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)

Rats bearing Reuber H-35 or Novikoff hepatomas and mice bearing L1210 or L5178Y murine leukemias exhibited elevated serum levels of fetuin : N-acetylneuraminic acid transferase (EC 2.4.99.1) activity. The serum transferase activity could be correlated with the growth rate of the tumor; in animals bearing the more rapidly growing Novikoff hepatoma, activity was higher than in animals bearing the Reuber H-35 hepatoma. Higher transferase levels were also found in L1210 leukemic mice than in mice with the slightly slower growing L5178Y leukemia. Serum from rats bearing Reuber H-35 hepatoma and mice bearing L1210 murine leukemia had elevated levels of alpha- and beta-glucosidase (EC 3.2.1.20 and EC 3.2.1.21), alpha- and beta-galactosidase (EC 3.2.1.22 and (3.2.1.23), beta mannosidase (EC 3.2.1.25), alpha- and beta-fucosidase (EC 3.2.1.- and EC 3.2.1.38), beta-N-acetylglucosaminidase (EC 3.2.1.30) and acid phosphatase (EC 3.1.3.2); alpha-mannosidase (EC 3.2.1.24), beta-N-acetylgalactosaminidase (EC 3.2.2.-) and beta-xylosidase (EC 3.2.1.37) were not elevated. In animals bearing Reuber H-35 hepatoma, host liver levels of glycosidases, beta-glucuronidase (EC 3.2.1.31) and acid phosphatase were elevated over both the control and the hepatoma values. The data are interpreted to mean that the tumors or various host tissues release large quantities of enzymes into the serum and that enzyme levels in host organs may also be affected by the tumor.
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PMID:Serum and host liver activities of glycosidases and sialyltransferases in animals bearing transplantable tumors. 17 98

The synthesis, transport and processing of lysosomal enzymes was examined in human hepatoma HepG2 cells and in human fibroblasts exposed to the Golgi alpha-mannosidase I inhibitor 1-deoxy-manno-nojirimycin. In HepG2 cells cathepsin D, beta-hexosaminidase and arylsulfatase B synthesized in the presence of 5 mM 1-deoxy-manno-nojirimycin contained exclusively endo-beta-N-acetylglucosaminidase H-cleavable oligosaccharides, indicating that alpha-mannosidase I had been inhibited efficiently. The proteolytic processing of intracellularly retained cathepsin D was retarded and the fraction of secreted cathepsin D was increased two-fold. In fibroblasts neither segregation nor maturation of cathepsin D were affected by 1-deoxy-manno-nojirimycin in spite of the inhibition of oligosaccharide processing. In the presence of the glucosidase I inhibitor 1-deoxynojirimycin, the precursor of cathepsin D (larger by about 1 kDa than the secreted form) accumulated transiently in light membranes in HepG2 cells. Release from the site of accumulation was accompanied by a decrease in size by about 1 kDa. This change was attributed to the removal of glucose residues. In fibroblasts the transient accumulation of larger precursors in the presence of 1-deoxynojirimycin was more pronounced than in HepG2 cells. The differential effects of alpha-mannosidase I and glucosidase I inhibitors on the transport of cathepsin D in HepG2 cells and fibroblasts may indicate that different intermediates in the biosynthetic pathway of asparagine-linked oligosaccharides participate in the transport of lysosomal enzymes in the two cell types.
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PMID:Cell type dependent inhibition of transport of cathepsin D in HepG2 cells and fibroblasts exposed to deoxy-manno-nojirimycin and deoxynojirimycin. 293 77

Four glycosidases (beta-galactosidase, alpha-mannosidase, alpha-fucosidase and beta-N-acetylglucosaminidase) were studied in chicken normal and regenerating liver, in turkey poult liver and in virus induced avian tumors--chicken hepatoma (strain Mc-29), Rous sarcoma (strain Schmidt-Ruppin) and turkey poult hemocytoblastoma nodules (strain Mc-31). The multiple forms of beta-N-acetylglucosaminidase were assayed as well. A particular enzyme pattern was found in the tumor lines under investigation. A characteristic property of hepatoma cells was the elevation of beta-galactosidase activity and of the former enzyme and that of beta-N-acetylglucosaminidase for the hemocytoblastoma. In Rous sarcoma the glycosidase activities (except that of alpha-fucosidase) were much lower, compared to the other two solid tumors. All enzyme activities were compared with those in the normal liver of the corresponding avian species, and with the liver of tumor bearing fowls and with regenerating chicken liver. Unlike the rat liver in the avian normal and tumor tissues the percentual ratio between the multiple forms A and B of beta-N-acetylglucosaminidase was found to be 30:70%.
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PMID:Glycosidases in normal and regenerating chicken liver, hepatoma Mc-29, Rous sarcoma, in turkey poult liver and hemocytoblastomes, provoked by the leukosis virus strain Mc-31. 298 24

