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

In human diploid cell strains, the substitution of galactose for glucose as the sole hexose in the medium had no measurable effect on the specific activity of the cell protein for any of the three enzymes of the Leloir pathway. These enzymes are galactokinase, alpha-D-galactose-1-phosphate: UDP glucose uridyl transferase and UDP galactose 4-epimerase. A cell strain from a patient with galactosemia had no detectable activity for the transferase. The substitution of galactose for glucose in the medium of these cells (which has been shown to cause the cells to accumulate galactose-1-phosphate) also failed to affect cellular activity for the three enzymes. Similarly, the three activities failed to respond to the substitution of galactose for glucose in cultures of a rat hepatoma line. Cells of this line have been shown by others to perform a number of the tissue-specific functions of liver. The failure of galactose to stimulate increasd cellular activity for the three enzymes represents a striking difference between the behavior of these enzymes in human diploid cell strains and their behavior in E. coli.
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PMID:Studies on the regulation of the three enzymes of the Leloir pathway in cultured mammalian cells. I. Effect of substitution of galactose for glucose as the sole hexose in the medium in human diploid cell strains and in a rat hepatoma line. 17 Feb 94

Gluconeogenesis is a liver-specific pathway which permits the synthesis of phosphorylated sugars from oxaloacetate, pyruvate, amino acids, or trioses. The absolute requirement for glucose or an alternative hexose which characterizes most mammalian cells probably reflects an inablility to perform gluconeogenesis rather than to generate sufficient energy by respiration alone. Cells of diverse histogenetic origins have been tested in glucose-free medium, supplemented with oxaloacetate or with dihydroxyacetone. The only cells able to grow are well-differentiated hepatoma cells which produce the relevant gluconeogenic enzymes: phosphoenolpyruvate carboxykinase, fructose diphosphatase, and triokinase. Reconstruction experiments demonstrate that glucose-free media permit the selective growth of cells producing gluconeogenic enzymes. These media should be useful for analysis of reexpression of differentiated functions in somatic cell hybrids and for the isolation of mutants.
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PMID:A selective system for hepatoma cells producing gluconeogenic enzymes. 20 52

Two tumour-cell-aggregation factors, derived from rat ascites hepatoma cells, had different antigenicity; one was not absorbed by immunoadsorbent chromatography with anti-rat serum antibody and the other was. Their activities were both lost by digestion with trypsin, but remained unchanged by oxidation with periodate, suggesting the role of the protein portions in their molecules. The potency of the unabsorbed factor was inhibited specifically by alpha-methyl-D-mannoside or D-mannose, while that of the absorbed factor was inhibited specifically by N-acetyl-D-glucosamine, suggesting that these carbohydrates may be concerned with the respective receptor structures at the tumour-cell surface. The unabsorbed factor induced not only cell aggregation (as shown in the form of simple apposition) but also cell adhesiveness characterized by development of intermediate junctions, desmosomes and tight junctions, while the absorbed factor produced only simple apposition, suggesting their functional difference.
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PMID:Biochemical and morphological comparison of two tumour-cell-aggregation factors from rat ascites hepatoma cells. 20 72

Detailed time courses of uptake of labeled 3-O-methyl-D-glucose and 2-deoxy-D-glycose by untreated and ATP-depleted Novikoff rat hepatoma cells were determined as function of concentration (0.2-10 mM) by a rapid mixing/sampling technique which allows uptake measurements in time intervals as short as 1.5 seconds. Intracellular accumulation of 3-O-methylglucose in untreated and ATP-depleted cells and of deoxyglucose in ATP-depleted cells to equilibrium followed pseudo-first order kinetics and initial velocities were computed from overall time courses of substrate accumulation. Initial velocity was a Michaelis-Menten function of exogenous substrate concentration. The estimated kinetic constants for zero-trans transport of 3-O-methylglucose were about the same for untreated and ATP-depleted cells (Kztm = 1.73 +/- 0.24 mM; Vztmax = 28.8 +/- 3.6 pmoles/microliter cell H2O. sec) and were similar to those for deoxyglucose transport in ATP-depleted cells (Kztm = 0.65 +/- 0.1 mM; Vztmax = 19.6 +/- 1.6 pmoles/microliter cell H2O. sec). Similar kinetic parameters were obtained for the transport of D-glucose and D-galactose in ATP-depleted cells. The transport of 3-O-methylglucose and deoxyglucose were inhibited by each other in a simple competitive manner with apparent Ki's similar to their transport Km's. In untreated cells, in which deoxyglucose was phosphorylated, intracellular steady-state levels of free deoxyglucose accumulated within 10 to 20 seconds of incubation regardless of its concentration in the medium. Thereafter, the rate of deoxyglucose incorporation into total cell material reflected the rate of phosphorylation rather than the transport rate. The rate of deoxyglucose transport exceeded the initial rate of its phosphorylation by 20-40 %. The intracellular steady-state-levels observed during the first 2 minutes of incubation decreased from about 40% of equilibrium level at 0.2 mM deoxyglucose to about 8% at 10 mM. Computer fits of a kinetic equation describing transport and phosphorylation as independent processes operating in tandem to these data are consistent with the observed kinetic constants for hexose transport and hexokinase activity with deoxyglucose as substrate. Upon longer incubation (2-10 minutes) the rate of deoxyglucose uptake by the phosphorylating cells decreased progressively, concomitant with a decrease in intracellular ATP and an increase in intracellular deoxyglucose to equilibrium levels. It is demonstrated that the rate of deoxyglucose uptake, measured at two or more minutes, seriously underestimates the hexose transport rate and yields misleading conclusions regarding the extent and type of inhibition by transport inhibitors, such as persantin or cytochalasin B. Persantin inhibited hexose transport in a simple non-competitive manner (Ki = 20 muM) indicating that the drug affects the function of the hexose carrier.
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PMID:Deoxyglucose and 3-O-methylglucose transport in untreated and ATP-depleted Novikoff rat hepatoma cells. Analysis by a rapid kinetic technique, relationship to phosphorylation and effects of inhibitors. 67 Mar 3

