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Mesothelioma: HELP
Articles from Korea
Based on 66 articles published since 2009
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These are the 66 published articles about Mesothelioma that originated from Korea during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors. 2017

Hendry, Shona / Salgado, Roberto / Gevaert, Thomas / Russell, Prudence A / John, Tom / Thapa, Bibhusal / Christie, Michael / van de Vijver, Koen / Estrada, M V / Gonzalez-Ericsson, Paula I / Sanders, Melinda / Solomon, Benjamin / Solinas, Cinzia / Van den Eynden, Gert G G M / Allory, Yves / Preusser, Matthias / Hainfellner, Johannes / Pruneri, Giancarlo / Vingiani, Andrea / Demaria, Sandra / Symmans, Fraser / Nuciforo, Paolo / Comerma, Laura / Thompson, E A / Lakhani, Sunil / Kim, Seong-Rim / Schnitt, Stuart / Colpaert, Cecile / Sotiriou, Christos / Scherer, Stefan J / Ignatiadis, Michail / Badve, Sunil / Pierce, Robert H / Viale, Giuseppe / Sirtaine, Nicolas / Penault-Llorca, Frederique / Sugie, Tomohagu / Fineberg, Susan / Paik, Soonmyung / Srinivasan, Ashok / Richardson, Andrea / Wang, Yihong / Chmielik, Ewa / Brock, Jane / Johnson, Douglas B / Balko, Justin / Wienert, Stephan / Bossuyt, Veerle / Michiels, Stefan / Ternes, Nils / Burchardi, Nicole / Luen, Stephen J / Savas, Peter / Klauschen, Frederick / Watson, Peter H / Nelson, Brad H / Criscitiello, Carmen / O'Toole, Sandra / Larsimont, Denis / de Wind, Roland / Curigliano, Giuseppe / André, Fabrice / Lacroix-Triki, Magali / van de Vijver, Mark / Rojo, Federico / Floris, Giuseppe / Bedri, Shahinaz / Sparano, Joseph / Rimm, David / Nielsen, Torsten / Kos, Zuzana / Hewitt, Stephen / Singh, Baljit / Farshid, Gelareh / Loibl, Sibylle / Allison, Kimberly H / Tung, Nadine / Adams, Sylvia / Willard-Gallo, Karen / Horlings, Hugo M / Gandhi, Leena / Moreira, Andre / Hirsch, Fred / Dieci, Maria V / Urbanowicz, Maria / Brcic, Iva / Korski, Konstanty / Gaire, Fabien / Koeppen, Hartmut / Lo, Amy / Giltnane, Jennifer / Rebelatto, Marlon C / Steele, Keith E / Zha, Jiping / Emancipator, Kenneth / Juco, Jonathan W / Denkert, Carsten / Reis-Filho, Jorge / Loi, Sherene / Fox, Stephen B. ·Departments of *Pathology §§§Medical Oncology, Peter MacCallum Cancer Centre, Melbourne †The Sir Peter MacCallum Department of Oncology Departments of **Pathology ∥∥Medicine, University of Melbourne ¶¶Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville #Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy ††Department of Medical Oncology, Austin Health ‡‡Olivia Newton-John Cancer Research Institute, Heidelberg §§School of Cancer Medicine, La Trobe University, Bundoora §§§§§Centre for Clinical Research and School of Medicine, The University of Queensland ∥∥∥∥∥Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane §§§§§§§§§§The Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst ∥∥∥∥∥∥∥∥∥∥Australian Clinical Labs, Bella Vista ‡‡‡‡‡‡‡‡‡‡‡‡Directorate of Surgical Pathology, SA Pathology §§§§§§§§§§§§Discipline of Medicine, Adelaide University, Adelaide, Australia ***********Department of Surgical Oncology, Netherlands Cancer Institute †††††††††††††Department of Pathology ##Divisions of Diagnostic Oncology & Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands ###Université Paris-Est ****INSERM, UMR 955 ††††Département de pathologie, APHP, Hôpital Henri-Mondor, Créteil ∥∥∥∥∥∥∥∥∥Service de Biostatistique et d'Epidémiologie, Gustave Roussy, CESP, Inserm U1018, Université-Paris Sud, Université Paris-Saclay ¶¶¶¶¶¶¶¶¶¶INSERM Unit U981, and Department of Medical Oncology, Gustave Roussy, Villejuif ##########Faculté de Médecine, Université Paris Sud, Kremlin-Bicêtre †††††††Department of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre ‡‡‡‡‡‡‡University of Auvergne UMR1240, Clermont-Ferrand, France ‡‡‡‡Department of Medicine, Clinical Division of Oncology §§§§Institute of Neurology, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna ††††††††††††††Institute of Pathology, Medical University of Graz, Austria ∥∥∥∥European Institute of Oncology ¶¶¶¶School of Medicine ######Department of Pathology, Istituto Europeo di Oncologia, University of Milan, Milan ¶¶¶¶¶¶¶¶¶¶¶¶¶Department of Surgery, Oncology and Gastroenterology, University of Padova #############Medical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy †††††Molecular Oncology Group, Vall