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

A test of the mitogenic activity of greater than 40 purified and crude sources of hormones and growth factors revealed that epidermal growth factor, high density lipoprotein, an extract of bovine pituitary, hypothalamus, or whole brain, and the medium conditioned by differentiated human hepatoma cells were mitogenic for cultured endothelial cells derived from human umbilical vein. The four active agents combined with an improved nutrient medium and a collagen- or fibronectin-coated culture surface supported the growth of the endothelial cell population at a rate of 0.70-0.80 generations per day at both low and high cell densities in serum-free medium. The brain-derived activity exhibited properties reported by Maciag et al. [Maciag, T., Hoover, A. & Weinstein, R. (1982) J. Biol. Chem. 257, 5333-5336] and Gordon et al. [Gordon, P. B., Sussman, I. I. & Hatcher, V. B. (1983) In Vitro 19, 661-671]. The liver cell-derived activity was a specific product of differentiated hepatoma cells. The medium from HeLa cells, relatively undifferentiated rat liver cell lines, and human fibroblasts was inactive. Purified plasma proteins of liver origin could not substitute for the hepatoma cell-conditioned medium. The hepatoma cell-derived activity was non-dialyzable, heat-labile, stable between pH 4 to 11, inactivated by trypsin and mercaptoethanol treatment, and stable after treatment with 6 M urea and phenylmethylsulfonyl fluoride. The results provide a simplified model for elucidation of the endocrinology of human endothelial cell growth, function, and aging. We suggest an endocrine role of both the nervous system and liver in the regeneration of endothelial cells.
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PMID:Brain- and liver cell-derived factors are required for growth of human endothelial cells in serum-free culture. 633 82

From rat-liver and ascites-hepatoma chromatins, NaCl-soluble fractions were prepared. The 0.35 M NaCl-soluble fraction from the hepatoma (AH) chromatin contained much non-histone protein of high-molecular weight, compared with the fraction from the rat-liver (RL) chromatin. The 0.35 M NaCl-insoluble, but 2 M NaCl/5 M urea-soluble fraction was composed mainly of 5 classes of histones. These histones were quantitatively not different between AH and RL chromatins. However, H1 histone was rather protease-resistant in AH chromatin, but not in RL chromatin. The proteolytic capacity was also lower in AH chromatin. In addition, in the micrococcal-nuclease digest of AH nuclei, the oligonucleosomes were considerably retained even by long-time digestion, but not in that of RL nuclei.
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PMID:Resistance of H1 histone to proteolytic attack in chromatin from rat-ascites hepatoma. 636 Mar 39

When freshly-dispersed rat hepatocytes are maintained in primary monolayer cultures, they quickly lose their capacity to synthesize the urea cycle enzyme, carbamoyl-phosphate synthase. The ability to synthesize many other proteins, e.g., serum proteins including albumin, is retained. After an initial recovery period following cell isolation (24-48 h), glucagon is able to restore the ability of cultured hepatocytes to make carbamoyl-phosphate synthase. mRNA encoding the enzyme is about 4-times higher in hepatocytes maintained for 48 h in the presence of glucagon compared to hepatocytes without the hormone, as judged by in vitro translational assays. The level of carbamoyl-phosphate synthase activity expressed in transformed hepatocytes is unique to each hepatoma. Here we show that Morris hepatoma 5123D has retained such expression, and actively synthesizes the enzyme when 5123D cells are placed in monolayer cultures. Unlike normal hepatocytes, however, synthesis continues uninterrupted at a high level whether or not glucagon is present. 5123D has higher levels of translatable carbamoyl-phosphate synthase mRNA than normal liver.
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PMID:Effects of glucagon on biosynthesis of the mitochondrial enzyme, carbamoyl-phosphate synthase I, in primary hepatocytes and Morris hepatoma 5123D. 661 42

