UMLS:C0019204 - FACTA Search

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

Listeria monocytogenes was examined for the presence of surface carbohydrates to ascertain whether surface sugars, if present, would interact with eucaryotic surface carbohydrate receptors. We found that a virulent, but not two avirulent strains had a surface alpha-D-galactose residue as determined by agglutination with Griffonia simplicifolia (GS-I) and other lectins. The virulent strain bound to a human hepatocarcinoma cell line (HepG2), which has a well characterized receptor for alpha-D-galactose. This interaction could be blocked by pretreatment of the HepG2 cells with either alpha-D-galactose or neuraminidase, the latter of which will render the galactose receptor functionally inactive. We propose that the attachment of the virulent Listeria to eucaryotic cells occurs as a result of the interaction of the microbial alpha-D-galactose with that of the eucaryotic galactose receptor. This surface carbohydrate may provide an explanation for the mechanism of attachment and penetration of virulent Listeria into host cells during infection. As such, this may allow for amplification of pathogenesis through intracellular multiplication in nonprofessional phagocytes prior to macrophage involvement.
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PMID:Adherence of a virulent strain of Listeria monocytogenes to the surface of a hepatocarcinoma cell line via lectin-substrate interaction. 215 70

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

The cellular metabolism of apoE-free HDL (HDL) was studied in rat hepatoma cells (FU5AH). Cells incubated with HDL showed a dose-dependent decreased incorporation of [14C]acetate into cell sterol, indicating a net cholesterol delivery to the cells. HDL was localized both at the cell surface and inside the cell. This conclusion was drawn from both the association of 125I-labeled HDL with the cells under different experimental conditions and morphological evidence based on the association of colloidal gold-labeled HDL with the cells. Up to 63% of the 125I-labeled HDL protein initially inside the cell was subsequently recovered in the media as trichloroacetic acid precipitable (TCA-ppt) protein after a 30-min, 37 degrees C chase with a 100-fold concentration of unlabeled HDL. About 27% of the TCA-ppt apoprotein originally inside the cell was recovered as TCA-soluble material. Thus, we conclude that of the HDL apoprotein taken up by the cells, the majority is resecreted by a retroendocytosis pathway. The quantity of HDL apoprotein reappearing in the media was stimulated by the presence of unlabeled HDL in the media, while the amount of TCA-soluble material produced was not. Retroendocytosis of HDL was inhibited at 0 degree C and by the presence of 10 mM NaCN, 20 mM 2-deoxy-D-glucose in the media. Thus, the pathway appears to be both temperature- and energy-sensitive. HDL resecreted by the cell were depleted of cholesteryl ester and showed an altered size distribution, indicative of lipoprotein catabolism and remodeling. This study provides evidence for the existence of an endocytosis-retroendocytosis pathway for HDL apoproteins in a rat hepatoma cell and for the possibility that the endocytosis-retroendocytosis pathway may be involved in lipid delivery to the cell.
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PMID:Metabolism of apoE-free high density lipoproteins in rat hepatoma cells: evidence for a retroendocytic pathway. 232 43

The metabolism of 2-deoxy-2-fluoro-D-galactose (dGalF) was studied in rodents using HPLC, enzymatic methods, and 19F-NMR spectroscopy in vivo and in vitro. The liver took up the major part of the administered dose of the 14C-labeled D-galactose analog. This was confirmed in vivo by use of the 18F-labeled sugar (1.5 mCi/kg; 25 mumol/kg) and examination by positron emission tomography. After a dose of 1 mmol/kg, dGalF-1-phosphate accumulated rapidly (5.3 +/- 0.4 mmol/kg after 30 min), followed by formation of UDP-dGalF and UDP-2-deoxy-2-fluoro-D-glucose (0.7 +/- 0.1 and 1.8 +/- 0.1 mmol/kg, respectively, after 5 hr). Good quantitative agreement was obtained between the measurements by HPLC and enzymatic analyses and by 19F-NMR. The noninvasive in vivo 19F-NMR technique is particularly advantageous, since it allows the simultaneous analysis of all dGalF metabolites. The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepatic UTP, UDP-glucose, and UDP-galactose. The UTP content was decreased to 11 +/- 6% of normal within 15 min after administration of dGalF at a dose of 1 mmol/kg. The UTP-depleting action was minimal, however, at a dose of 25 mumol/kg or less, indicating that interference in uridylate metabolism will be negligible at the doses required for positron emission tomography of the liver using the 18F-labeled compound. At higher doses the UTP deficiency induced by dGalF may be useful in the chemotherapy of D-galactose-metabolizing tumors such as hepatocellular carcinoma. At moderate doses of dGalF, 19F-NMR spectroscopy in vivo or in vitro could be used to pinpoint defects of the enzymes that cause galactosemia, i.e. of galactokinase, uridyltransferase, or 4-epimerase.
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PMID:In vivo metabolism and UTP-depleting action of 2-deoxy-2-fluoro-D-galactose. 240 33

