Toward a new understanding of vascular proliferative disease in children.

These studies provide the following evidence: (1) Angiogenesis is a multistep process. (2) The steps necessary to construct a capillary must occur in correct sequence, a motif that seems to be expressed entirely by vascular endothelial cells. (3) Primary tumors and their metastases are angiogenesis dependent, and angiogenesis may be a critical control point in tumor growth. (4) Heparin potentiates angiogenesis. (5) Heparin or its nonanticoagulant fragments, administered with cortisone, inhibit angiogenesis. (6) Heparin is degraded in the gastrointestinal tract and yields low molecular weight fragments, some of which are absorbed into the circulation. (7) There is a group of corticosteroids that inhibit angiogenesis in the presence of a heparin fragment, but have no glucocorticoid or mineralocorticoid activity. The compounds to which this new biologic activity has been assigned have been named "angiotropic" steroids. (8) There is a potential future role for angiogenesis inhibitors as a new class of pharmacologic agents.