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 mechanism of the accelerated syntheses of albumin and apolipoprotein B (apo B) in response to decreased oncotic pressure was investigated in cultured rat hepatoma H4-II-E cells. Addition of dextran (mol wt 6-9 x 10(4)) to the culture medium decreased the levels of albumin and apo B mRNAs in an oncotic pressure-dependent manner. The reductions of both mRNAs were attenuated with increase in the molecular weight of dextran, which resulted in a decrease in oncotic pressure. Addition of macromolecule increased the viscosity in medium; however, alteration of viscosity appeared not to correlate with albumin and apo B mRNA levels. Transcriptional run-on assays with isolated nuclei from dextran-treated vs. untreated hepatoma cells indicated that the changes in steady-state mRNA levels were mainly controlled at the transcriptional step. Treatment with cycloheximide increased albumin mRNA to the basal level, which was effectively suppressed by dextran, and resulted in superinduction of apo B mRNA. These changes occurred primarily at the transcriptional step. These results suggest that regulations of the expressions of the albumin and apo B genes for adaptive increases in the mRNAs may require the continued synthesis of a labile protein(s) or a limiting transcription factor(s). We conclude that oncotic pressure plays an important role in regulation of expression of the albumin and apo B genes at the transcriptional step.
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PMID:Oncotic pressure regulates gene transcriptions of albumin and apolipoprotein B in cultured rat hepatoma cells. 138 Nov 47

Ninety-one (11.4%) subjects with hypercholesterolaemia (serum cholesterol level more than 250 mg/dL) of 792 Chinese patients with hepatocellular carcinoma (HCC) were studied in Taiwan. All 91 patients had large tumours greater than 7 cm in diameter and a tumour volume greater than 50%; 56 (61%) of these patients manifested tumour involvement in both lobes of the liver. The HCC patients with hypercholesterolaemia had significantly higher mean serum levels of albumin, triglyceride and alpha-fetoprotein (AFP) compared with age-sex-tumour volume matched HCC patients without hypercholesterolaemia. The associated incidence of hypoglycaemia in hypercholesterolaemic HCC patients was significantly higher than in HCC patients without hypercholesterolaemia (15/90 vs 4/90; P = 0.01). There was no significant difference in the survival analysis between HCC patients with and without hypercholesterolaemia. Eight and 11 of hypercholesterolaemic HCC patients had their tumours surgically resected and received transcatheter hepatic arterial chemoembolization (TAE), respectively. Serum cholesterol levels fell to the normal range after treatment and rose to abnormal levels again when tumours recurred after surgery or progressively enlarged after TAE. The change in pattern of serum cholesterol was parallel to the change in serum AFP. Serum cholesterol levels may serve as another marker in identifying tumour recurrence and the presence of a viable tumour mass in hypercholesterolaemic HCC patients who have received surgical resection or TAE.
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PMID:Hypercholesterolaemia in patients with hepatocellular carcinoma. 138 58

The short-term effects of insulin and phorbol esters on the regulation of the albumin gene in rat H4IIE (H4) hepatoma cells were investigated and compared to the expression of a gene known to be inhibited by these agents, phosphoenol pyruvate carboxykinase (PEPCK). Both insulin and phorbol esters inhibited transcription of the albumin gene in a rapid, dose-dependent manner. Within 15 min, albumin transcription was reduced by approx. 80%. The inhibitory effects of insulin were evident at concentrations of insulin as low as 5.10(-11)M, suggesting that these effects were mediated through insulin-specific pathways. The ability of both phorbol esters and insulin to inhibit albumin transcription suggests that the negative control of this gene is a stable feature in H4 cells. The effect of phorbol esters to mimic insulin action on the albumin gene, and on several other genes in this cell line, implies that a common pathway may be shared by both insulin and phorbol esters.
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PMID:Rapid regulation of albumin transcription by insulin and phorbol esters in rat hepatoma cells. 138 14