d'Hebron Institute of Oncology, Barcelona †††††††††††Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain §Department of Pathology and TCRU, GZA ¶¶¶Department of Pathology, GZA Ziekenhuizen, Antwerp ∥Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven ‡‡‡‡‡‡‡‡‡‡‡Department of Pathology, University Hospital Leuven, Leuven, Belgium ¶Department of Pathology, AZ Klina, Brasschaat ††††††Department of Pathology, GZA Ziekenhuizen, Sint-Augustinus, Wilrijk ∥∥∥Molecular Immunology Unit ‡‡‡‡‡‡Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles ‡Breast Cancer Translational Research Laboratory/Breast International Group, Institut Jules Bordet **************European Organisation for Research and Treatment of Cancer (EORTC) Headquarters *******Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium §§§§§§§Department of Surgery, Kansai Medical School, Hirakata, Japan #######Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, South Korea ∥∥∥∥∥∥∥∥Tumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center ¶¶¶¶¶¶¶¶Institute of Oncology, Gliwice Branch, Gliwice, Poland ‡‡‡‡‡‡‡‡‡‡‡‡‡‡Pathology and Tissue Analytics, Roche Innovation Centre Munich, Penzberg †††††††††Institute of Pathology, Charité Universitätsmedizin Berlin ‡‡‡‡‡‡‡‡‡VMscope GmbH, Berlin ¶¶¶¶¶¶¶¶¶German Breast Group GmbH, Neu-Isenburg, Germany **********Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency ††††††††††Department of Biochemistry and Microbiology, University of Victoria, Victoria Departments of ‡‡‡‡‡‡‡‡‡‡Medical Genetics #########Pathology and Laboratory Medicine ¶¶¶¶¶¶¶¶¶¶¶Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, BC ###########Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada §§§§§§§§§§§Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Doha, Qatar ‡‡‡‡‡‡‡‡Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center §§§§§§§§Warren Alpert Medical School of Brown University, Providence ¶¶¶¶¶National Surgical Adjuvant Breast and Bowel Project Operations Center/NRG Oncology, Pittsburgh, PA †††Breast Cancer Research Program, Vanderbilt Ingram Cancer Center, Vanderbilt University Departments of ‡‡‡Pathology, Microbiology and Immunology ########Department of Medicine, Vanderbilt University Medical Centre *********Vanderbilt Ingram Cancer Center, Nashville §§§§§§§§§Department of Pathology, Yale University School of Medicine, New Haven ∥∥∥∥∥∥∥∥∥∥∥Department of Oncology, Montefiore Medical Centre, Albert Einstein College of Medicine ∥∥∥∥∥∥∥Montefiore Medical Center ¶¶¶¶¶¶¶The Albert Einstein College of Medicine, Bronx, NY ********Department of Pathology, Brigham and Women's Hospital #####Cancer Research Institute and Department of Pathology, Beth Israel Deaconess Cancer Center ******Harvard Medical School ¶¶¶¶¶¶¶¶¶¶¶¶Division of Hematology-Oncology, Beth Israel Deaconess Medical Center ††††††††Department of Cancer Biology ‡‡‡‡‡‡‡‡‡‡‡‡‡Dana-Farber Cancer Institute, Boston, MA ∥∥∥∥∥∥∥∥∥∥∥∥∥Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO ‡‡‡‡‡Department of Cancer Biology, Mayo Clinic, Jacksonville, FL ∥∥∥∥∥∥Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN ¶¶¶¶¶¶Cancer Immunotherapy Trials Network, Central Laboratory and Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA ††††††††††††Department of Pathology, New York University Langone Medical Centre ############New York University Medical School *************Perlmutter Cancer Center §§§§§§§§§§§§§Pulmonary Pathology, New York University Center for Biospecimen Research and Development, New York University ***************Department of Pathology, Memorial Sloan-Kettering Cancer Center ####Departments of Radiation Oncology and Pathology, Weill Cornell Medicine, New York, NY *****Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX ∥∥∥∥∥∥∥∥∥∥∥∥Pathology Department, Stanford University Medical Centre, Stanford ∥∥∥∥∥∥∥∥∥∥∥∥∥∥Department of Pathology, Stanford University, Palo Alto ***Department of Pathology, School of Medicine, University of California, San Diego §§§§§§§§§§§§§§Research Pathology, Genentech Inc., South San Francisco, CA *************Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda ¶¶¶¶¶¶¶¶¶¶¶¶¶¶Translational Sciences, MedImmune, Gaithersberg, MD §§§§§§Academic Medical Innovation, Novartis Pharmaceuticals Corporation, East Hanover ##############Translational Medicine, Merck & Co. Inc., Kenilworth, NJ. ·Adv Anat Pathol · Pubmed #28777143.

