Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Two-tumour-cell-aggregation factors derived from rat ascites hepatoma cells had different antigenicity; one, with a strong potency, was not absorbed by immunoadsorbent chromatography with anti-rat serum antibody and the other, with a weak potency, was. The unabsorbed factor possessed mitogenic activity on lymphocytes from thymus, spleen and lymph node of rats; its effect was compared with that of lectins (including phytohaemagglutinin, concanavalin A, pokeweed mitogen, lipopolysaccharide and soybean agglutinin) in the form of increased DNA and protein synthesis, blast transformation and mitosis. In the use of anti-thymocyte serum-resistant spleen cells and hydrocortisone-resistant thymocytes, the cells stimulated were assumed to be T-lymphocytes. DNA synthesis by this factor seemed to be characterized by a 2-step increase, suggesting the presence of 2 subpopulations of the cells activated, especially thymocytes. At high concentration this factor induced no depression of DNA synthesis. Favourable cell density for the response to this factor was 2-8 X 10(6) cells. Its effect was not influenced by treatment of the cells with neuraminidase.
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PMID:Rat lymphocyte mitogenesis by aggregation factor from rat ascites hepatoma cell surface. 35 20

Metalloproteinases and their specific inhibitors, believed to play a role in extracellular matrix metabolism, are regulated by inflammatory cytokines. Here we have addressed the question of whether liver, the major site of synthesis of plasma proteinase inhibitors, is also capable of synthesizing the tissue inhibitor of metalloproteinase-1 (TIMP-1). We show at mRNA and protein levels that TIMP-1 is expressed in differentiated human hepatoma cells (HepG2) and that its synthesis is up-regulated by interleukin-6 (IL-6), transforming growth factor beta 1 and phorbol 12-myristate 13-acetate. The physiological role of this phenomenon is underlined by the fact that lipopolysaccharide administration into rats in vivo, as well as IL-6-stimulation of rat hepatocytes in primary culture, also leads to an increase of TIMP-1 mRNA in liver cells.
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PMID:Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in human hepatoma cells (HepG2). Up-regulation by interleukin-6 and transforming growth factor beta 1. 133 Jul 2

The effect of conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.
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PMID:Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro. 137 63

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.
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PMID:BRM activities of low-toxic Bordetella pertussis lipopolysaccharides. 141 7

The hepatic production of the acute phase proteins in response to inflammatory cytokines, and the interaction of corticosteroids within this response, has been the subject of considerable recent research. In this study we have examined the effects of the corticosteroid prednisolone on the production of IL-1 alpha and IL-1 beta by lipopolysaccharide (LPS)-stimulated monocytes, and the ability of the monocyte conditioned media (MOCM) obtained under these conditions to induce human hepatoma HepG2 cells to produce serum amyloid A (SAA) and C-reactive protein (CRP). We also examined the production of SAA and CRP by HepG2 cells exposed to different combinations and concentrations of recombinant human (rh) IL-1 alpha, rhIL-1 beta, rhIL-6, recombinant human tumour necrosis factor-alpha (rhTNF-alpha) and prednisolone. The findings indicate: (i) prednisolone substantially inhibits the production of both IL-1 alpha and IL-1 beta by LPS-stimulated monocytes. The MOCM from prednisolone-treated monocytes induced less SAA and CRP production by HepG2 cells; (ii) IL-1 alpha and IL-1 beta both induced CRP and SAA synthesis by HepG2 cells, but only in the presence of IL-6. IL-1 beta was the more potent inducer for SAA production, but for CRP production IL-1 alpha and IL-1 beta were equivalent; (iii) prednisolone enhances the production of SAA by HepG2 cells, but does not enhance the production of CRP; (iv) TNF-alpha in the presence or absence of IL-6 and/or prednisolone did not induce the production of SAA or CRP by HepG2 cells. These findings offer a tenable solution to a disparate production of SAA compared with CRP in corticosteroid-treated cystic fibrosis (CF) patients.
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PMID:Production of serum amyloid A and C-reactive protein by HepG2 cells stimulated with combinations of cytokines or monocyte conditioned media: the effects of prednisolone. 142 89

