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 reticuloendothelial system function test using 131I-labeled aggregated human albumin (131IAA) as test particle is thought to be one of the best methods for the study of RES function of human beings. This method needs a large amount of 131IAA, but 131IAA has been used as a tracer of liver scintiscanning, and we tired to study RES function by using commercially available 131IAA specially made as tracer of liver scintiscanning. Because the amount of 131IAA used in this study was smaller than the critical dosis, our interest was focussed on the catabolic activity of 131IAA phagocytized by Kupffer's cells. The plasma obtained 60 min after 131IAA injection was fractionated into two distinct peaks by gel column chromatography; ionic 131I and protein-bound 131IAA. The ratio between ionic 131I and bound 131IAA (F/B ratio) was studied in various diseases. The F/B ratios of liver cirrhosis and hepatoma were significantly lower than that of the control. The lowered F/B ratio had no correlation with other liver function tests, data of hepatic scintiscanning, or with clinical findings. The F/B ratio was also not correlated with congo red index as RES function test.
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PMID:Reticuloendothelial system function test using 131I-labeled aggregated albumin. 16 66

Albumin molecules appeared to be synthesized in the light hepatocytes of rats by bound polysomers on rough and endoplasmic reticulum and the nuclear envelope. The molecules were discharged directly into the cytosol, then to the external cellular spaces. This conclusion failed to support the current theory from biochemical studies that albumin is synthesized by bound ribosomes, discharged into the cisternae of rough endoplasmic reticulum, and transported to the smooth endoplasmic reticulum and then to the Golgi apparatus. In addition to the liver, positive syntheic activities were observed in the aorta, kidney, and hepatoma cells of rat. Earlier investigators have reported that only liver cells can synthesize albumin.
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PMID:Electron microscopy of albumin synthesis. 17 Jun 82

The binding of the "activated" receptor-glucocorticoid complexes of cultured rat hepatoma cells to nuclei, chromatin, and DNA has been studied under cell-free conditions. A critical factor in determining the shape of the binding curve is shown to be an inhibitory material which is present in crude cytosol and which can be removed without destroying the receptor-steroid complex. These and other results argue that the apparent saturation observed in earlier experiments may have been due to the inhibitors. Thus, the actual number of acceptor sites in hepatoma tissue culture cell nuclei is much larger than previously estimated and their affinity for the complex is lower. Nuclear binding experiments indicate that the inhibitory material interacts with the receptor-steroid complex. The inhibitors appear to be macromolecular; but their effects cannot be mimicked by albumin or hemoglobin. The acceptor capacity at low ionic strength for binding receptor-glucocorticoid complexes increases when proceeding from nuclei to DNA. An analysis of the kinetics of association and dissociation and of the relative binding behavior of nuclei and DNA argues that the affinity of complex for nuclei is much greater than for DNA. DNA-associated histones reduce the amount of complex that binds to DNA. These and perhaps other chromosomal proteins may be responsible for the ordering of acceptor capacity. Evidence is presented that the difference in affinities of nuclear and DNA acceptors could also be due to chromosomal proteins. In nuclei, these proteins may thus both reduce the amount of complex binding by rendering regions of DNA less accessible and increase the binding affinity of some, or all, of those DNA binding sites which remain exposed.
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PMID:Interaction of glucocorticoid receptor-steroid complexes with acceptor sites. 17 16

