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A PRODUCTIVE TRIAL OF ANTI-ANGIGENIC AGENTS BASED ON A ELUCIDATION OF A MECHANISM OF bFGF AS A FIRST TRIGGER ON ANGIOGENIC PATHWAY

Research Project

Project/Area Number 09672343
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionTOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH

Principal Investigator

ASHINO Hiromi  TOKYO METROPOLITAN ORGANIZATION OF MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE / DEPARTMENT OF MOLECULAR BIOLOGY / RESEARCH SCIENTIST, 東京都臨床医学総合研究所, 研究員 (40222608)

Co-Investigator(Kenkyū-buntansha) SHIMAMURA Mariko  TOKYO METROPOLITAN ORGANIZATION OF MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE / DEPARTMENT OF MOLECULAR BIOLOGY / RESEARCH SCIENTIST, 東京都臨床医学総合研究所, 研究員 (00124462)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
KeywordsAngiogenesis / Acidic polysaccharides / bFGF / Herapan sulfate / chorioallantoic membrane / endothelial cells / bFGF / FGF
Research Abstract

In order to try the production of inhibitors of angiogenic diseases, which inhibit the activity of first angiogenic factor functioning as a trigger, we examined anti-angiogenic activities of various acidic polysaccharides using chick embryonic chorioallantoic membrane (CAM)s and bovine vascular endothelial cell culture.
We found that Dextran sulfate (DS) markedly inhibited angiogenesis of chick CAMs, that its inhibitory effect did not depend on molecular weight, but depended on sulfation, that DS inhibited cell migration unstimulated and stimulated by bFGF and that in heparitinase-treated endothelial cells the signal of bFGF to induce plasminogen activator was weakened.
These results indicate that DS may disrupt binding of bFGF or heparin / heparan sulfate(HS)-binding angiogenic factors to HS, resulting in the inhibition of angiogenesis. It is thought that functional inhibition of angiogenic factor as a trigger is important and effective to suppress the initiation of angiogenesis. Accordingly molecules like DS that modulate the activity of heparin / HS-binding growth factors by sequestering the growth factor are expected to suppress the early step of angiogenesis.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Ashino, H. et al.: "Inhibition of angiogenesis by ascorbic acid and its derivatives"Bulletin of the Philippine Society for Biochemistry and Molecular Biology. 16. A6 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimamura, M. et al.: "Anti-angiogenic and anti-metastatic effects of new hypoxic cell radiosensitizer"20th International Congress of Chemotherapy. 1997. (54)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ashino, H. et al.: "Inhibition of angiogenesis by dextran sulfate-effective structure and inhibitory activity-"Meeting of the Federation of European Biochemical Society(FEBS). 25P32.09. 178 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ashino, H. et al.: "Regulation of angiogenesis and plasminogen activator activity by calpain inhibitor I(ALLNal)"Rinshoken International Conference. 13 P29. 141 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ashino, H., Nakajima, H. and Kawashima, S.: "Inhibition of angiogenesis by ascorbic acid and its derivatives."Bulletin of the Phillippine Society for Biochemistry and Molecular Biology. 16. A6 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimamura, M., Hori, H., Ashino, H., Yamamoto, Y., Hzato, T. and Inayama, S.: "Anti-angiogenic and anti-metastatic effects of new hypoxic cell radiosensitizer."I.C.C.. 20. 2369 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ashino, H., Shimamura, M. and Kawashima, S.: "Inhibition of angiogenesis by dextran sulfate-Effective structure and inhibitory activity-."25th Silver Jubilee FEBS Meeting. 178. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ashino, H., Nakajima, H., Shimamura, M., Dombou, M., Kawanaka, S., Hattori, N., Iwaguchi, T. and Kawashima, S.: "Novel function of ascorbic acid as an angiogenesis inhibitor."(submitted.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ashino,H. et al.: "Inhibition of angiogenesis by dextran sulfate -effective structure and inhibitory activity-." Meeting of the Federation of European Biochemical Society (FEBS). 25P32.09. 178 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ashino,H. et al.: "Regulation of angiogenesis and plasminogen activator activity by calpain inhibitor I (ALLNal)." Rinshoken International Conference. 13 P29. 141 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ashino,H.et al.: "Inhibition of angiogenesis by ascorbic acid and its derivatives." Bulletin of the Philippine Society for Biochemistry and Molecular Biology. 16. A6 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimamura,M.et al.: "Anti-angiogenic and anti-metastatic effects of new hypoxic cell radiosensitizer." 20th International Congress of Chemotherapy. 54 (1997)

    • Related Report
      1997 Annual Research Report

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

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