Reconstituted Sendai-viral envelopes (RSVE) were fused with hepatoma tissue-culture (HTC) cells, thereby introducing viral membrane glycoproteins into the plasma membrane [Earl, Billett, Hunneyball & Mayer (1987) Biochem. J. 241, 801-807]. Fractionation of homogenized cells on Nycodenz gradients shows that much of the viral 125I-labelled HN and F proteins were rapidly sequestered into a dense fraction distinct from fractions containing plasma membrane, lysosomes and mitochondria. Electron microscopy (results not shown) indicates that the dense fraction contains nuclear residues, multivesicular structures, dense bodies and fibrous structures. Both the dense fraction and a hexosaminidase-enriched fraction contain trichloroacetic acid-insoluble radioactivity, including intact 125I-labelled viral proteins. The viral proteins are progressively transferred from the dense fraction to the hexosaminidase-enriched fraction; the transfer is retarded by 50 micrograms of leupeptin/ml. Trichloroacetic acid-soluble radiolabel is progressively released into the culture medium as the proteins are degraded. Within 5 h after transplantation of viral HN and F proteins into recipient cells, a proportion (approx. 45%) of the 125I-labelled glycoproteins cannot be extracted by sequentially treating cells with digitonin (1 mg/ml), Triton X-100 (1%, w/v) and 0.3 M-KI. HN and F proteins in the non-extractable residue are tightly associated with nuclear-intermediate-filament (vimentin) material, as shown by Western blots and electron microscopy. The viral proteins are progressively transferred out of the nuclear-intermediate-filament residue; the transfer is slowed when cells are cultured with leupeptin. The data are consistent with the notion that transplanted viral HN and F proteins are sequestered to a perinuclear site in tight association with intermediate filaments before transfer into the autophagolysosomal system for degradation.
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PMID:A putative protein-sequestration site involving intermediate filaments for protein degradation by autophagy. Studies with transplanted Sendai-viral envelope proteins in HTC cells. 303 75

When homogenates of rat liver and hepatomas were centrifuged at 78 000 X g, over 90% of liver N-acetylglucosaminyltransferase assayed with beta-galactosidase- and beta-N-acetylhexosaminidase-treated asialofetuin as acceptor was recovered in the particulate fraction, while as much as 24% of hepatoma transferase was in the supernatant fraction. The particulate transferase solubilized by 0.2% sodium deoxycholate emerged from a DEAE-cellulose column at 0.04 M NaCl (transferase A). The supernatant fractions from all the hepatomas tested contained a second N-acetylglucosaminyltransferase eluted from the column at 0.02 M NaCl (transferase B). Transferase B was absent from liver supernatant fraction. The activities of these transferases toward various acceptors and the effect of beta-N-acetylhexosaminidase on their products suggest that both transferases are UDP-N-acetylglucosamine : alpha-mannoside beta-N-acetylglucosaminyltransferase. Although ovalbumin and glycopeptide V, which was isolated from pronase digest of ovalbumin, were good acceptors, transferase A utilized ovalbumin and glycopeptide V with apparent Km values of 0.44 and 0.33 mM, respectively, whereas the corresponding values for transferase B were 4.5 and 0.050 mM.
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PMID:Studies on UDP-N-acetylglucosamine : alpha-mannoside beta-N-acetylglucosaminyltransferase of rat liver and hepatomas. 617 Mar 35

In various forms of liver disease, increased levels of the lysosomal enzyme beta-hexosaminidase (Hex) occur in serum. This may be caused by disturbances of the hepatocytic function, and we therefore studied the intracellular and extracellular isoenzyme pattern of Hex in a human hepatoma cell-line (Hep G2), using an immunoassay method, which separates Hex A and Hex B isoforms. This cell-line synthesizes and secretes Hex. The cumulative release of extracellular activity was about 3-10% of the intracellular activity. B-isoforms comprised one-third of intracellular activity but only 20% of extracellular activity. The proportion of extracellular B-isoforms increased with time, presumably due to instability of A-isoforms at 37 degrees C. Cycloheximide inhibited the release of Hex activity, whereas NH4Cl increased the extracellular fraction of Hex, even at a concentration of 1 mmol/l. We speculate that the increased concentration of NH4+ in patients with liver disease interferes with the distribution pathway of the lysosomal enzymes. This might be one reason for the increased serum Hex activity found in patients with liver disease.
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PMID:Liver disease and serum hexosaminidase levels. Studies in a human hepatoma cell-line (Hep G2 cells). 779 44

