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)

A phosphate-buffered saline extract of normal rat liver tissue almost completely inhibited DNA synthesis in Buffalo rat Morris hepatoma 7777 cells in vitro. This effect was tissue-specific because it did not occur with extracts of kidney, spleen, heart, lung, muscle, and hepatoma. The liver extracts did not inhibit in vitro human prostate carcinoma or phytohemagglutinin-stimulated human and rat peripheral blood lymphocyte cultures. The addition of 10% fetal calf serum in the incubation medium had no effect on this inhibition. We determined that doses of liver extract that inhibit thymidine incorporation were not toxic inasmuch as treated cells remained viable, as indicated by trypan blue exclusion. The liver extract may thus contain a cell-specific mitotic inhibitor, a chalone for hepatoma cells.
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PMID:In vitro inhibition of tritiated thymidine uptake in Morris hepatoma cells by normal rat liver extract: a possible liver chalone. 20 Jul 59

A novel alkaline phosphatase differing from the so-called liver-specific isoenzyme was found in four out of twenty-four normal adult livers. Although the mobility of this enzyme was the same as that of so-called liver-specific alkaline phosphatase on the polyacrylamide gel electrophoretogram, its mobility was not altered following neuraminidase treatment, while that of the liver-specific enzyme was affected by the same treatment. Both enzymes also differed in other enzymatic and immunologic properties. The enzyme, however, resembled the so-called intestinal alkaline phosphatase in many enzymatic and immunologic properties. Thus, the inhibition patterns by amino acids, EDTA and inorganic phosphate, the pH optima, KM values for phenyl phosphate and reactivity with anti-intestinal alkaline phosphatase antibody were quite similar for both enzymes. Differences in the properties of this enzyme and intestinal alkaline phosphatase were in sensitivity to denaturation by treatment with heat and urea and to inhibition by Levamisole. The possible origin of the enzyme in normal liver and its relationship to the Kasahara isoenzyme and fetal intestine-type in hepatoma is discussed.
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PMID:A novel alkaline phosphatase, a minor component of normal liver phosphatases. 20 20

The activities of pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and glycogen synthetase (GS) were determined in the cancerous and in the apparently uninvolved (host) regions of livers from primary hepatoma patients as well as in normal adult human livers and human fetal livers. The activities of these enzymes were also assayed in a fairly fast-growing, 3'-methyl-4-dimethylaminoazobenzene-induced transplantable rat hepatoma and in hepatoma cell lines derived from both rat and human tumors. In the human hepatoma, as in the rat hepatoma, the activities of PC, PEPCK, and G6Pase were considerably reduced, compared to those in the host liver. The activities of both the a (glucose 6-phosphate-independent) and b (glucose 6-phosphate-dependent) forms of GS were also lower in human and rat hepatomas than in the respective host livers. Activities of PC, PEPCK, and G6Pase in the human hepatomas were often comparable with those of fetal livers. In rat and human hepatoma cells, the activities of PC, PEPCK, and G6Pase were similar to or lower than the activities in the respective hepatomas; the activities of GS a were also similar to those in the hepatoma, whereas the activities of GS b were somewhat higher.
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PMID:Activities of key gluconeogenic enzymes and glycogen synthase in rat and human livers, hepatomas, and hepatoma cell cultures. 20 62

High activities of L-threonine and l-serine dehydratases were maintained in spontaneous hepatoma of mice strain CBA as distinct from transplantable hepatoma. The initial rate [v] versus substrate concentration [S]0 curves had complex shapes for the enzymes from the liver tissue of healthy animals (especially after extraction of the enzymes by means of buffers with low concentration of K+). Kinetic patterns of l-threonine and L-serine dehydratases from hepatoma were distinct from those of normal mice liver tissue. The shape of [v] versus [S]0 plots was altered in response to AMP (1.10(-3) M). Contrary to the enzymes from normal tissue, dehydratases from hepatoma did not alter the shape of [v] versus [S]0 curves in response to AMP. The enzymes from hepatoma were apparently desensitized with respect to their possible allosteric effector. Threonine dehydratases of normal mice liver were also dissimilar as compared with the enzymes from hepatoma in the affinity of the apoenzyme to pyridoxal 5'-phosphate. This affinity was 3-fold lower for threonine dehydratase from hepatoma as compared with the enzyme from liver tissue.
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PMID:[Characteristics of L-threonine- and L-serine dehydratases from mouse liver and spontaneous hepatomas]. 20 90

