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Mesothelioma: HELP
Articles from Okayama-Kurashiki
Based on 60 articles published since 2008
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These are the 60 published articles about Mesothelioma that originated from Okayama-Kurashiki during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos. 2018

Kumagai-Takei, Naoko / Yamamoto, Shoko / Lee, Suni / Maeda, Megumi / Masuzzaki, Hidenori / Sada, Nagisa / Yu, Min / Yoshitome, Kei / Nishimura, Yasumitsu / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. kumagai@med.kawasaki-m.ac.jp. · Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. s.yamamoto@med.kawasaki-m.ac.jp. · Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. slee@med.kawasaki-m.ac.jp. · Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, 1-1-1 Tsushima-Naka, Kita-Ku, Okayama 700-8530, Japan. mmaeda@okayama-u.ac.jp. · Department of Life Science, Faculty of Life and Environmental Science, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan. hmatsuzaki@pu-hiroshima.ac.jp. · Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. nagisada@okayama-u.ac.jp. · Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. nagisada@okayama-u.ac.jp. · Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. yumin06@hotmail.com. · Department of Occupational and Environmental Health Science, School of Public Health, Peking University, 38 Xueyuan Road, Beijing 100191, China. yumin06@hotmail.com. · Department of Occupational Diseases, Zhejiang, Academy of Medical Sciences, 182 Tian Mu Shan Road, Zhejiang 310013, China. yumin06@hotmail.com. · Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. kei_y@med.kawasaki-m.ac.jp. · Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. yas@med.kawasaki-m.ac.jp. · Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, 1-1-1 Tsushima-Naka, Kita-Ku, Okayama 700-8530, Japan. takemi@med.kawasaki-m.ac.jp. ·Int J Mol Sci · Pubmed #29419731.

ABSTRACT: Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure.

2 Review Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos. 2017

Matsuzaki, Hidenori / Kumagai-Takei, Naoko / Lee, Suni / Maeda, Megumi / Sada, Nagisa / Hatayama, Tamayo / Yamamoto, Shoko / Ikeda, Miho / Yoshitome, Kei / Min, Yu / Nishimura, Yasumitsu / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan. · Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, 1-1-1 Tsushimanaka, Kita-Ku, Okayama, 700-8530, Japan. · Department of Occupational Diseases, Zhejiang Academy of Medical Sciences, 182 Tian Mu Shan Road, Zhejiang, 310013, People's Republic of China. · Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan. takemi@med.kawasaki-m.ac.jp. ·Environ Health Prev Med · Pubmed #29165150.

ABSTRACT: The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos exposure and asbestos-induced cancers and suggested the usefulness of serum/plasma IL-10 and TGF-β, surface CXCR3 expression in Tresp, the secreting potential of IFN-γ in Tresp, intracellular perforin level in CTL, and surface expression NKp46 in NK cells. Although other unexplored cytokines in serum/plasma and molecules in these immunological cells, including Th17, should be investigated by experimental procedures in addition to a comprehensive analysis of screening methods, biomarkers based on immunological alterations may be helpful in clinical situations to screen the high-risk population exposed to asbestos and susceptible to asbestos-related cancers such as mesothelioma.

3 Review Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients. 2015

Nishimura, Yasumitsu / Kumagai-Takei, Naoko / Matsuzaki, Hidenori / Lee, Suni / Maeda, Megumi / Kishimoto, Takumi / Fukuoka, Kazuya / Nakano, Takashi / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. · Laboratory of Functional Glycobiochemistry, Department of Biofunctional Chemistry, Division of Agricultural and Life Science, Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan. · Okayama Rosai Hospital, Okayama 702-8055, Japan. · Department of Respiratory Medicine, Hyogo College of Medicine, Nishimomiya 663-8501, Japan ; Department of Medical Oncology, Faculty of Medicine, Kinki University, Sayama 589-8511, Japan. · Department of Respiratory Medicine, Hyogo College of Medicine, Nishimomiya 663-8501, Japan. ·Biomed Res Int · Pubmed #26161391.

ABSTRACT: Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme(+) cells in CD8(+) lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8(+) lymphocytes may be stimulated by some kind of "nonself" cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma.

4 Review Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases. 2013

Nishimura, Yasumitsu / Maeda, Megumi / Kumagai-Takei, Naoko / Lee, Suni / Matsuzaki, Hidenori / Wada, Yasuhiko / Nishiike-Wada, Tamako / Iguchi, Hiroshi / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. yas@med.kawasaki-m.ac.jp ·Environ Health Prev Med · Pubmed #23463177.

