Figure 5

Impact of gemcitabine and MK-8776 on two pancreas tumor xenografts. A. Mice were administered 150 mg/kg gemcitabine and tumors harvested at 18 h and 42 h. Serial sections from the tumors were stained for Ki67 and geminin and the ratio of geminin/Ki67 expressed as a percentage. Results represent the mean and SEM for at least 2 sections from 2–4 mice. B. Mice bearing AsPC-1 tumors were administered 150 mg/kg gemcitabine on days 1, 8, 15 (arrows); or 50 mg/kg MK-8776; or the combination of these two drugs with MK-8776 given either 30 min or 18 h after gemcitabine. Data are expressed as mean and SEM for each time point. “n” represents the number of mice in each group. After day 5, all gemcitabine-treated groups were significantly different from untreated mice (p < 0.05). Treatment with gemcitabine followed by MK-8776 after 30 min was not significantly different than gemcitabine alone. Treatment with gemcitabine followed by MK-8776 after 18 hours was significantly different from gemcitabine alone or when combined with MK-8776 after 30 minutes (p < 0.05). C. Mice bearing MiaPaCa-2 tumors were treated as in B. After 12 days, treatment with gemcitabine followed by MK-8776 after 18 hours was significantly different from either gemcitabine alone or when combined with MK-8776 after 30 minutes (p < 0.05).