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 transport of L-glutamine was examined in isolated adult and fetal human hepatocytes as well as in the human hepatoma cell lines HepG2 and SK-Hep. In all cells studied, glutamine uptake was at least 85% Na(+)-dependent. Kinetic analysis of the Na(+)-dependent component indicated mediation by a single transporter in three human hepatocyte preparations and in SK-Hep cells, whereas two transporters appeared to be responsible for glutamine uptake in HepG2 cells and in hepatocytes from the liver of one male patient. Amino acid inhibition analysis showed primary mediation by System N in fetal and adult hepatocytes, whereas System ASC was principally responsible for glutamine uptake in transformed cells. Similar to the rat transporter, human System N was pH-sensitive, stereospecific, and responsive to treatment with steroid hormones. Although the human carrier was less tolerant of Li(+)- for Na+ substitution, glutamine transport in primary human hepatocytes was stimulated by treatment with hypotonic buffer (cell swelling), as reported in rat parenchymal cells. In contrast, glutamine transport in hepatoma cells was relatively insensitive to changes in extracellular pH and failed to show enhanced activity in response to hypoosmotic challenge. Collectively, the data suggest that markedly distinct plasma membrane transporters mediate the concentrative uptake of glutamine in normal and transformed human hepatocytes, and that the salient properties of System N have been largely conserved from rat to man.
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PMID:Glutamine transport in isolated human hepatocytes and transformed liver cells. 784 25

Antineoplaston AS2-1 is a mixture of sodium salts of phenylacetic acid (PAA) and phenylacetylglutamine (PAG) in the ratio 4:1. The uptake of both compounds has been examined in human hepatoma cell line, Hep G-2. The accumulation of PAA was characterized by temperature sensitivity, saturability and energy dependency. Organic anions (probenecid, p-aminonohippuric acid and stilbene) inhibited PAA uptake suggesting the involvement of organic anion system in PAA transport. PAG cellular uptake exhibited dependency on metabolic energy, since the accumulation was sensitive to lowered temperature as well as to replacement of sodium ions by choline in the incubation medium. In contrast, the process showed tolerance to lithium ions as a substitute to sodium ions. This finding, together with the strong inhibition of PAG accumulation by histidine and glutamine, indicates that system N, known to be specific for hepatic tissue and the glutamine-preferring amino acid transport system, mediates PAG uptake. We conclude that PAG, through competition with glutamine for the same membrane carrier, may reduce glutamine transport leading to intracellular glutamine depletion. The physiological consequence of this biochemical event could be critical to cancer cells and therefore might contribute to the mechanism of antineoplaston AS2-1 action.
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PMID:Cellular accumulation of antineoplaston AS21 in human hepatoma cells. 785 Jul 66

We cloned from mouse hepatoma cells a cDNA which encodes the Ah receptor nuclear translocator (Arnt). Sequence comparisons reveal 89% nucleotide and 92% amino acid identity between mouse and human Arnt. Transfection of the cDNA into Arnt-defective mouse hepatoma cells fully restores their responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), indicating that the cDNA encodes a functional Arnt protein. Transfection of the cDNA into wild type mouse hepatoma cells increases the magnitude, but not the sensitivity, of the transcriptional response to TCDD. Analyses of mutants indicate that Arnt has a modular organization. The unit that mediates both heterodimerization with the liganded Ah receptor and DNA recognition is functionally distinct from the unit that mediates transcriptional activation. A 96-amino acid, C-terminal domain of Arnt, which includes a glutamine-rich region, confers transcriptional activation capability upon the protein.
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PMID:Transcriptional activation function of the mouse Ah receptor nuclear translocator. 796 46

