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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estramustine phosphate (estramustine phosphate sodium), a carbamate ester combining 17 beta-estradiol and nor-nitrogen mustard, is a cytotoxic drug used in the treatment of advanced prostatic carcinoma. Because of the radiosensitising effect of this drug there has been a recent increase in interest concerning estramustine phosphate and its clinical use. It has also been found that the early recommendations of drug administration together with food or milk were inappropriate, since calcium containing food and antacids hamper drug uptake. This may have obscured results from earlier clinical studies with estramustine phosphate. Estramustine phosphate is currently being re-evaluated for the treatment of other tumours such as glioma and mammary carcinoma. This review summarises the present relatively limited knowledge concerning the pharmacokinetic and pharmacodynamic aspects of estramustine phosphate and its metabolites.
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PMID:Pharmacokinetics and pharmacodynamics of estramustine phosphate. 951 86

Tricresyl phosphate (1 microg/ml) inhibited the outgrowth of axon-like processes in mouse N2a neuroblastoma and rat PC12 pheochromocytoma cell lines induced to differentiate by serum withdrawal and nerve growth factor addition, respectively. By contrast, it had no effect on the outgrowth of processes by rat C6 glioma cells induced to differentiate with sodium butyrate. The effect on axon outgrowth in the two neuronal cell lines correlated with altered distribution of neurofilament proteins, as determined by indirect immunofluorescence with monoclonal antibody RMd09. Western blots of neuronal cell extracts probed with the same antibody revealed decreased cross-reactivity after exposure to tricresyl phosphate. The results suggest that tricresyl phosphate has a selective effect on neuronal cell differentiation, which involves impaired axon outgrowth, reduced levels of the neurofilament heavy chain and disruption of the neurofilament network.
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PMID:Tricresyl phosphate inhibits the formation of axon-like processes and disrupts neurofilaments in cultured mouse N2a and rat PC12 cells. 953 4

Treatment of rat glioma C6 cells with the beta-adrenergic agonist L-isoproterenol leads to a rise in cAMP level and a subsequent change in cell morphology from an epithelial to an astrocytic type of appearance. This morphological response is reverted by the addition of sphingosine-1-phosphate (S1P) with an EC50 of 10 nM. In rat glioma C6 cells loaded with the Ca2+ indicator Fura-2, S1P evoked Ca2+ release from internal stores and Ca2+ influx from the external medium. Half-maximal stimulation of the Ca2+ increase was 10-20 nM. A similar Ca2+ signal was observed in primary rat astrocytes loaded with the Ca2+ indicator fluo-3. Pretreatment of the C6 cells with PMA (162 nM) prevented both the S1P-induced Ca2+ increase and the morphological reversion. Ca2+ ions therefore seem essential for the morphological reversion by S1P. Pretreatment of the cells with the Clostridium botulinum C3 exoenzyme did not affect the reversion of the morphological response by S1P, indicating that the small GTP-binding protein Rho is not involved in the S1P-induced reversion.
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PMID:Sphingosine-1-phosphate induces a Ca2+ signal in primary rat astrocytes and a Ca2+ signal and shape changes in C6 rat glioma cells. 958 87

The purpose of this study was to determine the mechanism by which adenosine, inosine, and guanosine delay cell death in glial cells (ROC-1) that are subjected to glucose deprivation and mitochondrial respiratory chain inhibition with amobarbital (GDMI). ROC-1 cells are hybrid cells formed by fusion of a rat oligodendrocyte and a rat C6 glioma cell. Under GDMI, ATP was depleted rapidly from ROC-1 cells, followed on a much larger time scale by a loss of cell viability. Restoration of ATP synthesis during this interlude between ATP depletion and cell death prevented further loss of viability. Moreover, the addition of adenosine, inosine, or guanosine immediately before the amobarbital retarded the decline in ATP and preserved cell viability. The protective effects on ATP and viability were dependent on nucleoside concentration between 50 and 1,500 microM. Furthermore, protection required nucleoside transport into the cell and the continued presence of nucleoside during GDMI. A significant positive correlation between ATP content at 16 min and cell viability at 350 min after the onset of GDMI was established (r = 0.98). Modest increases in cellular lactate levels were observed during GDMI (1.2 nmol/mg/min lactate produced); however, incubation with 1,500 microM inosine or guanosine increased lactate accumulation sixfold. The protective effects of inosine and guanosine on cell viability and ATP were >90% blocked after treatment with 50 microM BCX-34, a nucleoside phosphorylase inhibitor. Accordingly, lactate levels also were lower in BCX-34-treated cells incubated with inosine or guanosine. We conclude that under GDMI, the ribose moiety of inosine and guanosine is converted to phosphorylated glycolytic intermediates via the pentose phosphate pathway, and its subsequent catabolism in glycolysis provides the ATP necessary for maintaining plasmalemmal integrity.
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PMID:Adenosine, inosine, and guanosine protect glial cells during glucose deprivation and mitochondrial inhibition: correlation between protection and ATP preservation. 968 43

