Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC), the predominant histological subtype of primary human liver cancer, is one of the most prevalent cancer types worldwide, accounting for an estimated 500,000 deaths annually. The clinical management of HCC is challenging on many counts. HCC is a phenotypically and genetically heterogeneous polyclonal disease and is resistant to most conventional chemotherapy. Early manifestation of HCC is characteristically silent and slow growing with few symptoms, and HCC is therefore often diagnosed at an advanced stage, when potentially curative surgical or local ablative therapy is not feasible. Therefore, clinically validated biomarkers that could confer pathological and functional changes associated with the formation and progression of HCC are urgently needed to provide important molecular basis for the development of novel treatments. Recently, comprehensive molecular gene profiling of primary liver cancer tissues has been employed to identify specific genes that are linked to hepatocarcinogenesis. Current attempts to translate molecular knowledge to design strategies for the experimental gene therapy of HCC are reviewed.
Curr Opin Mol Ther 2007 Aug
PMID:Current approaches in the transcriptional-guided gene therapy of human hepatocellular carcinoma. 1769 50

Liver cancer is one of the most frequent solid cancers that kills more than 650,000 people around the world each year. Though great improvements have been done in last 10 years on the understanding the molecular mechanisms involved in liver oncogenesis, the prognosis of patients affected by liver cancer is still poor for most of them. Even in those where a relatively early diagnosis is done, the course of the disease is often fatal due to the underlying liver cirrhosis. In this review authors report the most recent findings on the pathogenesis of liver cancer and on therapeutic approaches, included those emerging from the most recent literature.
Mol Aspects Med
PMID:Hepatocellular carcinoma: epidemiology and clinical aspects. 1806 Dec 52

The neurite outgrowth inhibitor Nogo has attracted great interest, but its relevance with hepatocellular carcinoma has not been reported. This paper first found mutations of Nogo-C in HCC patients from Qidong in China: A172G (Thr58Ala), A340G (Arg114Gly), A571G (Ile191Val). In six examined patient cases from Qidong, the mutations occurred in five cases. The mutation Arg114Gly was predicted bioinformatically to affect Nogo-66 dimensional structure of Nogo-C. Our previous works also had indicated that mutant Nogo-C promoted liver cancer cell line apoptosis and resulted in molecular marker of HCC p53 gene transfer from nucleus to cytoplast. Above results revealed a new physiological role and clinical implications of Nogo-C on HCC.
Mol Biol Rep 2009 Feb
PMID:New mutations of Nogo-C in hepatocellular carcinoma. 1808 Jul 85

MiR-122 is one of the non-coding RNAs which showed its effects on the lipo-metablism, virus infection and HCC forming through regulation of liver gene expression. Its eukaryotic expression vector was constructed by using pSuper which was widely applied in the siRNA expression. The precursor of human miR-122 gene was amplified by polymerase chain reaction (PCR) from the human genomic DNA. The positive clones were screened by PCR and restriction enzyme digestion. The new expression vector of miR-122 was named pHsa-m122. PHsa-m122 and its controls were transfected to HepG2 cells. The miR-122 expression activity was evaluated by GFP122i sensor reporter plasmid through fluorescence detection and Western blot. It was shown that the fluorescence intensity of GFP122si and pHsa-m122 co-transfection group was weaker than that of the controls, so the functional activity of expressed miR-122 was detected. When HepG2 cells were co-transfected with HBV1.3 and pHsa-m122 plasmids, the results showed miR-122 may down-regulate the gene expression of HBV. The human liver specific microRNA eukaryotic expression vector of miR-122 was constructed successfully, which may facilitate further study of its function in the development of liver virus infection diseases and HCC.
Cell Mol Immunol 2007 Dec
PMID:Construction and identification of a human liver specific microRNA eukaryotic expression vector. 1816 60

The zinc-fingers and homeoboxes 2 (ZHX2) protein was shown previously to be involved in postnatal repression of alpha-fetoprotein (AFP) in mice. More recently, loss of ZHX2 expression was often found in human hepatcellular carcinoma (HCC), where AFP is frequently reactivated. Using HepG2 and HepG2.2.15, which express high AFP levels, we show that ZHX2 overexpression significantly decreases of AFP secretion in a dose dependent manner. Furthermore, using LO2 and SMMC7721 cells, which express low AFP levels, we use siRNA inhibition to show that AFP is de-repressed when ZHX2 levels are reduced. This represents the first direct evidence that ZHX2 represses AFP. Co-transfections of ZHX2 and AFP-luciferase reporter genes demonstrate ZHX2 repression is governed by the AFP promoter and requires intact HNF1 binding sites. These data support the idea that ZHX2 contributes to AFP repression in the liver after birth and may also be involved in AFP reactivation in liver cancer.
J Cell Mol Med 2008 Dec
PMID:ZHX2 is a repressor of alpha-fetoprotein expression in human hepatoma cell lines. 1819 54