ABSTRACT: Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

2 Review Radiologic Diagnosis of Asbestosis in Korea. 2016

Cha, Yoon Ki / Kim, Jeung Sook / Kim, Yookyung / Kim, Yoon Kyung. ·Department of Radiology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang 10326, Korea. · Department of Radiology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul 07985, Korea. · Department of Radiology, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea. ·Korean J Radiol · Pubmed #27587956.

ABSTRACT: Asbestosis is the most important change noted in the lung parenchyma after environmental and occupational exposure to asbestos fibers. It is characterized by diffuse interstitial pulmonary fibrosis. In Korea, the incidence of asbestosis will continue to increase for many years to come and the government enacted the Asbestos Damage Relief Law in 2011 to provide compensation to those suffering from asbestos-related diseases. Radiologic evaluation is necessary for diagnosis of asbestosis, and radiologists play a key role in this process. Therefore, it is important for radiologists to be aware of the various imaging features of asbestosis.

3 Review Occupational respiratory cancer in Korea. 2010

Lee, Hye-Eun / Kim, Hyoung Ryoul. ·Occupational Safety and Health Research Institute, KOSHA, Inchoen, Korea. ·J Korean Med Sci · Pubmed #21258597.

ABSTRACT: Malignant mesothelioma and lung cancer are representative examples of occupational cancer. Lung cancer is the leading cause of cancer death, and the incidence of malignant mesothelioma is expected to increase sharply in the near future. Although information about lung carcinogen exposure is limited, it is estimated that the number of workers exposed to carcinogens has declined. The first official case of occupational cancer was malignant mesothelioma caused by asbestos exposure in the asbestos textile industry in 1992. Since then, compensation for occupational respiratory cancer has increased. The majority of compensated lung cancer was due to underlying pneumoconiosis. Other main causative agents of occupational lung cancer included asbestos, hexavalent chromium, and crystalline silica. Related jobs included welders, foundry workers, platers, plumbers, and vehicle maintenance workers. Compensated malignant mesotheliomas were associated with asbestos exposure. Epidemiologic studies conducted in Korea have indicated an elevated risk of lung cancer in pneumoconiosis patients, foundry workers, and asbestos textile workers. Occupational respiratory cancer has increased during the last 10 to 20 yr though carcinogen-exposed population has declined in the same period. More efforts to advance the systems for the investigation, prevention and management of occupational respiratory cancer are needed.

4 Review Overview of asbestos issues in Korea. 2009

Kim, Hyoung Ryoul. ·Department of Preventive Medicine and Industrial Medical Center, the Catholic University of Korea, College of Medicine, Seoul, Korea. cyclor@catholic.ac.kr ·J Korean Med Sci · Pubmed #19543418.

ABSTRACT: Asbestos is a carcinogen that causes diseases such as mesothelioma and lung cancer in humans. There was a sharp increase in the use of asbestos in Korea in the 1970s as Korea's economy developed rapidly, and asbestos was only recently banned from use. Despite the ban of its use, previously applied asbestos still causes many problems. A series of asbestos-related events that recently occurred in Korea have caused the general public to become concerned about asbestos. Therefore, it is necessary to take proper action to deal with asbestos-related events, such as mass outbreaks of mesothelioma among residents who lived near asbestos textile factories or asbestos mines. Although there have been no rapid increases in asbestos-related illnesses in Korea to date, such illnesses are expected to increase greatly due to the amount of asbestos used and long latency period. Decreasing the asbestos exposure level to levels as low as possible is the most important step in preventing asbestos-related illnesses in the next few decades. However, there is a lack of specialized facilities for the analysis of asbestos and experts to diagnose and treat asbestos-related illnesses in Korea; therefore, national-level concern and support are required.

5 Article Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases. 2019

Kim, Moonsik / Kim, Hyun-Soo. ·Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. · Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea hyunsookim16@gmail.com. ·In Vivo · Pubmed #30804152.

ABSTRACT: BACKGROUND/AIM: Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases. MATERIALS AND METHODS: The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining. RESULTS: The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1. CONCLUSION: We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.

6 Article Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1. 2019

Hwang, Sung-Hyun / Kim, Myung-Chul / Ji, Sumin / Yang, Yeseul / Jeong, Yeji / Kim, Yongbaek. ·Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea. · BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Korea. · Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Korea. ·Cancer Sci · Pubmed #30689265.

ABSTRACT: Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose-starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m-chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.

7 Article Occupational Burden of Asbestos-Related Diseases in Korea, 1998-2013: Asbestosis, Mesothelioma, Lung Cancer, Laryngeal Cancer, and Ovarian Cancer. 2018

Kang, Dong-Mug / Kim, Jong-Eun / Kim, Young-Ki / Lee, Hyun-Hee / Kim, Se-Yeong. ·Department of Preventive, Occupational and Environmental Medicine, School of Medicine, Pusan National University, Yangsan, Korea. · Department of Occupational and Environmental Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea. · Environmental Health Center, Pusan National University Yangsan Hospital, Yangsan, Korea. · Busan Workers Health Center, Pusan National University, Busan, Korea. · Department of Occupational and Environmental Medicine, GoodGangAn Hospital, Busan, Korea. ·J Korean Med Sci · Pubmed #30140191.

