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)

In the present study we investigated some of the physicochemical properties of macrophage-activating factor(s) (MAF) produced by the tumor-immune Lyt-1+2- T cell subset. Supernatant from mixed culture of spleen and lymph node cells, obtained from C3H/HeN mice immunized with syngeneic MH134 hepatoma or MCH-1-A1 fibrosarcoma, with the corresponding tumor cells exhibited the capability of activating peritoneal exudate macrophages to exert their cytostatic and cytolytic activities on tumor cells. Such MAF production was abolished by treatment of tumor-immune spleen and lymph node cells with anti-Thy-1.2 or anti-Lyt-1.1 antibody plus complement (C) before culturing. Anti-Lyt-2.1 and/or anti-asialo GM1 plus C treatment, however, had only marginal effect on the generation of MAF by these cells, despite the complete disappearance of natural killer (NK) cell activity of spleen and lymph node cells after the treatment with anti-asialo GM1 plus C. Thus, the tumor-specific Lyt-1+2- T cell subset could fulfill a crucial role in generating MAF without the support of NK cells. The MAF activity was heat, acid, and trypsin sensitive. On Sephacryl S-300 column, MAF activity was eluated in a broad single peak around a molecular weight (m.w.) of 70,000 daltons. Antiviral activity was detected in the concentrated pool of MAF-containing fractions from Sephacryl S-300. Gel permeation analysis using HPLC also showed a coincident peak of MAF and antiviral activities at a m.w. of approximately 70,000 daltons. In addition, MAF activity was almost completely neutralized by incubation with rabbit antiserum against recombinant murine gamma-interferon (IFN gamma). Taken together, these results indicate that MAF generated by tumor-immune Lyt-1+2- T cell subset is closely related to IFN gamma.
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PMID:Studies on macrophage-activating factor (MAF) in antitumor immune responses. II. Molecular characterization of MAF produced by the tumor-immune Lyt-1+2- T cell subset. 311 13

Interleukin 6 (IL6) is the new definition of a group of cytokines previously named according to their biological activity, e.g. B cell stimulatory factor 2 (BSF-2), hybridoma plasmocytoma-growth factor (HGF), interferon-beta 2 (IFN-beta 2), hepatocyte stimulating factor (HSF). It has recently been suggested that IL6 may represent the major mediator of acute-phase protein response whereas IL1 beta and TNF-alpha could play a minor role. We compared the effect of the three cytokines on hepatic protein synthesis by performing in vitro as well as in vivo experiments. Human hepatoma cells (PLC/PRF5) were exposed to each cytokine separately for 20 h, and the effect was then studied at the protein and RNA level. All three cytokines reduced albumin and increased C3 and ceruloplasmin biosynthesis. The cytokines induced the same effect at the RNA level indicating that the modulation was pretranslational. The effect of the cytokines was specific since actin gene expression was not changed; furthermore the effect was blocked by specific antibodies against the cytokines. The effect of the single cytokines was dose and time dependent, and quantitatively comparable. None of the cytokines was able to alter alpha 1-anti-trypsin synthesis. In vivo experiments with mice showed that IL1 beta and TNF-alpha both induce serum amyloid A (SAA) mRNA in the mouse liver and increase factor B (Bf) gene expression. Human recombinant IL6 induced SAA gene expression and it also had a weak positive effect on Bf gene expression after i.p. injection. These data demonstrate that the three cytokines studied are quantitatively and qualitatively comparable, and that all three are probably involved in acute-phase protein response.
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PMID:Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. 313 37

