Figure 5.

Effect of PF-04554878 on growth of human human pancreatic neuroendocrine tumors (PanNETs) in vivo. A) Effect of daily oral administration of PF-04554878 on growth of CM-Luc cells in NOD/SCID mice as measured by bioluminescent luciferase signal intensity in CM-Luciferase model of PanNET carcinomatosis. Fold induction bioluminescent signal intensity was calculated for each mouse by normalizing bioluminescent signal value to first measurement (Day 10 post-injection). Based on bioluminescent imaging, mice were assigned on Day 15 to vehicle control (n = 3) or 50mg/kg of PF-04554878 (n = 4). B) Bioluminescent imaging of mice on final day of study (Day 26). C) Immunohistochemical staining of FAK (Y397) and AKT (S473) phosphorylation in PanNET patient-derived xenograft tumor model (scale bar = 200 µm). D) Effect of daily oral administration of PF-04554878 on growth of human PanNET patient-derived xenograft transplant model in NSG mice. Animals were implanted with a 3 x 3 x 3mm piece of a human PanNET tumor sample 10 days prior to treatment assignment and commencement (Day 1) with vehicle control or 50mg/kg of PF-04554878. Tumors were measured when palpable using calipers, and tumor volume was calculated using the formula V = L² x W x π/6. Statistical analysis of the effect of treatment intervention as compared with control was performed using a repeated measures two-tailed two-way analysis of variance. Error bars represent standard deviation of the mean.