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 examined whether oligodendrocytes, neurons, and astroglia derived from the human central nervous system differ in susceptibility to injury mediated by tumor necrosis factor (TNF)-alpha and by activated CD4+ T cells acting via a TNF-independent mechanism. Injury was assessed either as cell membrane-directed (lysis), measured by 51chromium (Cr) or lactate dehydrogenase (LDH) release, or nucleus-directed (apoptosis), measured by morphologic features based on propidium iodide (PI) staining and by DNA fragmentation measured by a terminal transferase (TdT)-mediated dUTP biotin nick end labeling technique (TUNEL). TNF did not induce 51Cr or LDH release in any cell targets, but did induce nuclear (66 +/- 2% of cells) and DNA (68 +/- 2% of cells) fragmentation selectively in the oligodendrocytes over 96 hr. At this time, there was no significant loss of oligodendrocyte cell number. Nuclear injury could be induced in neurons by serum deprivation and in malignant astrocytes by the combination of TNF and low serum. CD4+ T cells activated with phytohemagglutin (pha) or anti-CD3 plus interleukin-2 induced significant 51Cr and LDH release in all target cells tested; only pha-activated CD4+ T-cell cocultures showed reduced target cell numbers. Significant nuclear fragmentation was observed only for glioma cells (22 +/- 1% of cells). Differences in susceptibility to different immune effector mechanisms and in the nature of the injury response to the same effector mediator among human CNS-derived neural cells will need to be considered in design of therapeutic strategies aimed at protecting or limiting target cell injury consequent to disease or trauma.
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PMID:Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury. 747 83

The effect of intracarotid infusion of etoposide on the permeability of the blood-brain barrier (BBB) and brain-tumor barrier (BTB) was investigated using a model of rats injected with C6 glioma cells. Fifty four glioma-bearing rats were divided into 3 groups and treated with 0, 3, or 15 mg/kg of etoposide infused into the internal carotid artery. BBB or BTB permeability was evaluated qualitatively by the leakage of Evans blue (6 animals in each group) or quantitatively by the diffusion of carboplatin [cis-diammine (1,1-cyclobutane-dicarboxylato) platinum(II); CBDCA] (12 animals in each group) into the normal brain or the tumor tissue. BBB and BTB disruption augmented significantly in proportion to the dose of etoposide. The degree of disruption of BTB was greater than that of BBB, but the rate of disruption of BBB in proportion to increasing the dose of etoposide was higher than that in the BTB. Histopathologically, no obvious changes were observed in the animals of either the control group or the 3 mg/kg group but degenerative changes in the neurons of the hippocampus of the infused hemisphere were seen in the 15 mg/kg group. This change is thought to be caused by apoptosis because of the positive reaction with TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Our results suggest that intracarotid infusion of etoposide can increase drug delivery of concurrent antitumor agents into tumor tissue, but cerebral parenchymal cell damage is expected with a higher dosage of etoposide. Therefore, the dosage of etoposide for intracarotid infusion should be lower than 15 mg/kg in order to reduce neurotoxicity of both etoposide and concurrent anticancer drugs.
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PMID:Effect of intracarotid infusion of etoposide: modification of the permeability of the blood-brain barrier and the blood-tumor barrier in rat brain tumor model. 1009 32

Calpain, a Ca2+-activated cysteine protease, has been implicated in apoptosis of immune cells. Since central nervous system (CNS) is abundant in calpain, the possible involvement of calpain in apoptosis of CNS cells needs to be investigated. We studied calpain expression in rat C6 glioma cells exposed to reactive hydroxyl radical (.OH) [formed via the Fenton reaction (Fe2++H2O2+H+-->Fe3++H2O+.OH)], interferon-gamma (IFN-gamma), and calcium ionophore (A23187). Cell death, cell cycle, calpain expression, and calpain activity were examined. Diverse stimuli induced apoptosis in C6 cells morphologically (chromatin condensation as detected by light microscopy) and biochemically [DNA fragmentation as detected by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay]. Oxidative stress arrested a population of C6 cells at the G2/M phase of cell cycle. The levels of mRNA expression of six genes were analyzed by the reverse transcriptase-polymerase chain reaction (RT-PCR). Diverse stimuli did not alter beta-actin (internal control) expression, but increased calpain expression, and the upregulated bax (pro-apoptotic)/bcl-2 (anti-apoptotic) ratio. There was no significant increase in expression of calpastatin (endogenous calpain inhibitor). Western blot analysis showed an increase in calpain content and degradation of myelin-associated glycoprotein (MAG), a calpain substrate. Pretreatment of C6 cells with calpeptin (a cell-permeable calpain inhibitor) blocked calpain overexpression, MAG degradation, and DNA fragmentation. We conclude that calpain overexpression due to.OH stress, IFN-gamma stimulation, or Ca2+ influx is involved in C6 cell death, which is attenuated by a calpain-specific inhibitor.
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PMID:Diverse stimuli induce calpain overexpression and apoptosis in C6 glioma cells. 1035 May 26