Pure cholesterol associated in complexes with lipoproteins (whole serum and human low density lipoproteins) or esterified with succinic acid (cholesteryl succinate) and bound to albumin effectively suppresses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in hepatoma tissue culture (HTC) cells grown in lipoprotein-poor serum medium during short 4-hour) incubation periods. Simultaneous measurments of the kinetics of uptake of radioactive unesterified cholesterol of whole serum and cholesteryl succinate, their conversion to lipid products, and the decay in enzyme activity, suggest that the cholesterol-induced suppression is mediated by the sterol itself rather than by inhibitory lipid products derived from its metabolism. Several cholesterol derivatives such as cholestenone, 7-ketocholesterol, and 7alpha-and 25-hydroxycholesterol also suppress reductase activiy in HTC cells and are significantly more inhibitory than the pure cholesterol preparations. The decrease in enzyme activity produced by cholesterol and its derivatives is concentration-dependent and specific. [1-14C]Oleate incorporation experiments indicate that cholesterol ester formation in HTC cells is not increased at inhibitory concentrations of the steroids. These data suggest that sterol ester formation is not an obligatory process in the feedback control of HMG-CoA reductase activity. The half-life of the reductase (3 to 4 hours) is not significantly changed by cycloheximide, plus or minus whole serum, and cholesteryl succinate. In contrast, the half-life is strongly reduced when HTC cells are incubated with cycloheximide plus maximal concentrations of 25-hydroxycholesterol, 7-ketocholesterol, or cholestenone, resulting in t1/2 values of 24, 36, and 60 min, respectively. Increasing concentrations of whole serum and cholesteryl succinate have no significant effect on the apparent rate constant of inactivation of the enzyme, whereas its apparent rate of synthesis is decreased 3- and 10-fold, respectively. These results are reversed with oxygenated steroid inhibitors. The rate of synthesis of reductase is essentially unchanged as the concentrations of 25-hydroxycholesterol, 7-ketocholesterol, and cholestenone are increased in the culture medium, whereas the apparent rate constant for degradation is increased 9-, 7-, and 3-fold, respectively. HMG-CoA reductase activity in HTC cells thus appears to be modulated by two different mechanisms in which steroid structure is important. Whole serum and cholesteryl succinate specifically decrease the rate of enzyme synthesis, while 25-hydroxycholesterol, 7-ketocholesterol, and cholestenone increase the rate of inactivation of the reductase.
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PMID:Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in hepatoma tissue culture cells by pure cholesterol and several cholesterol derivatives. Evidence supporting two distinct mechanisms.20l. 17 60

The clonal variation in rate of albumin synthesis in hepatoma cells is described as a tool for the study of epigenetic control of differentiation. Previous studies have demonstrated that, from a population of hepatome cells, variant subclones can be readily isolated that produce albumin at different rates. Each clonal variant had a characteristic rate of albumin production, and the clones clustered around discrete values that formed a geometric progression. The present experiments, using a cell-free protein-synthesizing system from wheat germ; show that albumin messenger RNA activity is directly proportional to the rate of albumin synthesis in three different hepatoma clones, thus suggesting a pretranslational control of albumin production. Possible hypotheses to explain the geometric pattern of clonal variation are discussed with respect to the organization and control of the transcriptional unit.
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PMID:Clonal variation in albumin messenger RNA activity in hepatoma cells. 18 May 38

The mechanism of albumin biosynthesis was studied in Morris hepatoma 5123tc in vivo and in hepatoma cell suspensions obtained by solubilizing the intercellular matrix with collagenase and hyaluronidase. In the in vivo experiments, L-[-14C]leucine was injected i.v. into rats bearing hepatomas in the muscles of both hind legs. After 14 min, tumors were removed and homogenized. A protein fraction quantitatively precipitable with antialbumin was isolated from the homogenate by acetone fractionation and precipitation with antiserum against serum albumin. This protein fraction was not homogeneous. With the use of 3 consecutive chromatographies on diethylaminoethyl cellulose, a very highly radioactive albumin-like protein could be separated from a large amount of only slightly radioactive albumin. In hepatoma cell suspensions incubated with L-[1-14C]leucine followed by a chase with excess nonradioactive L-leucine, radioactivity was incorporated first into the albumin-like protein and transferred thereafter into albumin, suggesting that albumin was synthesized via the albuminlike protein as precursor. In vivo, 1.8% of newly synthesized hepatoma protein was albumin or its precursor, compared with 1.2% in cell suspensions.
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PMID:Biosynthesis of albumin via a precursor protein in Morris hepatoma 5123tc. 18 40

