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Newly Gene Therapy Targetting Inhibition of the Tumor Angiogenesis Using Decoy System

Research Project

Project/Area Number 14370605
Research Category

Grant-in-Aid for Scientific Research (B)

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  Kyushu University, GRADUATE SCHOOL OF DENTAL SCIENCE, ASS PROF, 大学院・歯学研究院, 助手 (90254630)

Co-Investigator(Kenkyū-buntansha) SHIRASUNA Kanemitsu  Kyushu University, GRADUATE SCHOOL OF DENTAL SCIENCE, PROF, 大学院・歯学研究院, 教授 (30093420)
NAKAGAWA Kazunori  Kyushu University, GRADUATE SCHOOL OF MEDICAL SCIENCE, ASS PROF, 大学院・歯学研究院, 講師 (50217668)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥11,600,000 (Direct Cost: ¥11,600,000)
KeywordsNEOPLASMS / ANGIONESIS / GENE THERAPY / 腫瘍血管新生
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 a(TNFα) via binding of transcription factor Spl 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 メdecoyモ could block the binding of Spl 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 Spl 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 Spl could be simultaneously suppressed.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Onimaru M, Yonemitsu Y, Tani M, Nakagawa K, Masaki I, Okano S, Ishibashi H, Shirasuna K, Sueishi K.: "Fibroblast growth factor-2 gene transfer can stimulate hepatocyte growth factor expression Irrespective of hypoxia-mediated downregulation in ischemic limbs."Circulation Research. 91. 923-930 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiratuchi T, Ishibashi H, Shirasuna K: "Inhibition of epidermal growth factor-induced invasion by dexamethosone and AP-1 decoy in human squamous cell carcinoma cell lines."Journal of Cell Physiology. 193. 340-348 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura K, Kiyoshima K, Shima K, Kobayashi I, Matsuo K, Ishibashi H, Komatau S, Sakai H.: "Immunohistochemical expression of CA19-9 and CA125 in mucoepidermoid and adenoid cystic carcinomas of the salivary gland."Oral Oncology. 38. 244-250 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurokawa H., Takeda S., Yamashita Y., Nakamura T.Murata T., Takahashi T., Fukuyama H., Zhang M., Ishibashi H.: "Estimation of tumor necrosis factor-α and correlation to tumor markers in patients with oral squamous cell carcinoma."Asian J Oral Maxillofac Surg. 14. 148-154 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamashita A., Yonemitsu Y., Okano S., Nakagawa K., Nakashima Y., Irisa Y., Hasegawa M., Sueishi K.: "Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats."Journal of Immunology. 168. 450-457 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Onimaru M, et al.: "FGF-2 stimulates HGF expression, regardless to hypoxia-mediated down regulation in ischemic limb."Circulation Research. 91. 923-930 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiratuchi T, et al.: "Inhibition of epidermal growth factor-induced invasion by dexamethasone in human squamous cell carcinoma cell lines."Journal of Cellu Physiol. 193. 340-348 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura, K: "Immunohistochemical expression of CA19-9 and CA125 in mucoepidermoid and adenoid cystic carcinomas of the salivary gland"Oral Oncology. 38. 244-250 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurokawa, H, et al.: "Estimation of serum tumor necrosis factor-α and correlation to tumor markers in patients with oral squamous cell carcinoma."Asian J Oral Maxillofac Surg. 14. 148-154 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamashita A, et al.: "Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats."Journal of Immunology. 168. 450-457 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Onimaru.M et al.: "Fibroblast growth factor-2 gene transfer con stimulate hepatocyte growth factor expression irrespective of hypoxia-mediated downregulation in ischemic limbs"Circulation Research. 91. 923-930 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiratuchi, T., lshibashi, H.et al.: "Inhibition of epidermal growth factor-induced invasion by dexametha-sone and AP-1 decoy in human squamous cell carcinoma cell lines"J Cell Physiol. 93. 340-348 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okamura, K et al.: "Immunohistochemical expression of CA19-9 and CA125 in mucoepidermoid and adenoid cystic carcinomas of the salivary gland"Oral Oncology. 38. 244-250 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurokawa, H et al.: "Estimation of serum tumor necrosis factor-α in patients with oral SCC"Asian J Oral Maxillofac Surg. 14. 148-154 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Onimaru.M et al.: "Fibroblast growth factor-2 gene transfer can stimulate hepatocyte growth factor expression irrespective of hypoxia-mediated downregulation in ischemic limbs"Circulation Research. 91. 923-930 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiratuchi, T.Ishibashi, H.et al.: "Inhibition of epidermal growth factor-induced invasion by dexamethasone and AP-1 decoy in human squamous cell carcinoma cell lines"J Cell Physiol. 93. 340-348 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okamura, K et al.: "Immunohistochemical expression of CA19-9 and CA125 in mucoepidermoid and adenoid cystic carcinomas of the salivary gland"Oral Oncology. 38. 244-250 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kurokawa, H et al.: "Estimation of serum tumor necrosis factor-α and correlation to tumor markers in patients with oral squamous cell carcinoma"Asian J Oral Maxillofac Surg. 14. 148-154 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishibashi, H et al.: "Hypoxia-induced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor releases"Oral Oncology. 37. 77-83 (2001)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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