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2007 Fiscal Year Final Research Report Summary

Molecular targeted gene therapy against hormone-refractoty prostate cancer by new ultrasonic gene transfection

Research Project

Project/Area Number 18390439
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

MIZUTANI Yoichi  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor (10243031)

Co-Investigator(Kenkyū-buntansha) AKIHIRO Kawanehi  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor (90240952)
KOJI Okihara  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor (80285270)
SOH Jintetsu  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor (40305587)
NAITOH Yasuyuki  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor (50405312)
MIKI Tsuneharu  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor (10243239)
Project Period (FY) 2006 – 2007
KeywordsUltrasonic gene transfection / Gene therapy / Molecular targeted therapy / Prostate cancer / Hormone-refractory / TS / DPD / TRAIL
Research Abstract

Dihydropyrimidine dehydrogenase ( DPD ), an enzyme involved in metabolism of 5-fluorouracil ( 5-FU) , is a key factor determining the sensitivity of tumors to 5-FU. Therefore, it is critical to know in advance how much DPD the tumor expresses. DPD expression has been measured in several cancer tissues such as gastric cancer obtained clinically. However, the clinical significance of DPD expression in prostate cancer has never been reported. We investigated DPD expression in prostate cancer. We also determined whether 5-chloro-2, 4-dihydroxypyridine ( CDHP ), a potent inhibitor of DPD, enhanced the antitumoral activity of 5-FU against prostate cancer.
Forty-four prostate tissue specimens were obtained form patients who underwent radical prostatectomy for prostate cancer without neoadjuvant hormonal therapy. We analyzed the cancerous tissue and normal prostate tissue for DPD expression using immunohistochemistry.
The expression of DPD was significantly higher in prostate cancers compared with the normal prostate tissues. Thirty-six of 44 (82%) specimens of prostate cancer expressed DPD, whereas only twenty-five (57%) of 44 specimens of normal prostate tissue expressed DPD. DPD expression was significantly lower in prostate cancers patients who received neoadjuvant hormonal therapy. In vitro treatment with 5-FU/CDHP resulted in enhanced cytotoxicity compared with 5-FU alone treatment. In vivo, the size of DU145 tumors treated with oral administration of 5-FU and CDHP in mice was significantly smaller than that in mice receiving oral administration of 5-FU.
The present study showed for the first time that the expression of DPD was highly detected in prostate cancer. In addition, DPD inhibitors may enhance the antitumor activity of 5-FU against prostate cancer.

  • Research Products

    (14 results)

All 2008 2007

All Journal Article (11 results) (of which Peer Reviewed: 5 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Smac/DIABLO : A proapoptotic molecular target in renal cell cancer2008

    • Author(s)
      Mizutani, Y., Kawauchi, A., Benjamin, B., Miki, T
    • Journal Title

      Renal Cell Carcinoma : Molecular Targets and Clinical Application. The Humana Pres Inc in press

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Overeipression of XIAP in renal cell carcinoma predicts a worse prognosis2007

    • Author(s)
      Mizutani, Y., Kawauchi, A., Miki, T., et. al.
    • Journal Title

      Int.J.Oncol 30

      Pages: 919-925

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Molecular featutes of hormone-refractory prostate cancer cells by genome-wide gene expression profiles2007

    • Author(s)
      Tamura, K., Mizutani, Y., Mild, T., et. al.
    • Journal Title

      Cancer Res. 67

      Pages: 5117-5125

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of X-linked inhibitor of apoptosis protein(XIAP)is a stromg predictor of human prostate cancer recurrence2007

    • Author(s)
      Seligson, D.B., Mizutani, Y., Miki, T., et. al.
    • Journal Title

      Clin.Cancer Res. 13

      Pages: 6056-6063

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Prognostic significance of thymidylate synthase expression in prostate cancer patients undergoing radical prostatectomy2007

    • Author(s)
      Li, Y.N., Mizutani, Y., Kawauchi, A., Miles, T., et. al.
    • Journal Title

      Urology 69

      Pages: 988-995

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer2007

    • Author(s)
      Li, Y.N., Mizutani.Y., Kawauchi, A., Miles.T., et. al.
    • Journal Title

      BJU Int. 99

      Pages: 663-668

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Overexpression of XIAP in renal cell carcinoma predicts a worse prognosis2007

    • Author(s)
      Mizutani, Y., Kawauchi, A., Miki, T., et. al.
    • Journal Title

      Int. J. Oncol 30

      Pages: 919-925

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular featutes of hormone-refractory prostate cancer cells by genome-wide gene expression profiles2007

    • Author(s)
      Tamura, K., Mizutani, Y., Miki, T., et. al.
    • Journal Title

      Cancer Res. 67

      Pages: 5117-5125

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of X-linked inhibitor of apoptosis protein ( XIAP ) is a stromg predictor of human prostate cancer recurrence2007

    • Author(s)
      Seligson, D. B., Mizutani, Y., Miki, T., et. al.
    • Journal Title

      Clin Cancer Res 13

      Pages: 6056-6063

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prognostic significance of thymidylate synthase expression in prostate cancer patients undergoing radical prostatectomy2007

    • Author(s)
      Li, Y. N., Mizutani, Y., Kawauchi, A., Miki, T., et. al.
    • Journal Title

      Urology 69

      Pages: 988-995

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer2007

    • Author(s)
      Li, Y. N., Mizutani, Y., Kawauchi, A., Miki, T., et. al.
    • Journal Title

      BJU Int 99

      Pages: 663-668

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Enhanced orotatephos phoribosyltransferase activity in renal cell carcinoma and its prognostic significance2007

    • Author(s)
      Mizutani, Y., Kawauchi, A., Miki, T., et. al.
    • Organizer
      43th Annual Meeting of American Society of Clinical Oncology
    • Place of Presentation
      Chicago,USA.
    • Year and Date
      20070601-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Enhanced orotate phosphoribosyltransferase activity in renal cell carcinoma and its prognostic significance2007

    • Author(s)
      Mizutani, Y., Kawauchi, A., Miki, T., et. al.
    • Organizer
      43th Annual Meeting of American Society of Clinical Oncology
    • Place of Presentation
      Chicago, USA.
    • Year and Date
      20070601-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Smac/DIABLO:A proapoptotic molecular target in renal cell cancer In:Renal Cell Carcinoma:Molecular Targets and Clinical Application2008

    • Author(s)
      Mizutani, Y., Kawauchi, A., Benjamin, B., Miki, T.
    • Publisher
      The Humana Pres Inc.(In press)
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2010-02-04  

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