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 lectin from the elderberry (Sambucus nigra L.) bark, shown to recognize the sequence neuraminic acid (alpha 2,6) galactose/N-acetylgalactosamine, was applied for detecting binding sites in Lowicryl K4M sections by light and electron microscopy. The lectin was used either directly complexed to colloidal gold or in a two-step cytochemical affinity technique. The lectin-gold complex proved to be superior and thus was extensively tested on rat liver, kidney and hepatoma cells as well as on sheep and bovine submandibular glands. Controls to establish specificity of lectin-gold binding included sugar and glycoprotein inhibition tests and enzymic removal of sialic acid. In agreement with biochemical data demonstrating the potentiating effect of sialic acid on the binding of the lectin to oligosaccharides, enzymic removal of sialic acid from liver sections resulted in abolition of lectin staining. However, in the submandibular glands, neuraminidase pretreatment of the sections had no effect on the subsequent lectin-gold binding. In rat kidney some structures became negative while others retained the lectin-gold staining due to binding to penultimate N-acetylgalactosamine exposed after sialic acid removal. In line with this, spot blot analysis demonstrated that the lectin-gold complex reacted with both fetuin and asialofetuin. Taken together, these results suggest that, for cytochemical staining, the sialic acid and the galactose/N-acetylgalactosamine lectin combining subsites of Sambucus nigra L. lectin are equally reactive with cellular glycoconjugates and that neuraminidase predigestion of tissue sections is of utmost importance to ensure specificity of staining for the sequence neuraminic acid (alpha 2,6) galactose/N-acetylgalactosamine.
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PMID:Elderberry bark lectin--gold techniques for the detection of Neu5Ac (alpha 2,6) Gal/GalNAc sequences: applications and limitations. 246 94

A daunorubicin (DNR)-resistant variant (AH66DR) of alpha-fetoprotein (AFP)-producing rat ascites hepatoma AH66 was established. AH66DR was 169 times more resistant to DNR than AH66. A growth-inhibitory effect due to the decrease in sugar uptake following treatment of the cell lines with specific antibody against highly purified rat AFP was also observed. Pre-incubation of both lines with antibody prior to the measurement of 2-deoxy-D-glucose (2dG) uptake resulted in a 45-55% decrease in 2dG uptake compared to control cells with a 2-fold reduction of Vmax value while the Km remained unchanged. Upon pre-incubating AH66DR with antibody, an increased intracellular level of DNR concentration with reduction of efflux rate was observed. A significantly superior cytotoxic effect against AH66DR, which reached almost the same level as the cytotoxic effect of DNR against AH66, was found, as compared to various other controls when tumor cells were cultured with a mixture of antibody and DNR. Our in vitro results suggest that the DNR-resistance of the AFP-producing tumor cells may be overcome if the cells are treated with specific antibody.
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PMID:Overcoming effect of antibody against rat alpha-fetoprotein (AFP) on the growth of daunorubicin-resistant mutant rat ascites hepatoma cell line AH66. 247 5

An N-acetylglucosaminyltransferase 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 structure of N-linked oligosaccharides of glycoproteins was measured in human serum, and liver and hepatoma tissues. The enzyme activity in serum was significantly elevated in patients with hepatomas and liver cirrhosis, and the activity markedly decreased on the transcatheter arterial embolization treatment. High activities were also found in the hepatoma and cirrhotic liver tissues, indicating that the serum activity reflected the activity in the tissues. The assaying of the enzyme activity in serum appears to be useful for the detection and monitoring of primary hepatomas.
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PMID:N-acetylglucosaminyltransferase III in human serum, and liver and hepatoma tissues: increased activity in liver cirrhosis and hepatoma patients. 248 96

In this study, binding and degradation of tissue-type plasminogen activator (t-PA) by the human hepatoma cell line Hep G2 was investigated. Binding at 4 degrees C was time-dependent and reached a maximum after ca. 2 hours. Scatchard analysis of saturation experiments showed about 170,000 high affinity binding sites for t-PA per cell with an apparent Kd of 90 nM. These binding sites were calcium-dependent. Part of the binding to the hepatoma cells was non-saturable, owing to a large amount of low affinity binding sites which are at least partially located on the extracellular matrix of the cells. Competition with mannose- and galactose-terminated glycoproteins had no effect on total binding of 125I-t-PA. Degradation products of 125I-t-PA were found in the supernatant after a short lag phase and then increased linearly for at least 5 hours at 37 degrees C. Degradation could be inhibited by chloroquine, NH4Cl and NaN3. We conclude that the human hepatoma cell line Hep G2 has a specific binding mechanism for t-PA which is not mediated by known carbohydrate receptor systems. Binding is followed by cellular uptake and degradation in the lysosomes.
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PMID:Binding and degradation of tissue-type plasminogen activator by the human hepatoma cell line Hep G2. 251 Mar 47

