@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}, 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 = {}, number = {}, pages = {}, doi = {10.1055/s-0043-1769097}, pmid = {37253383}, issn = {1098-9048}, 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 {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 {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 {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}, 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 = {}, number = {}, pages = {}, doi = {10.1093/annweh/wxad028}, pmid = {37247334}, issn = {2398-7316}, 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}, 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}, doi = {10.7717/peerj.15302}, pmid = {37220527}, issn = {2167-8359}, 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 {pmid37217834, year = {2023}, author = {Zambrano, E and Matoso, A and Reyes-Múgica, M}, title = {Mesotheliomas in Children.}, journal = {Advances in anatomic pathology}, volume = {}, number = {}, pages = {}, doi = {10.1097/PAP.0000000000000403}, pmid = {37217834}, issn = {1533-4031}, 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}, }
@article {pmid37199503, year = {2023}, author = {Giacobbe, C and Moliterni, A and Di Giuseppe, D and Malferrari, D and Wright, JP and Mattioli, M and Ranieri, 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 = {}, number = {}, pages = {}, doi = {10.1107/S2052252523003500}, pmid = {37199503}, issn = {2052-2525}, 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}, 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 = {}, doi = {10.3390/cancers15082364}, pmid = {37190292}, issn = {2072-6694}, 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 = {}, doi = {10.3390/cancers15082234}, pmid = {37190163}, issn = {2072-6694}, 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}, 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}, doi = {10.3389/ftox.2023.1161995}, 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 = {}, number = {}, pages = {105206}, doi = {10.1016/j.neubiorev.2023.105206}, pmid = {37178944}, issn = {1873-7528}, 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 = {}, doi = {10.3390/ijms24098183}, pmid = {37175892}, issn = {1422-0067}, 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}, 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}, doi = {10.7759/cureus.37305}, 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}, 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 = {}, number = {}, pages = {}, doi = {10.1002/cam4.6056}, pmid = {37165917}, issn = {2045-7634}, 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}, }
@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}, 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}, 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 = {}, number = {}, pages = {}, doi = {10.1002/jat.4493}, pmid = {37147272}, issn = {1099-1263}, abstract = {Asbestos is fibrous silicate mineral exhibiting biopersistence and carcinogen property and contribute to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with 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 to 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 GO and KEGG analysis. Cro-Met-5A[SETD2-KO] had strong migration but mild adhesion behavior as compared to Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5A[SETD2-KO] but inhibited migration of Met-5A when compared to 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 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}, 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}, doi = {10.1371/journal.pone.0274364}, pmid = {37146029}, issn = {1932-6203}, 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}, 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}, doi = {10.5090/jcs.22.107}, 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 = {2023}, 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 = {}, number = {}, pages = {10668969231167492}, doi = {10.1177/10668969231167492}, pmid = {37128670}, issn = {1940-2465}, 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 = {}, number = {}, pages = {}, doi = {10.1097/PAP.0000000000000399}, pmid = {37104724}, issn = {1533-4031}, 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. 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}, 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}, 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}, }
@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}, 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}, 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 = {}, 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 = {}, number = {}, pages = {}, pmid = {37058192}, issn = {1573-2983}, 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 = {}, doi = {10.3390/ijms24076689}, pmid = {37047661}, issn = {1422-0067}, 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 = {}, doi = {10.3390/ijms24076356}, pmid = {37047331}, issn = {1422-0067}, 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 = {}, number = {}, pages = {}, doi = {10.1111/his.14916}, pmid = {37040900}, issn = {1365-2559}, 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 {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 {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 = {}, number = {}, pages = {}, pmid = {37027032}, issn = {1432-1335}, 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 the neighborhood asbestos exposure due to a large-scale asbestos-cement plant.