Transforming growth factor-beta (TGF-beta) modulates some components of the acute phase response in hepatic cells. The mechanisms for these actions of TGF-beta are largely unknown. The authors recently found that the decrease in albumin mRNA after TGF-beta 1 treatment required de novo RNA and protein synthesis, suggesting that TGF-beta acts through induction of another gene. The purpose of the current study was to determine whether TGF-beta 1 could regulate the expression of both the jun and fos genes that encode transcriptional regulatory proteins that constitute the AP-1 complex, and to determine whether expression of these genes may be coordinated with the decrease in albumin mRNA. Northern blot hybridization was used to determine levels of specific mRNAs. Transforming growth factor-beta 1 increased the levels of both jun-B and fos-B mRNA by 60 minutes after treatment of mouse hepatoma (BWTG3) cells. When TGF-beta 1 was removed from the media after 4 hours, there was a sustained effect of increased jun-B and decreased albumin mRNA (greater than 48 hours), and the subsequent decrease in jun-B levels coincided with the increase in albumin mRNA. The tumor-promoting phorbol ester (phorbol 12-myristate 13-acetate [PMA]), known to induce jun and fos gene expression, caused increases in jun-B and fos-B that preceded the decrease in albumin mRNA levels at 24 hours. These observations are consistent with our hypothesis that jun-B and fos-B induction may participate in downregulation of albumin synthesis as well as other hepatic responses to TGF-beta.
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PMID:Transforming growth factor (TGF)-beta stimulates hepatic jun-B and fos-B proto-oncogenes and decreases albumin mRNA. 141 79

As an effective therapy for hepatocellular carcinoma, hepatic arterial chemo-embolization therapy has been widely used, and many embolizing materials have been extensively investigated. In the present study, we prepared various types of cis-diamminedichloroplatinum(II) (CDDP) albumin microspheres using chitin and chitosan, both of which have attracted considerable attention as new non-toxic biological polymer materials having favorable characteristics such as immune adjuvant activity, biological compatibility, and biodegradation. Hepatic artery of rabbit hepatic cancer models, which had transplanted VX2 tumors, were embolized with various types of microspheres. The anti-tumor effects and tumor-targeting of the microspheres, and the effects of the microspheres administration on the hepatic tissue were investigated. As a result, anti-tumor activity of the microspheres was increased by the addition of chitin-containing or chitosan treated materials; tumor growth rates of chitin addition and chitosan treated groups were approximately 160% and 120%, respectively, and were significantly lower than that of the non-treatment groups with a rate of approximately 580%. However, complete inhibition of tumor growth might have been impossible. Anti-tumor activity was increased by the addition of chitin-containing or chitosan treated materials. Whereas the growth inhibitory effect was insufficient, in order to potentiate anti-tumor activity, higher CDDP contents and sustained release of CDDP at a high level from microsphere and so on should be essentially improved for the near future. The CDDP level in hepatic tissue following the administration of microspheres was increased by adding chitin to the microspheres or by treating the microspheres with chitosan.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: antitumor effect of cis-diamminedichloroplatinum(II) albumin microspheres, containing chitin and treated with chitosan on rabbits with VX2 hepatic tumors. 146 14

The plasma triacylglycerol-decreasing effect of fish-oil fatty acids was studied in vitro by using the rapidly growing cultured rat hepatoma cell line McA-RH7777. Cells were exposed to albumin-complexed eicosapentaenoic acid (C20:5n-3; EPA), to oleic acid (C18:1n-9; OA), or to albumin alone. Cell growth was similar in albumin- and OA-supplemented cultures, but EPA treatment inhibited growth. As estimated by [14C]glycerol incorporation, OA stimulated both net triacylglycerol synthesis and secretion over control levels in a dose-dependent manner. EPA stimulated triacylglycerol synthesis in similar fashion to OA, but paradoxically decreased net triacylglycerol secretion and led to exaggerated intracellular accumulation of radiolabelled triacylglycerol. The EPA and OA effects were additive at low concentrations of total fatty acid, but at higher fatty acid concentrations OA appeared to negate some effects of EPA. Chemical analysis of albumin- and OA-treated cultures revealed OA-dominant profiles for both cellular and medium triacylglycerol-associated fatty acids. In contrast, EPA was the principal fatty acid in cellular triacylglycerol of EPA-supplemented cultures, whereas medium triacylglycerol from these cultures contained very little EPA. We conclude that McA-RH7777 hepatoma cells readily synthesize EPA-containing triacylglycerol molecules, but they have variable capacity for secreting them. We consider potential mechanisms to account for the effects of EPA in this system.
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PMID:Eicosapentaenoic acid inhibits cell growth and triacylglycerol secretion in McA-RH7777 rat hepatoma cultures. 152 Feb 81

A major, hitherto unknown protein which is shown to be developmentally regulated has been isolated from rat liver. The protein has a molecular mass of 150 kDa and constitutes 8-10% of the adult liver protein. Immunoblot experiments and immunofluorescence studies established its presence specifically in adult liver cells. This protein is not present in early embryonic liver cells, gets induced around day 18 of gestation and reaches near adult levels by 1 day after birth and is not found in the cells of an ascitic hepatoma. Unlike albumin and alpha-fetoprotein, the two well known developmentally regulated liver proteins, the 150 kDa protein is not secreted. Some of the characteristics of this liver-specific protein are discussed.
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PMID:Characterisation of a high-molecular-weight developmentally regulated adult rat liver-specific protein. 154 73