The relative abilities of insulin and the phorbol ester tumor promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA) to lead to the phosphorylation of ribosomal protein S6 in vivo were compared in a Reuber H35 hepatoma cell line shown previously to be highly responsive to these agents. In quiescent (serum-starved) cultures of H35 cells incubated with 32Pi, both insulin (10(-7) M) and TPA (1.6 X 10(-6) M) resulted in the marked phosphorylation of S6 compared to the unstimulated cultures as evidenced by an increase in radioactivity associated with S6 and by a corresponding shift in the mobility of phosphorylated S6 during two-dimensional electrophoresis. Following incubation with insulin or TPA, greater than 95% of the phosphate was in derivatives containing four to five phosphate groups. The site-specific phosphorylation of S6 in response to both optimal and suboptimal concentrations of insulin and/or TPA was examined by two-dimensional peptide mapping of the trypsin-digested ribosomal protein S6. The tryptic phosphopeptides of S6 obtained following treatment of the H35 cells with insulin and/or TPA were identical and were the same phosphopeptides as those observed previously following the phosphorylation in vitro of 40 S ribosomal subunits from reticulocytes with purified protease-activated kinase II (Perisic, O., and Traugh, J. A. (1983) J. Biol. Chem. 258, 13998-14002).
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PMID:Insulin- and phorbol ester-stimulated phosphorylation of ribosomal protein S6. 315 32

We used a conjugate of transferrin and horseradish peroxidase (Tf/HRP) to label the intracellular transferrin receptor route in the human hepatoma cell line HepG2. The recycling kinetics of [125I]Tf/HRP were similar to those of unmodified [125I]Tf, implying identical routes for both ligands. 3,3'Diaminobenzidine (DAB)-cytochemistry was performed on post-nuclear supernatants of homogenates of cells which were incubated with both Tf/HRP and [125I]Tf, and caused two different effects: (a) the equilibrium density of [125I]Tf containing microsomes in a Percoll density gradient was increased, and (b) the amount of immunoprecipitable [125I]Tf from density-shifted lysed microsomes was only 20% of that of nonDAB treated microsomes. The whole biosynthetic route of alpha 1-antitrypsin (AT), a typical secretory glycoprotein in HepG2 cells, was labeled during a 60-min incubation with [35S]methionine. DAB cytochemistry was performed on post-nuclear supernatants of homogenates of cells which were also incubated with Tf/HRP. DAB cytochemistry caused approximately 40% of microsome-associated "complex" glycosylated [35S]alpha 1-antitrypsin ([35S]c-AT) to shift in a Percoll density gradient. Only part of the density shifted [35S]c-AT could be recovered by immunoprecipitation. A maximum effect was measured already after 10 min of Tf/HRP uptake. The density distribution of the "high mannose" glycosylated form of 35S-alpha 1-anti-trypsin [( 35S]hm-AT) was not affected by Tf/HRP. If in addition to Tf/HRP also an excess of non-conjugated transferrin was present in the medium, [35S]c-AT was not accessible for Tf/HRP, showing the involvement of the transferrin receptor (TfR) in the process. Furthermore, we show that if Tf/HRP and [35S]c-AT were located in different vesicles, the density distribution of [35S]c-AT was not affected by DAB-cytochemistry. Pulse-labeling with [35S]methionine was used to show that [35S]c-AT became accessible to endocytosed Tf/HRP minutes after acquirement of the complex configuration. A common intracellular localization of endocytosed Tf/HRP and secretory protein could be confirmed by immuno-electron microscopy: cryosections labeled with anti-albumin (protein A-colloidal gold) as well as DAB reaction product showed double-labeling in the trans-Golgi reticulum.
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PMID:The pathways of endocytosed transferrin and secretory protein are connected in the trans-Golgi reticulum. 326 Feb 38

T Kininogen and High Molecular Weight Kininogen were characterized in the cell culture medium of Fao cells, a highly differentiated cell line derived from the Reuber H35 rat hepatoma. Immunoreactive T Kininogen and High Molecular Weight Kininogen identified by direct and specific RIAs were indistinguishable from standard kininogens. Immunoreactive T Kininogen was further identified by HPLC analysis of T kinin released after trypsin hydrolysis of the cell culture medium. The basal release rate of T kininogen was ten-fold higher than that of High Molecular Weight Kininogen. T Kininogen was not stored within the cells contrary to High Molecular Weight Kininogen. The production of the two kininogens in the cell medium was stimulated by dexamethasone up to five times in a dose-dependent manner. The specific antiglucocorticoid compound RU 38486 did not alter the basal rate of kininogen release by Fao cells, but abolished the stimulation by dexamethasone, indicating that dexamethasone exerts a true glucocorticoid type effect.
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PMID:Effect of dexamethasone on kininogen production by a rat hepatoma cell line. 340 90

