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)

Fumonisin B1 (FB1), produced by the fungus Fusarium moniliforme, belongs to a class of sphingosine analogue mycotoxins that occur widely in the food chain. Epidemiological studies have associated consumption of Fusarium moniliforme-contaminated food with human oesophageal cancer in China and South Africa. FB1 also causes equine leucoencephalomalacia. Evidence for induction of apoptosis by FB1 was first obtained when C6 glioma cells were incubated with fumonisin B1 (3-27 microM) causing DNA fragmentation profiles showing DNA laddering in gel electrophoresis and apoptotic bodies revealed by chromatin staining with acridine orange and ethidium bromide. Further confirmation experiments and comet assays have been performed under similar conditions. The results of the comet test show that FB1 at 9 and 18 microM induces respectively 50 +/- 2% and 40 +/- 1% of cells with a comet with an increased tail length of 93 +/- 9 microm and 102 +/- 17 microm respectively. Under these concentrations, FB1 induced DNA fragmentation and laddering and many apoptotic bodies. Pre-incubation of the cells with vitamin E (25 microM) for 24 h before FB1 (18 microM) significantly reduced DNA fragmentation and apoptotic bodies induced by FB1.
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PMID:Prevention by vitamin E of DNA fragmentation and apoptosis induced by fumonisin B1 in C6 glioma cells. 1083 79

Exposure to 1,3-dinitrobenzene (DNB) is associated with neuropathologic changes in specific brainstem nuclei, mediated by oxidative stress and mitochondrial dysfunction. The expression of Bcl-2-family proteins as a function of sensitivity to 1, 3-dinitrobenzene (DNB)-induced mitochondrial permeability transition (MPT) was examined in C6 glioma and SY5Y neuroblastoma cells. Neuroblastoma cells were 10-fold more sensitive than glioma cells to DNB-induced decreases in mitochondrial reducing potential, measured by reduction of the tetrazolium compound, 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The IC(50) values for DNB-related inhibition of MTT reduction were 107+/-25 microM in SY5Y cells and 1047+/-101 microM in C6 cells. Levels of reactive oxygen species (ROS) were increased in both SY5Y and C6 cells following DNB exposure by 4.6- and 6.0-fold above control, respectively. DNB caused abrupt depolarization of mitochondria in both neuroblastoma and glioma cells that was inhibited by trifluoperazine. The first order rate constants for mitochondrial depolarization were: C6, k=0.31+/-0.02 min(-1); SY5Y, k=0.14+/-0.01 min(-1). Onset of MPT occurred at 10-fold lower concentration of DNB in SY5Y cells than in C6 cells. The antioxidants, deferoxamine and alpha-tocopherol, effectively prevented DNB-induced MPT in C6 and SY5Y cells, suggesting involvement of ROS in the initiation of MPT. Exposure to DNB resulted in decreased cellular ATP content in SY5Y cells and efflux of mitochondrial calcium in both SY5Y and C6 cells, concurrent with onset of MPT. The expression of Bcl-2, Bcl-X(L), and Bax was evaluated in both cell types by Western blot analysis. C6 glioma cells strongly expressed Bcl-X(L) and only weakly expressed Bcl-2 and Bax, whereas SY5Y neuroblastoma cells expressed lower levels of Bcl-X(L) and higher levels of both Bcl-2 and Bax. Collectively, these results suggest that higher constitutive expression of Bcl-X(L), rather than Bcl-2, correlates with resistance to DNB-induced MPT in SY5Y and C6 cells and that differential regulation of the permeability transition pore may underlie the cell-specific neurotoxicity of DNB.
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PMID:Differential cellular regulation of the mitochondrial permeability transition in an in vitro model of 1,3-dinitrobenzene-induced encephalopathy. 1096 Jun 1

Five boronated DNA-intercalating compounds [5-ortho-carboranyl phenanthridinium (5-o-CP), 5-para-carboranyl phenanthridinium (5-p-CP), 6-para-carboranyl phenanthridinium, water-soluble boronated phenanthridinium and water-soluble boronated acridine (WSA1)], primarily developed for boron neutron capture therapy (BNCT), were analysed regarding their binding in cultured human malignant glioma spheroids. Comparisons were made with the corresponding DNA intercalators ethidium bromide and acridine orange. Octanol/phosphate buffered saline-water coefficients were determined for all compounds, and it was found that the most lipophilic (5-o-CP and 5-p-CP) were most toxic and accumulated high amounts of boron in monolayer cells. These compounds bound primarily in the outermost part of spheroids with poor penetration into the inner region, even after 2 days of continuous exposure. On the other hand, the most hydrophilic compound (WSA1) showed lower toxicity and lower boron accumulation in monolayer cells, and rapid binding in the inner region of spheroids. A reasonable explanation for this observation is that the lipophilic compounds interact mainly with lipophilic parts of the cells, like cellular membranes, and therefore rapidly binds to cells, preventing penetration and binding to cells in the deeper region of the spheroids. The possibility of using these compounds for BNCT are discussed.
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PMID:The influence of lipophilicity on binding of boronated DNA-intercalating compounds in human glioma spheroids. 1120 May 3

