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Therapeutic induction of apoptosis into musculoskeletal tumors

Research Project

Project/Area Number 09671529
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKurume University

Principal Investigator

KOMIYA Setsuro  Kurume Univ.School of Med.Associate Professor., 医学部, 講師 (30178371)

Co-Investigator(Kenkyū-buntansha) ZENMYO Michihisa  Kurume Univ.School of Med.Fellow, 医学部, 助手 (10289465)
HIRAOKA Koji  Kurume Univ.School of Med.Fellow, 医学部, 助手 (10268914)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsOsteosarcoma (OSA) / Giant cell tumor (GCT) / Fas / Soluble Fas / Apoptosis / Signal transduction
Research Abstract

Fas is a cell-surface antigen which could induce apoptosis, belonging to the superfamily of TNF-alpha. A study on Fas-mediated apoptosis has seldome been made in musculoskeletal tumors, including osteosarcoma. In this study using surgical samples and cell lines, Fas was searched in musculosketetal tumor cells, and the mechanism which could modulate Fas-mediated apoptosis was investigated. We also examined if apoptosis was induced in osteosarcoma cells by treatment with vitamins D and K.Furthermore, we investigated whether osteoclastoma cells could undergo apoptosis by treatment with bisphosphonates. In surgical samples, many positive cells were identified on TUNEL staining, and apoptotic bodies were seen in ultrastructural examinations. DNA samples demonstrated the ladder pattern characteristic to apoptosis. Fas was identified in 9 out of 14 osteosarcoma cell lines and in all of 4 osteoclastoma strains. The soluble form of Fas was also demonstrated. Treatment with cyclohexamide increased the induction of Fas-mdiated apoptosis in almost all of the cell lines. Treatment of osteosarcoma cells with vitamins D and K lead them to differentiation in accordance with the expression of p21, and apoptosis was then induced after the repression of p21. Bisphosphonates induced apoptosis in osteoclastoma cells. These results indicated that treat ment of those tumor cells to upregulate apoptosis may be essential for their treatment.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Koji Hiraoka Setsuro Komiya, Tetsuya Hamada, Michihisa Zenmyo, Akio Inoue: "Induction of Apoptosis by Selenium in Osteosarcoma Cells" J.Orthop.Res.(accepted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tetsuya Hamada, Setsuro Komi, Hirohisa Yano, Michihisa Zenmyo, Kohji Hiraoka, Akio Inoue, Minoru Morimatsu: "Modulation of Fas-mediated Apoptosis in Osteosarcoma Cell Lines" J.Orthop.Res.(accepted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary

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Published: 1997-04-01   Modified: 2016-04-21  

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