Immunocytochemical staining of tryptophan 2, 3-dioxygenase (TO, EC 1.13.11.11), which is a typical marker of terminal differentiation of rat hepatocytes, showed that TO was expressed as early as the first day after birth by a few hepatocytes, and that the number of hepatocytes expressing TO gradually increased during early neonatal development. In contrast, immature hepatocytes grew actively in culture even without growth factors and serum, showing a labelling index with [3H]thymidine of over 80% just after birth, but their ability to show autonomous growth decreased rapidly during postnatal development. Double staining of hepatocytes from neonatal rats indicated that hepatocytes showing DNA synthesis were distinct from those expressing TO, suggesting that immature cells proliferate, but do not express TO, and then become fully differentiated expressing TO, but not proliferating any more. On the contrary, albumin was fully expressed in most hepatocytes of 0-day-old rats, in which the hepatocytes were still growing. When immature hepatocytes without TO from 0-day-old rats were cultured on a feeder layer of adult rat hepatocytes for 3.5 days, their expression of TO increased rapidly to almost the adult level (over 70% of the cells became TO-positive). Conversely, this feeder layer strongly inhibited autonomous growth of the neonatal rat hepatocytes. Other feeder layers, such as non-parenchymal liver cells of adult rats, Reuber hepatoma, and Swiss 3T3 fibroblasts, had no effect on the reciprocal changes of terminal differentiation and autonomous growth of immature rat hepatocytes. A feeder layer of dead adult rat hepatocytes, obtained by treating the cells with cytosine arabinoside for 24 h or drying them at 37 degrees C, had the same ability as a feeder layer of living cells to induce cytodifferentiation of immature cells. When the dead feeder layer was treated with 1 N HCl or digested with 0.1% trypsin, its ability to induce differentiation was almost completely lost. These results suggest that a cell surface component of adult rat hepatocytes, probably an acid-labile protein, controls terminal differentiation and growth of immature hepatocytes.
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PMID:In vitro induction of terminal differentiation of neonatal rat hepatocytes by direct contact with adult rat hepatocytes [corrected]. 348 31

Treatment of H4 hepatoma cells with the lectin wheat germ agglutinin (WGA) in the concentration range of 10-25 micrograms/ml increased 125I-insulin binding fivefold as compared to control binding in untreated cells. The increased insulin binding was rapid, readily reversible, and correlated with a 10-fold increase in the binding affinity of the receptor for insulin. Kinetic studies indicate that this increased affinity resulted from a decrease in the dissociation rate. The effect was specifically mediated by the lectin since it was reversed by simultaneous incubation with the monosaccharide N-acetyl-D-glucosamine (50 mM) or the disaccharide N,N'-diacetylchitobiose (1 mM). The WGA-mediated increase in insulin binding was not caused by inhibited insulin degradation. While WGA (5 micrograms/ml) mimicked insulin to induce stimulated uptake of [3H]aminoisobutyrate, the lectin failed to enhance the biological sensitivity of H4 hepatoma cells to insulin. At higher concentrations of WGA (125 micrograms/ml), interference with the insulin-mediated response was observed. Trypsin treatment of H4 hepatoma cells prior to measuring binding of 125I-insulin in the presence of increasing concentrations of native insulin, led to a leftward shift of the competition curve, indicating an increased affinity of the receptor. No further increase was observed when the trypsin-treated cells were subsequently exposed to WGA. These results suggest that trypsin treatment and WGA exposure may increase the affinity of the receptor by a similar mechanism. The results are consistent with the concept that WGA and trypsin decrease interaction between insulin binding and receptor affinity regulating components in the plasma membrane, leading to an increase in the affinity of the receptor for insulin.
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PMID:Insulin receptor regulation in minimal deviation hepatoma cell line. 352 5

