapy/mortality/pathology ; Mesothelioma, Malignant ; MicroRNAs/*administration &amp; dosage ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/mortality/pathology ; *Patient Safety ; Patient Selection ; Pleural Neoplasms/diagnostic imaging/*drug therapy/mortality/pathology ; Positron Emission Tomography Computed Tomography/methods ; Risk Assessment ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma.<br><br>METHODS: In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged &#x2265;18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function. Patients were given TargomiRs via 20 min intravenous infusion either once or twice a week (3 days apart) in a traditional 3&#x2008;+&#x2008;3 dose-escalation design in five dose cohorts. The dose-escalation steps planned were 5&#x2008;&#xd7;&#x2008;10[9], 7&#x2008;&#xd7;&#x2008;10[9], and 9&#x2008;&#xd7;&#x2008;10[9] TargomiRs either once or twice weekly, but after analysis of data from the first eight patients, all subsequent patients started protocol treatment at 1&#x2008;&#xd7;&#x2008;10[9] TargomiRs. The primary endpoints were to establish the maximum tolerated dose of TargomiRs as measured by dose-limiting toxicity, define the optimal frequency of administration, and objective response (defined as the percentage of assessable patients with a complete or partial response), duration of response (defined as time from the first evidence of response to disease progression in patients who achieved a response), time to response (ie, time from start of treatment to the first evidence of response) and overall survival (defined as time from treatment allocation to death from any cause). Analyses were based on the full analysis set principle, including every patient who received at least one dose of TargomiRs. The study was closed for patient entry on Jan 3, 2017, and registered with ClinicalTrials.gov, number NCT02369198, and the Australian Registry of Clinical Trials, number ACTRN12614001248651.<br><br>FINDINGS: Between Sept 29, 2014, and Nov 24, 2016, we enrolled 27 patients, 26 of whom received at least one TargomiR dose (one patient died before beginning treatment). Overall, five dose-limiting toxicities were noted: infusion-related inflammatory symptoms and coronary ischaemia, respectively, in two patients given 5&#x2008;&#xd7;&#x2008;10[9] TargomiRs twice weekly; anaphylaxis and cardiomyopathy, respectively, in two patients given 5&#x2008;&#xd7;&#x2008;10[9] TargomiRs once weekly but who received reduced dexamethasone prophylaxis; and non-cardiac pain in one patient who received 5&#x2008;&#xd7;&#x2008;10[9] TargomiRs once weekly. We established that 5&#x2008;&#xd7;&#x2008;10[9] TargomiRs once weekly was the maximum tolerated dose. TargomiR infusions were accompanied by transient lymphopenia (25 [96%] of 26 patients), temporal hypophosphataemia (17 [65%] of 26 patients), increased aspartate aminotransferase or alanine aminotranferase (six [23%] of 26 patients), and increased alkaline phosphatase blood concentrations (two [8%]). Cardiac events occurred in five patients: three patients had electrocardiographic changes, one patient had ischaemia, and one patient had Takotsubo cardiomyopathy. Of the 22 patients who were assessed for response by CT, one (5%) had a partial response, 15 (68%) had stable disease, and six (27%) had progressive disease. The proportion of patients who achieved an objective response was therefore one (5%) of 22, and the duration of the objective response in that patient was 32 weeks. Median overall survival was 200 days (95% CI 94-358). During the trial, 21 deaths occurred, of which 20 were related to tumour progression and one was due to bowel perforation.<br><br>INTERPRETATION: The acceptable safety profile and early signs of activity of TargomiRs in patients with malignant pleural mesothelioma support additional studies of TargomiRs in combination with chemotherapy or immune checkpoint inhibitors.<br><br>FUNDING: Asbestos Diseases Research Foundation.}, }
@article {pmid28866609, year = {2017}, author = {Odgerel, CO and Takahashi, K and Sorahan, T and Driscoll, T and Fitzmaurice, C and Yoko-O, M and Sawanyawisuth, K and Furuya, S and Tanaka, F and Horie, S and Zandwijk, NV and Takala, J}, title = {Estimation of the global burden of mesothelioma deaths from incomplete national mortality data.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {851-858}, pmid = {28866609}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; Databases, Factual ; Environmental Exposure/*adverse effects ; Female ; *Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; World Health Organization ; }, abstract = {BACKGROUND: Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted.<br><br>OBJECTIVES: To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths.<br><br>METHODS: For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries.<br><br>RESULTS: The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15&#x2009;011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38&#x2009;400 per year, based on extrapolations for asbestos use.<br><br>CONCLUSIONS: Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values.}, }
@article {pmid28863229, year = {2018}, author = {Glynn, ME and Keeton, KA and Gaffney, SH and Sahmel, J}, title = {Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence between Urban and Rural Areas in the United States (1973-2012).}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {3}, pages = {454-471}, doi = {10.1111/risa.12887}, pmid = {28863229}, issn = {1539-6924}, mesh = {Age Factors ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced/*epidemiology ; Registries ; Rural Population ; SEER Program ; Sex Factors ; United States ; Urban Population ; }, abstract = {Over the past 40 years, measured ambient asbestos concentrations in the United States have been higher in urban versus rural areas. The purpose of this study was to determine whether variations in ambient asbestos concentrations have influenced pleural mesothelioma risk in females (who generally lacked historic occupational asbestos exposure relative to males). Male pleural mesothelioma incidence trends were analyzed to provide perspective for female trends. Annual age-adjusted incidence rates from 1973 to 2012 were obtained from the SEER 9, 13, and 18 databases for urban and rural locations, and standardized rate ratios were calculated. Female rural rates exceeded urban rates in almost half of the years analyzed, although the increases were not statistically significant, which is in line with expectations if there was no observable increased risk for urban locations. In contrast, male urban rates were elevated over rural rates for nearly all years examined and were statistically significantly elevated for 22 of the 40 years. Trend analyses demonstrated that trends for females remained relatively constant over time, whereas male urban and rural incidence increased into the 1980s and 1990s, followed by a decrease/leveling off. Annual female urban and rural incidence rates remained approximately five- to six-fold lower than male urban and rural incidence rates on average, consistent with the comparatively increased historical occupational asbestos exposure for males. The results suggest that differences in ambient asbestos concentrations, which have been reported to be 10-fold or greater across regions in the United States, have not influenced the risk of pleural mesothelioma.}, }
@article {pmid28855951, year = {2017}, author = {Eisenhawer, C and Felten, MK and Hager, T and Gronostayskiy, M and Bruners, P and Tannapfel, A and Kraus, T}, title = {Migrating pleural plaque in a patient with asbestos induced pleural disease: a case report.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {12}, number = {}, pages = {25}, pmid = {28855951}, issn = {1745-6673}, abstract = {BACKGROUND: Health surveillance of formerly asbestos exposed individuals focus on early detection of asbestos related diseases, such as lung fibrosis (asbestosis), pleural plaques, mesothelioma and lung cancer in particular. One main concern is the early and clear identification of lesions with a high risk of malignant changes and their undelayed clinical work-up. False positive results may lead to unnecessary and often painful diagnostic interventions, which create high costs when applied to a large cohort and also may discredit the whole program. We describe an unusual presentation of a common lesion among asbestos exposed individuals, which has to our knowledge never been described before. Being aware of this pathological pathway may prevent inadequate clinical decisions with disadvantages for the patient. Underlying implications regarding health surveillance and the reading of CT-scans of the thorax are important for the management of formerly asbestos exposed individuals.<br><br>CASE PRESENTATION: During follow-up of an asbestos exposed 72&#xa0;year old former power plant worker with known pleural changes, a nodule located next to the left costophrenic angle was newly discovered on CT-scan. As the previous scan 1 year before did not show any changes in that area, a fast growing tumour was suspected and an immediate biopsy performed. The tissue showed the characteristics of a pleural plaque with no signs of malignancy. After carefully reviewing all previous radiographs a rounded opacity attached to the mediastinal pleura close to the oesophagus and slightly cranial to the position of the removed nodule could be discerned. That nodule had increased in size over several years and was no longer visible on the latest scan. It appeared that the originally slow growing plaque had migrated to the costophrenic angle some time before it was discovered in the latest scan thus imposing as a fast growing tumour.<br><br>CONCLUSIONS: We concluded that asbestos related pleural plaques can under special circumstances get separated from the pleura and migrate to another position in the pleural cavity. The case provides new insights in the development and properties of pleural lesions and may offer new options for the management of formerly asbestos exposed patients.}, }
@article {pmid28852644, year = {2017}, author = {Ndlovu, N and Rees, D and Murray, J and Vorajee, N and Richards, G and teWaterNaude, J}, title = {Asbestos-related diseases in mineworkers: a clinicopathological study.}, journal = {ERJ open research}, volume = {3}, number = {3}, pages = {}, pmid = {28852644}, issn = {2312-0541}, support = {D43 ES018744/ES/NIEHS NIH HHS/United States ; }, abstract = {The accurate diagnosis of asbestos-related diseases is important because of past and current asbestos exposures. This study evaluated the reliability of clinical diagnoses of asbestos-related diseases in former mineworkers using autopsies as the reference standard. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. The 149 cases identified had clinical examinations 0.3-7.4 years before death. More asbestos-related diseases were diagnosed at autopsy rather than clinically: 77 versus 52 for asbestosis, 27 versus 14 for mesothelioma and 22 versus 3 for lung cancer. Sensitivity and specificity values for clinical diagnoses were 50.6% and 81.9% for asbestosis, 40.7% and 97.5% for mesothelioma, and 13.6% and 100.0% for lung cancer. False-negative diagnoses of asbestosis were more likely using radiographs of acceptable (versus good) quality and in cases with pulmonary tuberculosis at autopsy. The low sensitivity values are indicative of the high proportion of false-negative diagnoses. It is unlikely that these were the result of disease manifestation between the last clinical assessment and autopsy. Where clinical features suggest asbestos-related diseases but the chest radiograph is negative, more sophisticated imaging techniques or immunohistochemistry for asbestos-related cancers should be used. Autopsies are useful for the detection of previously undiagnosed and misdiagnosed asbestos-related diseases, and for monitoring clinical practice and delivery of compensation.}, }
@article {pmid28845826, year = {2017}, author = {Cardinale, L and Ardissone, F and Gned, D and Sverzellati, N and Piacibello, E and Veltri, A}, title = {Diagnostic Imaging and workup of Malignant Pleural Mesothelioma.}, journal = {Acta bio-medica : Atenei Parmensis}, volume = {88}, number = {2}, pages = {134-142}, pmid = {28845826}, issn = {2531-6745}, mesh = {Humans ; Lung Neoplasms/*diagnostic imaging ; Magnetic Resonance Imaging ; Mesothelioma/*diagnostic imaging ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnostic imaging ; Positron Emission Tomography Computed Tomography ; Radiography, Thoracic ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Malignant pleural mesothelioma is the most frequent primary neoplasm of the pleura and its incidence is still increasing.This tumor has a strong association with exposure to occupational or environmental asbestos, often after a long latent period of 30-40 years.Plain chest radiography (CXR) is usually the first-line radiologic examination, but the radiographic findings are nonspecific due to its limited contrast resolution and they need to be complemented by other imaging modalities such as computed tomography (CT), magnetic resonance Imaging (MRI), Positron emission tomography-computed tomography (PET-CT) and ultrasound (US).The aim of this paper is to describe the imaging features of this malignancy, underlining the peculiarity of CXR, CT, MRI, PET-CT and US and also focusing on diagnostic workup, based on the literature evidence and according to our experience.}, }
@article {pmid28838403, year = {2017}, author = {Lau, B and Kumar, S and Yan, T and Burn, J and Kennedy, C and McLean, J and Boyer, M and McCaughan, B and Kao, S}, title = {Pathological complete response in malignant pleural mesothelioma patients following induction chemotherapy: Predictive factors and outcomes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {111}, number = {}, pages = {75-78}, doi = {10.1016/j.lungcan.2017.07.010}, pmid = {28838403}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Induction Chemotherapy ; Kaplan-Meier Estimate ; Lung Neoplasms/*drug therapy/mortality/*pathology ; Male ; Mesothelioma/*drug therapy/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/mortality/*pathology ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {A small proportion of patients with malignant pleural mesothelioma (MPM) achieve pathological complete response (CR) following treatment with current practice induction chemotherapy. Our analysis of 58 patients with MPM treated with platinum-based chemotherapy showed 4 patients (7%) attained pathological CR at subsequent extrapleural pneumonectomy (EPP). Patient and tumour factors such as age, gender, smoking habit, histological subtype, and clinical stage were not found to be associated with pathological CR. Patients with pathological CR had longer disease-free survival (29.2 vs. 13.8 months; p=0.08) and overall survival (76.4 vs. 23.4 months; p=0.06) but this did not reach statistical significance. Our study suggests that patients who achieve pathological CR after chemotherapy may have improved survival in MPM.}, }
@article {pmid28838385, year = {2017}, author = {Scarlata, S and Finamore, P and Giannunzio, G and Santangelo, S and Antonelli Incalzi, R}, title = {Chest ultrasonography in health surveillance of asbestos related pleural disease.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {111}, number = {}, pages = {139-142}, doi = {10.1016/j.lungcan.2017.07.019}, pmid = {28838385}, issn = {1872-8332}, mesh = {Adult ; Asbestos/*adverse effects ; Carcinogens ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Diseases/*diagnosis/epidemiology/*etiology ; *Public Health Surveillance ; Time Factors ; Tomography, X-Ray Computed ; *Ultrasonography ; }, abstract = {High resolution computed tomography, (HRCT), is currently considered the diagnostic gold standard to diagnose early stage malignant pleural mesothelioma and other non-malignant pleural conditions, but it is expensive and exposes the patient to radiation dose. In a screening and population medicine perspective, Thoracic Ultrasounds may become a valuable alternative because it can detect minimal changes in pleural surface, is widely available and safe. On these bases, we therefore validated thoracic US in subjects with history of exposure to asbestos, having HRCT as the reference standard. One hundred-fifty subjects were screened and 117 were recruited. Pleural abnormalities at US and/or HRCT were detected in 66 out of 117 subjects (prevalence=57%), and their prevalence was unrelated to both mansion and smoking habit, while mean age and mean length of exposure were higher in those having pleural abnormalities (age=47±5 vs 44±6years, p<0.05;years of exposure=20±7 vs 17±5, p<0.05). Thirteen out of 19 subjects with pleural abnormalities at HRCT were also identified by thoracic US, whereas 47 participants had lesions seen at US, but not at the HRCT scan. Positive and negative percent agreement were 66.6% and 51.8%, respectively; the McNemar's test for equality showed a p-value <0.001. In conclusion, chest US might complement HRCT in the health surveillance of asbestos exposed population to detect earlier lesions or to follow up US approachable lesions. Further research is needed to clarify whether this approach may enhance early recognition of pleural mesothelioma and ameliorate prognosis.}, }
@article {pmid28833303, year = {2017}, author = {Oddone, E and Ferrante, D and Tunesi, S and Magnani, C}, title = {Mortality in asbestos cement workers in Pavia, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {60}, number = {10}, pages = {852-866}, doi = {10.1002/ajim.22750}, pmid = {28833303}, issn = {1097-0274}, mesh = {Adult ; Asbestos/adverse effects ; Asbestosis/*mortality ; Cohort Studies ; Construction Industry/*statistics &amp; numerical data ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; }, abstract = {BACKGROUND: The aim of this study was to describe the mortality of a cohort of asbestos-cement workers in the largest plant in the most industrialized Italian region (Lombardy).<br><br>METHODS: A cohort study was carried out on 1818 subjects, corresponding to 47&#x2009;536.1 person-years of observation. Standardized mortality ratios (SMRs) were computed for the major causes of death.<br><br>RESULTS: Increased SMRs were observed for pleural, peritoneal and lung cancers, and for asbestosis (SMR 26.73, 95% Confidence Interval (CI) 20.99-33.55; 9.15, 95%CI 5.00-15.34; 1.48, 95%CI 1.27-1.72; and 368.05, 95%CI 214.40-589.29, respectively). No excess in mortality for laryngeal cancer was observed (SMR 0.70, 95%CI 0.30-1.39). An increased mortality for ovarian cancer (SMR 3.64, 95%CI 0.99-9.33) was observed, although it was not statistically significant. Among men, mortality for pleural malignant mesothelioma was observed to be related to the duration of exposure, though not to latency.<br><br>CONCLUSIONS: The results of this study are generally consistent with present knowledge. Conversely, our results do not support the hypothesis that pleural malignant mesothelioma risk indefinitely increases after exposure, suggesting instead that the alternative hypothesis of a risk plateau or decrease after a time since first exposure of more than 40 years is more consistent with the observed data.}, }
@article {pmid28829357, year = {2017}, author = {Serio, G and Pezzuto, F and Marzullo, A and Scattone, A and Cavone, D and Punzi, A and Fortarezza, F and Gentile, M and Buonadonna, AL and Barbareschi, M and Vimercati, L}, title = {Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array.}, journal = {International journal of molecular sciences}, volume = {18}, number = {8}, pages = {}, pmid = {28829357}, issn = {1422-0067}, mesh = {Adult ; Asbestos/*adverse effects ; Biopsy ; Comparative Genomic Hybridization ; *Environmental Exposure ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*etiology ; Male ; Mesothelioma/*diagnosis/*etiology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnosis/*etiology ; }, abstract = {UNLABELLED: Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment which included cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).<br><br>METHODS AND RESULTS: Molecular analysis with comparative genomic hybridization (CGH)-array was performed on paraffin-embedded tumoral samples. Multiple chromosomal imbalances were detected. The gains were prevalent. Losses at 1q21, 2q11.1&#x2192;q13, 8p23.1, 9p12&#x2192;p11, 9q21.33&#x2192;q33.1, 9q12&#x2192;q21.33, and 17p12&#x2192;p11.2 are observed. Chromosome band 3p21 (BAP1), 9p21 (CDKN2A) and 22q12 (NF2) are not affected. Conclusions: the defects observed in this case are uncommon in malignant peritoneal mesothelioma. Some chromosomal aberrations that appear to be random here, might actually be relevant events explaining the response to therapy, the long survival and, finally, may be considered useful prognostic factors in peritoneal malignant mesothelioma (PMM).}, }
@article {pmid28827980, year = {2017}, author = {Khmou, M and Echcharif, S and Kabbaj, R and Khannoussi, BE}, title = {Malignant Deciduoid Mesothelioma: case presentation of an exceptional variant and review of the literature.}, journal = {BMC clinical pathology}, volume = {17}, number = {}, pages = {13}, pmid = {28827980}, issn = {1472-6890}, abstract = {BACKGROUND: Malignant Deciduoid Mesothelioma (MDM) is an extremely rare variant of epithelioid mesothelioma. It was first described in young females, in the peritoneum, and its relation with asbestos was not well defined. Later reports, have shown that this variant may also occur in the pleura, the pericardium and the tunica vaginalis of elderly people, who had been exposed to asbestos.<br><br>CASE PRESENTATION: We report a case of malignant deciduoid mesothelioma that occurred in the peritoneal cavity, and the omentum of a 35-year-old woman. The patient had never been exposed to asbestos.<br><br>CONCLUSIONS: Through this observation, we describe clinical, histopathological, and immunohistochemical findings of deciduoid mesothelioma, and review the literature reports.}, }
@article {pmid28823988, year = {2018}, author = {Boffetta, P and Pira, E and Romano, C and Violante, FS and Farioli, A and Zocchetti, C and La Vecchia, C}, title = {Response to: 'Dose-time-response association between occupational asbestos exposure and pleural mesothelioma' by Lacourt et al.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {2}, pages = {160}, doi = {10.1136/oemed-2017-104570}, pmid = {28823988}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, }
@article {pmid28823918, year = {2017}, author = {Hattori, K and Nakadate, K and Morii, A and Noguchi, T and Ogasawara, Y and Ishii, K}, title = {Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity.}, journal = {Biochemical and biophysical research communications}, volume = {492}, number = {2}, pages = {218-223}, doi = {10.1016/j.bbrc.2017.08.054}, pmid = {28823918}, issn = {1090-2104}, mesh = {Cell Line ; Crystallization ; DNA Damage/*drug effects ; Epithelial Cells/cytology/*drug effects/metabolism/pathology ; Humans ; Nanostructures/*toxicity ; Oxidative Stress/*drug effects ; Particle Size ; Pleura/cytology/drug effects/metabolism/pathology ; Reactive Oxygen Species/metabolism ; Titanium/*toxicity ; }, abstract = {Exposure to nanoparticles such as carbon nanotubes has been shown to cause pleural mesothelioma similar to that caused by asbestos, and has become an environmental health issue. Not only is the percutaneous absorption of nano-size titanium dioxide particles frequently considered problematic, but the possibility of absorption into the body through the pulmonary route is also a concern. Nevertheless, there are few reports of nano-size titanium dioxide particles on respiratory organ exposure and dynamics or on the mechanism of toxicity. In this study, we focused on the morphology as well as the size of titanium dioxide particles. In comparing the effects between nano-size anatase and rutile titanium dioxide on human-derived pleural mesothelial cells, the anatase form was shown to be actively absorbed into cells, producing reactive oxygen species and causing oxidative damage to DNA. In contrast, we showed for the first time that the rutile form is not easily absorbed by cells and, therefore, does not cause oxidative DNA damage and is significantly less damaging to cells. These results suggest that with respect to the toxicity of titanium dioxide particles on human-derived mesothelial cells, the crystal form rather than the particle size has a greater effect on cellular absorption. Also, it was indicated that the difference in absorption is the primary cause of the difference in the toxicity against mesothelial cells.}, }
@article {pmid28817672, year = {2017}, author = {Kwak, KM and Paek, D and Hwang, SS and Ju, YS}, title = {Estimated future incidence of malignant mesothelioma in South Korea: Projection from 2014 to 2033.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0183404}, pmid = {28817672}, issn = {1932-6203}, mesh = {History, 21st Century ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Registries ; Republic of Korea/epidemiology ; }, abstract = {Malignant mesothelioma is a malignant tumor on the pleura or the peritoneum caused mostly by asbestos. Although asbestos is not currently used in South Korea, the incidence of mesothelioma is increasing due to its long latent period. This study predicted the incidence of malignant mesothelioma in South Korea over the next 20 years using an age-period-cohort (APC) model. Data regarding mesothelioma incidence from 1994-2013 were acquired from the Korea Central Cancer Registry (KCCR). Demographic data, including prospective resident data, were acquired from the Korean Statistical Information Service (KOSIS) for 1994-2033. An APC model with Møller's power-link function was utilized to predict the incidence of mesothelioma. It was predicted that 2,380 and 1,199 new cases of mesothelioma in men and women, respectively, would occur over the next 20 years. For both sexes, the mesothelioma incidence rate was predicted to be greater in 2029-2033 compared to that in 2009-2013 (men, 0.282 vs 0.563; women, 0.155 vs 0.217). For men, the age-standardized incidence rate was predicted to be slightly greater in 2029-2033 relative to the rate in 2009-2013 (0.228 vs 0.235), while the age-standardized incidence rate in women decreased within the same timeframe (0.113 vs 0.109). The changes in mesothelioma incidence were mostly caused by changes in the population structure due to aging and not by changes in the mesothelioma risk ratio. The results of this study project a continuous increase in mesothelioma incidence in South Korea over the next 20 years. Although the projected increase in mesothelioma incidence was not related to an increase in the mesothelioma risk ratio, continuous preventive efforts are necessary to reduce the exposure to asbestos and prevent the trend from worsening.}, }
@article {pmid28810297, year = {2017}, author = {Wei, MC and Yang, SJ}, title = {[Clinical and pathologic features of extrapleural sarcomatoid mesothelioma].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {46}, number = {8}, pages = {559-564}, doi = {10.3760/cma.j.issn.0529-5807.2017.08.008}, pmid = {28810297}, issn = {0529-5807}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/*pathology ; Calbindin 2/analysis ; Diagnosis, Differential ; Female ; Fibrosarcoma/pathology ; Head and Neck Neoplasms/chemistry/*pathology ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Mesothelioma/chemistry/diagnosis/*pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Peritoneal Neoplasms/chemistry/*pathology ; Prognosis ; Sarcoma/pathology ; Vimentin/analysis ; }, abstract = {Objective: To investigate the morphological features, diagnosis and differential diagnosis of extrapleural sarcomatoid malignant mesothelioma (SMM). Methods: Six cases of extrapleural SMM were evaluated for their clinical, histological, immunohistochemical features, and prognosis. Results: Patients included 3 men and 3 women, with a median age of 60 years (range 41-75 years). All patients had no asbestos exposure in history and no pleural lesions. The tumors involved peritoneum (3 cases), bone (2 cases), and neck soft tissue (1 case). Histologically, the tumors were mainly composed of slender to plump spindle cells with occasional polymorphic cells, arranged in fascicular to storiform pattern or haphazardly organized, closely resembling those of fibromatosis, fibrosarcoma or malignant fibrous histiocytoma. The tumor cells were imunohistochemically positive for cytokeratin (pan, 6/6), calretinin (5/6), podoplanin (6/6), D2-40 (4/6), vimentin (6/6), WT1 (4/6), CD10 (3/6), SMA (4/6), and variably positive for CK7, and CK8/18, but were negative for other linage-specific markers. The Ki-67 proliferation indexes ranged from 25% to 55%, consistent with the diagnosis of malignant mesothelioma of the sarcomatous type. Ultrastructurally, the tumor cells possessed discontinuous external lamina, cytoplasmic processes, microfilaments and desmosomal intercellular junctions. Local recurrence or metastasis was seen in 1 case and 4 cases, respectively, after surgery, and all the patients died of the disease within 9 months. Conclusions: Extrapleural SMM, although rare, should be considered as a differential diagnosis among other benign or malignant sarcomatoid tumors and sarcomas. Along with clinical and radiological presentation, the combination of broad-spectrum cytokeratin, vimentin, and a series of mesothelial markers are useful for diagnosis of SMM.}, }
@article {pmid28791466, year = {2017}, author = {Velasco-García, MI and Cruz, MJ and Diego, C and Montero, MA and Álvarez-Simón, D and Ferrer, J}, title = {First Identification of Pulmonary Asbestos Fibres in a Spanish Population.}, journal = {Lung}, volume = {195}, number = {5}, pages = {671-677}, pmid = {28791466}, issn = {1432-1750}, support = {Fis PI07/90478//Instituto de Salud Carlos III/ ; CP12/03101//Instituto de Salud Carlos III/ ; }, mesh = {Aged ; Aged, 80 and over ; *Asbestos, Amphibole ; Asbestosis/*pathology ; Case-Control Studies ; Female ; Humans ; *Lung ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers ; *Occupational Exposure ; Pleural Neoplasms/*pathology ; Spain ; Spectrometry, X-Ray Emission ; }, abstract = {INTRODUCTION: This study aimed to characterize, for the first time in Spain, the type of asbestos fibres (AF) in the lungs of exposed and non-exposed populations.<br><br>MATERIALS AND METHODS: Lung samples from 38 subjects living in Barcelona and Ferrol, Spain, were studied, which were divided into three groups: Group A-five subjects without known respiratory disease; Group B-20 ex-shipyard workers and Group C-13 patients with lung cancer. After eliminating the organic material, the inorganic residue was analysed using electronic microscopy (EM). To identify the type of fibre, the samples were analysed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX).<br><br>RESULTS: All the fibres identified corresponded to amphiboles (crocidolite 45%, anthophyllite 22%, tremolite 16%, amosite 15% and actinolite 3%). In 14 patients (37%), a single type of asbestos was found in the lungs (amosite in two, actinolite in one, anthophyllite in four, crocidolite in five and tremolite in two). Forty-six percent of the AF analysed had a length&#xa0;>&#xa0;5&#xa0;&#xb5;m and a diameter&#xa0;<&#xa0;0.2&#xa0;&#xb5;m.<br><br>CONCLUSIONS: The results of this study provide the first data on the type of asbestos retained in the lung of Spanish population. A particularly striking finding is the exclusive retention of amphiboles, which suggests that chrysotile is eliminated after inhalation. Our findings support estimations considering Spain and other southern European countries with similar asbestos imports and consumption at a high risk to develop asbestos-related diseases in the years to come.}, }
@article {pmid28791219, year = {2017}, author = {Shaikh, AA and Naik, KV and Shetty, SN and Ansari, NN and Babhale, PS}, title = {Bilateral Malignant Mesothelioma of Tunica Vaginalis A Case Report on Rare Presentation.}, journal = {Urology case reports}, volume = {14}, number = {}, pages = {53-55}, pmid = {28791219}, issn = {2214-4420}, abstract = {Malignant mesothelioma involving the para-testicular tunica is extremely rare and an aggressive tumor. Bilateral malignant mesothelioma of the tunica vaginalis is not reported previously in the literature. Rarity of the disease, absence of any specific clinical and radiological findings makes the preoperative diagnosis difficult. Aggressive surgical approach is the key to successful management with high inguinal orchiectomy and scrotectomy appears to be optimal treatment in patients with localized disease.}, }
@article {pmid28777435, year = {2018}, author = {Muscella, A and Cossa, LG and Vetrugno, C and Antonaci, G and Marsigliante, S}, title = {Inhibition of ZL55 cell proliferation by ADP via PKC-dependent signalling pathway.}, journal = {Journal of cellular physiology}, volume = {233}, number = {3}, pages = {2526-2536}, doi = {10.1002/jcp.26128}, pmid = {28777435}, issn = {1097-4652}, mesh = {Adenosine Diphosphate/analogs &amp; derivatives/*pharmacology ; Antineoplastic Agents/*pharmacology ; Asbestos/adverse effects ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Dose-Response Relationship, Drug ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mesothelioma/*drug therapy/enzymology/genetics/pathology ; Phosphorylation ; Protein Kinase C-alpha/genetics/*metabolism ; Protein Kinase C-delta/genetics/*metabolism ; Protein Stability ; Purinergic P2Y Receptor Agonists/*pharmacology ; RNA Interference ; Receptors, Purinergic P2Y1/*drug effects/metabolism ; Signal Transduction/*drug effects ; Thionucleotides/pharmacology ; Time Factors ; Transfection ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Extracellular nucleotides can regulate cell proliferation in both normal and tumorigenic tissues. Here, we studied how extracellular nucleotides regulate the proliferation of ZL55 cells, a mesothelioma-derived cell line obtained from bioptic samples of asbestos-exposed patients. ADP and 2-MeS-ADP inhibited ZL55 cell proliferation, whereas ATP, UTP, and UDP were inactive. The nucleotide potency profile and the blockade of the ADP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 suggest that P2Y1 receptor controls ZL55 cell proliferation. The activation of P2Y1 receptor by ADP leads to activation of intracellular transduction pathways involving [Ca[2+] ]i , PKC-δ/PKC-α, and MAPKs, ERK1/2 and JNK1/2. Cell treatment with ADP or 2-MeS-ADP also provokes the activation of p53, causing an accumulation of the G1 cyclin-dependent kinase inhibitors p21[WAF1] and p27[Kip] . Inhibition of ZL55 cell proliferation by ADP was completely reversed by inhibiting MEK1/2, or JNK1/2, or PKC-δ, and PKC-α. Through the inhibition of ADP-activated transductional kinases it was found that PKC-δ was responsible for JNK1/2 activation. JNK1/2 has a role in transcriptional up-regulation of p53, p21[WAF1/CIP1] , and p27[kip1] . Conversely, the ADP-activated PKC-α provoked ERK1/2 phosphorylation. ERK1/2 increased p53 stabilization, required to G1 arrest of ZL55 cells. Concluding, the importance of the study is twofold: first, results shed light on the mechanism of cell cycle inhibition by ADP; second, results suggest that extracellular ADP may inhibit mesothelioma progression.}, }
@article {pmid28775133, year = {2017}, author = {Ferrante, D and Chellini, E and Merler, E and Pavone, V and Silvestri, S and Miligi, L and Gorini, G and Bressan, V and Girardi, P and Ancona, L and Romeo, E and Luberto, F and Sala, O and Scarnato, C and Menegozzo, S and Oddone, E and Tunesi, S and Perticaroli, P and Pettinari, A and Cuccaro, F and Mattioli, S and Baldassarre, A and Barone-Adesi, F and Cena, T and Legittimo, P and Marinaccio, A and Mirabelli, D and Musti, M and Pirastu, R and Ranucci, A and Magnani, C and , }, title = {Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {887-898}, doi = {10.1136/oemed-2016-104100}, pmid = {28775133}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/mortality ; Carcinogens ; Cause of Death/trends ; Cohort Studies ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Lung ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Ovarian Neoplasms/etiology/*mortality ; Ovary ; Peritoneal Neoplasms/etiology/*mortality ; Peritoneum ; Pleura ; Pleural Neoplasms/etiology/*mortality ; }, abstract = {OBJECTIVE: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers.<br><br>METHODS: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970&#xe2;&#x20ac;"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period.<br><br>RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after.<br><br>DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports.}, }
@article {pmid28757678, year = {2017}, author = {Mozzoni, P and Ampollini, L and Goldoni, M and Alinovi, R and Tiseo, M and Gnetti, L and Carbognani, P and Rusca, M and Mutti, A and Percesepe, A and Corradi, M}, title = {MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {9645940}, pmid = {28757678}, issn = {1875-8630}, mesh = {Aged ; Asbestosis/*blood/metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Lung/metabolism ; Lung Neoplasms/*blood/metabolism/pathology ; Male ; Mesothelioma/*blood/metabolism/pathology ; Mesothelioma, Malignant ; MicroRNAs/*blood/genetics/metabolism ; Middle Aged ; Pilot Projects ; }, abstract = {BACKGROUND: The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression.<br><br>AIMS: To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients.<br><br>METHODS: miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients.<br><br>CONCLUSIONS: All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.}, }
@article {pmid28756416, year = {2017}, author = {Tompa, E and Kalcevich, C and McLeod, C and Lebeau, M and Song, C and McLeod, K and Kim, J and Demers, PA}, title = {The economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {11}, pages = {816-822}, pmid = {28756416}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; *Cost of Illness ; Female ; Health Care Costs ; Humans ; Lung/drug effects ; Lung Neoplasms/chemically induced/*economics ; Male ; Mesothelioma/chemically induced/*economics ; Middle Aged ; Occupational Diseases/chemically induced/*economics ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/*economics ; Quality of Life ; Quality-Adjusted Life Years ; Work ; }, abstract = {OBJECTIVES: To estimate the economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure in Canada.<br><br>METHODS: We estimate the lifetime cost of newly diagnosed lung cancer and mesothelioma cases associated with occupational and para-occupational asbestos exposure for calendar year 2011 based on the societal perspective. The key cost components considered are healthcare costs, productivity and output costs, and quality of life costs.<br><br>RESULTS: There were 427 cases of newly diagnosed mesothelioma cases and 1904 lung cancer cases attributable to asbestos exposure in 2011 for a total of 2331 cases. Our estimate of the economic burden is $C831 million in direct and indirect costs for newly identified cases of mesothelioma and lung cancer and $C1.5 billion in quality of life costs based on a value of $C100 000 per quality-adjusted life year. This amounts to $C356 429 and $C652 369 per case, respectively.<br><br>CONCLUSIONS: The economic burden of lung cancer and mesothelioma associated with occupational and para-occupational asbestos exposure is substantial. The estimate identified is for 2331 newly diagnosed, occupational and para-occupational exposure cases in 2011, so it is only a portion of the burden of existing cases in that year. Our findings provide important information for policy decision makers for priority setting, in particular the merits of banning the mining of asbestos and use of products containing asbestos in countries where they are still allowed and also the merits of asbestos removal in older buildings with asbestos insulation.}, }
@article {pmid28756413, year = {2018}, author = {Reid, A and Merler, E and Peters, S and Jayasinghe, N and Bressan, V and Franklin, P and Brims, F and de Klerk, NH and Musk, AW}, title = {Migration and work in postwar Australia: mortality profile comparisons between Australian and Italian workers exposed to blue asbestos at Wittenoom.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {1}, pages = {29-36}, doi = {10.1136/oemed-2017-104322}, pmid = {28756413}, issn = {1470-7926}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Crocidolite/*adverse effects ; Asbestosis/etiology/*mortality ; Cohort Studies ; *Emigrants and Immigrants ; Employment ; *Ethnicity ; Female ; Humans ; Italy ; Lung Neoplasms/etiology/*mortality ; Male ; Manufacturing Industry ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Mining ; Occupational Exposure/*adverse effects/analysis ; Proportional Hazards Models ; Transients and Migrants ; Western Australia ; Young Adult ; }, abstract = {OBJECTIVES: Three hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom.<br><br>METHODS: A cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers.<br><br>RESULTS: 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL).<br><br>CONCLUSIONS: A hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers.<br><br>IMPACT: Poor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.}, }
@article {pmid28749105, year = {2017}, author = {Sawanyawisuth, K and Furuya, S and Park, EK and Myong, JP and Ramos-Bonilla, JP and Chimed Ochir, O and Takahashi, K}, title = {Compensation for Asbestos-Related Diseases in Japan: Utilization of Standard Classifications of Industry and Occupations.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {7}, pages = {1779-1782}, pmid = {28749105}, issn = {2476-762X}, abstract = {Background: Asbestos-related diseases (ARD) are occupational hazards with high mortality rates. To identify asbestos exposure by previous occupation is the main issue for ARD compensation for workers. This study aimed to identify risk groups by applying standard classifications of industries and occupations to a national database of compensated ARD victims in Japan. Methods: We identified occupations that carry a risk of asbestos exposure according to the International Standard Industrial Classification of All Economic Activities (ISIC). ARD compensation data from Japan between 2006 and 2013 were retrieved. Each compensated worker was classified by job section and group according to the ISIC code. Risk ratios for compensation were calculated according to the percentage of workers compensated because of ARD in each ISIC category. Results: In total, there were 6,916 workers with ARD who received compensation in Japan between 2008 and 2013. ISIC classification section F (construction) had the highest compensated risk ratio of 6.3. Section C (manufacturing) and section F (construction) had the largest number of compensated workers (2,868 and 3,463, respectively). In the manufacturing section C, 9 out of 13 divisions had a risk ratio of more than 1. For ISIC divisions in the construction section, construction of buildings (division 41) had the highest number of workers registering claims (2,504). Conclusion: ISIC classification of occupations that are at risk of developing ARD can be used to identify the actual risk of workers’ compensation at the national level.}, }
@article {pmid28744908, year = {2017}, author = {Kohyama, N and Fujiki, M and Kishimoto, T and Morinaga, K}, title = {Lung cancer in a patient with predominantly short tremolite fibers in his lung.}, journal = {American journal of industrial medicine}, volume = {60}, number = {9}, pages = {831-838}, doi = {10.1002/ajim.22748}, pmid = {28744908}, issn = {1097-0274}, mesh = {Aged, 80 and over ; Asbestos, Amphibole/*isolation &amp; purification/toxicity ; *Extraction and Processing Industry ; Humans ; Lung/pathology ; Lung Neoplasms/*etiology ; Male ; Occupational Diseases/*etiology ; Parenchymal Tissue/pathology ; Particle Size ; }, abstract = {The carcinogenicity of short tremolite fibers in human has not been cleared and has been argued hitherto. A lung cancer patient had worked at a gabbro quarry. Particles isolated from the excised lung parenchyma of the patient were measured for asbestos bodies (ABs) and asbestos fibers (AFs). The concentrations of ABs were 3964 AB/g dry lung, and AFs were 5.60 × 106 fibers/g dry lung (>5 um in length) and 22.5 × 106 fibers/g dry lung (>1 um in length). AFs were mostly tremolite fibers and under 7 um in length (mean length 4.0 um, standard deviation 2.8 um). Almost all fibers were <10 um in length and an aspect ratio (AR) of <20:1 and ≥3:1. The patient had never smoked. His wife, who had worked with him in the quarry, had died of pleural mesothelioma. This study strongly indicates that such short tremolite fibers will induce lung cancer and possibly mesothelioma in human.}, }
@article {pmid28740198, year = {2017}, author = {Granieri, A}, title = {The Drive For Self-Assertion And The Reality Principle In A Patient With Malignant Pleural Mesothelioma: The History of Giulia.}, journal = {American journal of psychoanalysis}, volume = {77}, number = {3}, pages = {285-294}, doi = {10.1057/s11231-017-9099-0}, pmid = {28740198}, issn = {1573-6741}, mesh = {Asbestos/*adverse effects ; Family/*psychology ; Humans ; Italy ; Mesothelioma/*psychology ; Pleural Neoplasms/*psychology ; *Social Support ; *Truth Disclosure ; }, abstract = {Life in a contaminated environment is often marked by a cumulative psychological trauma that exhibits a variety of social-environmental aspects. This is why I suggested a psychotherapeutic group intervention for the population of Casale Monferrato, a municipality in Northern Italy that is sadly renowned for asbestos-related events and the high mortality rate of its inhabitants. Groupality appears to show the point of contact between psyche and soma, while also promoting the birth of a more realistic approach to the various levels of suffering and their configuration. The multifamily approach seemed to be the most adequate to elaborate the feelings of rage and fear that are concurrent with the aerial contagion. In the "long wave" of group work we have learned to work with participants as well as with empty chairs, the ghosts of the dead: live traces in the mind. Whereas the mind recovers the possibility of entering into a dialogue with the feelings connected to the trauma, without bypassing them towards actions that are apparently more assertive of one's sense of Ego, the will of conciliation can reactivate a thought that is oriented towards the plane of reality.}, }
@article {pmid28724330, year = {2017}, author = {Bakker, E and Guazzelli, A and Ashtiani, F and Demonacos, C and Krstic-Demonacos, M and Mutti, L}, title = {Immunotherapy advances for mesothelioma treatment.}, journal = {Expert review of anticancer therapy}, volume = {17}, number = {9}, pages = {799-814}, doi = {10.1080/14737140.2017.1358091}, pmid = {28724330}, issn = {1744-8328}, mesh = {Adaptive Immunity/immunology ; Animals ; Biomarkers/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity, Innate/immunology ; Immunotherapy/*methods ; Mesothelioma/immunology/pathology/*therapy ; Prognosis ; Survival Rate ; Tumor Microenvironment ; }, abstract = {Mesothelioma is a rare type of cancer that is strongly tied to asbestos exposure. Despite application of different modalities such as chemotherapy, radiotherapy and surgery, patient prognosis remains very poor and therapies are ineffective. Much research currently focuses on the application of novel approaches such as immunotherapy towards this disease. Areas covered: The types, stages and aetiology of mesothelioma are detailed, followed by a discussion of the current treatment options such as radiotherapy, surgery, and chemotherapy. A description of innate and adaptive immunity and the principles and justification of immunotherapy is also included. Clinical trials for different immunotherapeutic modalities are described, and lastly the article closes with an expert commentary and five-year view, the former of which is summarised below. Expert commentary: Current efforts for novel mesothelioma therapies have been limited by attempting to apply treatments from other cancers, an approach which is not based on a solid understanding of mesothelioma biology. In our view, the influence of the hostile, hypoxic microenvironment and the gene expression and metabolic changes that resultantly occur should be characterised to improve therapies. Lastly, clinical trials should focus on overall survival rather than surrogate endpoints to avoid bias and inaccurate reflections of treatment effects.}, }
@article {pmid28713671, year = {2017}, author = {Chen, Z and Gaudino, G and Pass, HI and Carbone, M and Yang, H}, title = {Diagnostic and prognostic biomarkers for malignant mesothelioma: an update.}, journal = {Translational lung cancer research}, volume = {6}, number = {3}, pages = {259-269}, pmid = {28713671}, issn = {2218-6751}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, abstract = {Malignant mesothelioma (MM) is an aggressive and lethal cancer, mostly related to inhalation of asbestos and erionite fibers. MM is associated with poor prognosis, because of its resistance to current therapies, even if higher survival occurs in patients diagnosed and treated when at stage I of the disease. However, these do not exceed 5% of the total number of cases, due to the inadequacy of the existing biomarkers for early and accurate diagnosis. Therefore, new effective biomarkers are needed for MM detection at earlier stages and to develop tailored therapies. Here we review the most promising biomarkers in MM to date: mesothelin, soluble mesothelin-related peptides (SMRPs), megakaryocyte potentiating factor (MPF), Osteopontin (OPN), Fibulin-3, high mobility group B1 (HMGB1), microRNAs (miRNAs), multiplex protein signatures. The validation of these biomarkers will allow their use, alone or in combination, for monitoring individuals from cohorts at risk of MM and attaining early detection of MM that is instrumental in improving patient survival.}, }
@article {pmid28713670, year = {2017}, author = {Singh, A and Pruett, N and Hoang, CD}, title = {In vitro experimental models of mesothelioma revisited.}, journal = {Translational lung cancer research}, volume = {6}, number = {3}, pages = {248-258}, pmid = {28713670}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a biologically unusual, highly aggressive cancer that defies current multimodality treatments. Epidemiologic data suggest that this malignancy has not abated despite increasingly strict environmental regulations on asbestos, the putative causative agent for sporadic cases. An incomplete understanding of all the factors mechanistically driving mesothelioma is largely responsible for the current lack of curative treatments. Many approaches have been employed to ascertain the step-by-step molecular events involved in mesothelioma oncogenesis including in vitro, small animal in vivo, and human experimental models; though clearly defined, druggable mechanisms still are elusive. Importantly, the foundation of the latest accepted model of tumor initiation is derived from in vitro systems. A thorough review of in vitro mesothelioma oncogenesis models may suggest further opportunities for discovery.}, }
@article {pmid28706912, year = {2017}, author = {Sun, HH and Vaynblat, A and Pass, HI}, title = {Diagnosis and prognosis-review of biomarkers for mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {244}, pmid = {28706912}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers.}, }
@article {pmid28706907, year = {2017}, author = {Emri, SA}, title = {The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {239}, pmid = {28706907}, issn = {2305-5839}, abstract = {The epidemic of mesothelioma in Cappadocia, Turkey, is unprecedented in medical history. In three Cappadocian villages, Karain, Tuzkoy and "old" Sarihidir, about 50% of all deaths (including neonatal deaths and traffic fatalities) have been caused by mesothelioma. No other epidemic in medical history has caused such a high incidence of death. This is even more unusual when considering that (I) epidemics are caused by infectious agents, not cancer, and (II) mesothelioma is a rare cancer. World-wide mesothelioma incidence varies between 1/10[6] in areas with no asbestos industry to about 10-30/10[6] in areas with asbestos industry. This article reviews how the mesothelioma epidemic was discovered in Cappadocia by Dr. Baris (my mentor), how we initially linked the epidemic to erionite exposure, and later (with Dr. Carbone) to the interaction between genetic predisposition and environmental exposure. Our team's work had an important positive impact on the lives of those living in Cappadocia and also in many genetically predisposed families living around the world. I will discuss how the work that started in three remote Cappadocian villages led to the award of a NCI P01 grant to support our studies. Our studies proved that genetics modulates mineral fiber carcinogenesis and led to the discovery that carriers of germline BAP1 mutations have a very high risk of developing mesothelioma and other malignancies. A new, very active field of research developed following our discoveries to elucidate the mechanism by which BAP1 modulates mineral fiber carcinogenesis as well as to identify additional genes that when mutated increase the risk of mesothelioma and other environmentally related cancers. I am the only surviving member of this research team who saw all the phases of this research and I believe it is important to provide an accurate report, which hopefully will inspire others.}, }
@article {pmid28706906, year = {2017}, author = {Carbone, M and Yang, H}, title = {Mesothelioma: recent highlights.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {238}, pmid = {28706906}, issn = {2305-5839}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, abstract = {Recent discoveries have elucidated some of the mechanisms responsible for the development of mesothelioma. These discoveries are: (I) the critical role of chronic inflammation in promoting mesothelioma growth, driven by the release of high mobility group box protein-1 (HMGB1) following asbestos deposition in tissues and its potential role as a biomarker to identify asbestos exposed individuals and mesothelioma patients; (II) the discovery that inherited heterozygous germline mutations of the deubiquitylase BRCA-associated protein 1 (BAP1) cause a high incidence of mesothelioma in some families; and that (III) germline BAP1 mutations lower the threshold of asbestos required to cause mesothelioma in mice, evidence of gene X environment interaction. These findings together with the identification of novel serum biomarkers, including HMGB1, Fibulin-3, etc., promise to revolutionize screening and treatment of this malignancy in the coming years.}, }
@article {pmid28706904, year = {2017}, author = {Kim, J and Bhagwandin, S and Labow, DM}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {236}, pmid = {28706904}, issn = {2305-5839}, abstract = {Mesothelioma is a malignancy of serosal membranes. It is most commonly encountered in the visceral pleura with the second most common location in the peritoneum. The diagnosis is very rare and has been linked to toxic exposure to industrial pollutants, especially asbestos. Malignant peritoneal mesothelioma (MPM) commonly presents with diffuse, extensive spread throughout the abdomen with rare metastatic spread beyond the abdominal cavity. Due to its rarity and nonspecific symptoms, it is usually diagnosed late when the disease burden is extensive. Because pleural mesothelioma is more common than MPM, most research has been on the pleural variant and extrapolated for MPM. While treatment advances have been made for MPM, the disease is universally fatal from either abdominal complications secondary to the spread of disease or starvation. Untreated, the life expectancy is less than a year. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) has become the mainstay of therapy with systemic therapies still being developed. We will review the epidemiology of MPM and discuss diagnostic and treatment strategies.}, }
@article {pmid28706903, year = {2017}, author = {Murphy, DJ and Gill, RR}, title = {Overview of treatment related complications in malignant pleural mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {235}, pmid = {28706903}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant neoplasm of the pleura related to asbestos exposure. Despite recent advances in therapy for MPM, the prognosis remains poor, with considerable treatment associated morbidity. Radiological assessment plays a central role in the timely identification and subsequent management of treatment related complications in MPM. This review highlights common and uncommon complications associated with and encountered in the post treatment phase.}, }
@article {pmid28706902, year = {2017}, author = {Noonan, CW}, title = {Environmental asbestos exposure and risk of mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {234}, pmid = {28706902}, issn = {2305-5839}, support = {P30 GM103338/GM/NIGMS NIH HHS/United States ; }, abstract = {Mesothelioma is commonly considered an occupational disease occurring as a result of asbestos exposure in the workplace. Several avenues for environmental asbestos exposures have been described and may be associated with asbestos related disease, including mesothelioma. Worker take-home asbestos, or para-occupational exposure, has been well documented and is the most commonly reported pathway for asbestos exposure among mesothelioma cases that do not have history of occupational asbestos exposure. Observational studies have evaluated several communities with elevated mesothelioma incidence and environmental exposures attributed to local asbestos-related industries. Potential, but uncertain, mesothelioma risk also may be associated with general population asbestos exposure through contact with asbestos-containing commercial products, particularly housing materials that can be easily disturbed through normal activity. Finally, studies have described elevated mesothelioma incidence in several areas where populations are exposed to naturally occurring asbestos materials. These various environmental asbestos exposure pathways are poorly understood, and further studies should be pursued to evaluate their respective importance for population mesothelioma risk.}, }
@article {pmid28704762, year = {2017}, author = {Bonelli, MA and Digiacomo, G and Fumarola, C and Alfieri, R and Quaini, F and Falco, A and Madeddu, D and La Monica, S and Cretella, D and Ravelli, A and Ulivi, P and Tebaldi, M and Calistri, D and Delmonte, A and Ampollini, L and Carbognani, P and Tiseo, M and Cavazzoni, A and Petronini, PG}, title = {Combined Inhibition of CDK4/6 and PI3K/AKT/mTOR Pathways Induces a Synergistic Anti-Tumor Effect in Malignant Pleural Mesothelioma Cells.}, journal = {Neoplasia (New York, N.Y.)}, volume = {19}, number = {8}, pages = {637-648}, pmid = {28704762}, issn = {1476-5586}, mesh = {Antineoplastic Agents/pharmacology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cellular Senescence/drug effects ; Cyclin-Dependent Kinase 4/*antagonists &amp; inhibitors ; Cyclin-Dependent Kinase 6/*antagonists &amp; inhibitors ; Drug Synergism ; Humans ; Lung Neoplasms/metabolism ; Mesothelioma/metabolism ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/*metabolism ; Piperazines/pharmacology ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/*metabolism ; Pyridines/pharmacology ; Signal Transduction/*drug effects ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM is CDKN2A/ARF, encoding for the cell cycle inhibitors p16[INK4a] and p14[ARF], deleted in about 70% of MPM cases. Considering the high frequency of alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD-0332991), a highly selective inhibitor of cyclin-dependent kinase (CDK) 4/6. The analyses were performed on a panel of MPM cell lines and on two primary culture cells from pleural effusion of patients with MPM. All the MPM cell lines, as well as the primary cultures, were sensitive to palbociclib with a significant blockade in G0/G1 phase of the cell cycle and with the acquisition of a senescent phenotype. Palbociclib reduced the phosphorylation levels of CDK6 and Rb, the expression of myc with a concomitant increased phosphorylation of AKT. Based on these results, we tested the efficacy of the combination of palbociclib with the PI3K inhibitors NVP-BEZ235 or NVP-BYL719. After palbociclib treatment, the sequential association with PI3K inhibitors synergistically hampered cell proliferation and strongly increased the percentage of senescent cells. In addition, AKT activation was repressed while p53 and p21 were up-regulated. Interestingly, two cycles of sequential drug administration produced irreversible growth arrest and senescent phenotype that were maintained even after drug withdrawal. These findings suggest that the sequential association of palbociclib with PI3K inhibitors may represent a valuable therapeutic option for the treatment of MPM.}, }
@article {pmid28691999, year = {2017}, author = {Pira, E and Coggiola, M and Ciocan, C and Romano, C and La Vecchia, C and Pelucchi, C and Boffetta, P}, title = {Mortality of Talc Miners and Millers From Val Chisone, Northern Italy: An Updated Cohort Study.}, journal = {Journal of occupational and environmental medicine}, volume = {59}, number = {7}, pages = {659-664}, doi = {10.1097/JOM.0000000000000992}, pmid = {28691999}, issn = {1536-5948}, mesh = {Cause of Death ; Cohort Studies ; Gastrointestinal Neoplasms/mortality ; Humans ; Italy/epidemiology ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; *Mining ; Mouth Neoplasms/mortality ; Neoplasms/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/mortality ; Silicosis/*mortality ; Talc/*adverse effects ; Urinary Bladder Neoplasms/mortality ; }, abstract = {OBJECTIVE: The aim of this study was to update the analysis of mortality of a cohort of talc miners and millers in Northern Italy.<br><br>METHODS: We analyzed the mortality during 1946 to 2013 of 1722 male workers in an asbestos-free talc mine (1166 miners and 556 millers) employed during 1946 to 1995.<br><br>RESULTS: The overall standardized mortality ratio (SMR) was 1.24 [95% confidence interval (95% CI) 1.17 to 1.32]; no deaths were observed from pleural cancer; mortality from lung cancer was not increased. Mortality from pneumoconiosis was increased (SMR 26.62; 95% CI 20.71 to 33.69), in particular among miners, and was associated with duration of employment and time since first employment.<br><br>CONCLUSIONS: We confirmed the lack of association between exposure to asbestos-free talc, lung cancer, and mesothelioma. Increased mortality from pneumoconiosis among miners is attributable to past exposure to silica.}, }
@article {pmid28687356, year = {2017}, author = {Betti, M and Casalone, E and Ferrante, D and Aspesi, A and Morleo, G and Biasi, A and Sculco, M and Mancuso, G and Guarrera, S and Righi, L and Grosso, F and Libener, R and Pavesi, M and Mariani, N and Casadio, C and Boldorini, R and Mirabelli, D and Pasini, B and Magnani, C and Matullo, G and Dianzani, I}, title = {Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma.}, journal = {Cancer letters}, volume = {405}, number = {}, pages = {38-45}, doi = {10.1016/j.canlet.2017.06.028}, pmid = {28687356}, issn = {1872-7980}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Carcinogens/*toxicity ; DNA Repair/*genetics ; Environmental Exposure/*adverse effects ; Environmental Pollutants/*toxicity ; Female ; *Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/etiology/*genetics ; Risk Factors ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p = 0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment.}, }
@article {pmid28685333, year = {2018}, author = {Cui, Y and Ma, J and Ye, W and Han, Z and Dong, F and Deng, J and Zhang, Q}, title = {Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {23}, pages = {22328-22333}, pmid = {28685333}, issn = {1614-7499}, support = {41130746//Key Program of National Nature Science Project of China/ ; 41472046//National Natural Fund Project of China/ ; 14JC0126//Department of Sichuan Province Natural Science Foundation of China/ ; }, mesh = {Animals ; Asbestos, Serpentine/administration &amp; dosage/*toxicity ; Cell Line ; China ; Chromosome Aberrations/*drug effects ; Cricetulus ; DNA Damage/*drug effects ; Dose-Response Relationship, Drug ; Fibroblasts/drug effects/physiology ; Lung/*cytology/drug effects ; Micronucleus Tests ; Mineral Fibers/*toxicity ; Mutagens/toxicity ; Single-Cell Analysis/methods ; }, abstract = {According to global estimates, at least 107,000 people die each year from asbestos-related lung cancer, mesothelioma, and asbestosis resulting from occupational exposure. Chrysotile accounts for approximately 90% of asbestos used worldwide. Artificial substitutes can also be cytotoxic to the same degree as chrysotile. But only a few researchers focused on their genetic effects and mutagenicity information which is useful in evaluating the carcinogenicity of chemicals. In this study, chrysotile from Mangnai, Qinghai, China, and an artificial substitute, rock wool fiber were prepared as suspensions and were tested at concentrations of 50, 100, and 200 μg/ml in V79 lung fibroblasts. Chromosome aberrations were detected by micronucleus assay after exposure for 24 h, and DNA damage were estimated by single cell gel electrophoresis after exposure for 12, 24, or 48 h. According to the results, chrysotile and rock wool fibers caused micronuclei to form in a dose-dependent manner in V79 cells; olive tail moment values increased in a dose- and time-dependent manner. When V79 cells were exposed to a concentration of 200 μg/ml, the degree of DNA damage induced by chrysotile fibers was greater than rock wool fibers. Our study suggests that both chrysotile and rock wool fibers could induce chromosome aberrations and DNA damage. These materials are worthy of further study.}, }
@article {pmid28685091, year = {2017}, author = {Uguen, M and Dewitte, JD and Marcorelles, P and Loddé, B and Pougnet, R and Saliou, P and De Braekeleer, M and Uguen, A}, title = {Asbestos-related lung cancers: A retrospective clinical and pathological study.}, journal = {Molecular and clinical oncology}, volume = {7}, number = {1}, pages = {135-139}, pmid = {28685091}, issn = {2049-9450}, abstract = {Exposure to asbestos results in serious risks of developing mesothelioma and lung cancer. The link between asbestos exposure and lung carcinoma is well established. Nevertheless, precise histopathological data are poorly considered when investigating the asbestos-cancer link in a compensatory approach. In the present study, we aim to describe the features of individuals with compensated lung cancer who were referred to an occupational disease center, regarding occupational exposure to asbestos, smoking history and pathological data. We led a retrospective study of compensated ARLC cases seen in our occupational disease center between 2003 and 2013. A total of 146 men were included (mean age at diagnosis, 63.2 years) of whom approximately 90% were heavy current or former smokers (mean value, 30.4 packs/year). The major industries associated with the lung cancer cases were shipbuilding (69.9%), and building construction (7.5%) in this harbor region. The results of the present study showed that lung upper lobe was most prevalent (61.6%) and an excess of adenocarcinoma was found (45.9%), followed by squamous cell carcinoma (38.4%) as well as thoracic sarcomas (2.1%). Neoplasm was not histologically proven in 6.8% of the cases. Subsequent pathology examinations also reclassified 2 tumors as metastases from esophageal and laryngeal origins. In conclusion, smoking prevention should be encouraged in asbestos-exposed workers as reflected by the number of smokers with asbestos-related lung cancer. Thus, histological data should be considered further to evaluate the potent relationship between asbestos exposure and lung malignancy, especially in a compensatory approach.}, }
@article {pmid28680295, year = {2017}, author = {Abós-Herràndiz, R and Rodriguez-Blanco, T and Garcia-Allas, I and Rosell-Murphy, IM and Albertí-Casas, C and Tarrés, J and Krier-Günther, I and Martinez-Artés, X and Orriols, R and Grimau-Malet, I and Canela-Soler, J}, title = {Risk Factors of Mortality from All Asbestos-Related Diseases: A Competing Risk Analysis.}, journal = {Canadian respiratory journal}, volume = {2017}, number = {}, pages = {9015914}, pmid = {28680295}, issn = {1916-7245}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*mortality ; Cohort Studies ; Environmental Exposure/statistics &amp; numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mortality ; Occupational Diseases/mortality ; Occupational Exposure/*statistics &amp; numerical data ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Sex Factors ; Smoking/epidemiology ; Spain/epidemiology ; }, abstract = {BACKGROUND: The mortality from all malignant and nonmalignant asbestos-related diseases remains unknown. The authors assessed the incidence and risk factors for all asbestos-related deaths.<br><br>METHODS: The sample included 544 patients from an asbestos-exposed community in the area of Barcelona (Spain), between Jan 1, 1970, and Dec 31, 2006. Competing risk regression through a subdistribution hazard analysis was used to estimate risk factors for the outcomes.<br><br>RESULTS: Asbestos-related deaths were observed in 167 (30.7%) patients and 57.5% of these deaths were caused by some type of mesothelioma. The incidence rate after diagnosis was 3,600 per 100,000 person-years. In 7.5% of patients death was non-asbestos-related, while pleural and peritoneal mesothelioma were identified in 87 (16.0%) and 18 (3.3%) patients, respectively.<br><br>CONCLUSIONS: Age, sex, household exposure, cumulative nonmalignant asbestos-related disease, and single malignant pathology were identified as risk factors for asbestos-related death. These findings suggest the need to develop a preventive approach to the community and to improve the clinical follow-up process of these patients.}, }
@article {pmid28669341, year = {2018}, author = {Zanellato, I and Colangelo, D and Osella, D}, title = {JQ1, a BET Inhibitor, Synergizes with Cisplatin and Induces Apoptosis in Highly Chemoresistant Malignant Pleural Mesothelioma Cells.}, journal = {Current cancer drug targets}, volume = {18}, number = {8}, pages = {816-828}, doi = {10.2174/1568009617666170623101722}, pmid = {28669341}, issn = {1873-5576}, mesh = {A549 Cells ; Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Azepines/*pharmacology ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Proteins ; Cellular Senescence/drug effects ; Cisplatin/*pharmacology ; DNA Breaks/drug effects ; Drug Resistance, Neoplasm/*drug effects ; Drug Synergism ; Drug Therapy, Combination ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Nuclear Proteins/*antagonists &amp; inhibitors ; Pleural Neoplasms/*drug therapy/pathology ; Proto-Oncogene Proteins c-fos/antagonists &amp; inhibitors ; Proto-Oncogene Proteins c-myc/antagonists &amp; inhibitors ; Transcription Factors/*antagonists &amp; inhibitors ; Transcription, Genetic/drug effects ; Triazoles/*pharmacology ; beta-Galactosidase/metabolism ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an asbestos-associated tumor with poor prognosis and few therapeutic options. JQ1, a selective antagonist of BRD4, modulates transcription of oncogenes, including MPM chemoresistance-associated c-Myc and Fra-1.<br><br>OBJECTIVE: We investigated if JQ1 could enhance the efficacy of cisplatin against MPM.<br><br>METHODS: The antiproliferative activity of cisplatin in combination with JQ1 was assessed on MPM cell lines representative of the cellular phenotypes of this tumor (epithelioid, sarcomatoid and biphasic), and on one cisplatin resistant sub-line. The combination schedule was optimized adopting a 3Dspheroid model. Drug combination effects were correlated with cell cycle distribution and senescence- associated &#x3b2;-galactosidase positive cells. The expression of c-Myc and Fra-1 proteins and some apoptosis markers was assessed by immunoblotting and RT-qPCR. DNA damage and repair were evaluated by means of alkaline comet assay.<br><br>RESULTS: JQ1 in combination with cisplatin elicited additive or synergistic (superadditive) antiproliferative effects on MPM cells, depending on the cell line. The combination showed tumor regression on the 3D-spheroid model. It induced increased apoptosis, along with decreased c-Myc and, sometimes, Fra-1 expression. JQ1 decreased cisplatin-induced DNA breaks in all MPM cells and increased senescence even in less proficient cells, thus enhancing the DNA Damage Response (DDR).<br><br>CONCLUSION: The superadditive effect is due to c-Myc repression. The consequent DDR enhancement triggers to apoptosis induction and/or permanent growth arrest (senescence), depending on the MPM cellular context, leading to tumor regression. Thus, the pharmacological modulation of BET activity could represent a promising tool for future MPM therapy.}, }
@article {pmid28663314, year = {2017}, author = {Feder, IS and Tischoff, I and Theile, A and Schmitz, I and Merget, R and Tannapfel, A}, title = {The asbestos fibre burden in human lungs: new insights into the chrysotile debate.}, journal = {The European respiratory journal}, volume = {49}, number = {6}, pages = {}, pmid = {28663314}, issn = {1399-3003}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*adverse effects/*analysis ; Autopsy ; Germany ; Humans ; Longitudinal Studies ; Lung/pathology ; Lung Neoplasms/*etiology/surgery ; Male ; Mesothelioma/*etiology/surgery ; Microscopy, Electron ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.}, }
@article {pmid28651470, year = {2017}, author = {Finley, BL and Benson, SM and Marsh, GM}, title = {Cosmetic talc as a risk factor for pleural mesothelioma: a weight of evidence evaluation of the epidemiology.}, journal = {Inhalation toxicology}, volume = {29}, number = {4}, pages = {179-185}, doi = {10.1080/08958378.2017.1336187}, pmid = {28651470}, issn = {1091-7691}, mesh = {*Cosmetics ; Humans ; Mesothelioma/*chemically induced ; *Occupational Exposure ; Pleural Neoplasms/*chemically induced ; Risk Factors ; Talc/chemistry/*toxicity ; }, abstract = {OBJECTIVE: Due to some historical (and inaccurate) reports that asbestos might be present in some cosmetic talc products, questions are occasionally raised regarding the potential pleural mesothelioma risks associated with cosmetic talc products. Our objective was to determine the incidence of pleural mesothelioma of individuals exposed to cosmetic talc.<br><br>MATERIALS AND METHODS: We conducted a systematic review of the epidemiological literature for cosmetic talc miners and millers and found three occupational cohort studies that evaluated pleural mesothelioma incidence in workers in Italy, Norway, France, and Austria. We conducted a second literature review to evaluate the incidence and mortality of pleural mesothelioma among patients who received talc pleurodesis treatments before 1965 and found retrospective clinical studies including over 300 patients with follow-up ranging from 14 to 40&#x2009;years.<br><br>RESULTS: There were no mesotheliomas reported in any of the cosmetic talc miner and miller cohorts. A pooled analysis of data from the cohort mortality studies indicated that four mesothelioma deaths would have been expected from the 90,022 person-years of observation, and this was associated with 84% and 67% statistical power to observe a 3-fold or 2.5-fold increase in pleural mesothelioma mortality, respectively. None of the patients who received talc pleurodesis treatments developed mesothelioma.<br><br>CONCLUSION: We conclude that there is no epidemiological evidence to support the hypothesis that exposure to cosmetic talc is associated with the development of pleural mesothelioma.}, }
@article {pmid28634559, year = {2017}, author = {Ideguchi, R and Ashizawa, K and Akashi, S and Shindo, M and Minami, K and Fukuda, T and Irie, J and Fukuda, M and Uetani, M}, title = {Malignant Pleural Mesothelioma with Marked Lymphatic Involvement: A Report of Two Autopsy Cases.}, journal = {Case reports in oncological medicine}, volume = {2017}, number = {}, pages = {6195898}, pmid = {28634559}, issn = {2090-6706}, abstract = {We herein report two cases of malignant pleural mesothelioma with marked lymphangiosis. The patients included a 68-year-old man and a 67-year-old man who both had a history of exposure to asbestos. Computed tomography (CT) on admission showed pleural effusion with pleural thickening. In both cases, a histopathological examination of the pleura confirmed the diagnosis of epithelioid malignant mesothelioma. They received chemotherapy, but the treatment was only palliative. The chest CT assessments during admission revealed marked pleural effusion and mediastinal lymphadenopathy. CT also showed a consolidative mass with bronchovascular bundle and septal thickening in the lungs suggesting pulmonary parenchymal involvement and the lymphangitic spread of the tumor. These CT findings mimicked lung cancer with pleuritis and lymphangitic carcinomatosis. Autopsy was performed in both cases. Macroscopically, the tumor cells infiltrated the lung with the marked lymphatic spread of the tumor. Microscopy also revealed that the tumor had invaded the pulmonary parenchyma with the marked lymphatic spread of the tumor. Although this growth pattern is unusual, malignant pleural mesothelioma should be considered as the differential diagnosis, especially in patients with pleural lesions.}, }
@article {pmid28629895, year = {2017}, author = {Kao, SC and Cheng, YY and Williams, M and Kirschner, MB and Madore, J and Lum, T and Sarun, KH and Linton, A and McCaughan, B and Klebe, S and van Zandwijk, N and Scolyer, RA and Boyer, MJ and Cooper, WA and Reid, G}, title = {Tumor Suppressor microRNAs Contribute to the Regulation of PD-L1 Expression in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {9}, pages = {1421-1433}, doi = {10.1016/j.jtho.2017.05.024}, pmid = {28629895}, issn = {1556-1380}, mesh = {Aged ; B7-H1 Antigen/*biosynthesis/metabolism ; Female ; Humans ; Lung Neoplasms/*genetics/*metabolism/pathology ; Male ; Mesothelioma/*genetics/*metabolism/pathology ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Pleural Neoplasms/*genetics/*metabolism/pathology ; Prognosis ; Up-Regulation ; }, abstract = {INTRODUCTION: The upregulation of programmed death ligand 1 (PD-L1) is found in many cancers and contributes to evasion of the host's immune defense. In malignant pleural mesothelioma (MPM), PD-L1 expression is associated with the nonepithelioid histological subtype and poor prognosis, but the pathways involved in control of PD-L1 expression in MPM are poorly understood. To address one possible means of PD-L1 regulation we investigated the relationship between dysregulated microRNA levels and PD-L1 expression.<br><br>METHODS: PD-L1 expression was analyzed by immunohistochemistry in tissue microarrays prepared from samples from patients undergoing an operation (pleurectomy with or without decortication). MicroRNA expression was analyzed by reverse-transcriptase quantitative polymerase chain reaction. Regulation of PD-L1 expression in cell lines was assessed after transfection with microRNA mimics and small interfering RNAs. Interaction between microRNAs and PD-L1 was analyzed by using argonaute-2 immunoprecipitation and a luciferase reporter assay.<br><br>RESULTS: In a series of 72 patients with MPM, 18 (25%) had positive PD-L1 staining, and this was more common in patients with the nonepithelioid subtype (p&#xa0;= 0.01). PD-L1 expression was associated with poor survival (median overall survival 4.0 versus 9.2 months with positive versus negative PD-L1 expression [p < 0.001]), and in multivariate analyses, PD-L1 expression remained a significant adverse prognostic indicator (hazard ratio&#xa0;=&#xa0;2.2, 95% confidence interval: 1.2-4.1, p < 0.01). In the same patient series, PD-L1 expression was also associated with downregulation of microRNAs previously shown to have tumor suppressor activity in MPM. The median microRNA expression levels of miR-15b, miR-16, miR-193a-3p, miR-195, and miR-200c were significantly lower in the PD-L1-positive samples. Transfecting MPM cell lines with mimics corresponding to miR-15a and miR-16, both of which are predicted to target PD-L1, led to downregulation of PD-L1 mRNA and protein. In addition, miR-193a-3p, with an alternative G-U-containing target site, also caused PD-L1 downregulation.<br><br>CONCLUSIONS: Together, these data suggest that tumor suppressor microRNAs contribute to the regulation of PD-L1 expression in MPM.}, }
@article {pmid28625623, year = {2017}, author = {Świątkowska, B and Szeszenia-Dąbrowska, N}, title = {Mesothelioma continues to increase even 40 years after exposure - Evidence from long-term epidemiological observation.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {108}, number = {}, pages = {121-125}, doi = {10.1016/j.lungcan.2017.03.012}, pmid = {28625623}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; *Occupational Exposure ; Odds Ratio ; Pleural Neoplasms/epidemiology/etiology ; Poland/epidemiology ; Risk ; Time Factors ; }, abstract = {BACKGROUND: Because asbestos dust is considered one of the most dangerous types of dust for people's health, issues related to the effects of asbestos exposure still remain questions about the role of cessation of exposure.<br><br>OBJECTIVES: The aim of the present study was to determine the importance of temporal patterns, especially the time since the end of exposure in the risk of pleural mesothelioma.<br><br>METHODS: A total of 131 patients with pleural mesothelioma and 655 frequency matched by gender and year of birth controls enrolled in the health surveillance programme for asbestos-related diseases over the years 2000-2014, were included in the analysis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).<br><br>RESULTS: The results show that the risk of pleural mesothelioma continued to increase even after 40 years since the last exposure. The estimated odds ratio for the subjects who had their last exposure 40 years ago, compared with the odds ratio of those who had their last exposure 5 years ago, was 2.68 (95%CI: 1.16-.621). We also observed that crocidolite exposure was associated with a very high significant mesothelioma risk, 5-fold higher for those working with mixed exposure compared to the subjects who worked only with chrysotile.<br><br>CONCLUSIONS: Dose-response relationships in populations occupationally exposed are critical to the study related to environment asbestos contamination. Our findings confirm the strong evidence that mesothelioma risk increases along with the increasing time since exposure termination.}, }
@article {pmid28619093, year = {2017}, author = {McDonnell, AM and Cook, A and Robinson, BWS and Lake, RA and Nowak, AK}, title = {Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {417}, pmid = {28619093}, issn = {1471-2407}, mesh = {Antibodies, Monoclonal/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers ; CD40 Antigens/antagonists &amp; inhibitors ; Cisplatin/administration &amp; dosage ; Clinical Trials, Phase I as Topic ; Dendritic Cells/*immunology/metabolism ; Female ; Humans ; Immunomodulation/*drug effects ; Immunophenotyping ; Lymphocyte Activation ; Lymphocyte Count ; Male ; Neoplasms/diagnosis/drug therapy/*immunology/metabolism ; Prognosis ; Proportional Hazards Models ; T-Lymphocyte Subsets/*immunology/metabolism ; }, abstract = {BACKGROUND: CD40 signalling can synergise with chemotherapy in preclinical cancer models, and early clinical studies are promising. We set out to define the immunological changes associated with this therapeutic combination to identify biomarkers for a response to the therapy. Here, we present serial immunomonitoring examining dendritic cell and T cell subpopulations over sequential courses of chemoimmunotherapy.<br><br>METHODS: Fifteen patients with mesothelioma received up to six 21-day cycles of pemetrexed plus cisplatin chemotherapy and anti-CD40 (CP-870,893). Peripheral blood was collected weekly, and analysed by flow cytometry. Longitudinal immunophenotyping data was analysed by linear mixed modelling, allowing for variation between patients. Exploratory analyses testing for any correlation between overall survival and immunophenotyping data were undertaken up to the third cycle of treatment.<br><br>RESULTS: Large statistically significant cyclical variations in the proportions of BDCA-1+, BDCA-2+ and BDCA-3+ dendritic cells were observed, although all subsets returned to baseline levels after each cycle and no significant changes were observed between start and end of treatment. Expression levels of CD40 and HLA-DR on dendritic cells were also cyclically modulated, again without significant change between start and end of treatment. CD8 and CD4 T cell populations, along with regulatory T cells, effector T cells, and markers of proliferation and activation, showed similar patterns of statistically significant cyclical modulation in response to therapy without changes between start and end of treatment. Exploratory analysis of endpoints revealed that patients with a higher than average proportion of BDCA-2+ dendritic cells (p&#xa0;=&#xa0;0.010) or a higher than average proportion of activated (ICOS+) CD8 T cells (0.022) in pretreatment blood samples had better overall survival. A higher than average proportion of BDCA-3+ dendritic cells was associated with poorer overall survival at both the second (p&#xa0;=&#xa0;0.008) and third (p&#xa0;=&#xa0;0.014) dose of anti-CD40.<br><br>CONCLUSIONS: Substantial cyclical variations in DC and T cell populations during sequential cycles of chemoimmunotherapy highlight the critical importance of timing of immunological biomarker assessments in interpretation of results and the value of linear mixed modelling in interpretation of longitudinal change over a full treatment course.<br><br>TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry number ACTRN12609000294257 (18th May 2009).}, }
@article {pmid28614305, year = {2017}, author = {Bononi, A and Giorgi, C and Patergnani, S and Larson, D and Verbruggen, K and Tanji, M and Pellegrini, L and Signorato, V and Olivetto, F and Pastorino, S and Nasu, M and Napolitano, A and Gaudino, G and Morris, P and Sakamoto, G and Ferris, LK and Danese, A and Raimondi, A and Tacchetti, C and Kuchay, S and Pass, HI and Affar, EB and Yang, H and Pinton, P and Carbone, M}, title = {BAP1 regulates IP3R3-mediated Ca[2+] flux to mitochondria suppressing cell transformation.}, journal = {Nature}, volume = {546}, number = {7659}, pages = {549-553}, pmid = {28614305}, issn = {1476-4687}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/genetics ; Asbestos/toxicity ; Calcium/*metabolism ; Calcium Signaling ; Cell Nucleus/metabolism ; Cell Survival ; *Cell Transformation, Neoplastic/drug effects/radiation effects ; Cells, Cultured ; Cytoplasm/*metabolism ; DNA Damage ; Endoplasmic Reticulum/*metabolism ; Epithelium ; Fibroblasts ; Gene-Environment Interaction ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Mitochondria/*metabolism ; Protein Binding ; Protein Stability ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism ; Ubiquitin/metabolism ; Ubiquitin Thiolesterase/deficiency/genetics/*metabolism ; }, abstract = {BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1[+/-]) developed one and often several BAP1[-/-] malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity. The possible activity of BAP1 in the cytoplasm is unknown. Cells with reduced levels of BAP1 exhibit chromosomal abnormalities and decreased DNA repair by homologous recombination, indicating that BAP1 dosage is critical. Cells with extensive DNA damage should die and not grow into malignancies. Here we discover that BAP1 localizes at the endoplasmic reticulum. Here, it binds, deubiquitylates, and stabilizes type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), modulating calcium (Ca[2+]) release from the endoplasmic reticulum into the cytosol and mitochondria, promoting apoptosis. Reduced levels of BAP1 in BAP1[+/-] carriers cause reduction both of IP3R3 levels and of Ca[2+] flux, preventing BAP1[+/-] cells that accumulate DNA damage from executing apoptosis. A higher fraction of cells exposed to either ionizing or ultraviolet radiation, or to asbestos, survive genotoxic stress, resulting in a higher rate of cellular transformation. We propose that the high incidence of cancers in BAP1[+/-] carriers results from the combined reduced nuclear and cytoplasmic activities of BAP1. Our data provide a mechanistic rationale for the powerful ability of BAP1 to regulate gene-environment interaction in human carcinogenesis.}, }
@article {pmid28611824, year = {2017}, author = {Kresoja-Rakic, J and Sulemani, M and Kirschner, MB and Ronner, M and Reid, G and Kao, S and Schwaller, B and Weder, W and Stahel, RA and Felley-Bosco, E}, title = {Posttranscriptional Regulation Controls Calretinin Expression in Malignant Pleural Mesothelioma.}, journal = {Frontiers in genetics}, volume = {8}, number = {}, pages = {70}, pmid = {28611824}, issn = {1664-8021}, abstract = {Calretinin (CALB2) is a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM). We previously reported that calretinin expression is regulated at the mRNA level. The presence of a medium-sized (573 nucleotide) 3' untranslated region (3'UTR) predicted to contain binding sites for miR-30a/b/c/d/e and miR-9 as well as an adenine/uridine-rich element (ARE) in all three transcripts arising from the CALB2 gene, suggests that calretinin expression is regulated via posttranscriptional mechanisms. Our aim was to investigate the role of the CALB2-3'UTR in the posttranscriptional regulation of calretinin expression in MPM. CALB2-3'UTR was inserted downstream of the luciferase reporter gene using pmiRGLO vector and reporter expression was determined after transfection into MPM cells. Targeted mutagenesis was used to generate variants harboring mutated miR-30 family and ARE binding sites. Electrophoretic mobility shift assay was used to test for the presence of ARE binding proteins. CALB2-3'UTR significantly decreased luciferase activity in MPM cells. Analysis of mutation in the ARE site revealed a further destabilization of the reporter and human antigen R (HuR) binding to the ARE sequence was detected. The mutation of two miR-30 binding sites abolished CALB2-3'UTR destabilization effect; a transient delivery of miR-30e-5p mimics or anti-miR into MPM cells resulted in a significant decrease/increase of the luciferase reporter expression and calretinin protein, respectively. Moreover, overexpression of CALB2-3'UTR quenched the effect of miR-30e-5p mimics on calretinin protein levels, possibly by sequestering the mimics, thereby suggesting a competitive endogenous RNA network. Finally, by data mining we observed that expression of miR-30e-5p was negatively correlated with the calretinin expression in a cohort of MPM patient samples. Our data show the role of (1) adenine-uridine (AU)-binding proteins in calretinin stabilization and (2) miR-30e-5p in the posttranscriptional negative regulation of calretinin expression via interaction with its 3'UTR. Furthermore, our study demonstrates a possible physiological role of calretinin's alternatively spliced transcripts.}, }
@article {pmid28606736, year = {2017}, author = {An, JY and Kim, D and Tanakchi, S and Semerjian, AM and Thomas, A and Boyle, SL and Hassan, R and Metwalli, AR}, title = {Clinical Features and Outcomes of Tunica Vaginalis Mesothelioma: A Case Series From the National Institutes of Health.}, journal = {Clinical genitourinary cancer}, volume = {15}, number = {5}, pages = {e871-e875}, pmid = {28606736}, issn = {1938-0682}, support = {Z99 CL999999//Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/diagnosis/*surgery ; Male ; Mesothelioma/diagnosis/*surgery ; Mesothelioma, Malignant ; Middle Aged ; National Institutes of Health (U.S.) ; Orchiectomy ; Survival Analysis ; Testicular Neoplasms/diagnosis/*surgery ; Treatment Outcome ; United States ; }, abstract = {OBJECTIVE: To present our single-institution experience with management of seven patients with mesothelioma of the tunica vaginalis.<br><br>MATERIALS AND METHODS: Our institution database was queried from 2003 to 2014. Clinical, surgical and pathological features were retrospectively collected and evaluated.<br><br>RESULTS: Seven patients were identified with tunica vaginalis mesothelioma. Average age at the time of diagnosis was 63.6 years. Four patients presented with hydrocele, one with scrotal mass, one with inguinal mass, and one with spermatocele. Two (28.6%) patients reported possible asbestos exposure. Radical orchiectomy was performed in all patients. Two patients received adjuvant radiotherapy, one patient received both chemotherapy and radiation. All patients were followed up postoperatively with serial imaging detect for recurrence. One of 7 patients in our cohort experienced recurrence at 12 months. Our mean follow-up time on these patients is 52.2 months.<br><br>CONCLUSION: Previous reported cases have described poor prognosis of tunica vaginalis mesothelioma despite aggressive surgery and systemic therapy. Our single-institution experience suggests relatively good outcomes with surgery and limited adjuvant therapies. Post treatment surveillance is also imperative and should include imaging routinely within the first 2 years. Negative asbestos exposure screening during history should not eliminate clinical suspicion.}, }
@article {pmid28603777, year = {2016}, author = {Napolitano, A and Carbone, M}, title = {Malignant Mesothelioma: Time to Translate?.}, journal = {Trends in cancer}, volume = {2}, number = {9}, pages = {467-474}, pmid = {28603777}, issn = {2405-8033}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy/genetics/metabolism ; *Mesothelioma/drug therapy/genetics/metabolism ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Translational Research, Biomedical ; }, abstract = {Malignant mesothelioma is an aggressive cancer largely associated with asbestos exposure. In this review, we will discuss the significant advancements in our understanding of its genetics and molecular biology and their translational relevance. Remarkable findings included the discovery of germline and somatic mutations of BRCA1 associated protein-1 (BAP1) in patients, and the genome-wide characterization of pathways altered in mesothelioma that could be potentially exploited to design novel therapeutic approaches. Nevertheless, the clinical translation of these molecular findings has been slow and insufficient. In order to rapidly move translation from the bench to the bedside, we believe that cooperative research efforts have to be further endorsed and promoted at all levels.}, }
@article {pmid28594258, year = {2017}, author = {Fujimoto, E and Kijima, T and Kuribayashi, K and Negi, Y and Kanemura, S and Mikami, K and Doi, H and Kitajima, K and Nakano, T}, title = {First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {17}, number = {9}, pages = {865-872}, doi = {10.1080/14737140.2017.1340157}, pmid = {28594258}, issn = {1744-8328}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration &amp; dosage ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Male ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/administration &amp; dosage ; Pleural Neoplasms/*drug therapy/pathology ; Positron-Emission Tomography ; Retrospective Studies ; Survival Rate ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {BACKGROUND: Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM.<br><br>RESEARCH DESIGN AND METHODS: Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent [18]F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment.<br><br>RESULTS: Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0&#xa0;months and 15.8&#xa0;months, respectively. Wet- type MPeM had significantly longer survival (40.9&#xa0;months median) than other clinical types (15.5&#xa0;months) (P&#xa0;=&#xa0;0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5-16.77).<br><br>CONCLUSIONS: Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.}, }
@article {pmid28593073, year = {2017}, author = {Nynäs, P and Pukkala, E and Vainio, H and Oksa, P}, title = {Cancer Incidence in Asbestos-Exposed Workers: An Update on Four Finnish Cohorts.}, journal = {Safety and health at work}, volume = {8}, number = {2}, pages = {169-174}, pmid = {28593073}, issn = {2093-7911}, abstract = {BACKGROUND: We assessed the cancer risks of four different Finnish asbestos-exposed cohorts. We also explored if the cohorts with varying profiles of asbestos exposure exhibited varying relative risks of cancer.<br><br>METHODS: The incident cancer cases for the asbestos-exposed worker cohorts were updated to the end of 2012 using the files of the Finnish Cancer Registry. The previously formed cohorts consisted of asbestos mine workers, asbestosis patients, asbestos sprayers, and workers who had taken part in a screening study based on asbestos exposure at work.<br><br>RESULTS: The standardized incidence ratio (SIR) for mesothelioma varied from about threefold to >&#xa0;100-fold in the different cohorts. In the screening cohort the SIR for mesothelioma was highest in 2003-2007, In other cohorts it was more constant in 5-year period inspection. The SIR for lung cancer was about twofold to tenfold in all except the screening cohort. Asbestos sprayers were at the highest risk of mesothelioma and lung cancer.<br><br>CONCLUSION: The SIR for mesothelioma is high in all of the cohorts that represent different kinds of asbestos exposure. The smaller SIR for mesothelioma in the screening cohort with lowest level of asbestos exposure might suggest dose-responsiveness between asbestos exposure and mesothelioma. It does seem that the highest risk of lung cancer in these cohorts except in the youngest of the cohorts, the screening cohort, is over. The highest SIR for lung cancer of the asbestosis patient and sprayers cohort is explained by their heavy asbestos exposure.}, }
@article {pmid28577549, year = {2017}, author = {Sneddon, S and Patch, AM and Dick, IM and Kazakoff, S and Pearson, JV and Waddell, N and Allcock, RJN and Holt, RA and Robinson, BWS and Creaney, J}, title = {Whole exome sequencing of an asbestos-induced wild-type murine model of malignant mesothelioma.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {396}, pmid = {28577549}, issn = {1471-2407}, mesh = {Animals ; Asbestos/*toxicity ; DNA Copy Number Variations/genetics ; Disease Models, Animal ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Mice ; Mutation ; Neoplasm Proteins/*genetics ; Proto-Oncogene Mas ; Signal Transduction/drug effects/genetics ; *Exome Sequencing ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive cancer of the pleural and peritoneal cavities caused by exposure to asbestos. Asbestos-induced mesotheliomas in wild-type mice have been used extensively as a preclinical model because they are phenotypically identical to their human counterpart. However, it is not known if the genetic lesions in these mice tumours are similar to in the human disease, a prerequisite for any new preclinical studies that target genetic abnormalities.<br><br>METHODS: We performed whole exome sequencing of fifteen asbestos-induced murine MM tumour cell lines from BALB/c, CBA and C57BL/6 mouse strains and compared the somatic mutations and copy number variations with those recurrently reported in human MM. We then catalogued and characterised the mutational landscape of the wild-type murine MM tumours. Quantitative RT-PCR was used to interrogate the expression of key MM genes of interest in the mRNA.<br><br>RESULTS: Consistent with human MM tumours, we identified homozygous loss of the tumour suppressor Cdkn2a in 14/15 tumours. One tumour retained the first exon of both of the p16INK4a and p19ARF isoforms though this tumour also contained genetic amplification of Myc resulting in increased expression of the c-Myc proto-oncogene in the mRNA. There were no chromosomal losses in either the Bap1 or Nf2 regions. One tumour harbored homozygous loss of Trp53 in the DNA. Mutation rates were similar in tumours generated in the CBA and C57BL/6 strains when compared to human MM. Interestingly, all BALB/c tumour lines displayed high mutational loads, consistent with the known mutator phenotype of the host strain. The Wnt, MAPK and Jak-STAT signaling pathways were found to be the most commonly affected biological pathways. Mutations and copy number deletions also occurred in the Hedgehog and Hippo pathways.<br><br>CONCLUSIONS: These data suggest that in the wild-type murine model asbestos causes mesotheliomas in a similar way to in human MM. This further supports the notion that the murine model of MM represents a genuine homologue of the human disease, something uncommon in cancer, and is thus a valuable tool to provide insight into MM tumour development and to aide the search for novel therapeutic strategies.}, }
@article {pmid28572505, year = {2017}, author = {}, title = {Correction: Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {77}, number = {11}, pages = {3124}, doi = {10.1158/0008-5472.CAN-17-0575}, pmid = {28572505}, issn = {1538-7445}, }
@article {pmid28562724, year = {2017}, author = {Trotta, A and Santana, VS and Alazraqui, M}, title = {[Mesothelioma mortality in Argentina, 1980-2013].}, journal = {Salud colectiva}, volume = {13}, number = {1}, pages = {35-44}, doi = {10.18294/sc.2017.1027}, pmid = {28562724}, issn = {1851-8265}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Argentina/epidemiology ; Female ; Heart Neoplasms/*mortality ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Pericardium ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Young Adult ; }, abstract = {Mesothelioma mortality and its socio-demographic and temporal patterns in Argentina from 1980 to 2013 were estimated using data from death certificates obtained from the Vital Statistics System of Argentina's National Ministry of Health. There were 3,259 mesothelioma deaths corresponding to an age-adjusted mortality of 3.1/1,000,000 in 1980 and 5.7/1,000,000 in 2013, an average increase of 84.1% in 34 years. This raising trend became clearer after 1997. Males had higher mortality estimates compared with women in every year of the series; these findings suggest past exposure to asbestos. It is plausible that the asbestos exposure was mostly occupational, which is more common among men. Actions related to reinforcing the asbestos ban already in place and strengthening health surveillance directed at workplaces, previously exposed workers, and the population in general are recommended.}, }
@article {pmid28558669, year = {2017}, author = {Johnen, G and Gawrych, K and Raiko, I and Casjens, S and Pesch, B and Weber, DG and Taeger, D and Lehnert, M and Kollmeier, J and Bauer, T and Musk, AW and Robinson, BWS and Brüning, T and Creaney, J}, title = {Calretinin as a blood-based biomarker for mesothelioma.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {386}, pmid = {28558669}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Australia ; Biomarkers, Tumor/*blood ; Calbindin 2/*blood/genetics ; Germany ; Humans ; Lung Neoplasms/*blood/chemically induced/pathology ; Male ; Mesothelioma/*blood/chemically induced/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*blood/pathology ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin.<br><br>METHODS: For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype.<br><br>RESULTS: Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10&#xa0;years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00).<br><br>CONCLUSIONS: Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.}, }
@article {pmid28553954, year = {2017}, author = {Kato, T and Sato, T and Yokoi, K and Sekido, Y}, title = {E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells.}, journal = {Oncogene}, volume = {36}, number = {39}, pages = {5522-5531}, doi = {10.1038/onc.2017.147}, pmid = {28553954}, issn = {1476-5594}, mesh = {Antigens, CD ; Apoptosis/drug effects ; Cadherins/*biosynthesis ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm ; Focal Adhesion Kinase 1/*antagonists &amp; inhibitors ; Gene Expression ; Humans ; Lung Neoplasms/*drug therapy/*metabolism/pathology ; Mesothelioma/*drug therapy/*metabolism/pathology ; Mesothelioma, Malignant ; Neurofibromin 2/*deficiency/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Signal Transduction ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor commonly caused by asbestos exposure after a long latency. Focal adhesion kinase (FAK) inhibitors inhibit the cell growth of Merlin-deficient MM cells; however, their clinical efficacy has not been clearly determined. The aim of this study was to evaluate the growth inhibitory effect of the FAK inhibitor VS-4718 on MM cell lines and identify biomarkers for its efficacy. Although most Merlin-deficient cell lines were sensitive to VS-4718 compared with control MeT-5A cells, a subset of these cell lines exhibited resistance to this drug. Microarray and qRT-PCR analyses using RNA isolated from Merlin-deficient MM cell lines revealed a significant correlation between E-cadherin mRNA levels and VS-4718 resistance. Merlin- and E-cadherin-negative Y-MESO-22 cells underwent apoptosis upon treatment with a low concentration of VS-4718, whereas Merlin-negative, E-cadherin-positive Y-MESO-9 cells did not undergo VS-4718-induced apoptosis. Furthermore, E-cadherin knockdown in Merlin-negative MM cells significantly sensitized cells to VS-4718 and induced apoptotic cell death upon VS-4718 treatment. Together, our results suggest that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors.}, }
@article {pmid28551647, year = {2017}, author = {Rizzardi, C and Athanasakis, E and Cammisuli, F and Monego, SD and DE Spelorzi, YCC and Costantinides, F and Giudici, F and Pinamonti, M and Canzonieri, V and Melato, M and Pascolo, L}, title = {Puzzling Results from BAP1 Germline Mutations Analysis in a Group of Asbestos-Exposed Patients in a High-risk Area of Northeast Italy.}, journal = {Anticancer research}, volume = {37}, number = {6}, pages = {3073-3083}, doi = {10.21873/anticanres.11663}, pmid = {28551647}, issn = {1791-7530}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Germ-Line Mutation ; Humans ; Italy ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Risk ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BACKGROUND: Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies. The demonstration that BAP1 mutations are strongly associated with MM has provided a real breakthrough in the study of genetic predisposition in MM, that may explain why only a fraction of asbestos-exposed individuals go on to develop MM.<br><br>MATERIALS AND METHODS: To evaluate the possible role of BAP1 mutations in the epidemiology of sporadic MM, and their relationship with asbestos exposure, we determined the prevalence of germline BAP1 mutations by the Sanger method in a group of 29 asbestos-exposed patients, 21 of which were diagnosed with MM. They were residents of Trieste, a ship-building town in Northeast Italy with a very high incidence of mesothelioma.<br><br>RESULTS: We identified non-obviously pathogenetic germline sequence variants of BAP1 in 3/29 patients and in 2/21 MM cases (10%).<br><br>CONCLUSION: Non obviously pathogenic germline sequence variants of BAP1 were found. Nevertheless, limitations of predictive web tools allowed us to comment on some interesting peculiarities of our findings.}, }
@article {pmid28534416, year = {2017}, author = {Xu, R and Mesaros, C and Weng, L and Snyder, NW and Vachani, A and Blair, IA and Hwang, WT}, title = {Comparison of statistical methods for detection of serum lipid biomarkers for mesothelioma and asbestos exposure.}, journal = {Biomarkers in medicine}, volume = {11}, number = {7}, pages = {547-556}, pmid = {28534416}, issn = {1752-0371}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; T32 ES019851/ES/NIEHS NIH HHS/United States ; R03 CA211820/CA/NCI NIH HHS/United States ; K22 ES026235/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Blood Chemical Analysis/*methods ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Humans ; Lipids/*blood ; Mesothelioma/*blood ; Statistics as Topic/*methods ; }, abstract = {AIM: We compared three statistical methods in selecting a panel of serum lipid biomarkers for mesothelioma and asbestos exposure.<br><br>MATERIALS &amp; METHODS: Serum samples from mesothelioma, asbestos-exposed subjects and controls (40 per group) were analyzed. Three variable selection methods were considered: top-ranked predictors from univariate model, stepwise and least absolute shrinkage and selection operator. Crossed-validated area under the receiver operating characteristic curve was used to compare the prediction performance.<br><br>RESULTS: Lipids with high crossed-validated area under the curve were identified. Lipid with mass-to-charge ratio of 372.31 was selected by all three methods comparing mesothelioma versus control. Lipids with mass-to-charge ratio of 1464.80 and 329.21 were selected by two models for asbestos exposure versus control.<br><br>CONCLUSION: Different methods selected a similar set of serum lipids. Combining candidate biomarkers can improve prediction.}, }
@article {pmid28527639, year = {2017}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Epidemiology of mesothelioma of the pericardium and tunica vaginalis testis.}, journal = {Annals of epidemiology}, volume = {27}, number = {5}, pages = {348-359.e11}, doi = {10.1016/j.annepidem.2017.04.001}, pmid = {28527639}, issn = {1873-2585}, mesh = {Asbestos/*toxicity ; Female ; Heart Neoplasms/pathology ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Occupational Diseases ; Pericardium/*pathology ; Registries ; Testicular Neoplasms/*pathology ; Testis/*pathology ; United States ; }, abstract = {PURPOSE: Malignant mesothelioma most commonly arises in the pleura and peritoneum but also occurs rarely at other anatomical sites with mesothelial tissue, namely, the pericardium and tunica vaginalis testis (TVT). This review provides a better understanding of the epidemiology of mesothelioma of these extrapleural sites.<br><br>METHODS: We conducted a systematic review of the epidemiologic and clinical literature on pericardial mesothelioma and mesothelioma of the TVT. We also analyzed U.S. Surveillance, Epidemiology, and End Results cancer registry data to describe incidence patterns of these malignancies.<br><br>RESULTS: An etiologic role of asbestos exposure has been hypothesized for pericardial and TVT mesotheliomas, but no analytical case-control epidemiologic studies exist to test this relationship. A substantial proportion of cases with these malignancies report no known asbestos exposure. In large occupational cohorts with heavy asbestos exposures, no cases of pericardial or TVT mesothelioma have been reported. Trends in the incidence of these malignancies do not match those of pleural mesothelioma, which correspond to historical trends of commercial asbestos use. A male preponderance of pericardial mesothelioma is not evident.<br><br>CONCLUSIONS: In the absence of analytic epidemiologic studies, the etiologic role of environmental risk factors for mesothelioma of the pericardium and TVT remains elusive.}, }
@article {pmid28523158, year = {2017}, author = {D'Agostin, F and De Michieli, P and Chermaz, C and Negro, C}, title = {Pleural and peritoneal mesotheliomas in the Friuli Venezia Giulia register: data analysis from 1995 to 2015 in Northeastern Italy.}, journal = {Journal of thoracic disease}, volume = {9}, number = {4}, pages = {1032-1045}, pmid = {28523158}, issn = {2072-1439}, abstract = {BACKGROUND: The Friuli Venezia Giulia Mesothelioma Register contains a case-list of 1,109 mesotheliomas (1,034 pleural, 75 peritoneal) during 1995-2015. Exposure data are available for almost all cases. The aim was to assess mesothelioma incidence in the Region, an area with several shipyards, and to investigate determinants of mesothelioma latency among occupational cases.<br><br>METHODS: Incidence rates were calculated. Univariate and multivariate analyses were performed to estimate latency time by anatomical site, gender, diagnostic period and industry sector.<br><br>RESULTS: Mesothelioma incidence rates among men were higher than among women during the overall period. The incidence of pleural mesothelioma in men leveled off until 2009 (6.50 per 100,000) with a slight decrease thereafter. For women, the rate increased until 2006 (1.31 per 100,000) and then remained relatively stable. The incidence of peritoneal mesothelioma in men was constant whereas rate among women increased during 2010-2015. The number of cases diagnosed during three-year periods remained level. In multivariate model, site and gender were not relevant for latency period whereas construction workers had a shorter latency than shipyard workers.<br><br>CONCLUSIONS: Despite the asbestos ban since 1992, occupational exposure is still at risk. This highlights the need to assess exposure levels and to find a reliable health surveillance tool.}, }
@article {pmid28505004, year = {2017}, author = {Desmeules, P and Joubert, P and Zhang, L and Al-Ahmadie, HA and Fletcher, CD and Vakiani, E and Delair, DF and Rekhtman, N and Ladanyi, M and Travis, WD and Antonescu, CR}, title = {A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions.}, journal = {The American journal of surgical pathology}, volume = {41}, number = {7}, pages = {980-988}, pmid = {28505004}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Biomarkers, Tumor/*genetics ; Child ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; *Oncogene Fusion ; Oncogene Proteins, Fusion/*genetics ; Peritoneal Neoplasms/*genetics/pathology ; Pleural Neoplasms/*genetics/pathology ; RNA-Binding Protein FUS/*genetics ; Young Adult ; }, abstract = {Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality. As both index cases occurred as intra-abdominal tumors in young adults, we searched our files for pleural and peritoneal MM occurring in adults younger than age of 40. All cases were tested by fluorescence in situ hybridization using custom bacterial artificial chromosomes probes for EWSR1, FUS, and ATF1 genes. When available, immunohistochemistry for BAP1 was performed. A total of 25 MM from patients aged 40 or less were screened, either from peritoneum (n=13) or pleura (n=12), with a median age of 31 (range: 7 to 40 y). Two additional ATF1-rearranged tumors were identified at pleural and peritoneal sites with EWSR1 and FUS as fusion partners, respectively, for a total of 4 cases (16%, 4/25). The fusion-positive cases displayed classic epithelioid morphology, immunoreactivity for cytokeratins and WT1, and negativity for S100. BAP1 expression was retained in the 3 fusion-positive cases with available material, and in 80% (12/15) of the fusion-negative cases. Our results expand the spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions to include a subgroup of conventional epithelioid MM. Other features of this unique MM subset include young age at presentation, lack of asbestos exposure and retained BAP1 expression.}, }
@article {pmid28501798, year = {2017}, author = {Lacourt, A and Lévêque, E and Guichard, E and Gilg Soit Ilg, A and Sylvestre, MP and Leffondré, K}, title = {Dose-time-response association between occupational asbestos exposure and pleural mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {9}, pages = {691-697}, doi = {10.1136/oemed-2016-104133}, pmid = {28501798}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Dose-Response Relationship, Drug ; Female ; France ; Humans ; Logistic Models ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleura/*drug effects/pathology ; Pleural Neoplasms/*etiology/pathology ; Risk Factors ; }, abstract = {OBJECTIVES: Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose-response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case-control study.<br><br>METHODS: This study included 1196 male cases recruited in 1987-2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure.<br><br>RESULTS: Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95% CI 2.01 to 2.87)).<br><br>CONCLUSION: This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk.}, }
@article {pmid28500034, year = {2017}, author = {Freitas, DMM and Ramos, RL and Serpa Pinto, L and Ribeiro, R}, title = {Primary pericardial mesothelioma and asbestos exposure: a rare fatal disease.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, pmid = {28500034}, issn = {1757-790X}, mesh = {Aged ; Disease Progression ; Environmental Exposure/*adverse effects ; Female ; Heart Diseases/*chemically induced ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Pericardial Effusion/*chemically induced ; Pericardium ; Rare Diseases/*chemically induced ; }, }
@article {pmid28498408, year = {2017}, author = {Maeda, M and Chen, Y and Lee, S and Kumagai-Takei, N and Yoshitome, K and Matsuzaki, H and Yamamoto, S and Hatayama, T and Ikeda, M and Nishimura, Y and Otsuki, T}, title = {Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure.}, journal = {International journal of oncology}, volume = {50}, number = {6}, pages = {2024-2032}, doi = {10.3892/ijo.2017.3991}, pmid = {28498408}, issn = {1791-2423}, mesh = {Asbestos/toxicity ; CD4-Positive T-Lymphocytes/drug effects/immunology ; Coculture Techniques ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Interferon-gamma/*genetics ; Interleukin-17/*genetics/immunology ; Ionomycin/administration &amp; dosage ; Lung Neoplasms/chemically induced/*genetics/immunology/pathology ; Mesothelioma/chemically induced/*genetics/immunology/pathology ; Mesothelioma, Malignant ; Phorbol Esters/administration &amp; dosage ; Receptors, Antigen, T-Cell/genetics ; Receptors, CXCR3/*genetics ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; Th17 Cells/drug effects/immunology ; }, abstract = {We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.}, }
@article {pmid28481375, year = {2017}, author = {D' Agostin, F and de Michieli, P and Negro, C}, title = {Pleural mesothelioma in household members of asbestos-exposed workers in Friuli Venezia Giulia, Italy.}, journal = {International journal of occupational medicine and environmental health}, volume = {30}, number = {3}, pages = {419-431}, doi = {10.13075/ijomeh.1896.00890}, pmid = {28481375}, issn = {1896-494X}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/epidemiology/etiology ; Environmental Exposure/*adverse effects ; *Family Characteristics ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Malignant mesothelioma is closely associated to asbestos exposure. One such exposure may occur through contact with occupationally exposed household members and their belongings. This study examines the features of pleural mesothelioma attributable only to asbestos brought home by another family member.<br><br>MATERIAL AND METHODS: The data sources were 1063 mesothelioma cases diagnosed between 1995 and 2014, from the Friuli Venezia Giulia Mesothelioma Register. In all cases the diagnosis of mesothelioma was based on the pathology report. Exposure information and demographic data were acquired by an occupational medical standardized questionnaire/interview.<br><br>RESULTS: Household-exposure mesothelioma cases included 33 women and 2 men. Relationships were: wives (N = 22), daughters (N = 9), sons (N = 2), and mothers (N = 2). Asbestos exposure in the workers predominantly occurred in shipyards. Out of the 35 pleural cases, 19 were epithelial, 9 biphasic, 3 sarcomatoid, and 4 not specified. The mean age at diagnosis was 77 years old. The mean latency was 59 years, with wives having a significant shorter latency than offspring. Latency was not significantly related to morphology and asbestosis. The overall mean survival was 16 months (median 11 months) but treatment was beneficial (mean 16 months vs. 7 months). Biphasic/sarcomatoid histology and presence of asbestosis were associated with a decreased survival, although not with statistical significance.<br><br>CONCLUSIONS: Our data confirms that household exposure increases the risk for pleural mesothelioma amongst women with no history of occupational asbestos exposure. This is an ongoing problem in many countries, as well as in Italy, where the evaluation of a framework for the compensation of these cases is under debate. Int J Occup Med Environ Health 2017;30(3):419-431.}, }
@article {pmid28472171, year = {2017}, author = {Cavalleri, T and Angelici, L and Favero, C and Dioni, L and Mensi, C and Bareggi, C and Palleschi, A and Rimessi, A and Consonni, D and Bordini, L and Todaro, A and Bollati, V and Pesatori, AC}, title = {Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease.}, journal = {PloS one}, volume = {12}, number = {5}, pages = {e0176680}, pmid = {28472171}, issn = {1932-6203}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*genetics ; MicroRNAs/*genetics ; Middle Aged ; Pleural Neoplasms/chemically induced/*genetics ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE).<br><br>We investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and found 55 differential miRNAs using logistic regression models adjusted for age, sex, BMI, and smoking. Among the top-20 differential miRNAs chosen for validation by Real time PCR, 16 were confirmed. Using receiver operating characteristic (ROC) curve analysis, the most discriminating miRNA combination was given by miR-103a-3p + miR-30e-3p, which generated an AUC of 0.942 (95% CI 0.87-1.00), with a sensitivity of 95.5% and a specificity of 80.0%. Using multivariate Cox regression analysis including gender, age, BMI and smoking we found a Hazard Ratio for miR-103a-3p above the median of 0.37 (95%CI 0.13-1.13) and of 0.51 (95%CI 0.17-1.52) for miR-30e-3p.<br><br>CONCLUSIONS: This study suggests EV-associated miR-103a-3p and miR-30e-3p are able to discriminate MPM from PAE subjects. Larger and prospective studies are needed to confirm these two-miRNA signature alone or in combination with other biomarkers as diagnostic tools for MPM.}, }
@article {pmid28446737, year = {2017}, author = {Barbieri, PG and Somigliana, AB and Lombardi, S and Festa, R and Girelli, R and Sarnico, M}, title = {[Pleural mesothelioma in doll manufacture: possible asbestos exposure].}, journal = {La Medicina del lavoro}, volume = {108}, number = {2}, pages = {111-117}, doi = {10.23749/mdl.v108i2.6115}, pmid = {28446737}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; *Carcinogens ; Female ; Humans ; *Industry ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Play and Playthings ; Pleural Neoplasms/*etiology ; }, abstract = {BACKGROUND: The occurrence of malignant mesothelioma is almost always causally associated to asbestos exposure but, considering women occurrences, this association is often difficult to demonstrate and consequently the asbestos exposure is defined as 'unknown'.<br><br>OBJECTIVES: To describe the working activity and to give occupational asbestos exposure probability estimation related to an uncommon and poorly investigated productive sector: doll manufacture.<br><br>METHODS: From the Province of Brescia Mesothelioma Registry, established in 1993 on population-based criteria, we have extracted the certified mesothelioma diagnosis cases, related to patients who were employed for some time in doll manufacture.<br><br>RESULTS: Among the 757 total cases of malignant mesothelioma registered and studied up to 2016, we found 3 cases of pleural epithelial mesothelioma histologically diagnosed in young women who had worked in two doll manufacturing companies and whose asbestos exposure had been initially defined as 'unknown', because an environmental, family or extra-professional asbestos exposure was considered unlikely. However, the judicial autopsy performed on one of the 3 women had allowed examining lung tissue samples with Scanning Electron Microscopy. This technique showed a concentration of amphiboles fibers of about 12,000,000 per gram of dry lung tissue, with a consequent re-classification of asbestos exposure from 'unknown' to 'occupational certified'.<br><br>DISCUSSION: Mesotheliomas in women with no apparent occupational asbestos exposure are normally referred to life or family environmental exposure. Moreover, it is known that occupational asbestos exposure in women is difficult to recognize. Previously, only one publication had reported two cases of mesothelioma in cloth doll manufacture. The occurrence of two mesothelioma cases in the same company out of the three here presented was suggesting an occupational exposure. The finding of a high amphibole fibers lung concentration confirmed the previous hypothesis, despite the impossibility to determine the circumstances with good evidence.<br><br>CONCLUSION: The three cases of mesothelioma in doll production workers suggest that also in this restricted manufacturing sector had occurred an occupational asbestos exposure, which is up to now unknown and isn't due only to the use of sewing or ironing machines. The lung asbestos fibers burden analysis is confirmed to be a decisive factor in the assessment of mesothelioma cases with 'unknown' exposure.}, }
@article {pmid28438787, year = {2017}, author = {Pira, E and Romano, C and Donato, F and Pelucchi, C and Vecchia, C and Boffetta, P}, title = {Mortality from cancer and other causes among Italian chrysotile asbestos miners.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {8}, pages = {558-563}, doi = {10.1136/oemed-2016-103673}, pmid = {28438787}, issn = {1470-7926}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*adverse effects ; Cause of Death ; Chronic Disease/mortality ; Cohort Studies ; Environmental Monitoring ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Mining ; Mortality ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Poisson Distribution ; }, abstract = {OBJECTIVE: To investigate the long-term mortality of a cohort of Italian asbestos miners.<br><br>METHODS: The cohort included 1056 men employed in a chrysotile mine between 1930 and 1990, who were followed up during 1946-2014, for a total of 37&#x2009;471 person-years of observation. Expected deaths and SMRs were computed using national and local (after 1980, when available) reference.<br><br>RESULTS: A total of 294 (27.8%) subjects were alive and at the end of follow-up, 722 (68.4%) were dead and 40 (3.8%) were lost to follow-up. The SMR for overall mortality was 1.35 (95%CI 1.25 to 1.45). The SMR for pleural cancer, based on seven observed deaths, was 5.54 (95% CI 2.22 to 11.4) and related to time since first exposure, but not to duration of employment, cumulative exposure or time since last exposure. The SMR for lung cancer was 1.16 (95% CI 0.87 to 1.52; 53 observed deaths), with no excess among workers with cumulative exposure below 100 fibre/mL-years (SMR 0.82; 95%&#x2009;CI 0.44 to 1.40).<br><br>CONCLUSIONS: The update of the follow-up of this cohort confirmed an increased mortality from pleural cancer mortality in miners exposed to chrysotile and a lack of significant increase in lung cancer mortality.}, }
@article {pmid28435764, year = {2017}, author = {Bazine, A and Fetohi, M and Namad, T and Benzekri, A and Zainoun, B and Tanz, R and Ichou, M}, title = {A Case of Well-Differentiated Papillary Mesothelioma of the Male Peritoneum: Successful Treatment by Systemic Chemotherapy.}, journal = {Cureus}, volume = {9}, number = {3}, pages = {e1104}, pmid = {28435764}, issn = {2168-8184}, abstract = {Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epithelioid mesothelioma, which is usually seen in young women without a history of asbestos exposure, and generally, has an indolent course. The relative rarity of this neoplasm in males prompted us to report this case of a well-differentiated papillary mesothelioma of the peritoneum in a 36-year-old man. The patient, who had no history of asbestos exposure, presented with abdominal pain and ascites of unknown etiology. Computed tomography showed abundant ascites with nodules of the peritoneal cavity. Laparoscopic examination revealed a large number of white miliary nodules diffusely covering the peritoneum. Pathology revealed a diagnosis of well-differentiated papillary mesothelioma of the peritoneum, based on histomorphology and immunohistochemistry. The patient started chemotherapy with cisplatin and pemetrexed. After six cycles of chemotherapy, the effectiveness of this chemotherapy was checked by only the computed tomography. PET scan was not used because it is not routinely recommended in WDPMP. Few data are currently available in the literature regarding the performance of the PET scan in WDPMP. Nine months later, the patient was free of symptoms. Based on reviewing the literature and our observations in this case, consultation of other pathologists is highly recommended to discern WDPMP from other disseminated peritoneal diseases, in order to offer the most effective and safe therapeutic strategy. Chemotherapy should be strongly considered if the tumor is unresectable and accompanied by symptoms. Cisplatin and pemetrexed chemotherapy could be a promising therapeutic choice.}, }
@article {pmid28412495, year = {2017}, author = {Liu, B and van Gerwen, M and Bonassi, S and Taioli, E and , }, title = {Epidemiology of Environmental Exposure and Malignant Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {7}, pages = {1031-1045}, doi = {10.1016/j.jtho.2017.04.002}, pmid = {28412495}, issn = {1556-1380}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology/pathology ; Male ; Mesothelioma/*epidemiology/pathology ; Mesothelioma, Malignant ; }, abstract = {Although the association between exposure to asbestos and malignant mesothelioma (particularly malignant pleural mesothelioma) has been well established, the health impact of environmental exposure (EE) to asbestos has been less studied. This review summarizes the most recent studies on the association between malignant mesothelioma and EE with asbestos to identify features associated with EE and quantify the association with malignant mesothelioma. There were 44 studies from 18 countries that met our selection criteria, with a considerable amount of heterogeneity in their study design, measures of exposure, and health outcomes. The male-to-female ratio was close to or less than 1 and generally lower than the ratio reported when both occupational and environmental exposures were considered. Although recent studies have continued to improve our understanding of environmental exposure to asbestos, challenges remain. We have highlighted a few new research directions, such as a need for reliable matrices to identify common and less recognized types of EE, asbestos biomarker studies specifically focusing on EE, and research on populations and geographic areas that have not been previously studied.}, }
@article {pmid28409856, year = {2017}, author = {Mensi, C and Ciullo, F and Barbieri, GP and Riboldi, L and Somigliana, A and Rasperini, G and Pesatori, AC and Consonni, D}, title = {Pleural malignant mesothelioma in dental laboratory technicians: A case series.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {443-448}, doi = {10.1002/ajim.22716}, pmid = {28409856}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Dental Casting Technique ; Dentistry ; Female ; Humans ; Italy ; Laboratory Personnel ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*chemically induced/diagnostic imaging ; Occupational Exposure/*adverse effects ; Registries ; Surveys and Questionnaires ; }, abstract = {Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure.}, }
@article {pmid28399779, year = {2017}, author = {Domen, A and De Laet, C and Vanderbruggen, W and Gielis, J and Hendriks, JM and Lauwers, P and Janssens, A and Hiddinga, B and Van Meerbeeck, JP and Van Schil, PE}, title = {Malignant pleural mesothelioma: single-institution experience of 101 patients over a 15-year period.}, journal = {Acta chirurgica Belgica}, volume = {117}, number = {3}, pages = {157-163}, doi = {10.1080/00015458.2016.1272253}, pmid = {28399779}, issn = {0001-5458}, mesh = {Adult ; Aged ; Aged, 80 and over ; Belgium ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms/mortality/*pathology/therapy ; Male ; Mesothelioma/mortality/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive neoplasm that typically originates from the mesothelial surfaces of the pleural cavity. Exposure to asbestos is the principal etiological agent of MPM. The disease is characterized by difficult stage classification and limited consensus on therapeutic approach. We have evaluated the experience with MPM in the Antwerp University Hospital over the past 15 years.<br><br>METHODS: A database was created with all patients diagnosed with or treated for a MPM between 2001 and 2015. A total of 101 patients were included on which different survival analyses were performed combined with a reproduction of demographic, clinical, histologic and therapeutic data, and these were compared to literature data.<br><br>RESULTS: Vast majority of our 101 patients were male (80%) with a median age of 66 years at diagnosis with predominantly epitheloid histology (81%). Overall median survival was 18.3 months and overall 1-, 2- and 5-year survival rates were 68%, 37% and 7%, respectively. Kaplan-Meier analysis showed a non-significant difference in survival between the several best (b) TNM-stages (p&#x2009;=&#x2009;.356). A significant difference in survival was observed in patients undergoing surgery versus no surgery (p&#x2009;=&#x2009;.008), between the different histological types (p&#x2009;<&#x2009;.0001) and treatment with chemotherapy alone versus chemotherapy with surgery (p&#x2009;<&#x2009;.0001). Smoking at diagnosis and epitheloid histology have been identified as significant prognostic factors in the multivariate Cox regression model (HR 3.13 and 0.53, respectively).<br><br>CONCLUSION: Descriptive and survival analysis of our patient database confirmed the limitations of the current staging system and were concordant with literature regarding MPM.}, }
@article {pmid28395242, year = {2017}, author = {Rapisarda, V and Caltabiano, R and Musumeci, G and Castrogiovanni, P and Ferrante, M and Ledda, C and Lombardo, C and Graziano, ACE and Cardile, V and Loreto, C}, title = {Analysis of fibulin-3 after exposure to asbestos-like fibers.}, journal = {Environmental research}, volume = {156}, number = {}, pages = {381-387}, doi = {10.1016/j.envres.2017.03.055}, pmid = {28395242}, issn = {1096-0953}, mesh = {Air Pollutants/toxicity ; Animals ; Asbestos, Amphibole/*toxicity ; Biomarkers/*blood ; Calcium-Binding Proteins/*genetics/metabolism ; Disease Models, Animal ; Female ; Fibroblasts/*drug effects ; Gene Expression/*drug effects ; Humans ; Immunohistochemistry ; Italy ; Lung/*drug effects ; Male ; Sheep ; }, abstract = {A significantly increased incidence of malignant mesothelioma in Biancavilla (Sicily, Italy) has been ascribed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. Fibulin-3 is a highly conserved glycoprotein proposed as a biomarker for malignant mesothelioma that belongs to the family of extracellular matrix proteins. Previous studies demonstrated high Fibulin-3 plasma levels in workers with pleural plaques exposed to fluoro-edenite. Therefore, in order to gain insight into the biomolecular mechanisms of fluoro-edenite toxicity, we performed the analysis of Fibulin-3 expression by immunohistochemistry in the lung samples derived from sheep belonging to the area of Biancavilla. Furthermore, an in vitro model of exposed fluoro-edenite fibroblasts was used to perform functional experiments to better understand the modulation of Fibulin-3 expression. The percentage of immunostained area by Fibulin-3 was very much higher in exposed lungs compared with non-exposed ones. The Fibulin-3 protein level was significantly expressed in primary human lung fibroblasts exposed to 50 and 100µg/ml of fluoro-edenite fibers for 72h, compared to the unexposed controls. The results from the present study further demonstrate the implication of Fibulin-3 during fluoro-edenite exposure. This would endorse our previous results regarding the use of Fibulin-3 as a possible screening biomarker for fluoro-edenite exposed individuals, thereby contributing to the monitoring of the population at risk. The present study also suggested that the Fibulin-3 overexpression may reflect a defensive response of the tissues after exogenous stimuli and may be implicated in cancer development, especially in the context of fluoro-edenite contamination. However, further studies are necessary in order to make Fibulin-3 a customized screening tool.}, }
@article {pmid28387650, year = {2017}, author = {Creaney, J and Dick, IM and Leon, JS and Robinson, BW}, title = {A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ.}, journal = {Cancer genomics &amp; proteomics}, volume = {14}, number = {2}, pages = {103-117}, pmid = {28387650}, issn = {1790-6245}, mesh = {Aged ; Cell Line, Tumor ; Cells, Cultured ; Cluster Analysis ; Exosomes/genetics/metabolism ; Female ; Gene Ontology ; Humans ; Isotope Labeling/*methods ; Lung Neoplasms/metabolism/pathology ; Male ; Mass Spectrometry/*methods ; Mesothelioma/metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Principal Component Analysis ; Proteome/classification/genetics/*metabolism ; Proteomics/*methods ; }, abstract = {UNLABELLED: Backgound/Aim: Malignant mesothelioma (MM) is an aggressive and fatal pleural cancer. The cell secretome offers information allowing insight into the pathogenesis of MM while offering the possibility to identify potential therapeutic targets and biomarkers. In the present study the secretome protein profile of MM cell lines was compared to normal mesothelial cells.<br><br>MATERIALS AND METHODS: Six MM cell lines were compared against three primary mesothelial cell culture preparations using iTRAQ&#xae; mass spectrometry.<br><br>RESULTS: MM cell lines more abundantly secreted exosome-associated proteins than mesothelial cells. MM cell secretomes were enriched in proteins that are involved in response to stress, carbon metabolism, biosynthesis of amino acids, antigen processing and presentation and protein processing in the endoplasmic reticulum.<br><br>CONCLUSION: The MM cell secretome is enriched in proteins that are likely to enhance its growth and response to stress and help it inhibit an adaptive immune response. These are potential targets for therapeutic and biomarker discovery.}, }
@article {pmid28377727, year = {2017}, author = {Rouka, E and Vavougios, GD and Solenov, EI and Gourgoulianis, KI and Hatzoglou, C and Zarogiannis, SG}, title = {Transcriptomic Analysis of the Claudin Interactome in Malignant Pleural Mesothelioma: Evaluation of the Effect of Disease Phenotype, Asbestos Exposure, and CDKN2A Deletion Status.}, journal = {Frontiers in physiology}, volume = {8}, number = {}, pages = {156}, pmid = {28377727}, issn = {1664-042X}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor primarily associated with asbestos exposure. Early detection of MPM is restricted by the long latency period until clinical presentation, the ineffectiveness of imaging techniques in early stage detection and the lack of non-invasive biomarkers with high sensitivity and specificity. In this study we used transcriptome data mining in order to determine which CLAUDIN (CLDN) genes are differentially expressed in MPM as compared to controls. Using the same approach we identified the interactome of the differentially expressed CLDN genes and assessed their expression profile. Subsequently, we evaluated the effect of tumor histology, asbestos exposure, CDKN2A deletion status, and gender on the gene expression level of the claudin interactome. We found that 5 out of 15 studied CLDNs (4, 5, 8, 10, 15) and 4 out of 27 available interactors (S100B, SHBG, CDH5, CXCL8) were differentially expressed in MPM specimens vs. healthy tissues. The genes encoding the CLDN-15 and S100B proteins present differences in their expression profile between the three histological subtypes of MPM. Moreover, CLDN-15 is significantly under-expressed in the cohort of patients with previous history of asbestos exposure. CLDN-15 was also found significantly underexpressed in patients lacking the CDKN2A gene. These results warrant the detailed in vitro investigation of the role of CDLN-15 in the pathobiology of MPM.}, }
@article {pmid28361969, year = {2017}, author = {Tsuji, S and Washimi, K and Kageyama, T and Yamashita, M and Yoshihara, M and Matsuura, R and Yokose, T and Kameda, Y and Hayashi, H and Morohoshi, T and Tsuura, Y and Yusa, T and Sato, T and Togayachi, A and Narimatsu, H and Nagasaki, T and Nakamoto, K and Moriwaki, Y and Misawa, H and Hiroshima, K and Miyagi, Y and Imai, K}, title = {HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {45768}, pmid = {28361969}, issn = {2045-2322}, mesh = {Antibodies, Monoclonal/*immunology/metabolism ; Biomarkers, Tumor/immunology/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Glycosylation ; Humans ; Lung Neoplasms/*diagnosis/*immunology/metabolism ; Membrane Proteins/genetics/*immunology/metabolism ; Mesothelioma/*diagnosis/*immunology/metabolism ; Mesothelioma, Malignant ; Sensitivity and Specificity ; }, abstract = {The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.}, }
@article {pmid28351431, year = {2017}, author = {Mensi, C and Romano, A and Berti, A and Dore, R and Riboldi, L}, title = {A second case of pericardial mesothelioma mimicking systemic lupus erythematosus in the literature in over 30 years: a case report.}, journal = {Journal of medical case reports}, volume = {11}, number = {1}, pages = {85}, pmid = {28351431}, issn = {1752-1947}, mesh = {Diagnosis, Differential ; Echocardiography ; Fatal Outcome ; Female ; Heart Neoplasms/*diagnosis/pathology ; Humans ; Lupus Erythematosus, Systemic/*diagnosis ; Mesothelioma/complications/*diagnosis/pathology ; Middle Aged ; Pericardial Effusion/etiology/therapy ; Pericardiocentesis ; *Pericardium/diagnostic imaging ; Radiography ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Mesothelioma is a rare neoplasm which commonly develops in the pleura of people exposed to asbestos. Pericardial mesothelioma accounts for only 0.7 % of all malignant mesotheliomas and it usually presents with pericardial effusion, mimicking serositis. To date, there are approximately 200 cases of pericardial mesothelioma described in the medical literature, and little knowledge exists about the systemic manifestations of this pathology. The first and only described case of pericardial mesothelioma with autoimmune features dates back to 1984 and, in our case report, we describe the second.<br><br>CASE PRESENTATION: We report a case of a 45-year-old white woman whose pericardial mesothelioma was initially misdiagnosed as pericardial involvement of an autoimmune disease (systemic lupus erythematosus). After several relapses of pericardial effusion, a computed tomography scan and a biopsy with histological analysis were performed revealing neoplastic growth.<br><br>CONCLUSIONS: We describe a rare case of pericardial mesothelioma in a patient with a clinical presentation compatible with lupus serositis. Clinicians should consider malignant mesothelioma in the differential diagnosis of pericardial effusion, especially when it is recurrent and not clearly explained by other causes. Cytological samples should always be obtained and, if imaging tools are suggestive for solid processes, histological confirmation is mandatory.}, }
@article {pmid28348451, year = {2017}, author = {Ying, S and Jiang, Z and He, X and Yu, M and Chen, R and Chen, J and Ru, G and Chen, Y and Chen, W and Zhu, L and Li, T and Zhang, Y and Guo, X and Yin, X and Zhang, X and Lou, J}, title = {Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {5756102}, pmid = {28348451}, issn = {1875-8630}, mesh = {Aged ; Asbestosis/*blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; HMGB1 Protein/*blood ; Humans ; Lung Neoplasms/*blood ; Male ; Matrix Metalloproteinase 2/blood ; Matrix Metalloproteinase 9/blood ; Mesothelioma/*blood ; Mesothelioma, Malignant ; Middle Aged ; }, abstract = {High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.}, }
@article {pmid28348450, year = {2017}, author = {Bonotti, A and Foddis, R and Landi, S and Melaiu, O and De Santi, C and Giusti, L and Donadio, E and Ciregia, F and Mazzoni, MR and Lucacchini, A and Bovenzi, M and Comar, M and Pantani, E and Pistelli, A and Cristaudo, A}, title = {A Novel Panel of Serum Biomarkers for MPM Diagnosis.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {3510984}, pmid = {28348450}, issn = {1875-8630}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Blood Proteins/metabolism ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms/*blood ; Male ; Mesothelioma/*blood ; Mesothelioma, Malignant ; Middle Aged ; Proteome/metabolism ; }, abstract = {Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.}, }
@article {pmid28344849, year = {2017}, author = {Choi, S and Kang, D and Park, D and Lee, H and Choi, B}, title = {Developing Asbestos Job Exposure Matrix Using Occupation and Industry Specific Exposure Data (1984-2008) in Republic of Korea.}, journal = {Safety and health at work}, volume = {8}, number = {1}, pages = {105-115}, pmid = {28344849}, issn = {2093-7911}, abstract = {BACKGROUND: The goal of this study is to develop a general population job-exposure matrix (GPJEM) on asbestos to estimate occupational asbestos exposure levels in the Republic of Korea.<br><br>METHODS: Three Korean domestic quantitative exposure datasets collected from 1984 to 2008 were used to build the GPJEM. Exposure groups in collected data were reclassified based on the current Korean Standard Industrial Classification (9[th] edition) and the Korean Standard Classification of Occupations code (6[th] edition) that is in accordance to international standards. All of the exposure levels were expressed by weighted arithmetic mean (WAM) and minimum and maximum concentrations.<br><br>RESULTS: Based on the established GPJEM, the 112 exposure groups could be reclassified into 86 industries and 74 occupations. In the 1980s, the highest exposure levels were estimated in "knitting and weaving machine operators" with a WAM concentration of 7.48 fibers/mL (f/mL); in the 1990s, "plastic products production machine operators" with 5.12 f/mL, and in the 2000s "detergents production machine operators" handling talc containing asbestos with 2.45 f/mL. Of the 112 exposure groups, 44 groups had higher WAM concentrations than the Korean occupational exposure limit of 0.1 f/mL.<br><br>CONCLUSION: The newly constructed GPJEM which is generated from actual domestic quantitative exposure data could be useful in evaluating historical exposure levels to asbestos and could contribute to improved prediction of asbestos-related diseases among Koreans.}, }
@article {pmid28343162, year = {2017}, author = {De Santi, C and Pucci, P and Bonotti, A and Melaiu, O and Cipollini, M and Silvestri, R and Vymetalkova, V and Barone, E and Paolicchi, E and Corrado, A and Lepori, I and Dell'Anno, I and Pellè, L and Vodicka, P and Mutti, L and Foddis, R and Cristaudo, A and Gemignani, F and Landi, S}, title = {Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {6}, pages = {456-463}, doi = {10.1136/oemed-2016-104024}, pmid = {28343162}, issn = {1470-7926}, mesh = {Aged ; Alleles ; Analysis of Variance ; Asbestos/adverse effects ; Biomarkers, Tumor/blood/*genetics ; Female ; GPI-Linked Proteins/*blood/*genetics ; Genotype ; Humans ; Italy ; Luciferases ; Lung Neoplasms/blood/*diagnosis/*genetics ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Polymorphism, Single Nucleotide ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the mesothelin (MSLN) gene could affect the levels of SMRP.<br><br>OBJECTIVES: To focus on SNPs located within MSLN promoter as possible critical genetic variables in determining SMRP levels.<br><br>METHODS: The association between SMRP and SNPs was tested in 689 non-MPM subjects and 70 patients with MPM. Reporter plasmids carrying the four most common haplotypes were compared in a dual luciferase assay, and in silico analyses were performed to investigate the putative biological role of the SNPs.<br><br>RESULTS: We found a strong association between serum SMRP and variant alleles of rs3764247, rs3764246 (in strong linkage disequilibrium with rs2235504) and rs2235503 in non-MPM subjects. Inclusion of the genotype information led to an increase in SMRP specificity from 79.9% to 85.5%. Although not statistically significant, the group with MPM showed the same trend of association. According to the in vitro luciferase study, rs3764247 itself had a functional role. In silico approaches showed that the binding sites for transcription factors such as Staf and ZNF143 could be affected by this SNP. The other SNPs were shown to interact with each other in a more complex way.<br><br>CONCLUSIONS: These data support the suggestion that SMRP performance is affected by individual (ie, genetic) variables and that MSLN expression is influenced by SNPs located within the promoter regulatory region.}, }
@article {pmid28337371, year = {2017}, author = {Huang, L and Cai, M and Zhang, X and Wang, F and Chen, L and Xu, M and Yang, K and Chen, Z and Wang, X and Fu, L}, title = {Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma.}, journal = {American journal of cancer research}, volume = {7}, number = {2}, pages = {203-217}, pmid = {28337371}, issn = {2156-6976}, abstract = {Malignant pleural mesothelioma (MPM) is a relative rare but highly aggressive neoplasm which is associated with asbestos exposure in most patients. The majority of patients are diagnosed in advanced stages so patients neither benefit from chemotherapy (e.g. pemetrexed-platinum combination) nor from surgery. It has been reported that cellular-mesenchymal to epithelial transition factor (MET) and epidermal growth factor receptor (EGFR) were critical for MPM cell proliferation. Moreover, targeting MET and EGFR drugs have gained promising results on anti-tumor therapy. Here, a striking difference in overall survival was observed between the MET and EGFR co-expression group (median survival time = 13.5 months) and non-co-expression group (median survival time = 20.5 months). In addition, treatment with combination of crizotinib and afatinib showed stronger inhibition on cell proliferation of MPM than the treatment by either one in vitro and in vivo. In conclusion, our data illustrated that crizotinib combined with afatinib may be a potentially effective strategy for treating MPM patients with over-expression of MET and EGFR.}, }
@article {pmid28335760, year = {2017}, author = {Ak, G and Tada, Y and Shimada, H and Metintas, S and Ito, M and Hiroshima, K and Tagawa, M and Metintas, M}, title = {Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {212}, pmid = {28335760}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Cohort Studies ; Cytokines/*blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/*blood/diagnosis/*epidemiology ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Midkine ; Prognosis ; ROC Curve ; Turkey/epidemiology ; }, abstract = {BACKGROUND: We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker.<br><br>METHODS: Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy. The cut-off values were 1.5&#xa0;nmol/L for mesothelin and 421&#xa0;pg/mL for midkine.<br><br>RESULTS: Sensitivity and specificity of mesothelin were 51.6 and 71.4%, 51.6 and 85.2%, and 51.6 and 85% for differentiating mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Sensitivity and specificity of midkine were 61.1 and 41.1%, 61.1 and 48.1%, and 61.1 and 75% to distinguish mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Combination of both biomarkers did not improve the differential diagnostic efficacy. Mesothelin levels were elevated in the epitheloid type and in the advanced cases, but were not related to the prognosis. In contrast, elevated baseline levels of midkine were independently associated with a poor prognosis of mesothelioma patients after adjusting for the stage, the histological subtypes and treatment schedules (HR&#xa0;=&#xa0;1.84; 95% CI: 1.09-3.09) (p&#xa0;=&#xa0;0.022).<br><br>CONCLUSIONS: Serum mesothelin showed moderate sensitivity and high specificity to differentiate malignant pleural mesothelioma from metastatic malignancy to pleura and from benign pleural diseases. In contrast, midkine was a useful marker for predicting prognosis of mesothelioma patients.}, }
@article {pmid28322788, year = {2017}, author = {Raiko, I and Rihs, HP and Gleichenhagen, J and Sander, I and Kollmeier, J and Lehnert, M and Brüning, T and Johnen, G}, title = {A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma.}, journal = {Biochemical and biophysical research communications}, volume = {486}, number = {2}, pages = {526-532}, doi = {10.1016/j.bbrc.2017.03.077}, pmid = {28322788}, issn = {1090-2104}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Antibodies/chemistry/isolation &amp; purification ; Area Under Curve ; Biomarkers, Tumor/*blood/immunology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay/*methods ; Escherichia coli/genetics/metabolism ; Female ; GPI-Linked Proteins/*blood/immunology ; HeLa Cells ; Humans ; Lung Neoplasms/blood/*diagnosis/immunology/pathology ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peptides/administration &amp; dosage/*immunology/metabolism ; ROC Curve ; Rabbits ; Recombinant Proteins/administration &amp; dosage/biosynthesis/immunology ; }, abstract = {Malignant mesothelioma (MM) is a fatal disease mostly associated with asbestos exposure and difficult to detect by non-invasive methods. This study aimed to use recombinant fragments of the megakaryocyte potentiating factor (MPF) for the development of cost-effective MPF ELISAs. Three polypeptides spanning the MPF region (MPF1-148, MPF 34-288, MPF/MSLN254-400) were produced in E.coli as maltose-binding protein hybrids. After isolation, Factor Xa digest, and purification, the polypeptides were used for the generation of rabbit antibodies and development of ELISAs. Forty-one MM patients with known histological subtype before tumor-specific treatment and 70 asbestos-exposed individuals free of any cancer were matched according to age, gender, and smoking. Plasma of all subjects was tested with the three newly developed polyclonal antibody-based ELISAs and a commercial mesothelin assay (MESOMARK™). The latter differentiated patients (median concentration 1.95 nM) from controls (median 1.07 nM, p < 0.0001) and showed an area under curve (AUC) of 0.77 in receiver operating characteristics (ROC) analysis. Of the MPF variants, exclusively the ELISA based on antibodies against the MPF34-288 fragment displayed significantly (p = 0.0002) higher values in patients than in controls (median 1.61 nM versus 0.88 nM; AUC = 0.72). The combination of the MPF34-288 and mesothelin displayed an improved ROC performance (AUC = 0.80). The MPF34-288 ELISA could be a cost-effective and minimal-invasive contribution to support a diagnosis of mesothelioma, especially in regions with a limited medical care.}, }
@article {pmid28321148, year = {2017}, author = {Weber, DG and Gawrych, K and Casjens, S and Brik, A and Lehnert, M and Taeger, D and Pesch, B and Kollmeier, J and Bauer, TT and Johnen, G and Brüning, T}, title = {Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {9280170}, pmid = {28321148}, issn = {1875-8630}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*genetics ; Early Detection of Cancer ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*diagnosis/genetics ; Male ; Mesothelioma/*diagnosis/genetics ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Middle Aged ; Oligonucleotide Array Sequence Analysis/*methods ; Sensitivity and Specificity ; }, abstract = {The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance.}, }
@article {pmid28279517, year = {2017}, author = {Diego Roza, C and Cruz Carmona, MJ and Fernández Álvarez, R and Ferrer Sancho, J and Marín Martínez, B and Martínez González, C and Rodríguez Portal, JA and Romero Valero, F and Villena Garrido, V}, title = {Recommendations for the Diagnosis and Management of Asbestos-Related Pleural and Pulmonary Disease.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {8}, pages = {437-442}, doi = {10.1016/j.arbres.2016.12.014}, pmid = {28279517}, issn = {1579-2129}, mesh = {Asbestos/classification/toxicity ; Asbestosis/*diagnosis/diagnostic imaging/prevention &amp; control/*therapy ; Biomarkers, Tumor ; Carcinoma, Bronchogenic/diagnosis/etiology/therapy ; Humans ; Lung Neoplasms/diagnosis/etiology/therapy ; Mass Screening ; Mesothelioma/diagnosis/etiology/therapy ; Mineral Fibers/analysis/toxicity ; Occupational Exposure ; Occupational Health/legislation &amp; jurisprudence ; Pleural Diseases/diagnosis/diagnostic imaging/therapy ; Pleural Neoplasms/diagnosis/etiology/therapy ; Positron Emission Tomography Computed Tomography ; Respiratory Function Tests ; Smoking/epidemiology ; Spain ; }, abstract = {Asbestos is the term used for a set of mineral silicates that tend to break up into fibers. Its use has been associated with numerous diseases affecting the lung and pleura in particular, all of which are characterized by their long period of latency. Asbestos, moreover, has been recognized by the WHO as a Group IA carcinogen since 1987 and its use was banned in Spain in 2002. The publication in 2013 of the 3rd edition of the specific asbestos health monitoring protocol, together with the development of new diagnostic techniques, prompted the SEPAR EROM group to sponsor publication of guidelines, which review the clinical, radiological and functional aspects of the different asbestos-related diseases. Recommendations have also been made for the diagnosis and follow-up of exposed patients. These recommendations were drawn up in accordance with the GRADE classification system.}, }
@article {pmid28272659, year = {2018}, author = {Bianchi, C and Bianchi, T}, title = {Non-Hodgkin Lymphoma and Pleural Mesothelioma in a Person Exposed to Asbestos.}, journal = {Turk patoloji dergisi}, volume = {34}, number = {2}, pages = {190-193}, doi = {10.5146/tjpath.2015.01332}, pmid = {28272659}, issn = {1309-5730}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/etiology/*pathology ; Lymphoma, Non-Hodgkin/etiology/*pathology ; Mesothelioma/etiology/*pathology ; Mesothelioma, Malignant ; Neoplasms, Multiple Primary/*etiology/pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*pathology ; }, abstract = {Non-Hodgkin lymphoma and pleural mesothelioma may co-exist in the same patient. A large cell non-Hodgkin lymphoma of the inguinal lymph nodes was diagnosed in a 73-year-old woman. The patient was treated by chemotherapy. She did not receive radiotherapy. The patient had been exposed to asbestos having worked in a cotton mill and in a distillery. Four years after the diagnosis of lymphoma, she presented with a left pleural effusion. Large biopsies of the pleura showed a malignant mesothelioma, biphasic type, and pleural plaques. Epidemiological studies about the asbestos-lymphoma relationship gave conflicting results. The lymphoma-mesothelioma association is not exceptional, and suggests that asbestos plays a role in the etiology of both malignancies.}, }
@article {pmid28253224, year = {2017}, author = {Mazurek, JM and Syamlal, G and Wood, JM and Hendricks, SA and Weston, A}, title = {Malignant Mesothelioma Mortality - United States, 1999-2015.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {66}, number = {8}, pages = {214-218}, pmid = {28253224}, issn = {1545-861X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Cause of Death ; Female ; Humans ; Inhalation Exposure/adverse effects ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Mineral Fibers/adverse effects ; Occupational Diseases/etiology/mortality ; Occupational Exposure/adverse effects ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is a neoplasm associated with occupational and environmental inhalation exposure to asbestos* fibers and other elongate mineral particles (EMPs) (1-3). Patients have a median survival of approximately 1 year from the time of diagnosis (1). The latency period from first causative exposure to malignant mesothelioma development typically ranges from 20 to 40 years but can be as long as 71 years (2,3). Hazardous occupational exposures to asbestos fibers and other EMPs have occurred in a variety of industrial operations, including mining and milling, manufacturing, shipbuilding and repair, and construction (3). Current exposures to commercial asbestos in the United States occur predominantly during maintenance operations and remediation of older buildings containing asbestos (3,4). To update information on malignant mesothelioma mortality (5), CDC analyzed annual multiple cause-of-death records[†] for 1999-2015, the most recent years for which complete data are available. During 1999-2015, a total of 45,221 deaths with malignant mesothelioma mentioned on the death certificate as the underlying or contributing cause of death were reported in the United States, increasing from 2,479 deaths in 1999 to 2,597 in 2015 (in the same time period the age-adjusted death rates[§] decreased from 13.96 per million in 1999 to 10.93 in 2015). Malignant mesothelioma deaths increased for persons aged ≥85 years, both sexes, persons of white, black, and Asian or Pacific Islander race, and all ethnic groups. Despite regulatory actions and the decline in use of asbestos the annual number of malignant mesothelioma deaths remains substantial. The continuing occurrence of malignant mesothelioma deaths underscores the need for maintaining measures to prevent exposure to asbestos fibers and other causative EMPs and for ongoing surveillance to monitor temporal trends.}, }
@article {pmid28244608, year = {2017}, author = {Markowitz, SB and Moline, JM}, title = {Malignant mesothelioma due to asbestos exposure in dental tape.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {437-442}, doi = {10.1002/ajim.22696}, pmid = {28244608}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Dental Casting Technique/adverse effects ; Dentists ; Female ; Humans ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*chemically induced ; Occupational Exposure/*adverse effects ; United States ; }, abstract = {Although most cases of malignant mesothelioma of the pleura are caused by one or more readily recognized sources of exposure to asbestos, cases of the disease with more occult exposure occur, especially since asbestos has been used in over 3,000 products. Dental lining tape contained asbestos from the 1930s until at least the 1970s and was used in the lost wax method of casting crowns, bridges, and other metal dental prosthetic devices. We report six cases of pathology-verified malignant mesothelioma, mostly among dentists, following exposure to airborne dust from asbestos dental tape, which resulted in asbestos tort litigation. According to evidence available at present, chrysotile asbestos was the type of asbestos used in dental tape in the past in the United States, and the described cases followed relatively brief and intermittent exposure to this type of asbestos. These cases underscore the need for comprehensive exposure histories to determine exposure scenarios. Am. J. Ind. Med. 60:437-442, 2017. © 2017 Wiley Periodicals, Inc.}, }
@article {pmid28244606, year = {2017}, author = {Musk, B and Gordon, L and Alfonso, H and Reid, A and Olsen, N and Mina, R and Franklin, P and Peters, S and Brims, F and Hui, J and de Klerk, N}, title = {Risk factors for malignant mesothelioma in people with no known exposure to asbestos.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {432-436}, doi = {10.1002/ajim.22695}, pmid = {28244606}, issn = {1097-0274}, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Humans ; Interviews as Topic ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Registries ; Risk Factors ; Smoking ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a rare and generally fatal cancer, usually caused by asbestos, although about 5-10% of cases report no asbestos exposure. This study aimed to identify sources whereby people in Western Australia (WA) may be unknowingly exposed to asbestos or to other exposures which may cause MM.<br><br>METHODS: Cases with no known asbestos exposure were selected from the WA Mesothelioma Register (WAMR). Matched controls were selected from hospital patients admitted for conditions unrelated to asbestos. Occupational histories were coded by an industrial hygienist. Data were analyzed using conditional logistic regression.<br><br>RESULTS: Thirty-eight MM participants and 134 controls were recruited. Risk of MM was increased (OR&#x2009;=&#x2009;3.1, 95%CI 1.0-9.6) after no known, but likely, exposure to asbestos at work.<br><br>CONCLUSIONS: Because of its extensive use, few people in WA have never been exposed to asbestos. Unrecognized exposure may cause most MM cases initially regarded as "no exposure." Am. J. Ind. Med. 60:432-436, 2017. &#xa9; 2017 Wiley Periodicals, Inc.}, }
@article {pmid28241714, year = {2017}, author = {Ying, SB and Tong, Y and Jiang, ZQ}, title = {[Molecular mechanisms of HMGB1 extracellular secretion in asbestos-induced malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {35}, number = {1}, pages = {76-78}, doi = {10.3760/cma.j.issn.1001-9391.2017.01.022}, pmid = {28241714}, issn = {1001-9391}, }
@article {pmid28241368, year = {2017}, author = {Lipp, MJ and Jusufi, MS and Backer, C and Feyerabend, B and Weilert, H and Oldhafer, KJ}, title = {[Benign multicystic peritoneal mesothelioma (BMPM) - a surprising differential diagnosis in case of an expected intraabdominal abscess formation].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {55}, number = {3}, pages = {267-273}, doi = {10.1055/s-0043-100104}, pmid = {28241368}, issn = {1439-7803}, mesh = {Abdominal Abscess/*diagnosis/*etiology/therapy ; Adult ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma, Cystic/*complications/*diagnostic imaging/therapy ; Peritoneal Neoplasms/*complications/*diagnostic imaging/therapy ; }, abstract = {The benign multicystic peritoneal mesothelioma is a rare disease. Most frequently, young women in reproductive age are affected by this disease. Nevertheless, there are known cases of multicystic peritoneal mesothelioma in male patients. The pathogenesis remains uncertain. Whereas asbestos fibers can cause the development of malignant mesothelioma, the exposure to asbestos particles cannot induce this type of mesothelioma. An inflammatory genesis is discussed as well as the idea of a neoplastic development. Since a high rate of recurrence after surgery is observed, an aggressive surgical treatment is recommended. The complete resection of affected tissue is recently considered to be the therapy of choice. The combination of complete surgical tumor reduction with an intraperitoneal hyperthermic chemotherapy (HIPEC) seems to be promising. Although malignant transformation is detected very rarely a close follow up in centers with high surgical and oncological expertise is recommended.}, }
@article {pmid28236494, year = {2017}, author = {Ferrer, J and Sampol, J and Cruz, MJ}, title = {Malignant pleural mesothelioma in a young adult with no known exposure to asbestos. Can asbestos exposure be truly ruled out?.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {8}, pages = {469}, doi = {10.1016/j.arbres.2017.01.007}, pmid = {28236494}, issn = {1579-2129}, mesh = {Adult ; *Asbestos ; Environmental Exposure ; Humans ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; Young Adult ; }, }
@article {pmid28210162, year = {2016}, author = {Patel, SC and Dowell, JE}, title = {Modern management of malignant pleural mesothelioma.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {7}, number = {}, pages = {63-72}, pmid = {28210162}, issn = {1179-2728}, abstract = {Malignant pleural mesothelioma (MPM) is a deadly disease that produces a significant worldwide health care burden. The majority of cases are associated with prior asbestos exposure, but recent studies have identified a possible genetic predisposition in a minority of patients. Historically, obtaining a pathologic diagnosis of MPM was challenging, but with current pathological techniques, a secure diagnosis is possible in the majority of patients. Curative therapy for MPM remains elusive, and the primary treatment option for fit patients is platinum-based chemotherapy. Encouraging recent reports suggest that there may be a benefit to the addition of bevacizumab to standard chemotherapy as well as with the use of immune checkpoint inhibitors in MPM. Selected patients may be considered for aggressive surgical approaches, but there is considerable controversy regarding the true benefit of surgery and multimodality therapy in this disease.}, }
@article {pmid28204714, year = {2017}, author = {Swiatkowska, B and Szeszenia-Dabrowska, N}, title = {Long-term epidemiological observation of asbestos-related diseases in Poland, 1970-2015.}, journal = {Occupational medicine (Oxford, England)}, volume = {67}, number = {3}, pages = {182-187}, doi = {10.1093/occmed/kqx011}, pmid = {28204714}, issn = {1471-8405}, mesh = {Asbestos/*toxicity ; Asbestosis/epidemiology/etiology ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Male ; Mesothelioma/chemically induced/epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure ; Pleural Diseases/chemically induced/epidemiology ; Poland/epidemiology ; Population Surveillance ; }, abstract = {BACKGROUND: Occupational exposure to asbestos constitutes a major public health concern. Despite this in many countries, data and registration systems for occupational asbestos-related diseases are non-existent or poorly developed.<br><br>AIMS: To analyse the incidence of occupational asbestos-related diseases in Poland between the years 1970 and 2015, with particular emphasis on the periods after introduction of a ban on asbestos and following introduction of a surveillance programme.<br><br>METHODS: Analysis based on all medically recognized cases, certified as occupational diseases and reported obligatorily from all over the country to the Central Register of Occupational Diseases.<br><br>RESULTS: During the period 1970-2015, 4983 cases were reported as asbestos-related diseases. The most prevalent were asbestosis, lung cancer, diseases of pleura or pericardium and mesothelioma. A considerable increase in the number of such cases from the beginning of their registration until 2004 occurred after introduction of the Amiantus programme, a nationwide programme of periodic medical examinations for former asbestos workers.<br><br>CONCLUSIONS: Introduction of a medical surveillance programme improved case recognition and allowed a more reliable estimate of the number of reported asbestos-related diseases.}, }
@article {pmid28197633, year = {2017}, author = {Mawas, AS and Amatya, VJ and Suzuki, R and Kushitani, K and Mohi El-Din, MM and Takeshima, Y}, title = {PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells.}, journal = {International journal of oncology}, volume = {50}, number = {3}, pages = {1029-1034}, doi = {10.3892/ijo.2017.3863}, pmid = {28197633}, issn = {1791-2423}, mesh = {Apoptosis/genetics ; Cell Line, Tumor ; Cell Movement/*genetics ; Cell Proliferation/*genetics ; Cell Survival/genetics ; G1 Phase Cell Cycle Checkpoints/*genetics ; Humans ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins c-pim-1/*genetics ; RNA Interference ; RNA, Small Interfering/genetics ; }, abstract = {Malignant mesothelioma is a major asbestos-related cancer with prolonged time lapse from the first exposure of asbestos to the development of mesothelioma. Most of mesothelioma patients show very poor prognosis, thus, an urgent improvement of its treatment is required by development of novel therapeutic strategies. RNA interference (RNAi) is a powerful tool in post-genomic research and cancer therapy through inhibition of gene expression. In the present study, we analyzed the function of PIM1 on mesothelioma cell lines with its knockdown by siRNA transfection. Here, we report that the downregulation of PIM1 led to suppression of cell proliferation by cell cycle arrest at G1 phase and suppression of cell invasion and migration. Considering the mesothelioma as rapidly growing invasive cancer, downregulation of PIM1 may have a potential role for therapeutic management of malignant mesothelioma.}, }
@article {pmid28197626, year = {2017}, author = {Cregan, S and Breslin, M and Roche, G and Wennstedt, S and MacDonagh, L and Albadri, C and Gao, Y and O'Byrne, KJ and Cuffe, S and Finn, SP and Gray, SG}, title = {Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {50}, number = {3}, pages = {1044-1052}, doi = {10.3892/ijo.2017.3870}, pmid = {28197626}, issn = {1791-2423}, mesh = {Apoptosis/drug effects ; Benzazepines/*therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Cell Survival/drug effects ; Cisplatin/therapeutic use ; Cytokines/*biosynthesis ; Gene Expression Regulation, Neoplastic ; Histone Demethylases/*biosynthesis/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases/*biosynthesis/genetics ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mesothelioma/*drug therapy/genetics/pathology ; Mesothelioma, Malignant ; Nuclear Proteins/*biosynthesis/genetics ; Pemetrexed/therapeutic use ; Pyrimidines/*therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes. As such these genes could potentially represent novel candidate targets for intervention in MPM. Using RT-PCR we examined the expression of Kdm6aA and Kdm6b in a panel of MPM cell lines and in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic and sarcomatoid histologies. Both Kdm6a and Kdm6b were found to be significantly overexpressed in MPM at the mRNA level. However, tests examining if targeting therapeutically Kdm6a/b using a specific small molecule inhibitor (GSK-J4) was potentially useful for treating MPM, revealed that anti-proliferative activity was higher at lower drug concentrations in cell lines derived from normal mesothelial cells compared to those derived from malignant cells. Treatments with GSK-J4 were found to be associated with the induction of apoptosis and increased expression of pro-inflammatory cytokines. As such our results demonstrate that whilst members of the Kdm6 family are overexpressed in MPM they may not be suitable candidates for therapy and may elicit a cytokine storm.}, }
@article {pmid28191281, year = {2016}, author = {Nabavi, N and Bennewith, KL and Churg, A and Wang, Y and Collins, CC and Mutti, L}, title = {Switching off malignant mesothelioma: exploiting the hypoxic microenvironment.}, journal = {Genes &amp; cancer}, volume = {7}, number = {11-12}, pages = {340-354}, pmid = {28191281}, issn = {1947-6019}, abstract = {Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy. We then explore the concept that the intrinsic hypoxic microenvironment of mesotheliomas can be Achilles' heel for targeted, multimodal therapeutic intervention.}, }
@article {pmid28188891, year = {2017}, author = {Bonassi, S and Cellai, F and Munnia, A and Ugolini, D and Cristaudo, A and Neri, M and Milić, M and Bonotti, A and Giese, RW and Peluso, ME}, title = {3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers.}, journal = {Toxicology letters}, volume = {270}, number = {}, pages = {1-7}, pmid = {28188891}, issn = {1879-3169}, support = {P42 ES017198/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Asbestos/blood/*toxicity ; Biomarkers/blood ; Cross-Sectional Studies ; DNA Adducts/*blood ; Deoxyguanosine/blood/*toxicity ; Educational Status ; Humans ; Italy ; Lipid Peroxidation/drug effects ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Oxidative Stress/drug effects ; Purine Nucleosides/blood/*toxicity ; Reactive Oxygen Species/metabolism ; Smoking ; }, abstract = {Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. M1dG per 10[8] normal nucleotides were 4.0±0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3±0.1 (SE) in 171 controls (p<0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9±0.3 (SE)), and in 102 former asbestos workers (4.5±0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p=0.005). Our study gives additional support to the oxidative stress theory, where M1dG may reflect an additional potential mechanism of asbestos-induced toxicity.}, }
@article {pmid28186988, year = {2017}, author = {Pellegrini, L and Xue, J and Larson, D and Pastorino, S and Jube, S and Forest, KH and Saad-Jube, ZS and Napolitano, A and Pagano, I and Negi, VS and Bianchi, ME and Morris, P and Pass, HI and Gaudino, G and Carbone, M and Yang, H}, title = {HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {14}, pages = {22649-22661}, pmid = {28186988}, issn = {1949-2553}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Biomarkers, Tumor/*metabolism ; Cell Movement ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; HMGB1 Protein/*antagonists &amp; inhibitors/metabolism ; Humans ; Mesothelioma/metabolism/pathology/*prevention &amp; control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Staging ; Prognosis ; Pyruvates/*pharmacology ; Signal Transduction ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Human malignant mesothelioma (MM) is an aggressive cancer linked to asbestos and erionite exposure. We previously reported that High-Mobility Group Box-1 protein (HMGB1), a prototypic damage-associated molecular pattern, drives MM development and sustains MM progression. Moreover, we demonstrated that targeting HMGB1 inhibited MM cell growth and motility in vitro, reduced tumor growth in vivo, and prolonged survival of MM-bearing mice. Ethyl pyruvate (EP), the ethyl ester of pyruvic acid, has been shown to be an effective HMGB1 inhibitor in inflammation-related diseases and several cancers. Here, we studied the effect of EP on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model. We found that EP impairs HMGB1 secretion by MM cells leading to reduced RAGE expression and NF-κB activation. As a consequence, EP impaired cell motility, cell proliferation, and anchorage-independent growth of MM cells. Moreover, EP reduced HMGB1 serum levels in mice and inhibited the growth of MM xenografts.Our results indicate that EP effectively hampers the malignant phenotype of MM, offering a novel potential therapeutic approach to patients afflicted with this dismal disease.}, }
@article {pmid28168071, year = {2017}, author = {Ramirez Sevilla, C and Admella Salvador, C and Feliu Canaleta, J and Llopis Manzanera, J and Barranco Sanz, MA and Romero Martin, JA and Bernal Salguero, S}, title = {Two Case Reports of Benign Testicular Mesothelioma and Review of the Literature.}, journal = {Case reports in oncological medicine}, volume = {2017}, number = {}, pages = {5419635}, pmid = {28168071}, issn = {2090-6706}, abstract = {Mesothelioma is usually diagnosed in people over the age of 50 with large history of asbestos-related exposure. It is frequently located in pleural cavity, peritoneum, and pericardium. At the testicles the mesothelioma had been reported first in 1957 like a malignant non-germ-cells tumor. The objective is to present two case reports of benign testicular mesothelioma and review of the literature.}, }
@article {pmid28166467, year = {2018}, author = {Rusiecki, J and Stewart, P and Lee, D and Alexander, M and Krstev, S and Silverman, D and Blair, A}, title = {Mortality among Coast Guard Shipyard workers: A retrospective cohort study of specific exposures.}, journal = {Archives of environmental &amp; occupational health}, volume = {73}, number = {1}, pages = {4-18}, doi = {10.1080/19338244.2017.1289891}, pmid = {28166467}, issn = {2154-4700}, mesh = {Adult ; Baltimore/epidemiology ; Cohort Studies ; Construction Industry/*statistics &amp; numerical data ; Environmental Pollutants/*toxicity ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology/*mortality ; Male ; Mesothelioma/chemically induced/epidemiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/epidemiology/*mortality ; *Occupational Exposure ; Respiratory Tract Neoplasms/chemically induced/epidemiology/*mortality ; Retrospective Studies ; *Ships ; Young Adult ; }, abstract = {In a previous analysis of a cohort of shipyard workers, we found excess mortality from all causes, lung cancer, and mesothelioma for longer work durations and in specific occupations. Here, we expand the previous analyses by evaluating mortality associated with 5 chemical exposures: asbestos, solvents, lead, oils/greases, and wood dust. Data were gathered retrospectively for 4,702 workers employed at the Coast Guard Shipyard, Baltimore, MD (1950-1964). The cohort was traced through 2001 for vital status. Associations between mortality and these 5 exposures were calculated via standardized mortality ratios (SMRs). We found all 5 substances to be independently associated with mortality from mesothelioma, cancer of the respiratory system, and lung cancer. Findings from efforts to evaluate solvents, lead, oils/greases, and wood dust in isolation of asbestos suggested that the excesses from these other exposures may be due to residual confounding from asbestos exposure.}, }
@article {pmid28162043, year = {2017}, author = {Smargiassi, A and Pasciuto, G and Pedicelli, I and Lo Greco, E and Calvello, M and Inchingolo, R and Schifino, G and Capoluongo, P and Patriciello, P and Manno, M and Cirillo, A and Corbo, GM and Soldati, G and Iavicoli, I}, title = {Chest ultrasonography in health surveillance of asbestos-related lung diseases.}, journal = {Toxicology and industrial health}, volume = {33}, number = {6}, pages = {537-546}, doi = {10.1177/0748233716686916}, pmid = {28162043}, issn = {1477-0393}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/*diagnostic imaging ; Body Mass Index ; Cohort Studies ; Humans ; Lung/*diagnostic imaging/drug effects ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {OBJECTIVES: Exposure to asbestos fibers can lead to different lung diseases, such as pleural thickening and effusion, asbestosis, mesothelioma, and lung cancer. These diseases are expected to peak in the next few years. The aim of the study was to validate ultrasonography (US) as a diagnostic tool in the management of lung diseases in subjects with a history of occupational exposure to asbestos.<br><br>METHODS: Fifty-nine retired male workers previously exposed to asbestos were enrolled in the study. Chest US was performed in all the subjects. The US operator was blinded to earlier performed computed tomography (CT) scan reports and images. The sonographic pathological findings were pleural thickening (with or without calcifications), peripheral lung consolidation, and focal sonographic interstitial syndrome and diffuse pneumogenic sonographic interstitial syndrome (pulmonary asbestosis). Significant US findings were recorded, stored, and subsequently compared with CT scans.<br><br>RESULTS: With some patients falling into more than one category, on CT scan, pleural thickening was reported in 33 cases (56%, 26 with calcifications), focal interstitial peripheral alterations in 23 (39%), asbestosis in 6 (10%), and peripheral lung consolidation in 13 cases (22%). Comparing each pathological condition to CT scan reports, US findings had high levels of sensitivity, specificity, positive, and negative predictive values. US did not prove effective for the detection of central lung nodules or diaphragmatic pleural thickenings. Chest US was considered to be the best technique to detect minimal pleural effusions (six subjects, 10%).<br><br>CONCLUSIONS: Chest US might be considered an additional tool to follow up subjects occupationally exposed to asbestos who have already undergone CT scan examination and whose pathology is detectable by US as well.}, }
@article {pmid28153512, year = {2017}, author = {Petrella, F and Coccè, V and Masia, C and Milani, M and Salè, EO and Alessandri, G and Parati, E and Sisto, F and Pentimalli, F and Brini, AT and Pessina, A and Spaggiari, L}, title = {Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {87}, number = {}, pages = {755-758}, doi = {10.1016/j.biopha.2017.01.118}, pmid = {28153512}, issn = {1950-6007}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Delivery Systems/methods ; Drug Liberation ; Humans ; Lung Neoplasms/*drug therapy ; Mesenchymal Stem Cells/*drug effects ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Paclitaxel/*pharmacology ; Pemetrexed/pharmacology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare fatal asbestos-related malignancy originating in the mesothelial cells of the pleura. A platinum-based doublet containing a third-generation antifolate is the front-line standard of care whilst there are no approved second-line treatments for MPM which remains a disease setting to test the efficacy of new therapeutic agents.<br><br>METHODS: Bone marrow mesenchymal stromal cells (BM-MSCs) were loaded with pemetrexed (PMX) and paclitaxel (PTX) according to a standardized procedure. Drug release by both PMX- and PTX-primed BM-MSCs (BM-MSCs/PMX and BM-MSCs/PTX) was tested on the in vitro proliferation of a panel of tumor cell lines including NCI-H28 mesothelioma.<br><br>RESULTS: The in vitro anticancer activity of pure PTX was significantly higher than that of PMX against all the cell lines tested (14.7 times higher than that of PMX against NCI-H28). Whereas BM-MSCs did not take up and release PMX in amounts effective on mesothelioma, PTX-loaded BM-MSCs dramatically inhibited mesothelioma proliferation.<br><br>CONCLUSIONS: PTX-primed mesenchymal stromal cells successfully inhibit the in vitro proliferation of human mesothelioma cells. Further studies and in vivo testing are required to confirm our preliminary in vitro results as a potential new mesothelioma therapy based on cell drug delivery.}, }
@article {pmid28151477, year = {2017}, author = {Zonca, S and Pinton, G and Wang, Z and Soluri, MF and Tavian, D and Griffin, M and Sblattero, D and Moro, L}, title = {Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia.}, journal = {Cell death &amp; disease}, volume = {8}, number = {2}, pages = {e2592}, pmid = {28151477}, issn = {2041-4889}, mesh = {Adaptation, Biological/genetics ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cell Survival/*genetics ; GTP-Binding Proteins/*genetics ; Gene Expression Regulation, Neoplastic ; Gene Silencing/physiology ; Humans ; Hypoxia/*genetics/pathology ; Lung Neoplasms/*genetics/pathology ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/*genetics/pathology ; Protein Glutamine gamma Glutamyltransferase 2 ; Transglutaminases/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment.}, }
@article {pmid28139858, year = {2017}, author = {Linton, A and Soeberg, M and Broome, R and Kao, S and van Zandwijk, N}, title = {Geographic and socioeconomic factors in patients with malignant pleural mesothelioma in New South Wales and their impact upon clinical outcomes.}, journal = {Respirology (Carlton, Vic.)}, volume = {22}, number = {5}, pages = {978-985}, doi = {10.1111/resp.12981}, pmid = {28139858}, issn = {1440-1843}, mesh = {Adult ; Aged ; Female ; Humans ; Incidence ; Lung Neoplasms/*diagnosis/*epidemiology/therapy ; Male ; Mesothelioma/*diagnosis/*epidemiology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Multivariate Analysis ; New South Wales/epidemiology ; Pleural Neoplasms/*diagnosis/*epidemiology/therapy ; Pneumonectomy ; Prognosis ; Proportional Hazards Models ; Registries ; Socioeconomic Factors ; }, abstract = {BACKGROUND AND OBJECTIVE: Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM.<br><br>METHODS: We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed.<br><br>RESULTS: We identified 910 patients (67% residing in major cities; 92% <50&#x2009;km from MDT). Median overall survival was 10.0&#x2009;months. On multivariate analysis, age >70 (hazard ratio (HR)&#x2009;=&#x2009;1.39), male gender (HR&#x2009;=1.36), non-epithelioid histological subtype (HR&#x2009;=&#x2009;2.18) and IRSAD status by decreasing quintile (HR&#x2009;=&#x2009;1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6&#x2009;months vs 8.8&#x2009;months; P&#x2009;=&#x2009;0.162) or within 50&#x2009;km of MDT (10.3&#x2009;months vs 7.8&#x2009;months; P&#x2009;=&#x2009;0.539). Patient's geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P&#x2009;=&#x2009;0.001).<br><br>CONCLUSION: This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW.}, }
@article {pmid28133921, year = {2017}, author = {Gualtieri, AF}, title = {Sharing different perspectives to understand asbestos-induced carcinogenesis: A comment to Jiang et al. (2016).}, journal = {Cancer science}, volume = {108}, number = {1}, pages = {156-157}, pmid = {28133921}, issn = {1349-7006}, mesh = {*Asbestos ; *Carcinogenesis ; Humans ; Mesothelioma/chemically induced ; }, abstract = {This letter reports some constructive observations on the recent findings by Jiang et al. Cancer Sci (2016) that have inspired a more general comment on how the research on asbestos should take advantage of the different existing multidisciplinary perspectives so to flow into a final comprehensive model of asbestos‐induced carcinogenesis.}, }
@article {pmid28133000, year = {2017}, author = {Micolucci, L and Rippo, MR and Olivieri, F and Procopio, AD}, title = {Progress of research on microRNAs with diagnostic value in asbestos exposure: A call for method standardization.}, journal = {Bioscience trends}, volume = {11}, number = {1}, pages = {105-109}, doi = {10.5582/bst.2016.01249}, pmid = {28133000}, issn = {1881-7823}, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/metabolism ; Environmental Exposure/*analysis ; Humans ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/*genetics/metabolism ; Reference Standards ; }, abstract = {Malignant mesothelioma (MM) is an insidious, lethal asbestos-related cancer that is poorly responsive to current treatments. Specific and sensitive biomarkers providing early MM diagnosis in exposed subjects, who are at high-risk of developing it, are sorely needed. MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs with a well-established diagnostic role in cancer and pollution exposure. In a recent systematic review and qualitative meta-analysis followed by a functional investigation, we examined all the available data on the miRNA biomarkers involved in asbestos exposure and MM pathways. This invited commentary aims to provide an insightful critique into the state of the art of the research into clinically relevant miRNA biomarkers, highlighting the strengths and weaknesses of current research efforts in this field. It also reviews the suggestions advanced to improve biomarker development productivity and the translation of research results into clinical practice, stressing that multicenter multidisciplinary studies adopting standardized methods and protocol sharing are the key to move from the workbench to the clinic.}, }
@article {pmid28132991, year = {2016}, author = {Kaneko, M and Minamikawa, T and Taniguchi, H and Yamada, Y and Nakamura, J and Okihara, K and Nakauchi, H}, title = {[MALIGNANT MESOTHELIOMA OF THE TUNICA VAGINALIS TESTIS: A CASE REPORT].}, journal = {Nihon Hinyokika Gakkai zasshi. The japanese journal of urology}, volume = {107}, number = {1}, pages = {44-47}, doi = {10.5980/jpnjurol.107.44}, pmid = {28132991}, issn = {0021-5287}, mesh = {Aged, 80 and over ; Cytodiagnosis ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology/*surgery ; Magnetic Resonance Imaging ; Male ; Mesothelioma/complications/*diagnosis/pathology/*surgery ; Mesothelioma, Malignant ; Orchiectomy/methods ; Testicular Hydrocele/etiology/pathology/surgery ; Testicular Neoplasms/complications/*diagnosis/pathology/*surgery ; Ultrasonography ; }, abstract = {We report here a case of malignant mesothelioma of the tunica vaginalis testis. A 93-year-old man with no history of asbestos exposure complained of increase of right scrotum size with pain. Ultrasonography and magnetic resonance imaging revealed a right hydrocele testis. A cytologic examination of the hydrocele fluid demonstrated mesothelial cells but show less atypicality and lack of obvious malignant features (class IIIa). We performed right hydrocelectomy for hydrocele testis. The pathological diagnosis was epithelial type of malignant mesothelioma of the tunica vaginalis testis, therefore we performed radical orchidectomy with wide excision of hemi-scrotal wall. There is no evidence of recurrence after 6 months of follow up. Malignant mesothelioma of the tunica vaginalis is rare, and accurate preoperative diagnosis is difficult. When a rapid increasing hemorrhagic hydrocele testis or nodular masses of the tunica vaginalis was observed, malignant mesothelioma should be considered. Malignant mesothelioma is highly fatal disease. Even two stage operation, radical orchidectomy should be performed.}, }
@article {pmid28123552, year = {2017}, author = {Nakamura, K and Nakayama, K and Nagaoka, R and Nishisako, K and Ishikawa, M and Katagiri, H and Ishibashi, T and Sato, E and Amano, C and Kyo, S}, title = {The diagnostic utility of PAX8 immunostaining of malignant peritoneal mesothelioma presenting as serous ovarian carcinoma: A single-center report of two cases.}, journal = {Oncology letters}, volume = {13}, number = {1}, pages = {263-266}, pmid = {28123552}, issn = {1792-1074}, abstract = {Malignant peritoneal mesotheliomas (MPMs) are rare and progressive tumors, which may present similarly to primary peritoneal carcinoma or ovarian carcinoma (OC). The current study reports two cases of MPM that initially presented with the features of OC, for which paired box 8 (PAX8) immunostaining was found to be useful for diagnosis. The two patients were women, aged 58 and 56 years, respectively. The primary presenting symptoms and clinical findings included prolonged abdominal pain, abdominal swelling and cough. The two cases were initially diagnosed as OC and were treated with primary debulking surgery. The patient in case 1 had no history of asbestos exposure, while the patient in case 2 did. Final diagnoses were determined based on histological and immunohistochemical results, which included negative PAX8 immunostaining, and which were consistent with MPM. The present cases demonstrated that PAX8 negativity may be a useful diagnostic biomarker for differentiating MPM from OC.}, }
@article {pmid28105159, year = {2016}, author = {Fasano, M and Della Corte, CM and Vicidomini, G and Scotti, V and Rambaldi, PF and Fiorelli, A and Accardo, M and De Vita, F and Santini, M and Ciardiello, F and Morgillo, F}, title = {Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review.}, journal = {Oncology letters}, volume = {12}, number = {6}, pages = {4505-4509}, pmid = {28105159}, issn = {1792-1074}, abstract = {Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of 'acute abdomen', an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM.}, }
@article {pmid28095707, year = {2018}, author = {Si, S and Peters, S and Reid, A}, title = {Variations in mesothelioma mortality rates among migrants to Australia and Australian-born.}, journal = {Ethnicity &amp; health}, volume = {23}, number = {5}, pages = {480-487}, doi = {10.1080/13557858.2017.1280138}, pmid = {28095707}, issn = {1465-3419}, mesh = {Adolescent ; Adult ; Africa/ethnology ; Aged ; Asia/ethnology ; Australia/epidemiology ; Emigrants and Immigrants/*statistics &amp; numerical data ; Europe/ethnology ; Female ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Australia's use and consumption of asbestos occurred at the same time as its immigration boom. Our objective was to investigate mesothelioma death rates among migrants and Australian-born between 1981 and 2012.<br><br>METHODS: Australian national mesothelioma deaths from 1981 to 2002 and 2006 to 2012 together with national censuses from 1981 to 2011 were extracted and combined. Directly standardised rates and negative binomial regression were applied examining differences in mesothelioma death rates with regard to country of birth.<br><br>RESULTS: Migrants from the UK and Ireland, Italy and Germany had significantly higher mesothelioma death rates than Australian-born; lower rates were observed among migrants from other countries.<br><br>CONCLUSIONS: Our findings suggest there may have been differences in occupational health and safety between foreign and Australian-born. Because of changes in the demographics of migrants to Australia since the 1970s and changes in occupational circumstances over time, further comparisons of occupational-related health outcomes between foreign and Australian-born could identify potential occupational inequalities that may still exist today.}, }
@article {pmid28090191, year = {2016}, author = {Sohn, EJ and Won, G and Lee, J and Yoon, SW and Lee, I and Kim, HJ and Kim, SH}, title = {Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell.}, journal = {International journal of biological sciences}, volume = {12}, number = {11}, pages = {1279-1288}, pmid = {28090191}, issn = {1449-2288}, mesh = {Apoptosis/drug effects ; Blotting, Western ; Cell Cycle/drug effects ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/*drug effects ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Mesothelioma/*metabolism/*pathology ; Mesothelioma, Malignant ; MicroRNAs/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Transfection ; Triterpenes/*pharmacology ; Ursolic Acid ; }, abstract = {Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/β), β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, β-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.}, }
