Fig. 4. AZD0466 treatment results in tumor growth control of MPM xenografts.

A MSTO-211H xenograft tumor volumes measured during and following treatment with AZD0466 (100 mg/kg, days 1 and 8, IV) and Cisplatin (4 mg/kg, day 1 IP), the combination, or appropriate controls. B Tumor masses at Day 19 from start of treatment. Each point is the mass of an individual tumor (photographed) with the bar indicating the mean ± SEM (n = 3) and significance determined by Student’s t-test (unpaired). C Kaplan–Meier survival curves of mice treated with AZD0466, Cisplatin and combinations of both, with relevant vehicle controls. Survival endpoint was when tumors reached 1000mm³ as dictated by the ethics approval associated with this experiment. Significance determined by Log-rank (Mantel–Cox test). D Immunohistochemistry analysis of tumors for cleaved Caspase-3 (CC3) and Ki67. Values represent the mean % postively stained cells for each antibody in five different fields of view. Data are mean ± SEM (n = 3), significance determined by Student’s t-test (unpaired). E Effect of AZD0466 and Cisplatin treatment on indicated BCL-2 family protein expression determined by immunohistochemistry (H-scores) on tumors harvested at Day 19 for indicated BCL-2 family members. Sections were scored for staining by each antibody in 5 different fields of view. Data are mean ± SEM (n = 3 tumors per group), significance determined by Student’s t-test (unpaired). F Body weights of mice were measured during and after the treatment period. Data represent mean ± SEM (n = 6–10). G Platelet counts (units per μL blood) determined 48 h post AZD0466 or vehicle dosing on Day 10 in all treatment groups and in Cisplatin plus AZD0466 treated mice 3 weeks (3w) post start of the treatment phase. Data is mean ± SEM (n = 3 mice per group), significance determined by Student’s t-test (unpaired).