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 alpha-fetoprotein (AFP) and albumin localization were studied in the cells of rat Zaidel's ascitic hepatoma. It was shown in the paraffine sections of the hepatoma cells fixed by mixture of 96 degrees ethanol with 1% glacial acetic acid that 9.3% of hepatoma cells contained AFP and 0.6% of the cells--serum albumin. Small quantities of the tumour cells had both of these proteins simultaneously. There was no definite regularity in the distribution of the AFP and albumin-containing cells in the tumour islands.
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PMID:[Distribution of alpha-fetoprotein and albumin in paraffin sections of cells of Zaidel's ascitic hepatoma]. 5 59

The cytotoxic potential of heterologous rabbit antibody directed against mouse serum albumin (MSA) and alpha-fetoprotein (AFP) was investigated in vitro with a cell line (Hepa) derived from the mouse hepatoma BW7756. Anti-AFP in the presence of complement could kill Hepa cells at concentrations of anti-MSA that were virtually nontoxic. The specificity of the anti-AFP was defined by demonstrating that Hepa cell toxicity was dependent upon and paralleled the secretion of AFP in synchronized cultures. Furthermore, neither antiserum could be shown to be significantly toxic to mouse neuroblastoma cells (Neuro-2A). Immunoglobulin purified from pools of antisera was also highly effective in producing cytotoxicity even in a complement-free system. This reaction proceeded more slowly, requiring nearly 48 hr to reach maximum effect in comparison to the 12 hr for complement-mediated toxicity. MSA and AFP are secreted during different phases of the cell cycle. In cultures arrested by isoleucine starvation, labeled AFP appears in the medium 10 hr after release of the blockade in association with S phase. The appearance of labeled MSA is delayed until the first mitosis. Cytotoxic effects of anti-AFP parallel the secretion of AFP in synchronous cultures. Both antisera could be inhibitory to the secretion and synthesis of the proteins of their antigenic specificity. MSA synthesis was more susceptible to this inhibition than was AFP synthesis. The significance of this phenomenon and its association with the differential cytotoxicity of the antiserum are discussed.
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PMID:The influence of antisera specific for alpha-fetoprotein and mouse serum albumin on the viability and protein synthesis of cultured mouse hepatoma cells. 6 16

The bilirubin-binding ability of human alpha-fetoproteins, which were purified from fetal cord serum and from ascites fluid of a hepatoma-bearing patient, was examined by the difference spectrum and the Jacobsen peroxidase methods. The difference spectrum observed as a result of the specific binding of bilirubin to alpha-fetoprotein had a maximum at 482 nm, and this pattern was quite similar to that observed for serum albumin. The result obtained by the difference spectrum method showed that 1 mol of each alpha-fetoprotein bound 1 mol of bilirubin at pH 8.3 and that the dissociation constants of the complexes of bilirubin with fetal alpha-fetoprotein and hepatoma-derived alpha-fetoprotein were 2.6 x 10(-7) and 5.0 x 10(-7) M, respectively. The Jacobsen enzymatic method using horseradish peroxidase gave the same values for molar binding ratios and similar dissociation constants, 7.1 x 10(-7) M for fetal alpha-fetoprotein and 7.4 x 10(-7) M for hepatoma-derived alpha-fetoprotein. These results indicate that alpha-fetoprotein may function as a carrier protein for bilirubin as has been shown for serum albumin.
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PMID:alpha-Fetoprotein as a carrier protein in plasma and its bilirubin-binding ability. 8

Spermine, spermidine, putrescine and agmatine were examined for their cytotoxicity to mammalian cells in tissue culture. Spermine exhibited the highest cytotoxicity among them. It was followed by spermidine. Putrescine and agmatine showed little toxicity but rather acceleration of cell proliferation in some concentrations. Among 16 kinds of rat cells and strains and a mouse cell strain examined, liver cells, fibroblasts, and cells serially grown in a protein-free synthetic medium were sensitive to spermine in the order described. Normal liver cells were more sensitive than hepatoma cells, and normal fibroblasts were also more sensitive than sarcoma cells. Bovine serum albumin fraction markedly accelerated the cytotoxicity of spermine.
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PMID:Effects of polyamines on the proliferation of mammalian cells in tissue culture. 17 93

