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1.
Rev. Asoc. Méd. Argent ; 132(4): 15-19, dic. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1087168

RESUMO

El mesotelioma difuso es una neoplasia maligna poco frecuente que proviene de las células mesoteliales; la pleura es su localización más habitual y se estima que un 10% de los casos se localizan a nivel peritoneal. El mesotelioma es habitualmente diagnosticado en la quinta década de la vida, con un claro predominio en el sexo masculino, debido esto último a su relación con la exposición laboral al asbesto. Se expone un caso con factores de riesgo y diagnóstico asociado. (AU)


Diffuse mesothelioma is a rare malignant neoplasm that comes from mesothelial cells; the pleura are the most common location and is estimated that 10% of the cases are located at the peritoneal level. Mesothelioma is usually diagnosed in the fifth decade of life, with a clear predominance in the male sex, due to its relation to occupational exposureto asbestos. A case is presented with risk factors and associated diagnosis. (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Mesotelioma/etiologia , Mesotelioma/diagnóstico por imagem , Asbestos/efeitos adversos , Diagnóstico Diferencial , Mesotelioma/terapia , Estadiamento de Neoplasias
2.
Ig Sanita Pubbl ; 75(4): 303-312, 2019.
Artigo em Italiano | MEDLINE | ID: mdl-31887736

RESUMO

The term asbestos refers to six unique fibrous minerals mostly used in the production of asbestos cement sheets and pipes. According to the World Health Organization and the International Agency for Research on Cancer (IARC), there exists at least "sufficient evidence" that all types of asbestos may cause cancer in humans (mesothelioma, lung cancer, laryngeal tumor and ovarian cancer). The only asbestos limit in drinking water is 7 million fiber/liter. This study is a narrative synthesis about the possible hazards to human health related to the presence of asbestos in drinking water. The various scientific studies and epidemiological reports examined highlight that there is an ongoing debate on the possible carcinogenic risk associated with asbestos exposure through ingestion. Nevertheless, considering the latency with which diseases caused by asbestos may emerge, control measures should be adopted.


Assuntos
Asbestos/efeitos adversos , Água Potável/análise , Exposição Ambiental/efeitos adversos , Poluentes Químicos da Água/toxicidade , Asbestos/toxicidade , Carcinógenos , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Mesotelioma/etiologia , Mesotelioma/prevenção & controle
3.
EBioMedicine ; 48: 191-202, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31648983

RESUMO

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options. METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples. FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series. INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.


Assuntos
Suscetibilidade a Doenças , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Mesotelioma/diagnóstico , Mesotelioma/etiologia , Neovascularização Patológica/imunologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/etiologia , Microambiente Tumoral/imunologia , Biomarcadores Tumorais , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Transcriptoma
4.
Mutat Res ; 781: 1-10, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31416570

RESUMO

Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/etiologia , Mesotelioma/etiologia , Animais , Asbestos/toxicidade , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Exposição Ambiental/efeitos adversos , Mutação em Linhagem Germinativa/efeitos dos fármacos , Mutação em Linhagem Germinativa/genética , Humanos , Neoplasias Pulmonares/induzido quimicamente , Mesotelioma/induzido quimicamente , Fatores de Risco
5.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31455014

