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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, the effects of IFN gamma, TNF alpha and EGF on the expression of HLA class I antigen and the proliferation of human hepatocellular carcinoma-HepG2 cells were investigated. In response to IFN gamma or TNF alpha stimulation, the expression of HLA class I mRNA in HepG2 cells was increased by 2-4 fold. Cell surface HLA class I antigen was also increased, but in comparison, the increase was not as high as HLA class I mRNA expression. This is probably due to the limitation of protein translational and post-translational processing. The enhancing effect of EGF on cell surface HLA class I antigen could be noted but was not very significant. IFN gamma and TNF alpha could also inhibit the proliferation of HepG2 cells. Interestingly, the effect of EGF on the proliferation of HepG2 cells depended on its concentration. At low concentrations, EGF increased cell proliferation in terms of thymidine incorporation. However, if the concentration of EGF was relatively high, it could also exert an inhibitory effect on thymidine incorporation into HepG2 cells. The remarkable morphological alteration was observed when HepG2 cells were exposed to EGF at concentrations higher than 5 ng/ml. This morphological alteration might be associated with the inhibitory effect of EGF at high concentrations on the proliferation of HepG2 cells.
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PMID:Effects of IFN-gamma, TNF-alpha and EGF on the expression of HLA class I antigen and the proliferation of human hepatocellular carcinoma HepG2 cells. 906 49

Persistent infection with hepatitis B virus (HBV) is a leading cause of human liver disease and is strongly associated with hepatocellular carcinoma, one of the most prevalent forms of human cancer. Apoptosis (programmed cell death) is an important mediator of chronic liver disease caused by HBV infection. It is demonstrated that the HBV HBx protein acutely sensitizes cells to apoptotic killing when expressed during viral replication in cultured cells and in transfected cells independently of other HBV genes. Cells that were resistant to apoptotic killing by high doses of tumor necrosis factor alpha (TNFalpha), a cytokine associated with liver damage during HBV infection, were made sensitive to very low doses of TNFalpha by HBx. HBx induced apoptosis by prolonged stimulation of N-Myc and the stress-mediated mitogen-activated-protein kinase kinase 1 (MEKK1) pathway but not by up-regulating TNF receptors. Cell killing was blocked by inhibiting HBx stimulation of N-Myc or mitogen-activated-protein kinase kinase 1 using dominant-interfering forms or by retargeting HBx from the cytoplasm to the nucleus, which prevents HBx activation of cytoplasmic signal transduction cascades. Treatment of cells with a mitogenic growth factor produced by many virus-induced tumors impaired induction of apoptosis by HBx and TNFalpha. These results indicate that HBx might be involved in HBV pathogenesis (liver disease) during virus infection and that enhanced apoptotic killing by HBx and TNFalpha might select for neoplastic hepatocytes that survive by synthesizing mitogenic growth factors.
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PMID:Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. 923 48

Both C-reactive protein (CRP) and serum amyloid A protein (SAA) are determined as an indicator of inflammation and tissue damage. We found that CRP decreased extremely after administration of corticosteroid but SAA did not. However, the mechanism of the CRP decrease by corticosteroid therapy is unclear. In this study we have examined the effects of some immunosuppressive drugs and cytokines on the production of CRP and SAA by human hepatoma cells (HepG 2). A corticosteroid prednisolone did not enhance the production of CRP by HepG 2 cells but enhanced that of SAA, which indicate that prednisolone had no direct effect on the CRP production. Some immunosuppressants other than corticosteroids suppressed the SAA production but had no effect on the CRP production. IL-1 beta induced both CRP and SAA production but only in the co-presence of IL-6. A cytokine IL-6 induced the CRP production in the presence of IL-1 beta, but did not affect the constitutive production of SAA. Then we have examined the cytokine production by monocytes stimulated by lipopolysaccharide. Prednisolone inhibited the production of IL-1 alpha, IL-1 beta, IL-6 and TNF alpha.
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PMID:[Production of inflammatory markers by HepG 2 cells stimulated with monocyte conditioned media: the effects of corticosteroid and other immunosuppressants]. 925 9

The acute phase proteins alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antitrypsin (alpha 1-AT) were shown to inhibit, by a mechanism unidentified to date, the lethality induced by TNF both in normal mice and in mice sensitized with galactosamine. We found that both bovine alpha 1-AGP and human alpha 1-AT also inhibited specifically the induction of apoptosis of hepatocytes by TNF/ galactosamine in vivo. This inhibition is specific for TNF, since apoptosis induced by TNF and actinomycin D was also inhibited, while similar apoptosis of hepatocytes induced by anti-Fas remained unaffected. The observation that these acute phase proteins did not affect the induction by TNF of IL-6, nitric oxide, or serum amyloid P excludes a nonselective inhibition of the TNF-activated pathways. The protection conferred by alpha 1-AGP and alpha 1-AT is presumably indirect, since these proteins did not inhibit TNF/actinomycin D-induced apoptosis in the hepatoma cell lines HepG2 and BWTG3.
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PMID:Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice. 931 55

We previously reported that the number of TNF-alpha-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-alphaRI (p55) and -alphaRII (p75), and IL-10, all of which act as TNF-alpha buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-alphaR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-alphaRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-alphaRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.
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PMID:Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-alpha) receptors in type C chronic liver disease. 932 22