@article {pmid28079278, year = {2017}, author = {Egilman, D and Monárrez, R}, title = {Corporate corruption of science-Another asbestos example.}, journal = {American journal of industrial medicine}, volume = {60}, number = {2}, pages = {152-162}, doi = {10.1002/ajim.22686}, pmid = {28079278}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Australia/epidemiology ; Automobiles ; Carcinogens/*toxicity ; Humans ; *Industry ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Registries ; Research Design ; *Research Support as Topic ; }, abstract = {BACKGROUND: Kelsh et al. [2007]: Occup Med (Lond) 57:581-589 published a paper reanalyzing one of the few data sources publicly available on mesothelioma amongst brake workers, the Australian Mesothelioma Surveillance Registry (AMSR). This reanalysis was commissioned by lawyers representing the automobile manufacturing companies and did not align with an independent analysis published by Leigh and Driscoll [2003]: Occup Environ Health 9:206-217.<br><br>METHODS: We sought to reevaluate the AMSR data ourselves to understand how the company-sponsored research categorized the data.<br><br>RESULTS: In our re-analysis of the 78 brake-related folios in the AMSR, we determined that 57 were employed brake mechanics, 35 were employed brake mechanics with no other asbestos exposure besides brake work or repair, and 41 of these cases had no other asbestos exposure besides brake work or repair. Our classifications differed significantly from Kelsh et al.<br><br>CONCLUSIONS: We discuss how Kelsh et al. methodically reduced the relevant cases by following overly stringent criteria for inclusion. Am. J. Ind. Med. 60:152-162, 2017. &#xa9; 2017 Wiley Periodicals, Inc.}, }
@article {pmid28066892, year = {2017}, author = {Grosso, F and Croce, A and Trincheri, NF and Mariani, N and Libener, R and Degiovanni, D and Rinaudo, C}, title = {Asbestos fibres detected by scanning electron microscopy in the gallbladder of patients with malignant pleural mesothelioma (MPM).}, journal = {Journal of microscopy}, volume = {266}, number = {1}, pages = {48-54}, doi = {10.1111/jmi.12517}, pmid = {28066892}, issn = {1365-2818}, mesh = {Aged ; Asbestos/*analysis ; Female ; Gallbladder/*pathology ; Gallbladder Diseases/*pathology ; Histocytochemistry ; Humans ; Immunohistochemistry ; Lung Neoplasms/*complications ; Male ; Mesothelioma/*complications ; Mesothelioma, Malignant ; *Microscopy, Electron, Scanning ; Pleural Neoplasms/*complications ; Spectrometry, X-Ray Emission ; }, abstract = {Gallbladders from patients affected by both malignant pleural mesothelioma (MPM) and important gallbladder disorders were analyzed to verify the presence of asbestos fibres. Histological thin sections were analyzed by optical microscope and variable pressure scanning electron microscopy coupled with energy dispersive spectroscopy, allowing morphological and chemical characterization of each inorganic phase observed. Fibres of chrysotile and crocidolite, minerals regulated as asbestos, were identified. By immunohistochemical analysis, connective tissue was recognized as the incorporation site. These findings confirm that asbestos fibres can reach the gallbladders of patients with MPM, for whom the development of respiratory diseases confirms asbestos exposure.}, }
@article {pmid28066660, year = {2016}, author = {Wang, XB and Yin, Y and Miao, Y and Eberhardt, R and Hou, G and Herth, FJ and Kang, J}, title = {Flex-rigid pleuroscopic biopsy with the SB knife Jr is a novel technique for diagnosis of malignant or benign fibrothorax.}, journal = {Journal of thoracic disease}, volume = {8}, number = {11}, pages = {E1555-E1559}, pmid = {28066660}, issn = {2072-1439}, abstract = {Diagnosing pleural effusion is challenging, especially in patients with malignant or benign fibrothorax, which is difficult to sample using standard flexible forceps (SFF) via flex-rigid pleuroscopy. An adequate sample is crucial for the differential diagnosis of malignant fibrothorax (malignant pleural mesothelioma, metastatic lung carcinoma, etc.) from benign fibrothorax (benign asbestos pleural disease, tuberculous pleuritis, etc.). Novel biopsy techniques are required in flex-rigid pleuroscopy to improve the sample size and quality. The SB knife Jr, which is a scissor forceps that uses a mono-pole high frequency, was developed to allow convenient and accurate resection of larger lesions during endoscopic dissection (ESD). Herein, we report two patients with fibrothorax who underwent a pleural biopsy using an SB knife Jr to investigate the potential use of this tool in flex-rigid pleuroscopy when pleural lesions are difficult to biopsy via SFF. The biopsies were successful, with sufficient size and quality for definitive diagnosis. We also successfully performed adhesiolysis with the SB knife Jr in one case, and adequate biopsies were conducted. No complications were observed. Electrosurgical biopsy with the SB knife Jr during flex-rigid pleuroscopy allowed us to obtain adequate samples for the diagnosis of malignant versus benign fibrothorax, which is usually not possible with SFF. The SB knife Jr also demonstrated a potential use for pleuropulmonary adhesions.}, }
@article {pmid28056339, year = {2017}, author = {Thompson, JK and MacPherson, MB and Beuschel, SL and Shukla, A}, title = {Asbestos-Induced Mesothelial to Fibroblastic Transition Is Modulated by the Inflammasome.}, journal = {The American journal of pathology}, volume = {187}, number = {3}, pages = {665-678}, pmid = {28056339}, issn = {1525-2191}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Biomarkers/metabolism ; Caspase 1/metabolism ; Cell Line ; Cell Shape/genetics ; Epithelial Cells/metabolism/pathology ; Epithelium/metabolism/*pathology ; Fibroblasts/metabolism/*pathology ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammasomes/*metabolism ; Interleukin-1beta/metabolism ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Peritoneum/metabolism/pathology ; Signal Transduction/genetics ; }, abstract = {Despite the causal relationship established between malignant mesothelioma (MM) and asbestos exposure, the exact mechanism by which asbestos induces this neoplasm and other asbestos-related diseases is still not well understood. MM is characterized by chronic inflammation, which is believed to play an intrinsic role in the origin of this disease. We recently found that asbestos activates the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in a protracted manner, leading to an up-regulation of IL-1β and IL-18 production in human mesothelial cells. Combined with biopersistence of asbestos fibers, we hypothesize that this creates an environment of chronic IL-1β signaling in human mesothelial cells, which may promote mesothelial to fibroblastic transition (MFT) in an NLRP3-dependent manner. Using a series of experiments, we found that asbestos induces a fibroblastic transition of mesothelial cells with a gain of mesenchymal markers (vimentin and N-cadherin), whereas epithelial markers, such as E-cadherin, are down-regulated. Use of siRNA against NLRP3, recombinant IL-1β, and IL-1 receptor antagonist confirmed the role of NLRP3 inflammasome-dependent IL-1β in the process. In vivo studies using wild-type and various inflammasome component knockout mice also revealed the process of asbestos-induced mesothelial to fibroblastic transition and its amelioration in caspase-1 knockout mice. Taken together, our data are the first to suggest that asbestos induces mesothelial to fibroblastic transition in an inflammasome-dependent manner.}, }
@article {pmid28054314, year = {2017}, author = {Plönes, T and Fischer, M and Höhne, K and Sato, H and Müller-Quernheim, J and Zissel, G}, title = {Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis.}, journal = {Pathology oncology research : POR}, volume = {23}, number = {4}, pages = {723-730}, pmid = {28054314}, issn = {1532-2807}, mesh = {Cell Line, Tumor ; Cell Proliferation/genetics ; Chemotaxis/genetics ; Drug Resistance, Neoplasm/genetics ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Neoplasm Invasiveness/genetics ; Pleural Neoplasms/*genetics/*pathology ; WT1 Proteins/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the surface of the pleura and is associated with a history of asbestos exposure. The tumor is characterized by a strong local invasiveness and a poor response to any single modality therapy. Therefore clinical outcome of patients with MPM is poor and median survival time of untreated patients with MPM is 7 months from initial diagnosis. The Wilms Tumor Protein 1 (WT1) is a transcription factor which is highly expressed by MPM and is involved in cellular development and survival. We evaluated the role of WT1 in two human MPM cell lines (MSTO and H2052) expressing high levels of WT1. We performed a knockdown of WT1 using siRNA. Knockdown of WT1 was confirmed by Westernblotting. After knockdown of WT1 we investigated the effect on proliferation, chemoresistance, chemotaxis and migration. We could demonstrate that knockdown of WT1 suppresses chemoresistance in both cell lines compared with control (scrambled siRNA). Additionally, WT1 knockdown reduces proliferation, chemotaxis and invasiveness of mesothelioma cell lines. WT1 reduces malignancy of malignant mesothelioma cell lines and might be a new molecular target in mesothelioma therapy. Further investigations are needed to discover the mechanisms of chemoresistance depending on WT1.}, }
@article {pmid28051835, year = {2016}, author = {Fallahi, P and Ragusa, F}, title = {Mesothelioma and interferon-γ-dependent chemokine IP-10.}, journal = {La Clinica terapeutica}, volume = {167}, number = {6}, pages = {e192-e197}, pmid = {28051835}, issn = {1972-6007}, mesh = {Adult ; Animals ; Apoptosis/drug effects ; Asbestos/adverse effects ; Asbestosis/immunology ; CD8-Positive T-Lymphocytes ; Chemokine CXCL10/*metabolism ; Female ; Humans ; Interferon-gamma/metabolism ; Lung Neoplasms/*immunology ; Male ; Mesothelioma/*immunology ; Mesothelioma, Malignant ; Rats ; Receptors, CXCR3 ; }, abstract = {Recently it has been shown that interferon (IFN)-γ plays an important role in mesothelioma, mediated by the main IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ- induced protein 10 (IP-10). IP-10 is up-regulated in malignant mesothelioma (MM), suggesting a relationship with development of these tumors. Nanoparticles containing nickel, that increase the risk for pleural diseases, induced increased levels of IP-10 in rat pleural mesothelial cells. Chemokine (C-X-C motif) receptor (CXCR)3 expression in CD4(+) T cells from pleural plaques and MMs was significantly decreased compared with that from healthy donors suggesting that CXCR3, IFN-γ, and IP-10 may be candidates to detect and monitor disease status. In a patient with asbestos-related malignant pleural mesothelioma the oncolytic adenovirus (ONCOS-102) induced prominent infiltration of CD8(+) lymphocytes to tumor, marked induction of systemic antitumor CD8(+) T-cells and expression of IP-10. Furthermore, increased IP- 10 concentrations were observed in the sera of the asbestos-exposed workers and were associated with the severity of asbestos-related diseases. These findings suggest that IP-10 chemokine may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by nonmalignant asbestos-related diseases.}, }
@article {pmid28050426, year = {2016}, author = {Batahar, SA and Ouradi, O and Elidrissi, S and Amro, L}, title = {Pleural Mesothelioma with No Asbestos Exposure: A Case Report.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {10}, number = {11}, pages = {OD07-OD08}, pmid = {28050426}, issn = {2249-782X}, abstract = {Malignant Pleural Mesothelioma (MPM) is the primary malignant tumour of the pleura. It is highly aggressive and linked to the exposure to asbestos fibers. The prognosis of this cancer is bad with a median of survival around 12 months. The diagnosis of pleural mesothelioma is often done at an advanced stage of the disease because of the lack of specific clinical and radiological signs differentiating it from any malignant pleural effusion. The absence of an explicit asbestos exposure is another diagnosis problem. We report the case of a 60-year-old patient without any prior exposure to asbestos who presented for pleural effusion and a nodular thickening of the pleura on the CT scan. The diagnosis of MPM was confirmed after pathology study of the biopsies obtained by video assisted thoracoscopy.}, }
@article {pmid28038708, year = {2017}, author = {Wu, D and Hiroshima, K and Yusa, T and Ozaki, D and Koh, E and Sekine, Y and Matsumoto, S and Nabeshima, K and Sato, A and Tsujimura, T and Yamakawa, H and Tada, Y and Shimada, H and Tagawa, M}, title = {Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma.}, journal = {Annals of diagnostic pathology}, volume = {26}, number = {}, pages = {31-37}, doi = {10.1016/j.anndiagpath.2016.10.010}, pmid = {28038708}, issn = {1532-8198}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence/methods ; Male ; Mesothelioma/*diagnosis/*genetics ; Middle Aged ; Pleural Neoplasms/*diagnosis/genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.}, }
@article {pmid28034829, year = {2017}, author = {Leblay, N and Leprêtre, F and Le Stang, N and Gautier-Stein, A and Villeneuve, L and Isaac, S and Maillet, D and Galateau-Sallé, F and Villenet, C and Sebda, S and Goracci, A and Byrnes, G and McKay, JD and Figeac, M and Glehen, O and Gilly, FN and Foll, M and Fernandez-Cuesta, L and Brevet, M}, title = {BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {4}, pages = {724-733}, doi = {10.1016/j.jtho.2016.12.019}, pmid = {28034829}, issn = {1556-1380}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; *DNA Copy Number Variations ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/genetics/metabolism/*pathology ; Male ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; *Mutation ; Neoplasm Staging ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Pleural Neoplasms/genetics/metabolism/*pathology ; Prognosis ; Survival Rate ; Tumor Suppressor Proteins/*genetics/*metabolism ; Ubiquitin Thiolesterase/*genetics/*metabolism ; Young Adult ; }, abstract = {INTRODUCTION: Malignant mesothelioma is a deadly disease that is strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BRCA1 associated protein 1 (BAP1) is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germline and somatic inactivation of BRCA1 associated protein 1 gene (BAP1) is frequent in pleural mesothelioma; however, little is known about its status in peritoneal mesothelioma.<br><br>METHODS: Taking advantage of the extensive French National Network for the Diagnosis of Malignant Pleural Mesothelioma and Rare Peritoneal Tumors and the French National Network for the Treatment of Rare Peritoneal Surface Malignancies, we collected biological material and clinical and epidemiological data for 46 patients with peritoneal mesothelioma. The status of BAP1 was evaluated at the mutational and protein expression levels and combined with our previous data on copy number alterations assessed in the same samples.<br><br>RESULTS: We detected mutations in 32% of the malignant peritoneal mesotheliomas analyzed. In addition, we have previously reported that copy number losses occurred in 42% of the samples included in this series. Overall, 73% of&#xa0;the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele, but&#xa0;only 57% had a complete loss of its protein nuclear expression. Better overall survival was observed for patients with BAP1 mutations&#xa0;(p&#xa0;= 0.04), protein expression loss (p&#xa0;= 0.016), or at least one of these alterations (p&#xa0;= 0.007) independently of tumor histological subtype, age, and sex.<br><br>CONCLUSIONS: As in pleural mesothelioma, inactivation of BAP1 is frequent in peritoneal mesotheliomas. We found that BAP1 protein nuclear expression is a good prognostic factor and a more reliable marker for the complete loss of BAP1 activity than mutation or copy number loss.}, }
@article {pmid28026144, year = {2018}, author = {Paliogiannis, P and Putzu, C and Ginesu, GC and Cossu, ML and Feo, CF and Attene, F and Scognamillo, F and Nonnis, R and Cossu, A and Palmieri, G and Pirina, P and Fois, A}, title = {Deciduoid mesothelioma of the thorax: A comprehensive review of the scientific literature.}, journal = {The clinical respiratory journal}, volume = {12}, number = {3}, pages = {848-856}, doi = {10.1111/crj.12599}, pmid = {28026144}, issn = {1752-699X}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Chest Pain/etiology ; Cough/etiology ; Deciduoma/*pathology ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*pathology ; Prognosis ; Radiography, Thoracic/methods ; Thoracic Neoplasms/diagnostic imaging/pathology ; Tomography, X-Ray Computed/methods ; Weight Loss ; Young Adult ; }, abstract = {OBJECTIVE: Deciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available.<br><br>DATA SOURCE: English-language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database.<br><br>STUDY SELECTION: The search terms were "mesothelioma," "thoracic mesothelioma," "epithelial mesothelioma," "pleural mesothelioma," and "deciduoid mesothelioma."<br><br>RESULTS: Forty-four cases included in 16 articles, published in the period under investigation, were analyzed in detail.<br><br>CONCLUSIONS: The mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X-ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme.}, }
@article {pmid28025765, year = {2017}, author = {Lehnert, M and Kraywinkel, K and Heinze, E and Wiethege, T and Johnen, G and Fiebig, J and Brüning, T and Taeger, D}, title = {Incidence of malignant mesothelioma in Germany 2009-2013.}, journal = {Cancer causes &amp; control : CCC}, volume = {28}, number = {2}, pages = {97-105}, doi = {10.1007/s10552-016-0838-y}, pmid = {28025765}, issn = {1573-7225}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Germany/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Registries ; }, abstract = {PURPOSE: The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce.<br><br>METHODS: We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient's residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40&#xa0;years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany.<br><br>RESULTS: In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013-90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men.<br><br>CONCLUSION: Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.}, }
@article {pmid28013367, year = {2017}, author = {MacPherson, M and Westbom, C and Kogan, H and Shukla, A}, title = {Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro.}, journal = {Histochemistry and cell biology}, volume = {147}, number = {5}, pages = {595-604}, pmid = {28013367}, issn = {1432-119X}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; S10 RR019246/RR/NCRR NIH HHS/United States ; }, mesh = {Actins/antagonists &amp; inhibitors/*metabolism ; Asbestos/*adverse effects/antagonists &amp; inhibitors ; Cell Survival/drug effects ; Cells, Cultured ; Cytochalasin D/pharmacology ; Dose-Response Relationship, Drug ; Epithelial Cells/*drug effects/metabolism ; Humans ; Inflammasomes/*drug effects/metabolism ; Polymerization/drug effects ; Structure-Activity Relationship ; }, abstract = {Asbestos exposure leads to malignant mesothelioma (MM), a deadly neoplasm of mesothelial cells of various locations. Although there is no doubt about the role of asbestos in MM tumorigenesis, mechanisms are still not well explored. Recently, our group demonstrated that asbestos causes inflammasome priming and activation in mesothelial cells, which in part is dependent on oxidative stress. Our current study sheds light on yet another mechanism of inflammasome activation by asbestos. Here we show the role of actin polymerization in asbestos-induced activation of the nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Using human mesothelial cells, we first demonstrate that asbestos and carbon nanotubes induced caspase-1 activation and high-mobility group box 1, interleukin 1 beta and interleukin 18 secretion was blocked by Cytochalasin D (Cyto D) an actin polymerization inhibitor. Next, to understand the mechanism, we assessed whether phagocytosis of fibers by mesothelial cells is affected by actin polymerization inhibition. Transmission electron microscopy showed the inhibition of fiber uptake by mesothelial cells in the presence of Cyto D. Furthermore, localization of components of the inflammasome, apoptotic speck-like protein containing a CARD domain (ASC) and NLRP3, to the perinuclear space in mitochondria or endoplasmic reticulum in response to fiber exposure was also interrupted in the presence of Cyto D. Taken together, our studies suggest that actin polymerization plays important roles in inflammasome activation by fibers via regulation of phagocytosis and/or spatial localization of inflammasome components.}, }
@article {pmid28007630, year = {2017}, author = {Guo, Z and Carbone, M and Zhang, X and Su, D and Sun, W and Lou, J and Gao, Z and Shao, D and Chen, J and Zhang, G and Hu, J and Chen, K and Wang, F and Pass, HI and Yu, H and Napolitano, A and Yang, H and Mao, W}, title = {Improving the Accuracy of Mesothelioma Diagnosis in China.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {4}, pages = {714-723}, pmid = {28007630}, issn = {1556-1380}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adenocarcinoma/diagnosis/epidemiology ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Squamous Cell/diagnosis/epidemiology ; Case-Control Studies ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*diagnosis/epidemiology ; Male ; Mesothelioma/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Peritoneal Neoplasms/*diagnosis/epidemiology ; Pleural Neoplasms/*diagnosis/epidemiology ; Prognosis ; Young Adult ; }, abstract = {INTRODUCTION: In the Western world, malignant mesothelioma (MM) is most prevalent in the pleura of older males who have been professionally exposed to asbestos. Information about MM from rapidly industrializing countries such as China is minimal. There is concern that a proportion of MM diagnoses in China may be incorrect because most Chinese physicians do not have experience diagnosing this rare cancer. We recently reported an unusually high incidence of peritoneal MM among eastern Chinese female patients. Here, we review the accuracy of MM diagnoses in China and provide suggestions to improve the accuracy of diagnosis.<br><br>METHODS: We reviewed 92 pathological diagnosis of MM in 2002-2015 from two reference centers in the province of Zhejiang in eastern China. We performed a large set of immunohistochemistry analyses to increase the reliability of the diagnosis.<br><br>RESULTS: We confirmed the MM diagnosis in 12 of 34 of the pleural tumors (35.3%), in 38 of 56 of the peritoneal tumors (67.9%), and in two of two of the MMs of the tunica vaginalis (100%). MMs were characterized by tumor cells showing nuclear Wilms tumor 1 and calretinin staining and by strong membranous staining for cytokeratin CAM5.2. The results of staining for the epithelial markers carcinoembryonic antigen, thyroid transcription factor-1, MOC31, BerEP4, p63, p40, paired box 8, ER and PR were negative. BRCA1 associated protein 1 nuclear staining was lost in percentages similar to what has been reported for samples from Western countries.<br><br>CONCLUSIONS: Our findings suggest that MM-especially in its pleural localization-is often misdiagnosed in eastern China. Identifying pitfalls and possible solutions in the pathological diagnosis of MM will affect both the standard of care and research in China.}, }
@article {pmid28007619, year = {2017}, author = {Creaney, J and Robinson, BWS}, title = {Malignant Mesothelioma Biomarkers: From Discovery to Use in Clinical Practice for Diagnosis, Monitoring, Screening, and Treatment.}, journal = {Chest}, volume = {152}, number = {1}, pages = {143-149}, doi = {10.1016/j.chest.2016.12.004}, pmid = {28007619}, issn = {1931-3543}, mesh = {Biomarkers, Tumor/blood ; Early Detection of Cancer/*methods ; GPI-Linked Proteins/*blood ; Humans ; *Lung Neoplasms/blood/pathology/therapy ; Mesothelin ; *Mesothelioma/blood/pathology/therapy ; Mesothelioma, Malignant ; *Pleural Neoplasms/blood/pathology/therapy ; Prognosis ; }, abstract = {Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis with a median survival of < 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management, and the search for a mesothelioma biomarker has been ongoing for the last 30 years. Many traditional soluble (glyco)protein biomarkers have been evaluated over this time, and an ever-increasing list of new biomarkers, including messenger RNA, DNA, microRNA, and antibodies, is being reported from biomarker discovery projects. To date, soluble mesothelin is the only tumor biomarker to receive US Food and Drug Administration approval for clinical use in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface of mesothelial cells, and in the cancerous state it can be present in circulation. Mesothelin has a limited expression on normal, nonmalignant tissue and is thus an attractive therapeutic target for mesothelin-positive tumors. In this review we will focus on the discovery and clinical usages of mesothelin and provide an update on other mesothelioma biomarkers and show how such biomarker studies might impact on the management of this deadly tumor in the future.}, }
@article {pmid28002541, year = {2016}, author = {Raşcu, A and Naghi, E and OŢelea, MR and NiŢu, FM and Arghir, OC}, title = {Distinction between mesothelioma and lung adenocarcinoma based on immunohistochemistry in a patient with asbestos bodies in bronchoalveolar fluid - case report.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {57}, number = {3}, pages = {1171-1174}, pmid = {28002541}, issn = {2066-8279}, mesh = {Adenocarcinoma/*immunology/pathology ; Adenocarcinoma of Lung ; Asbestosis/pathology ; Bronchoalveolar Lavage Fluid/*cytology ; Humans ; Immunohistochemistry ; Lung Neoplasms/*immunology/pathology ; Male ; Mesothelioma/*immunology/pathology ; Middle Aged ; }, abstract = {Asbestos is a mineral-mined form the rocks, consisting in amosite (brown asbestos), crocidolite (blue asbestos) and÷or chrysotile (white asbestos) used in many industries. Researches about the exposure to asbestos dust and asbestosis related diseases started almost a century ago. The first case report of fatal asbestosis disease was published in 1906, in England, by Dr. Hubert Montague Murray. A decade after, asbestos "curious bodies" were firstly described in the lung tissue by Cooke (1926) and McDonald (1927). Occupational exposure to asbestos is now regulated in Romania, but past exposure is still a cause of asbestosis-related diseases (ARDs), including lung cancer. A peculiar association between a lung adenocarcinoma, a previously healed pulmonary tuberculosis (PTB) disease, is reported in a 61-year-old nonsmoker white man, a former factory worker with 29 years of occupational exposure history to cement and asbestos fibers. The positive diagnosis of asbestos exposure was facilitated by asbestos bodies determined in bronchoalveolar lavage fluid. The main purpose of this case report is to describe the development of a right pleural effusion which was not revelatory for a mesothelioma but for an adenocarcinoma of the lung. An accurate morphologic and immunohistochemistry assessment of a pleural biopsy sample excluded mesothelioma and was crucial in the positive diagnosis of adenocarcinoma. In conclusion, unilateral paraneoplastic pleural effusion in a nonsmoker male with occupational exposure to asbestosis fibers was suggestive for adenocarcinoma related asbestosis of the lung. Lung cancer and malignant pleural exudate developed after a long latency cumulative retention time of asbestos fibers.}, }
@article {pmid27993826, year = {2016}, author = {Yildiz, H and Andreea, SI and Hoton, D and Yombi, JC}, title = {Minimal change disease associated with malignant pleural mesothelioma: case report and review of the literature.}, journal = {BMJ case reports}, volume = {2016}, number = {}, pages = {}, pmid = {27993826}, issn = {1757-790X}, mesh = {Aged ; Biopsy ; Fatal Outcome ; Humans ; Kidney/*diagnostic imaging ; Lung Neoplasms/complications/*diagnosis ; Male ; Mesothelioma/complications/*diagnosis ; Mesothelioma, Malignant ; Nephrosis, Lipoid/complications/*diagnosis ; Pleura/*diagnostic imaging ; Pleural Neoplasms/complications/*diagnosis ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; }, abstract = {A 77-year-old man with a history of asbestos exposure was admitted to our internal medicine division for generalised weakness, fatigue, loss of weight, night sweats and difficulty for breathing since 3 months. Clinical examination revealed left fine crackles and bilateral leg oedema. Blood test showed elevated C reactive protein level at 142 mg/L, lactate dehydrogenase level at 421 UI, creatinine level at 5.75 mg/dL. Serum albumin level at 30 g/L, urinalysis showed significant proteinuria at 6.4 g/L. Chest X-ray showed left pleural effusion. Renal ultrasonography was normal. Thoracic CT and positron emission tomography showed mediastinal enlargement with lymphadenopathies and left pleural effusion and thickening. A pleural biopsy showed features compatible with malignant epithelioid mesothelioma. Renal biopsy showed minimal change disease and acute tubular necrosis. A diagnosis of malignant mesothelioma associated with minimal change disease and acute tubular necrosis secondary was then made. Given the poor general condition, palliative care was initiated and the patient died from respiratory failure 3 months later.}, }
@article {pmid27980793, year = {2016}, author = {Kang, DM and Kim, JE and Lee, YJ and Lee, HH and Lee, CY and Moon, SJ and Kang, MS}, title = {Environmental health centers for asbestos and their health impact surveys and activities.}, journal = {Annals of occupational and environmental medicine}, volume = {28}, number = {}, pages = {68}, pmid = {27980793}, issn = {2052-4374}, abstract = {In 2009, Korea banned the import, transport, and use of asbestos, and the Asbestos Injury Relief Act (AIRA) was promulgated in 2011. Two environmental health centers for asbestos (EHCA), including Pusan National University Yangsan Hospital (PNUYH) and SoonChunHyang University Cheonan Hospital (SCHUCH), were adapted to find environmental asbestos-related diseases (ARDs) and to support the purposes of AIRA. EHCA conducted a health impact survey (HIS) on persons who resided or reside near asbestos factories or mines. A total of 13,433 persons have taken screening examinations in PNUYH EHCA, and 623 persons (4.6%) have had secondary examinations. Of the 21,014 persons who had screening examinations in SCHUCH EHCA, 2490 persons (11.8%) had secondary examinations. Some of those who tested positive for ARDs through HISs filed applications for the asbestos victims' medical pocketbook (AVMP). Approximately 116 and 612 persons received AVMPs as a result of PNUYH and SCHUCH examinees, respectively. EHCAs have conducted HISs, public relations, and education for asbestos victims, ordinary citizens, and physicians. As HISs are based on voluntary participation, they does not monitor high-risk groups. Active surveillance focusing on high-risk groups has been blocked by the personal information protection act. Although important work has been performed in finding environmental asbestos victims and increasing public awareness on asbestos, it is necessary to improve the current system and registration.}, }
@article {pmid27979465, year = {2017}, author = {Siegert, CJ and Fisichella, PM and Moseley, JM and Shoni, M and Lebenthal, A}, title = {Open access phone triage for veterans with suspected malignant pleural mesothelioma.}, journal = {The Journal of surgical research}, volume = {207}, number = {}, pages = {108-114}, doi = {10.1016/j.jss.2016.08.031}, pmid = {27979465}, issn = {1095-8673}, mesh = {Aged ; Boston ; Feasibility Studies ; Health Services Accessibility/*statistics &amp; numerical data ; Humans ; Male ; Mesothelioma/*diagnosis ; Pleural Neoplasms/*diagnosis ; Referral and Consultation/statistics &amp; numerical data ; Retrospective Studies ; Telemedicine/*methods/statistics &amp; numerical data ; Telephone ; Triage/*methods/statistics &amp; numerical data ; United States ; United States Department of Veterans Affairs ; *Veterans Health ; }, abstract = {BACKGROUND: Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service.<br><br>METHODS: A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care.<br><br>RESULTS: Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14&#xa0;d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines.<br><br>CONCLUSIONS: Our initial experience demonstrates that in-network centralized care for&#xa0;Veterans with MPM is feasible within the VHA. National open access phone triage&#xa0;improves access to expert surgical advice and can be delivered in a timely manner for&#xa0;Veterans using our service. Guideline-based treatment recommendations ("intent to&#xa0;treat") changed the therapeutic course for the majority of patients who used our service.}, }
@article {pmid27941034, year = {2017}, author = {Ferrante, D and Mirabelli, D and Tunesi, S and Terracini, B and Magnani, C}, title = {Pleural mesothelioma and asbestos exposure: a case-control study with quantitative risk assessment-response to Marsh and Benson's letter.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {2}, pages = {157-158}, doi = {10.1136/oemed-2016-104091}, pmid = {27941034}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; Pleura ; *Pleural Neoplasms ; Risk Assessment ; }, }
@article {pmid27941033, year = {2017}, author = {Marsh, GM and Benson, SM}, title = {Response to: 'Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment' by Ferrante et al.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {2}, pages = {156-157}, doi = {10.1136/oemed-2016-104002}, pmid = {27941033}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; *Pleural Neoplasms ; Risk Assessment ; }, }
@article {pmid27919155, year = {2016}, author = {Di Ciaula, A and Gennaro, V}, title = {[Possible health risks from asbestos in drinking water].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {6}, pages = {472-475}, doi = {10.19191/EP16.6.P472.129}, pmid = {27919155}, issn = {1120-9763}, mesh = {Animals ; Asbestos/*adverse effects ; *Carcinogens ; Drinking Water/*analysis ; Environmental Exposure/*adverse effects ; *Gastrointestinal Neoplasms/epidemiology/etiology/prevention &amp; control ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology/prevention &amp; control ; Mineral Fibers/adverse effects ; Pleural Neoplasms/epidemiology/etiology/prevention &amp; control ; Risk Assessment ; Risk Factors ; Time Factors ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The recent finding of asbestos fibres in drinking water (up to 700.000 fibres/litres) in Tuscany (Central Italy) leads to concerns about health risks in exposed communities. Exposure to asbestos has been linked with cancer at several levels of the gastrointestinal tract, and it has been documented, in an animal model, a direct cytotoxic effect of asbestos fibres on the ileum. It has been recently described a possible link between asbestos and intrahepatic cholangiocarcinoma, and asbestos fibres have been detected in humans in histological samples from colon cancer and in gallbladder bile. Taken together, these findings suggest the possibility of an enterohepatic translocation of asbestos fibres, alternative to lymphatic translocation from lungs. In animal models, asbestos fibres ingested with drinking water act as a co-carcinogen in the presence of benzo(a) pyrene and, according to the International Agency for Research on Cancer (IARC), there is evidence pointing to a causal effect of ingested asbestos on gastric and colorectal cancer. The risk seems to be proportional to the concentration of ingested fibres, to the extent of individual water consumption, to exposure timing, and to the possible exposure to other toxics (i.e., benzo(a)pyrene). Furthermore, the exposure to asbestos by ingestion could explain the epidemiological finding of mesothelioma in subjects certainly unexposed by inhalation. In conclusion, several findings suggest that health risks from asbestos could not exclusively derive from inhalation of fibres. Health hazards might also be present after ingestion, mainly after daily ingestion of drinking water for long periods. In Italy, a systemic assessment of the presence of asbestos fibres in drinking water is still lacking, although asbestos-coated pipelines are widely diffused and still operating. Despite the fact that the existence of a threshold level for health risks linked to the presence of asbestos in drinking water is still under debate, the precautionary principle should impose all possible efforts in order to revise health policies concerning this topic, and a systematic monitoring of drinking water to quantify the presence of asbestos is certainly needed in all regions. Further epidemiological studies aimed to the identification of exposed communities and to an adequate health risk assessment in their specific geographical areas are urgently needed.}, }
@article {pmid27918607, year = {2017}, author = {Mao, W and Zhang, X and Guo, Z and Gao, Z and Pass, HI and Yang, H and Carbone, M}, title = {Association of Asbestos Exposure With Malignant Mesothelioma Incidence in Eastern China.}, journal = {JAMA oncology}, volume = {3}, number = {4}, pages = {562-564}, pmid = {27918607}, issn = {2374-2445}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; China/epidemiology ; Female ; Humans ; Lung Neoplasms/*epidemiology/*etiology/pathology ; Male ; Mesothelioma/*epidemiology/*etiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; }, }
@article {pmid27914752, year = {2017}, author = {Cruz, MJ and Curull, V and Pijuan, L and Álvarez-Simón, D and Sánchez-Font, A and de Gracia, J and Culebras, M and Ferrer, J}, title = {Utility of Bronchoalveolar Lavage for the Diagnosis of Asbestos-Related Diseases.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {6}, pages = {318-323}, doi = {10.1016/j.arbres.2016.08.016}, pmid = {27914752}, issn = {1579-2129}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestosis/diagnosis/etiology/pathology ; Bronchoalveolar Lavage Fluid/*chemistry ; Bronchoscopy ; Carcinoma/chemistry/diagnosis/etiology/pathology ; Female ; Humans ; Lung Diseases/diagnosis/*etiology/pathology ; Lung Neoplasms/chemistry/diagnosis/etiology/pathology ; Male ; Mesothelioma/chemistry/diagnosis/etiology/pathology ; Middle Aged ; Mineral Fibers/*analysis ; Occupations ; Pleural Neoplasms/chemistry/diagnosis/etiology/pathology ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD).<br><br>METHODS: BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue.<br><br>RESULTS: Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002).<br><br>CONCLUSIONS: BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content.}, }
@article {pmid27908590, year = {2017}, author = {Neyens, T and Lawson, AB and Kirby, RS and Nuyts, V and Watjou, K and Aregay, M and Carroll, R and Nawrot, TS and Faes, C}, title = {Disease mapping of zero-excessive mesothelioma data in Flanders.}, journal = {Annals of epidemiology}, volume = {27}, number = {1}, pages = {59-66.e3}, pmid = {27908590}, issn = {1873-2585}, support = {R01 CA172805/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Age Distribution ; Aged ; Bayes Theorem ; Belgium/epidemiology ; Female ; Geographic Mapping ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/ethnology ; Male ; Mesothelioma/diagnosis/*epidemiology/ethnology ; Mesothelioma, Malignant ; Middle Aged ; Pericardium ; Peritoneal Neoplasms/*epidemiology/ethnology/pathology ; Pleural Neoplasms/*epidemiology/ethnology/pathology ; Poisson Distribution ; *Registries ; Risk Assessment ; Sex Distribution ; Survival Analysis ; }, abstract = {PURPOSE: To investigate the distribution of mesothelioma in Flanders using Bayesian disease mapping models that account for both an excess of zeros and overdispersion.<br><br>METHODS: The numbers of newly diagnosed mesothelioma cases within all Flemish municipalities between 1999 and 2008 were obtained from the Belgian Cancer Registry. To deal with overdispersion, zero inflation, and geographical association, the hurdle combined model was proposed, which has three components: a Bernoulli zero-inflation mixture component to account for excess zeros, a gamma random effect to adjust for overdispersion, and a normal conditional autoregressive random effect to attribute spatial association. This model was compared with other existing methods in literature.<br><br>RESULTS: The results indicate that hurdle models with a random effects term accounting for extra variance in the Bernoulli zero-inflation component fit the data better than hurdle models that do not take overdispersion in the occurrence of zeros into account. Furthermore, traditional models that do not take into account excessive zeros but contain at least one random effects term that models extra variance in the counts have better fits compared to their hurdle counterparts. In other words, the extra variability, due to an excess of zeros, can be accommodated by spatially structured and/or unstructured random effects in a Poisson model such that the hurdle mixture model is not necessary.<br><br>CONCLUSIONS: Models taking into account zero inflation do not always provide better fits to data with excessive zeros than less complex models. In this study, a simple conditional autoregressive model identified a cluster in mesothelioma cases near a former asbestos processing plant (Kapelle-op-den-Bos). This observation is likely linked with historical local asbestos exposures. Future research will clarify this.}, }
@article {pmid27907819, year = {2017}, author = {Haji Ali, R and Khalife, M and El Nounou, G and Zuhri Yafi, R and Nassar, H and Aidibe, Z and Raad, R and Abou Eid, R and Faraj, W}, title = {Giant primary malignant mesothelioma of the liver: A case report.}, journal = {International journal of surgery case reports}, volume = {30}, number = {}, pages = {58-61}, pmid = {27907819}, issn = {2210-2612}, abstract = {INTRODUCTION: Malignant mesothelioma is a rare neoplasm of mesothelial cells arising most frequently in the pleura or peritoneum and less frequently in the liver.<br><br>CASE PRESENTATION: We present a case of primary hepatic mesothelioma of 41year old woman. She had no history of asbestos exposure or cancer. Abdominal computed tomography (CT) showed 21cm intrahepatic mass in the right lobe with many cystic lesions and few small calcifications. Pathology showed a biphasic cellular pattern. In addition, the tumor cells were positive for Calretinin, Creatine Kinase (CK)5/6, CK7, CKAEI 1/3, Wilms Tumor protein (WT-1), and Vimentin, but were negative for Alpha Feto protein (AFP), Thrombotic Thrombocytopenic Purpura (TTP-1), Anti-Hepatocyte Specific Antigen (HSA), Synaptophysin, CK20, and Homeobox protein (CDx-2).<br><br>DISCUSSION: Primary intrahepatic mesothelioma (PIHMM) is not included in the classification of the World Health Organization classification of hepatic tumors. Mesothelial cells are not normally found in the liver, but some reported cases suggest it may grow from the mesothelial cells of the Glisson's capsule.<br><br>CONCLUSION: The probability of hepatic mesothelioma should not be ruled out, even in a young woman without a clear history of asbestos exposure.}, }
@article {pmid27903668, year = {2016}, author = {Bibby, AC and Tsim, S and Kanellakis, N and Ball, H and Talbot, DC and Blyth, KG and Maskell, NA and Psallidas, I}, title = {Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {25}, number = {142}, pages = {472-486}, pmid = {27903668}, issn = {1600-0617}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; Lung Neoplasms/*diagnosis/pathology/*therapy ; Mesothelioma/*diagnosis/pathology/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/pathology/*therapy ; Predictive Value of Tests ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised.}, }
@article {pmid27900083, year = {2016}, author = {Kurosawa, T and Sugino, K and Isobe, K and Hata, Y and Fukasawa, Y and Homma, S}, title = {Primary malignant pericardial mesothelioma with increased serum mesothelin diagnosed by surgical pericardial resection: A case report.}, journal = {Molecular and clinical oncology}, volume = {5}, number = {5}, pages = {553-556}, pmid = {27900083}, issn = {2049-9450}, abstract = {A 37-year-old female smoker without a history of exposure to asbestos was referred to our hospital with persistent pericardial effusion. Chest computed tomography imaging examination revealed an irregular thickened pericardium with large amounts of pericardial effusion and a small pleural effusion. Fluorodeoxyglucose (FDG) positron emission tomography imaging demonstrated intrapericardial FDG accumulation. Blood tests revealed an increase in serum mesothelin levels. Examination of a surgically resected specimen revealed a grayish-white thickening of the pericardium, with a straw-colored mucinous pericardial effusion. Histopathological examination confirmed the diagnosis of epithelioid malignant mesothelioma. Although the patient's condition temporarily improved, with decreased levels of serum mesothelin during chemotherapy with carboplatin and pemetrexed, she succumbed to cardiac tamponade 18 months after the initial onset of the symptoms. Primary malignant pericardial mesothelioma (PMPM) is an extremely rare and refractory disorder. Thus, an early definitive diagnosis and timely treatment are crucial for the management of PMPM.}, }
@article {pmid27900005, year = {2016}, author = {Rapisarda, V and Salemi, R and Marconi, A and Loreto, C and Graziano, AC and Cardile, V and Basile, MS and Candido, S and Falzone, L and Spandidos, DA and Fenga, C and Libra, M}, title = {Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells.}, journal = {Oncology letters}, volume = {12}, number = {5}, pages = {3363-3367}, pmid = {27900005}, issn = {1792-1074}, abstract = {Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.}, }
@article {pmid27889700, year = {2017}, author = {Reinstein, L and Bersin, B}, title = {Clarence Borel.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {622-629}, doi = {10.1177/1048291116679964}, pmid = {27889700}, issn = {1541-3772}, mesh = {*Asbestos ; Asbestosis/*history ; History, 20th Century ; Humans ; Jurisprudence/*history ; Lung Neoplasms ; Male ; Mesothelioma ; Middle Aged ; United States ; }, abstract = {Borel v. Fibreboard Paper Products Corporation is the 1973 landmark case that paved the way for successful litigation against the asbestos industry. Clarence Borel's granddaughter shares recollections of the reluctant man behind the court case.}, }
@article {pmid27886205, year = {2016}, author = {Lansley, SM and Pedersen, B and Robinson, C and Searles, RG and Sterrett, G and van Bruggen, I and Lake, RA and Mutsaers, SE and Prêle, CM}, title = {A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {36349}, pmid = {27886205}, issn = {2045-2322}, mesh = {Adult ; Alkaline Phosphatase/metabolism ; Animals ; Biomarkers/*metabolism ; Cell Differentiation ; Cell Line, Tumor ; Core Binding Factor Alpha 1 Subunit/metabolism ; Dexamethasone/pharmacology/therapeutic use ; Female ; Humans ; Integrin-Binding Sialoprotein/genetics/metabolism ; Lung Neoplasms/drug therapy/genetics/*metabolism ; Mesothelioma/drug therapy/genetics/*metabolism ; Mesothelioma, Malignant ; Mice ; Neoplasm Transplantation ; Osteoblasts/*cytology/metabolism ; *Osteogenesis/drug effects ; Osteonectin/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors.}, }
@article {pmid27884852, year = {2016}, author = {Tsim, S and Kelly, C and Alexander, L and McCormick, C and Thomson, F and Woodward, R and Foster, JE and Stobo, DB and Paul, J and Maskell, NA and Chalmers, A and Blyth, KG}, title = {Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study.}, journal = {BMJ open}, volume = {6}, number = {11}, pages = {e013324}, pmid = {27884852}, issn = {2044-6055}, support = {15960/CRUK_/Cancer Research UK/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Biomarkers, Tumor/blood ; Cross-Sectional Studies ; Extracellular Matrix Proteins/*blood ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/*blood/*diagnostic imaging ; Magnetic Resonance Imaging ; Mesothelin ; Mesothelioma/*blood/*diagnostic imaging ; Mesothelioma, Malignant ; Prognosis ; Prospective Studies ; Proteomics/methods ; ROC Curve ; Research Design ; Scotland ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.<br><br>METHODS AND ANALYSIS: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13-20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created.<br><br>ETHICS AND DISSEMINATION: The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN10079972, Pre-results.}, }
@article {pmid27878235, year = {2017}, author = {Lee, S and Matsuzaki, H and Maeda, M and Yamamoto, S and Kumagai-Takei, N and Hatayama, T and Ikeda, M and Yoshitome, K and Nishimura, Y and Otsuki, T}, title = {Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers.}, journal = {International journal of oncology}, volume = {50}, number = {1}, pages = {66-74}, pmid = {27878235}, issn = {1791-2423}, mesh = {CD4-Positive T-Lymphocytes/immunology/pathology ; Cell Cycle/drug effects/immunology ; Cyclin D1/biosynthesis/blood/*immunology ; Forkhead Box Protein O1/*biosynthesis/immunology ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-10/biosynthesis/blood/immunology ; Killer Cells, Natural/immunology ; Lung Neoplasms/blood/chemically induced/*immunology/pathology ; Mesothelioma/blood/chemically induced/*immunology/pathology ; Mesothelioma, Malignant ; Natural Cytotoxicity Triggering Receptor 1/biosynthesis/blood/immunology ; Receptors, CXCR3/biosynthesis/immunology ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; Transforming Growth Factor beta/biosynthesis/blood/immunology ; }, abstract = {Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg.}, }
@article {pmid27872401, year = {2017}, author = {Castleman, B}, title = {Criminality and Asbestos in Industry.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {557-580}, doi = {10.1177/1048291116678435}, pmid = {27872401}, issn = {1541-3772}, mesh = {*Asbestos ; *Crime ; Disasters ; Humans ; Industry/*legislation &amp; jurisprudence ; Italy ; Mesothelioma ; *Occupational Exposure ; }, abstract = {Criminal prosecutions of individuals in the asbestos industry are reviewed, particularly the case of asbestos owner-executive Stephan Schmidheiny. Italian courts sentenced Schmidheiny to sixteen to eighteen years in jail for creating an environmental disaster causing three thousand deaths. The convictions were overturned on a technicality, and a murder case against Schmidheiny has started. His firm, Eternit, made asbestos-cement building products in many countries. Schmidheiny directed a cover-up that the Italian Court of Appeal blamed for delaying the ban of asbestos in Italy by ten years. Today, the asbestos industry is a criminal industry, profiting only by minimizing its costs for the prevention and compensation of occupational and environmental illness. The asbestos industry should only be consulted by governments for the purpose of closing it and dealing with the legacy of in-place asbestos.}, }
@article {pmid27870118, year = {2016}, author = {Boffetta, P}, title = {Re: Terracini et al. Comments on the causation of malignant mesothelioma: Rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma. Am J Ind Med 2016;59:506-507.}, journal = {American journal of industrial medicine}, volume = {59}, number = {12}, pages = {1177-1179}, doi = {10.1002/ajim.22672}, pmid = {27870118}, issn = {1097-0274}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid27869238, year = {2016}, author = {Smolková, P and Nakládalová, M and Zapletalová, J}, title = {Response to the letter to editors concerning "Validity of mesothelin in occupational medicine practice".}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {6}, pages = {881}, doi = {10.13075/ijomeh.1896.01101}, pmid = {27869238}, issn = {1896-494X}, mesh = {Asbestos ; *GPI-Linked Proteins ; Humans ; Mesothelin ; Mesothelioma ; Occupational Exposure ; *Occupational Medicine ; Pleural Neoplasms ; }, }
@article {pmid27869237, year = {2016}, author = {Taeger, D and Gawrych, K and Brüning, T}, title = {Validity of mesothelin in occupational medicine practice.}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {6}, pages = {879-880}, doi = {10.13075/ijomeh.1896.01062}, pmid = {27869237}, issn = {1896-494X}, mesh = {Asbestos ; *GPI-Linked Proteins ; Humans ; Mesothelin ; Mesothelioma ; Occupational Exposure ; *Occupational Medicine ; Pleural Neoplasms ; }, }
@article {pmid27866405, year = {2016}, author = {Plato, N and Martinsen, JI and Sparén, P and Hillerdal, G and Weiderpass, E}, title = {Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban.}, journal = {Epidemiology and health}, volume = {38}, number = {}, pages = {e2016039}, pmid = {27866405}, issn = {2092-7193}, mesh = {Adult ; Asbestos/poisoning ; Asbestosis/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; Registries ; Sweden/epidemiology ; }, abstract = {OBJECTIVES: We updated the Swedish component of the Nordic Occupational Cancer (NOCCA) Study through 2009 in order to investigate the incidence of mesothelioma of the peritoneum and pleura in both genders, and explored occupational exposures that may be associated with mesothelioma.<br><br>METHODS: The Swedish component of the NOCCA Study includes 6.78 million individuals. Data from this cohort were linked to the population-based Swedish Cancer Registry and Swedish Total Population Registry for three periods between 1961 and 2009, and then further linked to the Swedish NOCCA job-exposure matrix, which includes 25 carcinogenic substances and the corresponding exposure levels for 280 occupations. Multivariate analysis was used to calculate standardized incidence ratios (SIRs) for mesothelioma of the peritoneum and pleura by gender, occupational category, carcinogenic substance, and for multiple occupational exposures simultaneously.<br><br>RESULTS: A total of 3,716 incident mesotheliomas were recorded (21.1% in women). We found a significantly increased risk of mesothelioma in 24 occupations, as well as clear differences between the genders. Among men, increased risks of mesothelioma of the pleura were observed in male-dominated occupations, with the greatest elevation of risk among plumbers (SIR, 4.99; 95% confidence interval, 4.20 to 5.90). Among women, increased risks were observed in sewing workers, canning workers, packers, cleaners, and postal workers. In multivariate analysis controlling for multiple occupational exposures, significant associations were only observed between asbestos exposure and mesothelioma.<br><br>CONCLUSIONS: Asbestos exposure was associated with mesothelioma incidence in our study. The asbestos ban of 1982 has yet to show any clear effect on the occurrence of mesothelioma in this cohort. Among women, the occupations of canning workers and cleaners showed increased risks of mesothelioma of the pleura without evidence of asbestos exposure.}, }
@article {pmid27859460, year = {2017}, author = {Shinozaki-Ushiku, A and Ushiku, T and Morita, S and Anraku, M and Nakajima, J and Fukayama, M}, title = {Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma.}, journal = {Histopathology}, volume = {70}, number = {5}, pages = {722-733}, doi = {10.1111/his.13123}, pmid = {27859460}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Enhancer of Zeste Homolog 2 Protein/analysis/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Proportional Hazards Models ; Tumor Suppressor Proteins/analysis/*biosynthesis ; Ubiquitin Thiolesterase/analysis/*biosynthesis ; }, abstract = {AIMS: Malignant mesothelioma is a highly aggressive cancer that is usually diagnosed at advanced stages; thus, highly sensitive and specific markers are necessary for its early definitive diagnosis. The aim of this study was to evaluate the diagnostic utility and prognostic significance of BAP1 and EZH2 in malignant mesothelioma.<br><br>METHODS AND RESULTS: The expression of BAP1 and EZH2 was investigated by immunohistochemistry in 32 malignant mesotheliomas and 44 benign mesothelial proliferative lesions, including well-differentiated papillary mesothelioma (n = 4), mesothelial inclusion cyst (n = 22), and reactive mesothelial hyperplasia (n = 18). BAP1 loss and high EZH2 expression were observed in 17 (53%) and 22 (66%) malignant mesothelioma cases, respectively, whereas none of the benign lesions showed BAP1 loss or high EZH2 expression. The combination of BAP1 loss and high EZH2 expression as markers to differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions was highly sensitive (90%) and specific (100%). There were no statistically significant associations between parameters such as age and sex of patients, tumour location, asbestos exposure, treatment, histology, and BAP1 or EZH2 expression. Survival analysis revealed that BAP1 loss, but not high EZH2 expression, was associated with a better prognosis.<br><br>CONCLUSIONS: BAP1 loss and high EZH2 expression were highly specific to malignant mesothelioma in differentiating it from benign mesothelial proliferations, and the combination of these two markers improved the diagnostic accuracy.}, }
@article {pmid27840913, year = {2016}, author = {Kato, T and Lee, D and Wu, L and Patel, P and Young, AJ and Wada, H and Hu, HP and Ujiie, H and Kaji, M and Kano, S and Matsuge, S and Domen, H and Kanno, H and Hatanaka, Y and Hatanaka, KC and Kaga, K and Matsui, Y and Matsuno, Y and De Perrot, M and Yasufuku, K}, title = {SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {49}, number = {6}, pages = {2411-2420}, doi = {10.3892/ijo.2016.3765}, pmid = {27840913}, issn = {1791-2423}, mesh = {Adaptor Proteins, Signal Transducing/*antagonists &amp; inhibitors/biosynthesis/genetics ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Cell Cycle Proteins/*antagonists &amp; inhibitors/biosynthesis/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Female ; G2 Phase Cell Cycle Checkpoints/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*pathology ; Protein Serine-Threonine Kinases/*antagonists &amp; inhibitors/genetics ; Proto-Oncogene Proteins/*antagonists &amp; inhibitors/genetics ; Pteridines/pharmacology ; RNA Interference ; RNA, Small Interfering/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Polo-Like Kinase 1 ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLK1 gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs.}, }
@article {pmid27835874, year = {2017}, author = {Bruno, R and Alì, G and Giannini, R and Proietti, A and Lucchi, M and Chella, A and Melfi, F and Mussi, A and Fontanini, G}, title = {Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis.}, journal = {Oncotarget}, volume = {8}, number = {2}, pages = {2758-2770}, pmid = {27835874}, issn = {1949-2553}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Cluster Analysis ; Computational Biology/methods ; Diagnosis, Differential ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia ; Lung Neoplasms/*diagnosis/*genetics ; Male ; Mesothelioma/*diagnosis/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*diagnosis/*genetics ; Young Adult ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare asbestos related cancer, aggressive and unresponsive to therapies. Histological examination of pleural lesions is the gold standard of MPM diagnosis, although it is sometimes hard to discriminate the epithelioid type of MPM from benign mesothelial hyperplasia (MH).This work aims to define a new molecular tool for the differential diagnosis of MPM, using the expression profile of 117 genes deregulated in this tumour.The gene expression analysis was performed by nanoString System on tumour tissues from 36 epithelioid MPM and 17 MH patients, and on 14 mesothelial pleural samples analysed in a blind way. Data analysis included raw nanoString data normalization, unsupervised cluster analysis by Pearson correlation, non-parametric Mann Whitney U-test and molecular classification by the Uncorrelated Shrunken Centroid (USC) Algorithm.The Mann-Whitney U-test found 35 genes upregulated and 31 downregulated in MPM. The unsupervised cluster analysis revealed two clusters, one composed only of MPM and one only of MH samples, thus revealing class-specific gene profiles. The Uncorrelated Shrunken Centroid algorithm identified two classifiers, one including 22 genes and the other 40 genes, able to properly classify all the samples as benign or malignant using gene expression data; both classifiers were also able to correctly determine, in a blind analysis, the diagnostic categories of all the 14 unknown samples.In conclusion we delineated a diagnostic tool combining molecular data (gene expression) and computational analysis (USC algorithm), which can be applied in the clinical practice for the differential diagnosis of MPM.}, }
@article {pmid27829301, year = {2016}, author = {Dodge, DG and Beck, BD}, title = {Historical state of knowledge of the health risks of asbestos posed to seamen on merchant ships.}, journal = {Inhalation toxicology}, volume = {28}, number = {14}, pages = {637-657}, doi = {10.1080/08958378.2016.1244228}, pmid = {27829301}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/analysis/*history/*toxicity ; Animals ; Asbestos/analysis/*history/*toxicity ; History, 20th Century ; History, 21st Century ; Humans ; Naval Medicine/history ; Occupational Diseases/etiology/history/prevention &amp; control ; Occupational Exposure/adverse effects/analysis/history/prevention &amp; control ; Occupational Health ; Risk ; *Ships ; }, abstract = {We examined the development of knowledge concerning the risks posed by asbestos to seamen working aboard merchant ships at sea (i.e. commercial, rather than naval vessels). Seamen were potentially exposed to "in-place" asbestos on merchant ships by performing intermittent repair and maintenance tasks. We reviewed studies measuring airborne asbestos onboard merchant ships and health outcomes of merchant seamen, as well as studies, communications, and actions of U.S. organizations with roles in maritime health and safety. Up to the 1970s, most knowledge of the health risks of asbestos was derived from studies of workers in asbestos product manufacturing and asbestos mining and milling industries, and certain end-users of asbestos products (particularly insulators). We found that attention to the potential health risks of asbestos to merchant seamen began in the mid- to late 1970s and early 1980s. Findings of pleural abnormalities in U.S. seamen elicited some concern from governmental and industry/labor organizations, but airborne asbestos concentrations aboard merchant ships were found to be <1 f/cc for most short-term repair and maintenance tasks. Responses to this evolving information served to warn seamen and the merchant shipping industry and led to increased precautions regarding asbestos exposure. Starting in the 1990s, findings of modest increases in lung cancer and/or mesothelioma in some epidemiology studies of seamen led some authors to propose that a causal link between shipboard exposures and asbestos-related diseases existed. Limitations in these studies, however, together with mostly unremarkable measures of airborne asbestos on merchant ships, preclude definitive conclusions in this regard.}, }
@article {pmid27825201, year = {2016}, author = {Conti, S and Comba, P and Manno, V and Minelli, G and Nicita, C and Pasetto, R and Fazzo, L and Zona, A and Bruno, C}, title = {[SENTIERI-ReNaM: Integration of incidence, mortality, and hospitalization: general remarks and a focus on mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {109-115}, pmid = {27825201}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {The integration of current data sources is now a practice widely used in epidemiology, especially in the environmental field. To better describe the health profile of populations residing in proximity to areas characterized by a "strong environmental pressure", the combined use of multiple indicators (i.e., mortality, hospitalization, cancer incidence) is recommended. To choose an indicator is complex, as indicators should be contextualized and they need to be related to the several issues involved in the studied pathology. This chapter explores the general considerations that are to be addressed both at the time of the study design, during the selection of outcomes and of the proper data sources, and at the time of the discussion of the results, when different and complementary data are compared. A special focus is devoted to the case of mesothelioma.}, }
@article {pmid27825200, year = {2016}, author = {Zona, A and Fazzo, L and Binazzi, A and Bruno, C and Corfiati, M and Comba, P and Conti, S and Menegozzo, S and Nicita, C and Pasetto, R and Pirastu, R and Marinaccio, A and , }, title = {[SENTIERI-ReNaM: Discussion and concluding remarks].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {105-108}, pmid = {27825200}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {SENTIERI-ReNaM Project analysed the incidence of malignant mesothelioma (MM) for the period 2000-2011 in 39 National Priority Contaminated Sites (NPCSs), and assessed the overall impact of mesothelioma in different types of NPCSs. In the study period, 2,683 incident cases of malignant mesothelioma were recorded: 1,998 males (74.5%), 685 females (25.5%). Excluding cases with non attributable exposure and those non interviewed, exposure was identified in 1,926 cases (70% of all cases): 1,541 males (occupational exposure: 1,414; environmental exposure: 82), 385 females (occupational exposure: 103; environmental exposure: 141). Women experienced mainly environmental and domestic exposures to asbestos. Standard Incidence Ratio (SIR) excesses were observed in men in 27 out of 39 NPCSs and defects in the remaining 12; in women, 20 NPCSs showed SIR excesses, defects in 15; in 4 NPCSs no MM cases occurred among female population. The highest rates were found in NPCSs with asbestos-cement plants (Broni and Casale Monferrato), respectively, 98 per 100,000 per year and 68.6 in men, 72.1 and 45.8 in women. Excluding these two sites, the highest incidence rates were found in the group with harbours and shipyards, where the rates were, respectively, 13.2 among men and 2.5 among women. The results of this report will be communicated to national and local institutions, as well as to NPCSs resident populations.}, }
@article {pmid27825199, year = {2016}, author = {Pasetto, R and Fazzo, L and Zona, A and Bruno, C and Pirastu, R and Binazzi, A and Corfiati, M and Silvestri, S and Comba, P and Marinaccio, A}, title = {[SENTIERI-ReNaM: Burden of disease from mesothelioma in national priority contaminated sites in Italy].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {99-104}, pmid = {27825199}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {BACKGROUND: in Italy, National Priority Contaminated Sites (NPCSs) are defined as of concern for remediation; most of them are sites with a long-lasting industrial activity.<br><br>OBJECTIVE: the study aims to estimate the burden of disease from mesothelioma in NPCSs.<br><br>DESIGN: mesothelioma incidence in the period 2000-2011 was estimated for the populations residing in the 39 Italian NPCSs. Data were taken from the Italian National Mesothelioma Registry (ReNaM). NPCSs were ranked into risk groups (RGs) on the basis of the presence of the following asbestos-exposing activities: 1. asbestos-cement plants; 2. asbestos mines; 3. harbours with shipyards; 4. illegal dumping sites containing asbestos; 5. petrochemicals and/or refineries, and/or steel plants; 6. chemical plants and/or landfills without explicit mention of asbestos. For the population residing in each NPCS, crude rates per 100,000 per year and number of observed minus expected cases (Obs-Exp) by gender were computed. Expected cases were calculated using the age-class rates of a reference population (the geographical macroarea of every NPCS). For every RG, the meta-analytic estimate of the attributable proportion (AP), i.e., the proportion of cases attributable to the local context, was computed, being the AP for each NPCS expressed as (Obs-Exp/Obs) x100.<br><br>RESULTS: the total number of mesothelioma cases estimated in the considered period of 12 years is 2,741 (2,048 males, 693 females). The total number of Obs-Exp cases was 1,531 (1,178 in males, 353 in females). In males, crude rate ranges from 71.5 in the RG1 to 3.0 in RG4, while in females it ranges from 48.4 in RG1 to 0.6 in RG4. In males, AP in RGs from 1 to 3 is over 65%, in RG4 is 59%, in RG5 is 30%, in RG6 is -14%. AP in females gradually drops from 95% in RG1 to -64% in RG6.<br><br>CONCLUSIONS: the burden of mesothelioma in populations residing in NPCSs is high, with an AP gradient consistent with the a priori RG. This burden impacts on females in a different way: rates are lower than male ones; AP is similar to male ones in the RGs 1 and 3.}, }
@article {pmid27825198, year = {2016}, author = {Binazzi, A and Zona, A and Marinaccio, A and Bruno, C and Corfiati, M and Fazzo, L and Menegozzo, S and Nicita, C and Pasetto, R and Pirastu, R and De Santisi, M and Comba, P and , }, title = {[SENTIERI-ReNaM: Results].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {19-98}, pmid = {27825198}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {Mesothelioma incidence has been analyzed in National Priority Contaminated Sites (NPCSs) to estimate the health impact of asbestos exposure on resident people. The burden of professional and environmental exposures has been identified through data of the Regional Operational Centres (CORs), made available by the Italian National Mesothelioma Registry (ReNaM). An excess of mesothelioma incidence is confirmed in sites with a known past history of direct use of asbestos, such as Balangero, Casale Monferrato, Broni, Bari-Fibronit, and in coastal areas, where shipyards, harbours and other industries that involved a wide use of asbestos are represented (e.g., Trieste, La Spezia, Venice, and Leghorn). An excess of mesothelioma has been observed in settings where the asbestos is not mentioned as contaminant in the decree that included these sites among NPCSs, such as Cengio and Saliceto in Northern Italy; Falconara Marittima and the Bacino Idrografico Fiume Sacco in the Central Italy; the Litorale Domizio Flegreo and Agro Aversano, Milazzo, and Gela in the Southern Italy. Observed excess in the various NPCSs confirms the large-scale occurrence in contaminated Italian sites of a significant amount of total mesothelioma cases observed at national level. The analysis of occupational risk in epidemiological studies with an ecological design helps in defining the contribution of different factors to the overall risk.}, }
@article {pmid27825197, year = {2016}, author = {Marinaccio, A and Binazzi, A and Comba, P and Corfiati, M and Fazzo, L and Bruno, C and Pirastu, R and Pasetto, R and Zona, A}, title = {[SENTIERI-ReNaM: Materials and methods].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {16-18}, pmid = {27825197}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {In the framework of SENTIERI Project, this study is aimed to identify excess risks of malignant mesothelioma (MM) in Italian National Priority Contaminated Sites (NPCSs) included in the national environmental remediation programme and to discuss the results by means of data available from the Italian National Mesothelioma Registry (ReNaM). Re- NaM has a regional structure with Regional Operational Centres (CORs) in charge of identifying mesothelioma incident cases and defining the asbestos exposure modalities thought an individual questionnaire. Starting from the 44 NPCSs selected in SENTIERI Project, we excluded Calabria and Sardinia Regions from the analyses (3 NPCSs). Furthermore, for 2 sites (Emarese in Valle d'Aosta and Tito in Basilicata) no incident MM cases have been detected in the considered period. Incident cases of MM and Standardized Incidence Ratios (SIR), with corresponding 90% confidence intervals, have been estimated in each NPCS, for both gender, in the period 2000-2011. Age-standardized rates of Italian geographical macro-areas (North- East, North-West, Centre, South and Islands) have been used to estimate expected cases. For every analyzed site, the occupational and non-occupational asbestos exposure modalities are discussed.}, }
@article {pmid27825196, year = {2016}, author = {Comba, P and Zona, A and Pirastu, R and Bruno, C and Fazzo, L and Pasetto, R and Binazzi, A and Corfiati, M and Marinaccio, A}, title = {[SENTIERI-ReNaM: Rationale and objectives].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {13-15}, pmid = {27825196}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {The purpose of the SENTIERI-ReNaM Project is to analyse the incidence of mesothelioma in Italian National Priority Contaminated Sites (NPCSs) in order to estimate the health impact of asbestos on resident populations, disentangling the role of occupational and environmental exposures. SENTIERI Project has provided the relevant information on geographic and demographic structure of NPCSs and on existing sources of contamination. The Italian National Mesothelioma Registry (ReNaM), that covers the whole country through its Regional Operational Centres (CORs), has made available the procedures for estimating the incidence of mesothelioma in NPCSs and for assessing occupational and environmental asbestos exposure of the individual cases. The synergy between these two epidemiological surveillance systems lay also the ground for communication programmes with the affected communities.}, }
@article {pmid27825195, year = {2016}, author = {, }, title = {[SENTIERI - Epidemiological study of residents in national priority contaminated sites: incidence of mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {1-116}, doi = {10.19191/EP16.5S1.P001.097}, pmid = {27825195}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {The purpose of SENTIERI-ReNaM Project is to describe mesothelioma incidence in the Italian National Priority Contaminated Sites (NPCSs). The present report deals with 39 NPCSs (20 in Northern Italy, 8 in Central Italy and 11 in Southern Italy). Asbestos is specifically mentioned in the regulatory acts of recognition for 10 NPCSs and it is the only agent that has determined environmental contamination in 3 of them (Casale Monferrato, Broni, and Bari). The timeframe of the study is 2000-2011 for 34 out of 39 sites. The corresponding reference periods for the sites of Latium, Campania, Umbria, and Bolzano Province are, respectively, 2001-2011, 2005-2011, and 2006-2011. Standardized Incidence Ratios (SIRs) for mesothelioma, with their corresponding 90% Confidence Intervals, have been estimated for all sites. The interpretation of the study findings has been based on anamnestic information made available by the Italian National Mesothelioma Registry (ReNaM), and completed thanks to knowledge derived from the international scientific literature. In men, mesothelioma incidence has shown excesses in 27/39 sites and defects in the remaining 12; in women, excesses have been reported in 20 sites, defects in 15, and no cases have been detected in the remaining 4 sites. The highest annual incidence rates have been observed in the sites characterized only by the presence of asbestos- cement factories (Broni and Casale Monferrato): respectively, 98.0 and 68.6 per 100,000 per year in men, 72.1 and 45.8 in women. Besides these two sites, the highest rates have been observed in the sites with naval shipyards: 13.2 in men and 2.5 in women. Excesses of mesothelioma incidence have been confirmed (with respect to previous observations) in the sites of Broni, Casale Monferrato, Balangero, and in the coastal areas of Trieste, La Spezia, Venice, and Leghorn. Balangero has been the major European chrysotile quarry, while the other sites are characterized by the presence of naval shipyards with demonstrated use of asbestos before it was banned in 1992. An excess of mesothelioma incidence has also been confirmed in the site of Biancavilla, characterized by the presence of the fluoro-edenite fibrous amphibole, classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC). An increased incidence of mesothelioma was also observed in the areas where no direct use of asbestos had previously been documented, like Cengio and Saliceto (chemical industry), Falconara on Sea (oil refinery), and Litorale Domizio Flegreo and Agro Aversano (a large area including multiple hazardous waste dumping sites). These findings show that a relevant proportion of Italian mesothelioma cases is concentrated in NPCSs. About 1,500 extra cases of mesothelioma have been estimated in the overall series of 39 sites (2000-2011), corresponding to 125 extra cases per year. The excess has concerned the sites with manufacture of asbestos-cement products, but also the areas with asbestos quarries, naval shipyards, illegal hazardous waste dumping sites with asbestos-containing materials, petrochemical industries, refineries and steel plants. In some sites, particularly Casale Monferrato and Broni, analytical epidemiological studies have shown the causal role of not only occupational, but also environmental exposures, with special reference to paving of gardens and courtyards with asbestos-cement industry by-products. The main novelty generated by the collaborative SENTIERI-ReNaM Project concerns the detection of significant mesothelioma excesses not only in sites where asbestos is explicitly reported as a source of contamination, but also in a number of areas defined "of national interest" for environmental cleanup due to other sources of pollution. This confirms that the range of economic activities and working and living environments affected by asbestos exposure is very wide and it is not restricted to the industrial sectors characterized by the direct use of this material.}, }
@article {pmid27822122, year = {2016}, author = {Beebe-Dimmer, JL and Fryzek, JP and Yee, CL and Dalvi, TB and Garabrant, DH and Schwartz, AG and Gadgeel, S}, title = {Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results (SEER)-Medicare investigation of treatment patterns and overall survival.}, journal = {Clinical epidemiology}, volume = {8}, number = {}, pages = {743-750}, pmid = {27822122}, issn = {1179-1349}, abstract = {INTRODUCTION: Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and overall survival (OS) utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare database.<br><br>MATERIALS AND METHODS: Patients in this study were diagnosed with malignant mesothelioma of the pleura or peritoneum between January 1, 2005 and December 31, 2009 with follow-up for survival through December 31, 2010. We examined both patient and tumor characteristics at time of diagnosis and subsequent treatment patterns (surgery, radiation, and chemotherapy). Among patients treated with chemotherapy, we determined chemotherapy regimen and OS by line of therapy.<br><br>RESULTS: Of the 1,625 patients considered eligible for this investigation, the median age at diagnosis was 78 years. Nearly a third of patients (30%) had surgery as part of their treatment and 45% were given chemotherapy. The median OS was 8 months (range 1-69 months). Among chemotherapy patients, the most commonly (67%) prescribed regimen for first-line therapy was cisplatin or carboplatin (Ca/Ci) combined with pemetrexed (Pe). Among those prescribed Ca/Ci + Pe as first-line therapy, retreatment with Ca/Ci + Pe (28%) or treatment with gemcitabine (30%) were the most common second-line therapies. Median OS for those receiving first-line chemotherapy was 7 months, and among those receiving second-line therapy median OS was extended an additional 5 months.<br><br>CONCLUSION: Irrespective of surgical resection, mesothelioma patients receiving some form of chemotherapy survived longer than patients who did not, with an additional survival benefit among those patients receiving multimodal treatment.}, }
@article {pmid27821674, year = {2017}, author = {Merler, E and Somigliana, A and Girardi, P and Barbieri, PG}, title = {Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {3}, pages = {218-227}, doi = {10.1136/oemed-2015-103382}, pmid = {27821674}, issn = {1470-7926}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects/*isolation &amp; purification ; Female ; Humans ; Interviews as Topic ; Italy ; Lung/*pathology ; Lung Neoplasms/chemically induced/*pathology ; Male ; Mesothelioma/chemically induced/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Mineral Fibers ; Occupational Diseases/chemically induced/*pathology ; Occupational Exposure/*adverse effects/analysis ; }, abstract = {OBJECTIVES: To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed.<br><br>METHODS: The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either 'definite' or 'probable' or 'possible'.<br><br>RESULTS: The participants had finished working in asbestos exposure conditions more than 20&#x2005;years ago (on average 26.1&#xb1;11.0&#x2005;years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in <35% of cases among participant working in construction, in metallurgical industry, in chemical or textile industry and among those performing brake repair activities.<br><br>CONCLUSIONS: The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection.}, }
@article {pmid27819788, year = {2016}, author = {Gopar-Nieto, R and Cabello-López, A and Juárez-Pérez, CA and Haro-García, LC and Jiménez-Ramírez, C and Aguilar-Madrid, G}, title = {[Update on epidemiology, pathophysiology, diagnosis and treatment of malignant pleural mesothelioma].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {54}, number = {6}, pages = {770-776}, pmid = {27819788}, issn = {2448-5667}, mesh = {Combined Modality Therapy ; Humans ; *Mesothelioma/diagnosis/epidemiology/physiopathology/therapy ; Mexico/epidemiology ; *Occupational Diseases/diagnosis/epidemiology/physiopathology/therapy ; Palliative Care ; *Pleural Neoplasms/diagnosis/epidemiology/physiopathology/therapy ; }, abstract = {Malignant pleural mesothelioma is an occupational tumor caused by asbestos exposure. In Mexico, as asbestos usage is not prohibited, an increase in the number of cases is expected. Asbestos exposure is ubiquitous due to the great amount of products in which it is present. Its carcinogenicity is caused as the inhaled asbestos fibers cannot be eliminated by macrophages and, thus, they travel to the pleura through lymphatic pathways, producing a persistent inflammatory response. Diagnosis approach includes occupational history, along with clinical signs and symptoms, and paraclinical studies, such as pleural fluid cytology, chest x-rays, computed tomography, magnetic resonance imaging, and biopsy with immunohistochemistry. The main differential diagnosis is lung adenocarcinoma. Regarding the treatment of this tumor, it mainly comprises palliative care, even though chemotherapy, radiotherapy, and, in selected cases, surgical treatments have been used. There is an urgent need for general physicians and specialists to identify asbestos exposure, in order to make a timely diagnosis. Research is necessary to develop screening and prompt diagnostic tools, along with an epidemiological surveillance program for the workers and the general population exposed to asbestos.}, }
@article {pmid27813512, year = {2017}, author = {Joseph, NM and Chen, YY and Nasr, A and Yeh, I and Talevich, E and Onodera, C and Bastian, BC and Rabban, JT and Garg, K and Zaloudek, C and Solomon, DA}, title = {Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {30}, number = {2}, pages = {246-254}, pmid = {27813512}, issn = {1530-0285}, support = {DP5 OD021403/OD/NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Carcinogenesis/genetics/pathology ; DEAD-box RNA Helicases/*genetics ; *Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; Young Adult ; }, abstract = {Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies.}, }
@article {pmid27812913, year = {2016}, author = {Lowry, SJ and Weiss, NS}, title = {Geographic distribution of incidence of pericardial and paratesticular mesotheliomas in the USA.}, journal = {Cancer causes &amp; control : CCC}, volume = {27}, number = {12}, pages = {1487-1489}, doi = {10.1007/s10552-016-0825-3}, pmid = {27812913}, issn = {1573-7225}, mesh = {Heart Neoplasms/epidemiology/pathology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Pericardium/pathology ; Pleural Neoplasms/epidemiology/pathology ; Registries ; SEER Program ; Testicular Neoplasms/*epidemiology/pathology ; United States/epidemiology ; }, abstract = {PURPOSE: Exposure to asbestos is thought to cause the large majority of pleural mesotheliomas in the USA. It is unknown whether asbestos exposure plays a role in the etiology of rarer forms of mesothelioma, e.g., those located in the pericardium or in the tunica vaginalis of the testis. In order to address this question, we sought to determine whether geographic patterns of incidence of these mesotheliomas have paralleled those of pleural mesotheliomas.<br><br>METHODS: We used age-adjusted incidence data from the nine populations served by the National Cancer Institute's Surveillance, Epidemiology, and End Results program during 1973-2011. Among men ages &#x2265;50&#xa0;years, we compared the incidence of pericardial and paratesticular mesotheliomas, respectively, with the incidence of pleural mesothelioma across the nine populations.<br><br>RESULTS: The rate of pleural mesothelioma was approximately twice as high in the San Francisco-Oakland (SFO) and Seattle-Puget Sound (SPS) areas compared to the other regions. In contrast, rates of paratesticular and pericardial mesotheliomas were not elevated in SFO (n&#xa0;=&#xa0;3 paratesticular, 1 pericardial) or SPS (n&#xa0;=&#xa0;4 paratesticular, 1 pericardial) relative to other regions.<br><br>CONCLUSIONS: The results of this ecologic study do not support a role for asbestos exposure in the etiologies of either pericardial or paratesticular mesotheliomas; however, this study was limited by small numbers and was unable to directly ascertain asbestos exposure.}, }
@article {pmid27794408, year = {2016}, author = {Armato, SG and Blyth, KG and Keating, JJ and Katz, S and Tsim, S and Coolen, J and Gudmundsson, E and Opitz, I and Nowak, AK}, title = {Imaging in pleural mesothelioma: A review of the 13th International Conference of the International Mesothelioma Interest Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {101}, number = {}, pages = {48-58}, pmid = {27794408}, issn = {1872-8332}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; R01 CA193556/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Congresses as Topic ; Humans ; Lung Neoplasms/*diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; Male ; Mesothelioma/*diagnostic imaging/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*diagnostic imaging/pathology ; Radionuclide Imaging/*methods ; Response Evaluation Criteria in Solid Tumors ; Spectroscopy, Near-Infrared ; Tomography, Emission-Computed ; Tumor Burden ; United Kingdom ; }, abstract = {Imaging plays an important role in the detection, diagnosis, staging, response assessment, and surveillance of malignant pleural mesothelioma. The etiology, biology, and growth pattern of mesothelioma present unique challenges for each modality used to capture various aspects of this disease. Clinical implementation of imaging techniques and information derived from images continue to evolve based on active research in this field worldwide. This paper summarizes the imaging-based research presented orally at the 2016 International Conference of the International Mesothelioma Interest Group (iMig) in Birmingham, United Kingdom, held May 1-4, 2016. Presented topics included intraoperative near-infrared imaging of mesothelioma to aid the assessment of resection completeness, an evaluation of tumor enhancement improvement with increased time delay between contrast injection and image acquisition in standard clinical magnetic resonance imaging (MRI) scans, the potential of early contrast enhancement analysis to provide MRI with a role in mesothelioma detection, the differentiation of short- and long-term survivors based on MRI tumor volume and histogram analysis, the response-assessment potential of hemodynamic parameters derived from dynamic contrast-enhanced computed tomography (DCE-CT) scans, the correlation of CT-based tumor volume with post-surgical tumor specimen weight, and consideration of the need to update the mesothelioma tumor response assessment paradigm.}, }
@article {pmid27793915, year = {2016}, author = {Jennings, CJ and Zainal, N and Dahlan, IM and Kay, EW and Harvey, BJ and Thomas, W}, title = {Tamoxifen Suppresses the Growth of Malignant Pleural Mesothelioma Cells.}, journal = {Anticancer research}, volume = {36}, number = {11}, pages = {5905-5913}, doi = {10.21873/anticanres.11177}, pmid = {27793915}, issn = {1791-7530}, mesh = {Antineoplastic Agents, Hormonal/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cisplatin/administration &amp; dosage ; Cyclin-Dependent Kinases/antagonists &amp; inhibitors ; Humans ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; Tamoxifen/administration &amp; dosage/*pharmacology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy.<br><br>MATERIALS AND METHODS: We investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four MPM cell lines.<br><br>RESULTS: Tamoxifen inhibited the growth of MPM cells and also modulated their sensitivity to cisplatin. The MPM cell lines expressed ER&#x3b2;, but the actions of tamoxifen were not blocked by antagonism of nuclear ERs. Tamoxifen treatment repressed the expression of cyclins by MPM cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling.<br><br>CONCLUSION: The ER-independent actions of tamoxifen on MPM cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with MPM.}, }
@article {pmid27785864, year = {2016}, author = {Terracini, B and Mirabelli, D and Baur, X and Landrigan, PJ and Ramazzini, C}, title = {Re: Comments on the causation of malignant mesothelioma: Rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {American journal of industrial medicine}, volume = {59}, number = {12}, pages = {1180-1182}, doi = {10.1002/ajim.22663}, pmid = {27785864}, issn = {1097-0274}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid27783867, year = {2017}, author = {Harada, A and Uchino, J and Harada, T and Nakagaki, N and Hisasue, J and Fujita, M and Takayama, K}, title = {Vascular endothelial growth factor promoter-based conditionally replicative adenoviruses effectively suppress growth of malignant pleural mesothelioma.}, journal = {Cancer science}, volume = {108}, number = {1}, pages = {116-123}, pmid = {27783867}, issn = {1349-7006}, mesh = {Adenoviridae/genetics/*growth &amp; development ; Animals ; Cell Death ; Cell Line, Tumor ; Female ; Humans ; Lung Neoplasms/*pathology/*therapy/virology ; Mesothelioma/*pathology/*therapy/virology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; *Oncolytic Virotherapy ; Pleural Neoplasms/pathology/*therapy/virology ; Promoter Regions, Genetic/*genetics ; Transgenes/genetics ; Vascular Endothelial Growth Factor A/*genetics/metabolism ; Virus Replication/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma (MPM) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication-competent adenovirus as an oncolytic agent against MPM. We constructed a vascular endothelial growth factor promoter-based conditionally replicative adenovirus (VEGF-CRAd) that replicates exclusively in VEGF-expressing cells. All of the MM cell lines that we tested expressed VEGF mRNA, and VEGF-CRAd selectively replicated in these MM cells and exerted a direct concentration-dependent oncolytic effect in vitro. Furthermore, our in vivo studies showed that pre-infection of MM cells with VEGF-CRAd potently suppressed MPM tumor formation in nude mice, and that intrapleural instillation of VEGF-CRAd prolonged the survival time of tumor-bearing mice. Our results indicate that VEGF-CRAd exerts an oncolytic effect on MM cells and that intrapleural instillation of VEGF-CRAd is safe and might represent a promising therapeutic strategy for MPM.}, }
@article {pmid27761727, year = {2017}, author = {Sahin, N and Akatli, AN and Celik, MR and Ulutas, H and Samdanci, ET and Colak, C}, title = {The Role of CD90 in the Differential Diagnosis of Pleural Malignant Mesothelioma, Pulmonary Carcinoma and Comparison with Calretının.}, journal = {Pathology oncology research : POR}, volume = {23}, number = {3}, pages = {487-491}, pmid = {27761727}, issn = {1532-2807}, mesh = {Adenocarcinoma/*metabolism/pathology ; Adenocarcinoma of Lung ; Biomarkers, Tumor/metabolism ; Calbindin 2/*metabolism ; Carcinoma, Squamous Cell/metabolism/pathology ; Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*metabolism/pathology ; Sensitivity and Specificity ; Thy-1 Antigens/*metabolism ; }, abstract = {Pleural Malignant Mesothelioma (MM) is a fatal disease that has been associated with asbestos exposure. Differential diagnosis between the pleural infiltration of pulmonary carcinomas and MM is rather difficult particularly for epitheloid type mesothelioma.We aimed to investigate the utility of CD90, a cancer stem cell marker, in the differential diagnosis of MM and lung carcinoma, its prognostic significance and compare its value with that of Calretinin. Ninety pathology specimens including MM (n:30), pulmonary adenocarcinoma (n:30) and pulmonary squamous cell carcinoma (n:30) were used in this study. Immunohistochemical comparision of CD 90 and Calretinin was made in all groups. Calretinin was positive in 20 cases with MM (64.5 %), and was negative in 10 (32.3 %). CD 90 was positive in 25 of these cases (80 %) and negative in 5 (16 %). On the other hand pulmonary adenocarcinomas and squamous cell carcinomas showed positivity with CD90, 63,6 % and 73 %, respectively. We think that CD 90 has no place in the differential diagnosis between mesothelioma and pulmonary carcinoma because of the low specificity in spite of the high sensitivity.}, }
@article {pmid27751355, year = {2016}, author = {Ascoli, V and Cozzi, I and Vatrano, S and Izzo, S and Giorcelli, J and Romeo, E and Carnovale-Scalzo, C and Grillo, LR and Facciolo, F and Visca, P and Papotti, M and Righi, L}, title = {Mesothelioma families without inheritance of a BAP1 predisposing mutation.}, journal = {Cancer genetics}, volume = {209}, number = {9}, pages = {381-387}, doi = {10.1016/j.cancergen.2016.07.002}, pmid = {27751355}, issn = {2210-7762}, mesh = {Aged ; Female ; *Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/*genetics ; Middle Aged ; *Mutation ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Familial malignant mesothelioma clusters are ideal candidates to explore BAP1 genomic status as a predisposing risk factor. We report data on BAP1 analysis in four families with multiple mesothelioma cases to investigate possible BAP1 alterations associated with an inherited cancer syndrome. We also recorded family history of cancer and assessed asbestos exposure. By genomic direct sequencing, we found no evidence of a BAP1 germline mutation in tumor DNA samples (one mesothelioma per family: n = 3 epithelioid; n = 1 biphasic). On the other hand, we identified a novel BAP1 somatic alteration (c.329_335delinsTC) in exon 5 (n = 1 biphasic), and we hypothesized the occurrence of somatic inactivating events not identifiable by sequencing in the other cases (n = 3 epithelioid), as demonstrated by the loss of nuclear BAP1 immunostaining. History of other cancers was in sites not typical of the BAP1 cancer syndrome. Asbestos exposure was occupational (n = 2 clusters), household (n = 1), and unknown (n = 1). These family units without inheritance of a BAP1 predisposing mutation expand the number of unmutated germline BAP1 families with multiple mesothelioma cases. This suggests that besides the exposure to asbestos other currently unknown genetic or epigenetic factors may be responsible for the high incidence of mesothelioma in BAP1-unmutated families.}, }
@article {pmid27739317, year = {2016}, author = {Mrinakova, B and Kajo, K and Ondrusova, M and Simo, J and Ondrus, D}, title = {Malignant Mesothelioma of the Tunica Vaginalis Testis. A Clinicopathologic Analysis of Two Cases with a Review of the Literature.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {29}, number = {5}, pages = {369-374}, pmid = {27739317}, issn = {0862-495X}, mesh = {Adult ; Aged, 80 and over ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology/surgery ; Mesothelioma, Malignant ; Prognosis ; Testicular Hydrocele/*pathology/surgery ; Testicular Neoplasms/*pathology/surgery ; Young Adult ; }, abstract = {Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with only a limited number of reported cases. Its clinical differentiation is challenging, and its diagnosis is almost exclusively accidental. The major risk factor is exposure to asbestos, typically with a long latency between exposure and diagnosis. The current study presents the clinical data of two patients diagnosed with paratesticular malignant mesothelioma. We evaluated a large spectrum of risk factors in the patients histories. The histomorphological and immunohistochemical characteristics were analysed and put into the perspective of a broad differential diagnosis. Both cases of malignant epithelial mesothelioma of the tunica vaginalis testis clinically presented as unilateral hydroceles. Patients underwent surgery with the perioperative finding of a tumour. Radical inguinal orchiectomy was the treatment of choice for both patients. After comprehensive staging, the second patient underwent a second step of inguinal and pelvic lymph node dis- section. Follow-up visits revealed recurrence of the disease in the first patient. Resection of the tumour was performed. The histology confirmed the relapse of a tumour with identical features to those of the first tumour. Chemotherapy and radiotherapy were not indicated. Both patients are currently in complete remission. In conclusion, surgical treatment had a determinative role in the prognosis of these patients. Radical orchiectomy is the treatment of choice for localized disease. Lymph node dissection can be considered in the case of lymph node enlargement. There is a lack of evidence-based data for adjuvant chemotherapy and radiotherapy. Patients should be referred to experienced multidisciplinary cancer centres for a second opinion on histology, treatment, and a follow-up plan.Key words: mesothelioma - tunica vaginalis testis - hydrocele - asbestos exposure.}, }
@article {pmid27734057, year = {2016}, author = {Armstrong, B and Driscoll, T}, title = {Mesothelioma in Australia: cresting the third wave.}, journal = {Public health research &amp; practice}, volume = {26}, number = {2}, pages = {}, doi = {10.17061/phrp2621614}, pmid = {27734057}, issn = {2204-2091}, mesh = {Air Pollutants/*toxicity ; Asbestos/*toxicity ; Australia/epidemiology ; Construction Materials ; Environmental Exposure/*adverse effects ; Environmental Monitoring ; Housing ; Humans ; Incidence ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {There has been much recent commentary about the 'third wave' of asbestos-related disease, arising particularly from exposures of people repairing, renovating or demolishing buildings that contain asbestos. The presence and extent of a third wave, however, are difficult to assess, and the extent and risk of both occupational and nonoccupational third-wave exposures are largely unmeasured. Moreover, we lack information on the extent of deterioration of in situ asbestos, and its significance for ambient and third-wave exposures. This paper considers the available evidence about the third wave. It proposes approaches to obtaining the information needed to properly estimate the risk of third-wave exposures, and guide actions that will crest a likely third wave with minimum harm and cost to the community.}, }
@article {pmid27716620, year = {2016}, author = {Bononi, I and Comar, M and Puozzo, A and Stendardo, M and Boschetto, P and Orecchia, S and Libener, R and Guaschino, R and Pietrobon, S and Ferracin, M and Negrini, M and Martini, F and Bovenzi, M and Tognon, M}, title = {Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers.}, journal = {Oncotarget}, volume = {7}, number = {50}, pages = {82700-82711}, pmid = {27716620}, issn = {1949-2553}, mesh = {Area Under Curve ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood/genetics ; Case-Control Studies ; Circulating MicroRNA/*blood/genetics ; Gene Expression Profiling/methods ; Humans ; Lung Neoplasms/*blood/genetics/pathology ; Mesothelioma/*blood/genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/blood/genetics ; Occupational Exposure/*adverse effects ; *Occupational Health ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/*blood/genetics/pathology ; Predictive Value of Tests ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a cancerogenic mineral of different chemical composition, was widely employed in western Countries in industrial manufactures of different types. MPM may arise after a long latency period, up to five decades. MPM is resistant to conventional chemo- and radio-therapies. Altogether, these data indicate that the identification of new and specific markers are of a paramount importance for an early diagnosis and treatment of MPM. In recent years, microRNAs expression was found dysregulated in patients, both in cancer cells and sera, affected by tumors of different histotypes, including MPM. Cell and circulanting microRNAs, found to be dysregulated in this neoplasia, were proposed as new biomarkers. It has been reported that circulating microRNAs are stable in biological fluids and could be employed as potential MPM biomarkers. In this investigation, circulating microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665, an endogenous stable microRNA, as the internal control to quantify in our analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up-regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR-1281 and miR-32-3p are proposed as potential new MPM biomarkers.}, }
@article {pmid27714389, year = {2016}, author = {Korda, RJ and Clements, MS and Armstrong, BK and Trevenar, SM and Chalker, EB and Newman, LA and Kirk, MD}, title = {Mesothelioma trends in the ACT and comparisons with the rest of Australia.}, journal = {Public health research &amp; practice}, volume = {26}, number = {4}, pages = {}, doi = {10.17061/phrp2641646}, pmid = {27714389}, issn = {2204-2091}, mesh = {Australian Capital Territory/epidemiology ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Poisson Distribution ; Registries ; }, abstract = {OBJECTIVES: Inhalation of asbestos fibres is the predominant cause of malignant mesothelioma. Domestic exposure to asbestos is a major community concern in the Australian Capital Territory (ACT) because of loose-fill asbestos home insulation. Little is known about how trends in mesothelioma rates in the ACT compare with those elsewhere. The objective of this study was to describe trends in mesothelioma rates in the ACT and compare them with those for the rest of Australia.<br><br>METHODS: We used de-identified data from the ACT Cancer Registry (1982- 2014), and the Western Australia (WA) Cancer Registry and the Australian Cancer Database (1982-2011). We calculated crude mesothelioma rates, by 3-year periods, for the ACT and for the rest of Australia (excluding WA). We used Poisson regression to analyse mesothelioma trends from 1994 to 2011 (complete reporting period) using an indirect standardisation approach to adjust for age and sex.<br><br>RESULTS: There were 140 mesothelioma cases reported to the ACT Cancer Registry between 1982 and 2014 - 81% male and 19% female. Between 1994 and 2011, age- and sex-adjusted mesothelioma rates in the ACT increased over time, on average by 12% per 3-year period (relative risk [RR] 1.12; 95% confidence interval [CI] 0.99, 1.26). Compared with the rest of Australia (excluding WA), ACT rates were, on average, lower (RR 0.84; 95% CI 0.69, 1.02), but they increased at a higher rate (RR 1.12 per 3-year period; 95% CI 0.99, 1.27). These results are strongly influenced by the higher rate of mesothelioma observed in the ACT in 2009-2011, when ACT rates became similar to those for the rest of Australia (excluding WA).<br><br>CONCLUSIONS: Although mesothelioma rates may have increased more in the ACT than the rest of Australia (excluding WA) during the past two decades, there is considerable uncertainty in the trends. More information is needed regarding the health risks associated with living in a house with loose-fill asbestos insulation. This is the subject of further studies within the ACT Asbestos Health Study.}, }
@article {pmid27705551, year = {2016}, author = {Dodson, RF}, title = {Preface: Respirable elongated mineral particles and human health-Revisited.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {149-150}, doi = {10.1080/10937404.2016.1193358}, pmid = {27705551}, issn = {1521-6950}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/*chemically induced ; }, }
@article {pmid27705550, year = {2016}, author = {Levin, JL and Rouk, A and Shepherd, S and Hurst, GA and McLarty, JW}, title = {Tyler asbestos workers: A mortality update in a cohort exposed to amosite.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {190-200}, doi = {10.1080/10937404.2016.1195319}, pmid = {27705550}, issn = {1521-6950}, mesh = {Asbestos, Amosite/*toxicity ; Asbestosis/etiology/*mortality ; Cohort Studies ; Female ; Humans ; Male ; Occupational Diseases/chemically induced/*mortality ; *Occupational Exposure ; Texas/epidemiology ; }, abstract = {The Tyler asbestos plant produced pipe insulation from 1954 to 1972 and exclusively used amosite asbestos. There were 1130 former workers of this plant during the period of operation. A death certificate mortality analysis was published regarding this plant in 1998 for the period through 1993. This study represents an update of the mortality analysis with additional certificates collected for deaths occurring through 2011.Searches of the National Death Index database were conducted in 2004 and again in 2013. At the time of the latter search, only deaths occurring through 2011 were available. In total, 265 distinct additional death certificates were secured and added to 304 available from the original study. After the new certificates were coded (ICD-9), data were analyzed using the Centers for Disease Control and Prevention Life Table Analysis System (LTAS) and standard mortality ratios (SMR) generated with 95% confidence limits (CL). LTAS constructs cause-specific mortality rates by age, gender, race, and person-time at risk, and compares observed rates with a referent population in order to derive SMR. A significant excess number of deaths due to nonmalignant respiratory disease (asbestosis) and from select malignant neoplasms were identified. There were in total 23 mesothelioma deaths (4% of deaths), with 16 pleural and 7 peritoneal. The SMR for malignant neoplasms of the trachea, bronchus, and lung was 244 (with 95% CL 196, 300), suggesting that exposed workers from this cohort were nearly 2.5-fold (244 %) more likely to die from this cause as the general referent population. The analysis also showed that exposures of short duration (<6 mo) produced significantly elevated SMR for all respiratory cancers, lung cancer, and pleural mesothelioma. There was a significant difference in median duration of exposure for mesothelioma types, confirming association of peritoneal mesothelioma with longer duration of exposure. Deaths due to intestinal cancer (predominantly colon; not including rectum) were also found in excess. The mortality experience of the Tyler cohort continues to be followed with great interest, given the exclusivity of exposure to amosite. Data confirm the inherent pathogenicity of this fiber type for nonmalignant disease as well as select cancers, particularly relevant given the importance of this amphibole's use in the United States.}, }
@article {pmid27705549, year = {2016}, author = {Lemen, RA}, title = {Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {250-265}, doi = {10.1080/10937404.2016.1195323}, pmid = {27705549}, issn = {1521-6950}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Humans ; Incidence ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Socioeconomic Factors ; United States/epidemiology ; }, abstract = {Mesothelioma, a rare tumor, is highly correlated with asbestos exposure. Mesothelioma, similar to all asbestos-related diseases, is dose/intensity dependent to some degree, and studies showed the risk of mesothelioma rises with cumulative exposures. Multiple processes occur in an individual before mesothelioma occurs. The impact of mesothelioma in the United States has been continuous over the last half century, claiming between 2,000 and 3,000 lives each year. Mesothelioma is a preventable tumor that is more frequently reported as associated with asbestos exposure among men than women. However, the rate of asbestos-associated mesothelioma is on the rise among women due to better investigation into their histories of asbestos exposure. It is of interest that investigators detected asbestos-associated cases of mesothelioma in women from nonoccupational sources-that is, bystander, incidental, or take-home exposures. It is postulated that asbestos-associated mesotheliomas, in both men and women, are likely underreported. However, with the implementation of the most recent ICD-10 coding system, the correlation of mesothelioma with asbestos exposure is expected to rise to approximately 80% in the United States. This study examined the demographic and etiological nature of asbestos-related mesothelioma.}, }
@article {pmid27705548, year = {2016}, author = {Cook, PM and Swintek, J and Dawson, TD and Chapman, D and Etterson, MA and Hoff, D}, title = {Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {266-288}, doi = {10.1080/10937404.2016.1195326}, pmid = {27705548}, issn = {1521-6950}, mesh = {Animals ; Asbestos/*toxicity ; Complex Mixtures/*toxicity ; Dose-Response Relationship, Drug ; Mesothelioma/*chemically induced ; Models, Theoretical ; Pleural Neoplasms/*chemically induced ; Rats ; Retrospective Studies ; }, abstract = {Cancer potencies of mineral and synthetic elongated particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of elongated particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual elongated particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the elongated particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin elongated particles significantly degrades the resultant particle count and surface area dose-based predictive model fits; and (4) alternative biologically plausible model adjustments provide evidence for reduced potency of elongated particles with aspect ratios less than 8 and lengths greater than 80 µm. Regardless of these adjustments, the optimum predictive models strongly incorporate potency attributable to abundant short elongated particles in proportion to their surface area. Transmission electron microscopy analyses of low-temperature-ashed pleural membrane and lung tissues 5.5 mo post intrapleural exposures do not support hypotheses that short elongated particles that reach the pleural space are rapidly eliminated. Low-aspect-ratio elongated particles were still abundant in pleural membrane tissues but may have reduced potencies due to aggregation tendencies and therefore lower potential for intracellular presence.}, }
@article {pmid27705546, year = {2016}, author = {Andujar, P and Lacourt, A and Brochard, P and Pairon, JC and Jaurand, MC and Jean, D}, title = {Five years update on relationships between malignant pleural mesothelioma and exposure to asbestos and other elongated mineral particles.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {151-172}, doi = {10.1080/10937404.2016.1193361}, pmid = {27705546}, issn = {1521-6950}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Humans ; *Lung Neoplasms/chemically induced/epidemiology/genetics ; *Mesothelioma/chemically induced/epidemiology/genetics ; Mesothelioma, Malignant ; Minerals/toxicity ; Nanoparticles/*toxicity ; Occupational Exposure ; *Pleural Neoplasms/chemically induced/epidemiology/genetics ; }, abstract = {Despite the reduction of global asbestos consumption and production due to the ban or restriction of asbestos uses in more than 50 countries since the 1970s, malignant mesothelioma remains a disease of concern. Asbestos is still used, imported, and exported in several countries, and the number of mesothelioma deaths may be expected to increase in the next decades in these countries. Asbestos exposure is the main risk factor for malignant pleural mesothelioma, but other types of exposures are linked to the occurrence of this type of cancer. Although recent treatments improve the quality of life of patients with mesothelioma, malignant pleural mesothelioma remains an aggressive disease. Recent treatments have not resulted in appreciable improvement in survival, and thus development of more efficient therapies is urgently needed. The development of novel therapeutic strategies is dependent on our level of knowledge of the physiopathological and molecular changes that mesothelial cells acquired during the neoplastic process. During the past 5 years, new findings have been published on the etiology, epidemiology, molecular changes, and innovative treatments of malignant pleural mesothelioma. This review aims to update the findings of recent investigations on etiology, epidemiology, and molecular changes with a focus on (1) attributable risk of asbestos exposure in men and women and (2) coexposure to other minerals and other elongated mineral particles or high aspect ratio nanoparticles. Recent data obtained on genomic and gene alterations, pathways deregulations, and predisposing factors are summarized.}, }
@article {pmid27705545, year = {2016}, author = {Larson, D and Powers, A and Ambrosi, JP and Tanji, M and Napolitano, A and Flores, EG and Baumann, F and Pellegrini, L and Jennings, CJ and Buck, BJ and McLaurin, BT and Merkler, D and Robinson, C and Morris, P and Dogan, M and Dogan, AU and Pass, HI and Pastorino, S and Carbone, M and Yang, H}, title = {Investigating palygorskite's role in the development of mesothelioma in southern Nevada: Insights into fiber-induced carcinogenicity.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {213-230}, pmid = {27705545}, issn = {1521-6950}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Epithelial Cells/cytology/*drug effects ; Lung Neoplasms/chemically induced/*pathology ; Magnesium Compounds/*toxicity ; Mesothelioma/chemically induced/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Nevada ; Silicon Compounds/*toxicity ; }, abstract = {Similar to asbestos fibers, nonregulated mineral fibers can cause malignant mesothelioma (MM). Recently, increased proportions of women and young individuals with MM were identified in southern Nevada, suggesting that environmental exposure to carcinogenic fibers was causing the development of MM. Palygorskite, a fibrous silicate mineral with a history of possible carcinogenicity, is abundant in southern Nevada. In this study, our aim was to determine whether palygorskite was contributing to the development of MM in southern Nevada. While palygorskite, in vitro, displayed some cytotoxicity toward primary human mesothelial (HM) cells and reduced their viability, the effects were roughly half of those observed when using similar amounts of crocidolite asbestos. No Balb/c (0/19) or MexTAg (0/18) mice injected with palygorskite developed MM, while 3/16 Balb/c and 13/14 MexTAg mice injected with crocidolite did. Lack of MM development was associated with a decreased acute inflammatory response, as injection of palygorskite resulted in lower percentages of macrophages (p = .006) and neutrophils (p = .02) in the peritoneal cavity 3 d after exposure compared to injection of crocidolite. Additionally, compared to mice injected with crocidolite, palygorskite-injected mice had lower percentages of M2 (tumor-promoting) macrophages (p = .008) in their peritoneal cavities when exposed to fiber for several weeks. Our study indicates that palygorskite found in the environment in southern Nevada does not cause MM in mice, seemingly because palygorskite, in vivo, fails to elicit inflammation that is associated with MM development. Therefore, palygorskite is not a likely contributor to the MM cases observed in southern Nevada.}, }
@article {pmid27705544, year = {2016}, author = {Soeberg, MJ and Leigh, J and van Zandwijk, N}, title = {Malignant mesothelioma in Australia 2015: Current incidence and asbestos exposure trends.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {173-189}, doi = {10.1080/10937404.2016.1194254}, pmid = {27705544}, issn = {1521-6950}, mesh = {Age Factors ; Asbestos/*toxicity ; Australia/epidemiology ; *Environmental Exposure ; Geography ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Occupational Exposure ; Sex Factors ; }, abstract = {Australia is known to have had the highest per-capita asbestos consumption level of any nation, reaching a peak in the 1970s. Although crocidolite was effectively banned in the late 1960s, and amosite use ceased in the mid 1980s, a complete asbestos ban was not implemented until 2003. This resulted in an epidemic of asbestos-related disease, which has only now reached its peak. Between 1982 and 2011, 13,036 individuals were newly diagnosed with malignant mesothelioma, with 690 diagnosed in 2011. A further 778 cases were identified between 1945 and 1981 from retrospective searches and the first 2 years of the Australian Mesothelioma Program. The age-standardized malignant mesothelioma incidence rate has leveled off in the last 10 years (2.8 per 100,000 in 2011). There has been a marked increase over time in the age-specific incidence rates for individuals aged 75 years or older. Data from the current Australian Mesothelioma Registry on asbestos exposure history in Australia is available for 449 subjects diagnosed between July 1, 2010, and April 1, 2015. This asbestos exposure history data show that 60% (n = 268) of cases had probable or possible occupational asbestos exposure, with trade-based jobs being the most frequent sources of occupational asbestos exposure. In addition, out of the 449 cases, 377 were recorded as having probable or possible nonoccupational asbestos exposure. Continuous vigilance toward changes over time in the settings in which people are exposed to asbestos and in the descriptive epidemiology of malignant mesothelioma is recommended to enable a comprehensive understanding of the current and future impact of asbestos-related diseases in Australia.}, }
@article {pmid27705543, year = {2016}, author = {Baumann, F and Carbone, M}, title = {Environmental risk of mesothelioma in the United States: An emerging concern-epidemiological issues.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {231-249}, doi = {10.1080/10937404.2016.1195322}, pmid = {27705543}, issn = {1521-6950}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Exposure ; Risk Assessment ; Sex Factors ; United States/epidemiology ; Young Adult ; }, abstract = {Despite predictions of decline in mesothelioma following the ban of asbestos in most industrial countries, the incidence is still increasing globally, particularly in women. Because occupational exposure to asbestos is the main cause of mesothelioma, it occurs four- to eightfold more frequently in men than women, at a median age of 74 years. When mesothelioma is due to an environmental exposure, the M:F sex ratio is 1:1 and the median age at diagnosis is ~60 years. Studying environmental risk of mesothelioma is challenging because of the long latency period and small numbers, and because this type of exposure is involuntary and unknown. Individual-based methods cannot be used, and new approaches need to be found. To better understand the most recent trends of mesothelioma in the United States, all mesothelioma deaths reported to the Centers for Disease Control and Prevention (CDC) during 1999-2010 were analyzed. Among all mesothelioma deaths in the United States, the 1920s birth cohort significantly predominated, and the proportion of younger cohorts constantly decreased with time, suggesting a decline in occupational exposure in these cohorts. The M:F mesothelioma sex ratio fell with time, suggesting an increased proportion of environmental cases. Environmental exposures occur in specific geographic areas. At the large scale of a state, mesotheliomas related to environmental exposure are diluted among occupational cases. The spatial analysis at a smaller scale, such as county, enables detection of areas with higher proportions of female and young mesothelioma cases, thus indicating possible environmental exposure, where geological and environmental investigations need to be carried out.}, }
@article {pmid27699035, year = {2016}, author = {Pu, X and Dou, Y and Liu, D and Lu, S and Quan, S and Zhang, X and Ma, S and Zhao, Z}, title = {Membranous nephropathy associated with malignant pleural mesothelioma in an adult patient: A case report.}, journal = {Molecular and clinical oncology}, volume = {5}, number = {4}, pages = {407-410}, pmid = {27699035}, issn = {2049-9450}, abstract = {A 23-year-old man presented to our hospital with membranous nephropathy and received a detailed examination, including pleural biopsy, due to a feeling of chest oppression. The result of the pleural biopsy was malignant pleural mesothelioma. However, the patient did not have a history of asbestos or tobacco exposure. A review of the English literature identified only 7 reported cases of concomitant malignant mesothelioma and nephrotic syndrome. Furthermore, among the 7 cases reviewed, 6 had a history of asbestos exposure, 1 had a history of prolonged tobacco exposure and in only 1 case the renal pathology results revealed the presence of membranous nephropathy.}, }
@article {pmid27698933, year = {2016}, author = {Walter, RF and Vollbrecht, C and Werner, R and Mairinger, T and Schmeller, J and Flom, E and Wohlschlaeger, J and Barbetakis, N and Paliouras, D and Chatzinikolaou, F and Adamidis, V and Tsakiridis, K and Zarogoulidis, P and Trakada, G and Christoph, DC and Schmid, KW and Mairinger, FD}, title = {Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy.}, journal = {Journal of Cancer}, volume = {7}, number = {13}, pages = {1915-1925}, pmid = {27698933}, issn = {1837-9664}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumour leading to a dismal prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons for the rather poor efficacy of platinum compounds remain largely unknown.<br><br>MATERIAL AND METHODS: For this exploratory mRNA study, 24 FFPE tumour specimens were screened by digital gene expression analysis. Based on data from preliminary experiments and recent literature, a total of 366 mRNAs were investigated using a Custom CodeSet from NanoString. All statistical analyses were calculated with the R i386 statistical programming environment.<br><br>RESULTS: CDC25A and PARP1 gene expression were correlated with lymph node spread, BRCA1 and TP73 expression levels with higher IMIG stage. NTHL1 and XRCC3 expression was associated with TNM stage. CHECK1 as well as XRCC2 expression levels were correlated with tumour progression in the overall cohort of patients. CDKN2A and MLH1 gene expression influenced overall survival in this collective. In the adjuvant treated cohort only, CDKN2A, CHEK1 as well as ERCC1 were significantly associated with overall survival. Furthermore, TP73 expression was associated with progression in this subgroup.<br><br>CONCLUSION: DNA-damage response plays a crucial role in response to platin-based chemotherapeutic regimes. In particular, CHEK1, XRCC2 and TP73 are strongly associated with tumour progression. ERCC1, MLH1, CDKN2A and most promising CHEK1 are prognostic markers for OS in MPM. TP73, CDKN2A, CHEK1 and ERCC1 seem to be also predictive markers in adjuvant treated MPMs. After a prospective validation, these markers may improve clinical and pathological practice, finally leading to a patients' benefit by an enhanced clinical management.}, }
@article {pmid27696225, year = {2016}, author = {Valenzuela, M and Giraldo, M and Gallo-Murcia, S and Pineda, J and Santos, L and Ramos-Bonilla, JP}, title = {Recent Scientific Evidence Regarding Asbestos Use and Health Consequences of Asbestos Exposure.}, journal = {Current environmental health reports}, volume = {3}, number = {4}, pages = {335-347}, pmid = {27696225}, issn = {2196-5412}, mesh = {Asbestos, Serpentine/*adverse effects ; Asbestosis ; Carcinogens/toxicity ; Environmental Exposure/adverse effects ; Humans ; Mesothelioma/*epidemiology ; Occupational Diseases/chemically induced ; Occupational Exposure/*adverse effects ; }, abstract = {To justify the continuous use of two million tons of asbestos every year, it has been argued that a safe/controlled use can be achieved. The aim of this review was to identify recent scientific studies that present empirical evidence of: 1) health consequences resulting from past asbestos exposures and 2) current asbestos exposures resulting from asbestos use. Articles with evidence that could support or reject the safe/controlled use argument were also identified. A total of 155 articles were included in the review, and 87 % showed adverse asbestos health consequences or high asbestos exposures. Regarding the safe/controlled use, 44 articles were identified, and 82 % had evidence suggesting that the safe/controlled use is not being achieved. A large percentage of articles with evidence that support the safe/controlled use argument have a conflict of interest declared. Most of the evidence was developed in high-income countries and in countries that have already banned asbestos.}, }
@article {pmid27687963, year = {2016}, author = {Nowak, AK and Chansky, K and Rice, DC and Pass, HI and Kindler, HL and Shemanski, L and Billé, A and Rintoul, RC and Batirel, HF and Thomas, CF and Friedberg, J and Cedres, S and de Perrot, M and Rusch, VW and , }, title = {The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {12}, pages = {2089-2099}, doi = {10.1016/j.jtho.2016.08.147}, pmid = {27687963}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Lung Neoplasms/*classification/pathology ; Mesothelioma/*classification/pathology ; Mesothelioma, Malignant ; Neoplasm Staging/*classification ; Pleural Neoplasms/*classification/pathology ; }, abstract = {INTRODUCTION: The current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition.<br><br>METHODS: Data elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded. An electronic data capture system was established to facilitate data submission.<br><br>RESULTS: A total of 3519 cases were submitted to the database. Of those eligible for T-component analysis, 509 cases had only clinical staging, 836 cases had only surgical staging, and 642 cases had both available. Survival was examined for T categories according to the current seventh edition staging system. There was clear separation between all clinically staged categories except T1a versus T1b (hazard ratio&#xa0;= 0.99, p&#xa0;= 0.95) and T3 versus T4 (hazard ratio&#xa0;= 1.22, p&#xa0;= 0.09), although the numbers of T4 cases were small. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category; no current descriptors were shifted or eliminated. Tumor thickness and nodular or rindlike morphology were significantly associated with survival.<br><br>CONCLUSIONS: A recommendation to collapse both clinical and pathological T1a and T1b into a T1 classification will be made for the eighth edition staging system. Simple measurement of pleural thickness has prognostic significance and should be examined further with a view to incorporation into future staging.}, }
@article {pmid27687962, year = {2016}, author = {Rusch, VW and Chansky, K and Kindler, HL and Nowak, AK and Pass, HI and Rice, DC and Shemanski, L and Galateau-Sallé, F and McCaughan, BC and Nakano, T and Ruffini, E and van Meerbeeck, JP and Yoshimura, M and , }, title = {The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {12}, pages = {2112-2119}, doi = {10.1016/j.jtho.2016.09.124}, pmid = {27687962}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Lung Neoplasms/*classification/pathology ; Mesothelioma/*classification/pathology ; Mesothelioma, Malignant ; Neoplasm Staging/*classification ; Pleural Neoplasms/*classification/pathology ; }, abstract = {INTRODUCTION: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM.<br><br>METHODS: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases.&#xa0;The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS)&#xa0;between the clinical M0 (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases.<br><br>RESULTS: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p&#xa0;= 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of&#xa0;only cM1 in the stage IV group. Exploratory analyses suggest a&#xa0;possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation-generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1).<br><br>CONCLUSIONS: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings.}, }
@article {pmid27681566, year = {2016}, author = {Mensi, C and De Matteis, S and Catelan, D and Dallari, B and Riboldi, L and Pesatori, AC and Consonni, D}, title = {Geographical patterns of mesothelioma incidence and asbestos exposure in Lombardy, Italy.}, journal = {La Medicina del lavoro}, volume = {107}, number = {5}, pages = {340-355}, pmid = {27681566}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Young Adult ; }, abstract = {BACKGROUND: Measuring malignant mesothelioma (MM) occurrence is a useful means to monitor the impact of past asbestos exposure and possibly identify new sources of asbestos exposure.<br><br>OBJECTIVES: Aim of this study is to describe the results of the MM registry of the Lombardy Region, North-West Italy, the most populated (currently, 10 million inhabitants) and industrialised Italian region.<br><br>METHODS: We extracted from the Lombardy Region Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) database all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in 2000 through 2012. For each Province, we calculated crude and standardised incidence rates using Italy 2001, European, and world (Segi's) standard populations. To examine spatial patterns of MM occurrence across municipalities we drew maps of crude rates smoothed according to the Besag, York and Molli&#xe9; (BYM) method.<br><br>RESULTS: We recorded 4442 MM cases (2850 in men and 1592 in women), representing about one fourth of MM cases occurring in Italy. Occupational exposure was more frequent in men (73.6%) than in women (38.2%). The crude regional rates were 4.7 per 100,000 person-years in men and 2.5 per 100,000 person-years in women. The highest rates were observed in the Pavia Province (crude rates: 8.7 per 100,000 in men and 5.3 and per 100,000 person-years in women).<br><br>CONCLUSIONS: This study documented high MM occurrence in both genders, attributable to extensive asbestos exposure in the past.}, }
@article {pmid27669062, year = {2016}, author = {Lamote, K and Vynck, M and Van Cleemput, J and Thas, O and Nackaerts, K and van Meerbeeck, JP}, title = {Detection of malignant pleural mesothelioma in exhaled breath by multicapillary column/ion mobility spectrometry (MCC/IMS).}, journal = {Journal of breath research}, volume = {10}, number = {4}, pages = {046001}, doi = {10.1088/1752-7155/10/4/046001}, pmid = {27669062}, issn = {1752-7163}, mesh = {Adult ; Aged ; Breath Tests/*methods ; *Exhalation ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mass Spectrometry/*methods ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Models, Biological ; Pleural Neoplasms/*diagnosis ; ROC Curve ; Statistics as Topic ; Volatile Organic Compounds/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly caused by previous asbestos exposure. Diagnosis often happens in advanced stages restricting any therapeutic perspectives. Early stage detection via breath analysis was explored using multicapillary column/ion mobility spectrometry (MCC/IMS) to detect volatile organic compounds (VOCs) in the exhaled breath of MPM patients in comparison to former occupational asbestos-exposed and non-exposed controls. Breath and background samples of 23 MPM patients, 22 asymptomatic former asbestos (AEx) workers and 21 healthy non-asbestos exposed persons were taken for analysis. After background correction, we performed a logistic least absolute shrinkage and selection operator (lasso) regression to select the most important VOCs, followed by receiver operating characteristic (ROC) analysis. MPM patients were discriminated from both controls with 87% sensitivity, 70% specificity and respective positive and negative predictive values of 61% and 91%. The overall accuracy was 76% and the area under the ROC-curve was 0.81. AEx individuals could be discriminated from MPM patients with 87% sensitivity, 86% specificity and respective positive and negative predictive values of 87% and 86%. The overall accuracy was 87% with an area under the ROC-curve of 0.86. Breath analysis by MCC/IMS allows MPM patients to be discriminated from controls and holds promise for further investigation as a screening tool for former asbestos-exposed persons at risk of developing MPM.}, }
@article {pmid27660729, year = {2016}, author = {Gleason, JB and Tashtoush, B and Diacovo, MJ}, title = {Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor.}, journal = {Case reports in pulmonology}, volume = {2016}, number = {}, pages = {7560929}, pmid = {27660729}, issn = {2090-6846}, abstract = {Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma.}, }
@article {pmid27650313, year = {2016}, author = {Sayan, M and Mossman, BT}, title = {The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases.}, journal = {Particle and fibre toxicology}, volume = {13}, number = {1}, pages = {51}, pmid = {27650313}, issn = {1743-8977}, support = {P01 HL067004/HL/NHLBI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Inflammasomes/*metabolism ; Lung Diseases/*chemically induced ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; Particulate Matter/toxicity ; Pneumonia/*chemically induced ; Silicon Dioxide/toxicity ; }, abstract = {The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres. Most notably, inflammasome activation appears to regulate the balance between tissue repair and inflammation after inhalation of pathogenic pollutants such as asbestos, crystalline silica (CS), and airborne particulate matter (PM). Different types of fibres and particles may have distinct mechanisms of inflammasome interaction and outcome. This review summarizes the structure and function of inflammasomes, the interplay between various chemokines and cytokines and cell types of the lung and pleura after inflammasome activation, and the events leading to the development of non-malignant (allergic airway disease and chronic obstructive pulmonary disease (COPD), asbestosis, silicosis) and malignant (mesothelioma, lung cancer) diseases by pathogenic particulates. In addition, it emphasizes the importance of communication between cells of the immune system, target cells of these diseases, and components of the extracellular matrix (ECM) in regulation of inflammasome-mediated events.}, }
@article {pmid27644679, year = {2016}, author = {Kattan, J and Eid, R and Kourie, HR and Farhat, F and Ghosn, M and Ghorra, C and Tomb, R}, title = {Mesotheliomas in Lebanon: Witnessing a Change in Epidemiology.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {8}, pages = {4169-4173}, pmid = {27644679}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Humans ; Incidence ; Lebanon/epidemiology ; Lung Neoplasms/*epidemiology/*pathology ; Male ; Mesothelioma/*epidemiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/epidemiology/pathology ; Peritoneum/pathology ; Pleura/pathology ; Pleural Neoplasms/epidemiology/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Mesotheliomas are relatively rare tumors in Lebanon. The only previous study goes back to 14 years ago, when we published epidemiological characteristics of mesotheliomas in Lebanon, showing that the pleural location accounted for the vast majority of cases, with clear evidence of asbestos exposure from the Eternit factory of Chekka region. The objective of this current study was to estimate the incidence of mesothelioma in the past decade and to identify its epidemiological, clinical and therapeutic characteristics, making comparisons with our first study published in 2001.<br><br>MATERIALS AND METHODS: Between 2002 and 2014, patients diagnosed with malignant mesothelioma at Hotel-Dieu de France University Hospital were investigated. Epidemiological data focusing on asbestos exposure history were collected from medical records and interviews with the families.<br><br>RESULTS: A total of 26 patients were diagnosed with mesothelioma, 21 of which were successfully investigated. The mean age of these 21 patients is 62.5 (19-82). Only 3 (14.29%) are women. 18 (85.71%) were smokers. Among the 21 available mesotheliomas, 15 (71.4%) are pleural, while 5 (23.8%) are peritoneal and 1 (4.8%) pericardial. Only 60% of patients with pleural mesothelioma and 50% of those with an obvious exposure to asbestos lived and/or worked in Chekka region. The mean time of asbestos exposure in patients with mesothelioma is 24.5 (1-50) years and the mean latency is 37.4 (4-61) years. Of the 21 patients, 10 (47.6%) underwent surgery during their treatment, 16 (76.2%) received chemotherapy and 3 (14.3%) received best supportive care.<br><br>CONCLUSIONS: Compared to the previous study (1991-2000), substantial changes in the epidemiology of mesothelioma in Lebanon were observed, such as an increase in peritoneal localizations and a lower correlation with Chekka region asbestos contamination.}, }
@article {pmid27628605, year = {2016}, author = {Kanai, G and Kakuta, T and Hirukawa, T and Okamatsu, C and Fukagawa, M}, title = {A Case of Encapsulating Peritoneal Sclerosis Complicated by Malignant Peritoneal Mesothelioma.}, journal = {The Tokai journal of experimental and clinical medicine}, volume = {41}, number = {3}, pages = {135-138}, pmid = {27628605}, issn = {2185-2243}, mesh = {Biopsy ; Female ; Humans ; Kidney Failure, Chronic/complications/therapy ; Lung Neoplasms/*complications/*diagnosis/pathology ; Mesothelioma/*complications/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Dialysis ; Peritoneal Fibrosis/*diagnosis/*etiology ; Peritoneal Neoplasms/*complications/*diagnosis/pathology ; Tomography, X-Ray Computed ; }, abstract = {We report a case of peritoneal mesothelioma discovered in a patient during peritoneal dialysis. The patient was a 55-year-old woman who had no history of asbestos exposure. Owing to end-stage kidney failure, she had been undergoing peritoneal dialysis for over 8 years, and she had been diagnosed with encapsulating peritoneal sclerosis. She was admitted to the hospital for intestinal obstruction. Three months later, she noticed an enlarging mass in the epigastric region. Computed tomography showed a 10-cm mass originating in the abdominal wall that had invaded the liver. It was diagnosed as malignant mesothelioma via biopsy. Cases of sarcoma-like mass-forming peritoneal mesothelioma are rare, and there are no prior reports of encapsulating peritoneal sclerosis complicated by malignant peritoneal mesothelioma. Thus, this unique case of peritoneal mesothelioma can provide us with important knowledge about this rare entity.}, }
@article {pmid27623107, year = {2016}, author = {Kanteti, R and Riehm, JJ and Dhanasingh, I and Lennon, FE and Mirzapoiazova, T and Mambetsariev, B and Kindler, HL and Salgia, R}, title = {PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {32992}, pmid = {27623107}, issn = {2045-2322}, mesh = {Aminopyridines/administration &amp; dosage/pharmacology ; Animals ; Antineoplastic Agents/administration &amp; dosage/*pharmacology ; Apoptosis/drug effects ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Crizotinib ; Drug Synergism ; Female ; Humans ; Lung Neoplasms/*drug therapy/*metabolism/pathology ; Mesothelioma/*drug therapy/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; Microtubules/drug effects ; Morpholines/administration &amp; dosage/pharmacology ; *Phosphoinositide-3 Kinase Inhibitors ; Pleural Neoplasms/*drug therapy/*metabolism/pathology ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-met/*antagonists &amp; inhibitors ; Pyrazoles/administration &amp; dosage/pharmacology ; Pyridines/administration &amp; dosage/pharmacology ; Pyrimidines/pharmacology ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer that is commonly associated with prior asbestos exposure. Receptor tyrosine kinases (RTKs) such as MET and its downstream target PI3K are overexpressed and activated in a majority of MPMs. Here, we studied the combinatorial therapeutic efficacy of the MET/ALK inhibitor crizotinib, with either a pan-class I PI3K inhibitor, BKM120, or with a PI3K/mTOR dual inhibitor, GDC-0980, in mesothelioma. Cell viability results showed that MPM cells were highly sensitive to crizotinib, BKM120 and GDC-0980 when used individually and their combination was more effective in suppressing growth. Treatment of MPM cells with these inhibitors also significantly decreased cell migration, and the combination of them was synergistic. Treatment with BKM120 alone or in combination with crizotinib induced G2-M arrest and apoptosis. Both crizotinib and BKM120 strongly inhibited the activity of MET and PI3K as evidenced by the decreased phosphorylation of MET, AKT and ribosomal S6 kinase. Using a PDX mouse model, we showed that a combination of crizotinib with BKM120 was highly synergetic in inhibiting MPM tumor growth. In conclusion our findings suggest that dual inhibition of PI3K and MET pathway is an effective strategy in treating MPM as compared to a single agent.}, }
@article {pmid27621868, year = {2016}, author = {Sandri, A and Guerrera, F and Roffinella, M and Olivetti, S and Costardi, L and Oliaro, A and Filosso, PL and Lausi, PO and Ruffini, E}, title = {Validation of EORTC and CALGB prognostic models in surgical patients submitted to diagnostic, palliative or curative surgery for malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {8}, number = {8}, pages = {2121-2127}, pmid = {27621868}, issn = {2072-1439}, abstract = {BACKGROUND: To assess the trend of our surgical patients affected by malignant pleural mesothelioma (MPM) and submitted to diagnostic/palliative or curative surgical procedures and to validate the European Organisation for Research and Treatment of Cancer (EORTC) prognostic score in our patient population.<br><br>METHODS: This is a cohort study of patients submitted to surgery for MPM from January 2007 to December 2013. Primary outcome was overall survival (OS). Univariate and multivariate-adjusted comparisons by EORTC prognostic score for OS were accomplished using Cox method. Adjusted models included the following clinical variables: kind of procedure, smoking habit, asbestos exposure, Charlson's Comorbidity Index (CCI), clinical tumor stage, adjuvant chemotherapy, dyspnoea, chest pain and haematological variables according to the score features. Nomenclature of the surgical procedures matches the International Association for the Study Lung Cancer (IASLC)/International Mesothelioma Interest Group (iMIG).<br><br>RESULTS: One-hundred sixty-six consecutive cases were collected: the median age at surgery was 73 years and 123 patients (75%) had a history of asbestos exposure. Ninty patients (54%) were submitted to a palliative/diagnostic thoracoscopy, 30 to pleurectomy/decortication (P/D), and 6 to extra-pleural pneumonectomy (EPP). Clinical TNM stages were as follows: 99 (60%) stage I-II, 34 (20%) stage III and 33 (20%) stage IV. The median follow-up (FU) was 19 months [interquartile range (IQR), 9-31 months] and the FU-completeness was 98%. By the end of the study 130 patients died (78%). One- and 3-year OS was 60% and 36%, respectively. Patients submitted to EPP and P/D showed a better survival (P=0.013). Multivariable model showed an independent prognostic value of EORTC score (HR =2.86, P<0.001).<br><br>CONCLUSIONS: In selected patients, aggressive surgical approaches, although not radical, may still be beneficial. The EORTC prognostic index proved to be an independent prognostic factor in our cohort of patients and therefore is a reliable and valid instrument that may be implemented in the daily practice.}, }
@article {pmid27619223, year = {2016}, author = {Geltner, C and Errhalt, P and Baumgartner, B and Ambrosch, G and Machan, B and Eckmayr, J and Klikovits, T and Hoda, MA and Popper, H and Klepetko, W and , }, title = {Management of malignant pleural mesothelioma - part 1: epidemiology, diagnosis, and staging : Consensus of the Austrian Mesothelioma Interest Group (AMIG).}, journal = {Wiener klinische Wochenschrift}, volume = {128}, number = {17-18}, pages = {611-617}, pmid = {27619223}, issn = {1613-7671}, mesh = {Diagnosis, Differential ; Diagnostic Imaging/standards ; Evidence-Based Medicine/standards ; Humans ; Medical Oncology/standards ; Mesothelioma/*diagnosis/*epidemiology/pathology ; Neoplasm Staging ; Pleural Effusion, Malignant/*diagnosis/*epidemiology/pathology ; Pleural Neoplasms/*diagnosis/*epidemiology/pathology ; Practice Guidelines as Topic ; Prevalence ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma is a rare malignant disease that in the majority of cases is associated with asbestos exposure. The incidence in Europe is about 20 per million inhabitants and it is increasing worldwide. Initial symptoms are shortness of breath, pleural effusion, cough, and chest pain. The typical growth pattern is along the pleural surface; however, infiltration of the lung and/or mediastinal and chest wall structures can occur in a more advanced stage. Ultimately, distant metastases outside the chest can result. Several histological subtypes of pleural mesothelioma exist, which must be differentiated from either benign diseases or metastases in the pleural space by other tumor entities. This differential diagnosis can be very difficult and a large panel of immunohistochemical markers is required to establish the exact diagnosis. The standard procedure for confirming the disease and obtaining sufficient tissue for the diagnosis is videothoracoscopy. Full thickness biopsies are required, while transthoracic needle puncture of pleural fluid or tissue is considered to be insufficient for a cytological diagnosis. Complete and detailed staging is mandatory for categorization of the disease as well as for therapeutic decision making.}, }
@article {pmid27612329, year = {2016}, author = {Biancosino, C and Redwan, B and Krüger, M and Eberlein, M and Bölükbas, S}, title = {[Malignant Pleural Mesotheliomas].}, journal = {Zentralblatt fur Chirurgie}, volume = {141 Suppl 1}, number = {}, pages = {S61-73}, doi = {10.1055/s-0042-110248}, pmid = {27612329}, issn = {1438-9592}, mesh = {Biomarkers, Tumor/analysis ; Combined Modality Therapy ; Diagnosis, Differential ; Diagnostic Imaging ; Follow-Up Studies ; Humans ; Mesothelioma/diagnosis/pathology/*therapy ; Paraneoplastic Syndromes/diagnosis/pathology/therapy ; Pleural Neoplasms/diagnosis/pathology/*therapy ; }, abstract = {Malignant pleural mesotheliomas (MPM) are very aggressive tumors, which originate from the mesothelial cells of the pleural surface. The main risk factor associated with MPM is exposure to asbestos. The latency period between asbestos exposure and MPM can be 30-60 years. Clinical symptoms and signs are often nonspecifc. The diagnosis of MPM requires an adequate tissue specimen for pathological examination, and video assisted thoracoscopic surgey (VATS) is associated with the highest diagnostic yield. MPM are histologically classified into epitheloid, sacromatoid and biphasic (mixed) sub-types. Accurate staging with invasive tests, if needed, is an important step before an interdisciplinary team can decide on an optimal (multi-modal) treatment approach. A multi-modal treatment approach (surgery, radiation oncology and chemotherapy) is superior to all approaches relying only on a single modality, if the patient qualifies for it from an oncological and functional standpoint. The goal of the surgical therapy is to achieve macroscopic complete resection. There are two competing surgical approaches and philosophies: extrapleural pneumonectomy (EPP) and radical pleurectomy (RP). Over the last years a paradigm shift from EPP to RP occurred and RP is now often the preferred surgical option.}, }
@article {pmid27605433, year = {2016}, author = {Greening, DW and Ji, H and Chen, M and Robinson, BW and Dick, IM and Creaney, J and Simpson, RJ}, title = {Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {32643}, pmid = {27605433}, issn = {2045-2322}, mesh = {Cell Communication/genetics ; Cell Line, Tumor ; Exosomes/*genetics/pathology ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Neoplasm Proteins/*genetics ; *Proteomics ; Tumor Microenvironment/genetics ; }, abstract = {Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.}, }
@article {pmid27602956, year = {2016}, author = {Wang, S and Jiang, L and Han, Y and Chew, SH and Ohara, Y and Akatsuka, S and Weng, L and Kawaguchi, K and Fukui, T and Sekido, Y and Yokoi, K and Toyokuni, S}, title = {Urokinase-type plasminogen activator receptor promotes proliferation and invasion with reduced cisplatin sensitivity in malignant mesothelioma.}, journal = {Oncotarget}, volume = {7}, number = {43}, pages = {69565-69578}, pmid = {27602956}, issn = {1949-2553}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects/genetics ; Asbestos ; Cell Line, Tumor ; Cell Proliferation/*drug effects/genetics ; Cisplatin/*pharmacology ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/chemically induced/*genetics/metabolism ; Mesothelioma/chemically induced/*genetics/metabolism ; Mesothelioma, Malignant ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; RNA Interference ; Rats ; Receptors, Urokinase Plasminogen Activator/blood/*genetics/metabolism ; Transplantation, Heterologous ; }, abstract = {Malignant mesothelioma (MM) is a rare neoplasm associated with asbestos exposure. The prognosis of MM is poor because it is aggressive and highly resistant to chemotherapy. Using a rat model of asbestos-induced MM, we found elevated urokinase-type plasminogen activator receptor (uPAR; Plaur) expression in rat tissues, which was associated with poor prognosis. The proliferation, migration and invasion of MM cells were suppressed by uPAR knockdown and increased by overexpression experiments, irrespective of urokinase-type plasminogen activator (uPA; Plau) levels. More importantly, we found that uPAR expression is associated with sensitivity to cisplatin in MM through the PI3K/AKT pathway, which was demonstrated with specific inhibitors, LY294002 and Akti-1/2. uPAR knockdown significantly increased sensitivity to cisplatin whereas its overexpression significantly decreased cisplatin sensitivity. Furthermore, sera and tissues from MM patients showed significantly high uPAR levels, which suggested the pathogenic role of uPAR in the tumor biology of human MM. In conclusion, our findings indicate that uPAR levels are associated with malignant characteristics and cisplatin sensitivity of MM. In addition to the potential use of uPAR as a prognostic marker, the combination of uPAR abrogation and cisplatin may reveal a promising therapeutic approach for MM.}, }
@article {pmid27599565, year = {2016}, author = {Hashimoto, K and Okuma, Y and Hosomi, Y and Hishima, T}, title = {Malignant mesothelioma of the pleura with desmoplastic histology: a case series and literature review.}, journal = {BMC cancer}, volume = {16}, number = {1}, pages = {718}, pmid = {27599565}, issn = {1471-2407}, mesh = {Aged ; Female ; Humans ; Lung Neoplasms/*pathology/therapy ; Male ; Mesothelioma/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*pathology/therapy ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Desmoplastic malignant pleural mesothelioma (DMM) is rare histological subtype of diffuse malignant pleural mesothelioma (MPM), accounting for 5-10 % of cases. It has a poor prognosis, with direct invasion of the chest wall or lungs and distant metastases. Its pathological characteristics include dense collagen fibers in a storiform pattern. Its pretreatment pathological diagnosis is difficult, with fibrous pleuritis and reactive mesothelial hyperplasia as potential differential diagnoses.<br><br>CASE PRESENTATION: We retrospectively reviewed the medical charts of patients with MPM from 1996 to 2012. Among 60 patients with MPM, four patients with the desmoplastic subtype were identified and their clinical characteristics, including asbestos exposure, treatment, and prognosis, were reviewed. All of the patients with DMM were men, with a median age of 69&#xa0;years (range: 63-74&#xa0;years). All four patients had been exposed to asbestos. The definitive diagnosis was made histologically and the International Mesothelioma Interest Group classification was advanced (III/IV: 2/3) in all four patients. Three patients were treated with chemotherapy (two with cisplatin/pemetrexed and one with cisplatin/gemcitabine) and one patient underwent surgery. The median survival time in the patients with DMM was 3.8&#xa0;months (range: 0.9-11.5&#xa0;months), compared with 10.5&#xa0;months in patients with other subtypes of MPM in our institution.<br><br>CONCLUSIONS: DMM continues to have a poor prognosis. It is important to recognize this variant and distinguish it from pleural plaques, non-specific reactive pleural fibrosis, pleurisy, and other lung diseases.}, }
@article {pmid27587956, year = {2016}, author = {Cha, YK and Kim, JS and Kim, Y and Kim, YK}, title = {Radiologic Diagnosis of Asbestosis in Korea.}, journal = {Korean journal of radiology}, volume = {17}, number = {5}, pages = {674-683}, pmid = {27587956}, issn = {2005-8330}, mesh = {Asbestos/adverse effects ; Asbestosis/*diagnostic imaging/etiology ; Diagnosis, Differential ; Humans ; Idiopathic Pulmonary Fibrosis/diagnosis ; Lung/diagnostic imaging ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Exposure/adverse effects ; Radiography ; Tomography, X-Ray Computed ; }, abstract = {Asbestosis is the most important change noted in the lung parenchyma after environmental and occupational exposure to asbestos fibers. It is characterized by diffuse interstitial pulmonary fibrosis. In Korea, the incidence of asbestosis will continue to increase for many years to come and the government enacted the Asbestos Damage Relief Law in 2011 to provide compensation to those suffering from asbestos-related diseases. Radiologic evaluation is necessary for diagnosis of asbestosis, and radiologists play a key role in this process. Therefore, it is important for radiologists to be aware of the various imaging features of asbestosis.}, }
@article {pmid29903130, year = {2016}, author = {Jia, X and Mi, J and Yang, L and Wei, B and Cao, S and Hu, L and Lu, R}, title = {[A case-control study on the relationship between food preference and lung cancer and mesothelioma in a rural area with naturally occurring asbestos].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {45}, number = {5}, pages = {771-776}, pmid = {29903130}, issn = {1000-8020}, mesh = {Asbestos/*toxicity ; Case-Control Studies ; China/epidemiology ; Female ; *Food Preferences ; Humans ; Lung Neoplasms/ethnology/*etiology ; Male ; Mesothelioma/ethnology/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVE: To understand the relationship between food preference and lung cancer or malignant pleural mesothelioma and the interactive effect between food preference and asbestos exposure in a rural area with naturally occurring asbestos.<br><br>METHODS: At the basis of the cohort of Dayao in Yunnan, we performed a 1 &#x2236; 2 casecontrol study including 53 cases(23 cases for lung cancer and 26 cases for mesothelioma)and 106 age-and sex-matched normal healthy controls. In order to study the protective effect of food preference and the interactive effect between food preference and asbestos exposure, conditional logistic regression was used to estimate adjusted odds ratios(OR)and their 95% confidence intervals(CI) in both unvaried and multivariate analyses.<br><br>RESULTS: Both green tea and wild mushroom were inversely associated with lung cancer ormalignant pleural mesothelioma, and the adjusted ORs were: 0. 88(95% CI 0. 66-0. 87) for green tea, 0. 85(95% CI 0. 23- 0. 95) for wild mushroom intake. Food preference to wild mushroom modified the associations of Crocidolite ' s contacting, Respectively, relative excess risk due to interaction(RERI), attributable proportion due to interaction(API), synergy index(S) were 0. 86, 0. 26 and 0. 61.<br><br>CONCLUSION: Both green tea and wild mushroom might serve as protective factors on lung cancer or malignant pleural mesothelioma.}, }
@article {pmid27577310, year = {2016}, author = {Pearce, L}, title = {Charity support is making rewarding roles possible.}, journal = {Nursing standard (Royal College of Nursing (Great Britain) : 1987)}, volume = {31}, number = {1}, pages = {38-39}, doi = {10.7748/ns.31.1.38.s41}, pmid = {27577310}, issn = {2047-9018}, mesh = {*Charities ; Nurse's Role ; *Nursing Staff ; United Kingdom ; }, abstract = {Mesothelioma UK is one of many charities that provide money for specialist nursing posts. Currently, it funds 14 nurses, who are employed by trusts to support those with this rare form of asbestos-related cancer for 2 days each week.}, }
@article {pmid27570625, year = {2016}, author = {Luanpitpong, S and Wang, L and Davidson, DC and Riedel, H and Rojanasakul, Y}, title = {Carcinogenic Potential of High Aspect Ratio Carbon Nanomaterials.}, journal = {Environmental science. Nano}, volume = {3}, number = {3}, pages = {483-493}, pmid = {27570625}, issn = {2051-8153}, support = {R01 EB018857/EB/NIBIB NIH HHS/United States ; R01 ES022968/ES/NIEHS NIH HHS/United States ; }, abstract = {Engineered nanomaterials, including high aspect ratio carbon nanomaterials, are often commercialized without a complete human risk assessment and safety evaluation. A health concern has been raised that high aspect ratio nanomaterials such as carbon nanotubes may cause unintended health consequences, such as asbestos-like lung cancer and mesothelioma, when chronically inhaled. Considering the widespread industrial and clinical applications and the increasing incidence of human exposure to nanomaterials, it is important to address the issue of nanomaterial carcinogenicity in a timely manner. This review summarizes recent advances in nanomaterial genotoxicity and carcinogenicity with a focus on high aspect ratio carbon nanotubes, and discusses current knowledge gaps and future research directions.}, }
@article {pmid27549627, year = {2016}, author = {Huaux, F and d'Ursel de Bousies, V and Parent, MA and Orsi, M and Uwambayinema, F and Devosse, R and Ibouraadaten, S and Yakoub, Y and Panin, N and Palmai-Pallag, M and van der Bruggen, P and Bailly, C and Marega, R and Marbaix, E and Lison, D}, title = {Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells.}, journal = {Particle and fibre toxicology}, volume = {13}, number = {1}, pages = {46}, pmid = {27549627}, issn = {1743-8977}, mesh = {Animals ; Carcinogens/*toxicity ; Heterografts ; Humans ; Male ; Mesothelioma/*chemically induced/immunology ; Mice ; Mice, Inbred C57BL ; Monocytes/*immunology ; Nanotubes, Carbon/*toxicity ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells.<br><br>METHODS: Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12&#xa0;months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells.<br><br>RESULTS: We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development.<br><br>CONCLUSIONS: Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer.}, }
@article {pmid27542398, year = {2016}, author = {Franklin, P and Alfonso, H and Reid, A and Olsen, N and Shilkin, KB and Brims, F and de Klerk, N and Musk, AW}, title = {Asbestos exposure and histological subtype of malignant mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {11}, pages = {749-752}, doi = {10.1136/oemed-2016-103721}, pmid = {27542398}, issn = {1470-7926}, mesh = {Aged ; Asbestos ; Asbestos, Crocidolite/adverse effects ; Humans ; Logistic Models ; Lung Neoplasms/*chemically induced/*pathology ; Male ; Mesothelioma/*chemically induced/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Mining ; Occupational Diseases/chemically induced/pathology ; Occupational Exposure/*adverse effects ; Prognosis ; Registries ; Surveys and Questionnaires ; Western Australia ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) has distinct histological subtypes (epithelioid, sarcomatoid and biphasic) with variable behaviour and prognoses. It is well recognised that survival time varies with the histological subtype of MM. It is not known, however, if asbestos exposure characteristics (type of asbestos, degree of exposure) are associated with different histological subtypes.<br><br>AIM: To determine if the pathological MM subtype is associated with the type of asbestos or the attributes of asbestos exposure.<br><br>METHODS: Cases of MM for the period 1962 until 2012, their main histological subtype and their most significant source of asbestos exposure were collected from the Western Australian Mesothelioma Registry. Exposure characteristics included, degree of asbestos exposure (including total days exposed, years since first exposure and, for crocidolite only, calculated cumulative exposure), source of exposure (occupational or environmental), form of asbestos handled (raw or processed) and type of asbestos (crocidolite only or mixed fibres).<br><br>RESULTS: Patients with the biphasic subtype were more likely to have occupational exposure (OR 1.83, 1.12 to 2.85) and exposure to raw fibres (OR 1.58, 1.19 to 2.10). However, differences between subtypes in the proportions with these different exposure characteristics were small and unlikely to be biologically relevant. Other indicators of asbestos exposure were not associated with the histological subtype of mesothelioma.<br><br>CONCLUSIONS: There was no strong evidence of a consistent role of asbestos exposure indicators in determining the histological subtype of MM.}, }
@article {pmid27540559, year = {2016}, author = {Salamatipour, A and Mohanty, SK and Pietrofesa, RA and Vann, DR and Christofidou-Solomidou, M and Willenbring, JK}, title = {Asbestos Fiber Preparation Methods Affect Fiber Toxicity.}, journal = {Environmental science &amp; technology letters}, volume = {3}, number = {7}, pages = {270-274}, pmid = {27540559}, issn = {2328-8930}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; }, abstract = {To measure the toxic potential of asbestos fibers-a known cause of asbestosis, lung cancer, and malignant mesothelioma-asbestos minerals are generally first ground down to small fibers, but it is unknown whether the grinding condition itself changes the fiber toxicity. To evaluate this, we ground chrysotile ore with or without water for 5-30 min and quantified asbestos-induced reactive oxygen species generation in elicited murine peritoneal macrophages as an indicator of fiber toxicity. The toxicity of dry-ground fibers was higher than the toxicity of wet-ground fibers. Grinding with or without water did not materially alter the mineralogical properties. However, dry-ground fibers contained at least 7 times more iron than wet-ground fibers. These results indicate that grinding methods significantly affect the surface concentration of iron, resulting in changes in fiber-induced reactive oxygen species generation or toxicity. Therefore, fiber preparation conditions should be accounted for when comparing the toxicity of asbestos fibers between reported studies.}, }
@article {pmid27532369, year = {2016}, author = {Mercadante, S and Degiovanni, D and Casuccio, A}, title = {Symptom burden in mesothelioma patients admitted to home palliative care.}, journal = {Current medical research and opinion}, volume = {32}, number = {12}, pages = {1985-1988}, doi = {10.1080/03007995.2016.1226165}, pmid = {27532369}, issn = {1473-4877}, mesh = {Aged ; Aged, 80 and over ; Analgesics, Opioid/administration &amp; dosage/therapeutic use ; Cancer Pain/drug therapy ; Dyspnea ; Female ; Home Care Services/*statistics &amp; numerical data ; Humans ; Male ; *Mesothelioma/epidemiology/physiopathology/therapy ; Middle Aged ; *Palliative Care/methods/statistics &amp; numerical data ; Retrospective Studies ; }, abstract = {CONTEXT: Mesothelioma is a very aggressive cancer that is brought on by asbestos exposure. Because there is a long latency period between exposure to asbestos and symptoms of disease, most patients with mesothelioma present with advanced disease and survive an average of 8-12 months. Thus, best supportive care should be considered critical to optimally manage these patients.<br><br>AIM: The aim of this study was to examine the epidemiological characteristics and symptom burden of mesothelioma patients when admitted to home palliative care.<br><br>METHODS: The charts of a consecutive sample of patients admitted to the home palliative care program with a diagnosis of mesothelioma in an endemic industrialized area were reviewed. The estimated survival time was about two months from admission. Epidemiological characteristics were collected. Karnofsky status, characteristics of pain and analgesic treatment at time of admission were recorded. ESAS (Edmonton Symptom Assessment System) and other clinical problems reported in the charts at admission time were also recorded.<br><br>RESULTS: Of the 674 charts reviewed, 56 patients (8.3%) had a diagnosis of mesothelioma. About three quarters of those had pain, with 18 and 2 patients with moderate and severe pain, respectively, despite receiving medium to high doses of opioids. The principal pain site was the chest. Pain was significantly associated with opioid consumption (p&#x2009;<&#x2009;.0005) and dyspnea (p&#x2009;=&#x2009;.049). Symptom burden was relevant, with a global ESAS of about 40. Pain, weakness, poor appetite, poor well-being, and dyspnea were the most frequent symptoms with the highest intensity; cough and pleural effusion were more frequently present as clinical problems.<br><br>CONCLUSION: This study shows that mesothelioma is a devastating cancer with a relevant symptom burden, and that patients were referred to palliative care late in the course of their disease, suggesting that earlier integration of palliative care should be considered to relieve suffering in all disease stages - not only at the end of life.}, }
@article {pmid27516637, year = {2016}, author = {Świątkowska, B and Szeszenia-Dąbrowska, N and Wilczyńska, U}, title = {Medical monitoring of asbestos-exposed workers: experience from Poland.}, journal = {Bulletin of the World Health Organization}, volume = {94}, number = {8}, pages = {599-604}, pmid = {27516637}, issn = {1564-0604}, mesh = {*Asbestos ; Early Detection of Cancer ; *Health Services Accessibility/economics ; Humans ; Occupational Diseases/*diagnosis ; *Occupational Exposure ; Poland ; }, abstract = {In Poland, the use of asbestos was banned in 1997 and asbestos plants have been closed since then. Despite their closure, cases of asbestos-related occupational diseases among former asbestos workers are still being recorded in the Central Register of Occupational Diseases. Between 2001 and 2014, there were 2726 asbestos-related illnesses, classified and reported as diseases associated with occupational exposure to asbestos. In 2000, Poland introduced a programme called Amiantus, targeted at former asbestos-processing plant workers. The programme provided periodic medical examinations to workers and free access to medications for treatment of asbestos-related illnesses. Introduction of the programme provided additional data to generate a reliable estimation of the number of asbestos-related occupational diseases, including cancer. The average latency period for asbestosis, lung cancer and mesothelioma is about 40 years so there may still be some health impact to former workers necessitating follow-up. We present the Polish experience of implementing a medical examination programme for asbestos-exposed workers and provide a list of activities to consider when planning for such a programme.}, }
@article {pmid27509983, year = {2016}, author = {Tabata, C and Tabata, R and Nakano, T}, title = {Calpeptin Prevents Malignant Pleural Mesothelioma Cell Proliferation via the Angiopoietin1/Tie2 System.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {7}, pages = {3405-3409}, pmid = {27509983}, issn = {2476-762X}, mesh = {Angiopoietin-1/*metabolism ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Dipeptides/*pharmacology ; Humans ; Lung/drug effects/metabolism ; Lung Neoplasms/*drug therapy/metabolism ; Mesothelioma/*drug therapy/metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy/metabolism ; Pulmonary Fibrosis/drug therapy/metabolism ; RNA, Messenger/metabolism ; Receptor, TIE-2/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)1 and Tie2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang1induced proliferation of MPM cells through an NFkB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.}, }
@article {pmid27502004, year = {2016}, author = {Hofmann-Preiß, K and Rehbock, B}, title = {[Early recognition of lung cancer in workers occupationally exposed to asbestos].}, journal = {Der Radiologe}, volume = {56}, number = {9}, pages = {810-816}, pmid = {27502004}, issn = {1432-2102}, mesh = {Asbestosis/*diagnostic imaging/*epidemiology ; Early Detection of Cancer/methods/*statistics &amp; numerical data ; Germany/epidemiology ; Humans ; Lung Neoplasms/*diagnostic imaging/*mortality ; Mesothelioma/*diagnostic imaging/*mortality ; Mesothelioma, Malignant ; Occupational Exposure/*statistics &amp; numerical data ; Prevalence ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Tomography, X-Ray Computed/statistics &amp; numerical data ; }, abstract = {Despite the fact that working with asbestos and placing it on the market have been banned in Germany since 1993 according to the Ordinance on Hazardous Substances, asbestos-related diseases of the lungs and pleura are still the leading cause of death in occupational diseases. The maximum industrial usage of asbestos was reached in former West Germany in the late 1970s and in former East Germany the late 1980s. Occupational diseases, mainly mesotheliomas and lung cancer emerging now are thus caused by asbestos exposure which occurred 30-40 years earlier. It is known that the combination of smoking and asbestos exposure results in a superadditive increase in the risk to develop lung cancer. No suitable screening methods for early detection of malignant mesothelioma are currently available and the therapeutic options are still very limited; however, the national lung screening trial (NLST) has shown for the first time that by employing low-dose computed tomography (LDCT) in heavy smokers, lung cancer mortality can be significantly reduced. According to current knowledge the resulting survival benefits far outweigh the potential risks involved in the diagnostic work-up of suspicious lesions. These results in association with the recommendations of international medical societies and organizations were pivotal as the German statutory accident insurance (DGUV) decided to provide LDCT as a special occupational medical examination for workers previously exposed to asbestos and with a particularly high risk for developing lung cancer.}, }
@article {pmid27501894, year = {2016}, author = {Kato, K and Gemba, K and Fujimoto, N and Aoe, K and Takeshima, Y and Inai, K and Kishimoto, T}, title = {Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion.}, journal = {European journal of radiology}, volume = {85}, number = {9}, pages = {1594-1600}, doi = {10.1016/j.ejrad.2016.06.013}, pmid = {27501894}, issn = {1872-7727}, mesh = {Aged ; Asbestosis/diagnostic imaging/*pathology ; Female ; Humans ; Japan ; Lung Neoplasms/diagnostic imaging/*pathology ; Male ; Mediastinum/*pathology ; Mesothelioma/diagnostic imaging/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleura/diagnostic imaging/*pathology ; Pleural Effusion/diagnostic imaging/*pathology ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: To elucidate differences in the level and localization of pleural irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos pleural effusion (BAPE) using CT.<br><br>STUDY DESIGN: Retrospective assessment of CT findings of consecutive patients with BAPE at a single centre and patients with eMPM reported in Japanese vital statistics.<br><br>METHODOLOGY: Thirty-six patients with confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans, and clinical and pathologic details were obtained for all patients and were reviewed by one radiologist, two pathologists, and two pulmonologists. Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening were assessed in all patients.<br><br>RESULTS: Prevalence of asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening was significantly higher in the BAPE group. Low-level irregularity was more common in the BAPE group (p<0.001), whereas high-level irregularity, mediastinal localization, and interlobar fissure were more prevalent in the eMPM group (p<0.001). Interlobar pleural irregularity was not observed in any patients in the BAPE group, although 55% of patients in the eMPM group showed interlobar pleural irregularity. Mediastinal pleural involvement was observed in 74% of patients in the eMPM group and had a positive predictive value of 89%.<br><br>CONCLUSION: This study demonstrates that the level and localization of plural irregularities significantly differed between patients with BAPE and eMPM. Large-scale prospective studies are needed to fully establish the diagnostic utility of such differences.}, }
@article {pmid27489758, year = {2016}, author = {DeLapp, D and Chan, C and Nystrom, P}, title = {Recurrent hydropneumothorax: An unusual presentation for malignant pleural mesothelioma.}, journal = {Respiratory medicine case reports}, volume = {19}, number = {}, pages = {43-45}, pmid = {27489758}, issn = {2213-0071}, abstract = {Mesothelioma is a rare pulmonary malignancy commonly associated with asbestos exposure. Its presentation is insidious and non-specific, with complaints of chest pain, dyspnea and cough. Chest X-ray may demonstrate unilateral pleural effusion. CT and PET scans may highlight nodular pleural plaques. Diagnosis often times is difficult with negative imaging and negative pleural fluid studies. In rare cases, hydropneumothoraces may be seen. We report a case of malignant pleural mesothelioma presenting as recurrent hydropneumothorax with negative CT scan of the chest for pleural abnormalities and negative pleural fluid studies.}, }
@article {pmid27484913, year = {2017}, author = {Butnor, KJ and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Malignant peritoneal mesothelioma and Crohn disease.}, journal = {Journal of clinical pathology}, volume = {70}, number = {3}, pages = {228-232}, doi = {10.1136/jclinpath-2016-203945}, pmid = {27484913}, issn = {1472-4146}, mesh = {Aged ; Crohn Disease/*complications/pathology ; Female ; Humans ; Lung Neoplasms/*complications/pathology ; Male ; Mesothelioma/*complications/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*complications/pathology ; }, abstract = {AIMS: Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD.<br><br>METHODS: A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD.<br><br>RESULTS: Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65&#x2005;years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3&#x2005;years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure.<br><br>CONCLUSIONS: Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined.}, }
@article {pmid27468090, year = {2016}, author = {Barbiero, F and Giangreco, M and Pisa, FE and Negro, C and Bovenzi, M and Rosolen, V and Barbone, F}, title = {[Not Available].}, journal = {La Medicina del lavoro}, volume = {107}, number = {4}, pages = {307-314}, pmid = {27468090}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {INTRODUCTION: The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006.<br><br>OBJECTIVES: To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort.<br><br>METHODS: We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate.<br><br>RESULTS: During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively.<br><br>CONCLUSIONS: Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available.}, }
@article {pmid27466614, year = {2016}, author = {Oliver, LC and Welch, L and Frank, AL and Lemen, RA and Mutti, L}, title = {New standard for assessing asbestos exposure and its consequences?.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {10}, pages = {709-710}, doi = {10.1136/oemed-2016-103693}, pmid = {27466614}, issn = {1470-7926}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; Humans ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; }, }
@article {pmid27464904, year = {2016}, author = {Barbieri, PG and Sommigliana, AB}, title = {[Not Available].}, journal = {La Medicina del lavoro}, volume = {107}, number = {4}, pages = {315-326}, pmid = {27464904}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Female ; Humans ; Italy ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {BACKGROUND: Asbestos-related diseases among shipyard workers are well known in Italy but descriptive long-term studies are limited; asbestos has been extensively used but the past exposure intensity has never been estimated because data from environmental and biological monitoring are almost absent.<br><br>OBJECTIVES: To describe the asbestos-related dis-eases (1996-2015) diagnosed among shipbuilding workers from a very important shipyard in Northern Italy, and to assess past asbestos exposure levels by cumulative dose indices, fibres and asbestos bodies.<br><br>METHODS: The cases of workers suffering from asbestos-related diseases diagnosed from 1996 to 2015 were collected on the occasion of some legal trials; the diagnosis, and the asbestos occupational and non-occupational exposure, were carefully evaluated.Lung samples were obtained from subjects, taking advantage of the autopsies; asbestos fibers were counted by means of a Scanning Electron Microscope, equipped with x-ray fluorescence microanalyses at 12.0000 amplification, and asbestos bodies by means of an Optical Microscope at 500 amplification.<br><br>RESULTS: 192 malignant mesotheliomas (6 in women), 196 lung cancers and 14 asbestosis (without cancer) were observed (1996-2015); autopsies were carried out on 80% of all subjects and 98% of mesotheliomas were confirmed by autopsies. Pleural plaques occurred on 90% of mesotheliomas and 87% of lung cancers; histologically mild asbestosis were diagnosed on 28% of mesotheliomas and 48% of lung cancers. In malignant mesothelioma and lung cancer cases respectively, the duration of occupational exposure was on average 24 and 23 ys, the latency time 48 and 46 ys, hiring at the shipyard before 1970 24 and 23 ys. Out of 114 lung analysis, the burden of asbestos fibres was >10 million for 33.3% of subjects and out of 99 lung analysis asbestos bodies was >10.000 for 71.7%; the average time since last exposure was 31 ys. Both asbestos fibres and asbestos bodies concentrations were significantly higher (GMR 2,5) among mesothelioma vs lung cancer.<br><br>CONCLUSION: A relevant number of asbestos-related diseases among shipbuilding workers, mainly mesothelioma and lung cancer, exposed in shipyard until the 1980's were identified by an active search. Thanks to several autopsies, the diagnoses of cancer are confirmed as a cause of death, and a high frequency of histological asbestosis, previously ignored,was shown. The lung burden analysis of asbestos bodies and asbestos fibres, the largest ever performed among ship-building workers, confirms the spread and relevance of asbestos exposure. The best estimate of past exposure intensity was provided by both biological indices.}, }
@article {pmid27462362, year = {2016}, author = {Tomasson, K and Gudmundsson, G and Briem, H and Rafnsson, V}, title = {Malignant mesothelioma incidence by nation-wide cancer registry: a population-based study.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {11}, number = {}, pages = {37}, pmid = {27462362}, issn = {1745-6673}, abstract = {BACKGROUND: Malignant mesothelioma caused by asbestos exposure has a long latency period. A ban on asbestos use may not be apparent in decreased incidence in the population until after several decades. The aim was to evaluate changes in the incidence of malignant mesothelioma, and the possible impact of the asbestos ban implemented in Iceland in 1983.<br><br>METHODS: This is a population study on aggregate level; the source of data was the Icelandic Cancer Registry, the National Cause-of-Death Registry, and the National Register. Volume of asbestos import was obtained from Customs Tariff. The import figures reflect fairly accurately the amount used, as there are no mines in the country.<br><br>RESULTS: Asbestos import peaked in 1980 at 15.0&#xa0;kg/capita/year, diminishing to 0.3&#xa0;kg/capita/year ten years after the ban in 1983, and to zero in the most recent years. Seventy-nine per cent of the cases of malignant mesothelioma were men, and 72&#xa0;% were of pleural origin. Mesothelioma incidence increased steadily from 1965 to 2014, when it reached 21.4 per million among men, and 5.6 among women. Mortality in 2014 was 22.2 per million among men, and 4.8 among women.<br><br>CONCLUSION: Malignant mesothelioma incidence and mortality increased in the population during the period, despite the ban on asbestos use from 1983. This is in agreement with the long latency time for malignant mesothelioma. In line with the previously high per capita volume of asbestos import, many buildings, equipment, and structures contain asbestos, so there is an on-going risk of asbestos exposure during maintenance, renovations and replacements. It is thus difficult to predict when the incidence of malignant mesothelioma will decrease in the future. During the last ten-year period, the incidence in Iceland was higher than the recently reported incidence in neighbouring countries.}, }
@article {pmid27457873, year = {2016}, author = {Klikovits, T and Hoda, MA and Dong, Y and Arns, M and Baumgartner, B and Errhalt, P and Geltner, C and Machan, B and Pohl, W and Hutter, J and Eckmayr, J and Studnicka, M and Flicker, M and Cerkl, P and Kirchbacher, K and Klepetko, W}, title = {Management of malignant pleural mesothelioma - part 3 : Data from the Austrian Mesothelioma Interest Group (AMIG) database.}, journal = {Wiener klinische Wochenschrift}, volume = {128}, number = {17-18}, pages = {627-634}, pmid = {27457873}, issn = {1613-7671}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestosis/*mortality ; Austria/epidemiology ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/*mortality ; Middle Aged ; Pleural Effusion, Malignant/*mortality ; Pleural Neoplasms/*mortality ; Prevalence ; *Registries ; Risk Factors ; Sex Distribution ; Survival Rate ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor originating from the pleural cavity with a strong link to previous asbestos exposure. In order to determine the demographics, diagnostics, therapeutic strategies, and prognosis of MPM patients in Austria, the Austrian Mesothelioma Interest Group (AMIG) was founded in 2011. In this report the data from the AMIG MPM database collected to date are reported.<br><br>METHODS: A&#xa0;prospective observational registry was initiated, including patients with histologically verified MPM diagnosed and treated at specialized centers in Austria. Patient inclusion started in January 2011 and follow-up was completed until September 2015.<br><br>RESULTS: A&#xa0;total number of 210 patients were included. There were 167 male and 43&#xa0;female patients with a&#xa0;mean age of 67.0&#xa0;years (SD&#xa0;&#xb1; 11.3) at the time of diagnosis. Asbestos exposure was confirmed in 109 (69.4&#x2009;%) patients. The histological subtype was epithelioid in 141 (67.2&#x2009;%), sarcomatoid in 16 (7.6&#x2009;%), biphasic in 28 (13.3&#x2009;%), and MPM not otherwise specified in 25 (11.9&#x2009;%) patients. Of the patients, 30 (14.3&#x2009;%) received best supportive care (BSC) only, 71 (33.8&#x2009;%) chemotherapy (CHT) alone, four (1.9&#x2009;%) radiotherapy (RT) alone, 23 (11.9&#x2009;%) CHT/RT, two (0.9&#x2009;%) surgery alone, and 76 (36.2&#x2009;%) curative surgery within a multimodality treatment (MMT), which was more frequently performed for patients younger than 65&#xa0;years and with early-stage disease (I&#xa0;+ II). Median overall survival (OS) was 19.1&#xa0;months (95&#x2009;% CI 14.7-23.5). The 1&#x2011;, 3&#x2011;, and 5&#x2011;year OS rates were 66&#x2009;%, 30&#x2009;%, and 23&#x2009;%, respectively, and OS was significantly better in patients undergoing surgery within MMT (5-year survival 5&#x2009;% vs. 40&#x2009;%, p&#xa0;= 0.001).<br><br>CONCLUSION: Patients with earlier disease stages, younger age, good performance status, and epithelioid histology were more likely to undergo MMT including surgery, which resulted in a&#xa0;more favorable outcome.}, }
@article {pmid27457053, year = {2016}, author = {Pira, E and Romano, C and Violante, FS and Farioli, A and Spatari, G and La Vecchia, C and Boffetta, P}, title = {Updated mortality study of a cohort of asbestos textile workers.}, journal = {Cancer medicine}, volume = {5}, number = {9}, pages = {2623-2628}, pmid = {27457053}, issn = {2045-7634}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; Mesothelioma/epidemiology/etiology/mortality ; Mesothelioma, Malignant ; Neoplasms/epidemiology/*etiology/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology/mortality ; Population Surveillance ; Risk Factors ; *Textiles ; }, abstract = {Limited information is available on risk of peritoneal mesothelioma after asbestos exposure, and in general on the risk of cancer after cessation of asbestos exposure. We updated to 2013 the follow-up of a cohort of 1083 female and 894 male textile workers with heavy asbestos exposure (up to 100 fb/mL), often for short periods. A total of 1019 deaths were observed, corresponding to a standardized mortality ratio (SMR) of 1.68 (95% confidence interval [CI]: 1.57-1.78). SMRs were 29.1 (95% CI: 21.5-38.6) for peritoneal cancer, 2.96 (95% CI: 2.50-3.49) for lung cancer, 33.7 (95% CI: 25.7-43.4) for pleural cancer, and 3.03 (95% CI: 1.69-4.99) for ovarian cancer. For pleural and peritoneal cancer, there was no consistent pattern of risk in relation to time since last exposure, whereas for lung cancer there was an indication of a decline in risk after 25 years since last exposure. The findings of this unique cohort provide novel data for peritoneal cancer, indicating that - as for pleural cancer - the excess risk does not decline up to several decades after cessation of exposure.}, }
@article {pmid27455808, year = {2016}, author = {Akatsuka, S and Toyokuni, S}, title = {[Iron function and carcinogenesis].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {74}, number = {7}, pages = {1168-1175}, pmid = {27455808}, issn = {0047-1852}, mesh = {Animals ; Cell Transformation, Neoplastic/genetics/*metabolism ; DNA Damage ; Genome ; Humans ; Iron/*metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Though iron is an essential micronutrient for humans, the excess state is acknowledged to be associated with oncogenesis. For example, iron overload in the liver of the patients with hereditary hemocromatosis highly increases the risk of hepatocellular carcinoma. Also, as to asbestos-related mesothelioma, such kinds of asbestos with a higher iron content are considered to be more carcinogenic. Iron is a useful element, which enables fundamental functions for life such as oxygen carrying and electron transport. However, in the situation where organisms are unable to have good control of it, iron turns into a dangerous element which catalyzes generation of reactive oxygen. In this review, I first outline the relationships between iron and cancer in general, then give an explanation about iron-related animal carcinogenesis models.}, }
@article {pmid27454480, year = {2016}, author = {Yap, HS and Klebe, S and Rose, A}, title = {Endobronchial Diagnosis of a Malignant Mesothelioma.}, journal = {Journal of bronchology &amp; interventional pulmonology}, volume = {23}, number = {3}, pages = {e30-2}, doi = {10.1097/LBR.0000000000000294}, pmid = {27454480}, issn = {1948-8270}, mesh = {Asbestos/*adverse effects ; Conservative Treatment ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/*diagnosis/etiology ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care ; Thoracic Surgery, Video-Assisted/*methods ; }, }
@article {pmid27453164, year = {2016}, author = {Carbone, M and Kanodia, S and Chao, A and Miller, A and Wali, A and Weissman, D and Adjei, A and Baumann, F and Boffetta, P and Buck, B and de Perrot, M and Dogan, AU and Gavett, S and Gualtieri, A and Hassan, R and Hesdorffer, M and Hirsch, FR and Larson, D and Mao, W and Masten, S and Pass, HI and Peto, J and Pira, E and Steele, I and Tsao, A and Woodard, GA and Yang, H and Malik, S}, title = {Consensus Report of the 2015 Weinman International Conference on Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {8}, pages = {1246-1262}, pmid = {27453164}, issn = {1556-1380}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA111295/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; Consensus ; Environmental Exposure ; Female ; Genes, BRCA1 ; Humans ; Lung Neoplasms/diagnosis/*etiology/genetics/mortality ; Male ; Mesothelioma/diagnosis/*etiology/genetics/mortality ; Mesothelioma, Malignant ; Mutation ; Osteopontin/blood ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the Study of Lung Cancer, and the agenda was designed with significant input from staff at the U.S. National Cancer Institute and National Institute of Environmental Health Sciences. A multidisciplinary group of participants presented updates reflecting a range of disciplinary perspectives, including mineralogy, geology, epidemiology, toxicology, biochemistry, molecular biology, genetics, public health, and clinical oncology. The group identified knowledge gaps that are barriers to preventing and treating malignant mesothelioma (MM) and the required next steps to address barriers. This manuscript reports the group's efforts and focus on strategies to limit risk to the population and reduce the incidence of MM. Four main topics were explored: genetic risk, environmental exposure, biomarkers, and clinical interventions. Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. MM is an almost entirely preventable malignancy as it is most often caused by exposure to commercial asbestos or mineral fibers with asbestos-like health effects, such as erionite. In the past in North America and in Europe, the most prominent source of exposure was related to occupation. Present regulations have reduced occupational exposure in these countries; however, some people continue to be exposed to previously installed asbestos in older construction and other settings. Moreover, an increasing number of people are being exposed in rural areas that contain noncommercial asbestos, erionite, and other mineral fibers in soil or rock (termed naturally occurring asbestos [NOA]) and are being developed. Public health authorities, scientists, residents, and other affected groups must work together in the areas where exposure to asbestos, including NOA, has been documented in the environment to mitigate or reduce this exposure. Although a blood biomarker validated to be effective for use in screening and identifying MM at an early stage in asbestos/NOA-exposed populations is not currently available, novel biomarkers presented at the meeting, such as high mobility group box 1 and fibulin-3, are promising. There was general agreement that current treatment for MM, which is based on surgery and standard chemotherapy, has a modest effect on the overall survival (OS), which remains dismal. Additionally, although much needed novel therapeutic approaches for MM are being developed and explored in clinical trials, there is a critical need to invest in prevention research, in which there is a great opportunity to reduce the incidence and mortality from MM.}, }
@article {pmid27445546, year = {2016}, author = {Ross, RM}, title = {Software for Apportionment of Asbestos-Related Mesotheliomas.}, journal = {Canadian respiratory journal}, volume = {2016}, number = {}, pages = {5340676}, pmid = {27445546}, issn = {1916-7245}, mesh = {Animals ; Asbestos/administration &amp; dosage/*adverse effects ; Cost Allocation ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; *Software ; Time Factors ; }, abstract = {Patients with an asbestos-related mesothelioma may be legally entitled to financial compensation. In this context, a physician may be called upon to apportion the contribution of an asbestos containing product or facility where there was asbestos exposure in the development of that individual's mesothelioma. This task is mathematically not simple. It is a complex function of each and the entire individual's above-background asbestos exposures. Factors to be considered for each of these exposures are the amount of exposure to mesotheliogenic fibers, each of the asbestos containing products' potency to cause mesothelioma, and the time period when the exposures occurred relative to when the mesothelioma was diagnosed. In this paper, the known factors related to asbestos-related mesothelioma risk are briefly reviewed and the software that is downloadable and fully functional in a Windows® environment is also provided. This software allows for rapid assessment of relative contributions and deals with the somewhat tedious mathematical calculations. With this software and a reasonable occupational history, if it is decided that the mesothelioma was due to above-background asbestos exposure, the contribution of an asbestos containing product or a time period of asbestos exposure can be apportioned.}, }
@article {pmid27436254, year = {2016}, author = {Ferrante, P and Mastrantonio, M and Uccelli, R and Corfiati, M and Marinaccio, A}, title = {[Pleural mesothelioma mortality in Italy: time series reconstruction (1970-2009) and comparison with incidence (2003-2008)].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {3-4}, pages = {205-214}, doi = {10.19191/EP16.3-4.P205.087}, pmid = {27436254}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Mesothelioma/diagnosis/*etiology/*mortality ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*etiology/*mortality ; Population Surveillance ; Registries ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: the large amount of asbestos used in many Countries (including Italy) is causing an epidemic of asbestos related diseases, which is still ongoing because of their long latency.<br><br>OBJECTIVES: this study is aimed at reconstructing Italian time series of deaths for mesothelioma in the period 1970-2009 and comparing Italian incidence and mortality data.<br><br>deaths for pleural cancer (1970-2003,2006-2009) and mesothelioma (2003, 2006-2009) were recorded by the Italian Institute of Statistics (Istat) and provided by the Italian National Agency for New Technologies, Energy and the Environment (ENEA), incidence cases (1993-2008) were provided by the Italian mesotheliomas register (ReNaM) at the Italian National Workers' Compensation Authority (Inail). For the period before ICD-10 implementation (1970-2002) and when Istat data (2004-2005) are lacking, mesothelioma deaths were estimated through statistical models (logistic, Poisson). National incidence and mortality data were compared during the overlapping period (2003, 2006-2008).<br><br>RESULTS: the mortality curve strongly rises from 1970 and seems to be smoothed in the last years. Mortality caused by mesothelioma and incident cases with certain diagnosis are overlapping, as are mortality due to pleural cancer other than mesothelioma and mesothelioma incidence with uncertain diagnosis (probable/possible).<br><br>CONCLUSIONS: this epidemiological analysis of deaths encoded as pleural tumour suggests to carefully investigate space-temporal distribution before excluding they could be mesotheliomas. Some new lights have been thrown on the statistical behaviour of mesothelioma mortality.}, }
@article {pmid27436246, year = {2016}, author = {Mirabelli, D}, title = {[Every little bit counts in order to protect asbestos business].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {3-4}, pages = {154-155}, doi = {10.19191/EP16.3-4.P154.082}, pmid = {27436246}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Commerce/standards ; *Extraction and Processing Industry/standards ; Humans ; Italy/epidemiology ; Mesothelioma/*etiology/mortality/prevention &amp; control ; Occupational Exposure/*adverse effects ; Periodicals as Topic ; Pleural Neoplasms/*etiology/mortality/prevention &amp; control ; Risk Assessment ; Risk Factors ; Time Factors ; World Health Organization ; }, }
