The image contains six panels (A to F) showing various graphs related to the effects of different treatments on tumor growth, survival, m R N A expression, vessel area, and breathing patterns in mice. Panel A is a line graph showing tumor volume over treatment days for different treatment groups: vehicle, 1.21 S 9 N, P T 2385, 1.21 S 9 N with alpha-P D-1, and P T 2385 with alpha-P D-1. The horizontal axis represents treatment days, and the vertical axis represents tumor volume in cubic millimeters. Panel B is a Kaplan-Meier survival curve showing the percentage survival over days for the same treatment groups. Panel C is a box plot showing m R N A expression levels of various genes in tumors treated with vehicle, 1.21 S 9 N, or P T 2385. The vertical axis represents m R N A levels. Panel D includes images of tumor sections stained for C D 31 and a bar graph quantifying C D 31-positive vessel area. The horizontal axis lists treatment groups, and the vertical axis represents vessel area in square pixels per field. Panel E shows ventilatory tracings for mice pre- and post-treatment with vehicle, 1.21 S 9 N, or P T 2385. Panel F is a bar graph plotting the apnea index (events per hour) for each treatment group. The horizontal axis lists treatment groups, and the vertical axis represents the apnea index. The graphs collectively show the comparative effects of different treatments on tumor growth, survival, gene expression, vessel area, and breathing patterns. All data is approximate.
Effect of dual HIF-1/2 inhibition compared to selective HIF-2 inhibition. (A) Balb/c mice bearing CT26 tumors were treated by OG administration of vehicle, PT2385 (60 mg/kg QD), 1.21S9N (60 mg/kg QD) or by IP injection of α-PD-1 antibody (200 mg Q3D) in combination with either PT2385 or 1.21S9N, and tumor volumes were determined (mean + SD, n = 5). ‡‡‡‡P < 0.0001 for PT2385 vs vehicle; ****P < 0.0001 for 1.21S9N vs vehicle or PT2385; ####P < 0.0001 for 1.21S9N + α-PD-1 vs PT2385 + α-PD-1 by two-way ANOVA with Tukey's post-test. (B) Kaplan-Meier analysis of survival is shown. (C) Tumors were harvested 4 hours after the last dose for analysis of mRNA expression. Results are presented as mean ± SD (n = 5). *P < 0.05; **P < 0.01 vs vehicle; one-way ANOVA with Bonferroni post-test. (D) Tumor sections were analyzed by immunohistochemistry using anti-CD31 antibody. Results are presented as mean ± SD (n = 3). *P < 0.05; **P < 0.01 vs vehicle; one-way ANOVA with Sidak post-test. Scale bar, 500 µm. (E and F) Breathing was monitored in mice pre- and post-treatment with vehicle, 1.21S9N or PT2385 (30 mg/kg BID OG x 3 doses) by whole body plethysmography and representative ventilatory tracings are shown (E). The apnea index (events per hour) is plotted for each treatment group (mean ± SEM, n = 5 mice per group). ***P < 0.001 vs vehicle by two-way ANOVA with Holm-Sidak post-test (F).