UMLS:C0019204 - FACTA Search

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Query: UMLS:C0019204 (hepatocellular carcinoma)
71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

KOH digestion of methyl-labeled poly(A)+ mRNA purified by (dT)-cellulose chromatography produced mononucleotide and multiple peaks of a large oligonucleotide (-6 to -8 charge) when separated on the basis of charge by Pellionex-WAX high-speed liquid chromatography in 7 M urea. Heat denaturation of the RNA before application to (dT)-cellulose was required to release contaminants (mostly 18S rRNA) that persisted even after repeated binding to (dT)-cellulose at room temperature. Analysis of the purified poly(A)+ mRNA by enzyme digestion, acid hydrolysis, and a variety of chromatographic techniques has shown that the monucleotide (53%) is due entirely to N6-methyladenosine. The large oligonucleotides (47%) were found to contain 7-methylguanosine and the 2'-0-methyl derivatives of all four nucleosides. No radioactivity was found associated with the poly(A) segment. Periodate oxidation of the mRNA followed by beta elimination released only labeled 7-methylguanine consistent with a blocked 5' terminus containing an unusual 5'-5' bond. Alkaline phosphatase treatment of intact mRNA had no effect on the migration of the KOH produced oligonucleotides on Pellionex-WAX. When RNA from which 7-methylguanine was removed by beta elimination was used for the phosphatase treatment, distinct dinucleotides (NmpNp) and trinucleotides (NmpNmpNp) occurred after KOH hydrolysis and Pellionex-WAX chromatography. Thus Novikoff hepatoma poly(A)+ mRNA molecules can contain either one or two 2'-0-methylnucleotides linked by a 5'-5' bond to a terminal 7-methylguanosine and the 2'-0-methylation can occur with any of the four nucleotides. The 5' terminus may be represented by m7G5'ppp5' (Nmp)lor2Np, a general structure proposed earlier as a possible 5' terminus for all eucaryotic mRNA molecules (Rottman, F., Shatkin, A., and Perry, R. (1974), Cell 3, 197). The composition analyses indicate that there are 3.0 N6-methyladenosine residues, 1.0 7-methylguanosine residue, and 1.7 2'-0-methylnucleoside residues per average mRNA molecule.
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PMID:Characterization of Novikoff hepatoma mRNA methylation and heterogeneity in the methylated 5' terminus. 16 93

Phosphoprotein phosphatase which dephosphorylates 32P-labeled nucleolar protein substrates was found in nucleoli of Novikoff hepatoma ascites cells and normal rat liver. The activity was extracted in high yield from nucleoli with 0.01 M Bis/Tris (pH 7.0). Low ionic strength was also required for activity: the activity was only 50% of maximum in 0.075 M NaCl. Activity was affected differently by various divalent cations: MgCl2 had little effect: CaCl2, MnCl2 and CoCl2 above 4 mM inhibited the activity 30--60%; ZnCl2 above 2 mM completely destroyed the activity. EDTA had no effect, indicating that divalent cations are probably not required. The enzyme activity was enhanced 20% by 5--8 mM dithiothreitol and was inhibited 60% by 7--10 mM N-ethylmaleimide indicating a requirement for free sulfhydryl groups. The Km of the extracted enzyme for 32P-labeled nucleolar protein was 0.6 mg/ml. The phosphatase was capable of dephosporylating the major phosphorylated nucleolar proteins C23-24 and B23-24 and also histone H1. The enzyme was purified more than 200-fold on hydroxyapatite followed by DEAE-Sephadex, which resolved the activity into three major components. The activity of enzyme extracted from Novikoff hepatoma nucleoli was approximately 2.5 times greater than from normal liver nucleoli.
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PMID:Nucleolar phosphoprotein phosphatase from Novikoff hepatoma and rat liver: characterization and partial purification. 21 Aug 25

