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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In tissue culture experiments, cells derived from glioma 26, a transplantable tumor of C57B1/6 mice, were sensitive to both floxuridine (5-fluorodeoxyuridine) and 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl)phosphate, an enzyme-mediated drug activated by 5'-nucleotide phosphodiesterase. When these compounds were tested on the tumor in animals at a level of 5 mg/kg for 5 days, tumor growth was inhibited approximately 20% by both compounds. When higher levels of 5-fluorodeoxyuridine, 100 mg/kg four times weekly throughout the lifespan of the mouse, were given, the tumor, although inhibited at first, developed resistance and continued to grow until it killed the animal. Phosphodiesterase levels in the tumor rose as the tumor grew. On the other hand, thymidine kinase levels dropped as anticipated from the known 5-fluorodeoxyuridine-resistant hepatoma tissue culture data. This enzyme pattern was maintained in transplantable mouse glioma lines established from the resistant tumors. One of these lines, tested at a level of 5 mg/kg for 5 days, showed no response to 5-fluorodeoxyuridine but was still sensitive to 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl) phosphate. These experiments, therefore, offer a model system and a rationale for the design and study of more compounds that could be activated by the enzyme phosphodiesterase. Such compounds might be used alternatively when resistance to 5-fluorodeoxyuridine develops, a common clinical experience in the use of this anticancer drug.
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PMID:5'-nucleotide phosphodiesterase activity of floxuridine-resistant mouse glioma. 17 49

A series of triesters of adenosine cyclic 3',5'-phosphate was synthesized by treatment of the free acid with various diazoalkanes (R=H, CH3, C6H5,0-NO2C6H4, p-NO2C6H4, p-CH3C6H4). The resulting diastereomeric mixtures were separated into their axial and equatorial components. Hydrolysis of the compounds was examined as well as photolysis of the photolabile o-nitrobenzyl ester. All compounds were then tested for their ability to activate the cAMP-dependent protein kinase and for their ability to serve as a substrate for the cAMP phosphodiesterase showing almost no effect on either enzyme. In a biological assay the benzyl triesters were able to penetrate into C 6 rat glioma cells and to induce the typical morphological alteration of the cell shape known for high cellular levels of cAMP. It was concluded that the benzyl triesters of cAMP are useful derivatives which can be efficiently and specifically converted to the parent nucleotide. Benzyl derivatives of biologically active phosphodiesters may provide a useful tool for study in biology and pharmacology.
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PMID:Synthesis, structure, and reactivity of adenosine cyclic 3',5'-phosphate benzyl triesters. 19 57

Addition of 1 micronM 1-norepinephrine to cultures of C6TK- rat glioma cells caused a 2-fold increase in specific activity of the glial-specific enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase (nucleoside-2':3'-cyclic-phosphate 3'-nucleotidohydrolase, EC 3.1.4.16). Specific activity could also be stimulated by analogues of 3':5'-cyclic AMP, and the effect of norepinephrine could be blocked by beta-adrenergic receptor antagonists but not by alpha-adrenergic antagonists. Norepinephrine or cyclic AMP analogues also increased the specific activity of this enzyme in other clones of glioma and Schwannoma cells and in glioma X neuroblastoma cell hybrids. These results show that the stimulatory effect of norepinephrine on cyclic AMP concentrations in glioma cells leads ultimately to a stimulation of glial-specific cell funtion.
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PMID:Norepinephrine induces glial-specific enzyme activity in cultured plasma glioma cells. 20 Sep 19

The characteristics of 5'-nucleotidase in a clonal line (C6) of rat glioma cells has been examined in detail. The cells liberated 6.80 +/- 0.33 mumol of inorganic phosphate/mg of cell protein/hour, producing nearly equimolar amounts of adenosine and inorganic phosphate from AMP in the extracellular fluid. No 5'-nucleotidase was released by the cells into the medium. Most of the 5'-nucleotidase activity was found to be located in the outer surface of the plasma membrane of C6 cells and rapidly accessible to exogenous AMP, by experiments based upon differential labeling of extracellular and intracellular compartments with 32P and 33P. The ecto-enzyme was active in the absence of divalent cations. However, Mn2+ or Co2+ were somewhat stimulatory. Zn2+ suppressed activity very markedly. The relationship of enzymatic reaction velocity to pH was complex, with an optimum at pH 7.4 for all substrates tested. The ecto-5'-nucleotidase readily hydrolyzed 5'-AMP and 5'-UMP. Other 5'-nucleoside monophosphates, including 5'-deoxy-AMP, were also hydrolyzed, but more slowly; 2'- or 3'-nucleoside monophosphates were not attacked. The ecto-5'-nucleotidase in the intact cell obeyed Michaelis-Menten kinetics. Apparent Km for AMP was 0.22 mM; apparent Km values for other substrates were similar and ranged from 0.16 to 0.18 mM. ADP exerted a very powerful inhibitory effect, behaving as a competitive inhibitor, and 5'-UMP behaved as a strictly competitive substrate for 5'-AMP. ATP and ITP were inhibitory. Of these, ITP served to increase Km for AMP. ATP did likewise, but also greatly lowered Vmax. These findings indicate that the intact cell is capable of rapid hydrolysis of exogenous 5'-AMP, to produce adenosine at the cell surface at a rate which responds directly to extracellular AMP concentration but which can be suppressed by extracellular ADP or ATP.
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PMID:Ecto-5'-nucleotidase of intact cultured C6 rat glioma cells. 81 33

