Figure 4.

Impact of anti-angiogenic therapy on proliferation. A: Representative pictures of brain sections (10-μm thick) stained with anti-Ki67 after stereotactic injection of tumor cells (A, upper row, STX) and hematogenous metastases model (A, lower row, ICA) are shown. The experimental groups were indicated. Scale bar represents 50 μm. B, C: The number of Ki67-positive nuclei in brain metastases was determined with a 200-fold objective. The bars represent mean ±SD for the experimental groups as indicated after 16 d survival time (white) or for long surviving prefinal animals (grey). B: In the STX model, antiangiogenic treatment transiently reduces proliferation at 16 day survival time compared to untreated animals but not at the prefinal survival time of 24 days. C: Ki67-positive nuclei were also detected in brain tissue in the hematogenous metastases model. In this model, we found comparable numbers of proliferating cells in all experimental groups, even after therapy or long term survival (○ and ○○ difference versus wt group with p<0.05 and p<0.01, ● and ●● difference between treatment groups as indicated with p<0.05 and p<0.01, respectively., same abbreviations as in Figure 1).