Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted an extended clinical evaluation of localized proton magnetic resonance spectroscopy (MRS) of the brain, performed on various brain diseases using short stimulated echo times. Pathologies studied were mainly multiple sclerosis, stroke, leukoaraiosis, AIDS-related leukoencephalopathies and glial tumors. Other miscellaneous pathologies were also studied. Magnetic resonance examination of the brain was conducted on a Siemens Magnetom SP63 (equipped with a 1.5 T magnet). Localized proton MRS was performed on a routine basis immediately after imaging, using the STEAM (stimulated echo acquisition mode) with a short echo time (20 ms) combined with a CHESS (chemical shift selective excitation) sequence. One or two VOI (8 ml) were examined. Data on 125 spectra were processed by principal component analysis (PCA) and conventional variance analysis. The following metabolite resonances were studied: inositol-glycine, taurine-scyllo-inositol, choline derivatives, phosphocreatine-creatine, aspartate, glutamine glutamate, N-acetylaspartate, acetate and lactate. PCA demonstrates that the different metabolic variables are independent. The analysis of groups of spectra clearly demonstrates that the metabolic profiles detected by localized MRS in various pathologies (i) differ significantly from controls, and (ii) allow a metabolic discrimination between groups of pathologies. Results of PCA are confirmed by variance analysis. Strokes are characterized by an increase in lactate concentration and leukoaraiosis by a decrease in inositol-glycine resonance. AIDS-related leukodystrophies are characterized by increases in lactate and choline concentrations. Reduction in N-acetylaspartate which is observed in most pathologies is not significant in the small lesions of white matter. Lactate has often been found in MS plaques, but no variation in the choline/phosphocreatine ratio was observed. GABA was tentatively assigned in the spectrum of a patient with epilepsy under sodium valproate treatment. This study illustrates the clinical feasibility of the technique, the value of a multiparametric data analysis in the definition of the pertinent variables characterizing the metabolic impairment, and the impact of localized proton MR spectroscopy of the brain in the assessment of cerebral suffering.
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PMID:A multiparametric data analysis showing the potential of localized proton MR spectroscopy of the brain in the metabolic characterization of neurological diseases. 822 60

Glutamine, which is expected to be produced by C6 glioma cells, is not detected in both amino-acid analyses and 13C-NMR spectra of perchloric acid extracts of cells incubated for 4 h with [1-13C]glucose in the absence of extracellular glutamine. However, the resonances of a glutamate-linked product are observed in these spectra. The analysis of the pH dependence of chemical shifts from various glutamate-derived compounds shows that the observed resonances came from glutathione. Glutamine and glutathione signals are in close proximity on the frequency scale, leading to possible misinterpretation of the spectra.
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PMID:Glutathione, but not glutamine, is detected in 13C-NMR spectra of perchloric acid extracts from C6 glioma cells. 839 44

The question as to whether glutamine and glucose are both required for optimal growth of glioma cells is studied through the role of these substrates on the metabolism of the cells. C6 rat glioma cells grow only very slowly when glutamine is omitted from the culture medium. The rates of glucose consumption and lactate production on confluent cells in glutamine-free medium were 0.88 +/- 0.09 and 1.06 +/- 0.25 mumol/h/mg protein, respectively. In the presence of 4 mM glutamine, glucose utilization increase to 60% leading to a 45% increase of lactate production. We have studied the kinetics of enrichment of intracellular glutamate at C2, C3 and C4 positions on cells incubated with 5 mM 99% enriched [1-(13)C]glucose in the presence or the absence of glutamine in the incubation medium. The specific enrichments at metabolic steady state of all carbon positions were the same under both conditions, but we observed a significantly reduced rate of 13C incorporation in the presence of glutamine, showing an isotopic dilution of tricarboxylic acid cycle intermediates and indicating the use of this amino acid as an anaplerotic substrate. The fact that no dilution occurred at the level of pyruvate suggests strongly the lack of glutaminolysis in these cells. The main conclusion from this work is that glutamine metabolism in C6 cells appears complementary to that of glucose as far as energy production and carbon sources for the growing of the cells are concerned: glutamine is mainly utilized for anaplerosis as carbon donor to replenish the tricarboxylic acid cycle; it is not a substrate for energy metabolism. In contrast, glucose is poorly anaplerotic and is essentially used as energetic fuel by the C6 cells.
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PMID:Glucose and glutamine metabolism in C6 glioma cells studied by carbon 13 NMR. 883 46

