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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
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥14,620,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2007: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
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.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2008 2007 2006

All Journal Article (22 results) (of which Peer Reviewed: 10 results) Presentation (3 results) Book (3 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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Overexpression of XIAP in renal cell carcinoma predicts a worse prognosis.2007

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

      Int. J. Oncol 30

      Pages: 919-925

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular featutes of hormone-refractory prostate cancer cells by genome-wide gene expression profiles.2007

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

      Cancer Res. 67

      Pages: 5117-5125

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of X-linked inhibitor of apoptosis protein(XIAP)is a stromg predictor of human prostate cancer recurrence.2007

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

      Clin. Cancer Res. 13

      Pages: 6056-6063

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of thymidylate synthase expression in prostate cancer patients undergoing radical prostatectomy.2007

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

      Urology 69

      Pages: 988-995

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.2007

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

      BJU Int. 99

      Pages: 663-668

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of thymidylate synthase expression in prostate cancer patients undergoing radical prostatectomy.2007

    • Author(s)
      Li, Y.N., Mizutani, Y.et al.
    • Journal Title

      Urology (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical efficacy of alternative antiandrogen therapy in Japanese men with relapsed prostate cancer after first-line hormonal therapy.2007

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

      Int. J. Urol. 14

      Pages: 128-132

    • NAID

      10018849933

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A differential ligand-mediated response of green fluorescent protein-tagged androgen receptor in living prostate cancer and non-prostate cancer cell lines.2007

    • Author(s)
      Nakauchi, H., Mizutani, Y., Miki, T.et al.
    • Journal Title

      J. Histochem Cytochem. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gene therapy with rumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against renal cell carcinoma2006

    • Author(s)
      Matsubara, H., Mizutani, Y., Miki, T.et al.
    • Journal Title

      Mol. Cancer Ther 5

      Pages: 2165-2171

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.2006

    • Author(s)
      Li, Y.N., Mizutani, Y., et al.
    • Journal Title

      BJU Int. 99

      Pages: 663-668

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Complexed PSA improves prostate cancer detection : Results from a multicenter Japanese clinical trial.2006

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

      Urology 67

      Pages: 328-332

    • Related Report
      2006 Annual Research Report
  • [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.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Enhanced orotate phosphoribosyltransferase activity in renal cell carcinoma and its prognostic significance.2007

    • 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.
    • Related Report
      2007 Annual Research Report
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [Book] Renal Cell Carcinoma: Molecular Targets and Clinical Application.2008

    • Author(s)
      Mizutani, Y., Kawauchi, A., Benjamin, B., Miki, T.
    • Publisher
      Smac/DIABLO: A proapoptotic molecular target in renal cell cancer. Inpress,
    • Related Report
      2007 Annual Research Report
  • [Book] Significance of Smac/DIABLO in sensitization of renal cell carcinoma to apoptosis. In : Chemo-immuno-sensitization of resistant tumor cells to cell death by apoptosis.2006

    • Author(s)
      Mizutani, Y., Kawauchi, A., Benjamin, B, Miki, T.
    • Publisher
      Transworld Research Network. Kerala, India.
    • Related Report
      2006 Annual Research Report

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

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