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)

The hepatic acute phase response is accompanied by increased levels of Gal beta 1-4GlcNAc alpha 2,6-sialyltransferase activity in liver and in circulation. Previous studies suggested that cytokines and glucocorticoids mediate the induction of this sialyltransferase activity. In this study the regulation of sialyltransferase expression by dexamethasone in H35 rat hepatoma cells is assessed by Northern hybridization and enzyme activity assays. Exposure of H35 cells to 1 microM dexamethasone for 24 h causes a 3-4-fold enrichment of sialyltransferase mRNA and a corresponding increase in enzymatic activity. The induction of sialyltransferase mRNA begins within 3 h of dexamethasone treatment and reaches a plateau within 24 h. Sialyltransferase mRNA induction is dose dependent; the minimum concentration of dexamethasone necessary for induction is 10(-8) M, and induction was maximal at 10(-6) M. Induction is sensitive to actinomycin D, suggesting that regulation may be exerted by altering the rate of mRNA synthesis. Puromycin and cycloheximide are ineffective in blocking induction, suggesting that de novo protein synthesis is not required for induction. Finally, dexamethasone alone is sufficient for maximum induction of sialyltransferase mRNA. In contrast, maximal induction of alpha 1-acid glycoprotein, a well studied hepatic acute phase reactant, requires both dexamethasone and cytokines, implying that different pathways exist for the induction of participants in the acute phase response.
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PMID:Regulation of beta-galactoside alpha 2,6-sialyltransferase gene expression by dexamethasone. 291 88

Sialyltransferases responsible for the formation of sugar chains in glycoproteins were studied in rat hepatoma in comparison with rat liver. Hepatoma induced by feeding Wistar rats with 3'-methyl-4-dimethylaminoazobenzene (MeDAB) was more active than Wistar liver in sialylating asialo-orosomucoid, and this was due to an increased activity of Gal(beta 1----4)GlcNAc (alpha 2----6) sialyltransferase, the major sialyltransferase in these tissues. Gal(beta 1----3,4)GlcNAc (alpha 2----3) sialyltransferase and the sialyltransferase acting on asialo-bovine submaxillary mucin were, however, decreased in the hepatoma. A similar pattern of sialyltransferase alterations was observed in regenerating liver and other tumors such as AH-109A hepatoma and Sato lung cancer, both of which had been inoculated into Donryu rats. In contrast to these sialyltransferases, the activities of the sialyltransferases responsible for the formation of gangliosides were markedly different even between Wistar and Donryu livers. When compared with Wistar liver, MeDAB-induced hepatoma was higher in lactosylceramide- and lower in GM3-sialyltransferase activity, but these two activities were both lower in AH-109A compared with Donryu liver.
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PMID:Comparative study of the levels of sialyltransferases responsible for the formation of sugar chains in glycoproteins and gangliosides in rat liver and hepatomas. 313 1

A hybridoma producing monoclonal antibody (H11) directed to lactoneotetraosylceramide (paragloboside) has been established from spleen cells of a mouse immunized with paragloboside. The monoclonal antibody H11 (immunoglobulin M type) was selected from five clones showing different reactivities with paragloboside. The monoclonal antibody was highly specific to paragloboside and lacked reactivity with other glycolipids including glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, and GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4Glc beta 1-1Cer. However, the monoclonal antibody (H11) was found to bind to lactosamine-containing glycolipids at their terminals, such as i- and I-type glycolipids as well as paragloboside. A two-step sandwich radioimmunoassay method for paragloboside antigen in serum was established by using the monoclonal antibody. The mean paragloboside antigen concentration in the sera from 20 normal individuals was 25.3 ng/ml. If the cutoff value was set at 80.9 ng/ml [25.3 + 2 x 27.8 (SD)], only 1 of 20 healthy controls had an elevated paragloboside value in the serum, whereas sera from 9 of 12 (75.0%) hepatoma, 4 of 10 (40%) pancreatic cancer, 16 of 40 (40.0%) stomach cancer, and 6 of 10 (60%) lung cancer patients had elevated paragloboside values. Sera from 3 of 8 hepatitis patients and 7 of 10 liver cirrhosis patients were estimated to be positive but sera from 16 patients with benign disease had paragloboside levels lower than the cutoff value. A larger amount of the antigen was found in liver metastases from colorectal carcinoma compared to the normal counterpart. The antigen was also detected in the medium of various human cancer cells and meconium. However, the antigen in the sera, medium, meconium, and cancer tissue seemed to be associated with glycoprotein or lipoprotein, because most of the antigen activity was eluted in the void volume fraction on high-performance liquid chromatography with a gel filtration column.
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PMID:Detection of patients with cancer by monoclonal antibody directed to lactoneotetraosylceramide (paragloboside). 334 24