ABSTRACT: Background: Asbestos exposure causes asbestos-related diseases (ARDs) including asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer. Although Korea used substantial amounts of asbestos in the past, no study has focused on its occupational burden of disease (OBD). Therefore, this study aimed to determine the OBDs of ARDs in Korea. Methods: The CARcinogen Exposure (CAREX) database was used to determine the proportion of exposed population. Relative risks for lung cancer, laryngeal cancer, and ovarian cancer were used to determine the population-attributable fraction. Data for deaths caused by ARDs during 1998-2013 were obtained from the World Health Organization mortality database. The potential years of life lost (PYLL) and annual average PYLL (APYLL) indicated OBDs. Results: In Korea, the number of ARD-attributable deaths and PYLL due to all ARDs during 1998-2013 were 4,492 and 71,763.7, respectively. The number of attributable deaths and PYLL due to asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer were 37 and 554.2, 808 and 15,877.0, 3,256 and 47,375.9, 120 and 1,605.5, and 271 and 6,331.1, respectively; additionally, the APYLL were 15.0, 19.7, 14.6, 13.4, and 23.4, respectively, and the average age at death was 70.4, 62.6, 69.1, 69.9, and 61.8, respectively. Our study showed that although the use of asbestos has ceased in Korea, the incidence of ARDs tends to increase. Conclusion: Therefore, efforts to reduce future OBDs of ARDs, including early detection and proper management of ARDs, are needed in Korea.

8 Article Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma. 2018

Kim, Myung-Chul / Hwang, Sung-Hyun / Kim, Na-Yon / Lee, Hong-Seok / Ji, Sumin / Yang, Yeseul / Kim, Yongbaek. ·Laboratory of Clinical Pathology, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea. · BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea. · Laboratory of Clinical Pathology, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea. yongbaek@snu.ac.kr. · Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea. yongbaek@snu.ac.kr. ·BMC Cancer · Pubmed #30111297.

ABSTRACT: BACKGROUND: Hypoxia is a hallmark of the solid tumor microenvironment and is associated with poor outcomes in cancer patients. The present study was performed to investigate mechanisms underlying the hypoxia-induced phenotypic changes using human malignant mesothelioma (HMM) cells. METHODS: Hypoxic conditions were achieved by incubating HMM cells in the air chamber. The effect of hypoxia on phenotype changes in HMM cells was investigated by performing in vitro clonogenicity, drug resistance, migration, and invasion assays. Signaling pathways and molecules involved in the more aggressive behaviors of HMM cells under hypoxia were investigated. A two-tailed unpaired Student's t-test or one-way ANOVA with Bonferroni post-test correction was used in this study. RESULTS: Hypoxic conditions upregulated hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α in parallel with the upregulation of its target, Glut-1, in HMM cells. In vitro clonogenicity of HMM cells was significantly increased in hypoxic conditions, but the proliferation of cells at a high density in hypoxia was lower than that in normoxic conditions. The expression levels of HIF-2α and Oct4 were increased in hypoxic HMM cells. The percentage of cells with high CD44 expression was significantly higher in HMM cells cultured in hypoxia than those cultured in normoxia. Hypoxia significantly enhanced the resistance of HMM cells to cisplatin, which occurred through cytoprotection against cisplatin-induced apoptosis. While cisplatin treatment decreased the ratio of Bcl-2 to Bax in normoxic condition, hypoxia conversely increased the ratio in HMM cells treated with cisplatin. Hypoxia increased the mobility and invasiveness of HMM cells. Epithelial to mesenchymal transition was promoted, which was indicated by the repression of E-cadherin and the concomitant increase of vimentin in HMM cells. CONCLUSIONS: The data illustrated that hypoxic conditions augmented the aggressive phenotypes of HMM cells at the biological and molecular levels. The present study provides valuable background information beginning to understand aggressiveness of HMM in tumor microenvironments, suggesting that a control measure for tumor hypoxia may be an effective therapeutic strategy to reduce the aggressiveness of cancer cells in HMM patients.

9 Article Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo. 2018

Kooreman, Nigel G / Kim, Youngkyun / de Almeida, Patricia E / Termglinchan, Vittavat / Diecke, Sebastian / Shao, Ning-Yi / Wei, Tzu-Tang / Yi, Hyoju / Dey, Devaveena / Nelakanti, Raman / Brouwer, Thomas P / Paik, David T / Sagiv-Barfi, Idit / Han, Arnold / Quax, Paul H A / Hamming, Jaap F / Levy, Ronald / Davis, Mark M / Wu, Joseph C. ·Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands. · Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul 06591, Korea. · Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rossle Strasse 10, 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany. · Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. · Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department of Surgery, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands. · Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: levy@stanford.edu. · Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mmdavis@stanford.edu. · Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu. ·Cell Stem Cell · Pubmed #29456158.

ABSTRACT: Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models. As an adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection site and reduced metastatic tumor load, which was associated with fewer Th17 cells and increased CD11b

10 Article Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells. 2017

Lee, Yoon-Jin / Bae, Jin-Ho / Kim, Soo-A / Kim, Sung-Ho / Woo, Kee-Min / Nam, Hae-Seon / Cho, Moon-Kyun / Lee, Sang-Han. ·Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan, 31151, Korea. · Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31151, Korea. · Department of Physical Medicine and Rehabilitation, Cheonan Hospital, Cheonan 31151, Korea. · Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan 31538, Korea. ·Mol Cells · Pubmed #28835017.

ABSTRACT: The Na

11 Article Estimated future incidence of malignant mesothelioma in South Korea: Projection from 2014 to 2033. 2017

Kwak, Kyeong Min / Paek, Domyung / Hwang, Seung-Sik / Ju, Young-Su. ·Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea. · Department of Occupational and Environmental Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea. · Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea. · Department of Occupational and Environmental Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea. ·PLoS One · Pubmed #28817672.

