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)

This study was undertaken to evaluate the colorimetric MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] assay as a means of testing the sensitivity of gliomas to chemotherapeutic agents in vitro. Eight human glioma established cell lines were plated in 96-well tissue culture plates and incubated for 4 days with 10 different anti-cancer agents; 5 different concentrations of each drug were tested. The MTT dye was then added to the wells, and the resulting formazan precipitate was solubilized with dimethylsulfoxide (DMSO). The spectrophotometric absorbance (measured at 570 nm) of control and experimental wells was used to calculate the cytotoxicity index (CI). Values with a CI greater than 50% growth inhibition indicated cytotoxic efficacy (sensitivity to the chemotherapeutic drug). Six of the seven (85.7%) glioma cell lines were highly sensitive at varying concentrations to mitomycin C, cisplatin, and doxorubicin. Four of the seven (57.1%) cell lines demonstrated intermediate sensitivity to mitoxantrone and vinblastine. Five of the seven (71.4%) cell lines exhibited resistance to etoposide, bleomycin, cosmegen, and BCNU. One of the cell lines tested, U-138MG, failed to produce the MTT formazan precipitate, so that the sensitivity of this cell line to the panel chemotherapeutic drugs could not be determined. The variability of the results indicates the need for an in vitro screening method to evaluate the effectiveness of clinical and experimental chemotherapeutic agents. The MTT assay provides a rapid method of screening antineoplastic agents against gliomas for cytotoxicity.
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PMID:Test for chemotherapeutic sensitivity of cerebral gliomas: use of colorimetric MTT assay. 812 70

Previously, we have shown that rat oligodendrocytes release phospholipid and generate arachidonic acid (AA) and leukotriene B4 in response to sublytic C5b-9 formation. In the present study, we investigated the biochemical pathways by which C5b-9 generates AA from clone ROC-1, a fusion product of rat oligodendrocytes and C6 glioma. Cells were incubated for 24 h in the presence of [3H]AA or [3H]myoinositol. They were then sensitized with antibody against hybrid cell stroma and treated for 1 h with C9-depleted human serum (C9D-HS) or C9D-HS reconstituted with C9. Alternatively, cells were treated with C8,C9D-HS or C8,C9D-HS reconstituted with C8 or C8 plus C9 for 1 h. Qualitative and quantitative analysis of the released [3H]AA and [3H]myoinositol radiolabeled products were performed by thin layer chromatography/autoradiography and anion exchange chromatography, respectively. The major [3H]AA radiolabeled products after C5b-9 stimulation comigrated with intact phospholipid and AA standards, and the major [3H]myoinositol radiolabeled product was inositol-1-phosphate. Treatment of cells with phospholipase A2 inhibitors, mepacrine and bromophenacyl bromide, abolished AA release by C5b-9. In the absence of extracellular Ca2+, C5b-9 also failed to induce the release of AA. Interestingly, 1-(5-isoquinolinsulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinases, inhibited AA release by C5b-9, whereas AA release stimulated by the calcium ionophore A23187 was not blocked by H-7. The results suggest that AA generation by C5b-9 from the ROC-1 clone involves activation of Ca2+-dependent phospholipase A2 which is regulated by protein kinase-dependent mechanisms.
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PMID:Arachidonic acid mobilization and phosphoinositide turnover by the terminal complement complex, C5b-9, in rat oligodendrocyte x C6 glioma cell hybrids. 254 10

The high-affinity transport system for glycine in plasma membrane vesicles from C6 glioma cells is dependent on Na+ and also on the presence of Cl- in the incubation medium. This anion requirement is relatively specific for Cl-, since other anions are also capable of stimulating the glycine transport in the following order of decreasing efficacy: Cl- greater than Br- greater than SCN- congruent to I- greater than NO3- greater than F-. Chloride ions raise the Vmax for transport and, to a lesser extent, act on the Km. The data provided by direct measurements of the coupling of sodium and chloride to the transport of glycine by using a kinetic approach suggest a stoichiometry for the translocation cycle catalyzed by the glycine transporter of two sodium ions and one chloride ion per glycine zwitterion.
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PMID:The role of chloride ions on the transport of glycine in plasma membrane vesicles from glial cells. 292 73

