Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

Article Title: Novel Targeting of Transcription and Metabolism in Glioblastoma

doi: 10.1158/1078-0432.CCR-17-2032

Figure Lengend Snippet: Treatment of combined TG02 and TMZ has an antiglioma effect in GL261 mouse GBM model. A, Combined TG02/TMZ treatment has a synergistic antiglioma effect in GL261 cells. Cells were treated with various concentrations of TG02, TMZ, and TG02/TMZ for 72 hours, and cell viability was determined by cell counting (a). The synergistic effect of TG02/TMZ was evaluated by CI index in b. CI values were calculated by COMPUSYN software and are shown in c. B, TG02 downregulates CDK9 and phospho-CDK9 in vivo. The protein expressions of CDK9, phospho-CDK9, and GAPDH were determined from GL261 tumor tissues with or without TG02 treatment (a). The bar graph represents the normalized relative intensity quantification of each Western blot band. The intensity of each band was relative to the corresponding band of vehicle 1 and then normalized to the relative GAPDH (b). Imaging tumor size of orthotopic glioblastoma xenografts derived from luciferase-expressing GL261 was tracked by bioluminescence at 12 and 19 days (c). Hematoxylin and eosin stain of mice brain tissues in vehicle and TG02 treatment (d). The scale bar represents 1 mm (top) and 100 µm (bottom). C, Combination treatment of TG02/TMZ prolongs mice survival in the allograft model. a,A schematic illustration of drug administration. b, Kaplan–Meier survival plots of C57BL/6 albino mice (n = 5–7 per cohort) with GL261 allografts showing the median overall survivals of 24, 24.5, 27.5, and 32 days in cohorts which received vehicle, TG02, TMZ, or combination treatment, respectively. The result was analyzed using the Log-rank test for trends in GraphPad Prism software (χ2 = 9.063; df 1; **, P 0.0026). c, The intensity of BLI of tumors in cohorts received vehicle, TG02, TMZ, or combination treatment. The values were calculated and normalized to the initial intensity at day 5. d, Representative BLI of 2 mice from each cohort that were recorded at days 5, 12, and 20.

Article Snippet: Synergistic effect was analyzed by CompuSyn software (Combo-Syn Inc.; ref. 20 ).

Techniques: Cell Counting, Software, In Vivo, Western Blot, Imaging, Derivative Assay, Luciferase, Expressing, H&E Stain

Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

Article Title: Novel Targeting of Transcription and Metabolism in Glioblastoma

doi: 10.1158/1078-0432.CCR-17-2032

Figure Lengend Snippet: TG02 induces cell death and synergizes with TMZ in GBM. A and B, TG02 inhibits cell growth in both MGMT high-expressing (A, plots a–d) and MGMT low-expressing cells (B, plots a–d). Cell viability was determined after treatment with vehicle, TG02, TMZ, or TG02/TMZ for 72 hours. C and D, Combined TG02/TMZ treatment has a synergistic antiglioma effect in GSC923 (C) and GSC827 cells (D). Dose-response curves (plot a) were plotted from the cell viability following 72 hours of treatment. The synergistic effects of TG02/TMZ in the cells were determined by CI in b. CI values were calculated by COMPUSYN software and are shown in c. CI < 1 is a synergistic, CI = 1 is an additive, and CI > 1 is an antagonistic effect of the two compounds combined (20). **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

Article Snippet: Synergistic effect was analyzed by CompuSyn software (Combo-Syn Inc.; ref. 20 ).

Techniques: Expressing, Software