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)

Cultured C6 rat glioma cells contain mRNA coding for preproenkephalin (A), the precursor of methionine- and leucine-enkephalin. The abundance in untreated cells was determined by blot hybridization methods to be 3-6 pg per micrograms total RNA. Treatment of confluent cells for 12 h with 10 microM (-)-norepinephrine, which activates C6 adenylate cyclase, transiently elevated preproenkephalin mRNA to 3.3 and 7.7 times the control in the absence and presence of the glucocorticoid dexamethasone, respectively. Hydrocortisone and corticosterone also potentiated the effect of norepinephrine. However, glucocorticoids alone did not alter the preproenkephalin mRNA abundance. The effect of norepinephrine + dexamethasone was blocked by the beta-adrenergic antagonist propranolol but not by the alpha-adrenergic antagonist phentolamine. Forskolin, which directly activates adenylate cyclase, similarly elevated the preproenkephalin mRNA abundance; its effect was also potentiated by dexamethasone. C6 cells contain Met-enkephalin-containing protein resembling proenkephalin (apparent Mr 30,000) but little Met-enkephalin, suggesting a low level of proper precursor processing. Treatment with norepinephrine + dexamethasone raised the content of proenkephalin-like protein 11-fold. Thus, preproenkephalin mRNA levels in C6 cells are regulated synergistically by adenosine 3':5'-cyclic monophosphate and glucocorticoids. These results suggest modes of regulation of proenkephalin biosynthesis in normal rat enkephalinergic cells.
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PMID:Expression of the enkephalin precursor gene in C6 rat glioma cells: regulation by beta-adrenergic agonists and glucocorticoids. 287 71

Two series of dimeric enkephalin analogues were assayed for opioid activity in two isolated smooth muscle preparations: the guinea pig ileum (GPI) and the mouse vas deferens (MVD). Dimers have the general structure: X-(CH2)n-X, where X is H-Tyr-D-Ala-Gly-Phe-Leu-NH-(n = 0, 2, 4, 6, 8, 10, 12), for the first series of dimeric pentapeptide enkephalins (DPEn), and H-Tyr-D-Ala-Gly-Phe-NH-(n = 2, 4, 6, 8, 12), for the series of dimeric tetrapeptide enkephalins (DTEn). Comparison of biological activities with binding affinities revealed that: (1) the DPE series with n = 2-8 showed increased potency in the MVD assay relative to monomeric [D-Ala2, Leu5]enkephalinamide (DALEA); (2) there was an associated increase affinity for the delta receptor of rat brain or neuroblastoma-glioma hybrid cells. (however, the relative potencies were higher in the MVD assay then predicted on the basis of binding affinities); (3) the DTE series also showed an increase in delta receptor affinities and MVD potencies relative to DALEA, for n = 2-12; (4) for the DTE series, the increase in MVD activities was less than that expected on the basis of delta binding affinity; (5) for both the DPE and DTE series, activities in the GPI assay and mu-receptor affinities were highly correlated: as the length of the methylene bridge increased from 2 to 12, there was a progressive loss of activity in both assays, with a similar pattern for DPE and DTE. Two selected dimers and their corresponding monomers were also assayed for antinociceptive activity in vivo: results were consistent with GPI and mu-binding but not with MVD and delta-binding. Two alkylamide analogs of penta- and tetrapeptide monomers, representing the monomer with the attached spacer of the most active dimers, were also assayed in biological and binding assays. Comparison of these compounds with the corresponding dimers suggest that the changes in activities and selectivities induced by dimerization are not a spurious effect of the presence of an akylamide derivative of the carboxy terminal of enkephalin but rather may represent a specific effect due to the bivalent nature of the ligands.
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PMID:Receptor binding and biological activity of bivalent enkephalins. 298 28

A radioligand suitable for crosslinking studies to opioid receptors has been obtained by radioiodination and purification of the monoiodotyrosine-27 derivative of the synthetic human beta-endorphin (beta h-endorphin) analogue [5-leucine]beta h-endorphin. The derivative, [27-[125I]monoiodotyrosine,5-leucine]beta h-endorphin, was crosslinked to human striatal (caudate and putamen) and NG108-15 neuroblastoma-glioma cell membranes by using disuccinimidyl suberate. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis under reducing conditions revealed four specifically labeled bands at 68, 40, 30, and 25 kDa for both human caudate and putamen, whereas NG108-15 cell membranes gave specifically labeled bands at 92, 56, 38, and 23 kDa.
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PMID:Preparation of [125I-Tyr27,Leu5]beta h-endorphin and its use for crosslinking of opioid binding sites in human striatum and NG108-15 neuroblastoma-glioma cells. 301 99