RESUMO

In light of the promising results of immune checkpoint blockade (ICPB) in malignant pleural mesothelioma (MPM), we investigated the effect of different chemotherapeutic agents on the expression of immune checkpoints (ICPs) in order to rationally design a good treatment schedule for their combination with ICP blocking antibodies. Cisplatin, oxaliplatin and pemetrexed are interesting chemotherapeutic agents to combine with immunotherapy given their immunomodulatory capacities. We looked into cisplatin and pemetrexed because their combination is used as first-line treatment of MPM. Additionally, the effect of the immunogenic chemotherapeutic agent, oxaliplatin, was also studied. Three different MPM cell lines were used for representation of both epithelioid and sarcomatoid subtypes. The desired inhibitory concentrations of the chemotherapeutic agents were determined with the SRB-assay. Allogeneic co-cultures of MPM cells with healthy donor peripheral blood mononuclear cells (PBMC) were set up to assess the effect of these chemotherapeutic agents on the expression of ICPs (PD-1, LAG-3, TIM-3) and their ligands (PD-L1, PD-L2, galectin-9). Cisplatin might be a promising treatment to combine with ICP blocking antibodies since our MPM cell lines were most susceptible to this stand-alone treatment. We found that the expression of ICPs and their ligands on both MPM cells and PBMC was mostly downregulated or unaltered when treated with chemotherapeutic agents, though no clear trend could be determined.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Mesotelioma/etiologia , Mesotelioma/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/antagonistas & inibidores , Linhagem Celular Tumoral , Terapia Combinada , Expressão Gênica , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mesotelioma/patologia , Mesotelioma/terapia , Terapia de Alvo Molecular , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
6.
Occup Med (Lond) ; 69(5): 342-351, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31375830

RESUMO

BACKGROUND: Long-term health outcomes in cohorts of workers from the electricity supply industry have been studied. AIMS: The aim of the study was to examine updated cancer incidence findings among a cohort of UK electricity generation and transmission workers. METHODS: Cancer morbidity experienced by 81 616 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2015. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated based on national rates. RESULTS: Overall cancer morbidity was slightly below expectation in males. Significant excesses were found in male workers for mesothelioma (observed [Obs] 763, SRR 326), skin cancer (non-melanoma) (Obs 5616, SRR 106), and prostate cancer (Obs 4298, SRR 106), and in female workers for cancer of the small intestine (Obs 13, SRR 220), nasal cancer (Obs 11, SRR 407), and breast cancer (Obs 758, SRR 110). More detailed analyses showed important contrasts, particularly for mesothelioma, lung cancer, skin cancer, prostate cancer and breast cancer. CONCLUSIONS: A clear occupational excess of mesothelioma was not matched by a corresponding excess of asbestos-induced lung cancer. Confident interpretation of the excesses of cancers of the nasal cavities and small intestine is not possible, although occupational exposures received in this industry may well not be involved. An excess of skin cancer in transmission workers may be associated with outdoor working.


Assuntos
Neoplasias/epidemiologia , Doenças Profissionais/epidemiologia , Centrais Elétricas , Asbestos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Neoplasias/etiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Reino Unido/epidemiologia
7.
J Exp Clin Cancer Res ; 38(1): 349, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399037

RESUMO

BACKGROUND: Over the past decade, newly designed cancer therapies have not significantly improved the survival of patients diagnosed with Malignant Pleural Mesothelioma (MPM). Among a limited number of genes that are frequently mutated in MPM several of them encode proteins that belong to the HIPPO tumor suppressor pathway. METHODS: The anticancer effects of the top flower standardized extract of Filipendula vulgaris (Dropwort) were characterized in "in vitro" and "in vivo" models of MPM. At the molecular level, two "omic" approaches were used to investigate Dropwort anticancer mechanism of action: a metabolomic profiling and a phosphoarray analysis. RESULTS: We found that Dropwort significantly reduced cell proliferation, viability, migration and in vivo tumor growth of MPM cell lines. Notably, Dropwort affected viability of tumor-initiating MPM cells and synergized with Cisplatin and Pemetrexed in vitro. Metabolomic profiling revealed that Dropwort treatment affected both glycolysis/tricarboxylic acid cycle as for the decreased consumption of glucose, pyruvate, succinate and acetate, and the lipid metabolism. We also document that Dropwort exerted its anticancer effects, at least partially, promoting YAP and TAZ protein ubiquitination. CONCLUSIONS: Our findings reveal that Dropwort is a promising source of natural compound(s) for targeting the HIPPO pathway with chemo-preventive and anticancer implications for MPM management.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Metabolismo Energético/efeitos dos fármacos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Mesotelioma/etiologia , Mesotelioma/metabolismo , Extratos Vegetais/farmacologia , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Filipendula/química , Humanos , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Camundongos , Extratos Vegetais/química , Ligação Proteica
8.
CA Cancer J Clin ; 69(5): 402-429, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31283845

