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Analysis of mechanisms of the resistance of cisplatin in refractory or relapsed germ cell tumors

Research Project

Project/Area Number 16591611
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NOMOTO Takeshi  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教 (20301426)

Co-Investigator(Kenkyū-buntansha) MIKI Tsuneharu  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor, 医学研究科, 教授 (10243239)
MIZUTANI Yoichi  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 准教授 (10243031)
KAWAUCHI Akihiro  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 准教授 (90240952)
OKIHARA Koji  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 講師 (80285270)
MIKAMI Kazuya  Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教 (10291585)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsrefractory testicular tumor / Salvage chemotherapy / NALP7 / cisplatin / Paclitaxel / Salvage Chemotherapy / 救剤化学療法 / cDNA microarray / CDDP / CPT-11 / Paclitaxal / 遺伝子発現
Research Abstract

The overall response rate of cisplatin-based combination chemotherapy of patients with germ cell tumors (GCTs) has improved. Despite the high cure rate, 20-30 percent of patients with advanced GCTs failed to achieve a durable complete response. These refractory or relapsed GCTs remain a major problem in current treatment.
In clinical study, we investigated the chemotherapy with paclitaxel in combination with nedaplatin, which is a derivative of cisplatin, and ifosphamide as salvage chemotherapy for cisplatin refractory germ cell cancer. Fourteen patients were evaluated for response and toxicity. Response rate was 57.1 % (CR / PR^<m.> : 8 cases, NC : 5 cases、 PD : 1 cases ).Seven patients remain alive without disease. This study demonstrates that the chemotherapy with paclitaxel in combination with nedaplatin and ifosphamide showed a significant anticancer activity for patients with cisplatin refractory or relapsed germ cell cancer. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for cisplatin refractory or relapsed germ cell cancer.
In this study, to investigate new diagnostic markers and potential therapeutic targets for GCTs, we identified 347 genes that were commonly up-regulated in GCTs by using a cDNA microarray (Int J Oncol, 2003). Furthermore, we identified NALP7 that was significantly transactivated in GCTs and showed that NALP7 may be a promising candidate for development of targeted therapy for GCTs (Cancer Sci, 2004).

Report

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

    (17 results)

All 2007 2006 2005 2004

All Journal Article (17 results)

  • [Journal Article] Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis.2007

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

      Int J Oncol 30

      Pages: 919-925

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Paclitaxal, Ifosphamide, Nedaplatin(TIN 療法)を用いた難治性精巣腫瘍に対する救済化学療法2006

    • Author(s)
      野本剛史
    • Journal Title

      日本泌尿器科学会雑誌 97

      Pages: 630-635

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Salvage Chemotherapy with Paclitaxel, Nedaplatin and Ifosphamide for Relapsed or Refractory Germ Cell Cancer2006

    • Author(s)
      Nomoto, T
    • Journal Title

      Japanese Journal of Urology 97

      Pages: 630-635

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Paclitaxal, Ifosphamide, Nedaplatin (TIN療法)を用いた難治性精巣腫瘍に対する救済化学療法2006

    • Author(s)
      野本剛史
    • Journal Title

      日本泌尿器科学会雑誌 97

      Pages: 630-635

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Running suture for vesicourethral anastomosis in minilaparotomy radical retropubic prostatectomy.2006

    • Author(s)
      Miki T.
    • Journal Title

      Urology 67

      Pages: 410-412

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

    • 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 expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer2006

    • Author(s)
      Nonomura N, Miki T,. et al.
    • Journal Title

      Int J Clin Oncol 11

      Pages: 297-302

    • NAID

      10018768811

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differential response at the hGABP/E4TF1 site of retinoblastoma gene promoter in human testicular seminoma cells.2005

    • Author(s)
      Shiraishi, T.
    • Journal Title

      Oncology Reports 13

      Pages: 871-874

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors2005

    • Author(s)
      Nakai, Y.
    • Journal Title

      Biochemical and Biophysical Research Communications 337

      Pages: 289-296

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Downregulation of Smac/DIABLO expression in renal cell carcinoma and its prognostic significance2005

    • Author(s)
      Mizutani, Y
    • Journal Title

      Journal of Clinical Oncology 336

      Pages: 692-701

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Downregulation of Smac/DIABLO expression in renal cell carcinoma and its prognostic significance2005

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

      Journal of Clincal Oncology 23(3)

      Pages: 448-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Proteasome Inhibitor MG132 Induces Death Receptor 5 through CCAAT/Enhancer-Binding Protein Homologous Protein.2005

    • Author(s)
      Yoshida, T
    • Journal Title

      Cancer Research 65

      Pages: 5662-5667

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tunicamycin Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Human Prostate Cancer Cells2005

    • Author(s)
      Shiraishi, T
    • Journal Title

      Cancer Research 65

      Pages: 6364-6370

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of the transcription factor Yin Yang 1 activity by S-nitrosation2005

    • Author(s)
      Hongo, F
    • Journal Title

      Biochemical and Biophysical Research Communications 336

      Pages: 692-701

    • Related Report
      2005 Annual Research Report
  • [Journal Article] KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors2005

    • Author(s)
      Nakai, Y
    • Journal Title

      Biochemical and Biophysical Research Communications 337

      Pages: 289-296

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Oncogenic role of NALP7 in testicular seminomas2004

    • Author(s)
      Okada, K.
    • Journal Title

      Cancer Science 95

      Pages: 949-954

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oncogenic role of NALP7 in testicular seminomas2004

    • Author(s)
      Okada K, et al.
    • Journal Title

      Cancer Science 95(12)

      Pages: 949-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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

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