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

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

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

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and highly resistant to available chemotherapies. Mammalian target of rapamycin (mTOR) functions to regulate protein translation, angiogenesis and cell cycle progression in many cancers including HCC. In the present study, subcutaneous patient-derived HCC xenografts were used to study the effects of an mTOR inhibitor, RAD001 (everolimus), on tumour growth, apoptosis and angiogenesis. We report that oral administration of RAD001 to mice bearing patient-derived HCC xenografts resulted in a dose-dependent inhibition of tumour growth. RAD001-induced growth suppression was associated with inactivation of downstream targets of mTOR, reduction in VEGF expression and microvessel density, inhibition of cell proliferation, up-regulation of p27(Kip1) and down-regulation of p21(Cip1/Waf1), Cdk-6, Cdk-2, Cdk-4, cdc-25C, cyclin B1 and c-Myc. Our data indicate that the mTOR pathway plays an important role in angiogenesis, cell cycle progression and proliferation of liver cancer cells. Our study provides a strong rationale for clinical investigation of mTOR inhibitor RAD001 in patients with HCC.
J Cell Mol Med 2009 Jul
PMID:RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma. 1846 52

The identification of cancer genes differentially expressed in hepatocellular carcinoma (HCC) plays an important role in understanding the molecular mechanisms of hepatocarcinogenesis. Here, ARHI gene expression was analyzed by real-time RT-PCR and it was significantly downregulated in 33 of the 42 (78.6%, more than two folds) HCC specimens compared with adjacent noncancerous livers (P < 0.01). In addition, ARHI expression was reduced in some HCC samples at protein level confirmed by immunohistochemistry. Furthermore, our data suggested that the overexpression of ARHI can significantly inhibit cell growth and colony formation of Hep3B cells (P < 0.01), whilst silencing endogenous ARHI gene by RNAi could promote cell growth of Huh-7 and Focus. LOH of microsatellite markers D1S2806 and D1S2803 was only found in 2.4% (1 of 42 HCCs) of HCC cases. The expression of ARHI was obviously re-expressed in some HCC cells, Bel-7402, Bel-7405, QGY-7703 and Hep3B, by a demethylation agent, 5-aza-2'-deoxycytidine (DAC). DNA hypermethylation within ARHI promoter was identified in 47.1% of HCC specimens without ARHI expression. Our current observations provide evidences that ARHI downregulated in HCCs could play a role in liver cancer via acting as a tumor suppressor gene, which mainly was triggered by the epigenetic events in HCC specimens.
Mol Carcinog 2009 Feb
PMID:ARHI, as a novel suppressor of cell growth and downregulated in human hepatocellular carcinoma, could contribute to hepatocarcinogenesis. 1861 97

Transforming growth factor-beta (TGF-beta) has been shown to induce apoptotic cell death in normal and transformed hepatocytes. We recently identified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as an important mediator of TGF-beta-induced apoptosis in hepatoma cells. In this study, we have further explored the mechanism by which TGF-beta up-regulates TRAIL expression. The 5'-flanking region of the TRAIL gene was isolated and characterized. Deletion mutants of the 5'-untranslated region of the TRAIL gene revealed a region comprising nucleotides -1950 to -1100 responsible for TRAIL induction following treatment with TGF-beta. Within this region, we have identified an activator protein-1 (AP-1) site indispensable for TGF-beta-mediated induction of TRAIL. Activation of this AP-1 site is mediated by a JunD.FosB heterodimer. Expression of DNSmad4, DNJunD, or DNFosB significantly impairs TGF-beta-mediated activation of the TRAIL promoter. Furthermore, with tRNA interference targeting Smad4, junD, FosB, we could abolish TRAIL expression and, subsequently, TGF-beta-induced TRAIL-mediated apoptosis in hepatoma cells. Our results reveal a new AP-1 site within the TRAIL promoter functionally involved in TGF-beta-induced TRAIL expression and apoptosis in hepatomas and thus provide evidence for the underlying mechanism by which TGF-beta might regulate cell death in liver cancer.
Mol Cancer Res 2008 Jul
PMID:Transforming growth factor-beta-mediated tumor necrosis factor-related apoptosis-inducing ligand expression and apoptosis in hepatoma cells requires functional cooperation between Smad proteins and activator protein-1. 1864 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>