@article {pmid27431778, year = {2017}, author = {Bonelli, MA and Fumarola, C and La Monica, S and Alfieri, R}, title = {New therapeutic strategies for malignant pleural mesothelioma.}, journal = {Biochemical pharmacology}, volume = {123}, number = {}, pages = {8-18}, doi = {10.1016/j.bcp.2016.07.012}, pmid = {27431778}, issn = {1873-2968}, mesh = {Antineoplastic Agents/therapeutic use ; Humans ; Immunotherapy ; Lung Neoplasms/genetics/immunology/*therapy ; Mesothelioma/genetics/immunology/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/genetics/immunology/*therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. Therapeutic actions are limited due to the late stage at which most patients are diagnosed and the intrinsic chemo-resistance of the tumor. The recommended systemic therapy for MPM is cisplatin/pemetrexed regimen with a mean overall survival of about 12months and a median progression free survival of less than 6months. Considering that the incidence of this tumor is expected to increase in the next decade and that its prognosis is poor, novel therapeutic approaches are urgently needed. For some tumors, such as lung cancer and breast cancer, druggable oncogenic alterations have been identified and targeted therapy is an important option for these patients. For MPM, clinical guidelines do not recommend biological targeted therapy, mainly because of poor target definition or inappropriate trial design. Further studies are required for a full comprehension of the molecular pathogenesis of MPM and for the development of new target agents. This review updates pre-clinical and clinical data on the efficacy of targeted therapy and immune checkpoint inhibition in the treatment of mesothelioma. Finally, future perspectives in this deadly disease are also discussed.}, }
@article {pmid27431629, year = {2016}, author = {Morimoto, C and Ohnuma, K}, title = {[Development of New Therapy for Malignant Mesothelioma Based on CD26 Molecule].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {7}, pages = {855-862}, pmid = {27431629}, issn = {0385-0684}, mesh = {Animals ; Clinical Trials, Phase I as Topic ; Dipeptidyl Peptidase 4/chemistry/immunology/*metabolism ; Drug Design ; Humans ; Lung Neoplasms/*drug therapy/metabolism ; Mesothelioma/*drug therapy/metabolism ; Mesothelioma, Malignant ; Mice ; Signal Transduction ; T-Lymphocytes/immunology ; }, abstract = {CD26 is a 110 kDa, type II transmembrane glycoprotein with dipeptidyl peptidase IV activity and is capable of cleaving Nterminal dipeptides with either L-proline or L-alanine at the penultimate position. Malignant mesothelioma(MM)is an aggressive malignancy arising from the mesothelial cells. It is generally associated with a history of asbestos exposure and has a very poor prognosis. Due to lack of efficacy of conventional treatments, novel therapeutic strategies are urgently needed to improve outcomes. Recently we showed that CD26 is preferentially expressed on epithelial type of MM cells but not on normal mesothelial cells. We have developed a highly biological active humanized anti-CD26 monoclonal antibody(mAb)and have published previously extensive in vivo data demonstrating the anti-tumor activity of humanized anti-CD26 mAb(YS110)in mouse xenograft models. The use of a humanized anti-CD26 mAb may therefore be a rational therapy for patients with MM. The first-in-human(FIH)phase I study performed in France demonstrates that humanized anti-CD26 therapy is generally well-tolerated with preliminary evidence of activity in patients with advanced/refractory CD26-expressing cancers, particularly refractory malignant mesothelioma. From the above results, the phase I clinical trial for malignant mesothelioma in Japan is to be started in the very near future.}, }
@article {pmid27422997, year = {2016}, author = {He, X and Despeaux, E and Stueckle, TA and Chi, A and Castranova, V and Dinu, CZ and Wang, L and Rojanasakul, Y}, title = {Role of mesothelin in carbon nanotube-induced carcinogenic transformation of human bronchial epithelial cells.}, journal = {American journal of physiology. Lung cellular and molecular physiology}, volume = {311}, number = {3}, pages = {L538-49}, pmid = {27422997}, issn = {1522-1504}, support = {R01 EB018857/EB/NIBIB NIH HHS/United States ; P20 RR016440/RR/NCRR NIH HHS/United States ; R01 ES022968/ES/NIEHS NIH HHS/United States ; P30 RR032138/RR/NCRR NIH HHS/United States ; P20 RR016477/RR/NCRR NIH HHS/United States ; P20 GM103434/GM/NIGMS NIH HHS/United States ; P30 GM103488/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bronchioles/pathology ; Carcinogens/*toxicity ; Cell Line ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cyclin E/genetics/metabolism ; Epithelial Cells/*metabolism/pathology ; GPI-Linked Proteins/*physiology ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*metabolism/pathology ; Mesothelin ; Mice, Inbred NOD ; Mice, Nude ; Mice, SCID ; Nanotubes, Carbon/*toxicity ; Neoplasm Transplantation ; }, abstract = {Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated. MSLN overexpression was found in human lung tumors, lung cancer cell lines, and BSW cells. The functional role of MSLN in the BSW cells was then investigated by using stably transfected MSLN knockdown (BSW shMSLN) cells. MSLN knockdown resulted in significantly decreased invasion, migration, colonies on soft agar, and tumor sphere formation. In vivo, BSW shMSLN cells formed smaller primary tumors and less metastases. The mechanism by which MSLN contributes to these more aggressive behaviors was investigated by using ingenuity pathway analysis, which predicted that increased MSLN could induce cyclin E expression. We found that BSW shMSLN cells had decreased cyclin E, and their proliferation rate was reverted to nearly that of untransformed cells. Cell cycle analysis showed that the BSW shMSLN cells had an increased G2 population and a decreased S phase population, which is consistent with the decreased rate of proliferation. Together, our results indicate a novel role of MSLN in the malignant transformation of bronchial epithelial cells following CNT exposure, suggesting its utility as a potential biomarker and drug target for CNT-induced malignancies.}, }
@article {pmid27418105, year = {2016}, author = {Chéné, AL and d'Almeida, S and Blondy, T and Tabiasco, J and Deshayes, S and Fonteneau, JF and Cellerin, L and Delneste, Y and Grégoire, M and Blanquart, C}, title = {Pleural Effusions from Patients with Mesothelioma Induce Recruitment of Monocytes and Their Differentiation into M2 Macrophages.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {10}, pages = {1765-1773}, doi = {10.1016/j.jtho.2016.06.022}, pmid = {27418105}, issn = {1556-1380}, mesh = {Cell Differentiation ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*complications/pathology ; Macrophages/*metabolism ; Male ; Mesothelioma/*complications/pathology ; Mesothelioma, Malignant ; Monocytes/*metabolism ; }, abstract = {INTRODUCTION: Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PEs) from patients with mesothelioma contain high levels of the C-C motif chemokine ligand 2 (CCL2) inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples, particularly on monocyte recruitment. Then, we studied the fate of these monocytes in malignant pleural mesothelioma (MPM) PEs and their impact on tumor cells' properties.<br><br>METHODS: The implication of CCL2 in monocyte recruitment was evaluated using transmigration assays and a CCL2 blocking antibody. The phenotype of macrophages was determined by flow cytometry and enzyme-linked immunosorbent assay. Immunohistochemical analysis was used to support the results. Cocultures of macrophages with mesothelioma cells were performed to study cancer cell proliferation and resistance to treatment.<br><br>RESULTS: We showed that CCL2 is a major factor of monocyte recruitment induced by MPM samples. Macrophages obtained in MPM samples were M2 macrophages (high CD14, high CD163, and interleukin-10 secretion after activation). The colony-stimulating factor 1 receptor/macrophage colony-stimulating factor (M-CSF) pathway is implicated in M2 polarization, and high levels of M-CSF were measured in MPM samples compared with benign PE (4.17 &#xb1; 2.75 ng/mL and 1.94 &#xb1; 1.47 ng/mL, respectively). Immunohistochemical analysis confirmed the presence of M2 macrophages in pleural and peritoneal mesothelioma. Finally, we showed that M2 macrophages increased mesothelioma cell proliferation and resistance to treatment.<br><br>CONCLUSIONS: These results demonstrate the implication of CCL2 in MPM pathogenesis and designate M-CSF as a new potential biomarker of MPM. This study also identifies CCL2 and colony-stimulating factor 1 receptor/M-CSF as interesting new targets to modulate pro-tumorigenic properties of the tumor microenvironment.}, }
@article {pmid27408810, year = {2016}, author = {Lin, RC and Kirschner, MB and Cheng, YY and van Zandwijk, N and Reid, G}, title = {MicroRNA gene expression signatures in long-surviving malignant pleural mesothelioma patients.}, journal = {Genomics data}, volume = {9}, number = {}, pages = {44-49}, pmid = {27408810}, issn = {2213-5960}, abstract = {Malignant pleural mesothelioma (MPM) is a tumor originating in the mesothelium, the membrane lining the thoracic cavities, and is induced by exposure to asbestos. Australia suffers one of the world's highest rates of MPM and the incidence is yet to peak. The prognosis for patients with MPM is poor and median survival following diagnosis is 4-18 months. Currently, no or few effective therapies exist for MPM. Trials of targeted agents such as antiangiogenic agents (VEGF, EGFR) or ribonuclease inhibitors (ranpirnase) largely failed to show efficacy in MPM Tsao et al. (2009) [1]. A recent study, however, showed that cisplatin/pemetrexed + bevacizumab (a recombinant humanized monoclonal antibody that inhibit VEGF) treatment has a survival benefit of 2.7 months Zalcman et al. (2016) [2]. It remains to be seen if this targeted therapy will be accepted as a new standard for MPM. Thus the unmet needs of MPM patients remain very pronounced and almost every patient will be confronted with drug resistance and recurrence of disease. We have identified unique gene signatures associated with prolonged survival in mesothelioma patients undergoing radical surgery (EPP, extrapleural pneumonectomy), as well as patients who underwent palliative surgery (pleurectomy/decortication). In addition to data published in Molecular Oncology, 2015;9:715-26 (GSE59180) Kirschner et al. (2015) , we describe here additional data using a system-based approach that support our previous observations. This data provides a resource to further explore microRNA dynamics in MPM.}, }
@article {pmid27405014, year = {2016}, author = {Domínguez-Malagón, H and Cano-Valdez, AM and González-Carrillo, C and Campos-Salgado, YE and Lara-Garcia, A and Lopez-Mejia, M and Corona-Cruz, JF and Arrieta, O}, title = {Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma.}, journal = {Ultrastructural pathology}, volume = {40}, number = {5}, pages = {254-260}, doi = {10.1080/01913123.2016.1195469}, pmid = {27405014}, issn = {1521-0758}, mesh = {Adenocarcinoma/*diagnosis/ultrastructure ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Cytodiagnosis ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/ultrastructure ; Male ; Mesothelioma/*diagnosis/ultrastructure ; Microscopy, Electron, Transmission ; Middle Aged ; Pleural Effusion, Malignant/*pathology ; Pleural Neoplasms/*diagnosis/ultrastructure ; }, abstract = {The diagnosis of malignant pleural mesothelioma (MPM) is challenging and requires immunohistochemistry or electron microscopy assays to specifically differentiate MPM from lung adenocarcinoma. An ultrastructural study of fresh tissue is considered to be the "gold standard." In most cases, the first diagnostic approach is performed on pleural effusion, and in some patients, this is the only available sample for diagnosis. The aim of the present study is to evaluate if an examination of pleural effusion samples based on electron microscopy (EMpe) is a useful tool for the differential diagnosis of MPM and lung adenocarcinoma. An EMpe study was performed in 25 pleural effusion samples. Histological and immunohistochemical markers confirmed the diagnosis of either mesothelioma (5) or adenocarcinoma (20). Of the five cases that were diagnosed with mesothelioma, two samples (40%) showed cells with "bushy" microvilli, which are characteristic of mesothelioma, by EMpe, and three were acellular (60%). Of the 20 cases of adenocarcinoma, EMpe showed cells with short microvilli in 9 (45%), and 11 were acellular (55%). EMpe identifies unequivocal morphological changes that are useful for the differential diagnosis of MPM or adenocarcinoma when the pleural effusion sample contains evaluable tumor cells.}, }
@article {pmid27397058, year = {2017}, author = {Gaffney, SH and Grespin, M and Garnick, L and Drechsel, DA and Hazan, R and Paustenbach, DJ and Simmons, BD}, title = {Anthophyllite asbestos: state of the science review.}, journal = {Journal of applied toxicology : JAT}, volume = {37}, number = {1}, pages = {38-49}, doi = {10.1002/jat.3356}, pmid = {27397058}, issn = {1099-1263}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Environmental Exposure/*adverse effects/analysis ; Environmental Pollutants/*toxicity ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; *Mining ; }, abstract = {Anthophyllite is an amphibole form of asbestos historically used in only a limited number of products. No published resource currently exists that offers a complete overview of anthophyllite toxicity or of its effects on exposed human populations. We performed a review focusing on how anthophyllite toxicity was understood over time by conducting a comprehensive search of publicly available documents that discussed the use, mining, properties, toxicity, exposure and potential health effects of anthophyllite. Over 200 documents were identified; 114 contained relevant and useful information which we present chronologically in this assessment. Our analysis confirms that anthophyllite toxicity has not been well studied compared to other asbestos types. We found that toxicology studies in animals from the 1970s onward have indicated that, at sufficient doses, anthophyllite can cause asbestosis, lung cancer and mesothelioma. Studies of Finnish anthophyllite miners, conducted in the 1970s, found an increased incidence of asbestosis and lung cancer, but not mesothelioma. Not until the mid-1990s was an epidemiological link with mesothelioma in humans observed. Its presence in talc has been of recent significance in relation to potential asbestos exposure through the use of talc-containing products. Characterizing the health risks of anthophyllite is difficult, and distinguishing between its asbestiform and non-asbestiform mineral form is essential from both a toxicological and regulatory perspective. Anthophyllite toxicity has generally been assumed to be similar to other amphiboles from a regulatory standpoint, but some notable exceptions exist. In order to reach a more clear understanding of anthophyllite toxicity, significant additional study is needed. Copyright © 2016 John Wiley &amp; Sons, Ltd.}, }
@article {pmid27388398, year = {2016}, author = {Creaney, J and Lee, YC}, title = {Diagnoses (Not Diagnosis) of Pleural Effusion. Time to Consider Concurrent Etiologies.}, journal = {Annals of the American Thoracic Society}, volume = {13}, number = {7}, pages = {1003-1004}, doi = {10.1513/AnnalsATS.201604-320ED}, pmid = {27388398}, issn = {2325-6621}, mesh = {*Exudates and Transudates ; Humans ; *Pleural Effusion ; }, }
@article {pmid27388204, year = {2016}, author = {Soeberg, MJ and Luong, MA and Tran, VT and Tran, AT and Nguyen, TT and Bui, D and Nguyen, TH and Takahashi, K and van Zandwijk, N}, title = {Estimating the incidence of malignant mesothelioma in Vietnam: a pilot descriptive cancer registration study.}, journal = {International journal of occupational and environmental health}, volume = {22}, number = {2}, pages = {167-172}, pmid = {27388204}, issn = {2049-3967}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos ; Child ; Environmental Exposure ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnostic imaging/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Radiography ; Registries ; Vietnam/epidemiology ; Young Adult ; }, abstract = {INTRODUCTION: Global asbestos consumption has shifted toward lower income countries, particularly in the Asian region including Vietnam where asbestos and asbestos-containing products have been imported since the late 1960s.<br><br>METHODS: This pilot descriptive epidemiological study aimed to provide contemporary estimates of malignant mesothelioma incidence (histological subtype M9050/3; ICD-O-3) by gender and age group as recorded across nine cancer registries in Vietnam.<br><br>RESULTS: We identified 148 incident cases of malignant mesothelioma during 1987-2013. The majority of cases were recorded in the Hanoi region (n&#xa0;=&#xa0;93) and were aged 55&#xa0;years or older (n&#xa0;=&#xa0;96).<br><br>DISCUSSION: By carefully reviewing existing cancer registry records in Vietnam, we identified a larger number of malignant mesothelioma cases than previously estimated. We recommend the use of cancer registry data in tracking future asbestos-related disease in Vietnam.}, }
@article {pmid27381209, year = {2016}, author = {Azzopardi, M and Thomas, R and Muruganandan, S and Lam, DC and Garske, LA and Kwan, BC and Rashid Ali, MR and Nguyen, PT and Yap, E and Horwood, FC and Ritchie, AJ and Bint, M and Tobin, CL and Shrestha, R and Piccolo, F and De Chaneet, CC and Creaney, J and Newton, RU and Hendrie, D and Murray, K and Read, CA and Feller-Kopman, D and Maskell, NA and Lee, YC}, title = {Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters.}, journal = {BMJ open}, volume = {6}, number = {7}, pages = {e011480}, pmid = {27381209}, issn = {2044-6055}, mesh = {Adult ; Aged ; Australia/epidemiology ; Body Fluids ; *Catheters, Indwelling ; Clinical Protocols ; *Drainage/methods ; Dyspnea/physiopathology/*therapy ; Female ; Hong Kong/epidemiology ; Humans ; Lung Neoplasms/epidemiology/*prevention &amp; control ; Male ; Mesothelioma/epidemiology/*prevention &amp; control ; Mesothelioma, Malignant ; New Zealand/epidemiology ; Pleural Effusion, Malignant/epidemiology/physiopathology/*therapy ; *Pleurodesis/methods ; Prospective Studies ; Quality of Life ; Talc ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation.<br><br>METHODS AND ANALYSIS: A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs &#x2265;2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100&#x2005;mm visual analogue scale (VAS) over the first 60&#x2005;days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14&#x2005;mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9&#x2005;mm and a 10% lost to follow-up rate.<br><br>ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12615000963527; Pre-results.}, }
@article {pmid27376267, year = {2016}, author = {Driml, J and Pulford, E and Moffat, D and Karapetis, C and Kao, S and Griggs, K and Henderson, DW and Klebe, S}, title = {Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas.}, journal = {International journal of molecular sciences}, volume = {17}, number = {7}, pages = {}, pmid = {27376267}, issn = {1422-0067}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aquaporin 1/*metabolism ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; }, abstract = {(1) BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2) METHODS: A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3) RESULTS: Labelling of ≥50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4) CONCLUSION: AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists.}, }
@article {pmid27372959, year = {2016}, author = {Franklin, P and Reid, A and Olsen, N and Peters, S and de Klerk, N and Brims, F and Threlfall, T and Murray, R and Musk, AB}, title = {Incidence of malignant mesothelioma in Aboriginal people in Western Australia.}, journal = {Australian and New Zealand journal of public health}, volume = {40}, number = {4}, pages = {383-387}, doi = {10.1111/1753-6405.12542}, pmid = {27372959}, issn = {1753-6405}, mesh = {Adult ; Aged ; Asbestos ; Asbestos, Crocidolite ; Causality ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Mining/statistics &amp; numerical data ; Native Hawaiian or Other Pacific Islander/*statistics &amp; numerical data ; Occupational Exposure/*statistics &amp; numerical data ; Registries/statistics &amp; numerical data ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: To describe the incidence of malignant mesothelioma (MM) in Aboriginal people in Western Australia (WA) and determine the main routes of exposure to asbestos in this population.<br><br>METHODS: All MM cases in Western Australia, as well as the primary source of asbestos exposure, are recorded in the WA Mesothelioma Register. Aboriginal cases up to the end of 2013 were extracted from the register and compared with non-Aboriginal cases with respect to the primary means/source of exposure. Age-standardised incidence rates for each decade from 1980 were calculated for both Aboriginals and non-Aboriginals. Age-standardised mortality rates were calculated for the period 1994-2008 and compared with international rates.<br><br>RESULTS: There were 39 cases (77% male) of MM among WA Aboriginal people. Twenty-six (67%) were a direct result of the mining of crocidolite at Wittenoom and the subsequent contamination of the surrounding lands. Of the non-Aboriginal MM cases (n = 2070, 86.3% male), fewer than 25% can be attributed to Wittenoom. Aboriginals had consistently higher 10-year incidence rates than non-Aboriginals and, when compared to world populations, the highest mortality rate internationally.<br><br>CONCLUSION: When incidence rates in Aboriginal people are compared with non-Aboriginal people, the Wittenoom mining operation has had a disproportionate effect on MM incidence in the local Aboriginal population.}, }
@article {pmid27354997, year = {2016}, author = {Hancock, KL and Clinton, CM and Dinkelspiel, HE and Saab, J and Schneider, B and Caputo, TA}, title = {A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature.}, journal = {Gynecologic oncology reports}, volume = {17}, number = {}, pages = {26-28}, pmid = {27354997}, issn = {2352-5789}, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) can masquerade as an ovarian epithelial neoplasm, with very similar presenting clinical symptoms and imaging findings. The gold standard in differentiating between these two diagnoses lies in tissue pathology.<br><br>CASE REPORT: This is a case of MPM that was initially misdiagnosed as ovarian cancer based on family history, imaging, and surgical findings. Tissue diagnosis preoperatively would have changed the planned procedure. Retrospectively, after the diagnosis of MPM, the patient was found to have had an indirect exposure to asbestos through her father.<br><br>CONCLUSIONS: This case highlights the importance of keeping a broad differential when diagnosing ovarian malignancies, collecting both family and social histories (including screening for exposure to asbestos), and the benefit of obtaining tissue diagnosis when MPM is suspected.}, }
@article {pmid27349291, year = {2016}, author = {Musumeci, G and Loreto, C and Giunta, S and Rapisarda, V and Szychlinska, MA and Imbesi, R and Castorina, A and Annese, T and Castorina, S and Castrogiovanni, P and Ribatti, D}, title = {Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers.}, journal = {Experimental cell research}, volume = {346}, number = {1}, pages = {91-98}, doi = {10.1016/j.yexcr.2016.06.017}, pmid = {27349291}, issn = {1090-2422}, mesh = {Animals ; Antigens, CD/metabolism ; Asbestos, Amphibole/*toxicity ; Blotting, Western ; Densitometry ; Female ; Immunohistochemistry ; Lung/drug effects/*pathology ; Macrophages/drug effects/*metabolism ; Male ; Mast Cells/drug effects/enzymology/*metabolism ; *Neovascularization, Physiologic/drug effects ; Sheep ; Staining and Labeling ; Tryptases/metabolism ; Tubulin/metabolism ; }, abstract = {Angiogenesis plays a crucial role in progression of pleural malignant mesothelioma. A significantly increased incidence of pleural mesothelioma has been attributed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. In this study, we have investigated the expression of CD68-positive macrophages, tryptase-positive mast cells and CD31 positive areas, as expression of microvascular density, in lung tissue of sheeps exposed to fluoro-edenite fibers vs controls, by immunohistochemical, morphometric and Western blot analysis. The result have evidenced a significant increase in the expression of CD68-positive macrophages, tryptase-positive mast cells as well as a significant increase in microvascular density evaluated as CD31 positive areas in lung tissue of of sheeps exposed to fluoro-edenite fibers vs controls. These data confirmed the important role played by tumor microenvironment components, including macrophages and mast cells, in favour of angiogenesis in pleural mesothelioma induced by fluoro-edenite exposure.}, }
@article {pmid27325621, year = {2017}, author = {Meisenkothen, C}, title = {Malignant Mesothelioma in a Motor Vehicle Mechanic.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {524-542}, doi = {10.1177/1048291116655526}, pmid = {27325621}, issn = {1541-3772}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Motor Vehicles ; *Occupational Exposure ; }, abstract = {Case reports remain an important source of data in the debate over the carcinogenic effect of asbestos-containing automotive friction products. This report documents a case of pleural mesothelioma accompanied by asbestos bodies in the lung tissue of a career auto mechanic with no other known sources of exposure. Previously unreported historical and contemporary exposure data are also discussed in the context of providing additional support for the proposition that work with asbestos-containing automotive products presents a risk of significant exposure. While there remains a body of negative epidemiology that fails to find an increased risk of disease among auto workers, those data must be approached with caution. Many of those studies have drawn technical criticisms, which are beyond the scope of this report, but they remain a key part of the legal defense mounted by defendant-companies who are involved in asbestos-related litigation. This ongoing debate provides the context for the continued relevance of case reports such as this one, as well as the presentation of new and previously unpublished exposure data.}, }
@article {pmid27325080, year = {2016}, author = {Landrigan, PJ and , }, title = {Comments on the Causation of Malignant Mesothelioma: Rebutting the False Concept That Recent Exposures to Asbestos Do Not Contribute to Causation of Mesothelioma.}, journal = {Annals of global health}, volume = {82}, number = {1}, pages = {214-216}, doi = {10.1016/j.aogh.2016.01.017}, pmid = {27325080}, issn = {2214-9996}, mesh = {Asbestos/*toxicity ; Humans ; Italy ; *Mesothelioma ; Occupational Exposure/*adverse effects ; Pleural Neoplasms ; }, abstract = {BACKGROUND: European asbestos manufacturers and their expert witnesses have advanced the claim that recent exposures to asbestos are not of significance in the causation of malignant mesothelioma. They argue that in cases of prolonged exposure to asbestos only the earliest exposures contribute to mesothelioma induction.<br><br>METHODS: The Collegium Ramazzini examined this claim and compared it with the findings of the Epidemiology and Public Health Working Group of the Second Italian Consensus Conference on Pleural Mesothelioma. This independent Working Group noted that earlier exposures are more effective in inducing mesothelioma, but that subsequent exposures also contribute and cannot be excluded. They found convincing evidence to support the conclusion that mesothelioma incidence is proportional to cumulative asbestos exposure.<br><br>CONCLUSION: The Collegium Ramazzini concludes that risk of malignant mesothelioma is proportional to cumulative exposure to asbestos in which all exposures - early as well as late - contribute to the totality of risk. The Collegium Ramazzini rejects as false and scientifically unfounded the notion that only the earliest exposures to asbestos contribute to mesothelioma induction.}, }
@article {pmid27325079, year = {2016}, author = {Takahashi, K and Landrigan, PJ and , }, title = {The Global Health Dimensions of Asbestos and Asbestos-Related Diseases.}, journal = {Annals of global health}, volume = {82}, number = {1}, pages = {209-213}, doi = {10.1016/j.aogh.2016.01.019}, pmid = {27325079}, issn = {2214-9996}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*epidemiology/prevention &amp; control ; Developed Countries ; Developing Countries ; *Global Health ; Humans ; International Cooperation ; Occupational Exposure/*adverse effects ; }, abstract = {The Collegium Ramazzini (CR) reaffirms its long-standing position that responsible public health action is to ban all extraction and use of asbestos, including chrysotile. This current statement updates earlier statements by the CR with a focus on global health dimensions of asbestos and asbestos-related diseases (ARDs). The ARD epidemic will likely not peak for at least a decade in most industrialized countries and for several decades in industrializing countries. Asbestos and ARDs will continue to present challenges in the arena of occupational medicine and public health, as well as in clinical research and practice, and have thus emerged as a global health issue. Industrialized countries that have already gone through the transition to an asbestos ban have learned lessons and acquired know-how and capacity that could be of great value if deployed in industrializing countries embarking on the transition. The accumulated wealth of experience and technologies in industrialized countries should thus be shared internationally through global campaigns to eliminate ARDs.}, }
@article {pmid27320084, year = {2016}, author = {Cabibi, D and Tutino, R and Salamone, G and Cocorullo, G and Agrusa, A and Gulotta, G}, title = {Diffuse malignant biphasic peritoneal mesothelioma with cystic areas.}, journal = {Annali italiani di chirurgia}, volume = {87}, number = {}, pages = {}, pmid = {27320084}, issn = {2239-253X}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Appendicitis/diagnosis ; Asbestos/adverse effects ; Ascites/etiology ; Biomarkers, Tumor/analysis ; Cisplatin/administration &amp; dosage ; Crohn Disease/diagnosis ; Diagnosis, Differential ; Diagnostic Errors ; Humans ; Lung Neoplasms/diagnosis/drug therapy/etiology/*pathology ; Male ; Mesothelioma/diagnosis/drug therapy/etiology/*pathology ; Mesothelioma, Cystic/diagnosis/drug therapy/etiology/*pathology ; Mesothelioma, Malignant ; Occupational Exposure ; Pemetrexed/administration &amp; dosage ; Peritoneal Neoplasms/diagnosis/drug therapy/etiology/*pathology ; }, abstract = {UNLABELLED: We report a case of peritoneal biphasic mesothelioma with cystic areas in a patient with professional exposure to asbestos. It showed focal epithelial glandular and papillary proliferations, also presenting fluid filled cysts, whose wall consisted of a proliferation of spindle cells. Atypia and mitoses were very scanty. EMA, vimentin, CK5/6, D2-40, calretinin and P53 were positive and desmin was negative in both epithelial and spindle areas, including the ones surrounding the cystic spaces. These findings gave an essential aid in the differential diagnosis with a benign cystic mesothelioma and with a cystic epithelial mesothelioma with secondary pseudosarcomatous myofibroblastic proliferation. The presence of cystic areas in a malignant mesothelioma could make difficult the diagnosis. A large amount of tumour tissue is necessary for confirming the biphasic histotype, an aggressive histotype, even in the presence of mild histological features and of some others favourable clinical prognostic indices as in this case. To our knowledge this is the first case of malignant peritoneal biphasic mesothelioma with cystic features reported in the literature.<br><br>KEY WORDS: Cystic Mesothelioma, Immunohistochemistry, Malignant Mesothelioma, Peritoneal Diseases, Mesothelial Neoplasms.}, }
@article {pmid27318362, year = {2016}, author = {Webb, J and Yiu, YW and Giastefani, S and Carr-White, G}, title = {Pericardial mesothelioma.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {109}, number = {9}, pages = {631-632}, doi = {10.1093/qjmed/hcw099}, pmid = {27318362}, issn = {1460-2393}, mesh = {Aged ; Asbestos/*adverse effects ; Echocardiography/methods ; Fatal Outcome ; *Heart Neoplasms/etiology/pathology/physiopathology ; Humans ; Magnetic Resonance Imaging, Cine/methods ; Male ; *Mesothelioma/etiology/pathology/physiopathology ; *Pericardium/diagnostic imaging/pathology ; *Pleural Neoplasms/etiology/pathology/physiopathology ; Radiography, Thoracic/methods ; }, }
@article {pmid27312399, year = {2016}, author = {Mensi, C and De Matteis, S and Dallari, B and Riboldi, L and Bertazzi, PA and Consonni, D}, title = {Incidence of mesothelioma in Lombardy, Italy: exposure to asbestos, time patterns and future projections.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {9}, pages = {607-613}, pmid = {27312399}, issn = {1470-7926}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Incidence ; Interviews as Topic ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Poisson Distribution ; Registries ; Risk Factors ; Sex Distribution ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVES: In Italy, asbestos has been extensively used from 1945 to 1992. We evaluated the impact of exposure to asbestos on occurrence of malignant mesothelioma (MM) in the Lombardy Region, Northwest Italy, the most populated and industrialised Italian region.<br><br>METHODS: From the Lombardy Mesothelioma Registry, we selected all incident cases of MM diagnosed between 2000 and 2012. We described sources of exposure to asbestos and examined time trends of MM rates. Using Poisson age-cohort models, we derived projections of burden of MM in the Lombardy population for the period 2013-2029.<br><br>RESULTS: In 2000-2012, we recorded 4442 cases of MM (2850 men, 1592 women). Occupational exposure to asbestos was more frequent in men (73.6%) than in women (38.2%). Non-occupational exposure was found for 13.6% of women and 3.6% of men. The average number of cases of MM per year was still increasing (+3.6% in men, +3.3% in women). Incidence rates were still increasing in individuals aged 65+ years and declining in younger people. A maximum of 417 cases of MM (267 men, 150 women) are expected in 2019. We forecast there will be 6832 more cases (4397 in men, 2435 in women) in the period 2013-2029, for a total of 11&#x2005;274 cases of MM (7247 in men, 4027 in women) in 30&#x2005;years.<br><br>CONCLUSIONS: This study documented a high burden of MM in both genders in the Lombardy Region, reflecting extensive occupational (mainly in men) and non-occupational (mainly in women) exposure to asbestos in the past. Incidence rates are still increasing; a downturn in occurrence of MM is expected to occur after 2019.}, }
@article {pmid27302977, year = {2016}, author = {Yang, HY and Huang, SH and Shie, RH and Chen, PC}, title = {Cancer mortality in a population exposed to nephrite processing.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {8}, pages = {528-536}, doi = {10.1136/oemed-2016-103586}, pmid = {27302977}, issn = {1470-7926}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Carcinogens ; Cohort Studies ; Esophageal Neoplasms/*mortality ; Female ; Humans ; Hypopharyngeal Neoplasms/*mortality ; Laryngeal Neoplasms/*mortality ; Male ; Manufacturing Industry ; Mesothelioma/mortality ; Minerals ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Particle Size ; Particulate Matter/adverse effects ; Risk Factors ; Stomach Neoplasms/*mortality ; }, abstract = {OBJECTIVES: Although asbestos has been recognised as a strong carcinogen, many asbestos minerals exist in concrete masses, and the health risks of these materials remain inconclusive. Nephrite jade is a concrete mass of amphibole that consists of asbestiform and non-asbestiform particles. The objective of the study was to explore the carcinogenetic effect of nephrite.<br><br>METHODS: We examined cancer mortality between 1979 and 2011 in Fengtian, where nephrite was mass produced from 1970 to 1980, and calculated standardised mortality ratios (SMRs).<br><br>RESULTS: We observed significantly elevated mortality risks for cancer of the hypopharynx (SMR 2.31; 95% CI 1.37 to 3.65), larynx (SMR 2.51; 95% CI 1.55 to 3.83), oesophagus (SMR 2.04; 95% CI 1.62 to 2.54) and stomach (SMR 1.38; 95% CI 1.17 to 1.63). This study analysed the lengths, widths, structures, chemical compositions, aerodynamic diameters and distributions of elongated mineral particles (EMPs) in airways. The majority of the EMPs (68%) were short (<5&#x2005;&#x3bc;m) and thin (<0.5&#x2005;&#xb5;m), and possessed asbestiform structures. The median aerodynamic diameter of the EMPs was 1.2&#x2005;&#x3bc;m. The total deposition proportion in airways was 51.3%. The major deposition sites were the head airway (37.5%), followed by the alveolar region (10.6%) and the tracheobronchial region (3.2%).<br><br>CONCLUSIONS: The results have shown an association between EMPs and increased risk of respiratory and digestive cancers. Further research is needed that includes information on smoking habits and exposure to asbestos.}, }
@article {pmid27300447, year = {2016}, author = {Pessôa, FM and de Melo, AS and Souza, AS and de Souza, LS and Hochhegger, B and Zanetti, G and Marchiori, E}, title = {Applications of Magnetic Resonance Imaging of the Thorax in Pleural Diseases: A State-of-the-Art Review.}, journal = {Lung}, volume = {194}, number = {4}, pages = {501-509}, pmid = {27300447}, issn = {1432-1750}, mesh = {Empyema/diagnostic imaging ; Endometriosis/diagnostic imaging ; Female ; Fibroma/*diagnostic imaging ; Foreign Bodies/diagnostic imaging ; Humans ; Lymphoma/diagnostic imaging ; Magnetic Resonance Imaging/*methods ; Male ; Mesothelioma/*diagnostic imaging ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; Splenosis/diagnostic imaging ; Thorax/diagnostic imaging ; }, abstract = {The aim of this review was to present the main aspects of pleural diseases seen with conventional and advanced magnetic resonance imaging (MRI) techniques. This modality is considered to be the gold standard for the evaluation of the pleural interface, characterization of complex pleural effusion, and identification of exudate and hemorrhage, as well as in the analysis of superior sulcus tumors, as it enables more accurate staging. The indication for MRI of the thorax in the identification of these conditions is increasing in comparison to computerized tomography, and it can also be used to support the diagnosis of pulmonary illnesses. This literature review describes the morphological and functional aspects of the main benign and malignant pleural diseases assessed with MRI, including mesothelioma, metastasis, lymphoma, fibroma, lipoma, endometriosis, asbestos-related pleural disease, empyema, textiloma, and splenosis.}, }
@article {pmid27298458, year = {2016}, author = {Ferrante, D and Mirabelli, D and Tunesi, S and Terracini, B and Magnani, C}, title = {Authors's response: Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {10}, pages = {713-714}, doi = {10.1136/oemed-2016-103851}, pmid = {27298458}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; *Pleural Neoplasms ; Risk Assessment ; }, }
@article {pmid27293862, year = {2016}, author = {Kim, KC and Vo, HP}, title = {Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor.}, journal = {Journal of thoracic disease}, volume = {8}, number = {6}, pages = {E379-84}, pmid = {27293862}, issn = {2072-1439}, abstract = {Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies.}, }
@article {pmid27290892, year = {2016}, author = {Ruff, K and Mirabelli, D and Magnani, C}, title = {Scientific journal publishes second eratum regarding false information by scientists funded by asbestos interests.}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {2}, pages = {138-139}, doi = {10.19191/EP16.2.P138.069}, pmid = {27290892}, issn = {1120-9763}, abstract = {In a paper published on Epidemiology, Biostatistics and Public Health, Ilgren et al. claimed that cases of mesothelioma among workers of the Balangero (a municipality of the province of Turin, Northern Italy) chrysotile mine and nearby residents were not caused by chrysotile, but by other forms of asbestos. In support, they cited a reference where no pertaining evidence can be found. One year after the paper, an erratum was published by the journal editors in chief, warning that an erroneous citation was present. The erratum is weak and misleading, concealing the fact that a false statement was supported by such error and that it may serve the interests of the chrysotile industry, by dismissing evidence of chrysotile carcinogenicity. Some of the article authors, of the editors in chief and members of the journal editorial board had financial ties to asbestos interests.}, }
@article {pmid27288871, year = {2016}, author = {Hoda, MA and Dong, Y and Rozsas, A and Klikovits, T and Laszlo, V and Ghanim, B and Stockhammer, P and Ozsvar, J and Jakopovic, M and Samarzija, M and Brcic, L and Bendek, M and Szirtes, I and Reid, G and Kirschner, MB and Kao, SC and Opitz, I and Weder, W and Frauenfelder, T and Nguyen-Kim, TD and Aigner, C and Klepetko, W and van Zandwijk, N and Berger, W and Dome, B and Grusch, M and Hegedus, B}, title = {Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma - A multi-institutional study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {63}, number = {}, pages = {64-73}, doi = {10.1016/j.ejca.2016.04.018}, pmid = {27288871}, issn = {1879-0852}, mesh = {Activins/*blood ; Aged ; Biomarkers, Tumor/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrinogen/analysis ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*blood/pathology ; Prognosis ; }, abstract = {INTRODUCTION: The deregulation of activin expression is often observed in various malignancies. Previous studies indicate that activin A plays a protumourigenic role in malignant pleural mesothelioma (MPM). The aim of the study was to evaluate circulating activin A level as a biomarker in MPM.<br><br>METHODS: Plasma samples were collected from 129 MPM patients in four institutions at the time of diagnosis or before surgical resection. Samples from 45 healthy individuals and from 16 patients with non-malignant pleural diseases served as controls. Circulating activin A was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological variables.<br><br>RESULTS: Plasma activin A level was significantly elevated in MPM patients (862&#xa0;&#xb1;&#xa0;83&#xa0;pg/ml) when compared to healthy controls (391&#xa0;&#xb1;&#xa0;21&#xa0;pg/ml; P&#xa0;<&#xa0;0.0001). Patients with pleuritis or fibrosis only showed a modest increase (versus controls; 625&#xa0;&#xb1;&#xa0;95&#xa0;pg/ml; P&#xa0;=&#xa0;0.0067). Sarcomatoid (n&#xa0;=&#xa0;10, 1629&#xa0;&#xb1;&#xa0;202&#xa0;pg/ml, P&#xa0;=&#xa0;0.0019) and biphasic (n&#xa0;=&#xa0;23, 1164&#xa0;&#xb1;&#xa0;233&#xa0;pg/ml, P&#xa0;=&#xa0;0.0188) morphology were associated with high activin A levels when compared to epithelioid histology (n&#xa0;=&#xa0;94, 712&#xa0;&#xb1;&#xa0;75&#xa0;pg/ml). The tumour volume showed a positive correlation with increased circulating activin A levels. MPM patients with below median activin A levels had a significantly longer overall survival when compared to those with high activin A levels (median survival 735 versus 365&#xa0;d, P&#xa0;<&#xa0;0.0001). Importantly, circulating activin A levels were exclusively prognostic in epithelioid MPM.<br><br>CONCLUSIONS: Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis.}, }
@article {pmid27287512, year = {2016}, author = {Kuryk, L and Haavisto, E and Garofalo, M and Capasso, C and Hirvinen, M and Pesonen, S and Ranki, T and Vassilev, L and Cerullo, V}, title = {Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model.}, journal = {International journal of cancer}, volume = {139}, number = {8}, pages = {1883-1893}, doi = {10.1002/ijc.30228}, pmid = {27287512}, issn = {1097-0215}, mesh = {Adenoviridae/genetics/immunology/physiology ; Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Carboplatin/administration &amp; dosage ; Cell Line, Tumor ; Combined Modality Therapy ; Granulocyte-Macrophage Colony-Stimulating Factor/administration &amp; dosage/genetics/immunology ; Humans ; Lung Neoplasms/drug therapy/immunology/*therapy/virology ; Mesothelioma/drug therapy/immunology/*therapy/virology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Oncolytic Virotherapy/*methods ; Pemetrexed/administration &amp; dosage ; Virus Replication ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed-Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression-free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM-CSF. The safety and immune activating properties of ONCOS-102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS-102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS-102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti-tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti-tumor activity in the mesothelioma mouse model, ONCOS-102 was able to slow down tumor growth. Interestingly, a synergistic anti-tumor effect was seen when ONCOS-102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS-102 in combination with first-line chemotherapy in patients suffering from malignant mesothelioma.}, }
@article {pmid27286698, year = {2016}, author = {Novello, S and Pinto, C and Torri, V and Porcu, L and Di Maio, M and Tiseo, M and Ceresoli, G and Magnani, C and Silvestri, S and Veltri, A and Papotti, M and Rossi, G and Ricardi, U and Trodella, L and Rea, F and Facciolo, F and Granieri, A and Zagonel, V and Scagliotti, G}, title = {The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations.}, journal = {Critical reviews in oncology/hematology}, volume = {104}, number = {}, pages = {9-20}, doi = {10.1016/j.critrevonc.2016.05.004}, pmid = {27286698}, issn = {1879-0461}, mesh = {Animals ; Humans ; Incidence ; Italy/epidemiology ; *Lung Neoplasms/complications/diagnosis/epidemiology/therapy ; *Mesothelioma/complications/diagnosis/epidemiology/therapy ; Mesothelioma, Malignant ; Pleural Effusion/etiology ; *Pleural Neoplasms/complications/diagnosis/epidemiology/therapy ; Public Health ; Risk Factors ; }, abstract = {Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.}, }
@article {pmid27282309, year = {2016}, author = {Hylebos, M and Van Camp, G and van Meerbeeck, JP and Op de Beeck, K}, title = {The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {10}, pages = {1615-1626}, doi = {10.1016/j.jtho.2016.05.020}, pmid = {27282309}, issn = {1556-1380}, mesh = {Exome ; Genome/*genetics ; Humans ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/pathology ; Transcriptome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare yet aggressive tumor that is causally associated with-mostly professional-asbestos exposure. Given the long latency between exposure and disease, and because asbestos is still being used, MPM will remain a global health issue for decades to come. Notwithstanding the increasing incidence of MPM and the fact that patients with MPM face a poor prognosis, currently available treatment options are limited. To enable the development of novel targeted therapies, identification of the genetic alterations underlying MPM will be crucial. The first studies reporting on the genomic background of MPM identified recurrent somatic mutations in a number of tumor suppressor genes (i.e., cyclin-dependent kinase inhibitor 2A gene [CDKN2A], neurofibromin 2 (merlin) gene [NF2], and BRCA1 associated protein 1 gene [BAP1]). More recently, massively parallel sequencing strategies have been used and have provided a more genome-wide view on the genetic landscape of MPM. This review summarizes their results, describing alterations that cluster mainly in four pathways: the tumor protein p53/DNA repair, cell cycle, mitogen-activated protein kinase, and phosphoinisitide 3-kinase (PI3K)/AKT pathways. As these pathways are important during tumor development, they provide interesting candidates for targeting with novel drugs.}, }
@article {pmid27281118, year = {2016}, author = {de Ridder, GG and Kraynie, A and Pavlisko, EN and Oury, TD and Roggli, VL}, title = {Asbestos content of lung tissue in patients with malignant peritoneal mesothelioma: A study of 42 cases.}, journal = {Ultrastructural pathology}, volume = {40}, number = {3}, pages = {134-141}, doi = {10.3109/01913123.2016.1170085}, pmid = {27281118}, issn = {1521-0758}, mesh = {Adult ; Aged ; Asbestosis/*complications/*epidemiology ; Female ; Humans ; Lung Neoplasms/*complications/pathology ; Male ; Mesothelioma/*complications/pathology ; Mesothelioma, Malignant ; Microscopy, Electron, Scanning ; Middle Aged ; Peritoneal Neoplasms/*complications/pathology ; Spectrometry, X-Ray Emission ; }, abstract = {Lung tissue from 42 peritoneal mesothelioma cases was analyzed by light microscopy and scanning electron microscopy/energy dispersive spectrometry. There were 34 men and 8 women with a mean age of 61 ± 10 years. Also, 17% of cases had histologically confirmed asbestosis, and 26% had only parietal pleural plaques. The asbestos body count exceeded our normal range in 22 of 42 cases (52%). Cases with asbestos-related pulmonary disease had higher fiber burdens than those without. The vast majority of fibers were commercial amphiboles (amosite with lesser amounts of crocidolite). These findings concur with previously published epidemiological observations.}, }
@article {pmid27279560, year = {2016}, author = {Kato, T and Lee, D and Wu, L and Patel, P and Young, AJ and Wada, H and Hu, HP and Ujiie, H and Kaji, M and Kano, S and Matsuge, S and Domen, H and Kaga, K and Matsui, Y and Kanno, H and Hatanaka, Y and Hatanaka, KC and Matsuno, Y and de Perrot, M and Yasufuku, K}, title = {Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {49}, number = {2}, pages = {448-456}, doi = {10.3892/ijo.2016.3566}, pmid = {27279560}, issn = {1791-2423}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; Female ; Gene Knockdown Techniques ; Humans ; Kinesins/biosynthesis/*genetics ; Male ; Mesothelioma/*genetics/metabolism/pathology/*therapy ; Microtubule-Associated Proteins/biosynthesis/*genetics ; Middle Aged ; Molecular Targeted Therapy ; Pleural Neoplasms/*genetics/metabolism/pathology/*therapy ; RNA, Small Interfering/administration &amp; dosage/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Transfection ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.}, }
@article {pmid27259231, year = {2016}, author = {Micolucci, L and Akhtar, MM and Olivieri, F and Rippo, MR and Procopio, AD}, title = {Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis.}, journal = {Oncotarget}, volume = {7}, number = {36}, pages = {58606-58637}, pmid = {27259231}, issn = {1949-2553}, mesh = {Asbestos/*toxicity ; Biomarkers, Tumor ; Computational Biology ; Epigenesis, Genetic ; GPI-Linked Proteins/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*chemically induced/*diagnosis/genetics ; Mesothelin ; Mesothelioma/*chemically induced/*diagnosis/genetics ; Mesothelioma, Malignant ; MicroRNAs/blood/*genetics ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Tissue Array Analysis ; Tissue Distribution ; }, abstract = {BACKGROUND: Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM.<br><br>METHODS: The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential.<br><br>RESULTS: A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as "mesomiRs" (MM-associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets.<br><br>CONCLUSION: The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic.}, }
@article {pmid27245839, year = {2016}, author = {Cheng, YY and Wright, CM and Kirschner, MB and Williams, M and Sarun, KH and Sytnyk, V and Leshchynska, I and Edelman, JJ and Vallely, MP and McCaughan, BC and Klebe, S and van Zandwijk, N and Lin, RC and Reid, G}, title = {KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma.}, journal = {Molecular cancer}, volume = {15}, number = {1}, pages = {44}, pmid = {27245839}, issn = {1476-4598}, mesh = {3' Untranslated Regions ; Binding Sites ; Cell Line, Tumor ; Cell Movement ; Databases, Genetic ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/*genetics/metabolism ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Oligonucleotide Array Sequence Analysis/*methods ; Pleural Neoplasms/*genetics ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets.<br><br>METHODS: Utilizing mRNA-microRNA correlations based on differential gene expression using Gene Set Enrichment Analysis (GSEA), we systematically combined publicly available gene expression datasets with our own MPM data in order to identify candidate targets for MPM therapy.<br><br>RESULTS: We identified enrichment of target binding sites for the miR-17 and miR-30 families in both MPM tumors and cell lines. RT-qPCR revealed that members of both families were significantly downregulated in MPM tumors and cell lines. Interestingly, lower expression of miR-17-5p (P&#x2009;=&#x2009;0.022) and miR-20a-5p (P&#x2009;=&#x2009;0.026) was clearly associated with epithelioid histology. We interrogated the predicted targets of these differentially expressed microRNA families in MPM cell lines, and identified KCa1.1, a calcium-activated potassium channel subunit alpha 1 encoded by the KCNMA1 gene, as a target of miR-17-5p. KCa1.1 was overexpressed in MPM cells compared to the (normal) mesothelial line MeT-5A, and was also upregulated in patient tumor samples compared to normal mesothelium. Transfection of MPM cells with a miR-17-5p mimic or KCNMA1-specific siRNAs reduced mRNA expression of KCa1.1 and inhibited MPM cell migration. Similarly, treatment with paxilline, a small molecule inhibitor of KCa1.1, resulted in suppression of MPM cell migration.<br><br>CONCLUSION: These functional data implicating KCa1.1 in MPM cell migration support our integrative approach using MPM gene expression datasets to identify novel and potentially druggable targets.}, }
@article {pmid27245376, year = {2016}, author = {Martínez-Miranda, MD and Nielsen, B and Nielsen, JP}, title = {Simple benchmark for mesothelioma projection for Great Britain.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {8}, pages = {561-563}, doi = {10.1136/oemed-2015-103303}, pmid = {27245376}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Forecasting ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/mortality ; Occupational Exposure/adverse effects ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: It is of considerable interest to forecast the future burden of mesothelioma mortality. Data on deaths are available, whereas no measure of asbestos exposure is available.<br><br>METHODS: We compare two Poisson models: a response-only model with an age-cohort specification and a multinomial model with epidemiologically motivated frequencies.<br><br>RESULTS: The response-only model has 5% higher peak mortality than the dose-response model. The former performs slightly better in out-of-sample comparison.<br><br>CONCLUSIONS: Mortality is predicted to peak at about 2100 deaths around 2017 among males in cohorts until 1966 and below 90&#x2005;years of age. The response-only model is a simple benchmark that forecasts just as well as more complicated models.}, }
@article {pmid27240221, year = {2016}, author = {Candura, SM and Boeri, R and Teragni, C and Chen, Y and Scafa, F}, title = {Renal cell carcinoma and malignant peritoneal mesothelioma after occupational asbestos exposure: case report.}, journal = {La Medicina del lavoro}, volume = {107}, number = {3}, pages = {172-177}, pmid = {27240221}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinoma, Renal Cell/*etiology ; Humans ; Kidney Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Neoplasms, Multiple Primary/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*etiology ; }, abstract = {UNLABELLED: Asbestos is the main causal factor for malignant mesothelioma (MM), a relatively rare and aggressive malignancy. Some epidemiological evidence suggests a role of this agent also in the etiology of renal cell carcinoma (RCC), the most common form of kidney cancer.<br><br>CASE REPORT: After 7 years of asbestos exposure, a 76-year-old asbestos-cement worker came to our notice with left flank pain. Diagnostic imaging disclosed a neoplasm in the upper two thirds of the left kidney, without evidence of metastases. After surgery (nephrectomy with para-aortic lymphadenectomy), histopathology revealed clear cell RCC. One year later, the patient was hospitalized for abdominal pain. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum and liver. Histological and immunohistochemical examination of the bioptic samples led to the diagnosis of biphasic MM. The subject died 2 months later. Autopsy disclosed ascites and diffuse infiltration of the abdominal wall and viscera, without evidence of RCC relapse.<br><br>CONCLUSIONS: This is the second reported case of association between RCC and peritoneal MM in the scientific literature. Asbestos might be involved in the causation of both malignancies.}, }
@article {pmid27236568, year = {2016}, author = {Ledda, C and Pomara, C and Bracci, M and Mangano, D and Ricceri, V and Musumeci, A and Ferrante, M and Musumeci, G and Loreto, C and Fenga, C and Santarelli, L and Rapisarda, V}, title = {Natural carcinogenic fiber and pleural plaques assessment in a general population: A cross-sectional study.}, journal = {Environmental research}, volume = {150}, number = {}, pages = {23-29}, doi = {10.1016/j.envres.2016.05.024}, pmid = {27236568}, issn = {1096-0953}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos, Amphibole/*toxicity ; Carcinogens/*toxicity ; Cross-Sectional Studies ; *Environmental Exposure ; Environmental Pollutants/*toxicity ; Female ; Humans ; Lung Diseases/chemically induced/*epidemiology/pathology ; Male ; Middle Aged ; Parenchymal Tissue/drug effects ; Retrospective Studies ; Sicily/epidemiology ; Tomography, X-Ray Computed ; Young Adult ; }, abstract = {Natural carcinogenic fibers are asbestos and asbestiform fibers present as a natural component of soils or rocks. These fibers are released into the environment resulting in exposure of the general population. Environmental contamination by fibers are those cases occurred in: rural regions of Turkey, in Mediterranean countries and in other sites of the world, including northern Europe, USA and China. Fluoro-edenite(FE) is a natural mineral species first isolated in Biancavilla, Sicily. The fibers are similar in size and morphology to some amphibolic asbestos fibers, whose inhalation can cause chronic inflammation and cancer. The aim of the current study is to assess the presence and features of pleural plaques (PPs) in Biancavilla's general population exposed to FE through a retrospective cross-sectional study. All High-Resolution Computed Tomography (HRCT) chest scans carried out between June 2009 and June 2015 in Biancavilla municipality hospital site (exposed subjects) were reviewed. The exposed groups were 1:1 subjects, matched according to age and sex distributions, with unexposed subjects (n.1.240) randomly selected among HRCT chest scans carried out in a Hospital 30km away from Biancavilla. Subjects from Biancavilla with PPs were significantly more numerous than the control group ones (218 vs 38). Average age of either group was >60 years; the age of exposed subjects was significantly (p=0.0312) lesser than the unexposed group. In exposed subjects, in most PPs thickness ranged between 2 and 4.9cm(38%, n=83); while in unexposed ones PPs thickness was less than 2cm (55%, n=21). As to the size of PPs in exposed subjects, in most cases it ranged between 1cm and 24% of chest wall (53%, n=116); while in unexposed ones the size of PPs was lesser than 1cm (23%, n=58). Among exposed subjects, 36 cases (17%) PPs were detected with calcification, whereas in unexposed ones only three (8%) presented calcification. 137 lung parenchymal abnormalities were observed in exposed group; whereas, 12 lung parenchymal involvement were registered in unexposed subjects. The RR for PPs is 6,74 CI 95% (4,47-9,58) p<0,0001 in the exposed population. These findings, suggested the urge to extend the screening on the possible involvement of the respiratory tract to all Biancavilla's population, particularly in those aged more than 30. Besides, it seems essential to start indoor monitoring Biancavilla's municipality.}, }
@article {pmid27220441, year = {2016}, author = {Song, PP and Wang, Y and Sun, JL and Gao, Y and Liu, J and Chen, YX}, title = {[The incidence of asbestos-related diseases about on asbestos enterprises in Qingdao from 1988 to 2014].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {34}, number = {3}, pages = {203-205}, doi = {10.3760/cma.j.issn.1001-9391.2016.03.010}, pmid = {27220441}, issn = {1001-9391}, mesh = {Asbestos ; *Asbestosis ; Dust ; Female ; Humans ; Incidence ; Lung Neoplasms ; Male ; Mesothelioma ; Occupational Exposure ; Pleural Diseases ; Workplace ; }, abstract = {OBJECTIVE: It can provide statistics reference for the prevention and treatment by analysising the status and characteristics related to the asbestos disease of an asbestos products enterprises from 1988 to 2014.<br><br>METHODS: We have collected the data concerning the case of asbestos-related disease between 1988 and 2014, then the data were arranged, collecteted and analyzed using statistical method.<br><br>RESULTS: The total of patients is 625 (male: 225, female: 400). Diagnosis of asbestosis is 617 cases, Accordingly, stage &#x2160;is 500, stage &#x2161;is 112 and stage &#x2162; is 5. Average age of morbidity is 64.84&#xb1;9.87 and working age is 24.45&#xb1;7.40 years; The patients of lung cancer caused by asbestos are 12 people, and average age of morbidity is 66.25&#xb1;11.20 years, and the working age is 29.18&#xb1;7.77years; The patients of mesothelioma are 4 people, average age of morbidity is 49-78 (M=60) and working age is 27years. Asbestosis patients with complications of pleural plaque is 37.44%, complications of pulmonary tuberculosis is 5.19%., and there are 239 patients lose their lives, motality is 38.74%.<br><br>CONCLUSION: There is a high incidence of a disease about asbestos related disease in the asbestos products factory, it has close relationship with asbestos exposure time, the dust concentration of workplace and type of work et al. Asbestos related diseases are still the main problem in Qingdao.}, }
@article {pmid27219104, year = {2016}, author = {Egilman, D and Tran, T}, title = {A commentary on Roggli's "The So-Called Short-Fiber Controversy".}, journal = {International journal of occupational and environmental health}, volume = {22}, number = {3}, pages = {181-186}, pmid = {27219104}, issn = {2049-3967}, mesh = {Asbestos ; *Asbestos, Serpentine ; Carcinogens ; Humans ; Lung Neoplasms ; *Mesothelioma ; }, abstract = {Dr. Victor Roggli republished a "literature review and critical analysis" of the toxicity of short fiber asbestos. His paper was originally prepared and presented at a conference of asbestos defense lawyers. His review omitted published papers that indicate that short fiber asbestos is a carcinogen. We critically review his paper.}, }
@article {pmid27217757, year = {2016}, author = {Tural Onur, S and Sokucu, SN and Dalar, L and Iliaz, S and Kara, K and Buyukkale, S and Altin, S}, title = {Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio reliable parameters as prognostic indicators in malignant mesothelioma?.}, journal = {Therapeutics and clinical risk management}, volume = {12}, number = {}, pages = {651-656}, pmid = {27217757}, issn = {1176-6336}, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive asbestos-related pleural tumor. The incidence is increasing with intensive use of asbestos in developing countries. We need an easily accessible, inexpensive, and reliable method for determining the low survival time prognosis of this tumor. The aim of our study was to investigate the viability of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as prognostic indicators in MM.<br><br>PATIENTS AND METHODS: Thirty-six patients with MM, whose histopathologic diagnosis and follow-up were performed by our clinic and whose complete archive data were accessible, were included in this retrospective study. The patients' histopathologic disease types and stages, complete blood count parameters at diagnosis, and survival were recorded.<br><br>RESULTS: Eighteen of the patients with MM were male and the remaining 18 of them were female; the average follow-up period was 24.83&#xb1;3.61 months. The PLR levels of the patients were statistically significant (P<0.05). The NLR and PLR area under the receiver operating characteristic curve values were 0.559 and 0.749, respectively (P=0.631 and P=0.044, respectively).<br><br>CONCLUSION: PLR was a significant prognostic indicator of MM at diagnosis on complete blood count parameters; however, NLR was not a significant prognostic indicator. A large number of prospective studies are needed to prove the reliability of the parameters.}, }
@article {pmid27210080, year = {2016}, author = {Kishimoto, T and Fujimoto, N and Nishi, H}, title = {[Clinical Pathological Diagnosis, and Treatment for Pleural Mesothelioma].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {43}, number = {5}, pages = {513-517}, pmid = {27210080}, issn = {0385-0684}, mesh = {Antineoplastic Agents/therapeutic use ; Biopsy ; Humans ; Lung Neoplasms/complications/*diagnosis/genetics/*therapy ; Mesothelioma/complications/*diagnosis/genetics/*therapy ; Mesothelioma, Malignant ; Pleural Effusion/etiology ; Pleural Neoplasms/complications/*diagnosis/genetics/*therapy ; }, abstract = {For the differential diagnosis between fibrous pleuritis and other malignancies such as lung cancer, multiple immunostaining is essential to diagnose pleural mesothelioma. For cytological diagnosis of pleural effusions, differentiation between mesothelioma cells and reactive mesothelial cells is very difficult. Therefore, histological diagnoses of tumor tissues obtained via biopsy are essential. To diagnose epthelioid mesothelioma, more than 2 positive and negative markers must be consistent with those known for mesothelioma. To diagnose sarcomatoid mesothelioma, keratin is usually positive, differentiating the diagnosis from that for real sarcoma. For surgical treatment for pleural mesothelioma, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are usually performed. The proportion of P/D increases because of the low death rates with surgery and similar survivals. However, a trimodal approach, such as EPP with chemotherapy and radiotherapy, is best for longer survival and expected to be curative. For chemotherapy, only cisplatin (CDDP) combined with pemetrexed (PEM) is effective, and no other agents have been identified for this disease. Nowadays, clinical immunotherapy trials start with phase II study.}, }
@article {pmid27188278, year = {2016}, author = {Boffetta, P}, title = {Response to: Pleural mesothelioma, and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {10}, pages = {712}, doi = {10.1136/oemed-2016-103776}, pmid = {27188278}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Diseases ; Occupational Exposure ; *Pleural Neoplasms ; Risk Assessment ; }, }
@article {pmid27187383, year = {2016}, author = {Lai, J and Zhou, Z and Tang, XJ and Gao, ZB and Zhou, J and Chen, SQ}, title = {A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {17}, number = {5}, pages = {}, pmid = {27187383}, issn = {1422-0067}, mesh = {Aged ; Amino Acid Sequence ; Antigen Presentation/immunology ; Antigens, Neoplasm/*genetics ; Biomarkers, Tumor/*genetics ; Blotting, Western ; Female ; Frameshift Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Lung Neoplasms/*genetics ; Major Histocompatibility Complex ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Models, Biological ; Molecular Weight ; Peritoneal Neoplasms/*genetics ; *Precision Medicine ; Reproducibility of Results ; Signal Transduction ; Tumor Suppressor Proteins/chemistry/*genetics ; Ubiquitin Thiolesterase/chemistry/*genetics ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient's HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM.}, }
@article {pmid27185582, year = {2016}, author = {Reid, G and Kao, SC and Pavlakis, N and Brahmbhatt, H and MacDiarmid, J and Clarke, S and Boyer, M and van Zandwijk, N}, title = {Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer.}, journal = {Epigenomics}, volume = {8}, number = {8}, pages = {1079-1085}, doi = {10.2217/epi-2016-0035}, pmid = {27185582}, issn = {1750-192X}, mesh = {*Clinical Trials, Phase I as Topic ; Humans ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; RNAi Therapeutics/*methods ; Thoracic Neoplasms/*therapy ; }, abstract = {miRNAs are responsible for post-transcriptional control of gene expression, and are frequently downregulated in cancer. It has become well established that restoring miRNA levels can inhibit tumor growth, and many studies have demonstrated this in preclinical models. This in turn has led to the first clinical trials of miRNA replacement therapy. This special report focuses on the development of TargomiRs - miRNA mimics delivered by targeted bacterial minicells - and the very first clinical experience of a miRNA replacement therapy in thoracic cancer patients in the Phase I MesomiR-1 trial.}, }
@article {pmid27184482, year = {2016}, author = {Chirac, P and Maillet, D and Leprêtre, F and Isaac, S and Glehen, O and Figeac, M and Villeneuve, L and Péron, J and Gibson, F and Galateau-Sallé, F and Gilly, FN and Brevet, M}, title = {Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array.}, journal = {Human pathology}, volume = {55}, number = {}, pages = {72-82}, doi = {10.1016/j.humpath.2016.04.015}, pmid = {27184482}, issn = {1532-8392}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/*genetics ; Chromosomal Instability ; *Comparative Genomic Hybridization ; *DNA Copy Number Variations ; Female ; France ; *Gene Amplification ; *Gene Dosage ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Inhalation Exposure/adverse effects ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics/mortality/pathology/therapy ; Male ; Mesothelioma/*genetics/mortality/pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*genetics/mortality/pathology/therapy ; Phenotype ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Young Adult ; }, abstract = {Malignant peritoneal mesotheliomas (MPM) are rare, accounting for approximately 8% of cases of mesothelioma in France. We performed comparative genomic hybridization (CGH) on frozen MPM samples using the Agilent Human Genome CGH 180 K array. Samples were taken from a total of 33 French patients, comprising 20 men and 13 women with a mean (range) age of 58.4 (17-76) years. Asbestos exposure was reported in 8 patients (24.2%). Median (range) overall survival (OS) was 39 (0-119) months. CGH analysis demonstrated the presence of chromosomal instability in patients with MPM, with a genomic pattern that was similar to that described for pleural mesothelioma, including the loss of chromosomal regions 3p21, 9p21, and 22q12. In addition, novel genomic copy number alterations were identified, including the 15q26.2 region and the 8p11.22 region. Median OS was associated with a low peritoneal cancer index (P=.011), epithelioid subtype (P=.038), and a low number of genomic aberrations (P=.015), all of which constitute good prognostic factors for MPM. Our results provide new insights into the genetic and genomic background of MPM. Although pleural and peritoneal mesotheliomas have different risk factors, different therapeutics, and different prognosis; these data provide support to combine pleural and peritoneal mesothelioma in same clinical assays.}, }
@article {pmid27181379, year = {2016}, author = {Betti, M and Aspesi, A and Biasi, A and Casalone, E and Ferrante, D and Ogliara, P and Gironi, LC and Giorgione, R and Farinelli, P and Grosso, F and Libener, R and Rosato, S and Turchetti, D and Maffè, A and Casadio, C and Ascoli, V and Dianzani, C and Colombo, E and Piccolini, E and Pavesi, M and Miccoli, S and Mirabelli, D and Bracco, C and Righi, L and Boldorini, R and Papotti, M and Matullo, G and Magnani, C and Pasini, B and Dianzani, I}, title = {CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma.}, journal = {Cancer letters}, volume = {378}, number = {2}, pages = {120-130}, doi = {10.1016/j.canlet.2016.05.011}, pmid = {27181379}, issn = {1872-7980}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis/*genetics ; *Codon, Nonsense ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/analysis/*genetics ; DNA Mutational Analysis ; Databases, Factual ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Heredity ; Humans ; Immunohistochemistry ; Italy ; Male ; Melanoma/chemistry/*genetics/pathology ; Mesothelioma/chemistry/*genetics/pathology ; Middle Aged ; Pedigree ; Phenotype ; Risk Factors ; Skin Neoplasms/chemistry/*genetics/pathology ; Tumor Suppressor Proteins/analysis/*genetics ; Ubiquitin Thiolesterase/analysis/*genetics ; Young Adult ; }, abstract = {BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.}, }
@article {pmid27180335, year = {2016}, author = {Vangelova, K and Dimitrova, I}, title = {Asbestos exposure and mesothelioma incidence and mortality in Bulgaria.}, journal = {Reviews on environmental health}, volume = {31}, number = {2}, pages = {203-209}, doi = {10.1515/reveh-2016-0007}, pmid = {27180335}, issn = {2191-0308}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Bulgaria/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {Bulgaria totally banned the import, production and use of asbestos in 2005, but produced and used asbestos products during the last 3-4 decades of the 20th century. The aim of this study was to follow the incidence and mortality of mesothelioma in Bulgaria in relation to past occupational exposures. A literature search between 1960 and 2014 was conducted to obtain information on asbestos consumption, occupational exposure and asbestos-related diseases (ARDs). Data on registered mesotheliomas were provided by the National Cancer Register and data for recognized occupational ARDs were provided by the National Social Security Institute. An increase in the incidence of mesothelioma from 5 to 58 from 1993 to 2013, with 666 cases in the 21-year period, was registered. Incidence, mortality rates, deaths and male-to-female ratios and were lower in comparison to industrialized countries. The increase in mesothelioma incidence is considered as a consequence of more recent production and use of asbestos and asbestos products and the high occupational exposure between 1977 and 1989, while the lower rate of mesothelioma deaths and male-to-female ratio need to be investigated further.}, }
@article {pmid27171110, year = {2016}, author = {Benvenuto, M and Mattera, R and Taffera, G and Giganti, MG and Lido, P and Masuelli, L and Modesti, A and Bei, R}, title = {The Potential Protective Effects of Polyphenols in Asbestos-Mediated Inflammation and Carcinogenesis of Mesothelium.}, journal = {Nutrients}, volume = {8}, number = {5}, pages = {}, pmid = {27171110}, issn = {2072-6643}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogenesis/*drug effects ; Humans ; Inflammation/*chemically induced/*prevention &amp; control ; Lung Neoplasms/chemically induced/*prevention &amp; control ; Mesothelioma/chemically induced/*prevention &amp; control ; Mesothelioma, Malignant ; Polyphenols/*pharmacology ; }, abstract = {Malignant Mesothelioma (MM) is a tumor of the serous membranes linked to exposure to asbestos. A chronic inflammatory response orchestrated by mesothelial cells contributes to the development and progression of MM. The evidence that: (a) multiple signaling pathways are aberrantly activated in MM cells; (b) asbestos mediated-chronic inflammation has a key role in MM carcinogenesis; (c) the deregulation of the immune system might favor the development of MM; and (d) a drug might have a better efficacy when injected into a serous cavity thus bypassing biotransformation and reaching an effective dose has prompted investigations to evaluate the effects of polyphenols for the therapy and prevention of MM. Dietary polyphenols are able to inhibit cancer cell growth by targeting multiple signaling pathways, reducing inflammation, and modulating immune response. The ability of polyphenols to modulate the production of pro-inflammatory molecules by targeting signaling pathways or ROS might represent a key mechanism to prevent and/or to contrast the development of MM. In this review, we will report the current knowledge on the ability of polyphenols to modulate the immune system and production of mediators of inflammation, thus revealing an important tool in preventing and/or counteracting the growth of MM.}, }
@article {pmid27169472, year = {2016}, author = {Fritschi, L and Chan, J and Hutchings, SJ and Driscoll, TR and Wong, AY and Carey, RN}, title = {The future excess fraction model for calculating burden of disease.}, journal = {BMC public health}, volume = {16}, number = {}, pages = {386}, pmid = {27169472}, issn = {1471-2458}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*poisoning ; *Cost of Illness ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Risk ; Young Adult ; }, abstract = {BACKGROUND: Estimates of the burden of disease caused by a particular agent are used to assist in making policy and prioritizing actions. Most estimations have employed the attributable fraction approach, which estimates the proportion of disease cases or deaths in a specific year which are attributable to past exposure to a particular agent. While this approach has proven extremely useful in quantifying health effects, it requires historical data on exposures which are not always available.<br><br>METHODS: We present an alternative method, the future excess fraction method, which is based on the lifetime risk approach, and which requires current rather than historical exposure data. This method estimates the future number of exposure-related disease cases or deaths occurring in the subgroup of the population who were exposed to the particular agent in a specific year. We explain this method and use publically-available data on current asbestos exposure and mesothelioma incidence to demonstrate the use of the method.<br><br>CONCLUSIONS: Our approach to modelling burden of disease is useful when there are no historical measures of exposure and where future disease rates can be projected on person years at risk.}, }
@article {pmid27156205, year = {2016}, author = {Espinosa Muñoz, E and Ramírez Ocaña, D and Gutiérrez Cardo, AL}, title = {Malignant pleural mesothelioma in a young adult with no known exposure to asbestos.}, journal = {Archivos de bronconeumologia}, volume = {52}, number = {12}, pages = {615-616}, doi = {10.1016/j.arbres.2016.03.008}, pmid = {27156205}, issn = {1579-2129}, mesh = {Age of Onset ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos ; Diagnostic Errors ; Environmental Exposure ; Female ; Fever/etiology ; Humans ; Lung Neoplasms/complications/*diagnostic imaging/drug therapy/surgery ; Mesothelioma/complications/*diagnostic imaging/drug therapy/surgery ; Mesothelioma, Malignant ; Pelvic Inflammatory Disease ; Pleural Neoplasms/complications/*diagnostic imaging/drug therapy/surgery ; *Positron Emission Tomography Computed Tomography ; Risk Factors ; Shoulder Pain/etiology ; Young Adult ; }, }
@article {pmid27141331, year = {2016}, author = {Cook, AM and McDonnell, AM and Lake, RA and Nowak, AK}, title = {Dexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy strategies.}, journal = {Oncoimmunology}, volume = {5}, number = {3}, pages = {e1066062}, pmid = {27141331}, issn = {2162-4011}, abstract = {The glucocorticoid (GC) steroid dexamethasone (Dex) is used as a supportive care co-medication for cancer patients undergoing standard care pemetrexed/platinum doublet chemotherapy. As trials for new cancer immunotherapy treatments increase in prevalence, it is important to track the immunological changes induced by co-medications commonly used in the clinic, but not specifically included in trial design or in pre-clinical models. Here, we document a number of Dex -induced immunological effects, including a large-scale lymphodepletive effect particularly affecting CD4[+] T cells but also CD8[+] T cells. The proportion of regulatory T cells within the CD4[+] compartment did not change after Dex was administered, however a significant increase in proliferation and activation of regulatory T cells was observed. We also noted Dex -induced proportional changes in dendritic cell (DC) subtypes. We discuss these immunological effects in the context of chemoimmunotherapy strategies, and suggest a number of considerations to be taken into account when designing future studies where Dex and other GCs may be in use.}, }
@article {pmid27129173, year = {2016}, author = {Roulois, D and Deshayes, S and Guilly, MN and Nader, JS and Liddell, C and Robard, M and Hulin, P and Ouacher, A and Le Martelot, V and Fonteneau, JF and Grégoire, M and Blanquart, C and Pouliquen, DL}, title = {Characterization of preneoplastic and neoplastic rat mesothelial cell lines: the involvement of TETs, DNMTs, and 5-hydroxymethylcytosine.}, journal = {Oncotarget}, volume = {7}, number = {23}, pages = {34664-34687}, pmid = {27129173}, issn = {1949-2553}, mesh = {5-Methylcytosine/*analogs &amp; derivatives/metabolism ; Animals ; Asbestos, Crocidolite/toxicity ; Biomarkers, Tumor ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic/*pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*metabolism ; DNA (Cytosine-5-)-Methyltransferases/*metabolism ; DNA Methyltransferase 3A ; Epithelial Cells/pathology ; Epithelium/pathology ; Humans ; Karyotype ; Lung Neoplasms/chemically induced/*pathology ; Mesothelioma/chemically induced/*pathology ; Mesothelioma, Malignant ; Mixed Function Oxygenases/*metabolism ; Precancerous Conditions/*pathology ; Proto-Oncogene Proteins/*metabolism ; Rats ; Rats, Inbred F344 ; }, abstract = {Malignant mesothelioma (MM) is one of the worst cancers in terms of clinical outcome, urging the need to establish and characterize new preclinical tools for investigation of the tumorigenic process, improvement of early diagnosis and evaluation of new therapeutic strategies. For these purposes, we characterized a collection of 27 cell lines established from F344 rats, after 136 to 415 days of induction with crocidolite asbestos administered intraperitoneally. Four mesotheliomas were distinguished from 23 preneoplastic mesothelial cell lines (PN) according to their propensity to generate tumors after orthotopic transplantation into syngeneic rats, their growth pattern, and the expression profile of three genes. PN cell lines were further discriminated into groups / subgroups according to morphology in culture and the expression profiles of 14 additional genes. This approach was completed by analysis of positive and negative immunohistochemical MM markers in the four tumors, of karyotype alterations in the most aggressive MM cell line in comparison with a PN epithelioid cell line, and of human normal mesothelial and mesothelioma cells and a tissue array. Our results showed that both the rat and human MM cell lines shared in common a dramatic decrease in the relative expression of Cdkn2a and of epigenetic regulators, in comparison with PN and normal human mesothelial cells, respectively. In particular, we identified the involvement of the relative expression of the Ten-Eleven Translocation (TET) family of dioxygenases and Dnmt3a in relation to the 5-hydroxymethylcytosine level in malignant transformation and the acquisition of metastatic potential.}, }
@article {pmid27124367, year = {2016}, author = {Baur, X}, title = {Asbestos: Socio-legal and Scientific Controversies and Unsound Science in the Context of the Worldwide Asbestos Tragedy - Lessons to be Learned.}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {70}, number = {6}, pages = {405-412}, doi = {10.1055/s-0042-103580}, pmid = {27124367}, issn = {1438-8790}, mesh = {*Asbestos ; Asbestosis/*epidemiology ; Bias ; Causality ; Evidence-Based Medicine/ethics/legislation &amp; jurisprudence ; Global Health/ethics/legislation &amp; jurisprudence/*statistics &amp; numerical data ; Humans ; Lung Neoplasms/*epidemiology ; Prevalence ; Science/*legislation &amp; jurisprudence ; Social Justice/ethics/*legislation &amp; jurisprudence ; }, abstract = {Eight to fifteen per cent of lung cancer cases and nearly all mesothelioma cases are caused by asbestos. Problems in compensation issues ensue from strict legal requirements for eligibility and regulations of the statutory accident insurance institution pertaining to eligibility for occupational disease benefits. The latter include the unscientific requirement for set numbers of asbestos bodies or fibers to be found in lung tissue in order to "prove" disease causation if lung specimen are available. Although the validity of such evidence has been discredited by independent scientists, it is still used as evidence by an influential US pathology department. Frequently, epidemiological evidence regarding causal relationships and exposure histories is also often being ignored by insurance-affiliated medical experts.Similar misleading arguments are currently being used in newly industrialized countries where white asbestos - which is carcinogenic and fibrogenic like other asbestos types - is efficiently promoted as being less harmful. As a result, asbestos use is increasing in some of these countries. Behind the worldwide asbestos tragedy, a well-designed strategy orchestrated by certain transnational or multinational industrial interest groups can be perceived.Beyond the asbestos tragedy their covert plan is motivated by economic interests and discounts the ensuing damage to health and the impact of the diseases they create on public health systems.}, }
@article {pmid27123108, year = {2016}, author = {Maki, Y and Nishimura, Y and Toyooka, S and Soh, J and Tsukuda, K and Shien, K and Furukawa, M and Muraoka, T and Ueno, T and Tanaka, N and Yamamoto, H and Asano, H and Maeda, M and Kumagai-Takei, N and Lee, S and Matsuzaki, H and Otsuki, T and Miyoshi, S}, title = {The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells.}, journal = {Oncology letters}, volume = {11}, number = {5}, pages = {3308-3316}, pmid = {27123108}, issn = {1792-1074}, abstract = {Malignant mesothelioma (MM) is thought to arise from the direct effect of asbestos on mesothelial cells. However, MM takes a long time to develop following exposure to asbestos, which suggests that the effects of asbestos are complex. The present study examined the effects of asbestos exposure on the cell growth of MeT-5A human mesothelial cells via cytokines produced by immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with antibodies against cluster of differentiation (CD)3 and CD28 upon exposure to the asbestos chrysotile A (CA) or crocidolite (CR); the growth of MeT-5A cells in media supplemented with PBMC culture supernatants was subsequently examined. MeT-5A cells exhibited an increase in proliferation when grown in supernatant from the 7-day PBMC culture exposed to CA or CR. Analysis of cytokine production demonstrated increased levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos.}, }
@article {pmid27110327, year = {2016}, author = {Bakhshayesh Karam, M and Karimi, S and Mosadegh, L and Chaibakhsh, S}, title = {Malignant Mesothelioma Versus Metastatic Carcinoma of the Pleura: A CT Challenge.}, journal = {Iranian journal of radiology : a quarterly journal published by the Iranian Radiological Society}, volume = {13}, number = {1}, pages = {e10949}, pmid = {27110327}, issn = {1735-1065}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare malignant neoplasm of the pleura that typically affects individuals occupationally exposed to asbestos through a variety of industries. MPM presents with several CT features similar to more common pleural diseases such as metastatic pleural malignancy.<br><br>OBJECTIVES: The aim of this study is to differentiate malignant pleural mesothelioma from metastatic carcinoma of the pleura by pathological and radiological assessment in order to investigate accuracy of CT scan in this regard and to compare CT features of these two malignancies.<br><br>PATIENTS AND METHODS: Chest CT scans of 55 pleural malignancy patients including MPM and metastatic pleural malignancy were evaluated in this retrospective study. The pathologist made the definite diagnosis based on immunohistochemistry. A chest radiologist unaware of the pathology diagnosis observed all CT scans. Several parameters including pleural thickening, pleural effusion, thickening of inter lobar fissure, contralateral extension, contraction of involved hemithorax, parenchymal involvement (infiltration, nodules, fibrosis), pleural mediastinal involvement, lymphadenopathy, extrapleural invasion (hepatic, chest wall, diaphragm, intraperitoneal), and pericardial involvement were checked. Data analysis was carried out using SPSS version 16, and the ability of CT scan to differentiate malignant pleural mesothelioma and metastatic pleural diseases was investigated.<br><br>RESULTS: Totally 29 males and 26 females were assessed in this study. Based on pathology, 17 MPM and 38 metastatic pleural malignancies were diagnosed. According to CT study, about 82% of the patients with MPM and about 79% of the patients with metastatic pleural diseases were correctly diagnosed by a radiologist. The most common findings suggestive of MPM were pleural thickening (88.2%), loculated effusion (58.8%), and thickening of the interlobar fissure (47.1%). Whereas free pleural effusion (71.7%), parenchymal infiltration (65.8%) and pleural thickening (63.2%) were most prevalent parameters among metastatic cases.<br><br>CONCLUSION: CT scan is highly accurate in differentiating malignant pleural mesothelioma and metastatic pleural diseases. Pleural thickening and thickening of interlobar fissure lead us to the diagnosis of MPM and massive free pleural effusion is more commonly seen in metastatic pleural malignancy.}, }
@article {pmid27098557, year = {2016}, author = {Suzui, M and Futakuchi, M and Fukamachi, K and Numano, T and Abdelgied, M and Takahashi, S and Ohnishi, M and Omori, T and Tsuruoka, S and Hirose, A and Kanno, J and Sakamoto, Y and Alexander, DB and Alexander, WT and Jiegou, X and Tsuda, H}, title = {Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors.}, journal = {Cancer science}, volume = {107}, number = {7}, pages = {924-935}, pmid = {27098557}, issn = {1349-7006}, mesh = {Animals ; Carcinogenesis/*chemically induced ; Incidence ; Inflammation/chemically induced ; Lung/*metabolism ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Nanotubes, Carbon/*adverse effects/chemistry ; Organ Specificity ; *Particle Size ; Pleural Neoplasms/*chemically induced ; Rats ; Trachea/*metabolism ; }, abstract = {Multiwalled carbon nanotubes (MWCNT) have a fibrous structure and physical properties similar to asbestos and have been shown to induce malignant mesothelioma of the peritoneum after injection into the scrotum or peritoneal cavity in rats and mice. For human cancer risk assessment, however, data after administration of MWCNT via the airway, the exposure route that is most relevant to humans, is required. The present study was undertaken to investigate the carcinogenicity of MWCNT-N (NIKKISO) after administration to the rat lung. MWCNT-N was fractionated by passing it through a sieve with a pore size of 25 μm. The average lengths of the MWCNT were 4.2 μm before filtration and 2.6 μm in the flow-through fraction; the length of the retained MWCNT could not be determined. For the present study, 10-week-old F344/Crj male rats were divided into five groups: no treatment, vehicle control, MWCNT-N before filtration, MWCNT-N flow-through and MWCNT-N retained groups. Administration was by the trans-tracheal intrapulmonary spraying (TIPS) method. Rats were administered a total of 1 mg/rat during the initial 2 weeks of the experiment and then observed up to 109 weeks. The incidences of malignant mesothelioma and lung tumors (bronchiolo-alveolar adenomas and carcinomas) were 6/38 and 14/38, respectively, in the three groups administered MWCNT and 0/28 and 0/28, respectively, in the control groups. All malignant mesotheliomas were localized in the pericardial pleural cavity. The sieve fractions did not have a significant effect on tumor incidence. In conclusion, administration of MWCNT to the lung in the rat induces malignant mesothelioma and lung tumors.}, }
@article {pmid27094688, year = {2016}, author = {Terracini, B and Mirabelli, D and Baur, X and Landrigan, P and , }, title = {Comments on the causation of malignant mesothelioma: Rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {American journal of industrial medicine}, volume = {59}, number = {6}, pages = {506-507}, doi = {10.1002/ajim.22590}, pmid = {27094688}, issn = {1097-0274}, mesh = {Asbestos/*adverse effects ; Humans ; Industry/legislation &amp; jurisprudence ; Italy ; Liability, Legal ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects/legislation &amp; jurisprudence ; }, }
@article {pmid27091358, year = {2016}, author = {Naka, T and Hatanaka, Y and Marukawa, K and Okada, H and Hatanaka, KC and Sakakibara-Konishi, J and Oizumi, S and Hida, Y and Kaga, K and Mitsuhashi, T and Matsuno, Y}, title = {Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma.}, journal = {Diagnostic pathology}, volume = {11}, number = {}, pages = {38}, pmid = {27091358}, issn = {1746-1596}, mesh = {Adenocarcinoma/chemistry/*genetics/pathology/surgery ; Adenocarcinoma of Lung ; Aged ; Biomarkers, Tumor/analysis/*genetics ; *Comparative Genomic Hybridization ; DNA Copy Number Variations ; DNA Mutational Analysis ; Gene Dosage ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry/*genetics/pathology/surgery ; Male ; Mesothelioma/chemistry/*genetics/pathology/surgery ; Mesothelioma, Malignant ; Mutation ; Neoplasms, Multiple Primary/chemistry/*genetics/pathology/surgery ; Phenotype ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; }, abstract = {BACKGROUND: Although asbestos acts as a potent carcinogen in pleural mesothelial and pulmonary epithelial cells, it still remains unclear whether asbestos causes specific and characteristic gene alterations in these different kinds of target cells, because direct comparison in an identical patient is not feasible. We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.<br><br>METHODS: Formalin-fixed paraffin-embedded (FFPE) tissues of MPM and PAC lesions from the surgically resected specimen were used. Each of these MPM and PAC lesions exhibited a typical histology and immunophenotype. CNA analysis using SNP array was performed using the Illumina Human Omni Express-12_FFPE (Illumina, San Diego, CA, USA) with DNA extracts from each lesion. Somatic mutation analysis using next-generation sequencing was performed using the TruSeq Amplicon Cancer Panel (Illumina).<br><br>RESULTS: The CNA analysis demonstrated a marked difference in the frequency of gain and loss between MPM and PAC. In PAC, copy number (CN) gain was detected more frequently and widely than CN loss, whereas in MPM there was no such obvious difference. PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking. MPM exhibited CN loss at 9p21.2-3, which is the most common genetic alteration in mesothelioma.<br><br>CONCLUSION: In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC. This comparative genetic analysis of two different lesions with same amount of asbestos exposure and cigarette smoke exposure has provided information on differences in the cancer genome related to carcinogenesis.}, }
@article {pmid27088640, year = {2016}, author = {Jiang, L and Chew, SH and Nakamura, K and Ohara, Y and Akatsuka, S and Toyokuni, S}, title = {Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis.}, journal = {Cancer science}, volume = {107}, number = {7}, pages = {908-915}, pmid = {27088640}, issn = {1349-7006}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Asbestos/*toxicity ; Body Weight ; Carcinogenesis/*drug effects ; Cell Proliferation/drug effects ; Deferoxamine/*pharmacology ; Deoxyguanosine/analogs &amp; derivatives/metabolism ; Iron/chemistry/metabolism ; Iron Chelating Agents/*pharmacology ; *Iron Deficiencies ; Macrophages/drug effects ; Male ; Neoplasms, Mesothelial/*chemically induced/metabolism/pathology/*prevention &amp; control ; Rats ; Rats, Wistar ; }, abstract = {Asbestos-induced mesothelial carcinogenesis is currently a profound social issue due to its extremely long incubation period and high mortality rate. Therefore, procedures to prevent malignant mesothelioma in people already exposed to asbestos are important. In previous experiments, we established an asbestos-induced rat peritoneal mesothelioma model, which revealed that local iron overload is a major cause of pathogenesis and that the induced genetic alterations are similar to human counterparts. Furthermore, we showed that oral administration of deferasirox modified the histology from sarcomatoid to the more favorable epithelioid subtype. Here, we used i.p. administration of desferal to evaluate its effects on asbestos-induced peritoneal inflammation and iron deposition, as well as oxidative stress. Nitrilotriacetate was used to promote an iron-catalyzed Fenton reaction as a positive control. Desferal significantly decreased peritoneal fibrosis, iron deposition, and nuclear 8-hydroxy-2'-deoxyguanosine levels in mesothelial cells, whereas nitrilotriacetate significantly increased all of them. Desferal was more effective in rat peritoneal mesothelial cells to counteract asbestos-induced cytotoxicity than in murine macrophages (RAW264.7). Furthermore, rat sarcomatoid mesothelioma cells were more dependent on iron for proliferation than rat peritoneal mesothelial cells. Because inflammogenicity of a fiber is proportionally associated with subsequent mesothelial carcinogenesis, iron elimination from the mesothelial environment can confer dual merits for preventing asbestos-induced mesothelial carcinogenesis by suppressing inflammation and mesothelial proliferation simultaneously.}, }
@article {pmid27088262, year = {2016}, author = {Yokohira, M and Nakano-Narusawa, Y and Yamakawa, K and Hashimoto, N and Yoshida, S and Kanie, S and Imaida, K}, title = {Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats.}, journal = {Cancer science}, volume = {107}, number = {7}, pages = {1047-1054}, pmid = {27088262}, issn = {1349-7006}, mesh = {Animals ; Body Weight/drug effects ; Female ; Kidney/drug effects/pathology ; Liver/drug effects/pathology ; Lung/drug effects/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mice ; Mice, Inbred Strains ; Nitrosamines/toxicity ; Organ Size/drug effects ; Particle Size ; Pleural Cavity/*drug effects/pathology ; Rats ; Rats, Inbred F344 ; Species Specificity ; Titanium/chemistry/*toxicity ; }, abstract = {Fiber-shaped particles of potassium octatitanate (tradename TISMO; chemical formula K2 O·6TiO2), which are morphologically similar to asbestos particles, were shown to induce severe proliferative reactions in the pleural mesothelium in a previous experiment carried out over 21 weeks. The present study aims to determine whether these fibers induce malignant mesotheliomas in rodents, and to examine chronic toxicity induced. Additionally, we investigated the specific differences observable between the biological responses to the direct infusion of the fibers alone into the pleural cavity and those induced by the co-administration of the fibers with a known carcinogen. To detect the induction of malignant pleural mesotheliomas, two experiments were undertaken. In Experiment 1, four strains of mice, A/J, C3H, ICR, and C57BL, were examined for 52 weeks after experimental treatment with TISMO. In Experiment 2, the F344 rats were treated with TISMO alone, the lung carcinogen N-bis (2-hydroxypropyl) nitrosamine (DHPN) alone, both TISMO and DHPN, or left untreated and were then examined for 52 weeks. In this experiment, malignant lesion induction was expected in the co-administration group. TISMO fibers were observed in the alveoli, indicating penetration through the visceral pleura in mice and rats. The histopathological detection of TISMO fibers in the liver and kidneys of mice and rats indicated migration of the fibers out of the pleural cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. Among the rats, there were no observed malignant alterations in the mesothelium induced by DHPN-TISMO co-administration.}, }
@article {pmid27087035, year = {2016}, author = {Fazzo, L and Carere, M and Tisano, F and Bruno, C and Cernigliaro, A and Cicero, MR and Comba, P and Contrino, ML and De Santis, M and Falleni, F and Ingallinella, V and Madeddu, A and Marcello, I and Regalbuto, C and Sciacca, G and Soggiu, ME and Zona, A}, title = {Cancer incidence in Priolo, Sicily: a spatial approach for estimation of industrial air pollution impact.}, journal = {Geospatial health}, volume = {11}, number = {1}, pages = {320}, doi = {10.4081/gh.2016.320}, pmid = {27087035}, issn = {1970-7096}, mesh = {Air Pollution/*adverse effects/statistics &amp; numerical data ; Carcinogens, Environmental/adverse effects ; Cluster Analysis ; Environmental Exposure/adverse effects ; Female ; Humans ; Incidence ; Male ; Neoplasms/chemically induced/*epidemiology ; Sicily/epidemiology ; Spatial Analysis ; }, abstract = {The territory around the industrial Sicilian area of Priolo, Italy, has been defined as a contaminated site (CS) of national priority for remediation because of diffuse environmental contamination caused by large industrial settlements. The present study investigates the spatial distribution of cancer into the CS territory (period 1999-2006). Different geographical methods used for the evaluation of the impact of industrial air pollutants were adopted. Using the database of Syracuse Province Cancer Registry, gender-specific standardised incidence ratios were calculated for 35 tumour sites for the CS overall and for each municipality included in the CS. A cluster analysis for 17 selected neoplasms was performed at micro-geographical level. The identification of the priority index contaminants (PICs) present in environmental matrices and a review of their carcinogenicity have been performed and applied in the interpretation of the findings. The area has a higher cancer incidence with respect to the provincial population, in particular excess is registered among both genders of lung, bladder and breast cancers as well as skin melanoma and pleural mesothelioma and there is an a priori evidence of association with the exposure to PICs. The study highlights the need to provide different approaches in CSs where several exposure pathways might be relevant for the population. The presence of potential sources of asbestos exposure deserves specific concern.}, }
@article {pmid27083413, year = {2016}, author = {Gavett, SH and Parkinson, CU and Willson, GA and Wood, CE and Jarabek, AM and Roberts, KC and Kodavanti, UP and Dodd, DE}, title = {Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats.}, journal = {Particle and fibre toxicology}, volume = {13}, number = {}, pages = {17}, pmid = {27083413}, issn = {1743-8977}, mesh = {Adenocarcinoma, Bronchiolo-Alveolar/*chemically induced/genetics/metabolism/pathology ; Adenoma/*chemically induced/metabolism/pathology ; Animals ; Apoptosis/drug effects ; Asbestos, Amosite/*toxicity ; Asbestos, Amphibole/*toxicity ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/chemically induced ; Cytokines/genetics/metabolism ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects/metabolism/pathology ; Hyperplasia ; Inflammation Mediators/metabolism ; *Inhalation Exposure ; Lung/*drug effects/metabolism/pathology ; Lung Neoplasms/*chemically induced/genetics/metabolism/pathology ; Male ; Pneumonia/*chemically induced/genetics/metabolism/pathology ; Pulmonary Fibrosis/*chemically induced/genetics/metabolism/pathology ; Rats, Inbred F344 ; Risk Assessment ; Signal Transduction/drug effects ; Time Factors ; }, abstract = {BACKGROUND: Human exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time-course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following nose-only inhalation exposure.<br><br>METHODS: Rats were exposed to air, LA (0.5, 3.5, or 25.0 mg/m(3) targets), or AM (3.5 mg/m(3) target) for 10 days and assessed for markers of lung inflammation, injury, and cell proliferation. Short-term results guided concentration levels for a stop-exposure study in which rats were exposed to air, LA (1.0, 3.3, or 10.0 mg/m(3)), or AM (3.3 mg/m(3)) 6 h/day, 5 days/week for 13 weeks, and assessed 1 day, 1, 3, and 18 months post-exposure. Fibers were relatively short; for 10 mg/m(3) LA, mean length of all structures was 3.7 &#x3bc;m and 1% were longer than 20 &#x3bc;m.<br><br>RESULTS: Ten days exposure to 25.0 mg/m(3) LA resulted in significantly increased lung inflammation, fibrosis, bronchiolar epithelial cell proliferation and hyperplasia, and inflammatory cytokine gene expression compared to air. Exposure to 3.5 mg/m(3) LA resulted in modestly higher markers of acute lung injury and inflammation compared to AM. Following 13 weeks exposure, lung fiber burdens correlated with exposure mass concentrations, declining gradually over 18 months. LA (3.3 and 10.0 mg/m(3)) and AM produced significantly higher bronchoalveolar lavage markers of inflammation and lung tissue cytokines, Akt, and MAPK/ERK pathway components compared to air control from 1 day to 3 months post-exposure. Histopathology showed alveolar inflammation and interstitial fibrosis in all fiber-exposed groups up to 18 months post-exposure. Positive dose trends for incidence of alveolar epithelial hyperplasia and bronchiolar/alveolar adenoma or carcinoma were observed among LA groups.<br><br>CONCLUSIONS: Inhalation of relatively short LA fibers produced inflammatory, fibrogenic, and tumorigenic effects in rats which replicate essential attributes of asbestos-related disease in exposed humans. Fiber burden, inflammation, and activation of growth factor pathways may persist and contribute to lung tumorigenesis long after initial LA exposure. Fiber burden data are being used to develop a dosimetry model for LA fibers, which may provide insights on mode of action for hazard assessment.}, }
@article {pmid27070945, year = {2016}, author = {Kraynie, A and de Ridder, GG and Sporn, TA and Pavlisko, EN and Roggli, VL}, title = {Malignant mesothelioma not related to asbestos exposure: Analytical scanning electron microscopic analysis of 83 cases and comparison with 442 asbestos-related cases.}, journal = {Ultrastructural pathology}, volume = {40}, number = {3}, pages = {142-146}, doi = {10.3109/01913123.2016.1154633}, pmid = {27070945}, issn = {1521-0758}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Female ; Humans ; Lung/ultrastructure ; Male ; Mesothelioma/*pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Peritoneal Neoplasms/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {Epidemiological studies indicate that 80-90% of mesotheliomas are asbestos related. This suggests that 10-20% are not. Lung fiber burden analysis provides objective information about past exposures to asbestos. We have performed lung fiber burden analysis on a large cohort of mesothelioma cases and compared the findings with a reference population. Herein we report our findings along with demographic and exposure data.}, }
@article {pmid27069474, year = {2016}, author = {Su, SS and Zheng, GQ and Liu, YG and Chen, YF and Song, ZW and Yu, SJ and Sun, NN and Yang, YX}, title = {Malignant Peritoneum Mesothelioma with Hepatic Involvement: A Single Institution Experience in 5 Patients and Review of the Literature.}, journal = {Gastroenterology research and practice}, volume = {2016}, number = {}, pages = {6242149}, pmid = {27069474}, issn = {1687-6121}, abstract = {Malignant peritoneal mesothelioma with invasion of the liver is an invariably fatal disease. We aimed to clarify the characteristics of malignant peritoneal mesothelioma cases with liver involvement. The clinical presentation, computed tomography images, and immunohistochemical and histopathological features of 5 patients with malignant peritoneal mesothelioma and liver involvement were evaluated. The diagnosis was established by imaging and immune profiles of the tumours. A review of 8 cases with primary or invading malignant mesothelioma in liver is presented. All 5 mesothelioma cases were asbestos-related. CT images of malignant peritoneal mesothelioma with the liver involvement typically showed that the lesion grew inside the liver along the capsule and was possibly accompanied by capsule breakthrough and extrahepatic infiltration. The tumours exhibited a common epithelioid appearance in all 5 patients and most cases revealed positive Cal, CK, and MC with negative CEA and HeP. Different from our findings, the review of literature revealed that most malignant mesothelioma of liver was due to primary intrahepatic malignant mesothelioma. Finally, we concluded that the diagnosis of malignant peritoneal mesothelioma cases with liver invasion is reliably achieved by the history of asbestos exposure, the characteristic CT imaging, and immune profiles of the tumours.}, }
@article {pmid27068941, year = {2016}, author = {Thayaparan, T and Spicer, JF and Maher, J}, title = {The role of the HGF/Met axis in mesothelioma.}, journal = {Biochemical Society transactions}, volume = {44}, number = {2}, pages = {363-370}, doi = {10.1042/BST20150252}, pmid = {27068941}, issn = {1470-8752}, mesh = {Animals ; Hepatocyte Growth Factor/*physiology ; Humans ; Lung Neoplasms/pathology/*physiopathology ; Mesothelioma/pathology/*physiopathology ; Mesothelioma, Malignant ; Mutation ; Proto-Oncogene Proteins c-met/genetics/*physiology ; }, abstract = {Malignant mesothelioma is an asbestos-related cancer that occurs most commonly in the pleural space and is incurable. Increasing evidence suggests that aberrant receptor tyrosine kinase (RTK)-directed signalling plays a key role in the pathogenesis of this cancer. In the majority of mesotheliomas, up-regulated expression or signalling by Met, the receptor for hepatocyte growth factor (HGF) can be demonstrated. Following binding of ligand, Met relays signals that promote cell survival, proliferation, movement, invasiveness, branching morphogenesis and angiogenesis. Here we describe the HGF/Met axis and review the mechanisms that lead to the aberrant activation of this signalling system in mesothelioma. We also describe the cross-talk that occurs between HGF/Met and a number of other receptors, ligands and co-receptor systems. The prevalent occurrence of HGF/Met dysregulation in patients with mesothelioma sets the scene for the investigation of pharmaceutical inhibitors of this axis. In light of the inter-relationship between HGF/Met and other ligand receptor, combinatorial targeting strategies may provide opportunities for therapeutic advancement in this challenging tumour.}, }
@article {pmid27055148, year = {2016}, author = {Maggioni, C and Barletta, G and Rijavec, E and Biello, F and Gualco, E and Grossi, F}, title = {Advances in treatment of mesothelioma.}, journal = {Expert opinion on pharmacotherapy}, volume = {17}, number = {9}, pages = {1197-1205}, doi = {10.1080/14656566.2016.1176145}, pmid = {27055148}, issn = {1744-7666}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy/trends ; Humans ; Immunotherapy/adverse effects/trends ; Lung Neoplasms/diagnosis/*therapy ; Mesothelioma/diagnosis/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis/*therapy ; Prognosis ; *Therapies, Investigational/methods/trends ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon, aggressive cancer, derived from pleural mesothelial cells, that has a close relationship to asbestos exposure. To date, MPM prognosis is poor and very few treatment options are available for both localized and advanced MPM.<br><br>AREAS COVERED: The standard of care is still chemotherapy with platinum derivates and antifolate agents. In the last few years, several new agents have been studied on the basis of mesothelioma carcinogenesis and invasiveness mechanisms; however, the recent results are poor and few drugs have been tested in phase III trials because of toxicity or because they did not improve patient outcomes. The aim of this review is to focus on the current available treatment for MPM through the analysis of the results comes from the phase III trials and to discuss the future perspectives in the pathogenesis, diagnosis and treatment.<br><br>EXPERT OPINION: Many compounds are currently under investigation in different subsets of patients. Interesting data have come from preliminary studies on immunotherapy, but randomized studies are needed to confirm the preliminary positive results of this new strategy. A better comprehension of MPM pathogenesis should be obtained to improve and develop new diagnostic tools and target therapies.}, }
@article {pmid27042963, year = {2016}, author = {Matsuzaki, H and Lee, S and Maeda, M and Kumagai-Takei, N and Nishimura, Y and Otsuki, T}, title = {FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line.}, journal = {Journal of immunotoxicology}, volume = {13}, number = {5}, pages = {620-627}, doi = {10.3109/1547691X.2016.1143539}, pmid = {27042963}, issn = {1547-6901}, mesh = {Apoptosis/genetics ; Apoptosis Regulatory Proteins/genetics/metabolism ; Asbestos/administration &amp; dosage/adverse effects/*immunology ; Bcl-2-Like Protein 11/genetics/metabolism ; Cell Line ; Down-Regulation ; Fas Ligand Protein/genetics/metabolism ; Forkhead Box Protein O1/genetics/*metabolism ; Humans ; Lung Neoplasms/chemically induced/*immunology ; Mesothelioma/chemically induced/*immunology ; Proto-Oncogene Proteins/genetics/metabolism ; RNA, Messenger/analysis ; RNA, Small Interfering/genetics ; Signal Transduction ; T-Lymphocytes/*physiology ; }, abstract = {Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, over-expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.}, }
@article {pmid27041164, year = {2016}, author = {Hirooka, A and Tamiya, A and Kanazu, M and Nonaka, J and Yonezawa, T and Asami, K and Atagi, S}, title = {Brain Metastasis of Pleural Mesothelioma after a Subarachnoid Hemorrhage.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {55}, number = {7}, pages = {779-781}, doi = {10.2169/internalmedicine.55.3765}, pmid = {27041164}, issn = {1349-7235}, mesh = {Autopsy ; Brain/pathology ; Brain Neoplasms/*complications/*secondary/surgery ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Subarachnoid Hemorrhage/*complications ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon, fatal neoplasm induced by asbestos exposure. Brain metastases from MPM are extremely rare, with most such cases diagnosed only at the time of autopsy. This report describes what we believe to be the first case of MPM metastasizing to the brain after a subarachnoid hemorrhage, as well as the subsequent surgical removal of the brain metastasis.}, }
@article {pmid27040844, year = {2016}, author = {Butnor, KJ and Brownlee, NA and Mahar, A and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Diffuse malignant mesothelioma and synchronous lung cancer: A clinicopathological study of 18 cases.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {95}, number = {}, pages = {1-7}, doi = {10.1016/j.lungcan.2016.02.007}, pmid = {27040844}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers ; Biopsy ; Databases, Factual ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*epidemiology/etiology ; Male ; Mesothelioma/*diagnosis/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/*epidemiology/etiology ; Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: To examine the clinicopathologic characteristics of individuals with diffuse malignant mesothelioma (DMM) occurring concurrently with lung cancer (LC).<br><br>MATERIALS AND METHODS: A database of approximately 3800 patients with DMM was reviewed, from which 18 patients (0.5%) who had synchronous LC were identified. The clinicopathologic features, as well as the occupational exposure history and fiber burden analysis data were examined.<br><br>RESULTS: The patient median age was 68 years (range 58-84 years). Of the 18 patients (14 male, 4 female), 11 (61%) had epithelial, 5 (28%) had biphasic, and 2 (11%) had sarcomatoid DMM, with the majority (16 cases; 89%) originating in the pleura and only 2 were peritoneal. Among the histologic types of LC, adenocarcinoma was most frequent (12 cases; 67%), while 5 cases of squamous cell carcinoma, and 1 case of small cell carcinoma were observed. Three patients also had a history of prior malignancy (1 with testicular seminoma and bladder carcinoma and 2 with prostate carcinoma). Fifteen patients had a positive smoking history. All but 3 had documented asbestos exposure. Three had histologic features of asbestosis. Mineral analysis performed in 8 showed an elevated asbestos fiber burden in 4 (22%). Amosite was detected in 4 patients, crocidolite in 3, and non-commercial amphiboles in 5.<br><br>CONCLUSION: The finding of simultaneous carcinoma of the lung and DMM is distinctly unusual. The majority of patients are male smokers with pleural epithelial DMM and lung adenocarcinoma. This study represents the largest cohort of patients reported to date with synchronous malignant mesothelioma and lung cancer, and we propose guidelines for making a diagnosis of synchronous malignant mesothelioma and primary lung cancer.}, }
@article {pmid27040480, year = {2016}, author = {Ramazzini, C}, title = {Comments on the causation of malignant mesothelioma: rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {Journal of occupational health}, volume = {58}, number = {2}, pages = {228-229}, pmid = {27040480}, issn = {1348-9585}, mesh = {*Asbestos ; Humans ; Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid27034444, year = {2016}, author = {Teschke, K}, title = {Thinking about Occupation-Response and Exposure-Response Relationships: Vehicle Mechanics, Chrysotile, and Mesothelioma.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {4}, pages = {528-530}, doi = {10.1093/annhyg/mew015}, pmid = {27034444}, issn = {1475-3162}, mesh = {Asbestos, Amphibole/*toxicity ; Asbestos, Serpentine/*toxicity ; Automobiles ; Humans ; *Industry ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; }, }
@article {pmid27033611, year = {2016}, author = {Cavariani, F}, title = {Asbestos contamination in feldspar extraction sites: a failure of prevention? Commentary.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {52}, number = {1}, pages = {6-8}, doi = {10.4415/ANN_16_01_03}, pmid = {27033611}, issn = {2384-8553}, mesh = {Aluminum Silicates/*chemistry ; Asbestos/*chemistry ; Asbestos, Amphibole/chemistry ; Asbestosis/*etiology ; Carcinogens/*analysis ; Humans ; Italy ; *Mining ; Occupational Diseases/epidemiology ; Occupational Exposure/statistics &amp; numerical data ; Potassium Compounds/*chemistry ; }, abstract = {Fibrous tremolite is a mineral species belonging to the amphibole group. It is present almost everywhere in the world as a natural contaminant of other minerals, like talc and vermiculite. It can be also found as a natural contaminant of the chrysotile form of asbestos. Tremolite asbestos exposures result in respiratory health consequences similar to the other forms of asbestos exposure, including lung cancer and mesothelioma. Although abundantly distributed on the earth's surface, tremolite is only rarely present in significant deposits and it has had little commercial use. Significant presence of amphibole asbestos fibers, characterized as tremolite, was identified in mineral powders coming from the milling of feldspar rocks extracted from a Sardinian mining site (Italy). This evidence raises several problems, in particular the prevention of carcinogenic risks for the workers. Feldspar is widespread all over the world and every year it is produced in large quantities and it is used for several productive processes in many manufacturing industries (over 21 million tons of feldspar mined and marketed every year). Until now the presence of tremolite asbestos in feldspar has not been described, nor has the possibility of such a health hazard for workers involved in mining, milling and handling of rocks from feldspar ores been appreciated. Therefore the need for a wider dissemination of knowledge of these problems among professionals, in particular mineralogists and industrial hygienists, must be emphasized. In fact both disciplines are necessary to plan appropriate environmental controls and adequate protections in order to achieve safe working conditions.}, }
@article {pmid27032653, year = {2016}, author = {Demir, M and Kaya, H and Taylan, M and Ekinci, A and Yılmaz, S and Teke, F and Sezgi, C and Tanrikulu, AC and Meteroglu, F and Senyigit, A}, title = {Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure.}, journal = {Lung}, volume = {194}, number = {3}, pages = {409-417}, pmid = {27032653}, issn = {1432-1750}, mesh = {Aged ; Area Under Curve ; Asbestos/*blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; *Environmental Exposure ; ErbB Receptors/blood ; Extracellular Matrix Proteins/blood ; Female ; GPI-Linked Proteins/blood ; Humans ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis ; Middle Aged ; Peptides/blood ; Pleural Neoplasms/*blood/diagnosis ; Predictive Value of Tests ; Prospective Studies ; Syndecan-1/blood ; Thioredoxins/blood ; }, abstract = {INTRODUCTION: The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos.<br><br>METHODS: This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined.<br><br>RESULTS: Benign pleural plaques were present in 27 (58.3&#xa0;%) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p&#xa0;=&#xa0;0.023, p&#xa0;=&#xa0;0.011, and p&#xa0;<&#xa0;0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p&#xa0;=&#xa0;0.041, p&#xa0;=&#xa0;0.023, p&#xa0;=&#xa0;0.002, and p&#xa0;=&#xa0;0.001, respectively), and significantly lower mean SDC-1 levels (p&#xa0;=&#xa0;0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95&#xa0;% CI&#xa0;0.79-0.92 and p&#xa0;<&#xa0;0.001 for SMRP, and 95&#xa0;% CI&#xa0;0.62-0.81 and p&#xa0;<&#xa0;0.001 for TRX). The cut-off value for SMRP was 0.62&#xa0;nmol/l (sensitivity: 97.6&#xa0;%, specificity: 68.9&#xa0;%, positive predictive value (PPV): 56.2&#xa0;%, and negative predictive value (NPV): 98.3&#xa0;%) and for TRX was 156.67&#xa0;ng/ml (sensitivity: 92.9&#xa0;%, specificity: 77.6&#xa0;%, PPV: 41.4&#xa0;%, and NPV: 92.1&#xa0;%). The combination of the biomarkers reached a sensitivity of 100&#xa0;%, but had lower specificity (as high as 27.7&#xa0;%).<br><br>CONCLUSIONS: Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination.}, }
@article {pmid27031024, year = {2016}, author = {Pierce, JS and Ruestow, PS and Finley, BL}, title = {An updated evaluation of reported no-observed adverse effect levels for chrysotile asbestos for lung cancer and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {46}, number = {7}, pages = {561-586}, doi = {10.3109/10408444.2016.1150960}, pmid = {27031024}, issn = {1547-6898}, mesh = {Asbestos, Serpentine/standards/*toxicity ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; *No-Observed-Adverse-Effect Level ; Risk Assessment ; }, abstract = {Although consumption of chrysotile asbestos has decreased since the 1970s, the latency period of asbestos-related cancers is thought to be at least 20-30 years, and therefore the potential health risks associated with historical exposures is still actively researched. This analysis represents an update to a previous paper in which we evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. Here, we review several recently published studies as well as updated information from previous studies. For each of the 14 studies considered, we identified the "no-observed adverse effect level" (NOAEL) for lung cancer and/or mesothelioma. NOAEL values for lung cancer ranged from 1.1 to <20 f/cc-years to 1600-3200 f/cc-years, and for mesothelioma ranged from 100-400 f/cc-years to 800-1599 f/cc-years. The range of "best estimate" NOAELs was estimated to be 89-168 f/cc-years for lung cancer and 208-415 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased lung cancer risk at any exposure level, while all of the five studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Of the seven cases of peritoneal mesothelioma reported in the included studies, none were observed in the analyses of cement or friction product manufacturing workers in the absence of crocidolite exposure. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile exposures.}, }
@article {pmid27025411, year = {2017}, author = {Naik, SL and Lewin, M and Young, R and Dearwent, SM and Lee, R}, title = {Mortality from asbestos-associated disease in Libby, Montana 1979-2011.}, journal = {Journal of exposure science &amp; environmental epidemiology}, volume = {27}, number = {2}, pages = {207-213}, pmid = {27025411}, issn = {1559-064X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/mortality ; Cause of Death ; Death Certificates ; Female ; Gastrointestinal Diseases/chemically induced/mortality ; Humans ; Male ; Mesothelioma/chemically induced/mortality ; Middle Aged ; Mining ; Montana/epidemiology ; Occupational Diseases/*chemically induced/*mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/*chemically induced/*mortality ; Sex Distribution ; Young Adult ; }, abstract = {Research on asbestos exposure in Libby, MT, has focused on occupational exposure in vermiculite mining and processing, but less attention has been paid to asbestos-related mortality among community members without vermiculite mining occupational history. Our study reports on asbestos-related mortality in Libby over 33 years (1979-2011) while controlling for occupational exposure. We calculated sex-specific 33-year standardized mortality ratios (SMRs) for Libby residents who died from 1979 to 2011 with an asbestos-related cause of death. Decedent address at time of death was geocoded to confirm inclusion in the Libby County Division. We controlled for past W.R. Grace employment by including and then removing them from the SMR analysis. Six hundred and ninety-four decedents were identified as having at least one asbestos-related cause of death and residing in our study area boundary. Statistically significant (P<0.05) 33-year SMRs, both before and after controlling for W.R. Grace employment, were found for: male and female non-malignant respiratory diseases, female COPD, and asbestosis for both sexes combined. Eighty-five men and two women were matched to employment records. We observed elevated asbestos-related mortality rates among males and females. SMR results for asbestosis were high for both sexes, even after controlling for past W.R. Grace employment. These results suggest that the general population may be experiencing asbestos-related effects, not just former vermiculite workers. Additional research is needed to determine whether SMRs remain elevated after controlling for secondary exposure, such as living with vermiculite workers.}, }
@article {pmid27015029, year = {2016}, author = {Barbieri, PG and Somigliana, A and Girelli, R and Lombardi, S and Sarnico, M and Silvestri, S}, title = {[Pleural mesothelioma in a school teacher: asbestos exposure due to DAS paste].}, journal = {La Medicina del lavoro}, volume = {107}, number = {2}, pages = {141-147}, pmid = {27015029}, issn = {0025-7818}, mesh = {Aged ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/*adverse effects ; Asbestosis/*complications/etiology/pathology ; Autopsy ; *Faculty ; Female ; Humans ; Italy ; Lung Neoplasms/*etiology/pathology ; Mesothelioma/*etiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; *Play and Playthings ; Pleural Neoplasms/*etiology/pathology ; }, abstract = {BACKGROUND: Malignant mesothelioma cases among primary school teachers are usually linked with asbestos exposure due to the mineral contained in the building structure. Among the approximately 12,000 cases of mesothelioma described in the fourth report of the National Mesothelioma Register, 11 cases of primary school teachers are reported, in spite of the fact that the "catalogue of asbestos use" does not describe circumstances of asbestos exposure other than or different to that due to asbestos contained in the buildings. Four cases in the Brescia Provincial Mesothelioma Register are identified as teachers, without this circumstance of exposure.<br><br>OBJECTIVES: To characterize the asbestos concentration and fibre type retained in the lungs of a teacher reported as a new mesothelioma case and preliminarily classified as of unknown asbestos exposure.<br><br>METHODS: The mesothelioma case presented here was diagnosed at age 78 and malignant mesothelioma was confirmed at autopsy; the patient was interviewed directly for occupational history. Samples of lung parenchyma from necropsies were collected, stored and analyzed by scanning electron microscope (SEM) and samples of DAS paste were analyzed by SEM to detect asbestos fibre content.<br><br>RESULTS: It was possible to confirm past exposure to DAS paste in forming and finishing dry items and toys during school recreational activity almost every day from the mid-60s to about the mid-70s. Subsequent SEM analysis showed: i) chrysotile fibres were found in an old and unused pack of DAS paste; ii) a lung burden of 1,400 asbestos bodies, 310.000 total asbestos fibres (33% chrysotile, 67% amphibole) and 210.000 talc fibre per gr/dry lung tissue was detected from necropsies performed on the subject. These results seem to be in agreement with an occupational exposure to asbestos due to past use of DAS paste. After the investigation, this case was reclassified from "unknowun" to " sure" occupational asbestos exposure. The occupational origin of the tumour was recognized by the Italian Workers' Compensation Authority (INAIL).<br><br>CONCLUSION: This case suggests i) the need to carry out any possible detailed studies of the circumstances and exposure sources whenever any mesothelioma case is classified as "asbestos exposure unknown", according to the guidelines of the National Mesothelioma Register, ii) handling of DAS paste can be considered as sure asbestos exposure and iii) it should be borne in mind that mesothelioma cases can occur even after cumulative low, occupational exposure, even only to chrysotile.}, }
@article {pmid27009350, year = {2016}, author = {Creaney, J and Dick, IM and Musk, AW and Olsen, NJ and Robinson, BW}, title = {Immune response profiling of malignant pleural mesothelioma for diagnostic and prognostic biomarkers.}, journal = {Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals}, volume = {21}, number = {6}, pages = {551-561}, doi = {10.3109/1354750X.2016.1160429}, pmid = {27009350}, issn = {1366-5804}, mesh = {Aged ; Antibodies, Neoplasm/blood ; Antigens, Neoplasm/blood/immunology ; Asbestos/toxicity ; Autoantibodies/blood ; Biomarkers, Tumor/*blood/immunology ; Case-Control Studies ; Environmental Exposure ; Female ; Gene Ontology ; Humans ; Male ; Mesothelioma/blood/*diagnosis/immunology ; Middle Aged ; Molecular Sequence Annotation ; Pleural Neoplasms/blood/*diagnosis/immunology ; Prognosis ; Retrospective Studies ; rab GTP-Binding Proteins/immunology ; }, abstract = {The asbestos induced cancer malignant mesothelioma (MM) is difficult to diagnose and has a poor prognosis. MM is an immunological cancer, therefore autoantibodies may be suitable biomarkers and associated with prognosis. We used Protoarray(®) microarrays to determine immune responses to 8798 antigens in 10 MM and 10 asbestos exposed controls and developed diagnostic panels using 17 antigens from this. The AUC of these panels were independently tested in these 10 MM patients and controls and in a validation group of 36 controls and 35 MM patients using luminex assays; none of the antigens identified were validated. Immune responses to RAB38 were associated with a better prognosis.}, }
@article {pmid26998120, year = {2016}, author = {Thanh, TD and Tho, NV and Lam, NS and Dung, NH and Tabata, C and Nakano, Y}, title = {Simian virus 40 may be associated with developing malignant pleural mesothelioma.}, journal = {Oncology letters}, volume = {11}, number = {3}, pages = {2051-2056}, pmid = {26998120}, issn = {1792-1074}, abstract = {Malignant pleural mesothelioma (MPM) is associated with a history of heavy, long-term exposure to asbestos. However, MPM may also be associated with simian virus 40 (SV40), a polyomavirus. The association between SV40 and MPM remains unclear. The present study was conducted in order to investigate the proportion of SV40 presence in the histological specimens of Vietnamese patients with MPM. Histological specimens were obtained from 45 patients (19 men and 26 women) with MPM at the Pham Ngoc Thach Hospital in Ho Chi Minh City, Vietnam. The specimens were processed and examined in order to detect the presence of the SV40 large T antigen (SV40 Tag) expression using immunohistochemistry. Of the 45 patients, 23 (51%) were epithelioid, 7 (16%) were biphasic, 6 (13%) were sarcomatoid, 4 (9%) were desmoplastic, 4 (9%) were well-differentiated papillary and 1 (2%) was the anaplastic subtype. In total, 9/45 patients (20%) demonstrated SV40 Tag expression. The proportion of patients that demonstrated SV40 Tag expression was not significantly different between the epithelioid subtype and the other subtypes (22 vs. 18%; P=1.000) or between the patients with stage IV disease and other stages (20 vs. 20%; P=1.000). The median survival time was not significantly different between the patients with or without SV40 Tag expression (196 vs. 236 days, P=0.8949). In summary, a 5th of the Vietnamese patients with MPM were associated with infection with SV40. SV40 may be a potential cause of MPM in Vietnam and this potential association requires additional studies.}, }
@article {pmid26998119, year = {2016}, author = {Hong, S and Bi, MM and Zhao, PW and Wang, XU and Kong, QY and Wang, YT and Wang, L}, title = {Malignant peritoneal mesothelioma in a patient with intestinal fistula, incisional hernia and abdominal infection: A case report.}, journal = {Oncology letters}, volume = {11}, number = {3}, pages = {2047-2050}, pmid = {26998119}, issn = {1792-1074}, abstract = {Malignant mesothelioma is a rare type of cancer, most commonly associated with exposure to asbestos. Mesothelioma of the peritoneum, the membrane lining the abdominal cavity, is extremely rare. The current study reports the case of a 60-year-old female who presented with intestinal fistula, recurrent incisional hernia and abdominal infection, with no history of asbestos exposure, and was diagnosed with clear cell MPM. Computed tomography scans of the abdomen revealed extensive small bowel adhesions and massive peritoneal effusion. Histological examination of biopsy specimens indicated a diagnosis of malignant peritoneal mesothelioma with clear cell morphology. A laparotomy was performed, with subsequent resection of the bowel with fistula. Follow-up examination performed at 1-year post-surgery revealed that the patient was alive and in generally good health.}, }
@article {pmid26988890, year = {2016}, author = {Oddone, E and Imbriani, M}, title = {Pleural mesothelioma: Case-report of uncommon occupational asbestos exposure in a small furniture industry.}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {3}, pages = {523-526}, doi = {10.13075/ijomeh.1896.00597}, pmid = {26988890}, issn = {1896-494X}, mesh = {Aged ; Asbestos/*toxicity ; Humans ; Interior Design and Furnishings ; Male ; *Manufacturing Industry ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; }, abstract = {The relationship between asbestos exposure and malignant mesothelioma is no longer disputed, although it is not always easy to trace past occupational exposure. This report describes a case of uncommon asbestos exposure of a small furniture industry worker, who subsequently died of pleural malignant mesothelioma, to stress the crucial importance of a full reconstruction of the occupational history, both for legal and compensation purposes. Sarcomatoid pleural mesothelioma was diagnosed in a 70-year-old man, who was previously employed as a carpenter in a small furniture industry. He worked for about 6 years in the small factory, was exposed to asbestos during the assembly of the furniture inspired by classical architecture, in which asbestos cement tubes were used to reproduce classical columns. During this production process no specific work safety measures were applied, nor masks or local aspirators. No extra-professional exposure to asbestos was identified. This mesothelioma case was investigated by the Public Prosecutor's assignment that commissioned expert evidence on the legal accountability for the disease. Despite its uncommon expositive circumstance, the length of latency (about 30 years), the duration of exposure, the clinical and histochemical features are all consistent with literature evidence, accounting for the occupational origin of this malignancy.}, }
@article {pmid26988879, year = {2016}, author = {Smolková, P and Nakládalová, M and Zapletalová, J and Jakubec, P and Vildová, H and Kolek, V and Petřek, M and Nakládal, Z}, title = {Validity of mesothelin in occupational medicine practice.}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {3}, pages = {395-404}, doi = {10.13075/ijomeh.1896.00637}, pmid = {26988879}, issn = {1896-494X}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Longitudinal Studies ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Occupational Medicine/*methods ; Predictive Value of Tests ; Prospective Studies ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is the most serious asbestos-related disease. Its increasing incidence is alarming, suggesting the need for as early diagnosis as possible. This 4.5-year prospective longitudinal study aimed at assessing the benefit of measuring serum mesothelin as a marker for diagnosing malignant mesothelioma in individuals with previous occupational exposure to asbestos, as a part of their clinical follow-up care.<br><br>MATERIAL AND METHODS: The study comprised 309 participants (235 males, 74 females) with a mean age of 58.9 years (standard deviation (SD) = 9.8) and a mean duration of exposure to asbestos dust of 13.4 years (SD = 9.3). From 2009 to June 2013, all subjects were followed at a department of occupational medicine in Olomouc. Apart from the standard parts of medical examination (history, physical examination, simple chest radiographs and spirometry), the patients' serum mesothelin levels were determined by the Mesomark immunoenzymatic diagnostic assay. Statistical analysis of the validity of serum mesothelin level measurement was carried out with respect to the diagnosis of MM.<br><br>RESULTS: Among the participants, 16 (5.2%) individuals (14 males and 2 females) were diagnosed with malignant mesothelioma. Based on the detected mesothelin levels, their validity for prediction of malignant mesothelioma was calculated as follows: sensitivity - 0.75, specificity - 0.962, positive predictive value - 0.706, negative predictive value - 0.969, positive and negative likelihood ratios - 19.95 and 0.26, respectively, and diagnostic odds ratio - 76.8, at a 95% confidence interval.<br><br>CONCLUSIONS: The high specificity was identified indicating the low false positivity as well. In the case of detecting elevated soluble mesothelin-related peptides (SMRP) levels in formerly asbestos-exposed individuals, the possibility of the presence of MM should be included into the clinical consideration. The high negative predictive value denotes a lower probability of the presence of MM in patients with normal SMRP levels but due to the limiting lower sensitivity this possibility cannot be entirely excluded.}, }
@article {pmid26976999, year = {2016}, author = {Kato, K and Gemba, K and Fujimoto, N and Aoe, K and Takeshima, Y and Inai, K and Kishimoto, T}, title = {Computed Tomographic Features of Malignant Peritoneal Mesothelioma.}, journal = {Anticancer research}, volume = {36}, number = {3}, pages = {1067-1072}, pmid = {26976999}, issn = {1791-7530}, mesh = {Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging/*pathology ; Male ; Mesothelioma/*diagnostic imaging/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging/*pathology ; Pleural Neoplasms/pathology ; Retrospective Studies ; Tomography, X-Ray Computed ; }, abstract = {AIM: The objective of this study was to determine the computed tomographic (CT) features of malignant peritoneal mesothelioma (MPM).<br><br>PATIENTS AND METHODS: We analyzed CT features of MPM cases and compared them to those of other malignant conditions (non-MPM).<br><br>RESULTS: Multiple nodular lesions occurred more frequently in the MPM group compared to non-MPM cases (p=0.013). Thickening of the mesentery was detected more frequently in MPM cases than in non-MPM cases (56% vs. 18%, p=0.029). Pleural plaques were detected in 13 cases (45%) in the MPM group but were not detected in the non-MPM group. The MPM-CT index score, determined in each case as the sum of the findings which are potentially characteristic of MPM, was significantly higher in MPM than in non-MPM cases (p=0.001).<br><br>CONCLUSION: MPM presented characteristic CT findings, and the MPM-CT index may be useful for differential diagnosis of MPM.}, }
@article {pmid26976977, year = {2016}, author = {Sasai, M and Nakamura, H and Sougawa, N and Sakurai, Y and Suzuki, M and Lee, CM}, title = {Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.}, journal = {Anticancer research}, volume = {36}, number = {3}, pages = {907-911}, pmid = {26976977}, issn = {1791-7530}, mesh = {Animals ; Boron Neutron Capture Therapy/*methods ; Cell Line, Tumor ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Hyaluronic Acid/*administration &amp; dosage/pharmacology ; Mesothelioma/mortality/*therapy ; Mice ; Radiation-Sensitizing Agents/*administration &amp; dosage/pharmacology ; Survival Analysis ; Treatment Outcome ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells.<br><br>MATERIALS AND METHODS: In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model.<br><br>RESULTS: HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT.<br><br>CONCLUSION: Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM.}, }
@article {pmid26973208, year = {2016}, author = {Comar, M and Zanotta, N and Zanconati, F and Cortale, M and Bonotti, A and Cristaudo, A and Bovenzi, M}, title = {Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {94}, number = {}, pages = {61-67}, doi = {10.1016/j.lungcan.2016.01.020}, pmid = {26973208}, issn = {1872-8332}, mesh = {Asbestos/*adverse effects ; Biomarkers ; Chemokines/*metabolism ; Cross-Sectional Studies ; Cytokines/metabolism ; Female ; Humans ; Inflammation/*complications/*metabolism ; Inflammation Mediators/metabolism ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology/*metabolism ; Male ; Mesothelioma/epidemiology/*etiology/*metabolism ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*etiology/*metabolism ; }, abstract = {OBJECTIVES: Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM).<br><br>MATERIALS AND METHODS: A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area.<br><br>RESULTS: Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p<0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone.<br><br>CONCLUSIONS: Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.}, }
@article {pmid26969295, year = {2016}, author = {Peters, S and van Oyen, SC and Alfonso, H and Fritschi, L and de Klerk, NH and Reid, A and Franklin, P and Gordon, L and Benke, G and Musk, AW}, title = {Response to Kottek and Kilpatrick, 'Estimating Occupational Exposure to Asbestos in Australia'.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {4}, pages = {533-535}, doi = {10.1093/annhyg/mew010}, pmid = {26969295}, issn = {1475-3162}, mesh = {*Asbestos ; Australia ; Humans ; Mesothelioma ; Occupational Diseases ; *Occupational Exposure ; }, }
@article {pmid26952387, year = {2016}, author = {Zhang, Y and Afify, A and Gandour-Edwards, RF and Bishop, JW and Huang, EC}, title = {Small cell mesothelioma: A rare entity and diagnostic pitfall mimicking small cell lung carcinoma on fine-needle aspiration.}, journal = {Diagnostic cytopathology}, volume = {44}, number = {6}, pages = {526-529}, doi = {10.1002/dc.23460}, pmid = {26952387}, issn = {1097-0339}, mesh = {Aged ; Biopsy, Fine-Needle ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Small Cell Lung Carcinoma/*pathology ; }, abstract = {Small cell mesothelioma (SCM) is an extremely rare variant of epithelioid mesothelioma that can be mistaken for other forms of small round blue cell tumors, particularly small cell lung carcinoma (SCLC). Here, we describe a fine-needle aspiration (FNA) from a pleural lesion in a 75-year-old man with a history of known asbestos exposure. The FNA revealed cohesive clusters of uniform small round blue cells with high nuclear-to-cytoplasmic ratio, finely powdery chromatin, small inconspicuous nucleoli, and scant amount of cytoplasm. Mitoses were infrequent and nuclear molding was absent. Immunochemical profile supported a mesothelial origin, which was later confirmed by pleurectomy with a diagnosis of SCM. This report demonstrates the difficulties in cytologic evaluation of lung FNAs in differentiating SCM from SCLC or other small round blue cell tumors. As therapy differs for SCM, early recognition of the cytologic features is essential in making the correct diagnosis needed for appropriate clinical management. Diagn. Cytopathol. 2016;44:526-529. © 2016 Wiley Periodicals, Inc.}, }
@article {pmid26951736, year = {2016}, author = {Marchiori, L and Marangi, G and Ballarin, N and Valentini, F and D'Anna, M and Barbina, P and Franchi, A and Mastrangelo, G}, title = {[Proposal of an Italian national protocol of health surveillance for former asbestos workers: an ongoing project].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {68-73}, doi = {10.19191/EP16.1S1.P068.033}, pmid = {26951736}, issn = {1120-9763}, mesh = {Asbestos ; Humans ; Italy/epidemiology ; Lung Neoplasms/diagnosis ; Mesothelioma/epidemiology ; *Occupational Exposure ; Occupational Medicine ; Retrospective Studies ; }, abstract = {OBJECTIVES: to define an Italian national protocol of post-occupational health surveillance for asbestos workers according to effectiveness, appropriateness, saving, and social utility.<br><br>DESIGN: data for 1,071 former asbestos workers from several Italian Regions were collected and analysed. For these workers, a retrospective estimate of asbestos exposure was carried out. A cohort study of 1,588 asbestos workers recruited from 2000 onward during statutory health examinations in Veneto and followed-up for lung cancer mortality until December 2010 was executed. A literature search on methods of follow-up of asbestos workers (imaging, spirometry, and questionnaires) and diagnosis of non-malignant (asbestosis and pleural plaques) and malignant (lung cancer) asbestos disease was done. A consensus, i.e., a process of agreeing on one result among the participants, was made.<br><br>SETTING AND PARTICIPANTS: 19 Italian Regions (North: Veneto, Emilia-Romagna, Lombardia, Piemonte, Valle d'Aosta, Autonomous Province of Trento, Autonomous Province of Bolzano, Friuli Venezia Giulia, Liguria; Centre:Toscana, Umbria; South and Islands: Calabria, Abruzzo, Puglia, Campania, Basilicata,Marche, Sicilia, Sardegna), Department of Occupational Medicine at Italian National Institute for Compensation ofWork-Related Diseases and Accidents (INAIL), and Department of Cardiac, Thoracic, and Vascular Sciences at University of Padova.<br><br>MAIN OUTCOME MEASURES: analysis of current regional experiences on health surveillance; retrospective estimate of asbestos exposure; data collection and analysis of a cohort of asbestos workers; search of the relevant literature; final report with the consensus document.<br><br>RESULTS: the results obtained in each of the above areas of research, along with the relevant findings of the literature, were presented and discussed among the participants. The several phases of expression and evaluation of the participants' opinions were conducted according to an iterative method of investigation (Delphi method), which allows a progressive converging of different views into one shared result.<br><br>CONCLUSION: based on all the above, a consensus has been reached on a proposal for an Italian national protocol of health surveillance for asbestos workers.}, }
@article {pmid26951735, year = {2016}, author = {Magnani, C and Ancona, L and Baldassarre, A and Bressan, V and Cena, T and Chellini, E and Cuccaro, F and Ferrante, D and Legittimo, P and Luberto, F and Marinaccio, A and Mattioli, S and Menegozzo, S and Merler, E and Miligi, L and Mirabelli, D and Musti, M and Oddone, E and Pavone, V and Perticaroli, P and Pettinari, A and Pirastu, R and Ranucci, A and Romeo, E and Sala, O and Scarnato, C and Silvestri, S and , }, title = {[Time trend in mesothelioma and lung cancer risk in asbestos workers in Italy].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {64-67}, doi = {10.19191/EP16.1S1.P064.032}, pmid = {26951735}, issn = {1120-9763}, mesh = {Asbestos ; Asbestosis ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/epidemiology ; Male ; *Mesothelioma/epidemiology ; Occupational Diseases ; *Occupational Exposure ; }, abstract = {This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.}, }
@article {pmid26951730, year = {2016}, author = {Merler, E and Girardi, P and Panato, C and Bressan, V}, title = {[Increased risk of mesothelioma and lung cancer among workers exposed to asbestos who could require an anticipated retirement].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {26-34}, doi = {10.19191/EP16.1S1.P026.027}, pmid = {26951730}, issn = {1120-9763}, mesh = {Asbestos/adverse effects ; Humans ; Italy ; Lung Neoplasms/chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced ; Retirement ; }, abstract = {OBJECTIVES: to assess the association among malignant pleural mesothelioma (MPM) and lung cancer (LC) among workers who have been exposed to asbestos and have or not have required an anticipated leave from work, a possibility offered by the 1992 law banning asbestos in Italy, in the framework of the health surveillance programmes on going in the Veneto Region (Northern Italy).<br><br>SETTING AND PARTICIPANTS: a cohort of asbestos workers derived from the rosters of selected factories and alive in 1992, followed from 1992 to 2012.MPM cases have been identified through the Regional Mesothelioma Registry, while LC cases through a link with the Regional Cancer Registry, hospital discharges, and death certificates. Risks related to asbestos exposure were calculated by mixed effects Poisson regression model.<br><br>RESULTS: the risk of MPM and LC increases at any additional duration of work, up to very high values for long term durations of work for MPM, and up to a three fold increase for LC. Early retirements have been requested by a fraction only in the position of submitting it.<br><br>CONCLUSION: subjects who have been exposed to asbestos should be the target of a post-occupational surveillance, and further work is suggested to identify subjects at high risk of LC because of smoking habits and more heavy exposure to asbestos, in order to develop programmes for primary and secondary cancer prevention.}, }
@article {pmid26951729, year = {2016}, author = {Barone-Adesi, F and Mirabelli, D and Magnani, C}, title = {[Risk of lung cancer in individuals with previous exposure to asbestos].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {20-25}, doi = {10.19191/EP16.1S1.P020.026}, pmid = {26951729}, issn = {1120-9763}, mesh = {Asbestos ; Humans ; Italy ; *Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; *Occupational Exposure ; Smoking ; }, abstract = {Asbestos-related lung cancer is an important and partly unrecognized public health problem. The present review summarizes the knowledge regarding some specific aspects of the association between asbestos and lung cancer. It is difficult to estimate the exact number of lung cancers in a population that are attributable to asbestos exposure. However, this number is likely to greatly exceed the number of mesotheliomas. Epidemiological studies suggest that there is a linear relationship between cumulative exposure to asbestos and risk of lung cancer. Observed differences between different types of asbestos are lower than previously believed. This highlights the necessity of banning all types of asbestos worldwide. Risk of lung cancer changes with passing time from asbestos exposure, with the strongest effect observed 10-15 years after the exposure. This highlights the importance of quitting asbestos exposure as soon as possible, even for individuals with a long-term past exposure. Quitting smoking is the most important preventive action to be taken by individuals with a past exposure to asbestos. Results of recent studies show that smoking cessation is associated with a substantial reduction of lung cancer risk among individuals exposed to asbestos. This highlights the importance of promoting smoking cessation programmes specifically targeted to individuals with a past exposure to asbestos.}, }
@article {pmid26951727, year = {2016}, author = {Alessi, M}, title = {[The National Asbestos Plan in Italy].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {12-14}, doi = {10.19191/EP16.1S1.P012.024}, pmid = {26951727}, issn = {1120-9763}, mesh = {*Asbestos ; Humans ; Italy ; Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; }, }
@article {pmid26951690, year = {2016}, author = {Marinaccio, A}, title = {[Twenty years of data in the 5th Report of the Italian National Mesothelioma Register].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1}, pages = {3}, doi = {10.19191/EP16.1.P003.002}, pmid = {26951690}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/*etiology/prevention &amp; control ; Pleural Neoplasms/diagnosis/*epidemiology/etiology/*prevention &amp; control ; Registries/*statistics &amp; numerical data ; Retrospective Studies ; Risk Factors ; Sex Distribution ; }, }
@article {pmid26940471, year = {2016}, author = {Andersson, M and Selin, F and Järvholm, B}, title = {Asbestos exposure and the risk of sinonasal cancer.}, journal = {Occupational medicine (Oxford, England)}, volume = {66}, number = {4}, pages = {326-331}, doi = {10.1093/occmed/kqw018}, pmid = {26940471}, issn = {1471-8405}, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; Humans ; Male ; Middle Aged ; Neoplasms/epidemiology/etiology ; Occupational Diseases/complications/epidemiology ; Occupational Exposure/*adverse effects ; Paranasal Sinus Diseases/epidemiology/*etiology ; Retrospective Studies ; Sweden/epidemiology ; }, abstract = {BACKGROUND: While the increased risk of lung cancer and mesothelioma is well established, the relationship between exposure to asbestos dust and sinonasal cancer is less clear.<br><br>AIMS: To study the risk of sinonasal cancer in relation to asbestos dust exposure.<br><br>METHODS: A retrospective cohort study of construction workers, linked to the Swedish Cancer Registry. Participants were classified into four exposure groups; heavy, medium, low or very low exposure to asbestos, according to the incidence of pleural mesothelioma in their occupational group. Standardized incidence ratios (SIRs) and relative risks (RRs) were analysed, adjusted for age and smoking habits. The risks of adenocarcinoma and squamous cell carcinoma were investigated separately.<br><br>RESULTS: Among the 280222 subjects, there was no increased risk of sinonasal cancer compared to the general population [SIR 0.85, 95% confidence interval (CI) 0.68-1.03], or any dose-response relationship with exposure to asbestos. The highest RR was found in the low exposure group (RR 1.25, 95% CI 0.69-2.28) and the lowest RR was found in the group with the highest exposure to asbestos (RR 0.71, 95% CI 0.33-1.53). No significantly increased risk or dose-response association could be found for adenocarcinoma or squamous cell carcinoma when analysed separately.<br><br>CONCLUSIONS: This study did not find an increased risk of developing sinonasal cancer after asbestos exposure.}, }
@article {pmid26938529, year = {2016}, author = {Pietrofesa, RA and Velalopoulou, A and Albelda, SM and Christofidou-Solomidou, M}, title = {Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605).}, journal = {International journal of molecular sciences}, volume = {17}, number = {3}, pages = {322}, pmid = {26938529}, issn = {1422-0067}, support = {1R21AT008291-02/AT/NCCIH NIH HHS/United States ; 1P42ES023720-01/ES/NIEHS NIH HHS/United States ; 1P30 ES013508-02/ES/NIEHS NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R21 AT008291/AT/NCCIH NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antioxidants/*pharmacology ; Asbestos/*adverse effects ; Butylene Glycols/*pharmacology ; Cells, Cultured ; Glucosides/*pharmacology ; Macrophages, Peritoneal/*drug effects/metabolism ; Mice ; NF-E2-Related Factor 2/genetics/*metabolism ; *Oxidative Stress ; Signal Transduction ; }, abstract = {The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS) and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG) is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605) in asbestos-exposed, elicited murine peritoneal macrophages as an in vitro model of tissue phagocytic response to the presence of asbestos in the pleural space. Murine peritoneal macrophages (MFs) were exposed to crocidolite asbestos fibers (20 µg/cm[2]) and evaluated at various times post exposure for cytotoxicity, ROS generation, malondialdehyde (MDA), and levels of 8-iso Prostaglandin F2α (8-isoP). We then evaluated the ability of LGM2605 to mitigate asbestos-induced oxidative stress by administering LGM2605 (50 µM) 4-h prior to asbestos exposure. We observed a significant (p < 0.0001), time-dependent increase in asbestos-induced cytotoxicity, ROS generation, and the release of MDA and 8-iso Prostaglandin F2α, markers of lipid peroxidation, which increased linearly over time. LGM2605 treatment significantly (p < 0.0001) reduced asbestos-induced cytotoxicity and ROS generation, while decreasing levels of MDA and 8-isoP by 71%-88% and 41%-73%, respectively. Importantly, exposure to asbestos fibers induced cell protective defenses, such as cellular Nrf2 activation and the expression of phase II antioxidant enzymes, HO-1 and Nqo1 that were further enhanced by LGM2605 treatment. LGM2605 boosted antioxidant defenses, as well as reduced asbestos-induced ROS generation and markers of oxidative stress in murine peritoneal macrophages, supporting its possible use as a chemoprevention agent in the development of asbestos-induced malignant mesothelioma.}, }
@article {pmid26937070, year = {2015}, author = {Zhang, H and Lohcharoenkal, W and Sun, J and Li, X and Wang, L and Wu, N and Rojanasakul, Y and Liu, Y}, title = {Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure.}, journal = {Journal of micromechanics and microengineering : structures, devices, and systems}, volume = {25}, number = {7}, pages = {}, pmid = {26937070}, issn = {0960-1317}, support = {CC999999//Intramural CDC HHS/United States ; }, abstract = {Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 μg cm[-2]) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the mesothelioma hazard posed by nanomaterials.}, }
@article {pmid26935421, year = {2016}, author = {Kadariya, Y and Menges, CW and Talarchek, J and Cai, KQ and Klein-Szanto, AJ and Pietrofesa, RA and Christofidou-Solomidou, M and Cheung, M and Mossman, BT and Shukla, A and Testa, JR}, title = {Inflammation-Related IL1β/IL1R Signaling Promotes the Development of Asbestos-Induced Malignant Mesothelioma.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {9}, number = {5}, pages = {406-414}, pmid = {26935421}, issn = {1940-6215}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; R01 CA190542/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis Regulatory Proteins/deficiency ; Asbestos/adverse effects ; CARD Signaling Adaptor Proteins ; Disease Models, Animal ; Humans ; Immunoblotting ; Immunohistochemistry ; Inflammation/*metabolism/*pathology ; Interleukin-1beta/*metabolism ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Knockout ; Receptors, Interleukin-1/*metabolism ; Signal Transduction/physiology ; }, abstract = {Exposure to asbestos is causally associated with the development of malignant mesothelioma, a cancer of cells lining the internal body cavities. Malignant mesothelioma is an aggressive cancer resistant to all current therapies. Once inhaled or ingested, asbestos causes inflammation in and around tissues that come in contact with these carcinogenic fibers. Recent studies suggest that inflammation is a major contributing factor in the development of many types of cancer, including malignant mesothelioma. The NALP3/NLRP3 inflammasome, including the component ASC, is thought to be an important mediator of inflammation in cells that sense extracellular insults, such as asbestos, and activate a signaling cascade resulting in release of mature IL1β and recruitment of inflammatory cells. To determine if inflammasome-mediated inflammation contributes to asbestos-induced malignant mesothelioma, we chronically exposed Asc-deficient mice and wild-type littermates to asbestos and evaluated differences in tumor incidence and latency. The Asc-deficient mice showed significantly delayed tumor onset and reduced malignant mesothelioma incidence compared with wild-type animals. We also tested whether inflammation-related release of IL1β contributes to tumor development in an accelerated mouse model of asbestos-induced malignant mesothelioma. Nf2(+/-);Cdkn2a(+/-) mice exposed to asbestos in the presence of anakinra, an IL1 receptor (IL1R) antagonist, showed a marked delay in the median time of malignant mesothelioma onset compared with similarly exposed mice given vehicle control (33.1 weeks vs. 22.6 weeks, respectively). Collectively, these studies provide evidence for a link between inflammation-related IL1β/IL1R signaling and the development of asbestos-induced malignant mesothelioma. Furthermore, these findings provide rationale for chemoprevention strategies targeting IL1β/IL1R signaling in high-risk, asbestos-exposed populations. Cancer Prev Res; 9(5); 406-14. ©2016 AACR.}, }
@article {pmid26934117, year = {2016}, author = {Roggli, VL}, title = {Fiber analysis vignettes: Electron microscopy to the rescue!.}, journal = {Ultrastructural pathology}, volume = {40}, number = {3}, pages = {126-133}, doi = {10.3109/01913123.2016.1149531}, pmid = {26934117}, issn = {1521-0758}, mesh = {Asbestos/*analysis ; Asbestosis/*diagnosis ; Electron Probe Microanalysis/*methods ; Humans ; Mesothelioma/etiology ; }, abstract = {There has been considerable interest in the exposure doses that contribute to the various asbestos-associated diseases. Epidemiological studies have shown important differences in the contributions of the various fiber types to asbestos-related diseases, with the amphiboles showing a greater degree of potency as compared to chrysotile. However, epidemiological studies have occasionally provided misleading results. Over the past several decades, there have been several examples where fiber analysis using electron microscopy produced unexpected results which were important to our understanding of disease-exposure relationships. It is the purpose of this article to summarize these fiber analysis vignettes.}, }
@article {pmid26933413, year = {2016}, author = {Furukawa, M and Tao, H and Tanaka, T and Onoda, H and Murakami, T and Okabe, K}, title = {Chondrosarcoma of the Rib Mimicking Malignant Pleural Mesothelioma.}, journal = {Case reports in oncology}, volume = {9}, number = {1}, pages = {11-14}, pmid = {26933413}, issn = {1662-6575}, abstract = {A 62-year-old man with a history of long-term asbestos exposure was found to have a chest wall tumor invading the sixth rib on chest computed tomography. The computed tomography also revealed multiple plaques in the pleura. Malignant pleural mesothelioma was suspected, and thoracoscopic surgery was performed. Thoracoscopy revealed that the tumor location was extrapleural. Thus, excisional biopsy was performed. The tumor was histologically diagnosed as chondrosarcoma. Additional wide resection of the chest wall, including the fifth, sixth, and seventh ribs, was performed. Chest wall reconstruction was performed with a polypropylene mesh.}, }
@article {pmid26931176, year = {2016}, author = {Toyokuni, S}, title = {The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy.}, journal = {Pathology international}, volume = {66}, number = {5}, pages = {245-259}, doi = {10.1111/pin.12396}, pmid = {26931176}, issn = {1440-1827}, mesh = {Animals ; Carcinogenesis/*metabolism/pathology ; Disease Models, Animal ; Humans ; Iron/*metabolism ; Oxidative Stress/*physiology ; Rats ; }, abstract = {Helmut Sies established the concept of oxidative stress in 1985. However, it took some time to introduce this concept into pathology, where investigators count on formalin-fixed paraffin-embedded tissue sections. I sought out antigens for this purpose based on an oxidative stress-induced rat renal carcinogenesis model, which revealed that 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins are ideal. These two monoclonal antibodies successfully revealed the involvement of oxidative stress in numerous human diseases, including carcinogenesis and atherosclerosis. Shigeru Okada established the aforementioned ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model, which thus far has answered many questions regarding the presence of target genes in oxidative stress-induced carcinogenesis and the sites that are susceptible to oxidative stress in the genome. Particularly, the similarity of genomic alterations between Fe-NTA-induced renal cancer and human cancers suggests that excess iron plays a role also in human carcinogenesis. Furthermore, excess iron is a major pathology in asbestos-induced mesothelioma, including chrysotile. Despite an analogy to asbestos, multi-wall carbon nanotubes were distinct in that diameter is another responsible factor for mesothelial carcinogenesis. Recently, non-thermal plasma emerged as a candidate for medical intervention for wounds and cancers via manipulating oxidative stress. Counteracting excess iron is a promising preventive strategy for major diseases.}, }
@article {pmid26914008, year = {2015}, author = {Soberg, MJ and van Zandwijk, N}, title = {Incidence of malignant mesothelioma in New Zealand and Australia: a global snapshot.}, journal = {The New Zealand medical journal}, volume = {128}, number = {1427}, pages = {68-71}, pmid = {26914008}, issn = {1175-8716}, mesh = {Australia/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; New Zealand/epidemiology ; }, }
@article {pmid26904248, year = {2016}, author = {Nakano, T and Endo, S and Tetsuka, K and Fukushima, N}, title = {Asymptomatic localized pleural amyloidosis mimicking malignant pleural mesothelioma: report of a case.}, journal = {Journal of thoracic disease}, volume = {8}, number = {1}, pages = {E157-60}, pmid = {26904248}, issn = {2072-1439}, abstract = {We herein report an asymptomatic 65-year-old male with localized pleural amyloidosis mimicking malignant pleural mesothelioma. He had a history of exposure to asbestos and was admitted for investigation of an abnormal pleural thickness detected by chest radiography. Positron emission tomography showed elevation of standardized uptake value corresponding to the pleural thickness. Partial pleurectomy including the tumor was performed for the purpose of diagnosis and local disease control. The pathological examination showed that the tumor was pleural amyloidosis. The tumor was diagnosed as localized primary amyloidosis, because serum monoclonal protein concentration did not increase. Pleural amyloidosis should be considered as a differential diagnosis from pleural mesothelioma.}, }
@article {pmid26903779, year = {2016}, author = {Morré, DJ and Hostetler, B and Taggart, DJ and Morré, DM and Musk, AW and Robinson, BW and Creaney, J}, title = {Erratum to: ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms.}, journal = {Clinical proteomics}, volume = {13}, number = {}, pages = {3}, pmid = {26903779}, issn = {1542-6416}, abstract = {[This corrects the article DOI: 10.1186/s12014-016-9103-3.].}, }
@article {pmid26900461, year = {2016}, author = {Vazquez, MV and Selvendran, S and Cheluvappa, R and McKay, MJ}, title = {Peritoneal mesothelioma metastasis to the tongue - Comparison with 8 pleural mesothelioma reports with tongue metastases.}, journal = {Annals of medicine and surgery (2012)}, volume = {5}, number = {}, pages = {101-105}, pmid = {26900461}, issn = {2049-0801}, abstract = {PURPOSE: Malignant mesothelioma (MM) rarely arises from the peritoneum. We describe the 1st such case which metastasised to the head and neck region (tongue).<br><br>METHODS: We briefly surveyed the American Surveillance Epidemiology and End Results (SEER) database, and the British Cancer Research UK database for the latest trends in MM incidence. We did a systematic Pubmed search for other MM reports with tongue metastases.<br><br>American and British data show that MM incidence in men has stabilised in the last 10 years, earlier than previously predicted. The tongue is an unusual site for MM spread, with ours being only the 9th such case described. Our summary of published cases of MM metastasising to the tongue brings out our patient to be the least in age(35 years), and the only one to have peritoneal MM as the primary. Seven of the 9 cases were male. Only 2 had a recorded history of exposure to asbestos. All 9 patients had the epithelioid subtype of MM. Surgery was done as the exclusive reported intervention in 4 out of the 9 patients. Only 2 cases received radiotherapy, amongst whom, only our patient responded.<br><br>CONCLUSIONS: Metastasis of MM to the tongue is rare and usually in the uncommon context of MM with multiple sites of extra-thoracic or extra-abdominal spread. We have described a unique clinical manifestation of a rare subtype of mesothelioma. Moreover, we have tabulated and summarised details (including responses to surgery or/and radiotherapy) regarding all reported cases of mesotheliomas with tongue metastasis.}, }
@article {pmid26896281, year = {2016}, author = {Kadariya, Y and Cheung, M and Xu, J and Pei, J and Sementino, E and Menges, CW and Cai, KQ and Rauscher, FJ and Klein-Szanto, AJ and Testa, JR}, title = {Bap1 Is a Bona Fide Tumor Suppressor: Genetic Evidence from Mouse Models Carrying Heterozygous Germline Bap1 Mutations.}, journal = {Cancer research}, volume = {76}, number = {9}, pages = {2836-2844}, pmid = {26896281}, issn = {1538-7445}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Comparative Genomic Hybridization ; Disease Models, Animal ; Gene Knock-In Techniques ; *Genes, Tumor Suppressor ; Genetic Predisposition to Disease/genetics ; Genotype ; *Germ-Line Mutation ; Heterozygote ; Immunohistochemistry ; Laser Capture Microdissection ; Mice ; Mice, Knockout ; *Neoplastic Syndromes, Hereditary ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Individuals harboring inherited heterozygous germline mutations in BAP1 are predisposed to a range of benign and malignant tumor types, including malignant mesothelioma, melanoma, and kidney carcinoma. However, evidence to support a tumor-suppressive role for BAP1 in cancer remains contradictory. To test experimentally whether BAP1 behaves as a tumor suppressor, we monitored spontaneous tumor development in three different mouse models with germline heterozygous mutations in Bap1, including two models in which the knock-in mutations are identical to those reported in human BAP1 cancer syndrome families. We observed spontaneous malignant tumors in 54 of 93 Bap1-mutant mice (58%) versus 4 of 43 (9%) wild-type littermates. All three Bap1-mutant models exhibited a high incidence and similar spectrum of neoplasms, including ovarian sex cord stromal tumors, lung and mammary carcinomas, and spindle cell tumors. Notably, we also observed malignant mesotheliomas in two Bap1-mutant mice, but not in any wild-type animals. We further confirmed that the remaining wild-type Bap1 allele was lost in both spontaneous ovarian tumors and mesotheliomas, resulting in the loss of Bap1 expression. Additional studies revealed that asbestos exposure induced a highly significant increase in the incidence of aggressive mesotheliomas in the two mouse models carrying clinically relevant Bap1 mutations compared with asbestos-exposed wild-type littermates. Collectively, these findings provide genetic evidence that Bap1 is a bona fide tumor suppressor gene and offer key insights into the contribution of carcinogen exposure to enhanced cancer susceptibility. Cancer Res; 76(9); 2836-44. ©2016 AACR.}, }
@article {pmid26894775, year = {2016}, author = {Hispán, P and Pascual, JC and González, I and Bravo, D and Peiró, G}, title = {Cutaneous Metastases From Malignant Mesothelioma of the Tunica Vaginalis Testis.}, journal = {The American Journal of dermatopathology}, volume = {38}, number = {3}, pages = {222-225}, doi = {10.1097/DAD.0000000000000369}, pmid = {26894775}, issn = {1533-0311}, mesh = {Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lung Neoplasms/*secondary ; Male ; Mesothelioma/*secondary ; Mesothelioma, Malignant ; Skin Neoplasms/*secondary ; Testicular Neoplasms/*pathology ; }, abstract = {Mesotheliomas are uncommon tumors arising from mesothelial cells lining the serous membranes of the pleura, pericardium, peritoneum, and tunica vaginalis testis. Less than 100 cases arising from the tunica vaginalis testis have been published and, to our knowledge, only 5 cases of cutaneous involvement from these tumors have been reported. We report an additional case with fatal outcome. A 93-year-old man presented with multiple polypoid nodules on the left scrotum. Ulceration was also present, and a firm 5-cm palpable testicular mass was also found. The patient had been exposed to asbestos for 40 years. Histologic examination of a skin biopsy from one of the nodules showed diffuse dermal infiltration of markedly atypical cuboidal cells, with polymorphous and hyperchromatic nuclei. Mitotic figures were common. These cuboidal cells lined clefts, forming a tubular and micropapillary pattern throughout papillary and reticular dermis. Immunohistochemical study showed strong nuclear and cytoplasmic positivity for calretinin, epithelial membrane antigen (cytoplasmic), and cytokeratin-7 (cytoplasmic) and nuclear positivity for Wilms tumor-1. These findings were consistent with cutaneous infiltration from malignant mesothelioma of the tunica vaginalis testis. Treatment of this rare tumor remains challenging because there are currently no recommended guidelines, but radical inguinal orchiectomy is an optimal choice.}, }
@article {pmid26893272, year = {2016}, author = {Berardi, R and Fiordoliva, I and De Lisa, M and Ballatore, Z and Caramanti, M and Morgese, F and Savini, A and Rinaldi, S and Torniai, M and Tiberi, M and Ferrini, C and Onofri, A and Cascinu, S}, title = {Clinical and pathologic predictors of clinical outcome of malignant pleural mesothelioma.}, journal = {Tumori}, volume = {102}, number = {2}, pages = {190-195}, doi = {10.5301/tj.5000418}, pmid = {26893272}, issn = {2038-2529}, mesh = {Adult ; Aged ; Anemia/blood/*diagnosis/etiology ; Antineoplastic Agents/*therapeutic use ; CA-125 Antigen/blood ; Disease-Free Survival ; Female ; Hemoglobins/*metabolism ; Humans ; Italy/epidemiology ; Kaplan-Meier Estimate ; Karnofsky Performance Status ; Lung Neoplasms/*mortality/*pathology/therapy ; Male ; Mesothelioma/*mortality/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/administration &amp; dosage ; Platinum Compounds/administration &amp; dosage ; Pleural Neoplasms/*mortality/*pathology/therapy ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; }, abstract = {AIMS AND BACKGROUND: Although worldwide use of asbestos has decreased, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next few decades. A number of scoring systems has been proposed to assess clinicopathologic features and to predict the prognosis. We assessed the relationship between patients' features and disease evolution in order to choose the best treatment able to prolong overall survival (OS) and progression-free survival (PFS).<br><br>METHODS: We retrospectively analyzed patients with locally advanced or metastatic MPM, treated at the Department of Medical Oncology, Universit&#xe0; Politecnica Marche, Italy, from January 2003 to September 2013. Data on age, sex, smoking history, asbestos exposure, performance status, tumor stage, histology, type of treatment, and routine laboratory tests including complete blood count panel, date of death, or censored status were collected. The OS and PFS were estimated using Kaplan-Meier method and Cox analysis was performed to analyze the prognostic relevance of clinical parameters.<br><br>RESULTS: We enrolled a total of 62 patients. Univariate analysis showed that histologic type, performance status, response to first-line therapy, pretreatment hemoglobin levels, and plasmatic Ca125 were significant prognostic factors. Conversely, no significant correlation was found between age, sex, smoking history, reported exposure to asbestos, stages at diagnosis, treatments, and OS and PFS.<br><br>CONCLUSIONS: Our results showed that anemia and increased Ca125 might be considered negative prognostic parameters in MPM patients and confirmed the prognostic role of histotype, performance status, and response to first-line chemotherapy.}, }
@article {pmid26891694, year = {2016}, author = {Chernova, T and Sun, XM and Powley, IR and Galavotti, S and Grosso, S and Murphy, FA and Miles, GJ and Cresswell, L and Antonov, AV and Bennett, J and Nakas, A and Dinsdale, D and Cain, K and Bushell, M and Willis, AE and MacFarlane, M}, title = {Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.}, journal = {Cell death and differentiation}, volume = {23}, number = {7}, pages = {1152-1164}, pmid = {26891694}, issn = {1476-5403}, support = {MC_EX_G0902052/MRC_/Medical Research Council/United Kingdom ; MC_U132685863/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1024/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p18/genetics/metabolism ; Female ; Genomic Instability ; Humans ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; *Metabolome ; Middle Aged ; Neurofibromin 2/genetics/metabolism ; Oxygen Consumption ; Principal Component Analysis ; Tandem Repeat Sequences ; Transcriptome ; Tumor Cells, Cultured ; Tumor Suppressor Protein p14ARF/genetics/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; Up-Regulation ; }, abstract = {Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.}, }
@article {pmid26889976, year = {2016}, author = {Kao, SC and Kirschner, MB and Cooper, WA and Tran, T and Burgers, S and Wright, C and Korse, T and van den Broek, D and Edelman, J and Vallely, M and McCaughan, B and Pavlakis, N and Clarke, S and Molloy, MP and van Zandwijk, N and Reid, G}, title = {A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {114}, number = {5}, pages = {524-531}, pmid = {26889976}, issn = {1532-1827}, mesh = {Animals ; Biomarkers, Tumor/*metabolism ; Cell Line, Tumor ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*metabolism/pathology ; Male ; Mass Spectrometry ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Middle Aged ; Multivariate Analysis ; Neoplasm Transplantation ; Osteonectin/*metabolism ; Pleural Neoplasms/*metabolism/pathology ; Prognosis ; Proportional Hazards Models ; Proteomics ; Retrospective Studies ; Survival Rate ; Tissue Array Analysis ; }, abstract = {BACKGROUND: We aimed to identify prognostic blood biomarkers using proteomics-based approaches in malignant pleural mesothelioma (MPM).<br><br>METHODS: Plasma samples from 12 MPM patients were used for exploratory mass spectrometry and ELISA analyses. The significance of secreted protein acidic and rich in cysteine (SPARC) was examined in sera from a Dutch series (n=97). To determine the source of the circulating SPARC, we investigated SPARC expression in MPM tumours and healthy controls, as well as the expression and secretion from cell lines and xenografts.<br><br>RESULTS: Secreted protein acidic and rich in cysteine was identified as a putative prognostic marker in plasma. Validation in the Dutch series showed that the median survival was higher in patients with low SPARC compared with those with high SPARC (19.0 vs 8.8 months; P=0.01). In multivariate analyses, serum SPARC remained as an independent predictor (HR 1.55; P=0.05). In MPM tumour samples, SPARC was present in the tumour cells and stromal fibroblasts. Cellular SPARC expression was higher in 5 out of 7 cell lines compared with two immortalized mesothelial lines. Neither cell lines nor xenograft tumours secreted detectable SPARC.<br><br>CONCLUSIONS: Low circulating SPARC was associated with favourable prognosis. Secreted protein acidic and rich in cysteine was present in both tumour cells and stromal fibroblasts; and our in vitro and in vivo experiments suggest that stromal fibroblasts are a potential source of circulating SPARC.}, }
@article {pmid26889212, year = {2016}, author = {Miozzi, E and Rapisarda, V and Marconi, A and Costa, C and Polito, I and Spandidos, DA and Libra, M and Fenga, C}, title = {Fluoro-edenite and carbon nanotubes: The health impact of 'asbestos-like' fibres.}, journal = {Experimental and therapeutic medicine}, volume = {11}, number = {1}, pages = {21-27}, pmid = {26889212}, issn = {1792-0981}, abstract = {Several decades have passed since Wagner et al demonstrated a causal link between asbestos fibre inhalation and the development of pleural mesothelioma in 1960. It was later suggested that pleural plaques are a benign consequence of exposure to these fibres. Most recently, a significant association between exposure to asbestos and cancer diagnosed at various sites, such as the peritoneum, stomach, pharynx, colon and ovaries has been demonstrated. The great concerns about public health that arose from the scientific evidence presented above have led to the banning of asbestos in several countries. Over the years, the suspicion that particles with a high aspect ratio may have asbestos-like pathogenicity has been supported by increasing evidence. Natural occurring minerals, as well as man-made fibres, have proven capable of inducing either chronic inflammation of serous membranes, or, in some cases, the development of peritoneal and pleural mesothelioma. The pathogenic role of both fluoro-edenite and carbon nanotubes, two 'asbestos-like' fibres is summarized and discussed in this review. The data presented herein support the notion that occupational exposure to these two types of fibre contributes to the development of different types of cancer.}, }
@article {pmid26887267, year = {2015}, author = {Jiang, Z and Chen, J and Lou, J and Miao, C and Shao, D and Zhang, X}, title = {[Monitoring and analysis of asbestos concentration in working environment of different asbestos-producing technologies in a certain area].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {33}, number = {11}, pages = {833-837}, pmid = {26887267}, issn = {1001-9391}, mesh = {Asbestos/*analysis ; Asbestos, Crocidolite/analysis ; Asbestos, Serpentine/analysis ; China/epidemiology ; Dust/analysis ; Humans ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/epidemiology ; Silicon Dioxide/analysis ; *Workplace ; }, abstract = {OBJECTIVE: To analyze asbestos exposure level between 1984 and 2010 in a district of malignant mesothelioma with clustering incidence in Zhejiang Province, in order to improve the recognizing and early diagnosis of malignant mesothelioma, protect the health of workers.<br><br>METHODS: Monitoring data of total asbestos dust concentration in the air of workplace from 1984 to 2010 in asbestos textile enterprises, family hand spinning operation, brake production, and asbestos board production in Zhejiang Province were collected in the local CDC. A total of 766 TWA copies of mass concentration were collected, and 1233 copies of MAC data. Asbestos mass concentration and fibre counting concentration of 29 points of family hand spinning operation were parallel determinated in the same time and the same sampling point. Raw asesbtos materials and dust composition of local asbestos processing corporations were collected and analyzed using X-ray diffraction method.<br><br>RESULTS: Raw materials of asbestos used between 1984 and 2010 in this area were chrysotile from Sichuan, Qinghai, Xinjiang, Russia, Zimbabwe, and some were mixed with SiO2, CaCO3 and other impurities. Raw materials used in asbestos board production were blue asbestos. Dust concentration between 1960s and 1980s in asbestos processing plants far exceeded the national standard. After then the dust concentration decreased significantly, but still higher than the national standard. 95.2% of air dust concentrations in the workplaces of asbestos factories exceeded the standard, and dust concentrations of workplaces of raw material, spinning, weaving, carding and labor insurance were above 90% in which carding work had the highest median concentration. 37.9% of dust mass concentrations in hand spinning work exceeded the standard where textile machinery side had the highest value. Beating job in asbestos board manufacturing and grinding job in brake production had higher concentrations.<br><br>CONCLUSIONS: Most of production technologies in asbestos processing industry exceed the standard level, indicating that the workers were at risk for malignant mesothelioma and other asbestos related diseases, which should draw high attention.}, }
@article {pmid26884050, year = {2016}, author = {Boffetta, P and La Vecchia, C}, title = {Setting new standards for epidemiological research on mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {5}, pages = {289}, doi = {10.1136/oemed-2015-103479}, pmid = {26884050}, issn = {1470-7926}, mesh = {Asbestos ; *Asbestos, Amphibole ; Epidemiologic Studies ; Humans ; Lung ; Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid26881550, year = {2015}, author = {Patra, A and Kundu, S and Pal, A and Saha, S}, title = {Mesothelioma with superior vena cava obstruction in young female following short latency of asbestos exposure.}, journal = {Journal of cancer research and therapeutics}, volume = {11}, number = {4}, pages = {940-942}, doi = {10.4103/0973-1482.160924}, pmid = {26881550}, issn = {1998-4138}, mesh = {Adolescent ; Asbestos/*adverse effects ; Carcinogens/*pharmacology ; Female ; Humans ; Mesothelioma/chemically induced/*pathology ; Pleural Effusion ; Pleural Neoplasms/chemically induced/*pathology ; Superior Vena Cava Syndrome/chemically induced/*pathology ; Tomography, X-Ray Computed ; }, abstract = {An 18 years female was admitted with right-sided chest pain, dry cough, and low-grade fever and weight loss for last 1 month. On examination, patient had features of superior vena cava (SVC) syndrome with right-sided pleural effusion. Chest X-ray showed mediastinal widening with nonhomogenous opacity mainly in the periphery of right upper and mid zone with right-sided pleural effusion. Ultrasonography thorax confirmed mild pleural effusion. Pleural fluid analysis showed lymphocytic, exudative, low adenosine deaminase with negative for Pap smear. Contrast-enhanced computed tomography (CT) thorax revealed large extensive nodular soft tissue lesion along right mediastinum as well as costal pleura, with enlarged pretracheal lymphadenopathy and SVC obstruction. CT guided Tru-cut biopsy report came as malignant epithelial tumor with polygonal shape, abundant eosinophilic cytoplasm and nuclei with prominent nucleoli suggestive of mesothelioma of epithelioid type. The tumor cell expressed calretinin, WT-1, and immunonegative for thyroid transcription factor-1.}, }
@article {pmid26867567, year = {2016}, author = {Morgan, R and Simpson, G and Gray, S and Gillett, C and Tabi, Z and Spicer, J and Harrington, KJ and Pandha, HS}, title = {HOX transcription factors are potential targets and markers in malignant mesothelioma.}, journal = {BMC cancer}, volume = {16}, number = {}, pages = {85}, pmid = {26867567}, issn = {1471-2407}, mesh = {Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Homeodomain Proteins/*biosynthesis/genetics/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; Lung Neoplasms/drug therapy/*genetics/pathology ; Mesothelioma/drug therapy/*genetics/pathology ; Mesothelioma, Malignant ; Mice ; Peptides/*administration &amp; dosage ; Pre-B-Cell Leukemia Transcription Factor 1 ; Proto-Oncogene Proteins/genetics/*metabolism ; Transcription Factors/*biosynthesis/genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos.<br><br>METHODS: We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model.<br><br>RESULTS: We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival.<br><br>CONCLUSION: HOX genes are a potential therapeutic target in mesothelioma, and HOXB4 expression correlates with overall survival.}, }
@article {pmid26860323, year = {2016}, author = {Farioli, A and Ottone, M and Morganti, AG and Compagnone, G and Romani, F and Cammelli, S and Mattioli, S and Violante, FS}, title = {Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database.}, journal = {Cancer medicine}, volume = {5}, number = {5}, pages = {950-959}, pmid = {26860323}, issn = {2045-7634}, mesh = {Adult ; Aged ; Aged, 80 and over ; Dose-Response Relationship, Radiation ; Female ; Humans ; Incidence ; Longitudinal Studies ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Neoplasms/epidemiology/radiotherapy ; Neoplasms, Radiation-Induced/epidemiology/*etiology ; Neoplasms, Second Primary/epidemiology/*etiology ; Peritoneal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Radiotherapy/adverse effects ; SEER Program ; Survivors/statistics &amp; numerical data ; United States/epidemiology ; Young Adult ; }, abstract = {We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5 years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973-2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01-1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies ≥10 years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40 years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.}, }
@article {pmid26858099, year = {2016}, author = {Van der Bij, S and Vermeulen, RC and Portengen, L and Moons, KG and Koffijberg, H}, title = {Expected number of asbestos-related lung cancers in the Netherlands in the next two decades: a comparison of methods.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {5}, pages = {342-349}, doi = {10.1136/oemed-2014-102614}, pmid = {26858099}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; *Models, Biological ; Models, Statistical ; Netherlands ; Occupational Diseases/chemically induced ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced ; Risk Assessment ; Uncertainty ; }, abstract = {OBJECTIVES: Exposure to asbestos fibres increases the risk of mesothelioma and lung cancer. Although the vast majority of mesothelioma cases are caused by asbestos exposure, the number of asbestos-related lung cancers is less clear. This number cannot be determined directly as lung cancer causes are not clinically distinguishable but may be estimated using varying modelling methods.<br><br>METHODS: We applied three different modelling methods to the Dutch population supplemented with uncertainty ranges (UR) due to uncertainty in model input values. The first method estimated asbestos-related lung cancer cases directly from observed and predicted mesothelioma cases in an age-period-cohort analysis. The second method used evidence on the fraction of lung cancer cases attributable (population attributable risk (PAR)) to asbestos exposure. The third method incorporated risk estimates and population exposure estimates to perform a life table analysis.<br><br>RESULTS: The three methods varied substantially in incorporated evidence. Moreover, the estimated number of asbestos-related lung cancer cases in the Netherlands between 2011 and 2030 depended crucially on the actual method applied, as the mesothelioma method predicts 17&#x2005;500 expected cases (UR 7000-57&#x2005;000), the PAR method predicts 12&#x2005;150 cases (UR 6700-19&#x2005;000), and the life table analysis predicts 6800 cases (UR 6800-33&#x2005;850).<br><br>CONCLUSIONS: The three different methods described resulted in absolute estimates varying by a factor of &#x223c;2.5. These results show that accurate estimation of the impact of asbestos exposure on the lung cancer burden remains a challenge.}, }
@article {pmid26855127, year = {2016}, author = {Ledda, C and Loreto, C and Pomara, C and Rapisarda, G and Fiore, M and Ferrante, M and Bracci, M and Santarelli, L and Fenga, C and Rapisarda, V}, title = {Sheep lymph-nodes as a biological indicator of environmental exposure to fluoro-edenite.}, journal = {Environmental research}, volume = {147}, number = {}, pages = {97-101}, doi = {10.1016/j.envres.2016.01.043}, pmid = {26855127}, issn = {1096-0953}, mesh = {Animals ; Asbestos, Amphibole/analysis/*toxicity ; *Environmental Exposure ; Environmental Monitoring ; Environmental Pollutants/*toxicity ; Lung/chemistry/pathology/ultrastructure ; Lymph Nodes/*chemistry/pathology/ultrastructure ; Lymphatic Diseases/chemically induced/pathology/*veterinary ; Microscopy, Electron, Scanning/veterinary ; *Sheep ; Sheep Diseases/chemically induced/*pathology ; Sicily ; }, abstract = {A significantly increased incidence of pleural mesothelioma in Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite (FE), a fibrous amphibole extracted from a local stone quarry. The lymph-nodes draining the pulmonary lobes of sheep grazing around the town were examined, to gain insights into fibre diffusion. The pasture areas of six sheep flocks lying about 3km from Biancavilla were located using the global positioning system. The cranial tracheobronchial and one middle mediastinal lymph-node as well as four lung tissue samples were collected from 10 animals from each flock and from 10 control sheep for light and scanning electron microscopy (SEM) examination. The lymph-nodes from exposed sheep were enlarged and exhibited signs of anthracosis. Histologically, especially at the paracortical level, they showed lymph-follicle hyperplasia with large reactive cores and several macrophages (coniophages) containing grey-brownish particulate interspersed with elements with a fibril structure, forming aggregates of varying dimensions (coniophage nodules). Similar findings were detected in some peribronchiolar areas of the lung parenchyma. SEM examination showed that FE fibres measured 8-41µm in length and 0.4-1.39µm in diameter in both lymph-nodes and lung tissue. Monitoring of FE fibres in sheep lymph-nodes using appropriate techniques can help set up environmental pollution surveillance.}, }
@article {pmid26853494, year = {2016}, author = {Borczuk, AC and Pei, J and Taub, RN and Levy, B and Nahum, O and Chen, J and Chen, K and Testa, JR}, title = {Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration.}, journal = {Cancer biology &amp; therapy}, volume = {17}, number = {3}, pages = {328-335}, pmid = {26853494}, issn = {1555-8576}, support = {CA-175691/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Abdominal Neoplasms/*genetics/pathology ; *DNA Copy Number Variations ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/*genetics/pathology ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Mutation ; Peritoneal Neoplasms/*genetics/pathology ; Pleural Neoplasms/*genetics/pathology ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor arising from mesothelial linings of the serosal cavities. Pleural space is the most common site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. While histologically similar, tumors from these sites are epidemiologically and clinically distinct and their attribution to asbestos exposure differs. We compared DNA array-based findings from 48 epithelioid peritoneal MMs and 41 epithelioid pleural MMs to identify similarities and differences in copy number alterations (CNAs). Losses in 3p (BAP1 gene), 9p (CDKN2A) and 22q (NF2) were seen in tumors from both tumor sites, although CDKN2A and NF2 losses were seen at a higher rate in pleural disease (p<0.01). Overall, regions of copy number gain were more common in peritoneal MM, whereas losses were more common in pleural MM, with regions of loss containing known tumor suppressor genes and regions of gain encompassing genes encoding receptor tyrosine kinase pathway members. Cases with known asbestos causation (n = 32) were compared with those linked to radiation exposure (n = 9). Deletions in 6q, 14q, 17p and 22q, and gain of 17q were seen in asbestos-associated but not radiation-related cases. As reported in post-radiation sarcoma, gains outnumbered losses in radiation-associated MM. The patterns of genomic imbalances suggest overlapping and distinct molecular pathways in MM of the pleura and peritoneum, and that differences in causation (i.e., asbestos vs. radiation) may account for some of these site-dependent differences.}, }