Differential effects of total parenteral nutrition (TPN) on host nutrition and growth of cancer are unclear. Growth of adult ACI-N rats bearing transplanted Morris hepatocarcinoma no. 3924A given TPN with or without fat was studied in comparison with Purina Chow-fed, fasting, and semifasting (either amino acid or dextrose alone) rats over 5 days. The isocaloric, isonitrogenous TPN regimens with or without fat maintained body weight and nitrogen balance of cancer-bearing rats equally well. When compared with Chow-fed rats, the volume of the cancer, its weight, doubling time, protein content, and incorporation of thymidine into DNA were similar in rats given TPN either with or without fat. Although the volume of the cancer decreased in fasting and semifasting rats, the nutritional status of the host was also impaired. Administration of TPN to cancer-bearing rats was associated with an abnormal increase in serum lactic acid level, which was not ameliorated by the use of fat to reduce the carbohydrate load. Although TPN with and without fat maintains the nutritional status, hepatomegaly and hepatic steatosis limit the administration of carbohydrate and fat as energy substrates in this system.
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PMID:Total parenteral nutrition with and without fat as substrate for growth of rats and transplanted hepatocarcinoma. 241 57

The combination of 3 types of antipyrimidines was studied in AS-30D hepatoma cells in suspension culture and in the rat in vivo. Cellular UTP and CTP pools can be depleted most effectively by combining an inhibitor of de novo UMP synthesis with sugar analogs diverting UMP to UDP-sugar analogs. The following UMP-trapping sugar analogs were employed: D-galactosamine, D-galactosone, D-glucosone, and D-glucosamine. These D-galactose and D-glucose analogs intensified the depletion of UTP and CTP pools induced by the following inhibitors of de novo UMP synthesis: acivicin, PALA, lapachol, pyrazofurin, and 6-azauridine. The sugar analogs, in the absence of inhibitors of the de novo pathway, enhanced the rate of de novo UMP synthesis several-fold, as indicated by incorporation of 14CO2 into intermediates and products of the pathway and by the expansion of the acid-soluble uracil nucleotide pool. Reduction of UTP and CTP contents to less than 5 and 15% of control, respectively, by D-galactosamine and PALA resulted in a decrease of the rate of RNA synthesis to 19% of control as calculated from the changes in specific activities of [14C]CTP and of [14C]cytidine in RNA after labeling with [14C]uridine. Hepatoma cells released uridine and cytidine into the extracellular fluid. This release was reduced to one third in UTP-deficient cells, indicating that pyrimidine nucleoside excretion is regulated by pyrimidine nucleotide levels, possibly by UTP and CTP regulation of uridine kinase. Determination of the rates of de novo pyrimidine synthesis, of the formation of RNA pyrimidines, and of pyrimidine nucleoside excretion indicates that de novo synthesis provides only about 67% of the pyrimidines required for the consuming processes. The difference, as well as the dilution of labeled pyrimidine nucleotide pools under conditions of a blocked de novo pathway, suggests a considerable salvage of pyrimidine nucleosides derived from RNA. This salvage of pyrimidines may be intracellular and/or by an excretion and re-uptake process. Depletion of UTP and CTP pools, induced in hepatoma cells by D-galactosamine and 6-azauridine, leads to growth inhibition in suspension culture; this inhibition becomes irreversible in an increasing percentage of cells, killing all cells after 20 hr of UTP deficiency. The enhanced uptake of 5-fluorouridine by UTP-deficient cells was associated with an increase of FUMP incorporation into RNA up to 4-fold and with stronger inhibition of cell growth.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Uridylate-trapping sugar analogs in combination with inhibitors of uridylate synthesis de novo and 5-fluorouridine. 241 94

The effect of alpha-dihydrodecaprenyl phosphate, dolichyl phosphate and solanesyl phosphate on the lipid intermediate pathway for protein glycosylation was studied with crude membrane fraction prepared from AH 70Btc hepatoma cells. alpha-Dihydrodecaprenyl phosphate increased the incorporations of [14C]mannose from GDP-[14C]mannose into CHCl3-CH3OH (2:1, v/v) extract, oligosaccharide-lipid and proteins. The above and the other data showed that alpha-dihydrodecaprenyl phosphate may function as a mannose carrier in the lipid intermediate pathway.
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PMID:alpha-Dihydrodecaprenyl phosphate as a sugar carrier in the membrane of AH 70Btc hepatoma cells. 241 79