}, journal = {Cancer science}, volume = {}, number = {}, pages = {}, doi = {10.1111/cas.15802}, pmid = {37010194}, issn = {1349-7006}, abstract = {A causal relationship between mesothelioma and the occupational asbestos exposure is well known, while few 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 exposures due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, adjusting properly considerable 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 the neighborhood exposure, demonstrating that ORs in the highest quintile category were 21.4 (95% 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 the other non-occupational exposures separately, showed a dose-dependent association with the 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 = {}, doi = {10.3390/ijerph20064950}, pmid = {36981857}, issn = {1660-4601}, support = {75D30119P05558/CC/CDC HHS/United States ; }, 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 = {}, doi = {10.3390/genes14030729}, pmid = {36981000}, issn = {2073-4425}, 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 = {}, doi = {10.3390/cancers15061746}, pmid = {36980631}, issn = {2072-6694}, 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 {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}, 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 = {2022}, 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 = {}, number = {}, pages = {115085}, doi = {10.1016/j.envres.2022.115085}, pmid = {36965810}, issn = {1096-0953}, 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&#x202f;=&#x202f;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 {pmid36965808, year = {2022}, author = {Bogen, KT}, title = {Ultrasensitive dose-response for asbestos cancer risk implied by new inflammation-mutation model.}, journal = {Environmental research}, volume = {}, number = {}, pages = {115047}, doi = {10.1016/j.envres.2022.115047}, pmid = {36965808}, issn = {1096-0953}, 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 = {2022}, 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 = {}, number = {}, pages = {114791}, doi = {10.1016/j.envres.2022.114791}, pmid = {36965804}, issn = {1096-0953}, 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 = {2022}, author = {Darnton, L}, title = {Quantitative assessment of mesothelioma and lung cancer risk based on Phase Contrast Microscopy (PCM) exposure to asbestos: An update of 2000 data.}, journal = {Environmental research}, volume = {}, number = {}, pages = {114753}, doi = {10.1016/j.envres.2022.114753}, pmid = {36965802}, issn = {1096-0953}, 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 Carlina 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 = {2022}, author = {Nel, A}, title = {Carbon nanotube pathogenicity conforms to a unified theory for mesothelioma causation by pathogenic elongate materials and fibers.}, journal = {Environmental research}, volume = {}, number = {}, pages = {114580}, doi = {10.1016/j.envres.2022.114580}, pmid = {36965801}, issn = {1096-0953}, 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 allowed confirming 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 = {2022}, 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 = {}, number = {}, pages = {114530}, doi = {10.1016/j.envres.2022.114530}, pmid = {36965800}, issn = {1096-0953}, 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 = {2022}, author = {Moolgavkar, SH 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 = {}, number = {}, pages = {114582}, doi = {10.1016/j.envres.2022.114582}, pmid = {36965799}, issn = {1096-0953}, 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.}, }
@article {pmid36965797, year = {2022}, 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 = {}, number = {}, pages = {114578}, doi = {10.1016/j.envres.2022.114578}, pmid = {36965797}, issn = {1096-0953}, 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 = {2022}, author = {Chatfield, EJ}, title = {Asbestiform fibers and cleavage Fragments: Conceptual approaches for differentiation in laboratory practice and data analysis.}, journal = {Environmental research}, volume = {}, number = {}, pages = {114529}, doi = {10.1016/j.envres.2022.114529}, pmid = {36965795}, issn = {1096-0953}, 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, K and Conolly, R and Graham, U and Moolgavkar, S and Oberdorster, G and Roggli, V and Turci, F and Mossman, BT}, title = {Mechanisms and shapes of causal exposure-response functions for asbestos in mesotheliomas and lung cancers.}, journal = {Environmental research}, volume = {}, number = {}, pages = {115607}, doi = {10.1016/j.envres.2023.115607}, pmid = {36965793}, issn = {1096-0953}, 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 EMP pathogenicity.}, journal = {Environmental research}, volume = {}, number = {}, pages = {115608}, doi = {10.1016/j.envres.2023.115608}, pmid = {36965792}, issn = {1096-0953}, 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}, 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 = {}, number = {}, pages = {}, doi = {10.1002/jso.27243}, pmid = {36932968}, issn = {1096-9098}, 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}, 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 = {}, doi = {10.3390/jcm12051757}, 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 = {}, doi = {10.3390/ijerph20054295}, pmid = {36901302}, issn = {1660-4601}, 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 = {}, doi = {10.3390/cancers15051537}, 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 = {}, number = {}, pages = {}, doi = {10.1097/CEJ.0000000000000786}, pmid = {36896837}, issn = {1473-5709}, 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 = {}, number = {}, pages = {}, doi = {10.5507/bp.2023.008}, pmid = {36883200}, issn = {1804-7521}, 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}, 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 = {}, number = {}, pages = {}, doi = {10.1513/AnnalsATS.202209-802OC}, pmid = {36857650}, issn = {2325-6621}, abstract = {RATIONALE: Mesothelioma has become a major health burden since the second world war due to the use of asbestos. Although many countries have imposed a ban on asbestos, there remains significant mortality and morbidity from mesothelioma owing to its long latent period and aggressiveness. Also, the use of asbestos is increasing in low-income countries, potentiating risk of mesothelioma in the upcoming decades. Assessment of global burden of mesothelioma is required to take proper measures against the disease.