Using the simple thin layer polyacrylamide gel electrophoresis, serum alkaline phosphatase could be separated 5 isozyme bands in various digestive diseases, consisting of 54 cases of gastric cancer, 11 of colonic cancer, 12 of hepatoma, 4 of cholangioma, 14 of pancreatic cancer, 81 of benign hepatobilliary diseases, 13 of cancers of other organs and 61 of control. The obtained results were as follows: 1) The electrophoretic analysis of serum alkaline phosphatase showed the specific band remaining at the origin, already reported as "alkaline phosphatase O", in primary and metastatic cancer of the liver and cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cancerous metastasis to the liver, and it was also inclined to be positive with the progress of liver metastasis among them. 2) Intestinal alkaline phosphatase was usually found in higher frequency in blood group B and O than in the others, and it was apt to disappear in gastric or colonic cancer with an exacerbation of its cancerous lesions. 3) Heat-stable alkaline phosphatase was found in 10% of gastric or colonic cancer, all of which were histologically proved to be well differentiated adenocarcinoma.
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PMID:Serum alkaline phosphatase (Al-Pase) isozyme in gastric and colonic cancer (using a simple thin layer polyacrylamide gel electrophoresis). 21 41

Raised serum basic phosphatase was found incidentally in a woman aged 43 years. Investigation with biopsy revealed a hepatocellular adenoma. The tumour regressed after withdrawal of Neogentrol oral contraception which the patient had consumed for 17 years. The patient did not desire invasive treatment. Employment of oral contraceptive steroids for more than two years is associated with increased occurrence of hepatocellular adenomata. The hepatocellular adenoma is a clearly delimited, most frequently solitary, benign tumour with limited malignant potential but with a considerable risk of rupture with haemorrhage even after withdrawal of oral contraception. The hepatocellular adenoma has no malignant tumour vessels (in contrast to hepatocellular carcinoma) and it appears as a cold region on scintigraphy (in contrast to focal nodular hyperplasia), but the diagnosis can only be established with certainty by histological examination. The hepatocellular adenoma consists most frequently of large pale hepatocytes in trabeculae surrounded by a net of reticulin and separated by sinusoids. Biliary passage and portal spaces do not occur. The best treatment consists of excision of the tumour or embolisation. If invasive treatment is postponed, regular scanning should be performed to observe regression or progression of the tumour and oral contraception and pregnancy should be advised against on account of the risk of growth of the tumour.
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PMID:[Hepatocellular adenoma after oral contraception]. 132 98

Antineoplastic ether lipids have entered phase I clinical trial and, although their mechanism of action remains unclear, it is widely believed that the plasma membrane is the primary cellular drug target. In the present study the hypothesis was tested that metabolism of ether lipids acts as a detoxification process. [31P]-nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of the ether lipid SRI 62-834 (SRI) and the phosphate ester hexadecylphosphocholine (HPC) in the presence of both isolated phospholipases C and D and post-mitochondrial rat liver homogenate. Both SRI and HPC were slowly metabolised by phospholipase D to their alkyl phosphates and choline, and the alkyl phosphates were subsequently metabolised by phosphatase to yield the alcohols and inorganic phosphate. These studies failed to detect any metabolism of either SRI or HPC by phospholipase C, and the metabolism of platelet-activating factor (PAF) by this enzyme was not inhibited by the addition of either compound. The cytotoxicity of SRI, the related compound HPC and their metabolites was determined in vitro using three cell lines. Cytotoxicity was measured by analysis of cell growth kinetics, MTT assay and lactate dehydrogenase release. Closely similar results were obtained in the JB1 rat hepatoma cell line, in the non-transformed BL8 rat hepatocyte cell line, and in A549 human lung adenocarcinoma cells. SRI was the most toxic of the compounds analysed, the concentration required to produce 50% toxicity or growth inhibition (IC50) being 6-9 microM. The putative metabolite of SRI, 2,2'-bis(hydroxymethyl)tetrahydrofuran, and the known metabolites [2'-(octadecyloxymethyl)tetrahydrofuran-2'-yl]methyl phosphate and 2-hydroxymethyl-2-octadecyloxymethyltetrahydrofuran exhibited IC50 values of > 200, > 100 and 40-70 microM, respectively, consistent with metabolic detoxification. HPC was more cytotoxic (IC50, 37 microM) than its phosphate metabolite (IC50, 140 microM), but its toxicity was similar to that of its metabolite hexadecanol (IC50, 28 microM), suggesting that only the former metabolic route leads to detoxification.
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PMID:Is metabolism an important arbiter of anticancer activity of ether lipids? Metabolism of SRI 62-834 and hexadecylphosphocholine by [31P]-NMR spectroscopy and comparison of their cytotoxicities with those of their metabolites. 145 Dec 37