@article {pmid26845122, year = {2016}, author = {Lee, D}, title = {Genetic Basis of Mesothelioma--More Than Asbestos Exposure.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {2}, pages = {e27-8}, doi = {10.1016/j.jtho.2015.09.005}, pmid = {26845122}, issn = {1556-1380}, mesh = {DNA, Neoplasm/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; *Mutation ; Pleural Neoplasms/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, }
@article {pmid26845118, year = {2016}, author = {Billé, A and Krug, LM and Woo, KM and Rusch, VW and Zauderer, MG}, title = {Contemporary Analysis of Prognostic Factors in Patients with Unresectable Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {2}, pages = {249-255}, pmid = {26845118}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms/blood/drug therapy/*mortality ; Male ; Mesothelioma/blood/drug therapy/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/blood/drug therapy/*mortality ; Prognosis ; Proportional Hazards Models ; }, abstract = {INTRODUCTION: Previous prognostic scoring systems for malignant pleural mesothelioma (MPM) included patients managed surgically and predated the use of pemetrexed. We analyzed prognostic factors in a contemporary cohort of patients with unresectable MPM who received pemetrexed-based chemotherapy.<br><br>METHODS: This single-institution analysis included patients with MPM who were managed nonsurgically from 2000 to 2013. Variables correlated with overall survival (OS) included sex, performance status (PS), asbestos exposure, tumor laterality, histology, clinical stage, initial positron emission tomography maximum standardized uptake value, hemoglobin level, platelet count, lymphocyte count, white cell and neutrophil counts, treatment type, and clinical benefit from treatment. OS was analyzed by the Kaplan-Meier method, and significance (p < 0.05) of prognostic factors was analyzed by the log-rank test and Cox regression.<br><br>RESULTS: A total of 191 patients met the study criteria: median age 71 years (range 46-90), 147 men (77%), 128 epithelioid tumors (67%), and 157 cases of stage III or IV MPM (82%). Median OS for all patients was 13.4 months. According to a univariate analysis, histology (p < 0.001), platelet count (< or = 450,000 versus >450,000, p < 0.001), initial PS (0-1 versus > or = 2), maximum standardized uptake value (< or = 8.1 versus >8.1, p = 0.037), and lymphocyte counts (p = 0.019) were associated with OS. According to a multivariable analysis, only histology, platelet count, and PS were independent prognostic factors. Epithelioid histology, PS, and elevated lymphocyte count at diagnosis were significantly associated with clinical benefit from first-line chemotherapy.<br><br>CONCLUSIONS: Our results confirm the significance of elements of the Cancer and Leukemia Group B and European Organisation for Research and Treatment of Cancer prognostic scoring systems, identify factors associated with clinical benefit from chemotherapy, and emphasize the impact of histology and clinical benefit of chemotherapy on outcomes.}, }
@article {pmid26839332, year = {2016}, author = {Frank, EA and Carreira, VS and Birch, ME and Yadav, JS}, title = {Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice.}, journal = {Toxicologic pathology}, volume = {44}, number = {2}, pages = {211-225}, pmid = {26839332}, issn = {1533-1601}, support = {T32ES016646/ES/NIEHS NIH HHS/United States ; T42OH008432-07/OH/NIOSH CDC HHS/United States ; P30 ES006096/ES/NIEHS NIH HHS/United States ; 2P30ES006096-16A1/ES/NIEHS NIH HHS/United States ; T42OH008432/ACL/ACL HHS/United States ; T32 ES016646/ES/NIEHS NIH HHS/United States ; T42 OH008432/OH/NIOSH CDC HHS/United States ; }, mesh = {Alveolar Epithelial Cells/cytology/pathology ; Animals ; Apoptosis ; Asbestos, Crocidolite/*toxicity ; Histocytochemistry ; Inhalation Exposure/*analysis ; Lung/cytology/diagnostic imaging/*drug effects/pathology ; Male ; Mice ; Nanotubes, Carbon/*toxicity ; *Pneumonia/diagnostic imaging/pathology ; }, abstract = {Carbon nanotubes (CNTs) are emerging as important occupational and environmental toxicants owing to their increasing prevalence and potential to be inhaled as airborne particles. CNTs are a concern because of their similarities to asbestos, which include fibrous morphology, high aspect ratio, and biopersistence. Limitations in research models have made it difficult to experimentally ascertain the risk of CNT exposures to humans and whether these may lead to lung diseases classically associated with asbestos, such as mesothelioma and fibrosis. In this study, we sought to comprehensively compare profiles of lung pathology in mice following repeated exposures to multiwall CNTs or crocidolite asbestos (CA). We show that both exposures resulted in granulomatous inflammation and increased interstitial collagen; CA exposures caused predominantly bronchoalveolar hyperplasia, whereas CNT exposures caused alveolar hyperplasia of type II pneumocytes (T2Ps). T2Ps isolated from CNT-exposed lungs were found to have upregulated proinflammatory genes, including interleukin 1ß (IL-1ß), in contrast to those from CA exposed. Immunostaining in tissue showed that while both toxicants increased IL-1ß protein expression in lung cells, T2P-specific IL-1ß increases were greater following CNT exposure. These results suggest related but distinct mechanisms of action by CNTs versus asbestos which may lead to different outcomes in the 2 exposure types.}, }
@article {pmid26836920, year = {2016}, author = {Thomas, R and Cheah, HM and Creaney, J and Turlach, BA and Lee, YC}, title = {Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions.}, journal = {Chest}, volume = {149}, number = {6}, pages = {1494-1500}, doi = {10.1016/j.chest.2016.01.001}, pmid = {26836920}, issn = {1931-3543}, mesh = {Aged ; Aged, 80 and over ; Australia ; Blood Cell Count/methods ; Chemokine CCL2/analysis ; Cytokines/*analysis ; *Exudates and Transudates/immunology/metabolism ; Female ; Humans ; Longitudinal Studies ; *Lung Neoplasms/complications/pathology ; Male ; *Mesothelioma/complications/pathology ; Mesothelioma, Malignant ; Middle Aged ; *Pleural Effusion, Malignant/diagnosis/etiology/metabolism ; Tumor Necrosis Factor-alpha/analysis ; Vascular Endothelial Growth Factor A/analysis ; }, abstract = {BACKGROUND: Malignant pleural effusion (MPE) is common. Existing literature on pleural fluid compositions is restricted to cross-sectional sampling with little information on longitudinal changes of fluid biochemistry and cytokines with disease progression. Indwelling pleural catheters provide the unique opportunity for repeated sampling and longitudinal evaluation of MPE, which may provide insight into tumor pathobiology.<br><br>METHODS: We collected 638 MPE samples from 103 patients managed with indwelling pleural catheters over 95&#xa0;days (median, range 0-735&#xa0;days) and analyzed them for protein, pH, lactate dehydrogenase, and glucose levels. Peripheral blood was quantified for hematocrit, platelets, leukocytes, protein, and albumin. Cytokine levels (monocyte chemotactic protein [MCP]-1; vascular endothelial growth factor; interleukin-6, -8, and -10; tumor necrosis factor-&#x3b1;; and interferon-gamma) were determined in 298 samples from 35 patients with mesothelioma. Longitudinal changes of all parameters were analyzed using a linear mixed model.<br><br>RESULTS: Significant decreases were observed over time in pleural fluid protein by 8&#xa0;g/L&#xa0;per&#xa0;100&#xa0;days (SE, 1.32; P&#xa0;< .0001) and pH (0.04/100&#xa0;days; SE, 0.02; P&#xa0;= .0203), accompanied by a nonsignificant rise in lactate dehydrogenase. The ratio of pleural fluid to serum protein decreased by 0.06/100&#xa0;days (SE, 0.02; P&#xa0;= .04). MPEs from mesothelioma (n&#xa0;=&#xa0;63) had lower pleural fluid glucose (P&#xa0;= .0104) at baseline and a faster rate of decline in glucose (P&#xa0;= .0423) when compared with non-mesothelioma effusions (n&#xa0;= 38). A progressive rise in mesothelioma pleural fluid concentration of [log] MCP-1 ([log] 0.37 pg/mL per 100&#xa0;days; SE, 0.13; P&#xa0;= .0046), but not of other cytokines, was observed.<br><br>CONCLUSIONS: MPE fluids become less exudative and more acidic over the disease course. The rise in MCP-1 levels suggests a pathobiological role in MPE.}, }
@article {pmid26825970, year = {2016}, author = {Abakay, A and Tanrikulu, AC and Imamoglu, MS and Ayhan, M and Taylan, M and Kaplan, MA and Abakay, O}, title = {Erratum to: High-risk mesothelioma relation to meteorological and geological condition and distance from naturally occurring asbestos.}, journal = {Environmental health and preventive medicine}, volume = {21}, number = {2}, pages = {91}, doi = {10.1007/s12199-016-0508-4}, pmid = {26825970}, issn = {1347-4715}, }
@article {pmid26824986, year = {2016}, author = {Kang, HC and Kim, HK and Lee, S and Mendez, P and Kim, JW and Woodard, G and Yoon, JH and Jen, KY and Fang, LT and Jones, K and Jablons, DM and Kim, IJ}, title = {Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas.}, journal = {Oncotarget}, volume = {7}, number = {7}, pages = {8321-8331}, pmid = {26824986}, issn = {1949-2553}, mesh = {Blotting, Western ; Exome/*genetics ; Female ; Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Histone-Lysine N-Methyltransferase ; Humans ; Immunoenzyme Techniques ; Loss of Heterozygosity/*genetics ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation/*genetics ; Pleural Neoplasms/*genetics ; Prognosis ; Protein Methyltransferases/*genetics ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM.}, }
@article {pmid26822314, year = {2016}, author = {}, title = {Comments on the causation of malignant mesothelioma: rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {Industrial health}, volume = {54}, number = {1}, pages = {92-93}, pmid = {26822314}, issn = {1880-8026}, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; *Liability, Legal ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects/*legislation &amp; jurisprudence ; Pleural Neoplasms/*etiology ; }, abstract = {The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests.}, }
@article {pmid26822313, year = {2016}, author = {}, title = {The global health dimensions of asbestos and asbestos-related diseases.}, journal = {Industrial health}, volume = {54}, number = {1}, pages = {87-91}, pmid = {26822313}, issn = {1880-8026}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology/*prevention &amp; control ; *Developed Countries ; *Developing Countries ; *Global Health ; Humans ; International Cooperation ; Mesothelioma/*epidemiology/prevention &amp; control ; }, abstract = {The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests.}, }
@article {pmid26822249, year = {2016}, author = {Bianchi, C and Bianchi, T}, title = {[Non-Hodgkin lymphoma and asbestos exposure].}, journal = {La Medicina del lavoro}, volume = {107}, number = {1}, pages = {73-74}, pmid = {26822249}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; *Carcinogens ; Female ; Humans ; Lymphoma, Non-Hodgkin/*etiology ; Male ; Mesothelioma/*etiology ; Orchiectomy ; Pleural Neoplasms/*etiology ; Testicular Neoplasms/etiology ; }, }
@article {pmid26822244, year = {2016}, author = {Miscetti, G and Bodo, P and Lumare, A and Abbritti, EP and Garofani, P and Burani, V}, title = {[Asbestos exposure assessment in the first case of intrasplenic mesothelioma].}, journal = {La Medicina del lavoro}, volume = {107}, number = {1}, pages = {29-36}, pmid = {26822244}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Asbestos, Amosite/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; *Carcinogens ; *Food Packaging ; Humans ; Lung Neoplasms/diagnosis/*etiology ; Male ; *Medical History Taking ; Mesothelioma/diagnosis/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Risk Assessment ; Splenic Neoplasms/diagnosis/*etiology ; }, abstract = {BACKGROUND: In 2013 the International Journal of Surgical Pathology published a case report of intrasplenic malignant mesothelioma (MM) in a 48-year-old man: it was the first report in literature describing a case of primitive intra-splenic MM, described without a history of asbestos exposure.<br><br>OBJECTIVE: To verify the possible past exposure to asbestos, ignored by the patient himself, by studying in depth his environmental and occupational history.<br><br>METHODS: Information about the occupational and non-occupational history of the subject was collected by Experts of the Operational Unit of Occupational Health and Safety Control (UOC PSAL) of the Local Health Unit Umbria 1 - Perugia, using the Italian National Mesothelioma Register (ReNaM) questionnaire and guide lines; an inspection was&#xa0; carried out at the past canning industry where the patient worked in the period 1982-1990 and material was taken to be analysed by MOCF and SEM.<br><br>RESULTS: Samples showed the presence of asbestos&#xa0; fibres belonging to the amphibole class (amosite and crocidolite) and to the serpentine class (chrysotile).<br><br>CONCLUSIONS: The survey described the past occupational exposure to asbestos in a canning industry, where&#xa0; the subject worked in the period 1982-1990,&#xa0; unknown to the patient himself. The authors strongly confirm the&#xa0; usefulness of standardized methods, such as the ReNaM Questionnaire, and the importance of technical expertise of the investigator to find and analyse the suspect materials and to demonstrate&#xa0; possible past occupational exposure to asbestos.}, }
@article {pmid26822243, year = {2016}, author = {Mensi, C and Poltronieri, A and Romano, A and Dallari, B and Riboldi, L and Bertazzi, PA and Consonni, D}, title = {[Malignant mesotheliomas with unknown exposure to asbestos: a re-examination].}, journal = {La Medicina del lavoro}, volume = {107}, number = {1}, pages = {22-28}, pmid = {26822243}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Clothing/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/diagnosis/epidemiology/*etiology ; Male ; Manufactured Materials/adverse effects ; Mesothelioma/diagnosis/epidemiology/*etiology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/epidemiology/*etiology ; Retrospective Studies ; Risk Assessment ; }, abstract = {INTRODUCTION: Malignant Mesothelioma (MM) is a rare neoplasm associated with asbestos exposure. In 24,5% of MM cases reported to the Lombardy Mesothelioma Registry (LMR), asbestos exposure has been defined as "unknown".<br><br>OBJECTIVE: To evaluate the cases with "unknown exposure to asbestos" diagnosed in 2000-2004 in agreement with new knowledge about source of asbestos exposure.<br><br>METHODS: Information regarding exposure has been reviewed in order to select the cases susceptible of further investigations, including: interview of relatives and/or colleagues; further evaluations by local PSAL (Prevention and Security in workplace) services; contact of industrial hygienists; analysis of production processes. The same procedure has been followed for extra-occupational exposure. These cases have been subjected to the LMR evaluation group.<br><br>RESULTS: Fourthy four out of 364 (12,1%) MM have been reclassified. In 47,7% of the cases, a "possible occupational exposure" has been recognized, 15,9% have been attributed a "certain occupational exposure", while 36,4% an extra-occupational (domestic, environmental and leisure-time) exposure. No significant differences between age, sex, cancer site, diagnostic certainty, residence, year of diagnosis, interviewed subjects were detected. The occupational sector with the highest amount of reclassifications was the clothing production.<br><br>CONCLUSIONS: The detailed reconstruction of clinical and occupational history and of lifestyle habits of patients affected by MM, close cooperation with Local Services of Occupational Medicine and literature review make it possible for previously overlooked asbestos exposure to be acknowledged.}, }
@article {pmid26822071, year = {2016}, author = {Scherpereel, A}, title = {[Asbestos and respiratory diseases].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {45}, number = {1}, pages = {117-132}, doi = {10.1016/j.lpm.2015.12.011}, pmid = {26822071}, issn = {2213-0276}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Fibrosis/etiology ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Mesothelioma, Malignant ; Pleura/pathology ; Respiration Disorders/*chemically induced ; }, abstract = {Previous occupational asbestos exposure (more rarely environmental or domestic exposure) may induce various pleural and/or pulmonary, benign or malignant diseases, sometimes with a very long latency for malignant mesothelioma (MM). Asbestos has been widely extracted and used in Western countries and in emerging or developing countries, resulting in a peak of MM incidence in France around 2020 and likely in a world pandemic of asbestos-induced diseases. These patients have mostly benign respiratory diseases (pleural plugs) but may also be diagnosed with lung cancer or malignant pleural mesothelioma, and have a global poor outcome. New therapeutic tools (targeted therapies, immunotherapy…) with first promising results are developed. However, it is crucial to obtain a full ban of asbestos use worldwide, and to do a regular follow-up of asbestos-exposed subjects, mostly if they are already diagnosed with benign respiratory diseases. Finally, new cancers (larynx and ovary) were recently added to the list of asbestos-induced tumors.}, }
@article {pmid26821095, year = {2016}, author = {van Zandwijk, N and Soeberg, M and Reid, G}, title = {Using a multidisciplinary approach to combat the burden of asbestos-related disease.}, journal = {The Medical journal of Australia}, volume = {204}, number = {2}, pages = {52}, doi = {10.5694/mja15.01209}, pmid = {26821095}, issn = {1326-5377}, mesh = {Age Distribution ; Asbestosis/*complications/diagnosis/epidemiology/*prevention &amp; control ; Australia/epidemiology ; Evidence-Based Medicine ; Humans ; Incidence ; *Interdisciplinary Communication ; Mesothelioma/diagnosis/epidemiology/*etiology/*prevention &amp; control ; Pleural Neoplasms/diagnosis/epidemiology/*etiology/*prevention &amp; control ; Practice Guidelines as Topic ; Risk Factors ; Sex Distribution ; }, }
@article {pmid26821092, year = {2016}, author = {Musk, AW and de Klerk, NH and Nowak, AK}, title = {Asbestos exposure: challenges for Australian clinicians.}, journal = {The Medical journal of Australia}, volume = {204}, number = {2}, pages = {48-49}, doi = {10.5694/mja15.01072}, pmid = {26821092}, issn = {1326-5377}, mesh = {Age Distribution ; Asbestos/*adverse effects ; Australia/epidemiology ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Risk Factors ; Sex Distribution ; }, }
@article {pmid26820281, year = {2016}, author = {Markowitz, S}, title = {Erratum to: Asbestos-Related Lung Cancer and Malignant Mesothelioma of the Pleura: Selected Current Issues (Semin Respir Crit Care Med 2015;36(3):334-346).}, journal = {Seminars in respiratory and critical care medicine}, volume = {37}, number = {1}, pages = {143-144}, doi = {10.1055/s-0035-1570120}, pmid = {26820281}, issn = {1098-9048}, }
@article {pmid26818092, year = {2016}, author = {Crovella, S and Bianco, AM and Vuch, J and Zupin, L and Moura, RR and Trevisan, E and Schneider, M and Brollo, A and Nicastro, EM and Cosenzi, A and Zabucchi, G and Borelli, V}, title = {Iron signature in asbestos-induced malignant pleural mesothelioma: A population-based autopsy study.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {79}, number = {3}, pages = {129-141}, doi = {10.1080/15287394.2015.1123452}, pmid = {26818092}, issn = {1528-7394}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; *Autopsy ; Case-Control Studies ; Female ; Ferritins/genetics ; Gene Frequency ; Genetic Markers ; Humans ; Iron/*metabolism ; Lung Neoplasms/chemically induced/genetics/*pathology ; Male ; Membrane Proteins/genetics ; Mesothelioma/chemically induced/genetics/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Mutation, Missense ; Oxidoreductases ; Polymorphism, Single Nucleotide ; Transferrin/genetics ; Young Adult ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The development of MPM is frequently linked to inhalation of asbestos fibers. A genetic component of susceptibility to this disease is suggested by the observation that some individuals develop MPM following lower doses of asbestos exposure, whereas others exposed to higher quantities do not seem to be affected. This hypothesis is supported also by frequent reports of MPM familial clustering. Despite the widely recognized role of iron (Fe) in cellular asbestos-induced pulmonary toxicity, the role of the related gene polymorphisms in the etiology of MPM has apparently not been evaluated. Eighty-six single-nucleotide polymorphisms (SNPs) of 10 Fe-metabolism genes were examined by exploiting formalin-fixed paraffin-embedded postmortem samples from 77 patients who died due to MPM (designated AEM) and compared with 48 who were exposed to asbestos but from died in old age of cause other than asbestos (designated AENM). All subjects showed objective signs of asbestos exposure. Three SNPs, localized in the ferritin heavy polypeptide, transferrin, and hephaestin genes, whose frequencies were distributed differently in AEM and AENM populations, were identified. For ferritin and transferrin the C/C and the G/G genotypes, respectively, representing intronic polymorphisms, were significantly associated with protection against MPM and need to be considered as possible genetic markers of protection. Similarly, the C/C hephaestin SNP, a missense variation of this multicopper ferroxidase encoding gene, may be related, also functionally, with protection against MPM. In conclusion, it is proposed that three Fe metabolism-associated genes, significantly associated with protection against development of MPM, may serve as protective markers for this aggressive tumor.}, }
@article {pmid26811322, year = {2016}, author = {Kottek, M and Kilpatrick, DJ}, title = {Estimating Occupational Exposure to Asbestos in Australia.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {4}, pages = {531-532}, doi = {10.1093/annhyg/mew002}, pmid = {26811322}, issn = {1475-3162}, mesh = {*Asbestos ; Australia ; Humans ; Mesothelioma ; Occupational Diseases ; *Occupational Exposure ; }, }
@article {pmid26807072, year = {2016}, author = {Morré, DJ and Hostetler, B and Taggart, DJ and Morré, DM and Musk, AW and Robinson, BW and Creaney, J}, title = {ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms.}, journal = {Clinical proteomics}, volume = {13}, number = {}, pages = {2}, pmid = {26807072}, issn = {1542-6416}, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, caused primarily by exposure to asbestos. In this study, serum presence of mesothelioma-specific protein transcript variants of ecto-nicotinamide adenine dinucleotide oxidase disulfide-thiol exchanger 2 (ENOX2), a recently identified marker of malignancy, were investigated using the ONCOblot tissue of origin cancer detection test.<br><br>METHODS: Sequential serum samples collected from asbestos-exposed individuals prior to the development of frank mesothelioma were assayed for ENOX2 presence by 2-D gel immunoblot analysis to determine how long in advance of clinical symptoms mesothelioma-specific ENOX2 transcript variants could be detected.<br><br>RESULTS: Two mesothelioma-specific ENOX2 protein transcript variants were detected in the serum of asbestos-exposed individuals 4-10&#xa0;years prior to clinical diagnosis of malignant mesothelioma (average 6.2&#xa0;years). Either one or both ENOX2 protein transcript variants indicative of malignant mesothelioma were absent in 14 of 15 subjects diagnosed with benign pleural plaques either with or without accompanying asbestosis.<br><br>CONCLUSIONS: In a population of asbestos-exposed subjects who eventually developed malignant mesothelioma, ENOX2 protein transcript variants characteristic of malignant mesothelioma were present in serum 4-10&#xa0;years in advance of clinical symptoms. As with all biomarker studies, these observations require validation in a larger, independent cohort of patients and should include prospective as well as retrospective sampling.}, }
@article {pmid26800709, year = {2016}, author = {Soeberg, MJ and Leigh, J and Driscoll, T and Armstrong, B and Young, JM and van Zandwijk, N}, title = {Incidence and survival trends for malignant pleural and peritoneal mesothelioma, Australia, 1982-2009.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {3}, pages = {187-194}, doi = {10.1136/oemed-2015-103309}, pmid = {26800709}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Australia/epidemiology ; *Carcinogens ; Case-Control Studies ; Child ; Child, Preschool ; *Environmental Exposure ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Lung/pathology ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality ; Peritoneum/pathology ; Pleural Neoplasms/*epidemiology/mortality ; Young Adult ; }, abstract = {BACKGROUND: Australia is known to have had one of the highest per-capita asbestos consumption rates, yet there are few contemporary reports on malignant mesothelioma trends.<br><br>METHODS: Data on 10&#x2005;930 people with malignant pleural mesothelioma (MPM) and 640 people with malignant peritoneal mesothelioma diagnosed in Australia during 1982-2009 were analysed. Observed incidence rate trends were quantified. Incidence rates were projected up to 2030 using observed incident cases during 1982-2012. The relative per-decade change in excess mortality during 1999-2009 was estimated.<br><br>RESULTS: During 1982-2009, acceleration in MPM age-standardised incidence rates were highest for women and those aged 75&#x2005;years and above, with average annual percentage changes of +4.9 (95% CI 3.6 to 6.2) and +7.2 (95% CI 5.4 to 9.0), respectively. Age-standardised incidence rates for men with MPM aged 0-64&#x2005;years decelerated rapidly during 2003-2009, an average annual percentage change of -5.1% (95% CI -7.6% to -2.5%). Overall, male age-specific MPM incidence rates in the age group of 65-74&#x2005;year during 2010-2030 are projected to decline with rates projected to increase for older men and women with MPM. There was a statistically significant 16% relative reduction in the excess mortality rate (EMR) up to 5 years postdiagnosis for people diagnosed with malignant pleural and peritoneal mesothelioma combined in 2009 compared with those diagnosed in 1999, an EMR ratio of 0.84 (95% CI 0.77 to 0.92).<br><br>CONCLUSIONS: Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease.}, }
@article {pmid26788989, year = {2016}, author = {Cortez, BA and Rezende-Teixeira, P and Redick, S and Doxsey, S and Machado-Santelli, GM}, title = {Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression.}, journal = {Oncotarget}, volume = {7}, number = {8}, pages = {8979-8992}, pmid = {26788989}, issn = {1949-2553}, mesh = {*Aneuploidy ; Asbestos, Serpentine/*pharmacology ; Aurora Kinase B/metabolism ; Calcium-Binding Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Endosomal Sorting Complexes Required for Transport/metabolism ; Humans ; Lung Neoplasms/chemically induced/*pathology ; Microfilament Proteins/metabolism ; Mitosis/*drug effects ; Septins/metabolism ; }, abstract = {Chrysotile, like other types of asbestos, has been associated with mesothelioma, lung cancer and asbestosis. However, the cellular abnormalities induced by these fibers involved in cancer development have not been elucidated yet. Previous works show that chrysotile fibers induce features of cancer cells, such as aneuploidy, multinucleation and multipolar mitosis. In the present study, normal and cancer derived human cell lines were treated with chrysotile and the cellular and molecular mechanisms related to generation of aneuploid cells was elucidated. The first alteration observed was cytokinesis regression, the main cause of multinucleated cells formation and centrosome amplification. The multinucleated cells formed after cytokinesis regression were able to progress through cell cycle and generated aneuploid cells after abnormal mitosis. To understand the process of cytokinesis regression, localization of cytokinetic proteins was investigated. It was observed mislocalization of Anillin, Aurora B, Septin 9 and Alix in the intercellular bridge, and no determination of secondary constriction and abscission sites. Fiber treatment also led to overexpression of genes related to cancer, cytokinesis and cell cycle. The results show that chrysotile fibers induce cellular and molecular alterations in normal and tumor cells that have been related to cancer initiation and progression, and that tetraploidization and aneuploid cell formation are striking events after fiber internalization, which could generate a favorable context to cancer development.}, }
@article {pmid26780987, year = {2016}, author = {Cregan, S and McDonagh, L and Gao, Y and Barr, MP and O'Byrne, KJ and Finn, SP and Cuffe, S and Gray, SG}, title = {KAT5 (Tip60) is a potential therapeutic target in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {48}, number = {3}, pages = {1290-1296}, doi = {10.3892/ijo.2016.3335}, pmid = {26780987}, issn = {1791-2423}, mesh = {Apoptosis ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Separation ; Chemokines/metabolism ; Cytokines/metabolism ; Epithelium/metabolism ; *Gene Expression Regulation, Neoplastic ; Histone Acetyltransferases/*metabolism ; Humans ; Inflammation ; Lung Neoplasms/*metabolism ; Lysine Acetyltransferase 5 ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*metabolism ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Lysine acetyltransferases (KATs) including KAT5 have been linked with the development of cisplatin resistance. This gene may therefore be altered in MPM and could represent a novel candidate target for intervention. Using RT-PCR screening the expression of all known KAT5 variants was found to be markedly increased in malignant tumors compared to benign pleura. When separated according to histological subtype, KAT5 was significantly overexpressed in both the sarcomatoid and biphasic subgroups for all transcript variants. A panel of MPM cell lines including the normal pleural cells LP9 and Met5A was screened for expression of KAT5 variants. Treatment of cells with a small molecule inhibitor of KAT5 (MG-149) caused significant inhibition of cellular proliferation (p<0.0001), induction of apoptosis and was accompanied by significant induction of pro-inflammatory cytokines/chemokines.}, }
@article {pmid26776867, year = {2016}, author = {Brims, FJ and Meniawy, TM and Duffus, I and de Fonseka, D and Segal, A and Creaney, J and Maskell, N and Lake, RA and de Klerk, N and Nowak, AK}, title = {A Novel Clinical Prediction Model for Prognosis in Malignant Pleural Mesothelioma Using Decision Tree Analysis.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {4}, pages = {573-582}, doi = {10.1016/j.jtho.2015.12.108}, pmid = {26776867}, issn = {1556-1380}, mesh = {Aged ; Cohort Studies ; *Decision Trees ; Female ; Humans ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Mesothelioma, Malignant ; Models, Statistical ; Pleural Neoplasms/*diagnosis/mortality/pathology ; Prognosis ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare cancer with a heterogeneous prognosis. Prognostic models are not widely utilized clinically. Classification and regression tree (CART) analysis examines the interaction of multiple variables with a given outcome.<br><br>METHODS: Between 2005 and 2014, all cases with pathologically confirmed MPM had routinely available histological, clinical, and laboratory characteristics recorded. Classification and regression tree analysis was performed using 29 variables with 18-month survival as the dependent variable. Risk groups were refined according to survival and clinical characteristics. The model was then tested on an external international cohort.<br><br>RESULTS: A total of 482 cases were included in the derivation cohort; the median survival was 12.6 months, and the median age was 69 years. The model defined four risk groups with clear survival differences (p < 0.0001). The strongest predictive variable was the presence of weight loss. The group with the best survival at 18 months (86.7% alive, median survival 34.0 months, termed risk group 1) had no weight loss, a hemoglobin level greater than 153 g/L, and a serum albumin level greater than 43 g/L. The group with the worst survival (0% alive, median survival 7.5 months, termed risk group 4d) had weight loss, a performance score of 0 or 1, and sarcomatoid histological characteristics. The C-statistic for the model was 0.761, and the sensitivity was 94.5%. Validation on 174 external cases confirmed the model's ability to discriminate between risk groups in an alternative data set with fair performance (C-statistic 0.68).<br><br>CONCLUSIONS: We have developed and validated a simple, clinically relevant model to reliably discriminate patients at high and lower risk of death using routinely available variables from the time of diagnosis in unselected populations of patients with MPM.}, }
@article {pmid26773348, year = {2016}, author = {Tan, WK and Tan, MY and Tan, HM and Pathmanathan, R and Tan, WP}, title = {Well-differentiated Papillary Mesothelioma of the Tunica Vaginalis.}, journal = {Urology}, volume = {90}, number = {}, pages = {e7-8}, doi = {10.1016/j.urology.2015.12.046}, pmid = {26773348}, issn = {1527-9995}, mesh = {Adult ; Humans ; Male ; Mesothelioma/*pathology ; Testicular Neoplasms/*pathology ; }, abstract = {A 39-year-old man presented with painless scrotal swelling for 2 months. He denied any asbestos exposure but worked with wall and ceiling plaster. Physical exam revealed a large right scrotum which transilluminated. Scrotal ultrasonography revealed a large right hydrocele and a polypoidal mass along the anterior wall of the scrotum. Magnetic resonance imaging of the abdomen and computed tomography of the chest showed no metastases. He underwent a right inguinal scrotal exploration and wide excision of tunica vaginalis and a partial epididymectomy. Pathology revealed well-differentiated papillary mesothelioma of the tunica vaginalis. The patient had an uneventful recovery.}, }
@article {pmid29900099, year = {2016}, author = {Giusti, L and Ciregia, F and Bonotti, A and Da Valle, Y and Donadio, E and Boldrini, C and Foddis, R and Giannaccini, G and Mazzoni, MR and Canessa, PA and Cristaudo, A and Lucacchini, A}, title = {Comparative proteomic analysis of malignant pleural mesothelioma: Focusing on the biphasic subtype.}, journal = {EuPA open proteomics}, volume = {10}, number = {}, pages = {42-49}, pmid = {29900099}, issn = {2212-9685}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. In this work we performed a comparative proteomic analysis of biphasic pleural mesothelioma (B-PM). Tissue biopsies were obtained from 61 patients who were subjected to a diagnostic thoracoscopy. 2D/MS based approach was used for proteomic analysis. The 22 proteins found differentially expressed in B-PM, with respect to benign, were analyzed by Ingenuity Pathways Analysis and compared with those obtained for epitheliod pleural mesothelioma (E-PM). A different activation of transcription factors, proteins and cytokines were observed between two subtypes.}, }
@article {pmid26770440, year = {2015}, author = {Yao, W and Yang, H and Huang, G and Yan, Y and Wang, H and Sun, D}, title = {Massive localized malignant pleural mesothelioma (LMPM): manifestations on computed tomography in 6 cases.}, journal = {International journal of clinical and experimental medicine}, volume = {8}, number = {10}, pages = {18367-18374}, pmid = {26770440}, issn = {1940-5901}, abstract = {OBJECTIVE: Our study analyzed the clinical symptoms and computed tomography (CT) manifestations of massive localized malignant pleural mesothelioma (LMPM) patients to improve the knowledge and diagnosis of this disease.<br><br>METHODS: Our study collected 6 massive LMPM patients pathologically confirmed by CT in the department of Radiology of the People's Hospital of Yuyao, Zhejiang Province, from January, 2007 to June, 2013; data of patients were also collected. The clinical symptoms, clinicopathological characteristics, CT manifestations, treatments and prognosis of enrolled patients were analyzed.<br><br>RESULTS: Our study enrolled 6 LMPM patients (2 males; 4 females) classified to epitheliated type (n = 4) and sarcomatous type (n = 2) with mean age of 62.7 &#xb1; 7.4, and 5 of them had a history of asbestos exposure. CT manifestations revealed that large soft-tissue mass close to pleura, which was smooth and lobulated, was discovered in all patients with maximum diameter of 10~15 cm and mean diameter of 13.67 &#xb1; 1.15 cm; The mean value of CT was 36.29 &#xb1; 2.62 HU; after enhancement, the mean value was increased to 76.36 &#xb1; 7.73 HU; patients showed zones of small patchy necrosis and large patchy necrosis. The following presentations were founded: enlargement of tumor vessel which showed arborization (2 patients), mass wrap around the descending aorta in left lower chest (1 patient), strips of fat density in mediastinum superior (1 patient), pleural tail sign (3 patients). Among 6 patients, pleural effusion (n = 4), mediastinal lymph node enlargement (n = 3), invasion and destruction of local ribs (n = 2). Median survival time of patients were 20 months (2 cases conducted operation), 24 (2 cases chose combined radiotherapy and chemotherapy) and less than 6 months (2 cases underwent chemotherapy).<br><br>CONCLUSION: To sum up, CT showed important diagnostic values on massive LMPM patients; patients with a history of asbestos exposure, large soft-tissue mass of pleura with an abundant blood supply and wrap around large vessels might increase the risk of massive LMPM.}, }
@article {pmid26744692, year = {2015}, author = {Hara, N and Fujimoto, N and Miyamoto, Y and Yamagishi, T and Asano, M and Fuchimoto, Y and Wada, S and Ozaki, S and Kishimoto, T}, title = {Lymphoproliferative disorder in pleural effusion in a subject with past asbestos exposure.}, journal = {Respiratory medicine case reports}, volume = {16}, number = {}, pages = {169-171}, pmid = {26744692}, issn = {2213-0071}, abstract = {Primary effusion lymphoma (PEL) is a subtype of non-Hodgkin lymphoma that presents as serous effusions without detectable masses or organomegaly. Here we report a case of PEL-like lymphoma in a patient with past asbestos exposure. A 65-year-old man was referred to our hospital due to dyspnea upon exertion. He had been exposed to asbestos for three years in the construction industry. Chest X-ray and CT images demonstrated left pleural effusion. Cytological analysis of the pleural effusion revealed large atypical lymphocytes with distinct nuclear bodies and high nucleus-to-cytoplasm ratio. Immunohistochemical analyses showed that the cells were CD20(+), CD3(-), CD5(-), and CD10(-). These findings led to a diagnosis of diffuse large B-cell lymphoma. PEL or PEL-like lymphoma should be considered a potential cause of pleural effusion in subjects with past asbestos exposure.}, }
@article {pmid26744667, year = {2015}, author = {Nakasuka, T and Fujimoto, N and Hara, N and Miyamoto, Y and Yamagishi, T and Asano, M and Nishi, H and Kishimoto, T}, title = {Foreign body granuloma mimicking recurrence of malignant pleural mesothelioma.}, journal = {Respiratory medicine case reports}, volume = {16}, number = {}, pages = {95-96}, pmid = {26744667}, issn = {2213-0071}, abstract = {A 72-year-old man visited our hospital due to right pleural effusion. He had worked as a welder at a shipbuilding company and had been exposed to asbestos. Cytological examination and thoracoscopic pleural biopsy yielded a diagnosis of epithelial malignant pleural mesothelioma (MPM); extrapleural pneumonectomy (EPP) was performed. Two years later, he became aware of right-back swelling that became a fist-sized mass over 2 months. Microscopy of a tissue specimen revealed no malignant cells, but did indicate foreign body granuloma. Subcutaneous lesions that develop after EPP do not necessarily result from the recurrence of MPM, but could have benign etiologies.}, }
@article {pmid26743791, year = {2015}, author = {Gordon, R and Fitzgerald, S and Millette, J}, title = {Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {4}, pages = {347-348}, doi = {10.1080/10773525.2015.1122368}, pmid = {26743791}, issn = {2049-3967}, }
@article {pmid26743790, year = {2015}, author = {Gordon, RE}, title = {Response to RE: Gordon R, Fitzgerald S, and Millette J. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women. Int J Occup Environ Health. 2014;20(4):318-332.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {4}, pages = {342-346}, pmid = {26743790}, issn = {2049-3967}, mesh = {Asbestos/*toxicity ; Cosmetics/*toxicity ; Female ; Humans ; Mesothelioma/*chemically induced ; Talc/*toxicity ; }, }
@article {pmid26743789, year = {2015}, author = {Lee, R and Van Orden, D}, title = {Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {4}, pages = {337-341}, pmid = {26743789}, issn = {2049-3967}, mesh = {Asbestos/*toxicity ; Cosmetics/*toxicity ; Female ; Humans ; Mesothelioma/*chemically induced ; Talc/*toxicity ; }, }
@article {pmid26733616, year = {2016}, author = {Napolitano, A and Antoine, DJ and Pellegrini, L and Baumann, F and Pagano, I and Pastorino, S and Goparaju, CM and Prokrym, K and Canino, C and Pass, HI and Carbone, M and Yang, H}, title = {HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {22}, number = {12}, pages = {3087-3096}, pmid = {26733616}, issn = {1557-3265}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; G0700654/MRC_/Medical Research Council/United Kingdom ; MR/L006758/1/MRC_/Medical Research Council/United Kingdom ; U01 CA111295/CA/NCI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; P30 CA071789/CA/NCI NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; }, mesh = {Acetylation ; Adult ; Aged ; Asbestos/*blood/toxicity ; Biomarkers/*blood ; *Environmental Exposure ; Extracellular Matrix Proteins/blood ; Female ; GPI-Linked Proteins/blood ; HMGB1 Protein/*blood/metabolism ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Osteopontin/blood ; Pleural Effusion/blood/diagnosis ; Pleural Neoplasms/blood/*diagnosis ; Sensitivity and Specificity ; Young Adult ; }, abstract = {PURPOSE: To determine whether serum levels of high mobility group box protein 1 (HMGB1) could differentiate malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls.<br><br>EXPERIMENTAL DESIGN: Hyperacetylated and nonacetylated HMGB1 (together referred to as total HMGB1) were blindly measured in blood collected from malignant mesothelioma patients (n = 22), individuals with verified chronic asbestos exposure (n = 20), patients with benign pleural effusions (n = 13) or malignant pleural effusions not due to malignant mesothelioma (n = 25), and healthy controls (n = 20). Blood levels of previously proposed malignant mesothelioma biomarkers fibulin-3, mesothelin, and osteopontin were also measured in nonhealthy individuals.<br><br>RESULTS: HMGB1 serum levels reliably distinguished malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Total HMGB1 was significantly higher in malignant mesothelioma patients and asbestos-exposed individuals compared with healthy controls. Hyperacetylated HMGB1 was significantly higher in malignant mesothelioma patients compared with asbestos-exposed individuals and healthy controls, and did not vary with tumor stage. At the cut-off value of 2.00 ng/mL, the sensitivity and specificity of serum hyperacetylated HMGB1 in differentiating malignant mesothelioma patients from asbestos-exposed individuals and healthy controls was 100%, outperforming other previously proposed biomarkers. Combining HMGB1 and fibulin-3 provided increased sensitivity and specificity in differentiating malignant mesothelioma patients from patients with cytologically benign or malignant non-mesothelioma pleural effusion.<br><br>CONCLUSIONS: Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyperacetylated HMGB1 is an accurate biomarker to differentiate malignant mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings will start soon. Clin Cancer Res; 22(12); 3087-96. &#xa9;2016 AACR.}, }
@article {pmid26730866, year = {2016}, author = {Corcoran, JP and Psallidas, I and Ross, CL and Hallifax, RJ and Rahman, NM}, title = {Always Worth Another Look? Thoracic Ultrasonography before, during, and after Pleural Intervention.}, journal = {Annals of the American Thoracic Society}, volume = {13}, number = {1}, pages = {118-121}, doi = {10.1513/AnnalsATS.201508-559CC}, pmid = {26730866}, issn = {2325-6621}, support = {MR/L017091/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Asbestos/adverse effects ; *Blood Loss, Surgical ; Humans ; Image-Guided Biopsy/adverse effects/methods ; Male ; *Mesothelioma/complications/etiology/pathology ; Occupational Exposure/adverse effects ; Perioperative Care/*methods ; Pleural Effusion/*diagnosis/etiology ; *Pleural Neoplasms/complications/etiology/pathology ; Thoracoscopy/adverse effects/methods ; Thorax/*diagnostic imaging ; Treatment Outcome ; Ultrasonography ; }, }
@article {pmid26729015, year = {2016}, author = {Kawai, T and Tominaga, S and Hiroi, S and Ogata, S and Nakanishi, K and Kawahara, K and Sonobe, H and Hiroshima, K}, title = {Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses.}, journal = {Journal of clinical pathology}, volume = {69}, number = {8}, pages = {706-712}, doi = {10.1136/jclinpath-2015-203211}, pmid = {26729015}, issn = {1472-4146}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers/metabolism ; Cystadenocarcinoma, Serous/*diagnosis/genetics/metabolism ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia/diagnosis/genetics/metabolism ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*diagnosis/genetics/metabolism ; Male ; Mesothelioma/*diagnosis/genetics/metabolism ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/diagnosis/genetics/metabolism ; Peritoneum/metabolism/*pathology ; Young Adult ; }, abstract = {AIMS: Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging.<br><br>METHODS: To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs.<br><br>RESULTS: Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs.<br><br>CONCLUSIONS: Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.}, }
@article {pmid26725926, year = {2016}, author = {Egilman, D and Bird, T}, title = {Short fiber tremolite free chrysotile mesothelioma cohort revealed.}, journal = {American journal of industrial medicine}, volume = {59}, number = {3}, pages = {196-199}, doi = {10.1002/ajim.22552}, pmid = {26725926}, issn = {1097-0274}, mesh = {*Asbestos, Serpentine ; Cohort Studies ; Humans ; *Mesothelioma ; New Jersey ; *Occupational Exposure ; *Plastics ; *Respiratory Tract Neoplasms ; }, abstract = {In 1995, Dell and Teta published a cohort mortality study of asbestos molding compound workers at a Union Carbide Corporation (UCC) plastics manufacturing plant in Bound Brook, New Jersey. They reported that the factory workers were exposed to "asbestos (mostly chrysotile)," implying that the asbestos used at the Bound Brook plant occasionally contained amphiboles. However, UCC statements and testimony from recent litigation indicate that the Bound Brook plant exclusively used short fiber chrysotile asbestos. These recent documents also point to lower exposures than those reported by Dell and Teta. This chrysotile-only cohort should be included in analyses of chrysotile potency.}, }
@article {pmid26722325, year = {2015}, author = {Furukawa, M and Toyooka, S and Hayashi, T and Yamamoto, H and Fujimoto, N and Soh, J and Hashida, S and Shien, K and Asano, H and Aoe, K and Okabe, K and Pass, HI and Tsukuda, K and Kishimoto, T and Miyoshi, S}, title = {DNA copy number gains in malignant pleural mesothelioma.}, journal = {Oncology letters}, volume = {10}, number = {5}, pages = {3274-3278}, pmid = {26722325}, issn = {1792-1074}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an extremely poor prognosis. The incidence of MPM is increasing as a result of widespread exposure to asbestos. The molecular pathogenesis of MPM remains unclear. The present study analyzed the frequency of various genomic copy number gains (CNGs) in MPM using reverse transcription-quantitative polymerase chain reaction. A total of 83 primary MPMs and 53 primary lung adenocarcinomas were analyzed to compare the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2. In MPM, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 12 (14.5%), 8 (9.6%), 5 (6.0%), 4 (4.8%) and 1 (1.2%) of the samples, respectively. In lung adenocarcinomas, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%) of the samples, respectively. The CNGs of EGFR, KRAS and FGFR1 were significantly less frequent in the MPMs compared with the lung adenocarcinomas (P=0.0018, 0.048 and 0.018, respectively). Overall, the MPMs exhibited these CNGs less frequently compared with the lung adenocarcinomas (P=0.0002). The differences in CNGs between the two tumor types suggested that they are genetically different.}, }
@article {pmid26719535, year = {2016}, author = {Ohar, JA and Cheung, M and Talarchek, J and Howard, SE and Howard, TD and Hesdorffer, M and Peng, H and Rauscher, FJ and Testa, JR}, title = {Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {76}, number = {2}, pages = {206-215}, pmid = {26719535}, issn = {1538-7445}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; HEK293 Cells ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation, Missense ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; }, abstract = {Heritable mutations in the BAP1 tumor suppressor gene predispose individuals to mesothelioma and other cancers. However, a large-scale assessment of germline BAP1 mutation incidence and associated clinical features in mesothelioma patients with a family history of cancer has not been reported. Therefore, we examined the germline BAP1 mutation status of 150 mesothelioma patients with a family history of cancer, 50 asbestos-exposed control individuals with a family history of cancers other than mesothelioma, and 153 asbestos-exposed individuals without familial cancer. No BAP1 alterations were found in control cohorts, but were identified in nine of 150 mesothelioma cases (6%) with a family history of cancer. Alterations among these cases were characterized by both missense and frameshift mutations, and enzymatic activity of BAP1 missense mutants was decreased compared with wild-type BAP1. Furthermore, BAP1 mutation carriers developed mesothelioma at an earlier age that was more often peritoneal than pleural (five of nine) and exhibited improved long-term survival compared to mesothelioma patients without BAP1 mutations. Moreover, many tumors harboring BAP1 germline mutations were associated with BAP1 syndrome, including mesothelioma and ocular/cutaneous melanomas, as well as renal, breast, lung, gastric, and basal cell carcinomas. Collectively, these findings suggest that mesothelioma patients presenting with a family history of cancer should be considered for BAP1 genetic testing to identify those individuals who might benefit from further screening and routine monitoring for the purpose of early detection and intervention.}, }
@article {pmid26719230, year = {2016}, author = {Zalcman, G and Mazieres, J and Margery, J and Greillier, L and Audigier-Valette, C and Moro-Sibilot, D and Molinier, O and Corre, R and Monnet, I and Gounant, V and Rivière, F and Janicot, H and Gervais, R and Locher, C and Milleron, B and Tran, Q and Lebitasy, MP and Morin, F and Creveuil, C and Parienti, JJ and Scherpereel, A and , }, title = {Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial.}, journal = {Lancet (London, England)}, volume = {387}, number = {10026}, pages = {1405-1414}, doi = {10.1016/S0140-6736(15)01238-6}, pmid = {26719230}, issn = {1474-547X}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/*administration &amp; dosage/adverse effects ; Cisplatin/*administration &amp; dosage/adverse effects ; Creatinine/blood ; Female ; Humans ; Hypertension/epidemiology ; Lung Neoplasms/*drug therapy/mortality/pathology ; Male ; Mesothelioma/*drug therapy/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration &amp; dosage/adverse effects ; Pleural Neoplasms/*drug therapy/mortality/pathology ; Proteinuria/epidemiology ; Thrombosis/epidemiology ; Vascular Endothelial Growth Factor A/blood ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma.<br><br>METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin &#x2265;325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0&#xb7;8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m(2) pemetrexed plus 75 mg/m(2) cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456.<br><br>FINDINGS: From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18&#xb7;8 months [95% CI 15&#xb7;9-22&#xb7;6]) than with PC (16&#xb7;1 months [14&#xb7;0-17&#xb7;9]; hazard ratio 0&#xb7;77 [0&#xb7;62-0&#xb7;95]; p=0&#xb7;0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC.<br><br>INTERPRETATION: Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease.<br><br>FUNDING: Intergroupe Francophone de Canc&#xe9;rologie Thoracique (IFCT).}, }
@article {pmid26715106, year = {2016}, author = {Gilham, C and Rake, C and Burdett, G and Nicholson, AG and Davison, L and Franchini, A and Carpenter, J and Hodgson, J and Darnton, A and Peto, J}, title = {Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {5}, pages = {290-299}, pmid = {26715106}, issn = {1470-7926}, support = {MC_UU_12023/21/MRC_/Medical Research Council/United Kingdom ; MR/K006584/1/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Asbestos, Amosite/adverse effects/analysis ; Asbestos, Amphibole/*adverse effects/analysis ; Asbestos, Crocidolite/adverse effects/analysis ; Asbestos, Serpentine/adverse effects/analysis ; Asbestosis/complications ; Employment ; Female ; Humans ; *Lung/chemistry/pathology ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Diseases/*chemically induced/pathology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced/pathology ; Risk Assessment ; }, abstract = {BACKGROUND: We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens.<br><br>METHODS: Following personal interview asbestos fibres longer than 5&#x2005;&#xb5;m were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks.<br><br>RESULTS: Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%).<br><br>CONCLUSIONS: The approximate linearity of the dose-response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women.}, }
@article {pmid26713662, year = {2016}, author = {Soeberg, MJ and Creighton, N and Currow, DC and Young, JM and van Zandwijk, N}, title = {Patterns in the incidence, mortality and survival of malignant pleural and peritoneal mesothelioma, New South Wales, 1972-2009.}, journal = {Australian and New Zealand journal of public health}, volume = {40}, number = {3}, pages = {255-262}, doi = {10.1111/1753-6405.12503}, pmid = {26713662}, issn = {1753-6405}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Disease-Free Survival ; Drug Therapy, Combination ; Female ; Humans ; Incidence ; Male ; Mesothelioma/drug therapy/*epidemiology/mortality/pathology ; Middle Aged ; New South Wales/epidemiology ; Peritoneal Neoplasms/drug therapy/*epidemiology ; Pleural Neoplasms/drug therapy/*epidemiology ; Registries ; Sex Distribution ; Survival Analysis ; Young Adult ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPeM) are often grouped together in descriptive epidemiological analyses, resulting in limited understanding of epidemiological patterns for these tumour types.<br><br>METHODS: We studied patterns in the incidence, mortality and survival of people diagnosed with MPM (n=4,076) and MPeM (n=293) in New South Wales (NSW), Australia, 1972-2009. We also calculated 5-year relative survival for people diagnosed 1972-2006 followed up to 2007. We assessed patterns for each tumour type and histological subtype and, where possible, by combination of these categories.<br><br>RESULTS: Annual MPM cases steadily increased over time (n=208 in 2009). There was an increasing trend in the MPM age-standardised incidence rate from 1972 up to 1994. This rate increase has levelled off in the past 10 years. Since 1999, 11 cases of MPeM were diagnosed each year, on average. Five-year relative survival remained stable for MPM and MPeM. However, 5-year relative survival in 2002-2006 was substantially higher for people with MPM epithelioid histological subtype (11.7% [95%CI 6.8-18.2%]) compared to all other non-epithelioid histological subtypes (6.9% [95%CI 5.0-9.1%]), a 70% difference. Survival was also greater for women with MPM (13.4% [95%CI 8.5-19.4%]) compared to men (7.0% [95%CI 5.1-9.2%]).<br><br>INTERPRETATION: MPM incidence rates have stabilised since the mid-1990s, suggesting that maximum incidence levels have been reached. When more up-to-date data are available, survival estimates should be reanalysed to include people likely to benefit from the wide introduction of combination chemotherapy in 2007, including pemetrexed.}, }
@article {pmid26695618, year = {2015}, author = {Blum, W and Pecze, L and Felley-Bosco, E and Schwaller, B}, title = {Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration.}, journal = {Respiratory research}, volume = {16}, number = {}, pages = {153}, pmid = {26695618}, issn = {1465-993X}, mesh = {Animals ; Calbindin 2/deficiency/genetics/*metabolism ; Cell Cycle ; *Cell Movement ; *Cell Proliferation ; Cell Shape ; Cells, Cultured ; Epithelial Cells/*metabolism/pathology ; Genotype ; Mesothelin ; Mice, Inbred C57BL ; Mice, Knockout ; Peritoneum/*metabolism/pathology ; Phenotype ; Primary Cell Culture ; RNA Interference ; Signal Transduction ; Time Factors ; Transfection ; Up-Regulation ; }, abstract = {BACKGROUND: The Ca(2+)-binding protein calretinin is currently used as a positive marker for identifying epithelioid malignant mesothelioma (MM) and reactive mesothelium, but calretinin's likely role in mesotheliomagenesis remains unclear. Calretinin protects immortalized mesothelial cells in vitro from asbestos-induced cytotoxicity and thus might be implicated in mesothelioma formation. To further investigate calretinin's putative role in the early steps of MM generation, primary mesothelial cells from calretinin knockout (CR-/-) and wildtype (WT) mice were compared.<br><br>METHODS: Primary mouse mesothelial cells from WT and CR-/- mice were investigated with respect to morphology, marker proteins, proliferation, cell cycle parameters and mobility in vitro. Overexpression of calretinin or a nuclear-targeted variant was achieved by a lentiviral expression system.<br><br>RESULTS: CR-/- mice have a normal mesothelium and no striking morphological abnormalities compared to WT animals were noted. Primary mouse mesothelial cells from both genotypes show a typical "cobblestone-like" morphology and express mesothelial markers including mesothelin. In cells from CR-/- mice in vitro, we observed more giant cells and a significantly decreased proliferation rate. Up-regulation of calretinin in mesothelial cells of both genotypes increases the proliferation rate and induces a cobblestone-like epithelial morphology. The length of the S/G2/M phase is unchanged, however the G1 phase is clearly prolonged in CR-/- cells. They are also much slower to close a scratch in a confluent cell layer (2D-wound assay). In addition to a change in cell morphology, an increase in proliferation and mobility is observed, if calretinin overexpression is targeted to the nucleus. Thus, both calretinin and nuclear-targeted calretinin increase mesothelial cell proliferation and consequently, speed up the scratch-closure time. The increased rate of scratch closure in WT cells is the result of two processes: an increased proliferation rate and augmented cell mobility of the border cells migrating towards the empty space.<br><br>CONCLUSIONS: We hypothesize that the differences in proliferation and mobility between WT and CR-/- mesothelial cells are the likely result from differences in their developmental trajectories. The mechanistic understanding of the function of calretinin and its putative implication in signaling pathways in normal mesothelial cells may help understanding its role during the processes that lead to mesothelioma formation and could possibly open new avenues for mesothelioma therapy, either by directly targeting calretinin expression or indirectly by targeting calretinin-mediated downstream signaling.}, }
@article {pmid26692324, year = {2016}, author = {Abakay, A and Tanrikulu, AC and Ayhan, M and Imamoglu, MS and Taylan, M and Kaplan, MA and Abakay, O}, title = {High-risk mesothelioma relation to meteorological and geological condition and distance from naturally occurring asbestos.}, journal = {Environmental health and preventive medicine}, volume = {21}, number = {2}, pages = {82-90}, pmid = {26692324}, issn = {1347-4715}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Breast Neoplasms/chemically induced/epidemiology ; Climate ; *Environmental Exposure ; Female ; Geology ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Risk Factors ; Turkey/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: Very few studies have investigated the incidence and risk of malignant mesothelioma (MM) associated with distinct sources of asbestos exposure, especially exposure to naturally occurring asbestos (NOA).<br><br>METHODS: Subjects were MM, lung, and breast cancer patients who were diagnosed and followed in Diyarbakir Province between 2008 and 2013. The birthplaces of patients were displayed on a geologic map. Geological and meteorological effects on MM were analyzed by logistic regression.<br><br>RESULTS: A total of 180 MM, 368 breast, and 406 lung cancer patients were included. The median distance from birthplace to ophiolites was 6.26 km for MM, 31.06 km for lung, and 34.31 km for breast cancer (p < 0.001). The majority of MM cases were seen within 20 km from NOA areas. The MM incidence inside of NOA was 1059/100.000, and out of NOA was 397/100.000; this difference was significant (p = 0.014). The largest concentration of MM residential areas was within &#xb1; 30&#xb0; (34 residential areas 36.6%) of the dominant wind direction. Most MM patients were found in or near the dominant wind direction, especially in the acute angle defined by the dominant wind direction. MM incidence was directly proportional to {[area of NOA (km(2))] * [cosine &#x3b1; of wind direction angle]} and was inversely proportional to the square of the distance (R = 0.291, p = 0.023).<br><br>CONCLUSIONS: MM was higher near NOA and in the downwind direction. MM incidence and risk were affected by geological and meteorological factors.}, }
@article {pmid26689911, year = {2015}, author = {Westbom, C and Thompson, JK and Leggett, A and MacPherson, M and Beuschel, S and Pass, H and Vacek, P and Shukla, A}, title = {Inflammasome Modulation by Chemotherapeutics in Malignant Mesothelioma.}, journal = {PloS one}, volume = {10}, number = {12}, pages = {e0145404}, pmid = {26689911}, issn = {1932-6203}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Carrier Proteins/genetics/*metabolism ; Caspase 1/metabolism ; Cell Line, Tumor/drug effects ; Cisplatin/administration &amp; dosage/pharmacology ; Doxorubicin/pharmacology ; Feedback, Physiological/drug effects ; Humans ; Inflammasomes/*drug effects/metabolism ; Interleukin 1 Receptor Antagonist Protein/administration &amp; dosage/pharmacology ; Interleukin-18/metabolism ; Interleukin-1beta/metabolism ; Lung Neoplasms/*drug therapy/metabolism/pathology ; Male ; Mesothelioma/*drug therapy/metabolism/pathology ; Mesothelioma, Malignant ; Mice, SCID ; NLR Family, Pyrin Domain-Containing 3 Protein ; Receptors, Interleukin-1/antagonists &amp; inhibitors/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) is a fatal disease in dire need of therapy. The role of inflammasomes in cancer is not very well studied, however, literature supports both pro-and anti-tumorigenic effects of inflammasomes on cancer depending upon the type of cancer. Asbestos is a causative agent for MM and we have shown before that it causes inflammasome priming and activation in mesothelial cells. MM tumor cells/tissues showed decreased levels of inflammasome components like NLRP3 and caspase-1 as compared to human mesothelial cells or normal tissue counterpart of tumor. Based on our preliminary findings we hypothesized that treatment of MMs with chemotherapeutic drugs may elevate the levels of NLRP3 and caspase-1 resulting in increased cell death by pyroptosis while increasing the levels of IL-1β and other pro-inflammatory molecules. Therefore, a combined strategy of chemotherapeutic drug and IL-1R antagonist may play a beneficial role in MM therapy. To test our hypothesis we used two human MM tumor cell lines (Hmeso, H2373) and two chemotherapeutic drugs (doxorubicin, cisplatin). Through a series of experiments we showed that both chemotherapeutic drugs caused increases in NLRP3 levels, caspase-1 activation, pyroptosis and pro-inflammatory molecules released from MM cells. In vivo studies using SCID mice and Hmeso cells showed that tumors were smaller in combined treatment group of cisplatin and IL-1R antagonist (Anakinra) as compared to cisplatin alone or untreated control groups. Taken together our study suggests that chemotherapeutic drugs in combination with IL-1R antagonist may have a beneficial role in MM treatment.}, }
@article {pmid26689234, year = {2015}, author = {Fujimoto, N and Gemba, K and Aoe, K and Kato, K and Yokoyama, T and Usami, I and Onishi, K and Mizuhashi, K and Yusa, T and Kishimoto, T}, title = {Clinical Investigation of Benign Asbestos Pleural Effusion.}, journal = {Pulmonary medicine}, volume = {2015}, number = {}, pages = {416179}, pmid = {26689234}, issn = {2090-1844}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/complications/diagnosis ; Carcinogens ; Humans ; Lung Neoplasms/complications/diagnosis ; Male ; Middle Aged ; Pleural Diseases/complications/diagnosis ; Pleural Effusion/complications/*diagnostic imaging ; Pulmonary Atelectasis/complications/diagnosis ; Retrospective Studies ; Thoracentesis ; Thoracic Cavity/*chemistry ; Tomography, X-Ray Computed ; }, abstract = {There is no detailed information about benign asbestos pleural effusion (BAPE). The aim of the study was to clarify the clinical features of BAPE. The criteria of enrolled patients were as follows: (1) history of asbestos exposure; (2) presence of pleural effusion determined by chest X-ray, CT, and thoracentesis; and (3) the absence of other causes of effusion. Clinical information was retrospectively analysed and the radiological images were reviewed. There were 110 BAPE patients between 1991 and 2012. All were males and the median age at diagnosis was 74 years. The median duration of asbestos exposure and period of latency for disease onset of BAPE were 31 and 48 years, respectively. Mean values of hyaluronic acid, adenosine deaminase, and carcinoembryonic antigen in the pleural fluid were 39,840 ng/mL, 23.9 IU/L, and 1.8 ng/mL, respectively. Pleural plaques were detected in 98 cases (89.1%). Asbestosis was present in 6 (5.5%) cases, rounded atelectasis was detected in 41 (37.3%) cases, and diffuse pleural thickening (DPT) was detected in 30 (27.3%) cases. One case developed lung cancer (LC) before and after BAPE. None of the cases developed malignant pleural mesothelioma (MPM) during the follow-up.}, }
@article {pmid26681974, year = {2015}, author = {Hjerpe, A and Ascoli, V and Bedrossian, C and Boon, M and Creaney, J and Davidson, B and Dejmek, A and Dobra, K and Fassina, A and Field, A and Firat, P and Kamei, T and Kobayashi, T and Michael, CW and Önder, S and Segal, A and Vielh, P}, title = {Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.}, journal = {CytoJournal}, volume = {12}, number = {}, pages = {26}, pmid = {26681974}, issn = {0974-5963}, abstract = {To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.}, }
@article {pmid26680231, year = {2015}, author = {Robinson, C and Dick, IM and Wise, MJ and Holloway, A and Diyagama, D and Robinson, BW and Creaney, J and Lake, RA}, title = {Consistent gene expression profiles in MexTAg transgenic mouse and wild type mouse asbestos-induced mesothelioma.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {983}, pmid = {26680231}, issn = {1471-2407}, mesh = {Animals ; Antigens, Viral, Tumor/*genetics/metabolism ; Asbestos/*adverse effects ; Cell Cycle ; Cell Line, Tumor ; E2F Transcription Factors/genetics ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/chemically induced/*genetics/pathology ; Mice ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis/methods ; }, abstract = {BACKGROUND: The MexTAg transgenic mouse model of mesothelioma replicates many aspects of human mesothelioma, including induction by asbestos, pathogenicity and response to cytotoxic chemotherapy, despite high levels of the SV40 large T Antigen (TAg) in the mesothelial compartment. This model enables analysis of the molecular events associated with asbestos induced mesothelioma and is utilised here to investigate the molecular dynamics of tumours induced in these mice, using gene expression patterns as a read out.<br><br>METHODS: Gene expression of MexTAg mesothelioma cell lines bearing a high or low number of copies of the TAg transgene were compared to wild type mouse mesotheliomas and normal mouse mesothelial cells using Affymetrix microarray. These data were then compared to a similar published human microarray study using the same platform.<br><br>RESULTS: The main expression differences between transgenic mouse and wild type mouse mesotheliomas occurred for genes involved in cell cycle regulation and DNA replication, as would be expected from overexpression of the TAg oncogene. Quantitative PCR confirmed that E2F and E2F regulated genes were significantly more upregulated in MexTAg mesotheliomas and MexTAg mesothelial cells compared to wild type mesotheliomas. Like human mesothelioma, both MexTAg and wild type mesotheliomas had more genes underexpressed than overexpressed compared to normal mouse mesothelial cells. Most notably, the cdkn2 locus was deleted in the wild type mouse mesotheliomas, consistent with 80&#xa0;% human mesotheliomas, however, this region was not deleted in MexTAg mesotheliomas. Regardless of the presence of TAg, all mouse mesotheliomas had a highly concordant set of deregulated genes compared to normal mesothelial cells that overlapped with the deregulated genes between human mesotheliomas and mesothelial cells.<br><br>CONCLUSIONS: This investigation demonstrates that the MexTAg mesotheliomas are comparable with wild type mouse mesotheliomas in their representation of human mesothelioma at the molecular level, with some key gene expression differences that are attributable to the TAg transgene expression. Of particular note, MexTAg mesothelioma development was not dependent on cdkn2 deletion.}, }
@article {pmid26678224, year = {2016}, author = {Pietrofesa, RA and Velalopoulou, A and Arguiri, E and Menges, CW and Testa, JR and Hwang, WT and Albelda, SM and Christofidou-Solomidou, M}, title = {Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice.}, journal = {Carcinogenesis}, volume = {37}, number = {2}, pages = {177-187}, pmid = {26678224}, issn = {1460-2180}, support = {1R21AT008291-02/AT/NCCIH NIH HHS/United States ; 1P42ES023720-01/ES/NIEHS NIH HHS/United States ; 1P30 ES013508-02/ES/NIEHS NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R21 AT008291/AT/NCCIH NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antioxidants/pharmacology ; Asbestos, Crocidolite/*toxicity ; Butylene Glycols/*administration &amp; dosage ; Chromatography, Liquid ; Diet ; Dietary Supplements ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flax ; Glucosides/*administration &amp; dosage ; Inflammation/*pathology ; Lignans/*administration &amp; dosage ; Mesothelioma/pathology ; Mice ; Mice, Mutant Strains ; Oxidative Stress/drug effects ; Peritoneal Lavage ; Peritoneum/drug effects/*pathology ; Precancerous Conditions/drug therapy ; Reverse Transcriptase Polymerase Chain Reaction ; Seeds ; Tandem Mass Spectrometry ; Transcriptome ; }, abstract = {Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2(+/mu) mice. Mice (n = 16-17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM.}, }
@article {pmid26659652, year = {2016}, author = {Silvestri, S and Di Benedetto, F and Raffaell, C and Veraldi, A}, title = {Asbestos in toys: an exemplary case.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {42}, number = {1}, pages = {80-85}, doi = {10.5271/sjweh.3542}, pmid = {26659652}, issn = {1795-990X}, mesh = {Aluminum Silicates/history/*toxicity ; Art/history ; Asbestos/history/*toxicity ; Clay ; Consumer Product Safety ; Europe ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Play and Playthings/*injuries ; School Teachers ; }, abstract = {OBJECTIVES: DAS was an artificial clay which, once molded, hardened at room temperature. It was largely used as a toy between 1963 and 1975 in Italy, Netherlands, Germany, UK and Norway. This case report describes and reports the presence of asbestos in DAS.<br><br>METHODS: We investigated the presence of asbestos in DAS using light and electron microscopy on samples of the original material. We searched administrative documents at the State Archive of Turin and conducted interviews with past employees on annual production, suppliers, and purchasers.<br><br>RESULTS: The analytical tests confirmed the presence of asbestos fibers in DAS: about 30% of its composition. The documents found at the State Archive confirmed the annual purchase of hundreds tons of raw asbestos from the Amiantifera di Balangero, the Italian asbestos mine. DAS was found to be used also within craftsmanship.<br><br>CONCLUSIONS: Asbestos fibers in DAS may have caused exposure to production workers and a variety of users, including artists, teachers, and children. Over 13 years, about 55 million packs of DAS were produced and sold. The number of users is difficult to estimate but may have been in the order of millions. In Italy, a specific question on the use of DAS has been included in a routinely used mesothelioma questionnaire. As DAS was exported to other countries, our findings suggest that mesothelioma patients should be asked about their past use of DAS, in particular individuals not reporting a clear past asbestos exposure. Additionally, this discovery shows the incompleteness of records on asbestos uses and suggests to test items, including toys, imported from countries where asbestos is not forbidden.}, }
@article {pmid26655961, year = {2016}, author = {Lambert, CS and Alexander, BH and Ramachandran, G and MacLehose, RF and Nelson, HH and Ryan, AD and Mandel, JH}, title = {A case-control study of mesothelioma in Minnesota iron ore (taconite) miners.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {2}, pages = {103-109}, pmid = {26655961}, issn = {1470-7926}, support = {T32 HL007741/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Air Pollutants, Occupational/adverse effects ; Case-Control Studies ; Employment ; Female ; Ferric Compounds/adverse effects ; Humans ; Iron/*adverse effects ; Logistic Models ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Minerals ; *Mining ; Minnesota/epidemiology ; Occupational Diseases/*etiology/mortality ; Occupational Exposure/*adverse effects ; Particulate Matter/*adverse effects ; Risk Factors ; Silicates/*adverse effects ; Work ; }, abstract = {OBJECTIVES: An excess of mesothelioma has been observed in iron ore miners in Northeastern Minnesota. Mining and processing of taconite iron ore generate exposures that include elongate mineral particles (EMPs) of amphibole and non-amphibole origin. We conducted a nested case-control study of mesothelioma in a cohort of 68,737 iron ore miners (haematite and taconite ore miners) to evaluate the association between mesothelioma, employment and EMP exposures from taconite mining.<br><br>METHODS: Mesothelioma cases (N=80) were identified through the Minnesota Cancer Surveillance System (MCSS) and death certificates. Four controls of similar age were selected for each case with 315 controls ultimately eligible for inclusion. Mesothelioma risk was evaluated by estimating rate ratios and 95% CIs with conditional logistic regression in relation to duration of taconite industry employment and cumulative EMP exposure [(EMP/cc)&#xd7;years], defined by the National Institute for Occupational Safety and Health (NIOSH) 7400 method. Models were adjusted for employment in haematite mining and potential exposure to commercial asbestos products used in the industry.<br><br>RESULTS: All mesothelioma cases were male and 57 of the cases had work experience in the taconite industry. Mesothelioma was associated with the number of years employed in the taconite industry (RR=1.03, 95% CI 1.00 to 1.06) and cumulative EMP exposure (RR=1.10, 95% CI 0.97 to -1.24). No association was observed with employment in haematite mining.<br><br>CONCLUSIONS: These results support an association between mesothelioma and employment duration and possibly EMP exposure in taconite mining and processing. The type of EMP was not determined. The potential role of commercial asbestos cannot be entirely ruled out.}, }
@article {pmid26645426, year = {2016}, author = {Liang, YF and Zheng, GQ and Chen, YF and Song, H and Yin, WJ and Zhang, L}, title = {CT differentiation of diffuse malignant peritoneal mesothelioma and peritoneal carcinomatosis.}, journal = {Journal of gastroenterology and hepatology}, volume = {31}, number = {4}, pages = {709-715}, doi = {10.1111/jgh.13260}, pmid = {26645426}, issn = {1440-1746}, mesh = {Carcinoma/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Male ; Mesentery/diagnostic imaging/pathology ; Mesothelioma/*diagnostic imaging/pathology ; Middle Aged ; Omentum/diagnostic imaging/pathology ; Peritoneal Neoplasms/*diagnostic imaging/pathology ; Peritoneum/diagnostic imaging/pathology ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {BACKGROUND AND AIM: Diffuse malignant peritoneal mesothelioma (DMPM) and peritoneal carcinomatosis (PC) have similar imaging in computer tomography (CT). We aimed to distinguish them.<br><br>METHODS: Computer tomography findings were evaluated in 48 DMPM and 47 PC for the peritoneal, mesenteric, omentum, lymph nodes, viscera infiltration, ascites and pleural plaques.<br><br>RESULTS: Two groups had no difference in terms of thickness, clinical manifestation, diameter of lymph nodes, ascites, and viscera infiltration. But they showed differences in the following: Ratio of asbestos exposure in DMPM group was higher. Smooth and irregular peritoneal thickening were more seen in DMPM group; peritoneal nodules were more commonly detected in PC group. Forty-eight cases of peritoneum in DMPM showed mild enhanced, while 14 patients in PC showed severe enhanced. Nodular type of omentum was more common in PC group than in DMPM group; omental cake was more commonly detected in DMPM group. Mesentery involvement was more commonly seen in DMPM group. Location of enlarged lymph nodes in cardiophrenic region was more frequently identified in DMPM, whereas location of enlarged lymph nodes in retroperitoneal region was more frequently identified in PC. Lymph nodes fusion was more frequently visualized in PC. Fixation of the intestinal wall was more common in DMPM. Pleural plaque was more common in DMPM. PC had distant metastasis except primary foci and peritoneum. In PC, tumor origins were ovary in 10, digestive system in 21, breast in one.<br><br>CONCLUSION: Using a combination of CT findings may increase our ability to distinguish PC from DMPM.}, }
@article {pmid26638921, year = {2015}, author = {Rapisarda, V and Ledda, C and Migliore, M and Salemi, R and Musumeci, A and Bracci, M and Marconi, A and Loreto, C and Libra, M}, title = {FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {35-37}, doi = {10.2217/fon.15.271}, pmid = {26638921}, issn = {1744-8301}, mesh = {Asbestos, Amphibole/adverse effects ; Biomarkers/*blood ; Carcinogens/*toxicity ; Environmental Exposure/adverse effects ; Extracellular Matrix Proteins/*blood ; Humans ; Italy ; Lung Neoplasms/*blood/*chemically induced ; Male ; Mesothelioma/*blood/*chemically induced ; Mesothelioma, Malignant ; Middle Aged ; Pilot Projects ; Pleural Neoplasms/*blood/*chemically induced ; }, abstract = {FBLN-3 has recently been proposed as a biomarker for malignant mesothelioma. A significantly increased standardized mortality rate from malignant mesothelioma has been reported in Biancavilla, Italy. Its cause has been identified in environmental exposure to fluoro-edenite. The aim of this study was to seek a correlation between plasma FBLN-3 concentration and pleural plaques in subjects exposed to fluoro-edenite and in a nonexposed control group. Pleural plaques was never detected in the control group, whereas it was found in 52% of exposed subjects. Median FBLN-3 concentrations were 12.96 and 5.29 ng/ml in the exposed and the control group, respectively (p < 0.001). FBLN-3 plasma levels exhibited a high predictive value for the presence of pleural plaques.}, }
@article {pmid26638917, year = {2015}, author = {Rintoul, RC}, title = {The MesoVATS trial: is there a future for video-assisted thoracoscopic surgery partial pleurectomy?.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {15-17}, doi = {10.2217/fon.15.274}, pmid = {26638917}, issn = {1744-8301}, mesh = {Aged ; Clinical Trials as Topic ; Female ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Multicenter Studies as Topic ; Pleural Neoplasms/*pathology ; Quality of Life ; Randomized Controlled Trials as Topic ; Thoracic Surgery, Video-Assisted/methods ; }, abstract = {Malignant pleural mesothelioma, a uniformly fatal cancer caused by prior asbestos exposure, places a major burden on society. The MesoVATS trial was a multicenter randomized controlled trial that examined the role of video-assisted thoracoscopic partial pleurectomy (VAT-PP) versus talc pleurodesis in patients with malignant pleural mesothelioma. Overall there was no difference in survival between VAT-PP and talc pleurodesis. VAT-PP resulted in more complications, longer hospital stay and was more expensive. However, there was some evidence that VAT-PP improved EQ5D measured quality of life after 6 months particularly in the European Organisation for Research and Treatment of Cancer low-risk subgroup. At present the future role of VAT-PP is uncertain and may merit further investigation but this should be within the context of clinical trials. VAT-PP may also have a role to play in the specific situation of trapped lung.}, }
@article {pmid26638914, year = {2015}, author = {Treasure, T}, title = {The Second Mediterranean Symposium: considering mesothelioma from a local and international perspective.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {5-6}, doi = {10.2217/fon.15.259}, pmid = {26638914}, issn = {1744-8301}, mesh = {Humans ; Internationality ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; }, }
@article {pmid26638913, year = {2015}, author = {Migliore, M}, title = {Opening lecture to the Second Mediterranean Symposium in Thoracic Oncology. Foreword.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {1-3}, doi = {10.2217/fon.15.280}, pmid = {26638913}, issn = {1744-8301}, mesh = {Humans ; Medical Oncology/methods ; Mediterranean Region ; Thoracic Neoplasms/*pathology ; }, }
@article {pmid26621064, year = {2015}, author = {Zocchetti, C}, title = {[Mesothelioma and acceleration].}, journal = {La Medicina del lavoro}, volume = {106}, number = {6}, pages = {431-446}, pmid = {26621064}, issn = {0025-7818}, mesh = {Adult ; Age Distribution ; Age of Onset ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Carcinogens ; Case-Control Studies ; Humans ; Italy/epidemiology ; Kinetics ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; }, abstract = {INTRODUCTION: Taking a publication by Berry in 2007 (3) as a cue, this paper presents in didactic form the topic of acceleration of events as a consequence of a harmful exposure and extends the proposed approach to the case of the asbestos-mesothelioma relationship.<br><br>METHODS: Berry's approach was applied to lung cancer and mesothelioma data.<br><br>RESULTS: The effects of the acceleration of events are presented as a function of age at onset in exposed subjects, relative risk, scale factor, in addition to age and geographical variability of the relationship between age and mesothelioma rates.<br><br>DISCUSSION: The discussion regards the general characteristics of the method of acceleration, its meaning and interpretation, and the difficulties associated with its application in the context of diseases with low occurrence; the conditions, applicability constraints, and specific results in the case of mesothelioma; the epidemiologic meaning of acceleration and the difficulties of its extension to individual subjects.}, }
@article {pmid26620209, year = {2016}, author = {Yamagishi, T and Fujimoto, N and Miyamoto, Y and Asano, M and Fuchimoto, Y and Wada, S and Kitamura, K and Ozaki, S and Nishi, H and Kishimoto, T}, title = {Brain metastases in malignant pleural mesothelioma.}, journal = {Clinical &amp; experimental metastasis}, volume = {33}, number = {3}, pages = {231-237}, pmid = {26620209}, issn = {1573-7276}, mesh = {Aged ; Brain Neoplasms/mortality/*secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*secondary ; Male ; Mesothelioma/mortality/*secondary ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/mortality/*pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; }, abstract = {The brain is a rare site of metastasis in malignant pleural mesothelioma (MPM), and its clinical features and prognosis remain unclear. The aim of this study was to investigate the incidence, prognosis, and risk factors for brain metastases (BM) in MPM patients. Between July 1993 and October 2014, 150 patients with histologically proven MPM were included in this retrospective study. The cumulative incidence of BM was estimated with the Kaplan-Meier method, and differences between groups were analyzed by the log-rank test. Multivariate logistic regression analysis was applied to assess risk factors for BM. The median follow-up time was 11 months (range 0-154.0 months). A total of eight patients (5.3 %) developed BM during the course of their illness. Multivariate analysis identified age <65 years (odds ratio [OR] = 5.83, p = 0.038) and International Mesothelioma Interest Group stage IV (OR = 1.69, p = 0.040) as independent factors related to increased risk of developing BM. The 1-and 2-year cumulative rates of BM were 4.0 % (95 % confidence intervals [CI] 1.4-8.5 %) and 5.3 % (95 % CI 2.3-10.2 %), respectively. Our study showed that the overall survival (OS) of patients with BM was worse than that of patients without BM (median OS 6.5 vs. 11.0 months, p = 0.037). The prognosis for BM in MPM patients is poor. Clinicians should perform careful screening for BM, especially in patients with risk factors.}, }
@article {pmid26600776, year = {2015}, author = {Yaguchi, D and Ichikawa, M and Inoue, N and Kobayashi, D and Matsuura, A and Shizu, M and Imai, N and Watanabe, K}, title = {An Autopsied Case of Malignant Sarcomatoid Pleural Mesothelioma in Which Chest Pain Developed Several Months Earlier without Abnormality on Imaging.}, journal = {Case reports in oncology}, volume = {8}, number = {3}, pages = {439-446}, pmid = {26600776}, issn = {1662-6575}, abstract = {The patient experienced chest pain for about 7 months, but a diagnosis could not be made until after death. He was diagnosed with malignant sarcomatoid pleural mesothelioma on autopsy. In this case report, difficult aspects of the diagnosis are discussed. The 70-year-old Japanese man was a driver who transported ceramic-related products. Right chest pain developed in July 2013, but no abnormality was detected on a chest computed tomography (CT) performed in September 2013, and the pain was managed as right intercostal neuralgia. A chest CT performed in late October 2013 revealed a right pleural effusion, and the patient was referred to our hospital in early November 2013. Thoracentesis was performed, but the cytology was negative, and no diagnosis could be made. Close examination was postponed because the patient developed a subarachnoid hemorrhage. He underwent (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) after discharge from the neurosurgery department, and extensive right pleural thickening and (18)F-FDG accumulation in this region were observed. Based on these findings, malignant pleural mesothelioma was suspected, and a thoracoscopy was performed under local anesthesia in early December 2013, but no definite diagnosis could be made. The patient selected best supportive care and died about 7 months after the initial development of right chest pain. The disease was definitively diagnosed as malignant sarcomatoid pleural mesothelioma by a pathological autopsy. When chronic chest pain of unknown cause is observed and past exposure to asbestos is suspected, actions to prevent delay in diagnosis should be taken, including testing for suspicion of malignant pleural mesothelioma.}, }
@article {pmid26568009, year = {2015}, author = {Ushio, R and Yamamoto, M and Shibata, Y and Ishii, H and Watanabe, K and Takahashi, R and Sato, T and Kudo, M and Miyake, A and Kaneko, T and Ishigatsubo, Y}, title = {An Autopsy Case Report of Malignant Pleural Mesothelioma with Deciduoid Features.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {54}, number = {22}, pages = {2915-2917}, doi = {10.2169/internalmedicine.54.4940}, pmid = {26568009}, issn = {1349-7235}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols ; Asbestos/*adverse effects ; Autopsy ; Disease Progression ; Fatal Outcome ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. We experienced the case of a 73-year-old man with asbestos exposure who was diagnosed with malignant pleural mesothelioma with deciduoid features. He received chemotherapy containing six cycles of cisplatin and pemetrexed and survived for twenty-five months after the diagnosis. At autopsy, the final diagnosis was biphasic pleural mesothelioma. Cells with deciduoid features had mostly disappeared, and spindle cells markedly proliferated. To the best of our knowledge, this is the first autopsy case of malignant pleural mesothelioma with deciduoid features that exhibited a response to chemotherapy.}, }
@article {pmid26566053, year = {2016}, author = {Capella, S and Bellis, D and Belluso, E}, title = {Diagnosis of Asbestos-Related Diseases: The Mineralogist and Pathologist's Role in Medicolegal Field.}, journal = {The American journal of forensic medicine and pathology}, volume = {37}, number = {1}, pages = {24-28}, doi = {10.1097/PAF.0000000000000206}, pmid = {26566053}, issn = {1533-404X}, mesh = {Asbestos/*analysis ; Asbestosis/*diagnosis ; Humans ; Lung/chemistry/pathology/ultrastructure ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Microscopy, Electron, Scanning ; Mineral Fibers/analysis ; Pleural Neoplasms/*diagnosis ; Retrospective Studies ; Spectrometry, X-Ray Emission ; }, abstract = {Because asbestos diseases represent a complex pattern of legal, social, and political issue, the involvement of the mineralogist and pathologist for a multidisciplinary assessment of its diagnosis helps investigate the relationship between mesothelioma or lung cancer and occupational or environmental asbestos exposure.In the present study, we consider the concentrations of asbestos bodies (ABs) detected by optical microscopy (OM) and scanning electron microscopy (SEM) and the burden of different kinds of mineral fibers (among which is asbestos) identified by SEM combined with an energy dispersive spectrometer (EDS), in 10 lung tissue samples of subjects with occupational and nonoccupational exposure to asbestos.In all subjects with occupational exposure to asbestos, more than 1000 ABs per gram of dry weight were detected both with OM and SEM; this concentration is internationally accepted as suggesting high probability of past occupational exposure to asbestos.In 9 lung samples of the 10 investigated by SEM-EDS different inorganic fibers were found. Asbestos fibers have been identified too, and more than 100,000 fibers per gram of dry weight were detected in subjects with occupational exposure; this concentration is internationally accepted as suggesting high probability of past occupational exposure to asbestos.Instead, when the ABs burden is low or moderate (such as in subjects with absent or probable asbestos exposure), the correlation between ABs concentration determined by OM and those determined by SEM is lost. Therefore, when the ABs value in OM is borderline, the SEM investigation became essential. Furthermore, the mineralogical analysis by SEM-EDS (identification and quantification of inorganic fibers in general and asbestos in particular) of the fibers detected in the lung tissues is very useful, if not necessary, to complete the pathological diagnosis of asbestos-related malignancies in medicolegal field.}, }
@article {pmid26552696, year = {2016}, author = {Stayner, LT}, title = {Para-occupational exposures to asbestos: lessons learned from Casale Monferrato, Italy.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {3}, pages = {145-146}, doi = {10.1136/oemed-2015-103233}, pmid = {26552696}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*adverse effects ; Environmental Pollution/*adverse effects ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, }
@article {pmid26530353, year = {2016}, author = {You, BR and Park, WH}, title = {Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion.}, journal = {Oncology reports}, volume = {35}, number = {1}, pages = {546-551}, doi = {10.3892/or.2015.4382}, pmid = {26530353}, issn = {1791-2431}, mesh = {Apoptosis ; Auranofin/*pharmacology ; Caspases/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Glutathione/*metabolism ; Humans ; Mesothelioma/*metabolism ; Oxidative Stress/*drug effects ; Thioredoxin Reductase 1/metabolism ; }, abstract = {Mesothelioma is an aggressive tumor associated with asbestos exposure. Auranofin as an inhibitor of thioredoxin reductase (TrxR) affects many biological processes such as inflammation and proliferation. In the present study, we investigated the cellular effects of auranofin on patient-derived mesothelioma cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Basal TrxR1 levels have no difference between mesothelial cells and certain mesothelioma cells. In particular, ADA, CON and Hmeso mesothelioma cells showed lower levels of TrxR1 expression. Auranofin inhibited the proliferation of mesothelioma cells in a dose-dependent manner. Among mesothelioma cells were ADA and CON cells sensitive to auranofin. This agent also induced caspase-independent apoptosis and necrosis in ADA cells. In addition, auranofin increased ROS levels including O2(•-) and induced GSH depletion in mesothelioma cells. While N-acetyl cysteine (NAC) prevented cell death and decreased ROS levels in auranofin-treated mesothelioma cells, L-buthionine sulfoximine (BSO) intensified apoptosis and GSH depletion in these cells. In conclusion, auranofin induced mesothelioma cell death through oxidative stress and the death was regulated by the status of GSH content.}, }
@article {pmid26513124, year = {2016}, author = {Kim, SY and Kim, YC and Kim, Y and Hong, WH}, title = {Predicting the mortality from asbestos-related diseases based on the amount of asbestos used and the effects of slate buildings in Korea.}, journal = {The Science of the total environment}, volume = {542}, number = {Pt A}, pages = {1-11}, doi = {10.1016/j.scitotenv.2015.10.115}, pmid = {26513124}, issn = {1879-1026}, mesh = {*Asbestos ; Asbestos, Serpentine ; Asbestosis/*mortality ; Humans ; Industry ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; Occupational Exposure/*statistics &amp; numerical data ; Republic of Korea/epidemiology ; }, abstract = {Asbestos has been used since ancient times, owing to its heat-resistant, rot-proof, and insulating qualities, and its usage rapidly increased after the industrial revolution. In Korea, all slates were previously manufactured in a mixture of about 90% cement and 10% chrysotile (white asbestos). This study used a Generalized Poisson regression (GPR) model after creating databases of the mortality from asbestos-related diseases and of the amount of asbestos used in Korea as a means to predict the future mortality of asbestos-related diseases and mesothelioma in Korea. Moreover, to predict the future mortality according to the effects of slate buildings, a comparative analysis based on the result of the GPR model was conducted after creating databases of the amount of asbestos used in Korea and of the amount of asbestos used in making slates. We predicted the mortality from asbestos-related diseases by year, from 2014 to 2036, according to the amount of asbestos used. As a result, it was predicted that a total of 1942 people (maximum, 3476) will die by 2036. Moreover, based on the comparative analysis according to the influence index, it was predicted that a maximum of 555 people will die from asbestos-related diseases by 2031 as a result of the effects of asbestos-containing slate buildings, and the mortality was predicted to peak in 2021, with 53 cases. Although mesothelioma and pulmonary asbestosis were considered as asbestos-related diseases, these are not the only two diseases caused by asbestos. However the results of this study are highly important and relevant, as, for the first time in Korea, the future mortality from asbestos-related diseases was predicted. These findings are expected to contribute greatly to the Korean government's policies related to the compensation for asbestos victims.}, }
@article {pmid26511746, year = {2016}, author = {Barber, CM and Wiggans, RE and Young, C and Fishwick, D}, title = {UK asbestos imports and mortality due to idiopathic pulmonary fibrosis.}, journal = {Occupational medicine (Oxford, England)}, volume = {66}, number = {2}, pages = {106-111}, pmid = {26511746}, issn = {1471-8405}, mesh = {Age Distribution ; *Asbestos ; Asbestosis/*mortality/physiopathology ; Carcinogens ; Construction Materials/*adverse effects ; Female ; Humans ; Idiopathic Pulmonary Fibrosis/*mortality/physiopathology ; Lung Neoplasms/*mortality/physiopathology ; Male ; Mesothelioma/*mortality/physiopathology ; Occupational Diseases/chemically induced/*mortality ; Occupational Exposure/prevention &amp; control/*statistics &amp; numerical data ; Prevalence ; Registries ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Previous studies have demonstrated that the rising mortality due to mesothelioma and asbestosis can be predicted from historic asbestos usage. Mortality due to idiopathic pulmonary fibrosis (IPF) is also rising, without any apparent explanation.<br><br>AIMS: To compare mortality due to these conditions and examine the relationship between mortality and national asbestos imports.<br><br>METHODS: Mortality data for IPF and asbestosis in England and Wales were available from the Office for National Statistics. Data for mesothelioma deaths in England and Wales and historic UK asbestos import data were available from the Health &amp; Safety Executive. The numbers of annual deaths due to each condition were plotted separately by gender, against UK asbestos imports 48 years earlier. Linear regression models were constructed.<br><br>RESULTS: For mesothelioma and IPF, there was a significant linear relationship between the number of male and female deaths each year and historic UK asbestos imports. For asbestosis mortality, a similar relationship was found for male but not female deaths. The annual numbers of deaths due to asbestosis in both sexes were lower than for IPF and mesothelioma.<br><br>CONCLUSIONS: The strength of the association between IPF mortality and historic asbestos imports was similar to that seen in an established asbestos-related disease, i.e. mesothelioma. This finding could in part be explained by diagnostic difficulties in separating asbestosis from IPF and highlights the need for a more accurate method of assessing lifetime occupational asbestos exposure.}, }
@article {pmid26505785, year = {2015}, author = {Ying, C and Maeda, M and Nishimura, Y and Kumagai-Takei, N and Hayashi, H and Matsuzaki, H and Lee, S and Yoshitome, K and Yamamoto, S and Hatayama, T and Otsuki, T}, title = {Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos.}, journal = {Toxicology}, volume = {338}, number = {}, pages = {86-94}, doi = {10.1016/j.tox.2015.10.005}, pmid = {26505785}, issn = {1879-3185}, mesh = {Asbestos, Serpentine/*toxicity ; CTLA-4 Antigen/metabolism ; Cell Communication/drug effects ; Cell Line, Transformed ; Cell Transformation, Viral ; Coculture Techniques ; Forkhead Transcription Factors/metabolism ; Glucocorticoid-Induced TNFR-Related Protein/metabolism ; Human T-lymphotropic virus 1/pathogenicity ; Humans ; Interleukin-10/genetics/metabolism ; Lymphocyte Activation/*drug effects ; Phenotype ; RNA Interference ; T-Lymphocytes, Regulatory/*drug effects/immunology/metabolism/virology ; Time Factors ; Transfection ; Transforming Growth Factor beta1/genetics/metabolism ; Tumor Escape/drug effects ; }, abstract = {Asbestos exposure causes lung fibrosis and various malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos on immune cells have not been thoroughly investigated, although our previous reports showed that asbestos exposure reduced anti-tumor immunity. The effects of continuous exposure of regulatory T cells (Treg) to asbestos were examined using the HTLV-1 immortalized human T cell line MT-2, which possesses a suppressive function and expresses the Treg marker protein, Foxp3. Sublines were generated by the continuous exposure to low doses of asbestos fibers for more than one year. The sublines exposed to asbestos showed enhanced suppressive Treg function via cell-cell contact, and increased production of soluble factors such as IL-10 and transforming growth factor (TGF)-β1. These results also indicated that asbestos exposure induced the reduction of anti-tumor immunity, and efforts to develop substances to reverse this reduction may be helpful in preventing the occurrence of asbestos-induced tumors.}, }
@article {pmid26489154, year = {2015}, author = {Nakanishi, N and Shiojiri, M and Inoue, K and Moritaka, T}, title = {[A CASE OF NON-TUBERCULOUS MYCOBACTERIOSIS WITH PLEURAL EFFUSION AND THICKENING IN A PATIENT WITH AN OCCUPATIONAL HISTORY OF ASBESTOS EXPOSURE].}, journal = {Kekkaku : [Tuberculosis]}, volume = {90}, number = {5}, pages = {503-506}, pmid = {26489154}, issn = {0022-9776}, mesh = {Aged ; *Asbestos ; Humans ; Male ; Mycobacterium avium-intracellulare Infection/*diagnosis ; *Occupational Exposure ; Pleurisy/*diagnosis ; }, abstract = {We report a case of a 75-year-old man with pleural effusion and an occupational history of asbestos exposure. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) examination revealed FDG up-takes along his pleura, leading to an initial suspicion of pleural mesothelioma. Pathological findings of a diagnostic video-associated pleural biopsy showed epithelioid cell granuloma. Repeated sputum cultures were positive for Mycobacterium intracellulare. The patient was diagnosed with pleuritis caused by non-tuberculous mycobacteria (NTM). NTM should be considered a potential cause of pleuritis.}, }
@article {pmid26481865, year = {2016}, author = {Signorelli, D and Macerelli, M and Proto, C and Vitali, M and Cona, MS and Agustoni, F and Zilembo, N and Platania, M and Trama, A and Gallucci, R and Ganzinelli, M and Pelosi, G and Pastorino, U and de Braud, F and Garassino, MC and Lo Russo, G}, title = {Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy?.}, journal = {Tumori}, volume = {102}, number = {1}, pages = {18-30}, doi = {10.5301/tj.5000436}, pmid = {26481865}, issn = {2038-2529}, mesh = {Angiogenesis Inhibitors/therapeutic use ; Antineoplastic Agents/pharmacology/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/toxicity ; Carcinogens/toxicity ; Clinical Trials as Topic ; ErbB Receptors/antagonists &amp; inhibitors ; GPI-Linked Proteins/antagonists &amp; inhibitors ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; *Immunotherapy/methods ; Lung Neoplasms/chemically induced/*drug therapy/immunology/metabolism/pathology ; Mesothelin ; Mesothelioma/chemically induced/*drug therapy/immunology/metabolism/pathology ; Mesothelioma, Malignant ; *Molecular Targeted Therapy/methods ; Pleural Neoplasms/chemically induced/*drug therapy/immunology/metabolism/pathology ; Proteasome Inhibitors/therapeutic use ; }, abstract = {Malignant pleural mesothelioma is a rare cancer with a cause-effect relationship to asbestos exposure. The prognosis is poor and chemotherapy seems the best treatment option. In the last two decades a deeper understanding of mesothelioma carcinogenesis and invasiveness mechanisms has prompted research efforts to test new agents in patients with malignant pleural mesothelioma, but the results have been modest. Attractive preclinical data disappointed in subsequent experimental phases. Other promising agents failed to improve patient outcomes due to high toxicity. Interesting suggestions have come from preliminary data on immunotherapy. Several trials are ongoing and the results are eagerly awaited. The aim of this review is to discuss the most recent news on systemic therapy for advanced malignant pleural mesothelioma.}, }
@article {pmid26467803, year = {2016}, author = {Rintoul, RC and Rassl, DM and Gittins, J and Marciniak, SJ and , }, title = {MesobanK UK: an international mesothelioma bioresource.}, journal = {Thorax}, volume = {71}, number = {4}, pages = {380-382}, doi = {10.1136/thoraxjnl-2015-207496}, pmid = {26467803}, issn = {1468-3296}, support = {MC_U132685863/MRC_/Medical Research Council/United Kingdom ; PB-PG-0213-30098/DH_/Department of Health/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; 100140/WT_/Wellcome Trust/United Kingdom ; MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; G0601840/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biological Specimen Banks/*organization &amp; administration/standards/trends ; Biomedical Research/organization &amp; administration ; Foundations/organization &amp; administration ; Humans ; *International Cooperation ; *Lung Neoplasms/economics ; *Mesothelioma/economics ; Mesothelioma, Malignant ; *Pleural Neoplasms/economics ; United Kingdom ; }, abstract = {Malignant pleural mesothelioma causes the greatest societal burden of all the asbestos-related diseases. Progress in better understanding tumour biology will be facilitated by the availability of quality-assured annotated tissue. MesobanK has been created to establish a bioresource of pleural mesothelioma tissue linked to detailed anonymised clinical data. When complete, the bioresource will comprise a 750-patient tissue microarray and prospectively collected tissue, blood and pleural fluid from 300 patients with mesothelioma. Twenty-six new cell lines have also been developed. MesobanK meets all appropriate ethical and regulatory procedures and has recently opened to requests for tissue and data.}, }
@article {pmid26463840, year = {2016}, author = {Mäki-Nevala, S and Sarhadi, VK and Knuuttila, A and Scheinin, I and Ellonen, P and Lagström, S and Rönty, M and Kettunen, E and Husgafvel-Pursiainen, K and Wolff, H and Knuutila, S}, title = {Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing.}, journal = {Lung}, volume = {194}, number = {1}, pages = {125-135}, pmid = {26463840}, issn = {1432-1750}, mesh = {Adenocarcinoma/*genetics ; Asbestos/adverse effects ; Cell Adhesion Molecules/genetics ; Coatomer Protein/genetics ; DNA Mutational Analysis ; ErbB Receptors/genetics ; Exome/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics ; Male ; Membrane Glycoproteins/genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Mitochondrial Proteins/genetics ; Peptide Synthases/genetics ; Peritoneal Neoplasms/*genetics ; Phosphoric Monoester Hydrolases/genetics ; Pleural Neoplasms/*genetics ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; Receptors, Eph Family/genetics ; Ribosomal Proteins/genetics ; Semaphorins/genetics ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {BACKGROUND: Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM.<br><br>METHODS: Exome sequencing was performed on DNA from 47 tumor tissues of MM (21) and LAC (26) patients, 27 of whom had been asbestos-exposed (18 MM, 9 LAC). In addition, 9 normal lung/blood samples of LAC were sequenced. Novel mutations identified from exome data were validated by amplicon-based deep sequencing. Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM.<br><br>RESULTS: In asbestos-exposed MM patients, previously non-described NF2 frameshift mutation (one) and BAP1 mutations (four) were detected. Exome data mining revealed some genes potentially associated with asbestos exposure, such as MRPL1 and SDK1. BAP1 and COPG1 mutations were seen exclusively in MM. Pathogenic KRAS mutations were common in LAC patients (42 %), both in non-exposed (n = 5) and exposed patients (n = 6). Pathogenic BRAF mutations were found in two LACs.<br><br>CONCLUSION: BAP1 mutations occurred in asbestos-exposed MM. MRPL1, SDK1, SEMA5B, and INPP4A could possibly serve as candidate genes for alterations associated with asbestos exposure. KRAS mutations in LAC were not associated with asbestos exposure.}, }
@article {pmid26448888, year = {2015}, author = {Desouki, MM and Long, DJ}, title = {Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast.}, journal = {Case reports in oncological medicine}, volume = {2015}, number = {}, pages = {298523}, pmid = {26448888}, issn = {2090-6706}, abstract = {Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.}, }
@article {pmid26435024, year = {2015}, author = {Jankovichova, T and Jankovich, M and Ondrus, D and Kajo, K and Dubravicky, J and Breza, J}, title = {Extremely rare tumour--malignant mesothelioma of tunica vaginalis testis.}, journal = {Bratislavske lekarske listy}, volume = {116}, number = {9}, pages = {574-576}, doi = {10.4149/bll_2015_111}, pmid = {26435024}, issn = {0006-9248}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Mesothelioma, Malignant ; Testicular Hydrocele/etiology/*pathology ; Testicular Neoplasms/etiology/*pathology ; }, abstract = {INTRODUCTION: Malignant mesothelioma of tunica vaginalis testis is an extremely rare tumour. It is often caused by exposition to asbestos, however, more often its occurrence is sporadic. The diagnosis is usually set secondarily during hydrocele surgery. This type of tumour should be considered in cases with with atypical hydrocele, especially haematocele or atypical shape of seminal covering.<br><br>RESULTS: A case of an asbestos-exposed patient with described disease and long-term hydrocele is presented. The number of patients is so small that the guidelines are limited due to low statistical power (Fig. 2, Ref. 14).}, }
@article {pmid26433514, year = {2015}, author = {Marcq, E and Pauwels, P and van Meerbeeck, JP and Smits, EL}, title = {Targeting immune checkpoints: New opportunity for mesothelioma treatment?.}, journal = {Cancer treatment reviews}, volume = {41}, number = {10}, pages = {914-924}, doi = {10.1016/j.ctrv.2015.09.006}, pmid = {26433514}, issn = {1532-1967}, mesh = {Antigens, CD/immunology ; Antineoplastic Agents/*therapeutic use ; B7-H1 Antigen/antagonists &amp; inhibitors/immunology ; CTLA-4 Antigen/*antagonists &amp; inhibitors/immunology ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Immunologic Factors/*therapeutic use ; Lung Neoplasms/*drug therapy/immunology ; Membrane Proteins/antagonists &amp; inhibitors/immunology ; Mesothelioma/*drug therapy/immunology ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy/immunology ; Programmed Cell Death 1 Ligand 2 Protein/antagonists &amp; inhibitors/immunology ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors/immunology ; Lymphocyte Activation Gene 3 Protein ; }, abstract = {Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. Therefore, there is room for therapeutic improvement using a new strategy to prolong survival. Dealing with cancer cell induced immunosuppression is a promising approach. Reactivating immune responses that are silenced by immune checkpoints recently gained a lot of interest. Checkpoint blockade has already shown promising preclinical and clinical results in several cancer types and is currently also being investigated in mesothelioma. Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints. Furthermore, we review the clinical results of molecules blocking these immune checkpoints and point out their future opportunities with a special focus on mesothelioma.}, }
@article {pmid26433083, year = {2016}, author = {D'Antonio, A and Mastella, F and Colucci, A and Silvestre, G}, title = {Malignant Mesothelioma of Spermatic Cord in an Elderly Man With a History of Asbestos Exposure.}, journal = {Urology}, volume = {87}, number = {}, pages = {e1-3}, doi = {10.1016/j.urology.2015.09.020}, pmid = {26433083}, issn = {1527-9995}, mesh = {Aged, 80 and over ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced/diagnosis/surgery ; Male ; Mesothelioma/*chemically induced/diagnosis/surgery ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Orchiectomy/*methods ; *Spermatic Cord ; Testicular Neoplasms/*chemically induced/diagnosis/surgery ; }, abstract = {We report a case of malignant mesothelioma of the spermatic cord in 80-year-old man presented with retained testis, hydrocele, and right inguinal mass. The patient had a long history of asbestos exposure as a railway worker. The patient was submitted to inguinal radical orchiectomy. One year after surgery, the patient is alive without signs of disease. Malignant mesothelioma of spermatic cord is a very rare disease, but this diagnosis should be suspected in patient with a history of asbestos exposure.}, }
@article {pmid26431916, year = {2015}, author = {Santarelli, L and Staffolani, S and Strafella, E and Nocchi, L and Manzella, N and Grossi, P and Bracci, M and Pignotti, E and Alleva, R and Borghi, B and Pompili, C and Sabbatini, A and Rubini, C and Zuccatosta, L and Bichisecchi, E and Valentino, M and Horwood, K and Comar, M and Bovenzi, M and Dong, LF and Neuzil, J and Amati, M and Tomasetti, M}, title = {Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {90}, number = {3}, pages = {457-464}, doi = {10.1016/j.lungcan.2015.09.021}, pmid = {26431916}, issn = {1872-8332}, mesh = {Aged ; *Biomarkers, Tumor ; DNA Methylation ; *Epigenesis, Genetic ; Female ; GPI-Linked Proteins/blood/*genetics ; Humans ; Lung Neoplasms/blood/*diagnosis/etiology/*genetics/therapy ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/etiology/*genetics/therapy ; Mesothelioma, Malignant ; MicroRNAs/blood/genetics ; Middle Aged ; Multidrug Resistance-Associated Proteins/blood ; Prognosis ; Reproducibility of Results ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage.<br><br>MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated.<br><br>RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.}, }
@article {pmid26421826, year = {2015}, author = {Francisci, S and Minicozzi, P and Pierannunzio, D and Ardanaz, E and Eberle, A and Grimsrud, TK and Knijn, A and Pastorino, U and Salmerón, D and Trama, A and Sant, M and , }, title = {Survival patterns in lung and pleural cancer in Europe 1999-2007: Results from the EUROCARE-5 study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {51}, number = {15}, pages = {2242-2253}, doi = {10.1016/j.ejca.2015.07.033}, pmid = {26421826}, issn = {1879-0852}, abstract = {BACKGROUND: Survival of patients diagnosed with lung and pleura cancer is a relevant health care indicator which is related to the availability and access to early diagnosis and treatment facilities. Aim of this paper is to update lung and pleural cancer survival patterns and time trends in Europe using the EUROCARE-5 database.<br><br>METHODS: Data on adults diagnosed with lung and pleural cancer from 87 European cancer registries in 28 countries were analysed. Relative survival (RS) in 2000-2007 by country/region, age and gender, and over time trends in 1999-2007 were estimated.<br><br>RESULTS: Lung cancer survival is poor everywhere in Europe, with a RS of 39% and 13% at 1 and 5years since diagnosis, respectively. A geographical variability is present across European areas with a maximum regional difference of 12 and 5 percentage points in 1-year and 5-year RS respectively. Pleural cancer represents 4% of cases included in the present study with 7% 5-year RS overall in Europe. Most pleural cancers (83%) are microscopically verified mesotheliomas. Survival for both cancers decreases with advancing age at diagnosis for both cancers. Slight increasing trends are described for lung cancer. Survival over time is higher for squamous cell carcinoma and adenocarcinomas than for small and large cell carcinoma; and better among women than men.<br><br>CONCLUSIONS: Despite the generalised although slight increase, survival of lung and pleural cancer patients still remains poor in European countries. Priority should be given to prevention, with tobacco control policies across Europe for lung cancer and banning asbestos exposure for pleural cancer, and in early diagnosis and better treatment. The management of mesothelioma needs a multidisciplinary team and standardised health care strategies.}, }
@article {pmid26418833, year = {2016}, author = {Peng, WJ and Mi, J and Jiang, YH}, title = {Asbestos exposure and laryngeal cancer mortality.}, journal = {The Laryngoscope}, volume = {126}, number = {5}, pages = {1169-1174}, doi = {10.1002/lary.25693}, pmid = {26418833}, issn = {1531-4995}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Laryngeal Neoplasms/chemically induced/*mortality ; Male ; Occupational Exposure/*adverse effects ; Risk Factors ; Sex Factors ; }, abstract = {OBJECTIVES/HYPOTHESIS: Occupational exposure to asbestos occurs in many workplaces and is well known to cause asbestosis, lung cancer, and mesothelioma. However, the link between asbestos exposure and other malignancies was not confirmed. The aim of the current meta-analysis was to provide a summary measure of risk for laryngeal cancer associated with occupational asbestos exposure.<br><br>STUDY DESIGN: Systematic review and meta-analysis.<br><br>METHODS: Electronic databases were searched for studies characterizing the association between asbestos and laryngeal cancer. Standardized mortality rate (SMR) with its 95% confidence interval (CI) of each study was combined using a fixed or random effect model.<br><br>RESULTS: Significantly increased SMR for laryngeal cancer was observed when subjects were exposed to asbestos (SMR = 1.69, 95% CI = 1.45-1.97, P < .001), with little evidence of heterogeneity among studies (Q = 15.39, P = .803, I(2) = 0.0%). Effect estimates were larger for cohorts controlling for male subjects, Europe and Oceania, mining and textile industries, exposure to crocidolite, long study follow-up (>25 years), and SMR for lung cancer > 2.0. Publication bias was not detect by Begg test (P = .910) and Egger test (P = .340).<br><br>CONCLUSIONS: Our study supports the association of exposure to asbestos with an increased risk of laryngeal cancer mortality among male workers.<br><br>LEVEL OF EVIDENCE: NA Laryngoscope, 126:1169-1174, 2016.}, }
@article {pmid26409435, year = {2015}, author = {Cheung, M and Kadariya, Y and Talarchek, J and Pei, J and Ohar, JA and Kayaleh, OR and Testa, JR}, title = {Germline BAP1 mutation in a family with high incidence of multiple primary cancers and a potential gene-environment interaction.}, journal = {Cancer letters}, volume = {369}, number = {2}, pages = {261-265}, pmid = {26409435}, issn = {1872-7980}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 CA06927/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*metabolism ; Disease Susceptibility ; Gene-Environment Interaction ; Germ-Line Mutation ; Humans ; Incidence ; Melanoma/*genetics/metabolism/pathology ; Neoplasms/*genetics/metabolism ; Skin Neoplasms ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; Melanoma, Cutaneous Malignant ; }, abstract = {We report a high-risk cancer family with multiple mesotheliomas, cutaneous melanomas, basal cell carcinomas, and meningiomas segregating with a germline nonsense mutation in BAP1 (c.1938T>A; p.Y646X). Notably, most (four of five) mesotheliomas were peritoneal rather than the usually more common pleural form of the disease, and all five mesothelioma patients also developed second or third primary cancers, including two with meningiomas. Another family member developed both cutaneous melanoma and breast cancer. Two family members had basal cell carcinomas, and six others had melanocytic tumors, including four cutaneous melanomas, one uveal melanoma, and one benign melanocytic tumor. The family resides in a subtropical area, and several members had suspected exposure to asbestos either occupationally or in the home. We hypothesize that the concurrence of a genetic predisposing factor and environmental exposure to asbestos and UV irradiation contributed to the high incidence of multiple cancers seen in this family, specifically mesothelioma and various uveal/skin tumors, respectively.}, }
@article {pmid26398408, year = {2015}, author = {Baur, X}, title = {[Asbestos: Social Legal and Scientific Controversies and Unsound Science in the Context with the Worldwide Asbestos Tragedy - Lessions to be Learned].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {69}, number = {11}, pages = {654-661}, doi = {10.1055/s-0034-1393038}, pmid = {26398408}, issn = {1438-8790}, mesh = {*Asbestos ; Asbestosis/diagnosis/*epidemiology ; Evidence-Based Medicine/ethics/legislation &amp; jurisprudence ; Expert Testimony/ethics/*legislation &amp; jurisprudence ; Global Health/ethics/*legislation &amp; jurisprudence ; Humans ; Lung Neoplasms/diagnosis/*epidemiology ; Prevalence ; Social Justice/ethics/*legislation &amp; jurisprudence ; }, abstract = {8 to 15% of lung cancer cases and nearly all mesothelioma cases are caused by asbestos. Problems in compensation issues refer to high legal as well as insurance barriers in attesting the occupational diseases. Claiming of certain numbers of asbestos bodies or fibers in lung tissue is of special relevance in substantiating legal medical cases. Such evidence, which is disproved by a sound science, is also used by an influential US pathology department. Frequently, also epidemiological evidence with its causal relationships and exposure histories are ignored. Similar misleading arguments are currently found in industrializing countries where white asbestos which is carcinogenic and fibrogenic like other asbestos types, is efficiently promoted as less harm. As a result, the asbestos consumption is increasing in some of these countries. Beyond the worldwide asbestos tragedy a well-designed strategy of certain transnational or global acting industrial interest groups can be recognized. Their plan, hidden from the public eyes, follows rigorously sole economic interests, while leaving the resulting health harm to the public health systems.}, }
@article {pmid26391798, year = {2015}, author = {Kramer, D and McMillan, K and Gross, E and Kone Pefoyo, AJ and Bradley, M and Holness, DL}, title = {From Awareness to Action: The Community of Sarnia Mobilizes to Protect its Workers from Occupational Disease.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {25}, number = {3}, pages = {377-410}, doi = {10.1177/1048291115604427}, pmid = {26391798}, issn = {1541-3772}, mesh = {*Awareness ; Canada ; Capacity Building/*organization &amp; administration ; Communication ; Community-Institutional Relations ; *Cooperative Behavior ; Humans ; Interinstitutional Relations ; Leadership ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Neoplasms/*chemically induced/*prevention &amp; control ; Occupational Exposure/*prevention &amp; control ; Occupational Health ; Social Change ; }, abstract = {An exploratory qualitative case study investigated how different sectors of a highly industrialized community mobilized in the 1990s to help workers exposed to asbestos. For this study, thirty key informants including representatives from industry, workers, the community, and local politicians participated in semi-structured interviews and focus groups. The analysis was framed by a "Dimensions of Community Change" model. The informants highlighted the importance of raising awareness, and the need for leadership, social and organizational networks, acquiring skills and resources, individual and community power, holding shared values and beliefs, and perseverance. We found that improvements in occupational health and safety came from persistently communicating a clearly defined issue ("asbestos exposure causes cancer") and having an engaged community that collaborated with union leadership. Notable successes included stronger occupational health services, a support group for workers and widows, the fast-tracking of compensation for workers exposed to asbestos, and a reduction in hazardous emissions.}, }
@article {pmid26386124, year = {2015}, author = {Nowak, AK and Cook, AM and McDonnell, AM and Millward, MJ and Creaney, J and Francis, RJ and Hasani, A and Segal, A and Musk, AW and Turlach, BA and McCoy, MJ and Robinson, BW and Lake, RA}, title = {A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {26}, number = {12}, pages = {2483-2490}, doi = {10.1093/annonc/mdv387}, pmid = {26386124}, issn = {1569-8041}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/*administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*administration &amp; dosage ; CD40 Antigens/agonists/*metabolism ; Cisplatin/*administration &amp; dosage ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/diagnosis/*drug therapy/metabolism ; Male ; Mesothelioma/diagnosis/*drug therapy/metabolism ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration &amp; dosage ; Pleural Neoplasms/diagnosis/*drug therapy/metabolism ; Prospective Studies ; }, abstract = {BACKGROUND: Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM).<br><br>PATIENTS AND METHODS: Eligible patients had confirmed MPM, ECOG performance status 0-1, and measurable disease. Patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 and CP-870,893 on day 8 of a 21-day cycle for maximum 6 cycles with up to 6 subsequent cycles single-agent CP-870,893. Immune cell subset changes were examined weekly by flow cytometry.<br><br>RESULTS: Fifteen patients were treated at three dose levels. The MTD of CP-870,893 was 0.15 mg/kg, and was exceeded at 0.2 mg/kg with one grade 4 splenic infarction and one grade 3 confusion and hyponatraemia. Cytokine release syndrome (CRS) occurred in most patients (80%) following CP-870,893. Haematological toxicities were consistent with cisplatin and pemetrexed chemotherapy. Six partial responses (40%) and 9 stable disease (53%) as best response were observed. The median overall survival was 16.5 months; the median progression-free survival was 6.3 months. Three patients survived beyond 30 months. CD19+ B cells decreased over 6 cycles of chemoimmunotherapy (P < 0.001) with a concomitant increase in the proportion of CD27+ memory B cells (P < 0.001) and activated CD86+CD27+ memory B cells (P < 0.001), as an immunopharmacodynamic marker of CD40 activation.<br><br>CONCLUSIONS: CP-870,893 with cisplatin and pemetrexed is safe and tolerable at 0.15 mg/kg, although most patients experience CRS. While objective response rates are similar to chemotherapy alone, three patients achieved long-term survival.<br><br>ACTRN12609000294257.}, }
@article {pmid26384258, year = {2015}, author = {Magnani, C and Bianchi, C and Chellini, E and Consonni, D and Fubini, B and Gennaro, V and Marinaccio, A and Menegozzo, M and Mirabelli, D and Merler, E and Merletti, F and Musti, M and Oddone, E and Romanelli, A and Terracini, B and Zona, A and Zocchetti, C and Alessi, M and Baldassarre, A and Dianzani, I and Maule, M and Mensi, C and Silvestri, S}, title = {III Italian Consensus Conference on Malignant Mesothelioma of the Pleura. Epidemiology, Public Health and Occupational Medicine related issues.}, journal = {La Medicina del lavoro}, volume = {106}, number = {5}, pages = {325-332}, pmid = {26384258}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Humans ; Italy ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; Mesothelioma, Malignant ; *Occupational Diseases/epidemiology/etiology ; Occupational Medicine ; *Pleural Neoplasms/epidemiology/etiology ; Public Health ; }, abstract = {The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up-to-date methodology; 4) Necroscopy should be practiced for validation. Expert referral centres could contribute to the definition of uncertain cases. Health surveillance should aim to all asbestos effects. No diagnostic test is recommended for MM screening. Health surveillance should provide information on risks, medical perspective, and smoking cessation. The economic burden associated to MM was estimated in 250,000 Euro per case.}, }
@article {pmid26377289, year = {2015}, author = {Musk, AW and Olsen, N and Alfonso, H and Peters, S and Franklin, P}, title = {Pattern of malignant mesothelioma incidence and occupational exposure to asbestos in Western Australia.}, journal = {The Medical journal of Australia}, volume = {203}, number = {6}, pages = {251-2e.1}, doi = {10.5694/mja15.00337}, pmid = {26377289}, issn = {1326-5377}, mesh = {Asbestos/*poisoning ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; *Occupational Exposure ; Western Australia/epidemiology ; }, }
@article {pmid26376726, year = {2015}, author = {Isoda, R and Yamane, H and Nezuo, S and Monobe, Y and Ochi, N and Honda, Y and Nishimura, S and Akiyama, M and Horio, T and Takigawa, N}, title = {Successful palliation for an aged patient with primary pericardial mesothelioma.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {273}, pmid = {26376726}, issn = {1477-7819}, mesh = {Aged, 80 and over ; Asbestos/*adverse effects ; Carcinogens/pharmacology ; Cardiac Tamponade/etiology/pathology/*therapy ; Heart Neoplasms/*complications/pathology ; Humans ; Male ; Mesothelioma/*complications/pathology ; *Palliative Care ; Pericardial Effusion/etiology/pathology/*therapy ; Pericardiocentesis ; Pleural Neoplasms/*complications/pathology ; Prognosis ; }, abstract = {An 85-year-old Japanese man with a complaint of exertional dyspnea was admitted to our hospital. Sixty-three years prior to admission at our hospital, he handled asbestos for 2 years in a factory. His chest computed tomography showed a massive pericardial effusion leading to cardiac tamponade and right pleural plaque. After a pericardiocentesis was performed, he recovered from cardiac failure caused by the cardiac tamponade. Pathological examination of the pericardial effusion revealed malignant mesothelial cells. Therefore, he was diagnosed with primary pericardial mesothelioma (PPM) related to asbestos exposure. Although his disease slowly progressed over 18 months, he remained active without any adjuvant treatments such as chemotherapy. Long-term palliation in an aged patient with PPM is rarely obtained using supportive care alone because the prognosis of PPM has been consistently reported to be very poor and almost fatal within a year. Clinical oncologists and thoracic surgeons should be aware of this disease because the accumulation of knowledge on PPM may lead to successful treatment even in aged patients.}, }
@article {pmid26376466, year = {2015}, author = {Tsukamoto, Y and Otsuki, T and Hao, H and Kuribayashi, K and Nakano, T and Kida, A and Nakanishi, T and Funatsu, E and Noguchi, C and Yoshihara, S and Kaku, K and Hirota, S}, title = {Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case.}, journal = {Pathology, research and practice}, volume = {211}, number = {12}, pages = {1014-1019}, doi = {10.1016/j.prp.2015.07.013}, pmid = {26376466}, issn = {1618-0631}, mesh = {Aged ; Fatal Outcome ; Humans ; Lung Neoplasms/complications/*secondary ; Male ; Mesothelioma/complications/*secondary ; Mesothelioma, Malignant ; Nephrosis, Lipoid/*complications ; Pleural Neoplasms/complications/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome.}, }
@article {pmid26371785, year = {2015}, author = {Pavlisko, EN and Roggli, VL}, title = {Sarcomatoid Peritoneal Mesothelioma: Clinicopathologic Correlation of 13 Cases.}, journal = {The American journal of surgical pathology}, volume = {39}, number = {11}, pages = {1568-1575}, doi = {10.1097/PAS.0000000000000495}, pmid = {26371785}, issn = {1532-0979}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Autopsy ; Biomarkers, Tumor/analysis ; Biopsy ; Databases, Factual ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Incidence ; Inhalation Exposure/adverse effects ; Keratins/analysis ; Lung Neoplasms/chemistry/mortality/*pathology ; Male ; Mesothelioma/chemistry/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/chemistry/mortality/*pathology ; Predictive Value of Tests ; Prognosis ; Risk Factors ; Sarcoma/chemistry/mortality/*pathology ; Survival Analysis ; }, abstract = {Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases.}, }
@article {pmid26366399, year = {2015}, author = {Zhang, W and Wu, X and Wu, L and Zhang, W and Zhao, X}, title = {Advances in the diagnosis, treatment and prognosis of malignant pleural mesothelioma.}, journal = {Annals of translational medicine}, volume = {3}, number = {13}, pages = {182}, pmid = {26366399}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. The prognosis of MPM is poor due to the difficulty of making diagnosis in the early stage, the rapid progression, the high invasiveness and the lack of effective treatment. Although the incidence of MPM is low in China to date, it has a tendency to increase in the coming years. The variety of clinical features may cause the delay of diagnosis and high rate of misdiagnosis. The diagnosis of MPM is based on biopsy of the pleura and immunohistochemistry. As China has become the largest country in the consumption of asbestos, it would give rise to a new surge of MPM in the future. The current treatment of MPM is multimodality therapy including surgery, radiotherapy, chemotherapy and immunotherapy. Two surgical procedures are commonly applied: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). Three dimensional conformal radiotherapy is used to denote a spectrum of radiation planning and delivery techniques that rely on the 3D imaging to define the tumor. Cisplatin combined with pemetrexed (PEM) is the first-line chemotherapy for MPM. The principal targets in immunotherapy include T cells (Treg), CTLA-4 and PD-1. The diagnosis, treatment and prognosis still remain a major challenge for clinical research and will do so for years to come.}, }
@article {pmid26364960, year = {2017}, author = {Sim, JK and Oh, JY and Min, KH and Hur, GY and Shim, JJ and Kang, KH and Lee, SY}, title = {Malignant mesothelioma with fungating masses and multiple sites involvement.}, journal = {The clinical respiratory journal}, volume = {11}, number = {4}, pages = {524-528}, doi = {10.1111/crj.12383}, pmid = {26364960}, issn = {1752-699X}, mesh = {Asbestos/*adverse effects ; Drug Therapy/methods ; Dyspnea/*diagnosis/etiology ; Fatal Outcome ; Humans ; Lung Neoplasms/diagnostic imaging/drug therapy/*pathology ; Male ; Mesothelioma/diagnostic imaging/drug therapy/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Metastasis/pathology ; Pleura/cytology/*pathology/ultrastructure ; Pleural Effusion, Malignant/*diagnostic imaging ; Pleural Neoplasms/*pathology ; Positron-Emission Tomography ; Radiography ; Tomography, X-Ray Computed ; }, abstract = {Malignant mesothelioma (MM) is a rare tumor associated with asbestos exposure. It typically presents as thickening or nodularity of the pleura, although it can also originate from other sites consisting of mesothelia and have manifestations other than thickening or nodularity. Several studies have implied that these different manifestations are associated with a different tumor biology. We report the case of a 54-year-old man with multiple fungating masses diagnosed as MM on histological examination.}, }
@article {pmid26364129, year = {2015}, author = {Cheung, M and Kadariya, Y and Pei, J and Talarchek, J and Facciolo, F and Visca, P and Righi, L and Cozzi, I and Testa, JR and Ascoli, V}, title = {An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation.}, journal = {Cancer genetics}, volume = {208}, number = {10}, pages = {502-507}, pmid = {26364129}, issn = {2210-7762}, support = {P30 CA06927/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Male ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; *Mutation ; Oligonucleotide Array Sequence Analysis ; Pedigree ; Pleural Neoplasms/*chemically induced/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family.}, }
@article {pmid26361957, year = {2015}, author = {Liu, H and Wu, L and Ji, K and Wang, W}, title = {Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {10}, pages = {7375-7384}, pmid = {26361957}, issn = {1423-0380}, mesh = {Biomarkers, Tumor/*analysis ; Combined Modality Therapy ; Humans ; Lung Neoplasms/*diagnosis/metabolism/mortality/therapy ; Mesothelioma/*diagnosis/metabolism/mortality/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/metabolism/mortality/therapy ; Prognosis ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor of the pleura closely related to asbestos exposure. Rare as it is, the incidence of MPM is predicted to increase mainly as a result of a lengthy latency period from the initial asbestos exposure, making it a public health concern for the next decades. Moreover, the patients with MPM have an extremely poor prognosis due to its high resistance to conventional oncologic treatments and delayed diagnosis. Although the result of current therapeutic modalities based on patient features and clinical stages is very frustrating, great advances have been shown in the knowledge of molecular biology of MPM in recent years. This is accompanied by dozens of putative prognostic biomarkers that are actively involved in tumor biological activities. These prognostic candidates can offer us a new insight into the biological characteristics of MPM, contributing to development of individualized therapeutic strategies directed against oncogenesis and tumor progression. Thus, personalized approaches based on the molecular biology of the patient's tissue or body fluid will potentially improve the present disappointing outcome, bringing new hope for patients with MPM. This article reviews the principal and several novel biomarkers that can have an influence on prognosis, in the hope that they can provide us with a more profound understanding of the biology of this lethal disease.}, }
@article {pmid26358421, year = {2016}, author = {Urso, L and Calabrese, F and Favaretto, A and Conte, P and Pasello, G}, title = {Critical review about MDM2 in cancer: Possible role in malignant mesothelioma and implications for treatment.}, journal = {Critical reviews in oncology/hematology}, volume = {97}, number = {}, pages = {220-230}, doi = {10.1016/j.critrevonc.2015.08.019}, pmid = {26358421}, issn = {1879-0461}, mesh = {Animals ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Mesothelioma, Malignant ; Mice ; *Proto-Oncogene Proteins c-mdm2 ; Tumor Suppressor Protein p53/genetics ; }, abstract = {The tumor suppressor p53 regulates genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis and senescence. p53 is mutated in about 50% of the human cancers, while in tumors with wild-type p53 gene, the protein function may be lost because of overexpression of Murine Double Minute 2 (MDM2). MDM2 targets p53 for ubiquitylation and proteasomal degradation. p53 reactivation through MDM2 inhibitors seems to be a promising strategy to sensitize p53 wild-type cancer cells to apoptosis. Moreover, additional p53-independent molecular functions of MDM2, such as neoangiogenesis promotion, have been suggested. Thus, MDM2 might be a target for anticancer treatment because of its antiapoptotic and proangiogenetic role. Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumor where wild-type p53 might be present. The present review gives a complete landscape about the role of MDM2 in cancer pathogenesis, prognosis and treatment, with particular focus on Malignant Pleural Mesothelioma.}, }
@article {pmid26351019, year = {2015}, author = {Conti, S and Minelli, G and Ascoli, V and Marinaccio, A and Bonafede, M and Manno, V and Crialesi, R and Straif, K}, title = {Peritoneal mesothelioma in Italy: Trends and geography of mortality and incidence.}, journal = {American journal of industrial medicine}, volume = {58}, number = {10}, pages = {1050-1058}, doi = {10.1002/ajim.22491}, pmid = {26351019}, issn = {1097-0274}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Databases, Factual ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/*epidemiology ; Registries ; Young Adult ; }, abstract = {INTRODUCTION: Peritoneal mesothelioma, a very rare and lethal malignancy, has not been investigated as extensively as pleural mesothelioma, although the role of asbestos exposure in its occurrence is well-known. Data from Italy are relevant, as it was the largest European asbestos producer, and asbestos was widely used in many economic activities.<br><br>METHODS: A population-based mortality and incidence analysis was performed in Italy. Data sources were the National Multiple-causes-of-death Database (1995-2010) and the Italian Mesothelioma Register (1993-2008).<br><br>RESULTS: We found an increasing trend of age standardized mortality rates in men, but no clear trend in women; moreover, we showed significant risks of death in several northern regions, formerly heavy asbestos users; finally, mortality/incidence ratios similar for both genders (about 0.8) were estimated.<br><br>CONCLUSIONS: The study, based on national data, showed a higher risk of mortality from and incidence of peritoneal mesothelioma in areas with formerly heavy exposure to asbestos.}, }
@article {pmid26320384, year = {2015}, author = {Algranti, E and Saito, CA and Carneiro, AP and Moreira, B and Mendonça, EM and Bussacos, MA}, title = {The next mesothelioma wave: mortality trends and forecast to 2030 in Brazil.}, journal = {Cancer epidemiology}, volume = {39}, number = {5}, pages = {687-692}, doi = {10.1016/j.canep.2015.08.007}, pmid = {26320384}, issn = {1877-783X}, mesh = {Adult ; Asbestos/adverse effects ; Brazil/epidemiology ; *Developing Countries ; Female ; Forecasting ; Humans ; Incidence ; Industrial Development/trends ; Male ; Medical Oncology/*trends ; Mesothelioma/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; }, abstract = {BACKGROUND: There are limited data on mesothelioma mortality in industrializing countries, where, at present, most of the asbestos consumption occurs.<br><br>OBJECTIVES: To analyze temporal trends and to calculate mortality rates from mesothelioma and cancer of the pleura in Brazil from 2000 to 2012 and to estimate future mortality rates.<br><br>METHODS: We retrieved records of deaths from mesothelioma (ICD-10C45) and cancer of the pleura (ICD-10C38.4) from 2000 to 2012 in adults aged 30 years and over. Crude and age-standardized mortality rates (ASMR) were calculated. Rate ratios of mean crude mortality for selected municipalities were compared to the Brazilian rate. A regression was carried out of the annual number of deaths against asbestos consumption using a Generalized Additive Model (GAM). The best model was chosen to estimate the future burden and peak period of deaths.<br><br>RESULTS: There were 929C45 and 1379 C38.4 deaths. The ratio of men to women for C45 was 1.4. A positive trend in C45 numbers was observed in Brazil (p=0.0012), particularly in S&#xe3;o Paulo (p=0.0004) where ASMRs presented an increasing linear trend (p=0.0344). Selected municipalities harboring asbestos manipulation presented 3.7-11 fold rate ratios of C45 compared to Brazil. GAM presented best fits for latencies of 34 years or more. It is estimated that the peak incidence of C45 mortality will occur between 2021 and 2026.<br><br>CONCLUSIONS: The observed ASMRs and the gender ratio close to 1 suggest underreporting. Even so, deaths are increasing and mesothelioma clusters were identified. Compared to industrialized countries Brazil displays a 15-20 year lag in estimated peak mesothelioma mortality which is consistent with the lag of asbestos peak consumption in the country.}, }
@article {pmid26318158, year = {2016}, author = {Garabrant, DH and Alexander, DD and Miller, PE and Fryzek, JP and Boffetta, P and Teta, MJ and Hessel, PA and Craven, VA and Kelsh, MA and Goodman, M}, title = {Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {1}, pages = {8-26}, doi = {10.1093/annhyg/mev060}, pmid = {26318158}, issn = {1475-3162}, mesh = {Asbestos/adverse effects ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology ; *Motor Vehicles ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Risk Assessment ; }, abstract = {BACKGROUND: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis.<br><br>METHODS: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I (2) estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures.<br><br>RESULTS: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H <0.001, I (2) = 62.90). A similar SRRE was observed among the five Tier 1 studies with the highest quality ratings (SRRE = 0.76, 95% CI: 0.46-1.25), with no heterogeneity among studies (P-H = 0.912, I (2) = 0.00). Meta-analysis of the Tier 2 (n = 5) and Tier 3 (n = 6) studies resulted in SRREs of 1.09 (95% CI: 0.76-1.58) and 0.73 (95% CI: 0.49-1.08), respectively. Restricting the analysis to Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72-1.29). The SRRE specific to brake work (n = 4) was 0.64 (95% CI: 0.38-1.09).<br><br>CONCLUSIONS: This meta-analysis of the epidemiologic studies provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma.}, }
@article {pmid26316950, year = {2015}, author = {Saint-Pierre, MD and Pease, C and Mithoowani, H and Zhang, T and Nicholas, GA and Laurie, SA and Wheatley-Price, P}, title = {Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy.}, journal = {Lung cancer international}, volume = {2015}, number = {}, pages = {590148}, pmid = {26316950}, issn = {2090-3197}, abstract = {Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P = 0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.}, }
@article {pmid26310516, year = {2015}, author = {Imai, M and Hino, O}, title = {Environmental carcinogenesis - 100th anniversary of creating cancer.}, journal = {Cancer science}, volume = {106}, number = {11}, pages = {1483-1485}, pmid = {26310516}, issn = {1349-7006}, mesh = {Anniversaries and Special Events ; Environmental Exposure/*adverse effects/*history ; History, 20th Century ; History, 21st Century ; Humans ; Neoplasms/*etiology/*history ; }, abstract = {Asbestos is an environmental carcinogen, and asbestos-related diseases represent a global-scale environmental issue. Mesothelioma is an aggressive, malignant tumor that initially progresses along the surfaces of the pleura and peritoneum that is chiefly attributed to asbestos exposure. X-rays are commonly used for tumor screening in populations at risk for developing this cancer. We previously reported that the N-terminal of mesothelin may be a useful blood marker for early diagnosis method for mesothelioma and since then developed an N-terminal of mesothelin ELISA kit in collaboration with IBL Co., Ltd. and confirmed its utility as a diagnostic system for mesothelioma. Recently, we performed a large-scale research screening for mesothelioma and showed that it is a good model for early diagnosis in at-risk populations. The year 2015 is the 100th anniversary of Yamagiwa's great work on coaltar-induced carcinogenesis by formative stimulation in 1915 and the 10th year since 2005, "Kubota shock", people recognized that asbestos induces mesothelioma. We dedicate this review to this memorial year for environmental carcinogenesis.}, }
@article {pmid26308799, year = {2015}, author = {Bononi, A and Napolitano, A and Pass, HI and Yang, H and Carbone, M}, title = {Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies.}, journal = {Expert review of respiratory medicine}, volume = {9}, number = {5}, pages = {633-654}, pmid = {26308799}, issn = {1747-6356}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; CA120355/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; R01 CA160715-0A/CA/NCI NIH HHS/United States ; 1R01 CA198138-01/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Immunotherapy/methods ; Lung Neoplasms/etiology/*genetics/physiopathology/*therapy ; Mesothelioma/etiology/*genetics/physiopathology/*therapy ; Mesothelioma, Malignant ; *Molecular Targeted Therapy/methods ; Peritoneal Neoplasms/etiology/genetics/physiopathology/therapy ; Pleural Neoplasms/etiology/*genetics/physiopathology/*therapy ; }, abstract = {Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: molecular targeted approaches, that is the inhibition of vascular endothelial growth factor with bevacizumab; immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing.}, }
@article {pmid26304776, year = {2015}, author = {Boulanger, M and Morlais, F and Bouvier, V and Galateau-Salle, F and Guittet, L and Marquignon, MF and Paris, C and Raffaelli, C and Launoy, G and Clin, B}, title = {Digestive cancers and occupational asbestos exposure: incidence study in a cohort of asbestos plant workers.}, journal = {Occupational and environmental medicine}, volume = {72}, number = {11}, pages = {792-797}, doi = {10.1136/oemed-2015-102871}, pmid = {26304776}, issn = {1470-7926}, mesh = {Adult ; Asbestos ; Cohort Studies ; Digestive System/*pathology ; Digestive System Neoplasms/epidemiology/*etiology ; Esophageal Neoplasms/epidemiology/etiology ; Female ; France/epidemiology ; Humans ; Incidence ; Intestinal Neoplasms/epidemiology/*etiology ; Liver Neoplasms/epidemiology/etiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/epidemiology/etiology ; Sex Factors ; }, abstract = {OBJECTIVE: The aim of our study was to estimate the incidence of digestive cancers within a cohort of asbestos-exposed workers.<br><br>METHODS: Our study was based on a cohort of 2024 participants occupationally exposed to asbestos. The incidence of digestive cancers was calculated from 1 January 1978 to 31 December 2009 and compared with levels among the local general population using Standardised Incidence Ratios (SIRs). Asbestos exposure was assessed using the company's job-exposure matrix.<br><br>RESULTS: 119 cases of digestive cancer were observed within our cohort, for an expected number of 77 (SIR=1.54 (1.28 to 1.85)). A significantly elevated incidence was observed for peritoneal mesothelioma, particularly in women. Significantly elevated incidences were also observed among men for: all digestive cancers, even when excluding peritoneal mesothelioma (SIR=1.50 (1.23 to 1.82)), oesophageal cancer (SIR=1.67 (1.08 to 2.47)) and liver cancer (SIR=1.85 (1.09 to 2.92)). Concerning colorectal cancer, a significant excess of risk was observed for men with exposure duration above 25&#x2005;years (SIR=1.75 (1.05 to 2.73)).<br><br>CONCLUSIONS: Our results are in favour of a link between long-duration asbestos exposure and colorectal cancer in men. They also suggest a relationship between asbestos exposure and cancer of the oesophagus in men. Finally, our results suggest a possible association with small intestine and liver cancers in men.}, }
@article {pmid26297204, year = {2015}, author = {Lemjabbar-Alaoui, H and Hassan, OU and Yang, YW and Buchanan, P}, title = {Lung cancer: Biology and treatment options.}, journal = {Biochimica et biophysica acta}, volume = {1856}, number = {2}, pages = {189-210}, pmid = {26297204}, issn = {0006-3002}, support = {U01 CA168878/CA/NCI NIH HHS/United States ; 5U01 CA168878/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Drug Therapy/*trends ; Genetic Predisposition to Disease/genetics ; Humans ; Lung Neoplasms/*physiopathology/*therapy ; Molecular Targeted Therapy/*trends ; Neoplasm Proteins/genetics/*metabolism ; Radiotherapy/*trends ; Treatment Outcome ; }, abstract = {Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation.}, }
@article {pmid26290869, year = {2015}, author = {Lin, CK and Chang, YY and Wang, JD and Lee, LJ}, title = {Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {678598}, pmid = {26290869}, issn = {2314-6141}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/*epidemiology ; Retrospective Studies ; Taiwan ; }, abstract = {OBJECTIVE: This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.<br><br>METHODS: All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.<br><br>RESULTS: The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25-8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19-16.89) for the workers employed for more than 20 years in asbestos-related factories.<br><br>CONCLUSIONS: This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.}, }
@article {pmid26265669, year = {2016}, author = {Ferrante, D and Mirabelli, D and Tunesi, S and Terracini, B and Magnani, C}, title = {Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {3}, pages = {147-153}, doi = {10.1136/oemed-2015-102803}, pmid = {26265669}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; *Carcinogens ; Case-Control Studies ; Construction Industry ; Construction Materials/adverse effects ; Environmental Exposure/*adverse effects ; Environmental Pollution/*adverse effects ; Female ; Housing ; Humans ; Incidence ; Italy ; Logistic Models ; Lung/pathology ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Odds Ratio ; Pleural Neoplasms/*etiology ; Risk Assessment ; }, abstract = {OBJECTIVES: Casale Monferrato (north west Italy) is an area with an exceptionally high incidence of mesothelioma caused by asbestos contamination at work and in the general environment from the asbestos-cement Eternit plant that was operational until 1986. The purpose of this study was to quantify the association between pleural malignant mesothelioma (PMM) and asbestos cumulative exposure using individual assessment of environmental and domestic exposure, as well as of occupational exposure.<br><br>METHODS: This population-based case-control study included cases of PMM diagnosed between January 2001 and June 2006 among residents in the Casale Monferrato Local Health Authority. Population controls were randomly sampled, matched by age and sex to cases. Cumulative exposure was estimated to account for the lifelong exposure history. Analyses were conducted using unconditional logistic regression models adjusting for gender, age at diagnosis and type of interview (direct or proxy respondents).<br><br>RESULTS: 200 PMM cases of 223 eligible cases (89.7%) and 348 (63%) of 552 eligible controls accepted to be interviewed. ORs increased with cumulative exposure index (p<0.0001) from 4.4 (CI 95% 1.7 to 11.3) (<1&#x2005;f/mL-years) to 62.1 (CI 95% 22.2 to 173.2) (&#x2265;10&#x2005;f/mL-years). Among subjects never occupationally exposed, corresponding ORs were 3.8 (CI 95% 1.3 to 11.1) and 23.3 (CI 95% 2.9 to 186.9) (reference: background level of asbestos exposure). ORs of about 2, statistically significant, were observed for domestic exposure and for living in houses near buildings with large asbestos cement parts.<br><br>CONCLUSIONS: Risk of PMM increased with cumulative asbestos exposure and also in analyses limited to subjects non-occupationally exposed. Our results also provide indication of risk associated with common sources of environmental exposure and are highly relevant for the evaluation of residual risk after the cessation of asbestos industrial use.}, }
@article {pmid26263483, year = {2015}, author = {Kirschner, MB and Pulford, E and Hoda, MA and Rozsas, A and Griggs, K and Cheng, YY and Edelman, JJ and Kao, SC and Hyland, R and Dong, Y and László, V and Klikovits, T and Vallely, MP and Grusch, M and Hegedus, B and Dome, B and Klepetko, W and van Zandwijk, N and Klebe, S and Reid, G}, title = {Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis.}, journal = {British journal of cancer}, volume = {113}, number = {6}, pages = {963-969}, pmid = {26263483}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor/*metabolism ; Case-Control Studies ; Extracellular Matrix Proteins/*metabolism ; Female ; Heterografts ; Humans ; Male ; Mesothelioma/*diagnosis/*metabolism ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Proteins/*metabolism ; Pleural Effusion/metabolism ; Pleural Neoplasms/*diagnosis/*metabolism ; Prognosis ; }, abstract = {BACKGROUND: Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies.<br><br>METHODS: ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively.<br><br>RESULTS: FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (95% CI: 41.5-71.0), respectively). Although FBLN3 levels in pleural effusions were not significantly different between cases and controls, FBLN3 levels in pleural effusion fluid were found to be independently associated with prognosis (hazard ratio of 9.92 (95% CI: 2.14-45.93)).<br><br>CONCLUSIONS: These data confirm the potential prognostic value of pleural effusion FBLN3, but question the diagnostic value of this protein in MPM patients.}, }
@article {pmid26259877, year = {2015}, author = {Yamagishi, T and Fujimoto, N and Nishi, H and Miyamoto, Y and Hara, N and Asano, M and Fuchimoto, Y and Wada, S and Kitamura, K and Ozaki, S and Kishimoto, T}, title = {Prognostic significance of the lymphocyte-to-monocyte ratio in patients with malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {90}, number = {1}, pages = {111-117}, doi = {10.1016/j.lungcan.2015.07.014}, pmid = {26259877}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Female ; Humans ; Inflammation/blood/pathology ; Lung Neoplasms/*blood/*pathology/therapy ; Lymphocytes/*pathology ; Male ; Mesothelioma/*blood/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Monocytes/*pathology ; Neutrophils/pathology ; Prognosis ; ROC Curve ; Retrospective Studies ; }, abstract = {OBJECTIVES: Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Several inflammation-based prognostic scores including the lymphocyte-to-monocyte ratio (LMR), Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) reportedly predict survival in many malignancies, while the role of LMR in MPM remains unclear. The aim of this study was to evaluate the clinical value of LMR and to compare the prognostic value of these inflammation-based scores in predicting overall survival (OS) in MPM.<br><br>MATERIALS AND METHODS: One hundred and fifty patients with histologically proven MPM were included in this retrospective study. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for OS. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system.<br><br>RESULTS: An elevated LMR was significantly associated with prolonged OS. Patients with LMR <2.74 had significantly poor survival compared with LMR &#x2265;2.74 (median, 5.0 versus 14.0 months; p=0.000). The LMR consistently had a higher AUC value at 6 months (0.722), 12 months (0.712), and 24 months (0.670), compared with other scores. Multivariate analysis showed that the LMR was independently associated with OS.<br><br>CONCLUSIONS: The LMR is an independent prognostic marker for OS in patients with MPM and is superior to other inflammation-based prognostic scores with respect to prognostic ability.}, }
@article {pmid26248240, year = {2015}, author = {Amorim, E}, title = {Solitary fibrous tumor of the pleura: 3 case reports.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {61}, number = {3}, pages = {207-208}, doi = {10.1590/1806-9282.61.03.207}, pmid = {26248240}, issn = {1806-9282}, mesh = {Humans ; Male ; Middle Aged ; *Solitary Fibrous Tumor, Pleural/pathology/surgery ; Thoracotomy ; }, abstract = {INTRODUCTION: solitary fibrous tumor of the pleura (SFTP) is a rare tumor arising from mesenchymatous cells in submesothelial pleural tissue which, unlike mesothelioma, is not related to asbestos or smoking.<br><br>METHODS: report of four patients who underwent surgical treatment for giant SFTP and review of the pertinent literature.<br><br>RESULTS: of the four patients operated, two presented symptoms including cough, chest pain and feeling of compression, whereas the other two subjects were asymptomatic. All patients underwent complete surgical resection by wide posterolateral thoracotomy, and surgical specimens removed with minimum bleeding. None of the cases required complementary lobectomy or segmentectomy. All tumors were histologically benign.<br><br>CONCLUSION: complete resection of the lesion is the treatment of choice in all SFTP cases. Prognosis of the benign lesion is excellent, although close follow-up is necessary. In the rarer, more aggressive forms, treatment may be complemented by adjunctive chemotherapy or radiotherapy, the benefits of which have yet to be confirmed.}, }
@article {pmid26246155, year = {2015}, author = {Emi, M and Yoshikawa, Y and Sato, C and Sato, A and Sato, H and Kato, T and Tsujimura, T and Hasegawa, S and Nakano, T and Hashimoto-Tamaoki, T}, title = {Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level.}, journal = {Journal of human genetics}, volume = {60}, number = {10}, pages = {647-649}, pmid = {26246155}, issn = {1435-232X}, mesh = {Asian People ; *Base Sequence ; *Chromosomal Instability ; Chromosomes, Human, Pair 3/*genetics ; *Exons ; Female ; Humans ; Japan ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; *Sequence Deletion ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-related malignancy arising from surface serosal cells of pleural and peritoneal cavities. Somatic mutations of BRCA1 associated protein-1 (BAP1) gene were recently found in MM as well as in uveal melanoma and kidney cancer among the Caucasian and Japanese people. However, frequency of mutations varies among the reported studies, which might be due to presence of undetected gross rearrangements of BAP1 gene that might escape detection by sequencing strategy. We investigated the presence and frequency of gross genomic rearrangements in the BAP1 gene by multiplex ligation-dependent probe amplification (MLPA) in 17 Japanese cases of MM tumors. We found five tumors with partial deletion of BAP1 gene; each tumors displayed partial deletion of exons 1-4 (MM39), exons 1-5 (MM48), exons 11-17 (MM57), exons 1-15 (MM19) and exons 1-16 (MM21). Two tumors (MM34, MM14) had biallelic deletion and four tumors (MM29, MM35, MM45 and MM56) had monoallelic deletion of entire BAP1 gene. Therefore, MLPA analysis revealed large gene rearrangements of BAP1 gene in 65% of MM (11/17). Unusually high frequency of large deletions indicates that the 3p21 chromosomal region surrounding BAP1 gene is structurally unstable. MLPA was useful in characterizing both monoallelic and biallelic deletion of BAP1 gene precisely at exon level.}, }
@article {pmid26240051, year = {2016}, author = {Thellung, S and Favoni, RE and Würth, R and Nizzari, M and Pattarozzi, A and Daga, A and Florio, T and Barbieri, F}, title = {Molecular Pharmacology of Malignant Pleural Mesothelioma: Challenges and Perspectives From Preclinical and Clinical Studies.}, journal = {Current drug targets}, volume = {17}, number = {7}, pages = {824-849}, doi = {10.2174/1389450116666150804110714}, pmid = {26240051}, issn = {1873-5592}, mesh = {Animals ; Antineoplastic Agents/pharmacology/*therapeutic use ; Clinical Trials as Topic ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Neoplastic Stem Cells/*drug effects/pathology ; Pleural Neoplasms/*drug therapy/pathology ; Proto-Oncogene Mas ; Signal Transduction/drug effects ; }, abstract = {Malignant pleural mesothelioma (MPM) is one of the deadliest and most heterogeneous tumors, highly refractory to multimodal therapeutic approach, including surgery, chemo- and radiotherapy. Preclinical and clinical studies exploring the efficacy of drugs targeting tyrosine kinases, angiogenesis and histone deacetylases, did not fulfil the expected clinical benefits. Thus, novel molecular targets should be identified from a definite knowledge of the unique biology and most relevant transduction pathways of MPM cells. Cancer stem cells (CSCs) are a subset of malignant precursors responsible for initiation, progression, resistance to cytotoxic drugs, recurrence and metastatic diffusion of tumor cells. CSCs are putative driving factors for MPM development and contribute to its clinical and biological heterogeneity; hence, targeted eradication of CSCs represents an ineludible goal to counteract MPM aggressiveness. In this context, innovative preclinical models could be exploited to identify novel intracellular pathway inhibitors able to target CSC viability. Novel drug targets have been identified among key factors responsible for the oncogenic transformation of mesothelial cells, often directly induced by asbestos. These include mitogenic and anti-apoptotic signaling that may also be activated by autocrine and paracrine cytokine pathways controlling cell plasticity. Both signaling pathways affecting proto-oncogene and transcription factor expression, or genetic and epigenetic alterations, such as mutations in cell cycle genes and silencing of tumor suppressor genes, represent promising disease-specific targets. In this review we describe current knowledge of MPM cell biology, focusing on potential targets to be tested in pharmacological studies, and highlighting results and challenges of clinical translation.}, }
@article {pmid26236392, year = {2015}, author = {Borelli, V and Moura, RR and Trevisan, E and Crovella, S}, title = {NLRP1 and NLRP3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population-based autopsy study from North East Italy.}, journal = {Infectious agents and cancer}, volume = {10}, number = {}, pages = {26}, pmid = {26236392}, issn = {1750-9378}, abstract = {NRLP1 (rs12150220, rs9889625, rs9900356, rs6502867, rs2670660) and NLRP3 (rs35829419, rs10754558) polymorphisms have been analyzed in 69 subjects with documented asbestos exposure and death for malignant pleural mesothelioma and 59 patients with documented asbestos exposure but death for other causes, all from a North East Italy. No association was found between NLRP1 and NLRP3 polymorphisms and susceptibility to develop mesothelioma using the general, dominant or recessive models. Also haplotype analysis did not reveal any significant association with mesothelioma. Our findings, being controversial with respect to another study on Italian patients, do suggest the need of further studies to unravel the contribution of NLRP1 and NLRP3 in susceptibility to mesothelioma.}, }
@article {pmid26230599, year = {2015}, author = {Roggli, VL}, title = {The So-called Short-Fiber Controversy: Literature Review and Critical Analysis.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {139}, number = {8}, pages = {1052-1057}, doi = {10.5858/arpa.2014-0466-RA}, pmid = {26230599}, issn = {1543-2165}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/*etiology ; Mineral Fibers/*adverse effects/classification ; Pulmonary Fibrosis/*etiology ; }, abstract = {CONTEXT: Numerous articles in the scientific literature indicate that pathogenic fibers with respect to asbestos-related diseases are those that exceed 5 μm in length. Nonetheless, some authors have expressed concerns regarding pathogenicity of shorter fibers.<br><br>OBJECTIVE: To review the scientific evidence regarding pathogenicity (or lack thereof) of fibers less than or equal to 5 &#x3bc;m in length, with particular attention to publications indicating that such fibers might be hazardous.<br><br>DATA SOURCES: The scientific literature was reviewed for experimental animal studies and human studies that address the role of fiber size in causation of disease. Sources included original studies, as well as review articles related to the topic.<br><br>CONCLUSIONS: Experimental animal studies involving inhalation of fibers have demonstrated that fibers greater than 5 &#x3bc;m in length are associated with both pulmonary fibrosis (ie, asbestosis) and malignancies (carcinoma of the lung and mesothelioma). There is no convincing evidence for a pathogenic effect for fibers that are 5 &#x3bc;m or less in length. Fiber analyses of human lung tissue samples provide further support for pathogenicity of long fibers, particularly the more biopersistent amphibole fibers. Similar observations have been reported for nonasbestos mineral fibers. Concerns expressed by some authors (eg, the greater abundance of short fibers) do not alter these conclusions. Similarly, in vitro studies demonstrating biological activity of short fibers do not override inhalational studies of whole animals or the epidemiological findings in humans.}, }
@article {pmid26229210, year = {2015}, author = {Ogunseitan, OA}, title = {The asbestos paradox: global gaps in the translational science of disease prevention.}, journal = {Bulletin of the World Health Organization}, volume = {93}, number = {5}, pages = {359-360}, pmid = {26229210}, issn = {1564-0604}, mesh = {Asbestos/*adverse effects/supply &amp; distribution ; Commerce ; Global Health ; *Health Policy ; Humans ; International Cooperation ; Interprofessional Relations ; Mesothelioma/*chemically induced/*prevention &amp; control ; Translational Research, Biomedical ; }, }
@article {pmid26222965, year = {2015}, author = {Frontario, SC and Loveitt, A and Goldenberg-Sandau, A and Liu, J and Roy, D and Cohen, LW}, title = {Primary Peritoneal Mesothelioma Resulting in Small Bowel Obstruction: A Case Report and Review of Literature.}, journal = {The American journal of case reports}, volume = {16}, number = {}, pages = {496-500}, pmid = {26222965}, issn = {1941-5923}, mesh = {Aged ; Female ; Humans ; Intestinal Obstruction/diagnosis/*etiology/therapy ; *Intestine, Small ; Lung Neoplasms/diagnostic imaging/*pathology/therapy ; Mesothelioma/diagnostic imaging/*pathology/therapy ; Mesothelioma, Malignant ; Peritoneal Neoplasms/diagnostic imaging/*pathology/therapy ; Radiography ; }, abstract = {BACKGROUND: Peritoneal mesothelioma is a rare malignancy that affects the serosal surfaces of the peritoneum. The peritoneum is the second most common site of mesothelium affected following the pleura. The aggressive nature and vague presentation pose many obstacles in not only diagnosis but also the treatment of patients with this disease.<br><br>CASE REPORT: We present a case of a 76-year-old woman who presented with small bowel obstruction secondary to carcinomatosis secondary to primary peritoneal mesothelioma. The patient had multiple risk factors with asbestos exposure and prior therapeutic radiation.<br><br>CONCLUSIONS: We discuss the highly varied and elusive presentation of peritoneal mesothelioma. Cumulative asbestos exposure, either directly or indirectly, remains the leading cause of mesothelioma. However, there are other non-asbestos etiologies. Small bowel obstruction often is a late-presenting symptom of widespread tumor burden. A concise review of the current diagnostic and surgical treatment of primary peritoneal mesothelioma demonstrates that early diagnosis and implementation remains vital.}, }
@article {pmid26211743, year = {2015}, author = {Minami, D and Takigawa, N and Kato, Y and Kudo, K and Isozaki, H and Hashida, S and Harada, D and Ochi, N and Fujii, M and Kubo, T and Ohashi, K and Sato, A and Tanaka, T and Hotta, K and Tabata, M and Toyooka, S and Tanimoto, M and Kiura, K}, title = {Downregulation of TBXAS1 in an iron-induced malignant mesothelioma model.}, journal = {Cancer science}, volume = {106}, number = {10}, pages = {1296-1302}, pmid = {26211743}, issn = {1349-7006}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Biomarkers, Tumor/metabolism ; Calbindin 2/metabolism ; Cell Cycle Proteins ; Cell Line, Tumor ; Chromosome Deletion ; Deoxyguanosine/analogs &amp; derivatives/genetics ; Down-Regulation ; Ferric Compounds ; Ferric Oxide, Saccharated ; Glucaric Acid ; Humans ; Iron/*toxicity ; Iron Overload/genetics ; Lung Neoplasms/*chemically induced/*genetics/pathology ; Male ; Membrane Glycoproteins/metabolism ; Mesothelioma/*chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Neoplasms, Experimental/etiology/genetics/pathology ; Nuclear Proteins/metabolism ; RNA Splicing Factors ; Rats ; Rats, Wistar ; Thromboxane-A Synthase/*genetics ; }, abstract = {Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising from mesothelial cells. Evidence suggests that the major pathology associated with asbestos-induced mesothelioma is local iron overload. In the present study, we induced iron-induced mesothelioma in rats based on previous reports. Ten Wistar rats were given ferric saccharate and nitrilotriacetate i.p. for 5 days a week. Five of the ten rats exhibited widespread mesotheliomas in the peritoneum and tunica vaginalis. The tumor cells showed positive immunostaining for calretinin, wilms tumor-1, podoplanin and the oxidative DNA marker 8-hydroxy-2'-deoxyguanosine. In three of the five rats with mesothelioma, array-based comparative genomic hybridization analysis identified a common chromosomal deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene. Downregulation of the TBXAS1 gene was confirmed using quantitative PCR. TBXAS1 gene expression was also reduced in three of four human malignant pleural mesothelioma cell lines compared with normal bronchial epithelial cells. Immunohistochemistry revealed that TBXAS1 expression was weakly positive and positive in five and three out of eight human malignant mesothelioma samples, respectively. In conclusion, TBXAS1 gene expression was downregulated in rats with iron-induced mesothelioma. The relationship between iron overload and TBXAS1 downregulation should be pursued further.}, }
@article {pmid26202904, year = {2015}, author = {Thomas, A and Chen, Y and Yu, T and Gill, A and Prasad, V}, title = {Distinctive clinical characteristics of malignant mesothelioma in young patients.}, journal = {Oncotarget}, volume = {6}, number = {18}, pages = {16766-16773}, pmid = {26202904}, issn = {1949-2553}, support = {//Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Asbestos/adverse effects ; Child ; Epithelium/*pathology ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*diagnosis/*epidemiology/surgery ; Male ; Mesothelioma/*diagnosis/*epidemiology/surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/*epidemiology/surgery ; Prognosis ; SEER Program ; Young Adult ; }, abstract = {Although considered a disease of the elderly, a subset of patients with mesothelioma are young (<40 years). The goal of this study was to understand their characteristics and outcomes. The Surveillance, Epidemiology, and End Results (SEER) database was used to extract mesothelioma cases (1990-2010). We modeled Kaplan-Meyer survival curves stratified by site of disease, and age of presentation. 2% (207 of 12345) of mesothelioma patients are young. Sex distribution is comparable among the young (51% males, 49% females); males predominated (78%, 22%) in the older cohort. Frequency of pleural and peritoneal mesothelioma are similar in the young (47%, 48% respectively); pleural disease predominated in the old (90%, 9%). Cancer-directed surgeries are more frequent in the young. Regardless of histologic subtype, young patients with pleural (11 vs. 8 months) and peritoneal (not reached vs. 10 months) mesothelioma had significantly improved overall survival. In multivariate analysis, younger age was an independent prognostic factor. Although rare, mesothelioma do occur in the young; their characteristics are distinct from those of older patients. Further studies are needed to understand the interplay between genetic susceptibility and mineral fiber carcinogenesis in the pathogenesis of mesothelioma in the young.}, }
@article {pmid26194352, year = {2015}, author = {Järvholm, B and Burdorf, A}, title = {Emerging evidence that the ban on asbestos use is reducing the occurrence of pleural mesothelioma in Sweden.}, journal = {Scandinavian journal of public health}, volume = {43}, number = {8}, pages = {875-881}, pmid = {26194352}, issn = {1651-1905}, mesh = {Adult ; *Asbestos/adverse effects ; Cohort Studies ; Construction Industry/*legislation &amp; jurisprudence ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/chemically induced/*epidemiology ; Registries ; Sweden/epidemiology ; }, abstract = {AIMS: Several countries have banned the use of asbestos. The future health impacts of previous use have been modeled but there are to our knowledge no convincing studies showing a decreased occurrence of asbestos-related diseases due to a ban. The aim of our study was to estimate the effects of the ban and other measures to decrease the use of asbestos in Sweden.<br><br>METHODS: The effect was measured through comparing the incidence of pleural malignant mesothelioma in birth cohorts who started to work before and after the decrease in the use of asbestos, i.e. in mid-1970s. Cases were identified through the Swedish Cancer Registry and the analysis was restricted to persons born in Sweden.<br><br>RESULTS: Men and women born 1955-79 had a decreased risk of malignant pleural mesothelioma compared to men and women born 1940-49 (RR 0.16, 95% CI 0.11-0.25; and RR 0.47, 95% CI 0.23-0.97 respectively). The decreased use of asbestos prevented each year about 10 cases in men and two cases in women below the age of 57 years in 2012.<br><br>CONCLUSIONS: The ban and decreased use of asbestos in Sweden can be measured today in birth cohorts that started their working career after the decrease.}, }
@article {pmid26193793, year = {2015}, author = {Lesterhuis, WJ and Rinaldi, C and Jones, A and Rozali, EN and Dick, IM and Khong, A and Boon, L and Robinson, BW and Nowak, AK and Bosco, A and Lake, RA}, title = {Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {12298}, pmid = {26193793}, issn = {2045-2322}, mesh = {Animals ; Antineoplastic Agents/pharmacology/*therapeutic use ; CTLA-4 Antigen/immunology ; Drug Combinations ; Drug Repositioning ; Drug Synergism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; *Immunotherapy ; Mesothelioma/*drug therapy/genetics/*immunology ; Mice, Inbred BALB C ; Remission Induction ; }, abstract = {Cancer immunotherapy has shown impressive results, but most patients do not respond. We hypothesized that the effector response in the tumour could be visualized as a complex network of interacting gene products and that by mapping this network we could predict effective pharmacological interventions. Here, we provide proof of concept for the validity of this approach in a murine mesothelioma model, which displays a dichotomous response to anti-CTLA4 immune checkpoint blockade. Network analysis of gene expression profiling data from responding versus non-responding tumours was employed to identify modules associated with response. Targeting the modules via selective modulation of hub genes or alternatively by using repurposed pharmaceuticals selected on the basis of their expression perturbation signatures dramatically enhanced the efficacy of CTLA4 blockade in this model. Our approach provides a powerful platform to repurpose drugs, and define contextually relevant novel therapeutic targets.}, }
@article {pmid26192180, year = {2015}, author = {Wu, WT and Lin, YJ and Li, CY and Tsai, PJ and Yang, CY and Liou, SH and Wu, TN}, title = {Cancer Attributable to Asbestos Exposure in Shipbreaking Workers: A Matched-Cohort Study.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0133128}, pmid = {26192180}, issn = {1932-6203}, mesh = {Aged ; Asbestos/*toxicity ; Cohort Studies ; Esophageal Neoplasms/epidemiology/etiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Male ; Middle Aged ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/*etiology ; *Occupational Exposure ; Proportional Hazards Models ; Risk Assessment ; Risk Factors ; Taiwan/epidemiology ; }, abstract = {PURPOSE: Long-term follow-up studies of asbestos-related cancer in shipbreaking workers are lacking. This study examines the relationship between cancer incidence and asbestos exposure among former Taiwan shipbreaking workers.<br><br>METHODS: A total of 4,427 shipbreaking workers and 22,135 population-based matched controls were successfully followed in this study. The study cohort was linked to the Taiwan Cancer Registry for new cancer cases. The adjusted hazard ratio (aHR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores (TEP) for asbestos.<br><br>RESULTS: Follow-up generated 109,932 person-years, with 940 deaths and 436 cancer cases, among 4,427 shipbreaking workers from 1985 to 2008. The high asbestos exposure group also had a statistically significant increase in the risk of overall cancer (aHR= 1.71; 95% CI: 1.42-2.05), esophagus cancer (aHR= 2.31; 95% CI: 1.00-5.41), liver and intrahepatic bile duct cancer (aHR= 1.60; 95% CI: 1.08-2.36), and trachea, bronchus, and lung cancer (aHR= 3.08; 95% CI: 1.80-5.25). Mesothelioma cases were found in the high asbestos exposure group. Moreover, overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer were seen in a dose-dependent relationship with asbestos exposure.<br><br>CONCLUSIONS: This study presented the elevated trend of asbestos exposure with cancer incidence for overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer among shipbreaking workers. Those workers previously exposed to asbestos should receive persistent monitoring in order to early detect adverse health outcomes.}, }
@article {pmid26184317, year = {2015}, author = {Felley-Bosco, E and Opitz, I and Meerang, M}, title = {Hedgehog Signaling in Malignant Pleural Mesothelioma.}, journal = {Genes}, volume = {6}, number = {3}, pages = {500-511}, pmid = {26184317}, issn = {2073-4425}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo) or glioma-associated protein transcription factors (Gli) have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition.}, }
@article {pmid26179668, year = {2016}, author = {Loharamtaweethong, K and Puripat, N and Aoonjai, N and Sutepvarnon, A and Bandidwattanawong, C}, title = {Anaplastic lymphoma kinase (ALK) translocation in paediatric malignant peritoneal mesothelioma: a case report of novel ALK-related tumour spectrum.}, journal = {Histopathology}, volume = {68}, number = {4}, pages = {603-607}, doi = {10.1111/his.12779}, pmid = {26179668}, issn = {1365-2559}, mesh = {Anaplastic Lymphoma Kinase ; Child ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Microscopy, Electron, Transmission ; Peritoneal Neoplasms/*genetics/*pathology ; Polymerase Chain Reaction ; Receptor Protein-Tyrosine Kinases/*genetics ; Translocation, Genetic ; }, abstract = {AIMS: To report a case of paediatric malignant peritoneal mesothelioma (MPM) with evidence of anaplastic lymphoma kinase (ALK) translocation.<br><br>METHODS AND RESULTS: We describe a 10-year-old girl who presented with abdominal pain and progressive abdominal distension. She had no history of asbestos exposure. Histopathological, immunohistochemical and ultrastructural analyses were performed and&#xa0;showed a biphasic malignant mesothelioma. In addition, we also studied on a selected set of immunomarkers which may be the potential therapeutic molecular targets including ALK, c-kit (CD117), epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2)/neu, as well as corresponding molecular analysis. Consequently, we identified ALK expression by immunohistochemistry, together with evidence of ALK translocation by fluorescent in-situ hybridization (FISH) analysis.<br><br>CONCLUSIONS: Paediatric MPM is associated with ALK translocation in our case. The results may open up a new avenue for the study of molecular genesis of paediatric malignant mesothelioma in the future and help to determine whether patients MMs with ALK translocation would benefit from ALK inhibitor treatment.}, }
@article {pmid26174987, year = {2015}, author = {Burkin, DJ and Fontelonga, TM}, title = {Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients.}, journal = {The Journal of pathology}, volume = {237}, number = {3}, pages = {282-284}, doi = {10.1002/path.4587}, pmid = {26174987}, issn = {1096-9896}, mesh = {Antigens, CD/*metabolism ; *Cell Movement ; *Epigenesis, Genetic ; Humans ; Integrin alpha Chains/*metabolism ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Pleural Neoplasms/*metabolism ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {Mesothelioma is a disease of pleural cells lining the lungs which is often caused by exposure to asbestos. The molecular mechanism(s) that regulate the transformation of pleural mesothelioma cells to a migratory and malignant phenotype are unclear. In recent work published in this journal, Laszlo et al performed a set of elegant experiments to identify a key molecular mechanism that may explain the aggressive nature of this disease. Using patient-derived mesothelioma cells with high versus low migratory activity, the authors conducted a genome-wide expression analysis. They identified a significant reduction in ITGA7 expression only in highly migratory malignant pleural mesothelioma cells and showed that loss of ITGA7 expression was associated with methylation of the promoter. Forced expression of integrin α7 reversed the migratory phenotype of these cells. Finally, the authors identified a strong correlation between ITGA7 expression and patient survival. Together, these results identify expression of integrin α7 as a molecular mechanism for the aggressive migratory transformation of mesothelioma and identify a potentially novel diagnostic and therapeutic target.}, }
@article {pmid26163973, year = {2015}, author = {Leuzzi, G and Rea, F and Spaggiari, L and Marulli, G and Sperduti, I and Alessandrini, G and Casiraghi, M and Bovolato, P and Pariscenti, G and Alloisio, M and Infante, M and Pagan, V and Fontana, P and Oliaro, A and Ruffini, E and Ratto, GB and Leoncini, G and Sacco, R and Mucilli, F and Facciolo, F}, title = {Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis.}, journal = {The Annals of thoracic surgery}, volume = {100}, number = {3}, pages = {890-897}, doi = {10.1016/j.athoracsur.2015.04.087}, pmid = {26163973}, issn = {1552-6259}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*mortality/*surgery ; Middle Aged ; Pleural Neoplasms/*mortality/*surgery ; *Pneumonectomy/methods ; Prognosis ; Retrospective Studies ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score.<br><br>METHODS: From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using &#x3c7;(2), Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model.<br><br>RESULTS: Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free survival times were 60 (95% confidence interval [CI], 51 to 69), 63 (95% CI, 54 to 72), and 49 months (95% CI, 39 to 58), respectively. At multivariate analysis, age (odds ratio, 0.51; 95% CI, 0.31 to 0.82), epithelioid histology (odds ratio, 7.07; 95% CI, 1.56 to 31.93), no history of asbestos exposure (odds ratio, 3.13; 95% CI, 1.13 to 8.66), and the ratio between metastatic and resected lymph nodes less than 22% (odds ratio, 4.12; 95% CI, 1.68 to 10.12) were independent predictors of LTS. According to these factors, we created a scoring system for LTS that allowed us to correctly predict overall, cancer-specific, and disease-free survival in the total sample, obtaining two different groups with favorable or poor prognosis (area under the curve, 0.74; standard error, 0.04; p < 0.0001).<br><br>CONCLUSIONS: Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually, tailor postoperative treatment.}, }
@article {pmid26161391, year = {2015}, author = {Nishimura, Y and Kumagai-Takei, N and Matsuzaki, H and Lee, S and Maeda, M and Kishimoto, T and Fukuoka, K and Nakano, T and Otsuki, T}, title = {Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {238431}, pmid = {26161391}, issn = {2314-6141}, mesh = {Asbestos/*adverse effects ; Humans ; Inhalation Exposure/*adverse effects ; Killer Cells, Natural/*immunology ; Lung Neoplasms/*immunology ; Lymphocyte Culture Test, Mixed ; Mesothelioma/*immunology ; Mesothelioma, Malignant ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme(+) cells in CD8(+) lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8(+) lymphocytes may be stimulated by some kind of "nonself" cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma.}, }
@article {pmid26156324, year = {2015}, author = {Ak, G and Metintas, S and Akarsu, M and Metintas, M}, title = {The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {510}, pmid = {26156324}, issn = {1471-2407}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Deoxycytidine/administration &amp; dosage/adverse effects/analogs &amp; derivatives ; Female ; Humans ; Karnofsky Performance Status ; Lung Neoplasms/*drug therapy ; Male ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Middle Aged ; Organoplatinum Compounds/administration &amp; dosage/adverse effects ; Pemetrexed/administration &amp; dosage/adverse effects ; Pleural Neoplasms/*drug therapy ; Survival Analysis ; Gemcitabine ; }, abstract = {BACKGROUND: We aimed to evaluate the efficiency and safety of cis/carboplatin plus gemcitabine, which was previously used for mesothelioma but with no recorded proof of its efficiency, compared with cis/carboplatin plus pemetrexed, which is known to be effective in mesothelioma, in comparable historical groups of malignant pleural mesothelioma.<br><br>METHODS: One hundred and sixteen patients received cis/carboplatin plus pemetrexed (group 1), while 30 patients received cis/carboplatin plus gemcitabine (group 2) between June 1999 and June 2012. The two groups were compared in terms of median survival and adverse events to chemotherapy.<br><br>RESULTS: The mean ages of groups 1 and 2 were 60.7 and 60.8 years, respectively. Most of the patients (78.1%) had epithelial type tumors, and 47% of the patients had stage IV disease. There was no difference between the two groups in terms of age, gender, asbestos exposure, histology, stage, Karnofsky performance status, presence of pleurodesis, prophylactic radiotherapy, second-line chemotherapy and median hemoglobin and serum albumin levels. The median survival time from diagnosis to death or the last day of follow up with a 95% confidence interval was 12 &#xb1; 0.95 months (95% CI: 10.15-13.85) for group 1 and 11.0 &#xb1; 1.09 months (95% CI: 8.85-13.15) for group 2 (Log-Rank: 0.142; p = 0.706). The median survival time from treatment to death or the last day of follow-up with a 95% confidence interval was 11.0 &#xb1; 0.99 months (95% CI: 9.06-12.94) for group 1 and 11.0 &#xb1; 1.52 months (95% CI: 8.02-13.97) for group 2 (Log-Rank: 0.584; p = 0.445). The stage and Karnofsky performance status were found to be significant variables on median survival time by univariate analysis. After adjusting for the stage and Karnofsky performance status, the chemotherapy schema was not impressive on median survival time (OR: 0.837; 95% CI: 0.548-1.277; p = 0.409). The progression free survival was 7.0 &#xb1; 0.61 months for group I and 6.0 &#xb1; 1.56 months for group II (Log-Rank: 0.522; p = 0.470). The treatment was generally well tolerated, and the side effects were similar in both groups.<br><br>CONCLUSIONS: The study indicates that platinum-based gemcitabine is effective and a safe schema in malignant pleural mesothelioma. Further research should include large randomized phase III trials comparing these agents.}, }
@article {pmid26156176, year = {2015}, author = {Bruno, C and Bruni, B and Scondotto, S and Comba, P}, title = {Prevention of disease caused by fluoro-edenite fibrous amphibole: the way forward.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {51}, number = {2}, pages = {90-92}, doi = {10.4415/ANN_15_02_02}, pmid = {26156176}, issn = {2384-8553}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Carcinogens/*toxicity ; Environmental Monitoring ; Humans ; Mesothelioma/chemically induced/*prevention &amp; control ; Neoplasms/chemically induced/*prevention &amp; control ; Occupational Exposure/prevention &amp; control ; Pleural Neoplasms/epidemiology ; Sicily ; }, abstract = {Few months after the publication of the monographic section of Annali dell'Istituto Superiore di Sanità second issue of 2014 "Health impact of fibres with fluoro-edenitic composition", the carcinogenicity of fluoro-edenite was assessed by the International Agency for Research on Cancer (IARC) in the frame of Monograph 111. The IARC Working Group concluded that there is sufficient evidence in humans that exposure to fluoro-edenite fibrous amphibole causes mesothelioma, and sufficient evidence of carcinogenicity in experimental animals. Fluoro-edenite was allocated to Group 1 (the agent is carcinogenic to humans). Now, in view of the recent IARC evaluation, preventive action in Biancavilla requires an upgrade. First of all, environmental monitoring has to be further implemented. All operations of house cleaning should be performed employing wet tools, in order to avoid dust-raising. It is very important that environmental and biological monitoring be related to epidemiological surveillance. The recently approved act of the Sicilian Government concerning a plan of health interventions in Biancavilla will favour cooperation between national, regional and local health institutions with the common goal of improving the quality and appropriateness of diagnostic and therapeutics procedures offered by the health services.}, }
@article {pmid26152538, year = {2015}, author = {Petrucci, MS and De Lio, MC and D'Alò, D and Stracci, F and Masanotti, GM}, title = {Epidemiologic surveillance of mesothelioma in Umbria.}, journal = {Annali di igiene : medicina preventiva e di comunita}, volume = {27}, number = {3}, pages = {526-532}, doi = {10.7416/ai.2015.2043}, pmid = {26152538}, issn = {1120-9135}, mesh = {Asbestos/adverse effects ; Carcinogens/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/pathology ; Male ; Mesothelioma/*epidemiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/pathology ; Regression Analysis ; Sex Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is becoming a prominent health issue due to its low survival and for its increasing incidence in various countries. The objectives of this study were to evaluate epidemiological characteristics and trends of MM in the Umbrian Region for the period 2003-2013.<br><br>METHODS: All cases of MM reported to Umbrian Population Cancer Registry between 2003 and 2013. Incidence Annual Standardized Rates (ASRs) were analyzed for all histological types of MM. Estimated Annual Percent Change (APC) and joinpoint regression analysis were used to out light the time trend of MM. Geographical distribution of the relative risk for each municipality was calculated by Standardized Incidence Ratios SIRs.<br><br>RESULTS: 191 (156 males) MM cases were recorded in Umbrian residents in the period 2003-2013. Pleural mesothelioma affected 92.1% of the total. Gender ratio M/F was 5.9:1. ASRs for MM was 3.2 among men and 0.6 among women. Joinpoint analysis showed a decrease in females APC -8.4 (95% IC -33.7-26.6) and an increase in males APC 5.8 (95% IC -0.9-13.0). An occupational exposure was identified in 43.7% of females and in 90.7% of males.<br><br>CONCLUSIONS: The protracted cancer latency and the continued asbestos existence as environmental contaminant in existing buildings, as well as a carcinogenic risk for the workers involved in removing operations of material containing asbestos justifies the investment in a specific surveillance system. Also important would be to implement a national risk communication strategy addressed to the general population, environment surveillance of the high risk areas and guarantee that all workers involved that even may deal with asbestos are always fully equipped and trained, not only for their individual risk but also for the potential risk of non correct disposal.}, }
@article {pmid26150916, year = {2015}, author = {Reid, G}, title = {MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets.}, journal = {Journal of thoracic disease}, volume = {7}, number = {6}, pages = {1031-1040}, pmid = {26150916}, issn = {2072-1439}, abstract = {Malignant mesothelioma remains a difficult proposition in the clinic, with few accurate molecular markers available to guide diagnosis and patient management, and a dearth of effective treatments. Recent evidence implicates microRNAs-short non-coding RNAs involved in post-transcriptional regulation of gene expression-in mesothelioma biology. Emerging evidence suggests that exploring aberrant microRNA expression will not only improve our understanding of the disease, but will also lead to the identification of new molecular biomarkers and therapeutic targets.}, }
@article {pmid26150910, year = {2015}, author = {Batra, H and Antony, VB}, title = {Pleural mesothelial cells in pleural and lung diseases.}, journal = {Journal of thoracic disease}, volume = {7}, number = {6}, pages = {964-980}, pmid = {26150910}, issn = {2072-1439}, abstract = {During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and β-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-β, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need further exploration.}, }