For an understanding of the molecular basis of the marked decrease in catalase activity of various tumor cells, expression of the catalase gene was studied in rat and human hepatoma cell lines and in rat liver, which was used as a control with high activity. RNA blot hybridization profiles and run-on assays indicated that the decrease in catalase activity was due to depression of catalase gene transcription. Chloramphenicol acetyltransferase (CAT) assays for the fragments with various lengths of the 5'-flanking region (up to -4.5 kb from the ATG codon) of the catalase gene revealed the presence of several cis-acting elements involved in the negative regulation of transcription. The most-upstream element with the strongest activity (-3504 to -3364 bp), when linked to the catalase promoter region (-126 bp) of the CAT construct and subjected to an in vitro transcription assay, did not yield transcripts in experiments with the hepatoma nuclear extract, whereas the unlinked template did yield transcripts. A gel shift competition assay using hepatoma nuclear extract showed the core sequence of the silencer element to be 5'-TGGGGGGAG-3'. A homology search found that the same core sequence was also present in 5'-flanking regions of the albumin gene and of some other liver enzyme genes, the expression of which has been reported to be down regulated in some hepatoma cells. Southwestern (DNA-protein) analysis demonstrated that an approximately 35-kDa nuclear protein bound to the silencer element was present in hepatoma cells but not in rat liver cells.
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PMID:Negative regulation of catalase gene expression in hepatoma cells. 158 55

In a search for monocyte-specific nuclear factors, we analyzed in human cells the promoter of the chicken myelomonocytic growth factor, a gene that, in the chicken, is expressed in myeloid and myelomonocytic cells. Reporter gene constructs were active in monocytic Mono Mac 6 cells and in monoblastic THP-1 cells but not in the hematopoietic stem cell line K562. When a region with homology to the sequence recognized by CAAT enhancer-binding proteins (C/EBP) was inactivated by site-directed mutagenesis, the reporter activity was reduced by a factor of 10. Multimers of this region, termed F, in front of a heterologous promoter were active in Mono Mac 6 and THP-1 cells but not in K562 cells, WIL2 B cells, BT20 mammary carcinoma cells, MelJuso melanoma cells, or SK-Hep-1 hepatoma cells. Gel shift analysis with the F oligonucleotide identified DNA-binding activity in monocytic Mono Mac 6, monoblastic THP-1, and myelomonocytic HL60 cells. No binding was detected in myelomonocytic RC2A cells, in myeloid KG-1 cells, or in the hematopoietic stem cell line K562. Furthermore, a panel of solid tumor cell lines, representing various tissues, were also negative. Stimulation by PMA could not induce this binding factor in any of the negative cell lines. Analysis of primary cells (granulocytes, T cells, monocytes, and alveolar macrophages) revealed binding activity only in monocytes and macrophages. This DNA-binding factor, termed NF-M, was found to consist of two molecules, of 50 and 72 kDa, as determined by affinity cross-linking. Binding of NF-M was competed by the region F oligonucleotide and by the C/EBP motif from the albumin enhancer but not by an AP-2 motif. These data suggest that NF-M is a member of the C/EBP family of nuclear factors. The monocyte-restricted activity of NF-M suggests that this nuclear factor may be involved in regulation of monocyte-specific genes.
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PMID:Constitutive monocyte-restricted activity of NF-M, a nuclear factor that binds to a C/EBP motif. 160 56

Potential risk factors for hepatocellular carcinoma were investigated in a case-control study among inhabitants of north east Thailand. Sixty-five cases from 3 hospitals, with matched controls, were included. Infection with hepatitis-B virus was the major risk factor-chronic carriers of HB surface antigen had an estimated relative risk of 15.2. Infection with hepatitis-C virus appeared to be rare. No increase in risk was found with recent aflatoxin intake, as estimated by consumption of possibly contaminated foods, or by measuring aflatoxin-albumin adducts in serum. Regular use of alcohol (2 or more glasses of spirits per week) was associated with a non-significant elevation in risk (o.r. = 3.4, 95% c.i. 0.8-14.6), but the number of regular drinkers in the population was small. The meaning of an apparent protection conferred by certain food items is uncertain, but a possible role of betel nut in the aetiology deserves further investigation.
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PMID:Liver cancer in Thailand. II. A case-control study of hepatocellular carcinoma. 164 98


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