Supplemental glutamine prevents gut atrophy and enhances muscle protein synthesis in septic rats. This study investigated the effect of glutamine administration and mitomycin C treatment on protein turnover in tumor-bearing rats. AH109A rat ascites hepatoma cells (2 x 10(6)) were subcutaneously implanted in the back of male Donryu rats (n = 32, body weight 150-200 g) on Day 0. The animals were then fed rat chow ad libitum for 10 days. On Day 10, the rats were catheterized for TPN and randomized into four groups according to diet and treatment. The groups were: (i) standard total parenteral nutrition (STPN) + saline; (ii) glutamine-supplemented TPN (GTPN) + saline; (iii) STPN+mitomycin C (MMC); (iv) GTPN+MMC. GTPN was isocaloric (250 kcal/kg/day) and isonitrogenous (1.5 gN/kg/day) with STPN. The animals were maintained on TPN for 5 days and received mitomycin C (0.5 mg/kg) via the catheter every day. On the fifth day of TPN, [1-14C]leucine was given via a 5-hr continuous infusion (2.0 microCi/hr/rat) to determine the fractional synthesis rate of muscle, gut mucosa, liver, and tumor. Also, endogenous leucine production (not equal to whole body protein breakdown rate) was calculated. Body weight loss during TPN was reduced with GTPN. GTPN enhanced muscle FSR in untreated animals (STPN: 10.8 +/- 8.7%/day vs GTPN: 14.7 +/- 0.6%/day, P < 0.05) and in mitomycin C-treated animals (STPN+MMC: 9.6 +/- 0.9%/day, GTPN+MMC: 12.0 +/- 0.8%/day, P < 0.05). The whole body protein breakdown rate was reduced with GTPN. Mitomycin C reduced the mucosal fractional synthesis rate and GTPN did not prevent this reduction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of glutamine and chemotherapy on protein metabolism in tumor-bearing rats. 804 Nov 29

We describe an improved technique which allows the analysis of enzyme reaction kinetics for gamma-glutamyl transpeptidase (gamma-GT) by flow cytometry. This is technically difficult because of the location of the enzyme on the external surface of the cell membrane leading to the rapid escape of the product. The reaction is determined by monitoring the conversion of gamma-glutamyl aminomethylcoumarin to aminomethylcoumarin. Reaction kinetics are described for BL8 hepatocyte and JB1 hepatoma cells lines, together with inhibition kinetics for the active site-directed glutamine analogue L-(alpha-S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid. We show that it is possible to follow the reaction dynamics in a heterogeneous mixture of BL8 and JB1 cells allowing discrimination of the two cell types based on gamma-GT activity. Improvements for further optimizing the assay of this important enzyme are suggested.
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PMID:Can flow cytoenzymology be applied to measure membrane-bound enzyme kinetics? Assessment by analysis of gamma-glutamyl transpeptidase activity. 810 25

Limited resection can be a therapeutic approach in patients with cirrhosis with very low remnant hepatic function after resection. In this study, two hilar vascular clamping methods (hilar selective clamping [n = 13] and hilar lobar clamping method [n = 8]), which were used for resection of hepatocellular carcinoma in patients with cirrhosis, were compared based on cardiovascular stability during clamping, intraoperative bleeding, operative time and postoperative course. In the past, the Pringle method had been used (n = 19) and those instances were included for comparison. The mean operation time of the lobar clamping group was 209 +/- 41 minutes, which was significantly less than that of the selective clamping group (259 +/- 44 minutes, p < 0.05). Furthermore, the mean intraoperative blood loss of the lobar clamping group was 920 +/- 400 milliliters, which was significantly less than that of the selective clamping group (1,640 +/- 590 milliliters, p < 0.01). The postoperative total bilirubin and glutamine-oxaloacetic transaminase levels tended to be high in the Pringle group, but there was no significant difference between the groups. Although the blood pressure during clamping significantly decreased in all groups, the decrease was profound in the Pringle group as compared with those in the other two groups. Thus, as a method for controlling afferent blood flow during hepatic resection in patients with cirrhosis, we recommend the lobar clamping method as a simple, safe and effective way to minimize bleeding and maintain cardiovascular stability.
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PMID:Hilar lobar vascular occlusion for hepatic resection. 815 20

HNF1 and C/EBP alpha are transcription factors that bind to and trans-activate the human albumin gene proximal promoter. Various 5' deletions of the human albumin promoter were coupled to a luciferase reporter gene (alb-luc constructs) and co-electroporated with HNF1 and/or C/EBP alpha expression vectors into HeLa cells. Luciferase activities from co-electroporation of the HNF1 and C/EBP alpha expression vectors with the alb-luc constructs were approximately 10-fold greater than the sum of the activities achieved with HNF1 and C/EBP alpha alone. Analysis of COOH-terminal or internal deletions of the HNF1 expression vector revealed that the domain important for collaborative interaction with C/EBP alpha could be localized to a 157 amino acid region not previously described. This domain is proline and glutamine-rich and is highly homologous (66%) to a portion of vHNF1, an evolutionarily related gene first identified in dedifferentiated hepatoma cells. A construct linking the negatively charged activation domain of herpes simplex virus protein VP16 to the DNA-binding domain of HNF1 showed that it could also synergize with C/EBP alpha to trans-activate the human albumin gene promoter. Our studies delineate a domain in HNF1 important for synergistic activation with C/EBP alpha.
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PMID:The transcription factor HNF1 acts with C/EBP alpha to synergistically activate the human albumin promoter through a novel domain. 828 79