Partially purified extracts from neuroblastoma x glioma hybrid cells inhibit via opioid receptors the PGE1-elicited formation of cyclic AMP in the same hybrid cell system. The purification of extracts reveals two active fractions very similar to Met- and Leu-enkephalin by several criteria including treatment with cyanogen bromide. On an average, the intracellular concentration of opioids in hybrid cells is 0.1 pmol per mg protein. The concentration is strongly dependent on the cell density. Furthermore, the content in the hybrids of enkephalin-like peptides is specifically elevated by glucocorticoids.
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PMID:Production and regulation of enkephalin-like peptides in neuroblastoma x glioma cells. 712

The ATP signaling mechanism in neuroblastoma x glioma hybrid NG108-15 cells differentiated by exposure to dibutyryl-cAMP was characterized. In cells loaded with fura-2, ATP rapidly raised the cytosolic Ca2+ concentration ([Ca2+]i); the magnitude of the rise was inversely proportional to the extracellular Na+ concentration. Large increases in cytosolic Na+ concentration, measured with the fluorescent Na+ indicator sodium-binding benzofuran isophthalate, were dose-dependently elicited by ATP. ATP also evoked the entry of ethidium bromide into cells, and this process was inhibited by Mg2+. Inositol-1,4,5-trisphosphate (IP3) generation induced by ATP was totally blocked by removal of extracellular Ca2+, but residual IP3 generation still remained in nondifferentiated cells. In addition, ATP produced a concentration-, time-, and Mg(2+)-dependent biphasic uptake of 45Ca2+. A range of nucleotides and ATP analogues, including CTP, UTP, and GTP, induced only 9-29% of the ATP response. However, adenosine 5'-thiotriphosphate evoked 79% of ATP-induced 45Ca2+ uptake. 45Ca2+ uptake elicited by ATP could be potently blocked by purinoceptor antagonists, but other tested reagents less effectively blocked the action of ATP. When bradykinin was used as an agonist, the [Ca2+]i rise was transient and was insensitive to the extracellular Na+ concentration. Na+ influx, entry of ethidium bromide, and 45Ca2+ uptake were unaffected by bradykinin. Furthermore, bradykinin-evoked IP3 generation was insensitive to extracellular Ca2+. Neither ATP nor bradykinin had any effect on cAMP levels within cells. These data suggest that ATP induces a [Ca2+]i rise in differentiated NG108-15 cells via two distinct Ca2+ influx mechanisms, i.e., a receptor-operated cation channel and pores formed by ATP4-. These mechanisms are distinct from those elicited by bradykinin.
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PMID:Two distinct ATP signaling mechanisms in differentiated neuroblastoma x glioma hybrid NG108-15 cells. 751 80

The effects of tumor necrosis factor-alpha (TNF) on proliferation and cell cycle alterations in human malignant glioma cell lines, SF-188 and LN-382, were investigated by flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique. Low concentrations of TNF (1-100 U/ml) suppressed the growth of SF-188 assessed by cell count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and thymidine incorporation assay, but not that of LN-382. After TNF treatment, the percentage of SF-188 cells in the G0/G1 phase increased, while the percentage of cells in the S phase decreased. LN-382 cells did not show any marked change in cell kinetics. TNF arrests certain human glioma cells in the G0/G1 phase resulting in reduction of deoxyribonucleic acid synthesis in the subsequent S phase, suppressing the proliferation pathway.
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PMID:Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells linked with cell cycle arrest in G1 phase. 751 47

