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)

Primary astrocyte cultures, C6 glioma cells, and N18 neuroblastoma cells were assayed for nitric oxide synthase (NOS) activity with a bioassay of cyclic GMP production in RFL-6 fibroblasts. Treatment of astrocyte cultures for 16-18 h with lipopolysaccharide (LPS) induced NOS-like activity that was L-arginine and NADPH dependent, Ca2+ independent, and potentiated by superoxide dismutase. Induction was evident after 4 h, was dependent on the dose of LPS, and required protein synthesis. Treatment of astrocyte cultures with leucine methyl ester reduced microglial cell contamination from 7 to 1%, with a loss of 44% of NOS-like activity. C6 cells treated with LPS also showed Ca(2+)-independent and L-arginine-dependent NOS-like activity. N18 cells demonstrated constitutive Ca(2+)-dependent NOS-like activity that was not enhanced by LPS induction. These data indicate that NOS-like activity can be induced in microglia, astrocytes, and a related glioma cell line as it can in numerous other cell types, but not in neuron-like N18 cells.
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PMID:Induction of nitric oxide synthase in glial cells. 137 33

Biological effects of human natural tumor necrosis factor-alpha (TNF) on glioblastoma cells in vitro and on glioma patients were investigated. TNF treatment on glioblastoma cells, even at a high dose (256 U/ml), exhibited no remarkable cytocidal activity in MTT assay, but at lower doses significantly inhibited colony forming and DNA synthesis. TNF at a low dose (10 U/ml) stimulated production of prostaglandin E2, Mn-superoxide dismutase, interleukin (IL)-6 and IL-8 by glioblastoma cells. These results indicated that the direct effect of TNF on human glioblastoma cells is rather antiproliferative than cytotoxic and is to modulate their metabolic pathways. In an early Phase I clinical trial, TNF was administered intracranially to six patients bearing glioblastoma. In this trial, the author studied in vivo immunological responses in the cerebrospinal fluid and regional fluid after the regional TNF injections. TNF in these body fluids were detected with a half life of several hours. There occurred a substantial number of leukocyte migration after the TNF administration. Neutrophils appeared first peaking at 8 to 12 hours, and then CD4+CD8-T cells and CD11b+CD13+CD14+ monocytes followed. IL-8 activity in the cerebrospinal fluid simultaneously corresponded to peak of the neutrophil migration. Increases in IL-6, IL-1 beta and prostaglandin E2 levels in the cerebrospinal fluid, regional fluid or both occurred peaking at 8 to 12 hours after TNA infection. Neither IL-2 nor interferons was detected. In conclusion, TNF may act as an antineoplastic agent by its direct cytostatic effects and indirectly through immune modulatory effects.
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PMID:[In vitro and in vivo immunobiological responses of glioblastoma to human natural tumor necrosis factor-alpha]. 142 94

Disruption of blood brain barrier with increased vascular permeability is associated with genesis of peritumoural oedema. Oxygen free radicals play a role in increased vascular permeability. Recent studies have suggested that tumour cells can produce superoxide radicals and free radical scavengers such as superoxide dismutase (SOD) and catalase in tumour cells are impaired. In this study, we investigated the role of oxygen free radicals in the genesis of peritumoural brain oedema in experimental malignant brain tumours using V x 2 carcinoma cells and 9L glioma cells. In vitro data indicate that the V x 2 carcinoma cell and the 9L glioma cells produce superoxide radicals detected by nitroblue tetrazolium. Electron spin resonance spectroscopy using DMPO as a spin trap demonstrated that SOD activity was significantly lower in subcutaneous larger 9L glioma tumours than in normal brains and 9L glioma brain tumours. In the subcutaneous tumours, SOD activity was lower in the central portion of the tumour than in the peripheral portion of the tumour. In conclusion, we are not sure whether oxygen free radicals are major causative factors of peritumoural brain oedema, but the demonstration of oxygen free radicals in brain tumour cells needs further investigation.
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PMID:Oxygen free radicals in the genesis of peritumoural brain oedema in experimental malignant brain tumours. 196 70

The intensity of formation of superoxide radicals (O(-2)) and superoxide dismutase (SOD) activity in the tissue of two transplantable gliomas were examined. The cells of these tumors were marked by unbalance between the intensity of O(-2) formation by nuclear membranes and their detoxication of SOD. This unbalance was particularly demonstrable in glioma 35 which was marked by rapid growth and high sensitivity to adriamycin. Slow-growing glioma was noted for higher activity of SOD and was insensitive to adriamycin. Since it is known that anthracycline antibiotics raise the intensity of the formation of free oxygen radicals in tumor cells, the data obtained suggest that the intensity of formation and detoxication of O(-2) may be used for the assessment of the sensitivity to these drugs.
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PMID:[The role of the system of superoxide radical formation and detoxication in the mechanism of the antineoplastic effect of adriamycin]. 631 11

