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)

Nucleotide sugars derived from 5-fluorouridine were studied in cultured AS-30D hepatoma cells as well as in kinetic enzyme assays in vitro in comparison with the physiologic uridine diphospho sugars. Hepatoma cells converted 5-fluoro [14C]uridine to 5-fluorouridine diphospho (FUDP) glucose, FUDP-galactose, FUDP-N-acetylglucosamine, FUDP-N-acetylgalactosamine, and trace amounts of FUDP-glucuronate, as analyzed by different systems of high-performance liquid chromatography. 5-Fluoro[14C]uridine and [14C]uridine, at concentrations of 5 microM in the culture medium, were phosphorylated by the cells during 60 min to similar amounts of FUTP and UTP, respectively, while the synthesis of [14]FUDP-sugars was reduced to 14% as compared to that of [14C]UDP-sugars. FUDP-sugars, synthesized by chemical and enzymatic procedures, were assayed in vitro as substrates for enzymes of UDP-sugar metabolism. Km and V values in a range comparable to that of the respective UDP-sugars were determined for FUDP-sugars in the reactions catalyzed by UDP-glucose pyrophosphorylase, galactose-1-phosphate uridylyltransferase, UDP-glucose 4-epimerase, UDP-N-acetylglucosamine 2-epimerase, glycogen synthase, and UDP-glucose dehydrogenase. Our experiments in hepatoma cells and with enzymes in vitro have revealed additional reactions of FUDP-sugar metabolism demonstrating a metabolite pattern analogous to that of UDP-sugars. The amounts of FUDP-sugars formed relative to UDP-sugars in intact cells were smaller than suggested on the basis of their kinetic comparison in vitro.
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PMID:Substrate properties of 5-fluorouridine diphospho sugars detected in hepatoma cells. 646 51

The membrane-bound UDP-GalNAc:polypeptide N-acetylgalactosamine transferase from an ascites hepatoma, AH 66, has been purified 48,100-fold, mainly by affinity chromatography in aqueous Triton X-100 on apomucin (deglycosylated bovine submaxillary mucin) coupled to Sepharose. The purified preparation behaved homogeneously on gel filtration on Sephadex G-150 in aqueous Triton X-100 and on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with an apparent molecular weight of about 55,000. The enzyme requires Mn2+, and only UDP-GalNAc served as a sugar donor. Apomucin, A1 protein, kappa-casein, apofetuin, and apoantifreeze glycoproteins served as acceptors, but the rate and amount of the transfer varied considerably from one acceptor to another. The transfer reaction terminated at the level of glycosylation of from only a few to at most about 40% of the serine plus threonine residues from which mucin-type oligosaccharides had been removed. This indicates that the transferase requires a certain conformation surrounding the acceptor site, but suggests also that a special mechanism may be functioning in vivo for frequent glycosylation of the abundant serine plus threonine residues of mucins. Lacto-N-fucopentaose I, ceramide di- and trihexosides, and globoside were not acceptors.
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PMID:Purification and characterization of UDP-GalNAc:polypeptide N-acetylgalactosamine transferase from an ascites hepatoma, AH 66. 680 38

A human hepatoma cell line (SK-H-MA) released a large amount of sialyltransferase (ST) and galactosyltransferase (GT) into the culture medium, whereas cells derived from normal human liver (Chang) released a large amount of GT but very little ST. The characteristics of hepatoma GT were studied since an abnormal GT isoenzyme has been associated with human gastrointestinal neoplasms. Both hepatoma and Chang medium GT activities had an absolute requirement for MnCl2 (25 mmol/l) and a broad optimal pH between 6.5 and 7.0, and were not affected by 0.1% Triton X-100. These two enzyme preparations were inhibited to the same extent by N-acetylglucosamine and N-acetylgalactosamine, while N-acetylglucosamine was 100 times more potent than N-acetylgalactosamine. Various nucleotides inhibited both enzyme activities equally well. Uracil-containing nucleotides were better inhibitors than thymine-containing nucleotides, and other nucleotides were only slightly inhibitory. The most effective inhibitor was UDP. More of the GT activity in hepatoma medium (65%) as compared to Chang medium (35%) bound to concanavalin A-Sepharose, and was eluted with 2.5% alpha-methylmannoside. These results suggest that the GTs from hepatoma and Chang media are not different in their enzymatic activity but may differ in their carbohydrate contents, which may be another manifestation of the neoplastic nature of the hepatoma cell line.
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PMID:Characterization of galactosyltransferase released from human hepatoma cells. 681 23

