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)

Ascites hepatoma AH-66 and 3'-Me-DAB-induced hepatoma of rats contain highly active N-acetylglucosaminyltransferase III (GnT-III) which catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage (bisecting N-acetylglucosamine) to the beta-linked mannose of the trimannosyl core of asparagine-linked sugar chains, whereas normal rat liver contains very little. The high activity was also detected in fetal rat liver, newborn rat liver, hyperplastic nodules and various transplantable hepatomas.
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PMID:High expression of an N-acetylglucosaminyltransferase III in 3'-methyl DAB-induced hepatoma and ascites hepatoma. 298 Oct 47

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

131I labeled rabbit antibodies to the human epithelial intestinal antigen beta 1-MA was administered intravenously to nude mice together with human tumor grafts: colon cancer (CC), breast cancer, Ewing's sarcoma and hepatoma. Antibodies to beta 1-MA were selectively accumulated in CC only, excluding the other tumors. Iodinated nonspecific rabbit IgG in mice with CC were distributed like antibodies to beta 1-MA in the body of mice with control heterografts. A conclusion was made of the promising use of labeled antibodies to beta 1-MA in radioimmuno-scintigraphy of CC and its metastases.
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PMID:[Distribution of iodinated antibodies to the human organ-specific intestinal antigen in athymic mice with heterotransplanted tumors]. 395 7

A comparative study using hydrazinolysis has revealed that the oligosaccharide pattern of gamma-glutamyltranspeptidase purified from rat AH-66 hepatoma cells is very different from that of the enzyme from rat liver. Studies of oligosaccharides in each fraction have clarified the structural basis of the difference found in the sugar chains of the two enzymes. The sugar chains of the liver enzyme were all acidic, while 28% of those of the hepatoma enzyme were neutral, the latter being composed of high-man-nose-type and complex-type sugar chains. Three prominent structural differences were found in the acidic sugar chains of the two enzymes: (a) the sugar chains of the liver enzyme have complete outer chains, Gal beta 1 leads to 4GlcNAc beta 1 leads to, while many of those of the hepatoma enzyme have incomplete outer chains without galactose (Gal); (b) the Gal beta 1 leads to 4GlcNAc beta 1 leads to Gal beta 1 leads to 4GlcNAc beta 1 leads to group is found in the sugar chains of the liver enzyme but not in those of the hepatoma enzyme; (c) more than 40% of the sugar chains of the hepatoma enzyme contain bisect N-acetylglucosamine (GlcNAc) residue which is not found in those of the liver enzyme. Furthermore, the total number of asparagine-linked sugar chains in one molecule of hepatoma enzyme was about 4 times that found in one molecule of liver enzyme.
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PMID:Comparative study of the sugar chains of gamma-glutamyltranspeptidases purified from rat liver and rat AH-66 hepatoma cells. 613 77

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

A human hepatocyte line (HHY41) was established from normal human liver tissue. This cell line was derived from a primary culture of human hepatocytes maintained between two layers of collagen gel for 4 weeks. It differs from other human hepatocyte lines in that transfection with the simian virus 40 gene was not used for cellular transformation and nonhepatocellular coculture cells were not present. HHY41 cells have proliferated freely in serum and hormone-supplemented medium after more than 1 year in continuous culture, exhibiting typical morphological characteristics of hepatocytes. HHY41 cells retain glucose-6-phosphatase activity. They also retain the ability to secrete liver-specific proteins such as albumin, transferrin, and alpha-fetoprotein. Northern blot analysis confirmed the presence of albumin mRNA. Cytochromes P450 induced by polycyclic aromatic hydrocarbons are maintained in these cells. Detection of cell surface antigens revealed that HHY41 cells express alpha 1 beta 1-integrin, which is expressed by normal hepatocytes and not by bile duct epithelial cells. High-molecular-weight cytokeratin, a marker for bile duct cells, is also absent in HHY41. Cytogenetic analysis showed hyperdiploid karyotype with a consistent deletion in the short arm of chromosome 1. HHY41 can be considered a new human hepatocyte line which retains liver-specific functions of differentiated hepatocytes. Derived from normal liver tissue, not a hepatocellular carcinoma, it provides a new model system for studying the regulation of cell growth and differentiated functions in human hepatocytes.
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PMID:Establishment of a human hepatocyte line derived from primary culture in a collagen gel sandwich culture system. 749 48


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