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VASOHIBIN: POTENTIAL TARGETING INHIBITOR OF ANGIOGENESIS IN COLORECTAL CANCER

Abstract

Angiogenesis is a term that describes the blood vessels formation, a physiological process involved in growth and healing, which is also linked to the development of diseases, including cancer in its progression and metastasis development. Differently, tumor angiogenesis is characterized by the neovessels formation from of the endothelial proliferation of preexisting vessels stimulation and, thus is called neoangiogenesis. Among the most recently described angiogenesis regulators are vasohibins (VASHs). The vasohibin family is composed of two members, vasohibin-1 (VASH-1), which is expressed in vessels and in colorectal cancer and is prognostic-related, and vasohibin-2 (VASH-2), its homologue, which is expressed in the tumor tissue and appears as stimulatory action on angiogenesis. Currently, the antiangiogenic therapy is an option, especially in cancer advanced stages, but their side effects are still vast, due to their action on targets in tumor endothelium and in normal endothelium. In addition, the drug resistance development has been a problem in antiangiogenic drugs. The specific target identification, such as VASH, arouses interest in antiangiogenic therapy, however its role must be better understood in colorectal cancer. This project is divided into two distinct phases. In Phase I, it is intended to understand the VASH (1 and 2) behavior in colorectal cancer (CCR) carcinogenesis from biopsies of normal tissue samples, adenoma and adenocarcinoma, while in phase II a new antiangiogenic agent is searched in animal model of human colon cancer. For this, morphological methods, immunohistochemical, xenotransplantation techniques, cell culture, recombineants will be used. (AU)