Free radical damage has been implicated in the pathophysiology of motor neurone disease (MND); mutations have been identified in the gene encoding Cu/Zn superoxide dismutase (SOD1). There is evidence that glial cell dysfunction may contribute to motor neurone injury, but the exact role of glial cells in MND has yet to be established. The aim of this study was to determine whether expression of mutant SOD1 affects the response of glia to oxidative stress. Stable C6 glioma cells expressing mutant SOD1 and cortical astrocyte cultures from G93A-SOD1 transgenic mice were exposed to: xanthine/xanthine oxidase; hydrogen peroxide; A23187 and 3-morpholinosydonimine. Cell viability was measured using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Neither C6 glioma cells nor cortical astrocytes expressing mutant SOD1 were more susceptible to any of the free radical generating systems compared to control cells. These results suggest that astrocytes are resistant to the toxic effects of mutant SOD1 widely reported for neuronal cells.
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PMID:Cultured glial cells are resistant to the effects of motor neurone disease-associated SOD1 mutations. 1129 Apr 8

We investigated the effect of epigallocatechin-gallate (EGCG), the main constituent of green tea polyphenols, on human glioblastoma cell lines U-373 MG and U-87 MG, rat glioma cell line C6, and rat nonfunctioning pituitary adenoma cell line MtT/E. Cell viability was determined by assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and the extent of apoptosis was studied by flow cytometric analysis. Apoptosis was also characterized by morphology using fluorescent microscopy. The role of insulin-like growth factor-I (IGF-I) was studied by assay with MTT, immunohistochemistry, and immunoradiometric assay. After 72-h exposure, a statistically significant loss of viability (P = < 0.0001) was observed at concentrations of 12.5, 25, 50, and 100 microg/ml in U-373 MG cells and U-87 MG cells. EGCG at concentrations of 50 microg/ml and higher significantly reduced the viability of C6 cells. EGCG inhibited viability of MtT/E cells only at a concentration of 100 microg/ml. Quantitative study by flow cytometry demonstrated that lower doses of EGCG (12.5, 25, 50 microg/ml) induced apoptosis in U-373 MG, U-87 MG, and C6 cells; however, only the highest dose (100 microg/ml) induced apoptosis in MtT/E cells. Compared with other cell lines, MtT/E cells showed stronger IGF-I immunoreactivity. Neutralization of IGF-I with an antihuman IGF-I antibody reduced viability of the cell lines. It can be concluded that EGCG has an inhibitory effect on malignant brain tumors, and IGF-I may be involved in the effects of EGCG.
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PMID:Inhibitory effect of epigallocatechin-gallate on brain tumor cell lines in vitro. 1130 13

We examined the effects of dissolved nitric oxide (NO) gas on cytoplasmic calcium levels ([Ca(2+)](i)) in C6 glioma cells under anoxic conditions. The maximum elevation (27 +/- 3 nM) of [Ca(2+)](i) was reached at 10 microM NO. A second application of NO was ineffective if the first was >0.5 microM. The NO donor diethylamine/NO mimicked the effects of NO. Acute exposure of the cells to low calcium levels was without effect on the NO-evoked response. Thapsigargin (TG) increased [Ca(2+)](i) and was less effective if cells were pretreated with NO. Hemoglobin inhibited the effects of NO at a molar ratio of 10:1. 8-Bromo-cGMP was without effect on the NO-evoked response. If cells were pretreated with TG or exposed chronically to nominal amounts of calcium, NO decreased [Ca(2+)](i). The results suggest that C6 glioma cells have two receptors for NO. One receptor (NO(A)) elevates [Ca(2+)](i) and resides on the endoplasmic reticulum (ER). The other receptor (NO(B)) decreases [Ca(2+)](i) and resides on the plasmalemma or the ER. The latter receptor dominates when the level of calcium within intracellular stores is diminished.
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PMID:Regulation of cytoplasmic calcium levels by two nitric oxide receptors. 1150 65

