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)

1-14C-Acetic, 1-14C-palmitic, or 1-14C-stearic acid was incubated with minimal deviation hepatoma 7288C cells grown in culture to assess: de novo fatty acid synthesis, oxidation, desaturation, and elongation of saturated fatty acids, as well as the ability of media fatty acids to serve as precursors of cellular glycerolipids. Distribution of radioactivity in the individual lipid classes and the various fatty acids of triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine was determined. The radioactivity among the monoenoic acid isomers derived from triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine was analyzed by reductive ozonolysis. Only small amounts of the labeled substrates were oxidized to carbon dioxide. Except for labeled stearic acid, which also was incorporated heavily into phosphatidyl inositol and phosphatidyl serine, most radioactivity was recovered in triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine. Synthesis of cholesterol and long chain fatty acids from labeled acetic acid demonstrated that these cells can perform de novo synthesis of fatty acids and cholesterol. Both labeled palmitic and stearic acids were desaturated to the corresponding delta9 monoenes, and palmitic and palmitoleic acids were elongated. The nexadecenoic acid fraction isolated from triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine, when acetic or palmitic acid was the labeled substrate, showed that greater than 70 percent of the labeled acids were the delta9 isomer. Radioactivity of the octadecenoic acid fraction derived from labeled acetic or palmitic acids was nearly equally divided between the delta9 isomer, oleic acid, and the delta11 isomer, vaccenic acid. Desaturation of labeled stearic acid produced only oleic acid. These data demonstrate that the biosynthesis of vaccenic acid in these cultured neoplastic cells proceeds via the elongation of palmitoleic acid. The relatively high level of vaccenic acid synthesis in these cells suggests that the reported elevation of "oleic acid" in many neoplasms may result from increased concentration of vaccenic acid.
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PMID:Lipids of cultured hepatoma cells. VI. Glycerolipid and monoenoic fatty acid biosynthesis in minimal deviation hepatoma 7288C-1. 16 43

Triglycerides from normal liver, host liver, and heptoma of rats maintained on chow and fat-free diets were subjected to sterospecific analysis. Normal and host liver triglycerides from animals on the same diet did not exhibit significant differences. Fat-free diet reduced polyunsaturated fatty acids in normal and in host liver triglycerides. Each position of hepatoma and liver triglyceride glycerol exhibited a characteristic fatty acid composition. Palmitate concentrations were reduced dramatically and stearate levels were increased significantly at the 1 position of hepatoma triglycerides, relative to the corresponding position of liver triglycerides which were affected little by diet ot tumor. Except for higher percentages of C-20 and higher fatty acids, common to all three positions, the composition of hepatoma triglycerides at the 2 position appeared normal. The 3 position of hepatoma triglycerides contained significantly higher percentages of stearate than liver. Data obtained previously for Ehrlich ascites cell triglycerides were in good agreement with this hepatoma. Data from these two neoplasms suggest that the metabolic system that regulates or controls the fatty acid composition at the 1 and 3 positions of normal tissue triglycerides does not function normally in neoplasms.
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PMID:Sterospecific analysis of hepatoma, host liver, and normal rat liver triglycerides from animals on chow and fat free diets. 16 60

Monoenoic acid fractions were isolated from phosphatidycholine, phosphatidylethanolamine, triglycerides, and cholesteryl esters of hepatoma 7288CTC, host liver, and normal liver from animals maintained on chow and fat free diets. Hexadecanoate (16:1), octadecenoate (18:1), and eisosenoate (20:1) fractions were analyzed quantitatively for their isomeric composition. The fat free diet had little or no effect relative to the chow diet on the isomeric composition of 16:1, 18:1, and 20:1 from any lipid class in either heptoma, host liver, or normal liver. Host livers were reduced in palmitoleic acid, and oleic and eicos-11-enoic acids were increased relative to normal liver. The 16:1 fraction from triglyceride of normal liver, host liver, and hepatoma contained 90, 80, and 75% palmitoleic acid, respectively. The 20:1 fraction from triglycerides of normal liver, host liver, and hepatoma contained ca. 55, 70, and 60% eicos-11-enoic acid, respectively, with the remainder consisting of eicos-13-enoic acid. The proportion of vaccenic acid in the 18:1 fraction was 60, 50, 20, and 25% for phosphatidylethanolamine, phosphatidylcholine, triglycerides, and cholesteryl esters, respectively, with oleic acid making up the balance. In contrast, all hepatoma lipid classes exhibited the same proportion of oleic (70%) and vaccenic (30%) acids. These data appear to be the first to demonstrate lipid class specificity for isomeric octadecenoic acids in normal liver and the loss of this specificity in a neoplasm.
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PMID:Hepatoma, host liver, and normal rat liver lipids: distribution of isomeric monoene fatty acids in individual lipid classes. 17 62

