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)

We have demonstrated that rat liver contains at least four types of sialidase differing in subcellular location, in catalytic property and immunologically. They are intralysosomal, cytosolic and membrane-associated sialidases I and II. Membrane sialidase I locates mainly in plasma membrane and sialidase II in lysosomal membrane. Immunological study reveals that the same types of sialidase exist in various tissues of rat and of other mammalian species. Based on these results, we examined the sialidases in rat hepatomas and in transformed cells of JB6 mouse epidermal cell. Hepatomas were found to possess four types of sialidase and the three of them altered quantitatively. Intralysosomal sialidase activity was higher but cytosolic and lysosomal membrane sialidase activities were lower in hepatomas than in control liver. When the sialidases of transformants of JB6 cells were compared with those of control cells, the activities of two lysosomal sialidases were decreased and contrarily plasma membrane sialidase was increased. We discussed a possible significance of the sialidase alterations in carcinogenesis.
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PMID:Multiple forms of mammalian sialidase: altered expression in carcinogenesis. 130 7

The relationship between cell differentiation/tumorisation and plasma membrane glycoproteins was approached using peanut agglutinin (PNA) a lectin specific for the Gal-beta(1,3)GalNAc sequence and a homologous cell system consisted of normal rat hepatocytes (HyC) and a poorly differentiated hepatoma (ZHC). This work is focused on the molecular nature of PNA receptors. PNA bound strongly to ZHC, but bound very weakly, if at all to hepatocytes. After sialidase treatment this binding was slightly enhanced in ZHC and HyC. The total number of binding sites on ZHC was 9.6 x 10(6)/cell and 1.2 x 10(7)/cell before and after sialidase treatment respectively. In contrast, this number could not be calculated on HyC, even after sialidase treatment. The PNA receptors were isolated and identified from ZHC using affinity chromatography on immobilized PNA and lectin overlay. Two bands were revealed after SDS-PAGE of PNA receptors: a major one with a relative molecular mass of 160 kDa and a minor one of 110 kDa. The latter disappeared after sialidase treatment of ZHC suggesting the possibility that these two bands could be less and more sialylated forms of the PNA receptors, respectively. In contrast no PNA receptors could be detected on HyC. These PNA receptors could be considered O-linked glycoproteins containing the Gal-beta(1,3)GalNAc disaccharide because: i) PNA carbohydrate specificity toward this disaccharide found in this glycoprotein type; ii) their carbohydrate composition with Gal and GalNAc but not man residues; iii) their sensitivity to alkaline treatment; and iv) strong inhibition of PNA binding to ZHC with the Gal-beta(1,3)GalNAc structure. The absence of PNA receptors on HyC appeared to be related to the absence of this glycoprotein containing the disaccharide but not to the change or failure of glycosylation of the polypeptide chain of PNA receptors. The relationship between the presence of PNA receptors and differentiation/tumorisation phenomena as well as the mechanism that induced the expression of these receptors are discussed.
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PMID:Identification of peanut agglutinin receptors related to the state of tumoral liver cell differentiation. 157 2

Rat liver particulate fraction contains two types of membrane-associated and gangliosides-hydrolyzing sialidase, which have been shown to be identical to two membrane-associated sialidases of rat brain (I and II) chromatographically, immunologically and in substrate specificity. Chromatography on AH-Sepharose 4B of the membrane sialidases of rat primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (MeDAB) further revealed that hepatocarcinogenesis induces a marked decrease in sialidase II but no decrease in sialidase I. Using antisera against sialidases I and II of rat brain, immunoprecipitation studies of the solubilized particulate fractions of rat liver and MeDAB-hepatoma gave results similar to those obtained chromatographically. Using the same immunological technique, sialidase II but not sialidase I was found to be decreased in AH109 A hepatoma and in regenerating and fetal liver.
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PMID:Neoplastic alteration of a membrane-associated sialidase of rat liver. 212 93

