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)

Hepatitis B virus (HBV) is the most meaningful risk factor in chronic hepatitis, cirrhosis and primary hepatocellular carcinoma (PHC). The hepatitis B virus X protein (HBxAg) is a multifunctional protein with many important functions in hepatocellular carcinogenesis. A monoclonal anti-HBxAg antibody was developed in our laboratory and characterized by different methods. Using this antibody HBxAg was detected in formaldehyde fixed paraffin embedded tissue sections of 72 liver biopsies from patients with acute hepatitis, chronic hepatitis, cirrhosis and primary hepatocellular carcinoma. The co-expression of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and HBxAg was compared. The histological and cytological localization of the detected HBxAg showed a characteristic distribution in different stages of HBV infection. Strong and diffuse nuclear reaction was detected in PHC cases in contrast to the focal, cytoplasmic and nuclear labeling in the acute and chronic B hepatitis cases. Our antibody seems to be a suitable prognostic marker for routine pathohistological diagnosis and for comparative pathological and epidemiological research on the development of PHC.
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PMID:Immunohistochemical assessment and prognostic value of hepatitis B virus X protein in chronic hepatitis and primary hepatocellular carcinomas using anti-HBxAg monoclonal antibody. 1169 43

Fibrolamellar carcinoma (FLC) of the liver is a rare variant of hepatocellular carcinoma (HCC). Here we report the case of a 12-year-old Indian male with typical FLC with no apparent hepatitis B virus (HBV) infection and a non-cirrhotic liver. The patient, though seronegative for HBsAg, showed expression of HBcAg in both the liver and tumour tissue. RT-PCR analysis revealed the presence of full-length HBx-transcripts in both liver/tumour tissue, along with truncated HBx-transcripts only in the tumour tissue. The lymphocytes in both peripheral and liver/tumour compartments showed a proliferative response to either/or HBcAg and HBxAg, which could be further augmented on addition of rIL-2. This is the first study to show not only the presence of HBcAg in the liver/tumour tissue but also prior exposure of the FLC patient's lymphocytes to HBV antigens. Also, the presence of the full-length and truncated HBx-transcripts in the tumour tissue, a proposed tumorigenic marker for hepatocarcinogenesis in chronic HBV patients, suggests an oncogenic role of HBV in this rare variant of HCC.
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PMID:The detection of HBV antigens and HBx-transcripts in an Indian fibrolamellar carcinoma patient: a case study. 1190 24

In order to investigate inhibition of HLA-I expression by antisense oligonucleotides in vitro, three pieces of antisense phosphorothioate oligonucleotides (ASODN) complementary to hepatitis B virus (HBV) x gene key regions namely, 1510-1530, 1555-1581, 1768-1791 were synthesized. We also synthesized a SOND (sense strand) with same sequence of 1510-1530 as control. The specificity of inhibitory effect of the ASOND was determined using 2215 cell line by detection of HBxAg. In addition, we observed the inhibitory effect of ASODN on human HLA-I utilizing 2215 cells, the cells were stained with monoclonal antibody against human HLA-I heavy chain molecules, with fluorescenated sheep antimouse antibody as the second antibody and then analyzed on a EPICS profile II flow cytometer. HLA-I mRNA were assayed by in situ hybridization with a HLA-I heavy chain cDNA probe. The results indicated these ASODN could inhibit the expression of HBxAg, as well as HLA-I in cell surface. The result of 1 in situ hybridization showed that the decreased cell surface expression was correlated with steadily decreasing state of mRNA levels. The mechanism of action may be due to the inhibition of HBxAg by sequence specific ASODN, then resulting in decreasing of its transactivating effect on the HLA-I promoter.
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PMID:[Effect on HLA-I expression in the presence of antisense oligonucleotides complementary to hepatitis B virus x gene]. 1252 41

