ANALYSIS OF IMMUNOLOGICAL TARGET MOLECULES FOR MOLECULAR PREVENTION OF ASBESTOS-RELATED TUMOR FORMATIONIN CASES WHO EXPOSED ASBESTOS

• Project/Area Number: 18390186
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Kawasaki Medical School
• Principal Investigator: OTSUKI Takemi Kawasaki Medical School, SCHOOL OF MEDICINE, DEPARTMENT OF HYGINE, PROFESSOR (40160551)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Yasumitsu Kawasaki Medical School, SCHOOL OF MEDICINE, DEPARIMENT OF HYGINE, ASSISTANT PROFESSOR (90360271) ; MAEDA Megumi Kawasaki Medical School, SCHOOL OF MEDICINE, DEPARTMENT OF HYGINE, RESEARCH FELLOW (20434988) ; MURAKAMI Shuko Kawasaki Medical School, SCHOOL OF MEDICINE, DEPARTMENT OF HYGINE, RESEARCH FELLOW (50454848)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥16,830,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,130,000); Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
• Keywords: ASBESTOS / T CELL / TGF-BETA / IL-10 / REGULATORYT CELL / CXCR3 / MALIGNANT MESOTHELIOMA / CANCER PREVENTION / アポトーシス / Bcl-2 / 石綿肺 / T細胞受容体

Research Abstract

IT IS COMMON KNOWLEDGE THAT ASBESTOS EXPOSURE CAUSES ASBESTOS-RELATED DISEASES SUCH AS ASBESTOSIS, LUNG CANCER AND MALIGNANT MESOTHELIOMA (MM) NOT ONLY IN PEOPLE WHO HAVE HANDLED ASBESTOS IN THE WORK ENVIRONMENT, BUT ALSO IN RESIDENTS LIVING NEAR FACTORIES THAT HANDLE ASBESTOS. THESE FACTS HAVE BEEN AN ENORMOUS MEDICAL AND SOCIAL PROBLEM IN JAPAN SINCE THE SUMMER OF 2005. WE FOCUSED ON THE IMMUNOLOGICAL EFFECTS OF ASBESTOS AND SILICA ON THE HUMAN IMMUNE SYSTEM IN THIS BRIEF REVIEW, WE PRESENT IMMUNOLOGICAL CHANGES IN PATIENTS WITH MM AND OUTLINE THEIR EXPERIMENTAL DETECTION. FOR EXAMPLE, THERE IS OVER-EXPRESSION OF BCL-2 IN CD4+ PERIPHERAL T CELLS, HIGH PLASMA CONCENTRATIONS OF INI'ERLEUKIN (L)-l0 AND TRANSFORMING GROWTH FACTOR (TGF)-β AND MULTIPLE OVER ON OF T CELL RECEPTOR (TCR)-Vβ IN PERIPHERAL CD3+ T CELLS FOUND IN MM PATIENTS. WE ALSO DETAIL AN EXPERIMENTAL LONGTERM EXPOSURE T-CELL MODEL. ANALYSIS OF THE IMMUNOLOGICAL EFFECTS OF ASBESTOS MAY HELP OUR UNDERSTANDING OF THE BIOLOGICAL EFFECTS OF ASBESTOS. RECENT ADVANCES IN IMMUNOMOLECULAR STUDIES HAVE LED TO DETAILED ANALYSES OF THE IMMUNOLOGICAL EFFECTS OF ASBESTOS. ASBESTOS AFFECTS IMMUNOCOMPETENT CELLS AND THESE EFFECTS MAY RE ASSOCIATED WITH THE PATHOPHYSIOLOGICAL DEVELOPMENT OF COMPLICATIONS IN ASBESTOS-EXPOSED PATIENTS SUCH AS MALIGNANT TUMORS. IN ADDITION, IMMUNOLOGICAL ANALYSES MAY LEAD TO THE DISCOVERY OF NEW CLINICAL TOOLS FOR THE MODIFICATION OF PATHOPHYSIOLOGICAL ASPECTS OF DISEASES, SUCH AS THE REGULATION OF TUMOR IMMUNITY USING CELL-MEDLATED THERAPIES, VARIOUS CYTOKINES AND MOLECULE-TARGETING THERAPIES. AS THE INCIDENCE OF ASBESTOS-RELATED MALIGNANCIES INCREASES AGAINST THE GROWING CONCERN IN JAPAN SINCE THE SUMMER OF 2005 FOR MEDICAL AND SOCIAL PROBLEMS CREATED BY SUCH MALIGNANCIES, EFFORTS SHOULD RE FOCUSED ON DEVELOPING A CURE FOR THESE DISEASES IN ORDER TO ELIMINATE THE NATIONWIDE ANXIETY CONCERNING THESE MALIGNANCIES.

