FIGURE 2

(a) Tumor growth (A) and microvascular permeability (P). Implantation of M-07e cells led to exponential increase in tumor area until day 37. Thereafter tumor area per time displayed a slower increase. Initial tumor growth phase was associated with a significant peak of microvascular permeability with a subsequent decrease from day 13 to day 25 reaching a plateau phase from day 25 to the end of the observation period (^* P<0.05). (b) Vessel density (VD) and vessel diameter (D). Functional vessel density and diameter were measured after injection of fluorescein isothiocyanate-labeled Dextran. Vessel density increased significantly from day 6 to day 13 with a subsequent reduction from day 17 to day 25 and day 43, respectively. In contrast, vessel diameter showed an inverse slope with initially decreased vessel diameter from day 6 to day 13. Further tumor growth was associated with increased vessel diameters (^* P<0.05 for VD and ^# P<0.05 for D). All values are presented as means.e.m. (c) Vessel distribution. Analysis of vessel distribution, defined as the counts of vessels with defined diameters per observation area, revealed an increase in vessels with small diameter concordant with increased functional capillary density from day 6 to day 13 and day 17, respectively. The initial angiogenic wave was followed by a subsequent reduction in vessels with small diameters from day 17 to end of the observation period.