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Analysis of the mechanisms of action of angiogenesis inhibitor, endostatin and its dynamic localization in tumor blood vessels.

Research Project

Project/Area Number 16591250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YAMAGUCHI Noriko  Tokyo Med. & Dent.Univ., Med.Res.Inst., Instructor, 難治疾患研究所, 助手 (90251553)

Co-Investigator(Kenkyū-buntansha) AOYAGI Masaru  Tokyo Med. & Dent.Univ., Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40134704)
HORI Hisae  Tokyo Med. & Dent.Univ., Med.Res.Inst., Instructor, 難治疾患研究所, 助手 (80014190)
服部 俊治  ニッピバイオマトリックス研究所, 主任研究員
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsAngiogenesis / Cancer / Endostatin / Collagen / ガン
Research Abstract

Endostatin is an endogenous angiogenesis inhibitor and showed quite strong anti-cancer activity. In mouse tumor model, endostatin inhibits tumor progression, tumor metastasis and induces tumor regression. The final goal of this research is to elucidate the functional mechanisms of endostatin on molecular level, then to contribute the development of new anti-cancer drugs. During 2004 to 2005, we achieved those progression described below.
In addition to anti-cancer activity, endostatin showed the strong anti-inflammatory activity in animal model for rheumatoid arthritis. We confirmed the efficacy of endostatin in two different experimental models. Also, we discovered that endostatin has inhibitory activity against some kinds of matrix metalloproteinases, MMP-2, 9, 12, 13, 14 through the examination of functional study. Inhibitory activity against matrix metalloproteinases was considered to be one of the mechanisms of anti-inflammatory effects. MMP-14 is expressed on cell membrane and has been reported to participate the considerable contribution for tumor invasion and metastasis. Therefore, it is possible that endostatin binds MMP-14 and inhibits tumor invasion and metastasis through its blocking enzyme activity. We analyzed that the co-localization of endostatin and MMP-14 was observed by confocal microscopy after endostatin was exposed to HUVEC. However, we could not detect the co-localization. The experimental data for HUVEC migration inhibition assay demonstrated that some preparations of HUVEC did not respond to endostatin. We hypothesized that there was the difference of gene expression profile between responder and non-responder. Using gene chip microarray, gene expression was estimated and the results for comparison revealed that accelerated expression was observed in 1.86% of genes, 2.9% of genes showed decreased expression and 95% were unchanged for the responder cells in comparison with the non-responder cells.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (13 results)

All 2005 2004

All Journal Article (13 results)

  • [Journal Article] Usefulness of L-[methyl-11C]methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.2005

    • Author(s)
      Nariai, T. et al.
    • Journal Title

      J Neurosurg. 103 (3)

      Pages: 498-507

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpressed Skp2 within 5p amplification detected by array-based comparative genomic hybridization is associated with poor prognosis of glioblastoma2005

    • Author(s)
      Saigusa, K. et al.
    • Journal Title

      Cancer Sci. 96 (10)

      Pages: 676-683

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Usefulness of L-[methyl-11C]methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.2005

    • Author(s)
      Nariai, T. et al.
    • Journal Title

      J.Neurosurg. 103(3)

      Pages: 498-507

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpressed Skp2 within 5p amplification detected by array-based comparative genomic hybridization is associated with poor prognosis of glioblastoma2005

    • Author(s)
      Saigusa, K et al.
    • Journal Title

      Cancer Sci. 96(10)

      Pages: 676-683

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.2005

    • Author(s)
      Narai, T.et al.
    • Journal Title

      J Nerurosurg. 103(3)

      Pages: 498-507

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Overexpressed Skp2 within 5p amplification detected by array- based comparative genomic hybridization is associated with poor prognosis of glioblastomas.2005

    • Author(s)
      Saigusa, K. et al.
    • Journal Title

      Cancer Sci. 96(10)

      Pages: 676-683

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PET measured 11C-methionine uptake correlates with proliferation capacity and microvascular density of cerebral glioma.2005

    • Author(s)
      Nojiri, T et al.
    • Journal Title

      Nippon Rinsho Suppl.9

      Pages: 258-262

    • Related Report
      2005 Annual Research Report
  • [Journal Article] An analysis of the functional mechanisms of endostatin. -The anti-angiogenic activity of endostatin is mediated by its multiple binding ability-2004

    • Author(s)
      Yamaguchi, N.
    • Journal Title

      Connective Tissue 36

      Pages: 171-178

    • NAID

      110004014521

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.2004

    • Author(s)
      Hayashi, T. et al.
    • Journal Title

      J. Am. Coll. Cardiol. 44 (119)

      Pages: 2192-201

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy.2004

    • Author(s)
      Hayashi, T. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 313 (1)

      Pages: 178-84

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] An analysis of the functional mechanisms of endostalin. -the anti-angiogenic activity of endostatin is mediated by its multiple binding ability-2004

    • Author(s)
      Yamaguchi, N.
    • Journal Title

      Connective Tissue 36

      Pages: 171-178

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.2004

    • Author(s)
      Hayashi, T. et al.
    • Journal Title

      J.Am.Coll.Cardiol. 44(119)

      Pages: 2192-2201

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy.2004

    • Author(s)
      Hayashi, T. et al.
    • Journal Title

      Biochem, Biophys.Res.Commun. 313(1)

      Pages: 178-184

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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