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)

The expression of CD81, a cell receptor for hepatitis C virus, was examined on cancer cells in hepatocellular carcinoma (HCC) C (n=29) to clarify its clinical role. CD81 was expressed on hepatocyte membrane in non-tumor portions in all patients, however, this was not stained on the cancer cell membranes in 6 of 29. Reverse transcriptase-PCR revealed that CD81 gene expression was not detected in the tumorous portions in 3 of 7 samples. The loss of CD81 was prominent in poorly differentiated HCC (5 of 8) and extrahepatic metastasis patients (6 of 8). The loss of CD81 is associated with differentiation and metastasis of HCC.
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PMID:The CD81 expression in liver in hepatocellular carcinoma. 1111 11

Mechanisms determining the chronicity or the pattern of clinical course of hepatitis C virus (HCV) infections have not been clarified. Recently, CD81 was reported to bind the E2 protein of HCV and was suggested to function as a cellular receptor for HCV. Accordingly, the hypothesis was examined that CD81 polymorphism, if it exists, might correlate with certain clinical courses of HCV infection. CD81 cDNA sequences were determined from peripheral blood mononuclear cells (PBMCs). Twenty-four Japanese subjects were enrolled initially as follows: patients with chronic hepatitis C without cirrhosis (n = 3), patients with cirrhosis (n = 3), patients with cirrhosis complicated by hepatocellular carcinoma (HCC) (n = 3), patients with persistent HCV viremia without ALT elevation (n = 3), those with positive anti-HCV antibodies without evidence of HCV viremia (n = 3), and healthy volunteers (n = 9). In all PBMCs samples analyzed, no polymorphism was found in the CD81 cDNA sequence. The sequence was different, however, from the one reported previously at three nucleotide positions: a transversion to thymine instead of cytosine at nt 1130, a deletion at nt 1206, and a guanine insertion at nt 71. Subsequently, CD81 cDNA sequences from PBMCs and HCC tissue were compared among the other 6 patients with chronic hepatitis C bearing HCC. A comparative study of the CD81 sequences from HCC and PBMCs revealed that various nucleotide mutations existed only in the HCC samples in 3 out of 6 patients. Several mutations in the 3' non-coding region of CD81 cDNA were observed exclusively in HCC tissue suggesting its possible role in hepatocarcinogenesis. Because of the absence of polymorphisms, however, CD81 is unlikely to affect the progression of chronic hepatitis C in terms of chronicity, hepatitis activity, or disease stage.
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PMID:CD81 nucleotide mutation in hepatocellular carcinoma and lack of CD81 polymorphism in patients at stages of hepatitis C virus infection. 1113 Aug 83

Several studies have demonstrated some hepatitis C virus (HCV) replication in lymphocyte and hepatocyte cell lines such as in African green monkey Vero cells. The aim of the present study was to select other cell lines able to bind and replicate HCV. Human hepatoma PLC/PRF/5 cells, human lymphoma Namalwa cells, Vero and mosquito AP61 cells were inoculated with HCV-positive plasma, washed six times and examined for the presence of the viral genome at different times post infection, using an RT-PCR method. Binding of HCV to cells was estimated by HCV RNA detection in cells 2 hr after inoculation and in the last wash of these cells. Successive virus passages in cells were carried out. All the cells studied were able to bind HCV but only AP61 and Vero cells provided evidence of replication and production of infectious virus: virus RNA was detected during 28 days post-infection in four successive virus passages. CD81 molecules, a putative HCV receptor, were detected by cytofluorometric analysis. Vero cells express CD81 molecules whereas these molecules were not detected on AP61 cells. It is suggested that other receptors are involved in HCV binding to Vero and AP61 cells.
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PMID:Mosquito cells bind and replicate hepatitis C virus. 1128 62

Although hepatitis C virus E2 protein can bind to human cells by interacting with a putative viral receptor, CD81, the interaction alone is not sufficient to establish permissiveness for hepatitis C virus infection. Using an Epstein-Barr virus-based extrachromosomal replication system, we have screened through a human liver cDNA library and successfully identified a cDNA capable of supporting hepatitis C virus replication in an otherwise nonpermissive cell line. This cDNA encodes a protein exhibiting homology to a group of proteins derived from various evolutionarily distant species, including Oryza sativa submergence-induced protein 2A. The mRNAs encoding this factor are heterogeneous at the 5' ends and are ubiquitously expressed in multiple tissues, albeit in a very small amount. The longest mRNA contains an in-frame and upstream initiation codon and codes for a larger protein. This 5'-extended form of mRNA was detected in hepatocellular carcinoma, but not in normal liver tissue. Immunofluorescence analysis demonstrated that the hepatic factor was distributed evenly in cells, but occasionally formed aggregations in the peri- or intranuclear areas. In summary, we have identified a hepatic factor capable of supporting hepatitis C virus replication in an otherwise nonpermissive cell line. This factor belongs to a previously uncharacterized protein family. The physiological function of this protein awaits further study.
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PMID:Identification of a hepatic factor capable of supporting hepatitis C virus replication in a nonpermissive cell line. 1160 42