Glycoprotein MII2, the major cell surface glycoprotein (molecular mass 110 kDa) of Zajdela hepatoma ascites cells, contains about 25 O-glycosidic oligosaccharide chains per molecule. They were released as oligosaccharide-alditols by alkaline borohydride treatment of MII2, and purified by gel filtration on Bio-Gel P-6 followed by high-voltage paper electrophoresis. Four oligosaccharide-alditol fractions (A-D) were obtained in relative yields of 8:6:3:3. The structure of the components of fractions A-C was determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis, to be as follows. (A) NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)]GalNAc-ol; (B1) NeuAc alpha(2----3)Gal beta(1----3)[Gal beta(1----4)GlcNAc beta(1----6)]GalNAc-ol; (B2) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)]GalNAc-ol; (C) NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol. On the basis of sugar composition and characteristics on Bio-Gel P-6 filtration, paper electrophoresis and thin-layer chromatography, the structure of the carbohydrate component of fraction D is proposed to be as follows. (D) NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol
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PMID:The structure of the O-glycosidic oligosaccharide chains of the major Zajdela hepatoma ascites-cell-membrane glycoprotein. 375 66

The intracellular pathways taken by galactose-terminal glycoproteins were examined following endocytosis by the asialoglycoprotein receptor in monolayers of the human hepatoma cell line, Hep G2. In addition to a pathway leading to lysosomal degradation, single cohort kinetics revealed that up to 28% of surface-bound and internalized 125I-asialoorosomucoid (ASOR) eventually returned undegraded to the extracellular medium over 6 hr in the presence or absence of free ASOR in the exocytosis medium. This reappearance of ligand in the exocytosis medium represented a constant fraction of surface bound and internalized 125I-ASOR, and followed pseudo-first order kinetics with t1/2 = 84 min (long transit pool). Under conditions of enhanced ligand-receptor dissociation (incubation with 100 mM N-acetylgalactosamine (GalNAc), at least 50% of initially internalized 125I-ASOR returned to the cell surface as ligand-receptor complexes, followed by dissociation of free ligand into the exocytosis medium. This rapid transit pool of ligand also displayed pseudo-first order kinetics with t1/2 = 24 min. Exocytosis of 125I-Gal-cytochrome c, a synthesized ligand displaying rapid dissociation from the asialoglycoprotein receptor (ASGP-R), paralleled the kinetics of the rapid transit pool of 125I-ASOR (t1/2 = 28 min). Furthermore, in addition to spontaneous dissociation from ASPG-R following return to the cell surface, studies conducted in saponin-permeabilized monolayers support the return of free intracellular 125I-Gal-cytochrome c to the cell surface during exocytosis. The rapid transit pool of ligand was insensitive to inhibition by 10 mM sodium azide or 0.1 mM primaquine. In contrast, the long transit pool destined for exocytosis was inhibited 50% by 10 mM sodium azide, but insensitive to inhibition by 0.1 mM primaquine. These data suggest that, following internalization by the ASGP-R, a major pathway of ligand movement includes the rapid return of ligand-receptor complexes and/or free ligand to the cell surface. Return of ligand-receptor complexes or free ligand to the cell surface occurs prior to an acidic sorting compartment, can involve multiple cycles of return to the cell surface, and may involve passage through other nonlysosomal intracellular organelles.
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PMID:Cellular pathways of galactose-terminal ligand movement in a cloned human hepatoma cell line. 609

