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)

We have previously demonstrated increased levels of insulin-like growth factor (IGF)-II mRNAs and protein with re-expression of a fetal pattern of transcripts in human hepatocarcinoma. In the present study, we have investigated IGF-II transcripts and protein in liver tissues from patients with hepatocarcinoma infected with hepatitis B virus, by using in situ hybridization and immunohistochemical techniques. The IGF-II transcripts and protein have been localized to the hepatocytes, be they normal or tumoral with a gradient for IGF-II expression from normal to dysplastic and tumoral tissues. Hepatitis B virus mRNAs and viral surface antigen have only been detected in some hepatocytes in the peritumoral tissues. Therefore, the results show expression of IGF-II in hepatocytes. The increase of IGF-II expression in tumor hepatocytes support the hypothesis that it might represent a marker of hepatocytes differentiation.
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PMID:Localization of insulin-like growth factor-II and hepatitis B virus mRNAs and proteins in human hepatocellular carcinomas. 184 56

In this study we investigated the expression of insulin-like growth factor II (IGf-II) to explain a role for this growth factor in concert with hepatitis B virus (HBV) involvement in the development of hepatocellular carcinoma (HCC) from chronic hepatitis type B (CAH-B) and liver cirrhosis (LC). The expressions of IGF-II and HBsAg were tested in tissue samples from 38 patients with CAH-B, 32 with LC, and 31 with HCC, by immunohistochemical staining using monoclonal anti IGF-II and anti HBs. All patients were seropositive for the presence of HBsAg. The expression of IGF-II was observed in 30 out of 32 (93.8%) LC and all 31 (100%) HCC tissue samples tested. IGF-II was expressed in most hepatocytes of regenerating nodules and in tumorous as well as nontumorous cells of HCC tissues. Neither normal liver tissues nor CAH-B tissue samples expressed IGF-II. HBsAg was expressed in 34 out of 38 (89.5%) CAH-B, 24 out of 32 (75%) LC and 13 out of 31 (41.9%) HCC tissue samples. The expression sites of HBsAg were not correlated with those of IGF-II in any tissue samples tested. The present study indicates that IGF-II plays a role in cell proliferation of regenerating nodules as well as in the development of hepatocellular carcinomas. In addition, there was no direct evidence of HBV involvement in the overexpression of this growth factor.
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PMID:Expression of insulin-like growth factor II in chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. 766

Hepatitis B virus infection is associated with acute and chronic liver disease and the development of hepatocellular carcinoma (hcc). Several lines of evidence have suggested that hepatitis B virus X protein (HBx), which is a transcriptional trans-activator, plays a role in the process of liver carcinogenesis. We have investigated the expression of insulin-like growth factor I (IGF-I) receptor in human hepatocellular carcinoma cell lines using SNU368 cells containing HBx and SNU387 cells, which lack HBx gene transcript (J-G. Park et al., Int. J. Cancer, 62: 276-282, 1995), in an attempt to understand its possible relationship to the HBx-induced hcc. The binding of 125I-labeled IGF-I to the SNU368 cells was 5-fold higher than that of SNU387 cells. The Scatchard analysis of the binding data revealed a single class binding site for IGF-I with Kd of 7.6 and 8.8 nM and maximum binding capacities of 169 and 33 fmol/10(5) cells, respectively. Therefore, the difference observed in 125I-labeled IGF-I binding between SNU368 and SNU387 cells was due to an increase in the number of IGF-I binding sites with no change in affinity for the IGF-I receptor. An enhanced level of IGF-I receptors in SNU368 cells was also observed by fluorescence-activated cell sorting analysis using a monoclonal antibody against human IGF-I receptor, alpha IR3. The level of IGF-I receptor RNA and the basal IGF-I receptor gene promoter activity in SNU368 cells were 5 and 10 times higher than those observed in SNU387 cells, respectively. To substantiate further that HBx could transactivate the expression of the endogenous IGF-I receptor gene, Hep G2 cells were transiently transfected with a HBx expression vector. The transfection of Hep G2 cells with an HBx expression vector resulted in increased levels of IGF-I receptor RNA, promoter activity, and 125I-labeled IGF-I binding by 2.6-, 2.8-, and 2-fold, respectively. As a result of higher levels of IGF-I receptor, the mitogenic effect of IGFs (IGF-I and IGF-II) on SNU368 cells was 6 times higher than that of SNU387 cells. These results suggest that HBx may play a role in the process of hcc by activating IGF-I receptor gene expression.
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PMID:Increased expression of the insulin-like growth factor I (IGF-I) receptor gene in hepatocellular carcinoma cell lines: implications of IGF-I receptor gene activation by hepatitis B virus X gene product. 870 31

Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in bone mass during adult life. Despite the rarity of HCAO, understanding the mediator(s) of the skeletal disease is of great interest. The IGFs-I and -II have potent anabolic effects on bone, and alterations in the IGFs and/or IGF-binding proteins (IGFBPs) could be responsible for the increase in bone formation in this disorder. Thus, we assayed sera from seven cases of HCAO for IGF-I, IGF-II, IGF-IIE (an IGF-II precursor), and IGFBPs. The distribution of the serum IGFs and IGFBPs between their ternary ( approximately 150 kD) and binary (approximately 50 kD) complexes was also determined to assess IGF bioavailability. HCAO patients had normal serum levels of IGF-I and -II, but had markedly elevated levels of IGF-IIE. Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients. IGF-I and -II in sera from patients with HCAO were carried, as in the case of sera from control subjects, bound to IGFBP-3 in the approximately 150-kD complex, which is retained in the circulation. However, IGF-IIE was predominantly in the approximately 50-kD complex in association with IGFBP-2; this complex can cross the capillary barrier and access target tissues. In vitro, we found that IGF-II enhanced by over threefold IGFBP-2 binding to extracellular matrix produced by human osteoblasts and that in an extracellular matrix-rich environment, the IGF-II/IGFBP-2 complex was as effective as IGF-II alone in stimulating human osteoblast proliferation. Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function. Our findings in HCAO suggest a possible means to increase bone mass in patients with osteoporosis.
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PMID:Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults. 959 72

Although human hepatocellular carcinoma (HCC) is one of the most common types of tumors in the world, the molecular mechanisms underlying hepatitis-C-related human hepatocarcinogenesis are still not clear. HCC is accompanied by virus infections in most cases, and it is suggested that hepatitis B virus and hepatitis C virus (HCV) significantly influence the oncogenic process. The persistence of inflammation following HCV infection is reportedly related to carcinogenesis, and the mechanism of chronic inflammation has been approached by taking viral, immunologic, cytokine and apoptotic responses into consideration. With the progress made in molecular biology, the functional abnormality of oncogenes/tumor suppressor genes has been identified and, apart from the p53 gene, involvement of the IGF-II gene has also been described recently. Furthermore, it has been suggested that uncontrolled proliferation of cancer cells might be based on abnormal regulation of intracellular signal transduction pathways. Here we review the cutting edge of molecular hepatitis C virology in terms of virus-cell interactions, which may contribute to the development of human HCCs. We also discuss the recent progress made in the molecular and cell biology of human hepatocarcinogenesis.
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PMID:Hepatitis C virus and hepatocarcinogenesis. 1051 76

AIM:To investigate the characteristics of newly established four hepatocellular carcinoma cell lines (SNU-739, SNU-761, SNU-878 and SNU-886) from Korean hepatocellular cancer patients.METHODS:Morphologic and genetic studies were done.RESULTS:All four lines grew as a monolayer with an adherent pattern, and their doubling times ranged from 20 to 29 hours. The viability rate was relatively high (88%-94%).Neither mycoplasmal nor bacterial contamination was present.The lines showed different patterns in fingerprinting analysis. The hepatitis B virus (HBV) DNA was integrated in the genomes of all four lines, and in all of them HBx,HBc and HBs transcripts were detected by reverse transcriptase-PCR methods. Among the three cell lines used as control (Hep 3B, SK Hep1 and Hep G2),only Hep 3B showed HBx expression, and this line was used as a HBV integrated control.The RNA of albumin was detected in three lines (SNU-761, SNU-878 and SNU-886), that of transferrin in two lines (SNU-878, SNU-886), and that of IGF-II was detected in none of the cell lines.CONCLUSION:These well characterized cell lines may be very useful for studying the biology of hepatocellular carcinoma in association with the hepatitis Bvirus.
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PMID:Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA. 1181 50