A major cell surface sialoglycoprotein with Concanavalin A receptor activity has been isolated from rat Zajdela ascites hepatoma cells. The sialic acid residues of the plasma membrane glycoproteins were specifically labeled by oxidation and NaIO4 followed by reduction with NaB3H4. Surface-labeled glycoproteins were released by short incubations with TPCK-trypsin at 37 degrees C and then separated by gel filtration on Sepharose 6B column. The predominantly labeled fraction, GP II2, was then purified by chromatography on DEAE-cellulose equilibrated with 0.05 M phosphate buffer, pH 7.5, and eluted with increasing molarities of NaCl. It was shown to be homogeneous by protein and carbohydrate staining on SDS-polyacrylamide gels, isoelectric focusing, rechromatography on DEAE-cellulose and immunoelectrophoresis. It has an apparent molecular weight of 110,000 daltons. The location of GP II2 on the cell surface was confirmed by the fact that it could be labeled metabolically with D-(3H) glucosamine and externally through the nonpenetrating periodate-NaB3H4 system. GP II2 could not be removed from the cell surface by high salt concentrations, chelator, or chaotropic agents but was released from the membrane by detergents. This suggests that GP II2 could be an integral protein. Analysis of the carbohydrate composition of GP II2 revealed galactose, N-acetylglucosamine, N-acetylgalactosamine, and sialic acid as major constituents and mannose as a minor one. This suggests that it contains carbohydrate chains both O- and N-linked to the polypeptide chain, most of them being O-linked. Finally, GP II2 has a potent Concanavalin A receptor activity. It inhibits the interaction between Concanavalin A and hepatoma cells and suppresses its effects on hepatoma cell proliferation.
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PMID:Purification and characterization of a major cell surface glycoprotein in Zajdela ascites hepatoma cells which displays a potent concanavalin A receptor activity. 706 81

We have cloned a cDNA encoding beta 1-4N-acetylgalactosaminyltransferase (EC 2.4.1.92) (GalNAc-T) from rat ascites hepatoma of the free-cell type AH7974F. The cell line only expressed asialo-series glycosphingolipids (GSLs) including asialo-GM2 [Taki, T., Hirabayashi, Y., Ishiwata, Y., Matsumoto, M., and Kojima, K. (1979) Biochim. Biophys. Acta 572, 113-120]. The cDNA, pGNA56, was isolated by screening AH7974F cDNA library in lambda gt10 with a probe. The probe was obtained from AH7974F cDNA by PCR using primers with the nucleotide sequence of the human GalNAc-T cDNA. The amino acid sequence deduced from the nucleotide sequence of pGNA56 exhibited 88% similarity to the human GalNAc-T sequence. The enzyme was a typical type II membrane protein, which consisted of a short N-terminal residue, a transmembrane region, and a long C-terminal residue, including the catalytic domain. The substrate specificity of rat GalNAc-T was determined using homogenates from cells into which the cDNA clone was transfected. The enzyme catalysed not only the formation of GM2 and GD2 from GM3 and GD3 respectively, but also asialo-GM2 from CDH. It also acted on GSL substrates, including GM1b, sialylparagloboside and GD1 alpha. On the other hand, the enzyme did not transfer GalNAc to soluble substrates such as glycoproteins and oligosaccharide. The GSL compositional and immunocytochemical analyses of stable transfectants obtained by transfection of the cDNA showed simultaneous expression of asialo-GM2 and GM2 on the plasma membrane. Therefore, we concluded that the formation of asialo-GM2, GM2 and GD2 was catalysed by the single GalNAc-T. Northern-blot hybridization showed that the GalNAc-T mRNA was strongly expressed in rat brain, testis, and spleen. The gene was also expressed in rat normal liver to a lesser extent. We found the GSLs in asialo- and alpha-pathways such as asialo-GM1 and GD1 alpha in the rat tissues by using a sensitive t.l.c.-immunostaining method. These observations also supported our conclusion that the single GalNAc-T synthesizes asialo-GM2, GM2 and GD2 in vivo.
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PMID:beta 1-4N-acetylgalactosaminyltransferase can synthesize both asialoglycosphingolipid GM2 and glycosphingolipid GM2 in vitro and in vivo: isolation and characterization of a beta 1-4N-acetylgalactosaminyltransferase cDNA clone from rat ascites hepatoma cell line AH7974F. 798 Apr 68

Changes in the content of N-acetylneuraminic acid in rat erythrocyte membranes at different stages of experimental tumour (Morris hepatoma 5123) development were examined. Its content was lowered on the 30th and 40th day after transplantation of the tumour cells, as compared to the results for normal healthy rats. As a result of the tumour growth, the content of N-acetylgalactosamine, galactose and mannose in rat erythrocyte membranes became lowered, whereas that of glucose remained unchanged. The content of fucose was raised at early stage of tumour growth, and remained at this high level till the 40th day of experiment.
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PMID:The content of N-acetylneuraminic acid in glycoproteins of erythrocyte membranes in Morris hepatoma 5123 bearing rats. 803 Mar 69

