| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Research Abstract |
Endometrial cancer, one of the most common gynecologic malignancies, is increasing in Japan, nearly doubling over the last decade. High grade disease patients are often resistant to conventional chemotherapy with platinum agents; therefore discovery of efficacious new drugs in this setting is required to benefit chemo-refractory cases. Through bioinformatic analysis using the NCI60 panel of cell lines with in vivo endometrial cancer data (GSE2109) and in vitro data (GSE25458), we at first calculated susceptibility scores to identify candidate drugs for chemo-refractory cases. Fludarabine and Temsirolimus showed higher susceptibility scores in high grade cases compared with cisplatin, doxorubicin, and paclitaxel. Fludarabine significantly inhibited cell proliferation and increased apoptosis in the cisplatin-resistant endometrial cancer cell line, HEC1A, relative to HEC50B (p<0.001). Fludarabine treatment also enhanced Caspase 3/7 activity in HEC1A relative to HEC50B cells (p<0.001), and inhibited the growth of HEC1A xenograft tumors relative to cisplatin (p<0.05). Conclusions: These results support that identification and use of genomic signatures can lead to identification of n ew therapeutic candidates that may prove beneficial to chemo -resistant cases. Fludarabine may be useful in targeting high grade, chemo-refractory endometrial cancer.
|