ABSTRACT: Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. We focused on alveolar macrophages (AM) and natural killer (NK) cells in asbestosis and mesothelioma, respectively, and examined their functions upon exposure to asbestos or in patients with mesothelioma. Exposure to asbestos caused rat AM to exhibit high production of transforming growth factor-beta (TGF-β) with prolonged survival in the absence of other cells, not simultaneously with the apoptosis caused by asbestos. The NK cell line showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, and primary NK cells in culture with asbestos and peripheral blood NK cells in mesothelioma shared a decrease in expression of NKp46, a representative activating receptor. The AM finding indicates that AM contribute to asbestosis by playing a direct role in the fibrogenic response, as well as the inflammatory response. The response of NK cells indicates that exposure to asbestos has an immune-suppressive effect, as well as a tumorigenic effect. Our studies therefore reveal novel effects of asbestos exposure on AM and tumor immunity, which may represent valuable information for construction of a strategy for prevention and cure of asbestosis and malignant mesothelioma.

5 Review [Regarding the special feature of "the frontline of nanoparticle research": progress of the Study Group on Fibrous and Particulate Substances (SGFPS)]. 2012

Otsuki, Takemi / Hirano, Seishiro. ·Department of Hygiene, Kawasaki Medical School, Japan. takemi@med.kawasaki-m.ac.jp ·Nihon Eiseigaku Zasshi · Pubmed #22781011.

ABSTRACT: Among the symposia organized by various study groups in the Japanese Society of Hygiene (JSH), the Study Group on Fibrous and Particulate Substances (SGFPS) presented a symposium entitled "The frontline of nanoparticle research" chaired by Professor Takemi Otsuki (Kawasaki Medical School, Japan) and Dr. Seishiro Hirano (National Institute for Environmental Studies, Japan) on 26 March, 2012, as a part of the program of the 82nd Annual Meeting of JSH in Kyoto, Japan. Special features consist of three presentations given at the above-mentioned symposium. In this article, we introduce the progress of the Study Group on Fibrous and Particulate Substances (SGFPS) from the initial symposium entitled "Asbestos: Science and Society" held at the 76th Annual Meeting of JSH at Ube, Japan to the last above-mentioned symposium in Kyoto. The health-related issues caused by exposure to fibrous materials such as asbestos and also particulated substances such as nanoparticles will be lasting in the future and researchers including our study group have to make their best efforts to resolve these problems and to reduce health impairments due to exposure to environmental fibrous and particulated substances.

6 Review Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis. 2012

Matsuzaki, Hidenori / Maeda, Megumi / Lee, Suni / Nishimura, Yasumitsu / Kumagai-Takei, Naoko / Hayashi, Hiroaki / Yamamoto, Shoko / Hatayama, Tamayo / Kojima, Yoko / Tabata, Rika / Kishimoto, Takumi / Hiratsuka, Junichi / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan. ·J Biomed Biotechnol · Pubmed #22500091.

ABSTRACT: Asbestos causes lung fibrosis known as asbestosis as well as cancers such as malignant mesothelioma and lung cancer. Asbestos is a mineral silicate containing iron, magnesium, and calcium with a core of SiO(2). The immunological effect of silica, SiO(2), involves the dysregulation of autoimmunity because of the complications of autoimmune diseases found in silicosis. Asbestos can therefore cause alteration of immunocompetent cells to result in a decline of tumor immunity. Additionally, due to its physical characteristics, asbestos fibers remain in the lung, regional lymph nodes, and the pleural cavity, particularly at the opening sites of lymphatic vessels. Asbestos can induce chronic inflammation in these areas due to the production of reactive oxygen/nitrogen species. As a consequence, immunocompetent cells can have their cellular and molecular features altered by chronic and recurrent encounters with asbestos fibers, and there may be modification by the surrounding inflammation, all of which eventually lead to decreased tumor immunity. In this paper, the brief results of our investigation regarding reduction of tumor immunity of immunocompetent cells exposed to asbestos in vitro are discussed, as are our findings concerned with an investigation of chronic inflammation and analyses of peripheral blood samples derived from patients with pleural plaque and mesothelioma that have been exposed to asbestos.

7 Review Asbestos induces reduction of tumor immunity. 2011

Kumagai-Takei, Naoko / Maeda, Megumi / Chen, Ying / Matsuzaki, Hidenori / Lee, Suni / Nishimura, Yasumitsu / Hiratsuka, Junichi / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, Matsushima, Kurashiki, Japan. ·Clin Dev Immunol · Pubmed #22007251.

ABSTRACT: Asbestos-related cancers such as malignant mesothelioma and lung cancer are an important issue in the world. There are many conflicts concerning economical considerations and medical evidence for these cancers and much confusion regarding details of the pathological mechanisms of asbestos-induced cancers. For example, there is uncertainty concerning the degree of danger of the iron-absent chrysotile compared with iron-containing crocidolite and amosite. However, regarding bad prognosis of mesothelioma, medical approaches to ensure the recognition of the biological effects of asbestos and the pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect the early stage of mesothelioma, should result in better preventions and the cure of these malignancies. We have been investigating the immunological effects of asbestos in relation to the reduction of tumor immunity. In this paper, cellular and molecular approaches to clarify the immunological effects of asbestos are described, and all the findings indicate that the reduction of tumor immunity is caused by asbestos exposure and involvement in asbestos-induced cancers. These investigations may not only allow the clear recognition of the biological effects of asbestos, but also present a novel procedure for early detection of previous asbestos exposure and the presence of mesothelioma as well as the chemoprevention of asbestos-related cancers.