<br><br>OBJECTIVES: To assess the burden of mesothelioma from 1990 to 2019 at the global, regional, and national level and investigate patterns according to sex, age, socio-demographic index (SDI) and risk factors Methods: The numbers, rates, and age-standardised rates of incidence, deaths, 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. Relationship between SDI and age-standardised DALY rates was determined and DALYs attributable to occupational exposure to asbestos were calculated.<br><br>RESULTS: In 2019, there were 34511 (95% UI 31199 to 37771) incident cases of mesothelioma globally, with an age-standardised rate of 0.43 per 100 000 persons (0.38 to 0.47) which decreased between 1990 and 2019 by -12.6% (-21.8 to -2.3). Mesothelioma was responsible for 29251(26668 to 31006) deaths in 2019, with an age-standardised rate of 0.36 deaths per 100 000 persons (0.33 to 0.39), which decreased between 1990 and 2019 by -9.6% (-17.8 to -1.1). The age-standardised incidence rate increased in central Europe between 1990 and 2019 by 46.1% (16.6 to 72.4). Netherlands, Australia, and UK had the highest age-standardised incidence rates. The incidence rates were higher in males than in females from ages 45-49 to 90-94, peaking at ages 85-89. Occupational exposure to asbestos contributed to 91.9% (90.0 to 93.6) of DALYs.<br><br>CONCLUSION: Global burden of mesothelioma is decreasing in terms of age-standardised 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 = {}, doi = {10.3390/ijerph20042833}, pmid = {36833533}, issn = {1660-4601}, 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 = {}, doi = {10.3390/biomedicines11020538}, pmid = {36831074}, issn = {2227-9059}, 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}, 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}, 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 = {}, number = {}, pages = {}, doi = {10.1111/1759-7714.14827}, pmid = {36808895}, issn = {1759-7714}, 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 = {}, number = {}, pages = {}, doi = {10.5858/arpa.2022-0283-OA}, pmid = {36800547}, issn = {1543-2165}, 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}, 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}, 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 = {}, number = {}, pages = {}, pmid = {36781827}, issn = {1865-7265}, 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, MC}, 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 = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2023.01.095}, pmid = {36775192}, issn = {1556-1380}, 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 geographical locations, and investigate its risk factors on the population level.<br><br>METHODS: Global Cancer Observatory (GLOBOCAN), Cancer Incidence in Five Continents Plus (CI5 Plus), Global Burden of Disease (GBD) were accessed for mesothelioma incidence and its risk factors worldwide. The associations between mesothelioma incidence and asbestos were examined for each country by multivariable linear regression analysis by sex and age. Average Annual Percentage Change (AAPC) was calculated using Joinpoint regression to examine epidemiological trends of mesothelioma.<br><br>RESULTS: The age-standardised 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 females. Countries with higher HDI (&#x3b2;=0.119, CI 0.073 to 0.166, p<0.001), GDP per capita (&#x3b2;=0.133, CI 0.106 to 0.161, p<0.001), and asbestos exposure (&#x3b2;=0.087, CI 0.073 to 0.102, p<0.001; Figure) 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 to 8.24, p=0.001) and Korea (AAPC: 3.24, 95% CI 0.08 to 6.49, p=0.045).<br><br>CONCLUSION: There was a significant declining incidence trend of mesothelioma for 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 fibres.}, }
@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 = {}, doi = {10.3390/cancers15030641}, pmid = {36765599}, issn = {2072-6694}, 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}, 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}, 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 = {}, number = {}, pages = {}, doi = {10.1136/oemed-2022-108669}, pmid = {36754595}, issn = {1470-7926}, 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}, doi = {10.1002/ctm2.1190}, pmid = {36740402}, issn = {2001-1326}, support = {19-0238//Worldwide Cancer Research/United Kingdom ; 204804/Z/16/Z//Wellcome Trust/United Kingdom ; }, 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 = {}, number = {}, pages = {}, pmid = {36729166}, issn = {1573-7225}, 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 = {}, number = {}, pages = {1-11}, doi = {10.1159/000528670}, pmid = {36724751}, issn = {1423-0291}, 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 = {}, number = {}, pages = {}, doi = {10.1136/oemed-2022-108605}, pmid = {36720634}, issn = {1470-7926}, 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 = {}, doi = {10.1093/gigascience/giac128}, pmid = {36705549}, issn = {2047-217X}, support = {PRT-K 2016-039/CA/NCI NIH HHS/United States ; }, 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 {pmid36550787, year = {2022}, author = {Schelch, K and Eder, S and Zitta, B and Phimmachanh, M and Johnson, TG and Emminger, D and Wenninger-Weinzierl, A and Sturtzel, C and Poplimont, H and Ries, A and Hoetzenecker, K and Hoda, MA and Berger, W and Distel, M and Dome, B and Reid, G and Grusch, M}, title = {YB-1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13367}, pmid = {36550787}, issn = {1878-0261}, abstract = {Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y-box-binding protein-1 (YB-1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB-1 on target gene regulation and PM cell behavior. Whereas siRNA-mediated YB-1 knockdown reduced cell motility, YB-1 overexpression resulted in scattering, increased migration, and intravasation in vitro. Furthermore, YB-1 stimulated PM cell spreading in zebrafish. Combined knockdown and inducible overexpression of YB-1 allowed bidirectional control and rescue of cell migration, the pattern of which was closely followed by the mRNA and protein levels of EGFR and the protein level of snail, whereas the mRNA levels of MMP1, EPHA5, and PARK2 showed partial regulation by YB-1. Finally, we identified snail as a critical regulator of YB-1-mediated cell motility in PM. This study provides insights into the mechanism underlying the aggressive nature of PM and highlights the important role of YB-1 in this cancer. In this context, we found that YB-1 closely regulates EGFR and snail, and, moreover, that YB-1-induced cell migration depends on snail.}, }
