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Targeting antiangiogenesis inhibitor using antiangiogenesis molecular signals

Research Project

Project/Area Number 15390219
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SHICHIRI Masayoshi  Tokyo Medical and Dental University, Medical Hospital, Associate Professor, 医学部附属病院, 助教授 (10206097)

Co-Investigator(Kenkyū-buntansha) HIRATA Yukio  Tokyo Medical and Dental University, Dept.Clinical & Molecular Endocrinology, Professor, 大学院・医歯学総合研究科, 教授 (50135787)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsAntiangiogenesis signal / Endostatin / Endothelial cell migration / Endothelial cell growth / Anti-tumor effect / Endothelial apoptosis / Vascular endothelial cell / Metastasis / 血管新生 / 細胞遊走 / 細胞増殖
Research Abstract

Cancer progression and metastasis depend on recruitment of new blood vessels and are characterized by oncogene-driven tumor expression of pro-angiogenic proteins. Most pro-angiogenic factors are soluble endogenous proteins and their receptors are displayed on the surface of endothelial cells. Inhibition of tumor angiogenesis suppresses experimental tumor growth, and is considered a promising new therapeutic approach to treat human cancer. However, clinical application of anti-angiogenesis therapy for suppression of tumor progression would theoretically require long-term administration of angiogenesis inhibitors, but most of them entering clinical trials are rather large molecular weight protein and/or require intravenous administration. We have previously demonstrated that an anti-angiogenesis inhibitor, endostatin, markedly down regulates a variety of growth-, migration-, and angiogenesis-associated genes in exponentially growing human and rat microvascular endothelial cells. In the present study, we searched for compounds and peptides eliciting such anti-angiogenesis molecular signals in endothelial cells in an attempt to identify new therapeutic agents for human tumors. The results demonstrate that three ansamycin antibiotics and a fragment of vasoactive peptide induced antiangiogenesis signals similar to endostatin and that the former suppressed progression of human cancer xenografts as well.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (31 results)

All 2005 2004 2003 Other

All Journal Article (23 results) Book (2 results) Publications (6 results)

  • [Journal Article] Synthetic salusins as cardiac depressors in rat.2005

    • Author(s)
      Izumiyama H, Tanaka H, Egi K, Sunamori M, Hirata Y, Shichiri M
    • Journal Title

      Hypertension 45

      Pages: 419-425

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells.2005

    • Author(s)
      Yoshimoto T, Fukai N, Sugiyama T, Shichiri M, Hirata Y
    • Journal Title

      Hypertension Research 28

      Pages: 165-172

    • NAID

      10016430788

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues.2005

    • Author(s)
      Fukai N, Yoshimoto T, Sugiyama T, Ozwa N, Sato R, Shichiri M, Hirata Y
    • Journal Title

      American Journal of Physiology (Endocrinol Metab) 288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues.2005

    • Author(s)
      Fukai N, Yoshimoto T, Sugiyama T, Ozawa N, Sato R, Shichiri M, Hirata Y
    • Journal Title

      Am J Physiol (Endocrinol Metab) 288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells.2005

    • Author(s)
      Yoshimoto T, Gochou N, Fukai N, Sugiyama T, Shichiri M, Hirata Y
    • Journal Title

      Hypertens Res-Clinical & Experimental. 28

      Pages: 165-172

    • NAID

      10016430788

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthetic salusins as cardiac depressors in rat.2005

    • Author(s)
      Izumiyama H, Tanaka H, Egi K, Sunamori M, Hirata Y, Shichiri M
    • Journal Title

      Hypertension (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells.2005

    • Author(s)
      Yoshimoto T, Fukai N, Sugiyama T, Shichiri M, Hirata Y
    • Journal Title

      Hypertension Research (in press)

    • NAID

      10016430788

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues.2005

    • Author(s)
      Fukai N, Yoshimoto T, Sugiyama T, Ozawa N, Sato R, Shichiri M, Hirata Y
    • Journal Title

      American Journal of Physiology (Endocrinol Metab) (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Th2-predominant inflammation and blockade of interferon-γ signaling induce aneurysms in allografted aortas.2004

    • Author(s)
      Shimizu K, Shichiri M, Libby P, Lee RT, Mitchell RN
    • Journal Title

      Journal of Clinical Investigation00 114

      Pages: 300-308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of adrenomedullin gene transcription and degradation by the c-myc gene.2004

    • Author(s)
      Ozawa N, Shichiri M, Fukai N, Yoshimoto T, Hirata Y
    • Journal Title

      Endocrinology 145

      Pages: 4244-4250

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Antioxidant effect of adrenomedullin on angiotensin II-induced reactive oxygen species generation in vascular smooth muscle cells.2004

    • Author(s)
      Yoshimoto T, Fukai N, Sato R, Sugiyama T, Ozawa N, Shichiri M, Hirata Y
    • Journal Title

      Endocrinology 145

      Pages: 3331-3337

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Laminar shear stress upregulates inducible nitric oxide synthase in the endothelium.2004