The known effects of nerve growth factor (NGF) are induction of differentiation and promotion of survival. We analysed the effects of exogenously added NGF on rat C6 and 9L glioma cells and the rat pheochromocytoma cell line PC12. Cells were seeded into 96-well plates and exposed to different concentrations of FCS (10%, 5%, 1%, 0.5% and no FCS) supplemented with or without 50 ng/ml NGF for up to 120 hours. Cell survival was measured using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-assay. In this study we could clearly show two different effects: (1) proliferation was not influenced by NGF under high, medium or low serum and (2) survival rates increased under dramatic or complete serum deprivation, indicating that NGF acts as survival factor against cell death or cell cytostasis.
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PMID:NGF increases cell survival rates under serum deprived conditions. 1172 57

PLA2G4C, encoding cytosolic phospholipase A2-gamma (cPLA2-gamma), is a 17-exon gene located on chromosome 19q13.3 within the putative glioma tumor suppressor gene region. Given the clinical importance of assessing 1p and 19q loss in human gliomas, the development of convenient and practical assays for detecting allelic loss is of considerable priority in neuro-oncology. We report a minisatellite polymorphism in the untranslated region of exon 1, with allelic variants that have one, two or three 27-bp repeats. The polymorphism is informative in 55.7% of a reference population, and accurately detects allelic loss of 19q in human gliomas. This novel marker offers distinct advantages for assessing 19q status in malignant gliomas. The relatively large size of the repeats allows detection of allelic variants with standard ethidium bromide-stained agarose gels and the PLA2G4C marker is the closest polymorphism to the smallest common deletion area in the putative glioma tumor suppressor gene region. These characteristics suggest that the PLA2G4C polymorphism will be a convenient and practical assay for clinical and research evaluation of 19q status in human gliomas.
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PMID:Novel PLA2G4C polymorphism as a molecular diagnostic assay for 19q loss in human gliomas. 1195 71

We examined the mechanism of 17beta-estradiol (estrogen)-mediated inhibition of apoptosis in C6 (rat glioma) cells following exposure to hydrogen peroxide (H(2)O(2)). Cells were preincubated with 4 microM estrogen for 2 h and then exposed to 100 microM H(2)O(2) for 24 h. Exposure to H(2)O(2) caused significant increases in intracellular calcium (Ca(2+)), as determined by fura-2, which was attenuated by preincubation with estrogen. H(2)O(2) and ionomycin caused cell death in a dose-dependent manner, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Preincubation with estrogen restored viability in cells exposed to H(2)O(2) but not in cells exposed to ionomycin. Western blot analysis showed an increase in Bax/Bcl-2 ratio, calpain activity, and caspase-3 activity following treatment with H(2)O(2), and estrogen pretreatment decreased levels of all three. Cell morphology, as evaluated by Wright staining, indicated apoptosis in cells treated with H(2)O(2), and pretreatment with estrogen reduced apoptosis. Results from MTT and Wright staining were further supported by the terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) assay. These results indicate a role for estrogen in preventing apoptosis in C6 glial cells exposed to H(2)O(2). Our results suggest that estrogen may have a protective role in minimizing glial cell apoptosis in neurological diseases such as demyelinating disease or central nervous system trauma.
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PMID:Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells. 1270 34

The purpose of this paper is to investigate the antitumor effects of cytosine deaminase/5-fluorocytosine (CD/5-FC) suicide gene therapy system on human malignant glioma cells in vitro. The pCMVCD plasmid was constructed through the CD gene insertion in the multicloning site of eukaryotic expression vector pcDNA3.0, and confirmed by restriction endonuclease digestion/gene sequencing. The construct was subsequently transfected into the U251 human malignant glioma cells by using LipofectAMINE2000-mediated method. Resistant clones (named U251/CD cells) were isolated by screening with G418 presence. U251/CD cells were incubated with 5-FC in different concentrations to determine viability ratios (or cytotoxicity assay), measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The concentrations of 5-fluorouracil (5-FU) in the media were measured by high-performance liquid chromatography (HPLC) detector. Our results suggested that the untreated U251 cells were insensitive to 5-FC, with the IC(50) about 6500 micromol/L. After transfection, the IC(50) was dramatically reduced to about 10 micromol/L. Therefore, gene transfection made G418-resistant clones (U251/CD cells) be highly sensitive to 5-FC. HPLC analysis showed that 5-FU was detected in U251/CD cell medium. Study on U251 cells genetically modified by CD gene in vitro will play an essential role in glioma gene therapy in vivo. In conclusion, our results indicated that the CD/5-FC system was feasible to treat glioma.
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PMID:Effects of CD/5-FC suicide gene therapy system on human malignant glioma cells in vitro. 1276 3


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