The resistance of glioma cells to radiations may be diminished by previous ethanol or oxygen treatment. When rat glioma C6 cells were treated with either 50 mM or 100 mM ethanol in the culture medium before X ray irradiation (1000 rads), the surviving cells decrease two weeks later by about 40% compared with irradiated non treated cells. We suggest that the greater cell death after irradiation of alcohol treated glioma cells in culture may partially result from an accumulation of cytotoxic O = 2 radicals, since superoxide dismutase activity was reduced under these conditions.
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PMID:Sensitivity to X ray irradiation of alcohol treated glioma cells in culture. 652 48

Recent studies using a rat model of pneumococcal meningitis have shown that nitric oxide synthase (NOS) inhibitors greatly attenuated microvascular changes and brain edema formation. The site of NO production during bacterial meningitis is unknown. In this study we tested whether primary astrocyte cultures from neonatal rat cortex can be induced to release NO upon stimulation with pneumococci. NO production was assessed by measuring nitrite in the cell culture supernatant using the Griess reaction. Stimulation with heat-killed unencapsulated pneumococci (HKP) increased nitrite concentrations in astrocyte culture supernatants in a dose-dependent fashion. Administration of N-nitro-L-arginine (L-NA), aminoguanidine, L-canavanine, cycloheximide, and dexamethasone prevented the increase in nitrite concentrations. Addition of L-arginine, but not of D-arginine, partially reversed the inhibitory effect of L-NA. Administration of SOD increased nitrite accumulation. Moreover, at 72 h after stimulation with heat-killed pneumococci (10(7) cfu/ml) astrocytes showed an inducible NOS-like immunoreactivity. Accumulation of nitrite was also observed when rat cerebellar neurons and microglia were stimulated with HKP, whereas there was only a slight increase of nitrite in media of rat C6 glioma cells, but no increase of nitrite when the human glioblastoma cell line LN-229 was stimulated with HKP. There was a stronger increase in nitrite levels when astrocytes from Lewis rats were used compared to that from Wistar rats. In conclusion, our study indicates that astrocytes, neurons and microglia are inducible for NO production upon stimulation with pneumococci.
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PMID:Production of nitrite by primary rat astrocytes in response to pneumococci. 764 48

Although tumor necrosis factor-alpha (TNF) has been applied to early clinical trials for patients with malignant glioma, majority of human glioma cells has been reported to be resistant to TNF cytocidal effect in vitro. This study investigated antiproliferative effect of the TNF associated with induction of differentiation and expression of two distinct TNF receptors on human glioblastoma cell lines. The expression of p55 and p75 TNF receptors on 12 human glioblastoma cell lines was assessed by polymerase chain reaction and flow cytometry. p55 TNF receptor was detected in all cell lines, and only 4 cell lines concomitantly expressed p75 TNF receptor. Twelve human glioblastoma cell lines were treated with low-dose TNF, up to 256 U/ml for 7 days. TNF did not exhibit its cytocidal effect, but showed antiproliferative effects with inhibition of DNA synthesis in majority of cell lines tested. Flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique demonstrated that this antiproliferative effect of TNF was attributed to accumulation of glioblastoma cells in G0/G1 phase, suppressing the proliferative pathway. Furthermore the TNF stimulation increased glial fibrillary acidic protein and production of bioactive molecules including interleukin(IL)-6, IL-8, granulocyte-macrophage colony stimulating factor, prostaglandin E2 and manganous superoxide dismutase. In conclusion, human glioblastoma cells had p55 TNF receptor as a functional receptor and well responded to low-dose TNF stimulation, but not susceptible TNF cytocydal effect. The effect of TNF on glioblastoma cells appeared to modulate cell differentiation. TNF may be utilized as an agent for a differentiation therapy for human glioblastomas.
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PMID:[Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells]. 777 79

