Asbestos Exposure Research Articles

Do patterns of past asbestos use and production reflect current geographic variations of cancer risk?: mesothelioma in Ontario and British Columbia, Canada

PurposeCanada 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.MethodsWe 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.ResultsRegional 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.ConclusionThis 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.

BRCA1 haploinsufficiency impairs iron metabolism to promote chrysotile-induced mesothelioma via ferroptosis resistance.

Malignant mesothelioma (MM) is still a social burden associated with asbestos exposure. Local iron accumulation thereby represents the major pathogenesis, followed by oxidative DNA strand breaks and genomic alterations in the mesothelium. BRCA1 is a critical component of homologous recombination repair directed to DNA double-stranded breaks, whereas BRCA1 germline mutation is an established risk for breast/ovarian cancer, its role in MM development remains to be elucidated. Murine Brca1 mutant models so far have not reproduced human phenotypes. However, a rat Brca1 mutant model (Mut; L63X/+ ) recently reproduced them at least partially. Here we describe the differential induction of MM in Brca1 mutant rats by intraperitoneal injection of chrysotile or crocidolite. Only Mut males injected with chrysotile revealed a promotional effect on mesothelial carcinogenesis in comparison with wild-type and/or females, with all the MMs Brca1 haploinsufficient. Array-based comparative genomic hybridization of MMs disclosed a greater extent of chromosomal deletions in Brca1 mutants, including Cdkn2a/2b accompanied by Tfr2 amplification, in comparison with wild-type tumors. Mutant MMs indicated iron metabolism dysregulation, such as an increase in catalytic Fe(II) and Ki67-index as well as a decrease in Fe(III) and ferritin expression. Simultaneously, mutant MMs revealed ferroptosis resistance by upregulation of Slc7A11 and Gpx4. At an early carcinogenic stage of 4 weeks, induced Brca1 expression in mesothelial cells was significantly suppressed in chrysotile/Mut in comparison with crocidolite/Mut, whereas significant preference to iron with a decrease in Fe(III) has been already established. In conclusion, chrysotile exposure can be a higher risk for MM in BRCA1 mutant males, considering the rat results.

The assessment of asbestos exposure of mesothelioma cases registered in Italy: which problems more than thirty years after the birth of the first regional archives

More than 30 years have passed since the beginning of the epidemiological surveillance of mesothelioma (MM). The Italian National Mesothelioma Register (ReNaM), part of the research department of the National Institute for insurance against industrial injuries (INAIL), has published 7 reports with the description of the cas-es concerning the assessment of diagnoses and exposures to asbestos suffered mainly during working activities but also environmental, in the family premises and during personal activities.Today we are witnessing a reduction in the commitment by some regions which negatively affects those who develop the pathology. Reading the ReNaM reports it emerges, among others, the problem of the delay in reporting new cases which limits the collection of information directly from patients. This contribution, discussing various topics, invites to develop a debate that should allow to update and resolve the critical aspects that arise after decades of activity regarding, in particular, the asbestos exposure assessment. It is the primary interest of the authors to give continuity and improve the ReNaM which remains the most prestigious MM register among those active in other countries.

Asbestos Fibers Enhance the TMEM16A Channel Activity in Xenopus Oocytes.

The interaction of asbestos fibers with target cell membranes is still poorly investigated. Here, we detected and characterized an enhancement of chloride conductance in Xenopus oocyte cell membranes induced by exposure to crocidolite (Croc) asbestos fibers. A two-microelectrode voltage clamp technique was used to test the effect of Croc fiber suspensions on outward chloride currents evoked by step membrane depolarization. Calcium imaging experiments were also performed to investigate the variation of 'resting' oocyte [Ca2+]i following asbestos exposure. The increase in chloride current after asbestos treatment, was sensitive to [Ca2+]e, and to specific blockers of TMEM16A Ca2+-activated chloride channels, MONNA and Ani9. Furthermore, asbestos treatment elevated the 'resting' [Ca2+]i likelihood by increasing the cell membrane permeability to Ca2 in favor of a tonic activation of TMEME16A channels. Western blot analysis confirmed that TMEME16A protein was endogenously present in the oocyte cell membrane and absorbed by Croc. the TMEM16A channels endogenously expressed by Xenopus oocytes are targets for asbestos fibers and represent a powerful tool for asbestos-membrane interaction studies. Interestingly, TMEM16A channels are highly expressed in many types of tumors, including some asbestos-related cancers, suggesting them, for the first time, as a possible early target of crocidolite-mediated tumorigenic effects on target cell membranes.

YAP/TAZ activation predicts clinical outcomes in mesothelioma and is conserved in in vitro model of driver mutations.

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.

MiR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV

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. 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. 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. Conclusion: This study proposed that the miR-142-3p/ITGAV axis is involved in tumor progression in malignant mesothelioma.

