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)

At least 6 N-acetylglucosaminyltransferases (GlcNAc-T I, II, III, IV, V and VI) are involved in initiating the synthesis of the various branches found in complex asparagine-linked oligosaccharides (N-glycans), as indicated below: GlcNAc beta 1-6 GlcNAc-T V GlcNAc beta 1-4 GlcNAc-T VI GlcNAc beta 1-2Man alpha 1-6 GlcNAc-T II GlcNAc beta 1-4Man beta 1-4-R GlcNAc T III GlcNAc beta 1-4Man alpha 1-3 GlcNAc-T IV GlcNAc beta 1-2 GlcNAc-T I where R is GlcNAc beta 1-4(+/- Fuc alpha 1-6)GlcNAcAsn-X. HPLC was used to study the substrate specificities of these GlcNAc-T and the sequential pathways involved in the biosynthesis of highly branched N-glycans in hen oviduct (I. Brockhausen, J.P. Carver and H. Schachter (1988) Biochem. Cell Biol. 66, 1134-1151). The following sequential rules have been established: GlcNAc-T I must act before GlcNAc-T II, III and IV; GlcNAc-T II, IV and V cannot act after GlcNAc-T III, i.e., on bisected substrates; GlcNAc-T VI can act on both bisected and non-bisected substrates; both Glc-NAc-T I and II must act before GlcNAc-T V and VI; GlcNAc-T V cannot act after GlcNAc-T VI. GlcNAc-T V is the only enzyme among the 6 transferases cited above which can be essayed in the absence of Mn2+. In studies on the possible functional role of N-glycan branching, we have measured GlcNAc-T III in pre-neoplastic rat liver nodules (S. Narasimhan, H. Schachter and S. Rajalakshmi (1988) J. Biol. Chem. 263, 1273-1281). The nodules were initiated by administration of a single dose of carcinogen 1,2-dimethyl-hydrazine.2 HCl 18 h after partial hepatectomy and promoted by feeding a diet supplemented with 1% orotic acid for 32-40 weeks. The nodules had significant GlcNAc-T III activity (1.2-2.2 nmol/h/mg), whereas the surrounding liver, regenerating liver 24 h after partial hepatectomy and control liver from normal rats had negligible activity (0.02-0.03 nmol/h/mg). These results suggest that GlcNAc-T III is induced at the pre-neoplastic stage in liver carcinogenesis and are consistent with the reported presence of bisecting GlcNAc residues in N-glycans from rat and human hepatoma gamma-glutamyl transpeptidase and their absence in enzyme from normal liver of rats and humans (A. Kobata and K. Yamashita (1984) Pure Appl. Chem. 56, 821-832).
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PMID:The biosynthesis of highly branched N-glycans: studies on the sequential pathway and functional role of N-acetylglucosaminyltransferases I, II, III, IV, V and VI. 297 90

Transcatheter hepatic arterial embolization therapy (TAE) is an established method for the treatment of hepatocellular carcinoma (HCC). We have developed a new embolus consisting of microspheres with a mean diameter of about 200 microns which are composed of biodegradable polymolecular polylactic and the anti-cancer agent, aclarubicin -HCl, in a ratio of 12% w/w. These microspheres were applied to 28 patients with inoperable HCC using the following method microspheres containing 50 mg of aclarubicin-HCl were injected through a catheter placed in the hepatic artery or one of its branches, 2 or 3 times at intervals of 2 to 4 weeks. The effectiveness was confirmed by decreased levels of serum AFP and regression of the tumor size, and the accumulated survival rate for 6 months was 83.3%.
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PMID:[Transcatheter hepatic arterial embolization therapy using degradable polylactic acid microspheres]. 299 41

Incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone rapidly inhibits tissue-type plasminogen activator activity by inducing a specific plasminogen activator-inhibitor (PAI-1). Using immobilized polyclonal antibodies raised against HT-1080 human fibrosarcoma PAI-1, we have purified HTC PAI-1 from serum-free medium conditioned by dexamethasone-treated HTC hepatoma cells and shown it to be antigenically related to human PAI-1. Greater than 100-fold purification with greater than 75% yield was achieved in a single step. The purified PAI-1 migrates on SDS-polyacrylamide gels as a single major band of 49 kDa with a minor band of 46 kDa. Digestion of PAI-1 with endoglycosidase F causes a shift toward faster migrating species which retain inhibitory activity. The purified PAI-1 was stable at pH 2.5, lost 50% of its activity after 15 min at 45 degrees C, and showed marked activation after treatment with SDS or guanidine-HCl. Purified PAI-1 rapidly inhibited and formed complexes with both tissue-type and urokinase-type plasminogen activators. Polyclonal rabbit antirat PAI-1 antibodies were raised which immunoprecipitate both free and complexed PAI-1.
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PMID:Immunoaffinity purification of HTC rat hepatoma cell plasminogen activator-inhibitor-1. 312 13