In human brain tumors of neuro-ectodermal and meningo-vascular series, using the method of enzymoelectrophoresis and specific tetrazole blue staining, three isoforms of hexokinase were revealed, these differ from each other by their activity and electrophoretic mobility in agar gel. Three isoforms of hexokinase were also found in benign and malignant uterine tumors in females, in 22 A mice hepatoma and homologous intact tissues. Morever, in muscles and muscle tumors (MOP, CRM-1) of rats and of these animals embryos two isoforms of hexokinase were found. The increased rate of hexose phosphorylation in malignant uterine tumors of female patients and in blastomas of mice liver and rat muscles is associated with the increased activity of I and II isoforms of hexokinase. An analogous phenomenon is observed in muscles of rat embryos. On the other hand, the decreased activity of phosphotransferases in blastomas of human brain depends on a decrease in the activity of separate isoforms of hexokinase.
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PMID:[Isoforms of human and animal tumor hexokinase]. 93 28

The binding of tissue-type plasminogen activator (t-PA) to membranes prepared from human liver was investigated, and a specific, saturable, high-affinity binding site (Kd = 3.4 nM) was identified. The binding of t-PA to liver membranes was not affected by an excess of D-mannose or D-galactose, or by active urokinase (u-PA), whereas binding of t-PA to membranes prepared from human HepG2 hepatoma cells was inhibited by u-PA. HepG2-membrane-bound t-PA was fully complexed to PA inhibitor 1 (PAI-1), whereas liver-membrane-bound t-PA was not complexed. Gel filtration on Sephacryl S300 of membrane proteins solubilized in deoxycholate revealed that high-affinity t-PA binding activity elutes at an apparent molecular mass of 40 kDa. Monoclonal antibodies specific for the growth factor and the kringle 2 domains inhibited the binding of t-PA to liver membranes and the catabolism of t-PA by rat hepatoma cells. Human liver membranes also bound u-PA; binding was inhibited by pro-u-PA, the N-terminal fragment of u-PA, but not by the 33 kDa form of u-PA or by t-PA. Our results show that human liver membranes contain a specific 40 kDa binding protein for t-PA that is different from the PAI-1-dependent receptor described on HepG2 cells and the mannose receptor isolated from human liver.
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PMID:Characterization of the binding of plasminogen activators to plasma membranes from human liver. 144 49

Several hepatoma cell lines and hepatic ascite tumour cells were studied for the presence of glycoprotein ligands of an endogenous lectin, the "Cerebellar Soluble Lectin" (CSL). This lectin is also present in hepatocytes in vivo and in vitro and can be detected biochemically and immunologically. In transformed cells, the level of CSL glycoprotein ligands is increased 50-fold as compared to the control cells. Such an increase is not observed for the ligands of the plant lectin, concanavalin A, which is, as CSL, a D-mannose-binding lectin. These results indicated that the changes in glycans during malignant transformation, in these cells, is specifically important for minor glycans binding to CSL.
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PMID:Malignant transformation in hepatocytes is associated with the general increase of glycoprotein ligands specifically binding to the endogenous lectin CSL. 193 33

