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ESTBLISHMENT AND APPLIATCE OF NEWLY GENE THERAPY FOR INHIBITION OF TUMOR ANGIOGENESIS

Research Project

Project/Area Number 12671830
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionKyushu University

Principal Investigator

ISHIBASHI Hiroaki  GRADUATE SCHOOL OF DENTAL SCIENCE, KYUSHU UNIVERSITY, Research associate, 大学院・歯学研究院, 助手 (90254630)

Co-Investigator(Kenkyū-buntansha) SHIRASUNA Kanemitsu  GRADUATE SCHOOL OF DENTAL SCIENCE, KYUSHU UNIVERSITY, PROF., 大学院・歯学研究院, 教授 (30093420)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsANGIOGENESIS / NEOPLASMS / GENETHERAPY
Research Abstract

The development of newly capillary networks from the normal microvasculature of the surrounding tissue has thought to play a critical role for the growth of the solid tumors. Tumor cells influence the angiogenesis by stimulation of endothelial cells with producing several angiogenic factors. Among them, vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors, and endothelial cell specific mitogen. Several previous studies suggested that inhibition of VEGF using-antisense oligodeoxynucleotides or neutralizing antibodies against VEGF suppressed tumor growth in various in vivo and in vitro models. VEGF is well known to be hypoxia-inducible, and has been recently reported to be synthesized by stimulation with tumor necrosis factor α (TNFα) via binding of transcription factor Sp1 to the VEGF promoter. We hypothesized that transfection into the tumor cells nucleus of the synthetic double stranded DNA including consensus sequence of binding site of the Spl as cis-trans element "decoy" could block the binding of Sp1 to the VEGF promoter gene. Transfection of wild type Spl decoy, but mutant type decoy, revealed prominent inhibitory effects of VEGF synthesis of cultured human carcinoma cells stimulated by TNFα. This Sp1 decoy introduction into tumor cells may be a novel and useful therapeutic tool for induction of tumor domancy by its inhibitory effect on VEGF synthesis. In addition, the transfer of the Spl decoy would be more effective for regulating tumor growth and invasion than that of antisense oligonucleotide, since not all angiogenic factors but also growth and invasion related factors expression modulated by Sp1 could be simultaneously suppressed.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Ishibashi H, et al.: "Sp1 Decoy Transfected Cells Suppresses the Expression of VEGE, TGFβ1,and Tissue Facotr and also Cell Grwoth and Invasion Activites"Cancer Research. 60. 6531-6536 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishibashi H, et al.: "Hypoxia-Induced Angiogenesis of Cultured Human Salivary Gland Carcinoma CellsInvolves Enhancement VEGE Production and bFGF Release"Oral Oncology. 37. 77-83 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakagawa K, Chen Y, Ishibashi H, et al.: "Angiogenesis and its regulation : roles of vascular endothelial cell growth factor (VEGF)"Semin Thromb Hemost. 143. 201-206 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] LiC Y, Shirasuna K, Ishibashi H.: "Epithelial-myoepithelial carcinoma arising in pleomorphic adenoma of the palate"Oral Surg Oral Med Oral Pathol. 190. 154-156 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M Onimaru et al.: "FGF-2 stimulates HGF expression, regardless to hypoxia-mediated down regulation in ischemic limb"Circulation Res. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T Shiratuchi et al.: "Inhibition of epidermal growth factor-induced invasion by dexamethasone in human squamous cell carcinoma cell lines"J Cell Physiol. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Ishibashi, et al.: "Sp1 Decoy Transfected Cells Suppresses the Expression of VEGF, TGFβ1, and Tissue Facotr and also Cell Grwoth and Invasion Activites"Cancer Research. 60. 6531-6536 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Ishibashi, et al.: "Hypoxia-Induced Angiogenesis of Cultured Human Salivary Gland Carcinoma Cells Involves Enhancement VEGF Production and bFGF Release"Oral Oncology. 37. 77-83 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakagawa K, et al.: "Angiogenesis and its regulation: roles of vascular endothelial cell growth factor (VEGF)"Semin Thromb Hemost. 143. 201-206 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Li-Chen, et al.: "Epithlial-myoepithelial carcinoma arising in pleomorphic adenoma of the palate"Oral Surg Oral Med Oral Pathol. 194. 154-156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Sueishi, et al.: "Therapeutic Regulation of Angiogenesis, Gene Therapy for Inflammatory Angiogenic Disease"Clinical Immunology. 33(5). 551-556 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Onimaru, et al.: "FGF-2 stimulates HGF expression, regardless to hypoxia-mediated down regulation in ischemic limb"Circulation Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Shiratuchi, et al.: "Inhibtion of epedermal growth factor-induced invasion by dexamethasone in human squamous cell carcinoma cell lines"J Cell Physiol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishibashi H, et al.: "Sp1 Decoy Transfected Cells Suppresses the Expression of VEGE, TGFβ1, and Tissue Facotr and also Cell Grwoth and Invasion Activites"Cancer Research. 60. 6531-6536 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishibashi H, et al.: "Hypoxia-Induced Angiogenesis of Cultured Human Salivary Gland Carcinoma CellsInvolves Enhancement VEGF Production and bFGF Release"Oral Oncology. 37. 77-83 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakagawa K, Chen Y, Ishibashi H, et al.: "Angiogenesis and its regulation : roles of vascular endothelial cell growth factor (VEGE)"Semin Thromb Hemost. 143. 201-206 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] LiC Y, Shirasuna K, Ishibashi H: "Epithelial-myoepithelial carcinoma arising in pleomorphic adenoma of the palate"Oral Surg Oral Med Oral Pathol. 190. 154-156 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishibashi H, et al.: "Sp1 Decoy Transfected Cells Suppresses the Expression of VEGF, TGF β1, and Tissue Facotr and also Cell Grwoth and Invasion Activites."Cancer Research. 60. 6531-6536 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishibashi H, et al.: "Hypoxia-Induced Angiogenesis of Cultured Human Salivary Gland Carcinoma Cells Involves Enhancement VEGF Production and bFGF Release."Oral Oncology. (発表予定).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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