Aspartate aminotransferase in the sera of normal subjects and of patients with hepatic diseases has been immunologically separated into two isoenzymes, cytosolic aspartate aminotransferase and mitochondrial aspartate aminotransferase. The activity of the isoenzymes was measured in three different buffer solutions with or without pyridoxal 5'-phosphate. To attain maximal activation, the apoenzyme of mitochondrial fraction must be preincubated with pyridoxal 5'-phosphate longer than that of the cytosolic fraction in either of the three reaction mixtures. In most sera the activity of both isoenzymes increased substantially in the presence of pyridoxal 5'-phosphate regardless of the type of buffer solutions. Both the apoenzymatic activity and the ratio of apo- to holo-enzymatic activity of each of the isoenzymes varied among samples from the patients with hepatic diseases. However, significantly high ratios of apo- to holo-enzymatic activity of both isoenzymes were observed in the patients with hepatoma in contrast with those with other hepatic diseases. These findings suggest that the simultaneous measurement of both apo- and holo-enzyme activities of aspartate aminotransferase isoenzymes may be useful in the clinical assessment of hepatic diseases.
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PMID:Apoenzyme of aspartate aminotransferase isozymes in serum and its diagnostic usefullness for hepatic diseases. 22 64

The nature of nuclear proteins that are soluble in 8 M urea-50 mM phosphate, pH 7.6, was compared in rat liver and Morris hepatomas, Isoelectric focusing, using carrier ampholytes for a pH gradient of 3.5 to 10, indicated that with increasing growth rate of the hepatomas there was a progressive tendency for a decrease in nonhistone nuclear proteins with isoelectric points in the range 7.5 to 8.9 and an increase in the range 5.1 to 6.7. Studies on the influence of time on the pH gradient revealed that a nonuniform drift provided a better resolution of the pH range 7.5 to 8.9 at 7 hr than at 24 hr, while the latter time for electrofocusing gave an improved resolution of the pH range 5.1 to 6.7 Polyarcylamide gel electrophoresis in a urea-acetic acid system showed that 8 M urea-50 mM phosphate; pH 7.6 extracted a small part of the histones from nuclei of both liver and hepatomas. There was less extraction of histones from the hepatoma nuclei, especially in two rapidly growing hepatomas with the most notable difference being seen in the lysine-rich H1 histone. The results suggested that in addition to qualitative or quantitative changes in nonhistone nuclear proteins in liver cancer there are alterations in the binding of histones to chromatin.
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PMID:Nuclear protein changes in rat hepatomas correlating with growth rate. 23 25

The effect of methylglyoxal and other aldehydes on several biochemical variables has been studied. Aldehydes inhibit amino acid incorporation into proteins, both in reconstituted systems and in isolated hepatocytes. They also decrease the secretion of protein and lipoprotein from hepatocytes into the incubation medium. This inhibition is seen even with prelabelled proteins, which indicates damage to the secretory mechanism itself. This conclusion is strenghened by the fact that aldehydes also decrease the binding of colchicine to liver tubulin. Aldehydes decrease the respiratory rate of mitochondria, as well as mitochondrial swelling induced by phosphate, by Ca2+ or by K+ plus valinomycin. They also partially inhibit cytochrome P-450. When injected into normal rats, aldehydes produce a decrease in the mitotic index of bone marrow cells and of the epithelial lining of the small intestine. A decrease in mitotic index and in cellularity is seen after injecting aldehydes into the peritoneal cavity of rats bearing transplanted ascites AH-130 Yoshida hepatoma. Aldehydes also impair the function of liver cell ligandin and potentiate the increase in cell permeability induced by 5-hydroxytryptamine (serotonin). The meaning of these results is discussed with special reference to the pathogenesis of cellular lesions in carbon tetrachloride poisoning.
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PMID:Biological activity of methylglyoxal and related aldehydes. 25 1