@article {pmid26147229, year = {2015}, author = {Gao, Z and Hiroshima, K and Wu, X and Zhang, J and Shao, D and Shao, H and Yang, H and Yusa, T and Kiyokawa, T and Kobayashi, M and Shinohara, Y and Røe, OD and Zhang, X and Morinaga, K}, title = {Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women: Analysis of 28 cases in Southeast China.}, journal = {American journal of industrial medicine}, volume = {58}, number = {10}, pages = {1040-1049}, doi = {10.1002/ajim.22494}, pmid = {26147229}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; China/epidemiology ; Female ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*etiology ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/diagnosis/epidemiology/*etiology ; Occupational Exposure/*adverse effects/analysis/statistics &amp; numerical data ; Peritoneal Neoplasms/diagnosis/epidemiology/*etiology ; Pleural Neoplasms/diagnosis/epidemiology/*etiology ; Retrospective Studies ; Textile Industry ; }, abstract = {BACKGROUND: Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking.<br><br>METHODS: All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao People's Hospital were re-evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected.<br><br>RESULTS: Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%.<br><br>CONCLUSIONS: This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma.}, }
@article {pmid26142533, year = {2015}, author = {Paracha, UZ and Hayat, K and Ali, M and Qadir, MI}, title = {Review: New diagnostic and therapeutic avenues for mesothelioma.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {28}, number = {4}, pages = {1425-1432}, pmid = {26142533}, issn = {1011-601X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Complementary Therapies ; Genetic Therapy ; Humans ; Mesothelioma/*diagnosis/mortality/*therapy ; }, abstract = {Mesothelioma is a rare form of cancer affecting the mesothelium lining. It is usually caused by asbestos exposure or exposure to nanofibers. Median survival is less than one year in the mesothelioma patients. Due to its severity, there is a dire necessity to find out new diagnostic and therapeutic strategies. Some recent strategies could help us in fighting against mesothelioma. Diagnostic tools include a range of biomarkers or biotechnological procedure. Therapeutic tools include chemotherapeutic strategies along with immunotherapy, gene therapy and alternative therapy.}, }
@article {pmid26140232, year = {2015}, author = {Creaney, J and Ma, S and Sneddon, SA and Tourigny, MR and Dick, IM and Leon, JS and Khong, A and Fisher, SA and Lake, RA and Lesterhuis, WJ and Nowak, AK and Leary, S and Watson, MW and Robinson, BW}, title = {Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen.}, journal = {Oncoimmunology}, volume = {4}, number = {7}, pages = {e1011492}, pmid = {26140232}, issn = {2162-4011}, abstract = {A key to improving cancer immunotherapy will be the identification of tumor-specific "neoantigens" that arise from mutations and augment the resultant host immune response. In this study we identified single nucleotide variants (SNVs) by RNA sequencing of asbestos-induced murine mesothelioma cell lines AB1 and AB1-HA. Using the NetMHCpan 2.8 algorithm, the theoretical binding affinity of predicted peptides arising from high-confidence, exonic, non-synonymous SNVs was determined for the BALB/c strain. The immunoreactivity to 20 candidate mutation-carrying peptides of increased affinity and the corresponding wild-type peptides was determined using interferon-γ ELISPOT assays and lymphoid organs of non-manipulated tumor-bearing mice. A strong endogenous immune response was demonstrated to one of the candidate neoantigens, Uqcrc2; this response was detected in the draining lymph node and spleen. Antigen reactive cells were not detected in non-tumor bearing mice. The magnitude of the response to the Uqcrc2 neoantigen was similar to that of the strong influenza hemagglutinin antigen, a model tumor neoantigen. This work confirms that the approach of RNAseq plus peptide prediction and ELISPOT testing is sufficient to identify natural tumor neoantigens.}, }
@article {pmid26139392, year = {2015}, author = {Tunesi, S and Ferrante, D and Mirabelli, D and Andorno, S and Betti, M and Fiorito, G and Guarrera, S and Casalone, E and Neri, M and Ugolini, D and Bonassi, S and Matullo, G and Dianzani, I and Magnani, C}, title = {Gene-asbestos interaction in malignant pleural mesothelioma susceptibility.}, journal = {Carcinogenesis}, volume = {36}, number = {10}, pages = {1129-1135}, doi = {10.1093/carcin/bgv097}, pmid = {26139392}, issn = {1460-2180}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Female ; *Gene-Environment Interaction ; Genetic Association Studies ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Male ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/chemically induced/*genetics/pathology ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor.}, }
@article {pmid26134238, year = {2015}, author = {Baumann, F and Buck, BJ and Metcalf, RV and McLaurin, BT and Merkler, D and Carbone, M}, title = {Reply to "No Increased Risk for Mesothelioma in Relation to Natural-Occurring Asbestos in Southern Nevada".}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {7}, pages = {e64-5}, pmid = {26134238}, issn = {1556-1380}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*analysis ; Environmental Exposure/*analysis ; Female ; Humans ; *Inhalation Exposure ; Male ; Mesothelioma/*epidemiology ; }, }
@article {pmid26134237, year = {2015}, author = {Pinheiro, PS and Jin, H}, title = {No Increased Risk for Mesothelioma in Relation to Natural-Occurring Asbestos in Southern Nevada.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {7}, pages = {e62-3}, pmid = {26134237}, issn = {1556-1380}, support = {P20 GM103440/GM/NIGMS NIH HHS/United States ; }, mesh = {Asbestos/*analysis ; Environmental Exposure/*analysis ; Female ; Humans ; *Inhalation Exposure ; Male ; Mesothelioma/*epidemiology ; }, }
@article {pmid26125439, year = {2015}, author = {Williams, M and Kirschner, MB and Cheng, YY and Hanh, J and Weiss, J and Mugridge, N and Wright, CM and Linton, A and Kao, SC and Edelman, JJ and Vallely, MP and McCaughan, BC and Cooper, W and Klebe, S and Lin, RC and Brahmbhatt, H and MacDiarmid, J and van Zandwijk, N and Reid, G}, title = {miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {6}, number = {27}, pages = {23480-23495}, pmid = {26125439}, issn = {1949-2553}, mesh = {Adenocarcinoma/metabolism ; Animals ; Apoptosis ; Cell Line, Tumor ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Lung Neoplasms/genetics/*metabolism ; Mesothelioma/genetics/*metabolism ; Mesothelioma, Malignant ; Mice ; MicroRNAs/*genetics/*metabolism ; Myeloid Cell Leukemia Sequence 1 Protein/*genetics ; Necrosis ; Neoplasm Transplantation ; Pleural Neoplasms/genetics/*metabolism ; Prognosis ; RNA Interference ; Transfection ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention.}, }
@article {pmid26119930, year = {2016}, author = {Napolitano, A and Pellegrini, L and Dey, A and Larson, D and Tanji, M and Flores, EG and Kendrick, B and Lapid, D and Powers, A and Kanodia, S and Pastorino, S and Pass, HI and Dixit, V and Yang, H and Carbone, M}, title = {Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma.}, journal = {Oncogene}, volume = {35}, number = {15}, pages = {1996-2002}, pmid = {26119930}, issn = {1476-5594}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; P30CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; R01CA160715-0A/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/administration &amp; dosage/*toxicity ; Ascitic Fluid/chemistry ; Chemokines/analysis ; Cytokines/analysis ; Dose-Response Relationship, Drug ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Heterozygote ; Leukocytes/pathology ; Macrophages, Peritoneal/classification/physiology ; Male ; Mesothelioma/*etiology/genetics ; Mice ; Mice, Inbred C57BL ; Mineral Fibers/toxicity ; Peritoneal Neoplasms/*etiology/genetics ; Peritonitis/etiology/genetics ; Random Allocation ; Tumor Suppressor Proteins/deficiency/*genetics/physiology ; Ubiquitin Thiolesterase/deficiency/*genetics/physiology ; }, abstract = {Germline BAP1 mutations predispose to several cancers, in particular malignant mesothelioma. Mesothelioma is an aggressive malignancy generally associated with professional exposure to asbestos. However, to date, we found that none of the mesothelioma patients carrying germline BAP1 mutations were professionally exposed to asbestos. We hypothesized that germline BAP1 mutations might influence the asbestos-induced inflammatory response that is linked to asbestos carcinogenesis, thereby increasing the risk of developing mesothelioma after minimal exposure. Using a BAP1(+/-) mouse model, we found that, compared with their wild-type littermates, BAP1(+/-) mice exposed to low-dose asbestos fibers showed significant alterations of the peritoneal inflammatory response, including significantly higher levels of pro-tumorigenic alternatively polarized M2 macrophages, and lower levels of several chemokines and cytokines. Consistent with these data, BAP1(+/-) mice had a significantly higher incidence of mesothelioma after exposure to very low doses of asbestos, doses that rarely induced mesothelioma in wild-type mice. Our findings suggest that minimal exposure to carcinogenic fibers may significantly increase the risk of malignant mesothelioma in genetically predisposed individuals carrying germline BAP1 mutations, possibly via alterations of the inflammatory response.}, }
@article {pmid26115838, year = {2015}, author = {Stephens, RJ and Whiting, C and Cowan, K and , }, title = {Research priorities in mesothelioma: A James Lind Alliance Priority Setting Partnership.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {89}, number = {2}, pages = {175-180}, doi = {10.1016/j.lungcan.2015.05.021}, pmid = {26115838}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms/diagnosis/therapy ; *Mesothelioma/diagnosis/therapy ; Mesothelioma, Malignant ; *Research ; }, abstract = {BACKGROUND: In the UK, despite the import and use of all forms of asbestos being banned more than 15 years ago, the incidence of mesothelioma continues to rise. Mesothelioma is almost invariably fatal, and more research is required, not only to find more effective treatments, but also to achieve an earlier diagnosis and improve palliative care. Following a debate in the House of Lords in July 2013, a package of measures was agreed, which included a James Lind Alliance Priority Setting Partnership, funded by the National Institute for Health Research. The partnership brought together patients, carers, health professionals and support organisations to agree the top 10 research priorities relating to the diagnosis, treatment and care of patients with mesothelioma.<br><br>METHODS: Following the established James Lind Alliance priority setting process, mesothelioma patients, current and bereaved carers, and health professionals were surveyed to elicit their concerns regarding diagnosis, treatment and care. Research questions were generated from the survey responses, and following checks that the questions were currently unanswered, an interim prioritisation survey was conducted to identify a shortlist of questions to take to a final consensus meeting.<br><br>FINDINGS: Four hundred and fifty-three initial surveys were returned, which were refined into 52 unique unanswered research questions. The interim prioritisation survey was completed by 202 responders, and the top 30 questions were taken to a final meeting where mesothelioma patients, carers, and health professionals prioritised all the questions, and reached a consensus on the top 10.<br><br>INTERPRETATION: The top 10 questions cover a wide portfolio of research (including assessing the value of immunotherapy, individualised chemotherapy, second-line treatment and immediate chemotherapy, monitoring patients with pleural thickening, defining the management of ascites in peritoneal mesothelioma, and optimising follow-up strategy). This list is an invaluable resource, which should be used to inform the prioritisation and funding of future mesothelioma research.}, }
@article {pmid26111538, year = {2016}, author = {Yu, M and Chen, R and Jia, Z and Chen, J and Lou, J and Tang, S and Zhang, X}, title = {MWCNTs Induce ROS Generation, ERK Phosphorylation, and SOD-2 Expression in Human Mesothelial Cells.}, journal = {International journal of toxicology}, volume = {35}, number = {1}, pages = {17-26}, doi = {10.1177/1091581815591223}, pmid = {26111538}, issn = {1092-874X}, mesh = {Cell Line, Transformed ; Epithelium/enzymology/*metabolism ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Humans ; Microscopy, Electron, Transmission ; *Nanotubes, Carbon ; Phosphorylation ; Reactive Oxygen Species/*metabolism ; Superoxide Dismutase/*metabolism ; }, abstract = {Biological oxidative responses are involved in the toxicity of multiwall carbon nanotubes (MWCNTs), which may cause asbestos-like pathogenicity. Superoxide dismutase 2 (SOD-2) has been proposed as a biomarker of early responses to mesothelioma-inducing fibers. This study was conducted to investigate the alteration of SOD-2 expression in the human mesothelial cell lines Met-5A after exposure to nontoxic doses of MWCNTs and the potential signaling pathway. The parameters measured included the viability, morphological change, superoxide formation, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and messenger RNA (mRNA)/protein levels of SOD-2. Our results showed that MWCNTs upregulated SOD-2 expression at both mRNA and protein level. Coincidently, both superoxide formation and ERK1/2 phosphorylation were observed in Met-5A cells exposed to MWCNTs and were diminished by pretreatment with the reactive oxidative species (ROS) scavenger, N-acetyl-l-(+)-cysteine (NAC). To further investigate the role of ROS/ERK1/2 in MWCNTs-induced SOD-2 overexpression, prior to MWCNTs exposure, cells were pretreated with the Mitogen-activated protein kinase kinase 1/2 (MEK 1/2) inhibitor (U0126) or with NAC. Both pretreatments decreased the MWCNTs-induced overexpression of SOD-2. These results suggest that upregulation of SOD-2 in Met-5A cells exposed to MWCNTs is mediated by ROS formation and ERK1/2 activation.}, }
@article {pmid26109114, year = {2015}, author = {Van den Borre, L and Deboosere, P}, title = {Enduring health effects of asbestos use in Belgian industries: a record-linked cohort study of cause-specific mortality (2001-2009).}, journal = {BMJ open}, volume = {5}, number = {6}, pages = {e007384}, pmid = {26109114}, issn = {2044-6055}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*toxicity ; Asbestosis/mortality ; Belgium/epidemiology ; Cohort Studies ; Humans ; Industry/statistics &amp; numerical data ; Laryngeal Neoplasms/mortality ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/mortality ; Middle Aged ; Mouth Neoplasms/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/adverse effects ; Young Adult ; }, abstract = {OBJECTIVE: To investigate cause-specific mortality among asbestos workers and potentially exposed workers in Belgium and evaluate potential excess in mortality due to established and suspected asbestos-related diseases.<br><br>DESIGN: This cohort study is based on an individual record linkage between the 1991 Belgian census and cause-specific mortality information for Flanders and Brussels (2001-2009).<br><br>SETTING: Belgium (Flanders and Brussels region).<br><br>PARTICIPANTS: The study population consists of 1,397,699 male workers (18-65,years) with 72,074 deaths between 1 October 2001 and 31 December 2009. Using a classification of high-risk industries, mortality patterns between 2056 asbestos workers, 385,046 potentially exposed workers and the working population have been compared.<br><br>OUTCOME MEASURES: Standardised mortality ratios (SMRs) and 95% CIs are calculated for manual and non-manual workers.<br><br>RESULTS: Our findings show clear excess in asbestos-related mortality in the asbestos industry with SMRs for mesothelioma of 4071 (CI 2327 to 6611) among manual workers and of 4489 (CI 1458 to 10,476) among non-manual workers. Excess risks in asbestos-related mortality are also found in the chemical industry, the construction industry, the electrical generation and distribution industry, the basic metals manufacturing industry, the metal products manufacturing industry, the railroad industry, and the shipping industry. Oral cancer mortality is significantly higher for asbestos workers (SMR 383; CI 124 to 894), railroad workers (SMR 192; CI 112 to 308), shipping workers (SMR 172; CI 102 to 271) and construction workers (SMR 125; CI 100 to 153), indicating a possible association with occupational asbestos exposure. Workers in all four industries have elevated mortality rates for cancer of the mouth. Only construction workers experience significantly higher pharyngeal cancer mortality (SMR 151; CI 104 to 212).<br><br>CONCLUSIONS: The study identifies vulnerable groups of Belgian asbestos workers, demonstrating the current-day health repercussions of historical asbestos use. Results support the hypothesis of a possible association between the development of oral cancer and occupational asbestos exposure.}, }
@article {pmid26108245, year = {2016}, author = {Galetta, D and Catino, A and Misino, A and Logroscino, A and Fico, M}, title = {Sarcomatoid mesothelioma: future advances in diagnosis, biomolecular assessment, and therapeutic options in a poor-outcome disease.}, journal = {Tumori}, volume = {102}, number = {2}, pages = {127-130}, doi = {10.5301/tj.5000364}, pmid = {26108245}, issn = {2038-2529}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Lung Neoplasms/*diagnosis/drug therapy/*genetics/mortality/pathology ; Mesothelioma/*diagnosis/drug therapy/*genetics/mortality/pathology ; Mesothelioma, Malignant ; MicroRNAs/*analysis ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/drug therapy/*genetics/mortality/pathology ; Predictive Value of Tests ; Prognosis ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most frequent pleural neoplasm, with asbestos exposure as one of the recognized carcinogen agents, causative in 80% of cases. The prognosis is poor; median survival of untreated cases is 6-9 months, with fewer than 5% of patients surviving 5 years. Sarcomatoid mesothelioma (SM) represents the subtype with the worst outcome and median survival ranging from 3.5 to 8 months. In the last few years, an accurate differentiation between the subtypes of MPM has become a crucial issue, due to differences in chemosensitivity and clinical outcome, and several studies have evaluated different immunohistochemical markers to better define the diagnosis. The different and worse outcome of patients with SM and, in general, nonepithelioid subtypes makes it intriguing to select these cases to better study the biomolecular profile in order to find factors linked to prognosis and/or predictive of therapeutic response. Considering recent studies on miRNA and genetic mapping, further investigation of this rare subtype might represent a field for basic and clinical-translational research providing for more tailored therapies.}, }
@article {pmid26106244, year = {2015}, author = {Lange, JH and Cegolon, L}, title = {Non-asbestos Causes of mesothelioma and translocation of asbestos fibres.}, journal = {Singapore medical journal}, volume = {56}, number = {6}, pages = {361}, pmid = {26106244}, issn = {2737-5935}, mesh = {Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Testicular Hydrocele/*diagnosis ; Testicular Neoplasms/*diagnosis ; }, }
@article {pmid26100969, year = {2015}, author = {Hjerpe, A and Ascoli, V and Bedrossian, CW and Boon, ME and Creaney, J and Davidson, B and Dejmek, A and Dobra, K and Fassina, A and Field, A and Firat, P and Kamei, T and Kobayashi, T and Michael, CW and Önder, S and Segal, A and Vielh, P and ,  and , }, title = {Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.}, journal = {Diagnostic cytopathology}, volume = {43}, number = {7}, pages = {563-576}, doi = {10.1002/dc.23271}, pmid = {26100969}, issn = {1097-0339}, mesh = {Adenocarcinoma/diagnosis/pathology ; *Cytodiagnosis ; Diagnosis, Differential ; Histocytochemistry/standards ; Humans ; International Cooperation ; Lung Neoplasms/*diagnosis/pathology ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Neoplasms/diagnosis/pathology ; Pleural Effusion/*diagnosis/pathology ; Specimen Handling/*standards ; Staining and Labeling/standards ; }, abstract = {OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.<br><br>DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.<br><br>RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.}, }
@article {pmid26090445, year = {2015}, author = {Maruyama, K and Haniu, H and Saito, N and Matsuda, Y and Tsukahara, T and Kobayashi, S and Tanaka, M and Aoki, K and Takanashi, S and Okamoto, M and Kato, H}, title = {Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {793186}, pmid = {26090445}, issn = {2314-6141}, mesh = {Apoptosis/drug effects ; Asbestos/toxicity ; Autophagy/drug effects ; Bronchi/drug effects/pathology ; Endocytosis/*drug effects ; Epithelial Cells/drug effects/*pathology ; Humans ; Mesothelioma/chemically induced/*pathology ; Nanotubes, Carbon/*adverse effects ; Reactive Oxygen Species/metabolism ; }, abstract = {Bronchial epithelial cells and mesothelial cells are crucial targets for the safety assessment of inhalation of carbon nanotubes (CNTs), which resemble asbestos particles in shape. Intrinsic properties of multiwalled CNTs (MWCNTs) are known to cause potentially hazardous effects on intracellular and extracellular pathways. These interactions alter cellular signaling and affect major cell functions, resulting in cell death, lysosome injury, reactive oxygen species production, apoptosis, and cytokine release. Furthermore, CNTs are emerging as a novel class of autophagy inducers. Thus, in this study, we focused on the mechanisms of MWCNT uptake into the human bronchial epithelial cells (HBECs) and human mesothelial cells (HMCs). We verified that MWCNTs are actively internalized into HBECs and HMCs and were accumulated in the lysosomes of the cells after 24-hour treatment. Next, we determined which endocytosis pathways (clathrin-mediated, caveolae-mediated, and macropinocytosis) were associated with MWCNT internalization by using corresponding endocytosis inhibitors, in two nonphagocytic cell lines derived from bronchial epithelial cells and mesothelioma cells. Clathrin-mediated endocytosis inhibitors significantly suppressed MWCNT uptake, whereas caveolae-mediated endocytosis and macropinocytosis were also found to be involved in MWCNT uptake. Thus, MWCNTs were positively taken up by nonphagocytic cells, and their cytotoxicity was closely related to these three endocytosis pathways.}, }
@article {pmid26083165, year = {2015}, author = {Terracini, B and Pedra, F and Otero, U}, title = {Asbestos-related cancers in Brazil.}, journal = {Cadernos de saude publica}, volume = {31}, number = {5}, pages = {903-905}, doi = {10.1590/0102-311XPE010515}, pmid = {26083165}, issn = {1678-4464}, mesh = {Asbestos/*adverse effects/*toxicity ; Brazil ; Carcinogens/*toxicity ; Environmental Exposure/adverse effects ; Humans ; Mesothelioma/diagnosis/*etiology ; Occupational Diseases/diagnosis/*etiology ; Pleural Neoplasms/diagnosis/*etiology ; }, }
@article {pmid26082103, year = {2015}, author = {Kubo, S and Takagi-Kimura, M and Kasahara, N}, title = {Combinatorial anti-angiogenic gene therapy in a human malignant mesothelioma model.}, journal = {Oncology reports}, volume = {34}, number = {2}, pages = {633-638}, doi = {10.3892/or.2015.4058}, pmid = {26082103}, issn = {1791-2431}, mesh = {Angiogenesis Inhibitors/*genetics ; Angiostatins/genetics/metabolism ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Endostatins/genetics/metabolism ; Genetic Therapy/*methods ; Genetic Vectors/*administration &amp; dosage ; Humans ; Lentivirus/*genetics ; Mesothelioma/genetics/*therapy ; Mice ; Receptor, Fibroblast Growth Factor, Type 2/genetics/metabolism ; }, abstract = {Anti-angiogenic gene therapy represents a promising strategy for cancer; however, it has rarely been tested in malignant mesothelioma, a highly aggressive tumor associated with asbestos with poor prognosis. In the present study, we investigated whether anti-angiogenic factors such as angiostatin, endostatin and the soluble form of vascular endothelial growth factor receptor 2 (sFlk1) were able to inhibit endothelial cell proliferation via lentivirus-mediated gene transfer into malignant mesothelioma cells in culture. We also assessed whether a dual-agent strategy had greater therapeutic benefit. Human malignant pleural mesothelioma MSTO-211H cells were transduced using lentiviral vectors that individually expressed angiostatin, endostatin and sFlk1 and linked to enhanced green fluorescent protein (EGFP) marker gene expression via an internal ribosome entry site. The lentivirus expressing EGFP alone was used as a control. The resultant cells designated as MSTO-A, MSTO-E, MSTO-F and MSTO-C were confirmed by western blot analysis and fluorescence microscopy to stably express the corresponding proteins. No differences were observed in the in vitro growth rates between any of these cells. However, co-culture of MSTO-A, MSTO-E and MSTO-F showed significant suppression of human umbilical endothelial cell growth in vitro compared with that of MSTO-C. Furthermore, a combination of any two among MSTO-A, MSTO-E and MSTO-F significantly enhanced efficacy. These results suggest that combinatorial anti-angiogenic gene therapy targeting different pathways of endothelial growth factor signaling has the potential for greater therapeutic efficacy than that of a single-agent regimen.}, }
@article {pmid26078352, year = {2015}, author = {Benedetti, S and Nuvoli, B and Catalani, S and Galati, R}, title = {Reactive oxygen species a double-edged sword for mesothelioma.}, journal = {Oncotarget}, volume = {6}, number = {19}, pages = {16848-16865}, pmid = {26078352}, issn = {1949-2553}, mesh = {Cell Transformation, Neoplastic/metabolism ; Humans ; Mesothelioma/*etiology/*pathology ; Nanotubes, Carbon/*adverse effects ; Oxidative Stress/*physiology ; Reactive Oxygen Species/*adverse effects ; }, abstract = {It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10-15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display 'asbestos-like' pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review.}, }
@article {pmid26076085, year = {2015}, author = {Grzankowski, KS and Brightwell, RM and Kasznica, JM and Odusi, KO}, title = {Malignant peritoneal mesothelioma without asbestos exposure: An ovarian cancer imitator.}, journal = {Gynecologic oncology reports}, volume = {11}, number = {}, pages = {10-12}, pmid = {26076085}, issn = {2352-5789}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; T32 CA108456/CA/NCI NIH HHS/United States ; }, abstract = {•Malignant peritoneal mesothelioma is a rare aggressive tumor with approximately 400 new cases annually in the US.•In optimal cytoreduction HIPEC is the standard treatment.•In suboptimal cytoreduction IV cisplatin and pemetrexed have high efficacy.}, }
@article {pmid26075933, year = {2015}, author = {Maxim, LD and Niebo, R and Utell, MJ}, title = {Are pleural plaques an appropriate endpoint for risk analyses?.}, journal = {Inhalation toxicology}, volume = {27}, number = {7}, pages = {321-334}, doi = {10.3109/08958378.2015.1051640}, pmid = {26075933}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/toxicity ; Humans ; Lung Neoplasms/epidemiology ; Occupational Diseases/diagnosis/*epidemiology/physiopathology ; Occupational Exposure/*adverse effects ; Pleural Diseases/diagnosis/*epidemiology/physiopathology ; Risk Assessment ; }, abstract = {This review summarizes the literature on the relation between the development of pleural plaques and non-malignant and malignant disease in cohorts exposed to asbestos and other fibers. The available evidence indicates that, absent any other pleural disease, the presence of pleural plaques does not result in respiratory symptoms or clinically significant impacts on lung function. For certain types of asbestos, the development of pleural plaques is statistically correlated with malignant disease, but the evidence is consistent with the hypothesis that pleural plaques without other pleural disease are a marker of exposure, rather than an independent risk factor. Pleural plaques have also developed in cohorts exposed to other fibers that have not proven to be carcinogenic. Risk analyses should be based on the avoidance of known adverse conditions, rather than pleural plaques per se.}, }
@article {pmid26075427, year = {2015}, author = {Kao, SC and Fulham, M and Wong, K and Cooper, W and Brahmbhatt, H and MacDiarmid, J and Pattison, S and Sagong, JO and Huynh, Y and Leslie, F and Pavlakis, N and Clarke, S and Boyer, M and Reid, G and van Zandwijk, N}, title = {A Significant Metabolic and Radiological Response after a Novel Targeted MicroRNA-based Treatment Approach in Malignant Pleural Mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {191}, number = {12}, pages = {1467-1469}, doi = {10.1164/rccm.201503-0461LE}, pmid = {26075427}, issn = {1535-4970}, mesh = {Humans ; Lung/diagnostic imaging ; Lung Neoplasms/*diagnostic imaging/*drug therapy ; Male ; Mesothelioma/*diagnostic imaging/*drug therapy ; Mesothelioma, Malignant ; MicroRNAs/*therapeutic use ; Middle Aged ; Tomography, X-Ray Computed ; Treatment Outcome ; }, }
@article {pmid26070993, year = {2015}, author = {Pawełczyk, A and Božek, F}, title = {Health risk associated with airborne asbestos.}, journal = {Environmental monitoring and assessment}, volume = {187}, number = {7}, pages = {428}, pmid = {26070993}, issn = {1573-2959}, mesh = {Air Pollutants/*analysis/toxicity ; Asbestos/*analysis/toxicity ; Environmental Exposure/*analysis/statistics &amp; numerical data ; Environmental Monitoring ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Poland ; Risk Assessment/statistics &amp; numerical data ; Uncertainty ; }, abstract = {The following paper presents an assessment of health risks associated with air polluted with respirable asbestos fibers in towns of southwest Poland. The aim of the work was to determine whether or not any prevention measures are necessary in order to reduce the level of exposure to the pollutant. The risk assessment was carried out based on the air analyses and the latest asbestos toxicity data published by the Environmental Protection Agency (US EPA), USA and Office of Environmental Health Hazard Assessment (OEHHA). It was found that in some sites, the concentration of the asbestos fibers exceeded the acceptable levels, which should be a reason of special concern. The highest concentration of asbestos was found in town centers during the rush hours. In three spots, the calculated maximum health risk exceeded 1E-04 which is considered too high according to the adopted standards. So far, it has not yet been possible to find a reasonable method of ensuring the hazard reduction.}, }
@article {pmid26059286, year = {2015}, author = {Acencio, MM and Soares, B and Marchi, E and Silva, CS and Teixeira, LR and Broaddus, VC}, title = {Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells.}, journal = {Lung}, volume = {193}, number = {5}, pages = {831-837}, pmid = {26059286}, issn = {1432-1750}, mesh = {Animals ; Apoptosis/drug effects ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Cell Survival/drug effects ; Cells, Cultured ; Chemokine CXCL2/antagonists &amp; inhibitors/metabolism ; Cytokines/antagonists &amp; inhibitors/*metabolism ; Epithelial Cells/drug effects/*metabolism/*pathology ; Interleukin-1beta/antagonists &amp; inhibitors/metabolism ; Interleukin-6/antagonists &amp; inhibitors/metabolism ; Mice ; Necrosis/chemically induced ; Pleura/cytology ; }, abstract = {BACKGROUND: Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.<br><br>OBJECTIVE: To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.<br><br>METHODS: Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 &#x3bc;g/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1&#x3b2;, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1&#x3b2;, anti-IL-6, anti- IL-1&#x3b2;+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.<br><br>RESULTS: Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1&#x3b2;, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1&#x3b2; andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers.<br><br>CONCLUSIONS: Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1&#x3b2;, IL-6 and MIP-2 in cultured mouse PMC. IL-1&#x3b2; and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.}, }
@article {pmid26057448, year = {2015}, author = {Jennings, CJ and Murer, B and O'Grady, A and Hearn, LM and Harvey, BJ and Kay, EW and Thomas, W}, title = {Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients.}, journal = {British journal of cancer}, volume = {113}, number = {1}, pages = {69-75}, pmid = {26057448}, issn = {1532-1827}, mesh = {Cell Line, Tumor ; Cohort Studies ; Cyclin-Dependent Kinase Inhibitor Proteins/*metabolism ; Humans ; Mesothelioma/*drug therapy/metabolism/pathology ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence.<br><br>METHODS: The expression of cyclin-dependent kinase inhibitor p16/INK4A was evaluated by immunohistochemistry using tumour biopsy specimens from 88 MPM cases and a semi-quantitative score for p16/INK4A expression was obtained. Post-diagnosis survival and the survival benefit of chemotherapeutic intervention was correlated with p16/INK4A expression.<br><br>RESULTS: A low, intermediate and high score for p16/INK4A expression was observed for 45 (51.1%), 28 (31.8%) and 15 (17.1%) of the MPM cases, respectively. Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression (log-rank P<0.001). Those patients with sustained p16/INK4A expression who received chemotherapy also had a better survival than those treated patients whose tumours had lost p16/INK4A expression (log-rank P<0.001).<br><br>CONCLUSIONS: Sustained p16/INK4A expression predicts better post-diagnosis survival in MPM and also better survival following chemotherapeutic intervention.}, }
@article {pmid26052757, year = {2015}, author = {Hjerpe, A and Ascoli, V and Bedrossian, CW and Boon, ME and Creaney, J and Davidson, B and Dejmek, A and Dobra, K and Fassina, A and Field, A and Firat, P and Kamei, T and Kobayashi, T and Michael, CW and Önder, S and Segal, A and Vielh, P}, title = {Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: a secondary publication.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {26}, number = {3}, pages = {142-156}, doi = {10.1111/cyt.12250}, pmid = {26052757}, issn = {1365-2303}, mesh = {Cytodiagnosis ; Humans ; Mesothelioma/*diagnosis ; }, abstract = {OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.<br><br>DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.<br><br>RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.}, }
@article {pmid26046696, year = {2016}, author = {Kawabata, Y and Shimizu, Y and Hoshi, E and Murai, K and Kanauchi, T and Kurashima, K and Sugita, Y}, title = {Asbestos exposure increases the incidence of histologically confirmed usual interstitial pneumonia.}, journal = {Histopathology}, volume = {68}, number = {3}, pages = {339-346}, doi = {10.1111/his.12751}, pmid = {26046696}, issn = {1365-2559}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology/*pathology ; Female ; Humans ; Incidence ; Japan/epidemiology ; Lung Neoplasms/epidemiology/etiology/*pathology ; Male ; Mesothelioma/epidemiology/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Diseases/epidemiology/etiology/*pathology ; Pleural Neoplasms/epidemiology/etiology/*pathology ; Retrospective Studies ; Risk Factors ; }, abstract = {AIMS: We hypothesized that asbestos exposure increases the incidence of macroscopically visible and histologically confirmed usual interstitial pneumonia (histological UIP).<br><br>METHODS AND RESULTS: We retrospectively examined 1718 cases (1202 males; mean age 66.7 years) who underwent lobectomy for resection of pleuropulmonary tumours. Objective markers for asbestos exposure included: the presence of malignant pleural mesothelioma, the presence of pleural plaques (PPs) and asbestos bodies in the histological specimen. Risk factors for histological UIP were examined. Two separate groups were studied: 183 with asbestos exposure, and 239 with histological UIP. The 183 cases with asbestos exposure had higher rates of positive occupational history and histological UIP (31%) than the remaining 1535. Among the asbestos-exposed group, small numbers of asbestos bodies were found in histological specimens of 21 cases of histological UIP. PPs and asbestos bodies were more frequent in the 239 patients with histological UIP than in the remaining 1479 UIP-negative patients. Multivariate analysis showed that asbestos exposure, especially positivity for asbestos bodies, that does not meet the current criteria for asbestosis increases the risk of histological UIP (P < 0.0001).<br><br>CONCLUSIONS: Asbestos exposure causes asbestosis and increases the incidence of histological UIP.}, }
@article {pmid26045315, year = {2015}, author = {Marinaccio, A and Binazzi, A and Bonafede, M and Corfiati, M and Di Marzio, D and Scarselli, A and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Merler, E and Negro, C and Romanelli, A and Chellini, E and Silvestri, S and Cocchioni, M and Pascucci, C and Stracci, F and Ascoli, V and Trafficante, L and Angelillo, I and Musti, M and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and , }, title = {Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues.}, journal = {Occupational and environmental medicine}, volume = {72}, number = {9}, pages = {648-655}, doi = {10.1136/oemed-2014-102297}, pmid = {26045315}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Environmental Pollutants/*adverse effects ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*etiology ; Population Surveillance ; Public Health ; Sex Factors ; Young Adult ; }, abstract = {INTRODUCTION: Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160,000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure.<br><br>METHODS: The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases.<br><br>RESULTS: Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100,000) for men and 1.45 for women, respectively. Among the 15,845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12,065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily).<br><br>CONCLUSIONS: Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos.}, }
@article {pmid26039812, year = {2015}, author = {Mesaros, C and Worth, AJ and Snyder, NW and Christofidou-Solomidou, M and Vachani, A and Albelda, SM and Blair, IA}, title = {Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure.}, journal = {Bioanalysis}, volume = {7}, number = {9}, pages = {1157-1173}, pmid = {26039812}, issn = {1757-6199}, support = {T32 GM008076/GM/NIGMS NIH HHS/United States ; P42ES023720/ES/NIEHS NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; T32ES019851/ES/NIEHS NIH HHS/United States ; T32 ES019851/ES/NIEHS NIH HHS/United States ; P30ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Biomarkers/analysis ; Chemistry Techniques, Analytical/*methods ; Environmental Exposure/adverse effects/*analysis ; Humans ; Oxidative Stress/drug effects ; Pleura/drug effects/metabolism ; }, abstract = {Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.}, }
@article {pmid26024342, year = {2015}, author = {Markowitz, S}, title = {Asbestos-related lung cancer and malignant mesothelioma of the pleura: selected current issues.}, journal = {Seminars in respiratory and critical care medicine}, volume = {36}, number = {3}, pages = {334-346}, doi = {10.1055/s-0035-1549449}, pmid = {26024342}, issn = {1098-9048}, mesh = {Animals ; Asbestos/toxicity ; Asbestosis/complications/diagnosis ; Early Detection of Cancer ; Humans ; Lung Neoplasms/diagnosis/*etiology/pathology ; Mesothelioma/diagnosis/*etiology/pathology ; Mesothelioma, Malignant ; Occupational Diseases/diagnosis/etiology/pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/diagnosis/*etiology/pathology ; Risk Assessment/methods ; Smoking/adverse effects ; Tomography, X-Ray Computed ; }, abstract = {Asbestos-related diseases persist, because millions of workers have had prior exposure and many industrializing countries continue to use asbestos. Globally, an estimated 107,000 people die annually from lung cancer, malignant mesothelioma, and asbestosis due to occupational asbestos exposure. Malignant mesothelioma and lung cancer are caused by all major types of asbestos. Asbestos causes more lung cancer deaths than malignant mesothelioma of the pleura; most cases of the latter are due to asbestos exposure. The cancer risk increases with cumulative asbestos exposure, with increased risk even at low levels of exposure to asbestos. Based on empirical studies, an estimated cumulative occupational exposure to asbestos of 1 fiber/mL-year substantially raises malignant mesothelioma risk. No safe threshold for asbestos exposure has been established for lung cancer and mesothelioma. The validity of fiber-type risk assessments depends critically on the quality of exposure assessments, which vary considerably, leading to a high degree of uncertainty. Asbestos exposure without asbestosis and smoking increases the risk of lung cancer. The joint effect of asbestos and smoking is supra-additive, which may depend in part on the presence of asbestosis. Asbestos workers who cease smoking experience a dramatic drop in lung cancer risk, which approaches that of nonsmokers after 30 years. Studies to date show that longer, thinner fibers have a stronger association with lung cancer than shorter, less thin fibers, but the latter nonetheless also show an association with lung cancer and mesothelioma. Low-dose chest computed tomographic scanning offers an unprecedented opportunity to detect early-stage lung cancers in asbestos-exposed workers.}, }
@article {pmid26016578, year = {2015}, author = {Creaney, J and Dick, IM and Robinson, BW}, title = {Comparison of mesothelin and fibulin-3 in pleural fluid and serum as markers in malignant mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {21}, number = {4}, pages = {352-356}, doi = {10.1097/MCP.0000000000000167}, pmid = {26016578}, issn = {1531-6971}, mesh = {Biomarkers, Tumor ; Diagnosis, Differential ; Extracellular Matrix Proteins ; GPI-Linked Proteins ; Humans ; *Lung Neoplasms ; Mesothelin ; *Mesothelioma ; Mesothelioma, Malignant ; *Pleural Effusion/diagnosis ; }, abstract = {PURPOSE OF REVIEW: Malignant mesothelioma is an asbestos-induced, aggressive tumour, which frequently presents with pleural effusion. There are over 60 reported causes that can result in the development of a pleural effusion. Currently, there are no tumour biomarkers in widespread clinical use for the differential diagnosis of mesothelioma from other diseases. With the incidence of mesothelioma expected to continue to increase, it is timely to review the current status of effusion-based biomarkers for mesothelioma diagnosis.<br><br>RECENT FINDINGS: The majority of recent studies have evaluated soluble mesothelin in effusions in a diagnostic setting for mesothelioma. However, at high specificity, the sensitivity of the assay is limited to approximately 60% at the time of diagnosis. There is considerable research effort directed toward the identification of new markers for mesothelioma through a variety of genomic, proteomic and immunomic based platforms. One of the few new biomarkers to be identified through a biomarker discovery pipeline and evaluated in pleural effusions is fibulin-3. Preliminary results on the diagnostic accuracy of fibulin-3 have been inconsistent.<br><br>SUMMARY: To date, soluble mesothelin remains the best available biomarker for mesothelioma and a positive result is clinically useful in patients with pleural effusions in whom the diagnosis is uncertain.}, }
@article {pmid27476317, year = {2015}, author = {Aubier, M}, title = {[Asbestos: An up-to-date general review].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {199}, number = {2-3}, pages = {383-389}, pmid = {27476317}, issn = {0001-4079}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Occupational Exposure/*adverse effects ; }, abstract = {Major risks associated with asbestos exposure (mesothelioma, lung cancer and asbestosis) have been knownfor a long time. Various clinical and epidemiological studies, which include assessment of risk of developing cancer after discovering atypical computer-tomography (CT) images or pleural plaques in persons who had been exposed to asbestos, are still ongoing, however. This short report updates the risk of occupational exposure in 2014, the consequences of the former occupational exposures, the scale of compensation and recent legal dispositions intended to reduce the risk of occupational and non-professional exposure in France.}, }
@article {pmid27476313, year = {2015}, author = {Chamoux, A}, title = {[Review and perspective of a long-term follow-up of two cohorts of workers heavily exposed to asbestos].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {199}, number = {2-3}, pages = {321-39; discussion 339-40}, pmid = {27476313}, issn = {0001-4079}, mesh = {Aged ; Asbestos/administration &amp; dosage/*adverse effects ; Asbestosis/diagnosis/epidemiology/*etiology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Occupational Exposure/*adverse effects ; Time Factors ; }, abstract = {National screening programs for detection of breast, colon and cervical cancers have been set up in France. Occupational cancers are excluded from these programs. Surveillance is left to the initiative of former employees who can initiate post-professional medical monitoring. This study describes an experience of such monitoring organised by the health insurance in collaboration with "victims". The long term follow-up, every two years, of 324 workers directly and heavily exposed to asbestos confirms the high risk of developing lung cancer, mesothelioma or asbestosis, the latter at times rapidly evolving. The early discovery of 3 bronchopulmonary cancers points to the interest of an annual or biannual routine screening. While new imaging techniques reduce by a factor of 8 irradiation, without significantly affecting the diagnostic capacity, the health benefit provided by annual monitoring scanner in heavy smokers favors an early detection program for lung cancers. The population targeted for such a screening (active or former smoker with pleural plaques) should be defined in more detail. The increasingly frequent observation of lung or pleural changes besides the populations at risk should also be considered. Therefore the detecting procedures applied to those workers indirectly or discontinuously exposed should be reassessed (only 1 TDM at 60 y, or on retirement, for the relevant occupations). These data suggest that the recommendation HAS 2010 for post-professional screening of workers occupationally exposed to asbestos should be reconsidered, particularly in case of pleural plaques. An organized screening program needs to be overhauled.}, }
@article {pmid27350803, year = {2015}, author = {Yasui, M and Kamoshita, N and Nishimura, T and Honma, M}, title = {Mechanism of induction of binucleated cells by multiwalled carbon nanotubes as revealed by live-cell imaging analysis.}, journal = {Genes and environment : the official journal of the Japanese Environmental Mutagen Society}, volume = {37}, number = {}, pages = {6}, pmid = {27350803}, issn = {1880-7046}, abstract = {INTRODUCTION: Asbestos-induced formation of mesothelioma has been attributed to phenotypic and morphological changes in cells caused by polyploidization and aneuploidization, and multiwalled carbon nanotubes (MWCNTs) are suspected to have similar adverse effects due to the similarity in their physical form. MWCNTs and crocidolite, a kind of asbestos, show similar genotoxicity characteristics in vitro, including induction of binucleated cells. We here focused on the mechanisms underlying polyploidization during cell division on exposure to MWCNTs and conducted confocal live-cell imaging analysis using MDA-435 human breast cancer cells in which chromosomes and centromeres were visualized using fluorescent proteins.<br><br>FINDINGS: During anaphase, relatively short MWCNT fibers (approximately 5&#xa0;&#x3bc;m) migrated rapidly to either of the daughter cells, whereas some long MWCNT fibers (approximately 20&#xa0;&#x3bc;m) remained inside the contractile ring and induced the formation of binucleated cells through impairment of cytokinesis. This toxicity mechanism has also been observed with crocidolite.<br><br>CONCLUSIONS: Our findings indicate that the mechanism of polyploidization by MWCNTs is very similar to that observed with crocidolite.}, }
@article {pmid28548074, year = {2014}, author = {Gaudino, G and Yang, H and Carbone, M}, title = {HGF/Met Signaling Is a Key Player in Malignant Mesothelioma Carcinogenesis.}, journal = {Biomedicines}, volume = {2}, number = {4}, pages = {327-344}, pmid = {28548074}, issn = {2227-9059}, abstract = {Malignant mesothelioma (MM) is a highly aggressive cancer related to asbestos or erionite exposure and resistant to current therapies. Hepatocyte Growth Factor (HGF) and its tyrosine kinase receptor Met regulate cell growth, survival, motility/migration, and invasion. HGF and Met are expressed in MM cells, suggesting that the HGF/Met signaling plays a role in development and progression of this tumor, by autocrine and/or paracrine mechanisms. Upregulation and ligand-independent activation of Met, which is under suppressive control of miR-34 family members, correlate with enhanced invasion, migration and metastatic potential in several cancers, including MM. Moreover, Simian Virus 40 (SV40) Tag expression also induces a HGF autocrine circuit in an Rb-dependent manner in human mesothelial cells (HM) and possibly other cell types, enhancing cell adhesion, invasion and angiogenesis. The resulting activation of Met causes HM transformation and cell cycle progression, and contributes to virus particle assembling and infection of adjacent cells. The constitutive activation of Met, frequently occurring in MM, has been successfully targeted in preclinical models of MM. In conclusion, Met expression, activation state, subcellular localization and also HGF co-receptors expression, such as CD44, have clinical relevance for novel targeted therapies in a cancer for which no effective treatment is currently available.}, }
@article {pmid28652992, year = {2014}, author = {da Fonseca, LG and Marques, DF and Takahashi, TK and Aguiar, FN and Ravanini, JN and Saragiotto, DF}, title = {Malignant paratesticular mesothelioma.}, journal = {Autopsy &amp; case reports}, volume = {4}, number = {1}, pages = {45-51}, pmid = {28652992}, issn = {2236-1960}, abstract = {Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor that usually affects patients after the sixth decade of life. Exposure to asbestos is a known risk factor. Enlargement of the scrotal volume is the most common initial clinical manifestation, and about 15% of cases present metastasis at diagnosis. The treatment relies on surgical resection while the role of adjuvant chemotherapy and radiotherapy remains unclear. The prognosis for patients is generally poor, with a lethal outcome in 30% over a 24-month period. The authors report a case of a 62-year-old patient with the diagnosis of MTVT without a history of asbestos exposure. After surgical treatment, metastatic disease ensued. Chemotherapy was initiated, but could not be continued due to marked and fast clinical deterioration. The authors call attention to the difficulty of early diagnosis of MTVT due to a nonspecific clinical picture, the lack of action by the patient when the scrotal enlargement was first noticed, and the lack of tumor markers. Delayed diagnosis is definitely related to unfavorable prognosis.}, }
@article {pmid26766976, year = {2014}, author = {Kohno, M and Maruyama, R and Kitagawa, D and Sugimachi, K and Kinjo, M and Higashi, H}, title = {Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case.}, journal = {Thoracic cancer}, volume = {5}, number = {1}, pages = {74-77}, pmid = {26766976}, issn = {1759-7706}, abstract = {This report describes a rare case of localized malignant biphasic (mixed epithelioid and sarcomatoid) mesothelioma arising in the peritoneum. A 69-year-old male with a history of asbestos exposure, complaining of a painful mass in the left chest wall, was found via computed tomography (CT) to have a tumor in the left peritoneum. The resected tumor was histologically and immunohistochemically consistent with a malignant mesothelioma with mixed epithelioid and sarcomatoid type and no distant metastasis. The diagnosis of localized malignant biphasic mesothelioma arising in the peritoneum was appropriate because there was no evidence of any other primary tumor.}, }
@article {pmid26742297, year = {2014}, author = {Espinosa, CR and Rivera, LM and Rangell, TE}, title = {[Malignant peritoneal mesothelioma in patients without occupational exposure. Case report].}, journal = {Acta gastroenterologica Latinoamericana}, volume = {44}, number = {3}, pages = {243-245}, pmid = {26742297}, issn = {0300-9033}, mesh = {Asbestos ; Biopsy ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; *Occupational Exposure ; Paracentesis ; Peritoneal Neoplasms/*pathology ; Risk Factors ; }, abstract = {Peritoneal mesothelioma is a rare malignancy that affects more women than men, with an average of 53 years old. The most important risk factor for developing the disease is chronic exposure to asbestos, becoming a disease of occupational origin. This type of cancer is difficult to diagnose, even for pathologists, with few cases reported in the literature as the most common presentation is the pleural type. We report the case of a male patient, without asbestos exposure, who presented malignantperitoneal mesothelioma.}, }
@article {pmid26029551, year = {2014}, author = {Tertemiz, KC and Ozgen Alpaydin, A and Gurel, D and Savas, R and Gulcu, A and Akkoclu, A}, title = {Multiple distant metastases in a case of malignant pleural mesothelioma.}, journal = {Respiratory medicine case reports}, volume = {13}, number = {}, pages = {16-18}, pmid = {26029551}, issn = {2213-0071}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a malignant of mesodermal neoplasm and arises from multipotential mesothelial or subserosal cells of the pleura, pericardium and peritoneum.<br><br>CASE: A seventy five year-old male patient was admitted with chest and lower limb pain. He was a heavy smoker and exposed to environmental asbestos in his childhood. PET-CT scans showed multiple pathological FDG uptakes in lungs and other organs. Biopsies performed from lung and anterior thigh muscles were reported as epitheloid type malignant pleural mesothelioma.<br><br>DISCUSSION: We emphasize that unexpected distant metastases can be observed in MPM and occasionally primary diagnosis can be determined by the biopsy of the metastatic regions. This case also points out the role of PET-CT in the staging of malign mesothelioma by determining different metastatic sites.}, }
@article {pmid27158561, year = {2013}, author = {Kim, SJ and Williams, D and Cheresh, P and Kamp, DW}, title = {Asbestos-Induced Gastrointestinal Cancer: An Update.}, journal = {Journal of gastrointestinal &amp; digestive system}, volume = {3}, number = {3}, pages = {}, pmid = {27158561}, issn = {2161-069X}, support = {I01 BX000786/BX/BLRD VA/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; }, abstract = {Asbestos-related diseases, such as malignancies and asbestosis, remain a significant occupational and public health concern. Asbestos is still widely used in many developing countries despite being a recognized carcinogen that has been banned over 50 countries. The prevalence and mortality from asbestos-related diseases continue to pose challenges worldwide. Many countries are now experiencing an epidemic of asbestos-related disease that is the legacy of occupational exposure during the 20th century because of the long latency period (up to 40 years) between initial asbestos exposure and exhibition of disease. However, the gastrointestinal (GI) cancers resulting from asbestos exposure are not as clearly defined. In this review, we summarize some of the recent epidemiology of asbestos-related diseases and then focus on the evidence implicating asbestos in causing GI malignancies. We also briefly review the important new pathogenic information that has emerged over the past several years that may account for asbestos-related gastrointestinal cancers. All types of asbestos fibers have been implicated in the mortality and morbidity from GI malignancies but the collective evidence to date is mixed. Although the molecular basis of GI cancers arising from asbestos exposure is unclear, there have been significant advances in our understanding of mesothelioma and asbestosis that may contribute to the pathophysiology underlying asbestos-induced GI cancers. The emerging new evidence into the pathogenesis of asbestos toxicity is providing insights into the molecular basis for developing novel therapeutic strategies for asbestos-related diseases in future management.}, }
@article {pmid28920322, year = {2013}, author = {Okamoto, T and Yano, T and Haro, A and Yoshida, T and Kohno, M and Maehara, Y}, title = {Treatment for recurrence after extrapleural pneumonectomy for malignant pleural mesothelioma: A single institution experience.}, journal = {Thoracic cancer}, volume = {4}, number = {1}, pages = {66-70}, doi = {10.1111/j.1759-7714.2012.00138.x}, pmid = {28920322}, issn = {1759-7714}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a relatively rare, aggressive neoplasm associated with asbestos exposure. Extrapleural pneumonectomy (EPP) is often performed for resectable MPM as part of a multidisciplinary treatment; however, available data on treatments for recurrence after EPP are limited.<br><br>METHODS: &#x2002; The clinical records of consecutive MPM patients who underwent EPP at our institution from 2001 to 2010 were retrospectively reviewed. There were 10 patients who underwent EPP with or without perioperative chemotherapy; of these, recurrence was observed in eight patients.<br><br>RESULTS: &#x2002; The overall median survival time and time to recurrence were 49.6 months and 15.4 months, respectively, after EPP. The first recurrence occurred within the ipsilateral thorax in four patients. These patients all underwent local treatments for their recurrence, including surgery or radiotherapy and with or without systemic chemotherapy. Other first recurrences were seen in the peritoneal space of two patients and in the contralateral lung of two patients. These patients received platinum-based systemic chemotherapy for their recurrence. The median survival time after the first recurrence was 17.8 months, and the 2-year survival rate was 23.4%.<br><br>CONCLUSIONS: &#x2002; Most patients who underwent EPP developed tumor recurrences. Direct tumor extension may be a major mechanism of recurrence. Aggressive treatment for recurrent MPM after EPP, including locoregional control and/or systemic chemotherapy, was important for achieving long-term survival.}, }
@article {pmid28920270, year = {2012}, author = {Ambrogi, V and Mineo, TC and , }, title = {Clinical and biologic prognostic factors in malignant pleural mesothelioma.}, journal = {Thoracic cancer}, volume = {3}, number = {4}, pages = {289-302}, doi = {10.1111/j.1759-7714.2012.00127.x}, pmid = {28920270}, issn = {1759-7714}, abstract = {Malignant pleural mesothelioma is an extremely aggressive neoplasm of the pleura mainly attributable to asbestos exposure. Conventional medical, physical, and surgical treatments and their combinations are basically ineffective and just a few subjects experience some benefit. No definite guidelines can be provided in patient selection and therapeutic strategies. Currently, malignant pleural mesothelioma therapy is guided by clinical stage and patient characteristics, which are quite unreliable, rather than by the histological or molecular features of the tumor. In the present review the impact on prognosis of classic (i.e. etiology, age, gender, histology, staging), as well as relatively new clinical factors such as quality of life, positron emission tomography assessment, and occult residual disease, are firstly evaluated. In the second section of the review several biological variables and genetic markers, which have been recently recognized as the bases of the disease onset and development, are listed and discussed. There are serum and tissue markers. The latter are mainly related to cell cycle regulation, apoptosis, and growth factor pathways. These novel factors may play an important role in defining the prognosis of the disease and, subsequently, may have a place in addressing therapy.}, }
@article {pmid27755841, year = {2011}, author = {Adel, AM and Abdel Hafeez, ZM and El Sheikh, ET and El Sharawy, IA and Gobran, NS}, title = {Malignant pleural mesothelioma: A retrospective analysis of clinicopathological and survival data.}, journal = {Thoracic cancer}, volume = {2}, number = {1}, pages = {16-23}, doi = {10.1111/j.1759-7714.2010.00033.x}, pmid = {27755841}, issn = {1759-7714}, abstract = {BACKGROUND: The aim of this study was to analyze the clinicopathological features of malignant pleural mesothelioma (MPM) and evaluate the therapeutic measures offered to patients with MPM and their impact on survival.<br><br>METHODS: &#x2002; Data was retrospectively collected from the medical records of 304 patients who presented to the Department of Clinical Oncology and Nuclear Medicine, Ain Shams University between January 2003 and December 2008.<br><br>RESULTS: &#x2002; The mean age of patients was 52.1 years (range 24-87 years). One hundred and ninety patients (62.5%) came from endemic areas and/or gave history of occupational asbestos exposure. One hundred and sixty-nine patients received chemotherapy. There was a significant difference between the median survival for patients who received chemotherapy (9 months, 95% CI 7.69-10.30) and those who were offered best supportive care (2 months, 95% CI 0.09-3.91). Other factors that affected the survival negatively were: non-epithelial pathology (P= 0.001); age >50 years (P= 0.012); bad performance status (P= 0.001); non-platinum based chemotherapy (P= 0.0001); and progressive disease (P= 0.000). Cox regression analysis revealed that the factors that predicted shorter survival were patients being offered best supportive care rather than chemotherapy and progressive disease.<br><br>CONCLUSION: &#x2002; MPM is a growing health problem in Egypt that needs more attention. The current analysis of data reflects the importance of maintaining a high index of suspicion to allow for early diagnosis, especially for cases that live in areas with high asbestos exposure and for people who work in occupations that expose them to asbestos as well as their family members. Prospective randomized trials comparing multimodality approaches to other forms of treatment and including quality of life assessment are warranted.}, }
@article {pmid27755778, year = {2010}, author = {Hürmüz, P}, title = {Management of malignant pleural mesothelioma.}, journal = {Thoracic cancer}, volume = {1}, number = {2}, pages = {53-61}, doi = {10.1111/j.1759-7714.2010.00001.x}, pmid = {27755778}, issn = {1759-7714}, abstract = {Malignant pleural mesothelioma is a rare neoplasm arising from the surface serosal cells of the pleural cavity. More than 80% of cases of malignant pleural mesothelioma have been attributed to asbestos exposure. In its natural course median survival is 4 to 12 months. If untreated most of patients die due to local complications of the disease. Surgery improves local control but is not sufficient as a single treatment modality. The recommended treatment strategy for a select group of patients is multimodal therapy that includes surgery, radiotherapy and chemotherapy.}, }
@article {pmid26839029, year = {2010}, author = {Attanoos, RL}, title = {Asbestos-Related Lung Disease.}, journal = {Surgical pathology clinics}, volume = {3}, number = {1}, pages = {109-127}, doi = {10.1016/j.path.2010.04.003}, pmid = {26839029}, issn = {1875-9181}, abstract = {Asbestos is a high-profile health hazard. This article examines the assessment asbestos-related malignant mesothelioma and lung cancer. The risk of developing these diseases increases in proportion to the cumulative dose. As persons with heavy occupational asbestos exposures are diminishing, the observed latent period for asbestos-related disease extends making the assessment of an individual's cumulative dose is now more problematic.}, }
@article {pmid31394644, year = {2005}, author = {Mohr, S and Neuville, A and Bottin, MC and Micillino, JC and Keith, G and Rihn, BH}, title = {Immune Signature of Malignant Pleural Mesothelioma as Assessed by Transcriptome Analysis.}, journal = {Cancer genomics &amp; proteomics}, volume = {2}, number = {3}, pages = {125-135}, pmid = {31394644}, issn = {1790-6245}, abstract = {Malignant pleural mesothelioma (MPM) is a highly malignant tumor arising in patients previously exposed to asbestos fibers. Its increasing incidence and its social, financial and human impact have become a frequent problem in many industrialized countries. The unresponsiveness of malignant mesothelioma to conventional therapies has led clinicians to develop new treatments. As immunotherapy has been shown to offer promising and targeted treatment of MPM patients, the knowledge of the immunoresistance level of MPM may be a valuable tool for "à la carte" therapy. In a previous work, we profiled the gene expression of two MPM tissues compared to healthy mesothelial cells using a 10K cDNA microarray. Subsequent clustering analysis identified several clusters of differentially-expressed genes among those that are functionally-related to the immune system. In this report, we focus on genes with expression changes that may facilitate tumor escape from immune-mediated rejection. We also analyzed the immune reaction by staining the immunocompetent cells surrounding the tumor. Interestingly, the tumor with the strongest escape response, as shown by the expression of numerous immunoresistance-associated genes, displayed the strongest T cell infiltrate. The main genes conferring immunoresistance are CD74, HLADOA, HLADMB, PTGS1, IGFBP7 and TGFB3, by favoring immune tolerance, and CFLAR, DFFA, TNFRSF6, BNIP3L by impairing apoptosis. These observations have fundamental consequences in the understanding of immunological properties of MPM, and offer a new insight into the mechanisms whereby MPM may circumvent host-mediated immune activities and promotes its own development. For an immunomodulation strategy to cure mesothelioma, it is crucial to characterize the MPM "immune signature" to design adapted immunotherapies.}, }
@article {pmid26368633, year = {2000}, author = {Sandhu, H and Olbrück, H and Abel, J and Unfried, K}, title = {Differential Display Analysis of Fiber-Induced Carcinogenesis in Rat: Clue for Involvement of Integrin-Mediated Signal Transduction.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {337-343}, doi = {10.1080/08958378.2000.11463243}, pmid = {26368633}, issn = {0895-8378}, abstract = {In this study, mRNA expression patterns during mesothelioma carcinogenesis in the peritoneal cavity were investigated. To this purpose, the mRNA expression patterns of fiber-induced mesothelioma and of fiber-treated tissues were compared to untreated tissues, respectively. Suppression subtractive hybridization (SSH) and an array hybridization assay were used to perform differential display analyses. Genes found to be expressed differentially mainly represent proteins of signal transduction pathways and regulatory proteins of the cell cycle. The genes for components of the AP-1 transcription factor, c-jun, c-fos, and fra-1 (fos-related antigen-1) are upregulated in nontumorous tissue treated with asbestos. These data confirm in vivo the involvement of AP-I expression as response to fiber treatment. In addition, osteopontin, zyxin, and integrin-linked kinase were upregulated in tumors and in treated tissues. These genes code for proteins involved in the signal transduction from the extracellular matrix to the nucleus. Using integrin-specific inhibitors, the apoptotic effects of crocidolite fibers could be suppressed significantly. From these results we hypothesize that direct effects of the fibers on the target tissue are mediated by interaction of the fibers with the extracellular matrix molecules.}, }
@article {pmid26368632, year = {2000}, author = {Faux, SP and Houghton, CE}, title = {Cell Signaling in Mesothelial Cells by Asbestos: Evidence for the Involvement of Oxidative Stress in the Regulation of the Epidermal Growth Factor Receptor.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {327-336}, doi = {10.1080/08958378.2000.11463242}, pmid = {26368632}, issn = {0895-8378}, abstract = {Asbestos has been shown to stimulate the mitogen-activated protein kinase signaling cascade after autophosphoryiation of the epidermal growth factor recptor (EGF-R), an event important in regulating the response of cells to extracellular signals. In studies reported here, we have examined whether mineral fibers with known carcinogenicity can be discriminated from nonpathogenic fibers by their ability to upregulate expression of EGF-R protein in mesothelial cells. Crocidolite and erionite, two fibrous preparations known to induce mesothelioma, increased expression of EGF-R protein in a time- and dose-dependent manner, whereas milled (nonfibrous) crocidolite and chrysotile asbestos, two preparations with much less or no ability to induce mesothelioma, did not. Intense patterns of EGF-R protein expression were linked to mesothelial cells phagocytosing long fibers as observed by phase-contrast microscopy. To determine the importance of EGF-R expression in these cells, we assessed downstream signaling events in rat pleural mesothelial (RPM) cells by looking at the induction of activator protein-1 (AP-I), a transcription factor that controls the transition to S phase in the cell cycle, leading to cell proliferation. Crocidolite induced AP-I in RPM cells in a dose-dependent manner, and this induction of AP-I in RPM cells was inhibited by coincubation with tyrphostin AG 1478, a potent inhibitor of the EGF-R. To examine the mechanism of induction of EGF-R in RPM cells by asbestos, RPM cells were treated with crocidolite in the presence and absence of the antioxidant N-acetylcysteine (NAC). Reduced glutathione (GSH) was examined as a marker of oxidative stress and the expression of EGF-R protein was measured. Crocidolite asbestos caused a dose-dependent depletion of GSH in RPM cells, and the presence of NAC ameliorated the expression of EGF-R protein by crocidolite. Our data suggest that carcinogenic fibers induce EGF-R via a mechanism involving oxidative stress initiating cell signaling cascades in mesothelial cells leading to cell proliferation and carcinogenesis.}, }
@article {pmid26368614, year = {2000}, author = {McConnell, EE and Carbone, M}, title = {A Comparison of Pleural Mesotheliomas Induced by Asbestos or SV40 Virus in Syrian Golden Hamsters.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {173-181}, doi = {10.1080/08958378.2000.11463211}, pmid = {26368614}, issn = {0895-8378}, abstract = {Pleural mesotheliomas are a well-known consequence of exposure to asbestos in both humans and animals. However, there are cases of mesothelioma in humans for which there is little or no known exposure to asbestos. Mesotheliomas have also been produced in hamsters infected with simian virus 40 (SV40), a contaminant of early polio vaccines, which was shown to replicate in individuals inoculated with the vaccine. Recently, wild-type SV40 has been detected in human mesotheliomas as well as other types of neoplasms. Because the tumors were induced with such dissimilar agents, we evaluated mesotheliomas produced in hamsters after intrapleural injection of SV40 compared to those produced after inhalation exposure to amosite asbestos to see if there were differences in the development and morphology of the tumors. Although the mesotheliomas produced by both agents were clearly of mesothelial origin based on standard morphological criteria, there were clear differences. The SV40-induced tumors occurred with a short latency period, were large multicentric lesions with pleural effusion that always caused death within 3 to 6 mo, and were largely composed of small round cells growing in a uniformly tubulopapillary pattern with many areas of sarcomatous change. They had a minimal amount of stroma and tended to invade the adjacent tissues. The unaffected pleura showed no evidence of fibrosis. In contrast, the mesotheliomas induced by asbestos occurred much later (most after 18 mo), were rarely (<10%) the cause of death, and were typically very small with little evidence of pleural effusion. While they also had a tubulopapillary pattern, they were composed of larger cells with more abundant cytoplasm and sarcomatous change was rare. The adjacent pleura typically showed marked evidence of fibrosis and local invasion was rarely encountered. Whether these striking morphological differences between SV40- and asbestos-induced mesotheliomas in hamsters have a correlate in humans is not known. It would be useful to conduct a similar comparison of mesotheliomas from humans known to have been exposed to high levels of asbestos to those with no known exposure to see if similar morphological differences exist.}, }
@article {pmid26368611, year = {2000}, author = {Unfried, K and Sandhu, H and Schürkes, C and Albrecht, C and Abel, J}, title = {Effects of Crocidolite Fibers on the Peritoneal Mesothelium of Rats.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {149-155}, doi = {10.1080/08958378.2000.11463208}, pmid = {26368611}, issn = {0895-8378}, abstract = {The assay of intraperitoneal (ip) injection to rats was used as experimental system to study the mechanisms of carcinogenic effects of fibrous dusts. With this test system, fibers were shown to induce mesothelioma in the peritoneal cavity. Although the data of the ip assay are discussed controversially in terms of risk assessment, it is a valuable tool to investigate the molecular mechanisms of mesothelioma carcinogenesis in vivo. This test system allows one to investigate both the effects of fibers on signal transduction and the genotoxic potential of fibers. On the level of mRNA expression, different stages of fiber-induced tumor development in the peritoneal space were examined using differential display techniques. Genes of signal transduction pathways are mainly affected by the fiber treatment; for example, the activation of genes for the AP-1 transcription factor could be observed in the tissues of the peritoneal cavity. Thus, our in vivo data confirm the findings reported from cell culture systems. Moreover, our results from the differential display assays reveal that genes involved in the integrin-linked signal transduction are upregulated. In addition, the ip assay can be applied to transgenic animals to perform mutagenicity testing. Using the Big Blue transgenic animal system, we provide data of a significant increase in mutation frequency after treatment with crocidolite asbestos.}, }
@article {pmid26368610, year = {2000}, author = {Hei, TK and Xu, A and Louie, D and Zhao, YL}, title = {Genotoxicity Versus Carcinogenicity: Implications from Fiber Toxicity Studies.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {141-147}, doi = {10.1080/08958378.2000.11463207}, pmid = {26368610}, issn = {0895-8378}, abstract = {Although the association between exposure to asbestos fibers and the development of lung cancer and mesothelioma has been well established in humans, the carcinogenic potential of other natural and man-made fibers/particles is not clear. Various in vitro genotoxicity studies have been employed to assess their in vivo carcinogenic potential. Studies using mammalian cell models have suggested that fiber dimensions, surface properties, physical durability, and cell and tissue responses are important criteria for the carcinogenicity of the fibers. Studies using oncogenic transformation as an endpoint have shown that asbestos fibers can induce malignantly transformed foci in certain rodent cells and that oxygen radicals are important in the toxic, oncogenic transforming, and mutagenic effects of asbestos fibers. The mutagenicity of asbestos in mammalian cells have been demonstrated using several model systems that can detect large multilocus deletions. These findings provide a direct link between chromosomal abnormalities that have frequently been demonstrated in fiber-exposed human and rodent cell lines and carcinogenicity in vivo. Although asbestos has not been shown to malignantly transform primary human epithelial cells, it can induce neoplastic conversion of immortalized human bronchial epithelial cells in a stepwise fashion and provides a unique opportunity to assess the molecular alterations associated with each stage of the neoplastic process.}, }
@article {pmid26368609, year = {2000}, author = {Kane, AB}, title = {Oncogenes and Tumor Suppressor Genes in the Carcinogenicity of Fibers and Particles.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {133-140}, doi = {10.1080/08958378.2000.11463206}, pmid = {26368609}, issn = {0895-8378}, abstract = {Asbestos fibers and crystalline silica are carcinogenic to humans when inhaled into the lungs. Asbestos fibers and cigarette smoke most likely act as cofactors in the induction of lung cancer. Point mutations in the K-ras oncogene and the p53 tumor-suppressor gene are frequent in lung cancers and are consistent with the known mutagenic spectrum of tobacco-smoke carcinogens. The FHIT tumor suppressor gene is also frequently inactivated in lung cancers of smokers and in workers who were exposed to asbestos. Recent molecular studies of p53 tumor suppressor gene mutations and p53 protein expression in the lungs of patients with lung cancer and occupational exposure to crystalline silica and other dusts have been conducted. Mutations in the p53 gene were detected at a frequency similar to those in smoking-related lung cancers. Expression of p53 protein can be detected by immunohisto-chemistry in preneoplastic epithelial lesions in the lungs of smokers and workers. Human malignant mesotheliomas frequently show overexpression of p53 protein; however, point mutations at the p53 tumor suppressor gene or ras oncogene locus are rare. Most cases of malignant mesotheliomas have codeletions of the p15 and p16 tumor suppressor genes and alterations at the NF2 tumor suppressor gene locus with monosomy of chromosome 22. The molecular alterations characteristic of malignant mesotheliomas may develop during later stages of tumor progression and may not reflect the direct genotoxic effects of fibers on the target cell population.}, }
@article {pmid26016040, year = {2015}, author = {Szeszenia-Dąbrowska, N and Świątkowska, B and Sobala, W and Szubert, Z and Wilczyńska, U}, title = {Asbestos related diseases among workers of asbestos processing plants in relation to type of production and asbestos use.}, journal = {Medycyna pracy}, volume = {66}, number = {1}, pages = {1-9}, pmid = {26016040}, issn = {0465-5893}, mesh = {Aged ; Asbestosis/diagnosis/*epidemiology ; Female ; Humans ; Lung Neoplasms/diagnosis/*epidemiology ; Male ; Mass Screening/*statistics &amp; numerical data ; Middle Aged ; National Health Programs/organization &amp; administration ; Occupational Diseases/diagnosis/*epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; Occupations/*statistics &amp; numerical data ; Poland/epidemiology ; Population Surveillance ; Public Health ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Asbestos dust is one of the most dangerous pneumoconiotic and carcinogenic agents. The aim of this study was to assess the occurrence of asbestosis and pleural mesothelioma, depending on asbestos consumption and the type of manufactured products, among former asbestos workers in Poland.<br><br>MATERIAL AND METHODS: The study subjects included employees of 18 large state-owned asbestos processing enterprises operating in the Polish market in 1945-1998. The study is based on data obtained from asbestos company records and the Central Register of Occupational Diseases data on the cases of asbestosis and mesothelioma for the period from 1970 till 2012 as well as data from Amiantus Programme. The analysis was performed for 5 sectors comprising plants classified according to the products manufactured and applied production technology.<br><br>RESULTS: In the study period, 2160 cases of asbestosis and 138 cases of mesothelioma were reported. The plants processed a total of about 2 million tons of asbestos, including about 7.5% of crocidolite. Total asbestosis consumption was a strong predictor of the rate of asbestosis incidence (R2 = 0.68, p = 0.055). The highest risk occurrence of asbestosis was observed in the production of textiles and sealing products. Mesothelioma occurred only in plants where crocidolite had been ever processed.<br><br>CONCLUSIONS: Total asbestos consumption was a strong predictor of the rate of asbestosis incidence. The observation confirms the relationship between exposure to crocidolite and the occurrence of mesothelioma, regardless of the manufactured products, and suggests the absence of such a link for the total volume of asbestos consumption.}, }
@article {pmid26011325, year = {2015}, author = {Hountis, P and Chounti, M and Matthaios, D and Romanidis, K and Moraitis, S}, title = {Surgical treatment for malignant pleural mesothelioma: extrapleural pneumonectomy, pleurectomy/decortication or extended pleurectomy?.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {20}, number = {2}, pages = {376-380}, pmid = {26011325}, issn = {1107-0625}, mesh = {Humans ; Lung Neoplasms/*surgery ; Mesothelioma/*surgery ; Mesothelioma, Malignant ; Pleura/*surgery ; Pleural Neoplasms/*surgery ; Pneumonectomy/*methods ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related disease with a dismal prognosis. Ethic, social, legal and economic parameters are implicated in its management. It is quite clear that multimodality therapy is necessary to improve long-term results but precise treatment schemes have not yet been equivocally accepted. The extent of surgery is questioned and radical operations are highly debatable. On the other hand, debulking or cyto-reductive surgery have been also proposed within a multimodality approach. However, the role and order of adjuvant or neoadjuvant use of chemotherapy, radiotherapy and surgery has not been established. The aim of this study was to analyze contemporary studies on the impact of different surgical approaches on outcome of patients with MPM.}, }
@article {pmid25985714, year = {2015}, author = {Cowan, DM and Cheng, TJ and Ground, M and Sahmel, J and Varughese, A and Madl, AK}, title = {Analysis of workplace compliance measurements of asbestos by the U.S. Occupational Safety and Health Administration (1984-2011).}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {72}, number = {3}, pages = {615-629}, doi = {10.1016/j.yrtph.2015.05.002}, pmid = {25985714}, issn = {1096-0295}, mesh = {Agriculture ; Air Pollutants, Occupational/*analysis/history/standards ; Asbestos/*analysis/history/standards ; Databases, Factual ; Environmental Monitoring ; History, 20th Century ; History, 21st Century ; Industry ; Occupational Exposure/*analysis/history/standards ; Transportation ; United States ; United States Occupational Safety and Health Administration/*standards ; Workplace/*standards ; }, abstract = {The United States Occupational Safety and Health Administration (OSHA) maintains the Chemical Exposure Health Data (CEHD) and the Integrated Management Information System (IMIS) databases, which contain quantitative and qualitative data resulting from compliance inspections conducted from 1984 to 2011. This analysis aimed to evaluate trends in workplace asbestos concentrations over time and across industries by combining the samples from these two databases. From 1984 to 2011, personal air samples ranged from 0.001 to 175 f/cc. Asbestos compliance sampling data associated with the construction, automotive repair, manufacturing, and chemical/petroleum/rubber industries included measurements in excess of 10 f/cc, and were above the permissible exposure limit from 2001 to 2011. The utility of combining the databases was limited by the completeness and accuracy of the data recorded. In this analysis, 40% of the data overlapped between the two databases. Other limitations included sampling bias associated with compliance sampling and errors occurring from user-entered data. A clear decreasing trend in both airborne fiber concentrations and the numbers of asbestos samples collected parallels historically decreasing trends in the consumption of asbestos, and declining mesothelioma incidence rates. Although air sampling data indicated that airborne fiber exposure potential was high (>10 f/cc for short and long-term samples) in some industries (e.g., construction, manufacturing), airborne concentrations have significantly declined over the past 30 years. Recommendations for improving the existing exposure OSHA databases are provided.}, }
@article {pmid25979846, year = {2015}, author = {Panou, V and Vyberg, M and Weinreich, UM and Meristoudis, C and Falkmer, UG and Røe, OD}, title = {The established and future biomarkers of malignant pleural mesothelioma.}, journal = {Cancer treatment reviews}, volume = {41}, number = {6}, pages = {486-495}, doi = {10.1016/j.ctrv.2015.05.001}, pmid = {25979846}, issn = {1532-1967}, mesh = {Biomarkers, Tumor/*analysis ; Calbindin 2/analysis ; Extracellular Matrix Proteins/analysis ; Humans ; Hyaluronic Acid/analysis ; Immunohistochemistry ; Keratin-5/analysis ; Lung Neoplasms/*diagnosis ; Membrane Glycoproteins/analysis ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/analysis ; Pleural Neoplasms/*diagnosis ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; WT1 Proteins/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a result of historic asbestos exposure in industrialized countries and continued use of asbestos in developing countries. Lack of accurate biomarkers makes diagnosis, prognostication and treatment prediction of MPM challenging. The aim of this review is to identify the front line of MPM biomarkers with current or potential clinical impact. Literature search using the PubMed and PLoS One databases, the related-articles function of PubMed and the reference lists of associated publications until April 26th 2015 revealed a plethora of candidate biomarkers. The current gold standard of MPM diagnosis is a combination of two positive and two negative immunohistochemical markers in the epithelioid and biphasic type, but sarcomatous type do not have specific markers, making diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as adjuvant diagnostic with high specificity but low sensitivity. Circulating proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test, transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N-ERC mesothelin and deformability cytometry may be important future markers. Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1 gene are potential markers of MPM susceptibility. In conclusion, the current status of MPM biomarkers is not satisfactory but encouraging as more sensitive and specific non-invasive markers are emerging. However, prospective validation is needed before clinical application.}, }
@article {pmid25975982, year = {2015}, author = {Chew, SH and Toyokuni, S}, title = {Malignant mesothelioma as an oxidative stress-induced cancer: An update.}, journal = {Free radical biology &amp; medicine}, volume = {86}, number = {}, pages = {166-178}, doi = {10.1016/j.freeradbiomed.2015.05.002}, pmid = {25975982}, issn = {1873-4596}, mesh = {Animals ; Asbestos/toxicity ; Biomarkers, Tumor/metabolism ; DNA Damage ; Environmental Exposure ; Humans ; Lung Neoplasms/diagnosis/etiology/*metabolism ; Mesothelioma/diagnosis/etiology/*metabolism ; Mesothelioma, Malignant ; *Oxidative Stress ; Signal Transduction ; }, abstract = {Malignant mesothelioma (MM) is a relatively rare cancer that occurs almost exclusively following respiratory exposure to asbestos in humans. Its pathogenesis is closely associated with iron overload and oxidative stress in mesothelial cells. On fiber exposure, mesothelial cells accumulate fibers simultaneously with iron, which either performs physical scissor function or catalyzes free radical generation, leading to oxidative DNA damage such as strand breaks and base modifications, followed by activation of intracellular signaling pathways. Chrysotile, per se without iron, causes massive hemolysis and further adsorbs hemoglobin. Exposure to indigestible foreign materials also induces chronic inflammation, involving consistent generation of free radicals and subsequent activation of NALP3 inflammasomes in macrophages. All of these contribute to mesothelial carcinogenesis. Genomic alterations most frequently involve homozygous deletion of INK4A/4B, and other pathways such as Hippo and TGF-β pathways are also affected in MM. Recently, analyses of familial MM sorted out BAP1 as a novel responsible tumor suppressor gene, whose function is not fully elucidated. Five-year survival of mesothelioma is still ~8%, and this cancer is increasing worldwide. Connective tissue growth factor, a secretory protein creating a vicious cycle mediated by β-catenin, has been recognized as a hopeful target for therapy, especially in sarcomatoid subtype. Recent research outcomes related to microRNAs and cancer stem cells also offer additional novel targets for the treatment of MM. Iron reduction as chemoprevention of mesothelioma is helpful at least in an animal preclinical study. Integrated approaches to fiber-induced oxidative stress would be necessary to overcome this currently fatal disease.}, }
@article {pmid25950487, year = {2015}, author = {Echeverry, N and Ziltener, G and Barbone, D and Weder, W and Stahel, RA and Broaddus, VC and Felley-Bosco, E}, title = {Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors.}, journal = {Cell death &amp; disease}, volume = {6}, number = {5}, pages = {e1757}, pmid = {25950487}, issn = {2041-4889}, mesh = {Autophagy/drug effects ; Bridged Bicyclo Compounds, Heterocyclic/*pharmacology ; Cell Proliferation/drug effects ; Drug Synergism ; Humans ; Imidazoles/*pharmacology ; Lung Neoplasms/*drug therapy/*metabolism/pathology ; Mesothelioma/*drug therapy/*metabolism/pathology ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/metabolism ; *Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines/*pharmacology ; Quinolines/*pharmacology ; Signal Transduction ; TOR Serine-Threonine Kinases/*antagonists &amp; inhibitors/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) originates in most of the cases from chronic inflammation of the mesothelium due to exposure to asbestos fibers. Given the limited effect of chemotherapy, a big effort is being made to find new treatment options. The PI3K/mTOR pathway was reported to be upregulated in MPM. We tested the cell growth inhibition properties of two dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 on 19 MPM cell lines. We could identify resistant and sensitive lines; however, there was no correlation to the downregulation of PI3K/mTOR activity markers. As a result of mTOR inhibition, both drugs efficiently induced long-term autophagy but not cell death. Autophagy blockade by chloroquine in combination with the dual PI3K/mTOR inhibitors significantly induced caspase-independent cell death involving RIP1 in the sensitive cell line SPC212. Cell death in the resistant cell line Mero-82 was less pronounced, and it was not induced via RIP1-dependent mechanism, suggesting the involvement of RIP1 downstream effectors. Cell death induction was confirmed in 3D systems. Based on these results, we identify autophagy as one of the main mechanisms of cell death resistance against dual PI3K/mTOR inhibitors in MPM. As PI3K/mTOR inhibitors are under investigation in clinical trials, these results may help interpreting their outcome and suggest ways for intervention.}, }
@article {pmid25941579, year = {2014}, author = {Ranki, T and Joensuu, T and Jäger, E and Karbach, J and Wahle, C and Kairemo, K and Alanko, T and Partanen, K and Turkki, R and Linder, N and Lundin, J and Ristimäki, A and Kankainen, M and Hemminki, A and Backman, C and Dienel, K and von Euler, M and Haavisto, E and Hakonen, T and Juhila, J and Jaderberg, M and Priha, P and Vassilev, L and Vuolanto, A and Pesonen, S}, title = {Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8[+] T-cell response, prominent infiltration of CD8[+] lymphocytes and Th1 type polarization.}, journal = {Oncoimmunology}, volume = {3}, number = {10}, pages = {e958937}, pmid = {25941579}, issn = {2162-4011}, abstract = {Late stage cancer is often associated with reduced immune recognition and a highly immunosuppressive tumor microenvironment. The presence of tumor infiltrating lymphocytes (TILs) and specific gene-signatures prior to treatment are linked to good prognosis, while the opposite is true for extensive immunosuppression. The use of adenoviruses as cancer vaccines is a form of active immunotherapy to initialise a tumor-specific immune response that targets the patient's unique tumor antigen repertoire. We report a case of a 68-year-old male with asbestos-related malignant pleural mesothelioma who was treated in a Phase I study with a granulocyte-macrophage colony‑stimulating factor (GM-CSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in prominent infiltration of CD8[+] lymphocytes to tumor, marked induction of systemic antitumor CD8[+] T-cells and induction of Th1-type polarization in the tumor. These results indicate that ONCOS-102 treatment sensitizes tumors to other immunotherapies by inducing a T-cell positive phenotype to an initially T-cell negative tumor.}, }
@article {pmid25941264, year = {2015}, author = {Dummer, T and Gotay, C}, title = {Asbestos in Canada: time to change our legacy.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {187}, number = {10}, pages = {E315-E316}, pmid = {25941264}, issn = {1488-2329}, mesh = {Asbestos/adverse effects ; Asbestos, Serpentine/*adverse effects ; Canada ; *Health Policy ; Humans ; Industry/*legislation &amp; jurisprudence ; *International Cooperation ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; }, }
@article {pmid25940505, year = {2015}, author = {Xu, J and Alexander, DB and Iigo, M and Hamano, H and Takahashi, S and Yokoyama, T and Kato, M and Usami, I and Tokuyama, T and Tsutsumi, M and Tamura, M and Oguri, T and Niimi, A and Hayashi, Y and Yokoyama, Y and Tonegawa, K and Fukamachi, K and Futakuchi, M and Sakai, Y and Suzui, M and Kamijima, M and Hisanaga, N and Omori, T and Nakae, D and Hirose, A and Kanno, J and Tsuda, H}, title = {Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study.}, journal = {Cancer science}, volume = {106}, number = {7}, pages = {825-832}, pmid = {25940505}, issn = {1349-7006}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood ; Carcinogens/*toxicity ; Case-Control Studies ; Chemokine CCL3/*blood ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*blood/chemically induced ; Male ; Mesothelioma/*blood/chemically induced ; Mesothelioma, Malignant ; Middle Aged ; }, abstract = {Exposure to asbestos results in serious risk of developing lung and mesothelial diseases. Currently, there are no biomarkers that can be used to diagnose asbestos exposure. The purpose of the present study was to determine whether the levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum are elevated in persons exposed to asbestos. The primary study group consisted of 76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly exposed to asbestos. The secondary study group consisted of 535 subjects possibly exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All study subjects who were possibly exposed to asbestos had a certificate of asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare. For the primary study group, levels of serum CCL3 did not differ between the two groups. However, the detection rate of CCL3 in the serum of healthy subjects possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis, and lung cancer groups had serum CCL3 levels and detection rates similar to that of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three of the patients with malignant mesothelioma had exceptionally high CCL3 levels. Malignant mesothelioma cells from four biopsy cases and an autopsy case were positive for CCL3, possibly identifying the source of the CCL3 in the three malignant mesothelioma patients with exceptionally high serum CCL3 levels. In conclusion, a significantly higher percentage of healthy persons possibly exposed to asbestos had detectable levels of serum CCL3 compared to healthy unexposed control subjects.}, }
@article {pmid25927434, year = {2015}, author = {Creaney, J and Dick, IM and Robinson, BW}, title = {Discovery of new biomarkers for malignant mesothelioma.}, journal = {Current pulmonology reports}, volume = {4}, number = {1}, pages = {15-21}, pmid = {25927434}, issn = {2199-2428}, abstract = {Malignant mesothelioma is an asbestos-induced, aggressive tumour with limited treatment options and very poor outcome. Currently, there are no tumour biomarkers in widespread clinical use for this disease. Soluble mesothelin is the most intensively investigated mesothelioma biomarker and has been approved by the US FDA primarily as a tool for monitoring patient response and progression. Mesothelin is elevated in the blood and effusions of patients with mesothelioma, and is rarely elevated in people with benign disease with normal renal function. However, the sensitivity of mesothelin limits its use as a stand-alone tool for the screening of the asymptomatic asbestos-exposed population-one of the primary aims of mesothelioma biomarker studies. Thus, there is an intense research effort focused on the identification of new and/or novel biomarkers for mesothelioma. Some of the challenges associated with biomarker discovery in mesothelioma are discussed.}, }
@article {pmid25915724, year = {2015}, author = {Yamashita, K and Nagai, H and Toyokuni, S}, title = {Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {95}, number = {7}, pages = {749-764}, pmid = {25915724}, issn = {1530-0307}, mesh = {Adsorption ; Animals ; Annexin A2/antagonists &amp; inhibitors/genetics/*metabolism ; Antigens, CD/genetics ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Blotting, Western ; Cell Line, Tumor ; *Endocytosis ; Epithelium/metabolism ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/*chemically induced ; Mass Spectrometry ; Membrane Proteins/chemistry ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Rats ; Receptors, Transferrin/genetics ; }, abstract = {Asbestos-induced mesothelioma is a worldwide problem. Parietal mesothelial cells internalize asbestos fibers that traverse the entire lung parenchyma, an action that is linked to mesothelial carcinogenesis. Thus far, vitronectin purified from serum reportedly enhances the internalization of crocidolite by mesothelial cells via integrin αvβ5. To reveal another mechanism by which mesothelial cells endocytose (phagocytose) asbestos, we first evaluated the effects of serum on asbestos uptake, which proved to be nonessential. Thereafter, we undertook a study to identify proteins on the surface of mesothelial cells (MeT5A) that act as receptors for asbestos uptake based on the assumption that receptors bind to asbestos with physical affinity. To this end, we incubated the membrane fraction of MeT5A cells with crocidolite or chrysotile and evaluated the adsorbed proteins using sodium dodecyl sulfate polyacrylamide gel analysis. Next, we extensively identified the proteins using an in-solution or in-gel digestion coupled with mass spectrometry. Among the identified proteins, annexin A2 (ANXA2) and transferrin receptor protein 1 (TFRC) were distinguished because of their high score and presence at the cell surface. Crocidolite uptake by MeT5A cells was significantly decreased by shRNA (short hairpin RNA)-induced knockdown of ANXA2 and direct blockade of cell surface ANXA2 using anti-ANXA2 antibody. In addition, abundant ANXA2 protein was present on the cell membrane of mesothelial cells, particularly facing the somatic cavity. These findings demonstrate that ANXA2 has a role in the mesothelial phagocytosis of crocidolite and may serve as its receptor.}, }
@article {pmid25902174, year = {2015}, author = {Miyanaga, A and Masuda, M and Tsuta, K and Kawasaki, K and Nakamura, Y and Sakuma, T and Asamura, H and Gemma, A and Yamada, T}, title = {Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {5}, pages = {844-851}, doi = {10.1097/JTO.0000000000000493}, pmid = {25902174}, issn = {1556-1380}, mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Apoptosis Regulatory Proteins ; Cadherins/genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Exome ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Mesothelioma/*genetics/metabolism ; Monomeric GTP-Binding Proteins/genetics ; Mutation ; Neurofibromin 2/genetics/metabolism ; Oncogene Proteins, Fusion/*genetics ; Phosphoproteins/genetics/metabolism ; Presenilin-1/*genetics ; Protein Serine-Threonine Kinases/*genetics/metabolism ; Recombinant Fusion Proteins/genetics ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Signal Transduction/*genetics ; Transcription Factors/metabolism ; Transcriptome ; Tumor Suppressor Proteins/genetics/metabolism ; YAP-Signaling Proteins ; }, abstract = {INTRODUCTION: Malignant mesothelioma (MM) is an aggressive neoplasm causatively associated with exposure to asbestos. MM is rarely responsive to conventional cytotoxic drugs, and the outcome remains dismal. It is, therefore, necessary to identify the signaling pathways that drive MM and to develop new therapeutics specifically targeting the molecules involved.<br><br>METHODS: We performed comprehensive RNA sequencing of 12 MM cell lines and four clinical samples using so-called next-generation sequencers.<br><br>RESULTS: We found 15 novel fusion transcripts including one derived from chromosomal translocation between the large tumor suppressor 1 (LATS1) and presenilin-1 (PSEN1) genes. LATS1 is one of the central players of the emerging Hippo signaling pathway. The LATS1-PSEN1 fusion gene product lacked the ability to phosphorylate yes-associated protein and to suppress the growth of a MM cell line. The wild-type LATS1 allele was undetectable in this cell line, indicating two-hit genetic inactivation of its tumor suppressor function. Using pathway-targeted exon sequencing, we further identified a total of 11 somatic mutations in four Hippo pathway genes (neurofibromatosis type 2 [NF2], LATS2, RASSF1, and SAV1) in 35% (8 of 23) of clinical samples. Nuclear staining of yes-associated protein was detected in 55% (24 of 44) of the clinical samples. Expression and/or phosphorylation of the Hippo signaling proteins, RASSF1, Merlin (NF2), LATS1, and LATS2, was frequently absent.<br><br>CONCLUSIONS: The frequent alterations of Hippo pathway molecules found in this study indicate the therapeutic feasibility of targeting this pathway in patients with MM.}, }
@article {pmid25896339, year = {2015}, author = {Lee, YJ and Lee, DM and Lee, SH}, title = {Nrf2 Expression and Apoptosis in Quercetin-treated Malignant Mesothelioma Cells.}, journal = {Molecules and cells}, volume = {38}, number = {5}, pages = {416-425}, pmid = {25896339}, issn = {0219-1032}, mesh = {Antioxidants/*pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Drug Synergism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mesothelioma/drug therapy/genetics/*metabolism ; NF-E2-Related Factor 2/antagonists &amp; inhibitors/genetics/*metabolism ; Quercetin/*pharmacology ; RNA, Small Interfering/*pharmacology ; Up-Regulation/drug effects ; }, abstract = {NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2-upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-G0/G1 peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.}, }
@article {pmid25889843, year = {2015}, author = {Alakus, H and Yost, SE and Woo, B and French, R and Lin, GY and Jepsen, K and Frazer, KA and Lowy, AM and Harismendy, O}, title = {BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma.}, journal = {Journal of translational medicine}, volume = {13}, number = {}, pages = {122}, pmid = {25889843}, issn = {1479-5876}, support = {U54 HL108460/HL/NHLBI NIH HHS/United States ; U54HL108460/HL/NHLBI NIH HHS/United States ; R21 CA177519/CA/NCI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; P30CA023100/CA/NCI NIH HHS/United States ; TL1 TR000098/TR/NCATS NIH HHS/United States ; R21CA177519/CA/NCI NIH HHS/United States ; }, mesh = {DNA Copy Number Variations/genetics ; *Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Mutation/*genetics ; Peritoneal Neoplasms/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) arises from mesothelial cells that line the pleural, peritoneal and pericardial surfaces. The majority of MMs are pleural and have been associated with asbestos exposure. Previously, pleural MMs have been genetically characterized by the loss of BAP1 (40-60%) as well as loss of NF2 (75%) and CDKN2A (60%). The rare peritoneal form of MM occurs in ~10% cases. With only ~300 cases diagnosed in the US per year, its link to asbestos exposure is not clear and its mutational landscape unknown.<br><br>METHODS: We analyzed the somatic mutational landscape of 12 peritoneal MM of epitheloid subtype using copy number analysis (N&#x2009;=&#x2009;9), whole exome sequencing (N&#x2009;=&#x2009;7) and targeted sequencing (N&#x2009;=&#x2009;12).<br><br>RESULTS: Peritoneal MM display few copy number alterations, with most samples having less than 10 Mbp total changes, mostly through deletions and no high copy number amplification. Chromosome band 3p21 encoding BAP1 is the most recurrently deleted region (5/9), while, in contrast to pleural MM, NF2 and CDKN2A are not affected. We further identified 87 non-silent mutations across 7 sequenced tumors, with a median of 8 mutated genes per tumor, resulting in a very low mutation rate (median 1.3 10(-6)). BAP1 was the only recurrently mutated gene (N&#x2009;=&#x2009;3/7). In one additional case, loss of the entire chromosome 3 leaves a non-functional copy of BAP1 carrying a rare nonsense germline variant, thus suggesting a potential genetic predisposition in this patient. Finally, with targeted sequencing of BAP1 in 3 additional cases, we conclude that BAP1 is frequently altered through copy number losses (N&#x2009;=&#x2009;3/12), mutations (N&#x2009;=&#x2009;3/12) or both (N&#x2009;=&#x2009;2/12) sometimes at a sub-clonal level.<br><br>CONCLUSION: Our findings suggest a major role for BAP1 in peritoneal MM susceptibility and oncogenesis and indicate important molecular differences to pleural MM as well as potential strategies for therapy and prevention.}, }
@article {pmid25885893, year = {2015}, author = {Corfiati, M and Scarselli, A and Binazzi, A and Di Marzio, D and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Merler, E and Negro, C and Romanelli, A and Chellini, E and Silvestri, S and Cocchioni, M and Pascucci, C and Stracci, F and Romeo, E and Trafficante, L and Angelillo, I and Menegozzo, S and Musti, M and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and Iavicoli, S and Marinaccio, A and , }, title = {Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {286}, pmid = {25885893}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Bayes Theorem ; Child ; Child, Preschool ; Cluster Analysis ; Environmental Exposure/*adverse effects ; Female ; Geography ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Registries ; Spatial Analysis ; Young Adult ; }, abstract = {BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM).<br><br>METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster.<br><br>RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters.<br><br>CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs.}, }
@article {pmid25877069, year = {2015}, author = {Blum, W and Pecze, L and Felley-Bosco, E and Worthmüller-Rodriguez, J and Wu, L and Vrugt, B and de Perrot, M and Schwaller, B}, title = {Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line.}, journal = {In vitro cellular &amp; developmental biology. Animal}, volume = {51}, number = {7}, pages = {714-721}, pmid = {25877069}, issn = {1543-706X}, mesh = {Animals ; Antigens, Polyomavirus Transforming/metabolism ; Cell Line, Transformed ; *Cell Line, Tumor ; Cell Proliferation ; Epithelial Cells/pathology ; GPI-Linked Proteins/metabolism ; Lung Neoplasms/*pathology ; Mesothelin ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Neurofibromin 2/genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Mesothelial cells are susceptible to asbestos fiber-induced cytotoxicity and on longer time scales to transformation; the resulting mesothelioma is a highly aggressive neoplasm that is considered as incurable at the present time Zucali et al. (Cancer Treatment Reviews 37:543-558, 2011). Only few murine cell culture models of immortalized mesothelial cells and mesothelioma cell lines exist to date. We generated SV40-immortalized cell lines derived from wild-type (WT) and neurofibromatosis 2 (merlin) heterozygote (Nf2+/-) mice, both on a commonly used genetic background, C57Bl/6J. All immortalized mesothelial clones consistently grow in DMEM supplemented with fetal bovine serum. Cells can be passaged for more than 40 times without any signs of morphological changes or a decrease in proliferation rate. The tumor suppressor gene NF2 is one of the most frequently mutated genes in human mesothelioma, but its detailed function is still unknown. Thus, these genotypically distinct cell lines likely relevant for malignant mesothelioma formation are expected to serve as useful in vitro models, in particular to compare with in vivo studies in mice of the same genotype. Furthermore, we generated a novel murine mesothelioma cell line RN5 originating from an Nf2+/- mouse subjected to repeated crocidolite exposure. RN5 cells are highly tumorigenic.}, }
@article {pmid25876702, year = {2015}, author = {Lee, R and Van Orden, D}, title = {RE: Gordon R, Fitzgerald S, and Millette J. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women. Int J Occup Environ Health. 2014;20(4):318-332.}, journal = {International journal of occupational and environmental health}, volume = {}, number = {}, pages = {2049396715Y0000000005}, doi = {10.1179/2049396715Y.0000000005}, pmid = {25876702}, issn = {2049-3967}, }
@article {pmid25874240, year = {2015}, author = {Szeszenia-Dąbrowska, N and Świątkowska, B}, title = {An unjustified prognosis of the number of asbestos-related lung cancer cases caused by an increase in airborne asbestos concentrations as a result of removing of asbestos-cement products.}, journal = {TheScientificWorldJournal}, volume = {2015}, number = {}, pages = {264568}, pmid = {25874240}, issn = {1537-744X}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; }, }
@article {pmid25856259, year = {2015}, author = {Wolff-Bar, M and Dujovny, T and Vlodavsky, E and Postovsky, S and Morgenstern, S and Braslavsky, D and Nissan, A and Steinberg, R and Feinmesser, M}, title = {An 8-Year-Old Child with Malignant Deciduoid Mesothelioma of the Abdomen: Report of a Case and Review of the Literature.}, journal = {Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society}, volume = {18}, number = {4}, pages = {327-330}, doi = {10.2350/14-06-1511-CR.1}, pmid = {25856259}, issn = {1093-5266}, mesh = {Abdominal Pain/etiology ; Biopsy ; Child ; Female ; Humans ; Mesothelioma/complications/*pathology/therapy ; Peritoneal Neoplasms/complications/*pathology/therapy ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is an uncommon tumor that usually arises in the pleural cavity of adults with a history of asbestos exposure. Less frequently, it appears in the peritoneum or other mesothelial surfaces. Deciduoid mesothelioma is a rare subtype that has been found at both sites. Of the 3 reported cases in children, 2 originated in the mesenterium and 1 in the pleura. We describe a 4th case of pediatric, malignant, deciduoid mesothelioma and a third case in the mesenteric cavity. The patient was an 8-year-old girl who presented with abdominal pain and fullness. Workup revealed extensive involvement of the abdomen by a serosa-based tumor. The clinical and pathologic findings are described, and the pertinent literature is reviewed.}, }
@article {pmid25847205, year = {2015}, author = {Challita, S and Guerder, A and Charpentier, MC and Daher, M and Giraud, F and Roche, N}, title = {[Mesothelioma and familial Mediterranean fever: A relationship?].}, journal = {Revue des maladies respiratoires}, volume = {32}, number = {3}, pages = {271-274}, doi = {10.1016/j.rmr.2014.06.029}, pmid = {25847205}, issn = {1776-2588}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Causality ; Colchicine/therapeutic use ; Familial Mediterranean Fever/*complications/drug therapy/pathology ; Female ; Humans ; Inflammation ; Lebanon/ethnology ; Mesothelioma/diagnosis/drug therapy/*etiology ; Middle Aged ; Organoplatinum Compounds/administration &amp; dosage ; Pemetrexed/administration &amp; dosage ; Peritoneum/pathology ; Pleural Neoplasms/diagnosis/drug therapy/*etiology ; Serous Membrane/pathology ; }, abstract = {INTRODUCTION: The majority of pleural and peritoneal mesotheliomas are linked to asbestos exposure but, in around 20% of cases, no history of such exposure is found. Periodic disease is associated with recurrent serositis, which could favor the development of mesothelioma.<br><br>CASE REPORT: We report a case of pleural mesothelioma in a 50-year-old Lebanese woman, with no detectable exposure to asbestos but suffering from periodic disease (familial Mediterranean fever) with recurrent episodes of serositis.<br><br>DISCUSSION: Many cases of peritoneal mesothelioma in patients with FMF are reported in the literature. This is the second reported case of pleural mesothelioma associated with periodic disease. Because of the low incidence of both diseases, further publications are required to support the hypothesis of a causal link. It is important, therefore, that all cases of an association of periodic disease and mesothelioma are reported.}, }
@article {pmid25844559, year = {2015}, author = {Li, X and Brownlee, NA and Sporn, TA and Mahar, A and Roggli, VL}, title = {Malignant (Diffuse) Mesothelioma in Patients With Hematologic Malignancies: A Clinicopathologic Study of 45 Cases.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {139}, number = {9}, pages = {1129-1136}, doi = {10.5858/arpa.2014-0569-OA}, pmid = {25844559}, issn = {1543-2165}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Child ; Female ; Hematologic Neoplasms/*pathology/radiotherapy ; Hodgkin Disease/pathology ; Humans ; Kaplan-Meier Estimate ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Lung Neoplasms/etiology/mortality/*pathology ; Lymphoma, Non-Hodgkin/pathology ; Male ; Mesothelioma/etiology/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms, Multiple Primary/etiology/*pathology ; Neoplasms, Radiation-Induced/etiology/pathology ; Radiotherapy/adverse effects ; Risk Factors ; Time Factors ; Young Adult ; }, abstract = {CONTEXT: Ionizing radiation has a role in the development of malignant mesothelioma, in several epidemiologic studies, including patients with hematologic malignancies.<br><br>OBJECTIVE: To study the clinicopathologic characteristics of patients with malignant mesothelioma and hematologic malignancies with and without a history of radiotherapy.<br><br>DESIGN: From a database of approximately 3600 patients with malignant mesothelioma, we identified 45 patients (1%) who also had hematologic malignancies. We examined clinicopathologic features and noted whether the patient had received radiotherapy for malignancy, comparing those with and those without such exposure.<br><br>RESULTS: Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%) had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%) had chronic myelogenous leukemia; 20 patients (44%) had a history of radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of 18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of 12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so. Patients without radiation were older than patients who received radiotherapy (median, 73 versus 54 years, respectively; P < .001), had a shorter interval from diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24 years, respectively; P < .001), and had a shorter survival period (median, 6.0 versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were proportionately more common in patients with a history of radiotherapy.<br><br>CONCLUSIONS: Patients with mesothelioma and hematologic malignancies with a history of radiation tended to be younger, had a longer interval from diagnosis of hematologic malignancy to that of mesothelioma, had a longer survival period, and were more likely to have the epithelial variant compared with patients without radiotherapy.}, }
@article {pmid25842376, year = {2015}, author = {Finkelstein, MM}, title = {Asbestos fibres in the lungs of an American mechanic who drilled, riveted, and ground brake linings: a case report and discussion.}, journal = {The Annals of occupational hygiene}, volume = {59}, number = {4}, pages = {525-527}, doi = {10.1093/annhyg/mev008}, pmid = {25842376}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/adverse effects/*analysis ; Automobiles ; Fatal Outcome ; Humans ; Inhalation Exposure/*analysis ; Lung/*chemistry/ultrastructure ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Occupational Exposure/analysis ; }, abstract = {In North America and Europe, the use of asbestos in friction products was discontinued before the end of the 20th century. In the developing world, the use of asbestos-containing friction products continues. In 2010, Cely-Garcia and colleagues (Cely-Garcia et al., 2012) sampled three brake repair shops located in Bogota, Colombia. Both asbestos and non-asbestos containing brake linings were sold separately or attached to a shoe. When brake linings are sold separated from the shoe, they must be manipulated to attach them to the shoe before installation. The process starts with the removal of the old brake shoe from the vehicle's brake drum. If the existing brake shoe is to be reused, the old lining needs to be removed and the old shoe must be ground to prepare it for a new lining. Riveting requires drilling holes in the linings and shoes and before installing rivets, the lining must be countersunk. The borders of the lining are bevelled. On some occasions, the entire exposed surface of the lining is ground to make it thinner. Once attached to the shoe, the edges of brake linings may extend beyond the shoe. In this case, it is necessary to cut or grind the edges to match the lining to the shoe before bevelling or grinding. The authors reported that 'the sampling results indicate that the brake mechanics sampled are exposed to extremely high asbestos concentrations (i.e. based on transmission electron microscopy counts), suggesting that this occupational group could be at excess risk of asbestos-related diseases'.}, }
@article {pmid25841001, year = {2015}, author = {van Oyen, SC and Peters, S and Alfonso, H and Fritschi, L and de Klerk, NH and Reid, A and Franklin, P and Gordon, L and Benke, G and Musk, AW}, title = {Development of a Job-Exposure Matrix (AsbJEM) to Estimate Occupational Exposure to Asbestos in Australia.}, journal = {The Annals of occupational hygiene}, volume = {59}, number = {6}, pages = {737-748}, doi = {10.1093/annhyg/mev017}, pmid = {25841001}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/adverse effects/*analysis ; Asbestosis ; Australia ; Environmental Monitoring/*methods ; Humans ; Mesothelioma ; Occupational Diseases ; Occupational Exposure/*analysis ; *Occupations ; }, abstract = {INTRODUCTION: Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions.<br><br>OBJECTIVE: To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data.<br><br>METHODS: A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation.<br><br>RESULTS: Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; &#x2265;2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml(-1). Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite.<br><br>CONCLUSION: The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asbestos-related diseases and attribution of disease causation.}, }
@article {pmid25828940, year = {2015}, author = {Baas, P and Burgers, S}, title = {ASIA: asbestos stop in Asia.}, journal = {Respirology (Carlton, Vic.)}, volume = {20}, number = {4}, pages = {521}, doi = {10.1111/resp.12533}, pmid = {25828940}, issn = {1440-1843}, mesh = {*Asbestos ; *Asbestosis ; *Environmental Exposure ; Humans ; *Industry ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid25824152, year = {2015}, author = {Birnie, KA and Yip, YY and Ng, DC and Kirschner, MB and Reid, G and Prêle, CM and Musk, AW and Lee, YC and Thompson, PJ and Mutsaers, SE and Badrian, B}, title = {Loss of miR-223 and JNK Signaling Contribute to Elevated Stathmin in Malignant Pleural Mesothelioma.}, journal = {Molecular cancer research : MCR}, volume = {13}, number = {7}, pages = {1106-1118}, doi = {10.1158/1541-7786.MCR-14-0442}, pmid = {25824152}, issn = {1557-3125}, mesh = {Animals ; Australia ; Cell Line, Tumor ; Cell Movement ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Lung Neoplasms/*metabolism/pathology ; *MAP Kinase Signaling System ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; MicroRNAs/*metabolism ; Paraffin Embedding ; Primary Cell Culture ; Stathmin/genetics/*metabolism ; }, abstract = {UNLABELLED: Malignant pleural mesothelioma (MPM) is often fatal, and studies have revealed that aberrant miRNAs contribute to MPM development and aggressiveness. Here, a screen of miRNAs identified reduced levels of miR-223 in MPM patient specimens. Interestingly, miR-223 targets Stathmin (STMN1), a microtubule regulator that has been associated with MPM. However, whether miR-223 regulates STMN1 in MPM and the functions of miR-223 and STMN1 in this disease are yet to be determined. STMN1 is also regulated by c-Jun N-terminal kinase (JNK) signaling, but whether this occurs in MPM and whether miR-223 plays a role are unknown. The relationship between STMN1, miR-223, and JNK was assessed using MPM cell lines, cells from pleural effusions, and MPM tissue. Evidence indicates that miR-223 is decreased in all MPM tissue compared with normal/healthy tissue. Conversely, STMN1 expression was higher in MPM cell lines when compared with primary mesothelial cell controls. Following overexpression of miR-223 in MPM cell lines, STMN1 levels were reduced, cell motility was inhibited, and tubulin acetylation induced. Knockdown of STMN1 using siRNAs led to inhibition of MPM cell proliferation and motility. Finally, miR-223 levels increased while STMN1 was reduced following the re-expression of the JNK isoforms in JNK-null murine embryonic fibroblasts, and STMN1 was reduced in MPM cell lines following the activation of JNK signaling.<br><br>IMPLICATIONS: miR-223 regulates STMN1 in MPM, and both are in turn regulated by the JNK signaling pathway. As such, miR-223 and STMN1 play an important role in regulating MPM cell motility and may be therapeutic targets.}, }
@article {pmid25823924, year = {2015}, author = {Cho, JH and Lee, SJ and Oh, AY and Yoon, MH and Woo, TG and Park, BJ}, title = {NF2 blocks Snail-mediated p53 suppression in mesothelioma.}, journal = {Oncotarget}, volume = {6}, number = {12}, pages = {10073-10085}, pmid = {25823924}, issn = {1949-2553}, mesh = {Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Genes, Neurofibromatosis 2 ; Humans ; Lung Neoplasms/chemically induced/*etiology/genetics/pathology ; Mesothelioma/chemically induced/*etiology/genetics/pathology ; Mesothelioma, Malignant ; Naphthoquinones/pharmacology ; Neurofibromin 2/biosynthesis/genetics/*metabolism ; Phosphatidylethanolamine Binding Protein/metabolism ; Silicon Dioxide/toxicity ; Snail Family Transcription Factors ; Transcription Factors/*antagonists &amp; inhibitors/biosynthesis/genetics ; Transfection ; Tumor Suppressor Protein p53/*antagonists &amp; inhibitors/biosynthesis/*genetics ; }, abstract = {Although asbestos causes malignant pleural mesothelioma (MPM), rising from lung mesothelium, the molecular mechanism has not been suggested until now. Extremely low mutation rate in classical tumor suppressor genes (such as p53 and pRb) and oncogenes (including Ras or myc) indicates that there would be MPM-specific carcinogenesis pathway. To address this, we treated silica to mimic mesothelioma carcinogenesis in mesothelioma and non-small cell lung cancer cell lines (NSCLC). Treatment of silica induced p-Erk and Snail through RKIP reduction. In addition, p53 and E-cadherin were decreased by silica-treatment. Elimination of Snail restored p53 expression. We found that NF2 (frequently deleted in MPM) inhibited Snail-mediated p53 suppression and was stabilized by RKIP. Importantly, GN25, an inhibitor of p53-Snail interaction, induced p53 and apoptosis. These results indicate that MPM can be induced by reduction of RKIP/NF2, which suppresses p53 through Snail. Thus, the p53-Snail binding inhibitor such as GN25 is a drug candidate for MPM.}, }
@article {pmid25821338, year = {2015}, author = {Klebe, S and Griggs, K and Cheng, Y and Driml, J and Henderson, DW and Reid, G}, title = {Blockade of aquaporin 1 inhibits proliferation, motility, and metastatic potential of mesothelioma in vitro but not in an in vivo model.}, journal = {Disease markers}, volume = {2015}, number = {}, pages = {286719}, pmid = {25821338}, issn = {1875-8630}, mesh = {Aged ; Aged, 80 and over ; Animals ; Antineoplastic Agents/*therapeutic use ; Apoptosis ; Aquaporin 1/*antagonists &amp; inhibitors/genetics/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Female ; Humans ; Male ; Mesothelioma/drug therapy/*metabolism ; Mice ; Mice, Nude ; Pleural Effusion, Malignant/drug therapy/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1) was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM.<br><br>METHODS: Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050) or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies.<br><br>RESULTS: Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours.<br><br>CONCLUSIONS: Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo.}, }
@article {pmid25819225, year = {2015}, author = {Leong, SL and Zainudin, R and Kazan-Allen, L and Robinson, BW}, title = {Asbestos in Asia.}, journal = {Respirology (Carlton, Vic.)}, volume = {20}, number = {4}, pages = {548-555}, doi = {10.1111/resp.12517}, pmid = {25819225}, issn = {1440-1843}, mesh = {*Asbestos ; *Asbestosis ; Asia ; China ; *Environmental Exposure ; Humans ; Indonesia ; *Industry ; Japan ; Lung Diseases ; *Lung Neoplasms ; *Mesothelioma ; Republic of Korea ; Singapore ; }, abstract = {Asbestos is a global killer. Despite lessons learned in the developed world on the use of asbestos and its hazardous pulmonary consequences, its use continues to increase in Asia. Although some countries such as Japan, Korea and Singapore have curtailed the use of this mineral, there are numerous countries in Asia that continue to mine, import and use this fibre, particularly China, which is one of the largest consumers in the world. Numerous factors ranging from political and economic to the lack of understanding of asbestos and the management of asbestos-related lung disease are keys to this observed trend. Awareness of these factors combined with early intervention may prevent the predicted Asian 'tsunami' of asbestos diseases.}, }
@article {pmid25802741, year = {2015}, author = {Mitsui, A and Saji, H and Shimmyo, T and Mochizuki, A and Kurimoto, N and Nakamura, H}, title = {Malignant pleural mesothelioma presenting as a spontaneous pneumothorax.}, journal = {Respirology case reports}, volume = {3}, number = {1}, pages = {9-12}, pmid = {25802741}, issn = {2051-3380}, abstract = {Malignant pleural mesothelioma (MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath and have a history of asbestos exposure. MPM rarely presents as spontaneous pneumothorax. We report two male patients who presented with a spontaneous hydropneumothorax. One was exposed to asbestos and the other was not. Computed tomography showed tiny nodules with pleural thickness. They both underwent pleural effusion cytology and/or pleural biopsy. Therefore, the pathological diagnosis of MPM was obtained in both cases. We also reviewed 16 Japanese MPM cases with pneumothorax including our two patients. More than half of the patients suffered from pneumothorax repeatedly. We emphasize the need to obtain a pathological diagnosis of pleural effusion cytology and/or pleural biopsy in older patients presenting with a spontaneous hydropneumothorax.}, }
@article {pmid25797984, year = {2015}, author = {Toyokuni, S and Jiang, LI and Kitaura, R and Shinohara, H}, title = {Minimal inflammogenicity of pristine single-wall carbon nanotubes.}, journal = {Nagoya journal of medical science}, volume = {77}, number = {1-2}, pages = {195-202}, pmid = {25797984}, issn = {0027-7622}, abstract = {Carbon nanotubes (CNTs) are a novel synthetic material comprising only carbon atoms. Based on its rigidity, its electrical and heat conductivity and its applicability to surface manufacturing, this material is expected to have numerous applications in industry. However, due to the material's dimensional similarity to asbestos fibers, its carcinogenicity was hypothesized during the last decade, and indeed, we have shown that multi-wall CNTs (MWCNTs) of 50 nm in diameter are potently carcinogenic to mesothelial cells after intraperitoneal injection. Additionally, we suggested that inflammogenicity after intraperitoneal injection can predict mesothelial carcinogenesis. However, few data have been published on the intraperitoneal inflammogenicity of single-wall CNTs (SWCNTs). Here, we conducted a series of studies on SWCNTs using both intraperitoneal injection into rats and MeT5A mesothelial cells. Intraperitoneal injection of 10 mg SWCNTs caused no remarkable inflammation in the abdominal cavity, and the exposure of MeT5A cells to up to 25 μg/cm(2) SWCNTs did not alter proliferation. MWCNTs of 50 nm in diameter were used as a positive control, and tangled MWCNTs of 15 nm in diameter were used as a negative control. The results suggest that SWCNTs are a low-risk material with respect to mesothelial carcinogenesis.}, }
@article {pmid25796603, year = {2015}, author = {Sneddon, S and Leon, JS and Dick, IM and Cadby, G and Olsen, N and Brims, F and Allcock, RJ and Moses, EK and Melton, PE and de Klerk, N and Musk, AW and Robinson, BW and Creaney, J}, title = {Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.}, journal = {Gene}, volume = {563}, number = {1}, pages = {103-105}, doi = {10.1016/j.gene.2015.03.031}, pmid = {25796603}, issn = {1879-0038}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Australia ; Female ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Lung Neoplasms/chemically induced/*genetics ; Male ; Mesothelioma/chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM.}, }
@article {pmid25793652, year = {2015}, author = {Haberman, A}, title = {Unusual appearance of malignant peritoneal mesothelioma.}, journal = {Journal of computer assisted tomography}, volume = {39}, number = {3}, pages = {419-421}, doi = {10.1097/RCT.0000000000000240}, pmid = {25793652}, issn = {1532-3145}, mesh = {Adult ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma/*diagnosis ; Peritoneal Neoplasms/*diagnosis ; Tomography, X-Ray Computed/*methods ; Ultrasonography/*methods ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare and fatal cancer arising from the mesothelial cells lining the peritoneum. This typically occurs in men in their fifth and sixth decades, but can be seen in women and any age group. Pleural and extrapleural mesothelioma can arise in the setting of asbestos exposure, but other reported causes of MPM include exposure to silicate fibers and radiation therapy. Because it presents with vague symptoms such as abdominal pain, anorexia, and weight loss, it is generally advanced at diagnosis. This is a case of MPM that presented initially at contrast-enhanced computed tomography as a small focal lesion in the lesser sac, ultimately resulting in death from complications of the disease.}, }
@article {pmid25759902, year = {2014}, author = {Seldén, A and Lundgren, L and Plato, N}, title = {["Bear plug"--asbestos source in every home?].}, journal = {Lakartidningen}, volume = {111}, number = {42}, pages = {1850}, pmid = {25759902}, issn = {0023-7205}, mesh = {Asbestos, Amosite/*toxicity ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Construction Industry/history ; History, 20th Century ; Humans ; Mesothelioma/etiology ; Microscopy, Electron, Scanning ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology ; }, }
@article {pmid25759516, year = {2015}, author = {Funahashi, S and Okazaki, Y and Ito, D and Asakawa, A and Nagai, H and Tajima, M and Toyokuni, S}, title = {Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {56}, number = {2}, pages = {111-117}, pmid = {25759516}, issn = {0912-0009}, abstract = {Asbestos exposure is considered a social burden by causing mesothelioma. Despite the use of synthetic materials, multi-walled carbon nanotubes (MWCNTs) are similar in dimension to asbestos and produce mesothelioma in animals. The role of inflammatory cells in mesothelial carcinogenesis remains unclear. Here, we evaluated the differences in inflammatory cell responses following exposure to these fibrous materials using a luminometer and L-012 (8-amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H) dione) to detect reactive oxygen species (ROS). Rat peripheral blood or RAW264.7 cells were used to assess the effects on neutrophils and macrophages, respectively. Crocidolite and amosite induced significant ROS generation by neutrophils with a peak at 10 min, whereas that of chrysotile was ~25% of the crocidolite/amosite response. MWCNTs with different diameters (~15, 50, 115 and 145 nm) and different carcinogenicity did not induce significant ROS in peripheral blood. However, the MWCNTs induced a comparable amount of ROS in RAW264.7 cells to that following asbestos treatment. The peaks for MWCNTs (0.5-1.5 h) were observed earlier than those for asbestos (1-5 h). Apocynin and superoxide dismutase significantly inhibited ROS generation for each fiber, suggesting an involvement of NADPH oxidase and superoxide. Thus, asbestos and MWCNTs induce different oxidative responses in inflammatory cells, indicating the importance of mesothelial cell evaluation for carcinogenesis.}, }
@article {pmid25759091, year = {2015}, author = {Hida, T and Hamasaki, M and Matsumoto, S and Abe, S and Takakura, K and Hiroshima, K and Nabeshima, K}, title = {Diffuse intrapulmonary malignant mesothelioma presenting with miliary pulmonary nodules: A case report.}, journal = {Pathology international}, volume = {65}, number = {6}, pages = {318-323}, doi = {10.1111/pin.12282}, pmid = {25759091}, issn = {1440-1827}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Asbestos/adverse effects ; Biopsy ; Cisplatin/therapeutic use ; Fatal Outcome ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung/pathology ; Lung Neoplasms/drug therapy/*pathology ; Male ; Mesothelioma/drug therapy/*pathology ; Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; }, abstract = {A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2-40, and CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.}, }
@article {pmid25757056, year = {2015}, author = {Dragon, J and Thompson, J and MacPherson, M and Shukla, A}, title = {Differential Susceptibility of Human Pleural and Peritoneal Mesothelial Cells to Asbestos Exposure.}, journal = {Journal of cellular biochemistry}, volume = {116}, number = {8}, pages = {1540-1552}, pmid = {25757056}, issn = {1097-4644}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*toxicity ; Cell Line ; Cell Survival/drug effects ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammation/genetics ; Lung Neoplasms/chemically induced/*genetics/*pathology ; Male ; Mesothelioma/chemically induced/*genetics/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/chemically induced/*genetics/pathology ; Pleural Neoplasms/chemically induced/*genetics/pathology ; Sequence Analysis, RNA ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer of mesothelial cells of pleural and peritoneal cavities. In 85% of cases both pleural and peritoneal MM is caused by asbestos exposure. Although both are asbestos-induced cancers, the incidence of pleural MM is significantly higher (85%) than peritoneal MM (15%). It has been proposed that carcinogenesis is a result of asbestos-induced inflammation but it is not clear what contributes to the differences observed between incidences of these two cancers. We hypothesize that the observed differences in incidences of pleural and peritoneal MM are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis we characterized cellular responses to asbestos in a controlled environment. We found significantly greater changes in genome-wide expression in response to asbestos exposure in pleural mesothelial cells as compared to peritoneal mesothelial cells. In particular, a greater response in many common genes (IL-8, ATF3, CXCL2, CXCL3, IL-6, GOS2) was seen in pleural mesothelial cells as compared to peritoneal mesothelial cells. Unique genes expressed in pleural mesothelial cells were mainly pro-inflammatory (G-CSF, IL-1β, IL-1α, GREM1) and have previously been shown to be involved in development of MM. Our results are consistent with the hypothesis that differences in incidences of pleural and peritoneal MM upon exposure to asbestos are the result of differences in mesothelial cell physiology that lead to differences in the inflammatory response, which leads to cancer.}, }
@article {pmid25756049, year = {2015}, author = {Ak, G and Tomaszek, SC and Kosari, F and Metintas, M and Jett, JR and Metintas, S and Yildirim, H and Dundar, E and Dong, J and Aubry, MC and Wigle, DA and Thomas, CF}, title = {MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {635748}, pmid = {25756049}, issn = {2314-6141}, mesh = {Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/*biosynthesis/genetics ; Middle Aged ; Pleural Effusion/chemically induced/*genetics/pathology ; Proto-Oncogene Proteins c-met/biosynthesis/genetics ; RNA, Messenger/*biosynthesis/genetics ; }, abstract = {INTRODUCTION: We investigated the expression of microRNAs and mRNAs in pleural tissues from patients with either malignant pleural mesothelioma or benign asbestos-related pleural effusion.<br><br>METHODS: Fresh frozen tissues from a total of 18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion patients were studied. Expression profiling of mRNA and microRNA was performed using standard protocols.<br><br>RESULTS: We discovered significant upregulation of multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a-5p were able to discriminate malignant from benign disease. Dynamically regulated mRNAs were also identified. MET was the most highly overexpressed gene in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Integrated analyses examining microRNA-mRNA interactions suggested multiple altered targets within the Notch signaling pathway.<br><br>CONCLUSIONS: Specific microRNAs and mRNAs may have diagnostic utility in differentiating patients with malignant pleural mesothelioma from benign asbestos-related pleural effusion. These studies may be particularly helpful in patients who reside in a region with a high incidence of mesothelioma.}, }
@article {pmid25754500, year = {2015}, author = {Krupoves, A and Camus, M and De Guire, L}, title = {Incidence of malignant mesothelioma of the pleura in Québec and Canada from 1984 to 2007, and projections from 2008 to 2032.}, journal = {American journal of industrial medicine}, volume = {58}, number = {5}, pages = {473-482}, doi = {10.1002/ajim.22442}, pmid = {25754500}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Canada/epidemiology ; Carcinogens/*toxicity ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Poisson Distribution ; Quebec/epidemiology ; Registries ; }, abstract = {BACKGROUND: Continuous increase in male incidence of malignant mesothelioma of the pleura (MMP) despite the drop of asbestos production since 1980 in Québec motivated this study aiming to assess when the rates of MMP will decline.<br><br>METHODS: Age-standardized rates and trends were estimated over the 1984-2007 period by sex for Qu&#xe9;bec versus "Canada-excluding-Qu&#xe9;bec" (Can-Qc). An age-cohort regression was used to make projections for 2008-2032.<br><br>RESULTS: Average rates of MMP in Qu&#xe9;bec men and women were significantly higher than in Can-Qc. Projected rates peak between 2003 and 2012 in all four study populations and decline thereafter.<br><br>CONCLUSION: The higher MMP rates and observed/projected time patterns in Qu&#xe9;bec men are consistent with past asbestos production and occupational exposures. The excess in Qu&#xe9;bec women may also be explained by domestic and, for some, by neighborhood exposures. To pursue the decrease in MMP rates beyond 2032, efforts to reduce asbestos exposure should be maintained.}, }
@article {pmid25749175, year = {2015}, author = {Faig, J and Howard, S and Levine, EA and Casselman, G and Hesdorffer, M and Ohar, JA}, title = {Changing pattern in malignant mesothelioma survival.}, journal = {Translational oncology}, volume = {8}, number = {1}, pages = {35-39}, pmid = {25749175}, issn = {1936-5233}, abstract = {UNLABELLED: Survival for mesothelioma has been shown to be poor, with marginal improvement over time. Recent advances in the understanding of pathophysiology and treatment of mesothelioma may impact therapy to improve survival that may not be evident from available clinical trials that are often small and not randomized. Therapies may affect survival differently based on mesothelioma location (pleural vs peritoneal). Data are conflicting regarding the effect of asbestos exposure on mesothelioma location.<br><br>OBJECTIVES: We examined survival in a large cohort of mesothelioma subjects analyzed by tumor location and presence and mode of asbestos exposure.<br><br>METHODS: Data were analyzed from cases (n = 380) diagnosed with mesothelioma from 1992 to 2012. Cases were either drawn from treatment referrals, independent medical evaluation for medical legal purposes, or volunteers who were diagnosed with mesothelioma. Subjects completed an occupational medical questionnaire, personal interview with the examining physician, and physician review of the medical record.<br><br>RESULTS: This study reports better survival for mesothelioma than historical reports. Survival for peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001) after adjusting for gender and age at diagnosis. Non-occupational cases were more likely to be 1) diagnosed with peritoneal mesothelioma, 2) female, 3) exposed, and 4) diagnosed at a younger age and to have a 5) shorter latency compared to occupational cases (P < .001).<br><br>CONCLUSION: Peritoneal mesothelioma was more likely associated with non-occupational exposure, thus emphasizing the importance of exposure history in enhancing early diagnosis and treatment impact.}, }
@article {pmid25726562, year = {2015}, author = {Røe, OD and Stella, GM}, title = {Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {24}, number = {135}, pages = {115-131}, pmid = {25726562}, issn = {1600-0617}, mesh = {Animals ; Asbestos ; Asbestosis/epidemiology/*history ; Biomarkers/analysis ; History, 18th Century ; History, 20th Century ; Humans ; *Lung Neoplasms/epidemiology/history/physiopathology ; *Mesothelioma/epidemiology/history/physiopathology ; Mesothelioma, Malignant ; Occupational Diseases/epidemiology/history ; Occupational Exposure ; *Pleural Neoplasms/epidemiology/history/physiopathology ; Poliovirus Vaccines/adverse effects ; Simian virus 40 ; Viral Vaccines/adverse effects ; }, abstract = {Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.}, }
@article {pmid25724794, year = {2015}, author = {Lorkowski, J and Grzegorowska, O and Kotela, A and Weryński, W and Kotela, I}, title = {Shoulder ring complaints as a rare first symptom of malignant pleural mesothelioma.}, journal = {Advances in experimental medicine and biology}, volume = {852}, number = {}, pages = {5-10}, doi = {10.1007/5584_2015_113}, pmid = {25724794}, issn = {0065-2598}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Asbestosis/epidemiology ; Female ; Humans ; Lung Neoplasms/*complications/*diagnosis/epidemiology ; Male ; Mesothelioma/*complications/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/statistics &amp; numerical data ; Pleural Neoplasms/*complications/*diagnosis/epidemiology ; Poland/epidemiology ; Radiography, Thoracic ; Retrospective Studies ; Shoulder Pain/*diagnosis/epidemiology/*etiology ; }, abstract = {The prevalence of malignant pleural mesothelioma is often encountered in the areas highly exposed to asbestos. The aim of this paper was a retrospective analysis of shoulder pain as a rare, first symptom of pleural mesothelioma, which constitutes an interdisciplinary diagnostic problem concerning both orthopedics and pulmonology. The research was based on a retrospective review of the patients' medical records. The considered period of time included the years 2006-2012. The study group included a total of 49 patients. Seven patients (14.3%) presented a complain of shoulder pain, as the first symptom of mesothelioma. The remaining 42 mesothelioma patients, without this symptom, constituted a reference group. The intensity of shoulder pain was, on average, 4/10 on an analog scale. A concomitant limitation of mobility was observed in five out of the seven subjects. In one case, limitation of motion and dysfunction of the shoulder joint were at an advanced stage. Neuralgia of upper limbs was found in two cases. We conclude that shoulder pain may be a manifesting symptom of malignant pleural mesothelioma. The neoplasm appears to have a pleiotropic effect on human body, reflected in different ways of its primary manifestation which may also include the motor system.}, }
@article {pmid25722383, year = {2015}, author = {Stahel, RA and Weder, W and Felley-Bosco, E and Petrausch, U and Curioni-Fontecedro, A and Schmitt-Opitz, I and Peters, S}, title = {Searching for targets for the systemic therapy of mesothelioma.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {26}, number = {8}, pages = {1649-1660}, doi = {10.1093/annonc/mdv101}, pmid = {25722383}, issn = {1569-8041}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration &amp; dosage ; Everolimus/administration &amp; dosage ; Focal Adhesion Protein-Tyrosine Kinases/antagonists &amp; inhibitors/metabolism ; Humans ; Immunotherapy ; Lung Neoplasms/*drug therapy/metabolism ; Mesothelioma/*drug therapy/metabolism ; Mesothelioma, Malignant ; Molecular Targeted Therapy/*methods ; Pemetrexed/administration &amp; dosage ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Pleural Neoplasms/*drug therapy/metabolism ; Protein Kinase Inhibitors/administration &amp; dosage ; TOR Serine-Threonine Kinases/antagonists &amp; inhibitors/metabolism ; }, abstract = {Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma.}, }
@article {pmid25712482, year = {2015}, author = {Welch, L and Dement, J and West, G}, title = {Mortality among sheet metal workers participating in a respiratory screening program.}, journal = {American journal of industrial medicine}, volume = {58}, number = {4}, pages = {378-391}, doi = {10.1002/ajim.22421}, pmid = {25712482}, issn = {1097-0274}, support = {OH009762/OH/NIOSH CDC HHS/United States ; }, mesh = {Asbestosis/mortality ; Canada/epidemiology ; Cause of Death ; Female ; Forced Expiratory Volume ; Humans ; Lung Neoplasms/diagnostic imaging/*mortality/physiopathology ; Male ; Mesothelioma/*mortality ; Metallurgy/*statistics &amp; numerical data ; Middle Aged ; Occupational Diseases/*mortality ; Pleural Neoplasms/*mortality ; Pulmonary Disease, Chronic Obstructive/diagnostic imaging/*mortality ; Radiography ; Severity of Illness Index ; United States/epidemiology ; Vital Capacity ; }, abstract = {BACKGROUND: The Sheet Metal Occupational Health Institute Trust (SMOHIT) established a screening program in 1985 to examine the health hazards of the sheet metal industry in the U.S. and Canada.<br><br>METHODS: 17,345 individuals with over 20 years in the trade and who participated in the program were followed for causes of death between 1986 and 2010. Both SMRs and Cox proportional hazards models investigated predictors of death due to lung cancer, mesothelioma, and chronic obstructive pulmonary disease (COPD).<br><br>RESULTS: Significant excess mortality was seen for mesothelioma and asbestosis. Controlling for smoking, a strong trend for increasing lung cancer risk with increasing chest x-ray profusion >0/0 was observed. With an profusion score <1/0, FEV1 /FVC <80% was associated with lung cancer risk. COPD risk increased with increasing profusion score.<br><br>CONCLUSIONS: This study demonstrates asbestos-related diseases among workers with largely indirect exposures and an increased lung cancer risk with low ILO scores.}, }
@article {pmid25707292, year = {2015}, author = {Gopar-Nieto, R and Aguilar-Madrid, G and Sotelo-Martínez, L and Juárez-Pérez, CA and Kelly-García, J and Argote-Greene, L and Ochoa-Vázquez, MD and García-Bazán, EM and Ramírez-Pérez, J and Haro-García, L and Jiménez-Ramírez, C and Cabello-López, A}, title = {Malignant Pleural Mesothelioma: Accuracy of CT Against Immunohistochemical Test Among the Mexican Population.}, journal = {Archives of medical research}, volume = {46}, number = {2}, pages = {107-111}, doi = {10.1016/j.arcmed.2015.02.002}, pmid = {25707292}, issn = {1873-5487}, mesh = {Adenocarcinoma/diagnosis/*diagnostic imaging ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Immunohistochemistry/methods ; Incidence ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/diagnosis/*diagnostic imaging ; Male ; Mediastinum/diagnostic imaging ; Mesothelioma/diagnosis/*diagnostic imaging ; Mesothelioma, Malignant ; Mexico ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed/*methods ; }, abstract = {BACKGROUND AND AIMS: Malignant pleural mesothelioma (MPM) is associated with occupational and environmental exposure to asbestos. The incidence is expected to increase as the use of asbestos is not prohibited in many countries, such as in Mexico. We undertook this study to determine sensitivity, specificity, predictive values and likelihood ratios of computed tomography (CT) in a sample from Mexican population with suspected MPM and other pleuropulmonary diseases.<br><br>METHODS: CT films of 38 patients suspected of having MPM were analyzed. A single observer was blinded to MPM diagnoses. The frequencies of ten CT findings were identified. A cut-off point of &#x2265;5 CT findings was established to determine high MPM probability. Sensitivity, specificity, predictive values and likelihood ratio of the CT against biopsy using immunohistochemical testing (IHC) for MPM were calculated.<br><br>RESULTS: Of the 38 patients, 31 had MPM and seven had lung adenocarcinoma. The five key findings were mediastinal pleural thickening 96.7% (n = 30), nodular pleural thickening 93.3% (n = 29), pleural mass 83.9% (n = 26), diminished lung 70.9% (n = 22) and contracted hemithorax 70.9% (n = 22). Sensitivity 96.8% (83.2-99.4), specificity 85.7% (42.2-97.6), positive likelihood ratio 6.7 (1.1-41.6), and negative likelihood ratio of 0.04 (0.01-0.2) were reported.<br><br>CONCLUSIONS: Sensitivity and specificity in this study was greater than previously reported, 96.8% and 85.7 vs. 93.2 and 65.6%, respectively. CT is an easily accessible and useful tool that should be incorporated into the medical education of general physicians to improve MPM diagnosis of suspected cases.}, }
@article {pmid25701019, year = {2015}, author = {Chellini, E and Martino, G and Grillo, A and Fedi, A and Martini, A and Indiani, L and Mauro, L}, title = {Malignant mesotheliomas in textile rag sorters.}, journal = {The Annals of occupational hygiene}, volume = {59}, number = {5}, pages = {547-553}, doi = {10.1093/annhyg/meu114}, pmid = {25701019}, issn = {1475-3162}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; *Textile Industry ; }, abstract = {OBJECTIVES: To analyse the asbestos exposure characteristics and mesothelioma trend in textile workers operating in the larger Tuscan textile industrial province of Prato between 1988 and 2012.<br><br>METHODS: All cases of textile workers recorded by the Tuscan mesothelioma register are considered. The demographic and clinical characteristics and asbestos exposure of cases working in the province of Prato are examined. Crude incidence rates between 1988 and 2012 and their 95% confidence intervals (CI) are calculated in rag sorters and other textile workers. The trends of standardized rates are also evaluated, as well as the sources of occupational asbestos exposure from occupational histories of cases affected by other asbestos-related diseases in rag sorters.<br><br>RESULTS: One hundred and seventy-two malignant mesotheliomas (MMs) have been diagnosed in textile workers in Tuscany. Among these, 46.5% were residents in the province of Prato at the time of diagnosis, half of whom working as rag sorters. All rag sorters with MM are classified as occupationally asbestos exposed, while 71.7% are other textile workers exposed to asbestos. The estimated crude incidence rate in rag sorters in Prato ranges from 74.1&#xd7;100000 (95% CI: 52.5-101.8) to 166.8&#xd7;100000 (95% CI: 118.1-229.0). The standardized rates in Prato rag sorters appeared higher throughout the 1990s while in other Prato textile workers the rates increased later on, at the very end of the 1990s. Another 40 cases of asbestos-related diseases in rag sorters were also collected.<br><br>CONCLUSIONS: A very high incidence of MMs was observed in textile workers in Prato, especially among rag sorters. This result, together with the high number of other asbestos-related diseases in rag sorters, strongly supports the hypothesis of diffuse asbestos exposure in rag sorting, in the absence of any other relevant aetiological factor for malignant mesothelioma.}, }
@article {pmid25683976, year = {2015}, author = {Demirer, E and Ghattas, CF and Radwan, MO and Elamin, EM}, title = {Clinical and prognostic features of erionite-induced malignant mesothelioma.}, journal = {Yonsei medical journal}, volume = {56}, number = {2}, pages = {311-323}, pmid = {25683976}, issn = {1976-2437}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Pleura/diagnostic imaging ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*chemically induced/diagnostic imaging ; Prognosis ; Prospective Studies ; Retrospective Studies ; Tomography, X-Ray Computed ; Zeolites/*adverse effects ; }, abstract = {This review analytically examines the published data for erionite-related malignant pleural mesothelioma (E-MPM) and any data to support a genetically predisposed mechanism to erionite fiber carcinogenesis. Adult patients of age ≥18 years with erionite-related pleural diseases and genetically predisposed mechanisms to erionite carcinogenesis were included, while exclusion criteria included asbestos- or tremolite-related pleural diseases. The search was limited to human studies though not limited to a specific timeframe. A total of 33 studies (31042 patients) including 22 retrospective studies, 6 prospective studies, and 5 case reports were reviewed. E-MPM developed in some subjects with high exposures to erionite, though not all. Chest CT was more reliable in detecting various pleural changes in E-MPM than chest X-ray, and pleural effusion was the most common finding in E-MPM cases, by both tests. Bronchoalveolar lavage remains a reliable and relatively less invasive technique. Chemotherapy with cisplatin and mitomycin can be administered either alone or following surgery. Erionite has been the culprit of numerous malignant mesothelioma cases in Europe and even in North America. Erionite has a higher degree of carcinogenicity with possible genetic transmission of erionite susceptibility in an autosomal dominant fashion. Therapeutic management for E-MPM remains very limited, and cure of the disease is extremely rare.}, }
@article {pmid25669666, year = {2015}, author = {Rena, O and Boldorini, R and Papalia, E and Mezzapelle, R and Baietto, G and Roncon, A and Casadio, C}, title = {Persistent lung expansion after pleural talc poudrage in non-surgically resected malignant pleural mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {99}, number = {4}, pages = {1177-1183}, doi = {10.1016/j.athoracsur.2014.11.050}, pmid = {25669666}, issn = {1552-6259}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration &amp; dosage ; Biopsy, Needle ; Cohort Studies ; Confidence Intervals ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/diagnostic imaging/mortality/pathology/*therapy ; Male ; Mesothelioma/diagnostic imaging/mortality/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Pleural Neoplasms/diagnostic imaging/mortality/parasitology/*therapy ; Pleurodesis/*methods/mortality ; Radiography ; Retrospective Studies ; Risk Assessment ; Survival Analysis ; Talc/*administration &amp; dosage ; Thoracic Surgery, Video-Assisted/methods ; Tissue Expansion/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: To investigate the prognostic effect of persistent lung expansion after pleural talcage and other variables in non-surgically resected malignant pleural mesothelioma (MPM) patients.<br><br>METHODS: All consecutive patients submitted to video-assisted thoracoscopic (VAT) pleurodesis by talc poudrage for MPM between 2006 and 2011 were studied. The following parameters were prospectively recorded: age; sex; smoking history; asbestos exposure; C-reactive protein (CRP) levels; platelet (PLT) count; Eastern Cooperative Oncology Group performance status (ECOG PS); histologic subtype; clinical stage (cStage); chemotherapy; pleural fluid volume; and persistence of lung expansion at 3 months follow-up. Survival was assessed in June&#xa0;2013.<br><br>RESULTS: A total of 172 patients were considered; 146 of 172 patients demonstrated a complete lung expansion at discharge, whereas only 85 of 172 patients had persistent expanded lung on the affected side at the 3-month follow-up chest x-ray. Median survival was 11.5 months (95% confidence interval [CI], 10% to 14%) and 2-year disease-specific survival was 13% (95% CI, 7% to 24%) for the entire cohort. Multivariate analysis showed that non-epithelioid histology (hazard ratio [HR], 2.81; 95% CI, 1.82% to 5.09%), pleural fluid recurrence (HR 2.54; 95% CI, 1.73% to 4.40%), cStage greater than II (HR 2.36; 95% CI, 1.50% to 4.32%), ECOG PS greater than 1 (HR 2.19; 95% CI, 1.26% to 4.23%), CRP greater than 5 mg/L (HR 2.01; 95% CI, 1.18% to 4.12%), and PLT count greater than 400,000 (HR 1.76; 95% CI 1.14% to 3.92%) were independent predictors of poor prognosis.<br><br>CONCLUSIONS: Persistent lung expansion after pleural talc poudrage and absence of fluid recurrence is demonstrated to be a stronger factor in predicting survival rather than clinical stage and other clinical variables in not surgically resected MPM patients.}, }
@article {pmid25668121, year = {2015}, author = {Baumann, F and Buck, BJ and Metcalf, RV and McLaurin, BT and Merkler, DJ and Carbone, M}, title = {The Presence of Asbestos in the Natural Environment is Likely Related to Mesothelioma in Young Individuals and Women from Southern Nevada.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {5}, pages = {731-737}, pmid = {25668121}, issn = {1556-1380}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; P30CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Asbestos/*analysis ; Environmental Exposure/*analysis ; Female ; Geology ; Humans ; Incidence ; *Inhalation Exposure ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Nevada/epidemiology ; Sex Factors ; Weather ; }, abstract = {BACKGROUND: Inhalation of asbestos and other mineral fibers is known causes of malignant mesothelioma (MM) and lung cancers. In a setting of occupational exposure to asbestos, MM occurs four to eight times more frequently in men than in women, at the median age of 74 years, whereas an environmental exposure to asbestos causes the same number of MMs in men and women, at younger ages.<br><br>METHODS: We studied the geology of Nevada to identify mineral fibers in the environment. We compared MM mortality in different Nevada counties, per sex and age group, for the 1999 to 2010 period.<br><br>RESULTS: We identified the presence of carcinogenic minerals in Nevada, including actinolite asbestos, erionite, winchite, magnesioriebeckite, and richterite. We discovered that, compared with the United States and other Nevada counties, Clark and Nye counties, in southern Nevada, had a significantly higher proportion of MM that occurred in young individuals (<55 years) and in women.<br><br>CONCLUSIONS: The elevated percentage of women and individuals younger than 55 years old, combined with a sex ratio of 1:1 in this age group and the presence of naturally occurring asbestos, suggests that environmental exposure to mineral fibers in southern Nevada may be contributing to some of these mesotheliomas. Further research to assess environmental exposures should allow the development of strategies to minimize exposure, as the development of rural areas continues in Nevada, and to prevent MM and other asbestos-related diseases.}, }
@article {pmid25633928, year = {2015}, author = {Dahlgren, J and Talbott, P}, title = {Case report: peritoneal mesothelioma from asbestos in hairdryers.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {1}, pages = {1-4}, pmid = {25633928}, issn = {2049-3967}, mesh = {*Asbestos ; Female ; Humans ; Lung Neoplasms/chemically induced/*diagnosis/epidemiology ; Mesothelioma/chemically induced/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; *Occupational Exposure ; Peritoneal Neoplasms/chemically induced/*diagnosis/epidemiology ; Risk Assessment ; }, abstract = {BACKGROUND: The relationship between mesothelioma and exposure to asbestos is well established. As a result, the use of asbestos in buildings, construction sites, and mines, as well as the implications of disease for the workers has received considerable attention. However, asbestos was also used in household equipment and consumer products, including hairdryers.<br><br>PURPOSE: To examine one case of peritoneal mesothelioma in a hairdresser and review the relevant literature on asbestos exposure from hairdryers.<br><br>METHODS: The subject's medical and occupational records were obtained and reviewed and a physical examination was performed.<br><br>RESULTS: The results indicate that the subject developed peritoneal mesothelioma from her occupational exposure to asbestos containing hairdryers in accordance with the literature.<br><br>CONCLUSION: Hairdryers are possible sources of asbestos exposure in patients with mesothelioma, and the asbestos exposure risk is higher for those who use hairdryers occupationally.}, }
@article {pmid25613098, year = {2015}, author = {Petersen, R and Petersen, JA and Mikkelsen, S}, title = {[Non-occupational pleural mesothelioma].}, journal = {Ugeskrift for laeger}, volume = {177}, number = {3}, pages = {V09140480}, pmid = {25613098}, issn = {1603-6824}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced ; }, abstract = {Asbestos fibres is the only known cause of malignant mesothelioma (MM). The risk of MM is increased also by low and brief exposure. MM has a latency of 20-50 years. We report two cases of MM who were exposed to asbestos during do-it-yourself roof renovation including cutting and drilling in roof sheeting containing asbestos. A detailed occupational history revealed no occupational exposure. The two cases demonstrate the importance of careful handling of products containing asbestos, with emphasis on avoidance of inhaling asbestos fibres.}, }
@article {pmid25604170, year = {2014}, author = {Flores-Franco, RA and Ramos-Martínez, E and Luévano-Flores, E and Fierro-Murga, R and Barriga-Acevedo, R and Martínez-Tapia, ME and Luévano-González, A and Gómez-Díaz, A and Perea-Sánchez, RA}, title = {Malignant mesothelioma trends in Chihuahua, Mexico.}, journal = {Salud publica de Mexico}, volume = {56}, number = {4}, pages = {315-316}, pmid = {25604170}, issn = {1606-7916}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Carcinoma, Bronchogenic/epidemiology ; Environmental Exposure ; Female ; Health Surveys ; Humans ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/*epidemiology ; Mexico ; Middle Aged ; Morbidity/trends ; Pleural Effusion/epidemiology ; Pleural Neoplasms/*epidemiology ; Sex Distribution ; Tuberculosis, Pleural/epidemiology ; }, }
@article {pmid25598227, year = {2015}, author = {Tosun, AB and Yergiyev, O and Kolouri, S and Silverman, JF and Rohde, GK}, title = {Detection of malignant mesothelioma using nuclear structure of mesothelial cells in effusion cytology specimens.}, journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology}, volume = {87}, number = {4}, pages = {326-333}, pmid = {25598227}, issn = {1552-4930}, support = {P41 GM103712/GM/NIGMS NIH HHS/United States ; R01 GM090033/GM/NIGMS NIH HHS/United States ; R21 CA188938/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Cell Nucleus/*physiology ; Chromatin/physiology ; Cytodiagnosis/*methods ; Cytological Techniques/methods ; Epithelial Cells/pathology ; Humans ; Image Processing, Computer-Assisted ; Lung Neoplasms/*classification/*diagnosis ; Mesothelioma/*classification/*diagnosis ; Mesothelioma, Malignant ; Pleura/cytology/pathology ; Pleural Effusion, Malignant/*cytology/pathology ; }, abstract = {Mesothelioma is a form of cancer generally caused from previous exposure to asbestos. Although it was considered a rare neoplasm in the past, its incidence is increasing worldwide due to extensive use of asbestos. In the current practice of medicine, the gold standard for diagnosing mesothelioma is through a pleural biopsy with subsequent histologic examination of the tissue. The diagnostic tissue should demonstrate the invasion by the tumor and is obtained through thoracoscopy or open thoracotomy, both being highly invasive surgical operations. On the other hand, thoracocentesis, which is removal of effusion fluid from the pleural space, is a far less invasive procedure that can provide material for cytological examination. In this study, we aim at detecting and classifying malignant mesothelioma based on the nuclear chromatin distribution from digital images of mesothelial cells in effusion cytology specimens. Accordingly, a computerized method is developed to determine whether a set of nuclei belonging to a patient is benign or malignant. The quantification of chromatin distribution is performed by using the optimal transport-based linear embedding for segmented nuclei in combination with the modified Fisher discriminant analysis. Classification is then performed through a k-nearest neighborhood approach and a basic voting strategy. Our experiments on 34 different human cases result in 100% accurate predictions computed with blind cross validation. Experimental comparisons also show that the new method can significantly outperform standard numerical feature-type methods in terms of agreement with the clinical diagnosis gold standard. According to our results, we conclude that nuclear structure of mesothelial cells alone may contain enough information to separate malignant mesothelioma from benign mesothelial proliferations.}, }
@article {pmid25586016, year = {2015}, author = {Guerriero, A and Giovenali, P and La Starza, R and Mecucci, C and Montesi, G and Pasquino, S and Pierini, T and Ragni, T and Sidoni, A}, title = {Metachronous cardiac and cerebral sarcomas: case report with focus on molecular findings and review of the literature.}, journal = {Human pathology}, volume = {46}, number = {3}, pages = {482-487}, doi = {10.1016/j.humpath.2014.10.028}, pmid = {25586016}, issn = {1532-8392}, mesh = {12E7 Antigen ; Antigens, CD/analysis ; Brain Neoplasms/chemistry/diagnosis/genetics/*pathology/therapy ; Cell Adhesion Molecules/analysis ; Combined Modality Therapy ; Fatal Outcome ; Gliosarcoma/chemistry/diagnosis/genetics/*pathology/therapy ; Heart Neoplasms/chemistry/diagnosis/genetics/*pathology/therapy ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasms, Second Primary/chemistry/diagnosis/*pathology/therapy ; Sarcoma/chemistry/diagnosis/genetics/*pathology/therapy ; Vimentin/analysis ; }, abstract = {Although multiple primary malignancies are relatively rare, they have increased in frequency over the last decades, partly because of advances in diagnosis and therapy. This report describes for the first time the case of a patient with past occupational exposure to asbestos and no family history of cancer who developed 2 rare primary malignancies: a cardiac sarcoma and a gliosarcoma 11 months later. Molecular-cytogenetic studies did not identify common lesions to these 2 rare metachronous sarcomas. The gliosarcoma was associated with monosomy 10 and underlying PTEN monoallelic loss, which has been recurrently observed. In the cardiac sarcoma, MDM2 amplification and CDKN2AB/9p21 biallelic deletion suggested intimal sarcoma. No causal relationship was found between cardiac sarcoma and asbestos exposure, although MDM2 abnormalities were linked to malignant mesothelioma.}, }
@article {pmid25582747, year = {2015}, author = {Damiran, N and Davaajav, K and Erdenebayar, E and Gomboloi, B and Frank, AL}, title = {Mesothelioma in Mongolia: case report.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {2}, pages = {166-168}, pmid = {25582747}, issn = {2049-3967}, mesh = {Asbestos/*toxicity ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Mongolia ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; *Power Plants ; }, abstract = {BACKGROUND: More than 80% of cases of mesothelioma worldwide have a history of asbestos exposure. In Mongolia, workers in coal burning thermal power plants (TPP) have widely utilized asbestos as an insulation material.<br><br>METHODS: We describe the case of a 47-year-old woman diagnosed with a malignant pleural mesothelioma. She worked in a TPP in Ulaanbaatar, Mongolia for 28 years.<br><br>RESULTS: A computer tomography (CT) scan showed a circumferential ring around her left lung, and tissues' samples had a biphasic variant of mesothelioma with epithelioid and sarcomatoid components.<br><br>DISCUSSION: This is the first reported case of mesothelioma in Mongolia. We expect additional cases of mesothelioma, as well as other asbestos related diseases, will be identified in the future. In order to properly track asbestos related diseases in the country, we recommend the creation of an asbestos related disease registry.}, }
@article {pmid25572813, year = {2015}, author = {de Lima, VA and Sørensen, JB}, title = {Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {32}, number = {2}, pages = {458}, pmid = {25572813}, issn = {1559-131X}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration &amp; dosage ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Disease-Free Survival ; Doxorubicin/administration &amp; dosage/analogs &amp; derivatives ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma/*drug therapy/mortality ; Middle Aged ; Neoplasms, Mesothelial/*drug therapy/mortality ; Pleural Neoplasms/*drug therapy/mortality ; Polyethylene Glycols/administration &amp; dosage ; Retrospective Studies ; Salvage Therapy/*methods ; Gemcitabine ; }, abstract = {There is no well-defined standard third-line chemotherapy for advanced malignant pleural mesothelioma (MPM). However, combination of carboplatin, liposomised doxorubicin (Caelyx) and gemcitabine (CCG regimen) has revealed noteworthy activity when used as first-line treatment. The aim of this study is to assess efficacy and toxicity profile for patients with MPM receiving CCG regimen as a third-line treatment. Carboplatin (AUC 5), Caelyx (30 mg/m(2)) and Gemcitabine (1,000 mg/m(2)) day 1, together with Gemcitabine (800 mg/m(2)) day 8, were given in up to six cycles. Patients were unresectable, PS 0-2, and had previously received a first-line platinum-based regimen and either vinorelbine or pemetrexed as second line. Response to treatment was assessed by CT scan using Modified RECIST criteria for mesothelioma. Forty-three patients were treated between 2010 and 2014. Median age was 67 years (47-82), 72 % males, and 79 % had previous asbestos exposure. Ninety per cent had PS 0-1, 58 % had epitheloid subtype and 63 % IMIG stage IV. First-line treatment was platinum and pemetrexed in 42 cases. Second-line treatment was vinorelbine in 42 cases and pemetrexed in one patient. Median lead time from cessation of second-line treatment to start of third CCG was 1 month. Twenty-eight per cent of the patients received six cycles, while treatment was postponed due to toxicities, mainly haematological, in 56 % of cases. No toxicity-related deaths occurred. Partial response (PR) occurred in 14 %, and disease control rate (DCR) was 60 %. Medians of overall survival (OS) from diagnosis and from start of CCG treatment were 25.2 months (18.4-31.5 months) and 6.8 months (5.4-8.4 months), respectively. Progression-free survival (PFS) was 4.1 months (1.7-4.5 months). Third-line CCG revealed a noteworthy efficacy with a DCR of 60.4 %. It was, however, associated with considerable haematological toxicity. Less toxic and more active treatment options are clearly needed.}, }
@article {pmid25568603, year = {2014}, author = {Bianchi, C and Bianchi, T}, title = {Global mesothelioma epidemic: Trend and features.}, journal = {Indian journal of occupational and environmental medicine}, volume = {18}, number = {2}, pages = {82-88}, pmid = {25568603}, issn = {0973-2284}, abstract = {BACKGROUND: Mesothelioma incidence has taken epidemic proportions in various countries. The trend of the epidemic remains undefined.<br><br>OBJECTIVE: To collect the most recent available data on mesothelioma incidence in order to determine the present trend of the epidemic.<br><br>MATERIALS AND METHODS: Data of the Cancer and Mesothelioma Registries have been reviewed. In addition, numerous researchers were contacted to obtain supplementary information.<br><br>RESULTS: The highest incidence rates are reported from some countries in Europe (United Kingdom, The Netherlands, Malta, Belgium), and in Oceania (Australia, New Zealand). Relatively low incidence/mortality rates are reported from Japan and from Central Europe. In many countries a trend to increase continues to be observed. Data are not available for the mostly populous countries.<br><br>CONCLUSION: Mesothelioma epidemic does not show signs of attenuation. The lack of data for a large majority of the world does not allow that the consciousness of the risks related to asbestos exposure is reached.}, }
@article {pmid25560527, year = {2015}, author = {Tsukamoto, Y and Hao, H and Kajimoto, N and Katayama, A and Suzuki, C and Terada, T and Nakano, T and Hanaoka, K and Hirota, S}, title = {Sarcomatoid pleural mesothelioma with osteosarcomatous, chondrosarcomatous and rhabdomyoblastic elements: an extremely rare autopsy case.}, journal = {Pathology international}, volume = {65}, number = {1}, pages = {51-53}, doi = {10.1111/pin.12226}, pmid = {25560527}, issn = {1440-1827}, mesh = {Aged ; Asbestos/adverse effects ; Autopsy ; Humans ; Male ; Mesothelioma/*pathology ; Neoplasms, Complex and Mixed/*pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*pathology ; Smoking/adverse effects ; }, }
@article {pmid25559791, year = {2015}, author = {Sen, D}, title = {Working with asbestos and the possible health risks.}, journal = {Occupational medicine (Oxford, England)}, volume = {65}, number = {1}, pages = {6-14}, doi = {10.1093/occmed/kqu175}, pmid = {25559791}, issn = {1471-8405}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/diagnosis/*epidemiology ; *Health Status Indicators ; Humans ; Occupational Exposure/adverse effects/*legislation &amp; jurisprudence/*statistics &amp; numerical data ; Occupations/trends ; Work/standards/statistics &amp; numerical data/trends ; }, abstract = {BACKGROUND: The generic term asbestos refers to a group of crystalline mineral silicates that occur naturally in various forms. Because of their properties of strength, heat and electrical resistance and their ability to withstand corrosion by acids and sea water, asbestos was used extensively both in the UK and worldwide.<br><br>AIMS: To provide a historical perspective of this ubiquitous occupational hazard, consider the key changes in UK legislation aimed at improving the management of this occupational health risk and describe the evidence from the scientific literature concerning asbestos and disease.<br><br>METHODS: Original articles, reviews (including reference textbooks) and scientific literature in PubMed and other principal medical science databases, 1960-2014, were searched. Publications by regulatory agencies and by governmental organizations were also considered and included where relevant.<br><br>RESULTS: Asbestos remains the biggest cause of cancer deaths worldwide. For malignant mesothelioma deaths alone, it is estimated that in the UK, between 2015 and 2020, the number of cases will peak at 2500 cases annually. It is not clear whether there is a safe level of asbestos fibres in air. Evidence for the efficacy of health surveillance is lacking.<br><br>CONCLUSIONS: Although the use of asbestos was banned in the UK in 1985 (amosite and crocidolite) and 1999 (chrysotile), it remains a significant occupational risk factor for work-related morbidity and mortality, causing both benign and malignant diseases, often with long latency. Further research is needed regarding exposure levels and health surveillance.}, }
@article {pmid25558735, year = {2014}, author = {Binazzi, A and Scarselli, A and Massari, S and Bonafede, M and Corfiati, M and Di Marzio, D and Iavicoli, S and Marinaccio, A}, title = {[Active research, registration, and prevention of tumors of professional origin].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {36}, number = {4}, pages = {360-364}, pmid = {25558735}, issn = {1592-7830}, mesh = {Asbestos/adverse effects ; Biomedical Research ; Carcinogens/toxicity ; Data Collection ; Government Agencies ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology/prevention &amp; control ; National Health Programs/organization &amp; administration ; Neoplasms/*epidemiology/etiology/prevention &amp; control ; Occupational Diseases/*epidemiology/etiology/prevention &amp; control ; Occupational Exposure ; *Population Surveillance ; *Registries ; Workers' Compensation/organization &amp; administration ; }, abstract = {Occupational cancer is an important public health concern in Italy and in many industrialized countries. The difficulties in monitoring and the complexity in retrieving occupational cancer cases have required the enrolment of a national epidemiologic sureveillance system at national scale with active search methods. A structured system for the registration of occupational cancer cases is normed by the Decree No. 81/2008, that accounts for the previous legislative procedures and experiences. Research activities and prevention of occupational cancer should be integrated with insurance policies to the purpose of an efficient protection of workers health.}, }
@article {pmid25557874, year = {2015}, author = {Tamminen, JA and Yin, M and Rönty, M and Sutinen, E and Pasternack, A and Ritvos, O and Myllärniemi, M and Koli, K}, title = {Overexpression of activin-A and -B in malignant mesothelioma - attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth.}, journal = {Experimental cell research}, volume = {332}, number = {1}, pages = {102-115}, doi = {10.1016/j.yexcr.2014.12.010}, pmid = {25557874}, issn = {1090-2422}, mesh = {Activin Receptors, Type I/metabolism ; Activin Receptors, Type II/metabolism ; Activins/genetics/*metabolism ; Aged ; *Cell Movement ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Female ; Gene Expression ; Humans ; Lung Neoplasms/*metabolism/pathology ; MAP Kinase Signaling System ; Male ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Invasiveness ; Smad3 Protein/*metabolism ; }, abstract = {Activin-A and activin-B, members of the TGF-β superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cells in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth.}, }
@article {pmid25549453, year = {2014}, author = {Amanbekova, AU and Sakiev, KZ and Ibraeva, LK and Otarbaeva, MB}, title = {[Main results of research concerning asbestos-related diseases in Kazakhstan Republic].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {8}, pages = {13-18}, pmid = {25549453}, issn = {1026-9428}, mesh = {Asbestos/*adverse effects ; *Asbestosis/diagnosis/epidemiology/etiology/prevention &amp; control ; Environmental Health/methods/standards ; Humans ; Kazakhstan/epidemiology ; *Lung Neoplasms/diagnosis/epidemiology/etiology/prevention &amp; control ; *Mesothelioma/diagnosis/epidemiology/etiology/prevention &amp; control ; Needs Assessment ; *Occupational Exposure/adverse effects/analysis/prevention &amp; control ; Occupational Health Services/methods/organization &amp; administration ; Preventive Health Services/methods/organization &amp; administration ; }, abstract = {Problem of safety in asbestos usage attracts close attention of specialists and agencies responsible for public health preservation nowadays. According to European researchers, studies of uncontrolled usage of amphibole asbestos demonstrate high risk of asbestosis, lung cander and pleural mesothelioma among the workers and population exposed. The article covers results of research concerning influence of chrysotile asbestos on the workers, problems of asbestos-related diseases formation. The authors defined suggestions on a concept of controlled usage of chrysotile asbestos in Kazakhstan Republic.}, }
@article {pmid25544756, year = {2015}, author = {Lim, CB and Prêle, CM and Baltic, S and Arthur, PG and Creaney, J and Watkins, DN and Thompson, PJ and Mutsaers, SE}, title = {Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis.}, journal = {Oncotarget}, volume = {6}, number = {3}, pages = {1519-1530}, pmid = {25544756}, issn = {1949-2553}, mesh = {Apoptosis/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; G1 Phase/drug effects ; HCT116 Cells ; HT29 Cells ; Humans ; Lung Neoplasms/*drug therapy/genetics/*metabolism/pathology ; Mesothelioma/*drug therapy/genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Mitochondria/drug effects/*metabolism ; Oxidative Stress/drug effects/physiology ; Pyridines/*pharmacology ; Pyrimidines/*pharmacology ; Reactive Oxygen Species/*metabolism ; Transcription Factors/metabolism ; Zinc Finger Protein GLI1 ; }, abstract = {Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe.}, }
@article {pmid25530474, year = {2015}, author = {Li, P and Liu, T and Kamp, DW and Lin, Z and Wang, Y and Li, D and Yang, L and He, H and Liu, G}, title = {The c-Jun N-terminal kinase signaling pathway mediates chrysotile asbestos-induced alveolar epithelial cell apoptosis.}, journal = {Molecular medicine reports}, volume = {11}, number = {5}, pages = {3626-3634}, pmid = {25530474}, issn = {1791-3004}, support = {I01 BX000786/BX/BLRD VA/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; }, mesh = {Alveolar Epithelial Cells/*drug effects/*metabolism ; Apoptosis/*drug effects ; Asbestos, Serpentine/*pharmacology ; Caspase 9/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Poly(ADP-ribose) Polymerases/metabolism ; Proteolysis/drug effects ; Signal Transduction/*drug effects ; }, abstract = {Exposure to chrysotile asbestos exposure is associated with an increased risk of mortality in combination with pulmonary diseases including lung cancer, mesothelioma and asbestosis. Multiple mechanisms by which chrysotile asbestos fibers induce pulmonary disease have been identified, however the role of apoptosis in human lung alveolar epithelial cells (AEC) has not yet been fully explored. Accumulating evidence implicates AEC apoptosis as a crucial event in the development of both idiopathic pulmonary fibrosis and asbestosis. The aim of the present study was to determine whether chrysotile asbestos induces mitochondria‑regulated (intrinsic) AEC apoptosis and, if so, whether this induction occurs via the activation of mitogen‑activated protein kinases (MAPK). Human A549 bronchoalveolar carcinoma‑derived cells with alveolar epithelial type II‑like features were used. The present study showed that chrysotile asbestos induced a dose‑ and time‑dependent decrease in A549 cell viability, which was accompanied by the activation of the MAPK c‑Jun N‑terminal kinases (JNK), but not the MAPKs extracellular signal‑regulated kinase 1/2 and p38. Chrysotile asbestos was also shown to induce intrinsic AEC apoptosis, as evidenced by the upregulation of the pro‑apoptotic genes Bax and Bak, alongside the activation of caspase‑9, poly (ADP‑ribose) polymerase (PARP), and the release of cytochrome c. Furthermore, the specific JNK inhibitor SP600125 blocked chrysotile asbestos‑induced JNK activation and subsequent apoptosis, as assessed by both caspase‑9 cleavage and PARP activation. The results of the present study demonstrated that chrysotile asbestos induces intrinsic AEC apoptosis by a JNK‑dependent mechanism, and suggests a potential novel target for the modulation of chrysotile asbestos‑associated lung diseases.}, }
@article {pmid25527013, year = {2014}, author = {Donahoe, L and Cho, J and de Perrot, M}, title = {Novel induction therapies for pleural mesothelioma.}, journal = {Seminars in thoracic and cardiovascular surgery}, volume = {26}, number = {3}, pages = {192-200}, doi = {10.1053/j.semtcvs.2014.08.003}, pmid = {25527013}, issn = {1532-9488}, mesh = {Chemotherapy, Adjuvant ; Humans ; Lung Neoplasms/mortality/pathology/*therapy ; Mesothelioma/mortality/pathology/*therapy ; Mesothelioma, Malignant ; *Neoadjuvant Therapy/adverse effects/mortality ; Pleural Neoplasms/mortality/pathology/*therapy ; *Pneumonectomy/adverse effects/mortality ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is becoming increasingly common, and rates of diagnosis are expected to continue to increase in the coming years because of the extensive use of asbestos in industrialized countries and the long time interval between exposure and onset of disease. Although much research has been done on the optimal treatment for this disease, the overall prognosis remains grim. The main components of therapy are surgery, chemotherapy, and radiation therapy, but there is controversy in the literature about the optimal inclusion and sequencing of these treatments, as each has unique risk profiles. We have developed a new Surgery for Mesothelioma After Radiation Therapy protocol consisting of induction-accelerated hemithoracic radiation followed by extrapleural pneumonectomy. The rationale behind this protocol is to maximize both the tumoricidal and immunogenic potential of the radiotherapy while minimizing the radiation toxicity to the ipsilateral lung. Our initial trial demonstrated the feasibility of this approach and has shown encouraging results in patients with epithelial histology. In this article, we reviewed the current literature on induction chemotherapy for mesothelioma as well as described the Surgery for Mesothelioma After Radiation Therapy protocol and upcoming studies of novel induction therapies for mesothelioma.}, }
@article {pmid25526639, year = {2014}, author = {Fujimoto, N and Ohnuma, K and Aoe, K and Hosono, O and Yamada, T and Kishimoto, T and Morimoto, C}, title = {Clinical significance of soluble CD26 in malignant pleural mesothelioma.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e115647}, pmid = {25526639}, issn = {1932-6203}, mesh = {Aged ; Biomarkers, Tumor/blood/*metabolism ; Diagnosis, Differential ; Dipeptidyl Peptidase 4/blood/*metabolism ; Female ; Humans ; Lung Neoplasms/blood/enzymology/*pathology ; Male ; Mesothelioma/blood/enzymology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleura/*enzymology/pathology ; Pleural Neoplasms/blood/enzymology/*pathology ; Prognosis ; Survival Analysis ; }, abstract = {There is no established single diagnostic marker for malignant pleural mesothelioma (MPM). CD26 is a 110 kDa, multifunctional, membrane-bound glycoprotein that has dipeptidyl peptidase IV (DPPIV) enzyme activity. The aim of this study was to evaluate the clinical significance of soluble CD26 (sCD26) in patients with MPM. The study included 80 MPM patients, 79 subjects with past asbestos exposure (SPE), and 134 patients with other benign pleural diseases (OPD) that were included as a control group. sCD26 levels and DPPIV activity in serum and/or pleural fluid were determined using an ELISA kit. Serum sCD26 levels and DPPIV enzyme activity in patients with MPM were significantly decreased compared with those in the SPE group (P = 0.000). The level of serum sCD26 was significantly decreased in patients with advanced stages of MPM compared with those with earlier stages (P = 0.047). The median OS of patients with MPM who had higher DPPIV enzyme activity was significantly longer than that of those with lower DPPIV enzyme activity (P = 0.032). The sCD26 levels in the pleural fluid of MPM patients with an epithelioid subtype were significantly increased compared with the OPD cohort (P = 0.012). Moreover, DPPIV enzyme activity in the pleural fluid of patients with MPM with an epithelioid subtype were significantly increased compared with those in the OPD cohort (P = 0.009). Patients with MPM who had lower specific DPPIV activity, determined as DPPIV/sCD26, showed significantly prolonged survival compared with those with higher specific DPPIV activity (P = 0.028). Serum sCD26 and DPPIV enzyme activity appear to be useful biomarkers for differentiating patients with MPM from SPE. The sCD26 levels or DPPIV enzyme activity in pleural fluid appear to be biomarkers in patients with an epithelioid subtype of MPM. DPPIV activity in serum or pleural fluid appears to be predictive for the prognosis of patients with MPM.}, }
@article {pmid25522071, year = {2014}, author = {Fazzo, L and Menegozzo, S and Soggiu, ME and De Santis, M and Santoro, M and Cozza, V and Brangi, A and Menegozzo, M and Comba, P}, title = {Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {4}, pages = {322-327}, doi = {10.4415/ANN_14_04_05}, pmid = {25522071}, issn = {2384-8553}, mesh = {Adult ; Age of Onset ; Aged ; *Asbestos ; Environmental Exposure ; Environmental Pollution/*adverse effects ; Female ; Humans ; Incidence ; Industry ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Sex Factors ; }, abstract = {BACKGROUND: An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environmental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated.<br><br>METHODS: The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR) for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR) between the two subareas was computed.<br><br>RESULTS: Mesothelioma incidence in the study area was increased: 46 cases were observed with respect to 22.23 expected (SIR: 2.02). The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88); 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40). The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17) in the age-classes below 55 years.<br><br>CONCLUSIONS: The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks.}, }
@article {pmid25512155, year = {2014}, author = {Hashim, D and Boffetta, P}, title = {Occupational and environmental exposures and cancers in developing countries.}, journal = {Annals of global health}, volume = {80}, number = {5}, pages = {393-411}, doi = {10.1016/j.aogh.2014.10.002}, pmid = {25512155}, issn = {2214-9996}, mesh = {Air Pollution, Indoor ; Arsenic ; Asbestos ; *Carcinogens ; *Developing Countries ; Environmental Exposure/statistics &amp; numerical data ; Humans ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: Over the past few decades, there has been a decline in cancers attributable to environmental and occupational carcinogens of asbestos, arsenic, and indoor and outdoor air pollution in high-income countries. For low- to middle-income countries (LMICs), however, these exposures are likely to increase as industrialization expands and populations grow.<br><br>OBJECTIVE: The aim of this study was to review the evidence on the cancer risks and burdens of selected environmental and occupational exposures in less-developed economies.<br><br>FINDINGS: A causal association has been established between asbestos exposure and mesothelioma and lung cancer. For arsenic exposure, there is strong evidence of bladder, skin, lung, liver, and kidney cancer effects. Women are at the highest risk for lung cancer due to indoor air pollution exposure; however, the carcinogenic effect on the risk for cancer in children has not been studied in these countries. Cancer risks associated with ambient air pollution remain the least studied in LMICs, although reported exposures are higher than World Health Organization, European, and US standards. Although some associations between lung cancer and ambient air pollutants have been reported, studies in LMICs are weak or subject to exposure misclassification. For pulmonary cancers, tobacco smoking and respiratory diseases have a positive synergistic effect on cancer risks.<br><br>CONCLUSIONS: A precise quantification of the burden of human cancer attributable to environmental and occupational exposures in LMICs is uncertain. Although the prevalence of carcinogenic exposures has been reported to be high in many such countries, the effects of the exposures have not been studied due to varying country-specific limitations, some of which include lack of resources and government support.}, }
@article {pmid25511276, year = {2014}, author = {Liang, Y and Sun, X and Zhang, H and Cheng, Y and Gao, Y and Guo, J}, title = {[A case report of malignant peritoneal mesothelioma caused by asbestos].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {32}, number = {9}, pages = {695-696}, pmid = {25511276}, issn = {1001-9391}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*chemically induced ; }, }
@article {pmid25506632, year = {2015}, author = {Cyphert, JM and Carlin, DJ and Nyska, A and Schladweiler, MC and Ledbetter, AD and Shannahan, JH and Kodavanti, UP and Gavett, SH}, title = {Comparative long-term toxicity of Libby amphibole and amosite asbestos in rats after single or multiple intratracheal exposures.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {78}, number = {3}, pages = {151-165}, doi = {10.1080/15287394.2014.947455}, pmid = {25506632}, issn = {1528-7394}, support = {T32 ES007126/ES/NIEHS NIH HHS/United States ; }, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Asbestos, Amosite/toxicity ; Asbestos, Amphibole/*toxicity ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Inflammation/chemically induced/pathology/physiopathology ; Lung/*drug effects/pathology/physiopathology ; Lung Neoplasms/chemically induced/pathology ; Male ; Mesothelioma/chemically induced/pathology ; Rats ; Rats, Inbred F344 ; Toxicity Tests, Acute ; Toxicity Tests, Chronic ; }, abstract = {In former mine workers of Libby, MT, exposure to amphibole-containing vermiculite was linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies showed adverse effects following exposure to Libby amphibole (LA; a mixture of winchite, richterite, and tremolite), little is known regarding the relative toxicity of LA compared to regulated asbestos, or regarding the risks associated with acute high-dose exposures relative to repeated low-dose exposures. In this study, pulmonary function, inflammation, and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple IT instillations given every other week over a 13-wk period, and necropsied up to 20 mo after the initial IT. When comparing the two fiber types, in both studies LA resulted in greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. In addition, although no dose-response relationship was discerned, mesothelioma or lung carcinomas were found after exposure to low and high dose levels of LA or AM in both studies. Conversely, when comparing studies, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in lung at lower doses, despite the initially weaker acute inflammatory response. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately simulates chronic environmental exposures.}, }
@article {pmid25506370, year = {2014}, author = {Najmi, K and Khosravi, A and Seifi, S and Emami, H and Chaibakhsh, S and Radmand, G and Khodadad, K}, title = {Clinicopathologic and survival characteristics of malignant pleural mesothelioma registered in hospital cancer registry.}, journal = {Tanaffos}, volume = {13}, number = {2}, pages = {6-12}, pmid = {25506370}, issn = {1735-0344}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal thoracic tumor, which in the majority of patients is caused by prolonged exposure to asbestos fibers. We aimed at presenting clinicopathological and treatment outcomes of 60 patients of MPM registered in our hospital cancer registry.<br><br>MATERIALS AND METHODS: Demographic characteristics of patients, exposure to asbestos, smoking habit, their clinicopathologic characteristics and survival analysis were described.<br><br>RESULTS: Sixty patients had MPM. Forty patients (66.7%) were men. The mean age of patients was 55.8&#xb1;11 years. Chest pain and dyspnea were the most prevalent symptoms (31.7%, and 30%, respectively). Thirty-six (61.7%) patients reported asbestos exposure. The median survival and Progression free survival (PFS) were 10.5 months (0.95CI=9.22-11.78) and 7.57 months (0.95CI=5.68-9.45), respectively. In multivariate analysis, exposure to asbestos and epithelioid subtype significantly extended the survival time. Bilateral involvement, high blood level of LDH and platelet count &#x2265;400,000 significantly shortened the overall survival.<br><br>CONCLUSION: MPM is still an important health problem in Iran. Given the aforementioned results, developing a national program to eliminate asbestos-related diseases according to the world health organization (WHO) recommendation is necessary.}, }