Primary hepatocellular carcinoma (HCC) is one of the most common forms of malignant cancer with the fourth highest mortality rate worldwide. Major risk factors for the development of HCC include chronic infections with the hepatitis B or C virus, alcohol consumption, exposure to dietary aflatoxin B1, hereditary liver disease or liver cirrhosis of any etiology. Recent studies have discovered changes in the insulin-like growth factor (IGF) axis that affect the molecular pathogenesis of HCC, including the autocrine production of IGFs, IGF binding proteins (IGFBPs), IGFBP proteases, and IGF receptor expression. Characteristic alterations detected in HCC and hepatoma cell lines comprise the overexpression of IGF-II and the IGF-I receptor emerging as critical events in malignant transformation and growth of tumors. Simultaneous reduction of IGFBP expression and the increase in proteolytic cleavage of IGFBPs result in an excess of bioactive IGFs. Finally, defective functions of the IGF-II/mannose 6-phosphate receptor involved in degradation of IGF II, the activation of the growth inhibitor TGF-beta1, and the lysosomal targeting of cathepsin proteases capable to degrade extracellular matrix proteins may contribute to the development of HCC.
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PMID:The role of the IGF axis in hepatocarcinogenesis. 1471 Mar 47

Currently available evidence supports a role for the hepatitis B virus (HBV) x gene and protein in the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). HBx gene is often included, and remains functionally active, in the HBV DNA that is frequently integrated into cellular DNA during hepatocellular carcinogenesis. HBx protein promotes cell cycle progression, inactivates negative growth regulators, and binds to and inhibits the expression of p53 tumour suppressor gene and other tumour suppressor genes and senescence-related factors. However, the molecular mechanisms responsible for HBx protein-induced HCC remain uncertain. Only some of the more fully documented or more recently recognised mechanisms are reviewed. During recent years evidence has accumulated that HBx protein modulates transcription of methyl transferases, causing regional hypermethylation of DNA that results in silencing of tumour suppressor genes, or global hypomethylation that results in chromosomal instability, thereby playing a role in hepatocarcinogenesis. HBx protein has both anti-apoptotic and pro-apoptotic actions, apparently contradictory effects that have yet to be explained. Particularly important among the anti-apoptotic properties is inhibition of p53. Recent experimental observations suggest that HBx protein may increase the expression of TERT and telomerase activity, prolonging the life-span of hepatocytes and contributing to malignant transformation. The protein also interferes with nucleotide excision repair through both p53-dependent and p53- independent mechanisms. Carboxy-terminal truncated HBx protein loses its inhibitory effects on cell proliferation and pro-apoptotic properties, and it may enhance the protein's ability to transform oncogenes. Dysregulation of IGF-II enhances proliferation and anti-apoptotic effects of oncogenes, resulting in uncontrolled cell growth.
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PMID:Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma. 2119 26

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer mortality. Prognosis of this disease largely depends on its stage. An Enlarged liver, due to dysplasia, may be a critical point in the multi-step progression to HCC. The mechanism underlying hepatomegaly in human and mouse models are poorly understood. We previously reported we observed enlarged liver in hepatitis B virus X protein (HBx) expressing mice (HBx mice). Here we identify the critical role of HBx induced IGF-II in hepatomegaly in mice and abnormal cell growth in human hepatoma cells. We found that HBx induced IGF-II is essential to induce epithelial-mesenchymal transition (EMT) through loss of E-cadherin. In mouse liver, loss of E-cadherin was mediated by post-translational regulation, at least in part, by protease and SUMOylation not by transcriptional regulation. In contrast, in hepatoma cell line (HepG2 cells) Akt signal pathway controls the mRNA expression level of EMT-related transcription factors, especially Twist, in addition to post- translational modification through SUMOylation. Thus, IGF-II-mediated loss of E-cadherin is central in developing hepatomegaly in mice and abnormal cell growth in the hepatoma cell line. HBx induced IGF-II represents a potential biomarker, which is also a therapeutic target in HCC.
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PMID:IGF-II induced by hepatitis B virus X protein regulates EMT via SUMO mediated loss of E-cadherin in mice. 2748 70