Reuber rat hepatoma cells (R-Y121B) cultured at 0.5% serum accumulated apoalkaline phosphatase in intact cells. When R-Y121B cells were cultured in the presence of bovine serum albumin, alkaline phosphatase activity increased in the cells, and the associated increase in enzyme activity differed amongst bovine serum albumin preparations. The treatment of bovine serum albumin with activated charcoal not only enhanced the effect of serum albumin on alkaline phosphatase activity, but also cancelled the differences due to different preparations of serum albumin. In contrast, no effect from serum albumin was observed in the increase of alkaline phosphatase activity in R-Y121B cell homogenates incubated at 37 degrees C. The activated-charcoal treatment of bovine serum albumin increased the amount of Zn2+ bound to the protein. When R-Y121B cells were cultured with bovine serum albumin, the concentration of Zn2+ in the cytosol fraction slightly increased. However, the effect of serum albumin on Zn2+ concentration in the cytosol fractions was independent of charcoal treatment. It was concluded that serum albumin with Zn2+ induces the activation of apoalkaline phosphatase due to Zn2+ binding.
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PMID:Activation of apoalkaline phosphatase by serum albumin with Zn2+ in rat hepatoma cells. 147 56

In this study we describe the activation of a protein kinase which phosphorylates a peptide, T669, comprising amino acids 663-681 of the epidermal growth factor receptor and containing the phosphate acceptor site Pro-Leu-Thr669-Pro. In the human epidermoid carcinoma cell line KB, T669 kinase activity in cytosolic extracts peaked (up to 15-fold compared with basal levels) 15-30 min after addition of interleukin-1 (IL-1) and closely paralleled receptor occupancy with a half-maximally effective concentration of approximately 100 pM IL-1 alpha. IL-1 treatment elevated T669 kinase activity to a variable extent in selected fibroblast lines, the hepatoma cell line HepG2, and the murine thymoma EL4 6.1. An IL-1 receptor-negative EL4 variant and the B cell lines 70Z/3, CB23, and RPMI 1788 did not respond in this way. All of the cell lines except 70Z/3 showed increased levels of T669 kinase when treated with the protein kinase C activator phorbol myristate acetate and/or with epidermal growth factor. This finding is in agreement with a previous study (Countaway, J. L., Northwood, I. C., and Davis, R. J. (1989) J. Biol. Chem. 264, 10828-10835). Activators of protein kinase A did not mimic the ability of IL-1 to stimulate T669 kinase activity, nor did the protein kinase C inhibitor staurosporine abrogate the effect of IL-1. T669 kinase activity from IL-1-stimulated KB cells was partially purified by ion exchange, hydrophobic interaction, and size exclusion chromatography. The partially purified enzyme phosphorylated myelin basic protein, a characteristic substrate of microtubule-associated protein-2 kinase (MAP-2 kinase) and the peptide Arg-Arg-Arg-(Tyr-Ser-Pro-Thr-Ser-Pro-Ser)4 from RNA polymerase II. Western blotting of chromatographic fractions revealed that T669 kinase activity corresponded with two proteins of 43 and 45 kilodaltons which cross-reacted with antibodies raised against peptide sequences of rat extracellular signal-regulated kinase-1/microtubule-associated protein-2 kinase. T669 kinase activity was critically dependent on the presence of phosphatase inhibitors. Since both the 43- and 45-kDa proteins, immunoprecipitated from [32P]phosphate-labeled cells, demonstrated a dramatic increase in their levels of serine, threonine, and tyrosine phosphorylation after brief treatment with IL-1, we conclude that IL-1 modulates the activity of these extracellular signal-regulated kinase/microtubule-associated protein-2 kinases by altering the level of their phosphorylation.
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PMID:Interleukin-1 represents a new modality for the activation of extracellular signal-regulated kinases/microtubule-associated protein-2 kinases. 165 5