The adenylate cyclase (AC) of the neuroblastoma-glioma hybrid cells (NG108-15), is generally considered to be a model for the study of the biochemical correlates of opiate tolerance and dependence. However, the naloxone-induced rebound response of adenylate cyclase, described in some recent reports, is much smaller than that originally described by Sharma, Klee and Nirenberg (1975). Possible explanations for these discrepancies are: (1) a marked down-regulation of opioid receptors and tolerance produced by the use of delta agonists or (2) the use of etorphine, a relatively hydrophobic drug which has slower dissociation rates than morphine. To test these possibilities, neuroblastoma-glioma hybrid cells were treated cells with morphine, etorphine, [D-Ala2,D-Leu5]enkephalin (DADLE), [D-Ala2]Leu-enkephalinamide (DALAMID) or vehicle. In addition, some of the cells treated with etorphine were washed with DADLE to replace the etorphine without producing the rebound response of adenylate cyclase prior to the addition of naloxone. The cells treated with morphine, DADLE and DALAMID, and incubated with prostaglandin E1 (PGE1) and naloxone showed a significant rebound of adenylate cyclase when compared with control groups and opiate-treated cells, incubated only with PGE1. In contrast, naloxone did not induce any significant rebound response in cells treated with etorphine unless they were previously washed with DADLE. These results demonstrate that the lack of a rebound response in cells treated with etorphine was due to the slow dissociation rates of the opiate and not to tolerance or to down-regulation of opioid receptors produced by agonists of high intrinsic activity.
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PMID:The adenylate cyclase rebound response to naloxone in the NG108-15 cells. Effects of etorphine and other opiates. 302 77

[3H]Az-DTLET (Tyr-D-Thr-Gly-Phe(pN3)-Leu-Thr), a photoaffinity probe for delta opioid receptors binds to a single class of sites in rat brain membranes with a high affinity (KD = 1.66 nM). The selectivity index of Az-DTLET (KI delta/KI mu = 0.036) is better than that of its precursor DTLET (0.053). Rat brain or neuroblastoma glioma cells membranes were incubated with 10 nM [3H]Az-DTLET, washed and irradiated with U.V. After irradiation a fraction (20-30%) of specific binding was found to remain indissociable after 10 min at 60 degrees C and was considered as irreversible. This fraction increased as a function of the irradiation time. The radioactivity irreversibly bound to rat brain membranes, solubilized by sodium cholate, was associated with high molecular weight species (200,000 daltons). In denaturing conditions (SDS 2%), the [3H]Az-DTLET specific binding was associated with molecular components of 45-50 K and 90-100 K daltons. In contrast, when opioid receptors were prelabelled by [3H]Az-DTLET, solubilized by Na-cholate and irradiated, the radioactivity was only recovered with subunits of 45-50 K daltons. The autoradiographic localization of the irreversibly bound [3H]Az-DTLET in rat brain was identical to that of reversibly bound [3H]DTLET or [3H]Az-DTLET. These results suggest that [3H]Az-DTLET represents an adequate specific probe for studies on the structure, function and anatomical distribution at light and even electron microscopic level of delta-opioid receptors.
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PMID:Irreversible labelling of delta-opioid receptors in rat brain and neuroblastoma cells by [3H]azido-DTLET: characterization of subunits and autoradiographic visualization of the covalent binding. 303 96

The existence of insulin receptors and biological responses to insulin on macromolecular synthesis have been studied in C6 glioma cells. Binding of 125I-insulin to C6 glioma cells was specific, time- and PH-dependent. Porcine insulin competed for 125I-insulin binding in a dose-dependent manner. Unlabeled polypeptides, including glucagon, bovine growth hormone, bovine prolactin did not compete for 125I-insulin binding. Scatchard analysis of the binding data gave a curvilinear plot which may indicate negative co-operativity or the existence of both high and low affinity (Ka = 7.55 x 10(10) - 4.25 x 10(9] sites. Incubation of cultures with insulin caused a time and dose-dependent stimulation of DNA, RNA and protein synthesis in C6 glioma cells (measured by 3H-thymidine, 3H-uridine or 3H-leucine incorporation into DNA, RNA, or protein respectively). The increase of macromolecular synthesis was admitted at more than 2 nM concentration of insulin. Maximal stimulation of DNA synthesis (142% of control) occurred 6 hours after incubation with 167 nM insulin. The same concentration of insulin caused a 45% increase in 1 hour on RNA synthesis, a 37% increase in 2 hour on protein synthesis. These results indicate that C6 glioma cells have specific insulin receptors capable of mediating effects of insulin on macromolecular synthesis. Insulin in the brain and even blood may be an important growth factor in the glioma cells of the patients with disrupted blood-brain-barrier.
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PMID:Insulin binds to specific receptors and stimulates macromolecular synthesis in C6 glioma cells. 304 34

Gliomas are heterogeneous in their cellular composition, affecting therapeutic efforts such as surgical removal, radiotherapy, chemotherapy and immunotherapy. 106 gliomas were taken into culture in our laboratory and 12 cell lines could be established there from. Experiments were carried out in as many early cultures as possible and with the constant experimental system of the cell lines. To subdivide and possibly classify the heterogeneous group of gliomas the following approaches emerged: Immunostaining of cells for glial markers such as GFAP, A4, A2B5, Leu 7 as well as fibronectin will allow one to distinguish different groups of glial cultures. Performance of growth factor sensitivity tests allows the assessment of major aspects of growth control in cultured gliomas. Cytogenetic evaluation in early cultures and correlation with the expression of oncogenes may yield useful information on mechanisms of escape from normal growth control. One of our cell lines (NCE-G28) in which cells switch from GFAP to fibronectin expression and transiently express the x-hapten may serve as a model to study crucial aspects of cellular differentiation. Using different extracellular matrices for the initiation of cultures even from very benign lesions with low proliferative potential it is possible to include these into comparative studies with glioblastomas.
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PMID:Glioma biology in vitro: goals and concepts. 306 73

