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)

The binding of [3H]acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor, to soluble and particulate forms of CA was investigated. Sources for the assays were purified CA II, adult rat cortical, oligodendrocyte and neuronal enriched preparations; cultured murine glial cells, rat C-6 glioma, rat hepatoma and human glioblastoma cells. CA enzyme activity in the same preparations was also assayed by following change in pH during incubation. A gel permeation chromatographic method was developed to assess [3H]AZ binding to soluble CA, while glass fiber filter vacuum filtration was used for particulate CA binding. Saturable specific binding of [3H]AZ to rat cortical soluble and particulate CA preparations was demonstrated. Computer-assisted data analysis estimated the binding parameters of [3H]AZ to soluble rat cortical CA to be Bmax = 0.38 +/- 0.13 pmol/mg protein and Kd = 34.7 +/- 17.5 nM. The rat cortical particulate fraction Bmax was 2.05 +/- 0.28 pmol/mg protein with a Kd of 107.1 +/- 24.2 nM. Purified bovine CA-II bound 1.15 +/- 0.19 pmol [3H]AZ/mg protein with a Kd of 54.0 +/- 3.4 nM. The pH optima for [3H]AZ binding to soluble and particulate CA was between 6.5 and 7.5. Binding was linear with respect to protein up to 1.0 mg/mL. The particulate fraction bound 3-4 times more [3H]ligand per unit protein than the soluble fraction. Interestingly, no detectable CA enzyme activity or [3H]AZ binding was observed in the soluble or particulate fractions of human glioblastoma, rat C-6 glioma or rat hepatoma cells. Binding of [3H]AZ to other soluble enzymes or proteins was negligible. In competition binding experiments, a rank order of inhibition of [3H]AZ binding to rat cortical CA by established CA inhibitors was: dichlorphenamide greater than acetazolamide greater than or equal to benzolamide greater than methazolamide greater than hydrochlorothiazide greater than or equal to sulfanilamide. [3H]AZ binding was not affected by other classes of pharmacologic characterizing agents. The binding of [3H]AZ to the CA enzyme molecule is highly specific and sensitive and may prove useful in vitro or in situ as a probe for this enzyme.
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PMID:[3H]acetazolamide binding to carbonic anhydrase in normal and transformed cells. 190 Dec 9

The effects of Clostridium botulinum C3 ADP-ribosyltransferase and of Clostridium botulinum C2 toxin were studied on the cytoskeleton of rat hepatoma FAO and human glioma U333 cells. After treatment of these cells for 24 to 48 h with C3 (3-30 micrograms/ml), the actin microfilaments disappeared, and the intermediate filament network was found to collapse, while microtubules remained intact. Similar alterations of the cytoskeletal filaments without affecting microtubules were induced by the actin-ADP-ribosylating C2 toxin. In FAO cells, C3 caused the rounding up of cells. Concomitantly, cytosolic 22 to 24 kDa proteins were ADP-ribosylated in a guanine nucleotide-dependent manner. Rounding up of cells and ADP-ribosylation of proteins in intact cells were observed at similar concentration of the transferase. These data suggest a role of the protein substrates of C3 in the regulation of the cytoskeletal integrity.
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PMID:Alteration of the cytoskeleton of mammalian cells cultured in vitro by Clostridium botulinum C2 toxin and C3 ADP-ribosyltransferase. 190 79

Transferrin (TF), a major plasma protein, binds and transports ferric iron. Evidence exists for unique roles for TF in brain in oligodendrocyte differentiation, myelination and neuronal development. In this study, 5' flanking regions of the TF gene important in regulating gene expression were identified by transfected cell studies and a comparison of 5' flanking sequences of the human TF and TF receptor genes. Human glioma cell lines HTB-16 and HTB-17 were shown to synthesize TF identical in size and immunological reaction to TF synthesized by liver. The expression of a series of human chimeric TF genes in glioma cells was compared with hepatoma and HeLa cells. A difference in transient expression was observed in hepatoma and glioma cells transfected with TF chimeric genes containing 3.9 kb of the 5' region; hepatoma cells demonstrated significantly more expression than did glioma cells, suggesting that a DNA region present in the 3.9-kb construct is important either in liver-specific expression or in repression of brain expression, or in both. Smaller constructs containing less than or equal to 0.622 kb of the 5' regulatory region of the TF gene failed to demonstrate cell-specific expression; they were expressed in HeLa cells, a line that does not synthesize TF. High levels of expression of 0.15-kb TF constructs were also observed in hepatoma and glioma cell lines, but not in transgenic mice. Possible explanations of differences observed in expression of shorter TF constructs in vitro and in vivo are discussed.
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PMID:Expression of chimeric human transferrin genes in vitro. 207 22