ABSTRACT: Malignant mesothelioma is a malignant tumor on the pleura or the peritoneum caused mostly by asbestos. Although asbestos is not currently used in South Korea, the incidence of mesothelioma is increasing due to its long latent period. This study predicted the incidence of malignant mesothelioma in South Korea over the next 20 years using an age-period-cohort (APC) model. Data regarding mesothelioma incidence from 1994-2013 were acquired from the Korea Central Cancer Registry (KCCR). Demographic data, including prospective resident data, were acquired from the Korean Statistical Information Service (KOSIS) for 1994-2033. An APC model with Møller's power-link function was utilized to predict the incidence of mesothelioma. It was predicted that 2,380 and 1,199 new cases of mesothelioma in men and women, respectively, would occur over the next 20 years. For both sexes, the mesothelioma incidence rate was predicted to be greater in 2029-2033 compared to that in 2009-2013 (men, 0.282 vs 0.563; women, 0.155 vs 0.217). For men, the age-standardized incidence rate was predicted to be slightly greater in 2029-2033 relative to the rate in 2009-2013 (0.228 vs 0.235), while the age-standardized incidence rate in women decreased within the same timeframe (0.113 vs 0.109). The changes in mesothelioma incidence were mostly caused by changes in the population structure due to aging and not by changes in the mesothelioma risk ratio. The results of this study project a continuous increase in mesothelioma incidence in South Korea over the next 20 years. Although the projected increase in mesothelioma incidence was not related to an increase in the mesothelioma risk ratio, continuous preventive efforts are necessary to reduce the exposure to asbestos and prevent the trend from worsening.

12 Article Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells. 2017

Lee, Yoon-Jin / Lee, Sang-Han. ·Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330‑930, Republic of Korea. ·Mol Med Rep · Pubmed #28627624.

ABSTRACT: Sulforaphane (SFN) is an isothiocyanate compound derived from glucoraphanin, which is found in cruciferous vegetables, and has been heralded as a chemopreventive and/or chemotherapeutic agent. The present study investigated the effects of SFN on enhancing the anticancer role of cisplatin (cis-dichlorodiammineplatinum; CDDP) in H‑28 malignant mesothelioma cells. At concentrations demonstrating limited toxicity in MeT‑5A normal human mesothelial cells, combination treatment with the two compounds exhibited synergistic growth‑inhibiting and apoptosis‑promoting activities, as demonstrated by a series of proapoptotic events, including reactive oxygen species accumulation, loss of mitochondrial membrane potential, upregulation of p53 expression, increased B‑cell lymphoma 2 (Bcl‑2) associated X protein/Bcl‑2 ratio, activation of caspase‑3, the occurrence of a sub‑G0/G1 peak and an increase in cells with pyknotic and fragmented nuclei, Annexin V‑phycoerythrin‑positive staining and G2/M phase‑transition delay in the cell cycle. The phosphorylation levels of Akt and mammalian target of rapamycin were reduced by the combination treatment, which was accompanied by a significant increase in the level of autophagosomal marker protein microtubule‑associated protein 1 light chain 3B‑II and the accumulation of acidic vesicular organelles. Pretreatment with the antioxidant N‑acetylcysteine attenuated both apoptosis and autophagy, whereas inhibition of autophagy by bafilomycin A1 potentiated apoptotic cell death following the combination treatment with SFN and CDDP. Considering the pro‑oxidant‑based combinational approach, the results of the present study provide a rationale for targeting cytoprotective autophagy as a potential therapeutic strategy for malignant mesothelioma.

13 Article A subset of microRNAs defining the side population of a human malignant mesothelioma cell line. 2017

Kim, Myung-Chul / Kim, Na-Yon / Seo, Yu-Ri / Kim, Yongbaek. ·Laboratory of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Gwanak-Gu, Seoul 151-742, The Republic of Korea. · BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Gwanak-Gu, Seoul 151-742, The Republic of Korea. · Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Gwanak-Gu, Seoul 151-742, The Republic of Korea. ·Oncotarget · Pubmed #28467812.

ABSTRACT: This study was performed to investigate the global expression profile of microRNAs in distinct subpopulations of a human malignant mesothelioma cell line. Total RNAs were isolated from the sorted side population and non-side population of MS1. The RNAs were subjected to analysis using Affymetrix GeneChip microRNA Arrays. After data extraction and normalization, a subset of microRNAs defining cell subpopulations was identified using bioinformatics softwares. Based on the criteria of 2-fold difference and the p-value of < 0.05, a total of 95 microRNAs were differentially expressed in the side population compared to the non-side population. Functional ontology revealed that target genes of the miRNAs were categorized into various gene ontology terms, such as stem cell maintenance, cell proliferation, programmed cell death, cell migration, and cellular response to stress. The Kyoto Encyclopedia of Genes and Genomes analysis showed that ErbB-2 receptor tyrosine kinases signaling pathway was the most represented. Integrated analysis of MiRTarBase and RNA-seq identified 12 target genes of microRNAs defining side population, including DDIT4 and ROCK2. The present study indicates that a distinct set of microRNAs may be critically involved in the generation and maintenance of heterogeneous subpopulations of cancer cells. They could be a plausible target for the eradication of more aggressive cancer cell subpopulations.

