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Chimeric adenovirus vector enhances HSV-tk gene therapy for bladder cancer.

Research Project

Project/Area Number 16591618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKitasato University

Principal Investigator

SOH Shigehiro  Kitasato University, Medicine, Assistant Professor, 医学部, 講師 (30206669)

Co-Investigator(Kenkyū-buntansha) SATOH Takefumi  Kitasato University, Medicine, Assistant Professor, 医学部, 講師 (50286332)
BABA Shiro  Kitasato University, Medicine, Professor, 医学部, 教授 (00051889)
MATSUMOTO Kazumasa  Kitasato University, Medicine, Research associate, 医学部, 助手 (70306603)
FUJITA Tetsuo  Kitasato University, Medicine, Assistant Professor, 医学部, 講師 (00306599)
入江 啓  北里大学, 医学部, 講師 (50193694)
荒川 孝  北里大学, 医学部, 講師 (20151152)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsgene therapy / bladder cancer / adenovirus / receptor / immunohistochemistory / レセプター / アデノウイルス / アデノウイルスレセプター / キメラアデノウイルスベクター
Research Abstract

We investigated the new treatment modality for bladder cancer. We tested that the transduction efficacy of adenovirus (Ad)-mediated bladder cancer gene therapy would be enhanced with the use of a novel chimeric Ad vector that utilizes a CAR-independent entry mechanism. A chimeric Ad vector expressing herpes simplex virus I thymidine kinase (HSV-tk) was constructed by Ad35 fiber into an Ad5 backbone (Ad5/F35). In vitro experiment Ad5/F35 with HSV-tk was up to 30 times more effective than Ad5HSV-tk in terms of cell death in CAR-negative cells and equally efficient in CAR-positive cells. Experimental group in vivo was categorized as 11 groups consisted of control, GFP infection only, GCV administration only, Ad5HSV-tk (5×10^8PFU), Ad5F35HSV-tk (1×10^8, 5×10^8, 1×10^9 PFU), Ad5HSV-tk/GCV (5×10^8PFU), Ad5F35HSV-tk/GCV (1×10^8, 5×10^8, 1×10^9 PFU). We observed a 10-fold treatment effect with Ad5/F35HSV-tk over Ad5HSV-tk in growth suppression of CAR-negative bladder cancer animal models with comparable anti-tumor efficacy in CAR-positive cancer models. There were no side effect and toxicity in major organs. This finding demonstrates that the Ad5/F35 vector transduced bladder cancer cells independently of CAR status and augments HSV-tk suicide gene therapy in CAR-negative bladder cancer.
In addition, we also investigated immunohistochemical staining using S100A2, S100A4 and p53 in bladder cancer specimens taken form radical cystectomy. These proteins were associated with bladder cancer stage, grade and prognosis. These findings suggested that S100A2, S100A4 and p53 would play a role as target protein for gene therapy. According to the results, we demonstrated potential alternative as target specific treatment for bladder cancer using chimeric adenovirus vector.

Report

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

    (18 results)

All 2007 2006 2005 Other

All Journal Article (18 results)

  • [Journal Article] Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer2007

    • Author(s)
      T Fujita
    • Journal Title

      Gene Therapy 14

      Pages: 227-236

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer2007

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

      Gene Therapy 14

      Pages: 227-236

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] SUSTAINED LONG-TERM IMMUNE RESPONSES AFTER IN SITU GENE THERAPY COMBINED WITH RADIOTHERAPY AND HORMONAL THERAPYIN PROSTATE CANCER PATIENTS2006

    • Author(s)
      藤田哲夫 ほか
    • Journal Title

      Int. J. Radiation Oncology・Biology・Physics 65(1)

      Pages: 84-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Computer simulated additional deep apical biopsy enhances cancer detection in palpably benign prostate gland.2006

