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

The activity of ornithine decarboxylase (EC 4.1.1.17; L-ornithine carboxy-lyase) of C6-BU-1 glioma and N115 neuroblastoma cells increases significantly when confluent cultures are treated with compounds that increase cellular cAMP levels. These include norepinephrine or isoproterenol, and prostaglandin E1 or adenosine, which stimulate ornithine decarboxylase activity in C6-BU-1 glioma and N115 neuroblastoma cells, respectively. Ornithine decarboxylase activity is also elevated in confluent C6-BU-1 glioma cells treated with dibutyrylcAMP and theophylline, or after the glioma cells are fed with a serum-depleted medium in the presence of catecholamines and inhibitors of cyclic nucleotide phosphodiesterase. The activity of the enzyme increases 500- to 1000-fold, 2-6 hr after stationary-phase N115 neuroblastoma cells are fed with a serum-free medium, supplemented with phosphodiesterase inhibitors, adenosine, or prostaglandin E1. This stimulation is antagonized by carbamoyl choline and is blocked by actinomycin D or cycloheximide. These results suggest that the synthesis of ornithine decarboxylase of C6-BU-1 glioma and N115 neuroblastoma cells is controlled by cAMP.
 ...
PMID:Cyclic AMP-mediated induction of ornithine decarboxylase of glioma and neuroblastoma cells. 17 52

Polyamine (tissue) concentrations have been studied in hippocampus and temporal neocortex from patients with temporal lobe epilepsy. Depth electrode recordings demonstrated hippocampal origin of the seizures, the temporal neocortex being involved during the discharge propagation. Neuropathological examination of excised tissues showed glial proliferation or glioma in Ammon's horn (CA), whereas the temporal neocortex did not exhibit any histological abnormality. Polyamine (putrescine or PUT, spermidine or SPD, spermine or SPM) concentrations were determined on surgical samples from the hippocampus and various areas of temporal neocortex. Human post-mortem tissue from temporal lobe regions was used for controls. In post-mortem controls and temporal neocortex specimens from epileptic patients, polyamine levels were similar (in nmol/g wet weight: PUT = 40-100; SPD = 200-350; SPM = 100-200). In CA, polyamine levels exhibited striking changes: SPD content was significantly increased (350-700 nmol/g) while SPM was lowered (50-100). PUT was only increased in CA invaded by the tumoral process (100-180). Accordingly, a very high SPD/SPM molar ratio in the abnormal CA region was observed, indicating an acceleration of polyamine neosynthesis which is usually related to ornithine decarboxylase induction. Metabolic changes in polyamines appear to be selective of human epileptic hippocampus. A relationship between glial proliferation (gliosis or neoplasia), epileptic firing and polyamines is discussed.
 ...
PMID:Polyamine metabolism in epileptic cortex. 139 40

In cultured NG 108-15 neuroblastoma x glioma cells, opiates decreased cellular cyclic AMP and polyamine levels. This decrease was related to the inhibition of ornithine decarboxylase and cyclic AMP-dependent protein kinase activities during the acute exposure of the cells to the drugs. Growing the cells in the presence of opiates for several days led to drug addiction. In the tolerant-addicted cells, polyamine and cyclic AMP levels were close to normal values as were the activities of ornithine decarboxylase and cyclic AMP-dependent protein kinase. Removal of the opiate from 'addicted' cells, by either washing or by adding the antagonist naloxone, resulted in an increase in cyclic AMP and polyamine levels and the activities of ornithine decarboxylase and cyclic AMP-dependent protein kinase. The effect of opiates was closely related to their biological activities. Inactive enantiomorphs did not affect cyclic AMP or polyamine levels; neither did they decrease ornithine decarboxylase and cyclic AMP-dependent protein kinase activities.
 ...
PMID:Opiates and cultured neuroblastoma x glioma cells. Effect on cyclic AMP and polyamine levels and on ornithine decarboxylase and protein kinase activities. 298 99

Eflornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and mitoguazone (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase, were evaluated in a phase I-II study for patients with primary recurrent malignant brain tumors. All patients had failed prior radiation therapy and most had also failed prior chemotherapy. Two dose schedules were used, with the second schedule (Group II) a modification of the first schedule (Group I). The Group II schedule, with different dose levels, was better tolerated than the Group I schedule. Gastrointestinal and myelotoxicity were dose-limiting in most patients, and tinnitus was dose-limiting in two patients. Nineteen of 33 evaluable patients had anaplastic gliomas, in whom response was observed in 21%, stable disease in 53%, and immediate progression after one course of therapy in 26%. Of six patients with glioblastoma multiforme, two had brief stabilization of disease. An additional patient with brainstem glioma and ependymoma also had disease stabilization. Four patients with medulloblastoma, a spinal cord mixed glioma, and one with oligodendroglioma failed DFMO-MGBG. Based on this study, we believe that a combination of DFMO and MGBG is well-tolerated and deserves further evaluation for patients with anaplastic gliomas, particularly those that appear to be biologically slow growing.
 ...
PMID:Phase I-II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors. 310 81

Retinoic acid (RA) inhibited the growth and induced morphological changes in C6 rat glioma cells. The effects of RA on growth rate became apparent after 48 hr and were concentration-dependent and reversible. There was a 60% inhibition of growth using 10(-5) RA, which increased at low serum concentration to over 90% inhibition and was minimized at high concentration of serum. RA did not change the saturation density of the cells. The morphology of C6 cells, was altered from its normal pattern of randomly oriented spindle shaped cells, to cells which aligned to form palisades of fibroblast-like cells. Biochemical analysis of the cells showed no significant change in the activities of several lysosomal hydrolyses or the level of total protein in RA-treated cells compared to control cells. There was, however, a significant decrease in the activity of ornithine decarboxylase early during the treatment with RA, and an increase in the levels of fibronectin secreted into the media by the RA-treated cell. These results suggest that RA can suppress the expression of the transformed phenotype of glioma cells.
 ...
PMID:Effects of retinoic acid on expression of the transformed phenotype in C6 glioma cells. 360 Jan 88

When C6-2B rat glioma cells were stimulated with calf serum in the presence of calcium, ornithine decarboxylase activity increased maximally in 6-8 h after an initial 2-3 h lag period wherein RNA synthesis occurred. The increase of ornithine decarboxylase activity in serum-stimulated C6-2B cells was prevented by the calcium chelator EGTA, but EGTA had no effect upon RNA synthesis as judged by [3H]uridine incorporation into RNA. In addition, the calcium requirement for increased ornithine decarboxylase activity was temporally distal to the lag period. EGTA appeared to inhibit the synthesis of ornithine decarboxylase, because the half-life values of ornithine decarboxylase activity were similar (37-47 min) in the presence of EGTA or protein synthesis inhibitors such as cycloheximide or emetine. Also, calcium readdition rapidly reversed EGTA inhibition of ornithine decarboxylase activity by a mechanism which could be blocked by cycloheximide.
 ...
PMID:Dissociation of RNA synthesis from the calcium requirement for serum-increased ornithine decarboxylase activity in rat glioma cells. 643 60

Ornithine decarboxylase activity was inhibited by the antizyme inhibitor protein in extracts from C6-2B rat glioma cells. Antizyme activity in C6-2B cells was increased 3- to 10-fold by micromolar concentrations of putrescine, spermidine and spermine. The calcium chelator EGTA (pCa 6.4) inhibited basal and polyamine-stimulated antizyme activity, and this inhibition was prevented by concurrent incubation with calcium, but not with magnesium. EGTA appeared to block antizyme synthesis, because the half-life values of antizyme activity in the presence of EGTA or cycloheximide were similar (121-143 min). Also, calcium readdition rapidly reversed EGTA inhibition of antizyme activity by a mechanism which could be blocked by cycloheximide. The ability of EGTA to inhibit spermidine-stimulated antizyme activity was not due to reduced spermidine uptake, because EGTA actually stimulated [3H]spermidine accumulation in the trichloroacetic acid-soluble fraction of C6-2B cells after 3 h.
 ...
PMID:Calcium dependence for increased antizyme inhibitory activity of ornithine decarboxylase in rat glioma cells. 643 61