8 Review [Archives of "comprehensive approach on asbestos-related diseases" supported by the "special coordination funds for promoting science and technology (H18-1-3-3-1)"-- overview of group research project, care and specimen registration, cellular characteristics of mesothelioma and immunological effects of asbestos]. 2011

Otsuki, Takemi / Nakano, Takashi / Hasegawa, Seiki / Okada, Morihito / Tsujimura, Tohru / Sekido, Yoshitaka / Toyokuni, Shinya / Nishimoto, Hiroshi / Fukuoka, Kazuya / Tanaka, Fumihiro / Kumagai, Naoko / Maeda, Megumi / Nishimura, Yasumitsu. ·Department of Hygiene, Kawasaki Medical School, Matsushima, Japan. takemi@med.kawasaki-m.ac.jp ·Nihon Eiseigaku Zasshi · Pubmed #21701085.

ABSTRACT: The research project entitled "Comprehensive approach on asbestos-related diseases" supported by the "Special Coordination Funds for Promoting Science and Technology (H18-1-3-3-1)" began in 2006 and was completed at the end of the Japanese fiscal year of 2010. This project included four parts; (1) malignant mesothelioma (MM) cases and specimen registration, (2) development of procedures for the early diagnosis of MM, (3) commencement of clinical investigations including multimodal approaches, and (4) basic research comprising three components; (i) cellular and molecular characterization of mesothelioma cells, (ii) immunological effects of asbestos, and (iii) elucidation of asbestos-induced carcinogenesis using animal models. In this special issue of the Japanese Journal of Hygiene, we briefly introduce the achievements of our project. The second and third parts and the third component of the fourth part are described in other manuscripts written by Professors Fukuoka, Hasegawa, and Toyokuni. In this manuscript, we introduce a brief summary of the first part "MM cases and specimen registration", the first component of the fourth part "Cellular and molecular characterization of mesothelioma cells" and the second component of the fourth part "Immunological effects of asbestos". In addition, a previous special issue presented by the Study Group of Fibrous and Particulate Substances (SGFPS) (chaired by Professor Otsuki, Kawasaki Medical School, Japan) for the Japanese Society of Hygiene and published in Environmental Health and Preventive Medicine Volume 13, 2008, included reviews of the aforementioned first component of the fourth part of the project. Taken together, our project led medical investigations regarding asbestos and MM progress and contributed towards the care and examination of patients with asbestos-related diseases during these five years. Further investigations are required to facilitate the development of preventive measures and the cure of asbestos-related diseases, particularly in Japan, where asbestos-related diseases are predicted to increase in the next 10 to 20 years.

9 Review Medical treatment of mesothelioma: anything new? 2011

Takigawa, Nagio / Kiura, Katsuyuki / Kishimoto, Takumi. ·Department of General Internal Medicine 4, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505, Japan. ntakigaw@gmail.com ·Curr Oncol Rep · Pubmed #21503595.

ABSTRACT: In the present report, we review the current standard and investigational treatments of malignant pleural mesothelioma (MPM). Several studies have reported the use of gemcitabine and cisplatin as an induction chemotherapy in combination with extrapleural pneumonectomy (EPP) and thoracic radiation in a combined-modality approach for resectable MPM. Since the combination of cisplatin with pemetrexed was applied as the standard first-line regimen for unresectable MPM, the combination as an induction chemotherapy regimen has been proven effective in phase 2 trials. In addition, intensity-modulated radiation therapy and proton therapy have been introduced as new radiation methods into the combined modality. Hyperthermic intraoperative chemotherapy following EPP appears effective with acceptable toxicity. In addition, clinical studies that include molecular targeting agents, immunotherapy, and gene therapy have all been conducted. Thus, although there are numerous hopeful treatments for MPM, the benefits of these regimens remain to be proven in a randomized clinical setting.

10 Review [Immunological effects of silica/asbestos]. 2010

Kumagai, Naoko / Nishimura, Yasumitsu / Maeda, Megumi / Hayashi, Hiroaki / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, Matsushima, Kurashiki, Japan. ·Nihon Eiseigaku Zasshi · Pubmed #20885075.

ABSTRACT: Silica and asbestos cause pneumoconioses known as silicosis and asbestosis, respectively, that are each characterized by progressive pulmonary fibrosis. On the other hand, silicosis patients often suffer from a type of immunological dysregulation that gives rise to autoimmunity. These epidemiological findings suggest that silica may affect the immune system in humans. In addition, as asbestos itself is a mineral silicate, it may possess generalized immunotoxicological effects similar to those associated with silica particles. Because asbestos-exposed patients are well-known to often develop malignant diseases such as lung cancer and mesothelioma, one silica-like dysregulatory outcome that needs to be considered (apart from autoimmunity) is an alteration in host tumor immunity. In this review, the immunotoxicological effects of both silica and asbestos are presented and discussed in terms of immune system dysregulation as manifested by the onset of autoimmunity or alterations in host tumor immunity.

