Fig. 4.

Combination angiostatic therapy obliterates tumor vasculature, decreases tumor size, and increases survival. (A) Vessels are absent in tumors of animals treated for 3 days with triple combination therapy (Lower). Tumor vasculature is normal in control PBS treated tumors (Upper). (B) PBS treated tumors are highly proliferative (Upper) as indicated by ki-67 staining, whereas no proliferation is seen in the avascular triple combination-treated tumors (Lower). (C) Massive infiltrates of mononuclear cells are observed in avascular tumor regions after treatment with triple combination (Lower). In PBS controls (Upper) small areas of mononuclear cell infiltration are observed within large areas of normal tumor growth. (D) After 6 days of triple combination treatment, empty cavities (star), areas of mononuclear infiltrate (arrowhead), and smaller areas of reduced vasculature (diamond) are all observed within the tumor implantation areas (T). Normal brain vasculature in adjacent regions is not affected (N). (E) Rats with PBS-treated tumors have extensive, highly vascular tumors. (F) Triple combination significantly increases survival. Treatments were initiated 6 days after tumor implantation by using constant, local, convection-enhanced delivery to the central tumor. (Scale bars: 0.5 mm.)