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

Minimal deviation hepatoma 7288 C cells were cultured in Swim's medium containing 10% serum for 48 hr. The growth medium was replaced with serum free media containing different concentrations of [1-14C] eicosa-8,11,14-trienoic acid and the cells were incubated for 24 hr. Incorporation into cell lipids, oxidation to CO2, and desaturation to arachidonic acid were studied. The oxidation of the acid was very low. It was preferentially incorporated into the polar lipids of the cell. The incorporation depended on the number of cells and fatty acid concentration. Saturation of the cells with the acid was reached when 144.7 nmoles per mg of cellular protein were incorporated. The acid was desaturated readily to arachidonic acid. The nmoles of eicosatrienoic acid converted to arachidonic acid per mg of cellular protein were hyperbolic function of the acid incorporated. Maximal desaturation, 23 nmoles per mg of cellular protein, was reached when the cells were saturated with the acid. The calculations of the desaturation capacity and of the endogenous pool of eicosatrienoic acid available for desaturation in the cell are discussed.
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PMID:Uptake and metabolism of exogenous eicosa-8,11,14-trienoic acid in minimal deviation hepatoma 7288 C cells. 17 60

Fatty acid oxidation, reconstituted substrate shuttles, and the activity of the citric acid cycle were studied in mitochondria isolated from Becker transplantable hepatocellular carcinoma H-252 AND Host livers, and the results were compared with those obtained with Morris hepatomas 7288CTC and 5123C. Whereas the activities of the malate-aspartate and the alpha-glycerophosphate shuttles were only slightly lower than those of host livers, the activity of the fatty acid shuttle was much lower in H-252 mitochondria. Oxygen uptake and CO2 production associated with the oxidation of fatty acids was much lower in tumors H-252 and 7288CTC, compared with host livers, whereas tumor 5123C mitochondria show a high capacity to oxidize fatty acids. Ketogenesis and beta-hydroxybutyrate dehydrogenase activity were also lower in tumor H-252 mitochondria. However, neither oxygen uptake associated with the oxidation of other respiratory substrates nor CO2 production from succinate or malate was strikingly elevated in these tumors. These factors suggest that the respiratory phosphorylation chain and activity of the citric acid cycle are fully functional in tumors H-252 and 7288CTC. The defects responsbile for the lower rates of fatty acid oxidation in these tumors probably involves the beta-oxidation pathway, as well as the activation of fatty acids. The impairment of fatty acid oxidation may explain the lower activity of the reconstituted fatty acid shuttle for transporting reducing equivalents into H-252 mitochondria. The different properties with regard to fatty acid oxidation in Morris hepatoma 5123C, compared with those in Becker H-252- AND Morris hepatoma 7288CTC, may reflect the different extent of differentiation in these tumors, the former being a slow-growing, well-differentiated tumor, whereas the latter represent tumors that are less differentiated and of more rapid growth rate.
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PMID:Fatty acid oxidation, substrate shuttles, and activity of the citric acid cycle in hepatocellular carcinomas of varying differentiation. 18 36

Minimal deviation hepatoma 7288C cells (HTC) were incubated in serum-supplemented and serum-free Swim's 77 medium in the presence of D-[1-14C] glucose for 1, 2, 4, 8, 12 and 24 hr. Glucose oxidation to CO2, incorporation into total cell mass, and incorporation into cell and medium lipids were determined. The percentage distribution of total cell lipid radioactivity in individual neutral and polar lipid classes was followed as a function of time. Degradation studies of individual lipid classes were performed to ascertain the percentage of radioactivity in acyl and glycerol moieties. The percentage of D-[1-14C] glucose oxidized to 14CO2, incorporated into cell matter and cell lipids was elevated in cells incubated in serum-free medium as opposed to serum-supplemented medium. The percentage distribution of total cell lipid radioactivity into individual neutral lipid classes from both serum-free and serum-supplemented cultures was as follows: sterols greater than triglycerides greater than free fatty acids greater than sterol esters. The percentage distribution of total cell lipid radioactivity into individual polar lipid classes of serum-supplemented cultures was as follows: phosphatidylcholine greater than phosphatidylinositol greater than sphingomyelin greater than phosphatidylethanolamine greater than phosphatidylserine. The distribution of glucose radiolabel into individual polar lipid classes of serum-free HTC cells was different from their serum-supplemented counterparts: sphingomyelin greater than phosphatidylcholine greater than phosphatidylinositol greater than phosphatidylethanolamine greater than phosphatidylserine. Glycerol from glyceride classes contained a higher percentage of radioactivity than the acyl moieties, with this percentage significantly elevated in serum-free cultures. The data indicate that, although glucose is a substrate for HTC cell lipids, other precursors present in the culture system also contribute to the lipid constituency of this hepatoma cell line.
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PMID:Lipids of cultured hepatoma cells: VIII. Utilization of D-[1-14C] glucose for lipid biosynthesis. 19 18

