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Title: Delayed hepatocarcinogenesis through antiangiogenic intervention in the nuclear factor-kappa B activation pathway in rats. Author: Dong ZZ, Yao DF, Wu W, Yao M, Yu HB, Shen JJ, Qiu LW, Yao NH, Sai WL, Yang JL. Journal: Hepatobiliary Pancreat Dis Int; 2010 Apr; 9(2):169-74. PubMed ID: 20382589. Abstract: BACKGROUND: The active form of nuclear factor-kappa B (NF-kappaB) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappaB and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappaB activation. METHODS: Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappaB activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappaB mRNA was amplified by RT-nested PCR. The alterations of NF-kappaB and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting. RESULTS: Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappaB, NF-kappaB mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappaB (X2=9.93, P<0.001) and VEGF (X2=8.024, P<0.001) lower than that in the 2-FAA group. CONCLUSION: NF-kappaB is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappaB and VEGF, and delays the occurrence of HCC.[Abstract] [Full Text] [Related] [New Search]