A number of imidazole-based compounds were tested for their utility as (1)H NMR molecular probes of intracellular pH. Imidazole, previously found useful as a probe of erythrocyte pH, reported a pH in perfused canine glioma cells that was more than 1 pH unit lower than that reported by inorganic phosphate, consistent with the known lysosomal compartmentation of the molecule. Imidazole acetate, also proposed as an NMR probe of cellular pH, was found not to enter the cells of this study. Histidine was found to be readily taken up by cells and reported a pH consistent with that reported by inorganic phosphate. Using the chemical shift of the histidine H2 proton in cells incubated with 10 mM histidine, cellular pH measurements could be obtained in less than 1 s. This compares quite favorably with the measurement time, typically several minutes, needed to assess in vivo pH by (31)P NMR. The use of histidine as a probe of pH is demonstrated in perfused canine and rat glioma cells subjected to ischemia or to low extracellular pH.
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PMID:A study of imidazole-based nuclear magnetic resonance probes of cellular pH. 968 13

The early signaling mechanism of sphingosine 1-phosphate (S1P) on extracellular signal-regulated kinase (ERK) activation was investigated in C6 glioma cells. S1P activated the enzyme in association with a shift in the mobility on electrophoresis reflecting phosphorylation of both ERK1/ERK2 at as low as 10 nM. The lipid-induced ERK1/2 activation was partially inhibited by treatment of the cells with either phorbol 12-myristate 13-acetate (a long-term treatment to desensitize protein kinase C) or pertussis toxin (PTX) and was completely inhibited by a simultaneous treatment with both agents. Similarly, either calphostin C, an inhibitor of protein kinase C, or U73122, an inhibitor of phospholipase C, partially inhibited the S1Pinduced ERK1/2 activation in the nontreated cells with PTX and completely in the toxin-treated cells. On the other hand, the S1P-induced ERK activation was hardly affected by ethanol, which switched the product of phospholipase D from phosphatidic acid to metabolism-resistant phosphatidylethanol. S1P was able to activate ERK1/2 without a detectable increase in the intracellular content of the lipid, but sphingosine, a substrate of sphingosine kinase, which is an enzyme for S1P generation in the cells, hardly affected the ERK1/2 activation in spite of a marked elevation of intracellular S1P accumulation. This indicates that intracellular increase in S1P is not necessary for the S1P-induced ERK activation, and hence suggests the extracellular action mechanism of S1P. Supporting this idea, mRNAs of recently identified S1P specific receptors, Edg-1 and AGR16/H218, were expressed in C6 cells. Taken together, these results suggested that S1P acts on C6 cells extracellularly possibly through S1P receptors which are linked to at least two signaling pathways, i.e., the PTX-sensitive Gi/Go protein pathway and the toxin-insensitive Gq/G11-phospholipase C-PKC pathway, resulting in the activation of ERK.
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PMID:Possible involvement of cell surface receptors in sphingosine 1-phosphate-induced activation of extracellular signal-regulated kinase in C6 glioma cells. 988 6

