Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive. Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive. 7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti-HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. Our results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis.
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PMID:HCV-associated liver cancer without cirrhosis. 772 33

Chronic infection with the hepatitis B virus is a major health problem worldwide. The only established therapy is interferon-alpha, with an efficacy of only 30-40% in highly selected patients. Nucleoside analogues do not show a significant clinical benefit. Molecular therapeutic strategies aimed at blocking gene expression include antisense DNA/RNA and ribozymes acting at the posttranscriptional level and triple helix formation blocking at the transcriptional level. In vitro, antisense oligodeoxynucleotides inhibit viral replication and gene expression in human hepatoma cell lines. In vivo, an antisense oligodeoxynucleotide directed against the 5'-region of the pre-S gene of the duck hepatitis B virus inhibited viral replication and gene expression in ducks. In vitro, ribozymes accurately cleave HBV substrate RNA. Triple helix formation is another very promising molecular approach. Results in hepadnaviral infection are not yet available, however.
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PMID:Molecular therapeutic strategies in hepatitis B virus infection. 786 75

Chronic infection with hepatitis B virus (HBV) is accompanied by an increasing risk of developing hepatocellular carcinoma. There are indications that the HBx protein of HBV is involved in the process of tumour formation. HBx also transactivates several transcription factor binding sites. Recently, we reported that HBx can use a tumour promotor pathway for transactivation. In particular, we found that transactivation of the binding motif for transcription factor AP-1 (JUN/FOS) by HBx is dependent on functional protein kinase C (PKC), as indicated by abolition of the transcriptional stimulation following downregulation or inhibition of the enzyme. Moreover, HBx activates PKC, probably via increasing the endogenous PKC activator sn-1,2-diacylglycerol (DAG). Here we extend these data and report on the time course of PKC activation. We found that activation of PKC by HBx is transient and differs from activation of PKC by the ras oncogene product or phorbol ester in that it does not lead to rapid downregulation of the enzyme subsequent to the activation. Moreover, we provide evidence that an increase in cellular DAG is observable not only as an early event in response to HBx but also in cell lines transformed after transfection with HBV DNA and stably expressing HBx. Besides its important role in the regulation of cellular genes, PKC is also the intracellular receptor for tumour-promoting agents and an activator of proto-oncogenes, suggesting that our observations might provide an explanation for the oncogenic properties of HBx.
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PMID:The hepatitis B virus transactivator HBx causes elevation of diacylglycerol and activation of protein kinase C. 821 Jul 15

Chronic infection with hepatitis-B virus (HBV) is associated with high risk for the development of hepatocellular carcinoma (HCC). Several studies have implicated that the X gene product(s) of HBV are important to the pathogenesis of HCC. This study tests the hypothesis that immunohistochemical detection of hepatitis B x antigen (HBxAg) is closely associated with HCC. The patterns of HBxAg were determined by staining in tumor and non-tumor liver sections from 30 Chinese patients with HBV-associated HCC, and the results were compared with other markers of infection. HBxAg was the most prevalent marker of HBV infection both in tumor and in non-tumor tissues of HCC patients, as compared with the hepatitis-B surface and core antigens. This pattern was observed among carriers as well as several patients who were HBsAG- in serum. The HBxAg staining results were validated by Southern blotting with an X-region probe and by Western blotting with anti-HBx. These results suggest that the persistence of HBxAg is important to the pathogenesis of early HCC and that HBxAg expression in the liver during chronic HBV infection may be an important prognostic marker for the development of HCC.
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PMID:The value of hepatitis B x antigen as a prognostic marker in the development of hepatocellular carcinoma. 840 83

Chronic infection with the hepatitis B virus (HBV) is a major health problem worldwide. The only established therapy is alpha-interferon with an efficacy of only 30-40% in highly selected patients. Major theoretical problems of therapeutical strategies against hepadnaviral infections are the limited immune response and the presence of covalently closed HBV DNA in the nucleus. Many nucleoside analogues and inhibitors of viral reverse transcriptases were tested in vitro and in vivo with transient effects and often severe side effects. Molecular therapeutic strategies include antisense DNA/RNA and ribozymes. In vitro antisense oligodeoxynucleotides could be shown to inhibit viral replication and gene expression in human hepatoma cell lines. In vivo an antisense oligodeoxynucleotide directed against the 5'-region of the preS gene of the duck hepatitis B virus inhibited the viral replication and gene expression in ducks. These results demonstrate the potential clinical use of antisense DNA/RNA as antiviral therapeutics.
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PMID:Therapy of hepadnavirus infection using antisense oligonucleotides. 866 19

Hepatocellular carcinoma (HCC) is one of the most common cancers, especially in Asia and Africa. The prognosis of HCC is very poor because of the high malignancy and the failure of early diagnosis which is mainly dependent on the late onset of clinical symptoms. Chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is the most commonly known risk factor for developing HCC. Mass screening and monitoring of general population or of high-risk population, by measurement of serum alpha-fetoprotein (AFP), have been implemented in several countries. However, the use of AFP as a diagnostic marker for HCC is questionable due to its limited sensitivity and specificity. This article analyzed the serum level of AFP in 72 histopathologically confirmed hepatocellular carcinoma cases in Thailand. Elevation of serum AFP was detected in 75.6%, 88.9%, 79.2% and 80.0% of patients with HBsAg, anti-HCV antibody, HBV DNA, and HCV RNA, respectively. However, only 58.8% of HCC patients without any of the four markers had elevation of serum AFP. AFP is thus not a sensitive screening marker for HCC in general population, especially in those not associated with HBV or HCV. However, since elevated serum AFP was found in most patients with evidence of HBV or HCV infection, the monitoring of serum AFP level in those high-risk patients can be valuable for screening and monitoring of hepatocellular carcinoma.
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PMID:Hepatitis B- and hepatitis C-associated hepatocellular carcinoma: evaluation of alpha-fetoprotein as a diagnostic marker. 870 46

