Anti-CYP2E1 monoclonal antibody, clone 2-09-2

Background Accumulated studies reported abnormal gene expression profiles of hepatocellular carcinoma (HCC) by cDNA microarray. We tried to merge cDNA microarray data from different studies to search for stably changed genes, and to find out better diagnostic and prognostic markers for HCC. Methods A systematic review was performed by searching publications indexed in Pubmed from March 1, 2001 to July 1, 2016. Studies that reporting cDNA microarray profiles in HCC, containing both tumor and nontumor data and published in English-language were retrieved. The differentially expressed genes from eligible studies were summarized and ranked according to the frequency. High frequency genes were subjected to survival analyses. The expression and prognostic value of alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT) was further evaluated in HCC datasets in Oncomine and an independent HCC tissue array cohort. The role of AGXT in HCC progression was evaluated by proliferation and migration assays in a human HCC cell line. Results A total of 43 eligible studies that containing 1917 HCC patients were included, a list of 2022 non redundant abnormally expressed genes in HCC were extracted. The frequencies of reported genes were ranked. We finally obtained a list of only five genes (AGXT; ALDOB; CYP2E1; IGFBP3; TOP2A) that were differentially expressed in tumor and nontumor tissues across studies and were significantly correlated to HCC prognosis. Only AGXT had not been reported in HCC. Reduced expression of AGXT reflected poor differentiation of HCC and predicts poor survival. Knocking down of AGXT enhanced cell proliferation and migration of HCC cell line. Conclusions The present study supported the feasibility and necessity of systematic review on discovering new and reliable biomarkers for HCC. We also identified a list of high frequency prognostic genes and emphasized a critical role of AGXT deletion during HCC progression.

Purpose: In order to investigate mechanisms underlying the hepatoprotective action of S,S-palladaheterocycle, inhibition of cytochromes P450 has been modeled by molecular docking of four palladaheterocycle stereoisomers to the active sites of an enzymatic oxidase system. To obtain a deeper insight into biochemical aspects providing a basis for the therapeutic effects of five-membered palladacycles (as mixture of stereoisomers), a number of preclinical trials has been conducted Methods: 2D and 3D structures of palladaheterocycle stereoisomers were obtained via converting into SDF files by means of software MarvinSketch. Binding of palladaheterocycle at the active sites of cytochromes P450 2E1 and P450 2C9 has been studied by molecular docking using LeadIT 2.3.2. Hepatoprotective activity of palladaheterocycle at 2.5, 25 and 250 mg/kg doses has been studied based on a model of acute intoxication by CCl4 using in vivo methods. Results: By molecular docking it was identify amino acid fragments responsible for binding with palladacyclic isomers. The tested compound is comparable, in terms of its activity to the hepatoprotective drug SAM according to the in vivo and in vitro experiments such as animal survival data, the efficiency of correction of the cytolytic syndrome, the liver excretory function, carbohydrate, protein and lipid metabolism, and the correction efficiency of the liver antitoxic function (the latter has been determined based on the results of a hexobarbital control experiment). Conclusion:Taking into account results obtained in vivo, in vitro and in silico, it can be concluded that the five-membered S,S-palladaheterocycle effectively protect the liver against acute damage caused by CCl4, via activation of catalase and glucuronyltransferase, as well as via inhibition of the oxidative stress enzymes.