Research Products

• [Journal Article] Immunological effects of silica and asbestos (2007)
  • Author(s): Otsuki T, Maeda M, Murakami S, Hayashi H, Miura Y, Kusaka M, Nakano T, Fukuoka K, Kishimoto T, Hyodoh F, Ueki A, Nishimura Y.
  • Journal Title: Cell Mol Immnol 4 Pages: 261-268
  • NAID: 10029363262
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] IMMUNOTOXEOLOGICAL RESEARCHES AND PREVENTIVE MEDICINE. FOREWORD-THE RREPORT FROM THE 13TH ANNUAL MEETING OF THE JAPANESE SOCIETY OF IMMUNOTOXICOLOGY (JSIT 2006). (2007)
  • Author(s): OTSUKI T
  • Journal Title: ENVIRONHEALTHPREVMED 12(4) Pages: 151-152
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] KEYNOTE LECTURE IN THE 13TH JAPANESE SOCIETY OF IMMUNOTOXICOLOGY(JSIT 2006)-PATHOPHYSIOLOGICAL DEVELOPMENT AND IMMUNOTOXECOLOGY WHAT WE HAVE FOUND FROM THE RESEARCHES RELATED TO THE SIT ICAAND STI ICATE SUCHASASBFSTOS-. (2007)
  • Author(s): OTSUKI, T, MEURAY, MAEDAM, HAYASHI H, DONGM, NISHMURAY.
  • Journal Title: ENVIRONHEALTHPREVMED 12(4) Pages: 153-164
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] KEYNOTE LECTURE IN THE 13TH JAPANESE SOCIETY OF IMMUNOTOXICOLOGY(JSIT 2006)- PATHOPHYSTOLOGICAL DEVELOPMENT AND IMMUNOTOXICOLOGY WHAT WE HAVE FOUND FROM THE RESEARCHES RELATED TO THE SILICAAND SILICATE SUCHASASBESTOS-. (2007)
  • Author(s): OTSUKI T, MIURAY, HYODOH F, MAMAM, HAYASHI H, DONGM KATSUYAMA H, TOMITA M, UEKI A, NISHIMURA Y.
  • Journal Title: KAWASAKE MED J 33(3) Pages: 165-179
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IMMUNOLOGICAL EFFECTS OF SIT JCAANDASBESTOS. (2007)
  • Author(s): OTSUKI T, MAEDA M, MURAKAMI S, HAYASHI H, MIURA Y, KUSAKA M, NAKANO T, FUKUOKAK, KESHIMOTO T, HYODOH F, UEKI A, NESHMURAY.
  • Journal Title: CELLMOLIMMNOL 4(4) Pages: 261-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] LONG-LASTING PRODUCTION OF TGF-BETA1 BY ALVEOIAR MACROPHACES EXPOSED TO LOW DOSES OF ASBESTOS WITHOUT APOPTOSLS. (2007)
  • Author(s): NISHIMURA Y, NISHIEE-WADA T, WADA Y, MIURA OTSUKI T, IGUCHI H
  • Journal Title: INT JIMMUNOPATHOL PHARMACOL 20(4) Pages: 661-667
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alterations of Fas and Fas-related molecules in patients with silicosis. [Review article] (2006)
  • Author(s): Otsuki T, Miura Y, Nishimura Y, Hyodoh F, Takata A, Kusaka M, Katsuyama H, Tomita M, Ueki A, Kishimoto T
  • Journal Title: Exp Biol Med 231(5) Pages: 522-33
• [Journal Article] Expression of the T cell receptor Vβ repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases. (2006)
  • Author(s): Nishimura Y, Miura Y, Maeda M, Hayashi H, Dong M, Katsuyama H, Tomita M, Hyodoh F, Uesaka A, Kuribayashi K, Fukuoka K, Nakano T, Kishimoto T, Otsuki T.
  • Journal Title: Int J Immunopathol Pharmacol 19(4) Pages: 795-805
• [Journal Article] Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells. (2006)
  • Author(s): Miura Y, Nishimura Y, Katsuyama H, Maeda M, Hayashi H, Dong M, Hyodoh F, Tomita M, Mastuo Y, Uesaka A, Kuribayashi K, Nakano T, Kishimoto T, Otsuki T
  • Journal Title: Apoptosis 11(10) Pages: 1825-35
• [Journal Article] Reduced function of CD4+25+ regulatory T cell fraction in silicosis patients. (2006)
  • Author(s): Wu P, Miura Y, Hyodoh F, Nishimura Y, Hatayama T, Hatada S, Sakaguchi H, Kusaka M, Katsuyama H, Tomita M, Otsuki T.
  • Journal Title: Int J Immunopathol Pharmacol 19(2) Pages: 357-68
• [Journal Article] Asbestos-related carcinogenesis and immunological effects (Focus lecture 1) (2006)