Disialosyl globo-series gangliosides have previously been isolated from chicken skeletal muscle (E. L. Hogan, R. D. Happel, and J.-L. Chien (1982) Adv. Exp. Med. Biol. 152, 273-278; S. Dasgupta, J.-L. Chien, E. L. Hogan, and H. van Halbeek (1991) J. Lipid Res. 32, 499-506) and human erythrocytes (S. K. Kundu, B. E. Samuelsson, I. Pascher, and D. Marcus (1983) J. Biol. Chem. 258, 13857-13866). In both cases, the structure of this ganglioside was proposed to be NeuAc alpha 2-->3(NeuAc alpha 2-->6)Gal beta 1-->3GalNAc beta 1-->3Gal alpha 1-->Gal alpha 1-->4Gal beta 1-->1Cer (V3NeuAcV6NeuAcGb5Cer). We have reinvestigated the human erythrocyte antigen and now propose an alternative structure differing in the location of the NeuAc alpha 2-->6 residue: NeuAc alpha 2-->3Gal beta 1-->3 (NeuAc alpha 2-->6)GalNAc beta 1-->3Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->1 Cer (V3NeuAcIV6NeuAcGb5Cer). This novel structure is supported by results of 1H-NMR spectroscopy, negative ion fast atom bombardment mass spectrometry, and methylation linkage analysis with capillary gas chromatography--mass spectrometry in both electron impact and chemical ionization modes. Furthermore, based on new results from negative ion fast atom bombardment mass spectrometry and linkage analysis, we propose that the chicken skeletal muscle antigen also has this revised structure, differing only in ceramide composition. The terminal tetrasaccharide of these gangliosides is identical to that of GD1 alpha, NeuAc alpha 2-->3Gal beta 1-->3(NeuAc alpha 2-->6)GalNAc beta 1-->4Gal beta 1-->4Glc beta 1-->1 Cer(IV3NeuAcIII6NeuAcGg4Cer), previously identified in a rat ascites hepatoma cell line (T. Taki, Y. Hirabayashi, H. Ishikawa, S. Ando, K. Kon, Y. Tanaka, and M. Matsumoto (1986) J. Biol. Chem. 261, 3075-3078) and a murine lymphoma cell line with low metastatic potential (K. Murayama, S. B. Levery, V. Schirrmacher, and S. Hakomori (1986) Cancer Res. 46, 1395-1402), although they appear to be immunologically distinct.
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PMID:A revised structure for the disialosyl globo-series gangliosides of human erythrocytes and chicken skeletal muscle. 803 Nov 19

Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT.
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PMID:Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour. 1058 81

The effects of lectins with different carbohydrate-binding specificities on human hepatoma (H3B), human choriocarcinoma (JAr), mouse melanoma (B16) and rat osteosarcoma (ROS) cell lines were investigated. Cell viability was estimated by uptake of crystal violet. Wheat germ lectin was the lectin with the most deleterious effect on the viability of H3B, JAr and ROS cell lines. The cytotoxicity of lectins with similar sugar-binding specificity to wheat germ lectin, including Maackia amurensis lectin and Solanum tuberosum lectin, was weaker than that of wheat germ lectin. N-acetylgalactosamine-and galactose-binding Tricholoma mongolicum lectin ranked third, after wheat germ lectin and Maackia amurensis lectin, with regard to its effect on H3B, and ranked, together with Maackia amurensis lectin, as the lectins with the second most pronounced effects on ROS. However, the cytotoxic effects of Tricholoma mongolicum lectin on JAr were much weaker than those of Maackia amurensis lectin, Solanum tuberosum lectin and Anguilla anguilla lectin. Artocarpus integrifolia lectin, Lens culinaris lectin and Anguilla anguilla lectin possessed milder cytotoxicity than the remaining lectins. which were approximately equipotent. The mannose-binding Narcissus pseudonarcissus and Lens culinaris lectins were only weakly cytotoxic, the exception being a stronger effect on H3B. The N-acetylgalactosamine-binding Glycine max lectin and methylgalactose-binding Artocarpus integrifolia lectin similarly exhibited low cytotoxicity. It can thus be concluded that in general the ranking was wheat germ lectin > Maackia amurensis lectin approximately Trichloma mongolicum lectins > other aforementioned lectins in cytotoxicity. A particular lectin may manifest more conspicuous toxicity on certain cell lines and less on others.
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PMID:Effects of lectins with different carbohydrate-binding specificities on hepatoma, choriocarcinoma, melanoma and osteosarcoma cell lines. 1071 33

Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation.
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PMID:Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation. 1206 84

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