| Co-Investigator(Kenkyū-buntansha) |
OYAMA Tsunehiro University of Occupational&Environmental Health, Japan, School of Medicine, Associate Professor (00309965)
HANAGIRI Takeshi University of Occupational&Environmental Health, Japan, School of Medicine, Assistant Professor (30299614)
URAMOTO Hidetaka University of Occupational&Environmental Health, Japan, School of Medicine, Research Associate (90389445)
KENJI Ono University of Occupational&Environmental Health, Japan, School of Medicine, Research Associate (40369062)
YASUMOTO Kosei University of Occupational&Environmental Health, Japan, School of Medicine, Professor (30150452)
菅谷 将一 産業医科大学, 医学部, 助手 (40352306)
仲田 庄志 産業医科大学, 医学部, 助手 (40373154)
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| Budget Amount *help |
¥15,980,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥780,000)
Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Research Abstract |
(1) The analyses of gene expression such as K-ras, p53, p27, p16, E-cadherin, β -catenin, TSP-1, and methylation analyses (CDH1, p16, FHIT) were performed in NSCLC. The analyses of gene expression in multiple lung cancers (p53, p16, p27, c-erbB2) were also done. These data demonstrated biological features in NSCLC and we suggested molecular staging. (2) Carcinogenesis of adenocarcinoma of the lung: The mutation of EGFR and K-ras gene and p53 expression were examined in multiple lung adenocarcinomas, and the frequency of case with same gene type was higher than expected rate. These data suggested that same mechanism might exist in carcinogenesis for multiple lung cancer. (3) The analyses of molecule target: We screened the EGFR (exons 19 and 21) in 469 resected tumors of patients with lung cancer, and the EGFR mutations were found specifically in adenocarcinoma, and frequently found in women, in well differentiated tumors, in never smokers. The cases with EGFR mutation showed good respo
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nse for gefitinib treatment in both retrospective and prospective analyses. In prospective study, 19 patients with EGFR mutations were enrolled and the response rate was 63.2%, disease control rate was 89.5%, median PFS was 7.1 months, and median survival time was 20.0 months. We detected EGFR exon20 T790M acquired mutation in 5 of 7 gefitinib-refractory tumors. In addition, exon20 G796A mutation was detected in primary gefitinib-resistant tumor, and in-vitro assay revealed resistance to gefitinib. EGFR mutations in exons 19-21 are considered to a good predictor of the efficacy of gefitinib, and the treatment with gefitinib was also found to achieve a prolonged survival. (4) Development of the anticancer agent sorting method by the drug metabolizing enzyme expression analysis: We examined the expression of 96 genes about cytochrome P450 using Gene Array, and the expression of CYP1A1, 2A6, 2E 1, 3A was confirmed for about half of cases with lung adenocarcinoma. These data indicated a possibility of clinical application as biological markers for indicator of selection of anticancer. Summary: The molecular staging system and molecular targeting therapy is important for establishment of individualized therapy and improvement of prognosis for patients with lung cancer. Less
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