The binding of tritiated benzo(a)pyrene (BP) to liver DNA of 25 adult male rats (SIV 50) has been determined 50 h after a single intraperitoneal injection of doses between 40 ug/kg and 4 mg/kg. The dose-response relationship is linear up to 1 mg/kg, shows a sigmoid step towards 2 mg/kg and a shallow linear slope above that value. The observed binding ranges from 1.7 to 180 nmoles BP per mole DNA phosphate. The non-linearity between 1 and 2 mg/kg could be explained on the basis of an induction of metabolizing enzymes. A purely mathematical extrapolation of the tumour incidence from a carcinogenic dose (1 x 40 mg/kg for a 20% hepatoma incidence in newborn mice) to human exposure levels (about 0.1 ug/kg per day) would never have followed a step like the one found in our experiments. Our dose-effect study therefore shows how carcinogenicity data could be extrapolated in a biologically founded way to low doses.
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PMID:Extrapolation of carcinogenicity data to low doses with a dose-response study of the binding of benzo(a)pyrene to rat liver DNA. 27 32

Injection of L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) at a level of 10 mg/100 g body weight inhibited the incorporation of 3H-labeled amino acids into protein in Morris hepatomas 7777and 9618A2. The degree of inhibition was similar in cytoplasmic proteins and in histone and nonhistone nuclear protein fractions. There was no inhibitory effect on 3H-labeled amino acid incorporation in the livers of the tumor-bearing rats. The inhibitory effect of N-tosyl-L-lysine chloromethyl ketone (TLCK) on incorporation of 3H-labeled amino acids was observed in both the slowly growing hepatoma 7787 and the rapidly growing hepatoma 7777. In hepatoma 7777, TLCK (2.5 mg/100 g body wt) exerted a greater inhibitory effect on incorporation when administered 60 minutes before [3H]leucine injection than when injected simultaneously. Studies on tissue uptake of amino acids, thymidine, and phosphate indicated that inhibitory effects of TPCK and TLCK on active transport may be a major factor in the action of these drugs on macromolecular synthesis. The inhibitory effects of TPCK and TLCK seen in transplanted hepatomas and a colon tumor were not generally seen in normal tissues of the tumor-bearing rats.
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PMID:Selective effects of two chloromethyl ketones on amino acid and phosphate uptake in rat liver and tumors. 28 72

An acidic nucleolar phosphoprotein with a subunit M(r) of 70,000 was purified as an apparent dimer of 139,000 from isolated nuclei of the slime mold Physarum polycephalum. The protein was purified without the aid of strong dissociating agents after its selective phosphorylation in isolated nuclei by a polyamine-mediated reaction. Its amino acid composition resembled that of a nucleolar phosphoprotein from Novikoff hepatoma ascites cells. The phosphoprotein stimulated rRNA synthesis 5-fold by RNA polymerase I within a nucleolar, ribosomal deoxyribonucleoprotein complex isolated from nucleoli of P. polycephalum. It was also identified as a component of the complex. It bound with high affinity and specificity to the palindromic ribosomal DNA of 38 x 10(6)M(r) from P. polycephalum, which contained two coding sequences for 5.8S, 19S, and 26S rRNA. It also bound to three fragments of ribosomal DNA of M(r) 21.2 x 10(6), 17.1 x 10(6), and 8.1 x 10(6), prepared by cleavage with restriction endonucleases HindIII, PstI, and BamHI, respectively. All of these fragments included the symmetry axis of the palindromic ribosomal DNA. The phosphoprotein that had been treated with alkaline phosphataseagarose to hydrolyze the phosphate groups did not stimulate transcription and did not bind to ribosomal DNA or to the restriction fragments indicated. We have thus isolated a specific phosphoprotein with the capacity to stimulate transcription of a specific set of genes in a eukaryote. These findings suggest that this phosphoprotein may specifically regulate functions of ribosomal DNA in a manner dependent on its degree of phosphorylation.
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PMID:Polyamine-mediated phosphorylation of a nucleolar protein from Physarum polycephalum that stimulates rRNA synthesis. 28 43


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