C-6 glioma and C-1300 neuroblastoma cells were cultured in thiamine deficient and control media. Thiamine levels, transketolase and pyruvate decarboxylase activities, and high energy phosphate metabolites were all measured in deficient and control cells. Thiamine levels in the deficient cells were found to be below the level of detectability. Pyruvate decarboxylase activity was more susceptible to thiamine deficiency in both cell lines than transketolase. In spite of the large decrease in pyruvate decarboxylase activity, high energy phosphate metabolites were not decreased in either cell line. These data indicate that C-6 glioma and C-1300 neuroblastoma cells have the capacity to maintain normal energy metabolites in the presence of large changes in thiamine levels and thiamine dependent enzyme activity.
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PMID:Glycolytic metabolism in cultured cells of the nervous system. IV. The effects of thiamine deficiency on thiamine levels, metabolites and thiamine-dependent enzymes on the C-6 glioma and C-1300 neuroblastoma cell lines. 100 96

Because increasing evidence indicates that glial cells are a target of endothelin, we have characterized endothelin-induced phosphoinositide (PI) turnover and Ca2+ homeostasis in C6 glioma cells. Endothelin-1 (ET) increased formation of 3H-inositol phosphate (IP) from PI and elicited an increase in cytosolic free Ca2+ ([Ca2+]i) in rat C6 glioma. In the presence of Li+, the increase in 3H-inositol trisphosphate formation was rapid, reaching its peak at 5 min after stimulation. ET also elicited a rapid and sustained increase in [Ca2+]i in a dose-dependent manner (1-100 nM). The rank orders of efficacy for ET-related peptides in increasing [Ca2+]i were ET = ET-2 greater than sarafotoxin greater than ET-3. Both ET-mediated stimulation of IP formation and [Ca2+]i increase were largely inhibited in the absence of external Ca2+ but unaffected by the depletion of external Na+ and the presence of dihydropyridine derivatives or verapamil. Inorganic Ca2+ channel blockers Cd2+, La3+, and Mn2+ at 1 mM inhibited both responses induced by ET. Cross-desensitization and nonadditivity were observed for both events among ET-related peptides tested, but not between ET and ATP. Pretreatment of cells with pertussis toxin (PTX) attenuated the PI response to ET, but had no effect on ET-elicited [Ca2+]i increase. ET-induced Ca2+ mobilization (measured in Ca(2+)-free medium) was only transient and was inhibited by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate. Moreover, the intracellular Ca2+ pools mobilized by ET and ATP appeared to overlap, as indicated by their partial heterologous desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological characterization of endothelin-stimulated phosphoinositide breakdown and cytosolic free Ca2+ rise in rat C6 glioma cells. 131 33

We used 31P-NMR spectroscopy to investigate the response of living C6 glioma cells to stimulation by a beta-adrenergic agonist, isoproterenol. In the presence of 3-isobutyl-1-methylxanthine, stimulation induced an accumulation of cAMP, making possible the NMR detection of the second messenger in living cells grown on microcarrier beads and perfused in the NMR tube. The cAMP signal rose to a maximum level within 20-25 min of stimulation; thereafter it decreased to the detection threshold within 60 min. At the same time, 40% increases of phosphomonoester and diphosphodiester signals were observed, whereas no significant change in phosphocreatine and nucleotide signals was detected. The kinetics of changes of the cellular content in phosphorylated metabolites were analyzed after recording 31P-NMR spectra of cell perchloric acid extracts as a function of time of stimulation. cAMP accumulation in stimulated cells was evidenced by a near linear increase of its NMR signal as a function of incubation time (from 0 to 60 min). Concomitantly with the production of cAMP, the data showed 30% decreases of phosphocreatine and ATP levels within 60 min of stimulation, and an unexpected redistribution of pyrimidine and purine nucleoside triphosphates. At the same time, levels of phosphomonoesters (phosphorylcholine and phosphorylethanolamine) and phosphodiesters (glycerophosphorylcholine and glycerophosphorylethanolamine) rose (50% increase). 13C-NMR spectra of cell perchloric acid extracts prepared after isoproterenol stimulation of cells incubated in the presence of [1-13C]glucose indicated a higher glucose content in stimulated cells, whereas the resonance of ribose C1 was diminished. Moreover, the resonances of C1 of ethanolamine and choline (and their derivatives) were increased in spectra of stimulated cells, whereas that of C3 of serine was decreased. In addition, the 13C-NMR data indicated that neither the pattern of glutamate carbon enrichment nor the glutamate/glutamine ratio was modified in stimulated cells. On the other hand, the heteronuclear coupling pattern of the lactate (methyl group) resonance in 1H-NMR spectra of cell incubation media indicated that no change occurred in the carbon flux through the pentose-phosphate shunt under stimulation. The results of this multinuclear NMR approach are discussed in terms of metabolic responses of C6 cells to beta-adrenergic stimulation and cAMP overproduction.
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PMID:Beta-adrenergic stimulation of C6 glioma cells: effects of cAMP overproduction on cellular metabolites. A multinuclear NMR study. 133 May 56

