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)

3H-5-HT (serotonin) binding and its displacement by various specific subtype ligands and effects on the phosphoinositides (PI) turnover were studied in cultured C6 glioma and N2 neuroblastoma cells from rodents. Saturation analysis of 3H-5-HT binding to C6 cells revealed that its Kd and Bmax were 3.0 nM and 18.0 pmole/mg protein respectively. DOI.HCl (5-HT2 agonist) and ketanserin (5-HT2 antagonist) had the highest affinities in the drug-displacement of 3H-5-HT binding to C6 cells studied. The IC50 values for DOI-HCl and ketanserin were 7.5 x 10(-7) and 3.5 x 10(-8) M respectively. 5-HT also induced 3H-PI breakdown and generated 3H-IP. The EC50 values for 5-HT for this event were in the dose range between 0.5 to 1.5 microM, and this 5-HT-induced response could be blocked by 5-HT2 antagonist ketanserin more effectively than the 5-HT1 antagonist or 5-HT3 antagonist studied. 3H-5-HT binding to N2 cells revealed that its Kd and Bmax were 4.0 nM and 80 pmole/mg protein respectively in the saturation analysis study. The drug-displacement of this binding revealed that MDL 72222 (5-HT3 antagonist) had a higher affinity than ketanserin. The IC50 values for MDL 72222 and ketanserin were 10 nM and 10 microM respectively, when 3 nM of 3H-5-HT was used. Our results indicate that the predominant receptor subtype of 5-HT in C6 and N2 cells are 5-HT2, and 5-HT3 respectively, and that the PI turnover is linked to 5-HT2, but not 5-HT3 receptor activation.
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PMID:Characterization of 3H-serotonin (5-HT) binding and effects on the phosphoinositides (PI) turnover in cultured C6 glioma and N2 neuroblastoma cells from rodents. 133 7

Rat glioma C6 cells, cultured in the presence of the tricyclic antidepressant desipramine, lost a significant number of beta-adrenergic receptors in a time- and dose-dependent manner. A similar loss was observed whether binding was determined on intact cells with the hydrophilic beta-adrenergic antagonist (+/-)-[3H]4-(3-tert-butylamino-2-hydroxypropoxyl)benzimidazole-2-o n HCl ([3H]CGP-12177) or on cell lysates with the more hydrophobic antagonists [125I]iodocyanopindolol or [3H]dihydroalprenolol. When stimulated with the agonist isoproterenol, desipramine-treated cells accumulated less cyclic AMP than control cells. The affinity of the beta-adrenergic receptors for either antagonist or agonist was unchanged after desipramine treatment. Desipramine interacted only weakly with the receptors and competed for [125I]iodocyanopindolol binding with a Ki of 30 microM. The presence in the culture medium of alprenolol or propranolol, potent beta-adrenergic antagonists, however, did not prevent the reduction in receptors by desipramine. Desipramine also caused a loss of beta-adrenergic receptors from cells maintained in serum-free medium and the cells themselves did not contain or secrete endogenous catecholamines. Although desipramine is a potent inhibitor of catecholamine uptake, it appears unlikely that the observed loss of beta-adrenergic receptors in rat glioma C6 cells exposed to the drug is due to an increase in extracellular catecholamine levels or to a direct interaction with the receptors.
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PMID:Effect of the tricyclic antidepressant desipramine on beta-adrenergic receptors in cultured rat glioma C6 cells. 303 98

As a part of a pilot clinical study, a high-performance reversed-phase liquid chromatography analysis was developed to quantify temozolomide in plasma and urine of patients undergoing a chemotherapy cycle with temozolomide. All samples were immediately stabilized with 1 M HCl (1 + 10 of biological sample), frozen and stored at -20 degrees C prior to analysis. The clean-up procedure involved a solid-phase extraction (SPE) of clinical sample (100 microliters) on a 100-mg C18-endcapped cartridge. Matrix components were eliminated with 750 microliters of 0.5% acetic acid (AcOH). Temozolomide was subsequently eluted with 1250 microliters of methanol (MeOH). The resulting eluate was evaporated under nitrogen at RT and reconstituted in 200 microliters of 0.5% AcOH and subjected to HPLC analysis on an ODS-column (MeOH-0.5% AcOH, 10:90) with UV detection at 330 nm. The calibration curves were linear over the concentration range 0.4-20 micrograms/ml and 2-150 micrograms/ml for plasma and urine, respectively. The extraction recovery of temozolomide was 86-90% from plasma and 103-105% from urine over the range of concentrations considered. The stability of temozolomide was studied in vitro in buffered solutions at RT, and in plasma and urine at 37 degrees C. An acidic pH (< 5-6) should be maintained throughout the collection, the processing and the analysis of the sample to preserve the integrity of the drug. The method reported here was validated for use in a clinical study of temozolomide for the treatment of metastatic melanoma and high grade glioma.
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PMID:Determination of temozolomide in human plasma and urine by high-performance liquid chromatography after solid-phase extraction. 766 2