The pharmacology of PD 144418 (1-propyl-5-(3-p-tolyl-isoxazol-5-yl)-1,2,3,6-tetrahydropyridine) was characterized using neurochemical, biochemical and behavioral techniques. For sigma (sigma 1 and sigma 2 respectively) sites, PD 144418 affinities were determined using whole guinea pig brain membranes with [3H](+)-pentazocine and neuroblastoma x glioma cell membranes using [3H]1,3,di-O-tolylguanidine (DTG) in the presence of 200 nM (+)-pentazocine. PD 144418 exhibited an affinity for sigma 1 of 0.08 nM (Ki) versus a K1 of 1377 nM for sigma 2 site. Additional receptor binding studies indicated that PD 144418 lacked affinity for dopaminergic, adrenergic, muscarinic and a variety of other receptors. In vitro studies indicated that PD 144418 reversed the N-methyl-D-aspartate (NMDA)-induced increase in cyclic GMP (cGMP) in rat cerebellar slices without affecting the basal levels, suggesting that sigma 1 sites may be important in the regulation of glutamine-induced actions. PD 144418 potentiated the decrease in 5-hydroxytryptophan caused by haloperidol in the mesolimbic region, but by itself had no effect in 5-hydroxytrypamine (5-HT) and dopamine (DA) synthesis. Behaviorally, similar to other sigma ligands, PD 144418 antagonized mescaline-induced scratching at doses that did not alter spontaneous motor activity. This action is suggestive of potential antipsychotic property. It exhibited no anxiolytic and antidepressant properties in the models used. These results show that PD 144418 is a very selective sigma 1 agent, devoid of any significant affinity for other receptors and that sigma 1 site may modulate actions in the CNS.
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PMID:The pharmacology of the novel and selective sigma ligand, PD 144418. 914 41

The induction of glutamine starvation has been suggested as a potential target for antitumoral treatment using inhibitors of amidotransferase, an enzyme which mediates the conversion of glutamate to glutamine. Using multicellular aggregates from tumor cell lines, the effect of treatment with a suggested glutamine antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of treatment response, three different parameters were measured: aggregate size, uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the carcinoid cell line BON. In this cell line the maximum effect was reached already at 10 microM concentration. DON induced marked growth inhibition in the BON aggregates which lasted 3-4 weeks after which regrowth started. During this period the secretion of chromogranin and methionine uptake was also inhibited. These studies suggest that the neuroendocrine cell line BON is especially vulnerable to treatment by DON and show that strong inhibitory effects are found at concentrations lower than that achieved in patient blood in previous clinical trials.
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PMID:Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell aggregates. 925 48

Tumorous and contralateral rat brain was examined by in vivo single voxel proton NMR spectroscopy. Magnetization transfer (MT) experiments cause attenuation of various metabolite signals. Selective saturation of immobile metabolites was achieved by pulsed RF preirradiation. The method is compared with continuous wave MT generation. In contralateral tissue, MT attenuation is detected for both the CH3 and the CH2 protons of (phospho-)creatine (Cr + PCr) and for a signal at 3.44 ppm ascribed to taurine. Significant attenuation is also observed for a signal at 3.78 ppm that is commonly ascribed to the alphaCH proton of glutamate and glutamine (Glx); however, no effect is observed for the gammaCH2 protons of Glx. Within implanted F98 glioma tumors, only the CH3 signal of Cr + PCr shows significant MT attenuation. Although the MT effect detected for lactate in the tumors fails to reach significance, a significant effect is observed for the lactate signal acquired during 3 to 9 min postmortem.
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PMID:Magnetization transfer attenuates metabolite signals in tumorous and contralateral animal brain: in vivo observations by proton NMR spectroscopy. 958 5

Pattern recognition techniques (factor analysis and neural networks) were used to investigate and classify human brain tumors based on the 1H NMR spectra of chemically extracted biopsies (n = 118). After removing information from lactate (because of variable ischemia times), unsupervised learning suggested that the spectra separated naturally into two groups: meningiomas and other tumors. Principal component analysis reduced the dimensionality of the data. A back-propagation neural network using the first 30 principal components gave 85% correct classification of meningiomas and nonmeningiomas. Simplification by vector rotation gave vectors that could be assigned to various metabolites, making it possible to use or to reject their information for neural network classification. Using scores calculated from the four rotated vectors due to creatine and glutamine gave the best classification into meningiomas and nonmeningiomas (89% correct). Classification of gliomas (n = 47) gave 62% correct within one grade. Only inositol showed a significant correlation with glioma grade.
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PMID:Pattern recognition analysis of 1H NMR spectra from perchloric acid extracts of human brain tumor biopsies. 962 10