N-(4-hydroxyphenyl)retinamide (fenretinide) is a synthetic retinoid with anticancer properties. We investigated the effects of fenretinide on the growth of glioma cells. Four glioma cell lines (C6, 9L, Med3 and U87) were treated with fenretinide. Cell viability and independent growth was determined by MTS assay and soft agar assay, respectively. The induction of apoptosis was evaluated by microscopic examination, flow cytometric DNA content analysis, and in situ TdT methods. Fenretinide markedly reduced cell viability of all the glioma cell lines examined at a range of concentrations from 1 to 10 microM. In all cell lines examined, fenretinide also induced morphological changes consistent with apoptosis, including cellular shrinkage, chromatin condensation, and nuclear fragmentation. Flow cytometric analysis also revealed an apoptotic pattern of the DNA content, and in situ detection of apoptosis showed increased incorporation of digoxigenin-nucleotide triphosphate in fenretinide-treated glioma cells. These findings indicate that fenretinide inhibits the growth of glioma cells via the induction of apoptosis, suggesting potential clinical use of fenretinide for treatment of glioma patients.
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PMID:Induction of apoptosis by N-(4-hydroxyphenyl)retinamide in glioma cells. 1042 31

To facilitate investigation of the molecular mechanisms of tumor cell radiosensitivities, we have generated a set of clones with different radiosensitivities from a human glioma cell line U-251 MG-Ho. Forty-four colonies were isolated by subjecting parent cells to the mutagen N-methylnitrosourea and then irradiating these cells with increasing doses of x-rays. About half of the clones displayed different radiosensitivities than the parent cells. We selected one of the most sensitive clones (X3i) and one of the most resistant clones (Y6) for further study. Isoeffective doses for these two clones differed by about a factor of 1.7; the relative radiosensitivities of both clones were stable for at least 30 cell culture passages. These two clones do not differ significantly in either the induction or repair of radiation-induced DNA double-strand breaks as measured by pulsed field gel electrophoresis. Radiation-induced apoptosis measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay and micronucleus formation were similar in both clones. However, potentially lethal damage repair was greater in the radioresistant Y6 clone than in the radiosensitive X3i clone as determined by colony-forming efficiency assay.
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PMID:Induction and characterization of human glioma clones with different radiosensitivities. 1093 48

Cell death in gliomas may occur either by apoptosis, or, in the case of high grade tumours, by necrosis, but questions remain as to the pathogenesis and relationship between these processes. The development of cell death was investigated in multicellular glioma spheroid cultures. Spheroids model the development of cell death due to diffusion gradients in a three-dimensional system without confounding influences of immune response, pressure gradients, etc. Spheroid cultures were established from four malignant glioma cell lines: U87, U373, MOG-G-CCM and A172; harvested from culture at weekly intervals and stained with Haematoxylin and Eosin (H&E), TdT-mediated dUTP-X nick end labelling (TUNEL) and by immunohistochemistry for vimentin, Glial Fibrillary Acidic Protein (GFAP) and Ki67. Annexin V flow cytometry and counts of apoptotic cells on H & E stained sections were performed to assess levels of apoptosis. Modes of cell death were also characterized by electron microscopy. Spatially separate zones of proliferation, differentiation and central cell death developed with increasing spheroid diameter. Central cell death developed at a predictable radius (300-400 microm) for each cell line. Ultrastructural examination showed this to be necrotic in type. Apoptosis was most reliably assayed by morphological counts using H & E. Basal levels of apoptosis were low (< 0.5%), but increased with increasing spheroid diameter (> 2% in U87). In particular, levels of apoptosis rose following development of central necrosis and apoptoses were most abundant in the peri-necrotic zone. There were quantitative differences in the levels of apoptosis and necrosis between glioma cell lines. The predictable onset of necrosis in the spheroids will allow us to investigate the pathogenesis of necrosis and events in prenecrotic cells. There is a relationship between the development of necrosis and apoptosis in this model and these processes can be separately assayed. Further in vitro and genetic studies will enable us to study these events and interactions in greater detail than is possible using other cell culture and in vivo systems.
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PMID:The development of necrosis and apoptosis in glioma: experimental findings using spheroid culture systems. 1153 60

This study was made to investigate whether Chiropsalmus Quadrigatus toxins (CqTX), which isolated from box jellyfish C. Quadrigatus venom, could induce apoptosis in human U251 and rat C6 malignant glioma cells and transformed vascular endothelial ECV 304 cell lines. Cell viability was estimated by MTT assay. Apoptosis was evaluated using TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labeling (TUNEL) method and DNA gel electrophoresis. Furthermore, the expression of p53 protein was examined immunohistochemically in the U251 cells. After the CqTX treatment, the growth of all cell lines was inhibited, the fragmented DNA was observed and some cells became TUNEL positive. The expression of p53 protein was increased in the tested U251 cells. The results suggested that CqTX induced apoptosis in these cell lines. The promotion of the p53 expression might be one mechanism of apoptosis induced by CqTX in the glioma cells.
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PMID:Apoptosis induced by box jellyfish (Chiropsalmus quadrigatus) toxin in glioma and vascular endothelial cell lines. 1173 37