The soluble alpha-mannosidase of rat liver, originally described as a cytoplasmic alpha-mannosidase, has been purified to homogeneity by conventional techniques. The purified enzyme has an apparent molecular weight of 350,000 and is composed of 107-kDa subunits. The soluble alpha-mannosidase has the same enzymatic properties as the endoplasmic reticulum (ER) membrane alpha-mannosidase of rat liver (Bischoff, J., and Kornfeld, R. (1983) J. Biol. Chem. 258, 7909-7910) which is believed to play a role in oligosaccharide processing in the rough ER. Like the membrane-bound ER alpha-mannosidase, the soluble alpha-mannosidase can hydrolyze alpha-linked mannose from both p-nitrophenyl alpha-mannoside (Km = 0.14 mM) and high mannose oligosaccharides, is not inhibited by the mannose analogues swainsonine and 1-deoxymannojirimycin, is stabilized by MnCl2 or CoCl2, and does not bind to concanavalin A-Sepharose. A goat polyclonal antibody raised against the purified soluble alpha-mannosidase specifically recognizes the rat liver membrane-bound ER alpha-mannosidase, leading us to propose that they are two forms of the same enzyme and that the soluble form is derived from the ER membrane alpha-mannosidase by proteolysis. The antibody also cross-reacts with both the soluble and membrane-bound forms of ER alpha-mannosidase activity in cultured Chinese hamster ovary cells and rat H35 hepatoma cells. Since the ER alpha-mannosidase is presumed to be involved in the early steps of oligosaccharide processing, the action of the purified soluble form of the enzyme on high mannose oligosaccharides was examined. Surprisingly, the enzyme released free mannose from oligosaccharides ranging in size from Glc1Man9GlcNAc to Man5GlcNAc with almost equal efficiency. However, a long term incubation of the enzyme with Man9GlcNAc led to the accumulation of Man7GlcNAc and produced only small amounts of Man6GlcNAc and Man5GlcNAc. Structural analysis of these reaction products indicated that the purified soluble form of ER alpha-mannosidase shows little specificity for which mannose residues it removes from Man9GlcNAc. In contrast, as shown in the accompanying paper, the intracellular action of ER alpha-mannosidase on glycoprotein-bound Man9GlcNAc2 is highly specific.
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PMID:The soluble form of rat liver alpha-mannosidase is immunologically related to the endoplasmic reticulum membrane alpha-mannosidase. 242 Jul 91

Allomyrina dichotoma lectin (allo A) with a specificity to beta-D-galactose was used to fractionate human alpha-fetoprotein (AFP) by affinity electrophoresis. AFP from cord sera and serum of a patient with fulminant hepatitis showed single bands with a high affinity for allo A. Some patients with hepatocellular carcinoma and patients with gastric cancer and yolk sac tumor had two additional AFP bands, one weakly reactive and the other nonreactive with allo A. Patterns of AFP bands obtained with Ricinus communis agglutinin-I (RCA-I) and erythroagglutinating phytohemagglutinin from Phaseolus vulgaris were entirely different from those obtained with allo A. Of the two common bands reactive with RCA-I, the weakly reactive one was relatively intense in some malignant patients and the strongly reactive one was detected in patients with extrahepatic tumors. Thus, affinity electrophoresis with those lectins provides a potentially useful adjunct for the discrimination between benign and malignant conditions with increased serum levels of AFP.
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PMID:Allomyrina dichotoma lectin-nonreactive alpha-fetoprotein in hepatocellular carcinoma and other tumors: comparison with Ricinus communis agglutinin-I. 242 91

Previously, monoclonal antibody FDC-6 was established, which defines a structure specific for fibronectins isolated from fetal and malignant cells and tissues. The presence of the FDC-6-defined structure at type III connecting segment (III CS) is characteristic of oncofetal fibronectin (onf-FN), and its absence is characteristic of normal fibronectin (nor-FN) (Matsuura, H., and Hakomori, S. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 6517-6521). Hepatoma fibronectin was sequentially digested by various proteases, followed by subsequent chromatography on an FDC-6 affinity column and reverse-phase columns at each step of digestion. A single strongly active glycosylhexapeptide (glycopeptide 1) and an inactive glycosylpentapeptide (glycopeptide 3) were isolated from glycopeptide A containing 35 amino acid residues. The minimum essential structure required for the FDC-6 activity was found to be a hexapeptide sequence Val-Thr-His-Pro-Gly-Tyr having NeuAc alpha 2----3Gal beta 1----3GalNAc or its core (Gal beta 1----3GalNAc or GalNAc) linked at threonine. Various synthetic peptides including the Val-Thr-His-Pro-Gly-Tyr sequence and a glycopeptide having the Val-Thr-His-Pro-Gly pentapeptide with the same glycosylation at threonine were all inactive. Elimination of sialic acid slightly increased the activity, and subsequent elimination of galactose did not alter the activity; however, removal of the Gal beta 1----3GalNAc residue by endo-alpha-N-acetylgalactosaminidase from desialylated glycopeptide A resulted in total inactivation of the reactivity with FDC-6 antibody. Thus, a single glycosylation at a defined threonine residue of the III CS region may induce conformational changes in the peptide to form the specific oncofetal epitope recognized by FDC-6 antibody. This finding opens the possibility that a number of other oncofetal epitopes consist of a peptide and a common O-linked carbohydrate and that the combination produces a conformation specific to cancer or to a stage of development.
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PMID:The oncofetal structure of human fibronectin defined by monoclonal antibody FDC-6. Unique structural requirement for the antigenic specificity provided by a glycosylhexapeptide. 244 38

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