@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 = {}, doi = {10.3390/ijerph20020936}, pmid = {36673690}, issn = {1660-4601}, 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}, 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 = {}, number = {}, pages = {}, doi = {10.1136/oemed-2022-108706}, pmid = {36635096}, issn = {1470-7926}, 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 = {}, number = {}, pages = {}, pmid = {36630203}, issn = {1531-6971}, 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}, 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 = {}, doi = {10.3390/ijerph20010058}, pmid = {36612385}, issn = {1660-4601}, 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 = {}, doi = {10.3390/cancers15010125}, pmid = {36612122}, issn = {2072-6694}, 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 {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 = {}, doi = {10.3390/life12121969}, 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 = {}, doi = {10.3390/ijerph192416649}, pmid = {36554530}, issn = {1660-4601}, 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 = {}, doi = {10.3390/diagnostics12123009}, 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 = {}, doi = {10.3390/biology11121826}, 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 = {}, doi = {10.1136/bmjgh-2022-010553}, pmid = {36543384}, issn = {2059-7908}, 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 = {2022}, 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 = {}, number = {}, pages = {}, doi = {10.1111/cas.15705}, pmid = {36541514}, issn = {1349-7006}, 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-strand 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 thus 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 to 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 to wild-type tumors. Mutant MMs indicated iron metabolism dysregulation, such as increase in catalytic Fe(II) and Ki67-index as well as 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 to crocidolite/Mut whereas significant preference to iron with 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 = {2022}, 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 = {}, number = {}, pages = {115046}, doi = {10.1016/j.envres.2022.115046}, pmid = {36525994}, issn = {1096-0953}, 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}, doi = {10.21037/tlcr-22-199}, 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 = {}, doi = {10.3390/ijms232315438}, pmid = {36499762}, issn = {1422-0067}, support = {ES021110/NH/NIH HHS/United States ; }, 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 = {}, doi = {10.3390/ijerph192315934}, pmid = {36498008}, issn = {1660-4601}, 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}, doi = {10.23749/mdl.v113i6.13522}, pmid = {36475505}, issn = {0025-7818}, 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 = {}, doi = {10.3390/ijerph192214763}, 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 = {}, number = {}, pages = {}, doi = {10.1021/acs.chemrestox.2c00314}, pmid = {36410050}, issn = {1520-5010}, 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}, 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 = {2022}, 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 = {}, number = {}, pages = {}, doi = {10.1136/thorax-2021-217862}, pmid = {36357176}, issn = {1468-3296}, 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 = {}, number = {}, pages = {}, doi = {10.1093/carcin/bgac089}, pmid = {36355620}, issn = {1460-2180}, 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 were 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 = {2022}, 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 = {}, number = {}, pages = {}, doi = {10.1002/ijc.34339}, pmid = {36305648}, issn = {1097-0215}, support = {C8221/A29017//Cancer Research UK/United Kingdom ; 14136//Cancer Research UK/United Kingdom ; MR/M012190/1//Medical Research Council/United Kingdom ; 1000143//Medical Research Council/United Kingdom ; }, 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 = {MC_UU_00025/5 (RG94521)/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}, 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}, 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}, 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}, 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 = {NIH-R03 CA180548/NH/NIH HHS/United States ; 3P42ES023720-04S2/NH/NIH HHS/United States ; 1P30 ES013508-02/NH/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/cm[2]). 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 = {0970-258X}, 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 = {2022}, 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 = {}, number = {}, pages = {}, doi = {10.1016/j.amjms.2022.07.008}, pmid = {35940275}, issn = {1538-2990}, 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}, 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}, 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 = {CA148805/CA/NCI NIH HHS/United States ; CA06927/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}, 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}, 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}, 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}, doi = {10.1002/gcc.23074}, pmid = {35665561}, issn = {1098-2264}, 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}, 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}, 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}, 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}, 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 = {2022}, 