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)

Every malignant tumour examined contains aberrant tRNA methyltransferases and a few tRNAs which are absent from the normal tissue of origin. To determine whether tumour-specific tRNAs have different modifications from those in normal tissue, we purified the most frequently occurring tumour-specific isoaccepting tRNA from two malignant tissues. The isoaccepting phenylalanine tRNA from Novikoff hepatoma and Ehrlich ascites cells both contain two supernumerary methylated bases. One of these l-methylguanine, is absent from the phenylalanine tRNA of normal rat, mouse, rabbit and calf liver. An increase in the levels of 5-methylcytidine and dihydrouridine was also detected.
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PMID:Tumour-specific phenylalanine tRNA contains two supernumerary methylated bases. 20 73

1. Naturally-occurring and synthetic analogues of phenylalanine, tyrosine, histidine, arginine, proline, tryptophan and the sulphur amino acids have beeen tested in rat reticulocytes and in the Reuber H35 hepatoma for effects on protein synthesis and protein degradation and on the heat lability of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in the hepatoma cells. The experiments were designed to test whether the analogues could be incorporated into mammalian proteins and whether the resultant proteins would be degraded at an accelerated rate. 2. Several analogues, including thiazolylanine, triazolalanine and selenocystine both stimulated protein synthesis and produced labile protein in reticulocytes. Other analogues, such as dihydroxyphenylalanine, thioproline and pipecolic acid accelerated protein breakdown but probably indirectly via an inhibition of protein synthesis. Azetidine-2-carboxylic acid had the largest effect on protein breakdown in reticulocytes. 3. Labile protein was produced in hepatoma cells incubated in the presence of azetidine-2-carboxylic acid, canavanine, indospicine, triazolalanine, 2-, 3- and 4-fluorophenylalanine. These same analogues, together with 3,4-dehydroproline, beta-2-thienylalanine, dihydroxyphenylalanine, histidinol, 5- and 6-fluorotryptophan, selenocystine and selenomethionine produced heat-labile phosphoenolpyruvate carboxykinase. Enzyme induced in the presence of selenomethionine or indospicine showed the largest increases in heat lability, and for these analogues equimolar concentrations of methionine and arginine respectively were needed to nullify the enzyme abnormality. 4. The toxicity of the same naturally-occurring analogues has been discussed in terms of their ability to be incorporated into cell proteins.
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PMID:Effects of amino acid analogues on protein synthesis and degradation in isolated cells. 21 95

A girl with hereditary tyrosinemia, diagnosed at 6 months of age, was treated with a diet restricted in phenylalanine and tyrosine. At 9 1/2 years of age she developed an acutely enlarged liver and spleen, and the diagnosis of hepatocarcinoma was made. The patient received a liver transplant and tyrosine metabolites became normal while she was receiving a regular diet. Three months later, an infected thrombosis of the portal vein caused her death. Liver transplant appears to be an effective method of enzyme replacement in tyrosinemia and should be considered for prevention of hepatoma.
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PMID:Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia. 21 42

A Met-tRNAf binding factor (IF-2) from the microsomal fraction of rat liver and rat hepatoma ascites cells was partially purified by ammonium sulphate fractionation, DEAE-cellulose and phosphocellulose chromatography. The factor binds [3H]Met-tRNAf only in the presence of either GTP or GMPPCP. Maximal binding takes place at 37 degrees C and in the absence of Mg++. The factor is specific for Met-tRNAf and does not bind Phe-tRNA from rat liver or from E. coli. The ternary complex [Met-tRNAf . IF-2 . GTP1 binds to 40 S ribosomal subunits from rat liver in the absence of mRNA or poly(A, G, U) without GTP hydrolysis. GDP as well as aurintricarboxylic acid inhibit the ternary complex formation. Both factors are rapidly inactivated by N-ethylmaleimide treatment and by preincubation at 45 degrees C. Heat inactivation is partially prevented by GTP and GDP. With regard to the functional properties there are no significant differences between IF-2 from normal liver and hepatoma cells. On the other hand heat denaturation compared to the rat liver factor, which may be due to differences in contaminating proteins.
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PMID:Preparation and properties of a Met-tRNAf binding factor from rat liver and rat hepatoma. 21 43

Friend mouse erythroleukemia cells do not synthesize detectable levels of phenylalanine hydroxylase [phenylalanine 4-monooxygenase; L-phenylalanine, tetrahydropteridine:oxygen oxidoreductase (4-hydroxylating), EC 1.14.16.1] and hence are unable to grow in medium totally lacking tyrosine. These cells were fused with the cytoplasts of rat hepatoma cells that synthesize phenylalanine hydroxylase constitutively. Cytoplasmic hybrids [cybrids, Bunn, C. L., Douglas, C. W. & Eisenstadt, J. M. (1974) Proc. Natl. Acad. Sci. USA 71, 1681--1685] were selecte in medium without tyrosine. Cybrid clones expressed phenylalanine hydroxylase enzyme, which was of mouse type as determined by immunotitration and isoelectric focusing. This phenotype has been mainta ined even in the absence of any selective pressure. In contrast, in whole cell hybrids derived between the same parents, the expression of the phenylalanine hydroxylase gene was totally extinguished. One interpretation of these results is that the cytoplasm of rat hepatoma cells contain a positively acting factor(s) for the phenylalanine hydroxylase gene that brings about the activation of this gene in erythroleukemia cells.
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PMID:Epigenetic activation of phenylalanine hydroxylase in mouse erythroleukemia cells by the cytoplast of rat hepatoma cells. 29 Oct 52