Gangliosides of hepatomas have been analyzed by using a monoclonal antibody directed to N-acetylneuraminosyl(alpha 2-6)lactoneotetraosylceramide (sialyl(alpha 2-6)paragloboside), which was prepared by injecting the monosialoganglioside fraction of human meconium into BALB/c mice. The monoclonal antibody, named MSG-15, was found to bind sialyl(alpha 2-6)paragloboside, but it failed to react with other gangliosides, including N-acetylneuraminosyl(alpha 2-3)lactoneotetraosylceramide (sialyl (alpha 2-3)paragloboside) and "Ii"-type gangliosides. MSG-15 was found to recognize NeuAc alpha 2-6Gal beta structure of the ganglioside. Gangliosides obtained from human hepatomas were analyzed by immunostaining on high-performance thin-layer chromatography plates using the monoclonal antibody MSG-15. All primary hepatoma samples used in this study (nine samples) were found to contain sialyl(alpha 2-6)paragloboside, which accounted for 13-31% of the monosialoganglioside fractions in the hepatomas. Furthermore, MSG-15 recognized several monosialogangliosides in addition to sialyl(alpha 2-6)paragloboside. These gangliosides apparently also contain a terminal NeuAc alpha 2-6Gal beta structure. Other ganglioside fractions obtained from hepatoma and meconium were immunostained on thin layer chromatography plates with MSG-15. Additionally, another monoclonal antibody (H-11), which recognizes terminal lactosamine structure, was used to immunostain these fractions after sialidase treatment. Bands stained with both monoclonal antibodies showed similar mobilities to each other in the di- and trisialoganglioside fractions as well as monosialoganglioside fraction. In control liver, GM3 ganglioside accounted for 92% of monosialoganglioside fraction, and sialyl(alpha 2-6)paragloboside accounted for less than 1% of the fraction. Immunohistochemical study by using MSG-15 in tissue sections from hepatocellular carcinoma and normal liver tissues demonstrated that only hepatocellular carcinoma cells gave a positive reaction. These results suggest that the biosynthetic pathway of gangliosides containing NeuAc alpha 2-6Gal beta 1-4GlcNAc beta structure is activated in hepatoma cells.
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PMID:Accumulation of gangliosides with N-acetylneuraminosyl(alpha 2-6)lactosamine structure in primary human hepatoma. 215 56

An antibody-lectin enzyme immunoassay (EIA) technique was developed for the analysis of sugar chains of serum alpha-fetoprotein in various liver diseases. The anti-'alpha-fetoprotein'-IgG was coated on a microtiter plate and then treated with periodic acid. A serum sample was added to the plate and then a 'peroxidase'-conjugated lectin was added. The amount of lectin bound to the sugar chain of the 'alpha-fetoprotein' was estimated from the 'peroxidase' activity. The 'peroxidase' activities of 4 different lectins, LCA, Con A, LCA and EPHA, were compared. The LCA/'wheat germ agglutinin' activity ratio and LCA/EPHA activity ratio were increased in liver diseases and LCA/'wheat germ agglutinin' ratio showed a statistically significant difference between the chronic hepatitis and the liver cirrhosis groups (p less than 0.05). Furthermore, when serum samples were pretreated with sialidase, a statistically significant difference was observed in the LCA/EPHA and LCA/Con A ratios between the chronic hepatitis and the hepatoma groups (p less than 0.05). These results indicated that low sialylation at the non-reduced end of the sugar chains of 'alpha-fetoprotein' occurs in liver cirrhosis and that high fucosylation at the reduced end of N-acetylglucosamine residue of 'alpha-fetoprotein' occurs in hepatomas.
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PMID:Alpha-fetoprotein antibody-lectin enzyme immunoassay to characterize sugar chains for the study of liver diseases. 246 50

Gangliosides isolated from 5 cases of normal liver tissues, 11 cases of liver cirrhosis and 5 cases of hepatocellular carcinoma were compared in their concentrations and compositions. Quantitative analysis revealed no significant change of ganglioside levels between normal and cirrhotic liver tissues or hepatocellular carcinoma. There was also no significant difference (p greater than 0.05) between cirrhotic liver tissues and hepatocellular carcinoma. Two dimensional thin-layer chromatography of the total ganglioside preparations of liver tissues from both liver cirrhosis and hepatocellular carcinoma showed proliferation of GM2, GD3, GD1 and at least two unidentified components, named provisionally spots Nos. 1 and 2 in the present report, and loss of GM3. Sialidase treatment and thin-layer chromatography showed the components of these spots to be sialidase-labile monosialogangliosides and distinctly different from GD3 which was described elsewhere.
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PMID:Ganglioside variations in human liver cirrhosis and hepatocellular carcinoma as shown by two-dimensional thin-layer chromatography. 285 12

During the first stage of infection, the paramyxovirus Sendai virus attaches to host cells by recognizing specific receptors on the cell surface. Productive virus-cell interactions result in membrane fusion between the viral envelope and the cell surface membrane. It has recently been shown that the ganglioside GD1a and its more complex homologs GT1b and GQ1b are cell surface receptors for Sendai virus. We report in this paper that the temperature-sensitive mutant ts271 of the Enders strain of Sendai virus lacks the viral attachment protein HN and the biological activities of hemagglutination and sialidase activity associated with it when the virus is grown at 38 degrees C. This HN- virus was unable to infect or agglutinate conventional host cells that contained receptor gangliosides and were readily infected by the parental wild-type virus. The HN- virus did, however, attach to and infect Hep G2 cells, a line of hepatoma cells that retains the asialoglycoprotein receptor (ASGP-R) upon continuous culture. This receptor is a mammalian lectin that recognizes galactose- or N-acetylgalactosamine-terminated proteins. In accordance with the known properties of this receptor, infection by the HN- virus was abolished by treatment of Hep G2 cells with sialidase, by the presence of Ca2+ chelators, and by competition with N-acetylgalactosamine, asialoorosomucoid, and antibody to the receptor. F, the only glycoprotein on the HN- virus, was shown to compete with the galactose-terminated protein asialoorosomucoid for the ASGP-R. The ability of the HN- virus to cause cell-cell fusion of Hep G2 cells indicated that attachment of this virus to the ASGP-R still permitted viral entry by its usual mode--i.e., membrane fusion at the cell surface. These results open up the possibility that enveloped viruses, which contain glycosylated proteins or lipids, may make use of naturally occurring lectins in addition to their normal receptors as a means of attachment to host cells.
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PMID:An alternative route of infection for viruses: entry by means of the asialoglycoprotein receptor of a Sendai virus mutant lacking its attachment protein. 298 37