Comparative study by using hydrazinolysis has revealed that the carbohydrate moieties of gamma-glutamyl transpeptidases purified from rat liver and rat AH-66 hepatoma are quite different. The sugar chains of the liver enzyme were all acidic, while 29% of those of hepatoma enzyme was neutral. Three prominent structural differences were found in the acidic sugar chains of the two enzymes: 1) The liver enzyme has asparagine-linked sugar chains with complete outer chain, NeuAc alpha----Gal beta 1----4GlcNAc, while hepatoma enzyme has sugar chains incomplete in their outer chain moieties; 2) Gal beta 1----4GlcNAc beta 1----4GlcNAc group is found in the sugar chains of liver enzyme but not in those of hepatoma enzyme; 3) More than 40% of the sugar chains of hepatoma enzyme contain bisecting N-acetylglucosamine which is not found in those of liver enzyme.
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PMID:[Structural change of sugar chains of glycoproteins by cell transformation and its application to the diagnosis of cancer]. 614 30

Previous studies indicated that accumulation of alpha-fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) and alpha-galactosyl-alpha-fucosyl-GM1 (IV3GalIV2FucII3NeuAcGgOse4Cer) occurs in precancerous livers of rats fed the chemical carcinogen N-2-acetylaminofluorene, before development of hepatoma. Both fucogangliosides were completely absent in normal rat liver as well as in livers of rats fed a nonhepatic carcinogen and tumor promoters (Holmes, E.H., and Hakomori, S. (1982) J. Biol. Chem. 257, 7698-7703). The enzymatic basis of the chemical changes described above is reported in this paper. The alpha-L-fucosyltransferase activity toward GM1 (II2NeuAcGgOse4Cer) as well as asialo-GM1 (GgOse4Cer) was almost undetectable in extracts from normal rat liver, but significant activity of this enzyme was detected in extracts of rat livers after 4 weeks of feeding a diet containing N-2-acetylaminofluorene. The same enzyme activity in cultured rat hepatoma cells was 18- to 47-fold higher than in N-2-acetylaminofluorene-fed rat liver. In contrast, alpha-galactosyltransferase activity with a broad substrate specificity was detected in normal as well as in N-2-acetylaminofluorene-fed liver, although the specific activity of this enzyme in Golgi membranes in precancerous liver was significantly higher than that of normal rat liver. Thus, the appearance of alpha-fucosyl-alpha-galactosyl-GMI in precancerous liver is due to an induction of synthesis of alpha-fucosyl-GMI which is the substrate for the normally existing alpha-galactosyltransferase. The activity of alpha-fucosyltransferase was highly specific toward a substrate structure Gal beta 1 leads to 3GalNAc beta 1 leads to R in GMI or asialo-GMI and showed an anomalous inhibition by a large variety of detergents tested. In contrast, the alpha-galactosyltransferase showed a wide substrate specificity, activated by detergents and Mn2+ ion. Membrane alterations in precancerous and malignant transformation of rat liver is associated with an induction of an unusual alpha-fucosyltransferase which is the key step in synthesis of both fucogangliosides.
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PMID:Enzymatic basis for changes in fucoganglioside during chemical carcinogenesis. Induction of a specific alpha-fucosyltransferase and status of an alpha-galactosyltransferase in precancerous rat liver and hepatoma. 640 18