Glutamine synthesis, the major pathway of ammonia detoxification, and the intracellular concentration of organic osmolytes in primary astrocytes and F98 glioma cells were investigated with multinuclear magnetic resonance spectroscopy. Acute exposure to ammonia (3 h incubation with NH4Cl) raised the concentration of glutamine and other amino acids, such as glutamate and aspartate, and decreased myo-inositol, hypotaurine, and taurine concentrations. The loss of these osmolytes was partially reversed by co-treatment with the glutamine synthetase inhibitor, methionine sulphoximine. Glutamate, the precursor of glutamine, is provided by stimulated anaplerotic flux via pyruvate carboxylase and glutamate dehydrogenase activity. Thus, the glutamine increase and myo-inositol decrease observed by in vivo magnetic resonance spectroscopy on patients with hepatic encephalopathy may be due to the disturbed osmoregulation in astrocytes caused by accumulation of glutamine and the subsequent loss of organic osmolytes.
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PMID:Multinuclear NMR spectroscopy studies on NH4Cl-induced metabolic alterations and detoxification processes in primary astrocytes and glioma cells. 977 80

The energetic metabolism of rat C6 glioma cells has been investigated as a function of the proliferative and differentiation states under three-dimensional (3-D) growing conditions on microcarrier beads. First, the transient deprivation of glutamine from the culture medium induced a marked decrease in the growth rate and a differentiation of C6 cells through the oligodendrocytic phenotype. Second, the respiratory capacity of the C6 cells during short-term subcultures with or without glutamine continuously declined as a function of the cell density, in part due to the mitochondrial content decrease. During the transition from the early exponential to the plateau growth phase in glutamine-containing medium, the oxygen consumption rate per single cell decreased concomitantly with a decrease in the glucose consumption and lactate production rates. This phenomenon led to a sixfold decrease in the total ATP production flux, without significantly affecting the cellular ATP/ADP ratio, thus indicating that some ATP-consuming processes were simultaneously suppressed during C6 proliferation. In glutamine-free medium, the cellular ATP/ADP ratio transiently increased due to growth arrest and to a reduced ATP turnover. Moreover, the results indicated that glutamine is not an essential respiratory substrate for rat C6 glioma under short-term glutamine deprivation. Worth noting was the high contribution of the mitochondrial oxidative phosphorylation toward the total ATP synthesis (about 80%), regardless of the proliferation or the differentiation status of the C6 cells.
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PMID:Energetic and morphological plasticity of C6 glioma cells grown on 3-D support; effect of transient glutamine deprivation. 1020 76

C6 cells were used to establish a glioma-bearing rat model by stereotaxic injection in the left caudate nucleus. The tumor status was evaluated by magnetic resonance imaging and conventional histology. The glioma-bearing rats were infused for 1 h with a [1-(13)C]glucose solution. Perchloric acid extracts of the tumor and the ipsilateral and contralateral hemispheres were analyzed by 13C-NMR spectroscopy. The 13C-labeling patterns in compounds, mainly amino acids, indicated no drastic modification of carbon metabolism in both ipsilateral and contralateral hemispheres, as compared with control rats, whereas profound metabolic differences between brain tissue and tumor were observed. Glutamine C4 enrichment was lower in the glioma than in the brain [mean +/- SD values, 5.4 +/- 2.3 (n = 5) and 15.0 +/- 0.8% (n = 10), respectively] and also lower than the glutamate C4 enrichment in the glioma (mean +/- SD value, 22.6 +/- 4.2%; n = 5), indicating that tumor glutamine was neither synthesized inside the glioma nor taken up from the surrounding brain. The glutamine C4 enrichment in the serum (6.7 +/- 0.5%; n = 10) suggested that the glioma imported glutamine from the blood, a process probably connected with angiogenesis.
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PMID:[1-(13)C]glucose metabolism in the tumoral and nontumoral cerebral tissue of a glioma-bearing rat. 1034 54


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