Immunocytochemical staining of tryptophan 2, 3-dioxygenase (TO, EC 1.13.11.11), which is a typical marker of terminal differentiation of rat hepatocytes, showed that TO was expressed as early as the first day after birth by a few hepatocytes, and that the number of hepatocytes expressing TO gradually increased during early neonatal development. In contrast, immature hepatocytes grew actively in culture even without growth factors and serum, showing a labelling index with [3H]thymidine of over 80% just after birth, but their ability to show autonomous growth decreased rapidly during postnatal development. Double staining of hepatocytes from neonatal rats indicated that hepatocytes showing DNA synthesis were distinct from those expressing TO, suggesting that immature cells proliferate, but do not express TO, and then become fully differentiated expressing TO, but not proliferating any more. On the contrary, albumin was fully expressed in most hepatocytes of 0-day-old rats, in which the hepatocytes were still growing. When immature hepatocytes without TO from 0-day-old rats were cultured on a feeder layer of adult rat hepatocytes for 3.5 days, their expression of TO increased rapidly to almost the adult level (over 70% of the cells became TO-positive). Conversely, this feeder layer strongly inhibited autonomous growth of the neonatal rat hepatocytes. Other feeder layers, such as non-parenchymal liver cells of adult rats, Reuber hepatoma, and Swiss 3T3 fibroblasts, had no effect on the reciprocal changes of terminal differentiation and autonomous growth of immature rat hepatocytes. A feeder layer of dead adult rat hepatocytes, obtained by treating the cells with cytosine arabinoside for 24 h or drying them at 37 degrees C, had the same ability as a feeder layer of living cells to induce cytodifferentiation of immature cells. When the dead feeder layer was treated with 1 N HCl or digested with 0.1% trypsin, its ability to induce differentiation was almost completely lost. These results suggest that a cell surface component of adult rat hepatocytes, probably an acid-labile protein, controls terminal differentiation and growth of immature hepatocytes.
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PMID:In vitro induction of terminal differentiation of neonatal rat hepatocytes by direct contact with adult rat hepatocytes [corrected]. 348 31

In primary monolayer cultures of mature rat hepatocytes, cell growth and hepatocyte-specific functions were mediated by a cell surface component (named the cell surface modulator) via cell-cell contact. The modulator activity was heat-labile and trypsin-sensitive. Activity was also found in plasma membranes from kidney, brain, lung, and erythrocytes. The modulator was solubilized by 4% octylglucoside plus 4M guanidine HCl from liver membranes. The molecular weight of the modulator was 670KD determined by Sephacryl S-400 gel filtration. Hepatoma cells established from Reuber and Morris hepatoma did not show any cell density-dependency on either cell growth or hepatocyte-specific function. However, these hepatoma cells had strong cell surface modulator activity. These results suggest that hepatoma cells have lost their cell density-dependent regulation because they have lost the ability to respond to the cell surface modulator. Characterization of the cell surface modulator and its mechanism of transmitting a signal for gene regulation would be helpful in understanding the process by which cells assemble into tissues in vivo and the mechanism of changes in gene expression in tissue during development, regeneration and carcinogenesis.
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PMID:[Reciprocal regulation of growth and differentiation in hepatocytes by cell surface modulator and loss of regulation during carcinogenesis]. 398 39

Rat liver and hepatoma cells fixed with formaldehyde, embedded into Epon and treated on sections with 5 n HCl and then with aqueous uranylacetate show preferential DNase-sensitive reaction. The reaction is highly dependent upon proper fixation, hydrolysis improves its specificity. The binding of the contrast with DNA is of ionic nature. Because of its simplicity, sufficient contrast and resolution the suggested technique is recommended for ultrastructural studies of DNA-containing substrates.
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PMID:Staining of DNA with uranylacetate in hydrolysed ultrathin sections. 616 27

Cytoskeletal residues obtained after extraction of rat liver and cultured rat hepatoma cells (line MH1C1) were used to isolate cytokeratin subunit complexes by solubilization in low salt buffer containing 4 M-urea. Alternatively, the complexes were prepared by solubilization of total cytoskeletal proteins in 9.5 M-urea or 6 M-guanidinium hydrochloride (Gu . HCl), followed by separation using reversed phase high pressure liquid chromatography and dialysis first against either 9.5 M-urea or 6 M-Gu . HCl and then against buffers containing either 4 M-urea or 2 M-Gu . HCl, respectively. The complexes contained only two cytokeratin polypeptides in a 1 : 1 ratio as demonstrated by electrophoresis and isoelectric focusing, i.e. components A (Mr 55,000; isoelectric point in 9.5 M-urea, pH 6.4) and D (Mr 49,000; isoelectric point, pH 5.38) which were separated from each other at urea concentrations higher than 7 M. The complex had a sedimentation coefficient S25,w of 4.96 S in 2 M-Gu . HCl. Sedimentation equilibrium analysis gave an average Mr value of 207,000 which was interpreted as a tetramer containing two chains each of A and D. This complex was also directly demonstrated by gel electrophoresis under non-dissociating conditions. Using dimethyl suberimidate to cross-link the complex in solution of 4 M-urea or 2 M-Gu . HCl, we identified covalently linked heterodimers of A and D, and a tetrameric unit containing equal amounts of A and D which was the largest cross-link product obtained. This complex was similar to the tetrameric complex of rat and human vimentin formed under the same conditions. The constituents of the cross-linked products were identified by two-dimensional ("diagonal") gel electrophoresis, involving the cleavage of the bis(amidine) cross-links after the initial separation in the first dimension. Identical cross-link products were recognized when cytokeratin filaments were used. By electron microscopy the complexes appeared as threads of 2 to 3 nm diameter with a mean length of approximately 48 nm. On dialysis to low salt buffer, the complexes formed 2 to 3 nm protofilaments, intertwisted 3 to 4 nm protofilaments and typical 7 to 11 nm intermediate-sized filaments. Complexes formed from equivalent cytokeratins of other species such as man and cow, as well as heterologous recombinations such as human component A mixed with bovine component D and vice versa, showed the same characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Heterotypic tetramer (A2D2) complexes of non-epidermal keratins isolated from cytoskeletons of rat hepatocytes and hepatoma cells. 620 69

A low-molecular-weight fraction (M.W. approximately 700) that specifically impairs the induction of type II interferon in mice by purified protein derivative of tuberculin or OK-432 was isolated from the cell-free ascitic fluid of mice bearing Ehrlich ascites carcinoma. Purification was achieved by ultrafiltration and gel filtration. The inhibitory activity of the isolated fraction was 10 times greater than that of the unfractionated starting material in the impairment of type II interferon induction. The significant inhibition was observed even when 0.2 ml of the 10,000-fold dilution of the fraction, which was previously adjusted to 0.25 A unit at 290 nm absorption, was once treated i.p. in normal mice 48 hr before challenge of type II interferon inducers. This fraction was stable to heating at 56 degrees for 60 min. The active component, however, did not affect the in vivo induction of type I interferon by polyriboinosinic-polyribocytidylic acid or tilorone-HCl. In parallel experiments, an identical low-molecular-weight fraction that impairs the type II interferon induction in mice was isolated from the ascitic fluids of rats bearing AH-100B ascites tumor and from a human hepatoma case with advanced cancer metastatic to the peritoneal cavity. However, nontumorous ascitic fluids obtained from adjuvant-stimulated mice and a human liver cirrhosis case did not contain any such inhibitory activity.
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PMID:Isolation of an inhibitor of type II interferon induction from tumor ascitic fluids. 624 7

The metabolic transformations of labeled pyridoxine by hepatoma cells were studied. Buffalo rats were fed ad libitum a commercially prepared pyridoxine sufficient diet for 20 days at which time they were inoculated intramuscularly with hepatoma 7777 cells in both hind leg muscles. After tumor development, 50 microCi [6-3H] pyridoxine. HCl or 5 microCi [4,5-14C] pyridoxine. HCl was injected intraperitoneally per rat. Groups of animals were subsequently sacrificed at defined time intervals up to 9 days. Vitamin B6 labeled tumor metabolites were acid extracted and separated on a muBondapak C18 column by ion pairing reverse phase high performance liquid chromatography. A novel vitamin metabolite contributing up to 28.5% of extractable radioactivity was found with retention time different than any of the known vitamin B6 compounds. Its pattern of synthesis in vivo from labeled pyridoxine was PN leads to PNP leads to PLP leads to PMP leads to X. Preliminary GC-mass spectral data suggested the unknown consisted of more than one species. This communication reports on the metabolism of vitamin B6 and the isolation, synthesis in vivo and possible significance of the novel metabolite to the economy of the tumor cells.
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PMID:Metabolic interconversions of pyridoxine by Morris hepatoma No. 7777 cells. Synthesis of a novel metabolite. 683 Jan 50

Activity of chromatin-bound protease of rat liver and Morris hepatoma 7777 was studied. Proteolytic enzyme was copurified with histones during extraction of chromatin with 0.25 M HCl. Total histone was fractionated by Oliver's et al. method. Histone fractions were incubated in 0.01 M Tris-HCl buffer (pH 7.6) at 37 degrees C within different periods of time. The behavior of these fractions in polyacrylamide gel electrophoresis as well as the amounts of peptides soluble in 5% TCA released during incubation indicated that enzyme was coextracted with histone H2B only. It was shown that the activity of protease coextracted selectively with histone H2B was higher in tumor tissue than in normal liver.
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PMID:Activity of chromatin-bound protease in histone fractions from rat liver and Morris hepatoma. 700


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