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)

Antibody against the recombinant protein Y19 deriving from non-structural region 3 (NS3) of the hepatitis C virus (HCV) genome was measured in the serum from 300 patients with nonA-nonB chronic liver disease including serial serum samples from these patients by using an enzyme linked immuno-sorbent assay. Simultaneously, antibodies to a synthetic core peptide (AR142) and the recombinant peptide of NS 3-4 region (C-100) were tested. Anti-Y19 antibody was detected in 83.3%, 65.2% and 76.6% of patients with nonA-nonB chronic hepatitis (n = 144), liver cirrhosis (n = 46) and hepatocellular carcinoma (n = 43), respectively. In sera of other chronic liver disease, the detection rate of anti-Y19 antibody was significantly low comparing to nonA-nonB chronic liver disease. Positive rates of the patients for AR142 antibody and C-100 antibody were similar to the one for Y19 antibody. Patients positive for Y19 antibody have a tendency to be positive for C-100 antibody. Serum Y19 antibody level during and after treatment with natural interferon alpha (IFN-alpha; 5MU, 24 weeks) was studied in 33 patients with chronic hepatitis C. The effectiveness of IFN therapy did not correlate with the Y19 antibody level before the treatment. In most cases Y19 antibody level decreased relating to the improvement of the serum ALT level during the treatment. Y19 antibody level declined not only during IFN treatment but after the treatment in Responder group (as assessed by normal ALT for 6 months after the treatment; n = 14). Whereas, in Non-responder group (the rest of Responder group; n = 16) Y19 antibody level was maintained to the level at the end of the treatment or elevated again to the level before the treatment. In Responder group, 6 of 7 cases in whose serum HCV-RNA disappeared at 6 months after the treatment, had decrease of Y19 antibody to less than 20% of the pretreatment level and Y19 antibody became undetectable in 4 cases at 6 months after the treatment. One case in whom Y19 antibody did not decrease by the treatment had an increase of serum ALT level and a relapse of the disease at 12 months after the treatment. 5 of 6 cases in "Responder" group that HCV-RNA remained positive had more than 20% of Y19 antibody level of the pretreatment level at 6 months after the treatment. Therefore the decrease of Y19 antibody level was closely related to the efficacy in terms of serum ALT level and HCV-RNA level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinical significance of antibody to Y19 protein in nonA and nonB chronic liver disease]. 768 28

Chronic hepatitis C is endemic among chronic haemodialysis patients. There have been a number of reports on hepatocellular carcinoma developing in such patients in Japan. The present study reports on the treatment of 15 patients who showed elevated ALT levels due to biopsy proven chronic hepatitis C with interferon alpha-2a (IFN). The dose schedule was 6 mega units (MU) daily for the first two weeks followed by 3 doses per week for 5.5 months. Side effects were so severe that IFN treatment was discontinued early in one patient, the dosage reduced in 11 and only tolerated in the original schedule by three patients. Excluding one patient who only recently completed the therapy, 13 were able to be evaluated for therapy efficacy by assessment of serum ALT and viral RNA. The overall results showed that IFN was effective in eight of 13 patients, a rate somewhat higher than the reported figures in this country. It is concluded that IFN therapy is indicated in haemodialysis patients with progressive chronic hepatitis C, but the dose administered should be lower and the dose schedule more flexible, perhaps 3 MU three times a week, in order to minimize untoward side effects.
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PMID:Interferon treatment for chronic hepatitis C in haemodialysis patients: suggestions based on a small series. 896 42

The paper presents 66 hepatocellular carcinoma (HCC) patients (57 males, 9 females) with chronic hepatitis B virus (HBV) infection in the clinical, diagnostic and therapeutic aspects. In 60 cases, hepatic cirrhosis was the primary hepatic disease, in 5--chronic hepatitis, and in 1--neoplasm developed in morphologically normal liver. Forty out of 66 patients were HBsAg seropositive. In 96% of the cases, anti-HBc antibodies were detected. In 76% of the cases, the infection was subclinical. In all patients, neoplasm was diagnosed in the late, symptomatic stage of the disease. Okuda's classification was used to stage the disease. The following treatment methods were applied: surgical in 5 patients, embolization of hepatic artery with intra-arterial administration of cytostatics in 5, intravenous chemotherapy in 39, interferon alpha in lozenges in 15. In 44 patients, an objective response to treatment (according to WHO criteria) was achieved: in 5 (I and II Okuda's stage)--a complete response (CR) for the period of 0.5-4 years, in 2 (III Okuda's stage)--partial response (PR) with prolonged survival time up to 1 year, in 21--no change (NC). The average survival time of non-treated and treated patients was, respectively: in the I Okuda's stage 2.05 and 9.55 months, in stage II 1.36 and 7.36 months, in III stage 1.15 and 5.05 months. The differences in the average values are statistically significant. Only combined therapy, including both surgical and devascularization methods, applied to HCC patients results in achieving a long-lasting complete remission of the disease. Interferon alpha oral therapy improves the effects of the treatment.
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PMID:Primary hepatocellular carcinoma in patients with chronic hepatitis B virus infection. 901 46