RESUMO

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/análise , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Pneumonectomia/métodos , Asbestos/efeitos adversos , Austrália/epidemiologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Carcinogênese/patologia , Terapia Combinada/métodos , Erros de Diagnóstico , Europa (Continente)/epidemiologia , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Carga Global da Doença , Humanos , Incidência , Exposição por Inalação/efeitos adversos , Cooperação Internacional , Mesotelioma/diagnóstico , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Terapia de Alvo Molecular/métodos , Exposição Ocupacional/efeitos adversos , Pleura/efeitos dos fármacos , Pleura/patologia , Pleura/cirurgia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/etiologia , Prognóstico , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Estados Unidos/epidemiologia
9.
Occup Environ Med ; 76(8): 545-553, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285358

RESUMO

OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy. METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education. RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency. CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.


Assuntos
Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Mesotelioma/epidemiologia , Neoplasias Peritoneais/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Mesotelioma/etiologia , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Neoplasias Peritoneais/etiologia
10.
Health Phys ; 117(2): 187-192, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31225828

RESUMO

A cluster of nine mesothelioma cases was observed among 341 registrants' deaths in the US Transuranium and Uranium Registries. Descriptive analysis showed that mesothelioma cases had the highest average cumulative external radiation dose compared with lung cancer, other cancer, and noncancer deaths. Further analysis indicated that the mesothelioma cluster was very different demographically from lung cancer, other cancer, and noncancer deaths. Therefore, an internally matched case-control approach was applied to evaluate the differences in an average cumulative external radiation dose between mesothelioma deaths and other causes of death. A Monte Carlo t test was used to examine the statistical significance of the differences. The results showed that there were no significant statistical differences in an average cumulative external radiation dose between mesothelioma and lung cancer, other cancers, or noncancers for the internally matched cases and controls.


Assuntos
Neoplasias Pulmonares/etiologia , Mesotelioma/etiologia , Método de Monte Carlo , Neoplasias Induzidas por Radiação/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Urânio/envenenamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/patologia , Doenças Profissionais/patologia , Doses de Radiação , Sistema de Registros/estatística & dados numéricos , Urânio/análise
12.
Ann Ist Super Sanita ; 55(1): 80-89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968842

RESUMO

Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.


Assuntos
Amianto Amosita/efeitos adversos , Asbestose/epidemiologia , Recuperação e Remediação Ambiental/métodos , Neoplasias/epidemiologia , Adolescente , Adulto , Idoso , Asbestos , Asbestose/mortalidade , Criança , Surtos de Doenças , Feminino , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Mesotelioma/mortalidade , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Neoplasias/mortalidade , Exposição Ocupacional/estatística & dados numéricos , Adulto Jovem
13.
Ann Ist Super Sanita ; 55(1): 90-93, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968843

RESUMO

The study entitled "Candido's List" (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to "virtually' enter the remaining worksites and listen to these spaces "tell" their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.


Assuntos
Amianto Amosita/efeitos adversos , Mesotelioma/epidemiologia , Neoplasias Pleurais/epidemiologia , Amianto Amosita/história , Recuperação e Remediação Ambiental , Feminino , História do Século XIX , Humanos , Itália , Magnésio/efeitos adversos , Óxido de Magnésio/efeitos adversos , Masculino , Mesotelioma/etiologia , Mesotelioma/história , Doenças Profissionais/etiologia , Doenças Profissionais/história , Exposição Ocupacional , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/história
14.
Radiol Oncol ; 53(2): 206-212, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30893058

