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Research for molecular mechanism and clinical application of calponin-gene therapy against Peritoneal dissemination of ovarian cancer

Research Project

Project/Area Number 17591747
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKYUSHU UNIVERCITY

Principal Investigator

KOBAYASHI Hiroaki  Kyushu Univ., Hospital, Dept.of OB&Gyn, Assistant Professor, 大学病院, 講師 (70260700)

Co-Investigator(Kenkyū-buntansha) UEOKA Yousuke  Kyushu Univ., Hospital, Dept.of OB&Gyn, Research Associate, 大学病院, 助手 (50372743)
FUKUSHIMA Koutarou  Kyushu Univ., Hospital, Dept.of OB&Gyn, Research Associate, 大学病院, 助手 (40304779)
WAKE Norio  Kyushu Univ., Graduate School of Medical Sciences, Professor, 大学院医学研究院, 教授 (50158606)
TANIGUCHI Shun'ichiro  Shinshu Univ., Dept.of Molecular and An giology, Professor, 大学院医学研究科, 教授 (60117166)
平川 俊夫  九州大学, 大学病院, 講師 (20218770)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordscalponin / gene therapy / ovarian cancer / peritoneal dissemination
Research Abstract

Purpose : Calponin h1 (CNh1), one of the family of actin-binding proteins, stabilizes the filaments of actin and modulates various cellular biological phenotypes. Recent studies revealed the close correlation between the invasive tumor spread and the reduced expression of CNh1 and alpha-smooth muscle actin (α-SMA) in the surrounding stromal cells. The purpose of this study is to evaluate the efficacy of intraperitoneal CNh1-gene therapy against peritoneal dissemination of ovarian cancer.
Experimental Design : We used an adenoviral vector to induce the CNh1 gene into peritoneal cells and ovarian cancer cells, as a means of enhancing or inducing the expression of α-SMA as well as CNh1. The efficacy of gene transfer was examined by in vitro cell culture and in vivo animal experiments.
Results : The formation of longer and thicker actin fibers was observed in each transfected cell line, and the localization of these fibers coincided with that of externally transducted CIVh1. With respect to … More changes in cell behavior, the CNh1-transfected peritoneal cells acquired an ability to resist ovarian cancer-induced shrinkage in cell shape, and thus cancer cell invasion through the monolayer of peritoneal cells was inhibited. In addition, CNh1-transfected ovarian cancer cells showed suppressed anchorage-independent growth and invasiveness, the latter of which accompanied impaired cell motility. The concomitant CNh1 transfection into both peritoneal cells and ovarian cancer cells produced an additive inhibitory effect with respect to cancer cell invasion through the peritoneal cell monolayer.
By in vivo experiments designed to treat nude mice that had been intraperitoneally (i.p.) inoculated with ovarian cancer cells, we found that the i.p.injected CNh1-adenovirus successfully blocked cancer-induced morphological changes in peritoneal cell surface, and significantly prolonged the survival time of tumor-bearing mice. Moreover, CNh1-adenovirus could successfully enhance the therapeutic effect of an anticancer drug without increase in side effects.
Conclusions : Thus CNh1-gene therapy against peritoneal dissemination of ovarian cancer is bifuctionally effective, ie through inhibitory effects on the infected peritoneal cell layers which suppress cancer invasion and, second, through direct anti-tumor effects against invasion and growth properties of cancer cells. Less

Report

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

    (9 results)

All 2006 2005

All Journal Article (9 results)

  • [Journal Article] Adenovirus-mediated calponin hl gene therapy directed against peritoneal dissemination of ovarian cancer : bifunctional therapeutic effects on peritoneal cell layer and cancer cells.2006

    • Author(s)
      Ogura T, Kobayashi H et al.
    • Journal Title

      Clin Cancer Res 12

      Pages: 5216-5223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated calponin h1 gene therapy directed against peritoneal dissemination of ovarian cancer : bifunctional therapeutic effects on peritoneal cell layer and cancer cells2006

    • Author(s)
      T.Ogura, H.Kobayashi, et al.
    • Journal Title

      Clin.Cancer Res. 12

      Pages: 5216-5223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated calponin h1gene therapy directed against peritoneal dissemination of ovarian cancer : bifunctional therapeutic effects on peritoneal cell layer and cancer cells.2006

    • Author(s)
      Ogura T, Kobayashi H, et al.
    • Journal Title

      Clin Cancer Res 12

      Pages: 5216-5223

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 卵巣癌腹膜播種に対するアクチン結合蛋白質カルポニンh1に着目した遺伝子治療2005

    • Author(s)
      小林裕明, 小倉寛則, 他
    • Journal Title

      日本婦人科腫瘍学会雑誌 23(2)

      Pages: 214-224

    • NAID

      10020562271

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gene therapy against the peritoneal dissemination of ovarian cancer focusing on the actin-binding protein of calponin h12005

    • Author(s)
      H.Kobavashi, T.Ogura, et al.
    • Journal Title

      Jpn.J.Gynecol.Oncol. 23

      Pages: 214-224

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 卵巣癌腹膜播種に対するアクチン結合蛋白質カルポニンh1に着目した遺伝子治療2005

    • Author(s)
      小林裕明ら
    • Journal Title

      日本婦人科腫瘍学会雑誌 23(2)

      Pages: 214-224

    • NAID

      10020562271

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tumor necrosis factor and vascular endothelial growth factor induce endothelial integrin repertories, regulating endovascular differentiation and apoptosis in a human extravillous trophoblast cell line2005

    • Author(s)
      Fukushima K et al.
    • Journal Title

      Biology of Reproduction 73

      Pages: 125-131

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinical significance of heparin-binding epidermal growth factor-like in peritoneal fluid of ovarian cancer2005

    • Author(s)
      Yagi H et al.
    • Journal Title

      Br J Cancer 92

      Pages: 1737-1745

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Incidence and risk factors for paclitaxel hypersensitivity during ovarian cancer chemotherapy2005

    • Author(s)
      Sendo T et al.
    • Journal Title

      Gynecol Pathology 24

      Pages: 330-334

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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