We studied the effects of transfection of the normal c-Ha-ras gene, rasGly-12, and its oncogenic mutant, rasVal-12, on expression of the alpha-fetoprotein (AFP) and albumin genes in a human hepatoma cell line, HuH-7. The mutant and, to a lesser extent, the normal ras gene caused reduction of the AFP mRNA but not the albumin mRNA level in transfected HuH-7 cells. Cotransfection experiments with a rasVal-12 expression plasmid and a chloramphenicol acetyltransferase reporter gene fused to AFP regulatory sequences showed that rasVal-12 suppressed the activity of enhancer and promoter regions containing A + T-rich sequences (AT motif). In contrast, rasVal-12 did not affect the promoter activity of the albumin and human hepatitis B virus pre-S1 genes even though these promoters contain homologous A + T-rich elements. ras transfection appeared to induce phosphorylation of nuclear proteins that interact with the AFP AT motif, since gel mobility analysis revealed the formation of slow-moving complexes which was reversed by phosphatase treatment. However, similar changes in complex formation were observed with the albumin and hepatitis B surface antigen pre-S1 promoters. Therefore, this effect alone cannot explain the specific down regulation of the AFP promoter and enhancer activity. ras-mediated suppression of the AFP gene may reflect the process of developmental gene regulation in which AFP gene transcription is controlled by a G-protein-linked signal transduction cascade triggered by external growth stimuli.
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PMID:c-Ha-ras down regulates the alpha-fetoprotein gene but not the albumin gene in human hepatoma cells. 169 Aug 41

After rat liver nuclei had been treated with 10 mM dithiothreitol nuclear matrix contained 40 per cent less protein than without treatment. Protein composition did not change qualitatively. The protein with a molecular weight of 35 kD was not phosphorylated in the treated samples. After Zajdela hepatoma nuclei had been treated in the same way, nuclear-matrix contained 25% less protein. High molecular weight proteins (140, 150 and 220 kD) were solubilized by media containing dithiothreitol. After dithiothreitol treatment phosphatase and protein-phosphatase activities reduced dramatically both in rat liver and Zajdela hepatoma nuclear matrices.
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PMID:[Action of dithiothreitol on protein pattern and phosphorylation in nuclear matrix preparations isolated from the rat liver and Zajdela's hepatoma]. 189 52

The class I of the high mobility group (HMG) proteins is formed by phosphoproteins which are associated with AT-rich DNA sequences in the nucleus. Three HMGI proteins have previously been described in proliferating rodent cells (HMG Y, HMG I and HMGI-C). All three proteins exhibit microheterogeneity. The microheterogeneity of mouse HMG Y has been investigated in detail and shown to be due to phosphorylation of the protein which is sensitive to alkaline-phosphatase treatment. HMG I is similarly modified. Human cells have up to now only been found to contain HMG Y and HMG I. A search for the third protein, HMGI-C, in human cells was carried out and the protein was found in a hepatoma cell line, but not in normal or transformed T-cells. This HMGI-C protein was found to be modified by phosphorylation, part of which was found to be phosphatase insensitive. An unexpected additional finding in this study was that human cells contain two HMG17 proteins which differ in their N-terminal primary sequences.
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PMID:Comparison of multiple forms of the high mobility group I proteins in rodent and human cells. Identification of the human high mobility group I-C protein. 204 Feb 81

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