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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mononucleosomes obtained from cultured mouse hepatoma cells were incubated with RNA polymerase II from wheat germ. No free DNA was liberated as available templates under the experimental condition employed. Size analysis of the transcripts showed that the polymerase initiated transcription from either terminus and read through the DNA template of mononucleosomes. Sucrose density gradient centrifugation of the reaction mixture resolved mononucleosome-polymerase complexes from free materials. The complexes were characterized by the enrichment of DNA fragments containing the nucleosome linker region, the presence of H1 histone, and the increased susceptibility to DNase I. Both the complexes formed in the presence and absence of precursor nucleotides were susceptible. These suggest that RNA polymerase II prefers to bind to the linker region, and the polymerase-bound nucleosomes are structurally altered. The data were discussed in context with possible mechanisms of transcription of the nucleosome structure.
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PMID:Formation of transcribing mononucleosome-eukaryotic RNA polymerase II complexes in vitro as a simple model of active chromatin. 623 May 98

1. The iron contents, gel migration rates and isoelectric-focusing patterns of normal liver and hepatocellular carcinoma ferritins from the same patients were compared. 2. Sucrose-density-gradient centrifugation showed that the number of iron atoms per ferritin molecule was decreased to approximately half in carcinoma tissue when compared with normal liver. 3. On electrophoresis, hepatocellular carcinoma ferritin migrates faster and is therefore more negatively charged than normal liver ferritin, thus refuting the general view that the more negatively charged a ferritin molecule the greater its iron content. 4. Comparison of tumour and normal liver ferritin subunit compositions on acid/urea/polyacrylamide gels showed hepatocellular carcinoma ferritin to contain an additional, more negatively charged, subunit to normal liver ferritin. 5. Isoelectric focusing showed that hepatocellular carcinoma tissue contains isoferritins with isoelectric points intermediate between the ranges of normal liver and normal heart isoferritins.
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PMID:A biochemical comparison of normal human liver and hepatocellular carcinoma ferritins. 624 28

Reductively [3H]methylated 3H mitochondrial-outer-membrane vesicles from rat liver and vesicles where monoamine oxidase has been derivatized irreversibly by [3H]-pargyline have been deliberately miscompartmentalized by heterologous transplantation into hepatoma (HTC) cells by poly(ethylene glycol)-mediated vesicle-cell fusion. Fluorescein-conjugated mitochondrial-outer-membrane vesicles have also been used to show that transplanted material is patched, capped and internalized. Reductively methylated outer-membrane proteins and monoamine oxidase are destroyed at the same rate (t1/2 24 h). Mitochondrial-outer-membrane proteins are not degraded at the same rate as HTC plasma-membrane proteins, endogenous cell protein, or endocytosed protein. Transplanted radiolabelled mitochondrial-outer-membrane proteins accumulate intracellularly in structures that are distinct from plasma membrane and lysosomes. However, when mitochondrial-outer-membrane vesicles derivatized with [14C]sucrose are transplanted, the acid-soluble degradation products accumulate in the lysosomal fraction. [14C]Sucrose-conjugated HTC cell plasma membrane accumulates in intracellular structures that are again distinct from plasma membrane and lysosomes. In contrast with the above observations, homologously transplanted mitochondrial-outer-membrane proteins from rat liver are destroyed in hepatocytes at rates that are remarkably similar (t1/2 60-70 h) to the rates in rat liver in vivo [Evans & Mayer (1982) Biochem. Biophys. Res. Commun. 107, 51-58].
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PMID:Degradation of transplanted rat liver mitochondrial-outer-membrane proteins in hepatoma cells. 665 74

Inhibition assay of 125I-C1q binding to IgG-p-azobenzamidoethyl Sepharose 6B (IgG-Sepharose) by immune complexes was developed for the detection of circulating soluble immune complexes in the liver disease and was compared with polyclonal rheumatoid factor (pRF) binding inhibition assay and with C1q binding assay. The C1q inhibition assay was proved to be very sensitive, reproducible and rapid. Sucrose density gradient ultracentrifugal analysis showed that the assay could detect aggregates of human IgG (AHGG) larger than 19s. C1q inhibition activity (C1qIA) correlated with severity of the liver disease, defined by histological criteria. The highest C1qIA was observed in sera of patients with primary biliary cirrhosis, followed by liver cirrhosis, fulminant hepatitis, chronic aggressive hepatitis (2B), lupoid hepatitis and hepatocellular carcinoma in the order. There were correlations of C1qIA with serum gamma-globulin levels, sero-positivity for rheumatoid factor and hepatitis B surface antigen, and significant correlations existed also among pRFIA, C1qIA and C1qBA. Ultracentrifugal analysis of sera from patients with the liver disease showed that ClqIA demonstrated two sizes of immune complexes, 7s and larger than 19s, while complexes larger than 8s were seen in pRFIA.
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PMID:Studies on circulating soluble immune complexes of the liver disease. 6. Comparative studies of 125I-pRF inhibition assay, 125I-Clq inhibition assay and 125I-Clq binding assay. 697 71

Deletion mutations were introduced into the hepatitis B virus (HBV) capsid (core) gene to determine the effect on capsid formation, pregenome encapsidation, reverse transcription, and second-strand DNA synthesis. Carboxy-truncated HBV core proteins were expressed in insect cells using recombinant baculoviruses and were tested for capsid forming ability. Sucrose gradient sedimentation analysis revealed that core proteins missing 39 carboxy terminal amino acids produced capsids while removal of an additional 9 amino acids prevented capsid formation. Truncated core proteins co-expressed in the human hepatoma cell line Huh7 were assayed for their ability to complement in trans an HBV genomic plasmid containing a defective core gene. Mutants lacking 7 and 12 carboxy terminal residues complemented the defective core gene of the HBV plasmid as assayed by synthesis of HBV DNA via reverse transcription of the encapsidated RNA pregenome, although the mutant lacking 12 residues was partially defective in completing second-strand DNA synthesis. Capsids formed using a core deletion mutant missing 20 carboxy terminal residues contained HBV RNA but contained little if any HBV DNA. However, the largest encapsidated RNA species was only 1.7 kb, about half the size of the 3.5-kb RNA found in wild-type HBV capsids. Hybridization analysis revealed that the shorter RNA lacked sequences corresponding to the 3' half of the pregenomic RNA. Implications of these findings on HBV packaging are discussed.
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PMID:Carboxy-terminal truncations of the HBV core protein affect capsid formation and the apparent size of encapsidated HBV RNA. 768 72

The asparagine-linked sugar chains in serum transferrin purified from patients with hepatocellular carcinoma (n = 13), healthy individuals (n = 5) and patients with liver cirrhosis (n = 6) were compared. Sugar chains released with N-glycanase from desialylated and pepsin-digested transferrin were derivatized by reductive pyridylamination. Analysis of the sugar chains by high performance liquid chromatography in combination with exoglycosidase digestion revealed an increase of a biantennary complex-type sugar chain with a fucosylated trimannosyl core; Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3) Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc in 7 of 13 cancer patients and an increase of a sugar chain with a fucosylated trimannosyl core and bisecting N-acetylglucosamine; Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(GlcNAc beta 1-4) (Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc in one of the 13 cancer patients. Further, the fucosylated alteration of the sugar chain was detected also in alpha 1-antitrypsin, hemopexin, alpha 1-acid glycoprotein and alpha 2-HS glycoprotein from one of the patients with increased fucosylated transferrin.
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PMID:Alteration of asparagine-linked glycosylation in serum transferrin of patients with hepatocellular carcinoma. 817 73

Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariably contain simple deletions or complex rearrangements that have been thought to occur after integration. We report here the detection of mutant woodchuck hepatitis virus (WHV) genomes cloned from virions in serum that are strikingly similar to the rearranged hepadnaviral genomes found previously as integrated sequences in cellular DNA. Of 102 cloned genomes studied, 2 had large inverted duplications, 1 a 219-nucleotide direct duplication, and 1 a 219-nucleotide deletion. Virus-virus DNA junctions occurred either adjacent to DR1 or DR2 or in the cohesive overlap region at preferred topoisomerase I cleavage sites. Since these sites are located in the single-stranded regions of the genome, cleavage by topoisomerase I would produce linear molecules that would be expected to be highly recombinogenic since this enzyme, possessing nicking and ligating activities, would remain covalently attached. Sucrose density gradient centrifugation coupled with polymerase chain reaction studies confirmed that the mutant WHV DNA forms resided in virions and did not represent free viral DNA released from infected cells or were unlikely to be an artifact of the cloning process. Thus, the finding in virions of mutant WHV DNA similar to WHV DNA integrated into cellular DNA suggests that the processes of mutation and integration are linked in some instances. Furthermore, the mutant genomes that are preferentially integrated into cellular DNA may have an etiologic role in hepatocarcinogenesis.
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PMID:Mutant woodchuck hepatitis virus genomes from virions resemble rearranged hepadnaviral integrants in hepatocellular carcinoma. 823 78

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a diverse range of chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Although no endogenous physiological ligand for the AhR has yet been described, numerous studies support the existence of such a ligand(s). Here we have examined the ability of prostaglandins and related chemicals to activate the AhR signaling system. Using two AhR-based bioassay systems we report that relatively high concentrations of several prostaglandins (namely, PGB3, PGD3, PGF3alpha, PGG2, PGH1, and PGH2) can not only stimulate AhR transformation and DNA binding in vitro, but also induce AhR-dependent reporter gene expression in mouse hepatoma cells in culture. PGG2 also induced AhR-dependent reporter gene expression to a level three-to four fold greater than that observed with a maximal inducing dose of TCDD. Sucrose gradient ligand binding analysis revealed that PGG2 could competitively displace [3H]TCDD from the AhR. Overall, our results demonstrate that selected prostaglandins are weak agonists for the AhR and they represent a structurally distinct and novel class of activator of the AhR signal transduction pathway.
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PMID:Activation of the Ah receptor signaling pathway by prostaglandins. 1167 47

Exposure of the immortalized human breast epithelial cell line MCF10A to the Jun N-terminal kinase (JNK) inhibitor anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) suppressed, in a concentration-dependent manner (IC50 is approximately 2 microM), the induction of CYP1A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cotreatment with SP600125 also suppressed the accumulation of TCDD-induced nuclear aryl hydrocarbon receptor (AhR)-DNA complexes, as assessed by electrophoretic mobility shift assays. Concentrations of SP600125 < or = 50 microM did not transform the AhR into a DNA-binding species when added to rat liver cytosol. However, addition of SP600125 to cytosol just before TCDD addition completely suppressed AhR transformation and DNA binding (IC50 approximately 7 microM). Sucrose gradient analyses using rat liver and murine hepatoma 1c1c7 extracts demonstrated that SP600125 competed with TCDD for binding to the AhR. These results suggest that SP600125 is an AhR ligand and functions as an AhR antagonist at concentrations used to pharmacologically inhibit JNK.
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PMID:The Jun N-terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. 1457 Jul 54

In this study, we examined the antitumor activities of isoprenoid derivatives conjugated with substrates of energy metabolism in human hepatoma-bearing athymic mice. Among these compounds, N-geranylpyruvic amide, N-geranyl-p-pyruvaminobenzoic amide, N,N'-digeranylmalic diamide and N,N'-digeranyl-O-acetylmalic diamide had strong antitumor effects. These geranylamine derivatives also inhibited in vitro cell growth. Sugar conjugates of geranylamine, geranic acid and mevalonic acid did not show any antitumor effect in vivo or in vitro. Although the geranylamine derivatives had no impact on the cell cycle distribution at 24 h, a sub-G1 (apoptotic) peak of varying magnitude was seen in DNA histograms of cells treated with the derivatives for 48 h. However, the geranylamine derivatives did not inhibit protein isoprenylation, which has been reported in cancer cells treated with several natural isoprenoids. These results suggest that the geranylamine derivatives conjugated with malic acid and pyruvic acid have a different mechanism of antitumor activity from that of natural isoprenoids.
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PMID:Antitumor effect of geranylamine derivatives on human hepatoma. 1579 70


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