Hepatitis B virus (HBV) X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) by activation of signalling pathways such as NF-kappaB. To identify NF-kappaB target genes differentially expressed in HBxAg-positive compared to -negative cells, HepG2 cells consistently expressing HBxAg (HepG2X cells) were stably transfected with pZeoSV2 or pZeoSV2-IkappaBalpha. mRNA from each culture was isolated and compared by PCR select cDNA subtraction. The results showed lower levels of alpha(2)-macroglobulin (alpha(2)-M) in HepG2X-pZeoSV2 compared to HepG2X-pZeoSV2-IkappaBalpha cells. This was confirmed by Northern and Western blotting, and by measurement of extracellular alpha(2)-M levels. Elevated transforming growth factor-beta1 (TGF-beta1) levels were also seen in HepG2X compared to control cells. Serum-free conditioned medium (SFCM) from HepG2X cells suppressed DNA synthesis in a TGF-beta-sensitive cell line, Mv1Lu. The latter was reversed when the SFCM was pretreated with exogenous, activated alpha(2)-M or with anti-TGF-beta. Since elevated TGF-beta1 promotes the development of many tumour types, these observations suggest that the HBxAg-mediated alteration in TGF-beta1 and alpha(2)-M production may contribute importantly to the pathogenesis of HCC.
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PMID:Hepatitis B virus X antigen promotes transforming growth factor-beta1 (TGF-beta1) activity by up-regulation of TGF-beta1 and down-regulation of alpha2-macroglobulin. 1476 85

The hepatitis B virus (HBV)-encoded X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) through the upregulated expression of selected cellular genes. To identify these genes, RNAs isolated from HBxAg-positive and -negative HepG2 cells were compared by PCR select cDNA subtraction. One gene overexpressed in HBxAg-positive cells by Northern and Western blotting is the ribosomal protein S15a. The S15a mRNA is 535 base pairs, encoding a protein 130 amino acids long with a molecular weight of 14.3 kDa. S15a expression was upregulated in HBV-infected livers, where it costained with HBxAg. Overexpression of S15a stimulated cell growth, colony formation in soft agar, and tumor formation in SCID mice. Hence, HBxAg upregulated the expression of S15a, the latter of which participates in the development of HCC, perhaps by altering the integrity of translation.
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PMID:Human S15a expression is upregulated by hepatitis B virus X protein. 1510 28

In subjects with hepatitis B, carcinogenesis has been associated with the hepatitis B virus (HBV) X protein (HBX) and human telomerase reverse transcriptase (hTERT). In the experiments reported here, we used immunohistochemical methods to study the expression of hTERT and HBV antigens (HBsAg, HBcAg and HBxAg) in 34 cases of HCC and corresponding paratumor tissues, 30 cases of liver cirrhosis, and 6 normal livers. To examine the effect of HBX on hTERT expression and activity in hepatoma cells, we transiently and stably transfected the pCMV-X plasmid cloned HBx gene into H7402 hepatoma cells, then measured the expression of c-Myc and hTERT in these cells with the use of Western-blot analysis. Telomerase activity was detected with the use of the telomerase repeat amplification protocol (TRAP) in transiently and stably transfected cells. We found that hTERT expression was 67.6%, 73.5%, and 100% in tumor, paratumor, and cirrhosis samples, respectively, but found no hTERT positivity in samples of normal liver. HBsAg, HBcAg, and HBxAg were expressed in 58.8%, 26.5%, and 76.5% of tumor tissues, respectively; in 64.7%, 41.2%, and 85.3% of the corresponding paratumor tissues; and in 76.7%, 66.7%, and 100% of cirrhotic tissues. The chi 2 test revealed no significant difference between the expression of hTERT and HBxAg in these tissues. Western-blot analysis revealed that expression of c-Myc and hTERT in the transiently transfected cells was much greater than that in the control cells. We elicited a similar result when we used the TRAP method to measure telomerase activity. Our data collectively demonstrate that HBX up-regulates the expression and activity of hTERT in hepatoma cells, suggesting that hTERT is associated with tumor development.
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PMID:Effects of hepatitis B virus X protein on human telomerase reverse transcriptase expression and activity in hepatoma cells. 1574 53

Hepatitis B and related viruses that infect mammalian hosts encode the "X" protein that has been shown to contribute importantly to the pathogenesis of chronic liver disease (CLD) and to the development of hepatocellular carcinoma (HCC). In a variety of tissue culture systems, hepatitis B virus (HBV) X antigen, or HBxAg, has been shown to trigger apoptosis, while other evidence suggests that HBxAg inhibits apoptosis and stimulates the cell cycle by constitutively activating a number of signaling pathways that are important for hepatocellular growth and survival. These apparently contrasting properties of HBxAg may be associated with differences in the X protein itself, since carboxy-terminal truncated forms of HBxAg appear to be associated with HCC lesions. Alternatively, or in addition, these differences may be due to the cell type, state of cell differentiation, and whether expression occurs in resting or dividing cells. Further, the association between HBxAg expression and chromosomal instability, may also contribute to the apparently contrasting fates of HBxAg positive cells. It is proposed that in many of these systems, the different outcomes of HBxAg expression may be due to the nature of the cellular response to HBxAg, and not due to differences in the fundamental properties of HBxAg, the latter of which promote cell survival, cell cycle progression, and the development of HCC.
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PMID:Hepatitis B virus X antigen (HBxAg) and cell cycle control in chronic infection and hepatocarcinogenesis. 1576 46

The hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). The relationship was examined between HBV antigens and IAP (inhibitor of apoptosis) family in development of HCC. The expression levels of HBV antigens (HBsAg, HBcAg, and HBxAg) and members of the IAP family (survivin, XIAP, cIAP-1, and cIAP-2) were detected immunohistochemically in tissues from 34 cases of HCC and 30 cases of liver cirrhosis. The positive rate of survivin was higher than these three molecules in all three tissue types (P < 0.05). The positive rates of HBxAg and survivin were high in HCC (76.5% and 88.2%), paratumor (85.3% and 91.2%), and liver cirrhosis (100% and 93.3%) tissues, with no significant differences between the survivin- and HBxAg-positive rates (each P > 0.05). To examine the effect of HBx on survivin expression, plasmid pCMV-X (encoding the HBx gene) was transfected transiently with or without plasmid pcDNA3-sur (encoding the survivin gene) into H7402 hepatoma cells and L-O2 human normal liver cells. Cells over-expressing HBx alone showed increased apoptosis along with a dose-dependent increase in survivin levels. However, co-expression of survivin inhibited the HBx-induced apoptosis. To examine the effect of HBx on survivin in hepatoma cells without apoptosis, plasmid pCMV-X was transfected stably into human hepatoma H7402 cells and L-O2 cells. These H7402-X and L-O2-X cells showed high-level expression of both HBx and survivin, but did not show apoptosis. The addition of pSilencer 3.0-X, an RNAi vector targeting the HBx gene, reduced the expression levels of survivin protein in H7402-X cells. Collectively, these data demonstrate that HBx upregulates survivin expression in hepatoma tissues, suggesting that HBx and survivin may both be involved in carcinogenesis of HCC.
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PMID:Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues. 1617 17

The hepatitis B virus X protein (HBxAg) is responsible for severe complications of HBV infections including primary hepatocellular carcinoma. A sandwich type ELISA and a flow cytometric microbead assay for quantitative determination of serum levels of Hbx-Ag are introduced. We have previously developed monoclonal antibody families against well-conserved epitopes on HbxAg, characterized by different immunohistochemical and immunoserological techniques. Special selection of the antibody pairs provided highly sensitive and highly specific tools for quantitative immunoassay development. The resulting assays were tested on human sera (208 samples) collected from patients suffering from different clinical forms of HBV infection. The sensitivity range of the sandwich type ELISA was between 4 and 2000 ng/ml as measured on both the recombinant antigen and the sera of chronic hepatitis patients. A further flow cytometric microbead assay was established and tested in parallel with the ELISA. The quantitative results of these two immunoserological techniques were in strong correlation and they were found to be highly specific and sensitive on clinical samples. The HBxAg ELISA technique is applicable for routine clinical laboratory measurements, and our HBxAg microbead technique is recommended for complex multiparametric measurements combined with other markers.
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PMID:Sandwich type ELISA and a fluorescent cytometric microbead assay for quantitative determination of hepatitis B virus X antigen level in human sera. 1619 45

Hepatitis B virus (HBV)-encoded X antigen (HBxAg) contributes to the development of hepatocellular carcinoma (HCC). A frequent characteristic of HCC is reduced or absent expression of the cell adhesion protein, E-cadherin, although it is not known whether HBxAg plays a role. To address this, the levels of E-cadherin were determined in HBxAg-positive and -negative HepG2 cells in culture, and in tumor and surrounding nontumor liver from a panel of HBV carriers. The results showed an inverse relationship between HBxAg and E-cadherin expression both in tissue culture and in vivo. In HBxAg-positive cells, E-cadherin was suppressed at both the mRNA and protein levels. This was associated with hypermethylation of the E-cadherin promoter. Depressed E-cadherin correlated with HBxAg trans-activation function, as did the migration of HepG2 cells in vitro. Decreased expression of E-cadherin was also associated with the accumulation of beta-catenin in the cytoplasm and/or nuclei in tissues and cell lines, which is characteristic of activated beta-catenin. Additional work showed that HBxAg-activated beta-catenin. Together, these results suggest that the HBxAg is associated with decreased expression of E-cadherin, accumulation of beta-catenin in the cytoplasm and nucleus, and increased cell migration, which may contribute importantly to hepatocarcinogenesis.
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PMID:Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma. 1624 64


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