The effects of mast cells (MCs) isolated from rat peritoneal cavity on rat hepatoma cell line (CBRH7919) in vitro were studied with phase contrast microscopy, scanning and transmission electron microscopy. The results showed that different degrees of degeneration were present in all CBRH7919 cells and a few of them exhibited necrosis or disruption when CBRH7919 cells were cocultured with MCs for 24 hours. In situ hybridization demonstrated that the expression of c-myc mRNA in CBRH7919 cells was markedly reduced by MCs. MTT colorimetric assay indicated that the supernatants of MC cultures had suppressive effect on the proliferation of CBRH7919. A monoclonal anti-mouse TNF antibody could decrease the suppressive effect. These results suggest that MCs had anti-tumor effect.
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PMID:[Studies of mast cell-mediated cytotoxicity to hepatoma cells in vitro]. 938 20

To explore the mechanisms of immuno-modulatory activities of bleomycin, we investigated interferon gamma (IFN gamma) mRNA expression, tumor necrosis factor alpha (TNF alpha) production, nitric oxide (NO) production and macrophage tumoricidal activities in rats bearing KDH-8 hepatoma cells, which secreted a large amount of transforming growth factor beta (TGF beta), and these processes in KDH-8 tumor-bearing rats treated with bleomycin. We found that IFN gamma mRNA expression, TNF alpha production, NO production and macrophage cytotoxic activities were lower in the KDH-8-bearing rats than in normal rats. On the other hand, low-dose bleomycin restored the macrophage cytotoxic activities, NO production, IFN gamma mRNA expression and TNF alpha production in the KDH-8-bearing rats. In vitro experiments showed that KDH-8-derived TGF beta decreased the IFN gamma mRNA expression and TNF alpha production in splenocytes, and NO production in peritoneal macrophages. These results suggest that low-dose bleomycin restored the cytokine production and macrophage tumoricidal activities in the KDH-8-bearing rats by decreasing KDH-8-derived TGF beta.
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PMID:Restoration of macrophage tumoricidal activity by bleomycin correlates with the decreased production of transforming growth factor beta in rats bearing KDH-8 hepatoma cells. 939 Jan 97

The clinical outcomes of both hepatitis B and C virus infection are immensely variable, ranging from subclinical, self-limiting infection to end-stage liver disease with hepatocellular carcinoma. Knowledge of the host factors that determine these outcomes is important for the understanding and management of these diseases and may in the future guide rational drug development. Epidemiologic studies have elucidated the role of age (at the time of infection) and sex on disease outcome and the complex role of HIV coinfection has become clearer with time. More recently, investigation of genetic susceptibility to the most adverse outcomes of infection has identified the importance of polymorphisms in the MHC class I and II loci, mannose-binding protein, and the TNF alpha promoter. However, relative to malaria, the study of genetic susceptibility in viral hepatitis is still in its infancy.
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PMID:Host factors in chronic viral hepatitis. 940 70

Regenerating liver, hepatocyte primary cultures and differentiated hepatoma cell lines are widely used to study the proliferation/differentiation/apoptosis equilibrium in liver. In hepatocytes, priming factors (TNF alpha, IL6) target G0/G1 transition while growth factors (HGF, EGF, TGF alpha) control a mid-late G1 restriction point. A characteristic pattern of cdk/cyclin expression is observed in hepatocytes, presumably related to their ability to proliferate a limited number of times and to undergo a reversible differentiation. Interestingly, cell-cell interactions between hepatocytes and liver biliary cells in co-cultures, result in a cell cycle arrest in mid G1 of hepatocytes which are insensitive to mitogens. Apoptosis exists in hepatocytes but is still poorly documented. However, hepatoma cell lines stimulated by TGF beta undergo cell death in a p53-independent pathway. In conclusion, the interplay of growth and apoptosis regulators and cell-cell interactions control the proliferation/differentiation/apoptosis balance which is a specific feature of hepatocytes.
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PMID:Progression through G1 and S phases of adult rat hepatocytes. 955 81

Human hepatocytes infected by hepatitis B virus (HBV) produce the proinflammatory cytokine, tumor necrosis factor (TNF-). In this study, we explored the mechanism of induction of TNF- synthesis by HBV. We found that the stable HBV-transfected hepatoma cell line, 2. 2.15, expressed high-molecular-weight (HMW) TNF- mRNAs, which were absent in the parent HepG2 cells. Treatment of 2.2.15 cells with interferon alfa (IFN-) and/or interleukin-1beta (IL-1beta) reduced both viral gene transcription and TNF- mRNA expression. Transient or stable transfection of hepatocyte-derived cell lines with HBV X protein (HBx) expression vectors induced the production of biologically active TNF-. In these cells, the HBx-induced TNF- was detected both as cell-associated and soluble forms. Luciferase gene-expression assays showed that the TNF- gene promoter contained target sequences for HBx trans-activation within the proximal region of the promoter. These results indicate that the hepatocyte TNF- synthesis induced by HBV is transcriptionally up-regulated by HBx. Thus, HBx may have a role in the induction of the intrahepatic inflammatory processes that take place during acute and chronic hepatitis B.
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PMID:The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene expression in hepatocytes. 975 38


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