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 feasibility and efficacy of treating peritoneal cancer implants by applying heat to the peritoneal surfaces were studied in inbred Buffalo A rats given i.p. injections of Morris hepatoma 5123TC tumor cells. Heat was delivered to the peritoneum by contact with a heated physiological salt solution (Normosol-R) in the peritoneal cavity. A treatment temperature of 43.3 +/- 0.3 degrees was maintained for 30 min by an immersed stainless steel coil through which hot liquid circulated. Rats implanted with 0.5 to 1.0 x 10(8) tumor cells were treated at 1 to 4 hr (Group I), 4 to 5 days (Group II), and 22 to 24 days (Group III) after tumor implantation to simulate treatment for the clinical conditions of surgically spilled cancer cells, established microscopic cancer implants, and macroscopic cancer implants, respectively. A statistically significant improvement in survival was observed in Groups I and II compared with sham-treated control animals; 58% of the heat-treated animals were cured. Only a slight but statistically insignificant improvement was noted in Group III. These observations indicate that i.p. surface heat treatment of peritoneal implanted cancer is feasible and effective.
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PMID:Intraperitoneal hyperthermic treatment of implanted peritoneal cancer in rats. 747 Oct 53

The stability of cytokeratin during tumor transformation in hepatocellular carcinoma was studied. We applied biochemical methodology to look into the switching of cytokeratin molecules in tumor transformation. First, by centrifugation the cytokeratin molecules were extracted from both liver and hepatoma tissues. The extracts were then soaked with cyanogen bromide-activated Sepharose 4B beads previously coated by monoclonal anti-cytokeratin antibody. The bound molecules were then released from the resin with salt. Second, the isolated molecules of both were treated with lysosomal enzyme and analyzed on two-dimensional gels. The results demonstrated that there was a modulation in cytokeratin molecules, and the hepatoma cytokeratin was generated from the hepatocyte cytokeratin.
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PMID:Could the cytokeratin molecule be modulated during tumor transformation in hepatocellular carcinoma? 752 30

The role of nuclear protein phosphorylation in intracellular signal transduction of tumor-necrosis factor-alpha (TNF-alpha) in the human hepatoma cell line PLC(PRF/5) was investigated. TNF-alpha, which displays cytolytic activity against PLC hepatoma cells, elevated the in vitro phosphorylation of two nuclear proteins (21 kDa and 34 kDa) 16 h after treatment. The cytotoxicity and enhanced nuclear protein phosphorylation by TNF-alpha treatment decreased in the presence of dexamethasone. Both the 21-kDa and 34-kDa proteins were extracted with 2.2 M NaCl from nuclear pellets and phosphorylated in kinase reaction mixtures containing a high concentration of salt. By phosphoamino acid analysis, the specificity of the nuclear kinase was found to be directed toward serine residues. The protein kinase inhibitors H7, staurosporine and herbimycin A, inhibited the phosphorylation of the 21-kDa and 34-kDa proteins in vitro, but calphostin C and heparin did not. The treatment of cells with 4 beta-phorbol 12-myristate 13-acetate or okadaic acid did not affect the in vitro phosphorylation of the two nuclear proteins. An anti-Fas antibody increased the phosphorylation of the 21-kDa and 34-kDa proteins in PLC cells. DNA fragmentation was observed in PLC cells treated with TNF-alpha and anti-Fas antibody after 24 h treatment. These data suggest an involvement of nuclear protein kinase in signal-transduction pathways of apoptotic cell damage triggered by TNF-alpha in PLC hepatoma cells.
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PMID:Enhanced phosphorylation of nuclear 21-kDa and 34-kDa proteins in hepatoma cell death induced by tumor-necrosis factor-alpha. 755 42

The localisation of metallothionein isoform mRNAs in rat hepatoma (H4) cells was investigated using two approaches, namely Northern hybridisation of total RNA extracted from free, cytoskeletal-bound and membrane-bound polysomes isolated by a sequential detergent/salt extraction procedure and in situ hybridisation. The cytoskeletal-bound polysomes were enriched in metallothionein-I (MT-I) and c-myc mRNAs but showed a significantly lower enrichment in MT-II mRNA. These findings indicate that the MT-I mRNA is localised to the cytoskeleton during translation. In situ hybridisation using a biotin-labelled oligonucleotide probe revealed a predominantly perinuclear localisation for the MT-I mRNA.
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PMID:Localisation of metallothionein isoform mRNAs in rat hepatoma (H4) cells. 758 38

