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ELUCIDATION OF MECHANISM OF ANGIOGENESIS,A FUNDAMENTAL FUNCTION OF VASCULAR ENDOTHELIAL CELLS AND ITS CONTROL

Research Project

Project/Area Number 06836019
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 血管生物学
Research InstitutionTHE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE,DEPARTMENT OF CANCER THERAPEUTICS

Principal Investigator

OIKAWA Tsutomu  THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE,DEPARTMENT OF CANCER THERAPEUTICS,SENIOR RESEARCH SCIENTIST, 化学療法研究部門, 研究員 (40120141)

Co-Investigator(Kenkyū-buntansha) HAMADA Hiroshi  UNIVERSITY OF OSAKA,PROFESSOR, 細胞生体工学センター, 教授 (00208589)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsANGIOGENESIS / VASCULAR ENDOTHELIAL CELLS / ANGIOGENESIS INHIBITOR / TYROSINE KINASE / EPOXIDE GROUP / ANGIOGENIC DISEASE / ANTITUMOR ACTIVITY
Research Abstract

The present study provided the following four lines of evidence. First, 3 isoforms of platelet-derived growth factor, whose membrane receptors contain functional tyrosine kinase domains, are all indirect inducers of angiogenesis in vivo. Second, we previously showed that herbimycin A,a microbial tyrosine kinase inhibitor, is a potent inhibitor of angiogenesis using an in vivo assay system involving chorioallantoic membranes (CAMs) of growing chick embryos. The present experiment identified functional groups responsible for the antiangiogenic effect of herbimycin A under the same assay conditions. Third, based on our previous findings that eponemysin and radicicol, epoxide-containing microbial products, inhibit angiogenesis in a CAM assay system, we have a working hypothesis that the epoxide group will be a useful indicator in the search for novel angiogenesis inhibitors. As the first attempt to verify this, in vivo experiments were conducted to determine whether rhizoxin, amicrobial metabolite containing two epoxide groups, affects angiogenesis in a CAM or mouse dorsal air sac assay system. It was found to be a potent inhibitor of angiogenesis in both assay systems. Depudecin, another epoxide-containing microbial product, also has antiangiogenic activity. Finally, cytogenin, a microbial product, was found to have antitumor and anti-rheumatoid arthritis effects, but its mechanism of action was not fully established. We assumed that the inhibitory effects of cytogenin on these two diseases involve its antiangiogenic activity, because the two diseases are well-known to be angiogenic disorders. The microbial product had no effect on embryonic angiogenesis, but significantly affected tumor angiogenesis even when administered orally.
Based on these findings, we proposed that angiogenesis is an important target for overcoming angiogenesis-dependent diseases, including cancer, diabetic retinopathy and rheumatoid arthritis.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Oikawa, T.: "Possible functional groups reponsible for inhibition of in vivo angiogenesis by herbimycin A" Biol. Pharm. Bull.17. 1430-1432 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Oikawa, T.: "Three isoforms of platelet-derived growth factors all have the capability to induce angiogenesis in vivo" Biol. Pharm. Bull.17. 1686-1688 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "ガン増殖抑制に新たな手法-ガン細胞の栄養補給を断つ" 治療. 76. 1494-1496 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "ニワトリ胚漿尿膜、ウサギ角膜を用いた血管新生因子の検出" 現代医療. 26. 1849-1855 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "腫瘍血管新生" 医学のあゆみ. 170. 544-548 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Oikawa, T.: "Depudecin, a microbial metabolite containing two epoxide groups, exhibits anti-angiogenic activity in vivo." Biol. Pharm. Bull.18. 1305-1307 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Oikawa, T.: "Strategies to find novel angiogenesis inhibitors as potential therapeutic agents for cancer." Curr. Med. Chem.1. 406-417 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "癌増悪機能と血管新生" 最新医学. 50. 1178-1184 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "血管新生の制御に基づく癌克服" Biotherapy. 9. 494-500 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "血管新生抑制剤開発" ファルマシア. 31. 1152-1154 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "腫瘍の増殖、浸潤と血管新生" Practical Oncol.(1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "がんの侵潤・転移研究マニュアル" 金芳堂(がん転移研究開編), 252 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "今日の癌化学療法" 中外医学社(鶴尾 隆、西條長宏編), (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 及川 勉: "血管新生のメカニズムと疾患" 医薬ジャーナル社(室田誠逸、井藤英喜編), (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Oikawa, T.: "Depudecin, a microbial metabolite containing two epoxiede groups, exhibits anti-angiogenic activity in vivo." Biol. Pharm. Bull.18. 1305-1307 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Oikawa, T.: "Strategies to find novel angiogenesis inhibitors as potential therapeutic agents for cancer." Curr. Med. Chem.1. 406-417 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 及川 勉: "癌増悪機能と血管新生" 最新医学. 50. 1178-1184 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 及川 勉: "血管新生の制御に基づく癌克服" Biotherapy. 9. 494-500 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 及川 勉: "血管新生制御剤開発" ファルマシア. 31. 1152-1154 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 及川 勉: "腫瘍の増殖、浸潤と血管新生" Practical Oncol.(1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 及川 勉: "今日の癌化学療法" 中外医学社(鶴尾 隆、西條長宏編), (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 及川 勉: "血管新生のメカニズムと疾患" 医薬ジャーナル社(室田誠逸、井藤英喜編), (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Oikawa,T.: "Possible functional groups responsible for inhibition of in vivo angiogenesis by herbimycin A" Biol.Pharm.Bull.17. 1430-1432 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Oikawa,T.: "Three isoforms of platelet-derived growth factors all have the capability to induce angiogenesis in vivo" Biol.Pharm.Bull.17. 1686-1688 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Oikawa,T.: "Strategies to find novel angiogenesis inhibitors as potential therapeutic agents for cancer" Curr.Med.Chem.2. 406-417 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 及川勉: "ガン増殖抑制に新たな手法-ガン細胞の栄養補給を断つ" 治療. 76. 1494-1496 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 及川勉: "ニワトリ胚漿尿膜、ウサギ角膜を用いた血管新生因子の検出" 現代医療. 26. 1849-1855 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 及川勉: "腫瘍血管新生" 医学のあゆみ. 170. 544-548 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 及川勉: "がんの侵潤・転移研究マニュアル" 金芳堂(がん転移研究会編), 252 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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