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)

Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively.
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PMID:Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease. 127 66

Infection with hepatitis C virus (HCV) was analyzed by an enzyme-linked immunosorbent assay based on recombinant viral proteins encoded by regions of the putative viral core, NS3, NS4 and NS5, which were expressed in E. coli. Results showed that 106 of 124 cases (85.5%) of non-A, non-B chronic hepatitis and 43 of 45 cases (95.5%) of hepatocellular carcinoma, negative for HBV marker, were positive for antibodies against at least one of these viral proteins. One of 87 healthy individuals with normal alanine aminotransferase activity was positive for antibody against only the viral core, but was negative for HCV RNA. The serum of one patient with chronic hepatitis was positive for one of these proteins, but negative for HCV RNA. These findings in combination with results on detection of HCV RNA in the sera of patients with non-A, non-B chronic hepatitis indicated that 105 of 124 cases (84.6%) were positive for HCV infection. Sera that were negative for HCV antibodies against all these proteins were also negative for HCV RNA assayed by reverse transcription followed by the polymerase chain reaction. Screening of HCV infection by detecting viral antibodies in circulating blood using all these viral proteins is useful for reducing the number of ambiguous results in screening for viral infection. Thus, this assay system may be useful diagnostic purposes.
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PMID:Serodiagnostic assay of hepatitis C virus infection using viral proteins expressed in Escherichia coli. 131 40

In 1974, Prince et al. reported the existence of posttransfusion hepatitis with a long incubation period which was not related to hepatitis B virus (HBV). These cases were named "non-A, non-B" (NANB) hepatitis. The genome of NANB hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach. It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for the circulating HCV antibody (anti-HCV) was developed using a purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome. HCV is believed to be the main cause of blood-borne non-A, non-B hepatitis worldwide, which frequently evolves to chronic hepatitis and cirrhosis, and which may also be involved in the development of hepatocellular carcinoma. HCV is classified as part of the flaviviridae family and contains a positive-stranded RNA molecule by approximately 10 kb nucleotides. The HCV genome encodes a large polyprotein precursor, which is processed in structural nucleocapsid and envelope proteins and in non-structural proteins (NS1-NS5). Nucleotide sequence comparisons of distinct HCV isolates have shown a significant genetic variability between the different HCV strains. At present the diagnosis of HCV infection depends on various anti-HCV tests including second generation HCV Ab. Antigenic markers for HCV are being developed but the concentrations of HCV antigens in serum are at the lower limit of detectability by existing immunoassay technology. A polymerase chain reaction has been used to detect HCV RNA in the serum and liver. Serum HCV RNA disappears from serum after effective IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fundamental studies of hepatitis C virus: a review]. 133 74

The authors investigated the epidemiology of hepatitis C virus (HCV) related to liver diseases in Korea. Anti-HCV was studied by EIA in sera from patients with chronic liver diseases (CLD), individuals at high risk, healthy individuals, and family members of patients with CLD. We also evaluated the efficacy of a new anti-HCV assay kit, HCD EIA, consisting of 3 recombinant peptides derived from CORE, NS3 and NS5 regions of the HCV genome, for screening HCV infection. The prevalence of anti-HCV in HCD EIA was 15.4% of 1055 cases studied, while that in the anti-C100-3 EIA was 11.1%. The incidence of anti-HCV in HCD EIA was 5.9% of 17 cases with acute hepatitis, 18.1% of 293 cases with chronic hepatitis, 24.1% of 79 cases with liver cirrhosis, 28.0% of 100 cases with hepatocellular carcinoma, 19.8% of 81 cases maintained with hemodialysis, 31.3% of 16 cases with blood dyscrasias, 4.4% of 114 cases with fatty liver, 1% of 100 healthy persons, 1.3% of 150 blood donors, and 6.2% of 97 family members from 26 patients with type C CLD. Familial HCV clustering was detected in 3 (11.5%) of 26 patients with anti-HCV(+) CLD. The prevalence of anti-HCV in 190 HBsAg positive CLD was 8.4%. The relative proportions of positive anti-HCV, HBsAg, both positive 17.4%, 40.7%, and 3.7%, respectively, while 38.2% of the cases were negative for both anti-HCV and HBsAg. The prevalence of anti-HCV among CLD increased significantly in relation to age (p < 0.05), and it became higher than that of HBsAg after age 60.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of hepatitis C virus related to liver diseases in Korea. 768 3