11 Review Dysregulation of the immune system caused by silica and asbestos. 2010

Maeda, Megumi / Nishimura, Yasumitsu / Kumagai, Naoko / Hayashi, Hiroaki / Hatayama, Tamayo / Katoh, Minako / Miyahara, Naomi / Yamamoto, Shoko / Hirastuka, Junichi / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan. ·J Immunotoxicol · Pubmed #20849352.

ABSTRACT: Silica and asbestos cause pneumoconioses known as silicosis and asbestosis, respectively, that are each characterized by progressive pulmonary fibrosis. While local effects of inhaled silica particles alter the function of alveolar macrophages and sequential cellular and molecular biological events, general systemic immunological effects may also evolve. One well-known health outcome associated with silica exposure/silicosis is an increase in the incidence of autoimmune disorders. In addition, while exposure to silica--in the crystalline form--has also been seen to be associated with the development of lung cancers, it remains unclear as to whether or not silicosis is a necessary condition for the elevation of silica-associated lung cancer risks. Since asbestos is a mineral silicate, it would be expected to also possess generalized immunotoxicological effects similar to those associated with silica particles. However, asbestos-exposed patients are far better known than silicotic patients for development of malignant diseases such as lung cancer and mesothelioma, and less so for the development of autoimmune disorders. With both asbestos and crystalline silica, one important dysregulatory outcome that needs to be considered is an alteration in tumor immunity that allows for silica- or asbestos- (or asbestos-associated agent)-induced tumors to survive and thrive in situ. In this review, the immunotoxicological effects of both silica and asbestos are presented and contrasted in terms of their abilities to induce immune system dysregulation that then are manifest by the onset of autoimmunity or by alterations in host-tumor immunity.

12 Review Advances in the molecular biology of malignant mesothelioma. 2008

Toyooka, Shinichi / Kishimoto, Takumi / Date, Hiroshi. ·Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. toyooka@md.okayama-u.ac.jp ·Acta Med Okayama · Pubmed #18323865.

ABSTRACT: Malignant mesothelioma (MM) is a highly aggressive tumor with a dismal prognosis. The incidence of MM is increasing as a result of widespread exposure to asbestos. As for the molecular alterations that occur in MM, chromosome alterations including homo-deletion of the P16 and P14 genes located in the 9p21 are well known. Mutations are rare in the P53 and Ras genes, which are frequently present in epithelial solid tumors. However, mutations are frequently present in the neurofibromatosis type 2 gene. Epigenetic alterations including DNA methylation have been found in the MM, the profile of which is different from that of lung cancer, although differential diagnosis is sometimes clinically difficult. As in other malignant tumors, genes that are related to immortalization, proliferation, metastasis, angiogenesis, and anti-apoptosis are also overexpressed in MM, contributing to its malignant phenotype. It is of interest that simian virus 40 has been implicated to be one of the causative factors of MM in western countries. Although the causative role of asbestos is well-known in MM, much less information is available for MM than for other malignant tumors regarding the molecular alterations that occur in the disease. In terms of future tasks, it will be necessary to apply the knowledge that is learned about molecular alterations to clinical practice and to further elucidate the pathogenesis of MM with extensive research.

13 Clinical Trial A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol. 2018

Fujimoto, Nobukazu / Aoe, Keisuke / Kozuki, Toshiyuki / Oze, Isao / Kato, Katsuya / Kishimoto, Takumi / Hotta, Katsuyuki. ·Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan. Electronic address: nobufujimot@gmail.com. · Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan. · Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of Diagnostic Radiology 2, Kawasaki Medical School, Okayama, Japan. · Department of Medicine, Okayama Rosai Hospital, Okayama, Japan. · Center of Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. ·Clin Lung Cancer · Pubmed #29853412.

ABSTRACT: BACKGROUND: The purpose of this study is to assess the efficacy and safety of combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with untreated, advanced, or metastatic MPM who meet the inclusion and exclusion criteria will be included. A total of 18 patients will be enrolled from 4 Japanese institutions within 1 year. Combination chemotherapy with cisplatin (75 mg/m CONCLUSION: This phase II trial evaluating first-line combination chemotherapy for unresectable MPM commenced in January 2018. This is the first prospective trial to evaluate the effect of an anti-programmed death-1 antibody combined with cisplatin and pemetrexed for unresectable MPM.