Binding of plasmin(ogen) to rat C6 glioma cells is saturable and kringle-domain dependent. This interaction was studied as a model of plasmin(ogen) receptor interactions in nucleated mammalian cells. Apparent 125I-plasmin dissociation from C6 cell binding sites was slow; however, the dissociation rate was increased when the solution contained diisopropyl phosphoryl-plasmin (0.3 microM), fibrinogen (0.16 or 0.8 mg/ml), 1.08 mM D-Val-L-Leu-L-Lys-p-nitroanilide-HCl (S-2251), or epsilon-amino-n-caproic acid (EACA, 5.0 mM). EACA promoted the most rapid dissociation of plasmin. C6 cell-associated plasmin and plasmin in solution demonstrated similar amidase activity. Only specifically bound plasmin (75% of total binding) was active against S-2251. Plasmin that was initially bound to C6 cells digested fibrinogen in a time- and plasmin concentration-dependent manner. alpha 2-Antiplasmin (alpha 2AP, 0.1 microM) completely inhibited fibrinogenolysis by plasmin that was initially C6- or human umbilical vein endothelial-cell associated. Since alpha 2AP reacts selectively with plasmin in solution (minimally with plasmin bound to cells), fibrinogen digestion by cell-associated plasmin probably occurred only after the plasmin dissociated into solution. Crosslinked fibrin clots were formed in uniform layers over C6 cells. If the cells were incubated with plasmin before addition of fibrinogen and thrombin, the clots were rapidly lysed. alpha 2AP incompletely inhibited fibrinolysis when added after fibrin polymerization (44% inhibition with 0.1 microM alpha 2AP). Fibrinolysis was completely inhibited when alpha 2AP was added before fibrin polymerization. These studies suggest that plasmin must first dissociate from cellular binding sites to mediate fibrinogenolysis or fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrinogenolytic and fibrinolytic activity of cell-associated plasmin. 767 97

Anisoylated Lys-plasminogen streptokinase activator complex (APSAC) was purified from Eminase by chromatography on Superose-12. Purified APSAC did not significantly deacylate within 4 h at 4 degrees C in solution as determined by hydrolysis of D-Val-L-leu-L-lys-p-nitroanilide HCl (S-2251). At 37 degrees C, maximum amidase activity developed in 120 min; epsilon-amino-n-caproic acid (EACA) did not affect the apparent rate of APSAC deacylation but stabilized the streptokinase-plasmin(ogen) complex (SkPl) which formed. APSAC bound to C6 glioma cells and human umbilical vein endothelial cells (HUVECs) in culture. Binding as completely inhibited by EACA suggesting an essential role for the plasminogen kringle domains. Cell-associated APSAC deacylated to form active SkPl which hydrolyzed S-2251 and D-Val-Leu-Lys-7-amino-4-methyl coumarin. The rate of APSAC deacylation was increased when the APSAC was cell-associated. APSAC that was initially bound to C6 cells or HUVECs also activated 125I-plasminogen. This activity may have reflected cell-associated APSAC or APSAC but dissociated into solution. Plasmin was recovered bound to cells and in solution. These studies demonstrate that APSAC associates with cell-surfaces and retains activity. In the circulation, cell-surfaces may provide a significant pharmacologic compartment for intravenously administered APSAC.
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PMID:Binding of anisoylated Lys-plasminogen streptokinase activator complex to cells in culture. 838 80

Pharmacokinetics and antitumor activity of MX2.HCl (MX2), a new morpholino anthracycline, were investigated in rats transplanted 9L gliosarcoma cells in the brain. (1) Pharmacokinetics: AUC of MX2 in the brain tumors which received intracarotid and intravenous injection of 2mg/kg of MX2 were 117.50 and 55.94 micrograms.hr/g, respectively. AUC of the brain tissue was 1.38-3.90 micrograms.hr/g. (2) Antitumor activity: The inhibition of cell growth at the concentration of 0.1 micrograms/ml was 73.1% with MTT assay. The mean survival time in tumor-bearing rats after intracarotid and intravenous injection of 2mg/kg of MX2 prolonged significantly. Therefore, it seems that MX2 will become an efficacious drug for the treatment of malignant glioma.
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PMID:[Pharmacokinetics and antitumor activity of MX2, a new morpholino anthracycline in brain tumor intracerebral transplanted in rats]. 847 Sep 21

