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10.1016/j.ajpath.2014.03.006

http://scihub22266oqcxt.onion/10.1016/j.ajpath.2014.03.006
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C4076468!4076468!24952430
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suck abstract from ncbi


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pmid24952430      Am+J+Pathol 2014 ; 184 (7): 2099-110
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  • Hypercholesterolemia Induces Angiogenesis and Accelerates Growth of Breast Tumors in Vivo #MMPMID24952430
  • Pelton K; Coticchia CM; Curatolo AS; Schaffner CP; Zurakowski D; Solomon KR; Moses MA
  • Am J Pathol 2014[Jul]; 184 (7): 2099-110 PMID24952430show ga
  • Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo.
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