Viral hepatitis C is a serious public health problem in France by the number of infected patients, the evolutive profile and by the lack of fully efficient therapeutics. However, the risk of developing cirrhosis and hepatocellular carcinoma may not be so high as it has been stated until now. Interferon alpha is at the present time, the only approved drug for the treatment of chronic hepatitis C. Its efficiency on criteria such as normalization of aminotransferases values or negativation of viremia is obtained in less than 25% of patients. The present recommendation is to use 3 MU of interferon alpha, 3 times per week during 12 months. While interferon leads to improvement of histologic lesions, it is not yet proved that a treatment by interferon can reduce, years after, the incidence of cirrhosis and hepatocellular carcinoma. No therapeutic strategy has been defined yet for the frequent situations of "no response", relapses or presence of factors that reduce the efficacy of treatment (high initial viremia level, genotype 1b, cirrhosis). It is possible that the course of patients having low or no elevation of aminotransferases and/or minimal histologic lesions, is good without any treatment. The efficacy of interferon alone appears insufficient. Thus trials in progress concern associations of antiviral drugs such as vidarabine. In lack of vaccine, preventive treatment is essential and depends upon knowledge of conditions of transmission of the virus. Transmission through blood and intravenous drug addiction represent 60 to 70% of cases of hepatitis C.
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PMID:[Treatment of viral hepatitis C]. 903 17

Costimulation mediated by costimulatory molecules, such as B7-1 and B7-2, which are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)-4 counter-receptor, plays an important role in the induction of T cell-mediated antitumor immunity. We investigated the expressions of B7-1, B7-2, and human leukocyte antigen (HLA) class I in seven human hepatocellular carcinoma (HCC) cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. RT-PCR showed that all these human HCC cell lines were positive for B7-1 and B7-2 at the messenger RNA (mRNA) level. Flow cytometric analysis revealed that they all expressed B7-1, B7-2, and HLA class I on the cell surface. However, the expression levels of B7-1 and B7-2 were very low whereas those of HLA class I were high. B7-1 and B7-2 expression could be increased by treatment with interferon alpha and interferon gamma in a dose-dependent manner, although the expression levels of B7-1 and B7-2 after interferon treatment remained low. By transfecting Hep3B cells with a plasmid containing human B7-1 complementary cDNA (cDNA), we were able to establish Hep3B cell lines strongly expressing B7-1. From mixed lymphocytes and tumor cultures analysis, the primary cytolytic activity against parental Hep3B cells could be induced effectively by B71-transfected Hep3B cells. These findings suggested that B7-1 gene transfer is the best way to induce strong expression of this molecule and this might be useful for immuno-gene therapy against human HCC.
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PMID:Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma. 914 26

The therapy of viral hepatitis has great medical and socioeconomic impact. Today chronic viral hepatitis is the most important cause for chronic liver disease, liver cirrhosis, and hepatocellular carcinoma. Hepatitis A and E cause acute courses exclusively whereas infection with the hepatitis B, C, and D virus might result in chronic hepatitis as well. The goal of therapy of chronic viral hepatitis has to be a reduction/normalisation of elevated transaminases, decrease of the serologic parameters of active viral replication, improvement of histology and prevention of complications of chronic hepatitis. The only drug with proven benefit in the treatment of chronic viral hepatitis is interferon alpha. This therapy results in a sustained response in 25 to 40% for hepatitis B and 10 to 25% for hepatitis C infection. New developments under clinical evaluation are Lamivudine and Famciclovir in the treatment of HBV-infection and Ribavirin in combination with INFa for chronic HCV-infection.
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PMID:[Therapy of viral hepatitis]. 954 47

2',5'-adenylate oligonucleotide (2-5A)-dependent RNase and 2-5A-synthetase are two enzymes of the 2-5A system strongly implicated in the basal control of RNA decay of both interferon-treated and untreated cells. RNase is activated by a 2-5A produced by 2-5A-synthetase, both enzymes being overexpressed by type I-interferon (alpha/beta). We described here for the first time a cell line completely deficient in RNase and its mRNA, while p69 2-5A-synthetase was normally interferon alpha/beta-induced. The complete absence of this RNase in human hepatoma cells (HepG2) was shown using three different methods based on the binding of a [32P]-labeled 2-5A probe of high specific activity to its binding site. Negative Western blotting assay with a specific monoclonal antibody correlated the previous findings. RNase-specific mRNA was not detectable even after treatment of cells with 1000 units/ml of interferon alpha/beta. This is not due to a mutation of the gene because an intronless genomic DNA sequence encoding 2-5A-binding site was cloned and expressed. It is likely that the expression of 2-5A-dependent RNase was impaired at the transcriptional level while having the known IFN alpha/beta-transcriptional regulatory factors as revealed by induction of p69 2-5A-synthetase gene. This may account for a differential activation of 2-5A-dependent RNase and 2-5A-synthetase genes by type I-interferon, and suggests that other members of regulatory transcription factors, different from IRF-1 and STAT proteins, may participate in two different interferon alpha/beta signaling pathways.
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PMID:Lack of 2',5'-oligoadenylate-dependent RNase expression in the human hepatoma cell line HepG2. 956

