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)

Experimental brain tumours were produced in adult cats by stereotactic xenotransplantation of the rat glioma clone F98. Regional ATP, glucose and lactate were measured after 2-4 weeks on coronal cryostat sections by substrate-induced bioluminescence, potassium content was imaged by the histochemical sodium cobaltinitrite method, and regional pH by incubating cryostat sections with the fluorescent pH-indicator umbelliferone. The regional biochemical alterations were correlated with magnetic resonance imaging and tissue water content. Biochemical changes were heterogeneous in tumours but exhibited a rather uniform pattern in peritumoural oedema. ATP was consistently reduced, glucose and lactate were increased and pH was more alkaline than in normal white matter. The decrease of ATP matched the increase of water, indicating that ATP decline represents fractional dilution in the oedematous tissue rather than break-down of energy metabolism. The increased lactate levels, therefore, may originate from the tumour and not from a metabolic disturbance in the peritumoural oedematous tissue. The implications of this interpretation for the pathogenesis of peritumoural oedema are discussed.
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PMID:Experimental transplantation gliomas in the adult cat brain. 3. Regional biochemistry. 275 53

Effects of cellular energy metabolism on the radiation response of a cell derived from a human cerebral glioma have been studied under conditions of energy limitation produced by the presence of inhibitors of respiratory metabolism (KCN) and glycolysis (glucose analogues such as 2-DG, 5-TG, and 3-0-MG). Radiation 60Co induced DNA repair (Unscheduled DNA Synthesis) and micronuclei formation were studied as measures of radiation response. Glycolysis (lactate production) and levels of adenine and related nucleotides (UTP, GTP, ATP etc.) were measured as parameters of energy metabolism. Two 2-DG (5 mM) inhibited DNA repair and increased micronuclei frequency both in the presence and absence of respiration (KCN, 2 mM). Under similar experimental conditions, the presence of 2-DG also significantly reduced the cellular energy status. Five-TG and 3-0-MG on the other hand, neither significantly altered the energy status (sigma XTP) nor influenced the radiation response under respiratory proficient conditions. The results can be explained on the basis of a model postulating differential energy linked modulations of the repair and fixation processes acting on DNA lesions. Implications of the present results for the radiotherapy of brain tumors are discussed.
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PMID:Energy linked modifications of the radiation response in a human cerebral glioma cell line. 280 36

The enzymes of glycolysis and selected enzymes of the pentose phosphate pathways were measured by fluorometric methods in extracts prepared from cultures of normal cortical human astrocytes and from cultures derived from low-grade (II) or high-grade (IV) gliomas. The hexokinase and phosphofructokinase levels of the low-grade glioma-derived line were not significantly different from those of the normal astrocyte cultures. However, the activities of hexokinase and phosphofructokinase were consistently and significantly increased in the high-grade glioma-derived lines. The activity of glucose-6-phosphate dehydrogenase was significantly decreased in all glioma-derived lines and by more than 90% in the high-grade-derived lines. Other enzymes of the glycolytic pathway were not significantly different from those of normal astrocytes, or they showed a variation inconsistently related to the neoplastic state. Glucose flux is not apparently regulated to a significant degree of hexokinase in glioma-derived lines, since the measured Vmax values are in substantial excess over the measured flux rates. Reversible binding of hexokinase to the particulate fraction was observed in both the normal astrocytes cultures and the high-grade glioma-derived lines. A twofold displacement of particulate hexokinase by ATP, ADP, 1-O-methylglucose, sorbitol-6-phosphate, and dibutyryl cyclic AMP was observed in the high-grade glioma-derived lines. The degree of displacement by various agents and the basal ratio of free/bound was not significantly different between the transformers and the nontransformants. The hexokinase from both the gliomas and the normal astrocytes was noncompetitively inhibited by the glucose analogue 2-deoxy-d-glucose. Phosphofructokinase activity is close to the observed glucose flux rates in both the normal astrocyte and the glioma-derived cultures. The phosphofructokinase activity of normal astrocytes is activated twofold or more by ADP, AMP, fructose-2,6-diphosphate, and Pi. However, these same ligands activate phosphofructokinase by less than twofold in a typical high-grade glioma-derived line. ATP, dibutyryl cyclic AMP, and citrate inhibit glioma and normal astrocytic phosphofructokinase, but the magnitude of the inhibition is much less than in the glioma-derived lines.
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PMID:Enzymes of glucose metabolism in cultured human gliomas: neoplasia is accompanied by altered hexokinase, phosphofructokinase, and glucose-6-phosphate dehydrogenase levels. 297 16