@article {pmid25505814, year = {2014}, author = {Creaney, J and Segal, A and Olsen, N and Dick, IM and Musk, AW and Skates, SJ and Robinson, BW}, title = {Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma.}, journal = {Disease markers}, volume = {2014}, number = {}, pages = {413946}, pmid = {25505814}, issn = {1875-8630}, support = {//Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Female ; GPI-Linked Proteins/*metabolism ; Humans ; Male ; Mesothelin ; Mesothelioma/diagnosis/*metabolism ; Middle Aged ; Pleural Effusion, Malignant/diagnosis/*metabolism ; Prospective Studies ; ROC Curve ; Young Adult ; }, abstract = {RATIONALE: The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain.<br><br>OBJECTIVES: To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM.<br><br>METHODS AND MEASUREMENTS: Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined.<br><br>RESULTS: 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy.<br><br>CONCLUSIONS: A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis.}, }
@article {pmid25501304, year = {2015}, author = {Deng, XB and Xiao, L and Wu, Y and Jin, F and Mossman, B and Testa, JR and Xiao, GH}, title = {Inhibition of mesothelioma cancer stem-like cells with adenovirus-mediated NK4 gene therapy.}, journal = {International journal of cancer}, volume = {137}, number = {2}, pages = {481-490}, pmid = {25501304}, issn = {1097-0215}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; CA-114047/CA/NCI NIH HHS/United States ; }, mesh = {Adenoviridae/*genetics ; Animals ; Blotting, Western ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Genetic Therapy/*methods ; Genetic Vectors/genetics ; Hepatocyte Growth Factor/genetics/metabolism/*physiology ; Humans ; Indoles/pharmacology ; Lung Neoplasms/genetics/pathology/*therapy ; Mesothelioma/genetics/pathology/*therapy ; Mesothelioma, Malignant ; Mice, Nude ; Microscopy, Fluorescence ; Neoplastic Stem Cells/drug effects/*metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-met/metabolism ; Spheroids, Cellular/metabolism ; Sulfones/pharmacology ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism ; }, abstract = {Malignant mesothelioma (MM) is a highly invasive and chemoresistant malignancy induced by asbestos fibers. NK4, a hepatocyte growth factor antagonist and angiogenesis inhibitor, consists of the N-terminal hairpin domain and four kringle domains of the α-chain of hepatocyte growth factor. The therapeutic potential of NK4 has been demonstrated in a variety of tumor types. However, the mechanisms by which NK4 inhibits tumor growth have not been well delineated. In this study, it is shown that the NK4 adenovirus (Ad-NK4) potently inhibits cell viability, invasiveness and tumorigenicity of human MM cells. Significantly, this study demonstrates for the first time that Ad-NK4 inhibits cancer stem-like cell (CSC) properties as assessed by spheroid formation assay, side population analysis and flow cytometric sorting of CD24 cells. In addition to inhibiting phosphorylation of Met and AKT, Ad-NK4 markedly suppressed the active form of β-catenin, a key mediator of both Wnt and AKT pathways. It is further demonstrated that expression of NK4 suppresses β-catenin nuclear localization and transcriptional activity. Intriguingly, the expression levels of Oct4 and Myc, two critical stem cell factors and downstream targets of β-catenin, were also diminished by Ad-NK4. Furthermore, the strong antitumor effect of NK4 was found to be linked to its ability to inhibit CSCs as revealed by immunohistochemical examination of tumor specimens from a mouse xenograft model of human MM. These findings suggest that NK4 acts as a CSC inhibitor by impeding Met/AKT/β-catenin signaling and holds promise for achieving durable therapeutic responses in MM by constraining the CSC component of these aggressive tumors.}, }
@article {pmid25497279, year = {2015}, author = {Kirschner, MB and Cheng, YY and Armstrong, NJ and Lin, RC and Kao, SC and Linton, A and Klebe, S and McCaughan, BC and van Zandwijk, N and Reid, G}, title = {MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma.}, journal = {Molecular oncology}, volume = {9}, number = {3}, pages = {715-726}, pmid = {25497279}, issn = {1878-0261}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics/pathology/surgery ; Male ; Mesothelioma/*genetics/pathology/surgery ; Mesothelioma, Malignant ; MicroRNAs/*genetics/metabolism ; Middle Aged ; Multivariate Analysis ; Palliative Care ; Pneumonectomy ; Proportional Hazards Models ; Reproducibility of Results ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatment is difficult. Here we investigate the potential of microRNA expression to estimate prognosis of MPM patients.<br><br>METHODS: Candidate microRNAs from microarray profiling of tumor samples from 8 long (median: 53.7 months) and 8 short (median: 6.4 months) survivors following extrapleural pneumonectomy (EPP) were validated by RT-qPCR in 48 additional EPP samples. Kaplan-Meier log ranking was used to further explore the association between microRNA expression and overall survival (OS). Binary logistic regression was used to construct a microRNA signature (miR-Score) that was able to predict an OS of &#x2265;20 months. Performance of the miR-Score was evaluated by receiver operating characteristic (ROC) curve analysis and validated in a series of 43 tumor samples from patients who underwent palliative surgery [pleurectomy/decortication (P/D)].<br><br>RESULTS: The miR-Score, using expression data of six microRNAs (miR-21-5p, -23a-3p, -30e-5p, -221-3p, -222-3p, and -31-5p), enabled prediction of long survival with an accuracy of 92.3% for EPP and 71.9% for palliative P/D. Hazard ratios for score-negative patients were 4.12 (95% CI: 2.03-8.37) for EPP and 1.93 (95% CI: 1.01-3.69) for P/D. Importantly, adding the miR-Score to a set of clinical selection criteria (histology, age, gender) increased predictive accuracy in the independent validation set from 76.3% for clinical factors only to 87.3%.<br><br>CONCLUSIONS: This study has identified a novel 6-microRNA signature (miR-Score) that can accurately predict prognosis of MPM patients.}, }
@article {pmid25488749, year = {2015}, author = {Guo, G and Chmielecki, J and Goparaju, C and Heguy, A and Dolgalev, I and Carbone, M and Seepo, S and Meyerson, M and Pass, HI}, title = {Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma.}, journal = {Cancer research}, volume = {75}, number = {2}, pages = {264-269}, doi = {10.1158/0008-5472.CAN-14-1008}, pmid = {25488749}, issn = {1538-7445}, support = {5U01CA111295-07/CA/NCI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Cullin Proteins/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; DNA Mutational Analysis ; DNA, Neoplasm/genetics ; Exome ; Gene Dosage ; Humans ; Mesothelioma/*genetics ; Mutation ; Neurofibromin 2/*genetics ; Pleural Neoplasms/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although previous studies based on candidate gene approaches have identified important common somatic mutations in MPM, these studies have focused on small sets of genes and have provided a limited view of the genetic alterations underlying this disease. Here, we performed whole-exome sequencing on DNA from 22 MPMs and matched blood samples, and identified 517 somatic mutations across 490 mutated genes. Integrative analysis of mutations and somatic copy-number alterations revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM.}, }
@article {pmid25480441, year = {2015}, author = {Creaney, J and Robinson, BW}, title = {Author's response: Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies.}, journal = {Thorax}, volume = {70}, number = {4}, pages = {374-375}, doi = {10.1136/thoraxjnl-2014-206564}, pmid = {25480441}, issn = {1468-3296}, mesh = {Extracellular Matrix Proteins/*metabolism ; Female ; GPI-Linked Proteins/*metabolism ; Humans ; Lung Neoplasms/*metabolism ; Male ; Mesothelioma/*metabolism ; Pleural Neoplasms/*metabolism ; }, }
@article {pmid25479300, year = {2014}, author = {Järvholm, B and Aström, E}, title = {The risk of lung cancer after cessation of asbestos exposure in construction workers using pleural malignant mesothelioma as a marker of exposure.}, journal = {Journal of occupational and environmental medicine}, volume = {56}, number = {12}, pages = {1297-1301}, pmid = {25479300}, issn = {1536-5948}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Biomarkers ; *Construction Industry ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Registries ; Risk Assessment ; Sweden/epidemiology ; }, abstract = {OBJECTIVE: To study the risk of lung cancer in heavily asbestos-exposed workers after the exposure to asbestos has ended.<br><br>METHODS: Lung cancer was studied in a cohort of 189,896 Swedish construction workers through a linkage with the Swedish Cancer Registry. Asbestos exposure was estimated by the incidence of malignant mesothelioma in the occupational group.<br><br>RESULTS: There were in total 2835 cases of lung cancer. Workers with heavy exposure to asbestos had an increased risk of lung cancer (relative risks = 1.74; 95% confidence interval, 1.25 to 2.41) before exposure ended and a similar risk to those with low exposure 20 years after the exposure had ceased (relative risks = 0.94; 95% confidence interval, 0.77 to 1.15).<br><br>CONCLUSIONS: Workers with heavy exposure to asbestos have a similar risk of lung cancer as persons with low or no exposure 20 years after the exposure has ended.}, }
@article {pmid25475619, year = {2015}, author = {Ugolini, D and Bonassi, S and Cristaudo, A and Leoncini, G and Ratto, GB and Neri, M}, title = {Temporal trend, geographic distribution, and publication quality in asbestos research.}, journal = {Environmental science and pollution research international}, volume = {22}, number = {9}, pages = {6957-6967}, pmid = {25475619}, issn = {1614-7499}, mesh = {*Asbestos ; Australia ; *Bibliometrics ; Brazil ; Canada ; China ; Europe ; Humans ; Italy ; Journal Impact Factor ; Lung Neoplasms ; Neoplasms ; Occupational Diseases ; Publishing ; Research ; }, abstract = {Asbestos is a well-known cause of cancer and respiratory diseases. The aim of the current study was to investigate the scientific production in asbestos research evaluating temporal trend, geographic distribution, impact factor (IF) of published literature, and taking into account socioeconomic variables. The PubMed database was searched starting from 1970. Publication numbers and IF were evaluated as absolute values and after standardization by population and gross domestic product (GDP). Six thousand nine hundred seven articles related to asbestos were retrieved. Publications grew steeply in the 1970s, leveled off in the 1980s, decreased in the 1990s, and then increased again. Mesothelioma, lung neoplasms, and occupational diseases are the most commonly used keywords. In the period of 1988-2011, 4220 citations were retrieved, 3187 of whom had an impact factor. The US, Italy, and the UK were the most productive countries. European countries published about 20 % more asbestos-related articles than the US, although the latter reached a higher mean IF, ranking second after Australia. When the national scientific production (sum of IF) was compared taking into account socioeconomic variables, Australia and Scandinavian countries performed very well, opposite to all main asbestos producers like Russia, China, and Brazil (except for Canada). The American Journal of Industrial Medicine and the Italian La Medicina del Lavoro published the highest numbers of articles. This study provides the first bibliometric analysis of scientific production in asbestos research. Interest appears to be higher in selected countries, with strong national features, and is growing again in the new millennium.}, }
@article {pmid25471750, year = {2014}, author = {Comertpay, S and Pastorino, S and Tanji, M and Mezzapelle, R and Strianese, O and Napolitano, A and Baumann, F and Weigel, T and Friedberg, J and Sugarbaker, P and Krausz, T and Wang, E and Powers, A and Gaudino, G and Kanodia, S and Pass, HI and Parsons, BL and Yang, H and Carbone, M}, title = {Evaluation of clonal origin of malignant mesothelioma.}, journal = {Journal of translational medicine}, volume = {12}, number = {}, pages = {301}, pmid = {25471750}, issn = {1479-5876}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; P30CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; R01CA160715-0A/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Alleles ; Female ; Humans ; Mesothelioma/*pathology ; Middle Aged ; Receptors, Androgen/genetics ; }, abstract = {BACKGROUND: The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy.<br><br>METHODS AND RESULTS: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM.<br><br>CONCLUSIONS: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.}, }
@article {pmid25469901, year = {2014}, author = {Weber, DG and Casjens, S and Johnen, G and Bryk, O and Raiko, I and Pesch, B and Kollmeier, J and Bauer, TT and Brüning, T}, title = {Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e114483}, pmid = {25469901}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Middle Aged ; ROC Curve ; }, abstract = {BACKGROUND: For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma.<br><br>METHODS/PRINCIPAL FINDINGS: Mesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were calculated.<br><br>CONCLUSIONS/SIGNIFICANCE: The results of this study show that the combination of mesothelin and miR-103a-3p improves the diagnostic performance of individual blood-based biomarker to detect malignant mesothelioma. The obtained results indicate that the use of biomarkers of different molecular classes might be a reasonable approach to assemble a biomarker panel.}, }
@article {pmid25467107, year = {2015}, author = {Remon, J and Reguart, N and Corral, J and Lianes, P}, title = {Malignant pleural mesothelioma: new hope in the horizon with novel therapeutic strategies.}, journal = {Cancer treatment reviews}, volume = {41}, number = {1}, pages = {27-34}, doi = {10.1016/j.ctrv.2014.10.007}, pmid = {25467107}, issn = {1532-1967}, mesh = {Antineoplastic Agents/*therapeutic use ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy ; Prognosis ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy of the pleura, with a strong causal link to asbestos exposure. MPM incidence has been increasing in recent years and it is not expected to fall off in the next two decades. Prognosis of MPM patients is modest since the vast majority of patients are diagnosed at advanced stage and because platinum-based chemotherapy remains the cornerstone of treatment, with no standard second line treatment. Most current efforts to improve outcomes are based on a better understanding of the stromal compartment and deregulated pathways leading ultimately to the design of clinical trials based on novel therapeutic approaches such as immunotherapy or molecular-directed compounds. This review seeks to update the last clinical trials investigating novel agents in unresectable MPM.}, }
@article {pmid25460485, year = {2014}, author = {Perysinakis, I and Nixon, AM and Spyridakis, I and Kakiopoulos, G and Zorzos, C and Margaris, I}, title = {Primary intrahepatic malignant epithelioid mesothelioma.}, journal = {International journal of surgery case reports}, volume = {5}, number = {12}, pages = {1098-1101}, pmid = {25460485}, issn = {2210-2612}, abstract = {INTRODUCTION: Primary malignant hepatic mesotheliomas are extremely rare. We report the case of a patient with primary intrahepatic malignant mesothelioma who was treated in our department.<br><br>PRESENTATION OF CASE: A 66-year old male patient was admitted to our department for the evaluation of anemia. An abdominal computed tomography scan revealed a large space occupying lesion in the right liver lobe.<br><br>DISCUSSION: The tumor was subsequently resected and a diagnosis of primary intrahepatic malignant mesothelioma was made after pathologic examination. The patient did not receive adjuvant therapy and is currently alive and free of disease, 36 months after the resection.<br><br>CONCLUSION: To our knowledge this is the eighth adult case of primary intrahepatic malignant mesothelioma reported in the literature. These tumors are rarely diagnosed preoperatively. Absence of previous asbestos exposure does not exclude malignant mesothelioma from the differential diagnosis. Proper surgical treatment may offer prolonged survival to the patient, without adjuvant therapy.}, }
@article {pmid25459327, year = {2014}, author = {Pasetto, R and Terracini, B and Marsili, D and Comba, P}, title = {Occupational burden of asbestos-related cancer in Argentina, Brazil, Colombia, and Mexico.}, journal = {Annals of global health}, volume = {80}, number = {4}, pages = {263-268}, doi = {10.1016/j.aogh.2014.09.003}, pmid = {25459327}, issn = {2214-9996}, mesh = {Argentina/epidemiology ; Asbestos/*toxicity ; Brazil/epidemiology ; Carcinogens/*toxicity ; Colombia/epidemiology ; Female ; Humans ; Laryngeal Neoplasms/*mortality ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mexico/epidemiology ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Ovarian Neoplasms/*mortality ; }, abstract = {BACKGROUND: An estimate at the national level of the occupational cancer burden brought about by the industrial use of asbestos requires detailed routine information on such uses as well as on vital statistics of good quality. A causal association with asbestos exposure has been established for mesothelioma and cancers of the lung, larynx, and ovary.<br><br>OBJECTIVES: The aim of this study was to provide estimates of the occupational burden of asbestos-related cancer for the Latin American countries that are or have been the highest asbestos consumers in the region: Argentina, Brazil, Colombia, and Mexico.<br><br>METHODS: The burden of multifactorial cancers has been estimated through the approach suggested for the World Health Organization using the population attributable fraction. The following data were used: Proportion of workforce employed in each economic sector. Proportion of workers exposed to asbestos in each sector. Occupational turnover. Levels of exposure. Proportion of the population in the workforce. Relative risk for each considered disease for 1 or more levels of exposure. Data on the proportion of workers exposed to asbestos in each sector are not available for Latin American countries; therefore, data from the European CAREX database (carcinogen exposure database) were used.<br><br>FINDINGS: Using mortality data of the World Health Organization Health Statistics database for the year 2009 and applying the estimated values for population attributable fractions, the number of estimated deaths in 5 years for mesothelioma and for lung, larynx, and ovary cancers attributable to occupational asbestos exposures, were respectively 735, 233, 29, and 14 for Argentina; 340, 611, 68, and 43 for Brazil; 255, 97, 14, and 9 for Colombia, and 1075, 219, 18, and 22 for Mexico.<br><br>CONCLUSIONS: The limitations in compiling the estimates highlight the need for improvement in the quality of asbestos-related environmental and health data. Nevertheless, the figures are already usable to promote a ban on asbestos use.}, }
@article {pmid25459324, year = {2014}, author = {Marsili, D and Comba, P and Pasetto, R and Terracini, B}, title = {International scientific cooperation on asbestos-related disease prevention in Latin America.}, journal = {Annals of global health}, volume = {80}, number = {4}, pages = {247-250}, doi = {10.1016/j.aogh.2014.09.002}, pmid = {25459324}, issn = {2214-9996}, mesh = {Asbestos/*toxicity ; Asbestosis/prevention &amp; control ; Construction Materials ; Environmental Exposure/*prevention &amp; control ; Humans ; *International Cooperation ; Latin America ; Mesothelioma/*prevention &amp; control ; Pleural Neoplasms/*prevention &amp; control ; }, }
@article {pmid25454236, year = {2015}, author = {Mensi, C and Riboldi, L and De Matteis, S and Bertazzi, PA and Consonni, D}, title = {Impact of an asbestos cement factory on mesothelioma incidence: global assessment of effects of occupational, familial, and environmental exposure.}, journal = {Environment international}, volume = {74}, number = {}, pages = {191-199}, doi = {10.1016/j.envint.2014.10.016}, pmid = {25454236}, issn = {1873-6750}, mesh = {Aged ; Asbestos/*toxicity ; Carcinogens/*toxicity ; *Environmental Exposure ; Family Health ; Female ; Humans ; Incidence ; Industry ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Few studies have examined the incidence of malignant mesothelioma (MM) associated with distinct sources of asbestos exposure (occupational, familial, or environmental). We assessed the impact of asbestos exposure-global and by source-on the incidence of MM in Broni, an Italian town in which an asbestos cement factory once operated (1932-1993). Based on data collected by the Lombardy Mesothelioma Registry, we calculated the number of observed and expected MM cases among workers, their cohabitants, and people living in the area in 2000-2011. We identified 147 MM cases (17.45 expected), 138 pleural and nine peritoneal, attributable to exposure to asbestos from the factory. Thirty-eight cases had past occupational exposure at the factory (2.33 expected), numbering 32 men (26 pleural, six peritoneal) and six women (four pleural, two peritoneal). In the families of the workers, there were 37 MM cases (4.23 expected), numbering five men (all pleural) and 32 women (31 pleural, one peritoneal). Among residents in Broni or in the adjacent/surrounding towns, there were 72 cases of pleural MM (10.89 expected), numbering 23 men and 49 women. The largest MM excess was found in the towns of Broni (48 observed, 3.68 expected) and Stradella (16 observed, 1.85 expected). This study documents the large impact of the asbestos cement factory, with about 130 excess MM cases in a 12-year period. The largest MM burden was among women, from non-occupational exposure. Almost half of the MM cases were attributable to environmental exposure.}, }
@article {pmid25444537, year = {2015}, author = {Norbet, C and Joseph, A and Rossi, SS and Bhalla, S and Gutierrez, FR}, title = {Asbestos-related lung disease: a pictorial review.}, journal = {Current problems in diagnostic radiology}, volume = {44}, number = {4}, pages = {371-382}, doi = {10.1067/j.cpradiol.2014.10.002}, pmid = {25444537}, issn = {1535-6302}, mesh = {Asbestosis/*diagnosis/physiopathology ; *Diagnostic Imaging ; Disease Progression ; Humans ; Prognosis ; }, abstract = {Asbestos exposure can lead to a variety of adverse effects in the thorax. Although currently in the western world, levels of exposure are kept in check by strict regulations, history of previous asbestos exposure continues to have an effect on many, owing to the latent nature of the pathophysiological response of the body to the inhaled fibers. The adverse effects of asbestos generally fall under 3 categories: pleural disease, lung parenchymal disease, and neoplastic disease. Effects on the pleura include pleural effusions, plaques, and diffuse pleural thickening. In the parenchyma, rounded atelectasis, fibrotic bands, and asbestosis are observed. Differentiating asbestosis from other forms of interstitial lung diseases, such as idiopathic pulmonary fibrosis, usual interstitial pneumonia, smoking-related lung disease, and mixed interstitial lung diseases, is important because the prognosis, course of disease, and management of the patient should be tailored based on the specific etiology of the disease. In this review, imaging findings specific to asbestosis are discussed. Finally, exposure to asbestos can lead to neoplastic disease such as pleural mesothelioma, peritoneal mesothelioma, and bronchogenic carcinoma. The purpose of this article is to review the effects of asbestos exposure in the thorax, pathophysiology of these responses, and disease course. Particular emphasis is placed on the radiographic appearance of the disease, discussion of various imaging modalities and their utility, and the role of imaging in the management of patients with previous asbestos exposure and asbestos-related pulmonary disease.}, }
@article {pmid25438686, year = {2014}, author = {Hsu, LN and Sung, MT and Chiang, PH}, title = {Paratesticular malignant mesothelioma in a patient exposed to asbestos for more than 50 years.}, journal = {The Kaohsiung journal of medical sciences}, volume = {30}, number = {10}, pages = {537-538}, doi = {10.1016/j.kjms.2014.02.004}, pmid = {25438686}, issn = {2410-8650}, mesh = {Humans ; Male ; Mesothelioma/*pathology ; Testicular Neoplasms/*pathology ; }, }
@article {pmid25428276, year = {2015}, author = {Boelter, FW and Xia, Y and Dell, L}, title = {Comparative Risks of Cancer from Drywall Finishing Based on Stochastic Modeling of Cumulative Exposures to Respirable Dusts and Chrysotile Asbestos Fibers.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {35}, number = {5}, pages = {859-871}, doi = {10.1111/risa.12297}, pmid = {25428276}, issn = {1539-6924}, mesh = {*Asbestos, Serpentine ; *Dust ; Humans ; Inhalation Exposure ; Neoplasms/*etiology ; *Occupational Exposure ; *Risk Assessment ; *Stochastic Processes ; }, abstract = {Sanding joint compounds is a dusty activity and exposures are not well characterized. Until the mid 1970s, asbestos-containing joint compounds were used by some people such that sanding could emit dust and asbestos fibers. We estimated the distribution of 8-h TWA concentrations and cumulative exposures to respirable dusts and chrysotile asbestos fibers for four worker groups: (1) drywall specialists, (2) generalists, (3) tradespersons who are bystanders to drywall finishing, and (4) do-it-yourselfers (DIYers). Data collected through a survey of experienced contractors, direct field observations, and literature were used to develop prototypical exposure scenarios for each worker group. To these exposure scenarios, we applied a previously developed semi-empirical mathematical model that predicts area as well as personal breathing zone respirable dust concentrations. An empirical factor was used to estimate chrysotile fiber concentrations from respirable dust concentrations. On a task basis, we found mean 8-h TWA concentrations of respirable dust and chrysotile fibers are numerically highest for specialists, followed by generalists, DIYers, and bystander tradespersons; these concentrations are estimated to be in excess of the respective current but not historical Threshold Limit Values. Due to differences in frequency of activities, annual cumulative exposures are highest for specialists, followed by generalists, bystander tradespersons, and DIYers. Cumulative exposure estimates for chrysotile fibers from drywall finishing are expected to result in few, if any, mesothelioma or excess lung cancer deaths according to recently published risk assessments. Given the dustiness of drywall finishing, we recommend diligence in the use of readily available source controls.}, }
@article {pmid25421663, year = {2015}, author = {Zhang, X and Tang, N and Rishi, AK and Pass, HI and Wali, A}, title = {Methylation profile landscape in mesothelioma: possible implications in early detection, disease progression, and therapeutic options.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1238}, number = {}, pages = {235-247}, doi = {10.1007/978-1-4939-1804-1_12}, pmid = {25421663}, issn = {1940-6029}, mesh = {Biomarkers, Tumor/genetics ; *DNA Methylation ; *Disease Progression ; Early Detection of Cancer/*methods ; Epigenesis, Genetic ; Humans ; Mesothelioma/*diagnosis/genetics/*therapy ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy of the pleura associated with asbestos exposure. Incidence of MPM is expected to increase over the course of next decade in both Europe and the developing countries. Although significant progress has been made in terms of etiology and pathogenesis of this disease, currently available therapeutic options have not significantly improved the survival outcome of patients on standard chemotherapeutic regimens. Integrity of the cellular DNA is often altered in many cancers. Understanding of the molecular mechanisms that regulate cellular DNA alterations to facilitate cancer initiation and development has potential to allow better design of cancer cell inhibitory strategies. In this context, there is a need to explore the gamut of "omics" strategies to provide a comprehensive epigenetics profile for MPM. This chapter discusses the functional genomics and epigenetic patterns observed by various investigators studying MPM patient populations on global fronts, and attempts to present a holistic approach in combating this insidious disease. Here we provide investigators in this field with novel insights and methodologies used in other types of cancers that might have profound impact in the early detection, prognosis and potential therapeutic strategies for MPM.}, }
@article {pmid25410850, year = {2014}, author = {Assis, Ld and Isoldi, MC}, title = {The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40”.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {40}, number = {5}, pages = {586-587}, pmid = {25410850}, issn = {1806-3756}, mesh = {Humans ; Lung Neoplasms/*genetics/*metabolism ; Mesothelioma/*genetics/*metabolism ; }, }
@article {pmid25410479, year = {2014}, author = {Rittinghausen, S and Hackbarth, A and Creutzenberg, O and Ernst, H and Heinrich, U and Leonhardt, A and Schaudien, D}, title = {The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats.}, journal = {Particle and fibre toxicology}, volume = {11}, number = {}, pages = {59}, pmid = {25410479}, issn = {1743-8977}, mesh = {Abdominal Neoplasms/*chemically induced/metabolism/pathology ; Animals ; Carcinogenicity Tests ; Carcinogens/administration &amp; dosage/chemistry/*toxicity ; Dose-Response Relationship, Drug ; Immunohistochemistry ; Injections, Intraperitoneal ; Male ; Mesothelioma/*chemically induced/metabolism/pathology ; Microscopy, Electron, Scanning ; Nanotubes, Carbon/chemistry/*toxicity/ultrastructure ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Particle Size ; Rats, Wistar ; Serous Membrane ; Survival Analysis ; }, abstract = {BACKGROUND: Biological effects of tailor-made multi-walled carbon nanotubes (MWCNTs) without functionalization were investigated in vivo in a two-year carcinogenicity study. In the past, intraperitoneal carcinogenicity studies in rats using biopersistent granular dusts had always been negative, whereas a number of such studies with different asbestos fibers had shown tumor induction. The aim of this study was to identify possible carcinogenic effects of MWCNTs. We compared induced tumors with asbestos-induced mesotheliomas and evaluated their relevance for humans by immunohistochemical methods.<br><br>METHODS: A total of 500 male Wistar rats (50 per group) were treated once by intraperitoneal injection with 10&#x2079; or 5&#x2009;&#xd7;&#x2009;10&#x2079; WHO carbon nanotubes of one of four different MWCNTs suspended in artificial lung medium, which was also used as negative control. Amosite asbestos (10&#x2078; WHO fibers) served as positive control. Morbid rats were sacrificed and necropsy comprising all organs was performed. Histopathological classification of tumors and, additionally, immunohistochemistry were conducted for podoplanin, pan-cytokeratin, and vimentin to compare induced tumors with malignant mesotheliomas occurring in humans.<br><br>RESULTS: Treatments induced tumors in all dose groups, but incidences and times to tumor differed between groups. Most tumors were histologically and immunohistochemically classified as malignant mesotheliomas, revealing a predominantly superficial spread on the serosal surface of the abdominal cavity. Furthermore, most tumors showed invasion of peritoneal organs, especially the diaphragm. All tested MWCNT types caused mesotheliomas. We observed highest frequencies and earliest appearances after treatment with the rather straight MWCNT types A and B. In the MWCNT C groups, first appearances of morbid mesothelioma-bearing rats were only slightly later. Later during the two-year study, we found mesotheliomas also in rats treated with MWCNT D - the most curved type of nanotubes. Malignant mesotheliomas induced by intraperitoneal injection of different MWCNTs and of asbestos were histopathologically and immunohistochemically similar, also compared with mesotheliomas in man, suggesting similar pathogenesis.<br><br>CONCLUSION: We showed a carcinogenic effect for all tested MWCNTs. Besides aspect ratio, curvature seems to be an important parameter influencing the carcinogenicity of MWCNTs.}, }
@article {pmid25408576, year = {2014}, author = {Lee, YJ and Hwang, IS and Lee, YJ and Lee, CH and Kim, SH and Nam, HS and Choi, YJ and Lee, SH}, title = {Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells.}, journal = {Journal of Korean medical science}, volume = {29}, number = {11}, pages = {1464-1472}, pmid = {25408576}, issn = {1598-6357}, mesh = {Adenine Nucleotides/*pharmacology ; Antimetabolites, Antineoplastic/*pharmacology ; Apoptosis/*drug effects ; Arabinonucleosides/*pharmacology ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Clofarabine ; G2 Phase Cell Cycle Checkpoints/drug effects ; Gene Knockdown Techniques ; Humans ; Leupeptins/pharmacology ; Lung Neoplasms/metabolism/pathology ; M Phase Cell Cycle Checkpoints/drug effects ; Mesothelioma/metabolism/pathology ; Mesothelioma, Malignant ; Myeloid Cell Leukemia Sequence 1 Protein/antagonists &amp; inhibitors/genetics/metabolism ; RNA Interference ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; Resveratrol ; Stilbenes/*pharmacology ; bcl-X Protein/antagonists &amp; inhibitors/*genetics/*metabolism ; }, abstract = {Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.}, }
@article {pmid25388904, year = {2015}, author = {Zanker, F and Zellner, M and Busche, J and Woziwodski, J}, title = {[Paratesticular mesothelioma].}, journal = {Der Urologe. Ausg. A}, volume = {54}, number = {3}, pages = {394-396}, pmid = {25388904}, issn = {1433-0563}, mesh = {Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/*therapy ; Occupational Diseases/*diagnosis/*therapy ; Testicular Neoplasms/*diagnosis/*therapy ; Treatment Outcome ; }, abstract = {Paratesticular mesothelioma is a very rare entity of this aggressive malignancy. In 30-40 % of all cases an exposition to asbestos exists in the anamnesis. We report on a typical case of paratesticular mesothelioma in a roof slater and tiler who had had occupational contact with asbestos-containing materials over decades. The recommended diagnostics and therapy are discussed and the importance of the identification as an occupational disease is emphasized.}, }
@article {pmid25386835, year = {2015}, author = {Germine, M and Puffer, JH}, title = {Analytical Transmission Electron Microscopy of Amphibole Fibers From the Lungs of Quebec Miners.}, journal = {Archives of environmental &amp; occupational health}, volume = {70}, number = {6}, pages = {323-331}, doi = {10.1080/19338244.2014.918928}, pmid = {25386835}, issn = {2154-4700}, mesh = {Air Pollutants, Occupational/*analysis/chemistry ; Asbestos, Amphibole/*analysis/chemistry ; Cohort Studies ; Lung Neoplasms/chemically induced/pathology/*ultrastructure ; Mesothelioma/chemically induced/pathology/*ultrastructure ; Microscopy, Electron, Transmission ; *Miners ; Occupational Diseases/*pathology ; Quebec ; }, abstract = {The objective of this study is to describe the morphology, molecular structure, and chemistry of amphibole fibers from lung samples from workers in the chrysotile mines at Asbestos and Thetford Mines, Quebec. A fibrous tremolite-actinolite contaminant in an asbestos ore sample from the deposit at Asbestos was used for comparison. Lattice imaging was performed using high-resolution transmission electron microscopy (HRTEM). Silica-rich amorphous coatings (SIRA) that may be related to carcinogenesis are noted on all of the HRTEM photographs of fibers retained in lung, but not on fiber surfaces of the bulk comparison sample. Fibers found in lung samples and in a bulk comparison sample are produced primarily by splitting of thicker crystals and, as such, might not be considered asbestos fibers on the basis of certain mineralogical criteria. Implications of SIRA coatings with respect to carcinogenesis are worthy of further study.}, }
@article {pmid25382807, year = {2015}, author = {Kao, SC and van Zandwijk, N and Clarke, S and Vardy, J and Lumba, S and Tognela, A and Ng, W}, title = {Estimation of an optimal chemotherapy utilization rate for malignant pleural mesothelioma: an evidence-based benchmark for cancer care.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {11}, number = {1}, pages = {85-92}, doi = {10.1111/ajco.12306}, pmid = {25382807}, issn = {1743-7563}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*standards/*therapeutic use ; *Benchmarking ; *Evidence-Based Medicine ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Medical Oncology/*standards ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Models, Statistical ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/pathology ; Practice Guidelines as Topic/*standards ; Prognosis ; Quality of Health Care ; Quality of Life ; }, abstract = {AIMS: Chemotherapy with cisplatin and pemetrexed has been shown to provide a survival benefit and improvement in quality of life in patients with malignant pleural mesothelioma (MPM). The reported chemotherapy utilization rates range from 18% to 61%. This study aimed to estimate the proportion of MPM patients that should receive chemotherapy based on best available evidence.<br><br>METHODS: An optimal chemotherapy utilization model for MPM was constructed using indications for chemotherapy identified from evidence-based MPM treatment guidelines. Epidemiological data on the proportion of patients and their tumor-related attributes were combined with the chemotherapy indications to estimate the optimal chemotherapy utilization rate using decision analysis software (TreeAge Pro 2007). Sensitivity analyses were performed to assess the impact of major variations in the epidemiological data on the optimal chemotherapy utilization rate. The optimal rate was compared with the actual rate reported in the literature.<br><br>RESULTS: Chemotherapy is recommended at least once during the disease trajectory in 65% of MPM patients. Sensitivity analyses indicate an optimal utilization rate ranging from 50% to 65%. This optimal rate is relatively comparable to the rates mentioned in contemporary reports from Canada (61% between 2003 and 2005) and Australia (54% between 2007 and 2009) and high when compared with data from the Netherlands (36% during 2005-2006).<br><br>CONCLUSION: An evidence-based model provided an optimal chemotherapy utilization rate of 65% for patients with MPM. Chemotherapy for MPM may be underutilized and barriers are likely multifactorial.}, }
@article {pmid25378740, year = {2014}, author = {Kameda, T and Takahashi, K and Kim, R and Jiang, Y and Movahed, M and Park, EK and Rantanen, J}, title = {Asbestos: use, bans and disease burden in Europe.}, journal = {Bulletin of the World Health Organization}, volume = {92}, number = {11}, pages = {790-797}, pmid = {25378740}, issn = {1564-0604}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Asbestos/*toxicity ; Asbestosis/*mortality ; Databases, Factual ; Europe/epidemiology ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; World Health Organization ; }, abstract = {OBJECTIVE: To analyse national data on asbestos use and related diseases in the European Region of the World Health Organization (WHO).<br><br>METHODS: For each of the 53 countries, per capita asbestos use (kg/capita/year) and age-adjusted mortality rates (deaths/million persons/year) due to mesothelioma and asbestosis were calculated using the databases of the United States Geological Survey and WHO, respectively. Countries were further categorized by ban status: early-ban (ban adopted by 2000, n&#x2009;=&#x2009;17), late-ban (ban adopted 2001-2013, n&#x2009;=&#x2009;17), and no-ban (n&#x2009;=&#x2009;19).<br><br>FINDINGS: Between 1920-2012, the highest per capita asbestos use was found in the no-ban group. After 2000, early-ban and late-ban groups reduced their asbestos use levels to less than&#x2009;or equal to 0.1 kg/capita/year, respectively, while the no-ban group maintained a very high use at 2.2 kg/capita/year. Between 1994 and 2010, the European Region registered 106,180 deaths from mesothelioma and asbestosis, accounting for 60% of such deaths worldwide. In the early-ban and late-ban groups, 16/17 and 15/17 countries, respectively, reported mesothelioma data to WHO, while only 6/19 countries in the no-ban group reported such data. The age-adjusted mortality rates for mesothelioma for the early-ban, late-ban and no-ban groups were 9.4, 3.7 and 3.2 deaths/million persons/year, respectively. Asbestosis rates for the groups were 0.8, 0.9 and 1.5 deaths/million persons/year, respectively.<br><br>CONCLUSION: Within the European Region, the early-ban countries reported most of the current asbestos-related deaths. However, this might shift to the no-ban countries, since the disease burden will likely increase in these countries due the heavy use of asbestos.}, }
@article {pmid25374934, year = {2014}, author = {Hajok, I and Marchwińska, E and Dziubanek, G and Kuraszewska, B and Piekut, A}, title = {Environmentally related diseases and the possibility of valuation of their social costs.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {284072}, pmid = {25374934}, issn = {1537-744X}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; *Occupational Exposure ; Poland/epidemiology ; Risk Factors ; }, abstract = {The risks of the morbidity of the asbestos-related lung cancer was estimated in the general population of Poles as the result of increased exposure to asbestos fibers during the removal of asbestos-cement products and the possibility of the valuation of the social costs related to this risk. The prediction of the new incidences was made using linear regression model. The forecast shows that to the end of 2030 about 3,500 new cases of lung cancer can be expected as a result of occupational exposure to asbestos in the past which makes together with paraoccupational exposure about 14.000 new cases. The forecast shows the increasing number of asbestos-related lung cancer in Poland and indicates the priority areas where preventive action should be implemented.}, }
@article {pmid25358858, year = {2014}, author = {Maeda, M and Chen, Y and Hayashi, H and Kumagai-Takei, N and Matsuzaki, H and Lee, S and Nishimura, Y and Otsuki, T}, title = {Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2.}, journal = {International journal of oncology}, volume = {45}, number = {6}, pages = {2522-2532}, doi = {10.3892/ijo.2014.2682}, pmid = {25358858}, issn = {1791-2423}, mesh = {Adult ; Annexin A5/metabolism ; Apoptosis/genetics ; Asbestos/*toxicity ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Gene Knockdown Techniques ; Humans ; Immune System/drug effects/pathology ; Leukemia-Lymphoma, Adult T-Cell/chemically induced/*genetics/pathology ; Transforming Growth Factor beta1/biosynthesis/*genetics ; p38 Mitogen-Activated Protein Kinases/antagonists &amp; inhibitors/metabolism ; }, abstract = {Asbestos exposure causes various tumors such as lung cancer and malignant mesothelioma. To elucidate the immunological alteration in asbestos-related tumors, an asbestos-induced apoptosis-resistant subline (MT-2Rst) was established from a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-β1 (TGF-β1) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-β1, and acquired resistance to TGF-β1-mediated growth inhibition. We showed that exposure of MT-2Org cells to CB activated the mitogen-activated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-β1-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-β1 mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-β1 resistance in MT-2Rst cells was not directly involved in the acquisition of resistance to apoptosis that is triggered by CB exposure. The overall results demonstrate that long-term exposure of MT-2Org cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.}, }
@article {pmid25335827, year = {2015}, author = {García-Gómez, M and Menéndez-Navarro, A and López, RC}, title = {Asbestos-related occupational cancers compensated under the Spanish National Insurance System, 1978-2011.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {1}, pages = {31-39}, pmid = {25335827}, issn = {2049-3967}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Bronchial Neoplasms/chemically induced/*epidemiology/mortality ; Europe/epidemiology ; European Union/statistics &amp; numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology/mortality ; Male ; Mesothelioma/chemically induced/*epidemiology/mortality ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; *Occupational Exposure/statistics &amp; numerical data ; Spain/epidemiology ; }, abstract = {BACKGROUND: In 1978, asbestos-related occupational cancers were added to the Spanish list of occupational diseases. However, there are no full accounts of compensated cases since their inclusion.<br><br>OBJECTIVE: To analyze the cases of asbestos-related cancer recognized as occupational in Spain between 1978 and 2011.<br><br>METHODS: Cases were obtained from the Spanish Employment Ministry. Specific incidence rates by year, economic activity, and occupation were obtained. We compared mortality rates of mesothelioma and bronchus and lung cancer mortality in Spain and the European Union.<br><br>RESULTS: Between 1978 and 2011, 164 asbestos-related occupational cancers were recognized in Spain, with a mean annual rate of 0&#xb7;08 per 10(5) employees (0&#xb7;13 in males, 0&#xb7;002 in females). Under-recognition rates were an estimated 93&#xb7;6% (males) and 99&#xb7;7% (females) for pleural mesothelioma and 98&#xb7;8% (males) and 100% (females) for bronchus and lung cancer. In Europe for the year 2000, asbestos-related occupational cancer rates ranged from 0&#xb7;04 per 10(5) employees in Spain to 7&#xb7;32 per 10(5) employees in Norway.<br><br>CONCLUSIONS: These findings provide evidence of gross under-recognition of asbestos-related occupational cancers in Spain. Future work should investigate cases treated in the National Healthcare System to better establish the impact of asbestos on health in Spain.}, }
@article {pmid25331029, year = {2015}, author = {Cao, S and Jin, S and Cao, J and Shen, J and Hu, J and Che, D and Pan, B and Zhang, J and He, X and Ding, D and Gu, F and Yu, Y}, title = {Advances in malignant peritoneal mesothelioma.}, journal = {International journal of colorectal disease}, volume = {30}, number = {1}, pages = {1-10}, pmid = {25331029}, issn = {1432-1262}, mesh = {Diagnosis, Differential ; Female ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/therapy ; Male ; *Mesothelioma/diagnosis/epidemiology/therapy ; Mesothelioma, Malignant ; *Peritoneal Neoplasms/diagnosis/epidemiology/therapy ; Prognosis ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare, insidious, and aggressive tumor arising from the mesothelial surface of pleural and peritoneal cavities, the pericardium, or the tunica vaginalis, with an increasing incidence worldwide, high misdiagnosis rate, and overall negative prognosis. A total of 20% of all cases is peritoneum in origin.<br><br>METHODS: The present study is a review of literatures focusing on the advances in epidemiology, clinical presentations, radiological features, diagnosis, misdiagnosis, management, and prognostic factors of malignant peritoneal mesothelioma (MPM) occurred in the past decades.<br><br>RESULTS: Asbestos, SV40, and radiation exposures have been demonstrated to be correlated with the pathogenesis of MPM. The main presentations are abdominal distension and pain. Computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) play an important role in the preoperative imaging and staging. Definitive diagnosis is made on the basis of immunohistochemistry. Prognostic factors have been identified and verified. Negative indicators include advanced age, male gender, poor performance status, non-epithelial histology, and absence of surgery. The management of MPM has evolved from single chemotherapy to multimodality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), chemotherapy, radiotherapy, and immunotherapy. Promising results have been achieved after a combined treatment of CRS and HIPEC, with an elevated median survival time of 29.5-92 months and a 5-year survival rate of 39-63%.<br><br>CONCLUSIONS: CRS and HIPEC represent the standard treatment strategy for selected patients with MPM, and patients with unresectable tumors can benefit from the combined treatment of chemotherapy, radiotherapy, and immunotherapy.}, }
@article {pmid25325160, year = {2015}, author = {Palomäki, J and Sund, J and Vippola, M and Kinaret, P and Greco, D and Savolainen, K and Puustinen, A and Alenius, H}, title = {A secretomics analysis reveals major differences in the macrophage responses towards different types of carbon nanotubes.}, journal = {Nanotoxicology}, volume = {9}, number = {6}, pages = {719-728}, doi = {10.3109/17435390.2014.969346}, pmid = {25325160}, issn = {1743-5404}, mesh = {Apoptosis/drug effects ; Asbestos, Crocidolite/chemistry/toxicity ; Blotting, Western ; Cells, Cultured ; Cluster Analysis ; Culture Media, Serum-Free ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Humans ; Macrophages/*drug effects/*metabolism/pathology ; Nanotubes, Carbon/chemistry/*toxicity ; Proteins/*metabolism ; Surface Properties ; }, abstract = {Certain types of carbon nanotubes (CNT) can evoke inflammation, fibrosis and mesothelioma in vivo, raising concerns about their potential health effects. It has been recently postulated that NLRP3 inflammasome activation is important in the CNT-induced toxicity. However, more comprehensive studies of the protein secretion induced by CNT can provide new information about their possible pathogenic mechanisms. Here, we studied protein secretion from human macrophages with a proteomic approach in an unbiased way. Human monocyte-derived macrophages (MDM) were exposed to tangled or rigid, long multi-walled CNT (MWCNT) or crocidolite asbestos for 6 h. The growth media was concentrated and secreted proteins were analyzed using 2D-DIGE and DeCyder software. Subsequently, significantly up- or down-regulated protein spots were in-gel digested and identified with an LC-MS/MS approach. Bioinformatics analysis was performed to reveal the different patterns of protein secretion induced by these materials. The results show that both long rigid MWCNT and asbestos elicited ample and highly similar protein secretion. In contrast, exposure to long tangled MWCNT induced weaker protein secretion with a more distinct profile. Secretion of lysosomal proteins followed the exposure to all materials, suggesting lysosomal damage. However, only long rigid MWCNT was associated with apoptosis. This analysis suggests that the CNT toxicity in human MDM is mediated via vigorous secretion of inflammation-related proteins and apoptosis. This study provides new insights into the mechanisms of toxicity of high aspect ratio nanomaterials and indicates that not all types of CNT are as hazardous as asbestos fibers.}, }
@article {pmid25324587, year = {2014}, author = {Okada, F}, title = {Inflammation-related carcinogenesis: current findings in epidemiological trends, causes and mechanisms.}, journal = {Yonago acta medica}, volume = {57}, number = {2}, pages = {65-72}, pmid = {25324587}, issn = {0513-5710}, abstract = {Inflammation is a definite cancer-causing factor as revealed by cumulative basic, clinical and epidemiological studies. It is mostly induced by infectious agents. For instance, infection with papillomaviruses associates with anogenital cancers, especially cervical cancers; Helicobacter pylori infection of the stomach tends to increase the risk of stomach cancer; chronic hepatitis B &amp; C viruses and fluke infections of the liver increase liver cancers; autoimmune diseases, e.g., inflammatory bowel diseases, associate with development of colorectal cancer, and aerial irritants (foreign bodies) such as asbestos or fine particulate matter (PM2.5) in outdoor air increase malignant pleural mesotheliomas or lung cancers. These are typical examples of inflammation-related carcinogenesis. It is apparent that the pathogens to induce inflammatory reactions in specific organs are not related to each other. However, the underlying pathogenesis in common is to induce and/or sustain inflammation. In this article, I would like to review the up-to-date findings of epidemiological trends, causes and mechanisms of inflammation-related carcinogenesis.}, }
@article {pmid25316312, year = {2015}, author = {McDonnell, AM and Lesterhuis, WJ and Khong, A and Nowak, AK and Lake, RA and Currie, AJ and Robinson, BW}, title = {Tumor-infiltrating dendritic cells exhibit defective cross-presentation of tumor antigens, but is reversed by chemotherapy.}, journal = {European journal of immunology}, volume = {45}, number = {1}, pages = {49-59}, doi = {10.1002/eji.201444722}, pmid = {25316312}, issn = {1521-4141}, mesh = {Animals ; Antigen Presentation/genetics ; Antigens, Neoplasm/genetics/*immunology ; Antimetabolites, Antineoplastic/*pharmacology ; CD11b Antigen/genetics/immunology ; CD4-Positive T-Lymphocytes/immunology/pathology ; Cell Movement ; Coculture Techniques ; Cross-Priming/genetics ; Dendritic Cells/*immunology/pathology ; Deoxycytidine/*analogs &amp; derivatives/pharmacology ; Gene Expression ; Hemagglutinins/genetics/immunology ; Lymph Nodes/immunology/pathology ; Mesothelioma/*drug therapy/genetics/immunology/pathology ; Mice ; Mice, Transgenic ; Neoplasm Transplantation ; Skin Neoplasms/*drug therapy/genetics/immunology/pathology ; T-Lymphocytes, Cytotoxic/immunology/pathology ; Tumor Microenvironment ; Gemcitabine ; }, abstract = {Cross-presentation defines the unique capacity of an APC to present exogenous Ag via MHC class I molecules to CD8(+) T cells. DCs are specialized cross-presenting cells and as such have a critical role in antitumor immunity. DCs are routinely found within the tumor microenvironment, but their capacity for endogenous or therapeutically enhanced cross-presentation is not well characterized. In this study, we examined the tumor and lymph node DC cross-presentation of a nominal marker tumor Ag, HA, expressed by the murine mesothelioma tumor AB1-HA. We found that tumors were infiltrated by predominantly CD11b(+) DCs with a semimature phenotype that could not cross-present tumor Ag, and therefore, were unable to induce tumor-specific T-cell activation or proliferation. Although tumor-infiltrating DCs were able to take up, process, and cross-present exogenous cell-bound and soluble Ags, this was significantly impaired relative to lymph node DCs. Importantly, however, systemic chemotherapy using gemcitabine reversed the defect in Ag cross-presentation of tumor DCs. These data demonstrate that DC cross-presentation within the tumor microenvironment is defective, but can be reversed by chemotherapy. These results have important implications for anticancer therapy, particularly regarding the use of immunotherapy in conjunction with cytotoxic chemotherapy.}, }
@article {pmid25310424, year = {2014}, author = {Nickell, LT and Lichtenberger, JP and Khorashadi, L and Abbott, GF and Carter, BW}, title = {Multimodality imaging for characterization, classification, and staging of malignant pleural mesothelioma.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {34}, number = {6}, pages = {1692-1706}, doi = {10.1148/rg.346130089}, pmid = {25310424}, issn = {1527-1323}, mesh = {Contrast Media ; Humans ; Lung Neoplasms/*diagnosis/pathology/therapy ; Lymphatic Metastasis ; Mesothelioma/*diagnosis/pathology/therapy ; Mesothelioma, Malignant ; *Multimodal Imaging ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/pathology/therapy ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common primary malignancy of the pleura and is associated with asbestos exposure in approximately 80% of patients. The patient prognosis is poor, with a median survival of 9-17 months after diagnosis. However, improved survival and decreased morbidity and mortality have been demonstrated when the diagnosis is made in the early stages of disease and specific treatment strategies are implemented. A staging system that focuses on the extent of primary tumor (T), lymph node involvement (N), and metastatic disease (M) has been devised by the International Mesothelioma Interest Group and emphasizes factors related to overall survival. Radiologists should recognize the manifestations of MPM across multiple imaging modalities, translate these findings into the updated staging system, and understand the effects of appropriate staging on treatment and survival. Computed tomography (CT) remains the primary imaging modality used to evaluate MPM and efficiently demonstrates the extent of primary tumor, intrathoracic lymphadenopathy, and extrathoracic spread. However, additional imaging modalities, such as magnetic resonance (MR) imaging of the thorax and positron emission tomography (PET)/CT with fluorodeoxyglucose, have emerged in recent years and are complementary to CT for disease staging and evaluation of patients with MPM. Thoracic MR imaging is particularly useful for identifying invasion of the chest wall, mediastinum, and diaphragm, and PET/CT can accurately demonstrate intrathoracic and extrathoracic lymphadenopathy and metastatic disease.}, }
@article {pmid25299403, year = {2015}, author = {Wolff, H and Vehmas, T and Oksa, P and Rantanen, J and Vainio, H}, title = {Asbestos, asbestosis, and cancer, the Helsinki criteria for diagnosis and attribution 2014: recommendations.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {41}, number = {1}, pages = {5-15}, doi = {10.5271/sjweh.3462}, pmid = {25299403}, issn = {1795-990X}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis/etiology ; Biomarkers/blood ; Female ; Finland ; Guidelines as Topic/standards ; Humans ; Male ; Mesothelioma/diagnosis/etiology ; Neoplasms/*diagnosis/etiology ; Occupational Exposure ; Pleural Diseases/diagnosis/etiology ; Pulmonary Disease, Chronic Obstructive/diagnosis/etiology ; Retroperitoneal Fibrosis/diagnosis/etiology ; }, }
@article {pmid25297446, year = {2015}, author = {Jin, S and Cao, S and Cao, J and Shen, J and Hu, J and Che, D and Zhang, J and Yu, Y}, title = {Predictive factors analysis for malignant peritoneal mesothelioma.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {19}, number = {2}, pages = {319-326}, pmid = {25297446}, issn = {1873-4626}, mesh = {Abdominal Pain/etiology ; Adult ; Age Factors ; Aged ; Antineoplastic Agents/*therapeutic use ; Combined Modality Therapy ; *Cytoreduction Surgical Procedures ; Female ; Humans ; Male ; Mesothelioma/complications/*therapy ; Middle Aged ; Peritoneal Neoplasms/complications/*therapy ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an uncommon disease with a dismal prognosis and unclear natural history. The present study aims to assess potential prognostic factors and management of MPM.<br><br>METHODS: Clinical records of 39 patients with MPM between December 2003 and April 2014 were retrospectively reviewed. Overall survival was identified with Kaplan-Meier curves and Cox regression analysis.<br><br>RESULTS: Mean age of 39 patients was 55.0 years; asbestos exposure was recorded in two patients. Main presentations were abdominal distension, abdominal pain, and weight loss. Thrombocytosis, low serum albumin level, and anemia were principal laboratory abnormalities. Ascites, peritoneal cavity mass, and peritoneum thickening were the main signs on CT scans. Cytoreductive surgery (CRS) plus adjuvant therapies were performed in 22 patients, single chemotherapy in 13, and best supportive care in 4. Median survival time was 10.0 months after pathological diagnosis, with a 6-, 12-, 18-, and 24-month survival rate of 84.4, 31.6, 18.5, and 15.8 %, respectively. Significant prognostic factors were age, performance status (PS), abdominal pain, serum albumin level, thrombocytosis, and treatment strategy on univariate analysis, while only age, abdominal pain, and treatment strategy hold statistical significance on multivariate analysis.<br><br>CONCLUSIONS: Age &#x2264;65 years, abdominal pain, and CRS plus adjuvant therapy are independent positive prognostic factors of MPM.}, }
@article {pmid25296690, year = {2014}, author = {Nemo, A and Silvestri, S}, title = {Mesothelioma in a wine cellar man: detailed description of working procedures and past asbestos exposure estimation.}, journal = {The Annals of occupational hygiene}, volume = {58}, number = {9}, pages = {1168-1174}, doi = {10.1093/annhyg/meu062}, pmid = {25296690}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/analysis/*toxicity ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/*etiology ; Regression Analysis ; Risk Assessment ; *Wine ; }, abstract = {A pleural mesothelioma arose in an employee of a wine farm whose work history shows an unusual occupational exposure to asbestos. The information, gathered directly from the case and from a work colleague, clarifies some aspects of the use of asbestos in the process of winemaking which has not been previously reported in such details. The man had worked as a winemaker from 1960 to 1988 in a farm, which in those years produced around 2500 hectoliters of wine per year, mostly white. The wine was filtered to remove impurities; the filter was created by dispersing in the wine asbestos fibers followed by diatomite while the wine was circulating several times and clogging a prefilter made of a dense stainless steel net. Chrysotile asbestos was the sole asbestos mineralogical variety used in these filters and exposure could occur during the phase of mixing dry fibers in the wine and during the filter replacement. A daily and annual time weighted average level of exposure and cumulative dose have been estimated in the absence of airborne asbestos fiber monitoring performed in that workplace. Since 1993, the Italian National Mesothelioma Register, an epidemiological surveillance system, has recorded eight cases with at least one work period spent as winemaker. Four of them never used asbestos filters and presented exposures during other work periods, the other four used asbestos filters but had also other exposures in other industrial divisions. For the information hitherto available, this is the first mesothelioma case with exclusive exposure in the job of winemaking.}, }
@article {pmid25285978, year = {2014}, author = {Banks, DE}, title = {Clinical aspects of asbestos-related diseases--what are the unresolved topics?.}, journal = {Journal of occupational and environmental medicine}, volume = {56 Suppl 10}, number = {}, pages = {S8-S12}, doi = {10.1097/JOM.0000000000000242}, pmid = {25285978}, issn = {1536-5948}, mesh = {Age Factors ; Aged ; Asbestosis/*diagnosis/mortality/*prevention &amp; control ; Cross-Cultural Comparison ; Cross-Sectional Studies ; Humans ; Life Expectancy ; Male ; Maximum Allowable Concentration ; Mesothelioma/*diagnosis/mortality/*prevention &amp; control ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; Survival Analysis ; United States ; }, abstract = {OBJECTIVE: Despite awareness of the health risks associated with asbestos fiber inhalation and the decline in U.S. utilization (about 0.1% of the yearly peak amount), illnesses associated with exposure persist. Those with disease typically describe excessive exposures in the remote past, yet excessive exposures can occur today, most likely related to careless asbestos abatement procedures. The intent is to address unanswered questions associated with asbestos exposure.<br><br>METHODS: The author summarizes clinical information addressing the case definition of asbestosis, the world-wide rate of mesothelioma, and clinical follow-up for those with exposure.<br><br>RESULTS: The author describes information relevant to issues which remain unresolved.<br><br>CONCLUSION: Perhaps somewhat surprisingly, even though there have been a great number of manuscripts reporting on the health risks of asbestos exposure, there remain unanswered questions regarding the pathogenesis of this disease.}, }
@article {pmid25268063, year = {2015}, author = {Oczypok, EA and Oury, TD}, title = {Electron microscopy remains the gold standard for the diagnosis of epithelial malignant mesothelioma: a case study.}, journal = {Ultrastructural pathology}, volume = {39}, number = {2}, pages = {153-158}, pmid = {25268063}, issn = {1521-0758}, support = {F30 ES024045/ES/NIEHS NIH HHS/United States ; T32 HL094295/HL/NHLBI NIH HHS/United States ; 1F30ES024045/ES/NIEHS NIH HHS/United States ; }, mesh = {Biopsy ; Carcinoma, Renal Cell/diagnosis/*pathology ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; *Microscopy, Electron ; Middle Aged ; Neoplasms, Glandular and Epithelial/*diagnosis/pathology ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {This is a case of idiopathic epithelial malignant mesothelioma in a 47-year-old mechanic. The advent of a large battery of immunochemical markers has provided new tools for the diagnosis of mesothelioma in recent years; however, immunostaining can often be misleading or inconsistent, as demonstrated in this case. This report highlights the lasting utility of electron microscopy in the diagnosis of mesothelioma. Ultrastructural features of epithelial mesothelioma were discernable using electron microscopy even on somewhat poorly preserved chest wall biopsy specimens from paraffin blocks. These images, combined with immunostains and a fiber analysis from the lungs, allowed for a final diagnosis of a non-asbestos-related malignant epithelial mesothelioma in this patient.}, }
@article {pmid25264933, year = {2014}, author = {Greim, H and Utell, MJ and Maxim, LD and Niebo, R}, title = {Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers.}, journal = {Inhalation toxicology}, volume = {26}, number = {13}, pages = {789-810}, pmid = {25264933}, issn = {1091-7691}, mesh = {Animals ; Carcinogens/*toxicity ; Ceramics/*toxicity ; Humans ; Inhalation Exposure/adverse effects ; Kaolin/*toxicity ; Lung Neoplasms/*chemically induced ; Mineral Fibers/*toxicity ; Rats ; }, abstract = {In 2011, SCOEL classified RCF as a secondary genotoxic carcinogen and supported a practical threshold. Inflammation was considered the predominant manifestation of RCF toxicity. Intrapleural and intraperitoneal implantation induced mesotheliomas and sarcomas in laboratory animals. Chronic nose-only inhalation bioassays indicated that RCF exposure in rats increased the incidence of lung cancer and similar exposures resulted in mesothelioma in hamsters, but these studies may have been compromised by overload. Epidemiological studies in the US and Europe showed an association between exposure and prevalence of respiratory symptoms and pleural plaques, but no interstitial fibrosis, mesotheliomas, or increased numbers of lung tumors were observed. As the latency of asbestos induced mesotheliomas can be up to 50 years, the relationship between RCF exposure and respiratory malignances has not been fully determined. Nonetheless, it is possible to offer useful perspectives. RCF and rock wool have similar airborne fiber dimensions and biopersistence. Therefore, it is likely that these fibers have similar toxicology. Traditional rock wool has been the subject of numerous cohort and case control studies. For rock wool, IARC (2002) concluded that the epidemiological studies did not provide evidence of carcinogenicity. Based on analogies with rock wool (read across), it is reasonable to believe that increases in lung cancer or any mesotheliomas are unlikely to be found in the RCF-exposed cohort. RCF producers have developed a product stewardship program to measure and control fiber concentrations and to further understand the health status of their workers.}, }
@article {pmid25262213, year = {2014}, author = {Magouliotis, DE and Tasiopoulou, VS and Molyvdas, PA and Gourgoulianis, KI and Hatzoglou, C and Zarogiannis, SG}, title = {Airways microbiota: Hidden Trojan horses in asbestos exposed individuals?.}, journal = {Medical hypotheses}, volume = {83}, number = {5}, pages = {537-540}, doi = {10.1016/j.mehy.2014.09.006}, pmid = {25262213}, issn = {1532-2777}, mesh = {Asbestos/*toxicity ; Cholesterol/chemistry ; Cytotoxins/chemistry ; Epithelial Cells/drug effects/microbiology ; Humans ; Lung/drug effects/*microbiology ; Lung Neoplasms/*microbiology/*physiopathology ; Mesothelioma/*microbiology/*physiopathology ; Mesothelioma, Malignant ; Microbiota ; Models, Biological ; Pleura/drug effects/microbiology ; Pleural Neoplasms/microbiology/physiopathology ; Prognosis ; Streptococcus intermedius ; Streptococcus mitis ; Streptococcus pneumoniae ; Streptococcus pyogenes ; }, abstract = {Malignant pleura mesothelioma (MPM) is a rare type of cancer with devastating prognosis, which develops in the pleural cavity from transformed mesothelium. MPM has been directly associated with asbestos exposure however there are aspects of the pathophysiology involved in the translocation of asbestos fibers in the pleura that remain unclear. Here, we propose and discuss that certain proteins secreted by airways symbiotic microbiota create membrane pores to the airway epithelial cells, through which asbestos fibers can penetrate the lung parenchyma and reach the sub-pleural areas. We evaluate this hypothesis using data from the published literature regarding the airways microbiota toxins such as cholesterol-dependent cytolysins (CDCs).}, }
@article {pmid25260287, year = {2014}, author = {Acton, V}, title = {Preventing pleural mesothelioma in patients with recognizable asbestos-related pleural plaques.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {148}, number = {4}, pages = {1763}, doi = {10.1016/j.jtcvs.2014.03.030}, pmid = {25260287}, issn = {1097-685X}, mesh = {Female ; Humans ; Male ; Mesothelioma/*surgery ; Pleural Neoplasms/*surgery ; *Thoracic Surgical Procedures ; }, }
@article {pmid25250196, year = {2014}, author = {Ramachandran, R and Radhan, P and Santosham, R and Rajendiran, S}, title = {A rare case of primary malignant pericardial mesothelioma.}, journal = {Journal of clinical imaging science}, volume = {4}, number = {}, pages = {47}, pmid = {25250196}, issn = {2156-7514}, abstract = {Primary malignant pericardial mesothelioma (PMPM) is a rare tumor of the pericardium. The cause of this tumor is unknown and it has a very poor prognosis. Exposure to asbestos is correlated with the onset of pleural and peritoneal mesothelioma; however, the role of asbestos in pericardial mesothelioma is unclear. Here we highlight the radiological features of this rare tumor and its correlative pathological confirmation with the help of new immunohistochemical (IHC) markers.}, }
@article {pmid25238873, year = {2014}, author = {Gunatilake, S and Brims, FJ and Fogg, C and Lawrie, I and Maskell, N and Forbes, K and Rahman, N and Morris, S and Ogollah, R and Gerry, S and Peake, M and Darlison, L and Chauhan, AJ}, title = {A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.}, journal = {Trials}, volume = {15}, number = {}, pages = {367}, pmid = {25238873}, issn = {1745-6215}, mesh = {Affect ; Caregivers/psychology ; Clinical Protocols ; Cost of Illness ; Cost-Benefit Analysis ; Health Care Costs ; Health Resources/economics/statistics &amp; numerical data ; Health Status ; Humans ; Lung Neoplasms/complications/diagnosis/economics/mortality/psychology/*therapy ; Mesothelioma/complications/diagnosis/economics/mortality/psychology/*therapy ; Mesothelioma, Malignant ; Palliative Care/economics/*methods ; Pleural Neoplasms/complications/diagnosis/economics/mortality/psychology/*therapy ; *Quality of Life ; *Referral and Consultation/economics ; *Research Design ; Surveys and Questionnaires ; Time Factors ; Treatment Outcome ; United Kingdom ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma.<br><br>METHODS: This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost.<br><br>DISCUSSION: Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally.<br><br>TRIAL REGISTRATION: Current controlled trials ISRCTN18955704. Date ISRCTN assigned: 31 January 2014.}, }
@article {pmid25231672, year = {2015}, author = {Ortega-Guerrero, MA and Carrasco-Núñez, G and Barragán-Campos, H and Ortega, MR}, title = {High incidence of lung cancer and malignant mesothelioma linked to erionite fibre exposure in a rural community in Central Mexico.}, journal = {Occupational and environmental medicine}, volume = {72}, number = {3}, pages = {216-218}, doi = {10.1136/oemed-2013-101957}, pmid = {25231672}, issn = {1470-7926}, mesh = {Adult ; Carcinogens/*analysis/toxicity ; Environmental Exposure/adverse effects/*analysis ; Environmental Pollutants/*analysis/toxicity ; Female ; Humans ; Incidence ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Mexico/epidemiology ; Middle Aged ; Retrospective Studies ; Rural Population/*statistics &amp; numerical data ; Soil Pollutants/adverse effects/analysis ; Zeolites/*analysis/toxicity ; }, abstract = {OBJECTIVE: To report the high incidence of lung cancer (LC) and malignant mesothelioma (MM) linked to environmental exposure to erionite fibres in a rural village of central Mexico.<br><br>METHODS: This is a retrospective survey of clinical and mortality records from the years 2000-2012, accompanied by an environmental survey for nine Group-1 lung and pleura carcinogenic agents listed by the International Agency for Research on Cancer (IARC).<br><br>RESULTS: Out of a total of 45 deaths between 2000 and 2012, 14 deaths correspond to different neoplasms of the lung, and at least four deaths to MM. The ages at diagnosis of MM were between 30 and 54&#x2005;years. Annual age-standardised mortality rates per thousand due to LC and MM in the village (age >20&#x2005;years) are 7.09 and 2.48 for males, and 4.75 and 1.05 for females, respectively. Erionite fibres were found in exposed rocks and soils, which can easily become airborne and be carried into streets and recreational areas near schools and homes. Other carcinogenic elements and minerals are found only in trace amounts, except for quartz dust and asbestos (chrysotile) cement sheeting, which are also present in the neighbouring villages.<br><br>CONCLUSIONS: These results indicate that environmental exposure to erionite is the main cause of the high rates of MM mortality in the Village of Tierra Blanca, supporting previous similar reports for people exposed to erionite fibres in villages in Turkey.}, }
@article {pmid25231345, year = {2015}, author = {Betti, M and Casalone, E and Ferrante, D and Romanelli, A and Grosso, F and Guarrera, S and Righi, L and Vatrano, S and Pelosi, G and Libener, R and Mirabelli, D and Boldorini, R and Casadio, C and Papotti, M and Matullo, G and Magnani, C and Dianzani, I}, title = {Inference on germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area.}, journal = {Genes, chromosomes &amp; cancer}, volume = {54}, number = {1}, pages = {51-62}, doi = {10.1002/gcc.22218}, pmid = {25231345}, issn = {1098-2264}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure/*adverse effects ; Environmental Pollutants/*toxicity ; Female ; *Germ-Line Mutation ; Humans ; Lung Neoplasms/chemically induced/*genetics ; Male ; Mesothelioma/chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Risk Factors ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Inherited loss-of-function mutations in the BAP1 oncosuppressor gene are responsible for an inherited syndrome with predisposition to malignant mesothelioma (MM), uveal and keratinocytic melanoma, and other malignancies. Germline mutations that were inherited in an autosomal dominant fashion were identified in nine families with multiplex MM cases and 25 families with multiple melanoma, renal cell carcinoma, and other tumors. Germline mutations were also identified in sporadic MM cases, suggesting that germline mutations in BAP1 occur frequently. In this article, we report the analysis of BAP1 in five multiplex MM families and in 103 sporadic cases of MM. One family carried a new truncating germline mutation. Using immunohistochemistry, we show that BAP1 is not expressed in tumor tissue, which is in accordance with Knudson's two hits hypothesis. Interestingly, whereas the three individuals who were possibly exposed to asbestos developed MM, the individual who was not exposed developed a different tumor type, that is, mucoepidermoid carcinoma. This finding suggests that the type of carcinogen exposure may be important for the cancer type that is developed by mutation carriers. On the contrary, the other families or the 103 sporadic patients did not show germline mutations in BAP1. Our data show that BAP1 mutations are very rare in patients with sporadic MM, and we report a new BAP1 mutation, extend the cancer types associated with these mutations, and suggest the existence of other yet unknown genes in the pathogenesis of familial MM.}, }
@article {pmid25217189, year = {2014}, author = {Mansfield, AS and Symanowski, JT and Peikert, T}, title = {Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {86}, number = {2}, pages = {133-136}, pmid = {25217189}, issn = {1872-8332}, support = {K23 CA159391/CA/NCI NIH HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; Treatment Outcome ; }, abstract = {RATIONALE: Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes.<br><br>OBJECTIVES: Our objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials.<br><br>METHODS: We searched PubMed for "mesothelioma" with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors.<br><br>MEASUREMENTS AND MAIN RESULTS: We reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n=137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review.<br><br>CONCLUSION: Response rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete responses to systemic therapies appear to be less common among patients with sarcomatoid tumors.}, }
@article {pmid25210967, year = {2014}, author = {Assis, LV and Isoldi, MC}, title = {Overview of the biochemical and genetic processes in malignant mesothelioma.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {40}, number = {4}, pages = {429-442}, pmid = {25210967}, issn = {1806-3756}, mesh = {Carcinogenesis ; Humans ; Lung Neoplasms/*genetics/*metabolism ; Mesothelioma/*genetics/*metabolism ; Mesothelioma, Malignant ; Oncogenes ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and with other factors, such as erionite and simian virus 40 [corrected]. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.}, }
@article {pmid25208984, year = {2014}, author = {Lao, I and Chen, Q and Yu, L and Wang, J}, title = {[Sarcomatoid malignant mesothelioma: a clinicopathologic and immunohistochemical analysis of 22 cases].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {6}, pages = {364-369}, pmid = {25208984}, issn = {0529-5807}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Carcinoma/diagnosis/pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Prognosis ; Sarcoma/diagnosis/pathology ; Solitary Fibrous Tumors/diagnosis/pathology ; }, abstract = {OBJECTIVE: To elaborate on the clinical and pathologic features of sarcomatoid malignant mesothelioma (SMM), its diagnostic criteria and differential diagnoses.<br><br>METHODS: Twenty-two cases of SMM retrieved from in-house and consultation files (between January 2009 to September 2013) were reviewed with emphasis on the clinicopathologic characteristics, immunophenotypes and the prognostic impact.<br><br>RESULTS: The mean age of the patients was 54 years (ranged from 24-73 years). There was no sexual predilection and the majority of the patients did not have history of asbestos exposure. Overall, 14 tumors developed in the pleura and 8 cases arose from the peritoneal cavity. Clinically, patients presented signs and symptoms in accord with the location of the tumors, notably coughing, shortness of breath, and chest pain for patients with pleural origin, and nausea, abdominal distention and abdominal pain for those with peritoneal primary. In most cases, CT and MRI scan demonstrated lobulated masses (8/11). However, diffuse infiltrative growth patterns were observed exclusively in a minority of pleural cases (3/11). No visceral lesion was observed in any case. Histologically, 19 cases had either fibrosarcomatous or undifferentiated pleomorphic sarcoma-like appearance. Two cases were consistent with desmoplastic mesothelioma. One case contained osteosarcomatous element. All cases expressed pan-cytokeratin (AE1/AE3), and most cases were also positive for D2-40 (15/20). The staining of calretinin (9/21) and WT1 (10/14) was generally weak and focal. They were all negative for TTF-1, napsin A, SP-A, p63 and CD34. Follow-up information (range from 1 to 36 months) was available in 11 cases, 6 of which were alive with unresectable tumor, 1 patient with recurrent disease and 4 patients succumbed to disease. The overall survival was 5 months (mean 8 months).<br><br>CONCLUSIONS: The diagnosis of SMM is achieved by comprehensive evaluation of medical history, imageological and pathological findings. Since calretinin immunoreactivity is infrequently observed in SMM, application of pan-cytokeratin and D2-40 immunostains offers a reasonable alternative for diagnosis. Diagnosis of SMM can be made by excluding a variety of spindle cell neoplasms with overlapping features, such as sarcomatoid carcinoma, synovial sarcoma, solitary fibrous tumor and fibrous pleuritis.}, }
@article {pmid25200195, year = {2014}, author = {Girardi, P and Bressan, V and Merler, E}, title = {Past trends and future prediction of mesothelioma incidence in an industrialized area of Italy, the Veneto Region.}, journal = {Cancer epidemiology}, volume = {38}, number = {5}, pages = {496-503}, doi = {10.1016/j.canep.2014.08.007}, pmid = {25200195}, issn = {1877-783X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Bayes Theorem ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Sex Distribution ; }, abstract = {BACKGROUND: Malignant Mesothelioma (MM) is so associated with (professional, familial or environmental) asbestos exposure that trends in incidence and mortality parallel, after 30-40 years, the trend in asbestos consumption. In recent decades, the industrialized countries have witnessed a steady growth of pleural MM (MPM), following a stabilization or decline in rates in the countries that first adopted restrictive policies. The aim of this study was to evaluate the temporal variations of pleural MM incidence in the Veneto Region of Italy in the period 1987-2010.<br><br>METHODS: We included only MPM with histological or cytological diagnosis. Age-Period-Cohort (APC) models were used to assess the trend in the incidence of MPM in both genders. Future predictions were evaluated by using a Bayesian APC model.<br><br>RESULTS: In the period 1987-2010, 1600 MPMs have occurred. We observe a positive trend in the incidence in the whole period considered. The APC model showed that in both genders the cohort at higher risk is the one born between the years 1940-1945. Future projections indicate that the trend will decrease after the incidence peak of 2010; yet 1234 men are expected to develop a mesothelioma between 2011 and 2026. Among women, the future MPM rates will be stable or slightly decreasing.<br><br>CONCLUSIONS: The asbestos ban introduced in Italy in the year 1992 as a prospective result will certainly determine a decreasing incidence. However, the extremely long latency of MPM means that its influence is not yet observable.}, }
@article {pmid25188816, year = {2014}, author = {Schelch, K and Hoda, MA and Klikovits, T and Münzker, J and Ghanim, B and Wagner, C and Garay, T and Laszlo, V and Setinek, U and Dome, B and Filipits, M and Pirker, C and Heffeter, P and Selzer, E and Tovari, J and Torok, S and Kenessey, I and Holzmann, K and Grasl-Kraupp, B and Marian, B and Klepetko, W and Berger, W and Hegedus, B and Grusch, M}, title = {Fibroblast growth factor receptor inhibition is active against mesothelioma and synergizes with radio- and chemotherapy.}, journal = {American journal of respiratory and critical care medicine}, volume = {190}, number = {7}, pages = {763-772}, doi = {10.1164/rccm.201404-0658OC}, pmid = {25188816}, issn = {1535-4970}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Cell Survival/drug effects/genetics ; Cisplatin/pharmacology ; Combined Modality Therapy/methods ; Disease Models, Animal ; Humans ; Lung Neoplasms/*drug therapy/genetics/*radiotherapy ; Mesothelioma/*drug therapy/genetics/*radiotherapy ; Mesothelioma, Malignant ; Mice ; Protein Kinase Inhibitors/*pharmacology ; Receptor, Fibroblast Growth Factor, Type 1/*antagonists &amp; inhibitors/drug effects/genetics ; Signal Transduction/drug effects/genetics ; }, abstract = {RATIONALE: Malignant pleural mesothelioma is an aggressive malignancy characterized by frequent resistance to chemo- and radiotherapy, poor outcome, and limited therapeutic options. Fibroblast growth factors (FGFs) and their receptors are potential targets for cancer therapy, but their significance in mesothelioma has remained largely undefined.<br><br>OBJECTIVES: To investigate the antimesothelioma potential of FGF receptor 1 (FGFR1) inhibition.<br><br>METHODS: Expression of FGFs and their receptors was analyzed in mesothelioma cell lines and tissue specimens. Several cell models were used to investigate FGFR1 inhibition in vitro and in combination with cisplatin and irradiation. Mouse intraperitoneal xenotransplant models were used for in vivo validation.<br><br>MEASUREMENTS AND MAIN RESULTS: FGFR1, FGF2, and FGF18 were overexpressed in mesothelioma. Stimulation with FGF2 led to increased cell proliferation, migration, and transition to a more sarcomatoid phenotype in subsets of mesothelioma cell lines. In contrast, inhibition of FGFR1 by a specific kinase inhibitor or a dominant-negative FGFR1 construct led to significantly decreased proliferation, clonogenicity, migration, spheroid formation, and G1 cell cycle arrest in several mesothelioma cell lines, accompanied by apoptosis induction and decreased mitogen-activated protein kinase pathway activity. Reduced tumor growth, proliferation, mitogenic signaling, and apoptosis induction were observed in vivo. Inhibition of FGFR1 synergistically enhanced the cytotoxic effects of ionizing radiation and cisplatin.<br><br>CONCLUSIONS: Our data suggest that the malignant phenotype of mesothelioma cells depends on intact FGF signals, which should be considered as therapeutic targets with a promising chemo- and radiosensitizing potential.}, }
@article {pmid25188323, year = {2014}, author = {Linton, A and Pavlakis, N and O'Connell, R and Soeberg, M and Kao, S and Clarke, S and Vardy, J and van Zandwijk, N}, title = {Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales.}, journal = {British journal of cancer}, volume = {111}, number = {9}, pages = {1860-1869}, pmid = {25188323}, issn = {1532-1827}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*mortality/pathology/therapy ; Lymphocytes/pathology ; Male ; Mesothelioma/*mortality/pathology/therapy ; Mesothelioma, Malignant ; Neoplasm Staging ; Neutrophils/pathology ; New South Wales ; Pleural Neoplasms/*mortality/pathology/therapy ; Pneumonectomy/*mortality ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series.<br><br>METHODS: All patients registered with the NSW Dust Diseases Board (2002-2009) were included in an analysis of prognostic factors using Kaplan-Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)).<br><br>RESULTS: We identified 910 patients: 90% male; histology (epithelioid 60%; biphasic 13%; sarcomatoid 17%); stage (Tx-I-II 48%; III-IV 52%); and calretinin expression (91%).<br><br>TREATMENT: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil-lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC).<br><br>CONCLUSIONS: We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.}, }
@article {pmid25186542, year = {2014}, author = {Langhoff, MD and Kragh-Thomsen, MB and Stanislaus, S and Weinreich, UM}, title = {Almost half of women with malignant mesothelioma were exposed to asbestos at home through their husbands or sons.}, journal = {Danish medical journal}, volume = {61}, number = {9}, pages = {A4902}, pmid = {25186542}, issn = {2245-1919}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Denmark/epidemiology ; Environmental Exposure/*adverse effects/statistics &amp; numerical data ; Environmental Pollutants/*toxicity ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/diagnosis/epidemiology/*etiology/mortality ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects/statistics &amp; numerical data ; Pleural Neoplasms/diagnosis/epidemiology/*etiology/mortality ; Retrospective Studies ; Spouses ; Survival Rate ; }, abstract = {INTRODUCTION: Women often develop malignant mesothelioma (MM) without occupational asbestos exposure. Northern Jutland has a high prevalence of MM due to previously high occupational exposures to asbestos. The aim of this study was to elucidate a possible domestic exposure to asbestos through first-degree relatives in women who develop MM.<br><br>MATERIAL AND METHODS: This was a retrospective study in women with MM of the pleura. A total of 30 women were diagnosed with and treated for MM in Northern Jutland from 1996 to 2012. In all, 24 women were included. Demographic data, subtype of MM, time from first hospital contact to diagnosis, survival and information on occupational and domestic exposure to asbestos were obtained from hospital records.<br><br>RESULTS: A total of 12.5% of the study population were primarily exposed to asbestos. 46% had domestic exposure to asbestos through their husbands or sons. The median age of the study population was 66.5 years. In all, 75% suffered from the epitheloid subtype, 12.5% from the biphasic and 8.4% from the sarcomatoid subtype. Time from first hospital contact to diagnosis was one month and the median survival time was 12 months. The 1- and 5- year-survival were 58% and 0%, respectively.<br><br>CONCLUSION: Nearly 50% of the women affected by MM have been domestically exposed to asbestos through first-degree relatives.<br><br>FUNDING: not relevant.<br><br>TRIAL REGISTRATION: not relevant.}, }
@article {pmid25185462, year = {2014}, author = {Gordon, RE and Fitzgerald, S and Millette, J}, title = {Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women.}, journal = {International journal of occupational and environmental health}, volume = {20}, number = {4}, pages = {318-332}, pmid = {25185462}, issn = {2049-3967}, mesh = {Asbestos/analysis/*toxicity ; Cosmetics/*toxicity ; Female ; Humans ; Inhalation Exposure/adverse effects ; Mesothelioma/*chemically induced ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Pleural Neoplasms/chemically induced ; Talc/chemistry/*toxicity ; }, abstract = {BACKGROUND: Cosmetic talcum powder products have been used for decades. The inhalation of talc may cause lung fibrosis in the form of granulomatose nodules called talcosis. Exposure to talc has also been suggested as a causative factor in the development of ovarian carcinomas, gynecological tumors, and mesothelioma.<br><br>PURPOSE: To investigate one historic brand of cosmetic talcum powder associated with mesothelioma in women.<br><br>METHODS: Transmission electron microscope (TEM) formvar-coated grids were prepared with concentrations of one brand of talcum powder directly, on filters, from air collections on filters in glovebox and simulated bathroom exposures and human fiber burden analyses. The grids were analyzed on an analytic TEM using energy-dispersive spectrometer (EDS) and selected-area electron diffraction (SAED) to determine asbestos fiber number and type.<br><br>RESULTS: This brand of talcum powder contained asbestos and the application of talcum powder released inhalable asbestos fibers. Lung and lymph node tissues removed at autopsy revealed pleural mesothelioma. Digestions of the tissues were found to contain anthophyllite and tremolite asbestos.<br><br>DISCUSSION: Through many applications of this particular brand of talcum powder, the deceased inhaled asbestos fibers, which then accumulated in her lungs and likely caused or contributed to her mesothelioma as well as other women with the same scenario.}, }
@article {pmid25175318, year = {2014}, author = {Robinson, C and Alfonso, H and Woo, S and Olsen, N and Bill Musk, AW and Robinson, BW and Nowak, AK and Lake, RA}, title = {Effect of NSAIDS and COX-2 inhibitors on the incidence and severity of asbestos-induced malignant mesothelioma: evidence from an animal model and a human cohort.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {86}, number = {1}, pages = {29-34}, doi = {10.1016/j.lungcan.2014.08.005}, pmid = {25175318}, issn = {1872-8332}, mesh = {Aged ; Animals ; *Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Asbestos/*adverse effects ; Aspirin/therapeutic use ; Chemoprevention ; Cohort Studies ; *Cyclooxygenase 2 Inhibitors/therapeutic use ; Disease Models, Animal ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/drug therapy/*epidemiology/prevention &amp; control ; Male ; Mesothelioma/*chemically induced/drug therapy/*epidemiology/prevention &amp; control ; Mesothelioma, Malignant ; Mice ; Mice, Transgenic ; Middle Aged ; Risk Factors ; Severity of Illness Index ; Survival Analysis ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors have been associated with lower incidence rates of some cancers. Because asbestos can cause chronic inflammation at the pleural and peritoneal surfaces we hypothesised that NSAID and COX-2 inhibitors would inhibit the development of asbestos-induced mesothelioma.<br><br>MATERIALS AND METHODS: A murine model of asbestos-induced mesothelioma was used to test this hypothesis by providing the NSAID, aspirin, daily in the feed at 50mg/kg or 250 mg/kg. In a parallel study, the relationship between the use of NSAID and COX-2 inhibitors and mesothelioma was investigated in a human cohort of 1738 asbestos exposed people living or working in Wittenoom, Western Australia (a crocidolite mine site).<br><br>RESULTS: Aspirin did not alter the rate of disease development or increase the length of time that mice survived. Aspirin had a small but significant effect on disease latency (the time between asbestos exposure and first evidence of disease; p<0.05) but disease progression was not affected by the continued presence of the drug. In the Wittenoom cohort, individuals who reported use of NSAIDs, COX-2 inhibitors or both did not have a lower incidence of mesothelioma (HR=0.85; 95% CI=0.53-1.37, p=0.50), (HR=0.69; 95% CI=0.21-2.30, p=0.55) and (HR=0.43; 95% CI=0.16-1.13, p=0.087) respectively.<br><br>CONCLUSION: We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this result is confirmed in an autochthonous mouse model.}, }
@article {pmid25175133, year = {2014}, author = {Kanbay, A and Ozer Simsek, Z and Tutar, N and Yılmaz, I and Buyukoglan, H and Canoz, O and Demir, R}, title = {Non-asbestos-related malignant pleural mesothelioma.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {53}, number = {17}, pages = {1977-1979}, doi = {10.2169/internalmedicine.53.0900}, pmid = {25175133}, issn = {1349-7235}, mesh = {Asbestos ; Biopsy ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/surgery ; Male ; Mesothelioma/*diagnosis/surgery ; Mesothelioma, Malignant ; Neoplasm Grading ; Pleura/pathology ; Pleural Neoplasms/*diagnosis/surgery ; Radiography, Thoracic ; Thoracic Surgery, Video-Assisted/methods ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon tumor derived from mesothelial lining cells. MPM has been described as an insidious neoplasm because of its long latency period. The tumor is typically found in patients several decades after asbestos exposure. We herein describe a 26-year-old patient with MPM who presented with pleural effusion. The patient had not been exposed to asbestos or erionite. There are few case reports of non-asbestos-related MPM in young patients. We report this case to remind physicians to consider MPM in the differential diagnosis of pleural effusion in young patients without exposure to asbestos or erionitis.}, }
@article {pmid25169088, year = {2014}, author = {Ma, Q and Cao, C and Hong, X}, title = {[Diagnosis and analysis of asbestos induced peritoneal mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {32}, number = {5}, pages = {347}, pmid = {25169088}, issn = {1001-9391}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/chemically induced/*diagnosis ; Peritoneal Neoplasms/chemically induced/*diagnosis ; }, }
@article {pmid25168068, year = {2014}, author = {Lippmann, M}, title = {Toxicological and epidemiological studies on effects of airborne fibers: coherence and public [corrected] health implications.}, journal = {Critical reviews in toxicology}, volume = {44}, number = {8}, pages = {643-695}, doi = {10.3109/10408444.2014.928266}, pmid = {25168068}, issn = {1547-6898}, support = {ES 00260/ES/NIEHS NIH HHS/United States ; }, mesh = {Air Pollutants/chemistry/pharmacokinetics/*toxicity ; Animals ; Asbestos, Serpentine/chemistry/toxicity ; Epidemiologic Studies ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Particulate Matter/pharmacokinetics/*toxicity ; Public Health ; Pulmonary Fibrosis/chemically induced/epidemiology ; Risk Assessment ; Solubility ; }, abstract = {Airborne fibers, when sufficiently biopersistent, can cause chronic pleural diseases, as well as excess pulmonary fibrosis and lung cancers. Mesothelioma and pleural plaques are caused by biopersistent fibers thinner than ∼0.1 μm and longer than ∼5 μm. Excess lung cancer and pulmonary fibrosis are caused by biopersistent fibers that are longer than ∼20 μm. While biopersistence varies with fiber type, all amphibole and erionite fibers are sufficiently biopersistent to cause pathogenic effects, while the greater in vivo solubility of chrysotile fibers makes them somewhat less causal for the lung diseases, and much less causal for the pleural diseases. Most synthetic vitreous fibers are more soluble in vivo than chrysotile, and pose little, if any, health pulmonary or pleural health risk, but some specialty SVFs were sufficiently biopersistent to cause pathogenic effects in animal studies. My conclusions are based on the following: 1) epidemiologic studies that specified the origin of the fibers by type, and especially those that identified their fiber length and diameter distributions; 2) laboratory-based toxicologic studies involving fiber size characterization and/or dissolution rates and long-term observation of biological responses; and 3) the largely coherent findings of the epidemiology and the toxicology. The strong dependence of effects on fiber diameter, length, and biopersistence makes reliable routine quantitative exposure and risk assessment impractical in some cases, since it would require transmission electronic microscopic examination, of representative membrane filter samples, for determining statistically sufficient numbers of fibers longer than 5 and 20 μm, and those thinner than 0.1 μm, based on the fiber types.}, }
@article {pmid25166502, year = {2014}, author = {Frassy, F and Candiani, G and Rusmini, M and Maianti, P and Marchesi, A and Rota Nodari, F and Dalla Via, G and Albonico, C and Gianinetto, M}, title = {Mapping asbestos-cement roofing with hyperspectral remote sensing over a large mountain region of the Italian Western Alps.}, journal = {Sensors (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {15900-15913}, pmid = {25166502}, issn = {1424-8220}, mesh = {Adhesives/*analysis ; Aircraft/*instrumentation ; Altitude ; Asbestos/*analysis ; Construction Materials/*analysis ; Environmental Monitoring/*instrumentation ; Equipment Design ; Equipment Failure Analysis ; *Geographic Mapping ; Italy ; Remote Sensing Technology/*instrumentation ; }, abstract = {The World Health Organization estimates that 100 thousand people in the world die every year from asbestos-related cancers and more than 300 thousand European citizens are expected to die from asbestos-related mesothelioma by 2030. Both the European and the Italian legislations have banned the manufacture, importation, processing and distribution in commerce of asbestos-containing products and have recommended action plans for the safe removal of asbestos from public and private buildings. This paper describes the quantitative mapping of asbestos-cement covers over a large mountainous region of Italian Western Alps using the Multispectral Infrared and Visible Imaging Spectrometer sensor. A very large data set made up of 61 airborne transect strips covering 3263 km2 were processed to support the identification of buildings with asbestos-cement roofing, promoted by the Valle d'Aosta Autonomous Region with the support of the Regional Environmental Protection Agency. Results showed an overall mapping accuracy of 80%, in terms of asbestos-cement surface detected. The influence of topography on the classification's accuracy suggested that even in high relief landscapes, the spatial resolution of data is the major source of errors and the smaller asbestos-cement covers were not detected or misclassified.}, }
@article {pmid25162674, year = {2014}, author = {Comar, M and Zanotta, N and Bonotti, A and Tognon, M and Negro, C and Cristaudo, A and Bovenzi, M}, title = {Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e104848}, pmid = {25162674}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Biomarkers, Tumor/blood/*genetics ; Case-Control Studies ; Chemokine CCL5/blood/*genetics ; Cytokines/blood/genetics ; *Endemic Diseases ; Gene Expression ; Gene Expression Profiling ; Humans ; Lung Neoplasms/blood/diagnosis/etiology/*genetics ; Mesothelioma/blood/diagnosis/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Simian virus 40/genetics ; Viral Proteins/blood/*genetics ; }, abstract = {BACKGROUND: Asbestos-induced mesothelial inflammatory processes are thought to be the basic mechanisms underlying Malignant Mesothelioma (MM) development. Detection of MM often occurs at late stage due to the long and unpredictable latent period and the low incidence in asbestos exposed individuals. The aim of this study was to investigate early immunological biomarkers to characterize the prognostic profile of a possible asbestos-induced disease, in subjects from a MM hyperendemic area.<br><br>METHODS: The Luminex Multiplex Panel Technology was used for the simultaneous measurement of serum levels of a large panel of 47 analytes, including cytokines and growth factors, from workers previously exposed to asbestos (Asb-workers), asbestos-induced MM patients and healthy subjects. In addition, to explore the influence on serum cytokines profile exerted by SV40 infection, a cofactor in MM development, a quantitative real time PCR was performed for sequences detection in the N-terminal and intronic regions of the SV40 Tag gene. Statistical analysis was done by means of the Mann-Whitney test and the Kruskall-Wallis test for variance analysis.<br><br>RESULTS: A variety of 25 cytokines linked to pulmonary inflammation and tumor development were found significantly associated with Asb-workers and MM patients compared with healthy controls. A specific pattern of cytokines were found highly expressed in Asb-workers: IFN-alpha (p<0.05), EOTAXIN (p<0.01), RANTES (p<0.001), and in MM patients: IL-12(p40), IL-3, IL-1 alpha, MCP-3, beta-NGF, TNF-beta, RANTES (p<0.001). Notably, the chemokine RANTES measured the highest serum level showing an increased gradient of concentration from healthy subjects to Asb-workers and MM patients (p<0.001), independently of SV40 infection.<br><br>CONCLUSION: This study shows that, in subjects from an hyperendemic area for MM, the C-C chemokine RANTES is associated with the exposure to asbestos fibres. If validated in larger samples, this factor could have the potential to be a critical biomarker for MM prognosis as recently reported for breast tumor.}, }
@article {pmid25161804, year = {2014}, author = {Singhal, B and Kohli, S and Singhal, A and Kumar, V}, title = {Malignant pleural and peritoneal mesothelioma consequential to brief indirect asbestos exposure.}, journal = {Journal of clinical imaging science}, volume = {4}, number = {}, pages = {35}, pmid = {25161804}, issn = {2156-7514}, abstract = {This report highlights that pleural and peritoneal mesothelioma can occur without direct asbestos exposure as was seen in our young patient. The patient had indirect exposure for as short as 3 months as a child, 15 years earlier, when she was residing with her miner father in the district of Jharia, Jharkhand, which is an asbestos-rich mining area in eastern India. The patient presented with chest pain and breathlessness. Chest X-ray showed opaque right hemithorax. Typical contrast- computed tomography (CECT) enhanced radiological features included nodular, soft-tissue attenuation and homogenously enhancing rind-like mass causing scalloping of the underlying lung and liver. Similar lesions were also found involving the pelvis. Diagnosis of malignant mesothelioma was confirmed on lung biopsy. Under-reporting of exposure is usual because it is unrecognized by both patients and investigators.}, }
@article {pmid25135741, year = {2014}, author = {Lee, S and Matsuzaki, H and Kumagai-Takei, N and Yoshitome, K and Maeda, M and Chen, Y and Kusaka, M and Urakami, K and Hayashi, H and Fujimoto, W and Nishimura, Y and Otsuki, T}, title = {Silica exposure and altered regulation of autoimmunity.}, journal = {Environmental health and preventive medicine}, volume = {19}, number = {5}, pages = {322-329}, pmid = {25135741}, issn = {1347-4715}, mesh = {Autoimmunity/*drug effects ; *Construction Industry ; Humans ; Japan ; Lymphocytes/drug effects/immunology ; *Occupational Exposure ; Silicon Dioxide/*toxicity ; Silicosis/blood/etiology/*immunology ; }, abstract = {Silica particles and asbestos fibers, which are known as typical causatives of pneumoconiosis, induce lung fibrosis. Moreover, silicosis patients often complicate with autoimmune diseases, and asbestos-exposed patients suffer from malignant diseases such as pleural mesothelioma and lung cancer. We have been conducting experimental studies to investigate altered regulation of self-tolerance caused by silica exposure, including analyses using specimens such as plasma and immunocompetent cells obtained from silicosis patients, as a means of examining the supposition that silica exposure induces molecular and cellular biological alterations of immune cells. These approaches have resulted in the detection of several specific autoantibodies, alterations of CD95/Fas and its related molecules, and evidence of chronic activation of responder T cells and regulatory T cells following silica exposure. In this review, we present details of our investigations as an introduction to scientific approaches examining the immunological effects of environmental and occupational substances.}, }
@article {pmid25134629, year = {2014}, author = {Mastrangelo, G and Fadda, E and Comiati, V and Dell'Aquila, M and Zamprogno, E and Fedeli, U and Bellini, E}, title = {A rare occupation causing mesothelioma: mechanisms and differential etiology.}, journal = {La Medicina del lavoro}, volume = {105}, number = {5}, pages = {337-345}, pmid = {25134629}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; *Carcinogens ; Fatal Outcome ; Humans ; Italy ; Lung Neoplasms/*etiology ; Maintenance ; Male ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; *Railroads ; Risk Assessment ; }, abstract = {BACKGROUND: In a mesothelioma lawsuit, the Public Prosecutor commissioned an expert evidence on the legal accountability for the disease, because the patient experienced multiple exposures to asbestos in both occupational and environmental settings.<br><br>OBJECTIVES: To collect information on asbestos exposure from all available sources and to quantify the contribution of each source of exposure as a percentage of the total risk.<br><br>METHODS: We retrieved information on jobs done and asbestos exposure from a work colleague and a database maintained by the National Institute for Insurance of Occupational Accidents/Diseases, respectively. Information on environmental exposure was searched through the scientific literature. The contribution of each source of exposure was quantified with a method of risk apportionment, taking into account time elapsed since first and last exposure, intensity and frequency of exposure and carcinogenic potency of asbestos fiber mix.<br><br>RESULTS: The subject worked in the maintenance of railway electrification system. The mechanical compression stress induced on the ballast during passage of trains released chrysotile (from fragmented stones) and crocidolite (through abrasive action of crushed gravel on the underbody of rolling stocks insulated with friable crocidolite). Despite the low cumulative exposure (about 2 ff&#xd7;years/cc), 99% of the mesothelioma risk was attributable to the work done because of the high content of crocidolite of inhaled asbestos.<br><br>CONCLUSIONS: The report of an uncommon source of occupational asbestos exposure and a scientifically based method to allocate mesothelioma risk among multiple exposure could help to recognize mesothelioma as occupational disease in the workers employed in maintenance of the railway electrification system under the Italian National Railways.}, }
@article {pmid25132032, year = {2014}, author = {Yagi, Y and Maeda, T and Yoshimitsu, Y and Sakuma, H}, title = {[A case of malignant peritoneal mesothelioma diagnosed with laparoscopic biopsy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {41}, number = {8}, pages = {995-997}, pmid = {25132032}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Ascites/etiology ; Biopsy ; Carboplatin/administration &amp; dosage ; Female ; Glutamates/administration &amp; dosage ; Guanine/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Laparoscopy ; Lung Neoplasms/complications/drug therapy/*pathology ; Mesothelioma/complications/drug therapy/*pathology ; Mesothelioma, Malignant ; Pemetrexed ; Peritoneal Neoplasms/complications/drug therapy/*pathology ; }, abstract = {A 66-year-old woman was admitted to our hospital for massive ascites of unknown origin. Peritoneal mesothelioma was suspected because of her history of asbestos exposure. Diagnostic laparoscopy with biopsy of the peritoneum and greater omentum was performed. Pathological examination with immunostaining provided a definite diagnosis of malignant peritoneal mesothelioma. The patient underwent early postoperative induction therapy with pemetrexed and carboplatin, which resulted in a reduction in ascites. Laparoscopic biopsy contributed to the definite diagnosis of malignant peritoneal mesothelioma, and thereby, early induction of chemotherapy.}, }
@article {pmid25130001, year = {2014}, author = {Aierken, D and Okazaki, Y and Chew, SH and Sakai, A and Wang, Y and Nagai, H and Misawa, N and Kohyama, N and Toyokuni, S}, title = {Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis.}, journal = {Nagoya journal of medical science}, volume = {76}, number = {1-2}, pages = {149-160}, pmid = {25130001}, issn = {0027-7622}, mesh = {Animals ; Asbestos, Amphibole/chemistry/*toxicity ; Carcinogenicity Tests ; Cell Transformation, Neoplastic/*chemically induced/pathology ; Female ; Lung Neoplasms/*chemically induced/pathology/prevention &amp; control ; Male ; Mesothelioma/*chemically induced/pathology/prevention &amp; control ; Mesothelioma, Malignant ; Nitrilotriacetic Acid/toxicity ; Particle Size ; Rats ; Rats, Inbred BN ; Rats, Inbred F344 ; Risk Assessment ; Risk Factors ; Sex Factors ; Time Factors ; }, abstract = {Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma (MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown-Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data.}, }
@article {pmid25120691, year = {2014}, author = {Ohnishi, Y and Sugitatsu, M and Watanabe, M and Fujii, T and Kakudo, K}, title = {Metastasis of mesothelioma to the maxillary gingiva.}, journal = {Oncology letters}, volume = {8}, number = {3}, pages = {1214-1216}, pmid = {25120691}, issn = {1792-1074}, abstract = {Malignant mesothelioma predominantly arises from the serosal surfaces of the pleural or peritoneal cavity. There is currently no effective standard treatment for mesothelioma and the prognosis for patients is poor; the majority of patients with malignant mesothelioma succumb between 12 and 17 months following diagnosis. The association of all forms of malignant mesothelioma with asbestos exposure has been well documented. However, metastasis to the oral gingiva is rare, as only four cases have previously been reported; two cases of metastasis to the tongue and four cases to the jaw bone. In the current report, the case of a 62-year-old male with metastatic mesothelioma is presented. To the best of our knowledge, this is the first report regarding the metastasis of this type of neoplasm to the maxillary gingiva.}, }
@article {pmid25111229, year = {2014}, author = {Westbom, CM and Shukla, A and MacPherson, MB and Yasewicz, EC and Miller, JM and Beuschel, SL and Steele, C and Pass, HI and Vacek, PM and Shukla, A}, title = {CREB-induced inflammation is important for malignant mesothelioma growth.}, journal = {The American journal of pathology}, volume = {184}, number = {10}, pages = {2816-2827}, pmid = {25111229}, issn = {1525-2191}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; P20GM103449/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects ; CREB-Binding Protein/*metabolism ; Cell Line, Tumor ; Chemokine CCL2/metabolism ; Chemokines/metabolism ; Disease Models, Animal ; Doxorubicin/pharmacology ; Gene Expression Profiling ; Heterografts ; Humans ; Inflammation ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Lung Neoplasms/metabolism/*pathology ; Male ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, SCID ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor with no treatment regimen. Previously we have demonstrated that cyclic AMP response element binding protein (CREB) is constitutively activated in MM tumor cells and tissues and plays an important role in MM pathogenesis. To understand the role of CREB in MM tumor growth, we generated CREB-inhibited MM cell lines and performed in vitro and in vivo experiments. In vitro experiments demonstrated that CREB inhibition results in significant attenuation of proliferation and drug resistance of MM cells. CREB-silenced MM cells were then injected into severe combined immunodeficiency mice, and tumor growth in s.c. and i.p. models of MM was followed. We observed significant inhibition in MM tumor growth in both s.c. and i.p. models and the presence of a chemotherapeutic drug, doxorubicin, further inhibited MM tumor growth in the i.p. model. Peritoneal lavage fluids from CREB-inhibited tumor-bearing mice showed a significantly reduced total cell number, differential cell counts, and pro-inflammatory cytokines and chemokines (IL-6, IL-8, regulated on activation normal T cell expressed and secreted, monocyte chemotactic protein-1, and vascular endothelial growth factor). In vitro studies showed that asbestos-induced inflammasome/inflammation activation in mesothelial cells was CREB dependent, further supporting the role of CREB in inflammation-induced MM pathogenesis. In conclusion, our data demonstrate the involvement of CREB in the regulation of MM pathogenesis by regulation of inflammation.}, }
@article {pmid25093718, year = {2014}, author = {Robinson, C and Alfonso, H and Woo, S and Walsh, A and Olsen, N and Musk, AW and Robinson, BW and Nowak, AK and Lake, RA}, title = {Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e103025}, pmid = {25093718}, issn = {1932-6203}, mesh = {Adult ; Aged ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Asbestos/*adverse effects ; Atorvastatin ; Cohort Studies ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Female ; Heptanoic Acids/*therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Incidence ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mice ; Mice, Transgenic ; Middle Aged ; Pyrroles/*therapeutic use ; }, abstract = {Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.}, }
@article {pmid25093494, year = {2014}, author = {Farioli, A and Mattioli, S and Curti, S and Violante, FS}, title = {Comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)': the effect of left censoring.}, journal = {British journal of cancer}, volume = {111}, number = {11}, pages = {2197-2198}, pmid = {25093494}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, }
@article {pmid25093490, year = {2014}, author = {Frost, G}, title = {Response to comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)'.}, journal = {British journal of cancer}, volume = {111}, number = {11}, pages = {2198-2199}, pmid = {25093490}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, }
@article {pmid25078800, year = {2014}, author = {Silvestri, S and Nemo, A}, title = {[Reconstruction of past asbestos exposure of dockers in the Port of Livorno].}, journal = {La Medicina del lavoro}, volume = {105}, number = {3}, pages = {187-196}, pmid = {25078800}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; Ships ; Time Factors ; }, abstract = {INTRODUCTION: In the period 1957/1995 more than 200,000 tons of asbestos arrived at the Port of Livorno. This paper attempts to reconstruct the levels of exposure of the dockers during this period, given the absence of any environmental investigations.<br><br>METHODS: The estimates were calculated using the quantities unloaded annually, the number of dockers, the duration and frequency of the unloading operations, the type of packaging and the background pollution. The Time Weighted Average annual exposure allows calculation of a range of cumulative exposure for each worker with a known period of employment. The working methods were reconstructed interviewing employees and the levels of pollution used in the calculations were partly obtained from published data.<br><br>RESULTS: Significant doses were accumulated by dockers who worked at the port in the 60's and 70's. Non-coincidence of the period with the highest imports with that of highest exposure is worth highlighting. Since 1980 the annual average exposure levels were well below the level required for granting insurance compensation benefits. This suggests caution in the use of lists of beneficiaries for epidemiological purposes since the statistical power would be very low.<br><br>CONCLUSIONS: The strongest point of the research is the estimated annual TWA exposure that, regardless of the accuracy of the data, does however allow an epidemiological analysis of the cohort for subgroups with different exposure. The twenty-three cases of mesothelioma already recorded in this cohort were first employed before 1966. This method can be used to estimate exposure in other ports, where basic information is available.}, }
@article {pmid25077112, year = {2013}, author = {Del Bianco, A and Demers, PA}, title = {Trends in compensation for deaths from occupational cancer in Canada: a descriptive study.}, journal = {CMAJ open}, volume = {1}, number = {3}, pages = {E91-6}, pmid = {25077112}, issn = {2291-0026}, abstract = {BACKGROUND: Occupational cancer is the leading cause of work-related deaths, yet it is often unrecognized and under reported, and associated claims for compensation go unfiled. We sought to examine trends in deaths from occupational cancer, high-risk industries and exposures, and commonly compensated categories of occupational cancers. In addition, we compared deaths from occupational lung cancer for which compensation had been given with total deaths from lung cancer.<br><br>METHODS: We used data from the Association of Workers' Compensation Boards of Canada pertaining to the nature and source of the injury or disease and the industry in which it occurred (by jurisdiction) to describe trends in compensated claims for deaths from occupational cancer in Canada for the period 1997-2010. We used data published by the Canadian Cancer Society in Canadian Cancer Statistics to compare compensated occupational lung cancer deaths with total estimated lung cancer deaths for the period between 2006 and 2010.<br><br>RESULTS: Compensated claims for deaths from occupational cancer have increased in recent years and surpassed those for traumatic injuries and disorders in Canada, particularly in Ontario. Between 1997 and 2010, one-half of all compensated deaths from occupational cancer in Canada were from Ontario. High-risk industries for occupational cancer include manufacturing, construction, mining and, more recently, government services. Deaths from lung cancer and mesothelioma comprise most of the compensated claims for deaths from occupational cancer in Ontario and Canada. These diseases are usually the result of asbestos exposure. The burden of other occupational carcinogens is not reflected in claims data.<br><br>INTERPRETATION: Although the number of accepted claims for deaths from occupational cancers has increased in recent years, these claims likely only represent a fraction of the true burden of this problem. Increased education of patients, workers at high risk of exposure and health care providers is needed to ensure that people with work-related cancer are identified and file a claim for compensation.}, }
@article {pmid25069273, year = {2014}, author = {Varivonchik, DV}, title = {[Epidemiologic situation in Ukraine, concerning malignant mesothelioma prevalence].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {1}, pages = {18-22}, pmid = {25069273}, issn = {1026-9428}, mesh = {Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Prevalence ; Ukraine/epidemiology ; }, abstract = {Malignant mesothelioma is an "indicator" tumor for evaluating public exposure to asbestos (mostly amphibolitic). Over 2001-2011 in Ukraine a total of 2645 cases of malignant mesothelioma was registered (annual number is 240.5 +/- 29.0 cases). 1 case of malignant mesothelioma per 457.4 tons of asbestos consumed by industry. Median annual levels of malignant mesothelioma morbidity in Ukraine (world standard): males--0.60; females--0.31 per 100,000 of general population. These levels are lower than worldwide (males--1.11; females--0.30) and Europaen WHO ones (males--1.53; female--0.37). Medians of malignant mesothelioma morbidity age are not different between males and females in Ukraine (males 59.5 +/- 13.2 years; females 62.6 +/- 13.1 years; p > 0.05). Most frequent location of malignant mesothelioma is on pleura (males 95.3%; females 89.8%). Now Ukraine is among the countries with low level (< 0.8 per 100,000 general population) and moderate (19.0-0.1% per year) increase of malignant mesothelioma morbidity in European WHO region. Up to 2025, the prognosis is of increased malignant mesothelioma morbidity in Ukraine to 0.97 [0.70-1.18] per 100,000 general population, and in European WHO region--to 2.68. Over 1992-2011, in Ukraine 3 cases of occupational malignant mesothelioma were diagnosed (2 cases of them were connected with occupational exposure to asbestos dust).}, }
@article {pmid25068809, year = {2014}, author = {La Vecchia, C and Boffetta, P}, title = {A critique of a review on the relationship between asbestos exposure and the risk of mesothelioma: reply.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {23}, number = {5}, pages = {494-496}, doi = {10.1097/CEJ.0000000000000051}, pmid = {25068809}, issn = {1473-5709}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*statistics &amp; numerical data ; }, }
@article {pmid25068808, year = {2014}, author = {Terracini, B and Mirabelli, D and Magnani, C and Ferrante, D and Barone-Adesi, F and Bertolotti, M}, title = {A critique to a review on the relationship between asbestos exposure and the risk of mesothelioma.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {23}, number = {5}, pages = {492-494}, doi = {10.1097/CEJ.0000000000000057}, pmid = {25068808}, issn = {1473-5709}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*statistics &amp; numerical data ; }, }
@article {pmid25063896, year = {2013}, author = {Hernández-Solís, A and Garcia-Hernández, C and Reding-Bernal, A and Cruz-Ortiz, H and Cicero-Sabido, R}, title = {[Malignant mesothelioma risk factors: experience in the General Hospital of Mexico].}, journal = {Cirugia y cirujanos}, volume = {81}, number = {4}, pages = {312-316}, pmid = {25063896}, issn = {2444-054X}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Hospitals, General/statistics &amp; numerical data ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology/pathology ; Male ; Mesothelioma/diagnostic imaging/*etiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplastic Syndromes, Hereditary/epidemiology ; Occupational Diseases/etiology/pathology ; Pleural Neoplasms/diagnostic imaging/*etiology/pathology ; Retrospective Studies ; Risk Factors ; Rural Population/statistics &amp; numerical data ; Smoke/adverse effects ; Smoking/adverse effects/epidemiology ; Nicotiana ; Tomography, X-Ray Computed ; Urban Population/statistics &amp; numerical data ; Wood ; }, abstract = {BACKGROUND: Malignant mesothelioma is a neoplasm of bad prognosis, it is linked with asbestos contact, but there are cases without this antecedent.<br><br>OBJECTIVE: To investigate the relationship of asbestos exposition and other factors with malignant mesothelioma.<br><br>METHODS: Retrospective analysis of histologic confirmed cases of malignant mesothelioma, neoplasic familiar history, tobacco smoking, exposure to wood smoke and to asbestos, were annotated in a paired case/control study 1: 1-3 with logistic regression model to identify risk factors for OR.<br><br>RESULTS: 61 cases of malignant mesothelioma were confirmed by histopathologic study, 41 male and 20 female. Mean age was 56 years &#xb1; 13 years; 56 cases (91.8%) correspond to epithelial malignant mesothelioma, three sarcomatous (4.9%) one desmoplastic and one biphasic. One in eight (13.1%) had exposure to asbestos. Model of logistic regression with four variables: history of familiar cancer, tobacco smoking, wood smoke and asbestos exposition, the the last one with an OR= 3.083 and p > 0.05. No other variables found to be a risk factor for malignant mesothelioma.<br><br>CONCLUSIONS: Exposure to asbestos is a risk factor for malignant mesothelioma, which is confirmed in this study, however it is important to extend the investigation of other possible causal factors of this disease.}, }
@article {pmid25061089, year = {2014}, author = {Ai, J and Stevenson, JP}, title = {Current issues in malignant pleural mesothelioma evaluation and management.}, journal = {The oncologist}, volume = {19}, number = {9}, pages = {975-984}, pmid = {25061089}, issn = {1549-490X}, mesh = {Combined Modality Therapy ; Glutamates/therapeutic use ; Guanine/analogs &amp; derivatives/therapeutic use ; Humans ; Lung Neoplasms/diagnosis/genetics/*pathology/*therapy ; Mesothelioma/diagnosis/genetics/*pathology/*therapy ; Mesothelioma, Malignant ; Pemetrexed ; Pleura/*pathology ; Pneumonectomy ; *Prognosis ; Quality of Life ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment. Macroscopic complete resection of MPM can be achieved through extrapleural pneumonectomy (EPP) or extended (ie, radical) pleurectomy (e-P/D) in selected patients and can result in prolonged survival when incorporated into a multimodality approach. Given the morbidity associated with surgical resection of MPM, optimizing identification of appropriate patients is essential. Unfortunately, most patients are not candidates for EPP or e-P/D due to advanced stage, age, and/or medical comorbidity. Pemetrexed and platinum combination chemotherapy has become the cornerstone of therapy for patients with unresectable disease because the combination is associated with improved survival and quality of life in treated patients. However, MPM eventually becomes resistant to initial therapy, and benefit to further lines of therapy has not been substantiated in randomized clinical trials. Translational research has provided exciting insights into tumorigenesis, biomarkers, and immune response in MPM, leading to the development of multiple novel therapeutic agents that are currently in clinical trials. These advances hold the promise of a new era in the treatment of MPM and suggest that this disease will not be left behind in the war on cancer.}, }
@article {pmid25053605, year = {2014}, author = {Meisenkothen, C}, title = {The four most pernicious myths in asbestos litigation: Part II: safe thresholds for exposure and Tyndall lighting as junk science.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {24}, number = {1}, pages = {27-55}, doi = {10.2190/NS.24.1.b}, pmid = {25053605}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos, Serpentine/*toxicity ; Culture ; Environmental Exposure/*legislation &amp; jurisprudence ; Expert Testimony ; Humans ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; *Threshold Limit Values ; United States ; }, abstract = {Part I of this survey confronted the first two Most Pernicious Myths in Asbestos Litigation: the supposed harmlessness of chrysotile asbestos; and so-called idiopathic mesothelioma. Part II discusses the pernicious notions of safe exposure thresholds for asbestos and the unreliability of Tyndall lighting. Defendants' attempts to preclude plaintiffs' experts from testifying about these generally accepted scientific facts are a disservice to the legal system and to plaintiffs who have been harmed by asbestos. These defense tactics attempt to deny reality and to spin scientific facts in order to keep them from the jurors' eyes and ears. This undermines the legal system and harms the integrity of the scientific enterprise. Defendants' efforts to manufacture "controversy" over previously uncontroversial facts are bald attempts to infect the legal process with junk "doubt science." The role of this type of "doubt science" is being steadily exposed as legitimate researchers resist the degradation of their disciplines and the scientific literature by unprincipled purveyors of this insidious brand of junk science.}, }
@article {pmid25053604, year = {2014}, author = {Meisenkothen, C}, title = {The four most pernicious myths in asbestos litigation: Part I: safe chrysotile and idiopathic mesothelioma.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {24}, number = {1}, pages = {1-26}, doi = {10.2190/NS.24.1.a}, pmid = {25053604}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos, Serpentine/*toxicity ; Culture ; Environmental Exposure/*legislation &amp; jurisprudence ; Expert Testimony ; Humans ; Mesothelioma/*chemically induced/*pathology ; Occupational Diseases/*chemically induced ; United States ; }, abstract = {The now well documented phenomenon of "doubt science" has crept into litigation generally, but has had a particularly deleterious effect in asbestos litigation, giving rise to pernicious myths that are told and re-told every day in legal briefs and in court proceedings. Defendants routinely challenge the admissibility of testimony from plaintiffs' expert witnesses when those experts testify about certain key concepts in asbestos medicine and asbestos science. Defendants boldly proclaim plaintiffs' experts' opinions to be "junk science" and seek to have them precluded regardless of how well documented, well researched, well supported and well accepted those opinions are. This has become all too routine in asbestos litigation, where defendants predictably seek to preclude testimony about medical and scientific issues that have been settled for decades and that are not legitimately disputed outside of litigation by the unbiased scientific community of national and international regulatory agencies and scientific organizations.}, }
@article {pmid25045719, year = {2014}, author = {Kumagai-Takei, N and Nishimura, Y and Maeda, M and Hayashi, H and Matsuzaki, H and Lee, S and Kishimoto, T and Fukuoka, K and Nakano, T and Otsuki, T}, title = {Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma.}, journal = {Journal of immunology research}, volume = {2014}, number = {}, pages = {670140}, pmid = {25045719}, issn = {2314-7156}, mesh = {Asbestos/adverse effects ; Asbestosis/etiology/*immunology/*pathology ; Biomarkers/metabolism ; CD8-Positive T-Lymphocytes/*immunology/metabolism ; Cell Degranulation/immunology ; Cells, Cultured ; Granzymes/metabolism ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Leukocytes, Mononuclear/immunology/metabolism ; Lung Neoplasms/etiology/*immunology ; Mesothelioma/etiology/*immunology ; Mesothelioma, Malignant ; Perforin/metabolism ; Pleura/*pathology ; T-Lymphocyte Subsets/immunology/metabolism ; }, abstract = {It is known that asbestos exposure can cause malignant mesothelioma (MM) and that CD8(+) T cells play a critical role in antitumor immunity. We examined the properties of peripheral blood CD8(+) lymphocytes from asbestos-exposed patients with pleural plaque (PL) and MM. The percentage of CD3(+)CD8(+) cells in PBMCs did not differ among the three groups, although the total numbers of PBMCs of the PL and MM groups were lower than those of the healthy volunteers (HV). The percentage of IFN-γ (+) and CD107a(+) cells in PMA/ionomycin-stimulated CD8(+) lymphocytes did not differ among the three groups. Percentages of perforin(+) cells and CD45RA(-) cells in fresh CD8(+) lymphocytes of PL and MM groups were higher than those of HV. Percentages of granzyme B(+) and perforin(+) cells in PMA/ionomycin-stimulated CD8(+) lymphocytes were higher in PL group compared with HV. The MM group showed a decrease of perforin level in CD8(+) lymphocytes after stimulation compared with patients with PL. These results indicate that MM patients have characteristics of impairment in stimulation-induced cytotoxicity of peripheral blood CD8(+) lymphocytes and that PL and MM patients have a common character of functional alteration in those lymphocytes, namely, an increase in memory cells, possibly related to exposure to asbestos.}, }
@article {pmid25045139, year = {2014}, author = {Sato, T and Suzuki, Y and Mori, T and Maeda, M and Abe, M and Hino, O and Takahashi, K}, title = {Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma.}, journal = {Cancer medicine}, volume = {3}, number = {5}, pages = {1377-1384}, pmid = {25045139}, issn = {2045-7634}, mesh = {Enzyme-Linked Immunosorbent Assay/*methods/standards ; GPI-Linked Proteins/blood/*metabolism ; Humans ; Lung Neoplasms/*diagnosis/*metabolism ; Mesothelin ; Mesothelioma/*diagnosis/*metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/*metabolism ; Reproducibility of Results ; }, abstract = {Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to asbestos. The prognosis of mesothelioma remains disappointing despite multimodal treatment. We reported previously that N-ERC/mesothelin could be a useful biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme-linked immunosorbent assay (ELISA) system for its detection. However, the reproducibility of our previous 7-16 ELISA system has been revealed to be unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7-20 ELISA system. The subjects of this study were patients who were referred to our department with suspected pleural mesothelioma. The current study demonstrated that the newly established 7-20 ELISA system improved the sensitivity and specificity for diagnosing pleural mesothelioma compared with the previous system. Moreover, the 7-20 ELISA system showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum. Particularly for the epithelioid type, the area under the curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma. In conclusion, assessment of N-ERC/mesothelin with our newly established 7-20 ELISA system is clinically useful for the precise diagnosis of pleural mesothelioma.}, }
@article {pmid25040312, year = {2015}, author = {Exarchos, GD and Attanoos, RL}, title = {Pseudomesotheliomatous small-cell neuroendocrine carcinoma of the lung with calretinin expression.}, journal = {Histopathology}, volume = {66}, number = {6}, pages = {895-896}, doi = {10.1111/his.12484}, pmid = {25040312}, issn = {1365-2559}, mesh = {Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Calbindin 2/analysis ; Carcinoma, Neuroendocrine/*diagnosis/etiology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/diagnosis ; Occupational Exposure/adverse effects ; Small Cell Lung Carcinoma/*diagnosis/etiology ; }, }
@article {pmid25037982, year = {2014}, author = {Creaney, J and Dick, IM and Meniawy, TM and Leong, SL and Leon, JS and Demelker, Y and Segal, A and Musk, AW and Lee, YC and Skates, SJ and Nowak, AK and Robinson, BW}, title = {Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma.}, journal = {Thorax}, volume = {69}, number = {10}, pages = {895-902}, pmid = {25037982}, issn = {1468-3296}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; Biomarkers, Tumor ; Biopsy ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins/*metabolism ; Female ; Follow-Up Studies ; GPI-Linked Proteins/*metabolism ; Humans ; Immunohistochemistry ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelin ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*metabolism/pathology ; Prognosis ; Prospective Studies ; ROC Curve ; Young Adult ; }, abstract = {BACKGROUND: Pleural malignant mesothelioma (MM) is a deadly tumour predominantly associated with asbestos exposure. A reliable diagnostic and prognostic marker for MM will significantly enhance clinical care and is an area of intense research. Soluble mesothelin is the most studied and an FDA-approved biomarker for MM. A recent report showed promising results using fibulin-3 as a new diagnostic marker. The aim of this study was to compare the utility of fibulin-3 versus mesothelin, singly or in combination.<br><br>METHODS: Fibulin-3 and soluble mesothelin were determined by ELISA in the plasma and pleural fluid of 153 patients presenting with a pleural effusion including 82 with MM, 36 with non-MM malignant effusions and 35 with benign effusions. Biomarker concentrations were determined in the plasma of an additional 49 cases with benign asbestos-related disease.<br><br>RESULTS: Mesothelin provides better diagnostic accuracy than fibulin-3 for MM whether measured in plasma or pleural effusion: area under the curve (AUC) for plasma was 0.822 (95% CI 0.76 to 0.87) compared with 0.671 (0.61 to 0.73), respectively, and for pleural fluid AUC was 0.815 (0.74 to 0.87) compared with 0.588 (0.51 to 0.67), respectively. Effusion fibulin-3 was an independent significant prognostic factor for survival in MM patients; HR 2.08 (1.14 to 3.82), p=0.017. MM patients with effusion fibulin-3 levels below the median survived significantly longer than those with levels above the median (14.1 vs 7.9&#x2005;months, p=0.012). Mesothelin and neutrophil to lymphocyte ratio were not significant prognostic markers.<br><br>CONCLUSIONS: Soluble mesothelin is a superior diagnostic biomarker for MM compared with fibulin-3, whereas fibulin-3 provides superior prognostic information compared with mesothelin.}, }
@article {pmid25034569, year = {2014}, author = {Lacourt, A and Rinaldo, M and Gramond, C and Ducamp, S and Gilg Soit Ilg, A and Goldberg, M and Pairon, JC and Brochard, P}, title = {Co-exposure to refractory ceramic fibres and asbestos and risk of pleural mesothelioma.}, journal = {The European respiratory journal}, volume = {44}, number = {3}, pages = {725-733}, doi = {10.1183/09031936.00079814}, pmid = {25034569}, issn = {1399-3003}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Ceramics/*adverse effects ; France ; Humans ; Logistic Models ; Male ; Mesothelioma/*chemically induced/etiology ; Middle Aged ; Occupational Diseases/chemically induced/etiology ; Occupational Exposure ; Pleural Neoplasms/*chemically induced/etiology ; Registries ; Risk Factors ; Time Factors ; }, abstract = {The aim of this study was to investigate the hypothesis of an increased risk of pleural mesothelioma due to co-exposure to asbestos and refractory ceramic fibres (RCF) compared to asbestos exposure alone. Males were selected from a French case-control study conducted in 1987-1993 and from the French National Mesothelioma Surveillance Program in 1998-2006. Two population controls were frequency matched to each case by year of birth. Complete job histories were collected and occupational asbestos and RCF exposures were assessed using job exposure matrices. The dose-response relationships for asbestos exposure were estimated from an unconditional logistic regression model in subjects exposed to asbestos only (group 1) and subjects exposed to both asbestos and RCF (group 2). A total of 988 cases and 1125 controls ever-exposed to asbestos were included. A dose-response relationship was observed in both groups but it was stronger in group 2. In comparison with subjects exposed at the minimum value of the cumulative index of exposure, the odds ratio was 2.6 (95% CI 1.9-3.4) for subjects exposed to 75 fibres · mL(-1) · year(-1) in group 1 increasing to 12.4 (95% CI 4.6-33.7) in group 2. Our results suggest that the pleural carcinogenic effect of occupational asbestos exposure may be modified by additional exposure to RCF.}, }
@article {pmid25026285, year = {2014}, author = {Ortolan, E and Giacomino, A and Martinetto, F and Morone, S and Lo Buono, N and Ferrero, E and Scagliotti, G and Novello, S and Orecchia, S and Ruffini, E and Rapa, I and Righi, L and Volante, M and Funaro, A}, title = {CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome.}, journal = {Oncotarget}, volume = {5}, number = {15}, pages = {6191-6205}, pmid = {25026285}, issn = {1949-2553}, mesh = {ADP-ribosyl Cyclase/analysis/*biosynthesis ; Antigens, CD/analysis/*biosynthesis ; Biomarkers, Tumor/analysis/*biosynthesis ; Cell Line, Tumor ; Cell Proliferation/physiology ; Female ; GPI-Linked Proteins/analysis/biosynthesis ; Humans ; Lung Neoplasms/diagnosis/*metabolism/pathology ; Male ; Mesothelioma/diagnosis/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/diagnosis/*metabolism/pathology ; Prognosis ; Signal Transduction ; Survival Analysis ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a deadly tumor whose diagnosis and treatment remain very challenging. There is an urgent need to advance our understanding of mesothelioma biology and to identify new molecular markers for improving management of patients. CD157 is a membrane glycoprotein linked to ovarian cancer progression and mesenchymal differentiation. The common embryonic origin of ovarian epithelial cells and mesothelial cells and the evident similarities between ovarian and mesothelial cancer prompted us to investigate the biological role and clinical significance of CD157 in malignant pleural mesothelioma (MPM). CD157 mRNA and protein were detected in four of nine MPM cell lines of diverse histotype and in 85.2% of MPM surgical tissue samples (32/37 epithelioid; 37/44 biphasic). CD157 expression correlated with clinical aggressiveness in biphasic MPM. Indeed, high CD157 was a negative prognostic factor and an independent predictor of poor survival for patients with biphasic MPM by multivariate survival analysis (HR = 2.433, 95% CI 1.120-5.284; p = 0.025). In mesothelioma cell lines, CD157 gain (in CD157-negative cells) or knockdown (in CD157-positive cells) affected cell growth, migration, invasion and tumorigenicity, most notably in biphasic MPM cell lines. In these cells, CD157 expression was associated with increased activation of the mTOR signaling pathway, resulting in decreased platinum sensitivity. Moreover, a trend towards reduced survival was observed in patients with biphasic MPM receiving postoperative platinum-based chemotherapy. These findings indicate that CD157 is implicated in multiple aspects of MPM progression and suggest that CD157 expression could be used to stratify patients into different prognostic groups or to select patients that might benefit from particular chemotherapeutic approach.}, }
@article {pmid25013421, year = {2014}, author = {Erdogan, S and Acikalin, A and Zeren, H and Gonlusen, G and Zorludemir, S and Izol, V}, title = {Well-differentiated papillary mesothelioma of the tunica vaginalis: a case study and review of the literature.}, journal = {Korean journal of pathology}, volume = {48}, number = {3}, pages = {225-228}, pmid = {25013421}, issn = {1738-1843}, abstract = {Well-differentiated papillary mesothelioma is an uncommon tumor of the testes that usually presents as a hydrocele. Here, we present the case of one patient who did not have a history of asbestos exposure. The tumor was localized in the tunica vaginalis and was composed of three pedunculated masses macroscopically. Microscopically, branching papillary structures with focal coagulative necrosis were present. In addition to immunohistochemistry, simian virus 40 DNA was also tested by polymerase chain reaction. This report presents one case of this rare entity, its clinical and macroscopic features, and follow-up results.}, }
@article {pmid25010395, year = {2014}, author = {Kobayashi, S and Waragai, T and Sano, H and Mochizuki, K and Akaihata, M and Ohara, Y and Hosoya, M and Kikuta, A}, title = {Malignant peritoneal mesothelioma in a child: chemotherapy with gemcitabine and platinum was effective for the disease unresponsive to other treatments.}, journal = {Anti-cancer drugs}, volume = {25}, number = {9}, pages = {1102-1105}, doi = {10.1097/CAD.0000000000000143}, pmid = {25010395}, issn = {1473-5741}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Ascites/drug therapy ; Child ; Cisplatin/administration &amp; dosage ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Drug Resistance, Neoplasm ; Glutamates/therapeutic use ; Guanine/analogs &amp; derivatives/therapeutic use ; Humans ; Lung Neoplasms/*drug therapy ; Male ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Pemetrexed ; Peritoneal Neoplasms/*drug therapy ; Gemcitabine ; }, abstract = {Malignant peritoneal mesothelioma in children is a very rare disease and has a poor prognosis. Unlike malignant mesothelioma in adults, there is no clear causal association between this very rare malignancy in children and asbestos exposure. We report a case of peritoneal mesothelioma in an 11-year-old boy who presented with ascites. He was diagnosed with malignant mesothelioma on the basis of histopathological findings. His disease showed resistance to pemetrexed, but was treated successfully with platinum-based therapy with gemcitabine. He has achieved long-term survival in partial remission with stable disease.}, }
@article {pmid25006323, year = {2014}, author = {Kim, I and Kim, EA and Kim, JY}, title = {Compensation for occupational cancer.}, journal = {Journal of Korean medical science}, volume = {29 Suppl}, number = {Suppl}, pages = {S40-6}, pmid = {25006323}, issn = {1598-6357}, mesh = {Asbestos/toxicity ; Benzene/toxicity ; Carcinogens/toxicity ; Female ; Humans ; Insurance, Health/*economics ; Middle Aged ; Neoplasms/chemically induced/*economics ; Occupational Diseases/*economics/mortality ; Occupational Exposure/*adverse effects ; Republic of Korea ; Workers' Compensation/*economics/legislation &amp; jurisprudence/standards ; }, abstract = {The legal scope and criteria for occupational cancer in Korea was out of date. The aim of this study was to review the current criteria for occupational cancer and amend the existent criteria on the basis of recent scientific evidence. The scientific evidence and the legal list of occupational cancer were analyzed to identify the causes of occupational cancer on a global scale. The relationship between compensated occupational cancer cases and carcinogen exposure in Korea was examined. The factors associated with specific causes and target cancers were determined to produce additional criteria. Five-hundred and nineteen cases of 2,468 were awarded compensation for occupational cancer including lung, malignant mesothelioma, lymphohematopoietic, and liver cancers from January 2000 to October 2012. Between 1996 and 2005, benzene accounted for 84.4% of cases, and between 1999 and 2005, asbestos was associated with 62.3% of cases. Fourteen novel causative agents and 12 additional target cancers were identified and the final guidelines were amended to include 23 causative agents and 21 target cancers. This amendment of the criteria for occupational cancer represents the widest change in Korean history and is expected to improve the understanding of occupational cancer by providing an up-to-date and accurate reference guide.}, }
@article {pmid24999848, year = {2014}, author = {Van den Borre, L and Deboosere, P}, title = {Asbestos in Belgium: an underestimated health risk. The evolution of mesothelioma mortality rates (1969-2009).}, journal = {International journal of occupational and environmental health}, volume = {20}, number = {2}, pages = {134-140}, pmid = {24999848}, issn = {1077-3525}, mesh = {Belgium/epidemiology ; Female ; Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects/*statistics &amp; numerical data ; Sex Distribution ; }, abstract = {BACKGROUND: Although Belgium was once a major international manufacturer of asbestos products, asbestos-related diseases in the country have remained scarcely researched.<br><br>OBJECTIVES: The aim of this study is to provide a descriptive analysis of Belgian mesothelioma mortality rates in order to improve the understanding of asbestos health hazards from an international perspective.<br><br>METHODS: Temporal and geographical analyses were performed on cause-specific mortality data (1969-2009) using quantitative demographic measures. Results were compared to recent findings on global mesothelioma deaths.<br><br>RESULTS: Belgium has one of the highest mesothelioma mortality rates in the world, following the UK, Australia, and Italy. With a progressive increase of male mesothelioma deaths in the mid-1980s, large differences in mortality rates between sexes are apparent. Mesothelioma deaths are primarily concentrated in geographic areas with proximity to former asbestos industries.<br><br>CONCLUSIONS: Asbestos mortality in Belgium has been underestimated for decades. Our findings suggest that the location of asbestos industries is correlated with rates of mesothelioma, underlining the need to avert future asbestos exposure by thorough screening of potential contaminated sites and by pursuing a global ban on asbestos.}, }
@article {pmid24999846, year = {2014}, author = {Egilman, D and Bird, T and Lee, C}, title = {Dust diseases and the legacy of corporate manipulation of science and law.}, journal = {International journal of occupational and environmental health}, volume = {20}, number = {2}, pages = {115-125}, pmid = {24999846}, issn = {1077-3525}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestosis/etiology ; *Dust ; Humans ; Industry/*legislation &amp; jurisprudence ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Exposure/*legislation &amp; jurisprudence ; Occupational Health ; *Politics ; Silicosis/etiology ; United States/epidemiology ; United States Occupational Safety and Health Administration ; }, abstract = {BACKGROUND: The dust diseases silicosis and asbestosis were the first occupational diseases to have widespread impact on workers. Knowledge that asbestos and silica were hazardous to health became public several decades after the industry knew of the health concerns. This delay was largely influenced by the interests of Metropolitan Life Insurance Company (MetLife) and other asbestos mining and product manufacturing companies.<br><br>OBJECTIVES: To understand the ongoing corporate influence on the science and politics of asbestos and silica exposure, including litigation defense strategies related to historical manipulation of science.<br><br>METHODS: We examined previously secret corporate documents, depositions and trial testimony produced in litigation; as well as published literature.<br><br>RESULTS: Our analysis indicates that companies that used and produced asbestos have continued and intensified their efforts to alter the asbestos-cancer literature and utilize dust-exposure standards to avoid liability and regulation. Organizations of asbestos product manufacturers delayed the reduction of permissible asbestos exposures by covering up the link between asbestos and cancer. Once the decline of the asbestos industry in the US became inevitable, the companies and their lawyers designed the state of the art (SOA) defense to protect themselves in litigation and to maintain sales to developing countries.<br><br>CONCLUSIONS: Asbestos product companies would like the public to believe that there was a legitimate debate surrounding the dangers of asbestos during the twentieth century, particularly regarding the link to cancer, which delayed adequate regulation. The asbestos-cancer link was not a legitimate contestation of science; rather the companies directly manipulated the scientific literature. There is evidence that industry manipulation of scientific literature remains a continuing problem today, resulting in inadequate regulation and compensation and perpetuating otherwise preventable worker and consumer injuries and deaths.}, }
@article {pmid24986501, year = {2014}, author = {Pirastu, R and Ricci, P and Comba, P and Bianchi, F and Biggeri, A and Conti, S and Fazzo, L and Forastiere, F and Iavarone, I and Martuzzi, M and Musmeci, L and Pasetto, R and Zona, A and Crocetti, E}, title = {[SENTIERI Project: discussion and conclusions].}, journal = {Epidemiologia e prevenzione}, volume = {38}, number = {2 Suppl 1}, pages = {125-133}, pmid = {24986501}, issn = {1120-9763}, mesh = {Asbestos/adverse effects ; Breast Neoplasms/epidemiology/etiology ; Carcinogens/toxicity ; Environmental Exposure/*adverse effects ; Female ; Hazardous Substances/adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Lymphoma, Non-Hodgkin/epidemiology/etiology ; Melanoma/epidemiology/etiology ; Neoplasms/*epidemiology/*etiology/mortality/prevention &amp; control ; Patient Discharge/*statistics &amp; numerical data ; Public Health ; Respiratory Tract Diseases/epidemiology/etiology ; Risk Factors ; Sex Distribution ; Skin Neoplasms/epidemiology/etiology ; Survival Rate ; Thyroid Neoplasms/epidemiology/etiology ; Time Factors ; World Health Organization ; }, abstract = {The SENTIERI Project represents the first comprehensive analysis of the health impact of residence in National Priority Contaminated Sites (NPCSs). For the first time, it considers three distinct health outcomes: mortality (2003-2010), cancer incidence (1996- 2005) and hospital discharges (2005-2010). The Report includes a commentary explaining methodology and approach, as well as remarks on the causal association between environmental exposures and investigated health outcomes based on the a priori assessments of the epidemiological evidence; the main implications for public health and scientific research priorities are also presented. The approach put forward by SENTIERI was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. Results relating to individual diseases that can be traced back to a single agent, such as asbestiform fibres, can be easily analysed. The Biancavilla NPCS (where the fluoro-edenite asbestiform fibre was found) displays excesses of pleural mesothelioma and its proxy, malignant pleural tumours, as does Priolo, where asbestos coexists with other pollutants. Increased risk was also recorded in NPCSs adjacent to the coast hosting harbour areas (such as Trieste, Taranto and Venice) or comprising industrial areas specialising in the production of chemicals (Laguna di Grado e Marano, Priolo and Venezia) and steel (Taranto, Terni, Trieste). Increases of pathologies, such as cancer and respiratory diseases, connected to more than one agent, in industrial sites with multiple and diverse sources of exposures, prove harder to interpret. There are also more complex cases in which results do not appear consistent in the three databases or by gender (such as lung cancer in Venice, where mortality and hospital discharges have only increased among women). In order to adequately examine these we must consider factors such as the appropriateness of the health outcome showing the increase, considering latency and the length of the observation period. Of further interest are results relating to diseases of the urinary tract such as kidney failure in the NPCSs of Basso bacino del fiume Chienti, Taranto, Milazzo and Priolo. Overall, the results discussed above are consistent with the previous findings pertaining to mortality for 1995-2002. The present analysis also introduces a new element - the study of cancer incidence and hospital discharges - which can tell us a great deal about diseases with high survival rates or non lethal ones. The first is the case of thyroid cancer, which presents increases in both databases and for both genders in a number of NPCSs (Brescia-Caffaro, Laghi di Mantova, Milazzo, Sassuolo- Scandiano and Taranto). The study of cancer incidence and hospital discharges also revealed cancer excesses for melanoma, breast cancer and non Hodgkin lymphoma in Brescia-Caffaro NPCS where PCBs (Polychlorinated biphenyl) are the site's main pollutant. PCBs, according to the 2013 evaluation of the International Agency for Research on Cancer, are ascertained human carcinogens for melanoma and probable carcinogens for breast cancer and non-Hodgkin lymphoma. The results pertaining to cancer incidence in the 17 NPCSs can also be presented using rankings by area or disease analyzed by a multivariate hierarchical Bayesian model. These rankings reveal an overlapping of credibility intervals, such that it is not possible to speak of a limited number of cancer sites or of certain NPCSs as being particularly affected. Every NPCS, therefore, must be considered individually and ordering them by ranking of cancer incidence wouldn't be appropriate. Data collected concerning some of the NPCSs in the context of the SENTIERI Project is so conclusive that remediation measures can immediately be put in place. This is the case in the Biancavilla and Brescia-Caffaro NPCSs. A similar conclusion can be drawn for complex locations such as Taranto, where, based on the results of SENTIERI Projects and the whole available information, we can safely conclude that exposure to environmental agents played an important role, allowing us to set in place 'Integrated evaluation of environmental and health impact procedures'. SENTIERI approach does not allow definitive causal assessments. However, as stated above, these results do provide a topic for further study without getting in the way of initiatives promoting urgent environmental remediation.}, }
@article {pmid24973234, year = {2015}, author = {Samuels, A}, title = {Mesothelioma and the law.}, journal = {The Medico-legal journal}, volume = {83}, number = {1}, pages = {26-28}, doi = {10.1177/0025817214528433}, pmid = {24973234}, issn = {2042-1834}, mesh = {Asbestos/*adverse effects ; Humans ; *Jurisprudence ; *Malpractice ; Mesothelioma/*etiology/*pathology ; Occupational Diseases/etiology ; }, }
@article {pmid24968911, year = {2014}, author = {Ballan, G and Del Brocco, A and Loizzo, S and Fabbri, A and Maroccia, Z and Fiorentini, C and Travaglione, S}, title = {Mode of action of fibrous amphiboles: the case of Biancavilla (Sicily, Italy).}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {2}, pages = {133-138}, doi = {10.4415/ANN_14_02_05}, pmid = {24968911}, issn = {2384-8553}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Cell Line, Tumor ; *Endemic Diseases ; Humans ; Inhalation Exposure/adverse effects ; Mesothelioma/*epidemiology/etiology/veterinary ; Neoplasms/epidemiology/etiology/veterinary ; Particle Size ; Sicily/epidemiology ; }, abstract = {BACKGROUND: The inhalation of fibrous amphiboles can result in pulmonary fibrosis, lung cancer and mesothelioma. Although these fibres have the same disease-causing potential, their different morphologies and chemical composition can determine different biological activities. An unusual cluster of mesothelioma was evidenced in Biancavilla (Sicily) where no inhabitant had been significantly exposed to asbestos.<br><br>OBJECTIVE: We herein discuss the mechanism of action of amphiboles, focusing on the fibres identified in the study area.<br><br>RESULTS: Human lung carcinoma cells have been exposed to two different materials: prismatic fluoro-edenite and fibres with fluoro-edenitic composition. Only in the second case, they exhibit features typical of transformed cells, such as multinucleation, prosurvival activity and pro-inflammatory cytokine release. Accordingly, in vivo studies demonstrated that the fibrous sample only could induce a mesotheliomatogenic effect.<br><br>CONCLUSIONS: Fibres with fluoro-edenitic composition behave similarly to the asbestos crocidolite, whose connection with inflammation and lung cancer is well established.}, }
@article {pmid24968910, year = {2014}, author = {Conti, S and Minelli, G and Manno, V and Iavarone, I and Comba, P and Scondotto, S and Cernigliaro, A}, title = {Health impact of the exposure to fibres with fluoro-edenitic composition on the residents in Biancavilla (Sicily, Italy): mortality and hospitalization from current data.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {2}, pages = {127-132}, doi = {10.4415/ANN_14_02_04}, pmid = {24968910}, issn = {2384-8553}, mesh = {Asbestos, Amphibole/*adverse effects ; Environmental Exposure/*adverse effects ; Environmental Pollution/*adverse effects ; Hospitalization/statistics &amp; numerical data ; Humans ; Mesothelioma/etiology/*mortality ; Pneumoconiosis/etiology/*mortality ; Respiratory Tract Neoplasms/etiology/mortality ; Sicily/epidemiology ; }, abstract = {INTRODUCTION: The objective of this chapter is to study the health impact of the exposure to fibres with fluoro-edenitic composition on the residents in Biancavilla (Sicily, Italy), in terms of mortality and hospitalization. The diseases which international scientific literature indicates as associated with asbestos exposure were taken into consideration: mesothelioma of pleura, peritoneum, pericardium and tunica vaginalis testis, malignant neoplasm of larynx, malignant neoplasm of trachea, bronchus and lung, malignant neoplasm of ovary, pneumoconiosis; moreover, in order to describe the health profile of the study population, large groups of diseases were taken into consideration.<br><br>MATERIAL AND METHODS: Current data (available in the Data Bases of the Unit of Statistics of ISS) regarding mortality and hospitalization were analyzed. Standardized Mortality Ratios, Standardized Hospitalization Ratios and Age-standardized Death Rates were calculated. The demographic background of the population residing in Biancavilla was also outlined.<br><br>CONCLUSIONS: Our findings support the etiologic role of fibres with fluoro-edenitic composition in the occurrence of the above mentioned diseases, already observed in other studies.}, }
@article {pmid24968908, year = {2014}, author = {Bruno, C and Tumino, R and Fazzo, L and Cascone, G and Cernigliaro, A and De Santis, M and Giurdanella, MC and Nicita, C and Rollo, PC and Scondotto, S and Spata, E and Zona, A and Comba, P}, title = {Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy).}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {2}, pages = {111-118}, doi = {10.4415/ANN_14_02_02}, pmid = {24968908}, issn = {2384-8553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Amphibole/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Public Health Surveillance ; Sicily/epidemiology ; Soil/chemistry ; Soil Pollutants/adverse effects ; }, abstract = {INTRODUCTION: Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite.<br><br>MATERIALS AND METHODS: Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants.<br><br>RESULTS: The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50.<br><br>DISCUSSION AND CONCLUSIONS: Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected epidemiological investigations.}, }
@article {pmid24966347, year = {2014}, author = {Marek, LA and Hinz, TK and von Mässenhausen, A and Olszewski, KA and Kleczko, EK and Boehm, D and Weiser-Evans, MC and Nemenoff, RA and Hoffmann, H and Warth, A and Gozgit, JM and Perner, S and Heasley, LE}, title = {Nonamplified FGFR1 is a growth driver in malignant pleural mesothelioma.}, journal = {Molecular cancer research : MCR}, volume = {12}, number = {10}, pages = {1460-1469}, pmid = {24966347}, issn = {1557-3125}, support = {P50 CA058187/CA/NCI NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; R01 CA108610/CA/NCI NIH HHS/United States ; CA127105/CA/NCI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01 CA162226/CA/NCI NIH HHS/United States ; R01 CA127105/CA/NCI NIH HHS/United States ; P50 CA58187/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Autocrine Communication/drug effects/genetics ; Cell Line, Tumor ; Cell Proliferation ; Clone Cells ; Extracellular Signal-Regulated MAP Kinases/antagonists &amp; inhibitors/metabolism ; Female ; Fibroblast Growth Factor 2/metabolism ; *Gene Amplification ; Humans ; Imidazoles/pharmacology ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Mice, Nude ; Pleural Neoplasms/*genetics/*pathology ; Pyridazines/pharmacology ; RNA Interference ; Receptor, Fibroblast Growth Factor, Type 1/*genetics ; Signal Transduction ; }, abstract = {UNLABELLED: Malignant pleural mesothelioma (MPM) is associated with asbestos exposure and is a cancer that has not been significantly affected by small molecule-based targeted therapeutics. Previously, we demonstrated the existence of functional subsets of lung cancer and head and neck squamous cell carcinoma (HNSCC) cell lines in which fibroblast growth factor receptor (FGFR) autocrine signaling functions as a nonmutated growth pathway. In a panel of pleural mesothelioma cell lines, FGFR1 and FGF2 were coexpressed in three of seven cell lines and were significantly associated with sensitivity to the FGFR-active tyrosine kinase inhibitor (TKI), ponatinib, both in vitro and in vivo using orthotopically propagated xenografts. Furthermore, RNAi-mediated silencing confirmed the requirement for FGFR1 in specific mesothelioma cells and sensitivity to the FGF ligand trap, FP-1039, validated the requirement for autocrine FGFs. None of the FGFR1-dependent mesothelioma cells exhibited increased FGFR1 gene copy number, based on a FISH assay, indicating that increased FGFR1 transcript and protein expression were not mediated by gene amplification. Elevated FGFR1 mRNA was detected in a subset of primary MPM clinical specimens and like MPM cells; none harbored increased FGFR1 gene copy number. These results indicate that autocrine signaling through FGFR1 represents a targetable therapeutic pathway in MPM and that biomarkers distinct from increased FGFR1 gene copy number such as FGFR1 mRNA would be required to identify patients with MPM bearing tumors driven by FGFR1 activity.<br><br>IMPLICATIONS: FGFR1 is a viable therapeutic target in a subset of MPMs, but FGFR TKI-responsive tumors will need to be selected by a biomarker distinct from increased FGFR1 gene copy number, possibly FGFR1 mRNA or protein levels.}, }
@article {pmid24958746, year = {2015}, author = {Blackshear, PE and Pandiri, AR and Nagai, H and Bhusari, S and Hong, HH and Ton, TV and Clayton, NP and Wyde, M and Shockley, KR and Peddada, SD and Gerrish, KE and Sills, RC and Hoenerhoff, MJ}, title = {Gene expression of mesothelioma in vinylidene chloride-exposed F344/N rats reveal immune dysfunction, tissue damage, and inflammation pathways.}, journal = {Toxicologic pathology}, volume = {43}, number = {2}, pages = {171-185}, pmid = {24958746}, issn = {1533-1601}, support = {Z99 ES999999//Intramural NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; DNA Damage ; Dichloroethylenes/*toxicity ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Genes, cdc/drug effects ; Immune System Diseases/*chemically induced/immunology ; Inflammation/*chemically induced/physiopathology ; Lung Neoplasms/*chemically induced/*genetics ; Male ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Microarray Analysis ; Peritoneal Neoplasms/chemically induced/pathology ; RNA, Neoplasm/biosynthesis ; Rats ; Rats, Inbred F344 ; Signal Transduction/drug effects ; Testicular Neoplasms/chemically induced/pathology ; }, abstract = {A majority (∼80%) of human malignant mesotheliomas are asbestos-related. However, non-asbestos risk factors (radiation, chemicals, and genetic factors) account for up to 30% of cases. A recent 2-year National Toxicology Program carcinogenicity bioassay showed that male F344/N rats exposed to the industrial toxicant vinylidene chloride (VDC) resulted in a marked increase in malignant mesothelioma. Global gene expression profiles of these tumors were compared to spontaneous mesotheliomas and the F344/N rat mesothelial cell line (Fred-PE) in order to characterize the molecular features and chemical-specific profiles of mesothelioma in VDC-exposed rats. As expected, mesotheliomas from control and VDC-exposed rats shared pathways associated with tumorigenesis, including cellular and tissue development, organismal injury, embryonic development, inflammatory response, cell cycle regulation, and cellular growth and proliferation, while mesotheliomas from VDC-exposed rats alone showed overrepresentation of pathways associated with pro-inflammatory pathways and immune dysfunction such as the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, interleukin (IL)-8 and IL-12 signaling, interleukin responses, Fc receptor signaling, and natural killer and dendritic cells signaling, as well as overrepresentation of DNA damage and repair. These data suggest that a chronic, pro-inflammatory environment associated with VDC exposure may exacerbate disturbances in oncogene, growth factor, and cell cycle regulation, resulting in an increased incidence of mesothelioma.}, }
@article {pmid24940987, year = {2014}, author = {Sayan, M and Shukla, A and MacPherson, MB and Macura, SL and Hillegass, JM and Perkins, TN and Thompson, JK and Beuschel, SL and Miller, JM and Mossman, BT}, title = {Extracellular signal-regulated kinase 5 and cyclic AMP response element binding protein are novel pathways inhibited by vandetanib (ZD6474) and doxorubicin in mesotheliomas.}, journal = {American journal of respiratory cell and molecular biology}, volume = {51}, number = {5}, pages = {595-603}, pmid = {24940987}, issn = {1535-4989}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Antibiotics, Antineoplastic/pharmacology/toxicity ; Cell Line, Tumor ; Cell Survival/drug effects/physiology ; Cyclic AMP Response Element-Binding Protein/genetics/*metabolism ; Doxorubicin/*pharmacology/toxicity ; Drug Synergism ; Humans ; MAP Kinase Signaling System/drug effects/*physiology ; Mesothelioma/*drug therapy/metabolism ; Mitogen-Activated Protein Kinase 7/antagonists &amp; inhibitors/genetics/*metabolism ; Neoplasms, Connective Tissue/drug therapy/metabolism ; Phosphorylation/drug effects/physiology ; Piperidines/*pharmacology/toxicity ; Quinazolines/*pharmacology/toxicity ; RNA, Small Interfering/genetics ; Sarcoma/drug therapy/metabolism ; }, abstract = {Malignant mesothelioma (MM), lung cancers, and asbestosis are hyperproliferative diseases associated with exposures to asbestos. All have a poor prognosis; thus, the need to develop novel and effective therapies is urgent. Vandetanib (Van) (ZD6474, ZACTIMA) is a tyrosine kinase inhibitor that has shown equivocal results in clinical trials for advanced non-small cell lung cancer. However, tyrosine kinase inhibitors alone have shown no significant clinical activity in phase II trials of patients with unresectable MM. Using epithelioid (HMESO) and sarcomatoid (H2373) human MM lines, the efficacy of tumor cell killing and signaling pathways modulated by Van with and without doxorubicin (Dox) was examined. Van alone reduced total cell numbers in HMESO MM and synergistically increased the toxicity of Dox in HMESO and H2373 cells. Most importantly, we identified two novel cell survival/resistance pathways, ERK5 and cyclic AMP response element binding protein (CREB), that were inhibited by Van and Dox. After silencing of either ERK5 or CREB, significant decreases in cell numbers in the Dox-resistant sarcomatoid H2373 line were observed. Results suggest that a plethora of cell signaling pathways associated with cell survival are induced by Dox but inhibited by the addition of Van in MM. Data from our study support the combined efficacy of Van and Dox as a novel approach in the treatment of MM that is further enhanced by blocking ERK5 or CREB signaling cascades.}, }
@article {pmid24928783, year = {2014}, author = {Xu, J and Kadariya, Y and Cheung, M and Pei, J and Talarchek, J and Sementino, E and Tan, Y and Menges, CW and Cai, KQ and Litwin, S and Peng, H and Karar, J and Rauscher, FJ and Testa, JR}, title = {Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma.}, journal = {Cancer research}, volume = {74}, number = {16}, pages = {4388-4397}, pmid = {24928783}, issn = {1538-7445}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; CA175691/CA/NCI NIH HHS/United States ; R01 CA163761/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*toxicity ; Disease Models, Animal ; Epigenomics ; Female ; Genetic Predisposition to Disease ; Genotype ; *Germ-Line Mutation ; Lung Neoplasms/*etiology/*genetics/metabolism ; Mesothelioma/*etiology/*genetics/metabolism ; Mesothelioma, Malignant ; Mice ; Mice, Knockout ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; }, abstract = {Malignant mesotheliomas are highly aggressive tumors usually caused by exposure to asbestos. Germline-inactivating mutations of BAP1 predispose to mesothelioma and certain other cancers. However, why mesothelioma is the predominate malignancy in some BAP1 families and not others, and whether exposure to asbestos is required for development of mesothelioma in BAP1 mutation carriers are not known. To address these questions experimentally, we generated a Bap1(+/-) knockout mouse model to assess its susceptibility to mesothelioma upon chronic exposure to asbestos. Bap1(+/-) mice exhibited a significantly higher incidence of asbestos-induced mesothelioma than wild-type (WT) littermates (73% vs. 32%, respectively). Furthermore, mesotheliomas arose at an accelerated rate in Bap1(+/-) mice than in WT animals (median survival, 43 weeks vs. 55 weeks after initial exposure, respectively) and showed increased invasiveness and proliferation. No spontaneous mesotheliomas were seen in unexposed Bap1(+/-) mice followed for up to 87 weeks of age. Mesothelioma cells from Bap1(+/-) mice showed biallelic inactivation of Bap1, consistent with its proposed role as a recessive cancer susceptibility gene. Unlike in WT mice, mesotheliomas from Bap1(+/-) mice did not require homozygous loss of Cdkn2a. However, normal mesothelial cells and mesothelioma cells from Bap1(+/-) mice showed downregulation of Rb through a p16(Ink4a)-independent mechanism, suggesting that predisposition of Bap1(+/-) mice to mesothelioma may be facilitated, in part, by cooperation between Bap1 and Rb. Drawing parallels to human disease, these unbiased genetic findings indicate that BAP1 mutation carriers are predisposed to the tumorigenic effects of asbestos and suggest that high penetrance of mesothelioma requires such environmental exposure.}, }
@article {pmid24928677, year = {2014}, author = {Taioli, E and Wolf, AS and Camacho-Rivera, M and Flores, RM}, title = {Women with malignant pleural mesothelioma have a threefold better survival rate than men.}, journal = {The Annals of thoracic surgery}, volume = {98}, number = {3}, pages = {1020-1024}, doi = {10.1016/j.athoracsur.2014.04.040}, pmid = {24928677}, issn = {1552-6259}, support = {5R01TS000099-05/TS/ATSDR CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*mortality ; Sex Factors ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Many studies have reported that women with malignant pleural mesothelioma (MPM) experience longer survival compared with men, whereas others have not. To date, no large population-based studies have evaluated MPM outcome and its determinants in female patients.<br><br>METHODS: All pathologically confirmed cases of MPM in the Surveillance, Epidemiology and End Results database from 1973 to 2009 were evaluated. Age, year of diagnosis, race, stage, cancer-directed surgery, radiation, and vital status were analyzed according to gender. Cox proportional hazard models were derived to assess the association between prognostic factors and survival.<br><br>RESULTS: There were 14,228 cases of MPM, of which 3,196 (22%) were women. Despite similar baseline characteristics for both genders, 5-year survival was 13.4% in women and 4.5% in men (p < 0.0001). The effect of female gender on survival persisted when stratified by age (dichotomized at 50 years), stage, or race, but differed depending on treatment. Even when adjusted for age, stage, race, and treatment, female MPM patients experienced longer survival than men (hazard ratio = 0.78; 95% confidence interval 0.75 to 0.82).<br><br>CONCLUSIONS: This large data set confirms that although MPM is less common in women, they present with similar stage and are offered similar treatment options compared with men. Nevertheless, survival is far better in women compared with men, independent of confounders such as age, stage, and treatment. Differences in asbestos exposure, tumor biology, and the impact of circulating hormones on host response must be investigated to understand this survival advantage and improve prognosis for patients of both genders.}, }
@article {pmid24924397, year = {2015}, author = {Lee, YJ and Lee, YJ and Lee, SH}, title = {Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation.}, journal = {BMB reports}, volume = {48}, number = {3}, pages = {166-171}, pmid = {24924397}, issn = {1976-670X}, mesh = {Adenine Nucleotides/*pharmacology ; Apoptosis/*drug effects ; Arabinonucleosides/*pharmacology ; Caspase 3/*metabolism ; Cell Line, Tumor ; Clofarabine ; Down-Regulation/*drug effects ; Enzyme Activation ; Humans ; Mesothelioma/enzymology/metabolism/*pathology ; Myeloid Cell Leukemia Sequence 1 Protein/*metabolism ; Resveratrol ; Stilbenes/*pharmacology ; }, abstract = {We previously demonstrated that resveratrol and clofarabine elicited a marked cytotoxicity on malignant mesothelioma (MM) MSTO-211H cells but not on the corresponding normal mesothelial MeT-5A cells. Little is known of the possible molecules that could be used to predict preferential chemosensitivity on MSTO-211H cells. Resveratrol and clofarabine induced down-regulation of Mcl-1 protein level in MSTO-211H cells. Treatment of cells with cycloheximide in the presence of proteasome inhibitor MG132 suggested that Mcl-1 protein levels were regulated at the post-translational step. The siRNA-based knockdown of Mcl-1 in MSTO-211H cells triggered more growth-inhibiting and apoptosis-inducing effects with the resultant cleavages of procaspase-3 and its substrate PARP, increased caspase-3/7 activity, and increased percentage of apoptotic propensities. However, the majority of the observed changes were not shown in MeT-5A cells. Collectively, these studies indicate that the preferential activation of caspase cascade in malignant cells might have important applications as a therapeutic target for MM.}, }
@article {pmid24910640, year = {2014}, author = {Kerger, BD and James, RC and Galbraith, DA}, title = {Tumors that mimic asbestos-related mesothelioma: time to consider a genetics-based tumor registry?.}, journal = {Frontiers in genetics}, volume = {5}, number = {}, pages = {151}, pmid = {24910640}, issn = {1664-8021}, abstract = {The diagnosis of mesothelioma is not always straightforward, despite known immunohistochemical markers and other diagnostic techniques. One reason for the difficulty is that extrapleural tumors resembling mesothelioma may have several possible etiologies, especially in cases with no meaningful history of amphibole asbestos exposure. When the diagnosis of mesothelioma is based on histologic features alone, primary mesotheliomas may resemble various primary or metastatic cancers that have directly invaded the serosal membranes. Some of these metastatic malignancies, particularly carcinomas and sarcomas of the pleura, pericardium and peritoneum, may undergo desmoplastic reaction in the pleura, thereby mimicking mesothelioma, rather than the primary tumor. Encasement of the lung by direct spread or metastasis, termed pseudomesotheliomatous spread, occurs with several other primary cancer types, including certain late-stage tumors from genetic cancer syndromes exhibiting chromosomal instability. Although immunohistochemical staining patterns differentiate most carcinomas, lymphomas, and mestastatic sarcomas from mesotheliomas, specific genetic markers in tumor or somatic tissues have been recently identified that may also distinguish these tumor types from asbestos-related mesothelioma. A registry for genetic screening of mesothelioma cases would help lead to improvements in diagnostic criteria, prognostic accuracy and treatment efficacy, as well as improved estimates of primary mesothelioma incidence and of background rates of cancers unrelated to asbestos that might be otherwise mistaken for mesothelioma. This information would also help better define the dose-response relationships for mesothelioma and asbestos exposure, as well as other risk factors for mesothelioma and other mesenchymal or advanced metastatic tumors that may be indistinguishable by histology and staining characteristics.}, }
@article {pmid24885895, year = {2014}, author = {Thompson, JK and Westbom, CM and MacPherson, MB and Mossman, BT and Heintz, NH and Spiess, P and Shukla, A}, title = {Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to regulate inflammasome activation.}, journal = {Particle and fibre toxicology}, volume = {11}, number = {}, pages = {24}, pmid = {24885895}, issn = {1743-8977}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Acetylcysteine/pharmacology ; Antioxidants/pharmacology ; Apoptosis/drug effects ; Asbestos, Crocidolite/*toxicity ; Blotting, Western ; Caspase 1/metabolism ; Cell Line, Tumor ; Dehydroascorbic Acid/metabolism ; Dinitrochlorobenzene/toxicity ; Enzyme Activation/drug effects ; Epithelium/drug effects/pathology ; Gene Knockdown Techniques ; Humans ; Inflammation/*pathology ; L-Lactate Dehydrogenase/metabolism ; RNA, Small Interfering ; Reactive Oxygen Species/metabolism ; Real-Time Polymerase Chain Reaction ; Thioredoxin Reductase 1/metabolism ; Thioredoxins/*drug effects/genetics ; }, abstract = {BACKGROUND: Asbestos exposure is related to various diseases including asbestosis and malignant mesothelioma (MM). Among the pathogenic mechanisms proposed by which asbestos can cause diseases involving epithelial and mesothelial cells, the most widely accepted one is the generation of reactive oxygen species and/or depletion of antioxidants like glutathione. It has also been demonstrated that asbestos can induce inflammation, perhaps due to activation of inflammasomes.<br><br>METHODS: The oxidation state of thioredoxin was analyzed by redox Western blot analysis and ROS generation was assessed spectrophotometrically as a read-out of solubilized formazan produced by the reduction of nitrotetrazolium blue (NTB) by superoxide. Quantitative real time PCR was used to assess changes in gene transcription.<br><br>RESULTS: Here we demonstrate that crocidolite asbestos fibers oxidize the pool of the antioxidant, Thioredoxin-1 (Trx1), which results in release of Thioredoxin Interacting Protein (TXNIP) and subsequent activation of inflammasomes in human mesothelial cells. Exposure to crocidolite asbestos resulted in the depletion of reduced Trx1 in human peritoneal mesothelial (LP9/hTERT) cells. Pretreatment with the antioxidant dehydroascorbic acid (a reactive oxygen species (ROS) scavenger) reduced the level of crocidolite asbestos-induced Trx1 oxidation as well as the depletion of reduced Trx1. Increasing Trx1 expression levels using a Trx1 over-expression vector, reduced the extent of Trx1 oxidation and generation of ROS by crocidolite asbestos, and increased cell survival. In addition, knockdown of TXNIP expression by siRNA attenuated crocidolite asbestos-induced activation of the inflammasome.<br><br>CONCLUSION: Our novel findings suggest that extensive Trx1 oxidation and TXNIP dissociation may be one of the mechanisms by which crocidolite asbestos activates the inflammasome and helps in development of MM.}, }
@article {pmid24885398, year = {2014}, author = {Renganathan, A and Kresoja-Rakic, J and Echeverry, N and Ziltener, G and Vrugt, B and Opitz, I and Stahel, RA and Felley-Bosco, E}, title = {GAS5 long non-coding RNA in malignant pleural mesothelioma.}, journal = {Molecular cancer}, volume = {13}, number = {}, pages = {119}, pmid = {24885398}, issn = {1476-4598}, mesh = {Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation ; *Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Hedgehog Proteins/genetics/metabolism ; Humans ; Ki-67 Antigen/genetics/metabolism ; Luciferases/genetics/metabolism ; Lung Neoplasms/*genetics/metabolism/pathology ; Membrane Glycoproteins/*genetics/metabolism ; Mesothelioma/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Primary Cell Culture ; Promoter Regions, Genetic ; Protein Kinase Inhibitors/pharmacology ; RNA, Long Noncoding/antagonists &amp; inhibitors/*genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/antagonists &amp; inhibitors/genetics/metabolism ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer with short overall survival. Long non-coding RNAs (lncRNA) are a class of RNAs more than 200 nucleotides long that do not code for protein and are part of the 90% of the human genome that is transcribed. Earlier experimental studies in mice showed GAS5 (growth arrest specific transcript 5) gene deletion in asbestos driven mesothelioma. GAS5 encodes for a lncRNA whose function is not well known, but it has been shown to act as glucocorticoid receptor decoy and microRNA "sponge". Our aim was to investigate the possible role of the GAS5 in the growth of MPM.<br><br>METHODS: Primary MPM cultures grown in serum-free condition in 3% oxygen or MPM cell lines grown in serum-containing medium were used to investigate the modulation of GAS5 by growth arrest after inhibition of Hedgehog or PI3K/mTOR signalling. Cell cycle length was determined by EdU incorporation assay in doxycycline inducible short hairpinGAS5 clones generated from ZL55SPT cells. Gene expression was quantified by quantitative PCR. To investigate the GAS5 promoter, a 0.77&#xa0;kb sequence was inserted into a pGL3 reporter vector and luciferase activity was determined after transfection into MPM cells. Localization of GAS5 lncRNA was identified by in situ hybridization. To characterize cells expressing GAS5, expression of podoplanin and Ki-67 was assessed by immunohistochemistry.<br><br>RESULTS: GAS5 expression was lower in MPM cell lines compared to normal mesothelial cells. GAS5 was upregulated upon growth arrest induced by inhibition of Hedgehog and PI3K/mTOR signalling in in vitro MPM models. The increase in GAS5 lncRNA was accompanied by increased promoter activity. Silencing of GAS5 increased the expression of glucocorticoid responsive genes glucocorticoid inducible leucine-zipper and serum/glucocorticoid-regulated kinase-1 and shortened the length of the cell cycle. Drug induced growth arrest was associated with GAS5 accumulation in the nuclei. GAS5 was abundant in tumoral quiescent cells and it was correlated to podoplanin expression.<br><br>CONCLUSIONS: The observations that GAS5 levels modify cell proliferation in vitro, and that GAS5 expression in MPM tissue is associated with cell quiescence and podoplanin expression support a role of GAS5 in MPM biology.}, }
@article {pmid24876951, year = {2014}, author = {Pfau, JC and Serve, KM and Noonan, CW}, title = {Autoimmunity and asbestos exposure.}, journal = {Autoimmune diseases}, volume = {2014}, number = {}, pages = {782045}, pmid = {24876951}, issn = {2090-0422}, support = {P20 GM103408/GM/NIGMS NIH HHS/United States ; R01 TS000099/TS/ATSDR CDC HHS/United States ; }, abstract = {Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.}, }
@article {pmid24872671, year = {2013}, author = {Bianchi, C and Bianchi, T}, title = {Pleural mesothelioma in a couple of brothers.}, journal = {Indian journal of occupational and environmental medicine}, volume = {17}, number = {3}, pages = {122-123}, pmid = {24872671}, issn = {0973-2284}, abstract = {Malignant mesotheliomas of the pleura, epithelial type, were observed in two brothers. Both the patients had histories of severe exposure to asbestos, having worked as insulators. The latency periods in the two cases were 26 and 38 years, respectively. Available literature data suggest that mesothelioma occurrence among blood-related people is favored by a genetic predisposition.}, }
@article {pmid24868221, year = {2014}, author = {Ahn, S and Choi, IH and Han, J and Kim, J and Ahn, MJ}, title = {Pleural mesothelioma: an institutional experience of 66 cases.}, journal = {Korean journal of pathology}, volume = {48}, number = {2}, pages = {91-99}, pmid = {24868221}, issn = {1738-1843}, abstract = {BACKGROUND: Malignant mesothelioma of the pleura is an aggressive tumor known to be associated with asbestos. Histological diagnosis of mesothelioma is challenging and is usually aided by immunohistochemical markers.<br><br>METHODS: During an 18-year period (1995-2012), 66 patients with pleural mesothelioma were diagnosed at the Samsung Medical Center in Seoul. We reviewed hematoxylin and eosin and immunohistochemical slides of pleural mesothelioma and evaluated their pathological and clinical features.<br><br>RESULTS: The male-to-female ratio was 1.75:1, and age of patients ranged from 28 to 80 years with an average age of 56.84 years. Twenty-two out of 66 patients underwent curative pneumonectomy. Follow-up data was available in 60 patients (90.9%), and 50 of them (83.3%) died from the disease. The average overall survival was 15.39 months. Histologically, the epithelioid type was the most common, followed by the sarcomatoid and the biphasic types. Epidemiologic information was not available in most cases, and only one patient was confirmed to have a history of asbestos exposure.<br><br>CONCLUSIONS: Malignant mesothelioma of the pleura is a fatal tumor, and the therapeutic benefit of pneumonectomy remains unproven. The combination of calretinin, Wilms tumor 1, HMBE-1, and thyroid transcription factor-1 may provide high diagnostic accuracy in diagnosing mesothelioma.}, }
@article {pmid24848258, year = {2014}, author = {Shapiro, IM and Kolev, VN and Vidal, CM and Kadariya, Y and Ring, JE and Wright, Q and Weaver, DT and Menges, C and Padval, M and McClatchey, AI and Xu, Q and Testa, JR and Pachter, JA}, title = {Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship.}, journal = {Science translational medicine}, volume = {6}, number = {237}, pages = {237ra68}, pmid = {24848258}, issn = {1946-6242}, support = {R01 CA113733/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; R01CA113733/CA/NCI NIH HHS/United States ; CA148805/CA/NCI NIH HHS/United States ; }, mesh = {Aldehyde Dehydrogenase/metabolism ; Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Focal Adhesion Kinase 1/*antagonists &amp; inhibitors/genetics/metabolism ; Humans ; Lung Neoplasms/*drug therapy/enzymology/genetics/pathology ; Mesothelioma/*drug therapy/enzymology/genetics/pathology ; Mesothelioma, Malignant ; Mice ; Molecular Targeted Therapy ; Neoplastic Stem Cells/drug effects/enzymology ; Neurofibromin 2/*deficiency/genetics ; Protein Kinase Inhibitors/*pharmacology ; RNA Interference ; Signal Transduction/drug effects ; Time Factors ; Transfection ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {The goal of targeted therapy is to match a selective drug with a genetic lesion that predicts for drug sensitivity. In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin. Merlin expression is often lost in malignant pleural mesothelioma (MPM), an asbestos-induced aggressive cancer with limited treatment options. Our data demonstrate that low Merlin expression predicts for increased sensitivity of MPM cells to a FAK inhibitor, VS-4718, in vitro and in tumor xenograft models. Disruption of MPM cell-cell or cell-extracellular matrix (ECM) contacts with blocking antibodies suggests that weak cell-cell adhesions in Merlin-negative MPM cells underlie their greater dependence on cell-ECM-induced FAK signaling. This provides one explanation of why Merlin-negative cells are vulnerable to FAK inhibitor treatment. Furthermore, we validated aldehyde dehydrogenase as a marker of cancer stem cells (CSCs) in MPM, a cell population thought to mediate tumor relapse after chemotherapy. Whereas pemetrexed and cisplatin, standard-of-care agents for MPM, enrich for CSCs, FAK inhibitor treatment preferentially eliminates these cells. These preclinical results provide the rationale for a clinical trial in MPM patients using a FAK inhibitor as a single agent after first-line chemotherapy. With this design, the FAK inhibitor could potentially induce a more durable clinical response through reduction of CSCs along with a strong antitumor effect. Furthermore, our data suggest that patients with Merlin-negative tumors may especially benefit from FAK inhibitor treatment.}, }
@article {pmid24842786, year = {2014}, author = {Reid, A and de Klerk, NH and Magnani, C and Ferrante, D and Berry, G and Musk, AW and Merler, E}, title = {Mesothelioma risk after 40 years since first exposure to asbestos: a pooled analysis.}, journal = {Thorax}, volume = {69}, number = {9}, pages = {843-850}, doi = {10.1136/thoraxjnl-2013-204161}, pmid = {24842786}, issn = {1468-3296}, mesh = {Adolescent ; Adult ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Australia/epidemiology ; Child ; Child, Preschool ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Inhalation Exposure/*adverse effects ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40 years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time.<br><br>METHODS: The data from six cohort studies of exposed workers and two cohorts with residential exposure have been pooled. A nested case control design matched cases and controls on calendar period and age. Conditional logistic regression modelled the relationship between time since first exposure and risk of MM.<br><br>RESULTS: The combined data consisted of 22,048 people with asbestos exposure (5769 women), 707 cases of pleural MM (165 in women) and 155 cases of peritoneal MM (32 in women). Median time since first exposure for pleural MM cases was 38.4&#x2005;years (IQR 31.3-45.3). Median duration of exposure for pleural MM cases was 3.75&#x2005;years (IQR 0.7-18.2). The rate and risk of pleural MM increased until 45&#x2005;years following first exposure and then appeared to increase at a slower power of time since first exposure. The rate of increase in peritoneal MM over the 10-50&#x2005;years since first exposure continued to increase.<br><br>CONCLUSIONS: Exposure to asbestos confers a long-term risk of developing pleural and peritoneal mesothelioma which increases following cessation of exposure. While the rate of increase appears to start to level out after 40-50&#x2005;years no one survives long enough for the excess risk to disappear.}, }
@article {pmid24842043, year = {2014}, author = {Sezer, A and Sümbül, AT and Abalı, H and Mertsoylu, H and Ozyılkan, O}, title = {Malignant pleural mesothelioma: a single-center experience in Turkey.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {20}, number = {}, pages = {825-832}, pmid = {24842043}, issn = {1643-3750}, mesh = {Adult ; Aged ; Demography ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/*epidemiology/therapy ; Male ; Mesothelioma/*epidemiology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/therapy ; Turkey/epidemiology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is a rare lethal malignancy caused by asbestos exposure. It is more frequently seen in certain regions in Turkey. In this retrospective study, we aimed to analyse demographic, clinical, and pathological data and treatment-related features in 54 patients.<br><br>MATERIAL AND METHODS: The study included 54 patients diagnosed with malignant mesothelioma that were followed and treated.<br><br>RESULT: Of the 54 patients, 34 (55.6%) were male. The median age in men and women were 60.3 (38.2-77.2) and 65.8 (37.7-77.5) years, respectively. In 35 (64.8%), exposure to asbestosis was present. Epithelial type was found in 27 (50.0%), followed by mixed type in 7 (13.0%) patients, and in 20 (37.0%) patients the subtype could not be determined. The disease was staged as IV in 37 (68.5%) patients. In 28 patients (51.9%), it was right-sided and in 1 (1.9%) it was bilateral. The most frequent metastatic sites (in decreasing order) were lungs, mediastinum, diaphragm, liver, and thoracal wall. Of the 54 patients, 36 (66.6%) received 1st-line chemotherapy and 20 (37%) 2nd-line chemotherapy. Eighteen patients (33.3%) received radiotherapy; 11 (20.3%) with palliative intention and 7 (12.9%) with curative intention. Median overall survival (OS) was 12.03 months (95% CI 7.2-16.8). OS was not affected by sex (p=0.32), smoking history (p=0.51), alcohol consumption (p=0.36), family history (p=0.67), pleural effusion presence (p=0.80), operation (p=0.14), clinical stage (p=0.072), symptom at presentation (p=0.66), having mixed type histology (p=0.079), asbestos exposure (p=0.06), and type of 1st-line chemotherapy (p=0.161). On the contrary, it may be positively affected by good ECOG PS (0-1) (p<0.01), age below 65 (p=0.03), left-sided disease (p=0.01), receiving chemotherapy (p<0.01), having unilateral pleural effusion (p=0.018), and type of 2nd-line chemotherapy (p=0.025).<br><br>CONCLUSIONS: OS of our patients was better than that found in the literature, seeming to be positively affected by early stages, better ECOG PS, age below 65 years, left side involvement, and having second-line chemotherapy with cisplatin-gemcitabine or 3M. Overall treatment success seems to be comparable to what is currently expected.}, }