The lipid composition of Yoshida ascites hepatoma cells was analyzed together with that of ascitic plasma and of livers and blood plasma from host and normal rats. In comparison to normal livers, host livers showed no significant differences in the content of the various lipid classes, but contained a higher percentage of palmitic acid and a lower proportion of arachidonic acid in the major phospholipid classes. In addition, tumor growth induced a marked hypertriglyceridemia in host animals; changes in the concentration of other plasma lipid classes were not statistically significant. The ascitic plasma contained small amounts of lipids mainly constituted by cholesteryl esters and phospholipids. Yoshida hepatoma cells contained less phospholipids in comparison to both host and normal liver, while the increased level of triglycerides and the decrease of free fatty acids were not statistically significant. Hepatoma cells showed appreciable amounts of ether-linked lipids associated in part to neutral lipids (as glyceryl ether diesters) and, in part, to ethanolamine and choline phosphoglycerides. The alkyl groups in GEDE as well as in ethanolamine and choline phosphoglycerides were mainly constituted by C16:0 and C18:0 followed by C18:1. The alk-1-enyl groups in ethanolamine and choline phosphoglycerides were C16:0 and C18:0 with only a minor proportion of C18:1. In comparison to both host and normal liver, Yoshida hepatoma cells showed significant changes in the fatty acid composition of neutral lipids and phospholipids. Some of the major changes consisted of an increase of monoenoic acids associated with a decrease of arachidonic and docosahexaenoic acids in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol.
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PMID:Lipid composition of Yoshida ascites hepatoma and of livers and blood plasma from host and normal rats. 44 23

The lipid composition of Morris hepatoma 5123c was analyzed together with that of liver and blood plasma from both normal and tumor-bearing rats. The results showed that the liver of tumor-bearing rats contained higher amounts of glycerides, choelsteryl esters, free fatty acids and phospholipids than the liver of normal rats. In the blood plasma of tumor-bearing rats, there was an increase of free cholesterol and triglycerides; this latter difference, however, was not statistically significant. Acyl chain changes in the liver of tumor-bearing rats consisted of an increase of palmitic and oleic acids and a decrease of stearic and arachidonic acids in phosphatidylinositol. Morris hepatoma 5123c contained a lower amount of triglycerides than the livers (both host and normal) and showed a significant decrease of total phospholipids when compared to the host liver. The major acyl chain changes found in Morris hepatoma 5123c compared with both normal and host rat livers were: a) a higher percentage of arachidonic acid together with a lower proportion of palmitic acid in cholesteryl esters; b) an increase of stearic and arachidonic acids and a decrease of palmitic acid in triglycerides; and c) a higher level of palmitic and oleic acids associated with a lower percentage of stearic and C22 polyunsaturated acids in phosphatidylcholine.
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PMID:Lipid composition of Morris hepatoma 5123c, and of livers and blood plasma from host and normal rats. 49 62