Key challenges facing cancer therapy are the development of tumor-specific drugs and the implementation of potent multimodal treatment regimens. Oncolytic adenoviruses, featuring cancer-selective viral cell lysis and spread, constitute a particularly interesting drug platform towards both goals. First, as complex biological agents, adenoviruses allow for rational drug development by genetic incorporation of targeting mechanisms that exert their function at different stages of the viral replication cycle. Secondly, therapeutic genes implementing diverse cancer cell-killing activities can be inserted into the oncolytic adenovirus genome without loss of replication potential, thus deriving a "one-agent combination therapy". This article reviews an intriguing approach to derive oncolytic adenoviruses, which is to insert cellular genetic regulatory elements into adenovirus genomes for control of virus replication and therapeutic gene expression. This approach has been thoroughly investigated and optimized during the last decade for transcriptional targeting of adenovirus replication and gene expression to a wide panel of tumor types. More recently, further cellular regulatory mechanisms, such as mRNA stability and translation regulation, have been reported as tools for virus control. Consequently, oncolytic adenoviruses with a remarkable specificity profile for prostate cancer, gastrointestinal cancers, liver cancer, breast cancer, lung cancer, melanoma, and other cancers were derived. Such specificity profiles allow for the engineering of new generations of oncolytic adenoviruses with improved potency by enhancing viral cell binding and entry or by expressing therapeutic genes. Clearly, genetic engineering of viruses has great potential for the development of innovative antitumor drugs--towards targeted and multimodal cancer therapy.
J Mol Med (Berl) 2008 Apr
PMID:Cellular genetic tools to control oncolytic adenoviruses for virotherapy of cancer. 1821 11

Hepatocellular carcinoma is highly chemoresistant to currently available chemotherapeutic agents. In this study, 2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone (CHM-1), a synthetic 6,7-substituted 2-phenyl-4-quinolone, was identified as a potent and selective antitumor agent in human hepatocellular carcinoma. CHM-1 induced growth inhibition of HA22T, Hep3B, and HepG2 cells in a concentration-dependent manner but did not obviously impair the viability of normal cells at the IC(50) for liver cancer cells. CHM-1-induced apoptosis was also characterized by immunofluorescence microscopy. CHM-1 interacted with tubulin at the colchicine-binding site, markedly inhibited tubulin polymerization both in vitro and in vivo, and disrupted microtubule organization. CHM-1 caused cell cycle arrest at G(2)-M phase by activating Cdc2/cyclin B1 complex activity. CHM-1-induced cell death, activation of Cdc2 kinase activity, and elevation of MPM2 phosphoepitopes were profoundly attenuated by roscovitine, a specific cyclin-dependent kinase inhibitor. CHM-1 did not modulate the caspase cascade, and the pan-caspase-inhibitor z-VAD-fmk did not abolish CHM-1-induced cell death. However, CHM-1 induced the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus. Small interfering RNA targeting of AIF substantially attenuated CHM-1-induced AIF translocation. Importantly, CHM-1 inhibited tumor growth and prolonged the lifespan in mice inoculated with HA22T cells. In conclusion, we show that CHM-1 exhibits a novel antimitotic antitumor activity against human hepatocellular carcinoma both in vitro and in vivo via a caspase-independent pathway. CHM-1 is a promising chemotherapeutic agent worthy of further development into a clinical trial candidate for treating cancer, especially hepatocellular carcinoma.
Mol Cancer Ther 2008 Feb
PMID:CHM-1, a novel synthetic quinolone with potent and selective antimitotic antitumor activity against human hepatocellular carcinoma in vitro and in vivo. 1828 18

Human plasma is regarded the most complex and well-known clinical specimen that can be easily obtained; alterations in the levels of plasma proteins or their corresponding enzyme activities may reflect either a healthy or a diseased state. Given that there is no defined genomic information as to the intact protein components in plasma, protein profiling could be the first step toward its molecular characterization. Several problems exist in the analysis of plasma proteins, however. For example, the widest dynamic range of protein concentrations, the presence of high-abundance proteins, and post-translational modifications need to be considered before proteomic studies are undertaken. In particular, efficient depletion or pre-fractionation of high-abundance proteins is crucial for the identification of low-abundance proteins that may contain potential biomarkers. After the removal of high-abundance proteins, protein profiling can be initiated using two-dimensional electrophoresis (2DE), which has been widely used for displaying the differential proteome under specific physiological conditions. Here, we describe a typical 2DE procedure for plasma proteome under either a healthy or a diseased state (e.g., liver cancer) in which pre-fractionation and depletion are integral steps in the search for disease biomarkers.
Methods Mol Biol 2008
PMID:Protein profiling of human plasma samples by two-dimensional electrophoresis. 1828 68

Silymarin is a naturally available bioflavonoid and is a strong antioxidant with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated whether dietary supplementation of silymarin has any role in lipid components, lipid-metabolizing enzymes, free fatty acid profile, and expression of cyclooxygenase-2 (COX-2) in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in rats. NDEA-induced rats showed severe hyperlipidemia along with upregulated expression of COX-2 as revealed by western blotting and immunohistochemistry. Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2. Thus we conclude that compounds like silymarin with potent hypolipidemic effect are strong candidates as chemopreventive agents for the treatment of liver cancer.
Mol Cell Biochem 2008 Jun
PMID:Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma. 1837 78

Carbonic anhydrase III (CAIII) is distinguished from the other members of the CA family by low carbon dioxide hydratase activity, resistance to the CA inhibitor acetazolamide, and a predominant expression in the liver of males. In this report the effects of CAIII expression on liver cancer cells invasiveness were explored. Overexpression of CAIII in the HCC cell line SK-Hep1 resulted in increased anchorage-independent growth and invasiveness. And siRNA-mediated silencing of CAIII expression decreased the invasive ability of SK-Hep1 cells. Furthermore, CAIII transfectants showed elevated focal adhesion kinase (FAK) and Src activity. Silencing of FAK expression in CAIII transfectants led to suppression of HCC cell invasion. More importantly, the CAIII transfectants acidified the culture medium at an accelerated speed than the control cells did. Taken together, these data suggest that the CAIII-promoted invasive ability of HCC cells may probably be mediated through, at least in part, the FAK signaling pathway via intracellular and/or extracellular acidification.
Mol Carcinog 2008 Dec
PMID:Carbonic anhydrase III promotes transformation and invasion capability in hepatoma cells through FAK signaling pathway. 1844 44


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