14 Article Decrease in Intracellular Perforin Levels and IFN- 2018

Kumagai-Takei, Naoko / Nishimura, Yasumitsu / Matsuzaki, Hidenori / Lee, Suni / Yoshitome, Kei / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, 701-0192 Kurashiki, Japan. · Department of Life Science, Faculty of Life and Environmental Science, Prefectural University of Hiroshima, 727-0023 Shobara, Japan. ·J Immunol Res · Pubmed #30426024.

ABSTRACT: Although the tumorigenicity of asbestos, which is thought to cause mesothelioma, has been clarified, its effect on antitumor immunity requires further investigation. We previously reported a decrease in the percentage of perforin

15 Article Quality of life of survivors of malignant pleural mesothelioma in Japan: a cross sectional study. 2018

Nagamatsu, Yasuko / Oze, Isao / Aoe, Keisuke / Hotta, Katsuyuki / Kato, Katsuya / Nakagawa, Junko / Hara, Keiko / Kishimoto, Takumi / Fujimoto, Nobukazu. ·Graduate School of Nursing Science, St. Luke's International University, 10-1 Akashicho, Chuo-ku, Tokyo, 1040044, Japan. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chigusa-ku, Nagoya, 4648681, Japan. · National Hospital Organization Yamaguchi-Ube Medical Center, Department of Medical Oncology, 685 Higashikiwa, Ube, 7550241, Japan. · Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikatacho, Okayama, 7008558, Japan. · Department of Radiology, Kawasaki General Medical Center, 2-6-1 Nakasange, Okayama, 7008505, Japan. · Department of Nursing, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama, 7028055, Japan. · Department of Medicine, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama, 7028055, Japan. · Department of Medical Oncology, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama, 7028055, Japan. nobufujimot@gmail.com. ·BMC Cancer · Pubmed #29587685.

ABSTRACT: BACKGROUND: Previous studies have indicated that people with malignant pleural mesothelioma (MPM) have a poor quality of life (QOL); however, information about the QOL of people with MPM in Japan is anecdotal. The aims of this study were to investigate the QOL of survivors of MPM in Japan and to determine the factors that correlate with their QOL. METHODS: This was a cross sectional study. The included patients were those diagnosed with MPM in Japan. We created a self-administered questionnaire consisting of 64 questions. The questionnaires were sent to hospitals and patient advocacy groups, distributed to the patients, completed, and sent back to the researchers by postal mail. QOL was assessed with the European Organization for Research and Treatment of Cancer 16 questionnaire (QLQ) and the short version of the core domains of the Comprehensive Quality of Life Outcome questionnaire (CoQoLo). RESULTS: In total, 133 questionnaires were collected. The QLQ assessments demonstrated that the survivors of MPM most frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The symptom scales were acceptable, but the functional scales were significantly poorer for the patients with poor performance statuses (PSs). The short CoQoLo assessment was very unfavorable for 'Being free from physical pain.' Being a long-term survivor and a survivor with a poor PS were significantly correlated with poor global health status. CONCLUSIONS: Survivors of MPM have impaired function, a variety of symptoms, and lower QOL. Survivors of MPM, even those in good physical condition, need broad support.

16 Article Low-dose chest computed tomography screening of subjects exposed to asbestos. 2018

Kato, Katsuya / Gemba, Kenichi / Ashizawa, Kazuto / Arakawa, Hiroaki / Honda, Satoshi / Noguchi, Naomi / Honda, Sumihisa / Fujimoto, Nobukazu / Kishimoto, Takumi. ·Department of Diagnostic Radiology 2, Kawasaki Medical School, General Medical Center, 2-1-80 Nakasange, Okayama, 7008505, Japan. · Department of Respiratory Medicine, Chugoku-chuo Hospital, 148-13 Oazakamiiwanari, Miyukicho, Fukuyama, 7200001, Japan. · Department of Clinical Oncology, Nagasaki University Graduate School of Medicine, 1-7-1 Sakamoto, Nagasaki, 8528102, Japan. · Department of Radiology, Dokkyo Medical University, 880, Kita-Kobayashi, Mibu, Tochigi, 3210293, Japan. · Department of Radiology, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama, 7028055, Japan. · Department of Radiology, Tamano Mitsui Hospital, 3-2-1 Tama, Tamano, 7060012, Japan. · Department of Medical Oncology, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama, 7028055, Japan. Electronic address: nobufujimot@gmail.com. · Department of Internal Medicine, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama, 7028055, Japan. ·Eur J Radiol · Pubmed #29571785.