A fast-moving alkaline phosphatase band on polyacrylamide gel electrophoresis has been found in 6 patients with carcinoma of the liver and gastrointestinal tract. This isoenzyme resembled the placental isoenzyme in its inhibition by L-phenylalanine, its resistance to L-homoarginine inhibition and its molecular weight. However, it differed from the placental and Regan isoenzymes in its sensitivity to L-leucine and ethylenediaminetetra-acetic acid, its lower retardation by neuraminidase, its electrophoretic mobility and its decreased heat stability. The latter two properties also distinguished it from the Nagao isoenzyme. It was identified as the Regan Variant. The Regan Variant has hitherto been reported largely in hepatocellular carcinoma. In the presented paper we report its appearance in the sera of patients who have neoplasms in a variety of primary sites in the gastrointestinal tract. It is emphasized that, while the presence of the Regan Variant in serum may be taken as evidence of carcinoma, no conclusions can be drawn as to the site of the disease.
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PMID:Regan variant alkaline phosphatase in gastrointestinal carcinoma. 65 33

Protein 35/7.7 is an abundant cytosol protein of Morris hepatoma 3924A and Novikoff hepatoma which was not found in normal liver. Protein 35/7.7 was isolated from the cytosol of Novikoff hepatoma ascites cells by ammonium sulfate precipitation and DEAE-cellulose chromatography. It migrated as a single major spot on two-dimensional isoelectric focusing-SDS polyacrylamide gels. The N-terminal hexapeptide is Val-Asx-Pro-Thr-Val-Phe and its carboxyl-terminal amino acid is phenylalanine.
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PMID:Purification and partial characterization of protein 35/7.7 a cytosol protein that is abundant in rapidly growing hepatomas. 70 6

Protein synthesis was significantly enhanced in subcellular systems containing ribosomes and cytosol from the liver of Walker tumor-bearing rats from the second week following the tumor transplantation and this enhancement persisted for the whole period of tumor growth. Homologous systems from Zajdela hepatoma and host liver showed a markedly increased poly(U)-dependent peptide elongation when compared with normal liver tissue. A stimulation of polyphenylalanine synthesis resulted from the addition of cytosols from tumors or host liver to ribosomes from normal rat liver. Similar results were found for the binding of phenylalanyl-tRNA to ribosomes. Ribosomes from tumors and host liver are more active in peptide elongation than particles from normal liver tissue. A more than 10-fold stimulation of phenylalanine polymerization resulted from the addition of poly(U) to ribosomes from Zajdela hepatoma whereas only less than 2-fold enhancement was found when using ribosomes from normal or host liver. Hepatoma ribosomes apparently contain only a low proportion of polyribosomes carrying natural message. Enhanced protein synthesis in tumors and host liver is apparently due, in particular, to an increased activity of soluble factors required for protein synthesis and less due to an increased activity of ribosomes.
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PMID:Protein synthesis in tumor host. I. Enhanced peptide elongation in transplantable tumors and host liver. 74 61

The lysosomal cysteine proteinase cathepsin B is synthesized in cultured human hepatoma HepG2 cells as an inactive 44 kDa precursor and subsequently processed to the mature single-chain enzyme with a molecular mass of 33 kDa. Intralysosomal conversion into the two-chain form results in subunits of 27 kDa, 24 kDa (heavy chain) and 5 kDa (light chain). Enzymic deglycosylation reveals that the 27 kDa polypeptide is the glycosylated variant of the carbohydrate-free 24 kDa heavy-chain form. The intracellular transport to the lysosomes is dependent upon mannose 6-phosphate-containing N-linked oligosaccharides. Receptor-mediated endocytosis of human skin-fibroblast-derived procathepsin B by HepG2 cells resulted in processed molecular forms that are not distinguishable from endogenous cathepsin B, thus favouring rather a cell-type-specific processing than structural differences due to the source of the proenzyme. The conversion step of single-chain catehpsin B into the two-chain enzyme is inhibited in vivo by the irreversible cysteine-proteinase inhibitors Z-Phe-Ala-CHN2 and, albeit weaker, Z-Phe-Phe-CHN2. Both substances have no effect on the activation of procathepsin B to the mature enzyme. The carbohydrate moiety of cathepsin B exerts no significant influence on the stability and the enzymatic activity of the enzyme.
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PMID:Proteolytic processing and glycosylation of cathepsin B. The role of the primary structure of the latent precursor and of the carbohydrate moiety for cell-type-specific molecular forms of the enzyme. 131 33

We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.
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PMID:[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. 151 41


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