|Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
In order to improve the clinical outcome of patients with non-small cell lung cancer (NSCLC), we have been performing "tailor-made chemotherapy", the selection of the effective chemotherapy treatment based on evaluation of biomarkers associated with chemo-responsiveness (Huang, et. Al., Future Oncol 2006).Biomarkers associated with 5-FU responsiveness are its target enzyme TS, activating enzyme OPRT, and catabolic enzyme DPD. We have found that low TS expression, high OPRT expression, and low DPD expression are independent good prognostic factors in NSCLC patients postoperatively treated with oral 5-FU (Nakano, et. Al., Br J Cancer 2006). On the other hand, because epidermal growth factor receptor (EGFR) gene mutations are reported to be associated with responsiveness of EGFR-specific TKIs, we developed the clinically useful protocol to evaluate the EGFR gene mutations (Liu, et. Al.,〓ncol Rep 2006). In addition, we performed comprehensive studies on the tumor suppressor gene p53, which is involved in tumor apoptosis (Huang, et. Al., Future Oncol 2007). Consequently, we demonstrated a reduced expression of HAUSP to be associated with the downregulation of the p53 protein and its targets, such as p21 and bax (Masuya, et. Al., J Pathol 2006). Furthermore, regarding the apoptosis inhibitor survivin, we have found that the E2F1 over-expression is associated with the TS and Survivin expression (Clin Cancer Res 2007), and that splicing variants of Survivin have different biological functions associated with carcinogenesis (Nakano, et. Al., Br J Cancer 2008).Comprehensive analysis using cDNA microarray assays revealed the Wnt pathway to be associated with carcinogenesis. In addition, we found that the intratumoral Wntl expression is a poor prognostic factor of NSCLC patients, through the induction of its targets, such as c-Myc and MMP-7 (Liu, et. Al., Lung Cancer 2007; Nakashima, et. Al., Oncol Rep 2008).