We present here the results of investigations conducted by ourselves and others on the regulation of the expression of genes encoding the enzymes of the mammalian urea cycle as manifest in cultured cells of both hepatic and extrahepatic origin. Upon consideration of the recently discovered discrete non-hepatic arginase genetic locus in man and our consequent hypothesis that the form of arginase thus transcribed in such extrahepatic cells functions principally in providing ornithine for protein anabolism and polyamine biosynthesis, rather than in detoxifying ammonia through urea formation, we have chosen instead to study permanent cell lines that are derived from liver and continue to perform a variety of hepatic functions in culture as experimental models for probing the molecular mechanisms underlying the control of ureagenesis within the mature liver cell. Of two such arginase-positive rat-hepatoma lines, we have characterized extensively in one (H4-II-E-C3) the mode of action of glucocorticoids in augmenting the cellular levels of this enzyme as well as of argininosuccinate synthetase. To this end, we have recently demonstrated that these stimulations are both mediated by binding of the hormones to classical cytoplasmic steroid receptors in a specific and saturable fashion and have thus concluded that the H4-II-E-C3 line will provide a suitable cell culture system for subsequent more detailed experiments from which the information garnered will continue to be relevant to the ureagenic pathway as modulated in the differentiated hepatocyte in vivo.
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PMID:Regulation of expression of genes for enzymes of the mammalian urea cycle in permanent cell-culture lines of hepatic and non-hepatic origin. 662 18

We have examined and characterized the regulation by glucocorticoids of the levels of arginase and argininosuccinate synthetase in two rat hepatoma cell lines (H4-II-E-C3 and MH1C1). Hydrocortisone elevates the activity of both enzymes in a time- and dose-dependent fashion. This effect was blunted markedly by small amounts of ethanol (0.1 to 0.9% [v/v]) and blocked substantially by a high molar excess of the "anti-inducer" steroid fluoxymesterone. The other "optimal" inducers dexamethasone and corticosterone were as effective as hydrocortisone in elevating the levels of these enzymes at saturating concentrations. Inhibition of these stimulations by cycloheximide indicated that ongoing cellular protein synthesis was required for both effects, and the admixture of extracts from fully stimulated and basal cells gave no evidence for the existence of direct inhibitors or activators of either enzyme. The results corroborate findings from earlier whole-animal studies and provide evidence for the following conclusions. (i) This stimulation by hydrocortisone of urea-cycle enzymes in the cultured hepatoma cells is mediated by a classical glucocorticoid mechanism involving initial binding to specific cytoplasmic steroid receptors and the eventual accumulation of new enzyme molecules. (ii) These cell lines thus constitute valid experimental models for use in further detailed studies on the molecular mechanism(s) through which glucocorticoids and intermediary metabolites effect a selective modulation of arginase and argininosuccinate-synthetase gene expression in the differentiated mammalian liver.
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PMID:Regulation of glucocorticoids of arginase and argininosuccinate synthetase in cultured rat hepatoma cells. 706 21

The transport of cationic amino acids across the plasma membrane of several hepatoma cell lines (HTC, McA-RH7777, McA-RH8994, characterized in detail in the first of these) occurs by a saturable mediation which we designate System y+. Identical experiments with cultured rat hepatocytes usually yield nonsaturating kinetic cures. Accordingly, System y+ contributes little, if at all, to the flux of cationic amino acids in these cells. Analogous to the findings with other tissues, the influx of cationic amino acids into hepatoma cells is Na+- and pH-independent, stereoselective, inhibitable by neutral amino acids in the presence of Na+, and stimulated by cationic amino acids inside of the cell. This final characteristic, called trans-stimulation, is a kinetic property associated with the cationic amino acid transport system in all other eukaryotic cell types studied and provides evidence supporting the operation of System y+. Influx of cationic amino acids into hepatocytes displays no significant trans-stimulation which strongly suggests the absence or alteration of System y+ in this cell. Transport of arginine into hepatocytes is the rate-limiting step for its hydrolysis by arginase. Therefore, the relatively low influx of this amino acid under physiologic conditions due to the attenuation of System y+ activity apparently provides a kinetic barrier separating the extrahepatic arginine pool from the active cytoplasmic enzymes of the hepatic urea cycle. Such a separation may be required for the nutrition and survival of extrahepatic tissues.
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PMID:Cationic amino acid transport into cultured animal cells. II. Transport system barely perceptible in ordinary hepatocytes, but active in hepatoma cell lines. 706 44