  • Author(s): Otsuki T, Miura Y, Maeda M, Hayashi H, Dong M, Nishimura Y, Tomita M, Katsuyama H.
  • Journal Title: Biomed Res Trace Elements 17(s2) Pages: 9-103
• [Journal Article] 珪肺症と石綿関連疾患における抹消血T細胞受容体Vβレパトアの解析. (2006)
  • Author(s): 大槻剛巳, 西村泰光, 三浦由恵, 兵藤文則, 勝山博信, 上坂亜由子, 栗林康造, 中野孝司, 草加勝康, 岸本卓巳.
  • Journal Title: 日本職業・災害医学会会誌 51 Pages: 66-71
• [Journal Article] Immunological changes in mesothelioma patients and their experimental detection
  • Author(s): Maeda M, Miura Y, Nishimura Y, Murakami S, Hayashi H, Kumagai N, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Fukuoka K, Kishimoto T, Nakano T
  • Journal Title: Clin Med:Circ Resp Pulm Med (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Immunological alterations found in mesothelioma patients and their experimental evidences
  • Author(s): Miura Y, Nishimura Y, Maeda M, Murakami S, Hayashi H, Fukuoka K, Kishimoto T, Nakano T, Otsuki T.
  • Journal Title: Environ Health Prev Med (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] IMMUNOLOGICAL ALTERATIONS FOUND IN MESCYTHELIOMA PATIENTS AND THEIR EKPERIMENTAL EVIDENCES.
  • Author(s): MIURA Y, NLSHIMURA Y, MAEDA M, MURAKAMI S, HAYASHI H, FUKUOKAK, KISHIMOTO T, NAKANO T, CITSUKE T.
  • Journal Title: ENVIRONHEALTHPREVMED (IN PRESS)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IMMUNOLOGICAL CHANGES IN MESOTHELIOMAPATIENTSAND THEIR EXPERIMENTAL DETECTION.
  • Author(s): MAEDA M, MIUR Y, NISHIMURA Y, MURAKAMI S, HAYASHI H, KUMAGAI N, HATAYAMA T, KATOH M, MIYAHARA N, YAMAMOTO S, FUKUOKA K, KESHIMOTOT, NAKANO T.
  • Journal Title: CLINMED : CIRC, RESPPULMMED (IN PRESS)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NEGATIVELY-CHARGED AIR CONDITIONS AND RESPONSES OF THE HUMANPSYCHO-NEURO-ENDOCRINO-IMMUNE NETWORK.
  • Author(s): TAKAHASHI K, OTSUKI T, MASE A, KAWADO T, KOTANI M, AMI K, MATSUSHIMA H, NESHMURA Y, MIURA Y, MURAKAMI S, MAEDA M, HAYASHI H, KUMAGAI N, SHIRAHAMA T, YOSHIMATSU M, MORIMOTO K
  • Journal Title: ENVIRONINT (IN PRESS)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Immunological changes in mesothelioma patients and their experimental detection
  • Author(s): Maeda M, Miura Y, Nishimura Y, Murakami S, Hayashi H, Kumagai N, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Fukuoka K, Kishimoto T, Nakano T
  • Journal Title: Clin Med:Circ Resp Puhn Med (In press)
  • Peer Reviewed
• [Journal Article] Immunological alterations found in mesothelioma patients and their experimental evidences.
  • Author(s): Miura Y, Nishimura Y, Maeda M, Murakami S, Hayashi H, Fukuoka K, Kishimoto T, Nakano T, Otsuki T.
  • Journal Title: Environ Health Prev Med (In press)
  • Peer Reviewed
• [Presentation] Immunological effects of asbestos (2007)
  • Author(s): Otsuki T, Maeda M, Miura Y, Murakami S, Hayashi H, Nishimura Y, Kuribayashi K, Fukuoka K, Nakano T.
  • Organizer: 66th Annual Meeting of the Japanese Cancer Association (English Session)
  • Place of Presentation: Pacifica Yokohama,Yokohama,Kanagawa,Japan
  • Year and Date: 2007-10-04
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Immunological effects of asbestos (2007)
  • Author(s): Otsuki T, Maeda M, Miura Y, Murakami S, Hayashi H, Nishimura Y, Ikuribayashi K, Fukuoka K, Nakano T.
  • Organizer: 66th Annual Meeting of the Japanese Cancer Aseociation(English Session)
  • Place of Presentation: Pacifica Yokohama,Yokohama,Kanagawa,Japan
  • Year and Date: 2007-10-04