A novel fucoganglioside has been found to be accumulated in the liver of rats fed N-2-acetylaminofluorene before development of hepatoma. This new fucoganglioside persisted in hepatoma in vivo but was completely absent in normal rat liver as well as in livers of rats fed the nonhepatic carcinogen, acetylaminophenanthrene, and a tumor promoter, trichloro-2,2-bis-(chlorophenyl)ethane. The ganglioside was isolated by high performance liquid chromatography and the structure was determined by methylation analysis, sequential degradation by various exoglycosidases, and by direct probe mass spectrometry of the permethylated derivative. This ganglioside, present in precancerous liver and in hepatoma in vivo, was identified as having a new structure with a substitution identical with blood group B determinant as shown below: (formula, see text) A second fucoganglioside was detected in lower quantity in precancerous liver and in hepatoma in vivo but not in control tissue. This ganglioside co-migrated with the fucoganglioside isolated from H-35 hepatoma cells in vitro whose structure was identified (Baumann, H., Nudelman, E., Watanabe, K., and Hakomori, S. (1979) Cancer Res. 39, 2637-2643) as fucosylated GM1 ganglioside (Fuc alpha 1 leads to 2Gal beta 1 leads to 4GalNAc beta 1 leads to 4 [NeuAc alpha 2 leads to 3]Gal beta 1 leads to 4Glc beta 1 leads to 1Cer). The results indicate that synthesis of new fucolipids is already induced at an early stage during the process of chemical carcinogenesis in rat liver which could be a unique membrane marker for diagnosis and therapy of a hepatoma and its premalignancy.
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PMID:Isolation and characterization of a new fucoganglioside accumulated in precancerous rat liver and in rat hepatoma induced by N-2-acetylaminofluorene. 708 43

A ganglioside named GM1b (Hirabayashi, Y., Taki, T., and Matsumoto, M. (1979) FEBS Let. 100, 253-257) with a sugar composition identical with that of GM1, II3 alpha NeuAc-GgOse4Cer (Gal beta 1 leads to 3GalNAc beta 1 leads to 4Gal(3 leads from 2 alpha NeuAc) beta 1 leads to 4G1c beta 1 leads to 1'ceramide), isolated from rat ascites hepatoma was further characterized. In contrast to GM1, the sialic acid in this ganglioside was susceptible to clostridial sialidase in the absence of bile salts. Based on the sequential enzymic hydrolysis, permethylation analysis and direct probe mass spectrometric analysis, the structure of this ganglioside is determined to be: NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc beta 1 leads to 4Gal beta 1 leads to 4Glc leads to ceramide. The structure of this ganglioside is identical with that biosynthesized in vitro (Stoffyn, A., Stoffyn, P., and Yip, M. C. M. (1975) Biochim. Biophys. Acta 409, 97-103).
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PMID:Further characterization of the structure of GM1b ganglioside from rat ascites hepatoma. 728 5

The lacto-N-neotetraose-containing lipooligosaccharide (LOS) present on the surface of most Neisseria gonorrhoeae organisms may serve many important functions in gonococcal pathogenesis. This surface glycolipid contains the cross-reactive epitope to human paragloboside and can be sialylated by gonococci grown in the presence of CMP-N-acetylneuraminic acid. Another possible role for this glycolipid could be to mimic human asialocarbohydrates and act as a ligand for asialoglycoprotein receptors contained on numerous human cells. The most noted of this large family of receptors is that expressed on the surface of hepatic cells. In a model cell system, using the hepatoma tissue culture cell line HepG2, we wanted to investigate if the presence of this asialoglycoprotein receptor influenced the adherence and/or invasion of gonococci expressing the lacto-N-neotetraose structure. Piliated variants of the gonococcal wild-type strain 1291 and its isogeneic LOS mutant 1291E were used in adherence-invasion assays. This gonococcal strain is somewhat unusual in that it expresses large amounts of predominantly one species of LOS, thus reducing the complexity of interpreting the data. The data from these assays suggested that the Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc carbohydrate structure on the wild-type LOS affected the adherence-invasion of gonococci into the HepG2 cells. In studies to determine whether the major hepatic asialoglycoprotein receptor was involved in these interactions, we found that the HepG2 cells contained two receptors which bound gonococcal LOS. One of these was the asialoglycoprotein receptor, and the data concerning this receptor will be reported elsewhere. The data on the second receptor are reported here. Purified, 125I-labeled gonococcal LOS was used to identify specific high-affinity LOS-binding sites. These binding experiments revealed one major binding site corresponding to a protein with a molecular mass of 70 kDa (p70). Several lines of evidence in this study suggested that the oligosaccharide region of LOS played an important role in LOS binding to the p70 of HepG2 cells. In addition, we show that this human LOS receptor has some similarities to the gonococcal Opa proteins.
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PMID:A lipooligosaccharide-binding site on HepG2 cells similar to the gonococcal opacity-associated surface protein Opa. 753 7


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