The uptake of myristic (C14:0), palmitic (C16:0), palmitoleic (C:16,N-7), stearic (C18:0), oleic (C18:1,N-9), linoleic (C18:2,N-6) and arachidonic (C20:4,N-6) acids from plasma free fatty acids (FFA), triglycerides (TGA), phospholipids (PL) and cholesterol esters (CE) was measured in tissue-isolated hepatomas 7288CTC and 7777 in vivo. Adult tumour-bearing Buffalo rats were fed a normal chow diet ad libitum and were subjected to darkness from 1800 to 0600 h. Arterial plasma levels of FFA, TGA, PL and CE were increased during the dark period without change in fatty acid compositions. Arteriovenous difference measurements of tumour lipid uptake were performed between 0600 and 0900 h and included both high (dark) and low (light) arterial blood lipid concentrations. The rate of lipid uptake from each lipid class was directly dependent on the rate of supply of the lipid to the tumour. The efficiency of uptake, however, depended on the type of plasma lipid and the tumour. During one pass of arterial blood, hepatoma 7288CTC (n = 5 to 13) removed 46, 33, 36 and 31%, and hepatoma 7777 (n = 7 to 9) removed 48, 50, 52 and 49% of the fatty acids supplied in FFA, TGA, PL and CE, respectively. Perfusion of tissue-isolated tumours in situ with donor blood containing plasma free (1-14C)palmitic acid showed that 14C-palmitic acid was removed from the arterial blood and was incorporated into tumour lipids and that 14CO2 was released into the tumour venous blood. Uptake of the seven fatty acids over a 24 h period was greatest from PL greater than TGA greater than FFA greater than CE and was estimated to total 18.1 +/- 3.5 mg fatty acids g-1 for hepatoma 7288CTC and 25.9 +/- 3.5 mg fatty acids g-1 for hepatoma 7777. Both hepatoma 7288CTC and 7777 grew at a rate of about 1 g day-1 and contained 13.4 +/- 2.5 and 10.6 +/- 3.9 mg of these 7 fatty acids g-1 tumour wet weight, respectively. We conclude that these two tumours obtain all of the fatty acids needed for daily growth from host arterial blood.
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PMID:Uptake of plasma lipids by tissue-isolated hepatomas 7288CTC and 7777 in vivo. 150 1

The physiological importance of the glucose fatty acid cycle has been controversial. Many studies have failed to demonstrate an inhibitory effect of free fatty acids (FFA) on glucose utilization. Using both hepatoma cells (Hep G2) and human erythrocytes, which have poor oxidative capacity and metabolize glucose primarily anaerobically, we have demonstrated a unique stimulatory effect of FFA on glycolysis. Fructose 2,6-bisphosphate (F-2,6-P2) concentrations also increased significantly in Hep G2 cells incubated with palmitic acid. In contrast, F-2,6-P2 concentrations fell in primary cultured hepatocytes incubated with palmitic acid in association with increased oxidation of FFA and accumulation of beta-hydroxybutyrate. We propose that a stimulatory effect of FFA on glycolysis reported here for the first time may have been masked in previous studies performed in tissues in which the oxidation of FFA and the accumulation of intermediates such as citrate may have decreased F-2,6-P2 concentrations. We conclude that the spectrum of FFA effects in glycolysis probably depends on tissue oxidative capacity.
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PMID:A stimulatory effect of FFA on glycolysis unmasked in cells with impaired oxidative capacity. 216 2

The effect of insulin on the oxidative desaturation of 1-14C palmitic acid to palmitoleic acid (delta 9 desaturase) 1-14C linoleic acid to alpha-linolenic acid (delta 6 desaturase) on rat liver microsomes and 1-14C eicosa-8,11,14-trienoic acid to arachidonic acid (delta 5 desaturase) on rat liver microsomes and hepatoma tissue culture (HTC) cells was studied. After 12 h of insulin injection, at a dose of 2.5-12.5 U/kg no change was found in delta 9 desaturation activity while delta 5 desaturation activity decreased. The conversion of linoleic to alpha-linolenic acid decreased when the amount of insulin injected was 5 U/kg or more. The effect of insulin (5 U/kg) on delta 9, delta 6 or delta 5 desaturation activity was tested from 1 to 12 h after the injection. The conversion of palmitic acid to palmitoleic acid showed no important changes along the time, while delta 5 desaturation activity decreased at all the times tested. delta 6 Desaturation activity showed a slight increase after 1 h of insulin treatment and then decreased significantly up to the end of the experiment. The addition of 400 mU/ml or more of insulin to the incubation medium of HTC cells produced a significant decrease on the conversion of eicosatrienoic acid to arachidonic acid. The effect of insulin on fatty acid desaturation activity of liver microsomes of normal rats differs from that of diabetic rats. The role of this hormone in relation to other hormones, carbohydrate metabolism and lipid biosynthesis on the activity of the desaturases was discussed.
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PMID:Effect of insulin on the oxidative desaturation of fatty acids in non-diabetic rats and in isolated liver cells. 287 Jun 4