14 Article Activation of JNK and IRE1 is critically involved in tanshinone I-induced p62 dependent autophagy in malignant pleural mesothelioma cells: implication of p62 UBA domain. 2017

Lee, Jihyun / Sohn, Eun Jung / Yoon, Sangwook / Won, Gunho / Kim, Chang Geun / Jung, Ji Hoon / Kim, Sung-Hoon. ·College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Republic of Korea. ·Oncotarget · Pubmed #28212571.

ABSTRACT: The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells. Furthermore, autophagy flux was enhanced in Tan I-treated H28 cells transfected by RFP-GFP-LC3 constructs, with colocalization of GFP-LC3 punctae with LAMP1 or Lysotracker. Interestingly, C-terminal UBA domain is required for Tan 1 induced aggregation of p62 in H28 cells. Notably, Tan I upregulated CCAAT-enhancer-binding protein homologous protein (CHOP), inositol-requiring protein-1 (IRE1) and p-c-Jun N-terminal kinase (p-JNK), but silencing of IRE1 or p62 and JNK inhibitor SP600125 blocked the LC3II accumulation in Tan I-treated H28 cells. Overall, these findings demonstrate that Tan I exerts antitumor activity through a compromise between apoptosis and p62/SQSTM1-dependent autophagy via activation of JNK and IRE 1 in malignant mesothelioma cells.

15 Article Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell. 2016

Sohn, Eun Jung / Won, Gunho / Lee, Jihyun / Yoon, Sang Wook / Lee, Ilho / Kim, Hee Jeong / Kim, Sung-Hoon. ·College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. ·Int J Biol Sci · Pubmed #28090191.

ABSTRACT: Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/β), β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, β-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.

16 Article Hypomethylation reduced the aggressive potential of human malignant mesothelioma cells. 2016

Kim, N-Y / Kim, M-C / Kim, Y. ·Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. · BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. · Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. ·Cancer Gene Ther · Pubmed #27857059.

ABSTRACT: Epigenetic modifications have been implicated in the development of therapeutic resistance responsible for the poor prognosis of human malignant mesothelioma (HMM). To find a potential way to overcome this therapeutic resistance, this study investigated the anticancer effects of a DNA demethylating agent, 5-Aza-2'-Deoxycytidine (5-aza-dC), on HMM cells. The 5-aza-dC exhibited minimal detrimental effects on cell survival. However, treatment with 5-aza-dC significantly altered the biological characteristics associated with malignancy, such as cell migration and cell interaction, colony-forming capacity, and invasiveness. Moreover, it significantly reduced the fraction of side population (SP) cells, which are reportedly enriched for more aggressive cells. Large-scale methylation analysis based on methylated DNA immunoprecipitation revealed a more than two fold increase in the methylation level of major tumor suppressor genes in the SP fraction. The data indicated that SP cells might acquire malignancy by hypermethylation of tumor suppressor genes. Treatment with 5-aza-dC could attack more malignant cells through the modification of their methylation status. The results indicate that the modulation of DNA methylation might be a valuable strategy to overcome the therapeutic resistance of HMM. Moreover, ensuing changes in the biological characteristics provide a basis for further analysis of the role of methylation in HMM carcinogenesis.

17 Article Cisplatin and resveratrol induce apoptosis and autophagy following oxidative stress in malignant mesothelioma cells. 2016

Lee, Yoon-Jin / Lee, Gina J / Yi, Sun Shin / Heo, Su-Hak / Park, Cho-Rong / Nam, Hae-Seon / Cho, Moon-Kyun / Lee, Sang-Han. ·Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan, 330-930, Republic of Korea; Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan, 330-930, Republic of Korea. · Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA, 02115-5000, USA. · Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, 336-745, Republic of Korea. · R&D Center, C.L. Pharm Co., Ltd., Seongdong-Gu, Seoul 04788, Republic of Korea. · Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan, 330-930, Republic of Korea. · Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan, 330-930, Republic of Korea. · Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan, 330-930, Republic of Korea. Electronic address: m1037624@sch.ac.kr. ·Food Chem Toxicol · Pubmed #27591926.

ABSTRACT: Malignant mesothelioma (MM) is characterized by poor responsiveness to current chemotherapeutic drugs, usually owing to high resistance to apoptosis. Here, we investigated chemosensitizing effects of phytochemical resveratrol, in combination with cisplatin, on MM cells. The combination treatment of cisplatin and resveratrol (CDDP/RSV) synergistically induced apoptosis, as evidenced by typical cell morphological changes, the appearance of sub-G0/G1 peak, an increase in the Annexin V(+) cells and the cleavage of caspase-3 and PARP. CDDP/RSV increased ROS production and depolarization of mitochondrial membrane potential with an increase in the Bax/Bcl-2 ratio. These changes were attenuated by pretreatment with N-acetylcysteine, suggesting that CDDP/RSV induced apoptosis through oxidative mitochondrial damage. Compared with MSTO-211H cells, CDDP/RSV was less efficient in killing H-2452 cells. H-2452 cells exhibited an enhanced autophagy to CDDP/RSV, as observed by an increase in viable cells exhibiting intense LysoTracker Red staining and up-regulation of Beclin-1 and LC3A. Inhibition of autophagy by bafilomycin A1 rendered cells more sensitive to CDDP/RSV-induced cytotoxicity and this was associated with induction of apoptosis. These data indicate that the increased resistance of H-2452 cells to CDDP/RSV is closely related to the activation of self-defensive autophagy, and provide the rationale for targeting the autophagy regulation in the treatment of MM.