Malignant mesothelioma in two married couples exposed to asbestos

the relationship between past asbestos exposure and the onset of malignant mesothelioma (MM) is well established. However, defining the exposure is not always easy, as it occurs decades before the onset of the disease. this report describes four cases of MM diagnosed in two different married couples, both exposed to asbestos fibers: husbands at work and wives for cohabiting and washing their work overalls. case report. the information was collected through interviews using a semi-structured questionnaire and analyzed by occupational hygienists during the activity of epidemiological surveillance of this disease. The results of the mineral content of asbestos fibers performed on lung parenchymal from one of the female cases are available. these two cases show a longer latency in the lesser exposed confirming what an occupational epidemiological study has recently highlighted. whenever good quality information collected during interviews are available, skilled occupational hygienists are able to reconstruct past exposures in quali-quantitative terms.

Workers in Australian prebake aluminium smelters: update on risk of mortality and cancer incidence in the Healthwise cohort

ObjectivesTo investigate mortality and the rates of incident cancer among a cohort of aluminium industry workers.MethodsAmong 4507 male employees who worked in either of two Australian prebake smelters for at...

Asbestos Stocks and Flows Legacy in Australia

Information about asbestos stocks and flows is paramount for effective legacy management, both for understanding potential asbestos exposure risks from the different product types remaining in the built environment and proactive resource planning for their safe decommissioning, removal and disposal. This paper provides an overview of the Australian Stocks and Flows Model for Asbestos, a national model that provides best estimates to examine asbestos legacy stocks remaining in the built environment and flows to waste, now and into the future in Australia. The model was updated in 2021 to reflect new information from literature and input from industry experts and includes a Monte Carlo analysis to better reflect the range in the value estimates, as well as allowing for input of data from asbestos removal programs. Australia’s total asbestos stocks peaked at approximately 11 million tonnes in the 1980s. Over 95% of stocks comprise asbestos cement products, such as wall sheeting and water pipes. Australia’s current remaining asbestos stocks in the built environment are estimated at 6.2 million tonnes, with just under half of total consumption estimated to have gone to landfill as waste. The model can continue to be used with updated information to help track how much of Australia’s hazardous asbestos legacy is remaining and by how much it is reducing. The model can also be used to test scenarios and implications for predicted development trends and waste infrastructure needs. It is a valuable resource to assist with sustainable planning across a range of government departments that are responsible for managing asbestos waste in Australia.

Exposure to cosmetic talc and mesothelioma

AimMesothelioma 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.MethodsData 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.ResultsIn 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.ConclusionCumulative 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.

What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case–control study

BackgroundAsbestos has been hypothesised as the cause of the recent global increase in the incidence of ‘idiopathic’ pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association...

First Case of Abdominal and Tunica Vaginalis Multicystic Benign Mesothelioma: Management and Review of Literature.

Multicystic benign mesothelioma is a rare tumor that affects the serosa. Most cases present with peritoneal lesions exclusively. Some identified risk factors are chronic abdominal inflammation, woman of childbearing age, and asbestos exposure. The symptomatology is not specific and can delay the diagnosis. There are no guidelines for the treatment of this pathology. We describe one male patient with abdominal and tunica vaginalis localizations of multicystic benign mesothelioma. The diagnosis was suspected on imaging and confirmed with histological examination. The treatment on an expert center was complete cytoreduction surgery and HIPEC, but the patient had two recurrences during the 2-year of follow-up. This is the first case of simultaneous rare localizations of multicystic benign mesothelioma. No new risk factors were identified. The case underlines the importance of regular examination of all serosa localizations.

The Italian Experience in the Development of Mesothelioma Registries: A Pathway for Other Countries to Address the Negative Legacy of Asbestos.

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.

Mesotelioma epitelial maligno em vacas senis Sindi do Brasil

ABSTRACT: Mesotheliomas in cattle are often described as isolated case reports, and investigations of multiple cases within the same bovine herd are lacking. A series of cases of malignant epithelial mesothelioma, tubulopapilary type, is described in five 15 to 21-year-old Red Sindhi cows from the same herd. Clinical signs included three to eight months of progressive emaciation, dehydration, subcutaneous edema of the lower extremities, and abdominal distension. Grossly, severe subcutaneous edema and hydroperitoneum were noted. Multiple organs’ parietal and visceral serosal surfaces had multifocal to coalescing yellow, firm, sessile nodules ranging from 0.1 to 29.0cm. Similar free nodules floated in the peritoneal fluid. Histologically, the masses comprised a layer of cubic to columnar neoplastic cells forming papillary or cystic proliferation supported by a dense fibrovascular stroma. Neoplastic cells had strong and diffuse cytoplasmic immunolabeling for pan-cytokeratin but were negative for cytokeratin 7 and vimentin. Ultrastructurally, neoplastic cells had delicate microvilli and tight and anchoring junctions. Within the cytoplasm, a moderate amount of loose aggregate of intermediary filament with small mitochondria was observed. Epidemiological investigation evidenced endogamy in this herd. Asbestos exposure was not detected. The diagnosis was based on clinical, gross, histological, and immunohistochemical findings and confirmed by transmission electron microscopy features. A definitive underlying etiology remains unknown.