The metabolic fate of [U-14C]glucose has been examined in detail in adult rat hepatocytes in primary monolayer culture, as well as in two permanent cell lines--Buffalo rat liver (BRL) and transplantable rat hepatoma (HTC) cells-derived from normal rat liver and from rat hepatoma, respectively. Under defined conditions of incubation, at a glucose concentration of 5.5 mM, the three types of cultured liver cells exhibited pronounced differences in glucose metabolism. Primary cultures, like the intact liver, differed from the cell lines in consuming relatively small amounts of glucose and converting approximately 50% of the total metabolized glucose to lactate. By contrast, the permantent cell lines consumed glucose at a 40-fold greater rate than did primary cultures, converting 80--90% of the carbohydrate to lactate. Oxidative metabolism of glucose carbon also differed among the three types of liver culture. Of the total [U-14C]glucose consumed, primary cultures converted approximately 30% to labeled CO2 per hour, whereas the liver cell lines converted 5--10%. Finally, glucose metabolism in primary culture exhibited adaptation as hepatocytes aged in culture, shifting progressively toward the pattern exhibited by the permanent cell lines. This change occurred over a time course similar to that for other kinds of functional change in hepatocytes in primary culture and thus may be relevant to the general problem of phenotypic alteration in liver cell culture.
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PMID:Glucose metabolism by adult hepatocytes in primary culture and by cell lines from rat liver. 62 33

Novikoff kepatoma microsomes catalyze the hydroxylation of benzphetamine and ethylmorphine at rates less than 1% of those of liver microsomes but catalyze the hydroxylation of p-nitroanisole and p-nitrophenetole at rates about 40% of those of liver microsomes. Benzo[a]pyrene hydroxylation is also catalyzed by Novikoff hepatoma microsomes at about 2% of the rate of liver microsomes. Like the hepatic microsomal system the rates of substrate hydroxylation by Novikoff hepatoma microsomes can be increased by pretreatment with phenobarbital/hydrocortisone or beta-naphthoflavone and inhibited by carbon monoxide, SKF-525A, and 7,8-benzoflavone. In addition, NADPH-cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) has been partially purified from Novikoff hepatoma ascites cells and some properties are described. The induction and inhibition characteristics of the Novikoff hepatoma microsomal hydroxylation activities and the isolation of a cytochrome P-450 reductase from the hepatoma are consistent with the presence of a functional mixed function oxidase system in the Novikoff hepatoma, analogous to that present in liver endoplasmic reticulum.
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PMID:Drug metabolism in the Novikoff hepatoma: evidence for a mixed function oxidase system and partial purification of cytochrome P-450 reductase. 71 41

Transplantable rat liver tumors 5123 t.c., 7288 ct.c., 5123 t.c.(H) and the Novikoff hepatoma have active mixed function oxidase systems capable of metabolizing a variety of drug and polycyclic hydrocarbon substrates. The tumor drug metabolism systems are at best 20% as active as rat liver. The tumor drug metabolism activities are induced by pretreatment with phenobarbital or beta-naphthoflavone and can be inhibited with specific inhibitors such as carbon monoxide or 7,8-benzoflavone. Tumor drug metabolism systems appear to consist of cytochrome P-450 and cytochrome P-450 reductase. The properties of the two protein components from tumors are highly similar to the corresponding components of the liver drug metabolism system. Cytochrome P-450 reductase has been at least partially purified from the Novikoff hepatoma and hepatoma 5123 t.c.(H). The kinetic and physical properties of the tumor reductases are similar to those of the liver reductase except that the Km of hepatoma 5123 t.c.(H) reductase, but not of the Novikoff hepatoma reductase for NADPH, is elevated an order of magnitude over the Km of the liver reductase. The mechanism for the interaction of electron donor and electron acceptor with liver or tumor reductases seems to be a sequential reaction mechanism. Experiments on the NADP-inhibition of the interaction of NADPH and cytochrome c with liver reductase indicate that NADP is competitive with NADPH and noncompetitive with cytochrome c. This result is consistent with the postulate of a sequential reaction for NADPH-cytochrome P-450 reductases of liver and tumors. These data support the conclusions that an active drug metabolism system is present in liver tumors and that the tumor systems are constituted like the liver system.
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PMID:The drug metabolism systems of liver and liver tumors: a comparison of activities and characteristics. 74 99