Non-saturable penetration and the V and Km constants of saturable influx of leucine, lysine and glycine were always greater in cultured neuroblastoma (C1300) than in glioma (C6) cells. Aspartate uptake was detected only in glioma cells. Unstimulated efflux of the amino acids was initially fast in both cell types but soon slowed down. The efflux of glycine and aspartate exhibited no heteroexchange, the efflux of lysine was stimulated by extracellular leucine and that of leucine slightly by lysine and glycine but only in glioma cells.
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PMID:Transport of leucine, lysine, glycine and aspartate in neuroblastoma C1300 and glioma C6 cells. 312 24

The nature of vascular permeability factor (VPF) activity derived from serum-free conditioned medium containing cultured human malignant glial tumors has been further investigated. A 1000-fold purification was accomplished by sequential heparin-Sepharose affinity chromatography and high-performance liquid chromatography gel filtration chromatography steps. Vascular permeability factor activity falls into a molecular weight range of 41,000 to 56,000 D. Activity is bound to hydroxylapatite, carboxymethyl-Sepharose, phenyl-Sepharose, and heparin-Sepharose, whereas little or no activity was bound to diethylaminoethyl-Sephacel. Vascular permeability factor activity is trypsin- and pepsin-sensitive but is unaffected by treatment with ribonuclease A. This suggests that VPF is a hydrophobic, positively charged (cationic) polypeptide with a potentially biologically significant affinity for heparin. As most proteins are negatively charged (anionic) and have no affinity for heparin, a significant advantage was gained by performing these purification steps. The activity of VPF is not inhibited by coinjection of conditioned medium with soybean trypsin inhibitor; or hexadimethrine (both known antagonists of tissue plasminogen activator, Hageman factor, and serum kallikrein); or aprotinin (an antagonist of both plasmin and tissue kallikrein); or phenylmethanesulfonyl fluoride (a serine esterase (elastase) inhibitor); or pepstatin-A (an acid protease inhibitor which inactivates vascular permeability-inducing leukokinins). These data, together with the fact that VPF is produced and released into serum-free media, provides substantial evidence against it being one of the more commonly known serum-derived permeability mediators. Treatment with dithiothreitol inhibited VPF activity, indicating the presence of at least one essential disulfide bond in this molecule. Inhibition by dexamethasone of VPF expression in cultured malignant glial cells appears to be selective. Dexamethasone-induced inhibition of VPF was dose-responsive and was not associated with a parallel inhibition of cellular protein synthesis as determined by tritiated leucine incorporation into trichloroacetic acid-precipitable material. Inclusion of dexamethasone in the culture medium was not associated with altered cell viability or cell number. A series of in vivo studies confirmed the inhibition of VPF activity in test animals pretreated with dexamethasone. This steroid-induced inhibition was partially reversed by treatment of test animals with actinomycin D prior to exposure to dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Further characterization of malignant glioma-derived vascular permeability factor. 313 21

Chronological changes of glioma tissues treated with local immunotherapy with OK-432 were examined by immunohistochemical method. OK-432 was injected into glioma tissues through Ommaya's reservoir 3 days (3 patients), 7 days (2 patients) and 14 days (2 patients) prior to the operation. Frozen sections surgically obtained from these patients were stained with avidin-biotin-peroxidase complex method using Leu-series monoclonal antibodies for pan T lymphocytes (Leu-1), cytotoxic/suppressor T lymphocytes (Leu-2 a), helper/inducer T lymphocytes (Leu-3 a), B lymphocytes (Leu-12), MHC class I antigen (beta 2m) and MHC class II antigen (HLA-DR). In 2 out of 7 glioma tissues obtained before local injection of OK-432, only few T lymphocytes were found infiltrating around the small blood vessels. In all glioma tissues obtained 3 and 7 days after injection, coagulation necrosis of glioma tissues was observed within 1-2 cm from Ommaya's tube and many T lymphocytes granulocytes and macrophages were infiltrating diffusely in the glioma tissues. Whereas in all glioma tissues obtained 14 days after injection, coagulation necrosis was also observed, however granulocytes and macrophages were scarce. The most of the infiltrating cells were T lymphocytes. Examination of T lymphocytes phenotypes revealed that both cytotoxic/suppressor and helper/inducer phenotypes of T lymphocytes were intermingled with each other in all cases. beta 2m was expressed on the most of glioma cells in all cases before and after injection. Whereas HLA-DR antigen was expressed on the tumor cells in 4 out of 7 cases before injection, however this antigen was expressed in all cases after injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Local immunotherapy with OK-432 for malignant gliomas--immunohistochemical analysis of chronological changes of tumor tissues]. 322 36


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