A protein showing lower electrophoretic mobility in acidic urea polyacrylamide gels than did the usual histone H1 subfractions has been detected among the H1 histones extracted from chromatin of a transplantable hamster hepatoma, originally induced by Kirkman and Robbins. It was proved to be a true H1 histone subfraction. It differs from the remaining ones by the total chain length, amino acid composition, and isoelectric point value. It is not a phosphorylated or phosphoribosylated metabolic form of another subfraction. Its proteolytic degradation products (obtained by thrombin and trypsin digestion) closely resembled those obtained from other H1 subfractions. The investigated hepatoma seems to provide an interesting model of neoplastic cells showing a distinct difference in histone composition from the homologous normal tissue.
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PMID:A low-electrophoretic-mobility H1 histone subfraction from Kirkman-Robbins hamster hepatoma. 723 41

An enzymatic activation of N-methyl-N-nitrose urea (MNU) was studied in microsomes, isolated from hepatoma 22a ascites cells, using a procedure which enabled to reveal the MNU enzymatic activation in mice liver microsomes. The MNU metabolic activation was not observed in hepatoma cell microsomes; at the same time, the MNU activation occurred when the cells were incubated under conditions of a suspension culture. The enzymes, participating in metabolic activation of MNU, were apparently arranged at the surface of the tumoral cells. Alkylation of MNU macromolecules was shown to be a two-step process. At the first step alkylation was due to spontaneous degradation of MNU and at the second step it was responsible for formation of active products as a result of MNU metabolic activation. MNU appears to induce synthesis of enzymes required of its metabolic activation in hepatoma 22a cells within 30 min.
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PMID:[Metabolic activation of N-methyl-N-nitrosourea in tumor cells]. 728 82

The cell surface structure of AH-66 hepatoma ascites cells was examined by extracting the intact AH-66 cells with urea and analyzing the extracted proteins. When AH-66 cells were suspended in 1 M urea, material composed of approximately 90% protein and 10% carbohydrate was released. The extracted proteins amounted to about 3% of the total cell proteins and were composed of approximately 30 species as analyzed by sodium dodecyl sulfate gel electrophoresis. The major bands had apparent molecular weights of 84,000 and 50,000--60,000 on the gel. In marked contrast to chick embryo fibroblasts, the extracted proteins contained no components stainable with periodic acid-Schiff reagent. Lactoperoxidase-catalyzed iodination of intact AH-66 cells showed that most of the urea-extractable proteins were located on the outer surface of the plasma membranes of AH-66 cells. It was also found that there are two integral proteins exposed on the outer surface of the plasma membranes of AH-66 cells; one is a major glycoprotein (with a molecular weight of 165,000) and the other is a periodate-Schiff-negative protein with a molecular weight of 130,000.
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PMID:Cell surface proteins extracted with urea from AH-66 hepatoma ascites cells. 735 22

Proteoglycan (heparan sulfate-protein conjugate) was solubilized with 8 M urea from rat liver plasma membranes after enzymic (RNAase, neuraminidase) treatments and extensively purified by chromatography and gel filtration. The final products gave an average ratio of hexuronate to protein (weight) of approx. 1.5, contained hexosamine equimolar to hexuronate and were sensitive to beta-elimination (the molecular weight being reduced from 20 . 10(4) to 3 . 10(4) (gel filtration)). The proteoglycan fraction, when added to trypsinized and untrypsinized ascites hepatoma (AH-130F(N)) cells, inhibited the concanavalin A-mediated agglutination of the cells. However, the alkali-treated proteoglycan (beta-elimination) or acid mucopolysaccharide fraction prepared from liver plasma membranes by papain digestion were less effective, and a reference preparation of heparan sulfate was almost ineffective. It was confirmed that significant amounts of proteoglycan labelled with 35SO4(2-) were firmly bound to or taken up by the trypsinized ascites hepatoma cells. These results together with the sensitization of lectin-mediated agglutination by mild protease treatment of cells suggest that cell surface proteoglycans may act as a negative modulator in the lectin-mediated agglutination of cells.
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PMID:Cell surface proteoglycans as a negative modulator in concanavalin A-mediated agglutination of hepatoma cells. 739 52


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