Activation of muscarinic cholinergic receptors of 1321N1 human astrocytoma cells attenuates cyclic AMP accumulation. This effect results from an activation of phosphodiesterase with no direct inhibition of adenylate cyclase activity. In spite of this lack of coupling of muscarinic receptors to adenylate cyclase, guanine nucleotides reduce the apparent binding affinity of the agonist carbachol in a washed membrane preparation of 1321N1 cells. The order of potency for this effect is guanosine 5'-O-(3-thiotriphosphate) greater than 5'-guanylyl-imidodiphosphate = GTP = GDP; ATP has no effect. The occurrence of a Mr = 41,000 protein labeled in the presence of [32P]NAD and pertussis toxin as well as the occurrence of guanine nucleotide-mediated inhibition of forskolin-stimulated adenylate cyclase activity indicate that the functional inhibitory guanine nucleotide regulatory component of adenylate cyclase (Ni) is present in 1321N1 cells. Pertussis toxin pretreatment of NG108-15 neuroblastoma X glioma cells, which express muscarinic receptors that link through Ni to inhibit adenylate cyclase, blocked the GTP-sensitive, high affinity binding of carbachol. In contrast, pretreatment of 1321N1 cells with a concentration of pertussis toxin that blocked [32P]ADP ribosylation of the Mr = 41,000 substrate and GTP-mediated inhibition of forskolin-stimulated adenylate cyclase activity had no effect on GTP-sensitive high affinity binding of carbachol. These results suggest that muscarinic cholinergic receptors of 1321N1 cells couple to a guanine nucleotide regulatory protein that is distinct from Ni.
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PMID:Guanine nucleotide-sensitive, high affinity binding of carbachol to muscarinic cholinergic receptors of 1321N1 astrocytoma cells is insensitive to pertussis toxin. 298

When membranes from neuroblastoma X glioma NG108-15 hybrid cells were incubated in a cell-free system with opioid agonists, a time-, temperature-, and dose-dependent desensitization to opioid inhibition of adenylate cyclase activity was observed. The composition of the system during the incubation was manipulated to elucidate the biochemical mechanisms of desensitization. Receptor coupling appeared to be a prerequisite for desensitization, because both magnesium and sodium, which are necessary for coupling, were required for desensitization. Removal of ATP and addition of cyclic AMP or cyclic GMP had no effect on desensitization.
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PMID:Cell-free desensitization of opioid inhibition of adenylate cyclase in neuroblastoma X glioma NG108-15 hybrid cell membranes. 301 85

Incubation of membranes of neuroblastoma x glioma hybrid, NG108-15 cells with GDP beta S followed by immunoblotting of resolved membrane and supernatant fractions with specific anti-peptide antisera showed essentially all of the alpha subunit of Go to be associated with the membrane. Similar experiments with poorly hydrolyzed analogues of GTP caused release of a significant fraction (some 50% within 60 minutes) of Go alpha into the supernatant. This was not mimicked by analogues of ATP. Antisera directed against peptides corresponding to the extreme N and C-termini of GO alpha demonstrated that the released polypeptide was not proteolytically clipped. These experiments show that the alpha subunit of GO need not be invariably bound to the plasma membrane and that guanine nucleotide activation can release the alpha subunit of GO from its site of membrane attachment.
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PMID:GTP analogues cause release of the alpha subunit of the GTP binding protein, GO, from the plasma membrane of NG108-15 cells. 312 78

The major pertussis-toxin-sensitive guanine nucleotide-binding protein of rat glioma C6 BU1 cells corresponded immunologically to Gi2. Antibodies which recognize the alpha subunit of this protein indicated that it has an apparent molecular mass of 40 kDa and a pI of 5.7. Incubation of membranes of these cells with guanosine 5'-[beta gamma-imido]triphosphate, or other analogues of GTP, caused release of this polypeptide from the membrane in a time-dependent manner. Analogues of GDP or of ATP did not mimic this effect. The GTP analogues similarly caused release of the alpha subunit of Gi2 from membranes of C6 cells in which this G-protein had been inactivated by pretreatment with pertussis toxin. The beta subunit was not released from the membrane under any of these conditions, indicating that the release process was a specific response to the dissociation of the G-protein after binding of the GTP analogue. Similar nucleotide profiles for release of the alpha subunits of forms of Gi were noted for membranes of both the neuroblastoma x glioma hybrid cell line NG108-15 and of human platelets. These data provide evidence that: (1) pertussis-toxin-sensitive G-proteins, in native membranes, do indeed dissociate into alpha and beta gamma subunits upon activation; (2) the alpha subunit of 'Gi-like' proteins need not always remain in intimate association with the plasma membrane; and (3) the alpha subunit of Gi2 can still dissociate from the beta/gamma subunits after pertussis-toxin-catalysed ADP-ribosylation.
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PMID:GTP analogues promote release of the alpha subunit of the guanine nucleotide binding protein, Gi2, from membranes of rat glioma C6 BU1 cells. 314 Aug 1