The effect of arachidonic acid (AA, 20:4) was analyzed in vitro by employment of C6 glioma cells and astrocytes from primary culture. The cells were suspended in an incubation chamber under continuous control of pH, pO2, and temperature. Cell swelling was quantified by flow cytometry. After a control period, the suspension was added with AA at concentrations of 0.01 to 1.0 mM. Administration of AA induced an immediate, dose dependent swelling in C6 glioma cells or astrocytes. AA-concentrations of 0.01 mM led to an increase of the glial cell volume to 103.0 +/- 1.0% of control, 0.1 mM to 110.0 +/- 1.5%, and 1.0 mM to 118.8 +/- 1.5% within 10 min. The swelling response to linoleic acid (18:2) was only about half of what was found when AA was administered at a concentration of 0.1 mM, whereas stearic acid (18:0) did not induce any cell volume changes. Inhibition of the cyclo- and lipoxygenase pathway by BW 755C did not prevent glial swelling from AA, whereas it was reduced by SOD, or almost completely abolished by the aminosteroid U-74389F, an antagonist of lipid peroxidation. Replacement of Na(+)- and Cl- -ions in the suspension medium by choline chloride was also associated with complete abolishment of cell swelling from AA. The results demonstrate an impressive efficacy of arachidonic acid to induce glial swelling which might be attributable to activation of lipid peroxidation by the fatty acid, leading to an increased Na(+)-permeability and subsequent influx of water into the cells.
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PMID:Mechanisms of glial swelling by arachidonic acid. 797 45

Oxygen radicals induce cytotoxicity via a variety of mechanisms, including DNA damage, lipid peroxidation and protein oxidation. Here, we explore the use of a polyethylene glycol (PEG)-stabilised enzyme capable of producing reactive oxygen species (ROS), glucose oxidase (GO), for the purpose of harnessing the cytotoxic potential of ROS for treating solid tumours. PEG-GO (200 U), administered by two intratumoral injections 3 h apart, produced a significant growth delay in subcutaneous rat 9L gliomas as compared with control animals receiving heat-denatured PEG-GO. Rats were protected from systemic toxicity by subsequent i.v. administration of PEG-superoxide dismutase (PEG-SOD) and PEG-catalase. In vivo tumour metabolic changes, monitored using 31P magnetic resonance spectroscopy (31P-MRS) 6 h following initial administration of PEG-GO, revealed a 96 +/- 2% reduction in the ATP/Pi ratio and a 0.72 +/- 0.10 unit decline in intracellular pH. A 3-fold sensitisation of 9L glioma cells in vitro to hydrogen peroxide could be achieved by a 24 h preincubation with buthionine sulphoximine (BSO). This study suggests that oxidation therapy, the use of an intratumoral ROS-generating enzyme system for the treatment of solid tumours, is a promising area which warrants further exploration.
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PMID:Oxidation therapy: the use of a reactive oxygen species-generating enzyme system for tumour treatment. 798 Oct 65

The effects of intracellularly generated H2O2 on cell viability, morphology, and biochemical markers of injury have been investigated in a clonal cell line of neuronal origin (140-3, mouse neuroblastoma X rat glioma) as a cell culture model for the role of oxidative stress in the long-term loss of neurons in the brain. The H2O2 was generated from the redox cycling of menadione, or by the oxidation of serotonin catalyzed by monoamine oxidase, to simulate the effect of amine neurotransmitter turnover. Incubation with menadione at concentrations as low as 10 microM for several hours resulted in significant losses of cell viability and altered morphology. Similar effects were evident in the presence of serotonin only after incubation overnight with concentrations > 1 mM. The cytotoxicity of either agent was potentiated by preincubation with specific inhibitors of two enzymes important to cellular antioxidant defenses, 3-amino-1,2,4-triazole for catalase and 1,3-bis(chloromethyl)-1-nitrosourea for glutathione reductase. Activity of another antioxidant enzyme of particular importance to antioxidant defenses in brain, the selenoprotein glutathione peroxidase, was stimulated fourfold by growth of cultures in the presence of sodium selenite as a source of active-site Se for the enzyme. The only effect of the selenite on other functionally coupled antioxidant enzymes was a decrease in activity of superoxide dismutase at concentrations > 200 nM. The selenite substantially protected cells against oxidative stress induced by combinations of menadione, 3-amino-1,2,4-triazole, and 1,3-bis(chloromethyl)-1-nitrosourea, but was only marginally effective with serotonin as a source of oxidative stress. The monoamine oxidase inhibitor pargyline increased cell survival in the presence of serotonin, demonstrating the role of this enzyme in its cytotoxicity. DNA damage (single strand breaks), but not lipid peroxidation, correlated with the cytotoxic effects of menadione.
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PMID:Oxidative stress in a clonal cell line of neuronal origin: effects of antioxidant enzyme modulation. 849 17


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