Forty-two patients with hepatocellular carcinoma (HCC) were examined for hepatitis C virus (HCV) RNA in liver tissues by reverse transcription-polymerase chain reaction (RT PCR). Typing of HCV liver samples of 18 patients was dependent on the amplification of NS5 region by PCR using type-specific primers. Type-II was found in 14 of the 18 patients (78%), 7 of the 18 patients (39%) and 4 of the 18 patients (22%) were positive for type-II and I and for type-II and III or IV (III/IV), respectively. Type V or VI (V/VI) infection was not observed. These data indicate that HCV type-II may be the major type in HCC patients with HCV infection in China, and some patients can be coinfected with type-II and I or III/IV.
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PMID:[Genotyping of hepatitis C virus in patients with hepatocellular carcinoma]. 776 76

To investigate the regulation of expression of the human mdr1 gene, the response of the mdr1 promoter to signals involved in cell proliferation was examined. The activity of the mdr1 promoter was measured in transiently transfected NIH 3T3 cells, which were stimulated to enter the cell cycle by addition of serum, platelet-derived growth factor, or transforming growth factor alpha. Addition of serum to quiescent NIH 3T3 cells resulted in a 6-8-fold activation of mdr1 promoter activity, which peaked at 10 h, just prior to S-phase. Treatment of serum-starved cells with the serum mitogens platelet-derived growth factor and transforming growth factor alpha also activated the mdr1 promoter. To define components of the signal cascade resulting in mdr1 promoter activation, the role of c-Raf kinase, a serine/threonine kinase important in mitogen-activated signal transduction, was examined. We measured the effects of a constitutively activated Raf kinase, v-raf, and a dominant negative Raf mutant, c-Raf-C4, on mdr1 promoter activity in NIH 3T3 and HepG2 cells. In serum-starved NIH 3T3 cells, v-raf increased mdr1 promoter activity approximately 10-fold compared to a v-raf frame-shift control. Raf responsiveness of the mdr1 promoter was localized to sequences between -69 and -41, relative to the initiation site. Serum stimulation of the mdr1 promoter was blocked by co-transfection of NIH 3T3 cells with the dominant negative Raf mutant c-Raf-C4. In the human hepatoma cell line HepG2, which has high endogenous Raf kinase activity (Bruder, J. T., Heidecker, G., and Rapp, U. R. (1992) Genes & Dev. 6, 545-556), co-transfection with c-Raf-C4 decreased mdr1 promoter activity 20-fold. Taken together, these data suggest that the mdr1 gene is transcriptionally regulated by normal cellular signaling events involving activation of c-Raf kinase.
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PMID:A signal transduction pathway for activation of the mdr1 promoter involves the proto-oncogene c-raf kinase. 810 39

The high prevalence of hepatitis C virus (HCV) markers in alcoholic liver cirrhosis (AL-LC) and hepatocellular carcinoma (HCC) suggests a close aetiopathogenic relationship between alcoholic liver disease (ALD) and HCV infection. In the present study, HCV markers in ALD were measured by the highly sensitive methods, and the changes of sequential HCV markers after abstinence in ALD patients were analysed in order to elucidate the effect of alcohol on HCV. Antibodies to HCV-related antigen were determined using the first or second generation test kit. HCV-RNA genomes encoding the NS-5 region were detected using the RT-PCR method. In the HCV-NS5 negative serum, HCV genomes of the 5'-noncoding region were detected using the two-stage PCR method. Titres of HCV-RNA were measured by multiple cyclic PCR and cDNA dot blotting. Typing of HCV genomes was carried out on the PCR product from the NS-5 region by slot blot hybridization using type-specific cDNA probes, or by restriction fragment length polymorphisms analysis. In alcoholic fibrosis and alcoholic hepatitis, the prevalence of HCV markers was low, suggesting that the main aetiological factor is alcohol but not HCV in these types of ALD. HCV markers were positive in the half of the patients with AL-LC, and in more than 80% of patients with AL-CH and AL-HCC, indicating that HCV infection closely relates to these types of ALD. The ratio of the K1 type to the K2 type of HCV genomes was 4:1 in all types of NANB liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between alcoholic liver disease and HCV infection. 814 26

