PPARγ ligand therapy reduces vessel density and endothelial cell proliferation. (a, blue inset) Representative control and treated glioblastoma tumors on treatment day 40 are shown. Scale bar, 1 cm. (a–d, insets) Hematoxylin-and-eosin staining of tumors from control and rosiglitazone-treated mice show no signs of cytologic differentiation. In both liposarcoma and rhabdomyosarcoma, increased necrosis (n) was observed in treated tumors. Scale bar, 200 μm. (a–d) In each panel the x axis represents vessel density defined as the percentage of vessel area (CD31)/tumor area in each tumor field. The y axis indicates the percent of analyzed fields with the given vessel density. Bars further to the right represent fields with higher microvessel density. Upon rosiglitazone treatment, a significant decrease in vessel density was observed for all tumors as indicated by left-shifting of all histograms (P < 0.001). For example, in rosiglitazone-treated glioblastoma, 4% vessel density is present in 28% of all counted fields. Total fields scored per tumor (Ctr:Rosi): U87, 124:178; LLC, 163:131; LS, 186:178; RMS, 314:229. (e) Endothelial cell (EC) proliferation in rosiglitazone-treated and control U87 and LLC tumors as determined by immunofluorescent double staining (MECA-32 and PCNA). U87, P < 0.001; LLC, P < 0.05. Total fields scored per tumor (Ctr:Rosi): LLC, 36:26; U87, 34:33.