• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2002 Fiscal Year Final Research Report Summary

Roles of inducible cyclooxvgenase-2 in angiogenesis and its significance of therapeutic targets

Research Project

Project/Area Number 12470529
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKITASATO UNIVERSITY

Principal Investigator

MAJIMA Masataka  Kitasato Univ. School of Medicine, Professor, 医学部, 教授 (70181641)

Co-Investigator(Kenkyū-buntansha) HUJITA Tomoe  Kitasato Univ. School of Medicine, Research Associate, 医学部, 助手 (20296510)
HATANAKA Ko  Kitasato Univ. School of Medicine, Research Associate, 医学部, 助手 (00228470)
HAYASHI Izumi  Kitasato Univ. School of Medicine, Associate Professor, 医学部, 助教授 (90172999)
KAWAMURA Michiko  Kitasato Univ. School of Medicine, Research Associate, 医学部, 助手 (00154104)
Project Period (FY) 2000 – 2002
Keywordsangiogenesis / granuloma / tumor / prostaglandin E_2 / EP3 receptor / vascular endothelial growth factor / COX-1 / COX-2
Research Abstract

Angiogenesis in chronic glanuloma formed around sponge discs implanted into subcutaneous tissues of rats was increased over a 14-day experimental period. In sponge granuloma, mRNA of COX-1 was constitutively expressed, whereas that of COX-2 was increased with neovascularization in pararell with that of vascular endothelial growth factor (VEGF). Topical injections of bFGF increased the expression of COX-2 mRNA without affecting that of COX-1 mRNA. The angiogenesis with bFGF was inhibited by indomethacin or selective COX-2 inhibitors, NS-398, nimesulide, and JTE-522. The expression of VEGF mRNA in the granuloma was also enhanced by bFGF, and was reduced by NS-398. The enhanced angiogenesis by bFGF was significantly inhibited by topical injections of VEGF anti-sense oligonucleotide. These results suggested that COX-2 may enhance the neovascularization in sponge granuloma by PG-mediated expression of VEGF, and that a COX-2 inhibitor would facilitate the management of conditions involving a … More ngiogenesis. Using prostaglandin (PG) receptor knockout mice, we have evaluated a role of PGs in tumor-associated angiogenesis and tumor growth, and identified PG receptors involved. Sarcoma-180 cells implanted in wild type mice (WT) formed a tumor with extensive angiogenesis, which was greatly suppressed by specific inhibitors for cyclooxygenase(COX)-2 but not for COX-1. Angiogenesis in sponge implantation model, which can mimic tumor-stromal angiogenesis, was markedly suppressed in mice lacking EP3 (EP3-/-) with reduced expression of vascular endothelial growth factor (VEGF) around the sponge implants. Further, implanted tumor growth (sarcoma-180, Lewis lung carcinoma) was markedly suppressed in EP3-/-, in which tumor-associated angiogenesis was also reduced. Immunohistochemical analysis revealed that major VEGF-expressing cells in the stroma were CD3/Mac-1 double-negative fibroblasts, and that VEGF-expression in the stroma was markedly reduced in EP3-/-, compared with WT. These results demonstrate significance of host stromal PGE2-EP3 receptor signaling in tumor angiogenesis. An EP3 receptor antagonist may be a candidate of chemopreventive agents effective for malignant tumors. Less

