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2005 Fiscal Year Final Research Report Summary

Clinical research of gene therapy using tissue-specific promoter for the treatment of metastatic prostate cancer.

Research Project

Project/Area Number 14207063
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

KAMIDONO Sadao  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30030935)

Co-Investigator(Kenkyū-buntansha) GOTOH Akinobu  Hyogo College of Medicine, Professor, 教授 (70283885)
MAEDA Sakan  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50030911)
SUGIMURA Kazuro  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00136384)
MATSUO Masafumi  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10157266)
SHIRAKAWA Toshiro  Kobe University, Graduate School of Medicine, Associate Professor, 医学部, 助教授 (70335446)
Project Period (FY) 2002 – 2005
KeywordsGene Therapy / Clinical Research / Prostate cancer / Bone Metastasis / Tissue-specific promoter / Adenovirus / Suicide gene / Osteocalcin
Research Abstract

Background : The absence of effective therapies for hormone refractory prostate cancer establishes the need to develop novel therapeutic modality, such as a gene therapy, that can be applied either separately or in conjunction with current treatment modalities for the treatment of advanced prostate cancer. The phase I/II clinical trial of the Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter driven herpes-simplex-virus thymidine kinase gene) plus VAL (Valacyclovior) for the treatment of hormone-refractory prostate cancer was performed at the Kobe University Hospital, Japan.. Method : To date, six patients with localized recurrence or bone metastasis of hormone refractory prostate cancer were enrolled. The doses of a Ad-OC-TK injected directly to localized recurrent tumor or bone metastatic lesion was 2.5 x 10^9 or 10^<10> plaque-forming unit (PFU) / Day 1 and Day 8. Patient was given one gram of VAL twice daily for 21 days. Results : The initial patients tolerated this therapy without serious adverse events. Despite intralesional injections, both the hsvTK and adenoviral genes were able to detect in peripheral blood samples. Biopsies of each lesion demonstrated hsvTK, CAR and OC proteins after treatment demonstrating transcriptional expression in these specimens and increased apoptosis post-treatment observed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay. Initially, serum PSA levels declined in 4 out of 6 patients coincident with valacyclovir pro-drug activation of hsv-TK. The quantitative analysis of bone scintigraphy showed the decreased RI accumulation only in injected lesion. Conclusions : The Ad-OC-TK plus VAL therapy as a tissue-specific OC promoter-based toxic gene therapy has demonstrated the localized anti-tumor effect without any serious adverse events in the initial Japanese patients with hormone-refractory prostate cancer.

  • Research Products

    (12 results)

All 2005 2004 2003

All Journal Article (12 results)

  • [Journal Article] Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model.2005

    • Author(s)
      Terao S
    • Journal Title

      Anticancer Research 25・4

      Pages: 2527-2760

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model.2005

    • Author(s)
      Shuji, Terao
    • Journal Title

      Anticancer Research 25-4

      Pages: 2527-2760

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Development of human chorionic gonadotropin subunits (hCG-s) promoter-based toxic gene therapy for testicular cancer.2004

    • Author(s)
      Shirakawa T
    • Journal Title

      Urology 63・3

      Pages: 613-618

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A COX-2 promoter-based replication-selective adenoviral vector to target the COX-2-expressing human bladder cancer cells.2004

    • Author(s)
      Shirakawa T
    • Journal Title

      Clinical Cancer Research 10・13

      Pages: 4342-4348

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Development of human chorionic gonadotropin subunit s (hCG-s) promoter-based toxic gene therapy for testicular cancer.2004

    • Author(s)
      Toshiro, Shirakawa
    • Journal Title

      Urology 63-3

      Pages: 613-618

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A COX-2 promoter-based replication-selective adenoviral vector to target the COX-2-expressimg human bladder cancer cells.2004

    • Author(s)
      Toshiro Shirakawa
    • Journal Title

      Clinical Cancer Research 10-13

      Pages: 4342-4348

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The growth inhibitory effect of p21 adenovirus on androgen-dependent (AD) human prostate cancer cells.2003

    • Author(s)
      Gotoh A
    • Journal Title

      British Journal of Urology International 92・3

      Pages: 314-318

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Establishment of a prostatic small-cell carcinoma cell line (SO-MI)2003

    • Author(s)
      Okada H
    • Journal Title

      Prostate 56・3

      Pages: 231-238

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Combination with CD/5-FC gene therapy enhances killing of human bladder cancer cells by radiation.2003

    • Author(s)
      Zhang Z
    • Journal Title

      Journal of Gene Medicine 5・10

      Pages: 860-867

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The growth inhibitory effect of p21 adenovirus on androgen - dependent (AD) human prostate cancer cells.2003

    • Author(s)
      Akinobu, Gotoh
    • Journal Title

      British Journal of Urology International 92-3

      Pages: 314-318

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Establishment of a prostatic small-cell carcinoma cell line (SO-MI).2003

    • Author(s)
      Okada, Hiroshi
    • Journal Title

      Prostate 56-3

      Pages: 231-238

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Combination with CD/5-FC gene therapy enhances killing of human bladder cancer cells by radiation.2003

    • Author(s)
      Zhang Zhujun
    • Journal Title

      Journal of Gene Medicine 5-10

      Pages: 860-867

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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