A routine screening test used in the diagnosis of hepatitis C virus (HCV) infection is the anti-HCV antibody (anti-HCV) test containing core, NS3, NS4, and NS5 antigens of HCV. When HCV infection occurs in immunocompromised hosts, antibody formation against core, NS3, or NS4 antigens may be weak in the presence of HCV viremia and cannot be detected by routine anti-HCV tests. This study proposed that in immunocompromised hosts such as patients with chronic renal failure (whose capacity to form antibodies is diminished), antibody formation against the E2 region would be preserved, because the E2/NS1 region of HCV is strongly immunogenic. The aim of this study is to evaluate the significance of anti-E2 in the diagnosis of HCV infection among patients on maintenance hemodialysis who are anti-HCV-negative, using a conventional third-generation enzyme immunoassay (EIA) kit. The E2/NS1 gene of HCV encoding the amino acid sequence 388-664 was molecularly cloned into a vector containing an SV 40 promotor and was expressed in Chinese Hamster ovary cells. Using this E2 protein, the anti-E2 test was performed by EIA on 100 patients on maintenance hemodialysis, and on 50 patients with chronic hepatitis C who were anti-HCV-positive, to evaluate the antigenecity of the E2 protein. Of the 100 hemodialysis patients, 15 (15.0%) tested anti-HCV-positive using a third generation anti-HCV ELISA kit. Of the 85 patients who tested negative for anti-HCV, nine (10.6%) were anti-E2-positive and six (66.7%) of these anti-E2 positive patients showed HCV RNA viremia by HCV reverse transcription-polymerase chain reaction. Fourty-two (84.0%) of 50 patients with chronic hepatitis C were anti-E2-positive. As a control group, we tested for anti-E2 among 30 blood donors who were anti-HCV-negative, and also among 85 patients with hepatocellular carcinoma who were anti-HCV-negative, but in both groups, none (0%) was anti-E2-positive. In conclusion, these data suggest that the E2 protein of HCV should be included in a diagnostic anti-HCV kit for the detection of HCV infection in immunocompromised patients.
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PMID:Significance of anti-E2 in the diagnosis of HCV infection in patients on maintenance hemodialysis: anti-E2 is frequently detected among anti-HCV antibody-negative patients. 895 33

Chronic hepatitis C virus (HCV) infection has been clearly established as a major risk factor in the development of hepatocellular carcinoma. In the present study we have attempted to identify the HCV genotypes associated with hepatocellular carcinoma in patients from the USA and Japan. RNAs from tumorous and non-tumorous tissues from 11 HCV seropositive Japanese patients, and plasma from 4 American patients were analysed by reverse transcription-polymerase chain reaction (RT-PCR) methods employing primers specific for the 5'UTR, the NS5 and E2/NS1 regions. Amplified products were cloned and compared by nucleotide sequencing and phylogenetic analysis. The 5'UTR region could be successfully amplified and sequenced from all samples, and phylogenetic analysis of the nucleotide sequences demonstrated with the exception of two of Japanese viruses were closely related to HCV type 1. Type 2 was detected in these two cases. In addition, two of the Japanese patients who were found to have cholangiocarcinoma were also found to be infected with type 1. HCV amplification of the NS5 was successful in 7 of the Japanese and 1 USA sample and clearly demonstrated that genotype 1b was predominant. Amplification of the E2/NS1 regions proved to be extremely difficult and was unsuccessful in all HCC patients despite the fact that these regions could be consistently amplified in samples from patients with both acute and chronic HCV infection. These findings might suggest that with long term persistent HCV infection, there may be marked heterogeneity in both the structural and non-structural regions of the virus, and/or possibly that the viral genomes may be defective.
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PMID:[Analysis of hepatitis C virus (HCV) genotypes in hepatocellular carcinoma]. 899 37

We tested HGV RNA in serum in addition to HBV DNA and HCV RNA to study the causative agents involved in chronic non-B, non-C hepatitis. Twenty five patients diagnosed as having chronic non-B, non-C hepatitis(negative for HBsAg and HCV-Ab), were investigated in this study. HGV RNA was detected by nested RT-PCR using primers in 5'-untranslated, NS3 and NS5 regions. Of the 25 patients, 4(16%) were positive for HGV RNA, only 1(4%) was positive for HBV DNA and none were positive for HCV RNA. Of the 4 patients with HGV RNA, 2 histologically has mild fibrosis and the remaining 2 had cirrhosis. One patient with cirrhosis also had hepatocellular carcinoma; HBV DNA was positive in this patient. All 3 patients with only the HGV infection had a mild histological grade. In conclusion, HGV infection was involved in 16% of Japanese patients with chronic non-B, non-C hepatitis. Chronic hepatitis G seemed to exhibit mild hepatitis activity.
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PMID:[GB virus C/hepatitis G virus infection in patients with chronic non-B, non-C hepatitis]. 908 58


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