The authors investigated the effects of glioma cells and pharmacological agents on the permeability of an in vitro blood-brain barrier (BBB) to determine the following: 1) whether malignant glia increase endothelial cell permeability; 2) how glucocorticoids affect endothelial cell permeability in the presence and absence of malignant glia; and 3) whether inhibiting phospholipase A2, the enzyme that releases arachidonic acid from membrane phospholipids, would reduce any malignant glioma-induced increase in endothelial cell permeability. Primary cultures of rat brain capillary endothelium were grown on porous membranes; below the membrane, C6, 9L rat glioma. T98G human glioblastoma, or no cells (control) were cocultured. Dexamethasone (0.1 microM), bromophenacyl bromide (1.0 microM), a phospholipase A2 inhibitor, or nothing was added to culture media 72 hours prior to assaying the rat brain capillary endothelium permeability. Permeability was measured as the flux of radiolabeled sucrose across the rat brain capillary endothelium monolayer and then calculated as an effective permeability coefficient (Pe). When neither dexamethasone nor bromophenacyl bromide was present, C6 cells reduced the Pe significantly (p < 0.05), whereas 9L and T98G cells increased Pe significantly (p < 0.05) relative to rat brain capillary endothelium only (control). Dexamethasone reduced Pe significantly for all cell preparations (p < 0.05). The 9L and T98G cell preparations coincubated with dexamethasone had the lowest Pe of all cell preparations. The Pe was not affected in any cell preparation by coincubation with bromophenacyl bromide (p > 0.45). These in vitro BBB experiments showed that: 1) malignant glia, such as 9L and T98G cells, increase Pe whereas C6 cells probably provide an astrocytic influence by reducing Pe; 2) dexamethasone provided significant BBB "tightening" effects both in the presence and absence of glioma cells; 3) the in vivo BBB is actively made more permeable by malignant glia and not simply because of a lack of astrocytic induction; 4) tumor or endothelial phospholipase A2 activity is probably not responsible for glioma-induced increased in BBB permeability; and 5) this model is useful for testing potential agents for BBB protection and for studying the pathophysiology of tumor-induced BBB disruption.
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PMID:Neoplastic and pharmacological influence on the permeability of an in vitro blood-brain barrier. 776 Jan 77

To assess the interaction of carboplatin and hyperthermia in vitro, the thermochemosensitivities of three glioma cell lines, C6 rat glioma cell line, human glioma cell lines T98G and KMG4, were examined by 3-(4,5-dimethylthiazol-2-yl) -2,5 diphenyltetrazolium bromide (MTT) assay. The cell survival of each cell line decreased according to increasing CBDCA concentration and temperature. With a certain CBDCA concentration, the cell survival at following temperature was significantly decreased from that at 37 degrees: 43 degrees C and 44 degrees C for C6 cells (2.5 micrograms/ml); 41 degrees C, 42 degrees C, 43 degrees C and 44 degrees C for C6 cells (128 micrograms/ml); 42 degrees C, 43 degrees C and 44 degrees C for KMG4 cells (8 micrograms/ml) (CBDCA concentration within parentheses). It is generally considered that the highest tolerable temperature of normal brain is 42 degrees C for 60 minutes, while under 43 degrees C, there is a possibility that a sufficient tumoricidal effect might not be obtained. This study revealed enhanced cytotoxicity of CBDCA with hyperthermia at the temperature lower than 42 degrees C and suggests the possibility to gain increased tumoricidal effect without injuring normal brain by hyperthermia at the normal-tissue-tolerant temperature with systemic administration of relatively lower dose of CBDCA.
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PMID:[Synergistic effect of carboplatin and hyperthermia in rat and human glioma cell lines]. 781 71

A surface-associated sulphydryl (thiol) protein (SASP) constitutively present in most nucleated cells was purified from human THP-1 monocytes and rat C6 glioma cells. The human protein was similar in mass and isoelectric point and had the same N-terminal amino acid sequence to adult T-cell leukemia-derived factor (ADF), a growth factor secreted by human lymphoid cells which is able to induce increased expression of interleukin-2 receptors. A further internal amino acid sequence, determined following cleavage of human SASP with cyanogen bromide, was also identical to the corresponding sequence deduced for ADF. Samples of SASP were able to reductively depolymerize human immunoglobulin, a property shared with thioredoxin, a ubiquitous protein, almost identical to ADF, with an essential function in many thiol-dependent reducing reactions. Furthermore, SASP purified from rat C6 glioma cells had an identical N-terminal amino acid sequence to that deduced for rat liver thioredoxin, showing that they were both members of the same family of proteins. The use of membrane-impermeable thiol reagents indicated that SASP was predominantly a cell-surface protein, and was not normally secreted. This SASP protein appeared to be a surface-associated form of thioredoxin that was constitutively present in a wide range of cells and was related to ADF, a secreted form of the same protein.
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PMID:Characterization of a thioredoxin-related surface protein. 781 92

Activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic agents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT activity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. There were wide variations in AGT activity between individuals. No significant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recurrent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma, tumors possessing higher AGT activity tended to be less responsive to post-operation remission-induction therapy including CENUs. The result of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) chemosensitivity assay by using the corresponding surgical specimens suggested a close relationship between cellular resistance to CENUs and AGT activity. It was found to be unlikely that a short term administration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of the relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors.
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PMID:O6-alkylguanine-DNA alkyltransferase activity of human malignant glioma and its clinical implications. 786 Nov 89


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