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. The study of viral entry and infection has been hampered by the inability to efficiently propagate the virus in cultured cells and the lack of a small-animal model. Recent studies have shown that in insect cells, the HCV structural proteins assemble into HCV-like particles (HCV-LPs) with morphological, biophysical, and antigenic properties similar to those of putative virions isolated from HCV-infected humans. In this study, we used HCV-LPs derived from infectious clone H77C as a tool to examine virus-cell interactions. The binding of partially purified particles to human cell lines was analyzed by fluorescence-activated cell sorting with defined monoclonal antibodies to envelope glycoprotein E2. HCV-LPs demonstrated dose-dependent and saturable binding to defined human lymphoma and hepatoma cell lines but not to mouse cell lines. Binding could be inhibited by monoclonal anti-E2 antibodies, indicating that the HCV-LP-cell interaction was mediated by envelope glycoprotein E2. Binding appeared to be CD81 independent and did not correlate with low-density lipoprotein receptor expression. Heat denaturation of HCV-LPs drastically reduced binding, indicating that the interaction of HCV-LPs with target cells was dependent on the proper conformation of the particles. In conclusion, our data demonstrate that insect cell-derived HCV-LPs bind specifically to defined human cell lines. Since the envelope proteins of HCV-LPs are presumably presented in a virion-like conformation, the binding of HCV-LPs to target cells may allow the study of virus-host cell interactions, including the isolation of HCV receptor candidates and antibody-mediated neutralization of binding.
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PMID:Binding of hepatitis C virus-like particles derived from infectious clone H77C to defined human cell lines. 1177 94

Hepatitis C virus(HCV), discovered in 1989, is the major causative agent of chronic viral hepatitis. Most patients progress to liver cirrhosis and hepatocellular carcinoma. In the therapy of hepatitis C, only interferon has been used effectively as an anti-HCV reagent in Japan, but its effectiveness is limited to about 30% of cases. Using human hepatocyte cell line which could support efficient HCV replication, we previously found that lactoferrin inhibited HCV infection, and demonstrated that this inhibiting activity was due to the interaction of lactoferrin with HCV. Further analysis found that the carboxyl region of lactoferrin, which partially shows amino acid sequence homology to human CD81, specifically bound to the HCV E2 envelope protein, and identified a 33 amino acids as a critical binding domain of lactoferrin. On the other hand, it has been shown that bovine lactoferrin was effective in some patients with chronic hepatitis received an 8-week course of lactoferrin treatment. Further clinical trials showed that lactoferrin is a promising candidate for adjuvant therapy with interferon in patients with chronic hepatitis C.
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PMID:[Recent advances of basic research and clinical application of lactoferrin as an antiviral reagent against chronic hepatitis C]. 1196 95

Hepatitis C virus (HCV) infection is etiologically associated with the development of hepatocellular carcinoma (HCC) worldwide. HCV has been reported to exist and replicate in both HCC and adjacent non-cancerous liver tissue, but limited information was available on HCV viral load and quasispecies composition in HCC relative to adjacent non-cancerous hepatocytes. Previous study has also suggested CD81, a surface hepatocyte protein, as a receptor for HCV. To clarify the above, HCV-RNA and CD81-RNA titers in 20 paired hepatectomized liver and serum were quantitatively measured by chemiluminescent RT-cPCR. Hypervariable region 1 (HVR-1) variations of parallel specimens were analyzed after subcloning in 6 patients. HCV-RNA levels in serum and non-cancerous liver were markedly higher for HCV genotype 1 than genotype non-1. HCV levels were markedly higher in non-cancerous liver than in HCC (P = 0.001) in a genotype-independent manner, with a mean ratio of 56:1 for non-cancerous tissue to HCC. Both non-cancerous and HCC tissues had the same level of CD81-RNA expression, which was not linked to HCV load. HCV-RNA quantity in both HCC and non-cancerous liver correlated with the number of HVR-1 quasispecies in the tissue, and distinct HVR-1 subclones existed.
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PMID:Variation of hepatitis C virus load, hypervariable region 1 quasispecies and CD81 hepatocyte expression in hepatocellular carcinoma and adjacent non-cancerous liver. 1221 Apr 7