We have investigated the modulation of the intracellular calcium concentration ([Ca2+]i) in rat C6 glioma cells following their activation by the agonists 5-hydroxytryptamine.HCl (5-HT) and bradykinin, using single cell imaging of [Ca2+]i with the calcium-sensitive dye Fura-2. The majority of the signals observed involved release of calcium from intracellular stores, and after prolonged application of 5-HT, but not bradykinin, the cells exhibited oscillations in [Ca2+]i levels. These calcium oscillations were dependent on the presence of extracellular calcium, and were unaffected by the calcium channel antagonists nifedipine and verapamil. Caffeine, which in other cell types is able to release calcium from inositol trisphosphate-insensitive stores, had very little effect on [Ca2+]i levels in C6 cells. On the other hand, bradykinin, although able to elevate [Ca2+]i probably by acting via the B2-receptor subtype, was unable to induce any calcium oscillations in these cells.
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PMID:5-Hydroxytryptamine-evoked [Ca2+]i oscillations in rat C6 glioma cells. 879 39

A rat glioma model was employed to estimate the Ca2+ kinetics in the tumor arteriolar smooth muscle cells. Electron microcytochemistry revealed that the density of intracellular Ca2+ deposits in the intra-tumor arteriolar smooth muscle cells was significantly greater, with slightly higher membrane Ca(2+)-adenosine triphosphatase (ATPase) activity, compared to the contralateral cerebral arterioles. Furthermore, the administration of tyrphostin, a tyrosine kinase inhibitor, specifically increased only the intra-tumor blood flow. These findings suggest that the condition of the intra-tumor arteriole alters the susceptibility to contraction by the accelerated Ca2+ influx into the cytoplasm mediated through the tyrosine kinase pathway. After the administration of diltiazem, which also has a blocking effect on the Ca(2+)-channel mediated through this pathway, the local intra-tumor blood flow showed an increase of 39% with a marked decrease of intracellular Ca2+ concentration of the arteriolar smooth muscle cells in the tumor, while the blood flow in the basal ganglia increased by only 8%. The intra-tumor concentration of Nimustine-HCl (ACNU) with co-administration of diltiazem was significantly increased compared to that without the co-administration. Co-administration of diltiazem may be a valuable strategy in chemotherapy for glioma in affording the selective increase of intra-tumor concentration of the anti-cancer drug.
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PMID:A strategy for selective anti-cancer drug concentration increase in rat glioma tissue with Ca(2+)-channel blocker co-administration: calcium kinetics in intra-glioma arteriolar smooth muscle cells. 886

In order to understand if antiplatelet drugs possess direct antineoplastic property, we tested the apoptotic effect of 5 popularly marketed antiplatelet drugs in Taiwan in 6 cultured cancer cell lines (Hep 3B hepatocarcinoma, U87-MG malignant glioma, PC-3 prostate adenocarcinoma, HeLa cervical adenocarcinoma, HL-60 preleukemia and K-562 chronic myelogenous leukemia). While acetylsalicylate and flunarizine exerted no effect on these cancer cells, pentoxifyline (PTX), dipyridamole (DYA) and ticlopidine hydrochloride (T. HCl) displayed a time and dose-dependent apoptotic effect on them except for HL-60 and K-562 cells. PTX induced apoptosis in U87-MG, Hep 3B and HeLa cells, DYA in HeLa cells, while T. HCl in U87-MG, Hep 3B, PC-3 and HeLa cells. Adriamycin also provoked apoptotic effect in all 6 cell lines but neither PTX, DYA nor T. HCl acted synergy with adriamycin to HeLa cells, implicating that they may share a similar pathway for inducing apoptosis. Therefore, our results show that the antiplatelet drugs do possess antineoplastic property in vitro. A co-administration of antiplatelet drugs is noteworthy for an alternative adjunctive therapy in cancer patients.
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PMID:Antiplatelet drugs induce apoptosis in cultured cancer cells. 938 74

The patterns of ganglioside profiles were studied in 10 human glioma and one melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1-4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1-1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha 2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant constituents. The activities of the two key enzymes, GM3 synthetase and lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl showed more pronounced difference in the synthetic rate of each ganglioside type, in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines. On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the antibody binding to these gangliosides were examined in native forms in the cell membrane and in chemically-isolated forms. The intensity of reaction against chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and GM2 was more reactive than GM3; however, the reactivities on the cell surface did not correlate with the chemical content indicating other factors to influence their immunoreactivities.
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PMID:Chemical, metabolic and immunological characterization of gangliosides of human glioma cells. 992 80


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