ABSTRACT: OBJECTIVES: The primary aim was to reveal the prevalence of lung cancer (LC) and malignant pleural mesothelioma (MPM) in subjects with past asbestos exposure (AE). We also examined pulmonary or pleural changes correlated with the development of LC. MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional study. There were 2132 subjects enrolled between 2010 and 2012. They included 96.2% men and 3.8% women, with a mean age of 76.1 years; 78.8% former or current smokers; and 21.2% never smokers. We screened subjects using low-dose computed tomography (CT). The CT images were taken with a CT dose Index of 2.7 mGy. The evaluated CT findings included subpleural curvilinear shadow/subpleural dots, ground glass opacity or interlobular reticular opacity, traction bronchiectasia, honeycombing change, parenchymal band, emphysema changes, pleural effusion, diffuse pleural thickening, rounded atelectasis, pleural plaques (PQs), and tumor formation. RESULTS: The PQs were detected in most of subjects (89.4%) and emphysema changes were seen in 46.0%. Fibrotic changes were detected in 565 cases (26.5%). A pathological diagnosis of LC was confirmed in 45 cases (2.1%) and MPM was confirmed in 7 cases (0.3%). The prevalence of LC was 2.5% in patients with a smoking history, which was significantly higher than that in never smokers (0.7%, p = 0.027). The prevalence of LC was 2.8% in subjects with emphysema changes, which was higher than that of subjects without those findings (1.6%); although, the difference was not statistically significant (p = 0.056). The prevalence of LC in subjects with both fibrotic plus emphysema changes was 4.0%, which was significantly higher than that of subjects with neither of those findings (1.8%, p = 0.011). Logistic regression analysis revealed smoking history, fibrotic plus emphysema changes, and pleural effusion as significant explanatory variables. CONCLUSIONS: Smoking history, fibrotic plus emphysema changes, and pleural effusion were correlated with the prevalence of LC.

17 Article Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure. 2017

Maeda, Megumi / Chen, Ying / Lee, Suni / Kumagai-Takei, Naoko / Yoshitome, Kei / Matsuzaki, Hidenori / Yamamoto, Shoko / Hatayama, Tamayo / Ikeda, Miho / Nishimura, Yasumitsu / Otsuki, Takemi. ·Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, Okayama, Japan. · Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan. ·Int J Oncol · Pubmed #28498408.

ABSTRACT: We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.

18 Article Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma. 2017

Kuraoka, Masatsugu / Amatya, Vishwa J / Kushitani, Kei / Mawas, Amany S / Miyata, Yoshihiro / Okada, Morihito / Kishimoto, Takumi / Inai, Kouki / Nishisaka, Takashi / Sueda, Taijiro / Takeshima, Yukio. ·Departments of *Pathology ‡Surgery, Institute of Biomedical and Health Sciences ∥Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University †Department of Clinical Research and Laboratory, Hiroshima Prefectural Hospital #Pathologic Diagnostic Center Inc., Hiroshima, Japan ¶Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan §Department of Pathology and Clinical Pathology, South Valley University, Qena, Egypt. ·Am J Surg Pathol · Pubmed #28394802.

ABSTRACT: As there are currently no absolute immunohistochemical positive markers for the definite diagnosis of malignant epithelioid mesothelioma, the identification of additional "positive" markers that may facilitate this diagnosis becomes of clinical importance. Therefore, the aim of this study was to identify novel positive markers of malignant mesothelioma. Whole genome gene expression analysis was performed using RNA extracted from formalin-fixed paraffin-embedded tissue sections of epithelioid mesothelioma and pulmonary adenocarcinoma. Gene expression analysis revealed that disabled homolog 2 (DAB2) and Intelectin-1 had significantly higher expression in epithelioid mesothelioma compared with that in pulmonary adenocarcinoma. The increased mRNA expression of DAB2 and Intelectin-1 was validated by reverse transcriptase polymerase chain reaction of RNA from tumor tissue and protein expression was validated by Western blotting of 5 mesothelioma cell lines. The utility of DAB2 and Intelectin-1 in the differential diagnosis of epithelioid mesothelioma and pulmonary adenocarcinoma was examined by an immunohistochemical study of 75 cases of epithelioid mesothelioma and 67 cases of pulmonary adenocarcinoma. The positive rates of DAB2 and Intelectin-1 expression in epithelioid mesothelioma were 80.0% and 76.0%, respectively, and 3.0% and 0%, respectively, in pulmonary adenocarcinoma. Immunohistochemically, the sensitivity and specificity of DAB2 was 80% and 97% and those of Intelectin-1 were 76% and 100% for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma. In conclusion, DAB2 and Intelectin-1 are newly identified positive markers of mesothelioma and have potential to be included in future immunohistochemical marker panels for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma.

19 Article MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma. 2017

Amatya, Vishwa Jeet / Kushitani, Kei / Mawas, Amany Sayed / Miyata, Yoshihiro / Okada, Morihito / Kishimoto, Takumi / Inai, Kouki / Takeshima, Yukio. ·Department of Pathology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. · Department of Pathology and Clinical Pathology, South Valley University, Qena, Egypt. · Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. · Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan. · Pathologic Diagnostic Center, Inc., Hiroshima, Japan. ·Mod Pathol · Pubmed #28128276.

