Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Outline of Final Research Achievements |
Gemcitabine, a difluorinated deoxy cytidine analogue, shows clinical activity against various human solid tumors, including pancreas. Clinical application of the gemcitabine-base adjuvant therapy has improved progression-free survival of patients with pancreas cancer. Many clinical trials for gemcitabine-based chemotherapy with various drugs has been applied to patients with pancreas cancer. However, its benefit is modest. In this study, we screened anticancer agents that can potentiate gemcitabine against human pancreatic cancer cells. We found that combination of mTOR inhibitor and GEM synergistically inhibit cell growth in pancreatic cancer cells. We also elucidated mechanism how mTOR inhibitors can augment the cytotoxic effect of gemcitabine. Inhibitor of mTOR induced CDA mRNA expression via stabilization of CDA mRNA. Therefore, mTOR inhibitor might potentiate the therapeutic efficacy of gemcitabine through modification of nucleoside metabolism in pancreatic cancer cells.
|