The induction of proteolytic enzymes is an important mechanism in the migration of monocytes into tissues and body fluids. The monocytic cell line THP-1 was used as a model system to study the production of a particular gelatinase. Upon stimulation with phorbol myristate acetate (PMA) the cells differentiated to the adherent phenotype and produced significant amounts of a 96-kD gelatinase in a dose-dependent way. The secretion rate was maximal between 12 and 24 h after induction. Study of gelatinase mRNA steady state levels showed that the synthesis of THP-1 gelatinase is regulated by PMA at transcriptional or posttranscriptional levels. Stimulation of signal transduction pathways with other substances, including calcium ionophore A 23187, dibutyryl cyclic AMP, and dexamethasone, were ineffective in inducing gelatinase mRNA or enzyme activity. However, THP-1 cells were responsive to the cytokine interleukin (IL)-1 beta, to bacterial lipopolysaccharide (LPS), and the lectin concanavalin A (Con A), the kinetics of gelatinase induction being similar to those of induction by PMA. The THP-1 cells did not synthesize and/or secrete detectable levels of IL-6 after stimulation with PMA, Con A, LPS, or IL-1 beta. The 96-kD monocytic THP-1 gelatinase was shown to be a neutral metalloproteinase that cross-reacted with hepatoma-derived and neutrophil gelatinases in immunoprecipitation experiments. The active enzyme produced by THP-1 cells consistently showed, however, a molecular mass different from that of normal granulocyte-, monocyte-, and tumor cell-derived gelatinases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers. 165 55

Communication circuits operating between activated monocytes/macrophages and adjacent hepatocytes in the liver effect important alterations in hepatocyte function. We demonstrate here that primary human hepatocytes and hepatoma cells are able to function as effector cells in the recruitment of inflammatory cells in hepatic disease and inflammatory states by synthesizing a neutrophil/lymphocyte chemotactic factor, interleukin-8. We have further investigated the possibility that endogenous factors elaborated by activated peripheral blood monocytes and Kupffer cells in the liver are mediators of hepatocyte-derived interleukin-8 expression. Twenty-four-hour conditioned medium from lipopolysaccharide-stimulated peripheral blood monocytes and nonparenchymal human liver cells enriched for Kupffer cells induced a time-dependent increase in interleukin-8 messenger RNA levels in SK-hepatoma cells over a 24-hr period, similar to that seen for tumor necrosis factor-alpha or interleukin-1 beta induction of interleukin-8 in primary hepatocytes. Exogenously added lipopolysaccharide or recombinant interleukin-6 had no effect. Cell-associated interleukin-8 antigen was present in SK-hepatoma and primary hepatocytes that had been incubated with macrophage-conditioned medium, tumor necrosis factor or interleukin-1 beta. Similarly, neutrophil chemotactic activity was secreted by SK-hepatoma cells, a significant proportion of which could be blocked with interleukin-8--specific antiserum. Preincubation of macrophage-conditioned medium with neutralizing antibodies to tumor necrosis factor-alpha or interleukin-1 beta reduced its interleukin-8 messenger RNA-inducing capacity. Exposure of SK-hepatoma to conditioned medium followed by removal of the stimulus resulted in a rapid down-regulation of interleukin-8 messenger RNA to 50% of the maximum level within the first hour. These data suggest that products derived from activated Kupffer cells can modulate hepatoma cells and primary hepatocyte interleukin-8 gene expression. In addition, macrophage/monocyte-derived tumor necrosis factor-alpha and interleukin-1 beta have major roles in the positive regulatory component of this modulation.
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PMID:Kupffer cell-derived cytokines induce the synthesis of a leukocyte chemotactic peptide, interleukin-8, in human hepatoma and primary hepatocyte cultures. 166 18

