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Establishment of a novel therapy for glioma invasion by antisense inhibition of the targeting molecule.

Research Project

Project/Area Number 14571314
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OHNISHI Takanori  Ehime University, School of Medicine, professor, 医学部, 教授 (70233210)

Co-Investigator(Kenkyū-buntansha) HARADA Hironobu  Ehime University, University Hospital, Assistant, 医学部附属病院, 助手 (20335897)
NAKAGAWA Kou  Ehime University, University Hospital, Assistant professor, 医学部附属病院, 講師 (50155678)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsGLIOMA / TUMOR INVASION / LAMININ-8 / ANTISENSE
Research Abstract

In order to clarify the molecular mechanism of glioma invasion, we studied an expression of laminin-8 in brain tumors and investigated an effect of antisense inhibition of laminin-8 on migration and invasion of glioma cells. The protein and mRNA of laminin-8 were highly expressed in malignant gliomas, particulary in glioblastomas showing diffuse invasion. Antisense of laminin-8(α4 subunit) markedly inhibited the glioma cell migration and invasion in vitro without affecting the cell growth. In addtion, antisense of laminin-8 significantly inhibited the glioma cell invasion in both a rat brain slice model and a tumor-inoculated model. Antisense inhibition of laminin-8 resulted in weak formation of actin stress fibers in glioma cells but did not affect the expression of Rac and Cdc42. These results suggest that gene suppression of laminin-8 may inhibit the glioma cell motility through the inhibition of formation of focal adhesion.

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Harada H, Nakagawa K, Ohnishi T, et al.: "Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells."Cancer Lett. 191. 109-119 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kohno S, Nakagawa K, Ohnishi T, et al.: "Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy."Oncol Rep. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito M, Nakagawa K, Ohnishi T, et al.: "Introduction of p16 inhibits telomerase activity through transcriptional suppression of human telomerase reverse transcriptase expression in human gliomas."Int J Oncol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 大西丘倫: "アンチセンス核酸を用いた悪性脳腫瘍の放射線治療"遺伝子医学. 6. 31-35 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中川晃, 原田広信, 大西丘倫: "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. 173-177 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Harada H, Nakagawa K, Ohnishi T, et al.: "Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells."Cancer Lett. 191. 109-119 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kohno S, Nakagawa K, Ohnishi T, et al.: "Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy."Oncol Rep. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito M, Nakagawa K, Ohnishi T, et al.: "Introduction of p16 inhibits telomerase activity through transcriptional suppression of hIuman telomerase reverse transcriptase expression in human gliomas."Int J Oncol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohnishi T: "Radiation therapy for malignant gliomas by antisense inhibition of rad51"Gene and and Medicine. 6. 31-35 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakagawa k, Harada H, Ohnishi T, et al.: "Effects of p53 and p16 gene transfer on thrombospondins expression in human gliomas"Brain Tumor Research and Therapy in the Postsequence Era, (Tabuchi K, Shiraishi T(eds)(Kyushu University Press). 173-177 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Harada H, Nakagawa K, Ohnishi T, et al.: "Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells."Cancer Lett. 191. 109-119 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kohno S, Nakagawa K, Ohnishi T, et al.: "Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy."Oncol Rep. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Saito M, Nakagawa K, Ohnishi T, et al.: "Introduction of p16 inhibits telomerase activity through transcriptional suppression of human telomerase reverse transcriptase expression in human gliomas."Int J Oncol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Harada H, Nakagawa K, Ohnishi T, et al.: "Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells"Cancer Letter. 191. 109-119 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大西丘倫: "アンチセンス核酸を用いた悪性脳腫瘍の放射線治療"遺伝子医学. 6. 31-35 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中川晃, 原田広信, 大西丘倫: "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. 173-177 (2002)

    • Related Report
      2002 Annual Research Report

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

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