ABSTRACT: Sarcomatoid mesothelioma, a histological subtype of malignant pleural mesothelioma, is a very aggressive tumor with a poor prognosis. Histological diagnosis of sarcomatoid mesothelioma largely depends on the histomorphological feature of spindled tumor cells with immunohistochemical reactivity to cytokeratins. Diagnosis also requires clinico-radiological and/or macroscopic evidence of an extrapulmonary location to differentiate it from lung sarcomatoid carcinoma. Although there are promising immunohistochemical antibody panels to differentiate mesothelioma from lung carcinoma, a consensus on the immunohistochemical markers that distinguish sarcomatoid mesothelioma from lung sarcomatoid carcinoma has not been reached and requires further study. We performed whole gene expression analysis of formalin-fixed paraffin-embedded tissue from sarcomatoid mesothelioma and lung sarcomatoid carcinoma and observed significant differences in the expression of MUC4 and other genes between sarcomatoid mesothelioma and lung sarcomatoid carcinoma. Immunohistochemistry demonstrated that MUC4 was expressed in the spindled tumor cells of lung sarcomatoid carcinoma (21/29, 72%) but was not expressed in any sarcomatoid mesothelioma (0/31, 0%). To differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma, negative MUC4 expression showed 100% sensitivity and 72% specificity and accuracy rate of 87%, which is higher than immunohistochemical markers such as calretinin, D2-40 and Claudin-4. Therefore, we recommend to include MUC4 as a novel and useful negative immunohistochemical marker for differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma.

20 Article Distant Bystander Effect of REIC/DKK3 Gene Therapy Through Immune System Stimulation in Thoracic Malignancies. 2017

Suzawa, Ken / Shien, Kazuhiko / Peng, Huang / Sakaguchi, Masakiyo / Watanabe, Masami / Hashida, Shinsuke / Maki, Yuho / Yamamoto, Hiromasa / Tomida, Shuta / Soh, Junichi / Asano, Hiroaki / Tsukuda, Kazunori / Nasu, Yasutomo / Kumon, Hiromi / Miyoshi, Shinichiro / Toyooka, Shinichi. ·Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Collaborative Research Center for Okayama Medical Innovation Center, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. · Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University, Okayama, Japan. · Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan toyooka@md.okayama-u.ac.jp. ·Anticancer Res · Pubmed #28011506.

ABSTRACT: BACKGROUND: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. MATERIALS AND METHODS: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors. RESULTS: Ad-REIC treatment showed antitumor effect in many lung cancer and malignant mesothelioma cell lines in vitro. In an in vivo model, Ad-REIC treatment inhibited the growth not only of directly treated tumors but also of distant untreated tumors. By immunohistochemical analysis, infiltration of T-cells and natural killer (NK) cells and expression of the major histocompatibility complex (MHC) class I molecules were observed in bilateral tumors. CONCLUSION: Ad-REIC treatment not only had a direct antitumor effect but also an indirect bystander effect through stimulation of the immune system.

21 Article Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers. 2017

Lee, Suni / Matsuzaki, Hidenori / Maeda, Megumi / Yamamoto, Shoko / Kumagai-Takei, Naoko / Hatayama, Tamayo / Ikeda, Miho / Yoshitome, Kei / Nishimura, Yasumitsu / Otsuki, Takemi. ·Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan. · Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, Kita-Ku, Okayama 700-8530, Japan. ·Int J Oncol · Pubmed #27878235.

ABSTRACT: Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg.

22 Article Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma. 2017

Kushitani, Kei / Amatya, Vishwa J / Okada, Yasuko / Katayama, Yuya / Mawas, Amany S / Miyata, Yoshihiro / Okada, Morihito / Inai, Kouki / Kishimoto, Takumi / Takeshima, Yukio. ·Department of Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. · Faculty of Medicine, Hiroshima University, Hiroshima, Japan. · Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt. · Department of Surgical Oncology, Research Centre for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. · Pathologic Diagnostic Centre, Inc., Hiroshima, Japan. · Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan. ·Histopathology · Pubmed #27589012.

ABSTRACT: AIMS: The aims of this study were to clarify the usefulness of immunohistochemistry in the differential diagnosis of epithelioid mesothelioma with a solid growth pattern [solid epithelioid mesothelioma (SEM)] and poorly differentiated squamous cell carcinoma (PDSCC), and to confirm the validity of a specific type of antibody panel. Additionally, we aimed to clarify the pitfalls of immunohistochemical analyses. METHODS AND RESULTS: Formalin-fixed paraffin-embedded specimens from 36 cases of SEM and 38 cases of PDSCC were immunohistochemically examined for calretinin, podoplanin (D2-40), Wilms' tumour gene product (WT1), cytokeratin (CK) 5/6, p40, p63, carcinoembryonic antigen (CEA), epithelial-related antigen (MOC31), claudin-4, thyroid transcription factor-1 (TTF-1), and napsin A. WT1 showed the highest diagnostic accuracy (85.1%) as a mesothelial marker, and CEA, p40 and claudin-4 showed higher diagnostic accuracies (95.9%, 94.6%, and 93.2%, respectively) as carcinoma markers. Calretinin (diagnostic accuracy: 75.7%), D2-40 (diagnostic accuracy: 67.6%), CK5/6 (diagnostic accuracy: 63.5%), TTF-1 (diagnostic accuracy: 55.4%) and napsin A (diagnostic accuracy: 52.7%) could not differentiate between SEM and PDSCC. Among these markers, the combination of calretinin and WT1 showed the highest diagnostic accuracy (86.5%) as a positive marker, and the combination of p40 and CEA showed the highest diagnostic accuracy (97.3%) as a negative marker. The combination of CEA and claudin-4 also showed relatively high diagnostic accuracy (94.6%) as a negative marker. CONCLUSIONS: We recommend the combination of WT1 and calretinin as a positive maker, and the combination of CEA and claudin-4 as a negative marker, for differential diagnoses of SEM and PDSCC.

