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. 2015 Mar 12;107(5):djv040. doi: 10.1093/jnci/djv040

Figure 2.

Figure 2.

Effects of aerobic exercise on angiogenesis and vascular maturity in primary 4T1 breast tumors. Cellular nuclei were stained with Hoechst 33342 (blue). 5x objective, magnification 100%. A-C) Immunostaining for blood vessels shows that microvessel density (CD31, green) was statistically significantly higher in the tumors from exercised mice compared with sedentary controls. Scatter points = individual mice; gray lines = mean; black lines = 95% confidence intervals (CIs), P = .004, two-sided t test. D-E) Representative two-color composite images of vessel pericyte coverage determined by colocalization of CD31 and desmin (red) staining. Scale bar equals 40 µm. F) The percentage of tumor area containing pericyte-covered blood vessels (CD31-desmin colocalized pixels/total tumor area pixels x 100%) is significantly higher in the exercise group. Scatter points = individual mice; gray lines = mean; black lines = 95% CI, P = .006, two-sided t test. G) The percentage of vessel area covered by pericytes (CD31-desmin colocalized pixels/CD31+ pixels x 100%) was also significantly higher in tumors from running mice. Scatter points = individual mice; gray lines = mean; black lines = 95% CIs, P = .024, two-sided t test. H-J) Mice were injected with the hypoxia marker EF5 (red), which was detected by immunohistochemistry. Representative whole tumor images are shown. Quantification of hypoxic tumor percentage shows that exercise significantly reduces tumor hypoxia. Scatter points = individual mice; gray lines = mean; black lines = 95% CIs, P = .012, two-sided t test. K) Tumor response to voluntary aerobic exercise combined with cyclophosphamide chemotherapy. BALB/c mice bearing 4T1 mammary tumors were randomly assigned to voluntary wheel running or sedentary controls (n = 17 per group) starting on Day 0. Mice treated with chemotherapy received the maximal tolerated dose (100mg/kg) cyclophosphamide IP on days 7, 9, and 11. Data are presented as means; error bars are 95% CIs. Tumor growth rate is significantly slowed by exercise and cyclophosphamide monotherapies compared with sedentary controls (P < .001, ANCOVA). The combination of exercise and cyclophosphamide resulted in a statistically significant reduction in tumor growth rate relative to the groups that received no treatment, exercise alone, or cyclophosphamide alone (P < .01, ANCOVA). ANCOVA = Analysis of Covariance.