Angiogenesis is the growth of new blood vessels from existing ones. It is an important aspect of new tissue development, tissue growth, and tissue repair. It is also a component of many diseases, including cancer. Angiogenesis is necessary for the growth of tumors and their metastasis. The induction of Angiogenesis is mediated by angiogenic growth factors produced by either tumor or host cells.Chemopreventive, agents which inhibit or retard Angiogenesis are urgently needed. The purpose of this project is to screen selected chemopreventive agents for antiangiogenic activity in vitro. A main concern in the development of antiangiogenic therapies is the availability of sensitive and specific disease models. The present project focuses on the utilization of in vitro assay systems that can be used to screen antiangiogenic drugs. These in vitro assay systems include but are not limited to 1) chorioallantoic membrane in shelled or shelled - less chick embryos, 2) explants of rat aorta embedded in collagen gel grown in serum - free media, and 3) The contractor is using the most sensitive system of their choice, wherein the effects of the antiangiogenic factors are quantitated. For each agent, the system of choice shall be first calibrated in the presence of a well defined angiogenic factor as a positive control and in the absence of such factor as a negative control. The system of choice includes the presence of human tumor cells as a positive control. The absence of human tumor cells constitutes a negative control. The human tumor being used represent highly malignant cells or it consists of dysplastic cells. Human tumor cells that arose from early to moderate dysplastic lesions are preferred, provided that such cells have been shown to elicit angiogenesis in vitro.