23 Article Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion. 2016

Kato, Katsuya / Gemba, Kenichi / Fujimoto, Nobukazu / Aoe, Keisuke / Takeshima, Yukio / Inai, Kouki / Kishimoto, Takumi. ·Department of Radiology, Okayama University Hospital, 2-1-1 Shikatacho, Okayama 7008558, Japan. Electronic address: kato-rad@med.kawasaki-m.ac.jp. · Department of Medical Oncology, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama 7028055, Japan. · Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, 685 Higashikiwa, Ube 7550241, Japan. · Department of Pathology, Hiroshima University Graduate School of Medicine, 1-2-3 Kasumi, Hiroshima 7340037, Japan. · Department of Internal Medicine, Okayama Rosai Hospital, 1-10-25 Chikkomidorimachi, Okayama 7028055, Japan. ·Eur J Radiol · Pubmed #27501894.

ABSTRACT: OBJECTIVE: To elucidate differences in the level and localization of pleural irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos pleural effusion (BAPE) using CT. STUDY DESIGN: Retrospective assessment of CT findings of consecutive patients with BAPE at a single centre and patients with eMPM reported in Japanese vital statistics. METHODOLOGY: Thirty-six patients with confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans, and clinical and pathologic details were obtained for all patients and were reviewed by one radiologist, two pathologists, and two pulmonologists. Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening were assessed in all patients. RESULTS: Prevalence of asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening was significantly higher in the BAPE group. Low-level irregularity was more common in the BAPE group (p<0.001), whereas high-level irregularity, mediastinal localization, and interlobar fissure were more prevalent in the eMPM group (p<0.001). Interlobar pleural irregularity was not observed in any patients in the BAPE group, although 55% of patients in the eMPM group showed interlobar pleural irregularity. Mediastinal pleural involvement was observed in 74% of patients in the eMPM group and had a positive predictive value of 89%. CONCLUSION: This study demonstrates that the level and localization of plural irregularities significantly differed between patients with BAPE and eMPM. Large-scale prospective studies are needed to fully establish the diagnostic utility of such differences.

24 Article [Clinical Pathological Diagnosis, and Treatment for Pleural Mesothelioma]. 2016

Kishimoto, Takumi / Fujimoto, Nobukazu / Nishi, Hideyuki. ·Research Center for Asbestos-Related Diseases, Okayama Rosai Hospital. ·Gan To Kagaku Ryoho · Pubmed #27210080.

ABSTRACT: For the differential diagnosis between fibrous pleuritis and other malignancies such as lung cancer, multiple immunostaining is essential to diagnose pleural mesothelioma. For cytological diagnosis of pleural effusions, differentiation between mesothelioma cells and reactive mesothelial cells is very difficult. Therefore, histological diagnoses of tumor tissues obtained via biopsy are essential. To diagnose epthelioid mesothelioma, more than 2 positive and negative markers must be consistent with those known for mesothelioma. To diagnose sarcomatoid mesothelioma, keratin is usually positive, differentiating the diagnosis from that for real sarcoma. For surgical treatment for pleural mesothelioma, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are usually performed. The proportion of P/D increases because of the low death rates with surgery and similar survivals. However, a trimodal approach, such as EPP with chemotherapy and radiotherapy, is best for longer survival and expected to be curative. For chemotherapy, only cisplatin (CDDP) combined with pemetrexed (PEM) is effective, and no other agents have been identified for this disease. Nowadays, clinical immunotherapy trials start with phase II study.

25 Article FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line. 2016

Matsuzaki, Hidenori / Lee, Suni / Maeda, Megumi / Kumagai-Takei, Naoko / Nishimura, Yasumitsu / Otsuki, Takemi. ·a Department of Hygiene , Kawasaki Medical School , Kurashiki , Japan ; · b Department of Biofunctional Chemistry, Division of Bioscience , Okayama University Graduate School of Natural Science and Technology , Okayama , Japan. ·J Immunotoxicol · Pubmed #27042963.

ABSTRACT: Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, over-expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.

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