During acute inflammation, the serum amyloid A (apoSAA) proteins apoSAA1 and apoSAA2 are transiently associated with high density lipoproteins (HDL) in concentrations of as much as 1000-fold more than their concentrations during homeostasis; however, their effect on HDL function is unclear. Recombinant apoSAAp, a hybrid of the closely related human apoSAA1 and apoSAA2 isoforms, was found to exhibit a high affinity for cholesterol. The adsorption of apoSAAp to polystyrene microtiter wells at physiological pH, temperature, and salt concentration was inhibited and reversed by cholesterol. ApoSAAp, to a greater extent than apoA-I, albumin, or fetal bovine serum, enhanced diffusion of cholesterol from HDL across a membrane that retained molecules > 3.5 kDa. Cholesterol from 25 nM to 125 microM inhibited binding of [3H]cholesterol to 167 nM apoSAAp. A cholesterol binding assay was developed to determine the dissociation constant for binding of [3H]cholesterol to apoSAAp; Kd = 1.7 +/- 0.3 x 10(-7) M and the maximum binding capacity (Bmax) is 1.1 +/- 0.1 mol/mol. After binding cholesterol, the apparent size of apoSAAp as determined by gel filtration on Sephacryl S-100 was increased from 12 to 23 kDa. ApoSAAp enhanced free [14C]cholesterol uptake from tissue culture medium by HepG2 cells, an effect that was dose dependent and blocked by polyclonal antibodies to human apoSAA1 and apoSAA2. ApoSAAp, unlike apoA-I, was taken up from serum-free medium by HepG2 cells and appeared to be degraded by cell-associated enzymes. Unlike peritoneal exudate cells, human HepG2 hepatoma cells do not secrete an enzyme that degrades apoSAAp. These results suggest that apoSAA can potentially serve as a transient cholesterol-binding protein.
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PMID:Recombinant human serum amyloid A (apoSAAp) binds cholesterol and modulates cholesterol flux. 770 46

Methapyrilene (MPH) was a widely used antihistamine until it was found to produce hepatocellular carcinoma and cholangiocarcinoma in Fischer 344 rats. The structurally similar antihistamine pyrilamine (PYR) was marginally or noncarcinogenic in a similar study. The peroxisome proliferator Wy-14,643 was included in this study as a positive control. As part of a program to investigate the mechanisms whereby structurally similar chemicals produce different toxicities, we studied these three chemicals for the induction of cell proliferation in the liver of F344 rats. Male rats were treated for up to 13 weeks with feed dosed with MPH (HCl salt) at 0, 50, 100, 250, or 1000 ppm or PYR (maleate salt) at 1000 ppm to duplicate the route of administration and high-dose groups used in the carcinogenesis assay. In addition, the nongenotoxic hepatocarcinogen peroxisome proliferator Wy-14,643 was included as a positive cell-proliferating chemical. Cell proliferation was quantitated by measuring the incorporation of bromodeoxyuridine (BrDU) administered by osmotic minipump for 7 days and the appearance of proliferating cell nuclear antigen (PCNA) immunohistochemically. The BrDU-labeling index showed a large and sustained increase in rats treated with MPH at 250 and 1000 ppm, sustaining greater than 50% labeling in the higher dose group of 4-, 6-, and 13-week treatment groups. PYR at 1000 ppm demonstrated no significant increase in labeling above control levels at any time point. PCNA-labeling indexes showed similar but reduced increases for MPH and were comparable to control for the PYR dose groups. Two-dimensional gel electrophoresis was used for the detection of quantitative changes in gene expression and qualitative changes in the charges of specific mitochondrial and cytosolic proteins. Quantitative changes in 32 proteins induced by MPH and 39 changes induced by Wy-14,643 were detected throughout the 13-week study. Specific mitochondrial protein charge shifts were associated with high-dose MPH treatment that were not observed in animals treated with Wy-14,643. PYR induced no significant qualitative or quantitative protein alterations. Hepatocellular proliferation of the large magnitude observed following dietary administration of MPH, and not PYR may contribute to the mechanism of carcinogenesis of MPH.
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PMID:The hepatocarcinogen methapyrilene but not the analog pyrilamine induces sustained hepatocellular replication and protein alterations in F344 rats in a 13-week feed study. 771 64

Many of the acute inflammatory responses in critical illness are mediated by tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6). Furthermore, these cytokines are involved in mediating the characteristic changes of thyroid function during acute disease known as non-thyroidal illness. In the present studies we investigated in vitro whether TNF-alpha, IL-1 beta and IL-6 modify nuclear thyroid hormone receptor (TR) capacity and/or affinity. Regulation of TR synthesis was studied in the human hepatoma cell line Hep-G2. Subconfluent cells were incubated with recombinant cytokines in serum-free medium. Nuclear extracts were prepared by high-salt extraction of cell nuclei. Binding assays were performed with [125I]-triiodothyronine; bound and free hormone were separated by filtration. Interleukin 1 beta decreased TR capacity in a dose-dependent manner. Compared with unstimulated cells, the TR capacity was reduced to 87.9 +/- 3.9% (p < 0.05), 80.1 +/- 3.9% (p < 0.01) and 72.1 +/- 5.1% (p < 0.01) after incubation with 0.1, 1.0 and 100 micrograms/l IL-1 beta, respectively. Interleukin 6 and TNF-alpha significantly reduced receptor capacity only at concentrations of 10 micrograms/l or higher and the magnitude of the reduction was lower than with IL-1 beta. The TR capacity was reduced to 81.2 +/- 2.3% (p < 0.01) and 83.2 +/- 6.6% (p < 0.05) after stimulation with 10 micrograms/l IL-6 or TNF-alpha, respectively. TR affinity was not altered significantly after stimulation with any of the cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin 1 beta, tumor necrosis factor-alpha and interleukin 6 decrease nuclear thyroid hormone receptor capacity in a liver cell line. 792 Dec 16

