Figure 1.

Effect of ZD4190 on tumour outgrowth in a model of residual cancer in the muscle, recapitulating the clinical scenario where malignant cells remain in the muscle after surgery. (A) Morphology of a representative tumour tract in the rectus muscle 7 and 16 days after implantation of PDVC57B cells; magnification: × 240 (left) and × 280 (right). Identification of proliferating endothelial cells by double staining for CD31 (red arrow) and BrdU (black arrow) at the tumour periphery at day 8 and core at day 12 (magnification, × 1000). (B) Gavage with ZD4190 prevented the outgrowth when up to 5 × 10⁴ PDVC57B cells were implanted to create each tumour tract. Two representative examples of the fibrotic foci found at day 22 are shown (far left, × 100) together with a fibrotic focus with viable malignant cells (centre left, × 100). In contrast, control rodents developed large tumours (centre right, × 100), as did those receiving vehicle alone although some lesions that developed in this group were associated with peripheral areas of fibrosis (far right, × 100). (C) When higher numbers of malignant cells were implanted to create each tract (>1 × 10⁵), large tumours developed in the control and vehicle-treated groups by day 22 ( × 80). The tumours present in the ZD4190-treated rodents typically showed a more infiltrative pattern of growth with cords of cells, areas of necrosis and reduced microvascularity, as determined by CD31 staining, when compared with those that developed in the vehicle-treated group (far right, × 240).