1. Plasma membranes were isolated from normal liver, Morris hepatoma 7288C and regenerating liver, 6, 15, 24, and 48 hr after partial hepatectomy. 2. The cholesterol/phospholipid ratio was lower in regenerating liver 6 hr after partial hepatectomy (0.51) compared to the sham control (0.68), returning to normal after 15 hr. This was accompanied by a small increase in palmitic acid (16:0). There were no other changes in the lipid composition in regenerating hepatocytes in the first 48 hr after partial hepatectomy. 3. Analysis of lipid composition showed a higher cholesterol/phospholipid ratio in the hepatoma plasma membrane compared to normal liver accompanied by an increase in saturation of the fatty acyl groups of the phospholipids. There were also significant changes in the phospholipid classes. 4. There was no change in the two-dimensional electrophoretic profile of membrane proteins in the early stages of liver regeneration, however hepatoma membranes showed significant differences in protein profile. 5. These changes in the lipid composition of the hepatoma plasma membrane would have the effect of decreasing the average fluidity of the membrane and together with the changes in protein composition may be significant in the altered growth of the hepatoma. Changes in the lipid composition of the hepatocyte plasma membrane early in liver regeneration may reflect the onset of renewed cell division.
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PMID:Studies on regenerating liver and hepatoma plasma membranes--I. Lipid and protein composition. 339 37

This study identifies and partially characterizes an insulin-sensitive glycophospholipid in H35 hepatoma cells. The incorporation of [3H]glucosamine into cell lipids was investigated. A major labeled lipid was purified by sequential thin layer chromatography using first an acid followed by a basic solvent system. After hydrochloric acid hydrolysis and sugar analysis by thin layer chromatography, 80% of the radioactivity in the purified lipid was found to comigrate with glucosamine. H35 cells were prelabeled with [3H]glucosamine for either 4 or 24 h and treated with insulin causing a dose-dependent stimulation of turnover of the glycophospholipid which was detected within 1 min. The purified glycolipid was cleaved by nitrous acid deamination indicating that the glucosamine C-1 was linked to the lipid moiety through a glycosidic bond. [14C]Ethanolamine, [3H]inositol, and [3H]sorbitol were not incorporated into the purified glycolipid. The incorporation of various fatty acids into this glycolipid was also studied. [3H]Palmitate was found to be preferentially incorporated while myristic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid were either not incorporated or incorporated less than 10% of palmitate. The purified glycolipid labeled with [3H]palmitate was cleaved by treatment with phospholipase A2 but was resistant to mild alkali hydrolysis suggesting the presence of a 1-hexadecyl,2-palmitoyl-glyceryl moiety in the purified lipid. Treatment of labeled glycophospholipid with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus generated a compound migrating as 1-alkyl,2-acyl-glycerol and a polar head group with a size in the range from 800 to 3500. These findings coupled with the nitrous acid deamination demonstrate that glucosamine was covalently linked through a phosphodiester bond to the glyceryl moiety of the purified glycolipid. These findings suggest that insulin acts on this glycophospholipid by stimulating an insulin-sensitive phospholipase C. This unique glycophospholipid may play an important role in insulin action by serving as precursor of insulin-generated mediators.
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PMID:Identification of a novel insulin-sensitive glycophospholipid from H35 hepatoma cells. 354 86


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