Bile salt uptake, synthesis and secretion by the human hepatoma-derived cell line HepG2 were studied. The cells transported and secreted bile salts largely by means of passive mechanisms. The cells synthesized and secreted the normal human primary bile salts. The ratio of cholate to chenodeoxycholate was 1.5:1. The degree of conjugation, about 35%, was lower than normal, and the glycine-to-taurine ratio was abnormal (4.5:1). This was not due to amino acid deficiency in the medium. Contrary to the report of others, little 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid was secreted. This was confirmed by gas chromatography-mass spectrometry. The total rate of synthesis was about 33% that of normal liver. The specific activity of bile salts synthesized from [3H]mevalonate was about 20 times higher than that of the cellular cholesterol derived from the same precursor. The regulation of bile salt synthesis by two compounds that could alter the precursor pool of cholesterol was studied. After a 24-hr incubation in serum-free medium, the compound 25(OH)cholesterol inhibited the rate of bile salt synthesis compared with control values, possibly by depleting the intracellular free cholesterol pool. Surprisingly, however, progesterone, which inhibits cholesterol esterification and should have expanded this pool, also inhibited bile salt synthesis under those conditions. The effect of these compounds on the level of mRNA for cholesterol 7 alpha-hydroxylase was also determined by Northern-blot analysis. The cholesterol 7 alpha-hydroxylase mRNA was 3.7 kb, similar to that in the rat. The incubation of cells in 25(OH)cholesterol or progesterone, as above, resulted in a decreased level of mRNA. The reduction was proportional to the reduction in bile salt synthesis, suggesting that these compounds act at a pretranslational level. Taken together, these results suggest that our particular subclone of HepG2 cells will be useful for studies of the regulation of bile salt synthesis, but not of transport, by human liver-derived tissue.
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PMID:Characteristics and regulation of bile salt synthesis and secretion by human hepatoma HepG2 cells. 798 52

The biological activity of many cytokines is regulated by binding proteins present at the cell surface, in extracellular matrices or in soluble phase. We describe here a TGF-beta binding protein that is both an extracellular matrix and a cell surface protein. When intact extracellular matrices of HEP-G2 cells were affinity cross-linked with 125I-TGF-beta 1, two major binding components were seen: a 250-kD, proteoglycan-like molecule, presumed to be betaglycan, and a 60-kD protein. The 60-kD TGF-beta-binding protein was also present at the cell surface. It could be released from the cell surface by treating cells with high salt, heparin, chondroitin sulfate, heparitinase, or chondroitinase, indicating that it is bound to heparan sulfate and chondroitin sulfate proteoglycans. The 60-kD protein bound TGF-beta 1 with an apparent dissociation constant of 1.6 nM, and there were 30,000 binding sites per cell at the cell surface. In addition to the HEP-G2 cells and another hepatoma cell line, the 60-kD protein was also found in a human colon carcinoma (HT-29) cell line but not in rat kidney (NRK-49F) or human fibroblast (HUT-12) cell lines. The 60-kD protein could be extracted from cells containing it and transferred to the surface of previously negative cells. The 60-kD protein may serve to regulate the binding of TGF-beta to its signal transducing receptors by targeting TGF-beta to appropriate locations in the microenvironment of cells.
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PMID:A 60-kD protein mediates the binding of transforming growth factor-beta to cell surface and extracellular matrix proteoglycans. 833 95

Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of hepatocarcinogenesis were examined by monitoring both hepatocyte injury and hepatocellular carcinoma development in F344 rats bearing preneoplastic liver nodules induced by the Cayama-Farber procedure. Redox-enzyme modulation, which included increased cytochrome P450 reductase activity induced by phenobarbital-Na (100 mg/kg, i.p. for 3 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.), depletion of glutathione by phorone (200 mg/kg, i.p.), supplementation with the Fe(III) sodium salt of EDTA (50 mg/kg, i.p.) and redox-cycling activation by menadione (50 mg/kg, i.g.), exerted no prominent hepatocyte injury within nodules but did cause slight injury in the surrounding hepatocytes in nodule-bearing rats. The same treatments induced severe hepatocyte injury in non-treated normal rats. Redox-enzyme modulation performed every other week for 33 weeks significantly reduced the number of hepatocellular carcinomas developing in nodule-bearing rats. These results indicate that preneoplastic nodules are resistant to the oxidative stress induction caused by redox-enzyme modulation treatment and that, despite toxic effects in surrounding hepatocytes, no progression pressure is exerted. Indeed, the treatment rather demonstrates an inhibitory effect of the evolution of the nodules into hepatocellular carcinomas.
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PMID:Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of rat hepatocarcinogenesis. 842 75


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