RESUMO

Background Malignant mesothelioma (MM) is a rare aggressive tumour of mesothelium caused by asbestos exposure. It has been suggested that the genetic variability of proteins involved in DNA repair mechanisms affects the risk of MM. This study investigated the influence of functional polymorphisms in ERCC1 and XRCC1 genes, the interactions between these polymorphisms as well as the interactions between these polymorphisms and asbestos exposure on MM risk. Patients and methods In total, 237 cases with MM and 193 controls with no asbestos-related disease were genotyped for ERCC1 and XRCC1 polymorphisms. Results ERCC1 rs3212986 polymorphism was significantly associated with a decreased risk of MM (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.41-0.91; p = 0.014). No associations were observed between other genetic polymorphisms and MM risk. Interactions between polymorphisms did not significantly influence MM risk. Interaction between ERCC1 rs11615 and asbestos exposure significantly influenced MM risk (OR = 3.61; 95% CI = 1.12-11.66; p = 0.032). Carriers of polymorphic ERCC1 rs11615 allele who were exposed to low level of asbestos had a decreased risk of MM (OR = 0.40; 95% CI = 0.19-0.84; p = 0.016). Interactions between other polymorphisms and asbestos exposure did not significantly influence MM risk. Conclusions Our findings suggest that the genetic variability of DNA repair mechanisms could contribute to the risk of developing MM.


Assuntos
Reparo do DNA , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Variação Genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , Polimorfismo Genético , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Idoso , Asbestos/toxicidade , Carcinógenos/toxicidade , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Mesotelioma/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco
15.
Occup Environ Med ; 76(6): 407-413, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30804166

RESUMO

OBJECTIVE: To examine the risk of malignant mesothelioma (MM) in former pupils who attended primary school near an asbestos cement plant. METHODS: A cohort of 12 111 former pupils, born 1940-1970, was established from individual historical records from four primary schools located at a distance of 100-750 m in the prevailing wind direction from an asbestos cement plant operating from 1928 to 1984 in Aalborg, Denmark. The school cohort and a comparison cohort consisting of 108 987 gender and 5-year frequency-matched subjects were followed up (2015) for MM in the Danish Cancer Registry. Using Cox regression, HRs were estimated for the incidence of MM. Adjustments for occupational and familial asbestos exposure were made with a job exposure matrix. An SIR analysis including latency periods testing the cancer incidence rate was performed with the comparison cohort as the reference rate. RESULTS: The median person-years of follow-up were 62.5 years in the school cohort and 62.2 years in the comparison cohort. There were 32 males and 6 females of the former pupils who developed MM during the follow-up: HRmale 7.01 (95% CI 4.24 to 11.57), HRfemale 7.43 (95% CI 2.50 to 22.13). Those who attended school 250 m north of the plant had the highest HR for MM, 10.65 (95% Cl 5.82 to 19.48). No significant trend between school distance and risk of MM was established (p=0.35). CONCLUSION: Our results suggest that boys and girls who attended schools and lived in the neighbourhood of an asbestos cement plant later in life have a significantly increased risk of MM.


Assuntos
Asbestos/efeitos adversos , Mesotelioma/etiologia , Medição de Risco/métodos , Idoso , Estudos de Coortes , Dinamarca/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/epidemiologia , Metalurgia/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos
16.
Cancer Sci ; 110(3): 1076-1084, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30618090

RESUMO

Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause-specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos-related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow-up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long-term residents' cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10-1.13) in men and 1.07 (95% CI, 1.06-1.09) in women; lung cancer, 1.28 (95% CI, 1.23-1.34) in men and 1.23 (95% CI, 1.14-1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83-7.78) in men and 14.99 (95% CI, 12.34-18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long-term residents' cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades.


Assuntos
Asbestos/efeitos adversos , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Asbesto Crocidolita/efeitos adversos , Asbestos Serpentinas/efeitos adversos , Estudos de Coortes , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Pessoa de Meia-Idade , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/etiologia
17.
Int J Surg Pathol ; 27(4): 427-431, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30522362

