Sox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling

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A critical evaluation of high density lipoprotein cholesterol as an index of coronary artery disease risk in Malaysians.

ABSTRACT Fasting serum specimens from (a) 217 male and 46 female patients with coronary artery disease (CAD), aged 35-75 years, who had undergone angioplasty (PTCA) / coronary artery bypass graft (CABG), and (b) 160 apparently healthy controls (106 males, 54 females, aged 30-75 years), were assessed for serum lipid profile. Both sex and ethnicity significantly influenced the levels of serum high density lipoprotein cholesterol (HDLC); in the controls, females had higher HDLC levels than males (46.7 mg/dl vs 38.5 mg/dl, p<0.00l), while the Indian males possessed significantly lower HDLC values than the male Malay or Chinese. HDLC, triglycerides (TG) and the atherogenic index-LDLC/HDLC ratio were significantly different between the CAD patients and the healthy controls, while total cholesterol (TC) and LDLC did not seem to be of diagnostic value. Serum HDLC was lower in the CAD patients compared to the healthy controls in both sexes (p<0.001), either expressed as HDLC per se or as % HDLC. This observation combined with the odds ratio (OR) values of 0.24 and 0.28 for HDLC and % HDLC respectively in males, firmly establishes HDL as a protective factor of CAD in Malaysians. Significance testing for the X 2 values associated with the OR values for the various lipid indices, together with the findings on the receiver-operating characteristices (ROC) curves, i.e. plots of sensitivity vs 1-specificity, indicated that HDLC, % HDLC and TQ were equally efficient as a means of risk assessment to CAD in Malaysians

Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1

We previously demonstrated that the overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, advanced pathologic tumor metastasis (pTNM) stage and poor overall survival rate (Ng et al. Br J Cancer 2006;95:1050-5). In this study, short hairpin RNA (shRNA) interference approach was used to suppress the expression of Six1 in a metastatic HCC cell line MHCC97L. Stable transfectant MHCC97L-shSix1 carrying Six1-specific shRNA plasmid was established to downregulate Six1 expression to about 40% when compared with MHCC97L-Control. In vitro functional assays demonstrated that the growth rate and proliferation ability of MHCC97L-shSix1 cells were markedly decreased. Moreover, significant decrease of cell motility and invasiveness were observed in MHCC97L-shSix1 cells. Data from in vivo xenograft tumorigenesis model demonstrated that the size of tumor in MHCC97L-shSix1 group was dramatically reduced. Experimental and spontaneous metastasis models indicated that targeting Six1 suppression noticeably reduced the pulmonary metastasis in MHCC97L-shSix1 group. To identify Six1-regulated targets, cDNA microarray was employed to compare the expression profiles of MHCC97L-Control and MHCC97L-shSix1 cells. Twenty-eight downregulated and 24 upregulated genes with known functions were identified in MHCC97L-shSix1. The functions of these target genes are involved in diverse biological activities. Our data suggest that Six1 may be involved in regulation of proliferation and invasiveness of HCC; thus targeting suppression of Six1 is a viable option for treating HCC patients. © 2009 UICC.postprin

Gene expression profiling by cDNA array in human hepatoma cell line in response to cisplatin treatment

Gene expression profiling with cDNA array allows simultaneous analysis of the gene expression pattern of a large number of genes and may enhance the investigation of the molecular mechanisms involved in the treatment of hepatocellular carcinoma with cisplatin. We used cDNA array technology to assess the gene expression profiles related to cell cycle regulation and apoptosis in human hepatoma Hep3B cells in response to cisplatin treatment. In Hep3B cells, apoptosis induced by cisplatin was p53-independent, and was associated with up-regulation of cell cycle regulators, pro-apoptotic genes, growth receptors, and genes involved in signal transduction. These included p33ING1, c-Abl, Bax, insulin-like growth factor binding protein 3, Siva, cyclin D1, RhoA, and Raf-1. Down-regulation of cell cycle regulator CDC2 was observed. Semi-quantitative reverse transcription-polymerase chain reaction and/or Western blot analysis performed on seven of these genes confirmed their upregulation of gene expression. Such global analysis of the cytotoxic response to chemotherapeutic drugs may yield insight into the mechanisms of drug action and allow rational design of more effective treatment strategies. © 2002 Published by Elsevier Science Inc.link_to_subscribed_fulltex