Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although Pol III promoters synthesize shRNA and elicit RNAi efficiently, however, a major limitation is that they are constitutively expressed in all cell types. To circumvent this problem, in the present study, we described a novel shRNA vector based on Pol II/T7 dual-promoter couple system: the transcription of shRNA under the control of T7 promoter is dependent on the corresponding T7 RNA polymerase driven by Pol II promoter. Our results strongly demonstrated that such a dual-promoter system can efficiently mediate shRNA expression and specifically reduce the exogenous reporter gene expression in mammalian cells. Furthermore, when hepatoma specific AFP promoter was introduced to control T7 RNA polymerase expression, the RNA interference was permitted only in AFP-producing cells. To our knowledge, this is the first evidence that shRNA can be expressed in a cell-specific manner from Pol II/T7 dual-promoter system in mammalian cells.
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PMID:shRNA driven by Pol II/T7 dual-promoter system effectively induce cell-specific RNA interference in mammalian cells. 1760

The signal transducer and activator of transcription 3 (STAT3) is an IL-6-inducible transcription factor that mediates the hepatic acute phase response (APR). Using gamma-fibrinogen (FBG) as a model of the APR, we investigated the requirement of an IL-6-inducible complex of STAT3 with cyclin-dependent kinase 9 (CDK9) on gamma-FBG expression in HepG2 hepatocarcinoma cells. IL-6 induces rapid nuclear translocation of Tyr-phosphorylated STAT3 that forms a nuclear complex with CDK9 in nondenaturing co-immunoprecipitation and confocal colocalization assays. To further understand this interaction, we found that CDK9-STAT3 binding is mediated via both STAT NH2-terminal modulatory and COOH-terminal transactivation domains. Both IL-6-inducible gamma-FBG reporter gene and endogenous mRNA expression are significantly decreased after CDK9 inhibition using the potent CDK inhibitor, flavopiridol (FP), or specific CDK9 siRNA. Moreover, chromatin immunoprecipitation (ChIP) experiments revealed an IL-6-inducible STAT3 and CDK9 binding to the proximal gamma-FBG promoter as well as increased loading of RNA Pol II and phospho-Ser2 CTD Pol II on the TATA box and coding regions. Finally, FP specifically and efficiently inhibits association of phospho-Ser2 CTD RNA Pol II on the gamma-FBG promoter, indicating that CDK9 kinase activity mediates IL-6-inducible CTD phosphorylation. Our data indicate that IL-6 induces a STAT3.CDK9 complex mediated by bivalent STAT3 domains and CDK9 kinase activity is necessary for licensing Pol II to enter a transcriptional elongation mode. Therefore, disruption of IL-6 signaling by CDK9 inhibitors could be a potential therapeutic strategy for inflammatory disease.
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PMID:The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression. 1795 65

Hepatitis C virus (HCV) is a causative agent of chronic liver disease leading to cirrhosis, liver failure and hepatocellular carcinoma. The prevalence of HCV is estimated as 3% of the world population and the virus is a major public health problem all over the world. For over 16 years, since HCV had been discovered, studies of the mechanisms of the viral life cycle and virus-host interactions have been hampered by the lack of a cell culture system allowing the virus to be grown in laboratory conditions. However, in recent years some new model systems to study HCV have been developed. The major breakthrough of the last two years was the cell culture system for maintaining the virus in an adapted hepatocyte-derived cell line. This review describes the techniques and applications of most of the in vitro systems and animal models currently used for working with hepatitis C virus.
Acta Biochim Pol 2007
PMID:Hepatitis C--new developments in the studies of the viral life cycle. 1795 76

Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Entecavir (ETV) is an approved deoxyguanosine nucleoside for the treatment of chronic hepatitis B virus (HBV) infection that exhibits potent activity against viral reverse transcriptase. We assessed the potential for mitochondrial toxicity of ETV in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and levels of mitochondrial proteins COX II and COX IV. Furthermore, we tested the activity of ETV-triphosphate (ETV-TP) against mitochondrial DNA polymerase gamma (Pol gamma) in vitro. ETV concentrations as high as 100 times the maximal clinical exposure (C(max)) did not affect cell proliferation, levels of lactate, mitochondrial DNA, or mitochondrial proteins throughout the 15-day culture. The lack of mitochondrial toxicity was consistent with the finding that ETV-TP was not recognized by mitochondrial DNA Pol gamma and failed to be incorporated into DNA or inhibit the polymerase assay at the highest levels tested, 300 microM. Combinations of ETV with each of the other HBV NRTI antivirals, adefovir, tenofovir, and lamivudine at 10 times their respective C(max) levels also failed to result in cellular or mitochondrial toxicity. In summary, cell culture and enzymatic studies yielded no evidence that would predict mitochondrial toxicity of ETV at exposure levels in excess of those expected to be achieved clinically.
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PMID:Entecavir for treatment of hepatitis B virus displays no in vitro mitochondrial toxicity or DNA polymerase gamma inhibition. 1805 80

The laminin gamma1 chain, a critical component of the extracellular matrix, is encoded by the 125-kb-long Lamc1 locus. We profiled RNA polymerase II (Pol II) and histone modifications along the Lamc1 locus to explore transcription of this gene in its native chromatin environment. Treatment with 12-O-tetradecanoylphorbol-13-acetate increased Lamc1 mRNA in rat mesangial cells (RMC). This increase was matched by an increase in Pol II density along the entire length of the Lamc1 locus. In contrast, in the hepatocarcinoma cell line (HTC-IR) an increase in Pol II density was restricted to the promoter and was not followed by mRNA induction. The pattern of histone H3 methylation was similar for both cell types but an increase in H3 lysine 9 acetylation observed at the 5'-end was weaker in HTC-IR cells than in RMC. All of the histone modifications showed spatial patterns where levels differed greatly between the 5'- and 3'-ends of Lamc1. Conversely, at the short, highly induced egr-1 gene the differences in chromatin marks between the 5'- and 3'-ends were much smaller. The results of this study suggest that 1) Lamc1 transcription can be controlled after transcription initiation, to our knowledge, the first time this has been shown in an extracellular matrix gene, and 2) the length of a gene is a factor that can affect the chromatin environment for Pol II elongation.
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PMID:Transcription of laminin gamma1 chain gene in rat mesangial cells: constitutive and inducible RNA polymerase II recruitment and chromatin states. 1818 42

Some individuals have "occult" infection with hepatitis B virus (HBV), defined as presence of HBV genome in the serum or liver tissue without HBV surface antigen (HBsAg) in the serum. The aim of this study was to investigate whether serum antibodies against HBV core antigen in isolation ("anti-HBc alone") are a useful marker of "occult" HBV in patients with or without hepatitis C virus (HCV) infection. "Anti-HBc alone" was detected in the sera of 119/6,544 (1.8%) asymptomatic outpatients referred to the diagnostic laboratory for routine testing for viral hepatitis, 62/607 (10.2%) drug users, and 42/195 (21.5%) patients with hepatocellular carcinoma. Using three in-house nested-PCR amplification assays to detect HBV preS-S (S), precore-core (C), and Pol viral regions, respectively, "occult" HBV sequences were found in 9 of the 223 sera (4.0%) with "anti-HBc alone." The highest prevalence of "occult" HBV sequences (5.9%) was detected in "anti-HBV alone" sera of individuals referred to the diagnostic laboratory without HCV antibodies. Direct sequencing of all PCR products confirmed the specificity of the PCR reactions and revealed the predominance of HBV genotype D. The data presented in this study suggest that detection of "anti-HBc alone" could reflect unrecognized "occult" HBV infection and that physicians should consider investigating such patients with HBV molecular tests.
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PMID:Can the serological status of anti-HBc alone be considered a sentinel marker for detection of occult HBV infection? 1829 7