The quantity of tumor-associated antigens carrying type 2 chain polylactosamines with four types of fucosyl determinants, LeX (X-hapten), poly-LeX, sialyl LeX, and LeY (Y-hapten), present in sera of patients with various malignant and non-malignant disorders, as well as the qualitative chemical properties of the carrier molecules in sera, have been investigated using four monoclonal antibodies, each of which defines one of these determinants. The following findings are of particular importance: the serum levels of LeX defined by antibody FH2 and poly-LeX defined by ACFH18 in patients with cancer were occasionally high (incidence about 10%); however, the majority of patients did not show elevated levels; the serum level of the antigen, defined by monoclonal antibody FH6 (termed sialyl LeX-i since this determinant is carried by i antigen), was significantly high in patients with cancers originating from organs from which adenocarcinomas often develop. For example, among various types of lung cancer, only adenocarcinoma but not squamous cell carcinoma, small cell carcinoma, or large cell carcinoma showed a high level of sialyl LeX-i antigen in sera. The incidence of high antigen levels in sera of patients with adenocarcinomas of lung was as high as 76% of the observed cases; the serum level of Ley (Y-hapten) was frequently high in patients with hepatoma (incidence, 34%); sialyl LeX-i antigen was separated on gel filtration as a glycoprotein with an average molecular weight greater than 10(6). It was characterized by its susceptibility to basehydrolysis, Pronase digestion, and sialidase and endo-beta-galactosidase treatment and is assumed to be a high molecular weight mucin-type glycoprotein; sialyl LeX-i antigen expressed in sera of patients with cancer was soluble in perchloric acid, while the same antigen in sera of patients with noncancerous diseases and normal subjects was mostly insoluble in perchloric acid. LeX, a poly-LeX, and essentially all LeY antigens in sera of patients with cancer were perchloric acid-insoluble.
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PMID:Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing fucosyl or sialyl-fucosyl type 2 chain polylactosamine. 300 96

Using the particulate fraction of tissue homogenate, plasma membrane-associated sialidase was assayed at pH 4.5 with bovine brain mixed gangliosides as the substrate. The activity was lower in rat hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (MeDAB) and transplantable AH-109A rat hepatoma than in normal rat liver. The enzyme was almost quantitatively solubilized from liver particulate fraction by using 0.5% (w/v) sodium deoxycholate plus 0.2% (w/v) Triton X-100. When chromatographed on DEAE-cellulose, the solubilized activity emerged as a single peak. The enzyme thus obtained was maximally active at pH 4.5, and readily hydrolyzed mixed gangliosides but was less active toward 4-methylumbelliferyl-alpha-N-acetylneuraminic acid, 3'-sialyllactose and fetuin. The corresponding enzyme from MeDAB-induced hepatoma was indistinguishable from the liver enzyme in terms of ease of solubilization, pH-activity relationship, chromatographic behavior and substrate preference. It therefore appears that the plasma membrane-associated sialidase of hepatomas differs from that of liver only in the tissue level of activity.
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PMID:Membrane-associated sialidase of rat liver and its decrease in hepatomas. 312 7

The subcellular distribution of sialidase in rat hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene was studied by using sialyllactose as a substrate in the pH range of 4.0-7.0. As found in rat liver, the activity was recovered largely in the mitochondrial/lysosomal fraction with an optimal pH of 4.5 and in the cytosolic fraction with an optimal pH of 6.0, although hepatoma lysosomal (acidic) sialidase was also distributed in the microsomal fraction. The lysosomal and cytosolic sialidases of the hepatoma were indistinguishable from the corresponding enzymes of liver in chromatographic behavior, kinetics and substrate specificity. The levels of lysosomal and cytosolic sialidase activities in liver and hepatomas were then studied in the pellet and supernatant fractions, respectively, obtained by centrifuging the postnuclear supernatant at 105,000g for 1 hr. All the hepatomas tested, one primary and three transplanted, showed higher lysosomal sialidase and lower cytosolic sialidase activities as compared with liver. Quantitative changes similar to those seen in hepatomas were observed in regenerating liver after partial hepatectomy.
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PMID:Sialidase of rat hepatomas: qualitative and quantitative comparison with rat liver sialidase. 652 22


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