Astroglia cells seem to be closely involved in neuronal survival/death via neurotrophins, cytokines and so on. We found that a transient four-vessel occlusion/reperfusion induced glial iNOS expression and neuronal apoptosis in a CA1 region of the rat hippocampus. Bacterial endotoxin (LPS)/INFgamma induced iNOS expression in cultured C6 rat glioma cells. LPS caused intranuclear translocation of NF-kappaB, and IFNgamma induced phosphorylation of Jak2 and Stat1, followed by the translocation of Stat1 into the nucleus. A NO donor (SNP) caused chromosomal condensation and fragmentation of nuclei and internucleosomal DNA fragmentation in NG108-15 cells, suggesting NO-induced neuronal apoptosis. Koningic acid (KO), a chemical modifier and enzyme inhibitor of glyceraldehyde-3 phosphate dehydrogenase (GAPDH), induced the apoptosis too. In addition, a NO donor (NOC18)-induced apoptosis was inhibited by Z-Asp-CH2-DCB, a caspase inhibitor, in SH-SY5Y cells. NOC18 increased caspase 3-like proteolytic activity to a substrate (Ac-DEVD-MCA), indicating the involvement of caspase, at least caspase 3, in NO-induced neuronal apoptosis.
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PMID:A transient brain ischemia- and bacterial endotoxin-induced glial iNOS expression and NO-induced neuronal apoptosis. 1002 34

A technique of microscopy with computerised detection of early morphological changes during continuous perifusion was used to monitor the geometry changes of cultured glioma cells (MG-251) when exposed to 40 mg/L estramustine phosphate (EMP) alone or in combination with granisetron (0.1 mumol/L), ondansetron (0.1 mumol/L), or serotonin (1 mumol/L). When the cells were exposed to EMP, cell volume measured as projected cell area (PCA) rapidly increased. Serotonin and ondansetron, but not granisetron, prevented the acute EMP response (PCA). Serotonin, but none of the 5-HT3 receptor antagonists, protected against the cytotoxicity of EMP to the glioma cells as measured by a fluorometric microculture assay. Our results demonstrate hitherto unknown differences between selective 5-HT3 receptor antagonist on the cellular response to EMP and shows the necessity to study the receptor antagonists from viewpoint of interference with the antitumour drug effects on malignant cells. The perifusion technique could be used to study the effects of serotoninergic agonists and antagonists on cell volume regulation of cells exposed to anticancer drugs.
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PMID:Serotoninergic modulation of cell volume response to estramustine: an image-analysis study on perifused individual glioma cells. 1021 Nov 3

Although the mechanism of the capacitative Ca2+ entry is still a mysterious process, it has been presently accepted that it occurs through plasma membrane channel pores rather than through a carrier mechanism. As it has been proposed by Putney (Cell Calcium, 1986, 7, 1-12), Ca2+ entry is directly dependent on the state of filling of the endoplasmic reticulum Ca2+ stores, i.e. it is activated by the depletion of the endoplasmic reticulum Ca2+ pool. However, the nature of the signal for activation of Ca2+ entry is still unknown. The biphasic capacitative Ca2+ entry involves inositol phosphate system and is ubiquitous in all nonexcitable cells. We have shown that glioma C6 cells belong to such type of cells and are characterized by a typical capacitative Ca2+ entry pathway. The characteristics of this Ca2+ influx is summarized and the hypotheses about its mechanism of activation are discussed.
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PMID:Capacitative calcium entry. Glioma C6 as a model of nonexcitable cells. 1042 44

In the present study we investigate the effect of exogenous sphingosine, sphingosine 1-phosphate and sphingosylphosphorylcholine on phospholipase D (PLD) activity in glioma C6 cells. The cells were prelabeled with [1-14C]palmitic acid and PLD-mediated synthesis of [14C]phosphatidylethanol was measured. Sphingosine 1-phosphate and sphingosylphosphorylcholine did not stimulate [14C]phosphatidylethanol formation either at low (0.1-10 microM) or high (25-100 microM) concentrations. On the other hand, sphingosine at concentrations of 100-250 microM strongly stimulated PLD activity as compared to the effect of phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), known as a PLD activator. The effect of TPA on PLD is linked to the activation of protein kinase C. The present study also shows that sphingosine additively enhances TPA-mediated PLD activity. This is in contrast to the postulated role of sphingosine as a protein kinase C inhibitor. These results demonstrate that in glioma C6 cells sphingosine not only affects PLD independently of its effect on protein kinase C, but also is unable to block TPA-mediated PLD activity.
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PMID:Exogenous sphingosine 1-phosphate and sphingosylphosphorylcholine do not stimulate phospholipase D in C6 glioma cells. 1045 85


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