High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma.

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. 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. 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). 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.

Next Generation Sequencing for miRNA Detection on the Exhaled Breath Condensate: A Pilot Study.

Exhaled breath condensate (EBC) sampling has been suggested as a less-invasive and cost-effective method to detect biological macromolecules, including miRNA. To explore the feasibility of its use as a biomarker of early effects of asbestos exposure, we conducted a preliminary test on male volunteers by comparing the miRNA profile in the EBC and the plasma using 2 different sequencing platforms. Six male volunteers, all retired and unexposed to dust or fumes, participated in the test. RNA was extracted from 200 μL EBC samples and same-size plasma samples. Sample aliquots were processed in 2 laboratories using 2 different sequencing platforms: a MiSeq Illumina® platform and a more performing HiSeq Illumina® platform. The HiSeq3000® sequencing platform identified twice as many unique molecular indexes (UMI)-validated miRNA as the MiSeq® platform. The Spearman's correlation coefficient between EBC counts and plasma counts was significant in 5/6 subjects with either platform (MiSeq® = 0.128-0.508, P = .026-<.001; HiSeq® = 0.156-0.412, P = .001-<.001). The intraclass correlation coefficient confirmed the consistency of the miRNA profile over the 6 participants with both biospecimens. Exploring the agreement between the EBC and plasma samples with Bland-Altman plots showed that using the HiSeq3000® platform substantially improved the EBC miRNA detection rate. Our preliminary study confirms that, when using the HiSeq® sequencing platform, EBC sampling is a suitable, non-invasive method to detect the miRNA profile in healthy subjects.

Assessment of Asbestos Exposure Associated with a Brake Grinder

Assessment of Asbestos Exposure Associated with a Brake Grinder

Binary Classification of Malignant Mesothelioma: A Comparative Study

Malignant mesotheliomas are aggressive cancers that occur in the thin layer of tissue that covers most commonly the linings of the chest or abdomen. Though the cancer itself is rare and deadly, early diagnosis will help with treatment and improve outcomes. Mesothelioma is usually diagnosed in the later stages. Symptoms are similar to other, more common conditions. As such, predicting and diagnosing mesothelioma early is essential to starting early treatment for a cancer that is often diagnosed too late. The goal of this comprehensive empirical comparison is to determine the best-performing model based on recall (sensitivity). We particularly wish to avoid false negatives, as it is costly to diagnose a patient as healthy when they actually have cancer. Model training will be conducted based on k-fold cross validation. Random forest is chosen as the optimal model. According to this model, age and duration of asbestos exposure are ranked as the most important features affecting diagnosis of mesothelioma.

Distinguishing Occupational and Environmental Asbestos Exposures: Case Series

Distinguishing Occupational and Environmental Asbestos Exposures: Case Series

Association of Asbestos Exposure with Lung Cancer

Asbest, akciğer kanserine neden olduğu iyi bilinen bir mineraldir. Asbest ve akciğer kanseri arasındaki nedensel ilişki 1930'larda düşünülmüş ve 1955'te kanıtlanmıştır. 1960'lı yıllarda işçilerde mezotelyoma ve akciğer kanseri gibi durumların saptanmasıyla asbest kullanımı kısıtlanmaya ve yasaklanmaya başlamıştır. 20. yüzyılın ilk çeyreğinden sonra asbest, Dünya Sağlık Örgütü ve Uluslararası Kanser Araştırma Merkezi tarafından "Kanserojen Maddeler" listesinde 1A Grubu kanserojen olarak belirlenmiştir. Dünyada asbest işletmelerinin çoğu, asbestin insan sağlığına olumsuz etkileri nedeniyle doksanlı yılların sonundan itibaren faaliyetlerini durdurmuştur. Bugün tüm dünyada asbestin işletilmesi ve ticareti yasaklanmıştır.&#x0D; Gözle görülmeyen lifsi bir toz olan asbest, solunduğunda akciğerde birikir. Pürüzlü ve çengelli yapısı nedeniyle akciğerde doku hasarına neden olur. Epidemiyolojik çalışmalar, asbeste maruz kalmanın akciğer kanseri, mezotelyoma, gırtlak ve yumurtalık kanseri ve asbestoz gibi ölümcül sonuçlara yol açabilecek hastalıkların nedeni olduğunu kesin olarak ortaya koymuştur. Asbest temas noktaları çevresel temas ve mesleki (endüstriyel) maruziyettir ve asbest maruziyeti Türkiye'de önemli bir halk sağlığı sorunudur. Mezotelyoma, akciğer kanseri, asbestoz gibi ciddi akciğer hastalıklarını önlemek için asbest temizliği yetkili kişilerce yapılmalı ve doğal ortamlar rehabilite edilmelidir. Ayrıca kırsal alanlarda asbestin zararları konusunda toplumu bilinçlendirmeye yönelik eğitim faaliyetlerinin planlanması ve uygulanması gerekmektedir.