Interactions between endothelin-1 (ET)-induced phosphoinositide (PI) hydrolysis and agents that increase Ca2+ influx (i.e. A23187 and ionomycin) or induce depolarization (i.e. KCl) were investigated using C6 glioma. A23187 dose-dependently potentiated ET (30 nM)- and ATP (100 microM)-induced [3H]inositol phosphate (IP) accumulation. This potentiation was associated with an increase in the maximal stimulation elicited by both ET and ATP but their EC50 values were unchanged. This effect of A23187 occurred at concentrations that did not affect basal PI turnover; i.e. 10 nM-3 microM. Ionomycin within the range of 1 nM-1 microM also significantly enhanced ET-induced PI breakdown and this effect was associated with an increase of [Ca2+]i. KCl in a concentration-dependent manner (14.7-54.7 mM) markedly inhibited PI breakdown elicited by ET and ATP, but had much less inhibition on basal activity and no effect on A23187- and ionomycin-induced responses. In parallel, KCl added before or after ET, sharply attenuated the increase of ET-induced [Ca2+]i but did not affect basal level or ionomycin-induced [Ca2+]i response. Neither the potentiation by A23187 nor the inhibition by KCl of ET-induced PI turnover was observed in cultured cerebellar astrocytes. Our results suggest that the cell type-specific regulation by Ca2+ ionophores and KCl on ET-induced PI metabolism is closely related to perturbation of [Ca2+]i.
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PMID:Potentiation by Ca2+ ionophores and inhibition by extracellular KCl of endothelin-induced phosphoinositide turnover in C6 glioma cells. 133

Electrophysiological techniques and Xenopus oocytes were used to study the expression of neurotransmitter receptors encoded by mRNAs isolated from three human glioma cell lines. Oocytes injected with mRNAs from two glioblastoma cell lines did not show electrical responses to the various neurotransmitters tested. In contrast, oocytes injected with mRNA from an astrocytoma cell line (R-111) acquired acetylcholine and glutamate receptors as well as a small number of N-methyl-D-aspartate (NMDA) receptors. Acetylcholine elicited oscillatory Cl- currents that were abolished by muscarinic antagonists. The muscarinic receptors are coupled to the inositol phosphate-Ca2+ receptor-channel coupling system. Glutamate and its analogs kainate, quisqualate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid induced smooth currents. The non-NMDA responses were potently blocked by 6,7-dinitroquinoxaline-2,3 dione. Our results show that human astrocytoma cells contain mRNAs coding for functional acetylcholine and glutamate receptors that have properties similar to those of neurons. In contrast, human glioblastoma cells lacked those mRNAs. These differences might be useful for the development of new diagnostic and therapeutic procedures.
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PMID:mRNA coding for neurotransmitter receptors in a human astrocytoma. 134 61

The key enzymes of oxidative phosphorylation and glycolysis were evaluated histochemically in rat-implanted C6 gliomas using spot densitometry. Hexokinase, the initial enzyme for the glycolysis pathway, was 40% higher within tumour than the contralateral cerebral cortex. A similar increase within tumours for 2-deoxyglucose was observed by autoradiography. Glucose-6-phosphate dehydrogenase (G6PDH), which is the first enzyme in the pentose phosphate pathway, shunting glucose towards nucleic acid synthesis, was more than 300% higher in gliomas compared with the normal cortex. In contrast, enzymes in the energy producing tricarboxylic acid cycle (succinate-, isocitrate-, and malate-dehydrogenase) and in the electron-transport system (cytochrome c oxidase) were significantly reduced in tumour (58% less than the contralateral cortex). Lactate dehydrogenase activity, which converts pyruvate to lactate, was 50% higher within tumour. Significant reductions of enzymatic activities also occurred in non-neoplastic tissue in ipsilateral hemisphere, with larger tumours. Some enzymes showed heterogeneous activity within tumours, especially G6PDH. These results suggest that: (1) energy production is more dependent on lactate production than on oxidative phosphorylation in C6 glioma, and (2) a significant part of the increased glucose utilization in glioma cells is due to increased activity of the pentose phosphate shunt for increased DNA synthesis, and not energy production.
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PMID:Histochemical evaluation of energy metabolism in rat glioma. 136 Jun 22


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