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増殖型癌融解ウイルスの卵巣癌治療への応用

Research Project

Project/Area Number 18791146
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKanazawa University

Principal Investigator

高倉 正博  Kanazawa University, 医学部附属病院, 助教 (20313661)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords卵巣癌 / 遺伝子治療 / アデノウイルス / テロメレース
Research Abstract

hTERTプロモーターをアデノウイルス5型E1遺伝子上流に組み込み、テロメレース陽性細胞でのみ増殖可能なアデノウイルス(tumor-or telomerase-specific replication-component adenovirus, TRAD)を作成した。
卵巣癌細胞株SKOV3を用いてin vitroでの抗腫瘍効果を抗癌剤との併用効果も含めて検討するとともに、ヌードマウスに10^7個のSKOV3細胞を腹腔内投与して作成した腹膜播種モデルでも同様の検討を行った。また抗癌剤耐性株を樹立し、これらにおけるTRADの効果も確認した。
in vitroではTRADの増殖ならびに殺細胞効果はテロメレース陽性の癌細胞株でのみ認められた。この効果はシスプラチン(4μM)との併用により増強した。ヌードマウス腹膜播種モデルでは低濃度シスプラチン(0.5mg/kg)処理巣独では効果がなかったが、TRADとの併用により約80%の播種性病変の減少が認められた(P<0.001)また生存率の向上も認められた(P<0.05)。この際、TRADは播病巣に局在し、明確な有害事象も認められなかった。またCDDP耐性株においてTRADの殺細胞効果に変化はなく、交差耐性は認められなかった。
またウイルス局在を可視化するためにGFPを発現する組換え体TRAD-GFPも作成した。TRAD-GFPは癌細胞特異的に感染増殖し癌細胞の所在を視覚化するマーカーとして有用であったばかりでなく、GFPによるcellsortingを行うことで癌細胞を選択的に収集し遺伝子解析を行うといった臨床応用にむけた知見が得られた。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (11 results)

All 2007 2006 Other

All Journal Article (9 results) (of which Peer Reviewed: 3 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis.2007

    • Author(s)
      Mizumoto Y, Takakura M, et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 652-658

    • NAID

      120005830597

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Concomitant activation of AKT with ERK1/2 occurs independently of PTEN or PIK3CA mutations in endometrial cancer and may be associated with favorable prognosis.2007

    • Author(s)
      Mori N Takakura M, et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 1881-1888

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of outcome of stage I-III endometrial cancer treated with systemic operation omitting paraarotic lymphadenectomy.2007

    • Author(s)
      Kyo S, Takakura M, et. al.
    • Journal Title

      Eur. J. Gynecol. Oncol. 28

      Pages: 170-173

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis.2007

    • Author(s)
      Mizumoto Y, Takakura M, et al.
    • Journal Title

      Cancer Sci. (印刷中)

    • NAID

      120005830597

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Analysis of outcome of stage I-III endometrial cancer treated with systematic operation omitting paraaortic lymphadenectomy.2007

    • Author(s)
      Kyo S, Takakura M, et al.
    • Journal Title

      Eur.J.Gynecol.Oncol. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Establishment of long-term culture model to study endometrial biology and carcinogenesis.2007

    • Author(s)
      Kyo S, Takakura M, et al.
    • Journal Title

      Reprod.Oncol. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct telomere length regulation in uterine cervical and endometrial premalignant lesions; implication for the roles of telomeres in uterine carcinogenesis.2006

    • Author(s)
      Maida Y, Takakura M, Et al.
    • Journal Title

      J.Pathol. 210・2

      Pages: 214-223

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements.2006

    • Author(s)
      Mizumoto Y, Takakura M, et al.
    • Journal Title

      Oncogene 25・41

      Pages: 5673-5682

    • Related Report
      2006 Annual Research Report
  • [Journal Article] High Twist expression is involved in infiltrative feature of endometrial cancer and affects patient survival.2006

    • Author(s)
      Kyo S, Takakura M, et al.
    • Journal Title

      Hum.Pathol. 37・4

      Pages: 431-438

    • Related Report
      2006 Annual Research Report
  • [Presentation] 細胞不死化メカニズムの解明とその臨床応用2007

    • Author(s)
      高倉 正博
    • Organizer
      第55回日本産科婦人科学会北日本連合地方部会学術講演会特別講演
    • Place of Presentation
      新潟市
    • Year and Date
      2007-10-05
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://sanpu.jp/index.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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