RESUMO

Multilocular peritoneal inclusion cysts are mesothelial tumor-like lesions with or without small foci of florid papillary mesothelial hyperplasia that might simulate serous epithelial papillary lesions or well-differentiated papillary mesothelioma (WDPM) of the peritoneum. The papillary cores in papillary mesothelial hyperplasia and in WDPM display a variety of different histomorphologic features. To our knowledge, collagenous spherulosis in WDPM was not previously described or illustrated in the literature. Collagen spherules have been described in several miscellaneous benign and malignant lesions of the breast, prostate, salivary gland, and cutaneous adnexal tumors. They sometimes impose a diagnostically challenging cribriform growth pattern. We report a case of a young adult woman who presented with a large painful palpable multicystic mass in the right iliac fossa and pelvis. Histologically, it showed features of multilocular peritoneal inclusion cysts with an incidental finding of a small nodule demonstrating morphologic and immunohistochemical features of WDPM. The papillary cores revealed uniform homogenous eosinophilic round collagenous spheres with a cribriform pattern. The unusual finding of collagen spherules may expand the morphologic spectrum of mesothelial papillary lesions, the differential diagnosis of female pelvic peritoneal and omental epithelial and nonepithelial lesions and might cause some diagnostic confusion on small specimens. It may also shed some light on the pathophysiology and role of mesothelial and submesothelial stromal cells in the variable morphologic patterns of the stroma of papillary cores in different mesothelial lesions.


Assuntos
Colágeno/metabolismo , Cistos/complicações , Mesotelioma/diagnóstico , Neoplasias Peritoneais/diagnóstico , Peritônio/patologia , Adulto , Biomarcadores Tumorais/análise , Cistos/patologia , Cistos/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Achados Incidentais , Laparoscopia , Mesotelioma/etiologia , Mesotelioma/patologia , Mesotelioma/cirurgia , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Peritônio/diagnóstico por imagem , Peritônio/cirurgia , Tomografia Computadorizada por Raios X , Ultrassonografia
18.
J Thorac Oncol ; 14(3): 527-539, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30408567

RESUMO

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people. METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas. RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or excluding methylation, showed a significant increase in case/control discrimination when considering DNA methylation together with asbestos exposure (AUC = 0.81 versus AUC = 0.89, DeLong's test p = 0.0013). CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.


Assuntos
Asbestos/efeitos adversos , Biomarcadores Tumorais/genética , Metilação de DNA , DNA/sangue , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Exposição Ocupacional/efeitos adversos , Neoplasias Pleurais/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Carcinógenos/toxicidade , Estudos de Casos e Controles , DNA/química , DNA/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/sangue , Mesotelioma/etiologia , Mesotelioma/patologia , Neoplasias Pleurais/sangue , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Prognóstico , Curva ROC
19.
Toxicol Appl Pharmacol ; 361: 168-170, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30563645

RESUMO

The mining of crocidolite at Wittenoom from 1943 to 1966 is infamous due to the adverse health outcomes in the mining and milling workforce and the non-mining residents and families. Proportional latency risk analysis provided estimates that 6% of the mine workforce along with 1.9% of women and 1.1% of children residents who were environmentally exposed, have or will die from mesothelioma. The absence of environmental exposure data relevant to the period restricts the extrapolation of these historical risk outcomes being applied to the low level exposures from natural contaminant crocidolite and other amphibole fibres experienced in contemporary mining practices in the Pilbara region.


Assuntos
Asbesto Crocidolita/toxicidade , Exposição Ambiental/estatística & dados numéricos , Exposição por Inalação/análise , Mineração , Exposição Ocupacional/estatística & dados numéricos , Adulto , Asbestos/análise , Asbesto Crocidolita/análise , Austrália/epidemiologia , Criança , Poeira/análise , Feminino , Humanos , Indústrias , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Medição de Risco , Recursos Humanos
20.
BMJ Open ; 8(12): e021063, 2018 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-30530573

RESUMO

OBJECTIVE: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency. METHODS: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years. RESULTS: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ≥30 years, and the shipbuilding industry presented a significant eRR given a latency ≥40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed. CONCLUSIONS: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.


Assuntos
Asbestos/efeitos adversos , Instalações Industriais e de Manufatura/estatística & dados numéricos , Mesotelioma/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Neoplasias Pleurais/epidemiologia , Análise por Conglomerados , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/etiologia , Doenças Profissionais/etiologia , Neoplasias Pleurais/etiologia , Estudos Retrospectivos , Risco , Taiwan
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