  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Amano H. 他: "Host prostaglandin E(2)-EP3 signaling regulates tumor-associated Angiogenesis and tumor growth"J Exp Med.. 197・2. 221-232 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Amano H. 他: "Cyclooxygenase-2 and adenylate cyclase/protein kinase A signaling pathway enhances angiogenesis through induction of vascular endothelial growth factor in rat sponge implants"Hum Cell.. 15・1. 13-24 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayahi I. 他: "Suppressed angiogenesis in kininogen-deficiencies"Lab Invest.. 82・7. 871-880 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujita M. 他: "Blockade of angiotensin AT1a receptor signaling reduces tumor growth, angiogenesis, and metastasis"Biochem Biophys Res Commun.. 294・2. 441-447 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Amano H, 他: "Adenylate cyclase/protein kinase A signaling pathway enhances Angiogenesis through induction of vascular endothelial growth factor in vivo"Jpn J Pharmacol.. 87・3. 181-188 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Majima M, 他: "Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascular endothelial growth factor in rat sponge implants"Br J Pharmacol.. 130・3. 641-649 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 馬嶋 正隆: "医科薬理学 第4版 抗炎症薬(第12章)"南山堂(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Amano H, Hayashi I, Endo H, Kitasato H, Yamashina S, Maruyama T, Kobayashi M, Satoh K, Narita M, Sugimoto Y, Murata T, Yoshimura H, Narumiya S, Majima M: "Host prostaglandin E(2)-EP3 signaling regulates tumor-associated Angiogenesis and tumor growth"J Exp Med.. 197(2). 221-232 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito H, Hayashi I, Izumi T, Majima M: "Bradykinin inhibits development of myocardial infarction through B(2) receptor signaling by increment of regional blood flow around the ischaemic lesions in rats"Br J Pharmacol. 138(1). 225-233 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuzaki S, Hayashi I, Nara Y, Kamata K, Yamanaka M, Okamoto H, Hoka S, Majima M: "Role of kinin and prostaglandin in cutaneous thermal nociception"Int Immunopharmacol. 2(13-14). 2005-2012 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamanaka M, Hayashi I, Fujita T, Cha SH, Endou H: "Potassium-induced increase in renal kallikrein secretion is attenuated in dissected renal connecting tubules of young spontaneously hypertensive rats"Int Immunopharmacol. 2(13-14). 1957-1964 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okumura T, Hayashi I, Ikezawa T, Yamanaka M, Takata T, Fujita Y, Saigenji K, Yamashita S, Majima M: "Cyclooxygenase-2 inhibitors attenuate increased blood pressure in renovascular hypertensive models, but not in deoxycorticosterone-salt hypertension"Hypertens Res. 25(6). 927-938 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakamoto I, Takahashi T, Kakita A, Hayashi I, Majima M, Yamashina S: "Experimental study on hepatic reinnervation after orthotopic liver transplantation in rats"J Hepatol. 37(6). 814-823 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kamata K, Hayashi I, Mizuguchi Y, Arai K, Saeki T, Ohno T, Saigenji K, Majima M: "Suppression of dextran sulfate sodium-induced colitis in kininogen-deficient rats and non-peptide B2 receptor antagonist-treated rats"Jpn J Pharmacol. 90(1). 59-66 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujita T, Matsumoto Y, Kimura T, Yokota S, Sawada M, Majima M, Ohtani Y, Kumagai Y: "Pharmacokinetics and pharmacodynamics of TF-505, a novel nonsteroidal 5alpha-reductase inhibitor, in normal subjects treated with single or multiple doses"Br J Clin Pharmacol. 54(3). 283-294 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katada J, Muramatsu M, Hayashi I, Tsutsumi M, Konishi Y, Majima M: "Significance of vascular endothelial cell growth factor up-regulation mediated via a chymase-angiotensin-dependent pathway during angiogenesis in hamster sponge granulomas"J Pharmacol Exp Ther. 302(3). 949-956 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii K, Ito Y, Katagiri H, Matsumoto Y, Kakita A, Majima M: "Neutrophil elastase inhibitor attenuates lipopolysaccharide-induced hepatic microvascular dysfunction in mice"Shock. 18(2). 163-168 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito:M, Shima C, Takagi M, Ogino M, Katori M, Maiima: "exudation of fibrinogen into the perivascularinflammation triggered by neutrophil migration"InflammRes. 51(7). 324-331 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Amano H, Haysahi I, Yoshida S, Yoshimura H, Majima M: "Cyclooxygenase-2 and adenylate cyclase/protein kinase A signaling pathway enhances angiogenesis through induction of vascular endothelial growth factor in rat sponge implants"Hum Cell. 15(1). 13-24 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi I, Amano H, Yoshida S, Kamata K, Kamata M, Inukai M, Fujita T, Kumagai Y, Furudate S, Majima M: "Suppressed angiogenesis in kininogen-deficiencies"Lab Invest. 82(7). 871-880 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inamura H, Kurosawa M, Okano A, Kayaba H, Majima M: "Expression of the interleukin-8 receptors CXCR1 and CXCR2 on cord-blood-derived cultured human mast cells"Int Arch Allergy Immunol. 128(2). 142-150 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2004-04-14  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi