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)

1. The fraction of proteins extracted from nuclei with 0.35 M NaCl and soluble in 2% trichloroacetic acid was examined in five Morris hepatomas and rat liver. 2. This fraction was a much greater percentage of the total 0.35 M NaCl soluble proteins in the tumors than in normal or regenerating liver. 3. In part, this difference was due to proteins with molecular weights greater than high mobility group proteins. 4. The conditions for precipitation of high mobility group proteins 1 and 2 with trichloroacetic acid were found to differ in hepatoma and liver fractions.
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PMID:Increased fraction of acid-soluble proteins in 0.35 M NaCl extracts of nuclei from rat liver tumors. 685 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

3M-KCl extracts of the hepatoma D23 contain antigens that inhibit the complement-dependent cytotoxicity for D23 hepatoma cells of serum from D23 tumour-bearing rats (D23 TBS). Inhibition was not due to a general anticomplementary activity of the extracts. Although a minor part (25%) of the protein of D23-KCl extract was insoluble in PBS, this part contained most of the inhibitory activity. Fractionation of the PBS-soluble material of the extract on Concanavalin A-Sepharose showed that the inhibitory activity did not bind to the lectin. Analysis of D23-KCl extracts on a Sepharose CL-4B column showed that the antigens involved in the cytotoxicity were heterogeneously distributed in the high-mol. wt region (greater than 200,000). Precipitation with 10% trichloroacetic acid (TCA) of D23 KCl extracts revealed that most of the antigenicity was insoluble in TCA. Heating of D23 KCl extracts at 100 degrees C did not affect the antigenicity. Enzyme treatment of D23 extra nuclear membranes (D23 ENP) revealed that the inhibitory activity was not sensitive to proteolytic digestion, while treatment with phospholipase A2, C or D abrogated partly the inhibitory activity. The lipid nature of the antigenicity was indicated by its solubility in organic solvents as chloroform or n-butanol.
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PMID:Tumour-associated antigens reacting with cytotoxic antibodies in serum of hepatoma-bearing rats. 729 8

The P450/6 beta A (CYP3A2) gene encoding a testosterone 6 beta-hydroxylase is expressed predominantly in liver and induced by the treatment of rats with various compounds. To understand the mechanism of the basal transcriptional activation of the CYP3A2 gene, the cis-acting elements in the proximal promoter region (-165 to -73) of the CYP3A2 gene were identified in this study. Nuclear extract from rat livers interacted with three sites, 6 beta A-A (-106 to -87), 6 beta A-B (-140 to -119) and 6 beta A-C (-163 to -145). These sites were detectable by DNase I footprinting and gel mobility shift assays and found to share nucleotide sequence similarity with each other (T(A/C)(A/C)N(A/G)AAG(G/T)(C/T)CA). Direct repeats of AGTTCA (-134 to -120) and AG(G/C)TCA (-162 to -148) are also detected in 6 beta A-B and 6 beta A-C sites, respectively. To elucidate the relationship of these sites with basal transcriptional activation of the CYP3A2 gene, varying lengths of the proximal promoter region (-164 to +41) fused to a CAT reporter gene were transfected in human hepatoma (HepG2) and mouse adrenal tumor (Y-1) cells. The relative level of CAT activity in HepG2 cells was slightly increased by the deletion of the 5'-portion from -164 to -111 bp, but was reduced to 14% of the control (the construct including from -110 to +41) by the deletion from -110 to -81 including the 6 beta A-A site. On the other hand, these deletions have no clear effect on the level of the activity in Y-1 cells. Substitution mutations at two nucleotides in the 6 beta A-A site resulted in the reduction of CAT activity in HepG2 cells to 12% of the activity in the wild-type construct. The interaction of an oligonucleotide corresponding to the 6 beta A-A site (-106 to -87) with liver nuclear factors was completely inhibited by the addition of a typical oligonucleotide for hepatocyte nuclear factor-4 (HNF-4) binding site (F. M. Sladek, W. Zhong, E. Lai, and J. E. Darnell, Jr., 1990, Genes Dev. 4, 2353-2365) but not of oligonucleotides corresponding to 6 beta A-B or 6 beta A-C sites. These results suggest an essential role of the binding of HNF-4 and/or HNF-4-related nuclear factors to the 6 beta A-A site on the basal transcriptional activation of the CYP3A2 gene in liver cells.
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PMID:Transcriptional elements directing a liver-specific expression of P450/6 beta A (CYP3A2) gene-encoding testosterone 6 beta-hydroxylase. 772 76

Tenidap is a novel anti-inflammatory and anti-arthritic agent that lowers intracellular pH and suppresses anion transport when applied to cells in vitro. Both of these parameters are known to influence pro-inflammatory cell function. To investigate whether tenidap can modulate cellular responses to cytokine stimulation, several in vitro cytokine-driven assays were characterized with respect to their tenidap sensitivity. Human monocytes treated with granulocyte-macrophage colony stimulating factor (GM-CSF) demonstrated an increased production of IL-6 as well as an increased total translational activity. Tenidap dose-dependently inhibited both cytokine-induced responses; the effect on IL-6, however, occurred at lower tenidap concentrations than those required to prevent the increase in total translational activity. In contrast, the known translational inhibitor cycloheximide did not demonstrate selectivity for IL-6; this agent decreased the GM-CSF-induced increase in total translational activity in parallel with its effects on IL-6. GM-CSF-treated monocytes also produced greater amounts of IL-1 beta in response to LPS stimulation than did non-GM-CSF-treated cells, and tenidap again suppressed this cytokine-induced activation. Human Hep3B cells treated with a combination of interleukin (IL)-1 beta and IL-6 demonstrated an acute phase-type of response. These hepatoma cells increased production of the positive acute phase protein serum amyloid A (SAA) while they decreased production of a negative acute phase protein human serum albumin (HSA). Tenidap dose-dependently inhibited the cytokine-induced increase in SAA production without effecting synthesis of HSA or total TCA-precipitable macromolecules. Importantly, the ability of tenidap to alter these various cytokine responses was not shared with piroxicam, a potent cyclooxygenase inhibitor. Finally, human neutrophils treated with either GM-CSF or tumor necrosis factor (TNF)-alpha demonstrated an increased chloride conductance as measured by the loss of radioactive chloride from 36Cl-loaded cells. When tenidap was included within the medium during cytokine stimulation, loss of radioactive chloride was prevented. Thus, tenidap inhibited the cytokine-induced increase in anion transport. Together, these results indicate that tenidap can suppress cellular activation processes induced by a variety of cytokines. This functional antagonism is not dependent on cyclooxygenase inhibition but, rather, appears to link to tenidap's unique ability to alter ionic homeostasis. These in vitro observations, therefore, may help to explain how this novel anti-inflammatory agent acts to lower acute phase proteins and IL-6 levels in man.
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PMID:Inhibition of cytokine activation processes in vitro by tenidap, a novel anti-inflammatory agent. 778 40

Metabolic characteristics of experimental hepatoma cells include elevated rates of glycolysis and lipid synthesis. However, pyruvate derived from glucose is not redily oxidized, and the source of acetyl CoA for lipid synthesis in As-39D cells has not been characterized. In this study ketone bodies were examined as a possible source of acetyl CoA in AS-30D hepatoma cells. The major findings were: 1. Acetoacetate was utilized by AS-30D cells, with 14C-lipid and 14CO2 as major products of [3-14C] acetoacetate. 2. Lipid synthesis from acetoacetate was dependent on the presence of glucose in the medium. 3. Acetoacetate supported rapid respiration by AS-30D mitochondria in the presence of 0.1 mM malate. 4. Succinyl CoA acetoacetyl CoA transferase activity in AS-30D mitochondria was approximately 40 fold greater than that found in rat liver mitochondria. 5. Addition of acetoacetate, but not beta-hydroxybutyrate decreased conversion of [1-14C] acetate to 14CO2, presumably by diluting the specific radioactivity of the acetyl CoA derived from the acetate tracer. 6. In the presence of glucose, approximately one fourth of acetoacetate utilized was converted to lipid. This result is consistent with elevated lipogenesis postulated by the truncated TCA cycle hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetoacetate metabolism in AS-30D hepatoma cells. 784 66

Livers of LEC rats were histochemically stained for copper according to the modified Timm's method, which includes trichloroacetic acid (TCA) treatment. TCA pretreatment was effective in removing zinc and iron, leaving as the major metal in the liver. Hepatocytes in 3-month-old rats were stained intensely by the modified Timm's method, both in frozen sections and in paraffin-embedded specimens. The centrilobular hepatocytes were usually stained, but positive cells were also randomly distributed in the hepatic lobes, showing a mosaic pattern. The staining was intensified in 8- compared to 3-month-old LEC rats. In contrast hepatocytes from LEA rats, the normal counterpart of LEC rats, were faintly stained for copper. Proliferating cholangioles found in older LEC rats were shown to lack copper deposition, and hepatocellular carcinoma showed less copper deposits than the hepatocytes surrounding the tumor. The copper staining was augmented in livers of LEC rats subjected to copper-loading, but was less intense in the livers treated with D-penicillamine. The staining intensity under the various experimental conditions showed good correlation with the copper concentration. Lysosomal deposition of copper in hepatocytes was demonstrated by electron microscopic analysis for copper. Thus the modified Timm's method was shown to produce valuable results in demonstrating copper in LEC rat livers, providing important information for an understanding of the mechanism of copper deposition and hepatic disease of the animal.
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PMID:Histochemical demonstration of copper in LEC rat liver. 827 38

A study was undertaken to assess the role of a physiological concentration of glutamine in AS-30D cell metabolism. Flux of 14C-glutamine to 14CO2 and of 14C-acetate to glutamate was detected indicating reversible flux between glutamate and TCA cycle alpha-ketoglutarate. These fluxes were transaminase dependent. A flux analysis was compared using data from three tracers that label alpha-ketoglutarate carbon 5, [2-14C]glucose, [1-14C]acetate and [5-14C]glutamine. The analysis indicated that the probability of flux of TCA cycle alpha-ketoglutarate to glutamate was, at minimum, only slightly less than the probability of flux of alpha-ketoglutarate through alpha-ketoglutarate dehydrogenase. The apparent Km for oxidative flux of [14C]glutamine to 14CO2, 0.07 mM, indicated that this flux was at a maximal rate at physiological, 0.75 mM, glutamine. Although oxidative flux through alpha-ketoglutrate dehydrogenase was the major fate of glutamine, flux of glutamine to lipid via reductive carboxylation of alpha-ketoglutarate was demonstrated by measuring incorporation of [5-14C]glutamine into 14C-lipid. In media containing glucose (6 mM), and glutamine (0.75 mM) 47 per cent of the lipid synthesized from substrates in the media was derived from glutamine via reductive carboxylation and 49 per cent from glucose. These findings of nearly equal fluxes suggest that lipogenesis via reductive carboxylation may be an important role of glutamine in hepatoma cells.
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PMID:Glutamine metabolism in AS-30D hepatoma cells. Evidence for its conversion into lipids via reductive carboxylation. 875 Nov 55

The Bcl 10 gene was recently discovered to be involved in the pathogenesis of lymphoma of mucosa-associated lymphoid tissue and several types of tumorous cell lines. We examined the mutation of Bcl 10 gene in 31 hepatocellular carcinomas along with their corresponding non-tumorous tissues by single strand conformation polymorphism (SSCP) and direct sequencing. The results showed that 11.3% chromosomes had codon 5 GCA to TCA mutation, 4.8% chromosomes had codon 8 CTC to CTG mutation, and 12.9% chromosomes had codon 213 GGA to GAA mutation. These mutations were found not only in the hepatoma tissues but also in paired non-cancerous tissues and the normal population. We suggest that these three changes are polymorphisms, and there is no relationship with the development of hepatocellular carcinoma.
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PMID:Mutation analysis of the Bcl 10 gene in hepatocellular carcinoma. 1107 91

Dehydroepiandrosterone sulfotransferase (STD) is a hydroxysteroid sulfo-conjugating enzyme with preferential substrate specificity for C-19 androgenic steroids and C-24 bile acids. STD is primarily expressed in the liver, intestine and adrenal cortex. Earlier studies have shown that androgens inhibit the rat Std promoter function through a negative androgen response region located between -235 and -310 base pair positions (Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., and Chatterjee, B. (1998) J. Biol. Chem. 273, 21856-21866). Here we report that the primary bile acid chenodeoxycholic acid (CDCA) also acts as an important regulator of the Std gene promoter. CDCA is a potent inducer of the Std gene, and its inducing effect is mediated through the bile acid-activated farnesoid X receptor (FXR), a recently characterized member of the nuclear receptor superfamily. The ligand-activated FXR acts as a heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates the Std gene by binding to an upstream region at base pair positions -169 to -193. This specific binding region was initially identified by bile acid responsiveness of the progressively deleted forms of the Std promoter in transfected HepG2 hepatoma and enterocyte-like Caco-2 cells. Subsequently, the precise RXR/FXR binding position was established by protein-DNA interaction using in vitro footprinting and electrophoretic mobility shift analyses. Unlike all other previously characterized FXR target genes, which contain an inverted repeat (IR) of the consensus hexanucleotide half-site (A/G)G(G/T)TCA with a single nucleotide spacer (IR-1), the bile acid response element of the Std promoter does not contain any spacer between the two hexanucleotide repeats (IR-0). A promoter-reporter construct carrying three tandem copies of the IR-0 containing -169/-193 element, linked to a minimal thymidine kinase promoter, can be stimulated more than 70-fold in transfected Caco-2 cells upon CDCA treatment. Autoregulation of the STD gene by its bile acid substrate may provide an important contributing role in the enterohepatic bile acid metabolism and cholesterol homeostasis.
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PMID:Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor. 1153 40


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