Cloned T9-C2 glioma cells transfected with membrane macrophage colony-stimulating factor (mM-CSF) never formed subcutaneous tumors when implanted into Fischer rats, whereas control T9 cells did. The T9-C2 cells were completely killed within 1 day through a mechanism that resembled paraptosis. Vacuolization of the T9-C2 cell's mitochondria and endoplasmic reticulum started within 4 hours after implantation. By 24 hours, the dead tumor cells were swollen and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive. Bcl2-transduced T9-C2 cells failed to form tumors in rats. Both T9 and T9-C2 cells produced cytokine-induced neutrophil chemoattractant that recruited the granulocytes into the tumor injection sites, where they interacted with the tumor cells. Freshly isolated macrophages killed the T9-C2 cells in vitro by a mechanism independent of phagocytosis. Nude athymic rats treated with antiasialo GM1 antibody formed T9-C2 tumors, whereas rats treated with a natural killer cell (NK)-specific antibody failed to form tumors. When treated with antipolymorphonuclear leukocyte (anti-PMN) and antimacrophage antibodies, 80% of nude rats formed tumors, whereas only 40% of the rats developed a tumor when a single antibody was used. This suggests that both PMNs and macrophages are involved in the killing of T9-C2 tumor cells. Immunocompetent rats that rejected the living T9-C2 cells were immune to the intracranial rechallenge with T9 cells. No vaccinating effect occurred if the T9-C2 cells were freeze-thawed, x-irradiated, or treated with mitomycin-C prior to injection. Optimal tumor immunization using mM-CSF-transduced T9 cells requires viable tumor cells. In this study optimal tumor immunization occurred when a strong inflammatory response at the injection of the tumor cells was induced.
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PMID:Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a "paraptosis"-induced pathway that promotes systemic immunity against intracranial T9 gliomas. 1214 20

GD3 ganglioside induces apoptosis in several cell types, but the molecular events through which this occurs are largely unknown. We investigated the apoptotic effects of GD3 expression using U-1242 MG glioblastoma cells, as these cells synthesize almost exclusively GM3 and GM2 but not GD3. To express GD3 under the control of the TetOn system with minimum leakage, we modified the system by constructing a single tri-cistronic retrovirus vector containing three genes separated by two internal ribosome entry sites: (a) transcriptional silencer, tTS; (b) mutant of reverse transcriptional activator, rtTA2(S)-M2 (provided by H. Bujard, Heidelberg, Germany); and (c) enhanced green fluorescent protein (EGFP), as an indicator of the tri-cistronic gene expression. Using flow cytometry, we selected glioma cells (U1242MG-GD3 clone) that express high levels of GD3 in response to doxycycline. Expression of GD3 was associated with apoptosis as verified by annexin-V binding, TdT-mediated dUTPnick end-labelling assay (TUNEL), and EGFP degradation. GD3-induced apoptosis occurred via caspase-8 activation, as GD3 caused cleavage of caspase-8 and inhibition of caspase-8 activation by zlETD-fmk minimized GD3-induced apoptosis.
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PMID:Endogenous GD3 ganglioside induces apoptosis in U-1242 MG glioma cells. 1644 17

Resveratrol (Res) has been reported to inhibit tumor initiation, promotion, and progression in a variety of cell culture systems depending on the specific cell type and cellular environment. In the present study, we determined the effect of Res on the cell growth and apoptosis of rat glioma C6 cell line as well as mouse fibroblast 3T3 cell line, in vitro. Concurrently, we investigated whether caspase-3 is involved in the Res-induced apoptosis of rat glioma cells. Exposure to Res exhibits a significant anti-proliferative effect and induces an increase in the population of apoptotic cells on C6 cells in a concentration- and time-dependent manner, but not for normal 3T3 fibroblast cells, as measured by methyl thiazolyl tetrazolium assay and flow cytometer. Distinguished increase of C6 cells in S phase is observed after the treatment of Res as compared to insignificant change in cell cycle distribution of 3T3 cells. TdT-mediated dUTP nick end labeling fluorescence staining, HE staining, and scanning electron microscope revealed abnormal morphology and ultrastructure in C6 cells treated with Res. Our data showed that Res can increase the expression and induced the activation of caspase-3 in rat glioma C6 cells. These results suggest that Res has significant apoptosis-inducing effect on C6 glioma cells other than normal fibroblast 3T3 cells in vitro and caspase-3 may act as a potential mediator in the process.
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PMID:Resveratrol inhibits cell growth and induces apoptosis of rat C6 glioma cells. 1703 60


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