Serum alpha-fetoprotein (AFP) is a glycoprotein of which the sugar chain is considered to show structural changes with malignancies. Microheterogeneity of the serum AFP carbohydrate structure was studied in samples from 35 patients with benign and malignant diseases. Sera were digested directly, extensively, and sequentially with sialidase. beta-galactosidase and beta-N-acetylhexosaminidase. Before and after digestion, sera were examined by means of lectin affinity electrophoresis using eight lectins. Relationships between AFP carbohydrate structures and liver diseases were elucidated by the lectin-reactive profiles and the effect of glycosidase digestion. More than 94% of the AFP carbohydrate structures found in patients with benign and malignant liver diseases were biantennary complex-type oligosaccharides. Changes in the AFP carbohydrate structures at the early stage of hepatocellular carcinoma revealed the addition of alpha 1-->6 fucose to the reducing terminal N-acetylglucosamine and monosialylated AFPs. In both advanced hepatocellular carcinoma and AFP producing extrahepatic malignancies, AFP carbohydrate structures were characterized as the further addition of beta 1-->4 N-acetylglucosamine and heterogeneity in the galactose and N-acetylglucosamine residues. Sequential glycosidase digestion and lectin affinity electrophoresis is useful for analysing the carbohydrate structures of serum glycoprotein.
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PMID:Comparison of carbohydrate structures of serum alpha-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis. 889 7

It has previously been demonstrated that Ukrain administration (0.5 mg in mice of 20 g, five times) to A/Sn mice results in retardation of HA-1 tumor growth in the liver and a prolongation of lifespan compared with untreated controls. In the present study Ukrain was tested as a macrophage stimulator in intact mice and animals with HA-1 hepatoma. There were no changes to the carbon particles phagocytosis rate in the case of a single administration of Ukrain to intact mice. Significant secretion of procathepsin B into ascitic fluid was shown in tumor mice as well as marker enzyme of macrophages beta-hexosaminidase activity, suggesting an influx of macrophages into ascites. Single Ukrain administration increased this index, and repeated drug injections were followed by a tendency to normalization of secretion. The cytolytic effect of Ukrain against tumor cells (as a result of macrophage stimulation) is the most probable mechanism of its antitumor action, but this suggestion needs further experimental evidence with special attention paid to the balance of proteinases and endogenous proteinase inhibitors.
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PMID:Macrophage stimulation and antitumor effect of Ukrain. 1019 84

In hepatocellular carcinoma HepG2 cells, free polymannose-type oligosaccharides appearing in the cytosol during the biosynthesis and quality control of glycoproteins are rapidly translocated into lysosomes by an as yet poorly defined process (Saint-Pol, A., Bauvy, C., Codogno, P., and Moore, S. E. H. (1997) J. Cell Biol. 136, 45-59). Here, we demonstrate an ATP-dependent association of [2-3H]mannose-labeled Man5GlcNAc with isolated rat liver lysosomes. This association was only observed in the presence of swainsonine, a mannosidase inhibitor, which was required for the protection of sedimentable, but not nonsedimentable, Man5GlcNAc from degradation, indicating that oligosaccharides were transported into lysosomes. Saturable high affinity transport (Kuptake, 22.3 microM, Vmax, 7.1 fmol/min/unit of beta-hexosaminidase) was dependent upon the hydrolysis of ATP but independent of vacuolar H+/ATPase activity. Transport was inhibited strongly by NEM and weakly by vanadate but not by sodium azide, and, in addition, the sugar transport inhibitors phloretin, phloridzin, and cytochalasin B were without effect on transport. Oligosaccharide import did not show absolute specificity but was selective toward partially demannosylated and dephosphorylated oligosaccharides, and, furthermore, inhibition studies revealed that the free reducing GlcNAc residue of the oligosaccharide was of critical importance for its interaction with the transporter. These results demonstrate the presence of a novel lysosomal free oligosaccharide transporter that must work in concert with cytosolic hydrolases in order to clear the cytosol of endoplasmic reticulum-generated free oligosaccharides.
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PMID:Cytosol-to-lysosome transport of free polymannose-type oligosaccharides. Kinetic and specificity studies using rat liver lysosomes. 1022 24

Conjugated linoleic acid (CLA) is a powerful anti-carcinogenic fatty acid. Previously, we showed that 10trans 12cis (10t, 12c) CLA induced apoptotic cell death in rat hepatoma. Here, we demonstrated significant cytotoxic effects of 1 muM 10t, 12c-CLA, but not 9c, 11t-CLA, on dRLh-84 rat hepatoma cells. 9t, 11t and 9c, 11c-CLA also showed low levels of cytotoxic activity. 10t, 12c-CLA activated caspase-3, 9 followed by cytochrome c release from mitochondria into the cytosol. Inhibitors of caspase-3, 9 blocked the cytotoxicity of 10t, 12c-CLA. 10t, 12c-CLA also induced translocation of Bax protein into the mitochondrial membrane and cleavage of Bid protein. Lysosomal destabilization induced by 10t, 12c-CLA was observed by monitoring the re-localization of Acridine Orange and the leakage of beta-hexosaminidase from lysosomes. 10t, 12c-CLA directly degraded the isolated lysosomes from the rat liver. Our observations indicate that 10t, 12c-CLA induces mitochondria-related apoptosis accompanied by lysosomal destabilization in rat hepatoma cells.
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PMID:Trans10, cis12-conjugated linoleic acid induces mitochondria-related apoptosis and lysosomal destabilization in rat hepatoma cells. 1600 59


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