Starvation of a mouse hepatoma cell line, Hepa, for any essential amino acid results in the mono-ADP-ribosylation of an 80-kDa protein, P80. The ADP-ribose acceptor and its putative precursor were identified in two-dimensional gel patterns and isolated by electroelution. Amino-terminal sequence analysis showed they were the 78-kDa glucose-regulated protein, GRP78. Starvation of Hepa cells for tryptophan or glucose stimulated the relative rate of synthesis, and the ADP-ribosylation of GRP78. Inhibition of N-linked glycosylation by treatment with tunicamycin, 2-deoxy-D-glucose or glucosamine stimulated the synthesis of non-ADP-ribosylated GRP78 up to sixfold with relatively little effect on its ADP-ribosylation. Both forms were identified in mouse liver, lung, heart, kidney, spleen and brain.
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PMID:ADP-ribosylation of the 78-kDa glucose-regulated protein during nutritional stress. 251 84

A rat hepatoma cell line (Gershenson et al., Science, 170:859-861, 1970) contains a dynamic steady-state pool of free heparan sulfate (HS) chains in the nucleus that increases in amount when growing cells reach confluence (Fedarko and Conrad, J. Cell Biol., 102:587-599, 1986). In logarithmically growing cells labeled with 35SO4(2-) steady-state levels of [35SO4]HS in the nucleus are altered by a variety of culture conditions. Rapidly dividing cells (doubling time = 18-22 h) growing under optimized conditions had steady-state levels of nuclear HS within the range of 40-50 pmol 35SO4 in nuclear HS/10(6) cells. The steady-state levels of nuclear HS were lowered by several changes in culture conditions, including 1) additions of 1 mM p-nitrophenyl-beta-D-xyloside, 0.25-0.5 mM (+)-catechin, 0.5 ng/ml transforming growth factor beta, 20 ng/ml phorbol-12-myristate-13-acetate, 1 mM dibutyryl cAMP, or 1 mM inositol-2-PO4; 2) decreased levels of D-glucose; or 3) deletions of serum, insulin, or inositol. In all cases lowering of the nuclear HS level was accompanied by an increase in the cell doubling times, suggesting a correlation in which nuclear HS levels must be optimized for maximal growth rates. When cells cultured under optimal growth conditions reached confluence, the level of nuclear HS increased threefold and the cells stopped dividing. The same culture conditions that lowered the steady-state levels of HS in the logarithmically growing cells prevented this rise in the nuclear HS as the cells reached confluence and resulted in loss of contact inhibition and overgrowth of the confluent cultures. These observations suggest a second correlation in which elevated nuclear HS levels are found when cell growth is inhibited at confluence; prevention of this rise results in continued growth. Consistent with this correlation between elevated nuclear HS and reduced growth rates, it was observed that addition of either 0.5 microgram/ml hydrocortisone or 0.05 microgram/ml retinoic acid to the culture medium of logarithmically growing cultures resulted in increases in steady-state levels of nuclear HS that were accompanied by increased cell doubling times. The two agents that increased the levels of nuclear HS in logarithmically growing cultures had little effect on levels of nuclear HS in confluent cells or on contact inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Correlations between heparan sulfate metabolism and hepatoma growth. 252 57

We have compared the mechanisms of ricin binding to and entry into Zajdela hepatoma cells (ZHC) and normal rat hepatocytes (HyC). Lactose but not mannan was found to inhibit ricin binding to and toxicity on ZHC and HyC. This finding suggests that ricin binding, entry, and toxicity are expressed only through the galactose binding sites on ZHC and HyC. Nevertheless, the characteristics of ricin binding and its entry pathway appeared to be different in several respects in ZHC and HyC. Scatchard analysis of equilibrium data determined over a wide range of 125I-labeled ricin concentrations yielded a curvilinear plot for ZHC, while a straight line was obtained for HyC. These results indicate that only ZHC possess high-affinity receptors for ricin. Analysis of ricin toxicity on ZHC and HyC, in the presence of ammonium chloride or after K+-depletion in both cell types, suggests that the ricin bound to galactose receptors entered through neutral vesicles in ZHC, and through both neutral and acidic vesicles in HyC. The qualitative and quantitative differences found between the process of receptor-mediated endocytosis of ricin in ZHC and HyC might explain the differential sensitivity of the two cell types toward the toxin.
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PMID:Differential entry of ricin into malignant and normal rat hepatocytes. 253 9