Glutamate dehydrogenase (GDH) was purified to homogeneity from cerebellar tissue of three normal subjects and seven patients with four distinct types of degenerative neurological disorders. Nonequilibrium pH gradient gel electrophoresis showed that the purified enzyme consists of four major isoproteins designated GDH 1, 2, 3, and 4. With one exception, the relative abundance and isoelectric points of the GDH isoproteins decrease and the molecular weights increase progressively going from isoprotein 1 to isoprotein 4. The enzyme isolated from the brain of one patient with a variant form of multiple system atrophy displayed marked reduction of GDH isoprotein 1. The Km values of the patients' GDH for alpha-ketoglutarate, glutamate, NADH, and NADPH were significantly increased as compared to GDH obtained from normal and neurologic control subjects. In addition, glutamate levels were reduced markedly in the patient's cerebellum. Pulse-chase studies have shown that both the human hepatoma HepG2 and the human glioma U373 cell lines synthesize exclusively GDH isoprotein 2. The different GDH isoproteins do not have a precursor-product relationship and may represent products of different GDH mRNA species.
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PMID:Characterization of glutamate dehydrogenase isoproteins purified from the cerebellum of normal subjects and patients with degenerative neurological disorders, and from human neoplastic cell lines. 257 5

A monocyte chemotactic activity was found to be released by various types of cultured human cells after appropriate stimulation: normal diploid fibroblasts, peripheral blood mononuclear cells or monocytes isolated therefrom, and a number of tumor cell lines, including osteosarcoma (MG-63) and hepatoma (Malavu) but not melanoma (Bowes) cells. Cultures of diploid human fibroblasts and these tumor cells stimulated with interleukin (IL) 1 or double-stranded RNA [poly(rI).poly(rC)], or infected with viruses (measles or rubella viruses) were found to produce chemotactic activity for both monocytes and granulocytes. Media collected from fibroblasts treated with E. coli or IL 6 did not contain such activity. Granulocyte and monocyte chemotactic activities were serologically distinct, and could be separated by successive chromatographical procedures. While the granulocyte chemotactic activity of both fibroblasts and MG-63 cells had previously been identified as granulocyte chemotactic protein/IL 8, the monocyte chemotactic activity from MG-63 cells was identified by amino acid sequence analysis as a different protein recently described to be released by human glioma and myelomonocytic cell lines. In view of the similarity in their chromatographical behavior, monocyte chemotactic activities from fibroblasts, MG-63 cells and fresh monocytes can probably be assigned to identical molecules. Cultures of unfractionated peripheral blood cells, however, were found to release an additional monocyte chemotactic protein, identifiable by amino acid sequence analysis as platelet factor 4.
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PMID:Identification by sequence analysis of chemotactic factors for monocytes produced by normal and transformed cells stimulated with virus, double-stranded RNA or cytokine. 269 Dec 59

Treatment of mouse hepatoma (Hepa) cells with heme or cadmium chloride in serum-free medium causes a rapid increase in the steady-state level of heme oxygenase (HO) messenger RNA. This increase is both dose- and time-dependent. Maximum accumulation of HO mRNA is observed 3 h after addition of either agent. Treatment of Hepa cells with heme or CdCl2 also stimulates the transcription of the HO gene, as judged by in vitro nuclear transcription run-on assays. The maximum rate of HO gene transcription occurs 2 h after treatment with either agent. Comparison of the relative increase in the rate of HO gene transcription with the relative increase in the level of HO mRNA demonstrates that transcriptional activation is the primary mechanism by which heme and cadmium produce the accumulation of HO mRNA in Hepa cells. Cadmium may also influence other processes involved in the expression of HO, since the time course of mRNA accumulation diverges from that of gene transcription. However, neither heme nor cadmium alters the rate of HO mRNA degradation. Cobalt chloride and heat shock, which are potent inducers of HO mRNA in rat liver and rat C6 glioma cells, respectively, have only a small effect on the level of HO mRNA in mouse hepatoma cells.
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PMID:Transcriptional activation of the heme oxygenase gene by heme and cadmium in mouse hepatoma cells. 270 93