The major target organ for hepatitis B virus (HBV) is the liver. However, cells other than hepatocytes, including peripheral blood lymphocytes and monocytes, may become infected with HBV. The cell receptor binding site was assigned to the preS(21-47) segment of the HBV envelope protein. HBV receptors were detected on human liver and hepatoma cells, on B lymphocytes, and, as shown here, on monocytes, and T cell lines, activated by Escherichia coli lipopolysaccharide and concanavalin A, respectively. The cell receptors for HBV have not been characterized until now. The detection of HBV receptors and their "activation antigen" characteristic on distinct cells suggested paths for identification of the receptors with already defined cell surface proteins. This search revealed that interleukin 6 contains recognition sites for the preS(21-47) sequence and mediates HBV-cell interactions. Thus, HBV belongs to a group of viruses utilizing cytokines or cytokine receptors for replication and interference with the host immune system.
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PMID:Search for hepatitis B virus cell receptors reveals binding sites for interleukin 6 on the virus envelope protein. 173 12

Nitrate balance and N-nitrosodimethylamine (NDMA) excretion were studied in woodchucks chronically infected with woodchuck hepatitis virus (WHV). Twenty-four-h urinary recovery of a bolus dose of [15N]nitrate was 54 +/- 12% in woodchucks. WHV-infected animals formed 3-fold more nitrate endogenously than did control animals (P less than 0.01). Treatment of WHV-infected animals with Escherichia coli lipopolysaccharide increased nitrate excretion 15-fold, while uninfected animals increased nitrate excretion 4-fold. The endogenous formation of NDMA was higher in WHV-infected woodchucks than in uninfected controls. After administration of L-[15N2]arginine, [15N]nitrate, and [15N]NDMA were detected in urine indicating that arginine is a precursor of biosynthesized nitrate and the hepatocarcinogen NDMA. NDMA probably results from the formation of nitrosating agents during the oxidation of arginine to oxides of nitrogen and citrulline. Woodchucks chronically infected with WHV develop hepatocellular carcinomas with high frequency. Our observations suggest an additional mechanism that may be involved in the pathogenesis of hepatocellular carcinoma associated with chronic WHV infection.
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PMID:Elevated formation of nitrate and N-nitrosodimethylamine in woodchucks (Marmota monax) associated with chronic woodchuck hepatitis virus infection. 185 9

Conditioned medium from human monocyte-macrophages incubated under various conditions was tested for its ability to stimulate fibrinogen mRNA levels in the hepatoma cell line HepG2. Recombinant human interleukin-6 (IL-6) stimulated fibrinogen mRNA levels 4.4-fold over control levels; this response was blocked by an anti-IL-6 antibody. Conditioned medium from 3-day-cultured monocyte-macrophages produced a slight stimulation of fibrinogen synthesis in HepG2 cells which was enhanced when the monocyte-macrophages had been treated with lipopolysaccharide (LPS). This stimulation was blocked by the anti IL-6 antibody. The cytokines, interleukin-1 (IL-1) and tumour necrosis factor (TNF) were also detected in the conditioned medium from the 3-day-cultured monocyte-macrophages. Monocyte-macrophages were cultured for 17 days and then incubated with acetylated low density lipoprotein (AcLDL) for 48 h. Such cells were 'foamy' in appearance and showed a 4-fold increase in apoE mRNA and a 10 to 50-fold increase in apoE secretion. This increase in apoE production was suppressed by almost a third when cells were coincubated with AcLDL and LPS. Conditioned medium from these 17-day-cultured AcLDL-treated human monocyte-macrophages did not stimulate fibrinogen mRNA synthesis in HepG2 cells, nor did the conditioned medium contain detectable levels of cytokines. These results suggest that cytokine production from foam cells in the atherosclerotic lesion is unlikely to be a major contributing factor in determining the elevated fibrinogen levels seen in the plasma of patients with IHD.
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PMID:Cytokine production by cholesterol-loaded human peripheral monocyte-macrophages: the effect on fibrinogen mRNA levels in a hepatoma cell-line (HepG2). 193 38


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