Phloretin is an inhibitor of the mammalian glucose transporter and the iodothyronine-5'-deiodinase. We examined the effects of phloretin on cellular and nuclear uptake of [125I]T3 in cultured human Hep G2 hepatocarcinoma cells. The initial rate of T3 uptake was energy dependent and saturable with both a high affinity (Km = 3.6 nM) and a low affinity (Km = 503 nM) process. Phloretin produced a dose-dependent decrease in [125I]T3 uptake by Hep G2 cells (IC50 = 88 microM) and also inhibited nuclear uptake in intact cells and isolated nuclei. The solubilized nuclear receptor in the Hep G2 cells had a Kd of 0.14 nM for T3. Phloretin inhibited [125I]T3 binding to the solubilized nuclear receptor by competitive inhibition. Phlorizin, the beta-D-glucoside of phloretin, had no effect on T3 binding to the solubilized nuclear receptor. The inhibition of T3 cellular uptake and nuclear receptor binding is probably due to structural similarities between T3 and phloretin.
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PMID:Phloretin inhibits cellular uptake and nuclear receptor binding of triiodothyronine in human hep G2 hepatocarcinoma cells. 253 19

A series of copolymers were prepared containing 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-alpha-D-galactopyranose (0 to 99 mol %), methacryoyltyrosinamide and N-(2-hydroxypropyl)methacrylamide (99 to 0 mol %). The effect of galactose content on interaction with hepatoma cells in vitro was studied. Increased galactose content caused increased accumulation of N-(2-hydroxypropyl)methacrylamide copolymers by two human hepatoma cell lines (Hep G2 and SAH), but accumulation by rat and mouse hepatoma (HTC and NCTC) was not galactose dependent. Accumulation of N-(2-hydroxypropyl)methacrylamide copolymers by Hep G2 was shown to be an active process, being inhibited by low temperature and by the metabolic inhibitor 2,4-dinitrophenol. Addition of N-acetylgalactosamine and polymer-galactose to the incubation medium resulted in a concentration-dependent inhibition of accumulation of galactose-containing polymers. Addition of fucose or galactose was without effect at the concentrations used. Polymers bearing galactosamine or fucosylamine residues and, in addition, daunomycin were evaluated for cytotoxicity against Hep G2 and SAH. N-(2-Hydroxypropyl)methacrylamide copolymer-bound daunomycin produced a dose-dependent inhibition of DNA synthesis (measured by incorporation of [3H]thymidine), and the galactose-containing polymer showed greatest inhibition.
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PMID:Effect of galactose on interaction of N-(2-hydroxypropyl)methacrylamide copolymers with hepatoma cells in culture: preliminary application to an anticancer agent, daunomycin. 254 89

Transferrin synthesized by a human hepatocellular carcinoma cell line Hep G2 (called Hep G2 transferrin) was purified from culture media by immunoaffinity chromatography on a rabbit anti-(human serotransferrin) IgG column. The eluted transferrin was then resolved into five peaks on a cation-exchange column using the fast protein liquid chromatography system. The major fraction, named Hep G2 transferrin fraction C, having a molecular mass of 82.5 kDa was found to be homogeneous in polyacrylamide gel electrophoresis and in concanavalin-A-affinity crossed immunoelectrophoresis. A comparative analysis of the molar carbohydrate composition of normal human serotransferrin and of Hep G2 transferrin fraction C shows an increase in the latter in the number of galactose and N-acetylglucosamine residues and in the presence of fucose, which is absent in normal transferrin. By a combination of methylation analysis and NMR spectroscopy, the primary structure of the oligosaccharide alditols released from Hep G2 transferrin fraction C by reductive alkaline cleavage has been established as triantennary, tetraantennary and pentaantennary N-acetyllactosaminic structures with fucose residues (alpha 1-3)-linked to peripheral N-acetylglucosamine residues. These results indicate that the increase in the number of antennae in transferrin glycans synthesized by the hepatocarcinoma cell line is much more pronounced than in liver diseases such as alcoholic cirrhosis and that, in addition, the malignant transformation of human liver induces the presence of fucose.
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PMID:Presence of fucosylated triantennary, tetraantennary and pentaantennary glycans in transferrin synthesized by the human hepatocarcinoma cell line Hep G2. 255 87


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