A wide variety of agents are shown to mimic insulin action and inhibit rates of intracellular protein degradation in H35 hepatoma cells. For oxidizing agents such as NaNO2, H2O2 and oxidized glutathione, inhibition of protein breakdown is reversed by adding catalase. Phenylhydrazine behaves like an oxidant and mimics insulin action in a manner potentiated by superoxide dismutase and reversed by catalase. Similarly the effect of insulin itself is increased by superoxide dismutase and reduced by catalase. Sulfhydryl reagents also mimic insulin action: inhibition of protein breakdown is seen following addition of 2-mercaptoethanol or a brief pre-treatment with N-ethylmaleimide or iodoacetate. Mild pre-treatment with trypsin also inhibits subsequent rates of protein breakdown. A model is proposed suggesting that these insulinomimetic actions involve a common mechanism which links the generation of active oxygen species through the redox potential of the cell to the activation of a proteinase.
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PMID:The effect of insulinomimetic agents on protein degradation in H35 hepatoma cells. 353 45

The migration of ascites and cultured hepatoma cells, AH109A of rat (Donryu) origin and MH134 of mouse (C3H), was enhanced by collagen degradation products (CDP) in vitro using the modified Boyden chamber, but not by collagen. Both tumor cells demonstrated somewhat increased motility in the presence of CDP regardless of whether or not there was a gradient present, but the maximum response was seen in the presence of a gradient. MH134 cells responded more effectively to CDP than AH109A cells and showed similar migratory responses to type I and IV collagen degradation products (CDP-I and -IV). Synthetic di- or tripeptides containing hydroxyproline were less chemotactic for MH134 cells than CDP-I and -IV. Both proteases (collagenase and trypsin) and MH134 cells could degrade a collagen substrate and generate CDP. These findings suggest that CDP released during the process of invasion may play a role in the migration of tumor cells and consequent formation of metastases.
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PMID:Enhanced migration of tumor cells in response to collagen degradation products and tumor cell collagenolytic activity. 353 92

A growth factor has been isolated from HTC-SR rat hepatoma tissue culture cells which specifically stimulates DNA synthesis and cell proliferation of the HTC cells that produce it. The factor can be isolated from HTC cell conditioned medium or from an HTC cell extract. This autocrine factor has been purified 640-fold from a postmicrosomal supernatant by successive steps, involving ethanol precipitation, heating at 80 degrees C for 10 min, chromatography on a DEAE Bio-Gel A column, and chromatography on a heparin-sepharose affinity column. The major peak of activity eluted from the heparin column migrates as a single band on SDS-PAGE with an apparent Mr of 60,000. The factor is resistant to acid, heat, and neuraminidase but sensitive to trypsin, papain, and protease. The autocrine nature of the factor is indicated by the finding that several other types of cells do not respond with increased DNA synthesis. Mouse L-cells, BHK cells, Novikoff hepatoma cells, hepatocytes in primary culture, and an epithelial-like rat liver-derived cell line (Clone 9) were tested, and none of the cells could be stimulated. Small amounts of the factor could be extracted from the Clone 9 cells, however. This material had the same physical and purification properties as the factor extracted from HTC cells, but it did not stimulate DNA synthesis in Clone 9 cells, only in HTC cells. Addition of the factor resulted in an almost immediate stimulation of DNA synthesis in a proliferating HTC cell population. When the factor was added together with [3H]thymidine for 2 h, a significant stimulation of DNA synthesis was observed, provided the addition was made between 18 and 48 h after the cells had been plated. Autoradiographic studies indicated that the factor both accelerates DNA synthesis in cells already making DNA and increases the number of cells entering the S period. The stimulation of DNA synthesis was completely inhibited by 10 mM hydroxyurea, whether the factor was present for 2, 24, or 48 h in the culture. A significant increase in cell number due to addition of the factor was also observed. This accelerated proliferation was detectable only after the cells had been in culture for at least 48 h with the factor present.
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PMID:Isolation of an autocrine growth factor from hepatoma HTC-SR cells. 358 47


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