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Treatment of rat C6 meningeal dissemination model by intrathecal injection o frecomvinant soluble FasL

Research Project

Project/Area Number 14571318
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionSaga University

Principal Investigator

SHIRAISHI Tetsuya  Saga University, Faculty of Medicine, Lecturer, 医学部, 講師 (70206275)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Yusuke  Mochida Pharmaceutical, Co., Ltd., Research Scientist, 研究員
TABUCHI Kazuo  Saga University, Faculty of Medicine, Professor, 医学部, 教授 (50116480)
一ノ瀬 誠  佐賀医科大学, 医学部, 助手 (60336138)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsapoptosis / Fas / Fas ligand / glioma / meningeal dissemination / isoleucine zipper / グリオーマ / FasL / アポトーシス / イソロイシンジッパー / 髄膜播種モデル / Fasリガンド
Research Abstract

Fas (CD95) ligand (FasL) has the ability to induce apoptosis in Fas-expressing glioma cells by binding to with Fas: Several molecular species have been designed to be soluble Fas ligands for therapeutic purposes. Most of them possessing just only extracellular domain of Fas ligand (soluble FasL) cannot be used practically due to either insufficient biological activity or reduced productivity. We. successfully constructed a chimeric soluble. FasL by fusing a isoleucine zipper motif for se If-oligomerization and a FLAG sequence to the extracellular domain of the human Fas ligand (FIZ-shFasL). The cytotoxic effect of FIZ-shFasL on Jurkat cells was equivalent to that of membrane-bound FasL and approximately ten-fold stronger than that of agonistic anti-Fas antibody (CH-11). Expression of Fas and Bcl-2 on cell lines was determined using flow cytometry and compared with sensitivity to FIZ-shFasL. Flowcytometric analysis demonstrated that the differential Fas expression of human brain tumor cell lines partially correlated with levels of apoptosis through FIZ-shFasL. The intravenous administration of 1.0mg/kg of FIZ -shFasL resulted in a lethal effect in rats. A rat meningeal dissemination model with rat Fas-expressing C6 glioma cells can be treated successfully by intrathecal FIZ-shFasL administration without any apparent adverse effects. These results suggest that intrathecal administration of FIZ-shFasL maybe applied to the treatment of patients with leptomeningeal gliomatosis in the near future.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 田渕和雄, 白石哲也: "ポストシークエンス時代における脳腫瘍の研究と治療"脳神経外科. 30. 13-21 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 白石哲也, 田渕和雄: "癌分子標的治療薬開発の現況と脳腫瘍治療への応用"脳神経外科. 31. 365-381 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tetsuya Shiraishi, Kazuc Tabuchi: "Genetic alterations of human brain tumors as molecular prognostic factors"Neuropathology. 23. 95-108 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 白石哲也, 田渕和雄: "プロテオミクス-脳腫瘍のキーワード最新版"Clinical Neuroscience. 21. 514 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 白石哲也, 田渕和雄, 小谷秀示, 小長谷明彦: "脳腫瘍のシステムバイオロジー"蛋白質核酸酵素. 48. 795-801 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 白石哲也, 田渕和雄: "ポストシークエンス時代における脳腫瘍の研究と治療"九州大学出版会. 561 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tabuchi, K., Shiraishi, T.: "Brain tumor research and therapy in postsequence era."No Shinkei Geka. 30. 13-21 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiraishi, T., Tabuchi, K.: "Development of anti-cancer drugs based on molecular targeting and their application to brain tumor therapy."No Shinkei Geka. 31. 365-381 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiraishi, T., Tabuchi, K.: "Genetic alterations of human brain tumors as molecular prognostic factors."Neuropathlogy. 21. 95-108 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiraishi, T., Tabuchi, K.: "Proteomics -keywords of brain tumor -Clinical"Neuroscience. 21. 514 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiraishi, T., Tabuchi, K., Kotani S., Konagaya, A.: "System biological approach to research and treatment of brain tumors."Tanpaku Kakusan Kouso. 48. 795-801 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiraishi, T., Tabuchi, K.eds.: "Brain tumor research and therapy in postsequence era."Kyushu University Press. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 白石哲也: "癌分子標的治療薬開発の現況と脳腫瘍治療への応用"脳神経外科. 31. 365-381 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 白石哲也: "プロテオミクス-脳腫瘍のキーワード最新版"Clinical Neuroscience. 21. 21-21 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 白石哲也: "ポストシークエンス時代における脳腫瘍の研究と治療"九州大学出版会. 561 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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