18 Article Multidetector CT Findings and Differential Diagnoses of Malignant Pleural Mesothelioma and Metastatic Pleural Diseases in Korea. 2016

Kim, Yoon Kyung / Kim, Jeung Sook / Lee, Kyung Won / Yi, Chin A / Goo, Jin Mo / Jung, Soon-Hee. ·Department of Radiology, Gachon University Gil Medical Center, Incheon 21565, Korea. · Department of Radiology, Dongguk University Ilsan Hospital, Goyang 10326, Korea. · Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620, Korea. · Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea. · Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea. · Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea. ·Korean J Radiol · Pubmed #27390546.

ABSTRACT: OBJECTIVE: To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). MATERIALS AND METHODS: The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. RESULTS: Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. CONCLUSION: Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD.

19 Article Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway. 2016

Kim, Ka Hwi / Chae, Jung-Il / Oh, Hana / Cho, Jin Hyoung / Lee, Ra-Ham / Yoon, Goo / Cho, Seung-Sik / Cho, Young-Sik / Lee, Mee-Hyun / Liu, Kangdong / Lee, Hyun-Jeong / Shim, Jung-Hyun. ·Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea. · Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 651-756, Republic of Korea. · College of Pharmacy, Keimyung University, Dalseo-gu, Daegu 704-701, Republic of Korea. · The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450001, P.R. China. · Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Suwon 441-706, Republic of Korea. ·Oncol Rep · Pubmed #27176604.

ABSTRACT: Manumycin A (Manu A) is a natural product isolated from Streptomyces parvulus and has been reported to have anti-carcinogenic and anti-biotic properties. However, neither its molecular mechanism nor its molecular targets are well understood. Thus, the aim of the present study was to explore the possibility that Manu A has cancer preventive and chemotherapeutic effects on malignant pleural mesothelioma (MPM) through regulation of Sp1 and induction of mitochondrial cell death pathway. Manu A inhibited the cell viability of MSTO-211H and H28 cells in a concentration‑dependent manner as determined by MTS assay. IC50 values were calculated as 8.3 and 4.3 µM in the MSTO-311H and H28 cells following 48 h incubation, respectively. Manu A induced a significant increase in apoptotic indices as shown by DAPI staining, Annexin V assay, multi-caspase activity and mitochondrial membrane potential assay. The downregulation of Sp1 mRNA and protein expression by Manu A led to apoptosis by suppressing Sp1-regulated proteins (cyclin D1, Mcl-1 and survivin). Manu A decreased the protein levels of BID, Bcl-xL and PARP while it increased Bax levels. Manu A caused depolarization of the mitochondrial membrane with induction of CHOP, DR4 and DR5. Our results demonstrated that Manu A exerted anticancer effects by inducing apoptosis via inhibition of the Sp1-related signaling pathway in human MPM.

20 Article Dual B- and T-cell de-immunization of recombinant immunotoxin targeting mesothelin with high cytotoxic activity. 2016

Mazor, Ronit / Onda, Masanori / Park, Dong / Addissie, Selamawit / Xiang, Laiman / Zhang, Jingli / Hassan, Raffit / Pastan, Ira. ·Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · New Business Development Department, Medytox Inc., Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea. · Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ·Oncotarget · Pubmed #27167198.

ABSTRACT: Recombinant immunotoxins (RITs) are genetically engineered proteins being developed to treat cancer. They are composed of an Fv that targets a cancer antigen and a portion of a protein toxin. Their clinical success is limited by their immunogenicity. Our goal is to produce a new RIT that targets mesothelin and is non-immunogenic by combining mutations that decrease B- and T-cell epitopes. Starting with an immunotoxin that has B-cell epitopes suppressed, we added mutations step-wise that suppress T-cell epitopes. The final protein (LMB-T14) has greatly reduced antigenicity as assessed by binding to human anti-sera and a greatly decreased ability to activate helper T-cells evaluated in a T-cell activation assay. It is very cytotoxic to mesothelioma cells from patients, and to cancer cell lines. LMB-T14 produces complete remissions of a mesothelin expressing cancer (A431/H9) xenograft. The approach used here can be used to de-immunize other therapeutic foreign proteins.

21 Article The levels of HDAC1 and thioredoxin1 are related to the death of mesothelioma cells by suberoylanilide hydroxamic acid. 2016

You, Bo Ra / Park, Woo Hyun. ·Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju 561-180, Republic of Korea. ·Int J Oncol · Pubmed #26936390.