Deoxyribonucleic acid polymerase-beta (EC 2.7.7.7) FROM THE Novikoff hepatoma has been purified over 200 000-fold (based on the increase in specific activity), by ammonium sulfate fractionation and chromatography on DEAE-Sephadex, phosphocellulose, hydroxylapatite, and DNA-cellulose. The enzyme is remarkably stable through all stages of purification until DNA-cellulose chromatography when it must be kept in buffers containing 0.5 M NaCl and 1 mg/ml bovine serum albumin for stability. The enzyme appears to be homogeneous as evidenced by a single stainable band when subjected to electrophoresis in polyacrylamide gels of different porosity. The stainable band corresponds to the DNA polymerase as determined by slicing sister gels and assaying for enzyme activity. The specific activity of the homogeneous preparation is about 60 000 units/mg. The enzyme lacks detectable exonuclease or endonuclease activity. It has a molecular weight of 32 000 as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. In sucrose gradients, the molecular weight is estimated at 31 000. The isoelectric point of the hydroxylapatite fraction enzyme is 8.5. The Novikoff beta-polymerase requires all four deoxyribonucleoside triphosphates, primer-template, and a divalent cation for maximal activity. The apparent Km for total deoxyribonucleoside triphosphate is 7-8 muM and for DNA 125 mug/ml. Activated DNA, rendered 7% acid soluble by DNase I, is the preferred primer-template, although a number of synthetic polynucleotides can by efficiently utilized, particularly in the presence of Mm2+ optimum is 7 mM; the Mn2+ optimum is 1 mM. The pH optimum is 8.4 in Tris-HCl or 9.2 in glycine buffer. The beta-polymerase is sstimulated about twofold by NaCl or KCl at an optimum of 50-100 MM, and the enzyme maintains considerable activity at high ionic strengths. The DNA polymerase is inhibited by ethanol, acetone, and a variety of known polymerase inhibitors. Glycols stimulate the enzyme as does spermine or spermidine. Unlike most beta-polymerases, the Novikoff enzyme is moderately sensitive to N-ethylmaleimide.
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PMID:Novikoff hepatoma deoxyribonucleic acid polymerase. Purification and properties of a homogeneous beta polymerase. 18 3

Improvements in the technique of ultramicroinjection of macromolecules into animal cells are described. The method is based on the Sendai virus-induced fusion of animal cells with erythrocyte ghosts containing trapped macromolecules. Fusion of hepatoma tissue culture (HTC) cells with ghosts prepared by hemolysis of erythrocytes in the presence of cytochrome C is much more efficient than fusion with ghosts prepared in the presence of bovine serum albumin (BSA) as in previous investigations. La+++ is more fficient in promoting fusion and less toxic to cells than Mn++, which was used previously. Thus in all subsequent experiments, erythrocytes were hemolyzed in the presence of cytochrome C plus other macromolecules to be trapped, and the resultant ghosts fused in the presence of La+++. The percentage of HTC cells which fused with ghosts reached 80% in many experiments. Ghosts containing 125I-BSA were used to measure the number of BSA molecules injected into HTC cells. About 10(6) BSA molecules were injected per fused cell. The overall efficiency of injection was low (about 0.02% of the starting material).
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PMID:A quantitative study of ultramicroinjection of macromolecules into animal cells. 18 74

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

Mitonchondria isolated from the Morris hepatoma 7777 demonstrated a markedly different phospholipid composition from those of control mitochondria, both with respect to the amounts of the various types present and the fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, wheras there was an increase in the level of monounsaturated fatty acids. Moreover, the usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids; a high percentage of monounsaturated fatty acids was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was, however, some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% versus 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per molecule than those from liver mitochondria. The zeta potential of liposomes of the hepatoma phospholipids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. The calcium-stimulated phospholipase A activity of the hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. The maximal activity was lower, however, than that noted in liver mitochondria. Furthermore, by following the incorporation of [3H]ethanolamine into mitochondria phospholipids, it was established that the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of both the endoplasmic reticulum and the mitochondrion. Accompanying the changes in phospholipid compositon and metabolism were alterations in mitochondrial energy-linked processes. The hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1mM ethylenediaminetetraacetate and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration.
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PMID:Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma. 18 46

The effects of exogenous proteins on the incorporation of [3H]-thymidine into DNA was studied in Novikoff hepatoma ascites cells incubated in Eagle's minimal essential medium. A liver cytosol fraction (8 mg protein/ml) caused approximately 80% inhibition of isotope incorporation. The inhibitory activity of cytosol fractions from Morris hepatomas 9618A2, 5123C, and 20 were inversely related to their growth rate. Under conditions in which there appeared to be a density dependent inhibition of growth, a mean 10-20% stimulation of isotope incorporation was observed after addition of total calf thymus histones and individual fractions in the concentration range of 100-400 microgram/ml. In experiments with lower cell concentrations, a 60% or greater increase in [3H]-thymidine incorporation could be obtained with total calf thymus histone and with F1 and arginine-rich histones from rat liver. At concentrations of 1-2 mg/ml, histones inhibited DNA synthesis. Bovine serum albumin had little effect on DNA synthesis. Polylysine caused an 80-90% inhibition at a concentration of 1 mg/ml, but stimulatory effects were detected under certain conditions at 10 microgram/ml. The results suggest critical dependence on the ratio of cell and exogenous protein concentration in the action of proteins on DNA synthesis.
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PMID:Actions of exogenous histones and other proteins on [3H]-thymidine incorporation into DNA of Novikoff hepatoma cells. 19 83

Serum albumin and total globulin were determined in 22 healthy people, 29 patients with acute viral hepatitis, 27 patients with cirrhosis and 27 patients with primary hepatocellular carcinoma to see if they might be of discriminating value. The mean serum albumin values were found to be highest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. The mean serum total globulin values on the other hand, were found to be lowest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. Both the mean albumin and mean total globulin of each group of subjects were significantly different from the respective means of the other three groups. A probable explanation for the higher serum albumin and lower globulin levels found in primary hepatocellular carcinoma, as compared to cirrhosis, is that hepatocellular carcinoma occurs in reasonably well-compensated cases of cirrhosis.
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PMID:Serum albumin and total globulin levels in common liver diseases in Accra (Ghana). 20 91


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