Fig. 8
PCI-24781 and TMZ in combination decrease tumor burden in vivo. A Animals treated with both drugs had more significant decreases in tumor burden. U-118MG luciferase transfected cells (1X10^5 cells in 3 μl of PBS) were intracranially injected into 4 to 6 week-old mice. After 10 days, BLI measured tumor growth, and animals were randomized into 6 groups and treated with vehicle control, TMZ (25 mg/kg BW), PCI-24781 (12.5 mg/kg BW, BID), vorinostat (100 mg/kg/BW), PCI-24781+ TMZ or vorinostat + TMZ for 5 days a week. Qualitative BLI imaging is shown in (A), and quantitative measurements (total photon flux, photons/second) of the BLI from the tumor is shown in (B). ‘*‘p < 0.05 .“*” significantly different compared to vehicle control. BLI- bioluminescence imaging. Data presented as mean +/− SEM and analyzed using the natural log of photon levels on Day 32 compared to control and treatment groups using one-way ANOVA. Pairwise comparisons were adjusted for multiple comparisons with Dunnett’s method. C PCI-24781 improved survival over vorinostat, and PCI + TMZ significantly increased overall survival. Overall survival was estimated using the Kaplan-Meier method, and groups were compared using the log-rank test. Mice alive at the end of the study were treated as censored. ‘*‘p < 0.0001. “*” significantly different compared to vehicle control. D & E PCI-24781 decreases tumor burden in the GBM mouse model. MRI was done on a 7 Tesla scanner. (Bruker PharmaScan, Billerica, MA) operated by ParaVision 7 with a quadrature RF coil for signal transmission and reception. MRI on GBM mouse (PEPG - PTENflox/+; EGFRvIII+; p16Flox/− & GFAP Cre +). D; (i)-(vi) shows the pre-treatment axial T1post images of a mouse brain in rostral-caudal direction. E (i)-(vi) Axial T1post images acquired after 4 weeks of 5-days weekly PCI-24781 (12.5 mg/kg BW, BID, PO)