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

Research Project

Project/Area Number 16390539
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

ISHIBASHI Hiroaki  KYUSHU UNIVERSITY, SCHOOL OF DENTAL SCIENCE, ASS PROF, 歯学研究院, 講師 (90254630)

Co-Investigator(Kenkyū-buntansha) NAKAGAWA Kazunori  KYUSHU UNIVERSITY, SCHOOL OF DENTAL SCIENCE, ASS PROF, 医学研究院, 講師 (50217668)
SHIRASUNA Kanemitu  KYUSHU UNIVERSITY, SCHOOL OF DENTAL SCIENCE, PROF, 歯学研究院, 教授 (30093420)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
KeywordsOral cancer / Angiogenesis / Gene therapy / 悪性新生物
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 Sp1 as cis-trans element decoy could block the binding of Sp1 to the VEGF promoter gene. Transfection of wild type Sp1 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 dormancy by its inhibitory effect on VEGF synthesis. In addition, the transfer of the Sp1 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

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005

All Journal Article (12 results)

  • [Journal Article] Expression of tumor- associated antigen RCASI and its possible involvement in imuune evasion in oral squamous cell carcinoma.2006

    • Author(s)
      Toyoshima T, Nakamura S, Kumamaru W, Kawamura E, Ishibashi H, et al.
    • Journal Title

      J Oral Pathol Med. 35

      Pages: 361-368

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of tumor- associated antigen RCASI and its possible involvement in immune evasion in oral squamous cell carcinoma.2006

    • Author(s)
      Toyoshima T, Nakamura S, Kumamaru W, Kawamura E, Ishibashi H, et al.
    • Journal Title

      J Oral Pathol Med. 35

      Pages: 361-368

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of tumor-associated RCASI and its possible involvement in immune evasion in oral squamous cell carcinoma2006

    • Author(s)
      Toyoshima, T., Nakamura, S., Kumamaru, W., Kawamura, E., Ishibashi, H., et al.
    • Journal Title

      J Oral Pathol Med 3

      Pages: 361-368

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hypoxia-inducible factor-1(HIF-1)デコイによる培養口腔癌細胞の血管内皮増殖因子産生抑制2005

    • Author(s)
      今井美恵, 石橋浩晃ら
    • Journal Title

      日口科誌 54

      Pages: 22-28

    • NAID

      10014375629

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inhibition of vascular endothelial growth factor (VEGF) In oral cancer cells by HIF-1 decoy2005

    • Author(s)
      Imai M, Ishibashi H, et al.
    • Journal Title

      J Jpn Stomatol Soc 54(1)

      Pages: 22-28

    • NAID

      10014375629

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxia-inducible factor-1(HIF-1)デコイによる培養口腔癌細胞の血管内皮増殖因子産生抑制2005

    • Author(s)
      今井美恵, 石橋浩晃ら
    • Journal Title

      日本口腔科学会雑誌 54巻1号

      Pages: 22-28

    • NAID

      10014375629

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The Association between the Computed Tonography Findings.2005

    • Author(s)
      Nakayama E, Sugiura T, Kobayashi I, Ishibashi H, et al.
    • Journal Title

      J Oral Maxillofac Surg 63

      Pages: 311-318

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of the urokinase receptor regulates focal adhesion assembly and cell migration in adenoid cystic carcinoma cells.2005

    • Author(s)
      Abu-Ali, S., T.Sugiura, M
    • Journal Title

      J Cell Physiol 203

      Pages: 410-419

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Severity of oral mucositis correlates with the response of oral cancer to preoperative radiochemotherapy.2005

    • Author(s)
      Ikebe, T., K.Seki, et al.
    • Journal Title

      Int J Oral Maxillofac Surg 34

      Pages: 642-645

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effects of IkappaB kinase alpha on the differentiation of squamous carcinoma cells. Oral.2005

    • Author(s)
      Nakayama, H., T.Ikebe
    • Journal Title

      Oral Oncol 41

      Pages: 729-737

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Differentiation-inducing factor-1 induces cyclin D1 degradation through the osphorylation of Thr(286) in squamous cell carcinoma.2005

    • Author(s)
      Mori, J., F.Takahashi-Yanaga
    • Journal Title

      Exp Cell Res 84

      Pages: 913-918

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoxia-inducible fector-1(HIF-1)デコイによる培養口腔癌細胞の血管内皮増殖因子産生抑制2005

    • Author(s)
      今井美恵, 石橋浩晃, 河村隆造, 白砂兼光
    • Journal Title

      日本口腔外科学会雑誌 54(1)

      Pages: 22-28

    • Related Report
      2004 Annual Research Report

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

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