Sequence-specific resonance assignments provide the basis for interpreting multidimensional NMR spectra and for determining 3D structures of proteins from these data. We have developed an improved strategy for determining these sequence-specific NMR assignments in small proteins and applied this method in determining proton and nitrogen resonance assignments for an 8.2-kDa engineered domain (the Z-domain) of the cell wall protein A of Staphylococcus aureus. First, HCCNH-TOCSY [Lyons, B. A. & Montelione, G.T. (1993) J. Magn. Reson. 101B, 206] data were used together with 2D 2QF-COSY, TOCSY, and 15N-HSQC data to identify amino acid spin systems. Most asparagine and glutamine spin systems were also identified uniquely from these triple-resonance data. Next, complementary HCC(CO)-NH-TOCSY [Montelione, G. T., et al. (1992) J. Am. Chem. Soc. 114, 10975] data were used to identify sequential connections from the aliphatic H alpha, H beta, H gamma, H delta, and H epsilon resonances of residue i to the amide and nitrogen resonances of residue i + 1. By combined analysis of HCCNH-TOCSY and HCC(CO)NH-TOCSY spectra we have determined most of the proton and nitrogen resonance assignments for the Z-domain. This represents the first example of the use of this triple-resonance technique to determine extensive resonance assignments in a small protein.
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PMID:An improved strategy for determining resonance assignments for isotopically enriched proteins and its application to an engineered domain of staphylococcal protein A. 839 17

The effect has been studied of various media, hormones and of amino acids on the membrane potential of rat hepatoma cells in culture measured by microelectrode impalement. Cells in Eagle's minimal essential medium plus 5% serum had a value which varied daily from about 5-8 mV, inside negative. The membrane potential of rat hepatocytes was measured to be 8.7 +/- 0.2 mV, inside negative. The membrane potential of the hepatoma cells was decreased by insulin and increased by glucagon. Membrane potential was unaffected by change of medium to Hanks' or Earle's balanced salt solutions or deprivation of serum. It was, however, reduced in cells in phosphate-buffered saline and by reduction of pH. The former effect was shown to be due to the higher [Na+] of phosphate-buffered saline as opposed to the other media. Addition of alanine, glycine, serine, proline and methylaminoisobutyrate all reduced membrane potential by 2-3 mV. Smaller decreases were seen with methionine, leucine and phenylalanine, but none with glutamine, threonine, BCH (2-aminonorborane-2-carboxylic acid) and D-alanine. The results are compared with the effects of similar conditions on aminoisobutyrate uptake. Whilst there was a correlation under some conditions there was not under others. It is concluded that for the hepatoma cells factors additional to the membrane potential must exert some influence on the capacity for amino acid transport.
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PMID:Membrane potential of rat hepatoma cells in culture: influence of factors affecting amino acid transport. 856 68

Hepatitis delta virus (HDV) is a defective virus requiring the hepatitis B virus (HBV) to provide hepatitis B surface antigens as the envelope protein. The hepatitis B surface antigens are posttranslationally modified by N-linked glycosylation, and its significance in HDV assembly was investigated with a cotransfection system using human hepatoma cell line Huh-7. After the N-linked glycosylation of HBsAg was blocked by tunicamycin treatment, the packaging of HDV in the culture system could be suppressed to a level as low as 5-10% of the untreated control. The extent of inhibition correlated with the increased concentrations of tunicamycin. In contrast, the loss of HBsAg glycosylation did not affect the efficiency of assembly of HBV particles. When the N-linked glycosylation site of small HBsAg at amino acid 146 was mutated from asparagine to glutamine, the mutant HBsAg packaged only a modest amount of HDV particles. The quantity and kinetics of formation of HDV particles in culture system were reduced by the depletion of HBsAg glycosylation. Therefore HDV, similar to influenza and vesicular stomatitis viruses, depends on glycosylation of the envelope proteins as a signal for envelope protein maturation and for virion formation.
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PMID:N-linked glycosylation of hepatitis B surface antigens is involved but not essential in the assembly of hepatitis delta virus. 865 25


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