Preproenkephalin A (PPA) mRNA expression was studied by Northern blot and in situ hybridization in cell lines (rat glioma C6, rat hepatoma HTC, human neuroblastoma IMR32, mouse neuroblastoma NS20Y, rat fibroblast FR3T3, human bladder carcinoma EJ, human vulva carcinoma A431, myelocytic leukemia HL60, rat adrenal carcinoma Y1) and in brain tumours (implanted C6 cells). C6 glioma in cell culture, as well as in brain tumours, expressed high levels of PPA mRNA as compared to the caudate nucleus of the rat brain. EJ and FR3T3 cell lines also expressed the PPA mRNA, which was not detectable in A431, Y1, NS20Y, IMR32, HTC, HL60 cell lines as well as in the rat liver. This observation provides an interesting model to study the mechanisms by which the malignant transformation can induce in glial cells the derepression of a gene which is usually expressed in neurons or in neuron-like cells.
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PMID:Expression of the preproenkephalin A gene in tumor cells and brain glioma: a northern and in situ hybridization study. 273 83

The feasibility of 2-deoxy-2-[18F]fluoro-D-galactose ([ 18F]FdGal) for imaging galactose metabolism in tumors with positron emission tomography (PET), was investigated using two hepatomas, Yoshida sarcoma, or glioma in rats, and mouse mammary carcinoma. In hepatoma-bearing rats the highest uptake of [18F]FdGal was observed in the liver followed by the kidney and tumor. The tumor uptake increased with time, and the high uptake ratios of tumor to organ were observed except for the liver and kidney. Tumor uptake was also measured in all tumors. As main metabolites in all tumors, [18F]FdGal 1-phosphate and UDP-[18F]FdGal were found by HPLC. Two hepatomas showed a slightly higher uptake and a larger percentage of UDP derivative than the other three tumors. By autoradiography the brain tumor was visualized clearly. These results indicate that [18F]FdGal has potential as a tracer for imaging galactose metabolism in tumors with PET.
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PMID:2-Deoxy-2-[18F]fluoro-D-galactose as an in vivo tracer for imaging galactose metabolism in tumors with positron emission tomography. 278 12

The hormone-responsive enzymes tyrosine aminotransferase and glycerol-3-phosphate dehydrogenase were studied with respect to current models of the mechanism of glucocorticoid/cAMP interaction during the induction of enzyme activity in responsive cell hybrids between rat C6 glioma cells and rat FU5AH hepatoma cells. The results of experiments involving protein and mRNA synthesis inhibitors, sequential addition of inducers, and the assay of cyclic-AMP-dependent protein kinase could not be adequately explained by any one model of inducer interaction. Comparison of the hybrid clones revealed the presence of factors that may modify induction but that are not essential for synergistic induction.
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PMID:The synergistic interaction of hydrocortisone and dibutyryl cyclic AMP during enzyme induction in hybrids between rat C6 glioma cells and FU5AH hepatoma cells. 286 87

The growth stimulating properties of bovine serum and colostrum were compared in rat hepatoma (HTC) and glioma (C6) cell cultures. A colostrum concentration of 2% was optimal for HTC cells, which then reached a terminal density 40% of that in serum-supplemented medium. The corresponding figures for C6 cells were 10 and 81%, respectively. After 4 d in culture, levels of lipid hydroperoxides were measured and compared. Highest levels of lipid hydroperoxides were found in HTC and C6 cells grown in unsupplemented medium. HTC and C6 cells grown in serum supplemented medium contained levels of 52 and 64%, respectively, of that in unsupplemented medium. The corresponding levels for cells grown in presence of colostrum were 40% for HTC and 44% for C6 cells. To obtain information on any functional alterations in the cells due to the presence of colostrum the induction of tyrosine aminotransferase (EC 2.6.1.5) and glutamine synthetase (EC 6.3.1.2) by dexamethasone was studied. Although colostrum seemed to increase the basal activities of the enzymes, no significant effects on the degree of induction could be detected.
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PMID:Lipid peroxidation and activities of tyrosine aminotransferase and glutamine synthetase in hepatoma and glioma cells grown in bovine colostrum-supplemented medium. 287 99


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