The activity of ornithine decarboxylase (EC 4.1.1.17) increased in confluent cultures of glioma C6BU-1 cells 3 h after adding a complete serum-containing medium, and was maximal 5 h later. The activity of S-adenoxyl-L-methionine decarboxylase (EC 4.1.1.50) increased soon after addition of the complete medium to the cells, and reached its peak after 11 h. The activity of diamine oxidase (EC 1.4.3.6) also increased soon after adding complete medium and was maximal 8h later, when the activity of ornithine decarboxylase reached its peak. The increase in the activity of S-adenosyl-L-methionine decarboxylase was accompanied by changes in cellular spermidine and spermine concentrations, whereas the increase in the activity of diamine oxidase was followed by the accumulation of gamma-aminobutyric acid, which was detected both in the cells and in the medium. Asparagine enhanced the utilization of radioactive putrescine by glioma cells suspended in buffered-salt/glucose solution and increased intracellular and extracellular gamma-aminobutyric acid concentrations. Radioactive putrescine was converted into spermidine and spermine by glioma cells after addition of a serum-containing medium, but not after adding buffered--salt/glucose solutions, in the presence or absence of asparagine. The kinetics of ornithine decarboxylase 'induction' and the half-life of the enzyme differed in cells incubated with buffered asparagine solutions and serum-containing media.
 ...
PMID:Metabolism of polyamines by cultured glioma cells. Effect of asparagine on gamma-aminobutyric acid concentrations. 677 65

alpha-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, was used alone and in combination with various single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to treat animals bearing murine glioma 26 and rat 9L gliosarcoma intracerebral tumors. Used as a single agent, DFMO has little or no effect against these tumors. However, in both intracerebral tumor models, pretreatment with DFMO p.o. before i.p. administration of BCNU potentiates the effect of BCNU without increasing toxicity. The effects of DFMO administered p.o. after BCNU or before and after various doses of BCNU indicate that DFMO may also effectively slow the repopulation of these tumors after BCNU therapy.
 ...
PMID:Potentiation of the antitumor therapeutic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor. 679 58

Isogabaculine (3-amino-1,3-cyclohexadienyl carboxylic acid; RMI 71,932), an irreversible inhibitor of GABA transaminase, when added to mouse neuroblastoma cells in spinner culture at the time of induction of cell proliferation, increased ornithine decarboxylase (ODC) activity threefold above that of normal control cells and twofold above that of GABA (gamma-aminobutyric acid)-treated cells. Isogabaculine did not affect ODC activity of rat glioma (C6) or rat hepatoma (HTC) cells. As determined by half-life measurements of ODC and intracellular GABA concentrations, isogabaculine apparently has a direct stabilizing effect on ODC in neuroblastoma cells that is unrelated to the accumulation of GABA due to GABA transaminase inhibition. Putrescine metabolism to GABA or spermidine was determined in C6, HTC, and neuroblastoma cells in the presence or absence of isogabaculine and/or GABA. Neither GABA nor isogabaculine treatment dramatically altered the metabolism of putrescine to GABA or spermidine in neuroblastoma, C6 glioma, or HTC cells. However, the appreciable amount of labeled GABA formed from putrescine indicated that this metabolic route may be more important than was previously thought.
 ...
PMID:Effect of GABA and isogabaculine on ornithine decarboxylase and putrescine metabolism. 709 60


1 2 3 Next >>