Chronic infection with the hepatitis B virus (HBV) is a major cause of worldwide morbidity and mortality. A large number of therapeutic approaches has been tried, including interferon (IFN), nucleoside analogues and immunomodulators. To date controlled clinical trials have shown that only IFN is of long-term value but many patients fail to respond to treatment. New approaches to treating patients with IFN-resistant hepatitis B are currently undergoing clinical and experimental evaluation, and it seems likely that new therapeutic agents will be available in the near future.
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PMID:Treatment of chronic hepatitis B. 879 May 66

Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription-polymerase chain reaction (RT-PCR) with a median level of 1003 x 10(3) genomic equivalents ml-1 according to the branched-DNA assay (b-DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype 1a + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non-progressive liver disease groups. Serum HCV-RNA levels were similar in the liver diseased groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlying liver damage.
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PMID:Lack of association between type of hepatitis C virus, serum load and severity of liver disease. 887 79

Hepatitis B virus (HBV) is a co-factor in some hepatocellular carcinomas (HCC). Chronic infection with HBV is a risk factor for tumor development, suggesting the accumulation of cellular genetic changes. HBV DNA is frequently found integrated at random sites in HCC, with chromosomal deletions and rearrangements being common at the sites of viral integration. Tumor suppressor gene p53 is frequently altered in HCC. Environmental carcinogens are factors in HCC development in certain geographic locations. HBV encodes a protein (X) known to transactivate viral and cellular genes; the X gene is often retained in HCC. To learn more about X gene function. We employed the yeast two-hybrid genetic system to seek X-interactive proteins. A cellular protein, designated XAP-1, was recovered that interacts specifically with the X protein. XAP-1 is the human homologue of the monkey UV-damaged DNA-binding protein (UV-DDB); the UV-DDB protein functions in DNA repair and is defective in some xeroderma pigmentosum group E patients. The interaction between XAP-1 and HBV X protein was confirmed by several independent methods. This suggests that cellular DNA repair processes may be affected by HBV and that the resulting genetic instability may contribute to hepatocellular carcinogenesis. A unifying model of the molecular basis of HBV involvement in HCC development is presented. Fundamental components of the model are chronic infection by HBV and viral effects on cellular DNA repair. This model has implications for the possible role of HCV infection in the induction of HCV-associated HCC.
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PMID:Viral co-factors in liver cancer: lessons from hepatitis B virus. 887 24

Chronic infection with hepatitis B virus (HBV) is associated with the development of human hepatocellular carcinoma (HCC). One of the HBV genes, HBx, may have transforming potential, but this issue is still the subject of controversy. One of the major difficulties in addressing this question is the lack of a suitable in vitro model. We used a nontransformed, differentiated murine hepatocyte cell line (AML12) to transfect the HBx gene and examine its transforming capabilities. Because mutations of the p53 gene, in particular at codon 249, have been implicated in HCC development in geographical areas with high incidence of the tumor, we also studied the putative cooperative role in transformation between HBx and mutated p53 by cotransfecting HBx with a murine p53 mutant equivalent to human ser249 (ser246p53). Transfection with HBx plasmids containing the HBx gene under the control of two different promoters resulted in fewer colonies than in control plasmids. The toxic effect of HBx on colony formation was abolished by cotransfection with 246p53, suggesting that the inhibitory effect requires functionally intact p53. Clonal cell lines that stably expressed HBx messenger RNA (mRNA) (HBX lines) were tested for their growth characteristics and their ability to grow in soft agar and form tumors in nude mice. At passages 19-27 after transfection, one of four HBx-expressing lines showed the capacity for anchorage-independent growth in soft agar and produced poorly differentiated hepatocellular carcinomas in 8 of 13 sites of injection in nude mice. HBX lines as well as clonal cell lines of cells transfected with 246p53 (246 cell lines), cotransfected with HBx and 246p53 (246x lines) or transfected with control plasmids, were analyzed by flow cytometry to determine the fraction of cells in S phase (SPF). 246 and 246X lines had similar SPFs that were approximately twofold greater than control or HBX lines. 246x lines showed morphological changes in culture such as marked cellular heterogeneity, cell crowding, and the presence of multinucleated giant cells, but their tumorigenicity was not increased compared with the HBX lines. These data show that HBx has a weak tumorigenicity in murine hepatocytes and that the addition of mutation of p53 at codon 249 to HBx expression does not increase tumorigenicity in AML12 cells.
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PMID:Analysis of the tumorigenicity of the X gene of hepatitis B virus in a nontransformed hepatocyte cell line and the effects of cotransfection with a murine p53 mutant equivalent to human codon 249. 890 70


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