ABSTRACT: Mesothelioma is an aggressive tumor which is mainly derived from the pleura of lung. In the present study, we evaluated the anticancer effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor on human mesothelioma cells in relation to the levels of HDAC1, reactive oxygen species (ROS) and thioredoxin (Trx). While 1 µM SAHA inhibited cell growth in Phi and ROB cells at 24 h, it did not affect the growth in ADA and Mill cells. Notably, the level of HDAC1 was relatively overexpressed among Phi, REN and ROB cells. SAHA induced necrosis and apoptosis, which was accompanied by the cleavages of PARP and caspase-3 in Phi cells. This agent also increased the loss of mitochondrial membrane potential (MMP, ΔΨm) in Phi cells. All the tested caspase inhibitors attenuated apoptosis in SAHA-treated Phi cells whereas HDAC1 siRNA enhanced the apoptotic cell death. SAHA increased intracellular ROS levels including O2•- in Phi cells. N-acetyl cysteine (NAC) and vitamin C (Vit.C) significantly reduced the growth inhibition and death of Phi cells caused by SAHA. This drug decreased the mRNA and protein levels of Trx1 in Phi and ROB cells. Furthermore, Trx1 siRNA increased cell death and O2•- level in SAHA-treated Phi cells. In conclusion, SAHA selectively inhibited the growth of Phi and ROB mesothelioma cells, which showed the higher basal level of HDAC1. SAHA-induced Phi cell death was related to oxidative stress and Trx1 levels.

22 Article Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas. 2016

Kang, Hio Chung / Kim, Hong Kwan / Lee, Sharon / Mendez, Pedro / Kim, James Wansoo / Woodard, Gavitt / Yoon, Jun-Hee / Jen, Kuang-Yu / Fang, Li Tai / Jones, Kirk / Jablons, David M / Kim, Il-Jin. ·Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA. · Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. · Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · CureSeq Inc, Brisbane, CA, USA. · Department of Pathology, University of California San Francisco, San Francisco, CA, USA. ·Oncotarget · Pubmed #26824986.

ABSTRACT: Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM.

23 Article Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis). 2016

Kim, Su-Min / Oh, Yeonsu / Oh, Suk-Hun / Han, Jeong-Hee. ·Department of Veterinary Pathology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, Gangwon-do 24341, Republic of Korea. ·J Vet Med Sci · Pubmed #26568187.

ABSTRACT: A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk.

24 Article Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion. 2016

You, Bo Ra / Park, Woo Hyun. ·Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju 561‑180, Republic of Korea. ·Oncol Rep · Pubmed #26530353.

ABSTRACT: Mesothelioma is an aggressive tumor associated with asbestos exposure. Auranofin as an inhibitor of thioredoxin reductase (TrxR) affects many biological processes such as inflammation and proliferation. In the present study, we investigated the cellular effects of auranofin on patient-derived mesothelioma cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Basal TrxR1 levels have no difference between mesothelial cells and certain mesothelioma cells. In particular, ADA, CON and Hmeso mesothelioma cells showed lower levels of TrxR1 expression. Auranofin inhibited the proliferation of mesothelioma cells in a dose-dependent manner. Among mesothelioma cells were ADA and CON cells sensitive to auranofin. This agent also induced caspase-independent apoptosis and necrosis in ADA cells. In addition, auranofin increased ROS levels including O2(•-) and induced GSH depletion in mesothelioma cells. While N-acetyl cysteine (NAC) prevented cell death and decreased ROS levels in auranofin-treated mesothelioma cells, L-buthionine sulfoximine (BSO) intensified apoptosis and GSH depletion in these cells. In conclusion, auranofin induced mesothelioma cell death through oxidative stress and the death was regulated by the status of GSH content.

25 Article Predicting the mortality from asbestos-related diseases based on the amount of asbestos used and the effects of slate buildings in Korea. 2016

Kim, Su-Young / Kim, Young-Chan / Kim, Yongku / Hong, Won-Hwa. ·School of Architecture, Civil, Environmental and Energy Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Republic of Korea. · School of Architecture, Civil, Environmental and Energy Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Republic of Korea. Electronic address: yyoungchani@gmail.com. · Department of Statistics, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Republic of Korea. ·Sci Total Environ · Pubmed #26513124.

ABSTRACT: Asbestos has been used since ancient times, owing to its heat-resistant, rot-proof, and insulating qualities, and its usage rapidly increased after the industrial revolution. In Korea, all slates were previously manufactured in a mixture of about 90% cement and 10% chrysotile (white asbestos). This study used a Generalized Poisson regression (GPR) model after creating databases of the mortality from asbestos-related diseases and of the amount of asbestos used in Korea as a means to predict the future mortality of asbestos-related diseases and mesothelioma in Korea. Moreover, to predict the future mortality according to the effects of slate buildings, a comparative analysis based on the result of the GPR model was conducted after creating databases of the amount of asbestos used in Korea and of the amount of asbestos used in making slates. We predicted the mortality from asbestos-related diseases by year, from 2014 to 2036, according to the amount of asbestos used. As a result, it was predicted that a total of 1942 people (maximum, 3476) will die by 2036. Moreover, based on the comparative analysis according to the influence index, it was predicted that a maximum of 555 people will die from asbestos-related diseases by 2031 as a result of the effects of asbestos-containing slate buildings, and the mortality was predicted to peak in 2021, with 53 cases. Although mesothelioma and pulmonary asbestosis were considered as asbestos-related diseases, these are not the only two diseases caused by asbestos. However the results of this study are highly important and relevant, as, for the first time in Korea, the future mortality from asbestos-related diseases was predicted. These findings are expected to contribute greatly to the Korean government's policies related to the compensation for asbestos victims.

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