Protein C inhibitor (PCI) is the plasma inhibitor of activated protein C, which is the main protease of the anticoagulant protein C pathway. In this study the transcriptional regulation of human PCI gene in the human hepatoma cell line, HepG2, was characterized by evaluating the transient expression of a luciferase reporter gene. The 5' flanking region (residues -1587 to +2) of the PCI gene showed an adequate transcriptional activity, the maximum transcriptional activity being in a region between residues -452 and -94, which contains an Sp1-binding site, two AP2-binding sites and an inverted AP2-binding site. Transient expression assays with various deletion mutants and site-directed mutants showed that the Sp1-binding site (residues -302 to -294) has a potent promoter activity and that the upstream AP2-binding site (residues -350 to -343) has a potent enhancer activity; no activity was detected in the inverted (residues -413 to -404) and downstream (residues -136 to -127) AP2-binding sites. In addition, a region of the PCI gene (residues -452 to -414) containing the STATx-binding site, the A-activator (AA)-binding site, and the interferon alpha (IFN-alpha) response element, and another region of the PCI gene (residues -176 to -147) containing the GATA-1 and the IFN-gamma response element showed potent silencer activities. Gel mobility-shift assays with various DNA fragments indicated that the Sp1-binding site, the upstream AP2-binding site, the AA-binding site and the IFN-gamma response element interact with nuclear protein(s) of HepG2 cells. These findings suggest that the Sp1-binding site is the promoter, the AP2-binding site (residues -350 to -343) the enhancer, and both the AA-binding site and the IFN-gamma response element are the silencers of human PCI gene expression in HepG2 cells.
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PMID:Regulation of the human protein C inhibitor gene expression in HepG2 cells: role of Sp1 and AP2. 960 Oct 89

Infections with the hepatitis B, C or D virus can all lead to chronic hepatitis. Serological and molecular methods are essential for diagnosis and for differentiation between the different forms of chronic virus hepatitis. In adults between 5 and 10% of all infections with the hepatitis B virus become chronic while the rate is as high as 80% with the hepatitis C virus. All forms of chronic hepatitis are frequently asymptomatic for a long period of time. Complications are liver cirrhosis and hepatocellular carcinoma. During chronic hepatitis B infection in around 1% of the patients per year the virus is eliminated spontaneously while virus elimination occurs rarely in patients with chronic hepatitis C infection. In patients with chronic hepatitis C infection over a period of 30 years around 3% of the patients die due to chronic hepatitis C infection. As soon as chronic virus hepatitis is diagnosed treatment should be considered. Standard therapy for all forms of chronic viral hepatitis is interferon alpha. Additionally recent results indicate that nucleoside analogous are effective for chronic hepatitis B and C virus infection. For chronic hepatitis B infection studies with famciclovir and lamivudine show that viral replication can be effectively blocked. For chronic hepatitis C infection a combination therapy with interferon and ribavirin has been shown to reach higher elimination rates compared to interferon mono-therapy. The last treatment option for all forms of viral hepatitis is liver transplantation.
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PMID:[Chronic viral hepatitis--diagnosis, therapy and prognosis]. 1020 Jun 10

The clinical features and treatment of chronic hepatitis C in Chinese patients are the same as in Caucasian patients except that 27% of Chinese chronic hepatitis C patients have hepatitis C virus (HCV) genotype 6a. In contrast, Chinese patients with chronic hepatitis B (CHB) differ from Caucasian patients because the Chinese patients are immunologically tolerant to hepatitis B virus (HBV), having acquired hepatitis B infection perinatally or in early childhood. In the treatment of CHB, the short-term aims of loss of hepatitis B virus early antigen (HBeAg) and HBV-DNA need to be reassessed. In 1296 Chinese CHB patients, 67.7% of those who developed complications of cirrhosis or hepatocellular carcinoma, were HBeAg-antibody positive. Longer follow up of patients is, therefore, required to assess the time efficacy of a treatment regimen. After long-term follow up (median 90 months) of 206 Chinese CHB patients treated with interferon alpha (IFN alpha) compared with 203 untreated subjects, IFN alpha conferred no benefit in cumulative HBeAg seroconversion or in HBV-DNA negativity as determined by polymerase chain reaction assays or in decreasing long-term complications of cirrhosis and hepatocellular carcinoma. Lamivudine is a novel nucleoside analogue. In a recent 1 year study in 358 Chinese CHB patients, lamivudine treatment was associated with substantial histological improvement (including a reduction in fibrosis), with HBV-DNA suppression and normalization of alanine aminotransferase levels. However, lamivudine may have to be given on a long-term basis, as withdrawal of lamivudine results in rebound of HBV-DNA to pretreatment levels. The long-term effects of lamivudine are currently being assessed.
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PMID:Antiviral therapy for hepatitis B and C in Asians. 1038 33


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