@article {pmid24839947, year = {2014}, author = {Jiang, L and Yamashita, Y and Chew, SH and Akatsuka, S and Ukai, S and Wang, S and Nagai, H and Okazaki, Y and Takahashi, T and Toyokuni, S}, title = {Connective tissue growth factor and β-catenin constitute an autocrine loop for activation in rat sarcomatoid mesothelioma.}, journal = {The Journal of pathology}, volume = {233}, number = {4}, pages = {402-414}, doi = {10.1002/path.4377}, pmid = {24839947}, issn = {1096-9896}, mesh = {Animals ; Autocrine Communication/*physiology ; Biomarkers, Tumor/metabolism ; Connective Tissue Growth Factor/*metabolism ; Disease Models, Animal ; Epithelial-Mesenchymal Transition/physiology ; Epithelium/metabolism/pathology ; Female ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Lung Neoplasms/metabolism/pathology/*physiopathology ; Male ; Mesothelioma/metabolism/pathology/*physiopathology ; Mesothelioma, Malignant ; Rats ; Rats, Inbred F344 ; Sarcoma/metabolism/pathology/*physiopathology ; Signal Transduction/physiology ; TCF Transcription Factors/metabolism ; beta Catenin/*metabolism ; }, abstract = {Due to the formerly widespread use of asbestos, malignant mesothelioma (MM) is increasingly frequent worldwide. MM is classified into epithelioid (EM), sarcomatoid (SM), and biphasic subtypes. SM is less common than EM but is recognized as the most aggressive type of MM, and these patients have a poor prognosis. To identify genes responsible for the aggressiveness of SM, we induced EM and SM in rats, using asbestos, and compared their transcriptomes. Based on the results, we focused on connective tissue growth factor (Ctgf), whose expression was significantly increased in SM compared with EM; EM itself exhibited an increased expression of Ctgf compared with normal mesothelium. Particularly in SM, Ctgf was a major regulator of MM proliferation and invasion through activation of the β-catenin-TCF-LEF signalling pathway, which is autocrine and formed a positive feedback loop via LRP6 as a receptor for secreted Ctgf. High Ctgf expression also played a role in the epithelial-mesenchymal transition in MM. Furthermore, Ctgf is a novel serum biomarker for both early diagnosis and determining the MM prognosis in rats. These data link Ctgf to SM through the LRP6-GSK3β-β-catenin-TCF-Ctgf autocrine axis and suggest Ctgf as a therapeutic target.}, }
@article {pmid24837247, year = {2014}, author = {Wu, WT and Lin, YJ and Shiue, HS and Li, CY and Tsai, PJ and Yang, CY and Liou, SH and Wu, TN}, title = {Cancer incidence of Taiwanese shipbreaking workers who have been potentially exposed to asbestos.}, journal = {Environmental research}, volume = {132}, number = {}, pages = {370-378}, doi = {10.1016/j.envres.2014.04.026}, pmid = {24837247}, issn = {1096-0953}, mesh = {Adult ; Asbestos/*adverse effects ; Follow-Up Studies ; Humans ; Incidence ; Male ; Neoplasms/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; *Registries ; Retrospective Studies ; Taiwan/epidemiology ; }, abstract = {BACKGROUND: Shipbreaking remains one of the most dangerous jobs worldwide. Shipbreaking workers are exposed to many hazardous chemicals, especially asbestos. Unfortunately, long-term follow-up studies of cancer incidence patterns in shipbreaking workers are lacking. This study examines whether there is an increased risk of cancer among male shipbreaking workers over a 24-year follow-up period.<br><br>METHODS: 4155 male shipbreaking worker's information was retrospectively collected from Kaohsiung's Shipbreaking Workers Union database from 1985. The study cohort was linked to the Taiwan Cancer Registry from 1985 to 2008 for new cancer cases. The expected number of cancers for shipbreaking workers was calculated by using the age (5-year intervals) and calendar time-specific annual rates of cancer incidence with reference to the general population of Taiwan from 1985 to 2008. Standardized incidence ratios (SIRs) were calculated as relative risk estimates. The hazard ratio (HR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores for asbestos.<br><br>RESULTS: After consideration of a 5-year latency period, an elevated incidence of overall cancer (N=368; SIR=1.13 (1.01-1.25)), oral cavity cancer (N=83; SIR=1.99 (1.58-2.46)), and trachea, bronchus, and lung cancers (N=53; SIR=1.36 (1.02-1.78)) was found among male shipbreaking employees. Moreover, mesothelioma cases were found in those who had the occupation of flame cutter. The high asbestos exposure group was associated with an increased SIR of developing overall cancer and oral cancer, whether we considered a 5-year or 10-year latency period.<br><br>CONCLUSION: Asbestos-related diseases, including lung cancer and mesothelioma, were seen in excess in these shipbreaking workers and some cases appeared to have a dose-dependent relationship. Preventative measures among male shipbreaking workers should be researched further.}, }
@article {pmid24830353, year = {2015}, author = {Dodson, RF and Hammar, SP}, title = {Analysis of asbestos concentration in 20 cases of pseudomesotheliomatous lung cancer.}, journal = {Ultrastructural pathology}, volume = {39}, number = {1}, pages = {13-22}, doi = {10.3109/01913123.2014.906525}, pmid = {24830353}, issn = {1521-0758}, mesh = {Adenocarcinoma/chemistry/*etiology/*pathology/ultrastructure ; Adult ; Aged ; Asbestos/adverse effects/*analysis ; Diagnosis, Differential ; Humans ; Lung Neoplasms/chemistry/*etiology/*pathology/ultrastructure ; Male ; Mesothelioma/chemistry/*etiology/ultrastructure ; Mesothelioma, Malignant ; Microscopy, Electron, Transmission ; Middle Aged ; }, abstract = {Mesothelioma is a rare neoplasm caused by asbestos exposure. The majority of mesotheliomas arise from the pleural lining of the thoracic cavity, but also involve the peritoneal and pericardial cavities. Another type of neoplasm referred to as pseudomesotheliomatous adenocarcinoma is rare. Most "pseudomesotheliomas" arise in the pleural tissue of the chest cavity and resemble pleural mesotheliomas, macroscopically and histologically. While most arise in the pleura, there are some that metastasize to the pleura from another site. We evaluated asbestos fiber concentrations in 20 cases of pseudomesotheliomatous lung cancer and found a significant number to contain an elevated concentration of asbestos in their lung tissue, which is similar with our study of 55 mesothelioma cases published in 1997. This would provide evidence that some pseudomesotheliomatous lung cancers are caused by asbestos.}, }
@article {pmid24815191, year = {2014}, author = {Xu, J and Alexander, DB and Futakuchi, M and Numano, T and Fukamachi, K and Suzui, M and Omori, T and Kanno, J and Hirose, A and Tsuda, H}, title = {Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes.}, journal = {Cancer science}, volume = {105}, number = {7}, pages = {763-769}, pmid = {24815191}, issn = {1349-7006}, mesh = {Animals ; Cell Proliferation/drug effects ; Cytokines/metabolism ; Fibrosis/*chemically induced/pathology ; Inflammation/chemically induced/metabolism/pathology ; Lung/drug effects/metabolism/pathology ; Male ; Mesothelioma/chemically induced/pathology ; Nanotubes, Carbon/*toxicity ; Pleural Cavity/drug effects/*pathology ; Rats ; Rats, Inbred F344 ; }, abstract = {Multiwalled carbon nanotubes (MWCNT) have a fibrous structure similar to asbestos, raising concern that MWCNT exposure may lead to asbestos-like diseases. Previously we showed that MWCNT translocated from the lung alveoli into the pleural cavity and caused mesothelial proliferation and fibrosis in the visceral pleura. Multiwalled carbon nanotubes were not found in the parietal pleura, the initial site of development of asbestos-caused pleural diseases in humans, probably due to the short exposure period of the study. In the present study, we extended the exposure period to 24 weeks to determine whether the size and shape of MWCNT impact on deposition and lesion development in the pleura and lung. Two different MWCNTs were chosen for this study: a larger sized needle-like MWCNT (MWCNT-L; l = 8 μm, d = 150 nm), and a smaller sized MWCNT (MWCNT-S; l = 3 μm, d = 15 nm), which forms cotton candy-like aggregates. Both MWCNT-L and MWCNT-S suspensions were administered to the rat lung once every 2 weeks for 24 weeks by transtracheal intrapulmonary spraying. It was found that MWCNT-L, but not MWCNT-S, translocated into the pleural cavity, deposited in the parietal pleura, and induced fibrosis and patchy parietal mesothelial proliferation lesions. In addition, MWCNT-L induced stronger inflammatory reactions including increased inflammatory cell number and cytokine/chemokine levels in the pleural cavity lavage than MWCNT-S. In contrast, MWCNT-S induced stronger inflammation and higher 8-hydroxydeoxyguanosine level in the lung tissue than MWCNT-L. These results suggest that MWCNT-L has higher risk of causing asbestos-like pleural lesions relevant to mesothelioma development.}, }
@article {pmid24806876, year = {2014}, author = {Moolgavkar, SH and Anderson, EL and Chang, ET and Lau, EC and Turnham, P and Hoel, DG}, title = {A review and critique of U.S. EPA's risk assessments for asbestos.}, journal = {Critical reviews in toxicology}, volume = {44}, number = {6}, pages = {499-522}, doi = {10.3109/10408444.2014.902423}, pmid = {24806876}, issn = {1547-6898}, mesh = {Aluminum Silicates/toxicity ; Asbestos, Amphibole/*standards/*toxicity ; Endpoint Determination ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/chemically induced/pathology ; Mesothelioma/chemically induced/pathology ; Occupational Exposure/*adverse effects ; Ohio ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; United States ; United States Environmental Protection Agency/*legislation &amp; jurisprudence ; }, abstract = {U.S. Environmental Protection Agency (EPA) recently conducted a risk assessment for exposure to Libby amphibole asbestos that is precedent-setting for two reasons. First, the Agency has not previously conducted a risk assessment for a specific type of asbestos fiber. Second, the risk assessment includes not only an inhalation unit risk (IUR) for the cancer endpoints, but also a reference concentration (RfC) for nonmalignant disease. In this paper, we review the procedures used by the Agency for both cancer and nonmalignant disease and discuss the strengths and limitations of these procedures. The estimate of the RfC uses the benchmark dose method applied to pleural plaques in a small subcohort of vermiculite workers in Marysville, Ohio. We show that these data are too sparse to inform the exposure-response relationship in the low-exposure region critical for estimation of an RfC, and that different models with very different exposure-response shapes fit the data equally well. Furthermore, pleural plaques do not represent a disease condition and do not appear to meet the EPA's definition of an adverse condition. The estimation of the IUR for cancer is based on a subcohort of Libby miners, discarding the vast majority of lung cancers and mesotheliomas in the entire cohort and ignoring important time-related factors in exposure and risk, including effect modification by age. We propose that an IUR based on an endpoint that combines lung cancer, mesothelioma, and nonmalignant respiratory disease (NMRD) in this cohort would protect against both malignant and nonmalignant disease. However, the IUR should be based on the entire cohort of Libby miners, and the analysis should properly account for temporal factors. We illustrate our discussion with our own independent analyses of the data used by the Agency.}, }
@article {pmid24794734, year = {2014}, author = {Kozlowski, D and Provost, SC and Tucker, J and van der Zwan, R}, title = {Dusted community: piloting a virtual peer-to-peer support community for people with an asbestos-related diagnosis and their families.}, journal = {Journal of psychosocial oncology}, volume = {32}, number = {4}, pages = {463-475}, doi = {10.1080/07347332.2014.917142}, pmid = {24794734}, issn = {1540-7586}, mesh = {Asbestos/*adverse effects ; Caregivers/*psychology ; Female ; Humans ; *Internet ; Interpersonal Relations ; Male ; Mesothelioma/*etiology/*psychology ; *Peer Group ; Pilot Projects ; Program Evaluation ; Social Isolation/psychology ; *Social Support ; }, abstract = {Individuals with an asbestos-related diagnosis and their carers face burdens including debilitating and life-limiting physical symptoms and medico-legal stressors. Feelings of social isolation are common. Increasing social connectedness can lead to increased feelings of personal empowerment and may inhibit chronic stress responses. The authors report on the development, via a process of participatory action research, of an online peer-to-peer support group, and the first 30-day test phase of this virtual community. Initial indications are that individuals with an asbestos-related diagnosis and their carers can benefit, in psychosocial terms, from membership of an on-line support group comprised of experientially similar others.}, }
@article {pmid24781281, year = {2014}, author = {Consonni, D and Barone-Adesi, F and Mensi, C}, title = {Comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)': methodological problems with case-only survival analysis.}, journal = {British journal of cancer}, volume = {111}, number = {8}, pages = {1674}, pmid = {24781281}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, }
@article {pmid24781044, year = {2015}, author = {Jakubec, P and Pelclova, D and Smolkova, P and Kolek, V and Nakladalova, M}, title = {Significance of serum mesothelin in an asbestos-exposed population in the Czech Republic.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {159}, number = {3}, pages = {472-479}, doi = {10.5507/bp.2014.015}, pmid = {24781044}, issn = {1804-7521}, mesh = {Asbestos/*adverse effects ; Asbestosis/*blood/complications/epidemiology ; Biomarkers, Tumor/blood ; Czech Republic/epidemiology ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/epidemiology/etiology ; Male ; Mesothelin ; Mesothelioma/*blood/epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*blood/epidemiology/etiology ; ROC Curve ; }, abstract = {AIMS: Pleural mesothelioma is a highly aggressive and difficult-to-treat form of cancer induced by asbestos in 80-90% of cases. The population group most at risk of the condition are asbestos-exposed workers. Mesothelin or soluble mesothelin-related protein (SMRP) is studied as a potential marker of mesothelioma in the at-risk population.<br><br>METHODS: The study comprised 239 subjects with a mean duration of occupational exposure to asbestos of 19.9 years. In all of them, a complete medical history was taken, focused on exposure duration and a physical examination, a chest X-ray or other imaging investigations and a lung function test were performed. Their serum SMRP levels were measured and biopsy samples were taken to diagnose pleural disease. Based on the above examinations, the subjects were classified into subgroups and serum SMRP concentrations were statistically analyzed with respect to individual parameters.<br><br>RESULTS: In asbestos-exposed individuals, mesothelin levels were significantly higher in those with pathological X-ray findings than in those with normal X-ray results (0.78 &#xb1; 0.63 vs. 0.50 &#xb1; 0.35, P<0.0001). The group of patients with benign disease had statistically significantly higher mesothelin levels than those with normal X-ray findings (0.755 &#xb1; 0.543 vs. 0.50 &#xb1; 0.35, P<0.001). In the group with present malignant processes, mesothelin levels were higher than in individuals with benign disease (1.19 &#xb1; 0.89 vs. 0.76 &#xb1; 0.54, P=0.015). Only a weak correlation was found between mesothelin levels and asbestos exposure duration. There were relatively high sensitivity and high specificity (75% and 90.6%, respectively) of serum mesothelin for pleural mesothelioma. However, given the small number of mesothelioma cases in the group, the results cannot be considered as statistically significant.<br><br>CONCLUSIONS: In persons followed up for asbestos exposure, increased mesothelin levels signalize pathological processes in the chest and correlate with severity of the disease. The study suggests that mesothelin cannot be considered a reliable marker for the early stage of malignant degeneration of pleural disease but only an additional criterion for examination of the followed-up individuals.}, }
@article {pmid24780577, year = {2014}, author = {Baas, P and Burgers, JA}, title = {[Is one single exposure to asbestos life-threatening?].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {158}, number = {}, pages = {A7653}, pmid = {24780577}, issn = {1876-8784}, mesh = {Asbestos/*toxicity ; Carcinoma/*epidemiology ; Humans ; Laryngeal Neoplasms/*epidemiology ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; }, abstract = {The media occasionally reports on possible asbestos exposure during demolition of houses in an urban setting. The risk for the development of any asbestos-related cancer in these settings is considered to be lower than for that in occupational exposure. Offermans et al. examined a Dutch cohort of 58,279 workers in the period from 1986 to 2007. They concluded that the risk of lung cancer, laryngeal cancer and mesothelioma increased with exposure to asbestos. The risk of development of lung cancer was higher for anyone with increased years of exposure to asbestos fibre combined with a smoking habit. The study was well conducted, but exact data on fibre concentration and type of asbestos are lacking. We suggest that occasional exposure to asbestos poses hardly any risk for the general population. However, rules and regulations for the removal of asbestos-containing material remain important as asbestos exposure remains a serious health risk, especially in smokers.}, }
@article {pmid24778081, year = {2014}, author = {Varesano, S and Leo, C and Boccardo, S and Salvi, S and Truini, M and Ferro, P and Fedeli, F and Canessa, PA and Dessanti, P and Pistillo, MP and Roncella, S}, title = {Status of Anaplastic Lymphoma Kinase (ALK) in malignant mesothelioma.}, journal = {Anticancer research}, volume = {34}, number = {5}, pages = {2589-2592}, pmid = {24778081}, issn = {1791-7530}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anaplastic Lymphoma Kinase ; Child ; Child, Preschool ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*enzymology/*genetics ; Male ; Mesothelioma/*enzymology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation ; Receptor Protein-Tyrosine Kinases/*biosynthesis/*genetics ; Young Adult ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a particularly aggressive type of primary tumor, associated with exposure to asbestos, and characterized by high mortality. To date, there is no curative therapy for MM. The receptor anaplastic lymphoma kinase (ALK) was found to be mutated in many cases of cancer and used as a target in biological therapies. We investigated whether this pharmacological treatment could also be applicable to MM.<br><br>MATERIALS AND METHODS: The state of ALK was analyzed by immunohistochemistry and fluorescent in situ hybridization in 63 MM tissue specimens.<br><br>RESULTS: None of the 63 MM samples showed overexpression or translocation of ALK.<br><br>CONCLUSION: Our preliminary data exclude the utility of analysis of the ALK gene in MM and suggest that ALK inhibitor therapy is not applicable to MM.}, }
@article {pmid24766058, year = {2014}, author = {Boffetta, P and Donaldson, K and Moolgavkar, S and Mandel, JS}, title = {A systematic review of occupational exposure to synthetic vitreous fibers and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {44}, number = {5}, pages = {436-449}, doi = {10.3109/10408444.2014.899558}, pmid = {24766058}, issn = {1547-6898}, mesh = {Animals ; Asbestos/*toxicity ; Canada/epidemiology ; Disease Models, Animal ; Europe/epidemiology ; Half-Life ; Humans ; Incidence ; Mesothelioma/*epidemiology/etiology/*pathology ; Mineral Fibers/*toxicity ; Occupational Exposure/*adverse effects ; Rats ; Risk Assessment ; Toxicity Tests ; United States/epidemiology ; }, abstract = {OBJECTIVE: We investigated whether available epidemiological and toxicological data suggest an increased risk of mesothelioma among workers exposed to synthetic vitreous fibers (SVF).<br><br>METHODS: We conducted a systematic review of epidemiological studies on the risk of mesothelioma among workers exposed to SVF, and toxicological studies on SVF and mesothelioma.<br><br>RESULTS: Seven cohort studies were conducted among workers employed in production of rock/slag wool, glass wool, or continuous glass filament in the United States, Canada, and Europe. Of the six deaths from mesothelioma identified in these studies, three had exposure to asbestos. A review of death certificates in a study of rock wool production workers identified one additional probable death. A formal comparison with expected deaths is not feasible. Four community-based case-control studies were identified, of which three reported an increased risk among SVF-exposed workers. The number of cases not exposed to asbestos was less, and residual confounding from asbestos exposure misclassification may explain the association in these studies. The toxicology review of SVF suggested that they present a low hazard mostly due to their low biopersistence, typically with a half-life in rat studies of tens of days compared to amphibole asbestos which has a half-life of 400-500 days.<br><br>CONCLUSIONS: The combined evidence from epidemiology and toxicology provide little evidence that exposure to SVF increases the risk of mesothelioma.}, }
@article {pmid24762959, year = {2014}, author = {Zhou, S and Liu, L and Li, H and Eilers, G and Kuang, Y and Shi, S and Yan, Z and Li, X and Corson, JM and Meng, F and Zhou, H and Sheng, Q and Fletcher, JA and Ou, WB}, title = {Multipoint targeting of the PI3K/mTOR pathway in mesothelioma.}, journal = {British journal of cancer}, volume = {110}, number = {10}, pages = {2479-2488}, pmid = {24762959}, issn = {1532-1827}, mesh = {Antineoplastic Agents/*pharmacology ; Butadienes/pharmacology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Chromones/pharmacology ; Drug Screening Assays, Antitumor ; Enzyme Activation/drug effects ; Everolimus ; Humans ; Imidazoles/pharmacology ; Indazoles/pharmacology ; MAP Kinase Signaling System ; Mesothelioma/*enzymology/pathology ; Molecular Targeted Therapy ; Morpholines/pharmacology ; Neoplasm Proteins/*antagonists &amp; inhibitors/physiology ; Nitriles/pharmacology ; Phosphatidylinositol 3-Kinases/physiology ; *Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors/*pharmacology ; Quinolines/pharmacology ; RNA Interference ; RNA, Small Interfering/pharmacology ; Receptor Protein-Tyrosine Kinases/physiology ; Signal Transduction/*drug effects ; Sirolimus/analogs &amp; derivatives/pharmacology ; Sulfonamides/pharmacology ; TOR Serine-Threonine Kinases/*antagonists &amp; inhibitors/physiology ; raf Kinases/physiology ; }, abstract = {BACKGROUND: Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis.<br><br>METHODS: Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations.<br><br>RESULTS: We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation.<br><br>CONCLUSIONS: These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for therapeutic intervention.}, }
@article {pmid24755344, year = {2014}, author = {Neshatian, L and Halland, M and Arora, AS}, title = {Abdominal pain and bloating in an auto mechanic.}, journal = {Gastroenterology}, volume = {146}, number = {7}, pages = {1610-1611}, doi = {10.1053/j.gastro.2014.02.052}, pmid = {24755344}, issn = {1528-0012}, mesh = {Abdominal Pain/*etiology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/*adverse effects ; *Automobiles ; Biopsy ; Gastric Dilatation/*etiology ; Humans ; Lung Neoplasms/diagnosis/drug therapy/*etiology ; Male ; Mesothelioma/diagnosis/drug therapy/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; *Occupations ; Peritoneal Neoplasms/diagnosis/drug therapy/*etiology ; Predictive Value of Tests ; Risk Factors ; Tomography, X-Ray Computed ; }, }
@article {pmid24747072, year = {2014}, author = {Komiya, E and Ohnuma, K and Yamazaki, H and Hatano, R and Iwata, S and Okamoto, T and Dang, NH and Yamada, T and Morimoto, C}, title = {CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells.}, journal = {Biochemical and biophysical research communications}, volume = {447}, number = {4}, pages = {609-615}, doi = {10.1016/j.bbrc.2014.04.037}, pmid = {24747072}, issn = {1090-2104}, mesh = {Active Transport, Cell Nucleus ; Cell Adhesion Molecules/genetics/*metabolism ; Cell Line, Tumor ; Cell Movement/physiology ; Dipeptidyl Peptidase 4/genetics/*metabolism ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/genetics/*metabolism/*pathology ; Mesothelioma/genetics/*metabolism/*pathology ; Mesothelioma, Malignant ; Neoplasm Invasiveness/pathology/physiopathology ; Nuclear Proteins/metabolism ; Pleural Neoplasms/genetics/*metabolism/*pathology ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines/pharmacology ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; RNA, Small Interfering/genetics ; Twist-Related Protein 1/metabolism ; Up-Regulation ; src-Family Kinases/antagonists &amp; inhibitors/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on the enhanced motility and increased CD26 expression in MPM cells, with a particular focus on integrin adhesion molecules. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. Moreover, we showed that upregulation of periostin expression results from the nuclear translocation of the basic helix-loop-helix transcription factor Twist1, a process that is mediated by CD26-associated activation of Src phosphorylation. While providing new and profound insights into the molecular mechanisms involved in MPM biology, these findings may also lead to the development of novel therapeutic strategies for MPM.}, }
@article {pmid24735948, year = {2014}, author = {Lin, Z and Liu, T and Kamp, DW and Wang, Y and He, H and Zhou, X and Li, D and Yang, L and Zhao, B and Liu, G}, title = {AKT/mTOR and c-Jun N-terminal kinase signaling pathways are required for chrysotile asbestos-induced autophagy.}, journal = {Free radical biology &amp; medicine}, volume = {72}, number = {}, pages = {296-307}, pmid = {24735948}, issn = {1873-4596}, support = {I01 BX000786/BX/BLRD VA/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Serpentine/*toxicity ; Autophagy/*physiology ; Blotting, Western ; Cell Line ; Coculture Techniques ; Epithelial Cells/drug effects/metabolism ; Fibroblasts/cytology ; Fluorescent Antibody Technique ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Lung/drug effects/metabolism ; Mice ; Microscopy, Electron, Transmission ; Proto-Oncogene Proteins c-akt/*metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Signal Transduction/*physiology ; TOR Serine-Threonine Kinases/*metabolism ; Transfection ; }, abstract = {Chrysotile asbestos is closely associated with excess mortality from pulmonary diseases such as lung cancer, mesothelioma, and asbestosis. Although multiple mechanisms in which chrysotile asbestos fibers induce pulmonary disease have been identified, the role of autophagy in human lung epithelial cells has not been examined. In this study, we evaluated whether chrysotile asbestos induces autophagy in A549 human lung epithelial cells and then analyzed the possible underlying molecular mechanism. Chrysotile asbestos induced autophagy in A549 cells based on a series of biochemical and microscopic autophagy markers. We observed that asbestos increased expression of A549 cell microtubule-associated protein 1 light chain 3 (LC3-II), an autophagy marker, in conjunction with dephosphorylation of phospho-AKT, phospho-mTOR, and phospho-p70S6K. Notably, AKT1/AKT2 double-knockout murine embryonic fibroblasts (MEFs) had negligible asbestos-induced LC3-II expression, supporting a crucial role for AKT signaling. Chrysotile asbestos also led to the phosphorylation/activation of Jun N-terminal kinase (JNK) and p38 MAPK. Pharmacologic inhibition of JNK, but not p38 MAPK, dramatically inhibited the protein expression of LC3-II. Moreover, JNK2(-/-) MEFs but not JNK1(-/-) MEFs blocked LC3-II levels induced by chrysotile asbestos. In addition, N-acetylcysteine, an antioxidant, attenuated chrysotile asbestos-induced dephosphorylation of P-AKT and completely abolished phosphorylation/activation of JNK. Finally, we demonstrated that chrysotile asbestos-induced apoptosis was not affected by the presence of the autophagy inhibitor 3-methyladenine or autophagy-related gene 5 siRNA, indicating that the chrysotile asbestos-induced autophagy may be adaptive rather than prosurvival. Our findings demonstrate that AKT/mTOR and JNK2 signaling pathways are required for chrysotile asbestos-induced autophagy. These data provide a mechanistic basis for possible future clinical applications targeting these signaling pathways in the management of asbestos-induced lung disease.}, }
@article {pmid24730341, year = {2013}, author = {Imenpour, H and Ivaldi, GP and Brianti, A and Pastorino, G and Biggi, S and Auriati, L and Simonassi, C}, title = {Synchronous occurrence of pulmonary adenocarcinoma and pleural diffuse malignant mesothelioma.}, journal = {Pathologica}, volume = {105}, number = {6}, pages = {353-356}, pmid = {24730341}, issn = {0031-2983}, mesh = {Adenocarcinoma/*pathology ; Aged ; Humans ; Lung/*pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; *Neoplasms, Multiple Primary ; Pleura/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {We report a rare case of diffuse malignant pleural mesothelioma synchronous with a localized adenocarcinoma of lung in a 68-year old man with a suspicious history of asbestos exposure. Computed tomography revealed a sub-pleural mass in the lower lobe and an irregular dense area of medium lobe of right lung with thickening of pleura encasing the lung parenchyma and homolateral pleural effusion 1 cm thick. The patient underwent surgery and a right medium and lower lobectomy was performed. Upon frozen sections, intraoperative diagnosis was adenocarcinoma with a poorly differentiated component of lung infiltrating the pleura. The postoperative histological definitive diagnosis with an important contribution of immunostaining was synchronous pulmonary adenocarcinoma and pleural diffuse malignant epithelioid mesothelioma.}, }
@article {pmid24716080, year = {2014}, author = {Algın, MC and Yaylak, F and Bayhan, Z and Aslan, F and Bayhan, NA}, title = {Malignant peritoneal mesothelioma: clinicopathological characteristics of two cases.}, journal = {Case reports in surgery}, volume = {2014}, number = {}, pages = {748469}, pmid = {24716080}, issn = {2090-6900}, abstract = {Introduction. Peritoneal mesothelioma is a rare tumor, presenting difficulties in diagnosis and treatment. Peritoneum is the second most common area of the mesothelioma after pleura, and even synchronous pleural and peritoneal mesotheliomas are observed in 30-45% of all cases. The diagnosis may be difficult due to lack of specific symptoms and clinical findings. In addition, a delay in the diagnosis is not rare especially in the absence of previous asbestos exposure. Here we report two cases of malignant peritoneal mesotheliomas. The diagnostic and therapeutic approaches for these rare neoplasms are discussed. Case Presentation. The cases were two men (one aged 54 years old and the other 40 years old). Prolonged abdominal pain and swelling were the primary presentation symptoms and findings. The mesotheliomas were developed in the right upper quadrant of abdomen in both of the cases. Both cases were treated with surgical resection. Final diagnosis were possible with histological and immunohistochemical documentation of tumor characteristics, which were consistent with dictating a mesothelial origin. No history of asbestos exposure was reported. Conclusion. Peritoneal mesotheliomas are rare clinical entities. However, patients with prolonged abdominal pain and abdominal masses should be considered to have atypical pathologies such as peritoneal mesotheliomas.}, }
@article {pmid24714749, year = {2014}, author = {Meniawy, TM and Creaney, J and Lake, RA and Nowak, AK}, title = {Response to comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma'.}, journal = {British journal of cancer}, volume = {111}, number = {12}, pages = {2377}, pmid = {24714749}, issn = {1532-1827}, mesh = {*Biomarkers, Tumor ; Female ; Humans ; Lung Neoplasms/*mortality ; Lymphocytes/*cytology ; Male ; Mesothelioma/*mortality ; Neutrophils/*cytology ; }, }
@article {pmid24714747, year = {2014}, author = {Kao, SC and van Zandwijk, N and Clarke, S}, title = {Comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma'.}, journal = {British journal of cancer}, volume = {111}, number = {12}, pages = {2376}, pmid = {24714747}, issn = {1532-1827}, mesh = {*Biomarkers, Tumor ; Female ; Humans ; Lung Neoplasms/*mortality ; Lymphocytes/*cytology ; Male ; Mesothelioma/*mortality ; Neutrophils/*cytology ; }, }
@article {pmid24706728, year = {2014}, author = {Lamote, K and Nackaerts, K and van Meerbeeck, JP}, title = {Strengths, weaknesses, and opportunities of diagnostic breathomics in pleural mesothelioma-a hypothesis.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {23}, number = {6}, pages = {898-908}, doi = {10.1158/1055-9965.EPI-13-0737}, pmid = {24706728}, issn = {1538-7755}, mesh = {Breath Tests/methods ; Humans ; Lung Neoplasms/*diagnosis/metabolism ; Mesothelioma/*diagnosis/metabolism ; Mesothelioma, Malignant ; Prognosis ; }, abstract = {Past and present asbestos use will reflect in increasing numbers of mesothelioma cases in the next decades, diagnosed at a late stage and with a dismal prognosis. This stresses the need for early detection tools, which could improve patients' survival. Recently, breath analysis as a noninvasive and fast diagnostic tool has found its way into biomedical research. High-throughput breathomics uses spectrometric, chromatographic, and sensor techniques to diagnose asbestos-related pulmonary diseases based upon volatile organic compounds (VOC) in breath. This article reviews the state-of-the-art available breath analyzing techniques and provides the insight in the current use of VOCs as early diagnostic or prognostic biomarkers of mesothelioma to stimulate further research in this field. Cancer Epidemiol Biomarkers Prev; 23(6); 898-908. ©2014 AACR.}, }
@article {pmid24684899, year = {2014}, author = {Ascoli, V and Romeo, E and Carnovale Scalzo, C and Cozzi, I and Ancona, L and Cavariani, F and Balestri, A and Gasperini, L and Forastiere, F}, title = {Familial malignant mesothelioma: a population-based study in central Italy (1980-2012).}, journal = {Cancer epidemiology}, volume = {38}, number = {3}, pages = {273-278}, doi = {10.1016/j.canep.2014.02.014}, pmid = {24684899}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/poisoning ; Environmental Exposure/adverse effects/statistics &amp; numerical data ; Female ; Genetic Predisposition to Disease ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology/genetics ; Male ; Mesothelioma/*epidemiology/etiology/genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects/statistics &amp; numerical data ; }, abstract = {Malignant mesothelioma is a sporadic cancer linked to asbestos exposure. Its occurrence among blood relatives (familial mesothelioma) may point to genetic susceptibility or shared exposures. The burden of the familial disease is unknown. The aims of the study were to assess at population level the proportion of familial mesotheliomas among all mesotheliomas and to investigate the family history of cancer among relatives of mesothelioma cases. We actively searched familial clusters based on a mesothelioma registry from central Italy (5.5 million people, 10% of the Italian population) of the National Mesothelioma Register network (ReNaM) as well as a pathology-based archive. Among 997 incident mesotheliomas recorded in a 32-year-period (1980-2012), we detected 13 clusters and 34 familial cases, accounting for 3.4% of all mesotheliomas. The most common clusters where those with affected siblings and unaffected parents. Asbestos exposure was occupational (n=7 clusters), household (n=2), environmental (n=1), or not attributable for insufficient information (n=3). There were 25 additional cancers in nine families. Some were cancer sites for which there is sufficient evidence (lung and larynx) or limited evidence (stomach and colon) of causal association with asbestos. The results suggest potential genetic recessive effects in mesothelioma that interact with asbestos exposure, but it is not possible to estimate the specific proportion attributable to each of these components.}, }
@article {pmid24675492, year = {2014}, author = {Komurcuoglu, B and Cirak, AK and Kirakli, SC and Polat, G and Yucel, N and Usluer, O and Erer, O and Balci, G and Gayaf, M and Guldaval, F and Aktogu, S and Guclu, S and Ozsoz, A and Halilcolar, H}, title = {Prognostic factors affecting survival in malignant pleural mesothelioma: analysis of 125 subjects.}, journal = {Tumori}, volume = {100}, number = {1}, pages = {55-59}, doi = {10.1700/1430.15816}, pmid = {24675492}, issn = {2038-2529}, mesh = {Age Factors ; Aged ; Asbestos/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/blood/*mortality/*pathology/therapy ; Lymphatic Metastasis ; Male ; Mesothelioma/blood/*mortality/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/blood/*mortality/*pathology/therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Smoking/adverse effects ; Turkey/epidemiology ; }, abstract = {AIM OF THE STUDY: Determining the pre-treatment prognostic factors in malignant pleural mesothelioma is important in terms of estimating the course of the disease and selecting patients who are candidate for multimodal therapy. The aim of the study was to determine the prognostic factors affecting survival in patients with malignant pleural mesothelioma.<br><br>STUDY DESIGN: One hundred and twenty-five patients who had been diagnosed histologically as having malignant pleural mesothelioma over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC) and serum LDH values, histology, performance score and stage of disease were examined.<br><br>RESULTS: Advanced clinical stage, N2 nodal involvement and the presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be a poor prognostic factor independently of other factors.<br><br>CONCLUSIONS: We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate for multimodal treatment and in estimating the prognosis.}, }
@article {pmid24675242, year = {2014}, author = {Robella, M and Vaira, M and Mellano, A and Marsanic, P and Cinquegrana, A and Borsano, A and Barbera, M and Caneparo, A and Siatis, D and Sottile, A and De Simone, M}, title = {Treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery and HIPEC.}, journal = {Minerva chirurgica}, volume = {69}, number = {1}, pages = {9-15}, pmid = {24675242}, issn = {0026-4733}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*therapeutic use ; Biomarkers, Tumor/analysis ; Chemotherapy, Adjuvant ; Cisplatin/administration &amp; dosage ; Combined Modality Therapy ; Doxorubicin/administration &amp; dosage ; Female ; Humans ; Hyperthermia, Induced ; Infusions, Parenteral ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Laparoscopy ; *Laparotomy ; Lung Neoplasms/chemistry/diagnosis/drug therapy/*surgery ; Male ; Mesothelioma/chemistry/diagnosis/drug therapy/*surgery ; Mesothelioma, Malignant ; Middle Aged ; Patient Selection ; Peritoneal Neoplasms/chemistry/diagnosis/drug therapy/*surgery ; Preoperative Care ; Treatment Outcome ; Young Adult ; }, abstract = {AIM: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC).<br><br>METHODS: This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival.<br><br>RESULTS: The median follow-up period was 72 months (range 1-235 months). Thirty-five patients (83.3%) presented epithelial tumors and 7 were affected by multicystic mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate was 35.7% associated to a perioperative mortality of 7.1%. Median overall survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%, respectively.<br><br>CONCLUSION: The treatment of DMPM by CRS+HIPEC in selected patients is a feasible technique that allows to achieve encouraging results in terms of overall survival rate, with an acceptable morbidity rate. Further investigations are needed to clarify the role and the timing of this promising technique.}, }
@article {pmid24658968, year = {2014}, author = {Schonfeld, SJ and McCormack, V and Rutherford, MJ and Schüz, J}, title = {Regional variations in German mesothelioma mortality rates: 2000–2010.}, journal = {Cancer causes &amp; control : CCC}, volume = {25}, number = {5}, pages = {615-624}, doi = {10.1007/s10552-014-0368-4}, pmid = {24658968}, issn = {1573-7225}, support = {13275/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/poisoning ; Cohort Studies ; Female ; Germany/epidemiology ; Germany, East/epidemiology ; Germany, West/epidemiology ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; }, abstract = {PURPOSE: Germany has one of the highest age-adjusted mesothelioma mortality rates worldwide. As mesothelioma occurs ≥ 30 years after asbestos exposure, contemporary rates likely reflect exposures in the 1960-1970s. During this period, political division between West and East Germany led to differences regarding the import and consumption of asbestos. It is unclear whether mesothelioma rates also differ between these formerly separate countries which are now served by similar health and mortality reporting systems, thereby facilitating regional comparisons.<br><br>METHODS: We examined regional, temporal, and sex variations in mesothelioma mortality rates in Germany in 2000-2010, collapsing the federal states into West Germany, East Germany, and Berlin. We calculated truncated (&#x2265; 40 years) age-standardized mesothelioma mortality rates (ASRs(40+)) per 100,000 person-years, estimated sex-stratified mortality rate ratios (MRRs) (95 % confidence intervals (CIs)), adjusted for age and calendar year from Poisson models, and fitted age-period-cohort models.<br><br>RESULTS: There were 12,854 mesothelioma deaths at ages &#x2265; 40 years in Germany during 2000-2010. ASRs(40+) were higher in West (males 4.4; females 0.8) than East (males 1.7; females 0.6) Germany. MRRs for West versus East Germany were 2.68 (95 % CI 2.48-2.88) among males and 1.42 (95 % CI 1.27-1.59) among females. In both regions, mortality rates increased for birth cohorts until the mid 1940s and subsequently declined. The country's peak mesothelioma burden is predicted to occur by 2020.<br><br>CONCLUSIONS: Geographical differences in mesothelioma mortality rates are consistent with heterogeneous historical asbestos exposures. Differences may exist for other asbestos-related cancers and should be investigated in analytic studies with individual asbestos exposure information.}, }
@article {pmid24654472, year = {2014}, author = {Okuda, T and Ogino, Y and Yamashita, S and Ishii, H and Kin, S and Nagata, A and Otsubo, M and Kataoka, H and Kitawaki, J}, title = {Diagnostic laparoscopy identifies a peritoneal adenomatoid-like mesothelioma masquerading as ovarian cancer: a case report.}, journal = {European journal of gynaecological oncology}, volume = {35}, number = {1}, pages = {91-94}, pmid = {24654472}, issn = {0392-2936}, mesh = {Adenomatoid Tumor/diagnosis/pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Laparoscopy ; Mesothelioma/diagnosis/pathology/*surgery ; Middle Aged ; Ovarian Neoplasms/diagnosis/pathology/surgery ; Peritoneal Neoplasms/diagnosis/pathology/surgery ; }, abstract = {The authors report a rare case of peritoneal adenomatoid mesothelioma in a woman with no history of asbestos exposure. A 61-year-old woman was originally suspected of having a bilateral ovarian tumor based on chest radiography and magnetic resonance imaging (MRI). Upon referral to our hospital, the presence of two solid masses was confirmed by enhanced MRI and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG-PET/CT). Physical examination was normal, as were serum concentrations of the tumor markers CA 19-9, CA 125, and CEA. Laparoscopic surgery showed a right ovarian tumor and laparoscopic right salpingo-oophorectomy and adhesiotomy were performed. Two months later, the patient underwent laparoscopic segmental resection of the sigmoid colon, with histological analysis identifying an adenomatoid-like tumor. The final diagnosis was peritoneal adenomatoid-like mesothelioma with invasion of the right ovary. This case report demonstrates that imaging techniques must be coupled with laparoscopic surgery for an accurate diagnosis of peritoneal mesothelioma.}, }
@article {pmid24649303, year = {2014}, author = {Hirohashi, T and Igarashi, K and Abe, M and Maeda, M and Hino, O}, title = {Retrospective analysis of large-scale research screening of construction workers for the early diagnosis of mesothelioma.}, journal = {Molecular and clinical oncology}, volume = {2}, number = {1}, pages = {26-30}, pmid = {24649303}, issn = {2049-9450}, abstract = {The early diagnosis of mesothelioma, an aggressive malignant tumor, is considered to be important for prognosis. X-ray is commonly used for the assessment of a mass in a population exhibiting a risk factor. However, there are currently no available studies indicating that such an assessment may be used to achieve early diagnosis and improve the patient's outcome. We previously reported that N-ERC/mesothelin may be a useful blood tumor marker for mesothelioma. In order to investigate whether this tumor marker is useful for early diagnosis in a mass examination, in 2007 we initiated a 5-year large-scale screening of construction workers with a risk of asbestos exposure in Japan. Blood samples were collected annually and N-ERC/mesothelin levels were determined. Based on the results of those findings, along with medical history and related data, we screened the participants to identify a high-risk population. As a result, 62 subjects were identified among ~40,000 participants as the high-risk population. Two of these 62 participants subsequently developed mesothelioma, although the remaining participants have not yet developed mesothelioma. In conclusion, N-ERC/mesothelin may be useful as a blood tumor marker in the early diagnosis of mesothelioma in a mass examination. A future prospective study to confirm the findings of this research screening is currently under planning.}, }
@article {pmid24649274, year = {2013}, author = {Fukuoka, K and Kuribayashi, K and Yamada, S and Tamura, K and Tabata, C and Nakano, T}, title = {Combined serum mesothelin and carcinoembryonic antigen measurement in the diagnosis of malignant mesothelioma.}, journal = {Molecular and clinical oncology}, volume = {1}, number = {6}, pages = {942-948}, pmid = {24649274}, issn = {2049-9450}, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor associated with asbestos exposure. The identification of a marker specific for MM may be of considerable value for the early detection of this tumor and may be used in particular to screen groups with a history of asbestos exposure. The aim of this study was to evaluate serum soluble mesothelin-related peptide (SMRP) levels as a diagnostic marker for MM and investigate whether its diagnostic value is enhanced by combination with other biomarkers. Serum SMRP levels were measured using a quantitative enzyme-linked immunosorbent assay in 96 patients with MM, 55 patients with lung cancer and 39 individuals with a history of asbestos exposure. Receiver operating characteristic curves were constructed for performance evaluation. Stepwise logistic regression analysis was used to select marker combinations (MCs). Serum SMRP levels in patients with MM were significantly higher compared to those in the other groups (P<0.001). The sensitivity of SMRP levels in diagnosing MM was 56% and its specificity for MM vs. lung cancer and individuals with asbestos exposure was 87 and 92%, respectively. The area under the curve (AUC) was 0.76 [95% confidence interval (CI): 0.68-0.83] for the differentiation between MM and lung cancer and 0.78 (95% CI: 0.71-0.86) for the differentiation between MM and individuals with asbestos exposure. For the MC of presence of effusion, SMRP and carcinoembryonic antigen (CEA) levels, the AUC for the differentiation between MM and lung cancer (0.92; 95% CI: 0.88-0.97) and the differentiation between MM and individuals with asbestos exposure (0.93; 95% CI: 0.87-1.0) was significantly higher compared to that for SMRP alone (P=0.0001 and 0.0058, respectively). While the specificity of this MC was comparable to SMRP alone, its sensitivity was ∼20% higher compared to that of SMRP alone. Therefore, combining SMRP and CEA improves the diagnostic performance of SMRP alone. A combination of serum biomarkers, including SMRP, may facilitate the non-invasive diagnosis of MM.}, }
@article {pmid24645844, year = {2014}, author = {Kaya, H and Sezgı, C and Tanrıkulu, AC and Taylan, M and Abakay, O and Sen, HS and Abakay, A and Kucukoner, M and Kapan, M}, title = {Prognostic factors influencing survival in 35 patients with malignant peritoneal mesothelioma.}, journal = {Neoplasma}, volume = {61}, number = {4}, pages = {433-438}, doi = {10.4149/neo_2014_053}, pmid = {24645844}, issn = {0028-2685}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/etiology/*mortality/pathology ; Male ; Mesothelioma/etiology/*mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Peritoneal Neoplasms/etiology/*mortality/pathology ; Pleural Neoplasms/etiology/*mortality/pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {Malignant mesothelioma is a rare but highly lethal form of cancer that affects the serosal membranes. Malignant peritoneal mesothelioma (MPM) is the second most common form of malignant mesothelioma (pleural mesothelioma is the most common). The aim of this study was to evaluate prognostic factors influencing the survival of patients with MPM. A retrospective analysis was performed on 35 patients who were admitted to our hospital between March 2005 and July 2013. The patients' demographic and clinical data, laboratory results, radiological signs, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and treatment outcomes were evaluated. The mean age of the 35 patients was 59.0±14.4 years, the mean survival time was 16.2±12.9 months, and the majority of the histopathological types of MPM were epithelial (68.6%). 82.9% of the patients had been exposed to asbestos, and the mean duration of exposure was 28.3±14.5 years. The most frequent symptoms were abdominal distention/pain, weight loss, dyspnea, and chest pain. The mean interval between the onset of symptoms and the diagnosis was 4.6±3.3 months. Platinum-based combination chemotherapy in combination with supportive care was used in the treatment of 68.6% of the patients, while supportive treatment alone was used in the others. Our results revealed that patients who were >60 years old (p=0.019), who were exposed to asbestos >20 years (p=0.033), who had an ECOG PS of 3 (p=0.000) were more likely to have a poor MPM prognosis.In conclusion, increased age, duration of environmental asbestos exposure and ECOG PS are important factors that influence the prognosis of MPM patients.}, }
@article {pmid24630637, year = {2014}, author = {Galateau-Sallé, F and Gilg Soit Ilg, A and Le Stang, N and Brochard, P and Pairon, JC and Astoul, P and Frenay, C and Blaizot, G and Chamming's, S and Ducamp, S and Rousvoal, T and de Quillacq, A and Abonnet, V and Abdalsamad, I and Begueret, H and Brambilla, E and Capron, F and Copin, MC and Danel, C and de Lajartre, AY and Foulet-Roge, A and Garbe, L and Groussard, O and Giusiano, S and Hofman, V and Lantuejoul, S and Piquenot, JM and Rouquette, I and Sagan, C and Thivolet-Bejui, F and Vignaud, JM and Scherpereel, A and Jaurand, MC and Jean, D and Hainaut, P and Chérié-Challine, L and Goldberg, M and Luce, D and Imbernon, E}, title = {[The French mesothelioma network from 1998 to 2013].}, journal = {Annales de pathologie}, volume = {34}, number = {1}, pages = {51-63}, doi = {10.1016/j.annpat.2014.01.009}, pmid = {24630637}, issn = {0242-6498}, mesh = {France ; Humans ; *Mesothelioma/pathology ; Pathology, Clinical ; *Pleural Neoplasms/pathology ; Referral and Consultation ; Societies, Medical ; Time Factors ; }, abstract = {Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.}, }
@article {pmid24630634, year = {2014}, author = {Mery, &#xc9; and Hommell-Fontaine, J and Capovilla, M and Chevallier, A and Bibeau, F and Croce, S and Dartigues, P and Kaci, R and Lang-Averous, G and Laverriere, MH and Leroux-Broussier, A and Poizat, F and Robin, N and Valmary-Degano, S and Verriele-Beurrier, V and Villeneuve, L and Isaac, S}, title = {[Peritoneal malignant mesothelioma: review and recent data].}, journal = {Annales de pathologie}, volume = {34}, number = {1}, pages = {26-33}, doi = {10.1016/j.annpat.2014.01.004}, pmid = {24630634}, issn = {0242-6498}, mesh = {Diagnosis, Differential ; Humans ; *Lung Neoplasms/pathology ; *Mesothelioma/pathology ; Mesothelioma, Malignant ; *Peritoneal Neoplasms/pathology ; }, abstract = {Peritoneal malignant mesothelioma is a rare tumor, less common than its pleural counterpart. It develops from the mesothelial cells overlying peritoneum and preferentially occurs in male, with an average age ranging from 47 to 60.5 years. Asbestos whose impact is less strong than in pleural mesothelioma, SV 40 virus, chronic peritonitis could be implicated as factors favoring the development of peritoneal mesothelioma. Clinical symptoms are not specific, and the imagery remains little or not contributive. The 2004 WHO classification recognizes 3 different types, which differ in terms of presentation and prognosis: diffuse epithelioid mesothelioma (the most common), sarcomatoid mesothelioma and biphasic mesothelioma. Many variants are described within these groups. Immunohistochemistry is mandatory to affirm or disprove peritoneal malignant mesothelioma diagnosis, based on a panel of antibodies divided in positive markers and negative markers. Indeed an accurate diagnosis is necessary to define a therapeutic strategy more and more frequently based on the combination of radical surgery and hyperthermic intra peritoneal chemotherapy. Such an approach significantly improves the prognosis of these aggressive diseases.}, }
@article {pmid24620488, year = {2014}, author = {Reeve, P}, title = {Tackling asbestos- the hidden killer.}, journal = {Health estate}, volume = {68}, number = {2}, pages = {27-29}, pmid = {24620488}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/etiology/mortality/*prevention &amp; control ; Health Facility Environment/legislation &amp; jurisprudence/*standards ; Humans ; Lung Neoplasms/etiology/mortality/*prevention &amp; control ; Maintenance and Engineering, Hospital/legislation &amp; jurisprudence/methods/*standards ; Mesothelioma/etiology/mortality/*prevention &amp; control ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects/legislation &amp; jurisprudence/*prevention &amp; control ; Risk Assessment/methods ; United Kingdom/epidemiology ; }, }
@article {pmid24615668, year = {2014}, author = {Kurz, S and Grohé, C}, title = {[Malignant pleural mesothelioma: new aspects of medical therapy].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {68}, number = {5}, pages = {329-335}, doi = {10.1055/s-0034-1365025}, pmid = {24615668}, issn = {1438-8790}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Chemoradiotherapy/*trends ; Combined Modality Therapy/trends ; Humans ; Immunotherapy/*trends ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; }, abstract = {Malignant pleural mesothelioma, a typical long-term consequence of exposure to asbestos, represents a therapeutic challenge. In the early stages of the disease, trimodal therapy combining surgery, radiation and chemotherapy is used as standard care. In advanced stages, the combination of cisplatin and pemetrexed has been approved as first-line therapy, but there is a lack of randomised controlled drug trials for second-line treatment. Monotherapy with pemetrexed, vinorelbine or gemcitabine may provide some survival benefit compared to treatment aiming at symptom control only. Immunotherapy seems to be a promising new concept. The so-called frustrated phagocytosis, with continuing antigen presentation leading to persisting local inflammation and antigen tolerance, can be interrupted by blocking the T-cell surface protein CTLA-4. The monoclonal antibodies ipilimumab and tremelimumab that block CTLA-4 can stimulate immune response and thus increase the number of tumor-infiltrating lymphocytes. Clinical studies exploring this avenue of treatment are being awaited with great excitement.}, }
@article {pmid24615665, year = {2014}, author = {Biesterfeld, S and Schramm, M and Schad, A and Pomjanski, N}, title = {[Pleural effusion cytology of asbestos-associated malignant mesothelioma and lung carcinoma in the diagnosis of occupational diseases by the statutory accident insurance funds].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {68}, number = {4}, pages = {270-276}, doi = {10.1055/s-0034-1365157}, pmid = {24615665}, issn = {1438-8790}, mesh = {Aged ; Aged, 80 and over ; Asbestosis/*complications/*pathology ; Humans ; Insurance, Accident ; Lung Neoplasms ; Male ; Mesothelioma/*complications/*pathology ; Occupational Diseases/complications/pathology ; Pleural Effusion/*etiology/*pathology ; }, abstract = {Pleural effusion often represents the first clinical symptom of lung carcinoma and malignant mesothelioma. As pleural punctation is performed quite early in the diagnostic procedure, effusion cytology frequently gives the first evidence about the presence of tumour cells and tumor histogenesis. In this study, we report on seven cases which were evaluated in our institution for the Employers' Liability Insurance Association, based solely on cytology findings.The mean age of the seven patients with a given long-term asbestos exposure during their working life was 81.7 years. On average eight smears per patient were investigated. In addition to routine cytology, immunocytochemistry, DNA image cytometry, AgNOR-analysis and fluorescence in situ hybridization were applied in a case-specific way. The results were interpreted against the clinical and occupational history of the respective patient.Definitive diagnosis could be made in six cases. In three of them, the diagnosis of malignant mesothelioma was made. Two cases were diagnosed as malignant effusion due to metastatic lung cancer. In one case, cells of high-grade Non-Hodgkin's lymphoma (NHL) were diagnosed and a malignant mesothelioma was excluded. In the last case, malignant mesothelioma could not be diagnosed unequivocally by cytology. In all seven cases, our interpretation was accepted by Employers' Liability Insurance Association. The five mesothelioma or lung cancer cases were accepted as asbestos-associated occupational disease, while the NHL case was rejected. In the last case, malignant mesothelioma was diagnosed later by autopsy, and the case was retroactively accepted as occupational disease.Cytology-based tumor diagnosis including adjuvant methods is a useful and reliable approach in cases of asbestos-associated tumours. Acceptance of occupational disease on the basis of cytological diagnoses even by the Employers' Liability Insurance Association helps avoid invasive pleural or lung biopsies in cases with an unequivocally positive effusion cytology of lung cancer or malignant mesothelioma.}, }
@article {pmid24614240, year = {2014}, author = {Bayram, M and Bakan, ND}, title = {Environmental exposure to asbestos: from geology to mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {20}, number = {3}, pages = {301-307}, doi = {10.1097/MCP.0000000000000053}, pmid = {24614240}, issn = {1531-6971}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Geology ; Humans ; Lung Neoplasms/*chemically induced/prevention &amp; control ; Male ; Mesothelioma/*chemically induced/prevention &amp; control ; Risk Factors ; Soil ; *Urbanization ; }, abstract = {PURPOSE OF REVIEW: This article aims to review the geological background of environmental asbestos exposure and the distribution of asbestos-related disease (ARD) in association with naturally occurring asbestos (NOA), and discusses the potential health risks associated with exposure to non-occupational asbestos.<br><br>RECENT FINDINGS: With the motion of continental and oceanic plates, in some parts of the world serpentinites in the lower layer of the oceanic plate move into the continental plate and form the so-called ophiolites. Ophiolites consist of soil and rocks containing serpentine-type asbestos. There is an increase in ARDs in regions close to ophiolites. Indoor exposure and outdoor exposure to NOA, outdoor exposure to industrial asbestos and mines, urbanization and construction works in NOA regions are the known sources and types of environmental asbestos exposure.<br><br>SUMMARY: Although there is an expectance of decline in ARDs caused by industrial exposure to asbestos, the environmental exposure to asbestos is still a challenge waiting to be overcome.}, }
@article {pmid24605531, year = {2014}, author = {Kishimoto, T}, title = {[Asbestos-related diseases].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {72}, number = {2}, pages = {300-305}, pmid = {24605531}, issn = {0047-1852}, mesh = {*Asbestosis ; Humans ; Lung Neoplasms/etiology ; Pleurisy ; }, abstract = {Asbestosis shows peribronchiolar fibrosis with numerous asbestos bodies. Subpleural dots and curvilinear lines in HRCT are good indicators for the diagnosis of asbestosis. Asbestos-related lung cancer in Japanese Compensation System means lung cancer with asbestosis. Furthermore, pleural plaques and the content of asbestos bodies in the lung tissues with the term of occupational asbestos exposure are good indicators. Mesothelioma induced also by the low dense exposure to asbestos. For the definite diagnosis of mesothelioma, we need histological examination using biopsy and immunochemical staining for positive and negative markers. Benign asbestos pleurisy is diagnosed by cytological and biochemical examinations of pleural effusions and pleural biopsy. Diffuse pleural thickening depends on the extent of radiological findings and impairment of pulmonary function with occupational asbestos exposure.}, }
@article {pmid24602395, year = {2014}, author = {Lang-Lazdunski, L}, title = {Surgery for malignant pleural mesothelioma: why, when and what?.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {84}, number = {2}, pages = {103-109}, doi = {10.1016/j.lungcan.2014.01.021}, pmid = {24602395}, issn = {1872-8332}, mesh = {Humans ; Mesothelioma/*surgery ; Palliative Care ; Pleural Neoplasms/*surgery ; Quality of Life ; Thoracic Surgical Procedures/methods ; }, abstract = {Malignant pleural mesothelioma is a fatal cancer developing in the pleural cavity, linked to asbestos exposure. Various therapies have been tried in the past 50 years including surgery, radiotherapy, chemotherapy, immunotherapy and more recently, targeted therapy. Radical surgery remains controversial in malignant pleural mesothelioma and two procedures have been offered in the past to obtain maximal cytoreduction: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). Despite growing evidence that EPP might be detrimental, many believe that radical surgery should still be part of multimodality therapy in patients with malignant pleural mesothelioma. Recent evidence suggests that P/D is well tolerated and produces low mortality and morbidity. The role of adjuvant intrapleural therapies remains to be determined and evaluated in large prospective trials. Pleurectomy/decortication does not jeopardize the chance of having chemotherapy, or chemoradiotherapy either. Many now believe that it should be the default procedure in multimodality regimens. However, this remains to be proven in a large randomized trial. Palliative surgery still has an important role to play in mesothelioma, in establishing or refining diagnosis and in controlling symptoms and improving quality of life in many patients whose life expectancy is limited. Recent progress in molecular analyses and biomarkers should help with patient selection for surgery, immunotherapy and systemic therapies in the near future.}, }
@article {pmid24598827, year = {2014}, author = {Jamal, S and Cheriyan, VT and Muthu, M and Munie, S and Levi, E and Ashour, AE and Pass, HI and Wali, A and Singh, M and Rishi, AK}, title = {CARP-1 functional mimetics are a novel class of small molecule inhibitors of malignant pleural mesothelioma cells.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e89146}, pmid = {24598827}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Antineoplastic Agents/*pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Survival/drug effects ; Cisplatin/pharmacology ; Drug Screening Assays, Antitumor ; Epithelial-Mesenchymal Transition ; Humans ; Lung Neoplasms ; Matrix Metalloproteinases/metabolism ; Membrane Glycoproteins/metabolism ; Mesothelioma ; Mesothelioma, Malignant ; Molecular Mimicry ; NF-kappa B/metabolism ; Neoplasm Invasiveness ; Phosphorylation ; Pleural Neoplasms ; Protein Processing, Post-Translational/drug effects ; Signal Transduction ; Spiro Compounds/*pharmacology ; Thiadiazoles/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of pro-apoptotic stress-activated protein kinases (SAPKs) p38 and JNK, elevated CARP-1 expression, cleavage of PARP1, and loss of the oncogene c-myc as well as mitotic cyclin B1. Treatments of MPM cells with CFM-4 resulted in depletion of NF-κB signaling inhibitor ABIN1 and Inhibitory κB (IκB)α and β, while increasing expression of pro-apoptotic death receptor (DR) 4 protein. CFM-4 enhanced expression of serine-phosphorylated podoplanin and cleavage of vimetin. CFMs also attenuated biological properties of the MPM cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Both podoplanin and vimentin regulate processes of cell motility and invasion, and their expression often correlates with metastatic disease, and poor prognosis. The fact that phosphorylation of serines in the cytoplasmic domain of podoplanin interferes with processes of cellular motility, CFM-4-dependent elevated phosphorylated podoplanin and cleavage of vimentin underscore a metastasis inhibitory property of these compounds, and suggest that CFMs and/or their future analogs have potential as anti-MPM agents.}, }
@article {pmid24598051, year = {2014}, author = {Hiraku, Y and Sakai, K and Shibata, E and Kamijima, M and Hisanaga, N and Ma, N and Kawanishi, S and Murata, M}, title = {Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study.}, journal = {Journal of occupational health}, volume = {56}, number = {3}, pages = {186-196}, doi = {10.1539/joh.13-0231-oa}, pmid = {24598051}, issn = {1348-9585}, mesh = {Aged ; Asbestos/*analysis ; Biomarkers/chemistry ; Carcinogenesis ; Carcinogens/*analysis ; *DNA Damage ; Female ; Guanine/*analogs &amp; derivatives/metabolism ; Humans ; Lung/*chemistry/metabolism/pathology ; Lung Neoplasms/pathology ; Male ; Mesothelioma/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure ; Pilot Projects ; Staining and Labeling ; }, abstract = {OBJECTIVES: Asbestos causes lung cancer and malignant mesothelioma, and chronic inflammation is considered to participate in carcinogenesis. However, biomarkers to evaluate its carcinogenic risk have not been established. Reactive oxygen/nitrogen species are generated in biological systems under inflammatory conditions and may contribute to carcinogenesis by causing DNA damage. In this study, we examined the relationship between the formation of 8-nitroguanine (8-nitroG), a mutagenic DNA lesion formed during inflammation, and asbestos contents in human lung tissues.<br><br>METHODS: We obtained non-tumor lung tissues from patients with (n=15) and without mesothelioma (n=21). The expression of 8-nitroG and related molecules was examined by immunohistochemistry, and their staining intensities were semiquantitatively evaluated. Asbestos contents in lung tissues were analyzed by analytical transmission electron microscopy.<br><br>RESULTS: In subjects without mesothelioma, staining intensities of 8-nitroG and apurinic/apyrimidinic endonuclease 1 (APE1) were significantly correlated with total asbestos and amphibole contents (p<0.05), but not with chrysotile content. In mesothelioma patients, their staining intensities were not correlated with asbestos contents. The double immunofluorescence technique revealed that APE1 was expressed in 8-nitroG-positive cells, suggesting that abasic sites were formed possibly due to the removal of 8-nitroG. The staining intensities of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative DNA lesion, and its repair enzyme 8-oxoguanine DNA-glycosylase were correlated with age (p<0.05), but not with asbestos contents in subjects without mesothelioma.<br><br>CONCLUSIONS: This is the first study to demonstrate that 8-nitroG formation is associated with asbestos contents in human lung tissues. This finding raises a possibility that 8-nitroG serves as a biomarker that can be used to evaluate asbestos exposure and carcinogenic risk.}, }
@article {pmid24595274, year = {2014}, author = {Cheng, NC and van Zandwijk, N and Reid, G}, title = {Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e90374}, pmid = {24595274}, issn = {1932-6203}, mesh = {Cell Adhesion/*drug effects ; Cell Line, Tumor ; Humans ; Integrin alphaVbeta3/*antagonists &amp; inhibitors ; Mesothelioma/*pathology ; Neoplasm Invasiveness/*prevention &amp; control ; Pleural Neoplasms/*pathology ; Receptors, Vitronectin/*antagonists &amp; inhibitors ; Snake Venoms/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an almost invariably fatal, asbestos-related malignancy arising from the mesothelial membrane lining the thoracic cavities. Despite some improvements in treatment, therapy is not considered curative and median survival following diagnosis is less than 1 year. Although still classed as a rare cancer, the incidence of MPM is increasing, and the limited progress in treating the disease makes the identification of new therapies a priority. As there is evidence for expression of the integrins αvβ3 and αvβ5 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin αv heterodimer with high specificity for αvβ3 and αvβ5. In mesothelial cells (MC) and 7 MPM cell lines, growth inhibition by cilengitide was associated with the expression level of its target integrins. Furthermore, cilengitide caused cell detachment and subsequent death of anoikis-sensitive cells. It also suppressed invasion of MPM cells in monolayer and three-dimensional cultures. Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of αvβ3 and αvβ5.}, }
@article {pmid24592197, year = {2014}, author = {Sezgi, C and Taylan, M and Sen, HS and Evliyaoğlu, O and Kaya, H and Abakay, O and Abakay, A and Tanrıkulu, AC and Senyiğit, A}, title = {Oxidative status and acute phase reactants in patients with environmental asbestos exposure and mesothelioma.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {902748}, pmid = {24592197}, issn = {1537-744X}, mesh = {Acute-Phase Proteins/*analysis ; Adult ; Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Copper/blood ; Cross-Sectional Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*blood/chemically induced/diagnosis ; Male ; Mesothelioma/*blood/chemically induced/diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Oxidants/blood ; *Oxidative Stress ; }, abstract = {BACKGROUND AND OBJECTIVES: The aim of this study was to investigate inflammatory indicators and oxidative status in patients with asbestos exposure with and without mesothelioma and to compare results with data from healthy subjects.<br><br>METHODS: Eighty people with exposure to environmental asbestos and without any disease, 46 mesothelioma patients, and a control group of 50 people without exposure to environmental asbestos were enrolled in this prospective study. Serum total oxidant level (TOL), total antioxidant capacity (TAC), and oxidative stress index (OSI), CRP, transferrin, ceruloplasmin, &#x3b1;-1 antitrypsin, ferritin, and copper levels were measured.<br><br>RESULTS: Mesothelioma group exhibited higher TOL, OSI, &#x3b1;1-antitrypsin, ferritin and copper levels as compared to the other groups (P < 0.001, P = 0.007, P < 0.0001, P < 0.001, and P < 0.001, resp.). Transferrin was lower in the mesothelioma group than in the other two groups (P < 0.001). The asbestos group had higher TOL, TAC, &#x3b1;1-antitrypsin, and transferrin levels (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.), as well as lower OSI and ferritin levels as compared to the control group (P < 0.001 and P < 0.001).<br><br>CONCLUSIONS: We believe that elevated acute phase reactants and oxidative stress markers (TOL and OSI) in the mesothelioma group can be used as predictive markers for the development of asbestos-related malignancy.}, }
@article {pmid24577054, year = {2014}, author = {Mirabelli, D and Zugna, D}, title = {Comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)'.}, journal = {British journal of cancer}, volume = {111}, number = {8}, pages = {1675}, pmid = {24577054}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, }
@article {pmid24573972, year = {2014}, author = {Abakay, O and Tanrikulu, AC and Palanci, Y and Abakay, A}, title = {The value of inflammatory parameters in the prognosis of malignant mesothelioma.}, journal = {The Journal of international medical research}, volume = {42}, number = {2}, pages = {554-565}, doi = {10.1177/0300060513504163}, pmid = {24573972}, issn = {1473-2300}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Inflammation/*immunology ; Lung Neoplasms/*immunology/*mortality ; Lymphocyte Count ; Lymphocytes/immunology ; Male ; Mesothelioma/*immunology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Neutrophils/immunology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVE: This study investigated the relationship between potential prognostic parameters that may be associated with increased inflammation and survival in patients with malignant mesothelioma (MM).<br><br>METHODS: This retrospective study assessed potential prognostic parameters measured at the time of MM diagnosis. Data on asbestos exposure, histopathological subtype of MM and laboratory parameters were collected.<br><br>RESULTS: In 155 patients with MM (90 male), mean survival time was 13.9 months. In univariate analysis, age &#x2265; 60 years and neutrophil-to-lymphocyte ratio (NLR) &#x2265; 3 were associated with significantly shortened median survival times. In multivariate analysis, nonepithelial subtype, red cell distribution width (RDW) &#x2265; 20% and NLR &#x2265; 3 were associated with significantly shortened median survival times. Mortality rate was increased 2.77-, 1.67- and 1.52-fold in patients with RDW &#x2265; 20%, NLR &#x2265; 3 and nonepithelial subtype, respectively. Nonepithelial subtype, white blood cell count &#x2265; 11 200 &#xb5;l and platelet-to-lymphocyte ratio &#x2265; 300 at baseline were associated with a heightened NLR value.<br><br>CONCLUSIONS: The NLR and RDW were significant predictive factors for MM prognosis.}, }
@article {pmid24567297, year = {2014}, author = {Sage, EK and Kolluri, KK and McNulty, K and Lourenco, Sda S and Kalber, TL and Ordidge, KL and Davies, D and Gary Lee, YC and Giangreco, A and Janes, SM}, title = {Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma.}, journal = {Thorax}, volume = {69}, number = {7}, pages = {638-647}, pmid = {24567297}, issn = {1468-3296}, support = {091730/WT_/Wellcome Trust/United Kingdom ; 260290/ERC_/European Research Council/International ; G1000355/MRC_/Medical Research Council/United Kingdom ; WT091730AIA/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Administration, Topical ; Animals ; Apoptosis/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Infusions, Intravenous ; Lung Neoplasms/*metabolism/pathology ; Mesenchymal Stem Cell Transplantation/*methods ; Mesenchymal Stem Cells/metabolism/*physiology ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Pleural Neoplasms/*metabolism/pathology ; TNF-Related Apoptosis-Inducing Ligand/metabolism/*pharmacology ; Transfection ; Tumor Burden/drug effects ; Tumor Cells, Cultured ; }, abstract = {Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC homing was delineated using dual fluorescence and bioluminescent imaging, and we observed that higher levels of MSC engraftment occur after intravenous delivery compared with intrapleural delivery of MSCs. Finally, we show that intravenous delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma tumour growth in vivo via an increase in tumour cell apoptosis.}, }
@article {pmid24564337, year = {2014}, author = {Robinson, C and Woo, S and Nowak, AK and Lake, RA}, title = {Dietary vitamin D supplementation does not reduce the incidence or severity of asbestos-induced mesothelioma in a mouse model.}, journal = {Nutrition and cancer}, volume = {66}, number = {3}, pages = {383-387}, doi = {10.1080/01635581.2013.878733}, pmid = {24564337}, issn = {1532-7914}, mesh = {Animals ; Asbestos/*toxicity ; Dietary Supplements ; Disease Models, Animal ; Mesothelioma/*chemically induced/diet therapy/epidemiology/mortality/*prevention &amp; control ; Mice, Transgenic ; Vitamin D/blood/*pharmacology ; }, abstract = {Epidemiological studies suggest that vitamin and mineral intake is associated with cancer incidence. A prevention strategy based on diet or dietary supplementation could have enormous benefit, both directly, by preventing disease, and indirectly by alleviating fear in millions of people worldwide who have been exposed to asbestos. We have previously shown that dietary supplementation with the antioxidants vitamins A, E, and selenium does not affect overall survival nor the time to progression of asbestos-induced mesothelioma in MexTAg mice. Here we have extended our analysis to vitamin D. We compared survival of asbestos-exposed MexTAg mice provided with diets that were deficient or supplemented with 4500 IU/kg vitamin D (cholecalciferol). Survival of supplemented mice was significantly shorter than mice given a standard AIN93 diet containing 1000 IU/kg cholecalciferol (median survival was 29 and 32.5 weeks respectively). However, mice deficient in vitamin D had the same rate of mesothelioma development as control mice. Neither the latency time from asbestos exposure to diagnosis nor disease progression after diagnosis were significantly different between mice on these diets. We conclude that vitamin D is unlikely to moderate the incidence of disease in asbestos-exposed populations or to ameliorate the pathology in patients with established mesothelioma.}, }
@article {pmid24562347, year = {2014}, author = {Truini, A and Coco, S and Alama, A and Genova, C and Sini, C and Dal Bello, MG and Barletta, G and Rijavec, E and Burrafato, G and Boccardo, F and Grossi, F}, title = {Role of microRNAs in malignant mesothelioma.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {71}, number = {15}, pages = {2865-2878}, pmid = {24562347}, issn = {1420-9071}, mesh = {Animals ; Biomarkers, Tumor/genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; Lung/metabolism/pathology ; Lung Neoplasms/diagnosis/*genetics/therapy ; Mesothelioma/diagnosis/*genetics/therapy ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Oncogenes ; Prognosis ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor, mainly derived from the pleura, which is predominantly associated with exposure to asbestos fibers. The prognosis of MM patients is particularly severe, with a median survival of approximately 9-12 months and latency between exposure and diagnosis ranging from 20-50 years (median 30 years). Emerging evidence has demonstrated that tumor aggressiveness is associated with genome and gene expression abnormalities; therefore, several studies have recently focused on the role of microRNAs (miRNAs) in MM tumorigenesis. miRNAs are small non-protein coding single-stranded RNAs (17-22 nucleotides) involved in numerous cellular processes that negatively regulate gene expression by modulating the expression of downstream target genes. miRNAs are often deregulated in cancer; in particular, the differential miRNA expression profiles of MM cells compared to unaffected mesothelial cells have suggested potential roles of miRNAs as either oncogenes or tumor suppressor genes in MM oncogenesis. In this review, the mechanism of MM carcinogenesis was evaluated through the analysis of the published miRNA expression data. The roles of miRNAs as diagnostic biomarkers and prognostic factors for potential therapeutic strategies will be presented and discussed.}, }
@article {pmid24552091, year = {2014}, author = {Oddone, E and Ferrante, D and Cena, T and Tùnesi, S and Amendola, P and Magnani, C}, title = {[Asbestos cement factory in Broni (Pavia, Italy): a mortality study].}, journal = {La Medicina del lavoro}, volume = {105}, number = {1}, pages = {15-29}, pmid = {24552091}, issn = {0025-7818}, mesh = {Adult ; Asbestos/*adverse effects ; Cause of Death ; Cohort Studies ; Construction Materials/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Young Adult ; }, abstract = {BACKGROUND: To date, no study has reported cause-specific Standardized Mortality Ratios (SMR) for asbestos-cement workers at a manufacturing establishment in Broni (Pavia, Italy). This site is among those specifically targeted by Italian Law for reclamation (SIN - Site of National Interest for remediation).<br><br>OBJECTIVES: To provide cause-specific SMRs for asbestos-cement workers in the Broni (Pavia, Italy) factory, with particular regard to duration of employment and latency.<br><br>METHODS: Cause-specific SMRs for asbestos-cement workers (1296 workers hired since 1/1/1950 and with follow-up period 1/1/1970-30/06/2004: 1254 males and 42 females, 545 deaths, 523 males and 22 females) were calculated using the cause-specific mortality rates for the Lombardy Region. Similarly, for pleural and peritoneal mesothelioma and lung cancer among male workers, SMRs by duration of employment and latency were calculated.<br><br>RESULTS: Significantly increased SMRs were observed among male workers for pleural (SMR 17.99, 95% CI 11.75-26.36) and peritoneal (SMR 10.10, 95% CI 4.05-20.77) mesothelioma and lung cancer (SMR 1.26, 95% CI 1.02-1.55) and among female workers for pleural mesothelioma (SMR 68.90, 95% CI 8.33-248.90) and ovarian cancer (SMR 8.56, 95% CI 1.04-30.91). Only among male workers, was a significant risk trend observed for pleural mesothelioma by duration of employment and for lung cancer by latency. Significantly reduced SMRs were observed, among male workers for all causes of death, cardiovascular and respiratory diseases.<br><br>CONCLUSIONS: The results of this cohort study showed increased SMRs for pleural and peritoneal mesothelioma and lung cancer among male workers and for pleural mesothelioma and ovarian cancer among female workers. These results are consistent with the literature data.}, }
@article {pmid24550969, year = {2013}, author = {Ahmed, I and Ahmed Tipu, S and Ishtiaq, S}, title = {Malignant mesothelioma.}, journal = {Pakistan journal of medical sciences}, volume = {29}, number = {6}, pages = {1433-1438}, pmid = {24550969}, issn = {1682-024X}, abstract = {UNLABELLED: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase -II trials between 1973-2012.<br><br>DATA EXTRACTION: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data.<br><br>CONCLUSION: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high.}, }
@article {pmid24530353, year = {2014}, author = {Chen, T and Nie, H and Gao, X and Yang, J and Pu, J and Chen, Z and Cui, X and Wang, Y and Wang, H and Jia, G}, title = {Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway.}, journal = {Toxicology letters}, volume = {226}, number = {2}, pages = {150-162}, doi = {10.1016/j.toxlet.2014.02.004}, pmid = {24530353}, issn = {1879-3169}, mesh = {Actins/metabolism ; Animals ; Antigens, CD ; Biomarkers/metabolism ; Cadherins/metabolism ; Cell Line, Tumor ; Collagen/metabolism ; Disease Models, Animal ; Epithelial Cells/metabolism/pathology ; *Epithelial-Mesenchymal Transition ; Fibroblasts/metabolism/pathology ; Humans ; Lung/*metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; *Nanotubes, Carbon ; Particle Size ; Phosphorylation ; Pulmonary Fibrosis/chemically induced/*metabolism/pathology ; *Signal Transduction ; Smad2 Protein/*metabolism ; Time Factors ; Transforming Growth Factor beta1/*metabolism ; }, abstract = {Multi-walled carbon nanotubes (MWCNT) are a typical nanomaterial with a wide spectrum of commercial applications. Inhalation exposure to MWCNT has been linked with lung fibrosis and mesothelioma-like lesions commonly seen with asbestos. In this study, we examined the pulmonary fibrosis response to different length of MWCNT including short MWCNT (S-MWCNT, length=350-700nm) and long MWCNT (L-MWCNT, length=5-15μm) and investigated whether the epithelial-mesenchymal transition (EMT) occurred during MWCNT-induced pulmonary fibrosis. C57Bl/6J male mice were intratracheally instilled with S-MWCNT or L-WCNT by a single dose of 60μg per mouse, and the progress of pulmonary fibrosis was evaluated at 7, 28 and 56 days post-exposure. The in vivo data showed that only L-MWCNT increased collagen deposition and pulmonary fibrosis significantly, and approximately 20% of pro-surfactant protein-C positive epithelial cells transdifferentiated to fibroblasts at 56 days, suggesting the occurrence of EMT. In order to understand the mechanism, we used human pulmonary epithelial cell line A549 to investigate the role of TGF-β/p-Smad2 signaling pathway in EMT. Our results showed that L-MWCNT downregulated E-cadherin and upregulated α-smooth muscle actin (α-SMA) protein expression in A549 cells. Taken together, both in vivo and in vitro study demonstrated that respiratory exposure to MWCNT induced length dependent pulmonary fibrosis and epithelial-derived fibroblasts via TGF-β/Smad pathway.}, }
@article {pmid24518925, year = {2014}, author = {Zebedeo, CN and Davis, C and Peña, C and Ng, KW and Pfau, JC}, title = {Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice.}, journal = {Toxicology and applied pharmacology}, volume = {275}, number = {3}, pages = {257-264}, pmid = {24518925}, issn = {1096-0333}, support = {P20 GM103408/GM/NIGMS NIH HHS/United States ; R15 ES021884/ES/NIEHS NIH HHS/United States ; R15 ES-21884/ES/NIEHS NIH HHS/United States ; P20GM103408/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Antinuclear/*blood ; Antigen-Antibody Complex/metabolism ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Autoimmunity/*drug effects ; Biomarkers/blood ; Cell Survival/drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Female ; Inhalation Exposure ; Interleukin-17/*blood ; Kidney/drug effects/immunology/metabolism ; Macrophages/drug effects/immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Spleen/drug effects/immunology/metabolism ; Th1 Cells/drug effects/immunology/metabolism ; Th17 Cells/drug effects/immunology/metabolism ; Th2 Cells/drug effects/immunology/metabolism ; Time Factors ; Tumor Necrosis Factor-alpha/blood ; Up-Regulation ; Zeolites/*toxicity ; }, abstract = {BACKGROUND: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system.<br><br>OBJECTIVES: We performed this study to determine whether erionite evokes autoimmune reactions in mice.<br><br>METHODS: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60&#x3bc;g/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys.<br><br>RESULTS: Erionite and tremolite caused increased cytokine production belonging to the TH17 profile including IL-17, IL-6, TGF-&#x3b2;, and TNF-&#x3b1;. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-&#x3b1; were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite.<br><br>CONCLUSIONS: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities.}, }
@article {pmid24515241, year = {2014}, author = {Gorecka, M and Scott, J and Casey, R and Breen, D}, title = {The journey of mesothelioma: from postmortem to FNA.}, journal = {BMJ case reports}, volume = {2014}, number = {}, pages = {}, pmid = {24515241}, issn = {1757-790X}, mesh = {Aged ; Biopsy, Fine-Needle ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Pleura/pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {A 73-year-old man, non-smoker presented with an 8-week history of left-sided chest pain and shortness of breath on exertion. He had no significant medical history. He worked in construction for 40 years, but denied definite asbestos exposure. His initial chest X-ray demonstrated a large left-sided pleural effusion. Subsequent CT thorax revealed circumferential thickening of the pleura with associated pleural plaques and calcification. A provisional diagnosis of mesothelioma was made. Initial ultrasound-guided thoracocentesis revealed a transudate with negative cytology. In addition, thoracoscopy and CT-guided pleural biopsy failed to obtain a definitive diagnosis. A surgical biopsy was planned, but at the time of admission, the patient developed unilateral neck swelling. Ultrasound-guided fine-needle aspiration (FNA) and core biopsies of the lymph node were diagnostic for pleural mesothelioma. Treatment with palliative chemotherapy was planned, but the patient's clinical status rapidly deteriorated and he passed away prior to the beginning of therapy.}, }
@article {pmid24512074, year = {2014}, author = {Hwang, J and Ramachandran, G and Raynor, PC and Alexander, BH and Mandel, JH}, title = {The relationship between various exposure metrics for elongate mineral particles (EMP) in the taconite mining and processing industry.}, journal = {Journal of occupational and environmental hygiene}, volume = {11}, number = {9}, pages = {613-624}, doi = {10.1080/15459624.2014.890287}, pmid = {24512074}, issn = {1545-9632}, mesh = {Air Pollutants, Occupational/*analysis/chemistry ; Asbestos, Amphibole/analysis/chemistry ; Environmental Monitoring/instrumentation/*methods ; Humans ; Inhalation Exposure/*analysis ; *Iron ; Linear Models ; *Mining ; Minnesota ; Occupational Exposure/*analysis ; Particle Size ; Particulate Matter/*analysis/chemistry ; *Silicates ; }, abstract = {Different dimensions of elongate mineral particles (EMP) have been proposed as being relevant to respiratory health end-points such as mesothelioma and lung cancer. In this article, a methodology for converting personal EMP exposures measured using the National Institute for Occupational Safety and Health (NIOSH) 7400/7402 methods to exposures based on other size-based definitions has been proposed and illustrated. Area monitoring for EMP in the taconite mines in Minnesota's Mesabi Iron Range was conducted using a Micro Orifice Uniform Deposit Impactor (MOUDI) size-fractionating sampler. EMP on stages of the MOUDI were counted and sized according to each EMP definition using an indirect-transfer transmission electron microscopy (ISO Method 13794). EMP were identified using energy-dispersive x-ray and electron diffraction analysis. Conversion factors between the EMP counts based on different definitions were estimated using (1) a linear regression model across all locations and (2) a location-specific ratio of the count based on each EMP definition to the NIOSH 7400/7402 count. The highest fractions of EMP concentrations were found for EMP that were 1-3 μm in length and 0.2-0.5 μm in width. Therefore, the current standard NIOSH Method 7400, which only counts EMP >5 μm in length and ≥ 3 in aspect ratio, may underestimate amphibole EMP exposures. At the same time, there was a high degree of correlation between the exposures estimated according to the different size-based metrics. Therefore, the various dimensional definitions probably do not result in different dose-response relationships in epidemiological analyses. Given the high degree of correlation between the various metrics, a result consistent with prior research, a more reasonable metric might be the measurement of all EMP irrespective of size. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: figures detailing EMP concentration.].}, }
@article {pmid24510578, year = {2014}, author = {Nishikawa, S and Tanaka, A and Matsuda, A and Oida, K and Jang, H and Jung, K and Amagai, Y and Ahn, G and Okamoto, N and Ishizaka, S and Matsuda, H}, title = {A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma.}, journal = {Cancer medicine}, volume = {3}, number = {2}, pages = {416-425}, pmid = {24510578}, issn = {2045-7634}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Benzamides/pharmacology ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Female ; Glutamates/pharmacology ; Guanine/analogs &amp; derivatives/pharmacology ; Humans ; Lung Neoplasms/*drug therapy/metabolism/pathology ; Mesothelioma/*drug therapy/metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Molecular Targeted Therapy ; NF-kappa B/*antagonists &amp; inhibitors/*metabolism ; Pemetrexed ; Xenograft Model Antitumor Assays ; }, abstract = {Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G1 /G1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.}, }
@article {pmid24510539, year = {2014}, author = {Pukkala, E and Martinsen, JI and Weiderpass, E and Kjaerheim, K and Lynge, E and Tryggvadottir, L and Sparén, P and Demers, PA}, title = {Cancer incidence among firefighters: 45 years of follow-up in five Nordic countries.}, journal = {Occupational and environmental medicine}, volume = {71}, number = {6}, pages = {398-404}, doi = {10.1136/oemed-2013-101803}, pmid = {24510539}, issn = {1470-7926}, mesh = {Adenocarcinoma/epidemiology/etiology ; Adenocarcinoma of Lung ; Adult ; Age Factors ; Aged ; *Carcinogens ; Cohort Studies ; *Firefighters ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Male ; Melanoma/epidemiology/etiology ; Middle Aged ; Multiple Myeloma/epidemiology/etiology ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Prostatic Neoplasms/epidemiology/etiology ; Risk ; Scandinavian and Nordic Countries/epidemiology ; Skin Neoplasms/epidemiology/etiology ; Testicular Neoplasms/epidemiology/etiology ; Melanoma, Cutaneous Malignant ; }, abstract = {OBJECTIVES: Firefighters are potentially exposed to a wide range of known and suspected carcinogens through their work. The objectives of this study were to examine the patterns of cancer among Nordic firefighters, and to compare them with the results from previous studies.<br><br>METHODS: Data for this study were drawn from a linkage between the census data for 15 million people from the five Nordic countries and their cancer registries for the period 1961-2005. SIR analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates.<br><br>RESULTS: A total of 16 422 male firefighters were included in the final cohort. A moderate excess risk was seen for all cancer sites combined, (SIR=1.06, 95% CI 1.02 to 1.11). There were statistically significant excesses in the age category of 30-49 years in prostate cancer (SIR=2.59, 95% CI 1.34 to 4.52) and skin melanoma (SIR=1.62, 95% CI 1.14 to 2.23), while there was almost no excess in the older ages. By contrast, an increased risk, mainly in ages of 70 years and higher, was observed for non-melanoma skin cancer (SIR=1.40, 95% CI 1.10 to 1.76), multiple myeloma (SIR=1.69, 95% CI 1.08 to 2.51), adenocarcinoma of the lung (SIR=1.90, 95% CI 1.34 to 2.62), and mesothelioma (SIR=2.59, 95% CI 1.24 to 4.77). By contrast with earlier studies, the incidence of testicular cancer was decreased (SIR=0.51, 95% CI 0.23 to 0.98).<br><br>CONCLUSIONS: Some of these associations have been observed previously, and potential exposure to polycyclic aromatic hydrocarbons, asbestos and shift work involving disruption of circadian rhythms may partly explain these results.}, }
@article {pmid24508707, year = {2014}, author = {Lacourt, A and Gramond, C and Rolland, P and Ducamp, S and Audignon, S and Astoul, P and Chamming's, S and Gilg Soit Ilg, A and Rinaldo, M and Raherison, C and Galateau-Salle, F and Imbernon, E and Pairon, JC and Goldberg, M and Brochard, P}, title = {Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.}, journal = {Thorax}, volume = {69}, number = {6}, pages = {532-539}, doi = {10.1136/thoraxjnl-2013-203744}, pmid = {24508707}, issn = {1468-3296}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Case-Control Studies ; Environmental Exposure ; Female ; France/epidemiology ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleural Neoplasms/epidemiology/*etiology ; Retrospective Studies ; Sex Factors ; Time Factors ; }, abstract = {OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure.<br><br>METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression.<br><br>RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1&#x2005;f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10&#x2005;f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women.<br><br>CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.}, }
@article {pmid24492694, year = {2014}, author = {Suzuki, S and Toyoshima, M and Nihashi, F and Tsukui, H and Baba, S and Sugimura, H and Suda, T}, title = {An autopsy case of malignant pleural mesothelioma associated with nephrotic syndrome.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {53}, number = {3}, pages = {243-246}, doi = {10.2169/internalmedicine.53.1313}, pmid = {24492694}, issn = {1349-7235}, mesh = {Asbestos/*adverse effects ; Autopsy ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/*diagnosis/etiology ; Mesothelioma, Malignant ; Middle Aged ; Nephrotic Syndrome/*diagnosis/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*diagnosis/etiology ; }, abstract = {A 64-year-old man who had been exposed to asbestos was referred to our hospital for a detailed examination of left pleural effusion. A laboratory examination of the urine and blood revealed nephrotic syndrome. A thoracoscopic examination did not yield a definitive diagnosis. Twenty months later, a left pleural tumor became apparent, and the patient died of respiratory failure and cachexia. An autopsy revealed epithelioid malignant pleural mesothelioma. The glomeruli appeared normal under light microscopy. A review of the English literature revealed only three reports of malignant mesothelioma associated with minimal-change nephrotic syndrome. The natural course of malignant mesothelioma with nephrotic syndrome has not been previously reported.}, }
@article {pmid24491449, year = {2014}, author = {de Assis, LV and Locatelli, J and Isoldi, MC}, title = {The role of key genes and pathways involved in the tumorigenesis of Malignant Mesothelioma.}, journal = {Biochimica et biophysica acta}, volume = {1845}, number = {2}, pages = {232-247}, doi = {10.1016/j.bbcan.2014.01.008}, pmid = {24491449}, issn = {0006-3002}, mesh = {Asbestos/toxicity ; Carcinogenesis/*genetics ; Cell Transformation, Neoplastic/genetics/pathology ; Humans ; Lung Neoplasms/etiology/*genetics/pathology ; Mesothelioma/etiology/*genetics/pathology ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Signal Transduction/*genetics ; Simian virus 40/pathogenicity ; Zeolites/toxicity ; }, abstract = {Malignant Mesothelioma (MM) is a very aggressive cancer with low survival rates and often diagnosed at an advanced stage. Several players have been implicated in the development of this cancer, such as asbestos, erionite and the simian virus 40 (SV40). Here, we have reviewed the involvement of erionite, SV40, as well as, the role of several genes (p16(INK4a), p14(ARF), NF2, LATS2, SAV, CTNNB1 and among others), the pathways (RAS, PI3K, Wnt, BCL and Hippo), and their respective roles in the development of MM.}, }
@article {pmid24480869, year = {2014}, author = {Ollier, M and Chamoux, A and Naughton, G and Pereira, B and Dutheil, F}, title = {Chest CT scan screening for lung cancer in asbestos occupational exposure: a systematic review and meta-analysis.}, journal = {Chest}, volume = {145}, number = {6}, pages = {1339-1346}, doi = {10.1378/chest.13-2181}, pmid = {24480869}, issn = {1931-3543}, mesh = {Aged ; Asbestos/*adverse effects ; Early Detection of Cancer/methods ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging/etiology/mortality ; Male ; Mesothelioma/diagnostic imaging/etiology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Prevalence ; Smoking/adverse effects ; Survival Rate ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: Lung cancer is the most frequent malignant asbestos-related pathology and remains the most fatal cancer of industrialized countries. In heavy smokers, early detection of lung cancer with chest CT scan leads to a 20% mortality reduction. However, the use of CT scan screening for early detection of lung cancer in asbestos-exposed workers requires further investigation. This study aimed to determine whether CT scan screening in asbestos-exposed workers is effective in detecting asymptomatic lung cancer using a systematic review and meta-analysis.<br><br>METHODS: We reviewed all cohort studies involving chest CT scan screening in former asbestos-exposed workers. The search strategy used the following keywords: "asbestos," "lung cancer," "screening," and "occupation*" or "work." Databases were PubMed, Cochrane Library, Science Direct, and Embase.<br><br>RESULTS: Seven studies matched our inclusion criteria. Baseline screening detected 49 asymptomatic lung cancers among 5,074 asbestos-exposed workers. Of the 49 reported lung cancers, at least 18 were in the earliest stage (stage I), accessible to complete removal surgery. The prevalence of all lung cancers detected by CT scan screening in asbestos-exposed workers was 1.1% (95% CI, 0.6%-1.8%).<br><br>CONCLUSIONS: CT scan screening in asbestos-exposed workers is effective in detecting asymptomatic lung cancer. Detection of lung cancer in asbestos-exposed workers using CT scanning is at least equal to the prevalence in heavy smokers (1%; 95% CI, 0.09%-1.1%) and also shared a similar proportion of stage I diagnoses. Screening asbestos-exposed workers could reduce mortality in proportions previously observed among heavy smokers and, thus, should not be neglected, particularly for individuals combining both exposures.}, }
@article {pmid24472319, year = {2013}, author = {Kang, D and Myung, MS and Kim, YK and Kim, JE}, title = {Systematic Review of the Effects of Asbestos Exposure on the Risk of Cancer between Children and Adults.}, journal = {Annals of occupational and environmental medicine}, volume = {25}, number = {1}, pages = {10}, pmid = {24472319}, issn = {2052-4374}, abstract = {Children are considerably more susceptible to enviro006Emental hazards than adults. This study was conducted to investigate whether the first asbestos exposure in childhood increases the risk of asbestos-related cancer including mesothelioma and lung cancer. MEDLINE (PubMed), Embase, and Google Scholar were searched to find relevant studies published up to July 2012. Six studies reported the relationship between age, including age during childhood, at the first asbestos exposure and mesothelioma. Among them, 4 indicated that people exposed to asbestos in childhood have a higher risk of mesothelioma than those exposed in adulthood. Meanwhile, the other 2 studies showed that asbestos exposure later in life increases the risk of mesothelioma. The results of the 2 studies including non-occupational early childhood exposure report conflicting results. There were 3 studies regarding the relationship between age at first asbestos exposure and lung cancer. However, none of them reported an association between age at first asbestos exposure and the risk of lung cancer. All studies have limitations including small numbers of subjects, the validity of the standardized mortality ratio, and different age categories at first asbestos exposure. There are only a few studies on the harmful effects of asbestos in children in the literature. Therefore, the effect of asbestos exposure during childhood remains unclear and requires further study.}, }
@article {pmid24457242, year = {2013}, author = {Cheng, YY and Kirschner, MB and Cheng, NC and Gattani, S and Klebe, S and Edelman, JJ and Vallely, MP and McCaughan, BC and Jin, HC and van Zandwijk, N and Reid, G}, title = {ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {10}, pages = {1317-1328}, doi = {10.1097/JTO.0b013e3182a0840a}, pmid = {24457242}, issn = {1556-1380}, mesh = {Adult ; Aged ; Apoptosis ; Biomarkers, Tumor/genetics/metabolism ; Blotting, Western ; Cell Proliferation ; Chromatin Immunoprecipitation ; *DNA Methylation ; Female ; Fluorescent Antibody Technique ; Follow-Up Studies ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/*genetics/metabolism/mortality/pathology ; Male ; Mesothelioma/*genetics/metabolism/mortality/pathology ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/*genetics/metabolism/mortality/pathology ; Prognosis ; Promoter Regions, Genetic/genetics ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Transcription Factors/antagonists &amp; inhibitors/genetics/*metabolism ; Tumor Cells, Cultured ; }, abstract = {INTRODUCTION: Epigenetic inactivation of tumor suppressor genes is involved in the development of malignant pleural mesothelioma (MPM). ZIC1, a potential tumor suppressor gene involved in regulating cell growth and apoptosis, was investigated in MPM cell lines and tumors.<br><br>METHODS: ZIC1 expression and promoter methylation were evaluated in MPM cell lines and tumor samples by quantitative polymerase chain reaction (PCR), Combined Bisulfite Restriction Analysis, and methylation-specific PCR. ZIC1 was reexpressed in cell lines and functional effects were assessed. miRNA expression was quantified by microarray and reverse transcription quantitative PCR. ZIC1 knockdown and miRNA inhibitors were used to study the relationship between ZIC1 and miRNA expression and confirmed by chromatin immunoprecipitation PCR.<br><br>RESULTS: ZIC1 expression was low in MPM cells, and was correlated with ZIC1 promoter methylation and reversed upon decitabine treatment. ZIC1 reexpression inhibited proliferation and invasion in MPM cells whereas knockdown enhanced the growth of MeT-5A. In MPM tumor samples ZIC1 expression was either low or undetectable, with promoter methylation observed in 16 of 24 cases. The overexpression of miR-23a and miR-27a was reduced by ZIC1 reexpression, with inhibitors of miR-23a or miR-27a reducing colony formation. miR-23a overexpression was also associated with shorter survival of MPM patients.<br><br>CONCLUSION: ZIC1 is down-regulated in MPM through promoter methylation and acts as a tumor suppressor through down-regulation of its direct targets miR-23a and miR-27a.}, }
@article {pmid24455327, year = {2013}, author = {Humphrys, N and Downing, A and Evans, L and Sinclair, M}, title = {Traumatic implantation: a novel aetiology in the development of peritoneal mesothelioma.}, journal = {Case reports in emergency medicine}, volume = {2013}, number = {}, pages = {389130}, pmid = {24455327}, issn = {2090-648X}, abstract = {Peritoneal mesothelioma is a rare intra-abdominal malignancy. Its aetiology has been thought to be due to either inhalation or ingestion of asbestos particles. We present a case of peritoneal mesothelioma developing as a result of a novel third route and the inoculation of fibres into the peritoneal cavity by penetrating trauma and direct transport. This case report highlights the important long term consequences of penetrating abdominal trauma and the need for vigilance in undertaking peritoneal toilet.}, }
@article {pmid24429116, year = {2013}, author = {Lim, JY and Wolf, AS and Flores, RM}, title = {The use of surgery in mesothelioma.}, journal = {The Lancet. Respiratory medicine}, volume = {1}, number = {3}, pages = {184-186}, doi = {10.1016/S2213-2600(13)70028-6}, pmid = {24429116}, issn = {2213-2600}, mesh = {*Asbestos ; Biopsy ; Chemoradiotherapy, Adjuvant ; Combined Modality Therapy ; Congresses as Topic ; Diagnosis, Differential ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/epidemiology/etiology/physiopathology/surgery ; Neoplasm Staging ; Patient Care Team ; *Pleura/pathology/surgery ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/physiopathology/surgery ; Pneumonectomy/*methods ; Preoperative Care/*methods ; Prognosis ; Risk Factors ; Survival Analysis ; }, }
@article {pmid24415579, year = {2014}, author = {Giusti, L and Da Valle, Y and Bonotti, A and Donadio, E and Ciregia, F and Ventroni, T and Foddis, R and Giannaccini, G and Guglielmi, G and Cristaudo, A and Lucacchini, A}, title = {Comparative proteomic analysis of malignant pleural mesothelioma evidences an altered expression of nuclear lamin and filament-related proteins.}, journal = {Proteomics. Clinical applications}, volume = {8}, number = {3-4}, pages = {258-268}, doi = {10.1002/prca.201300052}, pmid = {24415579}, issn = {1862-8354}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Biomarkers, Tumor/*biosynthesis ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Lamin Type B/biosynthesis ; Lung Neoplasms/chemically induced/*genetics/pathology ; Male ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Proteins/biosynthesis ; Pleural Neoplasms/chemically induced/*genetics/pathology ; *Proteomics ; }, abstract = {PURPOSE: Malignant mesothelioma is a neoplastic disease linked to asbestos exposure whose diagnosis is limited, so detection methods for an early diagnosis and treatment result essential. Here, we compared proteomic profiles of malignant pleural mesothelioma (MPM) and benign biopsies to search potential biomarkers useful in differential diagnosis.<br><br>EXPERIMENTAL DESIGN: Tissue biopsies were obtained from 53 patients who were subjected to a diagnostic thoracoscopy. 2DE/MS based approach was used for proteomic analysis and protein validation was carried out by Western blot analysis versus benign and lung carcinoma samples.<br><br>RESULTS: Among the proteins identified we confirmed known MPM biomarkers such as calretinin and suggested the new ones as prelamin A/C, desmin, vimentin, calretinin, fructose-bisphosphate aldolase A, myosin regulatory light chain 2, ventricular/cardiac muscle isoform, myosin light chain 3 and myosin light chain 6B. Ingenuity software was used to identify the biological processes to which these proteins belong and to construct a potential network.<br><br>Overall, our results suggest potential biomarkers that can be useful in occupational medicine for the early identification of the onset of disease in health surveillance of past asbestos-exposed workers, for monitoring the progress of disease and for assessing the response to treatment.}, }
@article {pmid24409346, year = {2013}, author = {van Zandwijk, N}, title = {Clinical practice guidelines for malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {5}, number = {6}, pages = {724-725}, pmid = {24409346}, issn = {2072-1439}, }
@article {pmid24401539, year = {2014}, author = {Filiberti, R and Marroni, P and Spigno, F and Merlo, DF and Mortara, V and Caruso, P and Cioè, A and Michelazzi, L and Bruzzone, A and Bobbio, B and Simonassi, C and Del Corso, L and Galli, R and Racchi, O and Dini, G and Linares, R and Mencoboni, M}, title = {Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos.}, journal = {Oncology}, volume = {86}, number = {1}, pages = {33-43}, doi = {10.1159/000355687}, pmid = {24401539}, issn = {1423-0232}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Follow-Up Studies ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/blood/*diagnosis ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/blood/*diagnosis ; Prospective Studies ; }, abstract = {OBJECTIVE: Soluble mesothelin-related peptide (SMRP) may be useful in the diagnosis and detection of early stage mesothelioma. We investigated the SMRP upfront predictive role for mesothelioma in asbestos-exposed workers.<br><br>METHODS: A total of 1,715 subjects underwent a first visit and were invited for a follow-up after 1 and 2 years, with a clinical examination and blood sampling. SMRP was measured by an ELISA assay.<br><br>RESULTS: Median SMRP at the first visit was 0.45 [interquartile range (IQR) i.e. 25th-75th percentile: 0.30-0.67 nmol/l]. In all, 1,676 subjects (97.8%) were followed up for a median period of 47.1 months. SMRP was measured at the first visit and at both follow-up visits in 1,536 subjects. At follow-up, 3 subjects were diagnosed with an epithelioid mesothelioma. In these cases, SMRP at the first visit ranged from 0.17 to 0.52 nmol/l. Malignant pleural mesothelioma was diagnosed 9-17 months after the last SMRP evaluation. No SMRP variation was observed during the follow-up. Other 61 miscellaneous cancers were diagnosed (median SMRP at first visit: 0.50 nmol/l, IQR: 0.34-0.71 nmol/l).<br><br>CONCLUSIONS: Our results did not support the usefulness of SMRP as an early marker for the detection of the disease for a time interval of 1 year.}, }
@article {pmid24394956, year = {2014}, author = {Jennings, CJ and Walsh, PM and Deady, S and Harvey, BJ and Thomas, W}, title = {Malignant pleural mesothelioma incidence and survival in the Republic of Ireland 1994-2009.}, journal = {Cancer epidemiology}, volume = {38}, number = {1}, pages = {35-41}, doi = {10.1016/j.canep.2013.12.002}, pmid = {24394956}, issn = {1877-783X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Environmental Exposure ; Female ; Follow-Up Studies ; Humans ; Incidence ; Ireland/epidemiology ; Lung Neoplasms/*epidemiology/etiology/pathology ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Proportional Hazards Models ; Registries ; Risk Factors ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a rare malignancy associated with exposure to asbestos. The protracted latent period of MPM means that its incidence has continued to rise across Europe after the introduction of restrictions on asbestos use. In order to obtain a clearer indication of trends in the Republic of Ireland (ROI), incidence and survival were assessed based on all MPM cases reported since the establishment of the National Cancer Registry of Ireland (NCR).<br><br>METHODS: NCR recorded 337 MPM diagnoses in the ROI during 1994-2009. Survival was assessed for all cases diagnosed with adequate follow-up (n=330). Crude and European age-standardized incidence rates were calculated for all cases and for 4-year periods. A Cox model of observed (all-cause) survival was used to generate hazard ratios for the effect of: gender; age at diagnosis; diagnosis cohort; region of residence; histological type; and tumour stage. Single P-values for the variables indicated were calculated using either a stratified log-rank test or stratified trend test.<br><br>RESULTS: Over the study period the age-standardized MPM incidence in the ROI rose from 4.98cases per million (cpm) to 7.24cpm. The 1-year survival rate for all MPM cases was 29.6% (CI 24.7-34.6%). Excess mortality risk was associated with age at diagnosis (75-89 yrs vs. 55-64 yrs, HR 1.88, 95% CI 1.35-2.63, P<0.001) and tumour stage (III vs. I HR 1.57, 95% CI 1.00-2.48, P<0.05; IV vs. I HR 1.55, 95% CI 1.08-2.21, P<0.05). Age showed a significant survival trend (P<0.001) but tumour stage did not (P=0.150). There was significant heterogeneity between the survival of patients resident in different regions (P=0.027).<br><br>CONCLUSION: MPM incidence and mortality continued to rise in the ROI after the restrictions on asbestos use and the predictors of survival detected in this study are broadly consistent with those identified for other countries.}, }
@article {pmid24387944, year = {2014}, author = {Charbotel, B and Fervers, B and Droz, JP}, title = {Occupational exposures in rare cancers: A critical review of the literature.}, journal = {Critical reviews in oncology/hematology}, volume = {90}, number = {2}, pages = {99-134}, doi = {10.1016/j.critrevonc.2013.12.004}, pmid = {24387944}, issn = {1879-0461}, mesh = {Humans ; Neoplasms/classification/*etiology ; *Occupational Exposure ; }, abstract = {The contribution of occupational exposures to rare cancers, which represent 22% of all cancers diagnosed annually in Europe, remains insufficiently considered. We conducted a comprehensive review of occupational risk factors in 67 rare cancers (annual incidence <6/100,000). An examination of relevant articles in PubMed (1960-2012) and the International Agency for Research on Cancer (IARC) monographs revealed that 26 cancer sites, such as mesothelioma, nasal, larynx, liver, ovarian cancer, bone sarcoma, and hematopoietic malignancies were consistently linked to occupational factors. Main exposures included asbestos, wood dust, metals/metalloids, formaldehyde, benzene, vinyl chloride, and radiation. There was inconsistent evidence regarding 22 rare malignancies. We did not identify relevant data for 19 rare cancers. Despite limitations of published evidence, our review provides useful information that can facilitate the identification of work-related factors that contribute to rare cancers. International collaborations, development of improved exposure assessment methods, and molecular approaches can improve future studies.}, }
@article {pmid24375784, year = {2014}, author = {Silver, SR and Pinkerton, LE and Fleming, DA and Jones, JH and Allee, S and Luo, L and Bertke, SJ}, title = {Retrospective cohort study of a microelectronics and business machine facility.}, journal = {American journal of industrial medicine}, volume = {57}, number = {4}, pages = {412-424}, pmid = {24375784}, issn = {1097-0274}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {Adult ; Asbestos/adverse effects ; Cause of Death ; Cohort Studies ; *Computers ; *Electronics ; Female ; Humans ; Incidence ; Lymphoma, Non-Hodgkin/mortality ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/*epidemiology/mortality ; Nervous System Diseases/*epidemiology ; Occupational Diseases/*epidemiology/mortality ; Occupational Exposure/*statistics &amp; numerical data ; Pleural Neoplasms/epidemiology ; Proportional Hazards Models ; Rectal Neoplasms/mortality ; Regression Analysis ; Retrospective Studies ; Testicular Neoplasms/epidemiology ; Tetrachloroethylene/*adverse effects ; }, abstract = {OBJECTIVES: We examined health outcomes among 34,494 workers employed at a microelectronics and business machine facility 1969-2001.<br><br>METHODS: Standardized mortality ratio (SMR) and standardized incidence ratios were used to evaluate health outcomes in the cohort and Cox regression modeling to evaluate relations between scores for occupational exposures and outcomes of a priori interest.<br><br>RESULTS: Just over 17% of the cohort (5,966 people) had died through 2009. All cause, all cancer, and many cause-specific SMRs showed statistically significant deficits. In hourly males, SMRs were significantly elevated for non-Hodgkin's lymphoma and rectal cancer. Salaried males had excess testicular cancer incidence. Pleural cancer and mesothelioma excesses were observed in workers hired before 1969, but no available records substantiate use of asbestos in manufacturing processes. A positive, statistically significant relation was observed between exposure scores for tetrachloroethylene and nervous system diseases.<br><br>CONCLUSIONS: Few significant exposure-outcome relations were observed, but risks from occupational exposures cannot be ruled out due to data limitations and the relative youth of the cohort.}, }
@article {pmid24371224, year = {2014}, author = {Menges, CW and Kadariya, Y and Altomare, D and Talarchek, J and Neumann-Domer, E and Wu, Y and Xiao, GH and Shapiro, IM and Kolev, VN and Pachter, JA and Klein-Szanto, AJ and Testa, JR}, title = {Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis.}, journal = {Cancer research}, volume = {74}, number = {4}, pages = {1261-1271}, pmid = {24371224}, issn = {1538-7445}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; CA148805/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos ; *Cell Proliferation ; Cell Transformation, Neoplastic/*genetics ; Genes, Neurofibromatosis 2/physiology ; Genes, Tumor Suppressor/*physiology ; Genes, p53/physiology ; Mesothelioma/*genetics/pathology ; Mice ; Mice, SCID ; Mice, Transgenic ; MicroRNAs/physiology ; Mutation ; Neoplasm Invasiveness ; Neoplastic Stem Cells/pathology/*physiology ; Pleural Neoplasms/*genetics/pathology ; Proto-Oncogene Proteins c-met/physiology ; Signal Transduction/genetics ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma is a highly aggressive, asbestos-related cancer frequently marked by mutations of both NF2 and CDKN2A. We demonstrate that germline knockout of one allele of each of these genes causes accelerated onset and progression of asbestos-induced malignant mesothelioma compared with asbestos-exposed Nf2(+/-) or wild-type mice. Ascites from some Nf2(+/-);Cdkn2a(+/-) mice exhibited large tumor spheroids, and tail vein injections of malignant mesothelioma cells established from these mice, but not from Nf2(+/-) or wild-type mice, produced numerous tumors in the lung, suggesting increased metastatic potential of tumor cells from Nf2(+/-);Cdkn2a(+/-) mice. Intraperitoneal injections of malignant mesothelioma cells derived from Nf2(+/-);Cdkn2a(+/-) mice into severe combined immunodeficient mice produced tumors that penetrated the diaphragm and pleural cavity and harbored increased cancer stem cells (CSC). Malignant mesothelioma cells from Nf2(+/-);Cdkn2a(+/-) mice stained positively for CSC markers and formed CSC spheroids in vitro more efficiently than counterparts from wild-type mice. Moreover, tumor cells from Nf2(+/-);Cdkn2a(+/-) mice showed elevated c-Met expression/activation, which was partly dependent on p53-mediated regulation of miR-34a and required for tumor migration/invasiveness and maintenance of the CSC population. Collectively, these studies demonstrate in vivo that inactivation of Nf2 and Cdkn2a cooperate to drive the development of highly aggressive malignant mesotheliomas characterized by enhanced tumor spreading capability and the presence of a CSC population associated with p53/miR-34a-dependent activation of c-Met. These findings suggest that cooperativity between losses of Nf2 and Cdkn2a plays a fundamental role in driving the highly aggressive tumorigenic phenotype considered to be a hallmark of malignant mesothelioma.}, }
@article {pmid24366282, year = {2014}, author = {Pillai, K and Ehteda, A and Akhter, J and Chua, TC and Morris, DL}, title = {Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells.}, journal = {Anti-cancer drugs}, volume = {25}, number = {2}, pages = {150-160}, doi = {10.1097/CAD.0000000000000039}, pmid = {24366282}, issn = {1473-5741}, mesh = {Antineoplastic Agents/*pharmacology ; Bromelains/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cisplatin/*pharmacology ; Drug Interactions ; Fluorouracil/*pharmacology ; Humans ; Mesothelioma/*drug therapy ; Peritoneal Neoplasms/*drug therapy ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneum, causally related to asbestos exposure. Nonspecific symptoms with a late diagnosis results in poor survival (<1 year). Treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has improved survival in some patients (median 3-5 years). Hence, new therapies are urgently needed. MUC1 is a glycosylation-dependent protein that confers tumours with invasiveness, metastasis and chemoresistance. Bromelain (cysteine proteinase) hydrolyses glycosidic bonds. Therefore, we investigated the antitumour effect of bromelain on MUC1-expressing MPM cell lines. MUC1 expressions in cells were assessed using immunofluorescent probes with cells grown on cover slips and western blot analysis on cell lysates. The cell lines were treated with various concentrations of bromelain and after 4 and 72 h, their viability was assessed using standard sulforhodamine assays. The cells were also treated with combinations of bromelain and cytotoxic drugs (cisplatin or 5-FU) and their viability was assessed at 72 h. Finally, with western blotting, the effects of bromelain on cellular survival proteins were investigated. PET cells expressed more MUC1 compared with YOU cells. The cell viability of both PET and YOU cells was adversely affected by bromelain, with PET cells being slightly resistant. The addition of bromelain increased the cytotoxicity of cisplatin significantly in both cell lines. However, 5-FU with bromelain did not show any significant increase in cytotoxicity. Bromelain-induced cell death is by apoptosis and autophagy. Bromelain has the potential of being developed as a therapeutic agent in MPM.}, }
@article {pmid24365782, year = {2014}, author = {Indovina, P and Marcelli, E and Di Marzo, D and Casini, N and Forte, IM and Giorgi, F and Alfano, L and Pentimalli, F and Giordano, A}, title = {Abrogating G2/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma.}, journal = {Cancer biology &amp; therapy}, volume = {15}, number = {4}, pages = {380-388}, pmid = {24365782}, issn = {1555-8576}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Cycle Proteins/*antagonists &amp; inhibitors/metabolism ; Cell Line, Tumor ; Cisplatin/*pharmacology ; Drug Synergism ; *G2 Phase Cell Cycle Checkpoints ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Nuclear Proteins/*antagonists &amp; inhibitors/metabolism ; Protein-Tyrosine Kinases/*antagonists &amp; inhibitors/metabolism ; Pyrazoles/*pharmacology ; Pyrimidines/*pharmacology ; Pyrimidinones ; }, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related neoplasm of the serous membranes, whose incidence is increasing worldwide. Although the introduction of new drug combinations, such as cisplatin plus pemetrexed/gemcitabine, has determined an improvement in the patient quality of life, MM remains a universally fatal disease. The observation that key G 1/S checkpoint regulators are often functionally inactivated in MM prompted us to test whether the use of G 2/M checkpoint inhibitors, able to sensitize G 1/S checkpoint-defective cancer cells to DNA-damaging agents, could be successful in MM. We treated six MM cell lines, representative of different histotypes (epithelioid, biphasic, and sarcomatoid), with cisplatin in combination with MK-1775, an inhibitor of the G 2/M checkpoint kinase WEE1. We observed that MK-1775 enhanced the cisplatin cytotoxic effect in all MM cell lines, except the sarcomatoid cell line, which is representative of the most aggressive histotype. As expected, the enhancement in cisplatin toxicity was accompanied by a decrease in the inactive phosphorylated form of cyclin-dependent kinase 1 (CDK1), a key substrate of WEE1, which is indicative of G 2/M checkpoint inactivation. Consistently, we also observed a decrease in G 2/M accumulation and an increase in mitotic entry of DNA-damaged cells and apoptosis, probably due to the loss of the cell ability to arrest cell cycle in response to DNA damage, irrespectively of p53 mutational status. Notably, this treatment did not increase cisplatin cytotoxicity on normal cells, thus suggesting a possible use of MK-1775 in combination with cisplatin for a safe and efficient treatment of epithelioid and biphasic MM.}, }
@article {pmid24361865, year = {2014}, author = {Mundt, F and Johansson, HJ and Forshed, J and Arslan, S and Metintas, M and Dobra, K and Lehtiö, J and Hjerpe, A}, title = {Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.}, journal = {Molecular &amp; cellular proteomics : MCP}, volume = {13}, number = {3}, pages = {701-715}, pmid = {24361865}, issn = {1535-9484}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Computational Biology ; Discriminant Analysis ; Enzyme-Linked Immunosorbent Assay ; Female ; Galectin 1/*metabolism ; Humans ; Kaplan-Meier Estimate ; Least-Squares Analysis ; Lung Neoplasms/*diagnosis/*metabolism ; Male ; Mass Spectrometry ; Mesothelioma/*diagnosis/*metabolism ; Mesothelioma, Malignant ; Middle Aged ; Models, Biological ; Multivariate Analysis ; Pleural Effusion/*diagnosis/metabolism ; Principal Component Analysis ; Prognosis ; Proteome/*metabolism ; Proteomics/*methods ; ROC Curve ; Reproducibility of Results ; }, abstract = {Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome furthers our understanding of malignant mesothelioma, identified galectin 1 as a potential diagnostic biomarker, and highlighted several possible prognostic biomarkers of this disease.}, }
@article {pmid24354100, year = {2013}, author = {Voulgaridis, A and Apollonatou, V and Lykouras, D and Giannopoulos, A and Iliopoulou, M and Karkoulias, K and Kraniotis, P and Prokakis, C and Gkermpesi, M and Spiropoulos, K}, title = {Pleural mesothelioma in a young male patient.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {79}, number = {2}, pages = {96-99}, doi = {10.4081/monaldi.2013.100}, pmid = {24354100}, issn = {1122-0643}, mesh = {Adult ; Asbestosis/*complications ; Bronchoscopy ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/etiology/surgery ; Male ; Mesothelioma/*diagnosis/etiology/surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/etiology/surgery ; Pneumonectomy ; *Tomography, X-Ray Computed ; }, abstract = {We present the case of a 33-year-old male patient suffering from lymphocytic pleural effusion, as a result of pleural mesothelioma. Mesothelioma is a malignant tumor of the pleura that is mainly caused by chronic exposure to asbestos fibers and more than 40 years of exposure are needed to develop the disease. Early studies on the relationship of asbestos and mesothelioma were issued in the 1960s. Fibers migrate from the parenchyma of the lung to the visceral pleura. It is widely known that asbestos is an oncogenic factor which can cause damage to DNA. A chest x-ray may reveal pleural effusion with or without pleural thickening, whereas a chest CT may also reveal pleural thickening, uniform and/or lobular. Specific tests, such as immunohistochemical staining, are used in order to help differential diagnosis. Extrapleural pneumonectomy is used as a therapeutic option which involves removal of the lung as well as both the visceral and parietal pleura, the affected part of the pericardium and diaphragm. Surgery should be followed up by radiotherapy and chemotherapy. The surgery may lead to a mean survival rate of approximately 9-21 months. The case presented underlines that in the event of pleural effusion with a lymphocyte type physicians should consider the possibility of a pleural mesothelioma during differential diagnosis, even in relatively young patients.}, }
@article {pmid24351898, year = {2014}, author = {Offermans, NS and Vermeulen, R and Burdorf, A and Goldbohm, RA and Kauppinen, T and Kromhout, H and van den Brandt, PA}, title = {Occupational asbestos exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study.}, journal = {Journal of occupational and environmental medicine}, volume = {56}, number = {1}, pages = {6-19}, doi = {10.1097/JOM.0000000000000060}, pmid = {24351898}, issn = {1536-5948}, mesh = {Aged ; Asbestos/*toxicity ; Carcinoma/*epidemiology/etiology ; Follow-Up Studies ; Humans ; Laryngeal Neoplasms/*epidemiology/etiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Netherlands/epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: To study the association between occupational asbestos exposure and pleural mesothelioma, lung cancer, and laryngeal cancer, specifically addressing risk associated with the lower end of the exposure distribution, risk of cancer subtypes, and the interaction between asbestos and smoking.<br><br>METHODS: Using the Netherlands Cohort Study (n = 58,279 men, aged 55 to 69 years), asbestos exposure was estimated by linkage to job-exposure matrices. After 17.3 years of follow-up, 132 pleural mesothelioma, 2324 lung cancer, and 166 laryngeal cancer cases were available.<br><br>RESULTS: The multivariable-adjusted model showed overall positive associations between all levels of asbestos exposure and mesothelioma, lung cancer, and laryngeal cancer. Lung adenocarcinoma and glottis cancer showed only a positive association after prolonged higher asbestos exposure (hazard ratio per 10 years increment, 1.43 [95% confidence interval, 1.06 to 1.93] and 1.95 [95% confidence interval, 1.36 to 2.80], respectively). There was no statistically significant interaction between asbestos and smoking.<br><br>CONCLUSIONS: Asbestos levels encountered at the lower end of the exposure distribution may be associated with an increased risk of pleural mesothelioma, lung cancer, and laryngeal cancer.}, }
@article {pmid24345738, year = {2014}, author = {Di Marzo, D and Forte, IM and Indovina, P and Di Gennaro, E and Rizzo, V and Giorgi, F and Mattioli, E and Iannuzzi, CA and Budillon, A and Giordano, A and Pentimalli, F}, title = {Pharmacological targeting of p53 through RITA is an effective antitumoral strategy for malignant pleural mesothelioma.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {13}, number = {4}, pages = {652-665}, doi = {10.4161/cc.27546}, pmid = {24345738}, issn = {1551-4005}, mesh = {Antineoplastic Agents/administration &amp; dosage/pharmacology ; Apoptosis/*drug effects ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Cisplatin/administration &amp; dosage/pharmacology ; Drug Synergism ; Furans/*pharmacology ; Heterografts ; Humans ; Imidazoles/*pharmacology ; Lung Neoplasms/*metabolism/pathology ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mutation ; Piperazines/*pharmacology ; Pleural Neoplasms/*metabolism/pathology ; Tumor Suppressor Protein p53/*metabolism ; rho GTP-Binding Proteins/metabolism ; }, abstract = {Malignant mesothelioma, a very aggressive tumor associated to asbestos exposure, is expected to increase in incidence, and unfortunately, no curative modality exists. Reactivation of p53 is a new attractive antitumoral strategy. p53 is rarely mutated in mesothelioma, but it is inactivated in most tumors by the lack of p14(ARF). Here, we evaluated the feasibility of this approach in pleural mesothelioma by testing RITA and nutlin-3, two molecules able to restore p53 function through a different mechanism, on a panel of mesothelioma cell lines representing the epithelioid (NCI-H28, NCI-H2452, IST-MES 2), biphasic (MSTO-211H), and sarcomatoid (NCI-H2052) histotypes compared with the normal mesothelial HMC-hTERT. RITA triggered robust caspase-dependent apoptosis specifically in epithelioid and biphasic mesothelioma cell lines, both through wild-type and mutant p53, concomitant to p21 downregulation. Conversely, nutlin-3 induced a p21-dependent growth arrest, rather than apoptosis, and was slightly toxic on HMC-hTERT. Interestingly, we identified a previously undetected point mutation of p53 (p.Arg249Ser) in IST-MES 2, and showed that RITA is also able to reactivate this p53 mutant protein and its apoptotic function. RITA reduced tumor growth in a MSTO-211H-derived xenograft model of mesothelioma and synergized with cisplatin, which is the mainstay of treatment for this tumor. Our data indicate that reactivation of p53 and concomitant p21 downregulation effectively induce cell death in mesothelioma, a tumor characterized by a high intrinsic resistance to apoptosis. Altogether, our findings provide the preclinical framework supporting the use of p53-reactivating agents alone, or in combination regimens, to improve the outcome of patients with mesothelioma.}, }
@article {pmid24340607, year = {2013}, author = {Pylev, LN and Vasil'eva, LA and Smirnova, OV and Vezentsev, AI and Gudkova, EA and Ingel', FI}, title = {[Carcinogenic and mutagenic activity of chrysotile, processed with iron chloride (III)].}, journal = {Gigiena i sanitariia}, volume = {}, number = {4}, pages = {76-80}, pmid = {24340607}, issn = {0016-9900}, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; Carcinogenicity Tests ; Chlorides/*chemistry ; Erythrocytes/drug effects/pathology ; Female ; Ferric Compounds/*chemistry ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Mice ; Mice, Inbred Strains ; Micronuclei, Chromosome-Defective/*chemically induced ; Micronucleus Tests ; Rats ; Rats, Wistar ; Surface Properties ; }, abstract = {This work is devoted to the study of the role of iron ions in the carcinogenic and mutagenic activity of chrysotile. For this aim natural chrysotile was treated with ferric chloride (III), washed, crushed and intratracheally introduced into Wistar rats. When administered to rats intact chrysotile induced mesotheliomas in 27,9 + 4,6% of cases, and chrysotile modified with ferric chloride - in 1,3 +/- 1,3%. Mutagenicity of the same samples was studied in the micronucleus test when administered intraperitoneally to mice Fl (CBA x S57Bl6). Polychromatic erythrocytes in the bone marrow were investigated 24 hours after intraperitoneal administration. The frequency of polychromatic erythrocytes with micronuclei was decreased from 7,4 +/- 0,18 by 1000 due to the action of chrysotile, from 2,8 +/- 0,42 for 1000 after the introduction of a modified sample. It is hypothesized that the ferric chloride modifies the surface of asbestos fibers that reduces the induction of free radicals which are the primary cause of and carcinogenic effects of chrysotile.}, }
@article {pmid24336325, year = {2015}, author = {Tanaka, I and Osada, H and Fujii, M and Fukatsu, A and Hida, T and Horio, Y and Kondo, Y and Sato, A and Hasegawa, Y and Tsujimura, T and Sekido, Y}, title = {LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.}, journal = {Oncogene}, volume = {34}, number = {1}, pages = {73-83}, pmid = {24336325}, issn = {1476-5594}, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Cell Adhesion ; Cell Line, Tumor ; Cell Proliferation ; Cytoplasm/metabolism ; *Gene Expression Regulation, Neoplastic ; Hippo Signaling Pathway ; Humans ; Immunohistochemistry ; LIM Domain Proteins/*metabolism ; Lentivirus/genetics ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Neurofibromin 2/metabolism ; Phenotype ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Serine-Threonine Kinases/*metabolism ; RNA, Small Interfering/metabolism ; Signal Transduction ; Transcription Factors ; YAP-Signaling Proteins ; }, abstract = {Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually associated with asbestos exposure and is highly refractory to current therapeutic modalities. MMs show frequent activation of a transcriptional coactivator Yes-associated protein (YAP), which is attributed to the neurofibromatosis type 2 (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and acquisition of a malignant phenotype. However, the whole mechanism of disordered YAP activation in MMs has not yet been well clarified. In the present study, we investigated various components of the NF2-Hippo pathway, and eventually found that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a binding partner of large tumor suppressor type 2 (LATS2), which is one of the last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was independent of the alteration status of other Hippo pathway components, MM cell lines with AJUBA inactivation showed a more dephosphorylated (activated) level of YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in primary MMs, which was associated with YAP constitutive activation. We found that AJUBA transduction into MM cells significantly suppressed promoter activities of YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably canceled by knockdown of LATS2. In connection with these results, transduction of AJUBA-expressing lentivirus significantly inhibited the proliferation and anchorage-independent growth of the MM cells that harbored ordinary LATS family expression. Taken together, our findings indicate that AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in MM cell proliferation.}, }
@article {pmid24327015, year = {2014}, author = {Linton, A and Cheng, YY and Griggs, K and Schedlich, L and Kirschner, MB and Gattani, S and Srikaran, S and Chuan-Hao Kao, S and McCaughan, BC and Klebe, S and van Zandwijk, N and Reid, G}, title = {An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {110}, number = {2}, pages = {510-519}, pmid = {24327015}, issn = {1532-1827}, mesh = {Apoptosis/drug effects/genetics ; Blood Proteins/genetics ; CDC2 Protein Kinase/genetics/*metabolism ; Cell Cycle/drug effects/genetics ; Cell Cycle Checkpoints/drug effects/genetics ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line, Tumor ; Cisplatin/pharmacology ; Cytoskeletal Proteins ; DNA Repair/drug effects/genetics ; DNA Replication/drug effects/genetics ; Humans ; Lung Neoplasms/*drug therapy/genetics/*metabolism ; Mesothelioma/*drug therapy/genetics/*metabolism ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Nuclear Proteins/genetics/*metabolism ; Pleural Neoplasms/drug therapy/genetics/metabolism ; Prognosis ; Protein Serine-Threonine Kinases/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Purines/pharmacology ; *RNA Interference ; Retrospective Studies ; Roscovitine ; Polo-Like Kinase 1 ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed.<br><br>METHODS: Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients.<br><br>RESULTS: Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis.<br><br>CONCLUSION: These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.}, }
@article {pmid24324091, year = {2013}, author = {Corradi, M and Goldoni, M and Alinovi, R and Tiseo, M and Ampollini, L and Bonini, S and Carbognani, P and Casalini, A and Mutti, A}, title = {YKL-40 and mesothelin in the blood of patients with malignant mesothelioma, lung cancer and asbestosis.}, journal = {Anticancer research}, volume = {33}, number = {12}, pages = {5517-5524}, pmid = {24324091}, issn = {1791-7530}, mesh = {Adipokines/*blood ; Aged ; Asbestosis/*blood ; Biomarkers, Tumor/blood ; Case-Control Studies ; Chitinase-3-Like Protein 1 ; Cross-Sectional Studies ; Endothelin-1/blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Interleukin-8/blood ; Lectins/*blood ; Lung Neoplasms/*blood ; Male ; Mesothelin ; Mesothelioma/*blood ; Middle Aged ; Vascular Endothelial Growth Factor A/blood ; }, abstract = {BACKGROUND/AIM: In the diagnosis of malignant mesothelioma (MM) there still is a lack of specific and sensitive screening biomarkers: this study examined the discriminatory power of a panel of serum/plasma biomarkers.<br><br>PATIENTS AND METHODS: The study involved four groups: (a) individuals previously exposed to asbestos with asbestosis; (b) patients with MM; (c) patients with non-small cell lung cancer; and (d) controls without any evidence of malignancy. The concentrations of mesothelin, chitinase-3-like-1 (YKL-40), vascular endothelial growth factor (VEGF), endothelin-1, interleukin-8 (IL-8) and fibulin-3 in the serum of patients were determined.<br><br>RESULTS: Patients with MM had significantly higher serum levels of mesothelin (p<0.001), YKL-40 (p<0.001), IL-8 (p<0.001) and VEGF (p<0.01) than controls. The cut-off point for MM was 1.26 nM for mesothelin alone, and 167 pg/ml for YKL-40 alone; the presence of both markers above these cut-off levels improved diagnostic specificity.<br><br>CONCLUSION: The addition of YKL-40 may improve the specificity of mesothelin measurements alone for detecting patients with MM.}, }
@article {pmid24303696, year = {2013}, author = {Filon, FL and Negro, C and De Michieli, P and Bovenzi, M}, title = {[Asbestos related cancers in seamen].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {35}, number = {4}, pages = {206-210}, pmid = {24303696}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Mesothelioma/epidemiology/*etiology ; *Naval Medicine ; Occupational Diseases/epidemiology/*etiology ; }, abstract = {Seamen and marine engineers were formerly exposed to asbestos used in gasket, pipes, valves and machinery. Ship motion and vibration can release asbestos in the surrounding space. Asbestos fibres may also be inhaled by workers involved in maintenance operations of vessels built before 1992 in Italy. History of asbestos exposure has been reported by workers and confirmed by a higher prevalence of pleural abnormalities and a significant excess of mesothelioma with a Standardized Incidence Ratio (SIR) ranging between 1.83 and 4.8 as a function of years of exposure. SIR for lung cancer ranged between 1.10 and 1.62. Mesothelioma in seamen and marine engineers represents about 2.5% of the overall Italian mesothelioma cases with a very long latency period (47.6 +/- 9.6 years). There is no epidemiological evidence for an excess risk of mesothelioma in fishermen.}, }
@article {pmid24297134, year = {2013}, author = {Wright, CM and Kirschner, MB and van Zandwijk, N and Reid, G}, title = {Does miR-1 play a role in malignant pleural mesothelioma development and progression?.}, journal = {Chest}, volume = {144}, number = {6}, pages = {1971}, doi = {10.1378/chest.13-1657}, pmid = {24297134}, issn = {1931-3543}, mesh = {Apoptosis/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; MicroRNAs/*genetics ; RNA, Neoplasm/*genetics ; }, }
@article {pmid24257681, year = {2014}, author = {Toyokuni, S}, title = {Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis.}, journal = {Redox report : communications in free radical research}, volume = {19}, number = {1}, pages = {1-7}, pmid = {24257681}, issn = {1743-2928}, mesh = {Adsorption ; Animals ; Asbestos/*adverse effects ; Asbestosis/complications/epidemiology ; Benzoates/therapeutic use ; Carcinogens, Environmental/pharmacokinetics ; Carcinoma, Renal Cell/chemically induced/genetics ; *Cell Transformation, Neoplastic ; Comparative Genomic Hybridization ; Deferasirox ; Ferric Compounds/toxicity ; Ferric Oxide, Saccharated ; Genes, p16 ; Glucaric Acid/toxicity ; Humans ; Iron Chelating Agents/therapeutic use ; Iron Overload/drug therapy/*etiology/therapy ; Japan/epidemiology ; Kidney Neoplasms/chemically induced/genetics ; Male ; Mesothelioma/epidemiology/*etiology/genetics/prevention &amp; control ; Mineral Fibers/adverse effects ; Peritoneal Neoplasms/chemically induced ; Phlebotomy ; Pleural Neoplasms/epidemiology/*etiology/genetics/prevention &amp; control ; Rats ; Triazoles/therapeutic use ; }, abstract = {Few people expected that asbestos, a fibrous mineral, would be carcinogenic to humans. In fact, asbestos is a definite carcinogen in humans, causing a rare but aggressive cancer called malignant mesothelioma (MM). Mesothelial cells line the three somatic cavities and thus do not face the outer surface, but reduce the friction among numerous moving organs. MM has several characteristics: extremely long incubation period of 30-40 years after asbestos exposure, difficulty in clinical diagnosis at an early stage, and poor prognosis even under the current multimodal therapies. In Japan, 'Kubota shock' attracted considerable social attention in 2005 for asbestos-induced mesothelioma and, thereafter, the government enacted a law to provide the people suffering from MM a financial allowance. Several lines of recent evidence suggest that the major pathology associated with asbestos-induced MM is local iron overload, associated with asbestos exposure. Preclinical studies to prevent MM after asbestos exposure with iron reduction are in progress. In addition, novel target genes in mesothelial carcinogenesis have been discovered with recently recognized mesothelioma-prone families. Development of an effective preventive strategy is eagerly anticipated because of the long incubation period for MM.}, }
@article {pmid24248693, year = {2013}, author = {Chirieac, LR and Barletta, JA and Yeap, BY and Richards, WG and Tilleman, T and Bueno, R and Baldini, EH and Godleski, J and Sugarbaker, DJ}, title = {Clinicopathologic characteristics of malignant mesotheliomas arising in patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {31}, number = {36}, pages = {4544-4549}, doi = {10.1200/JCO.2013.49.9616}, pmid = {24248693}, issn = {1527-7755}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Female ; Hodgkin Disease/*radiotherapy ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/chemically induced/*diagnosis/*etiology/mortality/pathology ; Lymphoma, Non-Hodgkin/*radiotherapy ; Male ; Mesothelioma/chemically induced/*diagnosis/*etiology/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/chemically induced/*diagnosis/*etiology/mortality/pathology ; Predictive Value of Tests ; Radiotherapy/adverse effects ; Risk Factors ; }, abstract = {PURPOSE: Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established.<br><br>PATIENTS AND METHODS: We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival.<br><br>RESULTS: We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P < .001), age &#x2264; 65 years (P = .005), cytoreductive surgery (P < .001), and epithelioid histology (P < .001).<br><br>CONCLUSION: Patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and seem to have a longer overall survival compared with patients with asbestos-associated PDMM.}, }
@article {pmid24239893, year = {2014}, author = {Lee, YJ and Park, IS and Lee, YJ and Shim, JH and Cho, MK and Nam, HS and Park, JW and Oh, MH and Lee, SH}, title = {Resveratrol contributes to chemosensitivity of malignant mesothelioma cells with activation of p53.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {63}, number = {}, pages = {153-160}, doi = {10.1016/j.fct.2013.11.004}, pmid = {24239893}, issn = {1873-6351}, mesh = {Adenine Nucleotides/pharmacology ; Anticarcinogenic Agents/*pharmacology ; Antineoplastic Agents/*pharmacology ; Arabinonucleosides/pharmacology ; Base Sequence ; Cell Line, Tumor ; Clofarabine ; DNA Primers ; G1 Phase ; *Genes, p53 ; Humans ; Mesothelioma/drug therapy/*pathology ; Oncogene Proteins/genetics ; Polymerase Chain Reaction ; Resveratrol ; Stilbenes/*pharmacology ; }, abstract = {Resveratrol is a naturally occurring polyphenolic phytoalexin with chemopreventive properties. We previously reported a synergistic anti-proliferative effect of resveratrol and clofarabine against malignant mesothelioma (MM) cells. Here, we further investigated molecular mechanisms involved in the synergistic interaction of these compounds in MM MSTO-211H cells. Resveratrol, in combination with clofarabine, time-dependently induced a strong cytotoxic effect with the nuclear accumulation of phospho-p53 (p-p53) in MSTO-211H cells, but not in normal mesothelial MeT-5A cells. Combination treatment up-regulated the levels of p-p53, cleaved caspase-3, and cleaved PARP proteins. Gene silencing with p53-targeting siRNA attenuated the sensitivity of cells to the combined treatment of two compounds. Analyses of p53 DNA binding assay, p53 reporter gene assay, and RTP-CR toward p53-regulated genes, including Bax, PUMA, Noxa and p21, demonstrated that induced p-p53 is transcriptionally active. These results were further confirmed by the siRNA-mediated knockdown of p53 gene. Combination treatment significantly caused the accumulation of cells at G1 phase with the increases in the sub-G0/G1 peak, DNA ladder, nuclear fragmentation, and caspase-3/7 activity. Taken together, these results demonstrate that resveratrol and clofarabine synergistically elicit apoptotic signal via a p53-dependent pathway, and provide a scientific rationale for clinical evaluation of resveratrol as a promising chemopotentiator in MM.}, }
@article {pmid24231697, year = {2013}, author = {Nakano, T and Otsuki, T}, title = {[Environmental air pollutants and the risk of cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {40}, number = {11}, pages = {1441-1445}, pmid = {24231697}, issn = {0385-0684}, mesh = {Air Pollutants/*adverse effects ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Humans ; Nanotubes/adverse effects ; Neoplasms/*chemically induced ; Risk Factors ; }, abstract = {The increased combustion of fossil fuels is one of the main reasons for the hazardous changes in the atmospheric composition. The sources of air pollution in urban areas include diesel motor vehicles, residential wood burning, and certain industrial processes. The types of air pollution include gases(eg, carbon monoxide, sulfur dioxide, nitrogen oxides, ozone)and suspended particulate matter(PM)such as PM2.5 and PM10 in diesel exhaust particles. PM2.5 refers to particles less than 2.5 micrometers in diameter. Long-term exposure to PM2.5 can increase the cardiovascular disease risk and lung cancer mortality. Although the role of PM2.5 in the etiology of lung cancer is not very clear, some researchers have shown evidence of increases in lung cancer mortality associated with exposure to PM2.5. Asbestos is also an important cause of cancer of the respiratory tract, particularly lung cancer and mesothelioma. The oncogenic hazards of asbestos fiber have been noted in cases of lowdose environmental exposure, as well in cases of high-dose occupational exposure. The use of asbestos has been strictly prohibited in Japan since 2006. However, large-scale natural disasters such as earthquakes, tsunamis, and typhoons can destroy many buildings and houses that were constructed before the ban on asbestos was initiated, thus resulting in the exposure of human beings to asbestos fibers. In the Cappadocian villages of Tuzkoy, Karain, and Sarihidir in Turkey, 50% of all deaths among villagers are caused by mesothelioma. This condition has been attributed to exposure to erionite, which is a type of fibrous zeolite mineral commonly found in this area of Turkey. However, pedigree studies of these villages showed that mesothelioma was prevalent in certain families but not in others, and that erionite exposure typically causes mesothelioma in those with a genetic predisposition to this disease. Recently, the germline BAP1 mutation was demonstrated in 2 different familial clusters of mesothelioma in the US.}, }
@article {pmid24222877, year = {2013}, author = {Saba, R and Aronu, GN and Bhatti, RP and Mirrakhimov, AE and Anusim, N and Barbaryan, A and Kwatra, SG and Iroegbu, N}, title = {Malignant mesothelioma after household exposure to asbestos.}, journal = {Case reports in oncological medicine}, volume = {2013}, number = {}, pages = {570487}, pmid = {24222877}, issn = {2090-6706}, abstract = {Malignant mesothelioma (MM) is an aggressive cancer that has been closely linked to asbestos exposure. Initially recognized as an occupational cancer in male workers, MM was later found to occur in their family members as well. We report the case of an 89-year-old female who presented with abdominal distention, pain, and findings consistent with malignant ascites. Family history was significant for fatal mesothelioma in her husband of 40 years, who was a worker at a tile factory. The diagnosis of MM was confirmed on pathologic examination of the omental core biopsy.}, }
@article {pmid24210155, year = {2013}, author = {Fleury Feith, J and Jaurand, MC}, title = {[Pleural lymphatics and pleural diseases related to fibres].}, journal = {Revue de pneumologie clinique}, volume = {69}, number = {6}, pages = {358-362}, doi = {10.1016/j.pneumo.2013.09.007}, pmid = {24210155}, issn = {1776-2561}, mesh = {Asbestos/adverse effects ; Humans ; Lymphatic Diseases/*chemically induced/epidemiology ; Lymphatic Vessels/pathology ; Mineral Fibers/*adverse effects ; Pleura/immunology/pathology ; Pleural Diseases/*chemically induced/epidemiology ; }, abstract = {It is now well established that some pleural diseases, pleural plaques and malignant mesothelioma are related to asbestos fibre exposure although the mechanism of action of asbestos fibres is not fully understood. The development of artificial mineral fibres and carbon nanotubes, which share some morphological characteristics similar to asbestos fibres, is a present concern in the context of pleural diseases. Pleural plaques develop only in the parietal pleura, and in the 1990s, clinical observations have shown that the early development of mesothelioma also occurred on the parietal pleura. The peculiarity of the parietal pleura in contrast to the visceral pleura is the presence of "stomas" which are communication holes between the pleural cavity and the parietal pleura lymphatics. Morphological observations by thoracoscopy and experimental studies have shown that inhaled fibres translocate to the pleural space and, in human, are present in the parietal pleura at specific anthracotic areas (blackspots). Fibres accumulate on the stomas, up to block and locally induce an inflammatory reaction with cytokines release, that can be the bed of mesothelioma. However, despite the experimental data and observations in human pathology, the mechanisms of fibre translocation into the pleura is not yet clearly established.}, }
@article {pmid24200157, year = {2013}, author = {Nagai, H and Okazaki, Y and Chew, SH and Misawa, N and Miyata, Y and Shinohara, H and Toyokuni, S}, title = {Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats.}, journal = {Pathology international}, volume = {63}, number = {9}, pages = {457-462}, doi = {10.1111/pin.12093}, pmid = {24200157}, issn = {1440-1827}, mesh = {Animals ; Asbestos/adverse effects ; *Cell Transformation, Neoplastic/chemistry ; Disease Models, Animal ; Environmental Health ; Female ; Injections, Intraperitoneal ; Male ; Mesothelioma/chemically induced/*pathology ; *Nanotubes, Carbon/adverse effects ; Rats ; Rats, Inbred F344 ; }, abstract = {Multiwalled carbon nanotubes (MWCNTs) have attracted public attention not only for their potential applications in engineering and materials science but also for possible environmental risks. MWCNTs share similar properties with asbestos, a definite human carcinogen causing malignant mesothelioma (MM), in that they are both biopersistent thin fibers with a high aspect ratio. Certain types of MWCNTs do induce MM in animal experiments. Though there are many different types of MWCNTs awaiting use in industry, there is little evidence about what types of MWCNTs present a high risk for MM in vivo. We have previously shown that the diameter of MWCNTs is one of the critical factors for mesothelial injury, which eventually leads to MM. Because of the extensive commercial use of MWCNTs, the properties of MWCNTs that determine carcinogenic activity should be clarified. Here we report that a high dose (10 mg) of a tangled form of pristine MWCNT (with a diameter of 15 nm) did not induce MM after intraperitoneal administration in rats, which were followed for up to 3 years after injection. This observation strengthens our previous finding that the rigidity, diameter, length and surface properties of MWCNTs are important factors in MM induction in vivo.}, }
@article {pmid24195451, year = {2013}, author = {López-Abente, G and García-Gómez, M and Menéndez-Navarro, A and Fernández-Navarro, P and Ramis, R and García-Pérez, J and Cervantes, M and Ferreras, E and Jiménez-Muñoz, M and Pastor-Barriuso, R}, title = {Pleural cancer mortality in Spain: time-trends and updating of predictions up to 2020.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {528}, pmid = {24195451}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Child ; Child, Preschool ; Environmental Exposure/adverse effects ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Pleural Neoplasms/epidemiology/etiology/history/*mortality ; Sex Factors ; Spain/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: A total of 2,514,346 metric tons (Mt) of asbestos were imported into Spain from 1906 until the ban on asbestos in 2002. Our objective was to study pleural cancer mortality trends as an indicator of mesothelioma mortality and update mortality predictions for the periods 2011-2015 and 2016-2020 in Spain.<br><br>METHODS: Log-linear Poisson models were fitted to study the effect of age, period of death and birth cohort (APC) on mortality trends. Change points in cohort- and period-effect curvatures were assessed using segmented regression. Fractional power-link APC models were used to predict mortality until 2020. In addition, an alternative model based on national asbestos consumption figures was also used to perform long-term predictions.<br><br>RESULTS: Pleural cancer deaths increased across the study period, rising from 491 in 1976-1980 to 1,249 in 2006-2010. Predictions for the five-year period 2016-2020 indicated a total of 1,319 pleural cancer deaths (264 deaths/year). Forecasts up to 2020 indicated that this increase would continue, though the age-adjusted rates showed a levelling-off in male mortality from 2001 to 2005, corresponding to the lower risk in post-1960 generations. Among women, rates were lower and the mortality trend was also different, indicating that occupational exposure was possibly the single factor having most influence on pleural cancer mortality.<br><br>CONCLUSION: The cancer mortality-related consequences of human exposure to asbestos are set to persist and remain in evidence until the last surviving members of the exposed cohorts have disappeared. It can thus be assumed that occupationally-related deaths due to pleural mesothelioma will continue to occur in Spain until at least 2040.}, }
@article {pmid24189076, year = {2014}, author = {Goodman, JE and Peterson, MK and Bailey, LA and Kerper, LE and Dodge, DG}, title = {Electricians' chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {68}, number = {1}, pages = {8-15}, doi = {10.1016/j.yrtph.2013.10.008}, pmid = {24189076}, issn = {1096-0295}, mesh = {Asbestos, Amphibole/analysis/*toxicity ; Asbestos, Serpentine/analysis/*toxicity ; Electrical Equipment and Supplies ; Europe ; Humans ; Inhalation Exposure/*adverse effects/analysis ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects/analysis ; Risk Assessment ; United States ; }, abstract = {Both mechanistic and epidemiology studies indicate chrysotile asbestos has a threshold below which it does not cause mesothelioma or lung cancer. We conducted a critical review to determine whether electricians are at increased risk for these cancers and, if so, whether their exposure to chrysotile in electrical products could be responsible. We found that most, but not all, epidemiology studies indicate electricians are at increased risk for both cancers. Studies that evaluated electricians' exposure to asbestos during normal work tasks have generally reported low concentrations in air; an experimental study showed that grinding or drilling products containing encapsulated chrysotile resulted in exposures to chrysotile fibers far below the OSHA permissible exposure limit and the cancer no observed adverse effect level. Studies of other craftsmen who often work in the vicinity of electricians, such as insulators, reported asbestos (including amphibole) exposures that were relatively high. Overall, the evidence does not indicate that exposure to chrysotile in electrical products causes mesothelioma or lung cancer in electricians. Rather, the most likely cause of lung cancer in electricians is smoking, and the most likely cause of mesothelioma is exposure to amphibole asbestos as a result of renovation/demolition work or working in the proximity of other skilled craftsmen.}, }
@article {pmid24185840, year = {2013}, author = {Goswami, E and Craven, V and Dahlstrom, DL and Alexander, D and Mowat, F}, title = {Domestic asbestos exposure: a review of epidemiologic and exposure data.}, journal = {International journal of environmental research and public health}, volume = {10}, number = {11}, pages = {5629-5670}, pmid = {24185840}, issn = {1660-4601}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Risk Assessment ; }, abstract = {Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities) among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12) of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE) of 5.02 (95% confidence interval [CI]: 2.48-10.13). This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners). The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6), though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2). Several exposure-related studies describe results from airborne samples collected within the home (n = 3), during laundering of contaminated clothing (n = 1) or in controlled exposure simulations (n = 5) of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6) were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers' exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically.}, }
@article {pmid24183360, year = {2013}, author = {Shih, CA and Ho, SP and Tsay, FW and Lai, KH and Hsu, PI}, title = {Diffuse malignant peritoneal mesothelioma.}, journal = {The Kaohsiung journal of medical sciences}, volume = {29}, number = {11}, pages = {642-645}, doi = {10.1016/j.kjms.2013.05.003}, pmid = {24183360}, issn = {2410-8650}, mesh = {Biopsy ; Humans ; Lung Neoplasms/*diagnosis/diagnostic imaging/pathology ; Male ; Mesothelioma/*diagnosis/diagnostic imaging/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/diagnostic imaging/pathology ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma often originates in the pleura and less frequently in the peritoneum. This article describes a rare case of diffuse malignant peritoneal mesothelioma in a 54-year-old male construction worker who was admitted to our hospital with a 2-month history of progressive abdominal distention. Abdominal computed tomography revealed extensive peritoneal nodularity and omental cake along with massive ascites. Imaging findings initially suggested peritoneal carcinomatosis, primary peritoneal carcinoma, and tuberculous peritonitis. Laparoscopic biopsy of the omentum and peritoneum confirmed the diagnosis of malignant peritoneal mesothelioma of epitheloid type. Although systemic chemotherapy was administered, no tumor regression was found. The patient finally died of nosocomial infection.}, }
@article {pmid24180083, year = {2013}, author = {Mastrangelo, G and Marangi, G and Ballarin, MN and Bellini, E and De Marzo, N and Eder, M and Finchi, A and Gioffrè, F and Marcolina, D and Tessadri, G and Zannol, F and Altafini, I and Belluso, E and Zaina, S and Agnesi, R and Scoizzato, L and Fedeli, U and Cegolon, L and Valentini, F and Marchiori, L}, title = {Post-occupational health surveillance of asbestos workers.}, journal = {La Medicina del lavoro}, volume = {104}, number = {5}, pages = {351-358}, pmid = {24180083}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/blood/*epidemiology/etiology ; Biomarkers ; Early Detection of Cancer/economics/methods ; Follow-Up Studies ; Health Policy ; Humans ; Italy ; Liability, Legal ; Lung Neoplasms/diagnosis/economics/epidemiology/etiology/prevention &amp; control ; Male ; Mesothelioma/diagnosis/economics/epidemiology/etiology/prevention &amp; control ; Middle Aged ; Mineral Fibers/analysis ; *Occupational Exposure ; Occupations ; Osteopontin/blood ; Pleural Neoplasms/diagnosis/economics/epidemiology/etiology/prevention &amp; control ; *Population Surveillance/methods ; Program Evaluation ; Reproducibility of Results ; Respiratory Function Tests ; Retirement ; Retrospective Studies ; Smoking ; }, abstract = {BACKGROUND: Italian law requires an extensive health surveillance of workers after cessation of their employment status in the case of occupational exposure to carcinogens, including asbestos. Nonetheless, Italian law does not specify the timeframe of these clinical checks, nor who has financial and organizational responsibility for this surveillance. A literature search confirmed a lack of consensus around the objectives and methods to follow up workers with past occupational exposure to asbestos.<br><br>OBJECTIVES: To develop an updated evidence-based methodology for an appropriate health surveillance programme.<br><br>METHODS: We present an overview of the field experience developed by the Veneto Region from 2000 to 2011, and new studies that could contribute to establishing a national policy for the medical surveillance of workers with past asbestos exposure.<br><br>RESULTS: There were three specific topics: (1) definition of a reliable method to identify asbestos workers (through multiple sources and procedures that meet current confidentiality regulations); (2) detection of asbestos fibres in biological media (to support the etiological diagnosis of asbestos-related diseases); (3) creation of a national protocol of health surveillance (through the assessment of policies developed by other Regions in this field, and recruiting from these regions a cohort of past-exposed workers: the epidemiological study should offer relevant suggestions for specific surveillance approaches, based on either estimated cumulative asbestos exposure or detection of x-ray patterns of pleural plaques and/or asbestosis).<br><br>CONCLUSIONS: These studies will support the Regions in setting up health care policies directed at workers with past asbestos exposure.}, }
@article {pmid24179653, year = {2013}, author = {Günday, M and Erinanç, H and Geredeli, C}, title = {Unusual region for pericardial malignant mesothelioma: cutaneous manifestation in a Turkish woman.}, journal = {Rare tumors}, volume = {5}, number = {3}, pages = {e41}, pmid = {24179653}, issn = {2036-3605}, abstract = {Malignant mesothelioma is a disease that originates from mesenchymal cells. It is related to the occupational or environmental exposure to asbestos. The treatment remains controversial because it is commonly diagnosed at a very late stage, and the prognosis is very poor. In this report, we present a 37-year-old female patient who was admitted with shortness of breath, palpitation and inability to sleep on her back for the previous 10 days. A large pericardial effusion was detected on echocardiography. Pericardiocentesis was performed and the patient's symptoms were alleviated. However, approximately 7 months later, she was readmitted to the clinic with complaints of a mass at the incision site. Pathological examination of the mass yielded a diagnosis of pericardial malignant mesothelioma. Malignant mesothelioma is a rare occurrence, and to our knowledge, there are no reports in the English literature of pericardial malignant mesothelioma local invasion to an incision site.}, }
@article {pmid24170217, year = {2014}, author = {Bayram, M and Dongel, I and Akbaş, A and Benli, I and Akkoyunlu, ME and Bakan, ND}, title = {Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos.}, journal = {Lung}, volume = {192}, number = {1}, pages = {197-203}, pmid = {24170217}, issn = {1432-1750}, mesh = {Aged ; Area Under Curve ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Chi-Square Distribution ; Diagnosis, Differential ; GPI-Linked Proteins/*blood ; Humans ; Inhalation Exposure/adverse effects ; Linear Models ; Mesothelin ; Mesothelioma/*blood/diagnosis/etiology ; Middle Aged ; Osteopontin/*blood ; Pleura/*pathology ; Pleural Neoplasms/*blood/diagnosis/etiology ; Predictive Value of Tests ; ROC Curve ; Risk Factors ; Smoking/adverse effects ; Turkey ; }, abstract = {PURPOSE: This study investigated the diagnostic accuracy of the serum biomarkers osteopontin and mesothelin in discriminating mesothelioma patients from those with other, benign conditions and whether levels of the biomarkers differed in subjects who had inhaled naturally occurring asbestos compared with a non-exposed control group.<br><br>METHODS: This cross-sectional study studied 24 subjects with mesothelioma, 279 subjects with pleural plaques, 123 "healthy exposed," and 120 control subjects. The Kruskal-Wallis test was performed to compare mesothelin and osteopontin levels of the groups, and receiver operating characteristics curves were generated to determine diagnostic yields of both biomarkers. Multiple linear regression analyses were used to identify associated covariates with osteopontin and mesothelin levels.<br><br>RESULTS: Serum osteopontin and mesothelin levels were higher in mesothelioma than in benign asbestos-related diseases and healthy exposed subjects. Both biomarker levels were independently associated with mesothelioma, age and smoking pack years. Mesothelin levels were also associated with body mass index. The sensitivity and specificity of osteopontin in distinguishing mesothelioma from the three other groups were 75 and 86&#xa0;%, respectively; those of mesothelin were 58 and 83&#xa0;%, respectively. The sensitivity and specificity to discriminate mesothelioma from pleural plaques and healthy subjects were 93 and 73&#xa0;%, respectively, if osteopontin and mesothelin levels were higher than their optimal cut off levels.<br><br>CONCLUSIONS: The combination of serum osteopontin and mesothelin levels can help to distinguish mesothelioma from benign asbestos-related diseases and asbestos-exposed subjects.}, }
@article {pmid24168922, year = {2013}, author = {Muraoka, T and Soh, J and Toyooka, S and Aoe, K and Fujimoto, N and Hashida, S and Maki, Y and Tanaka, N and Shien, K and Furukawa, M and Yamamoto, H and Asano, H and Tsukuda, K and Kishimoto, T and Otsuki, T and Miyoshi, S}, title = {The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {82}, number = {3}, pages = {485-490}, doi = {10.1016/j.lungcan.2013.09.017}, pmid = {24168922}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; DNA/*analysis/blood ; DNA Methylation ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*diagnosis/genetics ; Male ; Mesothelioma/*diagnosis/genetics ; Mesothelioma, Malignant ; MicroRNAs/genetics/*metabolism ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/genetics ; Real-Time Polymerase Chain Reaction ; }, abstract = {OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP).<br><br>MATERIALS AND METHODS: A real-time MSP assay was performed using the SYBR Green method. The melting temperature (Tm) of each PCR product was examined using a melting curve analysis. For a digital MSP assay, 40 wells were analyzed per sample. A total of 110 serum samples from 48 MPM cases, 21 benign asbestos pleurisy (BAP) cases, and 41 healthy volunteers (HVs) were examined.<br><br>RESULTS: Positive range of Tm value for miR-34b/c methylation was defined as 77.71-78.79 &#xb0;C which was the mean &#xb1; 3 standard deviations of 40 wells of a positive control. The number of miR-34b/c methylated wells was counted per sample according to this criterion. The number of miR-34b/c methylated wells in MPM cases was significantly higher than that in BAP cases (P=0.03) or HVs (P<0.001). Advanced MPM cases tended to have higher number of miR-34b/c methylated wells than early MPM cases. Receiver-operating characteristic (ROC) curve analysis revealed that three number of miR-34b/c methylated wells per sample was the best cut-off of positivity of MPM with a 67% of sensitivity and a 77% specificity for prediction. The area under the ROC curve was 0.77.<br><br>CONCLUSIONS: Our digital MSP assay can quantify miR-34b/c methylation in serum-circulating DNA. The degree of miR-34b/c methylation in serum-circulating DNA is associated with MPM, suggesting that this approach might be useful for the establishment of a new detection system for MPM.}, }
@article {pmid24167356, year = {2013}, author = {Creaney, J and Sneddon, S and Dick, IM and Dare, H and Boudville, N and Musk, AW and Skates, SJ and Robinson, BW}, title = {Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum.}, journal = {Disease markers}, volume = {35}, number = {2}, pages = {119-127}, pmid = {24167356}, issn = {1875-8630}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Limit of Detection ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis ; Middle Aged ; Pleural Effusion, Malignant/*blood/diagnosis ; ROC Curve ; Renal Insufficiency, Chronic/blood ; }, abstract = {The MSLN gene products, soluble mesothelin and megakaryocyte potentiating factor (MPF), are being investigated as biomarkers for the asbestos-related cancer malignant mesothelioma (MM). Pleural fluid biomarkers of MM can be elevated when serum levels remain normal. The aim of this study was to determine if this was true for MPF and to compare levels of mesothelin. Biomarker concentrations were compared in 66 MM patients, 39 patients with other malignancies, 37 with benign disease, 18 asbestos-exposed healthy individuals, and 53 patients with chronic kidney disease. In pleural effusions, MPF and soluble mesothelin concentrations were both significantly elevated in MM patients relative to controls. No significant difference between the area under the receiver operator curve (AUC) for MPF (0.945 ± 0.02) and mesothelin (0.928 ± 0.03) when distinguishing MM from all other causes of effusion was observed. MPF and mesothelin serum concentrations were highly correlated and of equivalent diagnostic accuracy with AUCs of 0.813 ± 0.04 and 0.829 ± 0.03, respectively. Serum levels of both markers increased with decreasing kidney function. In conclusion, MPF is elevated in the pleural effusions of MM patients similar to that of mesothelin. Mesothelin and MPF convey equivalent diagnostic information for distinguishing MM from other diseases in pleural effusions as well as serum.}, }
@article {pmid24161718, year = {2013}, author = {Creaney, J and Dick, IM and Segal, A and Musk, AW and Robinson, BW}, title = {Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {82}, number = {3}, pages = {491-498}, doi = {10.1016/j.lungcan.2013.09.016}, pmid = {24161718}, issn = {1872-8332}, mesh = {Aged ; Biomarkers, Tumor/*metabolism ; Female ; GPI-Linked Proteins/metabolism ; Humans ; Hyaluronic Acid/*metabolism ; Lung Neoplasms/*diagnosis/mortality ; Male ; Mesothelin ; Mesothelioma/*diagnosis/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Cavity/metabolism ; Pleural Effusion/*diagnosis/mortality ; Pleural Neoplasms/*diagnosis/mortality ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM), a primarily asbestos-induced tumour, has a poor prognosis, with over-all 5-year survival less than 5%. Tumour biomarkers are being intensely investigated in MM as aids to diagnosis and prognosis. Hyaluronic acid (HA) is produced in MM but its role in prognostication remains uncertain.<br><br>MATERIALS AND METHODS: HA concentrations were determined in matching serum and pleural effusion of 96 MM patients, 26 lung cancer patients and 42 patients with benign effusions resulting from infectious, cardiac, renal, liver and rheumatoid diseases and compared to the current 'best practice' biomarker, mesothelin. Liver and kidney function were determined for each patient. Diagnostic accuracy was determined by area under the receiver operator characteristic curve (AUC) analysis following logistic regression modelling. Difference in survival between groups was determined by both log-rank test and Cox proportional hazards regression modelling.<br><br>RESULTS: For effusion HA, the AUC (IQ range) was 0.89 (0.82-0.94) and for effusion mesothelin, it was 0.85 (0.78-0.90). Serum HA was not diagnostically useful. A combined measure of effusion HA, and serum and effusion mesothelin had an AUC of 0.92 (0.86-0.96), which was significantly higher than effusion mesothelin alone. Effusion HA had a biphasic distribution in MM patients, dichotomised at a concentration of 75 mg/L. The median survival of MM patients with high effusion HA was 18.0 (13.7-22.4) months, significantly longer than those with low HA effusion levels (12.6 months (8.4-16.8), p=0.004). Serum HA, and effusion and serum mesothelin were not significant prognostic indicators.<br><br>CONCLUSION: This study demonstrates that a combined biomarker panel has greater diagnostic accuracy than effusion mesothelin alone, and that significant prognostic information is provided by effusion HA.}, }
@article {pmid24160326, year = {2013}, author = {Qi, F and Okimoto, G and Jube, S and Napolitano, A and Pass, HI and Laczko, R and Demay, RM and Khan, G and Tiirikainen, M and Rinaudo, C and Croce, A and Yang, H and Gaudino, G and Carbone, M}, title = {Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling.}, journal = {The American journal of pathology}, volume = {183}, number = {5}, pages = {1654-1666}, pmid = {24160326}, issn = {1525-2191}, support = {NCI R01 CA106567/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; NCI R01 CA160715-0A/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/*toxicity ; Cadherins/metabolism ; Cell Death/drug effects ; Cell Line ; Cell Shape/drug effects ; Cell Transformation, Neoplastic/*metabolism/*pathology ; Epithelium/drug effects/metabolism/*pathology ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Genome, Human/genetics ; HMGB1 Protein/blood/*metabolism ; Humans ; Mice ; Signal Transduction/*drug effects/genetics ; Transcription, Genetic/drug effects ; Tumor Necrosis Factor-alpha/*metabolism ; beta Catenin/metabolism ; }, abstract = {Malignant mesothelioma is strongly associated with asbestos exposure. Among asbestos fibers, crocidolite is considered the most and chrysotile the least oncogenic. Chrysotile accounts for more than 90% of the asbestos used worldwide, but its capacity to induce malignant mesothelioma is still debated. We found that chrysotile and crocidolite exposures have similar effects on human mesothelial cells. Morphological and molecular alterations suggestive of epithelial-mesenchymal transition, such as E-cadherin down-regulation and β-catenin phosphorylation followed by nuclear translocation, were induced by both chrysotile and crocidolite. Gene expression profiling revealed high-mobility group box-1 protein (HMGB1) as a key regulator of the transcriptional alterations induced by both types of asbestos. Crocidolite and chrysotile induced differential expression of 438 out of 28,869 genes interrogated by oligonucleotide microarrays. Out of these 438 genes, 57 were associated with inflammatory and immune response and cancer, and 14 were HMGB1 targeted genes. Crocidolite-induced gene alterations were sustained, whereas chrysotile-induced gene alterations returned to background levels within 5 weeks. Similarly, HMGB1 release in vivo progressively increased for 10 or more weeks after crocidolite exposure, but returned to background levels within 8 weeks after chrysotile exposure. Continuous administration of chrysotile was required for sustained high serum levels of HMGB1. These data support the hypothesis that differences in biopersistence influence the biological activities of these two asbestos fibers.}, }
@article {pmid24158772, year = {2014}, author = {Toyokawa, G and Takenoyama, M and Hirai, F and Toyozawa, R and Inamasu, E and Kojo, M and Morodomi, Y and Shiraishi, Y and Takenaka, T and Yamaguchi, M and Shimokawa, M and Seto, T and Ichinose, Y}, title = {Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy.}, journal = {International journal of clinical oncology}, volume = {19}, number = {4}, pages = {601-606}, pmid = {24158772}, issn = {1437-7772}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage ; Asbestos/toxicity ; Cisplatin/administration &amp; dosage ; Combined Modality Therapy ; Deoxycytidine/administration &amp; dosage/*analogs &amp; derivatives ; Disease-Free Survival ; Drug-Related Side Effects and Adverse Reactions/classification/pathology ; Female ; Glutamates/*administration &amp; dosage ; Guanine/administration &amp; dosage/*analogs &amp; derivatives ; Humans ; Lung Neoplasms/chemically induced/*drug therapy/pathology ; Male ; Mesothelioma/chemically induced/*drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pemetrexed ; Pleural Neoplasms/chemically induced/*drug therapy/pathology ; Vinblastine/administration &amp; dosage/*analogs &amp; derivatives ; Vinorelbine ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemotherapy. Although treatment with pemetrexed in combination with cisplatin serves as first-line chemotherapy for MPM, the optimal second-line and beyond therapy has not yet been fully examined.<br><br>METHODS: Between March 2008 and October 2011, 17 consecutive Japanese patients pretreated with at least one regimen of platinum plus pemetrexed chemotherapy received gemcitabine and vinorelbine. Responses, survival time, and toxicity were retrospectively evaluated.<br><br>RESULTS: Response [partial response (PR) + complete response (CR)] and disease control [stable disease (SD) + PR + CR] rates were 18 and 82 %, respectively. The median progression-free survival (PFS) after combination chemotherapy was 6.0 months, whereas the median overall survival (OS) was 11.2 months. Grade 3 or 4 neutropenia and anemia were observed in 41 and 29 % of patients, respectively, and one patient experienced febrile neutropenia. Grade 3 or 4 nonhematologic toxicities included constipation (6 %) and phlebitis (6 %).<br><br>CONCLUSION: Combination chemotherapy using gemcitabine with vinorelbine was shown to have moderate activity in Japanese MPM patients pretreated with platinum plus pemetrexed chemotherapy. A further multicenter phase II trial is warranted to confirm the efficacy and safety of this combination treatment.}, }
@article {pmid24148817, year = {2013}, author = {Reid, G and Pel, ME and Kirschner, MB and Cheng, YY and Mugridge, N and Weiss, J and Williams, M and Wright, C and Edelman, JJ and Vallely, MP and McCaughan, BC and Klebe, S and Brahmbhatt, H and MacDiarmid, JA and van Zandwijk, N}, title = {Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {24}, number = {12}, pages = {3128-3135}, doi = {10.1093/annonc/mdt412}, pmid = {24148817}, issn = {1569-8041}, mesh = {Animals ; Cell Line, Tumor ; Deoxycytidine/analogs &amp; derivatives/pharmacology ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Glutamates/pharmacology ; Guanine/analogs &amp; derivatives/pharmacology ; Humans ; Lung Neoplasms/*metabolism/pathology/therapy ; Mesothelioma/*metabolism/pathology/therapy ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; MicroRNAs/*genetics/metabolism ; Neoplasm Transplantation ; Pemetrexed ; Pleural Neoplasms/*metabolism/pathology/therapy ; RNA Interference ; Transfection ; Tumor Burden ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches to therapy are needed. Reduced expression of miR-15/16 in a range of cancer types has suggested a tumour suppressor function for these microRNAs, and re-expression has been shown to inhibit tumour cell proliferation. The miR-15/16 status in MPM is largely unknown.<br><br>MATERIALS AND METHODS: MicroRNA expression was analysed by TaqMan-based RT-qPCR in MPM tumour specimens and cell lines. MicroRNA expression was restored in vitro using microRNA mimics, and effects on proliferation, drug sensitivity and target gene expression were assessed. Xenograft-bearing mice were treated with miR-16 mimic packaged in minicells targeted with epidermal growth factor receptor (EGFR)-specific antibodies.<br><br>RESULTS: Expression of the miR-15 family was consistently downregulated in MPM tumour specimens and cell lines. A decrease of 4- to 22-fold was found when tumour specimens were compared with normal pleura. When MPM cell lines were compared with the normal mesothelial cell line MeT-5A, the downregulation of miR-15/16 was 2- to 10-fold. Using synthetic mimics to restore miR-15/16 expression led to growth inhibition in MPM cell lines but not in MeT-5A cells. Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine. In xenograft-bearing nude mice, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of MPM tumour growth.<br><br>CONCLUSIONS: The miR-15/16 family is downregulated and has tumour suppressor function in MPM. Restoring miR-16 expression represents a novel therapeutic approach for MPM.}, }
@article {pmid24142981, year = {2013}, author = {Langevin, SM and O'Sullivan, MH and Valerio, JL and Pawlita, M and Applebaum, KM and Eliot, M and McClean, MD and Kelsey, KT}, title = {Occupational asbestos exposure is associated with pharyngeal squamous cell carcinoma in men from the greater Boston area.}, journal = {Occupational and environmental medicine}, volume = {70}, number = {12}, pages = {858-863}, pmid = {24142981}, issn = {1470-7926}, support = {T32ES07272/ES/NIEHS NIH HHS/United States ; K01 OH009390/OH/NIOSH CDC HHS/United States ; R01CA078609/CA/NCI NIH HHS/United States ; R01CA100679/CA/NCI NIH HHS/United States ; R01CA121147/CA/NCI NIH HHS/United States ; T32 ES007272/ES/NIEHS NIH HHS/United States ; R01 CA078609/CA/NCI NIH HHS/United States ; R01 CA121147/CA/NCI NIH HHS/United States ; R01 CA100679/CA/NCI NIH HHS/United States ; K01OH009390/OH/NIOSH CDC HHS/United States ; }, mesh = {Asbestos/*toxicity ; Boston/epidemiology ; Carcinoma, Squamous Cell/epidemiology/*etiology ; Case-Control Studies ; Humans ; Incidence ; Male ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pharyngeal Neoplasms/epidemiology/*etiology ; Risk Factors ; }, abstract = {OBJECTIVES: Asbestos is the name given to a group of naturally occurring silicate mineral fibres that were widely used in industry during the 20th century due to their desirable physical properties. Although use in the USA has fallen over the last three decades, significant exposure in the developing world continues and the burden of disease is considerable. Asbestos is a known risk factor for several malignant diseases, including lung cancer and mesothelioma, and has more recently been implicated in pharyngeal and laryngeal cancer. However, studies of asbestos and cancers of the larynx or pharynx with adequate sample size that control for major head and neck squamous cell carcinoma (HNSCC) risk factors remain relatively sparse.<br><br>METHODS: We report findings from a case-control study of 674 incident male HNSCC cases from the greater Boston region and 857 population-based male controls, matched on age (&#xb1;3 years), sex, and town or neighbourhood of residence. Multivariable logistic regression was used to assess the association between occupational asbestos exposure and HNSCC by primary tumour site.<br><br>RESULTS: 190 cases (28.2%) and 203 controls (23.7%) reported occupational exposure to asbestos. Occupational asbestos exposure was associated with elevated risk of pharyngeal carcinoma in men (OR 1.41, 95% CI 1.01 to 1.97), adjusted for age, race, smoking, alcohol consumption, education, income and HPV16 serology, with borderline increasing risk for each decade in the exposed occupation (OR 1.10, 95% CI 0.99 to 1.23).<br><br>CONCLUSIONS: These observations are consistent with mounting evidence that asbestos is a risk factor for pharyngeal cancer.}, }
@article {pmid24142974, year = {2014}, author = {Daniels, RD and Kubale, TL and Yiin, JH and Dahm, MM and Hales, TR and Baris, D and Zahm, SH and Beaumont, JJ and Waters, KM and Pinkerton, LE}, title = {Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950-2009).}, journal = {Occupational and environmental medicine}, volume = {71}, number = {6}, pages = {388-397}, pmid = {24142974}, issn = {1470-7926}, support = {N02 PC015105/PC/NCI NIH HHS/United States ; CC999999//Intramural CDC HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; N01PC35136/CA/NCI NIH HHS/United States ; N01PC35139/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Cause of Death ; Chicago/epidemiology ; Cohort Studies ; Digestive System Neoplasms/epidemiology/*etiology/mortality ; Female ; *Firefighters ; Humans ; Incidence ; Lung Neoplasms/epidemiology/*etiology/mortality ; Male ; Mesothelioma/epidemiology/*etiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/epidemiology/etiology ; Occupational Diseases/epidemiology/*etiology/mortality ; Occupational Exposure/*adverse effects ; Philadelphia/epidemiology ; Respiratory Tract Neoplasms/epidemiology/*etiology/mortality ; San Francisco/epidemiology ; }, abstract = {OBJECTIVES: To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009.<br><br>METHODS: Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias.<br><br>RESULTS: Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques.<br><br>CONCLUSIONS: Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.}, }
@article {pmid24141556, year = {2014}, author = {Suzuki, H and Asami, K and Hirashima, T and Okamoto, N and Yamadori, T and Tamiya, M and Morishita, N and Shiroyama, T and Takeoka, S and Osa, A and Azuma, Y and Okishio, K and Kawaguchi, T and Atagi, S and Kawase, I}, title = {Stratification of malignant pleural mesothelioma prognosis using recursive partitioning analysis.}, journal = {Lung}, volume = {192}, number = {1}, pages = {191-195}, pmid = {24141556}, issn = {1432-1750}, mesh = {Aged ; Algorithms ; Asbestos/adverse effects ; Biomarkers/blood ; Chest Pain/etiology ; *Decision Support Techniques ; Female ; Hemoglobins/analysis ; Humans ; Japan ; Kaplan-Meier Estimate ; L-Lactate Dehydrogenase/blood ; Leukocyte Count ; Lung Neoplasms/blood/*diagnosis/etiology/mortality/pathology ; Male ; Mesothelioma/blood/*diagnosis/etiology/mortality/pathology ; Mesothelioma, Malignant ; Multivariate Analysis ; Neoplasm Staging ; Platelet Count ; Pleural Neoplasms/blood/*diagnosis/etiology/mortality/pathology ; Predictive Value of Tests ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; Time Factors ; }, abstract = {PURPOSE: Prognostic factors and complicated prognostic models have been proposed for malignant pleural mesothelioma (MPM). This study was designed to stratify MPM prognosis by using a simple model.<br><br>METHODS: Patients diagnosed with MPM in the past 10 years (n&#xa0;=&#xa0;122) were examined retrospectively. Data on the presence of chest pain, performance status (PS), asbestos exposure, smoking status, white blood cell count (WBC), haemoglobin (Hb) concentration, platelet count (PLT), lactate dehydronate (LD), histology, stage, and date of death or censored status were collected. After the factors were examined in the univariate analysis, recursive partitioning analysis was performed.<br><br>RESULTS: Statistically significant factors related to survival were the type of histology, stage, PS, WBC, PLT, Hb concentration, and LD. Histology, stage, PS, and Hb concentration were used in multivariate analysis. Stage and Hb concentration showed good statistical significance, whereas PS was borderline significant. The survival analyses were stratified into five groups by PS, stage, Hb concentration, and chest pain using recursive partitioning analysis. Group A comprised patients showing the most favourable prognoses (PS 0-2 and Hb concentration >12.1&#xa0;g&#xa0;dL(-1) or PS 0-2 and Hb concentration &#x2264;12.1&#xa0;g&#xa0;dL(-1) without pain), and group B comprised the remaining patients. The median overall survival in groups A and B was 563 days (95&#xa0;% confidence interval [CI] 502-779) and 157 days (95&#xa0;% CI 115-224), respectively (hazard ratio of 5.44 [3.46-8.53, P&#xa0;<&#xa0;0.0001]).<br><br>CONCLUSIONS: The MPM patients with PS 0-2 and Hb concentration >12.1 or &#x2264;12.1&#xa0;g&#xa0;dL(-1) without chest pain had favourable prognoses.}, }
@article {pmid24134457, year = {2014}, author = {Dodson, RF and Mark, EJ and Poye, LW}, title = {Biodurability/retention of Libby amphiboles in a case of mesothelioma.}, journal = {Ultrastructural pathology}, volume = {38}, number = {1}, pages = {45-51}, doi = {10.3109/01913123.2013.821194}, pmid = {24134457}, issn = {1521-0758}, mesh = {Aged, 80 and over ; Asbestos, Amphibole/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Microscopy, Electron, Transmission ; }, abstract = {Mesothelioma is considered a signal tumor for exposure to asbestos (fibrous materials) and can occur decades after first exposure. The present case study reports on tissue burden of fibrous dust in a person who used a vermiculite material (Zonolite) as an attic insulator some 50 years prior to her death. The exposure occurred in two construction/renovation projects in her private residencies. She potentially had exposures to wall board/joint compounds during renovations. She additionally was reported to occasionally be involved in occupational activity, including drilling holes in presumed asbestos-containing electrical boxes. The tissue burden analysis revealed the presence of noncommercial amphibole asbestos fibers and consistent presence in the lung and lymph samples of Libby amphibole fibers. The findings of Libby amphibole fibers in human tissue can be attributed to exposure to Libby vermiculite. This study illustrates that analytical transmission electron microscopy can distinguish these structures from "asbestos" fibers. Further, the findings indicate that a population of these structures is biodurable and retained in the tissue years after first/last exposure.}, }