    • Author(s)
      KAZUMASA MATSUMOTO
    • Journal Title

      International Journal of Urology 13

      Pages: 1290-1295

    • NAID

      10018302863

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] SUSTAINED LONG-TERM IMMUNE RESPONSES AFTER IN SITU GENE THERAPY COMBINED WITH RADIOTHERAPY AND HORMONAL THERAPY IN PROSTATE CANCER PATIENTS.2006

    • Author(s)
      Tetsuo Fujita, et al.
    • Journal Title

      Int.J.Radiation Oncology・Biology・Physics 65(1)

      Pages: 84-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Computer simulated additional deep apical biopsy enhances cancer detection in palpably benign prostate gland.2006

    • Author(s)
      KAZUMASA MATSUMOTO, et al.
    • Journal Title

      International Journal of Urology 13

      Pages: 1290-1295

    • NAID

      10018302863

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ハイリスク前立腺癌に対する術前8ヵ月ネオアジュバント内分泌療法の有用性に関する検討2006

    • Author(s)
      田畑健一, 佐藤威文 他
    • Journal Title

      日本泌尿器学会雑誌 97(5)

      Pages: 712-718

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 限局性前立腺癌の治療戦略 : QOLを考慮した治療の個別化 3.限局性前立腺癌に対する放射線治療 : LDR,HDR,および3D-CRTのhealth-related QOLに関する前向き比較検討2006

    • Author(s)
      佐藤威文, 藤田哲夫 他
    • Journal Title

      泌尿器外科 19(臨増)

      Pages: 419-421

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 特集 前立腺肥大症-日常診療の視点から 前立腺肥大症の治療温熱療法 -TUMT-2006

    • Author(s)
      松本和将, 馬場志郎
    • Journal Title

      カレントテラピー 24(4)

      Pages: 47-49

    • Related Report
      2006 Annual Research Report
  • [Journal Article] SUSTAINED LONG-TERM IMMUNE RESPONSES AFTER IN SITUGENE THERAPY COMBINED WITH RADIOTHERAPY AND HORMONAL THERAPYIN PROSTATE CANCER PATIENTS2006

    • Author(s)
      藤田哲夫 ほか
    • Journal Title

      Int. J. Radiation Oncology? Biology? Physics 65(1)

      Pages: 84-90

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Topographic distribution of lymphatic vessels in the normal human prostate.2005

    • Author(s)
      Soh S, Baba S, et al.
    • Journal Title

      Prostate 63

      Pages: 330-335

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Efficacy and morbidity of transrectal ultrasound guided 12-core biopsy or detection of prostate cancer in Japanese men.2005

    • Author(s)
      Matsumoto K, Baba S, et al.
    • Journal Title

      Int J Urol 12

      Pages: 353-360

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Occupational bladder cancer : from cohort study to biologic molecular marker2005

    • Author(s)
      Matsumoto K, Irie A, et al.
    • Journal Title

      Med Sci Monit 11

      Pages: 311-315

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cancer Core distribution on patients diagnosed by extended transperineal prostate biopsy2005

    • Author(s)
      Satoh T, Matsumoto K, et al.
    • Journal Title

      Urol 66

      Pages: 114-118

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Loss of coxsackie and adenovirus receptor expression is associated with features of aggressive bladder cancer2005

    • Author(s)
      Matsumoto K, Shariat SF, et al.
    • Journal Title

      Urol 66

      Pages: 441-446

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Urinary levels of soluble E-cadherin in the detection of transitional cell carcinoma of the urinary bladder..2005

    • Author(s)
      Shariat SF, Matsumoto K, et al.
    • Journal Title

      Eur Urol 48

      Pages: 114-118

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In situ gene therapy for prostate cancer.2005

    • Author(s)
      Satoh T, Irie A, et al.
    • Journal Title

      Curr Gene Ther. Jan:5(1)

      Pages: 111-119

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Current statues of gene therapy for urological cancer.

    • Author(s)
      Matsumoto K, Irie A, et al.
    • Journal Title

      Gene Therapy in Cancer. (accepted)

    • Related Report
      2004 Annual Research Report

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

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