Fig. 9
Antitumor activity of CTPI-2. a T1 cells were grown as monolayer or spheres were injected in Balb/c athymic nude mice at 5 million cells/injection site. The time at which tumors started to appear was recorded and plotted in the graph (n = 7 per group). Once tumors were fully established there were no differences in tumor volumes between the two groups (see b). b Tumor volumes of monolayer (blue bars) or spheres (red bars) treated with vehicle (DMSO) or CTPI-2 (N = 6 per group). CTPI-2 was administered at 26 mg/kg at alternate days intra-peritoneally. c T1 cells were injected in immunocompromised mice, which were randomized to receive vehicle, cisplatin (3 mg/kg every 3 days), alone or in combination with CTPI-2. The figure shows the growth curves of all tumors in each treatment group. The number of tumors is indicated at the top of each panel. The graph shows a dot plot analysis of all tumors volumes at the end of the experiments. Each point represents the mean ± SD of tumor volumes. Statistical significance was assessed using both unpaired, two-tailed Student's t-test and analysis of variance (ANOVA). d Tumor doubling times were calculated by using the formula employed by radiologists. An online calculator was used at: http://www.chestx-ray.com/index.php/calculators/doubling-time, by analyzing the difference between tumor volumes the day before starting each treatment and at the end of the experiment. e Cell extracts derived from T1 tumors treated with vehicle (1) or cisplatin (lane 2) or combination (lane 3), were processed in immunoblot with the indicated antibodies. The position of each band relative to the molecular weight marker is indicated. f T2 cells were injected in immunocompromised mice. When tumors reached a size of 30–50 mm3 mice were randomly assigned to either control vehicle, or AZD9291 treatment (10 mg/kg every other day) or combination treatment with CTPI-2 (n = 6 tumors per group). Individual growth curves for all tumors in each treatment group are shown and the end-tumors are analyzed in a dot plot