In Madin-Darby canine kidney (MDCK) cells, specific plasma membrane binding of [125I]insulin was undetectable. Correspondingly, neither insulin-stimulated incorporation of [14C]glucose into glycogen nor insulin-induced uptake of radiolabeled alpha-aminoisobutyrate ([ 3H]AIB) could be demonstrated. These results suggested that MDCK cells lack specific cell surface insulin receptors. To further examine this question intact MDCK cells were preincubated with antireceptor serum and subsequently labeled with [125I]protein A; however, insulin receptors were not detected. Control H4 hepatoma cells bound insulin, responded with increased glycogen synthesis and amino acid uptake, and possessed immunologically recognizable insulin receptor components. The insulin-associated response of stimulated [3H]AIB uptake was induced in MDCK cells by the insulinomimetic lectins concanavalin A (130-140% of basal value at concentrations of 10-40 micrograms/ml) and wheat germ agglutinin (140-160% of basal value at concentrations of 10-30 micrograms/ml). This stimulation was abolished by the respective lectin-specific monosaccharides D-mannose and N-acetyl-D-glucosamine. Together, these data indicate that the insulin-like activity of concanavalin A and wheat germ agglutinin can be elicited in MDCK cells even in the apparent absence of specific plasma membrane insulin-binding sites.
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PMID:Effect of wheat germ agglutinin and concanavalin A on insulin binding and response by Madin-Darby canine kidney cells. 217 60

Plasma membrane glycoproteins of rat hepatocytes undergo a rapid terminal deglycosylation in that the terminal sugars of the oligosaccharide side chains are rapidly removed from the otherwise intact glycoproteins [Tauber, R., Park, C.S. & Reutter, W. (1983) Proc. Natl Acad. Sci. USA 80, 4026-4029]. The present paper demonstrates that this rapid intramolecular turnover of plasma membrane glycoproteins is not restricted to peripheral sugars but, in contrast to liver, in hepatoma the core sugars of the oligosaccharide chains are also involved. Intramolecular turnover was measured in Morris hepatoma 7777 in five plasma membrane glycoproteins with Mr of 85,000 (hgp85), 105,000 (hgp105), 115,000 (hgp115), 125,000 (hgp125), 175,000 (hgp175) (hgp = hepatoma glycoprotein) that were isolated and purified to homogeneity by concanavalin-A--Sepharose affinity chromatography and semipreparative SDS gel electrophoresis. Analysis of the carbohydrates of hgp85, hgp105, hgp115 and hgp125 revealed the presence of N-linked oligosaccharides containing L-fucose, D-galactose, D-mannose and N-acetyl-D-glucosamine, but only of trace amounts of N-acetyl-D-galactosamine; hgp175 additionally contained significant amounts of N-acetyl-D-galactosamine, indicating the presence of both N- and O-linked oligosaccharides. As shown by digestion with endoglucosaminidase H, the N-linked oligosaccharides of hgp105, hgp115, hgp125 and hgp175 were of the complex type, whereas hgp85 also contained oligosaccharides of the high-mannose type. Half-lives of the turnover of the oligosacharide chains and of the protein backbone of the five glycoproteins were measured in the plasma membrane in pulse-chase experiments in vivo, using L-[3H]fucose as a marker of terminal sugars, D-[3H]mannose as marker of a core sugar and L-[3H]leucine for labelling the protein backbone. Protein backbones of the five glycoproteins were degraded with individual half-lives ranging over 41-90 h with a mean of 66 h. Compared to the degradation of the polypeptide backbone, both the terminal sugar L-fucose and the core sugar D-mannose turned over with much shorter half-lives averaging about 20 h in the five glycoproteins. The data show that, conversely to liver, within plasma membrane glycoproteins of hepatoma not only peripheral sugars but also core sugars of the oligosaccharides are split off during the life-span of the protein backbone. It may therefore be assumed that this reprocessing of plasma membrane glycoproteins is sensitive to malignant transformation.
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PMID:Rapid intramolecular turnover of N-linked glycans in plasma membrane glycoproteins. Extension of intramolecular turnover to the core sugars in plasma membrane glycoproteins of hepatoma. 259 40

A membrane filter procedure developed by Igarashi et al. (1984) for the measurement of glucose 6-phosphate uptake by the microsomes has been demonstrated to be a good method for assaying glucose-6-phosphate translocase, an obligatory component of the microsomal glucose-6-phosphatase system. When glucose-6-phosphate translocase was assayed in developing and diabetic rat livers independently of hexose-6-phosphate phosphohydrolase, another obligatory component of the glucose-6-phosphatase system, the two activities were found to undergo alterations, whose profiles, however, were quite distinct from each other. The profile of the microsomal glucose-6-phosphatase activity resembles the profile of the phosphohydrolase activity rather than that of the translocase activity, suggesting that the phosphohydrolase may be rate-limiting at least under these conditions. AH-109A, a strain of transplantable rat ascites hepatoma, was found to lack both glucose-6-phosphate translocase and hexose-6-phosphate phosphohydrolase activities.
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PMID:Analysis of glucose-6-phosphate translocase and hexose-6-phosphate phosphohydrolase, the two obligatory components of microsomal glucose-6-phosphatase system, in rat liver. 285 Jun 43


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