DELAYED VASCULAR CHANGES AFTER ANTIANGIOGENIC THERAPY WITH ANTIVASCULAR ENDOTHELIAL GROWTH-FACTOR ANTIBODIES IN HUMAN GLIOMA XENOGRAFTS IN NUDE-MICE

OBJECTIVE: The purpose of this study was to examine the delayed effect s of antivascular endothelial growth factor treatment on tumor growth and vascularity in a subcutaneous mouse tumor model of human glioblast oma. METHODS: Antivascular endothelial growth factor antibody treatmen t was administered for a period of 6 weeks, to suppress tumor growth. To detect late vascular effects, tumor vascular parameters for treated tumors and control tumors were analyzed 4 weeks thereafter. By that t ime, tumors had grown to adequate sizes (diameter, 8-10 mm) for compar ison with untreated control tumors. Vascular parameters were quantifie d by using an image-analysis system. RESULTS: Vascular density was sig nificantly lower in antivascular endothelial growth factor antibody-tr eated tumors, compared with control tumors of similar size. The vascul ar architecture of treated tumors was also distinctly different, compa red with control tumors, showing larger but sparser vessel structures. CONCLUSION: These findings suggest that antiangiogenic therapy may ha ve a prolonged effect on the vascular architecture of certain tumors, resulting in enduring changes in the tumor vessels. Because tumor vasc ulature plays an important role in the sensitivity to various treatmen t modalities, these changes are likely to influence the responses of t hese tumors to further therapy.