The effects of essential amino acids on albumin synthesis by a mouse hepatoma cell line have been investigated. The amino acids tested were tryptophan, phenylalanine, histidine, isoleucine and leucine. Cellular rates of synthesis (molecules albumin/cell per min) were determined from rates of [3H]leucine incorporation into immunoprecipitable albumin in the culture medium. The effects of amino acids on albumin synthesis fall into three distinct groups. The concentration of tryptophan producing half-maximal synthesis is 4 micronM. The corresponding concentration for leucine is 100 micronM. Histidine, phenylalanine and isoleucine were very similar, the half-maximal concentrations being approximately 15 micronM. The concentrations of amino acids producing half-maximal synthesis correlate directly with the amino acid composition of albumin. The levels of these essential amino acids necessary to saturate albumin synthesis have been compared with amino acid levels in normal plasma.
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PMID:Albumin synthesis in cultured hempatoma cells. Regulation by essential amino acids. 19 Oct 77

Total nuclear RNA was isolated under conditions of actinomycin D blocking ion-exchange chromatography on kieselguhr columns with methylated albumin detected differences in transpiration of rat liver nuclear RNA with intensive normal and malignant growth. Actinomycin D in doses blocking the appearance of peculiar proteins in the blood serum of rats with the regenerating liver and RS-1 hepatoma produces a different effect on the biosynthesis of nuclear DNA-like RNA of the rat liver. 24h after a partial hepatectomy the antibiotic inhibits considerably the biosynthesis of nuclear DNA-like RNA which is eluated during chromatographying with 0.2% solution of sodium dodecyl sulphate at 70 degrees C. With RS-1 hepatoma the actinomycin D effect is most pronounced with respect to nuclear DNA-like RNA of rats with a tumour which is washed off from the column with a 0.2% solution of sodium dodecyl sulphate at 37 degrees C.
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PMID:[Differences in transcription of nuclear RNA from rat liver with normal and malignant growth]. 19 75

The rat hepatoma cell H4-12 which synthesizes and secretes albumin was synchronized by growth in isoleucine-deficient medium followed by a second block with excess thymidine. Albumin synthesis and secretion was measured in the synchronized cells at different time intervals representative of early S, late S, G2, mitosis, early G1 and late G1 phases of the cell cycle. Maximal albumin synthesis occurred during G1 although significant synthesis also occurred during the other cell cyle phases. Most (75--80%) of the radioactive albumin produced during a 15 min pulse incubation with L-[4,5-3H] leucine was found in the microsomal cell fraction and this nascent albumin was secreted into the incubation medium during a 160 min chase period. Fifty percent of the nascent albumin was secreted by 50--55 min and this pattern of secretion did not change during the cell cycle. These data indicate that albumin synthesis occurs throughout the cell cycle but that it is preferred during G1. The rate of intracellular transport and secretion of albumin does not vary during the different phase of the cell cycle.
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PMID:Synthesis and secretion of albumin by a synchronized rat hepatoma cell line. 19 59

Cytoplasmic RNA of the rat regenerating liver and liver of rats with hepatoma PC-1 is separated into five fractions on the column of kieselgur with methylated albumin (MAK). Studies in the nucleotide composition showed that certain fractions of cytoplasm RNA are ribosomal and messenger RNA. The highest amount of radioactive precursor is incorporated into messenger RNA of the rat regenerating liver and liver of the rats with hepatoma PC-1 which is eluated from the column by 0.2% solution of sodium dodecyl sulphate at 37 degrees C (third fraction). Actinomycin D in doses inhibiting appearance of characteristic proteins in the blood serum of rats with the regenerating liver and heaptoma PC-1 blocks almost completely biosynthesis of ribosomal RNA eluated from the MAK column in the gradient of sodium chloride (second fraction), and that of messenger RNA, eluated by sodium dodecyl-sulphate at 37 degrees C (third fraction).
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PMID:[Study of cytoplasmic RNA in tissues of the rat, regenerating liver and in liver of rats with hepatoma PC-1]. 20 Oct 68


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