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Analysis of stress-inducible genes as predictive markers for response to chemotherapeutic drug in gastrointestinal cancer

Research Project

Project/Area Number 18591492
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTazuke Kofukai Medical Research Institute

Principal Investigator

UEDA Shugo  Tazuke Kofukai Medical Research Institute, 2nd Division, Medical Research Institute, Researcher (80372580)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Hajime  Kyoto University, Graduate School of Medicine, Associate Professor (70303914)
YODOI Junji  Kyoto University, Institute for Virus Research, Professor (80108993)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsanticancer drug / chemosensitivity / predictive marker / galectin-7 / thioredoxin / adverse event / stress / cisplatin / 進行胃癌 / 感受性マーカー / 肺癌 / 間質性肺炎
Research Abstract

Chemotherapeutic agents have an important role in treatment for advanced cancer, and it is necessary to develop predictive markers for the drug response. The purpose of this research was to identify the predictive markers among stress-inducible genes that regulate apoptosis signal using clinical cancer samples.
We showed that neoadjuvant chemotherapy with S-1 and cisplatin was effective for advanced gastric cancer patients. Although we examined the gene expression in the cancer samples collected endoscopically before chemotherapy, we could not specify genes that predict the chemo-sensitivity. We demonstrated that stress-inducible galectin-7 gene was highly expressed in cisplatin-sensitive urinary bladder cancer, and that galectin-7 augmented the cisplatin-induced apoptosis by generation of reactive oxygen species (ROS) and activation of c-Jun N-terminal kinase (JNK).
We measured plasma thioredoxin levels in non-small-cell lung cancer patients to identify predictive marker for adverse events during chemotherapy. We showed the plasma thioredoxin levels were high in patients with interstitial lung disease, severe adverse event associated with treatment with epidermal growth factor receptor (EGFR) inhibitor, gefitinib.
Our results suggest the future possibility of developing novel tailored therapeutic strategy for cancer by monitoring redox-regulating molecule and stress-inducible gene expression.

Report

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

    (13 results)

All 2007 2006

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

  • [Journal Article] Sensitizing effect of galectin-7 in urothelial cancer to cisplatin through the accumulation of intracellular reactive oxygen species2007

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

      Cancer Research 67

      Pages: 1212-1220

    • 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] Elevation of serum thioredoxin in patients with gefitinib-induced interstitial lung disease2007

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

      Internal Medicine 46

      Pages: 1905-1909

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sensitizing effect of galectin-7 in urothelial cancer to cisplatin throuth the accumulation of intracellular reactive oxygen species2007

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

      Cancer Research 67

      Pages: 1212-1220

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Elevation of serum thioredoxin in patients with gefitinib-induced interstitial lung disease2007

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

      Internal Medicine 46

      Pages: 1905-1909

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway2007

    • Author(s)
      Nakamura T., et. al.
    • Journal Title

      Free Radical Research 41

      Pages: 1089-1098

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Does thioredoxin-1 prevent mitochondria-and endoplasmic reticulum-mediated neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine2007

    • Author(s)
      Bai J., et. al.
    • Journal Title

      Antioxidants&Redox Signaling 9

      Pages: 603-608

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitizing effect of galectin-7 in urothelial cancer to cisplatin through the accumulation of intracellular reactive oxygen species.2007

    • Author(s)
      Mathui Y. et al.
    • Journal Title

      Cancer Research 67(3)

      Pages: 1212-1220

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat2006

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

      Life Sciences 79

      Pages: 1170-1177

    • 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] Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat2006

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

      Life Sciences 79

      Pages: 1170-1177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat.2006

    • Author(s)
      Ueda S.et al.
    • Journal Title

      Life Science 79(12)

      Pages: 1170-1177

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Isoflurane inhalation after circulatory arrest protects against warm ischemia reperfusion injury of the lungs.2006

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

      Transplantation 82(9)

      Pages: 1168-1174

    • Related Report
      2006 Annual Research Report
  • [Presentation] 進行胃癌に対するTS-1/CDDP併用術前化学療法の検討2007

    • Author(s)
      上田修吾
    • Organizer
      第45回日本癌治療学会総会
    • Place of Presentation
      京都国際会館
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Neoadjuvant chemotherapy with S-1 and CDDP for advanced gastric cancer2007

    • Author(s)
      Ueda S, et. al.
    • Organizer
      The 45th Annual Meeting of Japan Society of Clinical Oncology
    • Place of Presentation
      Kyoto
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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

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