Ultrasonographic (US) angiography enhanced with intraarterial CO2 microbubbles, a contrast material used in US imaging, was performed of 103 histologically proved hepatocellular carcinomas (HCCs) smaller than 3 cm in diameter in 95 patients. The detection rate for hypervascular HCC with US angiography was compared with the rate of detection with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil. Sensitivity in detection of hypervascular HCCs with US angiography was 86% (89 of 103 HCCs), compared with 63% (44 of 70 HCCs) detected with conventional angiography, 70% (23 of 33 HCCs) with DSA, and 82% (75 of 91 HCCs) with CT with iodized oil. US angiography depicted small hypervascular HCCs, especially those less than 1 cm in diameter, and helped clarify vascularity as isovascular or hypovascular in angiographically undetectable HCCs. Findings at US angiography assisted the choice of a therapeutic strategy for treatment of HCC, such as transarterial therapy, percutaneous ethanol injection therapy, or resection.
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PMID:Small hepatocellular carcinoma: diagnosis with US angiography with intraarterial CO2 microbubbles. 130 16

Differential diagnosis of small liver tumors is important, but is not always possible, even with angiography. To solve this problem, we introduced sonographic angiography, which combines sonography and angiography. The vascular pattern of a variety of hepatic nodules was evaluated with sonographic angiography, and the results were compared with those of conventional angiography. Sonographic angiography (sonography performed during intraarterial infusion of carbon dioxide microbubbles) was performed in 184 patients with a total of 222 hepatic nodules: 139 hepatocellular carcinomas, nine adenomatous hyperplasias, seven regenerative nodules, 21 hemangiomas, 33 metastases, seven lymphomas, one granuloma, and five focal nodular hyperplasias. Sonographic angiography detected a hypervascular pattern with peripheral blood supply in cases of hepatocellular carcinoma (sensitivity, 90%; specificity, 89%). Typical vascular patterns of adenomatous hyperplasia, hemangioma, metastasis, and focal nodular hyperplasia on sonographic angiography were hypovascularity (sensitivity, 100%; specificity, 91%), spotty pooling (sensitivity, 100%; specificity, 100%), peripheral hypervascularity (sensitivity, 64%; specificity, 100%), respectively. The detectability of hypervascularity was greater with sonographic angiography than with conventional angiography in hepatocellular carcinoma, metastasis, and hemangioma. Our experience indicates that sonographic angiography depicts characteristic vascular features that reflect the vascular anatomy of specific types of hepatic tumors, and thus is useful in the differential diagnosis of these lesions.
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PMID:Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): value in differential diagnosis of hepatic tumors. 130 20

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen in animals, has been linked to tobacco-related cancers in humans. The cytochrome(s) P-450 (P-450) responsible for the metabolic activation of NNK in humans has not been identified. The present work investigated the ability of human lung and liver microsomes and 12 forms of human P-450, expressed in Hep G2 (hepatoma) cells, to metabolize NNK. Of the 12 P-450 forms, P-450 1A2 had the highest activity in catalyzing the conversion of NNK to the keto alcohol, 4-hydroxy-1-(3-pyridyl)-1-butanone. P-450s 2A6, 2B7, 2E1, 2F1, and 3A5 also had measurable activities in the formation of keto alcohol. The apparent Km and Vmax for the formation of keto alcohol in the P-450 1A2-expressed Hep G2 cell lysate were 309 microM and 55 pmol/min/mg protein, respectively. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol, a reductive product, was the major metabolite formed, whereas the formation of keto alcohol and its aldehyde and acid derivatives (all alpha-hydroxylation products) constituted approximately 1% of the initial amount of NNK in P450-expressed Hep G2 cell lysate. A similar metabolite pattern was observed with human lung or liver microsomes. In human lung microsomes, the apparent Kms for the formation of 4-hydroxy-4-(3-pyridyl)butyric acid, 4-oxo-1-(3-pyridyl)-1-butanone, NNK-N-oxide, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 526, 653, 531, and 573 microM, respectively; the formation of keto alcohol was not observed. For human lung microsomes, there was no sex-related difference in NNK metabolism. Carbon monoxide (90% atmosphere) significantly inhibited the metabolism of NNK in human lung and liver microsomes. 7,8-Benzoflavone, an inhibitor of P-450s 1A1 and 1A2, had no effect on NNK metabolism in human lung microsomes but decreased the formation of keto alcohol by 47% in human liver microsomes. Similarly, antibodies against human P-450s 1A2 and 2E1 decreased keto alcohol formation by 42% and 53%, respectively, in human liver microsomes but did not affect NNK metabolism in lung microsomes. Inhibitory antibodies against P-450s 2A1, 2C8, 2D1, or 3A4 had little or no effect on the metabolism of NNK in human liver or lung microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human lung and liver microsomes and cytochromes P-450 expressed in hepatoma cells. 131 98


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