The initial binding of Hepatitis C virus (HCV) to the cell membrane is a critical determinant of pathogenesis. Two putative HCV receptors have been identified, CD81 and low-density lipoprotein receptor (LDLr). CD81 interacts in vitro with the HCV E2 envelope glycoprotein, and LDLr interacts with HCV present in human plasma. In order to characterize these potential receptors for HCV, virus from plasma, able to replicate in cell culture, was inoculated on Vero cells or human hepatocarcinoma cells. HCV adsorption was assessed by quantitating cell-associated viral RNA by a real-time RT-PCR method. Anti-LDLr antibody, low and very low density lipoproteins inhibited significantly HCV adsorption, confirming the role of LDLr as HCV receptor. Only one out of the two anti-CD81 antibodies used in this study led to a partial inhibition of HCV binding. This study also highlights a role for glycosaminoglycans (GAGs) in HCV adsorption: treatment of virus with heparin led to 70% inhibition of attachment, as did desulfation of cellular GAGs. Treatment of Vero cells with heparin-lyase significantly inhibited virus attachment but by only 30%. These results demonstrate the complexity of the HCV binding step in which LDLr interacts strongly with HCV, whereas the interaction of HCV with GAGs and particularly with CD81 seem to be more moderate.
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PMID:Cellular glycosaminoglycans and low density lipoprotein receptor are involved in hepatitis C virus adsorption. 1221 Apr 9

We discovered that the hepatitis C virus (HCV) envelope glycoprotein E2 binds to human hepatoma cell lines independently of the previously proposed HCV receptor CD81. Comparative binding studies using recombinant E2 from the most prevalent 1a and 1b genotypes revealed that E2 recognition by hepatoma cells is independent from the viral isolate, while E2-CD81 interaction is isolate specific. Binding of soluble E2 to human hepatoma cells was impaired by deletion of the hypervariable region 1 (HVR1), but the wild-type phenotype was recovered by introducing a compensatory mutation reported previously to rescue infectivity of an HVR1-deleted HCV infectious clone. We have identified the receptor responsible for E2 binding to human hepatic cells as the human scavenger receptor class B type I (SR-BI). E2-SR-BI interaction is very selective since neither mouse SR-BI nor the closely related human scavenger receptor CD36, were able to bind E2. Finally, E2 recognition by SR-BI was competed out in an isolate-specific manner both on the hepatoma cell line and on the human SR-BI-transfected cell line by an anti-HVR1 monoclonal antibody.
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PMID:The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. 1235 18

We cloned the complete complementary DNA of an isolate of the hepatitis C virus, HCV-S1, into a tetracycline-inducible expression vector and stably transfected it into two human hepatoma cell lines, Huh7 and HepG2. Twenty-six Huh7 and two HepG2-positive clones were obtained after preliminary screening. Two Huh7 (SH-7 and -9) and one HepG2 (G-19) clones were chosen for further characterisation. Expression of HCV proteins in these cells accumulated from 6 h to 4 days posttreatment. Full-length viral plus-strand RNA was detected by Northern analyses. Using RT-PCR and ribonuclease protection assay, we also detected the synthesis of minus-strand HCV RNA. Plus- and minus-strand viral RNA was still detected after treatment with actinomycin D. Indirect immunofluorescence staining with anti-E2, NS4B, and NS5A revealed that these proteins were mostly localised to the endoplasmic reticulum (ER). Culture media from tet-induced SH-9 cells was separated on sucrose density gradients and analysed for the presence of HCV RNA. Viral RNA levels peaked at two separate ranges, one with a buoyant density of 1.08 g/ml and another from 1.17 to 1.39 g/ml. Electron microscopy demonstrated the presence of subviral-like particles (approximately 20-25 nm in diameter) in the cytoplasm of SH-9 and G-19 cells, which were positively labelled by anti-HCV core antibodies. Anti-E2 antibodies strongly labelled cytoplasmic vesicular structures and some viral-like particles. Complete viral particles of about 50 nm which reacted with anti-E2 antibodies were observed in the culture media of tet-induced SH-9 cells following negative staining. Supernatant from tet-treated SH-9 cells was found to infect nai;ve Huh7 and stable Huh7-human CD81 cells.
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PMID:Inducible system in human hepatoma cell lines for hepatitis C virus production. 1248 60


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