Pub Date : 2020-01-08DOI: 10.5772/intechopen.90763
Y. Nishimura, N. Kumagai-takei, Suni Lee, K. Yoshitome, T. Otsuki
Mesothelioma is the most serious of the asbestos-related diseases. It is caused by exposure to relatively low doses of asbestos and takes a long period to develop, which suggests the enactment of gradual adverse effects other than cellular toxicity. The immune system, which can play a role in tumor prevention, is a presumable target of asbestos by accumulation in lymph nodes and then slowly affecting functions of immune cells. Here, we describe key findings obtained from our studies concerning the immune-suppressive effects of asbestos and functional alteration in immune cells of patients with mesothelioma as well as plaque-positive subjects. Asbestos exposure of cell cultures resulted in decreased natural and acquired cytotoxicity exerted by NK cells and CTLs and the ability of Th1 cells to activate and support antitumor immunity. In contrast, asbestos exposure augmented Treg cell function and generation of fibrogenic/suppressive macrophages. Mesothelioma patients also showed similar characteristics in certain alterations caused by asbestos exposure. Additionally, our recent study established immunological screening devices for mesothelioma and asbestos exposure on the basis of comprehensive analysis of peripheral blood. Those findings underscore the importance of the immunological effects of asbestos and should assist further understanding of the mechanism and early detection of mesothelioma.
{"title":"Suppressed Immune System Caused by Exposure to Asbestos and Malignant Mesothelioma","authors":"Y. Nishimura, N. Kumagai-takei, Suni Lee, K. Yoshitome, T. Otsuki","doi":"10.5772/intechopen.90763","DOIUrl":"https://doi.org/10.5772/intechopen.90763","url":null,"abstract":"Mesothelioma is the most serious of the asbestos-related diseases. It is caused by exposure to relatively low doses of asbestos and takes a long period to develop, which suggests the enactment of gradual adverse effects other than cellular toxicity. The immune system, which can play a role in tumor prevention, is a presumable target of asbestos by accumulation in lymph nodes and then slowly affecting functions of immune cells. Here, we describe key findings obtained from our studies concerning the immune-suppressive effects of asbestos and functional alteration in immune cells of patients with mesothelioma as well as plaque-positive subjects. Asbestos exposure of cell cultures resulted in decreased natural and acquired cytotoxicity exerted by NK cells and CTLs and the ability of Th1 cells to activate and support antitumor immunity. In contrast, asbestos exposure augmented Treg cell function and generation of fibrogenic/suppressive macrophages. Mesothelioma patients also showed similar characteristics in certain alterations caused by asbestos exposure. Additionally, our recent study established immunological screening devices for mesothelioma and asbestos exposure on the basis of comprehensive analysis of peripheral blood. Those findings underscore the importance of the immunological effects of asbestos and should assist further understanding of the mechanism and early detection of mesothelioma.","PeriodicalId":136471,"journal":{"name":"Asbestos-related Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115843827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-09DOI: 10.5772/intechopen.89438
A. Franko, V. Dolžan, K. Goričar, M. Fikfak
Asbestos-related diseases, including asbestosis, benign pleural diseases, lung cancer, other types of cancer, and especially malignant mesothelioma (MM), still represent an enormous problem all over the world and are among the most investigated occupational diseases. Considering that MM is a highly aggressive and severe malignant cancer of pleura, peritoneum and other serosal surfaces, new blood biomarkers for earlier diagnosis, following response to treatment and disease progression, have been intensively investigated. Several studies suggested that soluble mesothelin-related peptides, fibulin-3, survivin, osteopontin, vimentin, calretinin, and many others could be helpful in diagnosis, detecting the progression of MM and evaluating tumour response to treatment; however, these biomarkers have not been validated in clinical practice. Therefore, search for novel better stand-alone or composite biomarkers is under way. The aim of this chapter is to present the importance of blood biomarkers in evaluating the risk of developing asbestos-related diseases, early diagnosis, following the response to treatment and progression of these diseases, with special emphasis on MM.
{"title":"Asbestos-Related Diseases and Blood Biomarkers","authors":"A. Franko, V. Dolžan, K. Goričar, M. Fikfak","doi":"10.5772/intechopen.89438","DOIUrl":"https://doi.org/10.5772/intechopen.89438","url":null,"abstract":"Asbestos-related diseases, including asbestosis, benign pleural diseases, lung cancer, other types of cancer, and especially malignant mesothelioma (MM), still represent an enormous problem all over the world and are among the most investigated occupational diseases. Considering that MM is a highly aggressive and severe malignant cancer of pleura, peritoneum and other serosal surfaces, new blood biomarkers for earlier diagnosis, following response to treatment and disease progression, have been intensively investigated. Several studies suggested that soluble mesothelin-related peptides, fibulin-3, survivin, osteopontin, vimentin, calretinin, and many others could be helpful in diagnosis, detecting the progression of MM and evaluating tumour response to treatment; however, these biomarkers have not been validated in clinical practice. Therefore, search for novel better stand-alone or composite biomarkers is under way. The aim of this chapter is to present the importance of blood biomarkers in evaluating the risk of developing asbestos-related diseases, early diagnosis, following the response to treatment and progression of these diseases, with special emphasis on MM.","PeriodicalId":136471,"journal":{"name":"Asbestos-related Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115526923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-13DOI: 10.5772/intechopen.89247
Y. Kawabata
The progression of asbestosis is supposed to begin with the first order of respiratory bronchiole and extend outward. Recently, grade 4 asbestosis was reported to begin with the subpleural peripheral lobular area or the subpleural lobule. Grade 4 asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive numbers of asbestos fibers. Pathologically, the presence of more than two asbestos bodies/cm 2 on a glass slide is required. There are many cases of diffuse interstitial pneumonia, mainly usual interstitial pneumonia, that does not fulfill the above criteria among asbestos workers or high-grade environmentally exposed persons. I call these cases “usual interstitial pneumonia seen in asbestos workers” and not idiopathic pulmonary fibrosis. In this chapter, I discuss the above subjects, including the dose-response relationship for asbestos exposure, the heterogeneous response to asbestos exposure, and the relationship between asbestosis and idiopathic pulmonary fibrosis.