@article {pmid24130165, year = {2014}, author = {Cleaver, AL and Bhamidipaty, K and Wylie, B and Connor, T and Robinson, C and Robinson, BW and Mutsaers, SE and Lake, RA}, title = {Long-term exposure of mesothelial cells to SV40 and asbestos leads to malignant transformation and chemotherapy resistance.}, journal = {Carcinogenesis}, volume = {35}, number = {2}, pages = {407-414}, doi = {10.1093/carcin/bgt322}, pmid = {24130165}, issn = {1460-2180}, mesh = {Animals ; Antigens, Polyomavirus Transforming/*toxicity ; Apoptosis/drug effects ; Asbestos, Crocidolite/*toxicity ; Blotting, Western ; Cell Adhesion/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/genetics/metabolism/*pathology ; Cells, Cultured ; *Cocarcinogenesis ; *Drug Resistance, Neoplasm ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/genetics/metabolism/*pathology ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Peritoneum/drug effects/metabolism/pathology ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Simian virus 40 (SV40) has been implicated in the development of several cancers including malignant mesothelioma. A definitive role for the virus in human mesothelioma has not been unequivocally demonstrated but has been rigorously debated. The virus clearly has oncogenic potential: the TAg is one of the most potent transforming proteins known and acts synergistically with crocidolite asbestos to transform mesothelial cells. In this study, we show that SV40 oncogenes alone can cause malignant transformation and that asbestos-induced DNA damage and apoptosis occurs principally in cycling cells. After long-term exposure (up to 100 days) to both SV40 and asbestos, cells become resistant to stress-induced senescence. Significantly, these cells demonstrate resistance to chemotherapy-induced apoptosis. This finding has implications for the development of effective treatment options for patients with mesothelioma.}, }
@article {pmid24128712, year = {2013}, author = {Zauderer, MG and Bott, M and McMillan, R and Sima, CS and Rusch, V and Krug, LM and Ladanyi, M}, title = {Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {11}, pages = {1430-1433}, pmid = {24128712}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Germ-Line Mutation/*genetics ; Humans ; Lung Neoplasms/*genetics/pathology/therapy ; Male ; Mesothelioma/*genetics/pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*genetics/pathology/therapy ; Prognosis ; Smoking/adverse effects ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {INTRODUCTION: Genomic studies of malignant pleural mesothelioma (MPM) have recently identified frequent mutations in the BRCA-associated protein 1(BAP1) gene. In uveal melanoma and clear cell renal cell carcinoma, BAP1 mutations are associated with poor outcomes but their clinical significance in MPM is unknown. We therefore undertook this study to define the characteristics of patients whose MPM tumors harbor somatic BAP1 mutation and to examine the relationship between BAP1 mutation and survival.<br><br>METHODS: We reviewed the charts of 121 patients with MPM tumors diagnosed between 1991 and 2009 tested for BAP1 mutation, and extracted the following information: age at diagnosis, sex, histology, stage, smoking status, asbestos exposure, family or personal history of malignancy, and treatment including surgery, chemotherapy, and radiation as well as survival status.<br><br>RESULTS: Twenty-four of the 121 tumors (20%) harbored somatic BAP1 mutations. The percentage of current or former smokers among cases with BAP1 mutations was significantly higher than in BAP1 wild-type cases, (75% versus 42%; p = 0.006). However, the types of nucleotide substitutions in BAP1 did not suggest that this association was because of a causative role of smoking in BAP1 mutations. No other clinical feature was significantly different among those with and without BAP1 mutations in their MPM. There was also no difference in survival according to somatic BAP1 mutation status.<br><br>CONCLUSION: There is no apparent distinct clinical phenotype for MPM with somatic BAP1 mutation. The significance of the more frequent history of smoking among patients with BAP1-mutated MPM warrants further study.}, }
@article {pmid24124200, year = {2014}, author = {Sakai, K and Hisanaga, N and Shibata, E and Kamijima, M and Ichihara, G and Takeuchi, Y and Nakajima, T}, title = {Trends in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma.}, journal = {The Annals of occupational hygiene}, volume = {58}, number = {1}, pages = {103-120}, doi = {10.1093/annhyg/met055}, pmid = {24124200}, issn = {1475-3162}, mesh = {Aged ; Asbestos/*analysis ; Carcinogens/*analysis ; Female ; Humans ; Japan ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; Mineral Fibers/adverse effects/*analysis ; Occupational Diseases/*etiology/pathology ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVES: We aimed to elucidate changes in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma over time.<br><br>METHODS: Lung tissues were obtained from 46 patients with mesothelioma who died or underwent surgery between 1971 and 2005. All of the patients had a history of occupational asbestos exposure. We classified patients into four groups according to the period during which their lung tissue was obtained. Asbestos and non-asbestos fibre concentrations were determined by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure.<br><br>RESULTS: From the 1970s to the 2000s, we observed a decrease in the geometric mean of total asbestos concentration (67.4-1.05 million fibres per gram dry lung), chrysotile concentration (25.0-0.66 million fibres per gram dry lung), amphibole asbestos concentration (21.3-0.76 million fibres per gram dry lung), and non-asbestos fibre concentration (326-19.3 million fibres per gram dry lung). The mean duration of asbestos exposure decreased from 33.7 to 17.6 years, and the mean duration since the last exposure increased from 0.3 to 21.5 years. The percentage of longer fibres to total fibres tended to increase over time, whereas the mean fibre length did not differ significantly.<br><br>CONCLUSIONS: The present study suggested that asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma who have occupational histories of asbestos exposure may have decreased from the 1970s to the 2000s.}, }
@article {pmid24108505, year = {2014}, author = {Järvholm, B and Englund, A}, title = {The impact of asbestos exposure in Swedish construction workers.}, journal = {American journal of industrial medicine}, volume = {57}, number = {1}, pages = {49-55}, doi = {10.1002/ajim.22264}, pmid = {24108505}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Carcinogens/*toxicity ; *Construction Industry ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Occupations/statistics &amp; numerical data ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Risk Factors ; Sweden/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: To study the occurrence of pleural mesothelioma as a measure of the impact on health from asbestos exposure in the construction industry.<br><br>METHODS: The occurrence of pleural mesothelioma in different occupations, time periods and birth cohorts was studied in a cohort of construction workers. They were prospectively followed after they had participated in health examinations between 1971 and 1993. The analysis was restricted to men and in total 367,568 men was included in the analysis.<br><br>RESULTS: In total there were 419 cases of pleural mesotheliomas between 1972 and 2009. As expected the age adjusted incidence was high in insulation workers and plumbers (39 and 16 cases per 100,000 person-years, respectively). However, only 21% of the pleural mesotheliomas occurred in those occupational groups. Occupational groups with many cases of pleural mesothelioma were concrete workers (N&#x2009;=&#x2009;56), wood workers (N&#x2009;=&#x2009;55), painters (N&#x2009;=&#x2009;32), electricians (N&#x2009;=&#x2009;48), and foremen (N&#x2009;=&#x2009;37). The highest risk was in birth cohorts born between 1935 and 1945. Between 1995 and 2009 around one-third of all male cases in the country occurred in this birth cohort. The risk seemed to decrease considerably in men born after 1955.<br><br>CONCLUSION: In Sweden a considerable proportion of pleural mesotheliomas occur among construction workers; and not only in jobs traditionally associated with asbestos exposure such as insulators and plumbers but also among electricians, for example. The results shows that asbestos exposure occurs in many occupational groups, indicating that safe handling of asbestos is a very difficult or even impossible task in the construction industry.}, }
@article {pmid24108494, year = {2014}, author = {Bang, KM and Mazurek, JM and Wood, JM and Hendricks, SA}, title = {Diseases attributable to asbestos exposure: years of potential life lost, United States, 1999-2010.}, journal = {American journal of industrial medicine}, volume = {57}, number = {1}, pages = {38-48}, pmid = {24108494}, issn = {1097-0274}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Asbestosis/*mortality ; Cause of Death ; *Environmental Exposure ; Humans ; Life Expectancy/*trends ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; *Occupational Exposure ; United States/epidemiology ; }, abstract = {BACKGROUND: Although asbestos use has been restricted in recent decades, asbestos-associated deaths continue to occur in the United States.<br><br>OBJECTIVES: We evaluated premature mortality and loss of potentially productive years of life attributable to asbestos-associated diseases.<br><br>METHODS: Using 1999-2010 National Center for Health Statistics mortality data, we identified decedents aged &#x2265;25 years whose death certificate listed asbestosis and malignant mesothelioma as the underlying cause of death. We computed years of potential life lost to life expectancy (YPLL) and to age 65 (YPLL65).<br><br>RESULTS: During 1999-2010, a total of 427,005 YPLL and 55,184 YPLL65 were attributed to asbestosis (56,907 YPLL and 2,167 YPLL65), malignant mesothelioma (370,098 YPPL and 53,017 YPLL65). Overall and disease-specific asbestos-attributable total YPLL and YPLL65 and median YPLL and YPLL65 per decedent did not change significantly from 1999 to 2010.<br><br>CONCLUSIONS: The continuing occurrence of asbestos-associated diseases and their substantial premature mortality burden underscore the need for maintaining prevention efforts and for ongoing surveillance to monitor temporal trends in these diseases.}, }
@article {pmid24107344, year = {2013}, author = {Takahashi, K and Ishii, Y}, title = {[Asbestos and the Industrial Safety and Health Law - in reference to the ordinance on prevention of hazards due to specified chemical substances and the ordinance on prevention of health impairment due to asbestos].}, journal = {Journal of UOEH}, volume = {35 Suppl}, number = {}, pages = {121-126}, doi = {10.7888/juoeh.35.121}, pmid = {24107344}, issn = {0387-821X}, mesh = {Asbestosis/*prevention &amp; control ; Humans ; Occupational Health/*legislation &amp; jurisprudence ; }, abstract = {Recently in Japan, mesothelioma and lung cancer caused by asbestos are increasing in number and in proportion among occupational cancers. It is thus obvious that asbestos will remain an important theme in the field of occupational health and safety. We hereby report on the relationship between asbestos and the Industrial Safety and Health Law, the Ordinance on Prevention of Hazards due to Specified Chemical Substances, and the Ordinance on Prevention of Health Impairment due to Asbestos, in reference to laws and regulations as well as official notifications issued by the Ministry. In particular, we will focus on the process by which our country totally prohibited the use of asbestos, countermeasures to prevent exposure of workers, historical changes regarding administrative concentration levels, and measures for the management of health of workers handling and dealing with asbestos.}, }
@article {pmid24086716, year = {2013}, author = {Ishida, T and Alexandrov, M and Nishimura, T and Hirota, R and Ikeda, T and Kuroda, A}, title = {Molecular engineering of a fluorescent bioprobe for sensitive and selective detection of amphibole asbestos.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e76231}, pmid = {24086716}, issn = {1932-6203}, mesh = {Air Pollutants/*isolation &amp; purification ; Asbestos, Amphibole/*isolation &amp; purification/metabolism ; Binding Sites/genetics ; Bioengineering/*methods ; Biosensing Techniques/*methods ; Escherichia coli ; Escherichia coli Proteins/genetics/*metabolism ; Fimbriae Proteins/genetics/*metabolism ; Microscopy, Fluorescence/methods ; Protein Binding ; Sensitivity and Specificity ; Static Electricity ; Streptavidin/metabolism ; }, abstract = {Fluorescence microscopy-based affinity assay could enable highly sensitive and selective detection of airborne asbestos, an inorganic environmental pollutant that can cause mesothelioma and lung cancer. We have selected an Escherichia coli histone-like nucleoid structuring protein, H-NS, as a promising candidate for an amphibole asbestos bioprobe. H-NS has high affinity to amphibole asbestos, but also binds to an increasingly common asbestos substitute, wollastonite. To develop a highly specific Bioprobe for amphibole asbestos, we first identified a specific but low-affinity amosite-binding sequence by slicing H-NS into several fragments. Second, we constructed a streptavidin tetramer complex displaying four amosite-binding fragments, resulting in the 250-fold increase in the probe affinity as compared to the single fragment. The tetramer probe had sufficient affinity and specificity for detecting all the five types of asbestos in the amphibole group, and could be used to distinguish them from wollastonite. In order to clarify the binding mechanism and identify the amino acid residues contributing to the probe's affinity to amosite fibers, we constructed a number of shorter and substituted peptides. We found that the probable binding mechanism is electrostatic interaction, with positively charged side chains of lysine residues being primarily responsible for the probe's affinity to asbestos.}, }
@article {pmid24084442, year = {2013}, author = {Alì, G and Borrelli, N and Riccardo, G and Proietti, A and Pelliccioni, S and Niccoli, C and Boldrini, L and Lucchi, M and Mussi, A and Fontanini, G}, title = {Differential expression of extracellular matrix constituents and cell adhesion molecules between malignant pleural mesothelioma and mesothelial hyperplasia.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {11}, pages = {1389-1395}, doi = {10.1097/JTO.0b013e3182a59f45}, pmid = {24084442}, issn = {1556-1380}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Cell Adhesion Molecules/genetics/*metabolism ; Extracellular Matrix/genetics/*metabolism/pathology ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Hyaluronan Receptors/genetics/metabolism ; Hyperplasia/genetics/*metabolism/pathology ; Immunoenzyme Techniques ; Integrin alpha3/genetics/metabolism ; Lung Neoplasms/genetics/*metabolism/pathology ; Male ; Matrix Metalloproteinase 14/genetics/metabolism ; Matrix Metalloproteinase 7/genetics/metabolism ; Mesothelioma/genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/genetics/*metabolism/pathology ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm associated with asbestos exposure. Currently, the molecular mechanisms that induce MPM development are still unknown. The purpose of this study was to identify new molecular biomarkers for mesothelial carcinogenesis.<br><br>METHODS: We analyzed a panel of 84 genes involved in extracellular matrix remodeling and cell adhesion by polymerase chain reaction (PCR) array in 15 samples of epithelioid mesothelioma and 10 samples of reactive mesothelial hyperplasia (MH; 3 of 25 samples were inadequate for mRNA analysis). To validate the differentially expressed genes identified by PCR array, we analyzed 27 more samples by immunohistochemistry, in addition to the 25 samples already studied.<br><br>RESULTS: Twenty-five genes were differentially expressed in MPM and MH by PCR array. Of these we studied matrix metalloproteinase 7 (MMP7), MMP14, CD44, and integrin, alpha3 expression by immunohistochemistry in 26 epithelioid MPM and 26 MH samples from the entire series of 52 cases. We observed higher MMP14 and integrin, alpha3 expression in MPM samples compared with MH samples (p = 0.000002 and p = 0.000002, respectively). Conversely, CD44 expression was low in most (57.7%) mesothelioma samples but only in 11.5% of the MH samples (p = 0.0013). As regards MMP7, we did not observe differential expression between MH and MPM samples.<br><br>CONCLUSIONS: We have extensively studied genes involved in cell adhesion and extracellular matrix remodeling in MPM and MH samples, gaining new insight into the pathophysiology of mesothelioma. Moreover, our data suggest that these factors could be potential biomarkers for MPM.}, }
@article {pmid24084028, year = {2013}, author = {Kagan, E}, title = {Asbestos-induced mesothelioma: is fiber biopersistence really a critical factor?.}, journal = {The American journal of pathology}, volume = {183}, number = {5}, pages = {1378-1381}, doi = {10.1016/j.ajpath.2013.09.005}, pmid = {24084028}, issn = {1525-2191}, mesh = {Animals ; Asbestos, Serpentine/*toxicity ; Cell Transformation, Neoplastic/*metabolism/*pathology ; Epithelium/*pathology ; HMGB1 Protein/*metabolism ; Humans ; Signal Transduction/*drug effects ; Tumor Necrosis Factor-alpha/*metabolism ; }, abstract = {This Commentary highlights the research by Qi et al detailing the similarities and differences between crocidolite and chrysotile asbestos in terms of their transcriptional effects and transforming actions in human mesothelial cells.}, }
@article {pmid24083862, year = {2013}, author = {Bonde, JP}, title = {No indication that mineral wool causes mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {188}, number = {7}, pages = {873}, doi = {10.1164/rccm.201304-0655LE}, pmid = {24083862}, issn = {1535-4970}, mesh = {Asbestos/*toxicity ; Calcium Compounds/*toxicity ; Humans ; Male ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced ; Silicates/*toxicity ; Silicon Dioxide/*toxicity ; }, }
@article {pmid24083861, year = {2013}, author = {Lacourt, A}, title = {Reply: No indication that mineral wool causes mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {188}, number = {7}, pages = {873-874}, doi = {10.1164/rccm.201305-0901LE}, pmid = {24083861}, issn = {1535-4970}, mesh = {Asbestos/*toxicity ; Calcium Compounds/*toxicity ; Humans ; Male ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced ; Silicates/*toxicity ; Silicon Dioxide/*toxicity ; }, }
@article {pmid24081673, year = {2014}, author = {de Assis, LV and Isoldi, MC}, title = {The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {2}, pages = {889-901}, pmid = {24081673}, issn = {1423-0380}, mesh = {Asbestos/*toxicity ; Carcinogens/toxicity ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology/virology ; Membrane Proteins/*genetics/metabolism ; Mesothelioma/chemically induced/*genetics/pathology/virology ; Mesothelioma, Malignant ; PTEN Phosphohydrolase/*genetics/metabolism ; Simian virus 40/pathogenicity ; Tumor Suppressor Protein p53/*genetics/metabolism ; }, abstract = {The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16(INK4A), p14(ARF), and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.}, }
@article {pmid24071603, year = {2013}, author = {Marsili, D and Comba, P}, title = {Asbestos case and its current implications for global health.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {49}, number = {3}, pages = {249-251}, doi = {10.4415/ANN_13_03_03}, pmid = {24071603}, issn = {2384-8553}, mesh = {Asbestos ; Asbestosis/*prevention &amp; control ; Humans ; Industry ; Italy ; Mesothelioma ; Occupational Exposure ; Public Health ; World Health Organization ; }, abstract = {Notwithstanding a major body of evidence on the carcinogenicity of all asbestos fibres and a general consensus of the scientific community on the health impact of this agent, asbestos is still produced and used in a large number of countries, thus determining further harm for future generations. Prevention of asbestos-related disease requires international cooperation, transfer of know-how and dissemination of successful procedures in order to contrast asbestos exposure in the frame of a global environmental health approach.}, }
@article {pmid24066870, year = {2013}, author = {Stolnicu, S and Quiñonez, E and Boros, M and Molnar, C and Dulcey, I and Nogales, FF}, title = {Case report: Papillary mesothelioma of the peritoneum with foamy cell lining.}, journal = {Diagnostic pathology}, volume = {8}, number = {}, pages = {162}, pmid = {24066870}, issn = {1746-1596}, mesh = {Adult ; Asbestos/*adverse effects ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Epithelial Cells/chemistry/*pathology ; Female ; Humans ; Immunohistochemistry ; Immunophenotyping ; Mesothelioma/chemistry/etiology/*pathology/surgery ; Peritoneal Neoplasms/chemistry/etiology/*pathology/surgery ; Predictive Value of Tests ; Treatment Outcome ; }, abstract = {UNLABELLED: A 34-year-old female, with a history of continued asbestos exposure, presented with a papillary peritoneal mesothelioma with a diffuse, prominent clear foamy cell change, with microvacuolation in its papillary lining, that expressed cytokeratins 7, 5/6 and calretinin as well as nuclear WT-1 and apical membrane staining for thrombomodulin, podoplanin D2-40 and HBME-1. In contrast, lining cells were CD68 negative. Foamy cell change has been reported in isolated cases as solid cords but not as a diffuse change in the mesothelial papillary lining. This phenomenon prompts differential diagnoses with abdominal and renal papillary clear cell tumours, which were discarded after a characteristic mesothelial immunophenotype was demonstrated.<br><br>VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4679576081031834.}, }
@article {pmid24055913, year = {2013}, author = {Kassir, R and Forest, F and Kaczmarek, D}, title = {Pulmonary mucinous cystadenocarcinoma presenting as a pleural mesothelioma.}, journal = {International journal of surgery case reports}, volume = {4}, number = {11}, pages = {942-944}, pmid = {24055913}, issn = {2210-2612}, abstract = {INTRODUCTION: Primary Pulmonary Mucinous Cystadenocarcinoma PPMC is an extremely rare subtype of pulmonary adenocarcinoma, with only a few dozen cases reported in the literature to date.<br><br>PRESENTATION OF CASE: We report a extremely rare case of pulmonary mucinous cystadenocarcinoma presenting as a pleural mesothelioma. 53-year-old man exposed to asbestos, he is admitted in hospital with a 5cm mass in right pleura. He was treated by wedge resection. Sparse groups of malignant cells were microscopically observed in pools of mucin. The postoperative histopathological findings were in accordance with the diagnosis of pulmonary mucinous cystadenocarcinoma on cystic adenoid malformation of lung. 5 years later, the patient has no recurrence.<br><br>DISCUSSION: PPMC is usually asymptomatic; hemoptysis is seen occasionally. Preoperative diagnosis is very difficult to establish. Both FNA cytology and transbronchial lung biopsy seem inadequate. Our patient went on to undergo open lung biopsy and histopathological testing that confirmed the diagnosis of PMC.<br><br>CONCLUSION: It is important to differentiate this rare pathological feature of the lung from other lung tumors as the treatment is surgical rather than medical. Thoracic surgeons should bear in mind this rare tumor for the differential diagnosis of a pleural mesothelioma because this tumor has a favorable prognosis.}, }
@article {pmid24050959, year = {2014}, author = {Giansanti, M and Bellezza, G and Guerriero, A and Pireddu, A and Sidoni, A}, title = {Localized Intrasplenic Mesothelioma: A Case Report.}, journal = {International journal of surgical pathology}, volume = {22}, number = {5}, pages = {451-455}, doi = {10.1177/1066896913503492}, pmid = {24050959}, issn = {1940-2465}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Incidental Findings ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Splenic Neoplasms/diagnostic imaging/metabolism/*pathology ; Ultrasonography ; }, abstract = {Malignant mesothelioma is a primary neoplasm of the serosal membranes that usually presents with a diffuse pattern of growth. However, cases of localized mesotheliomas have been described. The predominant localization is the pleura; peritoneum and pericardium being rarer localizations. Only few cases of true intraparenchymal mesothelioma arising in organs such as liver, gonads, lung, and pancreas have been described. We report a case of an otherwise healthy 48-year-old man without asbestos exposure with a nodule of 3 cm in diameter, localized in the spleen, discovered incidentally at the ultrasonographic examination, for which histopathological and immunohistochemical findings were consistent with epithelioid mesothelioma: large round cells with eosinophil dense cytoplasm and macronucleoli and with immunohistochemical positivity for pancytokeratins, calretinin, Wilms tumor-1, and others markers of mesothelial differentiation. The diagnosis of localized intrasplenic epithelioid malignant mesothelioma was carried out. To the best of our knowledge, this is the first case of a localized intrasplenic mesothelioma published in the indexed literature.}, }
@article {pmid24041698, year = {2013}, author = {Fox, SA and Richards, AK and Kusumah, I and Perumal, V and Bolitho, EM and Mutsaers, SE and Dharmarajan, AM}, title = {Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells.}, journal = {Biochemical and biophysical research communications}, volume = {440}, number = {1}, pages = {82-87}, doi = {10.1016/j.bbrc.2013.09.025}, pmid = {24041698}, issn = {1090-2104}, mesh = {Cell Line, Tumor ; Cell Proliferation ; *Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/*genetics/metabolism/pathology ; Pleura/metabolism/pathology ; Pleural Neoplasms/*genetics/metabolism/pathology ; Proto-Oncogene Proteins/genetics/metabolism ; Wnt Proteins/*genetics/metabolism ; *Wnt Signaling Pathway ; Wnt3 Protein/genetics/metabolism ; beta Catenin/genetics/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer.}, }
@article {pmid24033215, year = {2013}, author = {Park, EK and Yates, DH and Hyland, RA and Johnson, AR}, title = {Asbestos exposure during home renovation in New South Wales.}, journal = {The Medical journal of Australia}, volume = {199}, number = {6}, pages = {410-413}, doi = {10.5694/mja12.11802}, pmid = {24033215}, issn = {1326-5377}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Construction Materials/*adverse effects ; Cross-Sectional Studies ; *Housing ; Humans ; *Maintenance ; Middle Aged ; New South Wales ; Self Report ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Asbestos exposure is causally associated with the development of malignant mesothelioma (MM), which is increasingly being reported after exposure to asbestos fibro sheeting in Australia. In this study, we investigate self-reported non-occupational asbestos exposure during home renovation in New South Wales.<br><br>DESIGN AND SETTING: Cross-sectional mailed questionnaire examining renovation activity, tasks undertaken during renovation and self-reported exposure to asbestos among respondents and their family members in NSW between January and June 2008.<br><br>PARTICIPANTS: 10&#xa0;000&#xa0;adults aged 18-99&#xa0;years, randomly selected from the NSW electoral roll. We received 3612&#xa0;responses, while 365&#xa0;questionnaires did not reach addressees, giving an overall response rate of 37.5%.<br><br>MAIN OUTCOME MEASURES: Differences in self-reported asbestos exposure between do-it-yourself (DIY) and non-DIY renovators.<br><br>RESULTS: 1597&#xa0;participants (44.2%) had renovated their home and among these, 858&#xa0;participants (53.7%) self-reported as DIY renovators. Of these, 527&#xa0;(61.4%) reported asbestos exposure during home renovations, 337&#xa0;(39.3%) reported that their partner had been exposed to asbestos during renovations, and 196&#xa0;(22.8%) reported that their children had been exposed. More than 20% of renovators planned to further renovate their current homes within the next 5&#xa0;years.<br><br>CONCLUSIONS: Self-reported asbestos exposure during home renovation is common. This preventable exposure could place adults and children at risk of MM many years into the future. Although such exposure is self-reported and ideally should be verified, this study identifies a potentially important problem in NSW.}, }
@article {pmid24027648, year = {2013}, author = {Makarawate, P and Chaosuwannakit, N and Chindaprasirt, J and Ungarreevittaya, P and Chaiwiriyakul, S and Wirasorn, K and Kuptarnond, C and Sawanyawisuth, K}, title = {Malignant mesothelioma of the pericardium: a report of two different presentations.}, journal = {Case reports in oncological medicine}, volume = {2013}, number = {}, pages = {356901}, pmid = {24027648}, issn = {2090-6706}, abstract = {Malignant mesothelioma of the pericardium is a rare and fatal condition that clinicians should be aware of due to its variability of clinical manifestation. The diagnosis may be delayed as a result of delayed treatment. Here, we report two cases of malignant pericardial mesothelioma with two different clinical aspects: cardiac tamponade and mimic tuberculous pericarditis. Both patients: may have indirect exposure to asbestos. Despite chemotherapy, both patients died at 2 weeks and 3 months after the diagnosis. Malignant mesothelioma of the pericardium is fatal, has a variety of presentation, and may not be related to asbestosis exposure.}, }
@article {pmid24027214, year = {2013}, author = {Nagai, H and Okazaki, Y and Chew, SH and Misawa, N and Yasui, H and Toyokuni, S}, title = {Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {6}, number = {11}, pages = {1222-1230}, doi = {10.1158/1940-6207.CAPR-13-0244}, pmid = {24027214}, issn = {1940-6215}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Benzoates/*toxicity ; Cell Transformation, Neoplastic/drug effects/*pathology ; Deferasirox ; Epithelial-Mesenchymal Transition/*drug effects ; Female ; Iron/*metabolism ; Iron Chelating Agents/*toxicity ; Male ; Mesothelioma/chemically induced/*pathology ; Phlebotomy ; Rats ; Spleen/drug effects/metabolism/pathology ; Triazoles/*toxicity ; }, abstract = {Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported on the basis of animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here, we undertook to find an effective strategy to prevent, delay, or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks, and the preventive measures were via repeated oral administration of 25 to 50 mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The animals were observed until 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction.}, }
@article {pmid24024776, year = {2013}, author = {Macura, SL and Steinbacher, JL and Macpherson, MB and Lathrop, MJ and Sayan, M and Hillegass, JM and Beuschel, SL and Perkins, TN and Spiess, PC and van der Vliet, A and Butnor, KJ and Shukla, A and Wadsworth, M and Landry, CC and Mossman, BT}, title = {Microspheres targeted with a mesothelin antibody and loaded with doxorubicin reduce tumor volume of human mesotheliomas in xenografts.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {400}, pmid = {24024776}, issn = {1471-2407}, support = {R41 CA126155/CA/NCI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*administration &amp; dosage ; Body Weight ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Doxorubicin/*administration &amp; dosage ; *Drug Delivery Systems ; GPI-Linked Proteins/*antagonists &amp; inhibitors/metabolism ; Humans ; Inflammation/metabolism/pathology ; Injections, Intraperitoneal ; Ki-67 Antigen/metabolism ; Macrophages/pathology ; Mesothelin ; Mesothelioma/drug therapy/*metabolism/*pathology ; Mice ; *Microspheres ; Necrosis/drug therapy ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant mesotheliomas (MMs) are chemoresistant tumors related to exposure to asbestos fibers. The long latency period of MM (30-40 yrs) and heterogeneity of tumor presentation make MM difficult to diagnose and treat at early stages. Currently approved second-line treatments following surgical resection of MMs include a combination of cisplatin or carboplatin (delivered systemically) and pemetrexed, a folate inhibitor, with or without subsequent radiation. The systemic toxicities of these treatments emphasize the need for more effective, localized treatment regimens.<br><br>METHODS: Acid-prepared mesoporous silica (APMS) microparticles were loaded with doxorubicin (DOX) and modified externally with a mesothelin (MB) specific antibody before repeated intraperitoneal (IP) injections into a mouse xenograft model of human peritoneal MM. The health/weight of mice, tumor volume/weight, tumor necrosis and cell proliferation were evaluated in tumor-bearing mice receiving saline, DOX high (0.2 mg/kg), DOX low (0.05 mg/kg), APMS-MB, or APMS-MB-DOX (0.05 mg/kg) in saline.<br><br>RESULTS: Targeted therapy (APMS-MB-DOX at 0.05 mg/kg) was more effective than DOX low (0.05 mg/kg) and less toxic than treatment with DOX high (0.2 mg/kg). It also resulted in the reduction of tumor volume without loss of animal health and weight, and significantly decreased tumor cell proliferation. High pressure liquid chromatography (HPLC) of tumor tissue confirmed that APMS-MB-DOX particles delivered DOX to target tissue.<br><br>CONCLUSIONS: Data suggest that targeted therapy results in greater chemotherapeutic efficacy with fewer adverse side effects than administration of DOX alone. Targeted microparticles are an attractive option for localized drug delivery.}, }
@article {pmid24010773, year = {2013}, author = {Mikami, K and Tabata, C and Tabata, R and Nogi, Y and Terada, T and Honda, M and Kamiya, H and Nishizaki, T and Nakano, T}, title = {Clinical significance of serum angiopoietin-1 in malignant peritoneal mesothelioma.}, journal = {Cancer investigation}, volume = {31}, number = {8}, pages = {511-515}, doi = {10.3109/07357907.2013.830734}, pmid = {24010773}, issn = {1532-4192}, mesh = {Angiopoietin-1/*blood ; Asbestos/toxicity ; Asbestosis/blood ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*blood/epidemiology/*mortality ; Middle Aged ; Peritoneal Neoplasms/*blood/epidemiology/*mortality ; Pulmonary Fibrosis/complications ; Survival ; }, abstract = {We have previously reported that angiopoietin-1 was correlated with pulmonary fibrosis. Here, we investigated the serum levels of angiopoietin-1 in patients with malignant peritoneal mesothelioma, which originate from mesenchymal cells similar to lung fibroblasts. We showed that patients with peritoneal mesothelioma had significantly higher serum levels of angiopoietin-1 in comparison with a population with a history of asbestos exposure without peritoneal mesothelioma, and the Kaplan-Meier method revealed a significant correlation between serum angiopoietin-1 levels and survival. This is the first report about the relationship between angiopoietin-1 and peritoneal mesothelioma.}, }
@article {pmid23989951, year = {2013}, author = {Frost, G}, title = {The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005).}, journal = {British journal of cancer}, volume = {109}, number = {7}, pages = {1965-1973}, pmid = {23989951}, issn = {1532-1827}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/epidemiology/mortality ; Female ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Occupational Diseases/epidemiology/mortality ; Occupational Exposure/*adverse effects ; Prospective Studies ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: The Great Britain (GB) Asbestos Survey is a prospective cohort of asbestos workers in GB. The objective of this study was to investigate determinants of mesothelioma latency, paying particular attention to indicators of intensity of asbestos exposure such as occupation, sex, and presence of asbestosis.<br><br>METHODS: The analysis included members of the cohort who died with mesothelioma between 1978 and 2005. The primary outcome was the latency period defined as the time from first occupational exposure to asbestos to death with mesothelioma. Generalised gamma accelerated failure-time models were used to estimate time ratios (TRs).<br><br>RESULTS: After excluding missing data, there were 614 workers who died with mesothelioma between 1978 and 2005. Total follow-up time was 9280 person-years, with a median latency of 22.8 years (95% confidence interval (CI) 16.0-27.2 years). In the fully adjusted model, latency was around 29% longer for females compared with males (TR=1.29, 95% CI=1.18-1.42), and 5% shorter for those who died with asbestosis compared with those who did not (TR=0.95, 95% CI=0.91-0.99). There was no evidence of an association between latency and occupation.<br><br>CONCLUSION: This study did not find sufficient evidence that greater intensity asbestos exposures would lead to shorter mesothelioma latencies.}, }
@article {pmid23983468, year = {2013}, author = {Granieri, A and Tamburello, S and Tamburello, A and Casale, S and Cont, C and Guglielmucci, F and Innamorati, M}, title = {Quality of life and personality traits in patients with malignant pleural mesothelioma and their first-degree caregivers.}, journal = {Neuropsychiatric disease and treatment}, volume = {9}, number = {}, pages = {1193-1202}, pmid = {23983468}, issn = {1176-6328}, abstract = {Asbestos exposure causes significant pleural diseases, including malignant pleural mesothelioma (MPM). Taking into account the impact of MPM on emotional functioning and wellbeing, this study aimed to evaluate the quality of life and personality traits in patients with MPM and their first-degree caregivers through the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF). The sample was composed of 27 MPM patients, 55 first-degree relatives enrolled in Casale Monferrato and Monfalcone (Italy), and 40 healthy controls (HC). Patients and relatives reported poorer physical health than the HC. Patients had a higher overall sense of physical debilitation and poorer health than relatives and the HC, more numerous complaints of memory problems and difficulties in concentrating, and a greater belief that goals cannot be reached or problems solved, while often claiming that they were more indecisive and inefficacious than the HC. First-degree relatives reported lower opinions of others, a greater belief that goals cannot be reached or problems solved, support for the notion that they are indecisive and inefficacious, and were more likely to suffer from fear that significantly inhibited normal activities than were HC. In multinomial regression analyses, partial models indicated that sex, physical comorbidities, and the True Response Inconsistency (TRIN-r), Malaise (MLS), and Behavior-Restricting Fears (BRF) dimensions of the MMPI-2-RF had significant effects on group differences. In conclusion, health care providers should assess the ongoing adjustment and emotional wellbeing of people with MPM and their relatives, and provide support to reduce emotional distress.}, }
@article {pmid23982605, year = {2013}, author = {Meniawy, TM and Creaney, J and Lake, RA and Nowak, AK}, title = {Existing models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma.}, journal = {British journal of cancer}, volume = {109}, number = {7}, pages = {1813-1820}, pmid = {23982605}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Female ; Humans ; Leukocyte Count ; Lung Neoplasms/drug therapy/*mortality ; Lymphocyte Count ; Lymphocytes/*cytology ; Male ; Mesothelioma/drug therapy/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Neutrophils/*cytology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Recent studies proposed neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in malignant pleural mesothelioma (MPM). We examined baseline prognostic variables including NLR and the EORTC and CALGB models as predictors of overall survival (OS) in MPM.<br><br>METHODS: In this retrospective study, 274 consecutive eligible, newly presenting patients with MPM were included. Of these, 159 received chemotherapy, 10 had tri-modality therapy, 2 underwent surgery only and 103 received supportive care alone. Univariate analyses and multivariate Cox models were calculated for OS.<br><br>RESULTS: In univariate analysis, poor prognostic factors were: age &#x2265;65 years, nonepithelioid histology, stage III-IV, poor performance status (PS), weight loss, chest pain, low haemoglobin and high platelet count. A baseline NLR&#x2265; 5 did not predict worse OS (hazard ratio (HR) 1.25; P=0.122). On multivariate analysis, age, histology, PS, weight loss, chest pain and platelet count remained significant. The EORTC and CALGB prognostic groups were validated as predictive for OS (HR 1.62; P<0.001 and HR 1.65; P<0.001, respectively).<br><br>CONCLUSION: Our findings validate standard prognostic variables and the existing EORTC and CALGB models, but not NLR, at initial diagnosis of MPM. In guiding patient management at diagnosis, it is important to consider multiple baseline variables that jointly predict survival.}, }
@article {pmid23977546, year = {2012}, author = {Linton, A and van Zandwijk, N and Reid, G and Clarke, S and Cao, C and Kao, S}, title = {Inflammation in malignant mesothelioma - friend or foe?.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {516-522}, pmid = {23977546}, issn = {2225-319X}, }
@article {pmid23977545, year = {2012}, author = {Nowak, AK}, title = {Chemotherapy for malignant pleural mesothelioma: a review of current management and a look to the future.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {508-515}, pmid = {23977545}, issn = {2225-319X}, }
@article {pmid23977542, year = {2012}, author = {Robinson, BM}, title = {Malignant pleural mesothelioma: an epidemiological perspective.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {491-496}, pmid = {23977542}, issn = {2225-319X}, abstract = {This paper reviews the aetiology, distribution and projected future incidence of malignant mesothelioma. Asbestos exposure is the most thoroughly established risk factor. Debate continues regarding the relative importance of the different asbestos fibre types and the contribution of Simian virus 40 (SV40). Disease incidence varies markedly within and between countries. The highest annual rates of disease, approximately 30 case per million, are reported in Australia and Great Britain. The risk of disease increases with age and is higher in men. Time from asbestos exposure to disease diagnosis is on average greater than 40 years. Non-occupational asbestos exposures contribute an increasing proportion of disease. With the exception of the United States, incidence continues to increase. In developed countries peak incidence is expected to occur before 2030.}, }
@article {pmid23977540, year = {2012}, author = {van Zandwijk, N and Reid, G and Linton, A and Kao, S}, title = {Radical surgery for malignant pleural mesothelioma: have we identified the appropriate selection tools?.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {481-486}, pmid = {23977540}, issn = {2225-319X}, }
@article {pmid23976967, year = {2013}, author = {Wright, CM and Kirschner, MB and Cheng, YY and O'Byrne, KJ and Gray, SG and Schelch, K and Hoda, MA and Klebe, S and McCaughan, B and van Zandwijk, N and Reid, G}, title = {Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM).}, journal = {PloS one}, volume = {8}, number = {8}, pages = {e70940}, pmid = {23976967}, issn = {1932-6203}, mesh = {Adult ; Aged ; Case-Control Studies ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; Humans ; Lung Neoplasms/diagnosis/*genetics/mortality/pathology ; Male ; Mesothelioma/diagnosis/*genetics/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/diagnosis/*genetics/mortality/pathology ; RNA, Long Noncoding/*genetics ; ROC Curve ; Survival Analysis ; Up-Regulation ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.}, }
@article {pmid23974964, year = {2014}, author = {Serrier, H and Sultan-Taieb, H and Luce, D and Bejean, S}, title = {Estimating the social cost of respiratory cancer cases attributable to occupational exposures in France.}, journal = {The European journal of health economics : HEPAC : health economics in prevention and care}, volume = {15}, number = {6}, pages = {661-673}, pmid = {23974964}, issn = {1618-7601}, mesh = {Absenteeism ; *Cost of Illness ; Costs and Cost Analysis/economics/statistics &amp; numerical data ; Female ; France/epidemiology ; Health Care Costs/statistics &amp; numerical data ; Humans ; Laryngeal Neoplasms/economics/epidemiology/etiology/mortality ; Lung Neoplasms/economics/epidemiology/etiology/mortality ; Male ; Mesothelioma/economics/epidemiology/etiology/mortality ; Middle Aged ; Occupational Exposure/adverse effects/*economics ; Paranasal Sinus Neoplasms/economics/epidemiology/etiology/mortality ; Pleural Neoplasms/economics/epidemiology/etiology/mortality ; Respiratory Tract Neoplasms/*economics/epidemiology/etiology/mortality ; }, abstract = {PURPOSE: The objective of this article was to estimate the social cost of respiratory cancer cases attributable to occupational risk factors in France in 2010.<br><br>METHODS: According to the attributable fraction method and based on available epidemiological data from the literature, we estimated the number of respiratory cancer cases due to each identified risk factor. We used the cost-of-illness method with a prevalence-based approach. We took into account the direct and indirect costs. We estimated the cost of production losses due to morbidity (absenteeism and presenteeism) and mortality costs (years of production losses) in the market and nonmarket spheres.<br><br>RESULTS: The social cost of lung, larynx, sinonasal and mesothelioma cancer caused by exposure to asbestos, chromium, diesel engine exhaust, paint, crystalline silica, wood and leather dust in France in 2010 were estimated at between 917 and 2,181 million euros. Between 795 and 2,011 million euros (87-92%) of total costs were due to lung cancer alone. Asbestos was by far the risk factor representing the greatest cost to French society in 2010 at between 531 and 1,538 million euros (58-71%), ahead of diesel engine exhaust, representing an estimated social cost of between 233 and 336 million euros, and crystalline silica (119-229 million euros). Indirect costs represented about 66% of total costs.<br><br>CONCLUSION: Our assessment shows the magnitude of the economic impact of occupational respiratory cancers. It allows comparisons between countries and provides valuable information for policy-makers responsible for defining public health priorities.}, }
@article {pmid23963927, year = {2014}, author = {Arzt, L and Quehenberger, F and Halbwedl, I and Mairinger, T and Popper, HH}, title = {BAP1 protein is a progression factor in malignant pleural mesothelioma.}, journal = {Pathology oncology research : POR}, volume = {20}, number = {1}, pages = {145-151}, pmid = {23963927}, issn = {1532-2807}, mesh = {Asbestos/adverse effects ; Disease Progression ; Female ; Humans ; Immunohistochemistry/methods ; Lung Neoplasms/*genetics/*pathology ; Male ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Mutation ; Pleural Neoplasms/*genetics/*pathology ; Prognosis ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma. Our study aimed to clarify if asbestos exposure has an influence on BAP1 expression and if BAP1 expression could be used as a prognostic factor of outcome. An immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and the expression levels have been correlated with asbestos exposure and overall survival time. BAP1 expression was not associated with asbestos exposure but we detected a significant effect of BAP1 expression on overall survival time--the higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival. BAP1 mutation has been linked to non-asbestos induced familial mesotheliomas, which usually belong to the long survivor group and BAP1 is most probably functioning differently than in sporadic cases. Further investigations need to be performed to characterize the BAP1 mutations and to identify the BAP1 downstream targets in MPM.}, }
@article {pmid23961336, year = {2013}, author = {Pham, VH and Lan Tran, TN and Le, GV and Movahed, M and Jiang, Y and Pham, NH and Ogawa, H and Takahashi, K}, title = {Asbestos and Asbestos-related Diseases in Vietnam: In reference to the International Labor Organization/World Health Organization National Asbestos Profile.}, journal = {Safety and health at work}, volume = {4}, number = {2}, pages = {117-121}, pmid = {23961336}, issn = {2093-7911}, abstract = {This paper describes progress on formulating a national asbestos profile for the country of Vietnam. The Center of Asbestos Resource, Vietnam, formulated a National Profile on Asbestos-related Occupational Health, with due reference to the International Labor Organization/World Health Organization National Asbestos Profile. The Center of Asbestos Resource was established by the Vietnamese Health Environment Management Agency and the National Institute of Labor Protection, with the support of the Australian Agency for International Development, as a coordinating point for asbestos-related issues in Vietnam. Under the National Profile on Asbestos-related Occupational Health framework, the Center of Asbestos Resource succeeded in compiling relevant information for 15 of the 18 designated items outlined in the International Labor Organization/World Health Organization National Asbestos Profile, some overlaps of the information items notwithstanding. Today, Vietnam continues to import and use an average of more than 60,000 metric tons of raw asbestos per year. Information on asbestos-related diseases is limited, but the country has begun to diagnose mesothelioma cases, with the technical cooperation of Japan. As it stands, the National Profile on Asbestos-related Occupational Health needs further work and updating. However, we envisage that the National Profile on Asbestos-related Occupational Health will ultimately facilitate the smooth transition to an asbestos-free Vietnam.}, }
@article {pmid23959774, year = {2014}, author = {Thompson, JK and Westbom, CM and Shukla, A}, title = {Malignant mesothelioma: development to therapy.}, journal = {Journal of cellular biochemistry}, volume = {115}, number = {1}, pages = {1-7}, pmid = {23959774}, issn = {1097-4644}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; 1R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Humans ; Lung Neoplasms/chemically induced/diagnosis/*etiology/pathology/*therapy ; Mesothelioma/chemically induced/diagnosis/*etiology/pathology/*therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by asbestos. Asbestos use has been reduced but not completely stopped. In addition, natural or man-made disasters will continue to dislodge asbestos from old buildings into the atmosphere and as long as respirable asbestos is available, MM will continue to be a threat. Due to the long latency period of MM development, it would still take decades to eradicate this disease if asbestos was completely removed from our lives today. Therefore, there is a need for researchers and clinicians to work together to understand this deadly disease and find a solution for early diagnosis and treatment. This article focuses on developmental mechanisms as well as current therapies available for MM.}, }
@article {pmid23956266, year = {2013}, author = {Andrews, W and Paul, S and Narula, N and Altorki, NK}, title = {Localized mesothelioma tumour arising synchronously with a primary contralateral lung cancer.}, journal = {Interactive cardiovascular and thoracic surgery}, volume = {17}, number = {6}, pages = {1061-1062}, pmid = {23956266}, issn = {1569-9285}, mesh = {Adenocarcinoma/chemistry/*pathology/surgery ; Adenocarcinoma of Lung ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Carcinoma, Non-Small-Cell Lung/chemistry/*pathology/surgery ; Humans ; Lung Neoplasms/chemistry/*pathology/surgery ; Male ; Mesothelioma/chemistry/*pathology/surgery ; *Neoplasms, Multiple Primary ; Pleural Neoplasms/chemistry/*pathology/surgery ; Pneumonectomy/methods ; Thoracic Surgery, Video-Assisted ; Thoracotomy ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Mesothelioma is a malignant growth of mesothelial cells found in the serosal membrane of pleural, peritoneal and pericardial surfaces as a result of prolonged exposure to asbestos. Malignant pleural mesothelioma (MPM) typically presents itself in a diffuse pattern of growth over the pleura of the lung or in more rare cases as a localized focus (LMPM). We present the first reported case of a synchronous LMPM and non-small adenocarcinoma of the lung treated by sequential resections.}, }
@article {pmid23953740, year = {2013}, author = {Baadh, AS and Xiong, X and Singh, S and Kapoor, R and Zhou, J and Katz, DS}, title = {Radiology-pathology conference: primary peritoneal mesothelioma.}, journal = {Clinical imaging}, volume = {37}, number = {6}, pages = {1142-1145}, doi = {10.1016/j.clinimag.2013.07.009}, pmid = {23953740}, issn = {1873-4499}, mesh = {Aged ; Asbestos/toxicity ; Fatal Outcome ; Humans ; Liver/diagnostic imaging/*pathology ; Male ; Mesothelioma/diagnostic imaging/etiology/*pathology ; Neoplasm Invasiveness ; Peritoneal Neoplasms/diagnostic imaging/etiology/*pathology ; Prognosis ; Smoking/adverse effects ; Tomography, X-Ray Computed ; }, abstract = {Primary peritoneal mesothelioma is a rare neoplasm which carries a dismal prognosis. These highly aggressive tumors arise from mesothelial cells lining the peritoneum and are rapidly fatal. The neoplasm is typically associated with crocidolite asbestos exposure. We present the case of a 75-year-old man with primary peritoneal mesothelioma, with invasion into the right hepatic lobe.}, }
@article {pmid23953254, year = {2014}, author = {Bourgault, MH and Gagné, M and Valcke, M}, title = {Lung cancer and mesothelioma risk assessment for a population environmentally exposed to asbestos.}, journal = {International journal of hygiene and environmental health}, volume = {217}, number = {2-3}, pages = {340-346}, doi = {10.1016/j.ijheh.2013.07.008}, pmid = {23953254}, issn = {1618-131X}, mesh = {Asbestos/*adverse effects ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mining ; Particulate Matter/*adverse effects ; Prospective Studies ; Quebec/epidemiology ; Risk ; Risk Assessment ; }, abstract = {Asbestos-related cancer risk is usually a concern restricted to occupational settings. However, recent published data on asbestos environmental concentrations in Thetford Mines, a mining city in Quebec, Canada, provided an opportunity to undertake a prospective cancer risk assessment in the general population exposed to these concentrations. Using an updated Berman and Crump dose-response model for asbestos exposure, we selected population-specific potency factors for lung cancer and mesothelioma. These factors were evaluated on the basis of population-specific cancer data attributed to the studied area's past environmental levels of asbestos. We also used more recent population-specific mortality data along with the validated potency factors to generate corresponding inhalation unit risks. These unit risks were then combined with recent environmental measurements made in the mining town to calculate estimated lifetime risk of asbestos-induced lung cancer and mesothelioma. Depending on the chosen potency factors, the lifetime mortality risks varied between 0.7 and 2.6 per 100,000 for lung cancer and between 0.7 and 2.3 per 100,000 for mesothelioma. In conclusion, the estimated lifetime cancer risk for both cancers combined is close to Health Canada's threshold for "negligible" lifetime cancer risks. However, the risks estimated are subject to several uncertainties and should be confirmed by future mortality rates attributed to present day asbestos exposure.}, }
@article {pmid23940847, year = {2013}, author = {Heederik, D and Lenters, V and Vermeulen, R}, title = {Reply: response to the letter by Drs Berman and Case.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {5}, pages = {675-677}, doi = {10.1093/annhyg/met017}, pmid = {23940847}, issn = {1475-3162}, mesh = {*Asbestos ; Humans ; Mesothelioma/*chemically induced ; Research/*standards ; Risk Assessment/*standards ; }, }
@article {pmid23939988, year = {2013}, author = {Camiade, E and Gramond, C and Jutand, MA and Audignon, S and Rinaldo, M and Imbernon, E and Luce, D and Galateau-Sallé, F and Astoul, P and Pairon, JC and Brochard, P and Lacourt, A}, title = {Characterization of a French series of female cases of mesothelioma.}, journal = {American journal of industrial medicine}, volume = {56}, number = {11}, pages = {1307-1316}, doi = {10.1002/ajim.22229}, pmid = {23939988}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*poisoning ; *Carcinogens ; Causality ; Environmental Exposure/statistics &amp; numerical data ; Female ; France/epidemiology ; Humans ; Mesothelioma/*epidemiology ; Middle Aged ; Neoplasms, Radiation-Induced/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; Pleural Neoplasms/*epidemiology ; Radiotherapy/adverse effects ; Retrospective Studies ; Risk Factors ; X-Rays/adverse effects ; }, abstract = {BACKGROUND: More than 80% of mesothelioma cases in men are attributable to occupational asbestos exposure compared to only 40% in women. The objective of the study was to characterize a series of female pleural mesotheliomas according to known and suspected risk factors.<br><br>METHODS: From the exhaustive recording of 318 female mesothelioma cases in the French National Mesothelioma Surveillance Program between 1998 and 2009, multiple correspondence analysis and hybrid clustering were performed to characterize these cases according to expert assessed occupational and non-occupational exposure to asbestos and man-made vitreous fibers, X-ray exposure, and history of cancer and non-malignant respiratory diseases.<br><br>RESULTS: Four clusters were identified: (1) occupational exposure to asbestos and man-made vitreous fibers (7.9% of subjects); (2) radiation exposure during radiotherapy (12.9%); (3) increased asbestos exposure (19.8%); and (4) "non-exposure" characteristics (59.4%).<br><br>CONCLUSION: These results will allow hypotheses to be generated about associations between mesothelioma and non-occupational asbestos exposure, X-ray exposure and history of respiratory disease.}, }
@article {pmid23937860, year = {2013}, author = {Hillegass, JM and Miller, JM and MacPherson, MB and Westbom, CM and Sayan, M and Thompson, JK and Macura, SL and Perkins, TN and Beuschel, SL and Alexeeva, V and Pass, HI and Steele, C and Mossman, BT and Shukla, A}, title = {Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells.}, journal = {Particle and fibre toxicology}, volume = {10}, number = {}, pages = {39}, pmid = {23937860}, issn = {1743-8977}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; *Autocrine Communication ; Carrier Proteins/*metabolism ; Cell Line, Tumor ; Cytokines/genetics/*metabolism ; Dose-Response Relationship, Drug ; Epithelium/*drug effects/immunology/pathology ; Humans ; Inflammasomes/*drug effects/immunology ; Inflammation Mediators/*metabolism ; Interleukin 1 Receptor Antagonist Protein/pharmacology ; Mesothelioma/*chemically induced/drug therapy/genetics/immunology/pathology ; Mice ; Mice, SCID ; NLR Family, Pyrin Domain-Containing 3 Protein ; Primary Cell Culture ; RNA, Messenger/metabolism ; Receptors, Interleukin-1/antagonists &amp; inhibitors/metabolism ; Time Factors ; Transcription, Genetic/drug effects ; Xenograft Model Antitumor Assays ; Zeolites/*toxicity ; }, abstract = {BACKGROUND: Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear.<br><br>RESULTS: We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1&#x3b2;, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model.<br><br>CONCLUSIONS: These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis.}, }
@article {pmid23937772, year = {2013}, author = {Schuberth, PC and Hagedorn, C and Jensen, SM and Gulati, P and van den Broek, M and Mischo, A and Soltermann, A and Jüngel, A and Marroquin Belaunzaran, O and Stahel, R and Renner, C and Petrausch, U}, title = {Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells.}, journal = {Journal of translational medicine}, volume = {11}, number = {}, pages = {187}, pmid = {23937772}, issn = {1479-5876}, mesh = {Adoptive Transfer ; Animals ; Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Cytotoxicity, Immunologic ; Endopeptidases ; Gelatinases/*metabolism ; Humans ; Immunohistochemistry ; *Immunotherapy ; Lung Neoplasms/*immunology/*therapy ; Membrane Proteins/*metabolism ; Mesothelioma/*immunology/*therapy ; Mesothelioma, Malignant ; Mice ; Peritoneum/pathology ; Pleural Neoplasms/*immunology/*therapy ; Recombinant Proteins/metabolism ; Serine Endopeptidases/*metabolism ; Stromal Cells/metabolism ; T-Lymphocytes/*immunology/metabolism ; Transduction, Genetic ; Xenograft Model Antitumor Assays ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an incurable malignant disease, which results from chronic exposition to asbestos in at least 70% of the cases. Fibroblast activation protein (FAP) is predominantly expressed on the surface of reactive tumor-associated fibroblasts as well as on particular cancer types. Because of its expression on the cell surface, FAP is an attractive target for adoptive T cell therapy. T cells can be re-directed by retroviral transfer of chimeric antigen receptors (CAR) against tumor-associated antigens (TAA) and therefore represent a therapeutic strategy of adoptive immunotherapy.<br><br>METHODS: To evaluate FAP expression immunohistochemistry was performed in tumor tissue from MPM patients. CD8+ human T cells were retrovirally transduced with an anti-FAP-F19-&#x2206;CD28/CD3&#x3b6;-CAR. T cell function was evaluated in vitro by cytokine release and cytotoxicity assays. In vivo function was tested with an intraperitoneal xenograft tumor model in immunodeficient mice.<br><br>RESULTS: FAP was found to be expressed in all subtypes of MPM. Additionally, FAP expression was evaluated in healthy adult tissue samples and was only detected in specific areas in the pancreas, the placenta and very weakly for cervix and uterus. Expression of the anti-FAP-F19-&#x2206;CD28/CD3&#x3b6;-CAR in CD8+ T cells resulted in antigen-specific IFN&#x3b3; release. Additionally, FAP-specific re-directed T cells lysed FAP positive mesothelioma cells and inflammatory fibroblasts in an antigen-specific manner in vitro. Furthermore, FAP-specific re-directed T cells inhibited the growth of FAP positive human tumor cells in the peritoneal cavity of mice and significantly prolonged survival of mice.<br><br>CONCLUSION: FAP re-directed CD8+ T cells showed antigen-specific functionality in vitro and in vivo. Furthermore, FAP expression was verified in all MPM histotypes. Therefore, our data support performing a phase I clinical trial in which MPM patients are treated with adoptively transferred FAP-specific re-directed T cells.}, }
@article {pmid23932389, year = {2013}, author = {Niccoli-Asabella, A and Notaristefano, A and Rubini, D and Altini, C and Ferrari, C and Merenda, N and Fanelli, M and Rubini, G}, title = {18F-FDG PET/CT in suspected recurrences of epithelial malignant pleural mesothelioma in asbestos-fibers-exposed patients (comparison to standard diagnostic follow-up).}, journal = {Clinical imaging}, volume = {37}, number = {6}, pages = {1098-1103}, doi = {10.1016/j.clinimag.2013.06.009}, pmid = {23932389}, issn = {1873-4499}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lung Neoplasms/*diagnosis/diagnostic imaging ; Lymph Nodes/diagnostic imaging ; Male ; Mesothelioma/*diagnosis/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/diagnostic imaging ; Occupational Exposure ; Pleural Neoplasms/*diagnosis/diagnostic imaging ; Positron-Emission Tomography/*methods ; Respiratory Mucosa/diagnostic imaging/pathology ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {This retrospective study evaluated the role of 18-fluorine-labeled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with previous occupational or environmental exposure to asbestos, with histopathological diagnosis of epithelial malignant pleural mesothelioma and suspected recurrences, comparing the data from 18F-FDG PET/CT and computed tomography with contrast enhancement (CECT). 18F-FDG PET/CT has greater sensitivity than CECT in identifying local extent, lymph nodes, and metastasis. 18F-FDG PET/CT whole-body explorations are useful to monitor the follow-up and evaluate the metabolic response to chemo- and radiotherapy, modifying the scheduled treatment plan.}, }
@article {pmid23924264, year = {2013}, author = {Lohcharoenkal, W and Wang, L and Stueckle, TA and Dinu, CZ and Castranova, V and Liu, Y and Rojanasakul, Y}, title = {Chronic exposure to carbon nanotubes induces invasion of human mesothelial cells through matrix metalloproteinase-2.}, journal = {ACS nano}, volume = {7}, number = {9}, pages = {7711-7723}, pmid = {23924264}, issn = {1936-086X}, support = {P20 RR016440/RR/NCRR NIH HHS/United States ; R01 HL095579/HL/NHLBI NIH HHS/United States ; P30 RR032138/RR/NCRR NIH HHS/United States ; R01-HL095579/HL/NHLBI NIH HHS/United States ; P20 RR016477/RR/NCRR NIH HHS/United States ; P30 GM103488/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/drug effects/*metabolism ; Cells, Cultured ; Dose-Response Relationship, Drug ; Epithelial Cells/*drug effects/*pathology ; Humans ; Matrix Metalloproteinase 2/*metabolism ; Mesothelioma/*chemically induced/*pathology ; Nanotubes, Carbon/*toxicity ; Neoplasm Invasiveness ; }, abstract = {Malignant mesothelioma is one of the most aggressive forms of cancer known. Recent studies have shown that carbon nanotubes (CNTs) are biopersistent and induce mesothelioma in animals, but the underlying mechanisms are not known. Here, we investigate the effect of long-term exposure to high aspect ratio CNTs on the aggressive behaviors of human pleural mesothelial cells, the primary cellular target of human lung mesothelioma. We show that chronic exposure (4 months) to single- and multiwalled CNTs induced proliferation, migration, and invasion of the cells similar to that observed in asbestos-exposed cells. An up-regulation of several key genes known to be important in cell invasion, notably matrix metalloproteinase-2 (MMP-2), was observed in the exposed mesothelial cells as determined by real-time PCR. Western blot and enzyme activity assays confirmed the increased expression and activity of MMP-2. Whole genome microarray analysis further indicated the importance of MMP-2 in the invasion gene signaling network of the exposed cells. Knockdown of MMP-2 in CNT and asbestos-exposed cells by shRNA-mediated gene silencing effectively inhibited the aggressive phenotypes. This study demonstrates CNT-induced cell invasion and indicates the role of MMP-2 in the process.}, }
@article {pmid23917077, year = {2014}, author = {Chew, SH and Okazaki, Y and Nagai, H and Misawa, N and Akatsuka, S and Yamashita, K and Jiang, L and Yamashita, Y and Noguchi, M and Hosoda, K and Sekido, Y and Takahashi, T and Toyokuni, S}, title = {Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production.}, journal = {Carcinogenesis}, volume = {35}, number = {1}, pages = {164-172}, doi = {10.1093/carcin/bgt267}, pmid = {23917077}, issn = {1460-2180}, mesh = {3T3-L1 Cells ; Adipocytes/metabolism/*pathology ; Adipokines/metabolism ; Adipose Tissue/drug effects/metabolism ; Animals ; Asbestos/pharmacokinetics/*toxicity ; Chemokine CCL2/genetics/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Lung Neoplasms/*chemically induced/*pathology ; Male ; Mesothelioma/*chemically induced/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred Strains ; }, abstract = {Like many other human cancers, the development of malignant mesothelioma is closely associated with a chronic inflammatory condition. Both macrophages and mesothelial cells play crucial roles in the inflammatory response caused by asbestos exposure. Here, we show that adipocytes can also contribute to asbestos-induced inflammation through dysregulated adipocytokine production. 3T3-L1 preadipocytes were differentiated into mature adipocytes prior to use. These cells took up asbestos fibers (chrysotile, crocidolite and amosite) but were more resistant to asbestos-induced injury than macrophages and mesothelial cells. Expression microarray analysis followed by reverse transcription-PCR revealed that adipocytes respond directly to asbestos exposure with an increased production of proinflammatory adipocytokines [e.g. monocyte chemoattractant protein-1 (MCP-1)], whereas the production of anti-inflammatory adipocytokines (e.g. adiponectin) is suppressed. This was confirmed in epididymal fat pad of mice after intraperitoneal injection of asbestos fibers. Such dysregulated adipocytokine production favors the establishment of a proinflammatory environment. Furthermore, MCP-1 marginally promoted the growth of MeT-5A mesothelial cells and significantly enhanced the wound healing of Y-MESO-8A and Y-MESO-8D human mesothelioma cells. Our results suggest that increased levels of adipocytokines, such as MCP-1, can potentially contribute to the promotion of mesothelial carcinogenesis through the enhanced recruitment of inflammatory cells as well as a direct growth and migration stimulatory effect on mesothelial and mesothelioma cells. Taken together, our findings support a potential cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis.}, }
@article {pmid23915043, year = {2013}, author = {Rosell-Murphy, MI and Abós-Herràndiz, R and Olivella, JT and Alberti-Casas, C and Allas, IG and Artés, XM and Günther, IK and Malet, IG and Martínez, RO and Canela-Soler, J}, title = {Risk factors associated with asbestos-related diseases: a community-based case-control study.}, journal = {BMC public health}, volume = {13}, number = {}, pages = {723}, pmid = {23915043}, issn = {1471-2458}, mesh = {Adult ; Analysis of Variance ; Asbestos/adverse effects ; Asbestosis/*epidemiology/prevention &amp; control ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/prevention &amp; control ; Male ; Mesothelioma/*epidemiology/prevention &amp; control ; Mesothelioma, Malignant ; Occupational Exposure/statistics &amp; numerical data ; *Research Design ; Residence Characteristics ; Risk ; Risk Factors ; Spain ; }, abstract = {BACKGROUND: Asbestos is a first level carcinogen. However, few epidemiological studies analyse the risk and protective factors associated with asbestos-related diseases and follow up these conditions in the general population. Pleural mesothelioma, caused by inhalation of asbestos fibres at work, at home or in the environment, is the most representative asbestos-related disease.The objectives of this study are to analyse the risk and protective factors associated with asbestos-related diseases and to investigate the incidence of new clinical manifestations in patients already diagnosed with some form of ARD.<br><br>METHODS/DESIGN: We have designed a matched case-control study with follow up of both cohorts from a population of a health district of the Barcelona province that has been exposed to asbestos for a period of 90 years.<br><br>DISCUSSION: A better understanding of asbestos-related diseases should improve i) the clinical and epidemiological follow up of patients with this condition; ii) the design of new treatment strategies; iii) and the development of preventive activities. At the end of the study, the two cohorts created in this study (affected cases and healthy controls) will constitute the basis for future research.}, }
@article {pmid23907860, year = {2013}, author = {Diandini, R and Takahashi, K and Park, EK and Jiang, Y and Movahed, M and Le, GV and Lee, LJ and Delgermaa, V and Kim, R}, title = {Potential years of life lost (PYLL) caused by asbestos-related diseases in the world.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {993-1000}, doi = {10.1002/ajim.22206}, pmid = {23907860}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/*mortality ; *Cost of Illness ; Databases, Factual ; Female ; Global Health/*statistics &amp; numerical data ; Humans ; *Life Tables ; Male ; Mesothelioma/*mortality ; Middle Aged ; }, abstract = {BACKGROUND: We applied the well-established, but rather under-utilized, indicator of Potential Years of Life Lost (PYLL) to estimate the global burden of mesothelioma and asbestosis.<br><br>METHODS: We analyzed all deaths caused by mesothelioma and asbestosis that were reported by 82 and 55 countries, respectively, to the World Health Organization (WHO) from 1994 to 2010.<br><br>RESULTS: The 128,015 and 13,885 persons who died of mesothelioma and asbestosis, potentially lost a total of 2.18 million and 180,000 years of life (PYLL), or, an annual average PYLL of 201,000 years and 17,000 years, respectively. The average PYLL per decedent were 17.0 and 13.0 years for mesothelioma and asbestosis, respectively.<br><br>CONCLUSIONS: The current burden of asbestos-related diseases (ARDs) in terms of PYLL is substantial. The future burden of ARDs can be eliminated by stopping the use of asbestos.}, }
@article {pmid23905972, year = {2013}, author = {Barlow, CA and Lievense, L and Gross, S and Ronk, CJ and Paustenbach, DJ}, title = {The role of genotoxicity in asbestos-induced mesothelioma: an explanation for the differences in carcinogenic potential among fiber types.}, journal = {Inhalation toxicology}, volume = {25}, number = {9}, pages = {553-567}, doi = {10.3109/08958378.2013.807321}, pmid = {23905972}, issn = {1091-7691}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mutagens/*toxicity ; }, abstract = {The mechanism(s) underlying asbestos toxicity associated with the pathogenesis of mesothelioma has been a challenge to unravel for more than 60 years. A significant amount of research has focused on the characteristics of different fiber types and their potential to induce mesothelioma. These mechanistic studies of fiber toxicity have proceeded along two lines: those demonstrating biochemical mechanisms by which fibers induce disease and those investigating human susceptibility. Most recent studies focused on in vitro genotoxic effects induced by asbestos as the mechanism responsible for asbestos-induced disease. Although asbestos exerts a genotoxic effect at certain concentrations in vitro, a positive response in these tests does not indicate that the chemical is likely to produce an increased risk of carcinogenesis in exposed human populations. Thus far, findings from studies on the effects of fiber type in mesothelial cells are seriously flawed by a lack of a dose response relationship. The common limitation of these in vitro experiments is the lack of attention paid to the complexities of the human anatomy, biochemistry and physiology, which make the observed effects in these experimental systems difficult to extrapolate to persons in the workplace. Mechanistic differences between carcinogenic and genotoxic processes indicate why tests for genotoxicity do not provide much insight regarding the ability to predict carcinogenic potential in workers exposed to asbestos doses in the post-Occupational Safety and Health Administration era. This review discusses the existing literature on asbestos-induced genotoxicity and explains why these studies may or may not likely help characterize the dose-response curve at low dose.}, }
@article {pmid23899865, year = {2013}, author = {Donaldson, K and Poland, CA and Murphy, FA and MacFarlane, M and Chernova, T and Schinwald, A}, title = {Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences.}, journal = {Advanced drug delivery reviews}, volume = {65}, number = {15}, pages = {2078-2086}, doi = {10.1016/j.addr.2013.07.014}, pmid = {23899865}, issn = {1872-8294}, support = {G0901697/MRC_/Medical Research Council/United Kingdom ; MC_U132685863/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Asbestos/*toxicity ; Environmental Exposure/adverse effects ; Humans ; Inflammation/chemically induced/pathology ; Inhalation Exposure/adverse effects ; Lung/drug effects/pathology ; Lung Diseases/*chemically induced/pathology ; Nanotubes, Carbon/*toxicity ; Oxidative Stress/drug effects ; Pleural Diseases/chemically induced/pathology ; }, abstract = {Carbon nanotubes are a valuable industrial product but there is potential for human pulmonary exposure during production and their fibrous shape raises the possibility that they may have effects like asbestos, which caused a worldwide pandemic of disease in the20th century that continues into present. CNT may exist as fibres or as more compact particles and the asbestos-type hazard only pertains to the fibrous forms of CNT. Exposure to asbestos causes asbestosis, bronchogenic carcinoma, mesothelioma, pleural fibrosis and pleural plaques indicating that both the lungs and the pleura are targets. The fibre pathogenicity paradigm was developed in the 1970s-80s and has a robust structure/toxicity relationship that enables the prediction of the pathogenicity of fibres depending on their length, thickness and biopersistence. Fibres that are sufficiently long and biopersistent and that deposit in the lungs can cause oxidative stress and inflammation. They may also translocate to the pleura where they can be retained depending on their length, and where they cause inflammation and oxidative stress in the pleural tissues. These pathobiological processes culminate in pathologic change - fibroplasia and neoplasia in the lungs and the pleura. There may also be direct genotoxic effects of fibres on epithelial cells and mesothelium, contributing to neoplasia. CNT show some of the properties of asbestos and other types of fibre in producing these types of effects and more research is needed. In terms of the molecular pathways involved in the interaction of long biopersistent fibres with target tissue the events leading to mesothelioma have been a particular area of interest. A variety of kinase pathways important in proliferation are activated by asbestos leading to pre-malignant states and investigations are under way to determine whether fibrous CNT also affects these molecular pathways. Current research suggests that fibrous CNT can elicit effects similar to asbestos but more research is needed to determine whether they, or other nanofibres, can cause fibrosis and cancer in the long term.}, }
@article {pmid23899648, year = {2014}, author = {Budroni, M and Cossu, A and Paliogiannis, P and Palmieri, G and Attene, F and Cesaraccio, R and Tanda, F}, title = {Epidemiology of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy). A population-based report.}, journal = {Annali italiani di chirurgia}, volume = {85}, number = {3}, pages = {244-248}, pmid = {23899648}, issn = {2239-253X}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Carcinogens ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology/mortality ; Male ; Mesothelioma/*epidemiology/*etiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/*etiology/mortality ; Registries ; Retrospective Studies ; Risk Factors ; Sex Distribution ; Survival Rate ; }, abstract = {UNLABELLED: The aim of this population-based study was to analyze and describe the epidemiological characteristics and trends of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy), in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. The overall number of malignant pleural mesothelioma cases registered was 70. The male-to-female ratio was 4:1 and the mean age 65.1 years for males and 63.4 years for females. The standardized incidence rates were 1.2/100,000 and 0.3/100,000 and the standardized mortality rates 0.6/100,000 and 0.2/100,000 for males and females respectively. A trend to increase in incidence in recent years was evidenced. This trend seems to follow the general national tendency and it depends on a large diffusion of asbestos usage in the past, delayed legislative interventions and probably a cleaning strategy of residual contamination fonts to intensify. The relative 5 years survival was low, suggesting the necessity to further intensify research and cure methods for the treatment of this extremely aggressive disease.<br><br>KEY WORDS: Asbestos exposure, Mesothelioma, Pleura, Sassari.}, }
@article {pmid23896078, year = {2013}, author = {Meisenkothen, C}, title = {Malignant mesothelioma, airborne asbestos, and the need for accuracy in chrysotile risk assessments.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {23}, number = {2}, pages = {389-405}, doi = {10.2190/NS.23.2.k}, pmid = {23896078}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos, Serpentine/*toxicity ; Connecticut ; Humans ; Lung Neoplasms/*etiology ; Male ; *Manufactured Materials ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects/legislation &amp; jurisprudence ; Public Health ; *Risk Assessment ; }, abstract = {A man diagnosed with pleural mesothelioma sought legal representation with the author's law firm. He worked 33 years in a wire and cable factory in the northeastern United States (Connecticut) that exclusively used chrysotile asbestos in its manufacturing process. This is the first report of mesothelioma arising from employees of this factory. This report provides additional support for the proposition that chrysotile asbestos can cause malignant mesothelioma in humans. If chrysotile risk assessments are to be accurate, then the literature should contain an accurate accounting of all mesotheliomas alleged to be caused by chrysotile asbestos. This is important not just for public health professionals but also for individuals and companies involved in litigation over asbestos-related diseases. If reports such as these remain unknown, it is probable that cases of mesothelioma among chrysotile-exposed cohorts would go unrecognized and chrysotile-using factories would be incorrectly cited as having no mesotheliomas among their employees.}, }
@article {pmid23887168, year = {2013}, author = {Goparaju, C and Donington, JS and Hsu, T and Harrington, R and Hirsch, N and Pass, HI}, title = {Overexpression of EPH receptor B2 in malignant mesothelioma correlates with oncogenic behavior.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {9}, pages = {1203-1211}, doi = {10.1097/JTO.0b013e31829ceb6a}, pmid = {23887168}, issn = {1556-1380}, mesh = {*Apoptosis ; Blotting, Western ; Case-Control Studies ; Cell Movement ; *Cell Proliferation ; Cells, Cultured ; Epithelium/metabolism/*pathology ; Fluorescent Antibody Technique ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/genetics/metabolism/*pathology ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; Peritoneum/metabolism/*pathology ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Receptor, EphB2/antagonists &amp; inhibitors/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MM) is an aggressive asbestos-associated malignancy with limited therapeutic options. This study describes the overexpression of Ephrin B2 receptor (EPHB2) in MM cell lines and tumors, and the effect of its manipulation on proliferative and invasive qualities of the disease.<br><br>METHODS: Using expression arrays, we investigated EPHB2 in MM tumors compared with normal mesothelium. EPHB2 and downstream target expression were evaluated using reverse-transcriptase polymerase chain reaction and immunoblotting methods. The biological significance of EPHB2 in MM was evaluated using in vitro functional assays with and without targeting by EPHB2-short hairpin RNA or blocking peptide in two mesothelioma cell lines, HP-1 and H2595.<br><br>RESULTS: EPHB2 is overexpressed in all MM cell lines, but not in benign mesothelial cells, and is significantly elevated in MM tumor tissue compared with matched normal peritoneum. Targeted knockdown of EPHB2 in HP-1 and H2595 cell lines reduced its expression and that of EPHB2 downstream targets such as matrix metalloproteinase (MMP-2) and vascular endothelial growth factor, whereas caspase 2 and caspase 8 had increased expression. Inhibition of EPHB2 resulted in a significant decrease in scratch closure (1.25-fold-1.8-fold), proliferation (1.5-fold), and invasion (1.7-fold-1.8-fold) compared with the controls. Most notably, however, EPHB2 silencing resulted in a significant increase in apoptotic proteins and activity.<br><br>CONCLUSION: EPHB2 seems to play an important role in MM pathogenesis and these findings indicate that EPHB2 could serve as a potential novel therapeutic target for treatment of the disease.}, }
@article {pmid23886156, year = {2013}, author = {Kim, MC and Cui, FJ and Kim, Y}, title = {Hydrogen peroxide promotes epithelial to mesenchymal transition and stemness in human malignant mesothelioma cells.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {6}, pages = {3625-3630}, doi = {10.7314/apjcp.2013.14.6.3625}, pmid = {23886156}, issn = {2476-762X}, mesh = {Apoptosis ; Blotting, Western ; Cadherins/genetics/metabolism ; Cell Adhesion ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/*drug effects ; Homeodomain Proteins/genetics/metabolism ; Humans ; Hydrogen Peroxide/*pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Immunoenzyme Techniques ; Lung Neoplasms/drug therapy/metabolism/*pathology ; Mesothelioma/drug therapy/metabolism/*pathology ; Mesothelioma, Malignant ; Nanog Homeobox Protein ; Neoplastic Stem Cells/*drug effects/metabolism/pathology ; Octamer Transcription Factor-3/genetics/metabolism ; Oxidants/*pharmacology ; Oxidative Stress/drug effects ; RNA, Messenger/genetics ; Reactive Oxygen Species/*metabolism ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; SOXB1 Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta1/genetics/metabolism ; Tumor Cells, Cultured ; Vimentin/genetics/metabolism ; }, abstract = {Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by H2O2 in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with H2O2, followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with H2O2 promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with H2O2. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-1α) and transforming growth factor beta 1 (TGF-β1). Considering that treatment with H2O2 results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.}, }
@article {pmid23885834, year = {2013}, author = {Kamp, DW and Liu, G and Cheresh, P and Kim, SJ and Mueller, A and Lam, AP and Trejo, H and Williams, D and Tulasiram, S and Baker, M and Ridge, K and Chandel, NS and Beri, R}, title = {Asbestos-induced alveolar epithelial cell apoptosis. The role of endoplasmic reticulum stress response.}, journal = {American journal of respiratory cell and molecular biology}, volume = {49}, number = {6}, pages = {892-901}, pmid = {23885834}, issn = {1535-4989}, support = {R01ES020357/ES/NIEHS NIH HHS/United States ; P01 HL071643/HL/NHLBI NIH HHS/United States ; P01HL071643/HL/NHLBI NIH HHS/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; I01 BX000786/BX/BLRD VA/United States ; P30 HL101292/HL/NHLBI NIH HHS/United States ; }, mesh = {Alveolar Epithelial Cells/*drug effects/*pathology/physiology ; Animals ; Antioxidants/pharmacology ; Apoptosis/*drug effects/physiology ; Asbestos, Amosite/*toxicity ; Calcium Signaling/drug effects ; Cell Line ; Cells, Cultured ; DNA-Binding Proteins/genetics/metabolism ; Endoplasmic Reticulum Chaperone BiP ; Endoplasmic Reticulum Stress/*drug effects/physiology ; Endoribonucleases/genetics/metabolism ; Heat-Shock Proteins/genetics/metabolism ; Humans ; Membrane Proteins/genetics/metabolism ; Organometallic Compounds/pharmacology ; Phenylbutyrates/pharmacology ; Protein Serine-Threonine Kinases/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Regulatory Factor X Transcription Factors ; Salicylates/pharmacology ; Thapsigargin/pharmacology ; Transcription Factor CHOP/genetics/metabolism ; Transcription Factors/genetics/metabolism ; bcl-X Protein/genetics/metabolism ; }, abstract = {Asbestos exposure results in pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) apoptosis is important in the development of pulmonary fibrosis after exposure to an array of toxins, including asbestos. An endoplasmic reticulum (ER) stress response and mitochondria-regulated (intrinsic) apoptosis occur in AECs of patients with idiopathic pulmonary fibrosis, a disease with similarities to asbestosis. Asbestos induces AEC intrinsic apoptosis, but the role of the ER is unclear. The objective of this study was to determine whether asbestos causes an AEC ER stress response that promotes apoptosis. Using human A549 and rat primary isolated alveolar type II cells, amosite asbestos fibers increased AEC mRNA and protein expression of ER stress proteins involved in the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein-1, as well as ER Ca[2](2+) release ,as assessed by a FURA-2 assay. Eukarion-134, a superoxide dismutase/catalase mimetic, as well as overexpression of Bcl-XL in A549 cells each attenuate asbestos-induced AEC ER stress (IRE-1 and X-box-binding protein-1 protein expression; ER Ca[2](2+) release) and apoptosis. Thapsigargin, a known ER stress inducer, augments AEC apoptosis, and eukarion-134 or Bcl-XL overexpression are protective. Finally, 4-phenylbutyric acid, a chemical chaperone that attenuates ER stress, blocks asbestos- and thapsigargin-induced AEC IRE-1 protein expression, but does not reduce ER Ca[2](2+) release or apoptosis. These results show that asbestos triggers an AEC ER stress response and subsequent intrinsic apoptosis that is mediated in part by ER Ca[2](2+) release.}, }
@article {pmid23879063, year = {2013}, author = {Magnani, C and Fubini, B and Mirabelli, D and Bertazzi, PA and Bianchi, C and Chellini, E and Gennaro, V and Marinaccio, A and Menegozzo, M and Merler, E and Merletti, F and Musti, M and Pira, E and Romanelli, A and Terracini, B and Zona, A}, title = {Pleural mesothelioma: epidemiological and public health issues. Report from the Second Italian Consensus Conference on Pleural Mesothelioma.}, journal = {La Medicina del lavoro}, volume = {104}, number = {3}, pages = {191-202}, pmid = {23879063}, issn = {0025-7818}, mesh = {Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; *Public Health ; }, abstract = {Malignant mesothelioma is closely connected to asbestos exposure, with epidemiological patterns closely reshaping the geography and history of asbestos exposure. Mechanisms of causation and of interaction of asbestos fibres with pleura are complex and currently not yet completely understood. Curative efforts so far provided little results. Italy shows one of the highest incidence of MM and developed a network of specialized cancer registries in order to monitor disease occurrence and describe its epidemiology in details. The second Italian Consensus Conference on Pleural Mesothelioma convened in Torino on November 24th-25th, 2011. Besides the main consensus report summarizing the contribution of the different expertises, that was published elsewhere, the participants in 'Public Health and Epidemiology' section decided to report in major details the evidence and the conclusions regarding epidemiology, causative mechanisms and the public health impact of the disease.}, }
@article {pmid23874067, year = {2013}, author = {Yamashita, K and Nagai, H and Kondo, Y and Misawa, N and Toyokuni, S}, title = {Evaluation of two distinct methods to quantify the uptake of crocidolite fibers by mesothelial cells.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {53}, number = {1}, pages = {27-35}, pmid = {23874067}, issn = {0912-0009}, abstract = {Exposure to asbestos fibers increases the risk of mesothelioma in humans. One hypothetical carcinogenic mechanism is that asbestos fibers may directly induce mutations in mesothelial cells. Although the uptake of asbestos fibers by mesothelial cells is recognized, methods for the quantification of the uptake have not been well established. In the present study, we evaluated two distinct methods, using crocidolite fibers and MeT5A mesothelial cells. One method is histological evaluation using the cell-block technique, which allows for the direct cross-sectional observation of cells and fibers. We found the bright field observation with ×1000 magnification (oil-immersion) of the sample with Kernechtrot staining was most suitable for this purpose. The other method is flow cytometric analysis, which permits the evaluation of a much larger number of cells. We observed that the side scatter (SSC) increased with the intracellular fibers, and that the "mean SSC ratio (treated/control)" was useful for quantification. We could collect the cells with abundant internalized crocidolite fibers by sorting. Results of the two methodologies were correlated well in the experiments. The quantities of internalized fibers increased with incubation time and loaded dosage, but they were inversely associated with cellular density in culture.}, }
@article {pmid23866375, year = {2013}, author = {Bahk, J and Choi, Y and Lim, S and Paek, D}, title = {Authors' reply. Why countries ban asbestos: the roots of political will.}, journal = {International journal of occupational and environmental health}, volume = {19}, number = {2}, pages = {137-138}, doi = {10.1179/1077352513Z.00000000061}, pmid = {23866375}, issn = {1077-3525}, mesh = {Air Pollutants/*toxicity ; Air Pollution, Indoor/*legislation &amp; jurisprudence ; Asbestos/*toxicity ; Delivery of Health Care/*organization &amp; administration ; Humans ; *International Cooperation ; Mesothelioma/*epidemiology ; *Policy ; }, }
@article {pmid23863542, year = {2013}, author = {Carrillo, MC and Alturkistany, S and Roberts, H and Nguyen, E and Chung, TB and Paul, N and Herman, S and Weisbrod, G and Patsios, D}, title = {Low-dose computed tomography (LDCT) in workers previously exposed to asbestos: detection of parenchymal lung disease.}, journal = {Journal of computer assisted tomography}, volume = {37}, number = {4}, pages = {626-630}, doi = {10.1097/RCT.0b013e31828e1b8e}, pmid = {23863542}, issn = {1532-3145}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/*diagnostic imaging/epidemiology ; Comorbidity ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Monitoring/methods/*statistics &amp; numerical data ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging/epidemiology ; Male ; Mesothelioma/*diagnostic imaging/epidemiology ; Middle Aged ; Ontario/epidemiology ; Prevalence ; Radiation Dosage ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Smoking/epidemiology ; Tomography, X-Ray Computed/*methods/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: To evaluate the lungs of asymptomatic asbestos-exposed workers who were screened for lung cancer and mesothelioma using low-dose computed tomography (LDCT) for parenchymal abnormalities.<br><br>METHODS: Three hundred fifteen baseline LDCT studies of the chest of participants with at least 20 years' exposure to asbestos or presence of pleural plaques before enrollment on chest radiographs were analyzed.<br><br>RESULTS: Three hundred fifteen subjects were studied. The mean age was 61.7 years, and the mean exposure to asbestos was 26.9 years. One hundred seventy-five (56%) participants had absence of parenchymal findings with a mean age of 58.7 years, mean exposure of 24.6 years, and a mean smoking pack years of 19. One hundred forty subjects (44%) had parenchymal findings (138 men and 2 women) with a mean age of 65.3 years, mean exposure of 29.73 years, and a mean smoking pack years of 21.5 years. Participants who had parenchymal manifestations were more likely to be older and have longer exposure to asbestos compared to participants who had no relevant parenchymal findings. There was no statistical difference in the mean smoking pack years between the groups with and without parenchymal findings.<br><br>CONCLUSIONS: Low-dose CT could demonstrate parenchymal lung manifestations in this higher-risk asymptomatic group with prior exposure to asbestos in the setting of screening for lung cancer and mesothelioma. Individuals with longer exposure to asbestos and of higher age have more pulmonary abnormalities. The age and the latency of exposure play an important role given that the asbestos-related parenchymal abnormalities on LDCT were more prevalent in the elderly participants and with longer periods of exposure.}, }
@article {pmid23846589, year = {2013}, author = {Yao, S and Chen, HH and Harte, E and Ventura, GD and Petibois, C}, title = {The role of asbestos morphology on their cellular toxicity: an in vitro 3D Raman/Rayleigh imaging study.}, journal = {Analytical and bioanalytical chemistry}, volume = {405}, number = {27}, pages = {8701-8707}, doi = {10.1007/s00216-013-7143-3}, pmid = {23846589}, issn = {1618-2650}, abstract = {Amphiboles caused cohorts of deaths in exposed workers, leading to some of the largest class actions in the industry. Once inhaled, these inorganic fibers are thought to be both chemically and morphologically toxic, and their biopersistence in the lungs over decades lead to progressive pathologies, mesothelioma, and asbestosis. However, this exceptionally long chronicity for human pathologies suggests that chemical toxicity is certainly low, suggesting that morphological parameters could be more relevant in the pathology. Here, we developed a 3D Raman/optical imaging methodology in vitro to characterize both morphological and chemical parameters of cell/fiber interactions. We determined that lung cells could vesiculate amphiboles with length below 5 μm or could embed those not exceeding 15 μm in their fibrous extracellular matrix. Lung cells can thus develop defense strategies for handling the biopersistence of inorganic species, which may thus have major impact for biosafety issues related to nanomaterials.}, }
@article {pmid23846294, year = {2013}, author = {Lee, M and Alexander, HR and Burke, A}, title = {Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy.}, journal = {Pathology}, volume = {45}, number = {5}, pages = {464-473}, doi = {10.1097/PAT.0b013e3283631cce}, pmid = {23846294}, issn = {1465-3931}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Cell Proliferation ; Combined Modality Therapy ; Drug Therapy/*methods ; Female ; Humans ; Hyperthermia, Induced/*methods ; Lung Neoplasms/metabolism/*pathology/*therapy ; Male ; Mesothelioma/metabolism/*pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Invasiveness/pathology ; PAX8 Transcription Factor ; Paired Box Transcription Factors/metabolism ; Peritoneal Neoplasms/metabolism/*pathology/*therapy ; Peritoneum/metabolism/pathology/*surgery ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Diffuse peritoneal mesothelioma (DPM) forms a spectrum of indolent surface tumours to malignant invasive cancers. There are few pathological series that span well and poorly differentiated lesions that show diffuse peritoneal spread.<br><br>METHODS: Sixty-four DPM treated by initial cytoreductive therapy were retrospectively reviewed. Tumours were classified by surface and invasive growth pattern and correlated with risk factors, peritoneal cancer index (PCI) and completeness of cytoreduction (CCR). Degree of invasion was quantitated as absent (0), into stroma (I), into fat (II), and into adjacent structures (III) and was correlated with cytological features. Selected immunohistochemical stains were performed.<br><br>RESULTS: There were three well differentiated papillary mesotheliomas (WDPM; type A), four multicystic mesothelioma (type B), 22 tubulopapillary epithelioid mesotheliomas (type C), and 35 poorly differentiated epithelioid mesotheliomas with solid or sarcomatoid growth (Type D). Seven type D tumours had prominent sarcomatoid areas, 12 deciduoid areas, and four lymphohistiocytoid features. Risk factors were present in all groups except type A, and included prior abdominal surgery (n=24), asbestos exposure (n=5) and radiation (n=2). Extra-pleural mesothelioma was present in all groups except type B (total n=7, 11%). Two type A and eight type C tumours lacked invasion; only type D showed level III invasion. The invasive portion of one type A tumour and two type B tumours showed adenomatoid features. PCI and CCR were greater in type D compared to the other groups (p=0.02), as well as mitotic rate, degree of necrosis, and nuclear pleomorphism (p<0.001). Degree of invasion was strongly correlated with CCR (p=0.007), necrosis (p<0.0001), nuclear grade (p<0.0001), and mitotic rate (p=0.001), but not PCI (p=0.1). Immunohistochemical results were similar across groups, with frequent positivity for CA125 (94%), EGFR (94%) and calretinin (93%), followed by p16 (85%), cytokeratin 5,6 (76%), D2-40 (71%) and WT-1 (47%). PAX-8 was negative in all tumours, except one type A tumour that showed diffuse nuclear positivity.<br><br>CONCLUSIONS: Diffuse peritoneal mesotheliomas can be classified into four groups that reflect invasive potential, degree of adverse histological features, and amenability for CCR. Non-invasive tumours include both type A and type C tumours.}, }
@article {pmid23841030, year = {2013}, author = {Pillai, K and Pourgholami, MH and Chua, TC and Morris, DL}, title = {Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?.}, journal = {American journal of cancer research}, volume = {3}, number = {3}, pages = {312-322}, pmid = {23841030}, issn = {2156-6976}, abstract = {UNLABELLED: Background Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneal membrane that is causally related to asbestos exposure. Survival after treatment is poor. Current therapy involving hyperthermic intraperitoneal chemotherapy has improved survival in selective patients. In the past, several prognostic factors have been identified in MPM patients and this has prompted the development of new therapies and patient management. Since BCL2, an antiapoptotic oncoprotein, is a favourable prognostic factor in breast cancer, we investigated to determine the significance of BCL2 in MPM. Materials and Methods Forty two archival patient tumour sections embedded in paraffin blocks were sectioned and subjected to immunohistochemistry to detect BCL2. The staining intensity and abundance was classified using standard procedures and classified into two groups (0-4 = low &amp; 5-8 = high expression). The distribution of BCL2 groups was examined in the different clinicopathological categories to determine prognosis using Kaplan-Meier survival analysis.<br><br>RESULTS: Univariate analysis revealed that in almost all clinicopathological categories, high BCL2 expression predisposed patients to a favourable prognosis. Independent of BCL2 expression, univariate analysis also showed that male gender, sarcomatoid histology, high PCI and age at diagnosis &#x2265; 60 years were associated poor prognosis. Multivariate analysis indicated that for all tumours, males and females, high BCL2 expression was associated with good prognosis. Further, independent of BCL2, age &#x2265; 60 years is an unfavourable prognostic factor.<br><br>CONCLUSION: Expression of BCL2 may serve to distinguish prognosis within the individual clinicopathological categories. BCL2 is also an independent variable in all tumours, males and females, with high expression being associated with good prognosis.}, }
@article {pmid23837546, year = {2013}, author = {Berman, DW and Cox, LA and Popken, DA}, title = {Resisting the urge to act on random patterns: a reply to Schenker et al.}, journal = {Critical reviews in toxicology}, volume = {43}, number = {7}, pages = {609-610}, doi = {10.3109/10408444.2013.813439}, pmid = {23837546}, issn = {1547-6898}, mesh = {Asbestos/*analysis/toxicity ; Causality ; Health Policy ; Humans ; Logistic Models ; Mesothelioma/*chemically induced ; Public Health ; Regression Analysis ; }, }
@article {pmid23828611, year = {2013}, author = {Mohammad-Taheri, Z and Nadji, SA and Raisi, F and Mohammadi, F and Bahadori, M and Mark, EJ}, title = {No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients.}, journal = {American journal of industrial medicine}, volume = {56}, number = {10}, pages = {1221-1225}, doi = {10.1002/ajim.22160}, pmid = {23828611}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Iran/epidemiology ; Male ; Mesothelioma/epidemiology/*virology ; Middle Aged ; Pleural Neoplasms/epidemiology/*virology ; Polymerase Chain Reaction ; Polyomavirus Infections/epidemiology/*virology ; Simian virus 40/genetics ; Tumor Virus Infections/epidemiology/*virology ; }, abstract = {BACKGROUND: Diffuse malignant mesothelioma (DMM) is increasing in incidence on a worldwide basis and is linked to exposure to asbestos. Simian virus 40 (SV40), a DNA virus, was introduced inadvertently to human populations through contaminated polio vaccine during the years 1956-1963. It has been associated with various types of malignancy in animal experiments. There have been suggestions that SV40 might play a role in the pathogenesis of DMM.<br><br>OBJECTIVE: To evaluate the association between SV40 and DMM in Iranian patients.<br><br>METHOD: In a case-control study between the years 2007-2008, isolated DNA from 60 paraffin blocks of patients with DMM and 60 controls was assessed to detect three human polyomaviruses (JCV, BKV, and SV40) using three different sets of primers by multiplex nested PCR analysis. We related the patients with diffuse malignant mesothelioma to possible sites of exposure to asbestos.<br><br>RESULTS: None of the DMMs nor any patient in the control group had SV40 genome on polymerase chain reaction (PCR). All of the cases were SV40 T antigen negative.<br><br>CONCLUSION: This study suggests that DMM is independent of SV40 infection in Iran.}, }
@article {pmid23827383, year = {2013}, author = {Cadby, G and Mukherjee, S and Musk, AW and Reid, A and Garlepp, M and Dick, I and Robinson, C and Hui, J and Fiorito, G and Guarrera, S and Beilby, J and Melton, PE and Moses, EK and Ugolini, D and Mirabelli, D and Bonassi, S and Magnani, C and Dianzani, I and Matullo, G and Robinson, B and Creaney, J and Palmer, LJ}, title = {A genome-wide association study for malignant mesothelioma risk.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {82}, number = {1}, pages = {1-8}, doi = {10.1016/j.lungcan.2013.04.018}, pmid = {23827383}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Case-Control Studies ; Cell Adhesion Molecules/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Immunoglobulins/*genetics ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk Factors ; ras Guanine Nucleotide Exchange Factors/*genetics ; }, abstract = {Malignant mesothelioma (MM) is a uniformly fatal tumour of mesothelial cells. MM is caused by exposure to asbestos however most individuals with documented asbestos exposure do not develop MM. Although MM appears to aggregate within families, the genetics of MM susceptibility is a relatively unexplored area. The aim of the current study was to identify genetic factors that contribute to MM risk. A genome-wide association analysis of 2,508,203 single nucleotide polymorphisms (SNPs) from 428 MM cases and 1269 controls from Western Australia was performed. Additional genotyping was performed on a sample of 778 asbestos-exposed Western Australian controls. Replication of the most strongly associated SNPs was undertaken in an independent case-control study of 392 asbestos-exposed cases and 367 asbestos-exposed controls from Italy. No SNPs achieved formal genome-wide statistical significance in the Western Australian study. However, suggestive results for MM risk were identified in the SDK1, CRTAM and RASGRF2 genes, and in the 2p12 chromosomal region. These findings were not replicated in the Italian study, although there was some evidence of replication in the region of SDK1. These suggestive associations will be further investigated in sequencing and functional studies.}, }
@article {pmid23816056, year = {2013}, author = {Scherpereel, A and Grigoriu, BD and Noppen, M and Gey, T and Chahine, B and Baldacci, S and Trauet, J and Copin, MC and Dessaint, JP and Porte, H and Labalette, M}, title = {Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusions compared to normal pleural fluid.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {324}, pmid = {23816056}, issn = {1471-2407}, mesh = {Aged ; CD4-Positive T-Lymphocytes/immunology/pathology ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Exudates and Transudates/*immunology ; Female ; Flow Cytometry ; Humans ; Immunologic Memory/immunology ; Killer Cells, Natural/immunology/pathology ; Male ; Mesothelioma/*immunology/pathology ; Middle Aged ; Pleural Effusion/immunology/pathology ; Pleural Effusion, Malignant/*immunology/pathology ; Pleural Neoplasms/*immunology/pathology ; T-Lymphocyte Subsets/immunology/pathology ; }, abstract = {BACKGROUND: Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM). MPE animal models and immunotherapy trials in MPM patients previously suggested defects of the cellular immunity in MPE. However only few observational studies of the immune response were done in MPM patients, using questionable control groups (transudate…).<br><br>METHODS: We compared T cell populations evaluated by flow cytometry from blood and pleural effusion of untreated patients with MPM (n&#x2009;=&#x2009;58), pleural metastasis of adenocarcinoma (n&#x2009;=&#x2009;30) or with benign pleural lesions associated with asbestos exposure (n&#x2009;=&#x2009;23). Blood and pleural fluid were also obtained from healthy subjects, providing normal values for T cell populations.<br><br>RESULTS: Blood CD4+ or CD8+ T cells percentages were similar in all groups of patients or healthy subjects. Whereas pleural fluid from healthy controls contained mainly CD8+ T cells, benign or malignant pleural effusions included mainly CD4+ T cells. Effector memory T cells were the main T cell subpopulation in pleural fluid from healthy subjects. In contrast, there was a striking and selective recruitment of central memory CD4+ T cells in MPE, but not of effector cells CD8+ T cells or NK cells in the pleural fluid as one would expect in order to obtain an efficient immune response.<br><br>CONCLUSIONS: Comparing for the first time MPE to pleural fluid from healthy subjects, we found a local defect in recruiting effector CD8+ T cells, which may be involved in the escape of tumor cells from immune response. Further studies are needed to characterize which subtypes of effector CD8+ T cells are involved, opening prospects for cell therapy in MPE and MPM.}, }
@article {pmid23815672, year = {2013}, author = {Pinton, G and Manente, AG and Tavian, D and Moro, L and Mutti, L}, title = {Therapies currently in Phase II trials for malignant pleural mesothelioma.}, journal = {Expert opinion on investigational drugs}, volume = {22}, number = {10}, pages = {1255-1263}, doi = {10.1517/13543784.2013.816281}, pmid = {23815672}, issn = {1744-7658}, mesh = {Antineoplastic Agents/adverse effects/pharmacology/*therapeutic use ; Clinical Trials, Phase II as Topic ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/blood supply/*drug therapy/immunology/metabolism ; Mesothelioma/blood supply/*drug therapy/immunology/metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/blood supply/*drug therapy/immunology/metabolism ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure, whose incidence will peak within the next years. Despite an overall low response rate, the current first-line therapy is represented by combined chemotherapy with cisplatin and antifolate. Moreover, there are no currently approved regimens for relapsed or refractory MPM. Therefore, it is clear how both preclinical and clinical researches aimed at identifying new therapeutic targets and testing them in early clinical settings are badly needed.<br><br>AREAS COVERED: The aim of this review is to summarize and critically comment the ongoing Phase II trials for MPM.<br><br>EXPERT OPINION: Over the past few years, there has been a significant endeavor of addressing the clinical research for MPM beyond the very modest results of chemotherapy. Nonetheless, our understanding is that the treatment of MPM should not be merely 'copied' from that of other much better studied tumors. In the light of recent results, studies toward the metabolic characteristics of this tumor are being progressively addressed. These evidences are disclosing a rather unusual model of malignancy, very likely to be more sensitive to novel 'MPM cells- and microenvironment-tailored' therapy addressing these characteristics rather than the sole cancer proliferation.}, }
@article {pmid23807166, year = {2013}, author = {Lemen, RA and Frank, AL and Soskolne, CL and Weiss, SH and Castleman, B}, title = {Comment on 'estimating the asbestos-related lung cancer burden from mesothelioma mortality' - IARC and chrysotile risks.}, journal = {British journal of cancer}, volume = {109}, number = {3}, pages = {823-825}, pmid = {23807166}, issn = {1532-1827}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; }, }
@article {pmid23807162, year = {2013}, author = {McCormack, V and Peto, J and Byrnes, G and Straif, K and Boffetta, P}, title = {Reply: comment on 'estimating the asbestos-related lung cancer burden from mesothelioma mortality'.}, journal = {British journal of cancer}, volume = {109}, number = {3}, pages = {825-826}, pmid = {23807162}, issn = {1532-1827}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; }, }
@article {pmid23798235, year = {2013}, author = {Berra, A}, title = {[Letter to the Editors: Still on Asbestos. A Brief Review].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {35}, number = {1}, pages = {61-62}, pmid = {23798235}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/diagnosis/*epidemiology/etiology ; *Carcinogens ; European Union/statistics &amp; numerical data ; Guidelines as Topic ; Humans ; Internet ; Italy/epidemiology ; Mesothelioma/diagnosis/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; }, }
@article {pmid23796498, year = {2013}, author = {Vandenbos, F and Figueredo, M and Dumon-Gubeno, MC and Nicolle, I and Tarhini, A and Butori, C and Mouroux, J}, title = {[Malignant pleural mesothelioma after radiation treatment for Hodgkin lymphoma].}, journal = {Revue de pneumologie clinique}, volume = {69}, number = {5}, pages = {291-293}, doi = {10.1016/j.pneumo.2013.04.004}, pmid = {23796498}, issn = {1776-2561}, mesh = {Adult ; Hodgkin Disease/*radiotherapy ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/*diagnosis/etiology ; Mesothelioma, Malignant ; Neoplasms, Radiation-Induced/*diagnosis ; Pleural Neoplasms/*diagnosis/etiology ; Pleurisy/etiology ; Radiography, Thoracic ; }, abstract = {Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the role of ionizing radiation is more controversial. We report the case of a 41-year-old male who developed pleural mesothelioma. He had both, a prior short asbestos exposure and a thoracic radiotherapy for Hodgkin's disease 26years before. The evidence for radiotherapy as cause for mesothelioma is expanding and the diagnosis of mesothelioma in patients who had previous irradiation should be kept in mind.}, }
@article {pmid23790737, year = {2013}, author = {Fujimoto, N and Gemba, K and Asano, M and Fuchimoto, Y and Wada, S and Ono, K and Ozaki, S and Kishimoto, T}, title = {Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma.}, journal = {Respiratory investigation}, volume = {51}, number = {2}, pages = {92-97}, doi = {10.1016/j.resinv.2013.02.002}, pmid = {23790737}, issn = {2212-5353}, mesh = {Diagnosis, Differential ; Female ; Humans ; Hyaluronic Acid/*analysis ; Lung Neoplasms/diagnosis/*metabolism ; Mesothelioma/diagnosis/*metabolism ; Mesothelioma, Malignant ; Pleural Effusion/*metabolism ; Pleural Neoplasms/diagnosis/*metabolism ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: We retrospectively analyzed hyaluronic acid (HA) concentrations in pleural fluid and evaluated its utility for the differential diagnosis of malignant pleural mesothelioma (MPM).<br><br>METHODS: Pleural fluid HA concentrations were measured in 334 patients, including 50, 48, 85, 18, 86, 6, and 41 patients with MPM, benign asbestos pleurisy (BAP), lung cancer (LC), other malignant conditions (OMCs), infectious pleuritis (IP), collagen disease (CD), and other conditions, respectively.<br><br>RESULTS: The median (range) HA concentrations in pleural fluid were 78,700 (7920-2,630,000)ng/ml in the MPM group, 35,950 (900-152,000)ng/ml in the BAP group, 19,500 (2270-120,000)ng/ml in the LC group, 14,200 (900-101,000)ng/ml in the OMC group, 23,000 (900-230,000)ng/ml in the IP group, 24,600 (9550-80,800)ng/ml in the CD group, and 8140 (900-67,800)ng/ml in the other diseases group. HA levels were significantly higher in the MPM group than in the other groups. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve value of 0.832 (95% confidence interval, 0.765-0.898) for the differential diagnosis of MPM. With a cutoff value of 100,000ng/ml, the sensitivity and specificity were 44.0 and 96.5%, respectively. In the MPM group, HA values were significantly higher for the epithelioid subtype than for the sarcomatous subtype (p=0.007), and higher in earlier stages (I and II) than in advanced stages (III and IV) (p=0.007).<br><br>CONCLUSIONS: A diagnosis of MPM should be strongly considered in patients with pleural fluid HA concentrations exceeding 100,000ng/ml.}, }
@article {pmid23789518, year = {2013}, author = {Romeo, E and Ascoli, V and Ancona, L and Balestri, A and Scalzo, CC and Cavariani, F and Compagnucci, P and Gasperini, L and Mataloni, F and Forastiere, F}, title = {[Occupational exposure to asbestos and incidence of malignant mesothelioma in the Lazio region, years 2001-2009: results of the activities of the regional register].}, journal = {La Medicina del lavoro}, volume = {104}, number = {2}, pages = {115-125}, pmid = {23789518}, issn = {0025-7818}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Construction Materials ; Environmental Exposure ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Metallurgy ; Middle Aged ; Military Personnel ; *Occupational Exposure ; Pericardium ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Sex Distribution ; }, abstract = {BACKGROUND: The Lazio Regional Mesothelioma Registry records the incident cases of Malignant Mesothelioma (MM) in residents in the Region since 2001.<br><br>OBJECTIVES: Estimate the incidence of MM in the Lazio Region (2001-2009) and assess possible asbestos exposures.<br><br>METHODS: The MM cases, notified by hospitals, regional protection and workplace safety units, Italian Workers' Compensation Authority, other regions, or extracted from hospital information systems and the regional registry of causes of death, are included in the register after analysis of diagnostic procedures (CT scan, chest X-ray, pathology reports and patients' records). Possible asbestos exposure is investigated by standardized interview and thereafter defined by a panel of experts, according to RENAM guidelines. The incidence of MM of the pleura and peritoneum (per 100,000 inhabitants) for the period 2001-2009 is calculated.<br><br>RESULTS: The incidence of MM among Lazio residents in the period 2001-2009 (600 cases) was estimated to be 1.8 among men and 0.5 among women per 100,000 inhabitants. Information on exposures was collectedfor 54% of the cases (251 men and 78 women); 72% of men (n. 179) and 9% of women (n. 7) had been occupationally exposed to asbestos. The study found that the largest number of cases with occupational exposure was among workers in the construction industry. The number of cases with unknown exposure was very high.<br><br>CONCLUSIONS: The registry's work revealed the existence of asbestos exposure circumstances that were not sufficiently characterized,for which it is suggested that more detailed industrial hygiene investigations be performed, as well as measurement of asbestos bodies and/or fibres in lung tissue.}, }
@article {pmid23794323, year = {2013}, author = {Finkelstein, M}, title = {Reply to letter by Nolan and colleagues--re: the carcinogenicity of New York state talc dusts in humans.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {1119-1124}, doi = {10.1002/ajim.22208}, pmid = {23794323}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Humans ; Male ; Mesothelioma/*epidemiology ; *Mining ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Talc/*toxicity ; }, }
@article {pmid23792972, year = {2013}, author = {Hwang, J and Ramachandran, G and Raynor, PC and Alexander, BH and Mandel, JH}, title = {Comprehensive assessment of exposures to elongate mineral particles in the taconite mining industry.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {8}, pages = {966-978}, doi = {10.1093/annhyg/met026}, pmid = {23792972}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/*analysis ; Analysis of Variance ; Asbestos, Amphibole/analysis ; Humans ; Inhalation Exposure/analysis ; Iron/*adverse effects ; Lung Neoplasms/etiology ; Mesothelioma ; *Mining ; Minnesota/epidemiology ; Occupational Exposure/adverse effects/*analysis ; Reproducibility of Results ; Respiratory Tract Diseases ; Silicates/*adverse effects ; United States/epidemiology ; }, abstract = {Since the 1970s, concerns have been raised about elevated rates of mesothelioma in the vicinity of the taconite mines in the Mesabi Iron Range. However, insufficient quantitative exposure data have hampered investigations of the relationship between cumulative exposures to elongate mineral particles (EMP) in taconite dust and adverse health effects. Specifically, no research on exposure to taconite dust, which includes EMP, has been conducted since 1990. This article describes a comprehensive assessment of present-day exposures to total and amphibole EMP in the taconite mining industry. Similar exposure groups (SEGs) were established to assess present-day exposure levels and buttress the sparse historical data. Personal samples were collected to assess the present-day levels of worker exposures to EMP at six mines in the Mesabi Iron Range. The samples were analyzed using National Institute for Occupational Safety and Health (NIOSH) methods 7400 and 7402. For many SEGs in several mines, the exposure levels of total EMP were higher than the NIOSH Recommended Exposure Limit (REL). However, the total EMP classification includes not only the asbestiform EMP and their non-asbestiform mineral analogs but also other minerals because the NIOSH 7400 cannot differentiate between these. The concentrations of amphibole EMP were well controlled across all mines and were much lower than the concentrations of total EMP, indicating that amphibole EMP are not major components of taconite EMP. The levels are also well below the NIOSH REL of 0.1 EMP cc(-1). Two different approaches were used to evaluate the variability of exposure between SEGs, between workers, and within workers. The related constructs of contrast and homogeneity were calculated to characterize the SEGs. Contrast, which is a ratio of between-SEG variability to the sum of between-SEG and between-worker variability, provides an overall measure of whether there are distinctions between the SEGs. Homogeneity, which is the ratio of the within-worker variance component to the sum of the between-worker and within-worker variance components, provides an overall measure of how similar exposures are for workers within an SEG. Using these constructs, it was determined that the SEGs are formed well enough when grouped by mine for both total and amphibole EMP to be used for epidemiological analysis.}, }
@article {pmid23790315, year = {2013}, author = {Vandermeers, F and Neelature Sriramareddy, S and Costa, C and Hubaux, R and Cosse, JP and Willems, L}, title = {The role of epigenetics in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {81}, number = {3}, pages = {311-318}, doi = {10.1016/j.lungcan.2013.05.014}, pmid = {23790315}, issn = {1872-8332}, mesh = {Antineoplastic Agents/pharmacology/therapeutic use ; Cell Transformation, Neoplastic/genetics ; Clinical Trials as Topic ; DNA (Cytosine-5-)-Methyltransferases/antagonists &amp; inhibitors ; *Epigenesis, Genetic/drug effects ; Epigenomics ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase Inhibitors/pharmacology/therapeutic use ; Humans ; Lung Neoplasms/drug therapy/*genetics ; Mesothelioma/drug therapy/*genetics ; Mesothelioma, Malignant ; Pleural Neoplasms/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an almost invariably fatal cancer of the pleura due to asbestos exposure. Increasing evidence indicates that unresponsiveness to chemotherapy is due to epigenetic errors leading to inadequate gene expression in tumor cells. The availability of compounds that modulate epigenetic modifications, such as histone acetylation or DNA methylation, offers new prospects for treatment of MPM. Here, we review latest findings on epigenetics in mesothelioma and present novel strategies for promising epigenetic therapies.}, }
@article {pmid23788253, year = {2013}, author = {Roelofs, CR and Kernan, GJ and Davis, LK and Clapp, RW and Hunt, PR}, title = {Mesothelioma and employment in massachusetts: analysis of cancer registry data 1988-2003.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {985-992}, doi = {10.1002/ajim.22218}, pmid = {23788253}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Logistic Models ; Male ; Massachusetts/epidemiology ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Odds Ratio ; Public Health Surveillance/*methods ; *Registries ; }, abstract = {BACKGROUND: Cancer registries can be used to monitor mesothelioma cases and to identify occupations and industries previously and newly associated with mesothelioma-causing asbestos exposure by using standard registry data on the "usual" occupation and industry of the case.<br><br>METHODS: We used the National Institute for Occupational Safety and Health's Standardized Occupational Industry Coding Software to code 564 mesothelioma cases for occupation and 543 for industry of the 1,424 incident mesothelioma in the Massachusetts Cancer Registry from 1988 to 2003. Additionally, we coded the occupation and industry of 80,184 comparison cancer cases (35% of comparison cases in our database). These were used to compute Standardized Morbidity Odds Ratios (SMORs).<br><br>RESULTS: Seventeen occupations and 11 industries had statistically significant elevated SMORs for mesothelioma. Occupations and industries historically associated with mesothelioma remained elevated in these results. However, we also found statistically significant elevated SMORs for several occupations and industries for which there was previously weak or no association such as chemical engineers, machine operators, and automobile mechanics and machine manufacturing, railroads, and the U.S. Postal Service.<br><br>CONCLUSIONS: Incident cases of mesothelioma do not appear to be declining in Massachusetts, as legacy exposures to asbestos continue to produce cases in individuals involved in shipbuilding and construction. Exposures in occupations and industries not previously associated with mesothelioma also contribute cases. Cancer registries, with improved data collection, should continue to be monitored for mesothelioma cases and asbestos exposures.}, }
@article {pmid23787063, year = {2013}, author = {Nowak, AK and Brown, C and Millward, MJ and Creaney, J and Byrne, MJ and Hughes, B and Kremmidiotis, G and Bibby, DC and Leske, AF and Mitchell, PLR and Pavlakis, N and Boyer, M and Stockler, MR}, title = {A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {81}, number = {3}, pages = {422-427}, doi = {10.1016/j.lungcan.2013.05.006}, pmid = {23787063}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Benzofurans/administration &amp; dosage/adverse effects/*therapeutic use ; Biomarkers/blood/metabolism ; Female ; GPI-Linked Proteins/blood/metabolism ; Humans ; Lung Neoplasms/diagnostic imaging/*drug therapy/mortality/*pathology ; Male ; Mesothelin ; Mesothelioma/diagnostic imaging/*drug therapy/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Organophosphates/administration &amp; dosage/adverse effects/*therapeutic use ; Pleural Neoplasms/diagnostic imaging/*drug therapy/mortality/*pathology ; Radiography ; Treatment Outcome ; Tubulin Modulators/administration &amp; dosage/adverse effects/*therapeutic use ; Tumor Burden ; }, abstract = {BNC105P is a tubulin polymerisation inhibitor that selectively disrupts tumour vasculature and suppresses cancer cell proliferation. This agent has exhibited preclinical and phase I activity in Malignant Pleural Mesothelioma (MPM). This phase II, single arm trial investigated the efficacy and safety of BNC105P as second line therapy in MPM. Participants had progressive MPM after first line pemetrexed/platinum chemotherapy, ECOG PS 0-1, adequate organ function, and measurable disease. BNC105P 16 mg/m(2) was administered intravenously on day 1 and 8 every 21 days until progression or undue toxicity. The primary endpoint was centrally reviewed objective response rate (RR). Tumour response was assessed every two cycles using modified RECIST. 30 patients were enrolled in 10 months, predominantly male (90%), ECOG PS 1 (77%), epithelioid histology (67%), and non-metastatic disease (67%). All patients received at least one dose of study drug, with a median of 2 cycles. No significant haematologic, biochemical, or cardiac adverse events (AEs) were observed. Grade 3 or 4 AEs occurred in 10 patients (33%). There were 2 deaths on study: 1 cardiorespiratory, the other to pneumonia. We observed 1 partial response (3%); 13 patients had stable disease (43%). Median progression free survival was 1.5 months (95% CI 1.4-2.4); median overall survival was 8.2 months (95% CI 3.8-11.9). BNC105P was safe and tolerable. The sole response was insufficient to warrant further research as a single agent.}, }
@article {pmid23780761, year = {2013}, author = {Hodgson, JT}, title = {Quality of evidence must guide risk assessment of asbestos, by Lenters, V; Burdorf, A; Vermeulen, R; Stayner, L; Heederik, D.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {5}, pages = {670-674}, doi = {10.1093/annhyg/met016}, pmid = {23780761}, issn = {1475-3162}, mesh = {*Asbestos ; Humans ; Mesothelioma/*chemically induced ; Research/*standards ; Risk Assessment/*standards ; }, }
@article {pmid23780760, year = {2013}, author = {Berman, DW and Case, BW}, title = {Quality of evidence must guide risk assessment of asbestos, by Lenters, V; Burdorf, A; Vermeulen, R; Stayner, L; Heederik, D.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {5}, pages = {667-669}, doi = {10.1093/annhyg/met015}, pmid = {23780760}, issn = {1475-3162}, mesh = {*Asbestos ; Humans ; Mesothelioma/*chemically induced ; Research/*standards ; Risk Assessment/*standards ; }, }
@article {pmid23777840, year = {2013}, author = {Muley, T and Dienemann, H and Herth, FJ and Thomas, M and Meister, M and Schneider, J}, title = {Combination of mesothelin and CEA significantly improves the differentiation between malignant pleural mesothelioma, benign asbestos disease, and lung cancer.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {7}, pages = {947-951}, doi = {10.1097/JTO.0b013e31828f696b}, pmid = {23777840}, issn = {1556-1380}, mesh = {Asbestosis/blood/*diagnosis ; Biomarkers, Tumor/blood ; Carcinoembryonic Antigen/*blood ; Carcinoma, Large Cell/blood/diagnosis ; Carcinoma, Squamous Cell/blood/diagnosis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/blood/*diagnosis ; Prognosis ; ROC Curve ; Retrospective Studies ; Small Cell Lung Carcinoma/blood/*diagnosis ; }, abstract = {INTRODUCTION: Soluble mesothelin-related peptides (SMRP) have been reported as potential markers for the diagnosis of malignant pleural mesothelioma (MPM). We wondered, whether a combination with a carcinoembryonic antigen (CEA) test might improve the relatively low diagnostic yield of the SMRP test.<br><br>METHODS: In a retrospective study, SMRP (mesothelin) and CEA serum concentrations were measured, using commercially available kits, in 93 previously untreated MPM patients, 75 patients with benign asbestos disease, and 139 patients suffering from lung cancer (LC).<br><br>RESULTS: The differentiation between MPM, LC, and benign asbestos disease could be improved by applying the ratio mesothelin/CEA. Whereas CEA expression was found to be low in MPM, most LC patients had elevated CEA serum levels. The area under curve (AUC) of the receiver operator characteristics curve for mesothelin alone was found to be only 0.708. For mesothelin/CEA the AUC of the receiver operator characteristics curve increased to 0.978. The sensitivity was 93% (69%) at 95% (100%) specificity for the differentiation between MPM and LC. Comparison of MPM and benign asbestos disease showed that the AUC was 0.887 and the sensitivity 56% (47%) at 95% (100%) specificity. In contrast, the AUC for the mesothelin test alone was only 0.715, and for the CEA test alone it was 0.16. An average increment in sensitivity of 38% (range, 16%-63%) could be achieved by the quotient mesothelin/CEA compared with the sensitivity of mesothelin alone.<br><br>CONCLUSION: The diagnostic yield of the mesothelin test can be considerably improved when combined with a CEA test with regard to the differential diagnosis between MPM and LC and between MPM and benign asbestos disease.}, }
@article {pmid23776320, year = {2012}, author = {Bianchi, C and Bianchi, T}, title = {Mesothelioma among shipyard workers in Monfalcone, Italy.}, journal = {Indian journal of occupational and environmental medicine}, volume = {16}, number = {3}, pages = {119-123}, pmid = {23776320}, issn = {0973-2284}, abstract = {BACKGROUND: The high mesothelioma incidence in Monfalcone, Italy, is mainly attributable to shipbuilding activity. Mesothelioma risk among shipyard workers in Monfalcone is poorly defined.<br><br>MATERIALS AND METHODS: Workers hired at the Monfalcone shipyards in the period 1950-1959 were identified by surveying shipyard roll. The list of the workers was coupled with the archive data of Monfalcone and Trieste Hospitals. Mesotheliomas diagnosed in the above people were reexamined.<br><br>RESULTS: Of 1,403 workers hired in 1950-1959, 35 were diagnosed with mesothelioma (34 pleural, one peritoneal) between 1978 and 2012. Latency periods exceeded 40 years in 31 cases. The highest percentage of mesotheliomas was observed among people aged 14-19 years at hiring time (3.4%). Four mesothelioma patients had a blood relative with the same tumor.<br><br>CONCLUSIONS: The present findings show high mesothelioma percentage among shipyard workers hired at young ages. The effects of asbestos exposure begun in 1950-1959 cannot be considered as exhausted.}, }
@article {pmid23772303, year = {2013}, author = {Meng, X and Guzzo, TJ and Bing, Z}, title = {Malignant mesotheliomas in spermatic cords: reports of two cases and a brief review of literature.}, journal = {Rare tumors}, volume = {5}, number = {1}, pages = {e4}, pmid = {23772303}, issn = {2036-3605}, abstract = {Primary malignant mesothelioma (MM) of spermatic cord is extremely rare. We presented two malignant mesotheliomas involving the spermatic cords; one was primary, one secondary. The secondary one represented the direct involvement by a peritoneal MM. No occupational exposure to asbestos was identified in either patient. Both of them presented with a painless inguinal mass. Microscopically the primary MM was epithelioid type with tumor nests infiltrating adjacent adipose tissue, while the secondary MM grew in mixed type. No tumor necrosis was seen in the primary MM, while extensive necrosis was seen in the secondary one. Rare mitotic figure was seen in the primary MM while the mitosis in the secondary tumor was brisk, and with atypical mitosis. Immunohistochemically the tumor cells were positive for calretinin and CK5/6 and negative for BER-EP4 and BRST3 in both cases. The reported cases of primary MM from spermatic cord in English literature were briefly reviewed.}, }
@article {pmid23760546, year = {2014}, author = {Datta, A and Smith, R and Fiorentino, F and Treasure, T}, title = {Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position.}, journal = {Thorax}, volume = {69}, number = {2}, pages = {194-197}, pmid = {23760546}, issn = {1468-3296}, support = {//British Heart Foundation/United Kingdom ; }, mesh = {Aged ; England ; Humans ; Lung Neoplasms/*surgery ; Mesothelioma/*surgery ; Mesothelioma, Malignant ; *Patient Selection ; Pleural Neoplasms/*surgery ; Pneumonectomy/*methods ; Prognosis ; Randomized Controlled Trials as Topic ; Registries ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model.<br><br>CONCLUSION: Whenever the question arises `Might an operation help me?' there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials.}, }
@article {pmid23756640, year = {2013}, author = {Fisseler-Eckhoff, A}, title = {[Surgical aspects of malignant pleural mesothelioma: from the perspective of pathology].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {84}, number = {6}, pages = {479-486}, pmid = {23756640}, issn = {1433-0385}, mesh = {Asbestosis/complications/mortality/pathology ; Cell Proliferation ; Combined Modality Therapy ; Diagnosis, Differential ; Germany ; Guideline Adherence ; Humans ; Mesothelioma/mortality/*pathology/*surgery ; Neoplasm Grading ; Neoplasm Staging ; Pleura/pathology/surgery ; Pleural Neoplasms/mortality/*pathology/*surgery ; Pneumonectomy/methods ; Prognosis ; Survival Rate ; Thoracic Surgery, Video-Assisted/methods ; }, abstract = {The increased use of asbestos in Germany in the mid 1970s led occupational physicians, pulmonologists, thoracic surgeons and pathologists to the expectation of an increasing incidence and mortality in patients with pleural mesothelioma up to 2020. Prerequisite for curative surgery is a pathological anatomical tumor diagnosis on the basis of a biopsy and accurate tumor staging. In order to achieve reproducible results in the assessment of malignant pleural diseases, the pathological anatomical diagnosis of malignant pleural mesothelioma should be made according to the guidelines of the international mesothelioma interest group (IMIG). Currently used multimodal thoracic surgery therapeutic concepts present new challenges and problems to the pathological anatomical diagnosis and are discussed in this article.}, }
@article {pmid23751780, year = {2013}, author = {Toyokuni, S}, title = {Genotoxicity and carcinogenicity risk of carbon nanotubes.}, journal = {Advanced drug delivery reviews}, volume = {65}, number = {15}, pages = {2098-2110}, doi = {10.1016/j.addr.2013.05.011}, pmid = {23751780}, issn = {1872-8294}, mesh = {Animals ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Inhalation Exposure/adverse effects ; Mutagenicity Tests ; Nanotubes, Carbon/chemistry/*toxicity ; Neoplasms/etiology/pathology ; Occupational Diseases/etiology/*prevention &amp; control ; Occupational Exposure/*adverse effects ; Particle Size ; Rats ; Risk Assessment ; }, abstract = {Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.}, }
@article {pmid23749908, year = {2013}, author = {Kuramitsu, Y and Tominaga, W and Baron, B and Tokuda, K and Wang, Y and Kitagawa, T and Nakamura, K}, title = {Up-regulation of DDX39 in human malignant pleural mesothelioma cell lines compared to normal pleural mesothelial cells.}, journal = {Anticancer research}, volume = {33}, number = {6}, pages = {2557-2560}, pmid = {23749908}, issn = {1791-7530}, mesh = {Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; DEAD-box RNA Helicases/*metabolism ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*metabolism ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is a malignant tumor originating from mesothelial cells existing in pleura. Since its incidence, it is closely related to the amount and time of exposure to asbestos, and the latency period after exposure to asbestos is very long, the incidence may increase over the next two decades. Since early detection is very difficult and there is no standard curative therapy, it is important to understand the biology of MPM, and to find biomarkers and molecular targets for its therapy. DDX39 is one of the Asp-Glu-Ala-Asp (DEAD)-box RNA helicases, which are required for the export of mRNA out of the nucleus, and transcription, splicing and transport of mRNA. Some reports have shown differential expression of DDX39 in tumor cells or tissues such as lung squamous cell cancer, gastrointestinal stromal tumor and urinary bladder cancer. In the present study, the protein levels of DDX39 in the human MPM cell lines NCI-H28, NCI-H2052 and NCI-H2452, and the human pleural mesothelial cell line MeT-5A were investigated by western blotting. The protein levels of DDX39 were found to be higher in NCI-H28, NCI-H2052 and NCI-H2452 compared to MeT-5A. The intensity of the bands of DDX39 in NCI-H28, NCI-H2052 and NCI-H2452 cells were increased by 1.351-, 1.887- and 2.024-fold, respectively, compared to MPM cells. These results suggest that DDX39 is a possible candidate biomarker for molecular-targeting of MPM.}, }
@article {pmid23743993, year = {2013}, author = {Ried, M and Speth, U and Potzger, T and Neu, R and Diez, C and Klinkhammer-Schalke, M and Hofmann, HS}, title = {[Regional treatment of malignant pleural mesothelioma: results from the tumor centre Regensburg].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {84}, number = {11}, pages = {987-993}, pmid = {23743993}, issn = {1433-0385}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Asbestosis/complications ; Biopsy ; *Cancer Care Facilities ; Cross-Sectional Studies ; Female ; Germany ; Humans ; Male ; Mesothelioma/epidemiology/mortality/pathology/*surgery ; Middle Aged ; Neoplasm Staging ; Palliative Care ; Pleura/pathology/surgery ; Pleural Neoplasms/epidemiology/mortality/pathology/*surgery ; Pleurodesis ; Population Dynamics ; Retrospective Studies ; Survival Rate ; Thoracoscopy ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive, malignant tumor of the pleural surface and is strongly associated with asbestos exposure. Incidence of MPM will reach its peak over the coming years. Most patients present with advanced tumor stages and therefore surgical options are limited.<br><br>PATIENTS AND METHODS: Retrospective analysis of all patients with MPM reported to the tumor centre Regensburg between January 1998 and August 2011.<br><br>RESULTS: A total of 118 patients (85 % male) with cytologically or histologically confirmed MPM were reported. The mean age at diagnosis was 67 years (range 45-84 years) and 65 % of patients had a history of asbestos exposure. The incidence of MPM at the tumor centre Regensburg was 0.8/100,000 inhabitants with obvious regional differences depending on asbestos exposure. Staging was completed in 81 patients (67 %): stage I 9 %, stage II 22 %, stage III 23 % and stage IV 46 %. Of the patients 87 (74 %) underwent at least one surgical procedure: diagnostic thoracoscopy with biopsy (n = 37, 43 %), debulking surgery or talcum pleurodesis (n = 33, 38 %) and potentially curative resection (n = 17, 19 %). After a mean follow-up of 20 months the overall median survival was 14 months (1 year survival rate 62 %, 3 year survival rate 15 %). Patients had a significantly better median survival of 18 months after curative resection.<br><br>CONCLUSIONS: The distribution of MPM varies according to regional and industrial asbestos exposure. Screening and diagnostics should concentrate on locations with higher incidence of MPM to facilitate surgical therapy in a multimodal treatment regime.}, }
@article {pmid23743702, year = {2013}, author = {di Orio, F and Zazzara, F}, title = {[Asbestos and harmful health effects: from denial theories to epidemiological evidence].}, journal = {Igiene e sanita pubblica}, volume = {69}, number = {2}, pages = {229-238}, pmid = {23743702}, issn = {0019-1639}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/*etiology ; Humans ; Mesothelioma/chemically induced/epidemiology ; Pleural Neoplasms/chemically induced/epidemiology ; }, abstract = {The recent episode involving Eternit, a factory in Casale Monferrato (Turin, Italy), culminated in February 2012 with a guilty verdict for the owners of the factory. The indiscriminate use of asbestos, however, continues worldwide, despite evidence of increased risk for conditions such as asbestosis and malignant pleural mesothelioma. In this study we investigate the relationship between epidemiological evidence and denial theories, over the decades and until the present time. Many countries in the world still promote the use of asbestos, with a view to profit and globalization but at the expense of public health.}, }
@article {pmid23732197, year = {2013}, author = {Zurbriggen, R and Capone, L}, title = {[Pulmonary disease due to asbestos in steel industry workers].}, journal = {Medicina}, volume = {73}, number = {3}, pages = {224-230}, pmid = {23732197}, issn = {0025-7680}, mesh = {Aged ; Aged, 80 and over ; Argentina/epidemiology ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*etiology/pathology ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/pathology ; Male ; *Metallurgy ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Diseases/diagnostic imaging/*etiology/pathology ; Pleural Neoplasms/diagnostic imaging/pathology ; Radiography ; Smoking/epidemiology ; Steel ; }, abstract = {Asbestos-related diseases are caused by the inhalation of asbestos fibers in their variety chrysotile or white asbestos. Although the ban in Argentina dates from 2003, there are numerous industries where work continues with this mineral, including iron and steel industries. It is currently known the high pathogenicity of this material, so that in many countries there are programs to monitoring the exposed workers. Here we describe the general characteristics and pulmonary manifestations in 27 patients who had worked in a very huge steel factory in South America. The diagnosis of asbestos-related diseases was made by a medical-occupational record, history of asbestos exposure, additional studies of lung function and chest images. Then the sources of exposure (occupational, domestic and environmental), exposure time and latency period were analyzed, in those patients in whom a related disease was detected. Smoking history was also taken into account. Twenty-two patients had benigns pathologies (81.4%), sixteen of them with lesions localyzed in pleura, and other six pulmonary asbestosis. The malignant pathologies occurred in five patients (18.5%), in four of them mesothelioma and in other one lung cancer. The problem of asbestos exposure has contemporary relevance. Hence the need for a surveillance program in workers exposed to asbestos in the past or currently, to detect, report, record and investigate the characteristics of these pathologies.}, }
@article {pmid23729401, year = {2013}, author = {Nuvoli, B and Galati, R}, title = {Cyclooxygenase-2, epidermal growth factor receptor, and aromatase signaling in inflammation and mesothelioma.}, journal = {Molecular cancer therapeutics}, volume = {12}, number = {6}, pages = {844-852}, doi = {10.1158/1535-7163.MCT-12-1103}, pmid = {23729401}, issn = {1538-8514}, mesh = {Aromatase/*genetics/metabolism ; Asbestos/toxicity ; Cyclooxygenase 2/*genetics ; ErbB Receptors/*genetics/metabolism ; Humans ; Inflammation/genetics/*pathology ; Lung Neoplasms/chemically induced/*genetics/pathology/therapy ; Mesothelioma/chemically induced/*genetics/pathology/therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Pleural Neoplasms/chemically induced/genetics/pathology/therapy ; Signal Transduction ; }, abstract = {Malignant mesothelioma or mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is directly linked to asbestos exposure, which acts as a carcinogen by initiating the carcinogenic process. Because of their shape, asbestos fibers can cross the membrane barriers inside the body and cause inflammatory and fibrotic reactions. Such reactions are believed to be the mechanism by which asbestos fibers may trigger malignant mesothelioma in the pleural membrane around the lungs. Carcinogens are known to modulate the transcription factors, antiapoptotic proteins, proapoptotic proteins, protein kinases, cell-cycle proteins, cell adhesion molecules, COX-2, and growth factor signaling pathways. This article reviews recent studies regarding some malignant mesothelioma molecular targets not only for cancer prevention but also for cancer therapy.}, }
@article {pmid23721559, year = {2013}, author = {Liu, R and Ferguson, BD and Zhou, Y and Naga, K and Salgia, R and Gill, PS and Krasnoperov, V}, title = {EphB4 as a therapeutic target in mesothelioma.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {269}, pmid = {23721559}, issn = {1471-2407}, support = {1R43 CA 168158-01/CA/NCI NIH HHS/United States ; 1R43 CA 171538-01/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*administration &amp; dosage ; Bevacizumab ; Cell Line, Tumor ; Drug Delivery Systems ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Mesothelioma/*metabolism ; Mice ; Mice, Inbred BALB C ; Pleural Neoplasms/*metabolism ; Receptor, EphB4/administration &amp; dosage/*metabolism ; Serum Albumin/administration &amp; dosage ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis.<br><br>METHODS: We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied.<br><br>RESULTS: EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression.<br><br>CONCLUSION: EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted.}, }
@article {pmid23720698, year = {2013}, author = {Neumann, V and Löseke, S and Nowak, D and Herth, FJ and Tannapfel, A}, title = {Malignant pleural mesothelioma: incidence, etiology, diagnosis, treatment, and occupational health.}, journal = {Deutsches Arzteblatt international}, volume = {110}, number = {18}, pages = {319-326}, pmid = {23720698}, issn = {1866-0452}, mesh = {Asbestosis/*diagnosis/mortality/*therapy ; Causality ; Comorbidity ; Evidence-Based Medicine ; Humans ; Mesothelioma/*diagnosis/mortality/*therapy ; Occupational Exposure/*statistics &amp; numerical data ; Occupational Health/statistics &amp; numerical data ; Pleural Effusion, Malignant/*diagnosis/mortality/*therapy ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors ; Survival Analysis ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: The incidence of malignant mesothelioma in Germany is about 20 cases per million persons per year. Its association with asbestos exposure, usually occupational, has been unequivocally demonstrated. Even though the industrial use of asbestos was forbidden many years ago, new cases of mesothelioma continue to appear because of the long latency of the disease (median, 50 years). Its diagnosis and treatment still present a major challenge for ambulatory and in-hospital care and will do so for years to come.<br><br>METHODS: This article is based on a selective review of the literature, along with data from the German Mesothelioma Register.<br><br>RESULTS: 1397 people died of mesothelioma in Germany in 2010. A plateau in the incidence of the disease is predicted between 2015 and 2030. Most mesotheliomas arise from the pleura. The histological subtype and the Karnofsky score are the main prognostic factors. Only limited data are now available to guide treatment with a combination of the available methods (chemotherapy, surgery, radiotherapy). The prognosis is still poor, with a median survival time of only 12 months. Symptom control and the preservation of the patient's quality of life are the main aspects of care for patients with mesothelioma.<br><br>CONCLUSION: The incidence of mesothelioma is not expected to drop in the next few years. The available treatments are chemotherapy, surgery, and radiotherapy. Specialized treatment centers now increasingly provide multimodal therapy for treatment of mesothelioma.}, }
@article {pmid23714495, year = {2013}, author = {Kindler, HL}, title = {Peritoneal mesothelioma: the site of origin matters.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {}, number = {}, pages = {182-188}, doi = {10.14694/EdBook_AM.2013.33.182}, pmid = {23714495}, issn = {1548-8756}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/toxicity ; Cytoreduction Surgical Procedures ; Female ; Germ-Line Mutation ; Humans ; Hyperthermia, Induced ; Lung Neoplasms/*diagnosis/*etiology/mortality/*therapy ; Male ; Mesothelioma/*diagnosis/*etiology/mortality/*therapy ; Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/*etiology/mortality/*therapy ; Pleural Neoplasms/etiology/therapy ; Survivors ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; United States ; }, abstract = {The etiology, gender distribution, pathology, natural history, and treatment options for mesothelioma (MM) differ substantially depending on the site of origin. Peritoneal mesothelioma (MPeM) is a rare disease, comprising only approximately 10% to 15% of the 2,500 cases of MM diagnosed in the United States each year. Patients with MPeM are younger than patients with pleural MM, and a higher proportion, mostly women, are long-term survivors. Most MPeM is caused by asbestos exposure. Germ-line mutations of BAP1 (BRCA associated protein 1) can predispose to MM, uveal melanoma, and potentially other cancers. MPeM can be challenging to diagnose, and cytology is rarely helpful. Review by an experienced pathologist using a panel of at least two positive and two negative immunohistochemical stains is essential. The three major pathologic subtypes are epithelial, sarcomatoid, and biphasic. Most cases are epithelial; the others have a dismal prognosis. Two indolent subtypes of borderline malignant potential-well-differentiated papillary mesothelioma and benign multicystic mesothelioma-are more common in the peritoneum and are treated surgically. In highly selected patients receiving treatment at experienced referral centers, an aggressive locoregional strategy that combines cytoreductive surgery to remove all gross disease and hyperthermic intraperitoneal chemotherapy to treat residual microscopic tumors yields a 3-year survival of 60% and a median survival approaching 5 years, far better than expected from historic controls. This approach also provides durable palliation of malignant ascites in nearly all patients. Pemetrexed is the only U.S. Food and Drug Administration (FDA)-approved systemic chemotherapy for pleural MM. Largely on the basis of data from pharmaceutical registry studies, the activity of pemetrexed-based chemotherapy appears to be similar in pleural MM and MPeM.}, }
@article {pmid23711077, year = {2014}, author = {Prazakova, S and Thomas, PS and Sandrini, A and Yates, DH}, title = {Asbestos and the lung in the 21st century: an update.}, journal = {The clinical respiratory journal}, volume = {8}, number = {1}, pages = {1-10}, doi = {10.1111/crj.12028}, pmid = {23711077}, issn = {1752-699X}, mesh = {Asbestosis/complications/diagnosis ; Developing Countries ; Humans ; Lung Diseases/etiology ; Mesothelioma/etiology ; *Occupational Exposure/statistics &amp; numerical data ; Pleura/pathology ; Pleural Effusion/etiology ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; }, abstract = {The asbestos-related disorders (ARDs) are currently of significant occupational and public health concern. Asbestos usage has been banned in most developed countries, but asbestos is still used in many developing countries and the number of cases of ARDs worldwide is rising. Many countries are now experiencing an epidemic of ARDs that is the legacy of occupational exposure in the 1960s-1980s because of the long latency period between asbestos exposure and manifestation of disease. It is likely that asbestos-related mortality and morbidity will continue to increase. Although the most feared complications of asbestos inhalation are the malignant conditions such as mesothelioma and lung cancer, asbestos inhalation more frequently results in benign conditions such as pleural plaques, diffuse pleural thickening, and asbestosis (pulmonary fibrosis due to asbestos exposure). Over recent years, there have been changes in the epidemiology of mesothelioma, in clinical management of ARDs and developments in new techniques for early detection of malignancy. This review provides an update on the respiratory manifestations of asbestos exposure and also considers advances in screening methods that may affect future management in the workplace.}, }
@article {pmid23702885, year = {2013}, author = {Farioli, A and Violante, FS and Mattioli, S and Curti, S and Kriebel, D}, title = {Risk of mesothelioma following external beam radiotherapy for prostate cancer: a cohort analysis of SEER database.}, journal = {Cancer causes &amp; control : CCC}, volume = {24}, number = {8}, pages = {1535-1545}, pmid = {23702885}, issn = {1573-7225}, mesh = {Aged ; Aged, 80 and over ; Cohort Studies ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology ; Neoplasms, Radiation-Induced/epidemiology/*etiology ; Neoplasms, Second Primary/epidemiology/*etiology ; Prognosis ; Prostatic Neoplasms/complications/*radiotherapy ; Radiotherapy/*adverse effects ; Risk Factors ; SEER Program ; United States/epidemiology ; }, abstract = {PURPOSE: To investigate the association between external beam radiotherapy (EBRT) for prostate cancer and mesothelioma using data from the US Surveillance, Epidemiology, and End Results (SEER) cancer registries.<br><br>METHODS: We analyzed data from the SEER database (1973-2009). We compared EBRT versus no radiotherapy. Incidence rate ratios (IRR) and 95&#xa0;% confidence intervals (95&#xa0;% CI) of mesothelioma among prostate cancer patients were estimated with multilevel Poisson models adjusted by race, age, and calendar year. Confounding by asbestos was investigated using relative risk of mesothelioma in each case's county of residence as a proxy for asbestos exposure.<br><br>RESULTS: Four hundred and seventy-one mesothelioma cases (93.6&#xa0;% pleural) occurred in 3,985,991 person-years. The IRR of mesothelioma was increased for subjects exposed to EBRT (1.28; 95&#xa0;% CI 1.05, 1.55) compared to non-irradiated patients, and a population attributable fraction of 0.49&#xa0;% (95&#xa0;% CI 0.11, 0.81) was estimated. The IRR increased with latency period: 0-4&#xa0;years, IRR 1.08 (95&#xa0;% CI 0.81, 1.44); 5-9&#xa0;years, IRR 1.31 (95&#xa0;% CI 0.93, 1.85); &#x2265;10&#xa0;years, IRR 1.59 (95&#xa0;% CI 1.05, 2.42). Despite the fairly strong evidence of association with EBRT, the population attributable rate of mesothelioma was modest-3.3 cases per 100,000 person-years. The cumulative incidence of mesothelioma attributable to EBRT was 4.0/100,000 over 5&#xa0;years, 24.5/100,000 over 10&#xa0;years, and 65.0/100,000 over 15&#xa0;years.<br><br>CONCLUSIONS: Our study provides evidence that EBRT for prostate cancer is a small but detectable risk factor for mesothelioma. Patients should be advised of risk of radiation-induced second malignancies.}, }
@article {pmid23695414, year = {2013}, author = {Tarrés, J and Albertí, C and Martínez-Artés, X and Abós-Herràndiz, R and Rosell-Murphy, M and García-Allas, I and Krier, I and Cantarell, G and Gallego, M and Canela-Soler, J and Orriols, R}, title = {Pleural mesothelioma in relation to meteorological conditions and residential distance from an industrial source of asbestos.}, journal = {Occupational and environmental medicine}, volume = {70}, number = {8}, pages = {588-590}, doi = {10.1136/oemed-2012-101198}, pmid = {23695414}, issn = {1470-7926}, mesh = {Aged ; Air Pollutants/adverse effects ; Asbestos/*adverse effects ; Chemical Industry ; Construction Materials ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; *Industry ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; *Residence Characteristics ; Retrospective Studies ; Risk Factors ; Spain/epidemiology ; *Wind ; }, abstract = {OBJECTIVES: Few studies have focused on pleural mesothelioma and environmental exposure in individuals residing around an industrial source of asbestos. The aim of this study is to determine whether residential distance and wind conditions are related to the risk of developing pleural mesothelioma.<br><br>METHODS: In this retrospective cohort study carried out in an area of Barcelona province (Catalonia, Spain), 24 environmental pleural mesothelioma cases were diagnosed between 2000 and 2009. We calculated the age-standardised incidence rate ratios of developing this disease in the population studied, taking into account the residential distance from the plant. For cases living within a 500-m radius of the plant, the geographical location in relation to the factory was also assessed.<br><br>RESULTS: The incidence rate of environmental pleural mesothelioma was higher in the population living within 500 m of the plant than in those living in a radius of 500-2000 m and much higher than those living at 2000-10 000 m. The highest incidence rate ratio for pleural mesothelioma (161.9) was found in the southeast quadrant of the 500-m area, coinciding with the predominant wind direction.<br><br>CONCLUSIONS: Residential distance from an industrial source of asbestos and local wind conditions have a considerable impact on the risk of developing environmental pleural mesothelioma.}, }
@article {pmid23687495, year = {2013}, author = {Gutzeit, A and Reischauer, C and Hergan, K and Kos, S and Roos, JE}, title = {Secondary malignant peritoneal mesothelioma of the greater omentum after therapy for primary pleural mesothelioma.}, journal = {Case reports in oncology}, volume = {6}, number = {1}, pages = {236-241}, pmid = {23687495}, issn = {1662-6575}, abstract = {Mesothelioma is the most common malignant primary tumor of the pleura and usually associated with inhalation of asbestos fibers. In contrast, peritoneal mesothelioma is a rare entity whose pathomechanism is not yet fully understood. The coexistence of pleural mesothelioma with secondary involvement of the abdominal cavity has not been addressed in the literature. In this case report, we describe secondary malignant mesothelioma of the greater omentum. A 69-year-old man with histologically proven pleural mesothelioma on the right side and no past medical history of asbestos exposure received palliative treatment consisting of a talc pleurodesis. After a 6-month interval of stable disease, a local progressive tumor of the right pleura was seen on a CT scan. Eleven months later, during follow-up, the patient presented at our emergency department with a sudden onset of diffuse abdominal pain. Abdominal ultrasound revealed a mass within the greater omentum and the coexistence of free fluid. Subsequent abdominal CT scans demonstrated tumor infiltration from the right pleura by a transdiaphragmatic route into the abdomen, where diffuse infiltration of the greater omentum was observed. Aspiration of the ascites and the biopsy of the greater omentum confirmed the diagnosis of secondary malignant mesothelioma of the peritoneum. In conclusion, we present the extremely rare diagnosis of secondary malignant mesothelioma of the abdomen, which arose as a result of local progression from the right pleura into the abdomen.}, }
@article {pmid23685846, year = {2013}, author = {Tabata, C and Kanemura, S and Tabata, R and Masachika, E and Shibata, E and Otsuki, T and Nishizaki, T and Nakano, T}, title = {Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma.}, journal = {Journal of clinical gastroenterology}, volume = {47}, number = {8}, pages = {684-688}, doi = {10.1097/MCG.0b013e318297fa65}, pmid = {23685846}, issn = {1539-2031}, mesh = {Aged ; Asbestos/toxicity ; Asbestosis/blood/diagnosis/pathology ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; HMGB1 Protein/*blood ; Humans ; Male ; Mesothelioma/blood/*diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/blood/*diagnosis/pathology ; }, abstract = {BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, early diagnosis of DMPM is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. DMPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells, similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM.<br><br>STUDY: The serum concentrations of HMGB1 were measured in 13 DMPM patients and 45 individuals with benign asbestos-related diseases.<br><br>RESULT: We demonstrated that the patients with DMPM had significantly higher serum levels of HMGB1 compared with the population who had been exposed to asbestos but did not develop DMPM.<br><br>CONCLUSION: Our data suggest that serum HMGB1 concentration is a useful serum marker for DMPM.}, }
@article {pmid23684920, year = {2013}, author = {Knipscheer, BJ and Kromontono, RC and de Bruin, PC and van Strijen, MJ and Herder, GJ}, title = {Two malignancies or an unusual presentation of a pleural malignancy?.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {81}, number = {2}, pages = {306-307}, doi = {10.1016/j.lungcan.2013.04.002}, pmid = {23684920}, issn = {1872-8332}, mesh = {Bone Neoplasms/diagnosis/*pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {Malignant mesothelioma is primarily located in the pleura. Progression usually involves adjacent tissue invasion. Both lymphatic and haematogenous spreads are possible, but rare. Bone involvement usually means locally invasive disease and rarely bone marrow metastases. In this report we presented two patients with a mesothelioma and bone marrow metastases.}, }
@article {pmid23684272, year = {2013}, author = {Frank, AL}, title = {Why countries ban asbestos: some alternative thoughts.}, journal = {International journal of occupational and environmental health}, volume = {19}, number = {2}, pages = {136}, doi = {10.1179/1077352513Z.00000000060}, pmid = {23684272}, issn = {1077-3525}, mesh = {Air Pollutants/*toxicity ; Air Pollution, Indoor/*legislation &amp; jurisprudence ; Asbestos/*toxicity ; Delivery of Health Care/*organization &amp; administration ; Humans ; *International Cooperation ; Mesothelioma/*epidemiology ; *Policy ; }, }
@article {pmid23684271, year = {2013}, author = {Bahk, J and Choi, Y and Lim, S and Paek, D}, title = {Why some, but not all, countries have banned asbestos.}, journal = {International journal of occupational and environmental health}, volume = {19}, number = {2}, pages = {127-135}, doi = {10.1179/2049396712Y.0000000011}, pmid = {23684271}, issn = {1077-3525}, mesh = {Air Pollutants/*toxicity ; Air Pollution, Indoor/*legislation &amp; jurisprudence ; Asbestos/*toxicity ; Delivery of Health Care/*organization &amp; administration ; Health Services Accessibility ; Humans ; *International Cooperation ; Mesothelioma/*epidemiology/mortality ; *Policy ; }, abstract = {BACKGROUND: Out of 143 countries that consumed asbestos between 2003 and 2007, only 44 have banned asbestos. This study tried to explain why some countries have banned asbestos while others have not, based on a synthesis that asbestos ban policy of a country will rely on a process of cognition of threats and exploration of safer alternatives.<br><br>METHOD: As we hypothesized that increased social cost of mesothelioma, capacity of health-related infrastructures, and policy diffusion from adjacent countries were related to asbestos ban adoption, published databases of asbestos ban years, mesothelioma mortality, country rankings in health care and human rights standings, and distribution of banning countries over 14 regions were analyzed accordingly.<br><br>RESULTS: The average mesothelioma death rate was significantly higher for countries with asbestos bans than in those with no ban (4&#xb7;59 versus 1&#xb7;83/million). No-ban countries had less well-developed health-related infrastructures. Among European countries, there was a tendency toward geographical diffusion of asbestos ban policy from Nordic to Western and then other European countries over the years. Even though aberrant cases were also noted where bans were instituted even without mesothelioma database, these were rather exceptions than rules.<br><br>CONCLUSION: Risk cognition is a complex process, but the presence of well-functioning health infrastructures, as well as the increased social cost of mesothelioma, that can make the plight of asbestos victims visible to the eyes of public and policy makers, may have contributed to this process. Asbestos ban policy from adjacent countries might have facilitated the adoption of alternative solutions.}, }
@article {pmid23682089, year = {2013}, author = {Fayed, HE and Woodcock, VK and Grayez, J}, title = {Simultaneous bilateral spontaneous hydropneumothorax: a rare presentation of bilateral malignant pleural mesothelioma.}, journal = {BMJ case reports}, volume = {2013}, number = {}, pages = {}, pmid = {23682089}, issn = {1757-790X}, mesh = {Aged ; Humans ; Hydropneumothorax/*diagnosis/etiology ; Lung Neoplasms/complications/*diagnosis ; Male ; Mesothelioma/complications/*diagnosis ; Mesothelioma, Malignant ; Pleural Neoplasms/complications/*diagnosis ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; }, abstract = {This is a case of a 69-year-old man with a history of asbestos exposure who presented with acute shortness of breath. His chest x-ray showed bilateral hydropneumothorax. Further investigations including CT chest and video-assisted thoracoscopic surgery revealed bilateral pleural thickening and histology confirmed epithelioid mesothelioma. This case highlights the need for clinicians to be aware of atypical presentations of malignant pleural mesothelioma as well as the importance of considering underlying secondary causes such as malignancy in the older patient presenting with spontaneous pneumo/hydropneumothorax.}, }
@article {pmid23677068, year = {2013}, author = {Sekido, Y}, title = {Molecular pathogenesis of malignant mesothelioma.}, journal = {Carcinogenesis}, volume = {34}, number = {7}, pages = {1413-1419}, doi = {10.1093/carcin/bgt166}, pmid = {23677068}, issn = {1460-2180}, mesh = {Asbestos/*adverse effects ; Cell Transformation, Neoplastic/chemically induced/genetics/pathology ; Disease Progression ; Disease Susceptibility/pathology ; Epigenesis, Genetic ; *Gene Expression Regulation, Neoplastic ; Gene Frequency ; Genes, p16 ; Humans ; Mesothelioma/chemically induced/genetics/*pathology ; Neurofibromin 2/genetics/metabolism ; TOR Serine-Threonine Kinases/genetics/metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; Ubiquitin Thiolesterase/genetics/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor arising primarily from the pleural or peritoneal cavities. It develops by asbestos exposure after a long latency, which is characterized by insidious growth and clinical presentation at an advanced stage of disease. MM is highly refractory to conventional therapies even with a combination of aggressive surgical intervention and multimodality strategies, with cure remaining elusive. Molecular genetic analysis has revealed several key genetic alterations, which are responsible for the development and progression of MM. The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells; the alterations of the latter two are relatively characteristic of MM. Merlin, which is encoded by NF2, regulates multiple cell signaling cascades including the Hippo and mammalian target of rapamycin pathways, which regulate cell proliferation and growth. BAP1 is involved in histone modification and its inactivation induces the disturbance of global gene expression profiling. The discovery of a new familial cancer syndrome with germline mutation of BAP1 also indicates the importance of genetic factors in MM susceptibility. Meanwhile, although frequent expression and functional activations of oncogene products such as receptor tyrosine kinases are observed in MM cells, activating mutations of these genes are rare. With further comprehensive genome analyses, new genetic and epigenetic alterations in MM cells are expected to be revealed more precisely, and the new knowledge based on them will be applied for developing new diagnostic tools and new target therapies against MMs.}, }
@article {pmid23676545, year = {2013}, author = {Busto Martin, L and Portela Pereira, P and Sacristan Lista, F and Busto Castañon, L}, title = {Mesothelioma of the tunica vaginalis. Case report.}, journal = {Archivos espanoles de urologia}, volume = {66}, number = {4}, pages = {384-388}, pmid = {23676545}, issn = {1576-8260}, mesh = {Biomarkers, Tumor/blood ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*pathology/surgery ; Middle Aged ; Orchiectomy ; Scrotum/*pathology/surgery ; Testicular Hydrocele/diagnostic imaging/pathology/surgery ; Testicular Neoplasms/*pathology/surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {OBJECTIVE: To report a case of a mesothelioma of the tunica vaginalis and to review the published literature. METHODS / RESULTS: A 61-year-old patient complained of one-month increase of right scrotum size with pain. An ultrasound showed a right hydrocele with a mass attached to the tunica vaginalis. He didn't refer any urological history or known exposure to asbestos. Blood levels of tumor markers (alpha-fetoprotein and beta-HCG) were within normal limits. We performed a radical inguinal orchiectomy with an en-bloc resection of the tunica vaginalis. The pathology described a potentially malignant biphasic mesothelioma. The patient has remained asymptomatic with negative extension studies after 10 years of follow up.<br><br>CONCLUSIONS: Paratesticular mesotheliomas are rare tumors (approximately 250 cases reported)with uncertain etiology (only 30-40% are associated with asbestos exposure). The age range is between 50-70 years. Its presentation is usually as a scrotal mass with recurrent reactive hydrocele, which may delay early diagnosis. During surgery, intraoperative biopsy is recommended. It is important to do a differential diagnosis with other benign diseases. Treatment is only curative in early stages with radical orchidectomy and resection in-block of the tunica vaginalis. Despite being multidisciplinary, it is not curative in most cases due to rapid local and distant spread.}, }
@article {pmid23672436, year = {2013}, author = {Taylor, ES and Wylie, AG and Mossman, BT and Lower, SK}, title = {Repetitive dissociation from crocidolite asbestos acts as persistent signal for epidermal growth factor receptor.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {29}, number = {21}, pages = {6323-6330}, doi = {10.1021/la400561t}, pmid = {23672436}, issn = {1520-5827}, mesh = {Asbestos, Crocidolite/*chemistry ; Cell Line, Tumor ; ErbB Receptors/*chemistry ; Humans ; Particle Size ; Surface Properties ; }, abstract = {Mesothelioma is an incurable form of cancer located most commonly in the pleural lining of the lungs and is associated almost exclusively with the inhalation of asbestos. The binding of asbestos to epidermal growth factor receptor (EGFR), a transmembrane signal protein, has been proposed as a trigger for downstream signaling of kinases and expression of genes involved in cell proliferation and inhibition of apoptosis. Here, we investigate the molecular binding of EGFR to crocidolite (blue asbestos; Na2(Fe(2+),Mg)3Fe2(3+)Si8O22(OH)2) in buffer solution. Atomic force microscopy measurements revealed an attractive force of interaction (i.e., bond) as EGFR was pulled from contact with long fibers of crocidolite. The rupture force of this bond increased with loading rate. According to the Bell model, the off-rate of bond dissociation (k(off)) for EGFR was 22 s(-1). Similar experiments with riebeckite crystals, the nonasbestiform variety of crocidolite, yielded a k(off) of 8 s(-1). These k(off) values on crocidolite and riebeckite are very rapid compared to published values for natural agonists of EGFR like transforming growth factor and epidermal growth factor. This suggests binding of EGFR to the surfaces of these minerals could elicit a response that is more potent than biological hormone or cytokine ligands. Signal transduction may cease for endogenous ligands due to endocytosis and subsequent degradation, and even riebeckite particles can be cleared from the lungs due to their short, equant habit. However, the fibrous habit of crocidolite leads to lifelong persistence in the lungs where aberrant, repetitious binding with EGFR may continually trigger the activation switch leading to chronic expression of genes involved in oncogenesis.}, }
@article {pmid23667371, year = {2013}, author = {Eom, M and Abdul-Ghafar, J and Park, SM and Han, JH and Hong, SW and Kwon, KY and Ko, ES and Kim, L and Kim, WS and Ha, SY and Lee, KY and Lee, CH and Yoon, HK and Choi, YD and Chung, MJ and Jung, SH}, title = {No detection of simian virus 40 in malignant mesothelioma in Korea.}, journal = {Korean journal of pathology}, volume = {47}, number = {2}, pages = {124-129}, pmid = {23667371}, issn = {1738-1843}, abstract = {BACKGROUND: Simian virus 40 (SV40), a polyomavirus, was discovered as a contaminant of a human polio vaccine in the 1960s. It is known that malignant mesothelioma (MM) is associated with SV40, and that the virus works as a cofactor to the carcinogenetic effects of asbestos. However, the reports about the correlation between SV40 and MM have not been consistent. The purpose of this study is to identify SV40 in MM tissue in Korea through detection of SV40 protein and DNA.<br><br>METHODS: We analyzed 62 cases of available paraffin-blocks enrolled through the Korean Malignant Mesothelioma Surveillance System and performed immunohistochemistry for SV40 protein and real-time polymerase chain reaction (PCR) for SV40 DNA.<br><br>RESULTS: Of 62 total cases, 40 had disease involving the pleura (64.5%), and 29 (46.8%) were found to be of the epithelioid subtype. Immunostaining demonstrated that all examined tissues were negative for SV40 protein. Sufficient DNA was extracted for real-time PCR analysis from 36 cases. Quantitative PCR of these samples showed no increase in SV40 transcript compared to the negative controls.<br><br>CONCLUSIONS: SV40 is not associated with the development of MM in Korea.}, }
@article {pmid23661263, year = {2013}, author = {Zhang, J and Cole, SR and Richardson, DB and Chu, H}, title = {A Bayesian approach to strengthen inference for case-control studies with multiple error-prone exposure assessments.}, journal = {Statistics in medicine}, volume = {32}, number = {25}, pages = {4426-4437}, pmid = {23661263}, issn = {1097-0258}, support = {P30 CA077598/CA/NCI NIH HHS/United States ; R01 CA117841/CA/NCI NIH HHS/United States ; R01-CA117841/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Bayes Theorem ; *Bias ; *Case-Control Studies ; Data Interpretation, Statistical ; Humans ; Likelihood Functions ; Linear Models ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; Probability ; Regression Analysis ; }, abstract = {In case-control studies, exposure assessments are almost always error-prone. In the absence of a gold standard, two or more assessment approaches are often used to classify people with respect to exposure. Each imperfect assessment tool may lead to misclassification of exposure assignment; the exposure misclassification may be differential with respect to case status or not; and, the errors in exposure classification under the different approaches may be independent (conditional upon the true exposure status) or not. Although methods have been proposed to study diagnostic accuracy in the absence of a gold standard, these methods are infrequently used in case-control studies to correct exposure misclassification that is simultaneously differential and dependent. In this paper, we proposed a Bayesian method to estimate the measurement-error corrected exposure-disease association, accounting for both differential and dependent misclassification. The performance of the proposed method is investigated using simulations, which show that the proposed approach works well, as well as an application to a case-control study assessing the association between asbestos exposure and mesothelioma.}, }
@article {pmid23626745, year = {2013}, author = {Lesterhuis, WJ and Salmons, J and Nowak, AK and Rozali, EN and Khong, A and Dick, IM and Harken, JA and Robinson, BW and Lake, RA}, title = {Synergistic effect of CTLA-4 blockade and cancer chemotherapy in the induction of anti-tumor immunity.}, journal = {PloS one}, volume = {8}, number = {4}, pages = {e61895}, pmid = {23626745}, issn = {1932-6203}, mesh = {Animals ; Antibodies, Monoclonal/*pharmacology ; CD4-Positive T-Lymphocytes/drug effects/immunology/pathology ; CD8-Positive T-Lymphocytes/drug effects/immunology/pathology ; Carcinoma, Lewis Lung/*drug therapy/immunology/mortality/pathology ; Deoxycytidine/*analogs &amp; derivatives/pharmacology ; Drug Synergism ; Drug Therapy, Combination ; Immunity, Innate/*drug effects ; Immunologic Factors/*pharmacology ; Lung Neoplasms/*drug therapy/immunology/mortality/pathology ; Lymphocyte Depletion ; Mesothelioma/*drug therapy/immunology/mortality/pathology ; Mice ; Mice, Transgenic ; Neoplasm Transplantation ; Survival Analysis ; Tumor Burden/drug effects ; Gemcitabine ; }, abstract = {Several chemotherapeutics exert immunomodulatory effects. One of these is the nucleoside analogue gemcitabine, which is widely used in patients with lung cancer, ovarian cancer, breast cancer, mesothelioma and several other types of cancer, but with limited efficacy. We hypothesized that the immunopotentiating effects of this drug are partly restrained by the inhibitory T cell molecule CTLA-4 and thus could be augmented by combining it with a blocking antibody against CTLA-4, which on its own has recently shown beneficial clinical effects in the treatment of patients with metastatic melanoma. Here we show, using two non-immunogenic murine tumor models, that treatment with gemcitabine chemotherapy in combination with CTLA-4 blockade results in the induction of a potent anti-tumor immune response. Depletion experiments demonstrated that both CD4(+) and CD8(+) T cells are required for optimal therapeutic effect. Mice treated with the combination exhibited tumor regression and long-term protective immunity. In addition, we show that the efficacy of the combination is moderated by the timing of administration of the two agents. Our results show that immune checkpoint blockade and cytotoxic chemotherapy can have a synergistic effect in the treatment of cancer. These results provide a basis to pursue combination therapies with anti-CTLA-4 and immunopotentiating chemotherapy and have important implications for future studies in cancer patients. Since both drugs are approved for use in patients our data can be immediately translated into clinical trials.}, }
@article {pmid23626673, year = {2013}, author = {Matullo, G and Guarrera, S and Betti, M and Fiorito, G and Ferrante, D and Voglino, F and Cadby, G and Di Gaetano, C and Rosa, F and Russo, A and Hirvonen, A and Casalone, E and Tunesi, S and Padoan, M and Giordano, M and Aspesi, A and Casadio, C and Ardissone, F and Ruffini, E and Betta, PG and Libener, R and Guaschino, R and Piccolini, E and Neri, M and Musk, AW and de Klerk, NH and Hui, J and Beilby, J and James, AL and Creaney, J and Robinson, BW and Mukherjee, S and Palmer, LJ and Mirabelli, D and Ugolini, D and Bonassi, S and Magnani, C and Dianzani, I}, title = {Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.}, journal = {PloS one}, volume = {8}, number = {4}, pages = {e61253}, pmid = {23626673}, issn = {1932-6203}, mesh = {Aged ; Asbestos/*adverse effects ; Australia ; Case-Control Studies ; Female ; *Genetic Loci ; Genetic Markers ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Italy ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Neoplasm Proteins/*genetics ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleural Neoplasms/etiology/*genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.}, }
@article {pmid23624458, year = {2013}, author = {Singh, A and Chatterjee, P and Pai, MC and Chacko, RT}, title = {Multicystic peritoneal mesothelioma: not always a benign disease.}, journal = {Singapore medical journal}, volume = {54}, number = {4}, pages = {e76-8}, doi = {10.11622/smedj.2013085}, pmid = {23624458}, issn = {2737-5935}, mesh = {Adult ; Cell Differentiation ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma, Cystic/*diagnosis ; Neoplasm Metastasis ; Ovarian Neoplasms/diagnosis ; Ovary/pathology ; Peritoneal Neoplasms/*diagnosis ; Reproducibility of Results ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma is a slow-growing insidious lesion of neoplastic aetiology arising from the pleural, peritoneal or pericardial mesothelium. It shows a predilection for the surfaces of the pelvic viscera and has a high rate of recurrence after excision. Cystic mesotheliomas are not associated with asbestos exposure. We report a case of cystic mesothelioma of the peritoneum encasing the ovary, which presented as a cystic adnexal mass. As highlighted in this case and other recent reports, a cystic mesothelioma should not be referred to as a benign cystic mesothelioma, as it has potential for locoregional invasion, as well as distant nodal and serosal metastases. This tumour should be treated with aggressive cytoreductive surgery and appropriate chemotherapy. We review the differential diagnosis of this rare entity and suggest guidelines for its differentiation.}, }
@article {pmid23621518, year = {2013}, author = {Okazaki, Y and Nagai, H and Chew, SH and Li, J and Funahashi, S and Tsujimura, T and Toyokuni, S}, title = {CD146 and insulin-like growth factor 2 mRNA-binding protein 3 predict prognosis of asbestos-induced rat mesothelioma.}, journal = {Cancer science}, volume = {104}, number = {8}, pages = {989-995}, pmid = {23621518}, issn = {1349-7006}, mesh = {Animals ; Asbestos/*toxicity ; Biomarkers, Tumor/*biosynthesis/genetics/metabolism ; CD146 Antigen/*biosynthesis/genetics/metabolism ; Cyclin D1/genetics/metabolism ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Immunohistochemistry/methods ; Insulin-Like Growth Factor Binding Protein 3/*biosynthesis/genetics/metabolism ; Ki-67 Antigen/genetics/metabolism ; Male ; Mesothelioma/etiology/genetics/*metabolism/pathology ; Peritoneal Neoplasms/etiology/genetics/*metabolism/pathology ; Prognosis ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Inbred BN ; }, abstract = {Malignant mesothelioma (MM), which is associated with asbestos exposure, is one of the most deadly tumors in humans. Early MM is concealed in the serosal cavities and lacks specific clinical symptoms. For better treatment, early detection and prognostic markers are necessary. Recently, CD146 and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) were reported as possible positive markers of MM to distinguish from reactive mesothelia in humans. However, their application on MM of different species and its impact on survival remain to be elucidated. To disclose the utility of these molecules as early detection and prognostic markers of MM, we injected chrysotile or crocidolite intraperitoneally to rats, thus obtaining 26 peritoneal MM and establishing 11 cell lines. We immunostained CD146 and IMP3 using paraffin-embedded tissues and cell blocks and found CD146 and IMP3 expression in 58% (15/26) and 65% (17/26) of MM, respectively, but not in reactive mesothelia. There was no significant difference in both immunostainings for overexpression among the three histological subtypes of MM and the expression of CD146 and IMP3 was proportionally associated. Furthermore, the overexpression of CD146 and/or IMP3 was proportionally correlated with shortened survival. These results suggest that CD146 and IMP3 are useful diagnostic and prognostic markers of MM.}, }
@article {pmid23617783, year = {2013}, author = {Tabata, C and Shibata, E and Tabata, R and Kanemura, S and Mikami, K and Nogi, Y and Masachika, E and Nishizaki, T and Nakano, T}, title = {Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {205}, pmid = {23617783}, issn = {1471-2407}, mesh = {Adenocarcinoma/*blood ; Aged ; Area Under Curve ; Asbestosis/blood ; Biomarkers, Tumor/*blood ; Carcinoma, Squamous Cell/*blood ; Case-Control Studies ; Cell Line, Tumor ; Female ; HMGB1 Protein/*blood/metabolism ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*blood ; Male ; Mesothelioma/*blood/metabolism/pathology ; Middle Aged ; Pleural Neoplasms/*blood/metabolism/pathology ; Proportional Hazards Models ; ROC Curve ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to conventional chemotherapy and radiotherapy. Therefore, diagnosing MPM early is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. MPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM.<br><br>METHODS: HMGB1 production from MPM cell lines was measured using ELISA. Serum HMGB1 levels were also examined in 61 MPM patients and 45 individuals with benign asbestos-related diseases.<br><br>RESULTS: HMGB1 concentrations of 2 out of 4 MPM cell lines were higher than that of normal mesothelial cell line, Met-5A. We demonstrated that patients with MPM had significantly higher serum levels of HMGB1 than the population who had been exposed to asbestos but had not developed MPM. The difference in overall survival between groups with serum HMGB1 levels that were lower and higher than assumed cut-off values was significant.<br><br>CONCLUSIONS: Our data suggest that serum HMGB1 concentration is a useful prognostic factor for MPM.}, }
@article {pmid23609252, year = {2013}, author = {Baççioğlu, A and Kaba, E and Ozmen, SA and Demirci, M}, title = {Desmoplastic malignant mesothelioma.}, journal = {Journal of bronchology &amp; interventional pulmonology}, volume = {20}, number = {2}, pages = {155-158}, doi = {10.1097/LBR.0b013e31828e1aa2}, pmid = {23609252}, issn = {1948-8270}, mesh = {Aged ; Female ; Humans ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma. A 72-year-old woman from East Anatolia presented with chest pain. The images of body positron emission tomography revealed irregular, left pleural thickening involving mediastinal and diaphragmatic surfaces with hypermetabolic characterization. The diagnosis of desmoplastic malignant mesothelioma was confirmed by minithoracotomy and immunohistochemical staining with pan-cytokeratin, cytokeratin 5/6, calretinin, carcinoembryonic antigen, thyroid transcription factor-1, CD15, and HMB-45 on the biopsy specimen. This case is unique in terms of the reporting patient being from a nonendemic area for asbestos-related diseases and in terms of its rare histopathology.}, }
@article {pmid23606987, year = {2013}, author = {Melnikova, N and Wu, J and Kaye, W and Orr, M}, title = {Reliability of Family Proxy Data for Studies of Malignant Mesothelioma: Results from the ATSDR Pilot Surveillance.}, journal = {ISRN oncology}, volume = {2013}, number = {}, pages = {325409}, pmid = {23606987}, issn = {2090-5661}, abstract = {Objective. To evaluate the validity of proxy interviews in obtaining information on persons with rapidly fatal diseases such as malignant mesothelioma (MM). Methods. Persons with MM diagnosed in 2002 through 2005 in New York and New Jersey and 1997-2004 in Wisconsin were eligible for inclusion in the project. Persons with MM and their family member proxy were interviewed using the same questionnaire designed by ATSDR to collect information on potential direct or indirect occupational and environmental exposure to asbestos, genetic, and health related malignancy predisposition, and exposure to tobacco products. Descriptive statistics and the McNemar/Durkalski test were used to analyze 33 matched pairs. Results. The overall study confirmed a generally high ability of proxies to give interviews of comparable quality and completeness when asked dichotomous questions. The reliability of information collected from proxies varied by topic and family relationship. Conclusions. Family proxy interviews, using dichotomous responses, can serve as an acceptable source of information about health and exposure-related risk factors for MM.}, }
@article {pmid23595591, year = {2013}, author = {Blum, W and Schwaller, B}, title = {Calretinin is essential for mesothelioma cell growth/survival in vitro: a potential new target for malignant mesothelioma therapy?.}, journal = {International journal of cancer}, volume = {133}, number = {9}, pages = {2077-2088}, doi = {10.1002/ijc.28218}, pmid = {23595591}, issn = {1097-0215}, mesh = {Animals ; Apoptosis/drug effects ; Blotting, Western ; Calbindin 2 ; Cell Cycle ; Cell Proliferation ; Cells, Cultured ; Epithelium/metabolism/*pathology ; Humans ; In Vitro Techniques ; Lentivirus/genetics ; Mesothelioma/metabolism/*pathology ; Mice ; Pleural Neoplasms/metabolism/*pathology ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/genetics ; S100 Calcium Binding Protein G/antagonists &amp; inhibitors/genetics/*metabolism ; Sarcoma/metabolism/*pathology ; }, abstract = {Malignant mesothelioma (MM) are highly aggressive asbestos-related neoplasms, which show strong chemotherapy resistance, and there is no effective cure for MM so far. Calretinin (CR) is widely used as a diagnostic marker for epithelioid and mixed (biphasic) mesothelioma; however, little is known about CR's putative functions in tumorigenesis. CR protects against asbestos-induced acute cytotoxicity mediated by the AKT/PI3K pathway, and furthermore, SV40 early region genes are able to upregulate CR in mesothelial cells. However, the precise role of CR in mesothelioma is still unknown. Downregulation of CR via lentiviral-mediated short-hairpin RNA significantly decreased the viability and proliferation of mesothelioma cells in vitro. The effect was strong in epithelioid-dominated cell lines (ZL55 and MSTO-211H). A weaker and delayed effect was observed in mesothelioma cells with prevalent sarcomatoid morphology (SPC111, SPC212 and ZL34). The specificity of the effect was confirmed by stable enhanced green fluorescent protein-CR expression in mesothelioma cell lines and subsequent downregulation. Depletion of CR led these cancer cell lines to enter apoptosis within 72 hr postinfection via strong activation of the intrinsic caspase 9-dependent pathway. Downregulation of CR in immortalized mesothelial cells LP9/TERT-1 strongly blocked proliferation and caused a G1 block without decreasing viability or activating apoptosis pathways. These results demonstrate that downregulation of CR had a strong effect on the viability of MM cells and that CR is essential for cells derived from MM. The authors anticipate these findings to reveal CR as a highly interesting new putative therapeutic target for mesothelioma treatment of especially the epithelioid, as well as of the mixed and sarcomatoid type.}, }
@article {pmid23585512, year = {2013}, author = {Ribeiro, C and Campelos, S and Moura, CS and Machado, JC and Justino, A and Parente, B}, title = {Well-differentiated papillary mesothelioma: clustering in a Portuguese family with a germline BAP1 mutation.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {24}, number = {8}, pages = {2147-2150}, doi = {10.1093/annonc/mdt135}, pmid = {23585512}, issn = {1569-8041}, mesh = {Adult ; Asbestos/adverse effects ; Cluster Analysis ; Environmental Exposure ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Melanoma/*genetics ; Mesothelioma/*genetics/mortality ; Middle Aged ; Peritoneal Neoplasms/*genetics ; Pleural Neoplasms/*genetics ; Portugal ; Prognosis ; Siblings ; Survival ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; Uveal Neoplasms/*genetics ; }, abstract = {BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) is a rare variant of epithelioid mesothelioma and is considered to be associated with good prognosis due to its clinically indolent behavior and long survival. Most reported cases involve the peritoneum of women at reproductive age with no history of exposure to asbestos, with pleural involvement being less common. The optimal management, including the role of chemotherapy in the treatment of WDPM, remains unsettled.<br><br>PATIENTS AND METHODS: The authors describe two cases of WDPM in women of the same family (siblings); the elder with WDPM of the pleura and peritoneum with a 12-year survival period and the younger with a WDPM of the peritoneum diagnosed in 2011 and uveal melanoma diagnosed in 2012. Neither patient had any known exposure to asbestos fibers or any other mineral carcinogens.<br><br>RESULTS: After the concurrent diagnosis of WDPM and uveal melanoma, genetic diagnosis was carried out taking into consideration that these two malignancies were recently associated with hereditary BAP1 gene mutations and it was positive for both the patients.<br><br>CONCLUSIONS: To our knowledge, this is the first description of WDPM in two siblings who also presented with a germline BAP1 mutation. This article provides evidence of the wide clinical spectrum of cancer susceptibility associated with a BAP1 germline mutation.}, }
@article {pmid23585433, year = {2013}, author = {Chellini, E and Martini, A and Cacciarini, V and Badiali, AM and , }, title = {[Considerations about the epidemiologic surveillance system on mesothelioma in Tuscany (Italy) after 25 years of activity].}, journal = {Epidemiologia e prevenzione}, volume = {37}, number = {1}, pages = {43-50}, pmid = {23585433}, issn = {1120-9763}, mesh = {Asbestos/poisoning ; Epidemiological Monitoring ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Survival Analysis ; }, abstract = {OBJECTIVE AND DESIGN: To present problems and opportunities related to the operating procedures developed by the Tuscan epidemiological surveillance system on mesothelioma during its 25 years of activity.<br><br>SETTING AND PARTICIPANTS: All 1,224 mesotheliomas, registered up to 31.12. 2011, diagnosed in Tuscan residents during 1988-2009 by the Tuscan Operating Centre of the Italian registry, have been considered.<br><br>MAIN OUTCOME MEASURES: In order to evaluate accuracy and completeness of cases, the following indicators by period are used for pleural mesotheliomas diagnosed during 1988-2009: the distribution of the sources of cases' diagnosis and report to the regional registry, the latency time between diagnosis and report, the age and sex specific rates, the ratio between standardized mortality and incidence rates. The distribution of type of interview and exposure classification by period for all cases were used to evaluate the collected and classified exposure information.<br><br>RESULTS: Histology with immunohistochemistry became the chosen method (97.4% of histological cases in 2005- 2009). Since the second half of the Nineties, other Italian regional Operating Centres and, more recently, the Workers Compensation Authority (INAIL) became new important sources of case report. Nowadays, the mortality/incidence ratio is closer to 1. The latency time between diagnosis and case report have been reducing with a consequent increase in direct interviews to cases (from 20.3% in 1988-1993 to 71.4% in 2005-2009