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 = {}, number = {}, pages = {}, doi = {10.1136/thoraxjnl-2021-218214}, pmid = {35410957}, issn = {1468-3296}, 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}, 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}, doi = {10.1016/S1470-2045(22)00061-4}, pmid = {35358455}, issn = {1474-5488}, mesh = {Adolescent ; Adult ; Arthrogryposis ; Cholestasis ; Humans ; *Immunoconjugates/adverse effects ; Maytansine/analogs &amp; derivatives ; Mesothelin ; *Mesothelioma, Malignant/drug therapy ; Neoplasm Recurrence, Local/pathology ; Renal Insufficiency ; 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}, 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}, 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}, 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}, 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 = {2022}, 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 = {}, number = {}, pages = {1-5}, doi = {10.1080/10803548.2022.2035510}, pmid = {35098897}, issn = {2376-9130}, 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}, 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 ; 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}, 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}, 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 = {2021}, 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 = {}, number = {}, pages = {}, doi = {10.1272/jnms.JNMS.2022_89-605}, pmid = {34840219}, issn = {1347-3409}, abstract = {INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma type mesothelioma, comprising about 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, this may not be useful for DMPM due to its desmoplastic nature and bland cellular atypia. We hereby report a case of DMPM diagnosed through autopsy along with its cytological features that have not been described previously.<br><br>CASE PRESENTATION: A male in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. Chest computed tomography scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. In autopsy, the scrape-imprint smear and the pleural effusions cytology were performed. The scrape-imprint smear samples exhibited spindle cells with mild nuclear atypia and grooves with fibrous stroma. In the pleural effusion cytology, spindle cells having mild nuclear atypia and grooves with loose epithelial connections were observed. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in cytological samples, thus rendering the diagnosis of DMPM. Diagnosis was confirmed by fluorescence in situ hybridization.<br><br>CONCLUSION: Cytological procedures, such as pleural effusion cytology and scrape-imprinting method, may be useful as an ancillary tool in the diagnosis of 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 ; Male ; Mesothelin ; *Mesothelioma, Malignant ; Pleural Effusion ; Prognosis ; }, 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}, 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}, 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}, 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}, 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}, 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}, 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 = {}, 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}, 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}, 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}, 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}, 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 ; MC_UP_A600_1024/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 ; 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 ; A21139/CRUK_/Cancer Research UK/United Kingdom ; PCL/18/06/CSO_/Chief Scientist Office/United Kingdom ; MC_UU_00025/7/MRC_/Medical Research Council/United Kingdom ; MC_EX_G0902052/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; A29252/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 ; }, 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}, 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}, 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}, 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}, 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}, 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}, 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}, 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 = {2021}, 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 = {}, number = {}, pages = {}, pmid = {34172838}, issn = {1559-064X}, 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 = {A17196/CRUK_/Cancer Research UK/United Kingdom ; A31287/CRUK_/Cancer Research UK/United Kingdom ; A29801/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}, 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}, 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}, 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}, 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}, doi = {10.1002/mc.23301}, pmid = {33872411}, issn = {1098-2744}, 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 ; }, 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}, 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}, 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 {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 ; }, 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 ; Whole 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}, 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}, 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}, doi = {10.1080/15287394.2021.1889424}, pmid = {33678145}, issn = {1528-7394}, 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 ; }, 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}, 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 ; }, 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 ; }, 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 ; }, }
@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}, 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 beyon