{"title":"Asbestos Exposure Results in Asbestosis and Usual Interstitial Pneumonia Similar to Other Causes of Pneumoconiosis","authors":"Y. Kawabata","doi":"10.5772/intechopen.89247","DOIUrl":"https://doi.org/10.5772/intechopen.89247","url":null,"abstract":"The progression of asbestosis is supposed to begin with the first order of respiratory bronchiole and extend outward. Recently, grade 4 asbestosis was reported to begin with the subpleural peripheral lobular area or the subpleural lobule. Grade 4 asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive numbers of asbestos fibers. Pathologically, the presence of more than two asbestos bodies/cm 2 on a glass slide is required. There are many cases of diffuse interstitial pneumonia, mainly usual interstitial pneumonia, that does not fulfill the above criteria among asbestos workers or high-grade environmentally exposed persons. I call these cases “usual interstitial pneumonia seen in asbestos workers” and not idiopathic pulmonary fibrosis. In this chapter, I discuss the above subjects, including the dose-response relationship for asbestos exposure, the heterogeneous response to asbestos exposure, and the relationship between asbestosis and idiopathic pulmonary fibrosis.","PeriodicalId":136471,"journal":{"name":"Asbestos-related Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131521342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-05DOI: 10.5772/intechopen.89116
N. Fujimoto
Targeting immunocheckpoint with immunomodulatory monoclonal antibodies has proven to be an effective antitumor strategy across a variety of cancers. The immunosuppressive tumor microenvironment in malignant pleural mesothelioma (MPM) has suggested that MPM might benefit from this kind of immunotherapy. In recent years, immunocheckpoint inhibitors (ICIs) have shown encouraging results for patients with MPM. Antibodies against programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) have demonstrated favorable response, progression-free survival, and overall survival. The toxicity profiles were similar to those observed with ICIs in other malignancies, like melanoma and non-small cell lung cancer, and they appeared to be manageable. Nivolumab, an anti-PD-1 antibody, was approved in Japan for advanced or metastatic MPM patients resistant or intolerant to other chemotherapies. Important future issues include developing a combination therapy, where ICIs are combined with other agents (including other ICIs), and developing biomarkers for determining which patients might respond well and which might experience unacceptable toxicities. first-line therapy in unresectable MPM. The primary endpoint of the study, OS, will be reported in the near future.
{"title":"Immunocheckpoint Blockade in Malignant Pleural Mesothelioma","authors":"N. Fujimoto","doi":"10.5772/intechopen.89116","DOIUrl":"https://doi.org/10.5772/intechopen.89116","url":null,"abstract":"Targeting immunocheckpoint with immunomodulatory monoclonal antibodies has proven to be an effective antitumor strategy across a variety of cancers. The immunosuppressive tumor microenvironment in malignant pleural mesothelioma (MPM) has suggested that MPM might benefit from this kind of immunotherapy. In recent years, immunocheckpoint inhibitors (ICIs) have shown encouraging results for patients with MPM. Antibodies against programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) have demonstrated favorable response, progression-free survival, and overall survival. The toxicity profiles were similar to those observed with ICIs in other malignancies, like melanoma and non-small cell lung cancer, and they appeared to be manageable. Nivolumab, an anti-PD-1 antibody, was approved in Japan for advanced or metastatic MPM patients resistant or intolerant to other chemotherapies. Important future issues include developing a combination therapy, where ICIs are combined with other agents (including other ICIs), and developing biomarkers for determining which patients might respond well and which might experience unacceptable toxicities. first-line therapy in unresectable MPM. The primary endpoint of the study, OS, will be reported in the near future.","PeriodicalId":136471,"journal":{"name":"Asbestos-related Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132362677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-19DOI: 10.5772/INTECHOPEN.88783
Shibo Ying, Yanbin Wang, Lyuyang Lyu
Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is primary induced by exposure to asbestos fibers. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in metastasis, and their overexpression correlates with tumor cell invasion and metastasis because they degrade the extracellular matrix (ECM) and process adhesion and cytoskeletal proteins, growth factors, chemokines, and cytokines. Recent evidence has shown that MMPs participate in MM progression, indicating that they are potential novel biomarkers and attractive targets for cancer therapy. In this chapter, we will describe MMPs in carcinogenic mechanisms based on in vivo and in vitro experimental evidence, outline the clinical findings, and speculate the possible roles of MMPs in MM.
{"title":"Potential Roles of Matrix Metalloproteinases in Malignant Mesothelioma","authors":"Shibo Ying, Yanbin Wang, Lyuyang Lyu","doi":"10.5772/INTECHOPEN.88783","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.88783","url":null,"abstract":"Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is primary induced by exposure to asbestos fibers. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in metastasis, and their overexpression correlates with tumor cell invasion and metastasis because they degrade the extracellular matrix (ECM) and process adhesion and cytoskeletal proteins, growth factors, chemokines, and cytokines. Recent evidence has shown that MMPs participate in MM progression, indicating that they are potential novel biomarkers and attractive targets for cancer therapy. In this chapter, we will describe MMPs in carcinogenic mechanisms based on in vivo and in vitro experimental evidence, outline the clinical findings, and speculate the possible roles of MMPs in MM.","PeriodicalId":136471,"journal":{"name":"Asbestos-related Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126621244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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