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Publication : Ezetimibe is an inhibitor of tumor angiogenesis.

First Author  Solomon KR Year  2009
Journal  Am J Pathol Volume  174
Issue  3 Pages  1017-26
PubMed ID  19179610 Mgi Jnum  J:146660
Mgi Id  MGI:3838098 Doi  10.2353/ajpath.2009.080551
Citation  Solomon KR, et al. (2009) Ezetimibe is an inhibitor of tumor angiogenesis. Am J Pathol 174(3):1017-26
abstractText  Epidemiological and preclinical observations have suggested a role for one or more products of the mevalonate/cholesterol biosynthesis pathway in the progression of prostate cancer. In this study, we used ezetimibe (Zetia), a specific, FDA-approved, cholesterol uptake-blocking drug, in combination with either a hyper- or hypocholesterolemic diet, to show that elevated circulating cholesterol levels promote, whereas a reduction in circulating cholesterol levels retard, the growth of human prostate cancer xenograft tumors in mice. Circulating cholesterol levels also modified tumor angiogenesis; higher cholesterol levels increased microvessel density and other indicators of vascularity. Consistent with these data, the reduction of cholesterol levels also increased the levels of the angiogenesis inhibitor thrombospondin-1 in the xenografts. Our results thus suggest that hypercholesterolemia directly accelerates the growth of prostate carcinomas, and that the pharmacological reduction of serum cholesterol levels may retard prostate cancer growth by inhibiting tumor angiogenesis.
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