The angiogenesis process is an important target for cancer chemoprevention. This study has two primary objectives: A) To characterize 5 of the standard chemoprevention models which are employed by NCI measuring angiogenesis related endpoints; B) Employing one of the models which have been characterized for angiogenesis in part A and examine two chemicals to be supplied by the NCI for their effects on angiogenesis as well as their effects on more fully characterized histologic endpoints. C) To characterize a further eight experiments with antiangiogenic compounds. The objective of a preliminary study is to characterize five tumor models routinely employed by the Chemoprevention Branch with respect to angiogensesis. Candidate models include rat mammary tumor model, mouse colon adenoma model, mouse bladder tumor model, mouse U.V. induced skin model and mouse B(a)P induced lung tumor model . The study involves examining five to ten paraffin embedded blocks of each of the five tumor types listed above which were obtained at the end of a previously completed chemoprevention experiment. The lesions to be sent will have been characterized histopathologically. In addition concurrent """"""""normal"""""""" blocks of either uninvolved tissue and or tissue from untreated animals are included as a control. Employing the morphologic, histologic or immunohistologic techniques, the study is determining the average microvessel density in tumor and in normal tissue where applicable. The tissus are bing stained for at least three other angiogenic factors (e.g., FGF`, FGF and VEGF). Five animals per group are being studied for a period of six weeks. The study also measures altered vessel density, apoptosis/necrosis in vessels or altered expression of specific factors or receptors related to angiogenesis etc. To further characterize the effects of antiangiogenic agents groups of animals (10 per group) are being treated with the antiangiogenic agents for only a limited time period (<3 weeks) prior to sacrifice .