The in vivo high-energy phosphorus metabolic profile and pH of an experimental intracerebral C6 glioma in rats was examined using surface coil 31P NMR spectroscopy. Initially, phosphorus-containing metabolites of the glioma were characterized by in vivo 31P surface coil spectroscopy of subcutaneously implanted tumors and by high-resolution NMR studies of perchloric acid (PCA) extracts of both freeze-clamped subcutaneous tumor tissue and cultured cells. These studies demonstrated that the C6 glioma has reduced levels of phosphocreatine (PCr) compared to the levels found in normal rat brain. Thus, reduced spectral PCr levels were useful as a metabolic indicator for monitoring the spatial selectivity of tumor metabolism distinct from that of adjacent normal brain tissue. To maximize 31P NMR signals from intracerebral tumors, tumor cells were stereotaxically placed superficially in the brain. Proton magnetic resonance imaging (1H MRI) was used to determine the size and location of the resultant brain tumors in order to preselect rats with large superficial tumors for spectroscopic study. 31P NMR spectra of the glioma tumors revealed a consistent reduction in the PCr/ATP ratio, an increase in the Pi/ATP ratio, and a slightly increased tissue pH. No correlation was found between levels of Pi/ATP and tumor pH in subcutaneous or intracerebral gliomas and the amount of necrosis as determined histologically. This study demonstrates that phosphorus metabolites of an experimental brain tumor in the rat can be monitored in vivo with minimal contributions from adjacent normal brain tissue metabolites using surface coil 31P NMR spectroscopy.
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PMID:31P NMR spectroscopy of the in vivo metabolism of an intracerebral glioma in the rat. 338 2

The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by fluorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I-III gliomas had a glucose consumption rate of 2-3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by 18F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measured in situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the glioma-derived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomas in situ and (2) are significantly altered in several aspects of their glycolytic metabolism.
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PMID:Glucose metabolism in human gliomas: correspondence of in situ and in vitro metabolic rates and altered energy metabolism. 350 47

Positron emission computed tomographic (PECT) scanning studies have demonstrated that high grade gliomas exhibit increased 2-[18F]fluoro-2-deoxyglucose (18FDG) uptake compared to cerebral white matter and low grade gliomas. Hexokinase catalyzes the phosphorylation of glucose, as well as 18FDG and 2-deoxyglucose (2DG), thereby "trapping" these slowly metabolized analogues intracellularly. We hypothesize that a similar hexokinase-mediated uptake of glucose and glucose analogues occurs in vitro. Hexokinase activity was assayed in homogenates of tissue-cultured lines derived from high (IV) and low (II) grade gliomas and in fibroblasts derived from skin. With glucose as substrate, the maximal activity (Vmax) in the Grade IV lines was 200% of the activity found in the Grade II line, fibroblasts, and astrocytes; however, the Michaelis substrate affinity constant (Km) bore no relationship to tumor grade. With 2DG as substrate, the Vmax of all cell lines decreased, but the Grade IV lines still tended to have greater activity than the others. The Km values for 2DG were 5 times higher than those for glucose. Hexokinase is found in two subcellular compartments: an active form reversibly bound to mitochondria and a less active, cytosolic form. Up to 20% of the total hexokinase was found in the cytosol in all lines tested. High energy phosphate compounds (ATP, ADP, CTP, and others) displaced mitochondria-bound hexokinase, which increased the cytosolic form by 2-fold in the glioma lines, but fibroblast hexokinase distribution was unaffected. Our results suggest that: (a) high grade gliomas have increased hexokinase activity, which may explain the grade-related differences in 18FDG uptake observed by PECT scanning, and (b) human glioma hexokinases may be regulated by reversible subcellular compartmentation.
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PMID:Regulation of hexokinase in cultured gliomas. 387 50


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