| 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)
木下 盛敏 大塚ライフサイエンス事業部, NBC遺伝子解析センター, センター長
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| 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.
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