    • Author(s)
      Ozawa N, Shichiri M, Iwashina M, Fukai N, Yoshimoto T, Hirata Y
    • Journal Title

      Hypertens Res-Clinical & Experimental. 27

      Pages: 93-99

    • NAID

      10012843557

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Th2-predominant inflammation and blockade of interferon-γ signaling induce aneurysms in allografted aortas.2004

    • Author(s)
      Shimizu K, Shichiri M, Libby P, Lee RT, Mitchell RN
    • Journal Title

      J Clin Invest 114

      Pages: 300-308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Non-viral in vivo thrombomodulin gene transfer prevents early loss of thromboresistance of grafted veins.2004

    • Author(s)
      Tabuchi N, Shichiri M, Shibamiya A, Koyama T, Nakazawa F, Chung J, Hirosawa S, Sunamori M
    • Journal Title

      Eur J Cardiothor Surg 26

      Pages: 995-1001

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] High molecular weight form insulin-like growth factor II-producing mesenteric sarcoma causing hypoglycemia.2004

    • Author(s)
      Sato R, Tsujino M, Nishida K, Otani Y, Minami T, Shichiri M, Hizuka N, Aiba M, Hitara Y
    • Journal Title

      Intern Med 43

      Pages: 967-971

    • NAID

      10013733559

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Endothelin-1 induces cyclooxygenase-2 expression and generation of reactive oxygen species in endothelial cells.2004

    • Author(s)
      Sugiyama T, Yoshimoto T, sato R, Fukai N, Ozawa N, Shichiri M, Hirata Y
    • Journal Title

      J Cardiovasc Pharmacol 44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Th2-predominant inflammation and blockade of interferon-γ signaling induce aneurysms in allografted aortas.2004

    • Author(s)
      Shimizu K, Shichiri M, Libby P, Lee RT, Mitchell RN
    • Journal Title

      Journal of Clinical Investigation 114

      Pages: 300-308

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Coexpresssion of calcitonin receptor-like receptor and receptor activity-modifying protein 2 or 3 mediates the antimigratory effect of adrenomedullin.2003

    • Author(s)
      Fukai N, Shichiri M, Ozawa N, Matsushita M, Hirata Y
    • Journal Title

      Endocrinology 144

      Pages: 447-453

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Octoreotide-sensitive ectopic ACTH production by islet cell carcinoma with multiple liver metastases.2003

    • Author(s)
      Doi M, Imai T, Shichiri M, Tateno T, Fukai N, Ozawa N, Sato R, Teramoto K, Hirata Y
    • Journal Title

      Endocrine J. 50

      Pages: 135-143

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adrenomedullin is an autocrine/paracrine growth factor for rat vascular smooth muscle cells.2003

    • Author(s)
      Shichiri M, Fukai N, Ozawa N, Iwasaki H, Hirata Y
    • Journal Title

      Regulatory Peptides 112

      Pages: 167-173

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Urotensin II is an autocrine/paracrine growth factor for porcine renal epithelial cell line, LLCPK1.2003

    • Author(s)
      Matsushita M, Shichiri M, Fukai N, Ozawa N, Yoshimoto T, Takasu N, Hirata Y
    • Journal Title

      Endocrinology 144

      Pages: 1825-1831

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Intravenous gene therapy for familial hypercholesterolemia using ligand-facilitated transfer of a liposome : LDL receptor gene complex.2003

    • Author(s)
      Shichiri M, Tanaka A, Hirata Y
    • Journal Title

      Gene Therapy 10

      Pages: 827-831

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Salusins ; newly identified bioactive peptides with hemodynamic and mitogenic activities.2003

    • Author(s)
      Shichiri M, Ishimaru S, Ota T, Nishikawa T, Isogai T, Hirata Y
    • Journal Title

      Nature Medicine 9

      Pages: 1166-1172

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Annual Review 20052005

    • Author(s)
      七里眞義, 平田結喜緒
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Annual Review 20052005

    • Author(s)
      七里眞義, 平田結喜緒
    • Related Report
      2004 Annual Research Report
  • [Publications] Fukai N: "Coexpresssion of calcitonin receptor-like receptor and receptor activity-modifying protein 2 or 3 mediates the antimigratory effect of adrenomedullin"Endocrinology. 144. 447-453 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Doi M: "Octoreotide-sensitive ectopic ACTH production by islet cell carcinoma with multiple liver metastases"Endocrine Journal. 50. 135-143 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shichiri M: "Adrenomedullin is an autocrine/paracrine growth factor for rat vascular smooth muscle cells"Regulatory Peptides. 112. 167-173 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsushita M: "Urotensin II is an autocrine/paracrine growth factor for porcine renal epithelial cell line LLCPK1"Endocrinology. 144. 1825-1831 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shichiri M: "Intravenous gene therapy for familial hypercholesterolemia using ligand-facilitated transfer of a liposome : LDL receptor gene complex"Gene Therapy. 10. 827-831 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shichiri M: "Salusins ; newly identified bioactive peptides with hemodynamic and mitogenic activities"Nature Medicine. 9. 1166-1172 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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