|Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
We collected VEGFR2 tyrosine kinase inhibitor (VEGFR2-TKI)-resistant cancer tissue from a cancer-bearing mouse model. We divided themice into groups that were given the VEGFR2-TKI Ki8751 in a dose of 10 mg/kg/day and20 mg/kg/day and an untreated control group, and after it had regressed, we collectedtumor tissue from the Ki8751 groups and used it resistant tissue. Blood plasma was collected at the time the tissue was collected. It was possible to collect resistant tissue from 3 (resistant group) of the 6 mice in the 10 mg/kg/day group, at 8 weeks after the start ofadministration. We extracted RNA from the tumor tissue of the resistant group and the control group and measured gene expression of angiogenesis-related factors (VEGFA, MET, HGF, IL-8, FGF7, KDR, EGF, FGF1, FGF2, KIT, VEGFB, VEGFC). Expression of one of the genes, IL-8, had increased after resistance developed, and expression of two of the genes, VEGFR2 and HGF, had decreased. Measurement of the plasma concentration of IL-8 by an ELISA yielded a concentration of 40.06 pg/mL in the resistant group and 26.90pg/mL in the control group, and the concentration in the resistant group was elevated. IL-8is suspected of being related to the mechanism of VEGFR2-TKI resistance.