Hepatocellular carcinoma and glioblastoma are both very aggressive forms of human neoplasms. The most effective treatment includes the combination of surgery, chemotherapy and radiation. Sodium butyrate (NaB) demonstrates a high efficiency and low toxicity. It inhibits proliferation and cell cycle of the cancer cells. The aim of this study was to investigate the effect of sodium butyrate on HepG2 and C6 cell line viability. Hepatocellular cancer (HepG2) and glioblastoma cell line (C6) were cultured in DMEM/Ham's F12 medium with 10% FBS and antibiotics. Different NaB concentrations (0-10 mM) were tested. The control consisted of cells without tested substance. The incubation times were 24 and 48 h. Cell viability was studied using Trypan Blue exclusion test. Inhibitory influence of sodium butyrate on cell viability in both examined cell lines was confirmed. Strong correlation between NaB concentration and cell viability after 24 h was noticed (correlation coefficient was 0.94 and 0.98 for C6 and HepG2, respectively). IC50 values after 24 h were 8.44 mM and 6.17 mM for C6 and HepG2, respectively. The strongest effect was observed after 48 h of incubation with NaB. IC50 values were 3.44 mM and 1.47 mM for C6 and HepG2 (correlation coefficients after 48 h were 0.91 and 0.631 for C6 and HepG2, respectively). C6 line was more resistant to NaB than HepG2. Both cell lines were sensitive to NaB treatment, which gives the promise that NaB can be used against broader spectrum of neoplasms in the future.
Acta Pol Pharm
PMID:Influence of sodium butyrate on hepatocellular carcinoma (hepG2) and glioblastoma (C6) cell lines in vitro. 1832 52

Numerous studies have focused on the growth regulation effect of vanadium compounds. In our preliminary investigation we have observed growth inhibition of rat hepatoma cell line H35-19 by inorganic vanadium salts. The aim of the present study was to determine the effect of vanadyl sulphate (VOSO4) on autocrine growth and survival of tumorogenic lung (A549) and prostate (DU145) human cell lines. Additionally, non-carcinogenic human cell lines BEAS-2B (as a lung control) and PNT-2 (as a prostate control) were investigated. MTT, modified crystal violet staining, differential staining (HOECHST33258 and PI) methods and assay for anchorage-independent colony formation were used to investigate the effect of vanadyl sulphate. The results showed that VOSO4 significantly inhibited autocrine growth, decreased carcinoma cells viability and increased the ratio of apoptotic and necrotic cells compared to the controls. However, it should be noted that the examined "drug" significantly decreased viability of non-carcinogenic human cell lines (BEAS-2B, PNT-2).
Pol J Pathol 2008
PMID:The effect of vanadyl sulphate (VOSO4) on autocrine growth of human epithelial cancer cell lines. 1865 64

Glypicans are core proteins of heparan sulfate proteoglycans that have numerous functions. Glypican-3 (GPC3) expression has been detected to be altered in several tumors, including hepatocellular carcinoma, breast carcinoma, and embryonic malignancies. To date, no information on GPC3 status in renal cell carcinoma is available. The material for the study consisted of 625 cases of renal tumors diagnosed at our institution. Tissue microarrays were constructed using all acceptable quality tissue blocks. Immunohistochemistry for GPC3 was performed with 1G12 antibody (BioMosaics). We found strong positive staining in 15 cases, moderate in 4 and weak in 68. The reactivity was particularly evident in chromophobe renal cell carcinomas (32/40). Our findings are of note in cases when GPC3 may be used in differential diagnosis of tumors of uncertain primary location.
Pol J Pathol 2008
PMID:Glypican-3 is expressed in chromophobe renal cell carcinomas. 1865 66

Non-alcoholic steatohepatitis (NASH) is a part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which can progress to hepatic cirrhosis and end-stage liver disease or hepatocellular carcinoma (HCC). Its pathogenesis is associated with insulin resistance (IR) and the metabolic syndrome. Hepatic steatosis has also been considered an early marker of IR. It is now accepted that NASH is a multistep process with a prominent role for IR, where oxidative stress and cytokines retain a central role. Markers for predicting NAFLD with advanced fibrosis are needed. Once considered irreversible, liver fibrosis is now recognized a dynamic process with significant prospects for remission. The liver biopsy is still a gold standard in assessment of liver fibro-inflammatory activity in the injured liver, but has its own limitations: invasiveness, small tissue sample and inter- and intra-observer error. The lack of non-invasive tests limits the ability of monitoring progression of hepatic fibrosis and response to treatment. Therefore, clinical trials focused on finding of new non-invasive diagnostic tools giving possibilities of frequent, more accurate and reproducible assessment of hepatic fibrosis are constantly conducted.
Pol Merkur Lekarski 2008 Aug
PMID:[Non invasive markers of non-alcoholic steatohepatitis]. 1894 40


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