| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
We demonstrated schedule-dependent cytotoxicity of VP-16 and 4-HPC (preactivated form of cyclophosphamide) in K-562 cells. When K-562 cells were pretreated with low concentrations of 4-HCP, cells subsequently exposed to VP-16 showed reduced viability. In contrast, there was no change in the viability of K-562 cells pretreated with low concentrations of VP-16, followed by exposure to 4-HPC. It was shown that 4-HPC caused cell cycle arrest at S phase. It was suggested that since VP-16 have cell cycle specificity for cell killing from early-S to mid-S phase, the effect of VP-16 was increased by pretreatment with 4-HPC. We also demonstrated schedule-dependent cytotoxicity of VP-16 and 4-HPC in P-gp-overexpressed K-562/P-gp cells. Cytotoxicity of VP-16 was enhanced in K-562/P-gp cells that were pretreated with a non-cytotoxic concentration of 4-HPC compared to that of cells not treated with 4-HPC. The findings may lead to improvements in clinical combination chemotherapy.
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