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2005 Fiscal Year Final Research Report Summary

Tailor-made therapy based on genetic analyses for non-small cell lung cancers

Research Project

Project/Area Number 16591401
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKagawa University

Principal Investigator

LIU Dage  Kagawa University, Faculty of Medicine, Research Associate, 医学部, 助手 (30314941)

Co-Investigator(Kenkyū-buntansha) HUANG Cheng-long  Kagawa University, Faculty of Medicine, Associated professor, 医学部, 助教授 (10271511)
YOKOMISE Hiroyasu  Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (80231728)
UENO Masaki  Kagawa University, Faculty of Medicine, Associated professor, 医学部, 助教授 (30322267)
Project Period (FY) 2004 – 2005
Keywordsnon-small cell lung cancer / genetic analysis / tailor-made therapy / multi-discipline therapy / chemotherapy / thymidylate synthase / EGFR / tumor proliferation
Research Abstract

We performed various genetic analyses in non-small cell lung cancer (NSCLC). Genetic mutations were evaluated for p53, K-ras, and epidermal growth factor receptor (EGFR). Quantitative RT-PCR assays were performed to determine gene expressions of HAUSP, ING1b, CD9, CD82, E-cadherin, thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD). In addition, immunohistochemistry was done to evaluate protein expressions of p53, mdm2, CD9CD82, E-cadherin, TS, DPD, VEGF-A, VEGF-C, the Ki-67 index, and the intratumoral microvessel density. Consequently, biomarkers associated with angiogenesis or metastasis, including a VEGF-A expression, a VEGF-C expression, and an E-cadherin expression, proved to be prognostic factors for early stage NSCLCs. On the other hand, the tumor proliferation rate and a TS expression were prognostic factors for advanced stage NSCLCs. In particular, the survival of patients with TS-negative tumors who were postoperatively treated with 5-FU derived antitumor agents was the highest among advanced stage NSCLCs. These results demonstrated the importance of multi-disciplinary therapy with effective chemotherapy, tailor-made therapy, even in advanced stage NSCLCs. We are performing prospective clinical studies on tailor-made therapy, using 5-FU derived agents against TS-negative and DPD-negative tumors, and Gefitinib against tumors with EGFR mutations. The prospective clinical study demonstrated UFT to be effective for TS-negative tumors. Recently, S-1 was developed for clinical use as a new 5-FU derived antitumor agents with a stronger DPD inhibitor. We will perform a further study to evaluate the efficacy of S-1 against TS-negative and DPD-positive NSCLCs. Furthermore, we studied gene expressions and protein expressions using cDNA microarray assays and proteomics in order to find new biomarkers associated with NSCLCs. Consequently, we have found the Wnt signal pathway to be associated tumor progression in NSCLCs.

  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] A useful protocol for analyses of mutations of the epidermal growth factor receptor gene2006

    • Author(s)
      Dage Leu, et al.
    • Journal Title

      Oncology Reports (in-press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A useful protocol for analyses of mutations of the epidermal growth factor receptor gene.2006

    • Author(s)
      Liu D, et al.
    • Journal Title

      Oncology Reports (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Wnt5a expression is associated with the tumor proliferation and the stromal vascular endothelial growth factor-an expression in non-small-cell lung cancer2005

    • Author(s)
      Cheng-long Huang, et al.
    • Journal Title

      Journal of Clinical Oncology 23・34

      Pages: 8765-8773

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical application of biological markers for the treatments of resectable non-small cell lung cancer2005

    • Author(s)
      Cheng-long Huang, et al.
    • Journal Title

      British Journal of Cancer 92・7

      Pages: 1231-1239

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer2005

    • Author(s)
      Jun Nakano, et al.
    • Journal Title

      International Journal of Oncology 27・5

      Pages: 1215-1221

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Wnt5a expression is associated with tumor proliferation and the stromal vascular endothelial growth factor - an expression in non-small-cell lung cancer.2005

    • Author(s)
      Huang C, Liu D, et al.
    • Journal Title

      Journal of Clinical Oncology 23(34)

      Pages: 8765-8773

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical application of biological markers for the treatments of respectable non-small cell lung cancer.2005

    • Author(s)
      Huang C, Liu D, et al.
    • Journal Title

      British Journal of Cancer 92(7)

      Pages: 1231-1239

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer.2005

    • Author(s)
      Nakano J, Liu D, et al.
    • Journal Title

      International Journal of Oncology 27(5)

      Pages: 1215-1221

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal pathways2004

    • Author(s)
      Cheng-long Huang, et al.
    • Journal Title

      Oncogene 23・45

      Pages: 7475-7483

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The tumor-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small cell lung cancer patients2004

    • Author(s)
      Daiki Masuya, et al.
    • Journal Title

      British Journal of Cancer 90・8

      Pages: 1555-1562

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal pathways.2004

    • Author(s)
      Huang C, Liu D, et al.
    • Journal Title

      Oncogene 23(45)

      Pages: 7475-7483

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The tumour-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small cell lung cancer patients.2004

    • Author(s)
      Masuya D, Liu D, et al.
    • Journal Title

      British Journal of Cancer 90(8)

      Pages: 1555-1562

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

URL: 

Published: 2007-12-13  

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