Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The GLUT1 isoform of the glucose transporter is normally expressed at high levels in differentiated brain vessels that also express a permeability barrier. In contrast, malignant brain neoplasms have relatively undifferentiated vessels that are highly permeable, proliferate to high vascular densities, and often lose GLUT1 expression. Using the rat intracerebral 9L glioma model, we investigated whether dexamethasone-induced changes in permeability are associated with the appearance of other differentiated vascular properties. The percentage of vessels expressing immunohistochemically detectable GLUT1 (74.2 +/- 6.1%) and the tumor vessel density as assessed by laminin immunostaining (282 +/- 37 vessels/mm2) did not vary with control tumor size. Dexamethasone treatment resulted in an 83% reduction of vascular permeability to intravenous Evans blue, an increased percentage of vessels expressing GLUT1 (106.4 +/- 10.5%), lower vascular density (102 +/- 64 vessels/mm2), and smaller tumor size (control cross-sectional area, 17.0 +/- 3.4 mm2; treated, 4.6 +/- 1.0 mm2). Essentially all vessels became GLUT1-positive after dexamethasone treatment. Increased GLUT1 expression by glioma vessels in association with the appearance of other signs of differentiation (low vascular density, slow tumor growth) suggests that immunostaining for GLUT1 may identify neoplasms that are biologically less aggressive.
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PMID:Vascular differentiation and glucose transporter expression in rat gliomas: effects of steroids. 159 83

Dexamethasone is frequently used in the therapy of brain tumor patients. We investigated the effect of dexamethasone on the proliferation of three short-term and four established human glioma cell lines in vitro, using a microculture tetrazolium assay to determine growth rates. In one short-term culture and in one established cell line dexamethasone consistently stimulated the proliferation in a concentration-dependent way. The proliferation was maximally enhanced at a concentration of approximately 0.1 microM. In these two cell lines a relatively high level of glucocorticoid receptors was present, whereas low levels of glucocorticoid receptors were found in the other cell lines. In addition, we demonstrated that the stimulatory effects of dexamethasone on the proliferation of the glioma cell lines can be antagonized by the antiglucocorticoid RU38486. The results demonstrate unequivocally that the glucocorticoid receptor plays a role in the growth stimulating effect of dexamethasone.
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PMID:Implication of glucocorticoid receptors in the stimulation of human glioma cell proliferation by dexamethasone. 164 May 3

Glucocorticoids enhance proenkephalin gene expression in several cell types. To elucidate the mechanism(s) involved, we analyzed the potentiation by dexamethasone of the cAMP-dependent increase in proenkephalin mRNA levels elicited by forskolin in C6 rat glioma cells. This potentiation did not require ongoing protein synthesis. In nuclear run-on transcription assays, dexamethasone alone did not alter proenkephalin transcription, but strongly increased the magnitude and duration of transcriptional elevation by forskolin through a direct action not requiring ongoing protein synthesis. Dexamethasone did not alter basal or stimulated cAMP levels. To search for functionally cooperative glucocorticoid and cAMP regulatory elements, we transfected C6 cells with plasmids containing the chloramphenicol acetyltransferase (CAT) gene under the control of rat proenkephalin sequences from bases -5800 to +703. Maximum stimulation of transiently expressed CAT activity by forskolin required more than 145 and 190 or fewer base pairs of 5'-flanking sequence, implicating sequences up-stream from the previously described cAMP-inducible enhancer. Dexamethasone reduced forskolin-stimulated CAT expression from plasmids with 190 or more base-pairs of 5'-flanking sequence, an effect apparently involving multiple up-stream regions. Dexamethasone also reduced forskolin-stimulated CAT mRNA levels in C6 cells stably transfected with proenkephalin/CAT chimeric genes in the presence or absence of proteins synthesis. In summary, we demonstrate that glucocorticoids and cAMP synergize positively in regulating transcription of the endogenous gene, but interact negatively in regulating the chimeric constructs, which may lack the context or distal element(s) required for positive synergism.
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PMID:Proenkephalin gene expression in C6 rat glioma cells: potentiation of cyclic adenosine 3',5'-monophosphate-dependent transcription by glucocorticoids. 165 36

Northern blot hybridization analysis was used to study regulation of nerve growth factor receptor (NGFR) mRNA content by glucocorticoids. Treatment for 6 h with dexamethasone (1 microM) caused a 40% decrease of NGFR mRNA content in PC12 cells and a 60% decrease in C6-2B glioma cells which was time and dose dependent. Dexamethasone (1 microM/kg) administered s.c. for two days to 21-day-old rats, elicits a 60% decrease in NGFR mRNA content in septum. These results suggest that the expression of NGFR gene in the brain could be inhibited by endogenous glucocorticoids. Whether dexamethasone inhibits NGFR gene expression by directly affecting cis-regulatory elements in the promoter regions of the gene remains to be elucidated.
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PMID:Regulation of nerve growth factor receptor mRNA content by dexamethasone: in vitro and in vivo studies. 217 3

Voltage-gated sodium currents and acetylcholine-elicited currents in clonal rat pheochromocytoma cells (PC12) were studied using the whole-cell patch-clamp technique. After treatment of cultures with nerve growth factor (NGF, 2-4 nM) for 5 or more days, both Na currents and ACh responses increased by 5-7-fold. We tested the ability of a number of treatments reported to induce physiological differentiation in neuroblastoma or neuroblastoma-glioma hybrid cells. We found that no treatment was as effective as NGF, and mitotic inhibitors and 8-bromocyclic AMP reduced the efficacy of NGF at increasing both sodium currents and ACh responses. Some treatments were able to selectively reduce or enhance the ability of NGF to induce ACh responses or sodium currents. Dexamethasone, in particular, completely blocked the NGF-induced increase in ACh response, while leaving Na currents unaffected. Furthermore, in individual cells the Na current density and ACh current density are uncorrelated. These observations indicate that physiological differentiation in PC12 cells is regulated differently than in neuroblastoma cells and, further, in PC12 cells sodium currents and ACh responses are independently regulated.
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PMID:Regulation of sodium currents and acetylcholine responses in PC12 cells. 230 64

Twenty-eight patients with high-grade cerebral gliomas (16 biopsy-proven and 12 diagnosed clinically and by computed tomography scan) were treated with altered fraction radiation and concomitant cisplatin (C-DDP). Twenty cases (Groups IA and IB) whose Karnofsky performance status (KPS) was 60% or less received hypofractionation and C-DDP. All these patients had received high-dose Decadron (Merck Sharp & Dohme, West Point, PA), and their conditions were not improving or progressively deteriorating. The first 11 patients (Group IA) received from 600 cGy twice weekly to 3600 cGy over 3 weeks combined with C-DDP IV at 40 mg/M2 every 2 weeks for two courses. The nine subsequent patients (Group IB) received from 600 cGy weekly to 3600 cGy over 5 to 6 weeks with C-DDP IV at 40 mg/M2 every 1 to 2 weeks for four courses. The target volume in all cases was confined to the tumor as defined on computed tomography (CT) scan with a 2 cm to 3 cm margin. The C-DDP at 40 mg/M2 was administered immediately (within 5 minutes after radiation). Eight cases (Group II) with a KPS of more than 60% were treated with hyperfractionation, i.e., from 200 cGy twice daily to 4800 cGy in just under 3 weeks. The C-DDP was administered every 2 weeks for a total of two courses, as for Group IA. In Group I, 15 of 20 (75%) patients experienced rapid improvement in their performance status, which usually becoming evident within 1 to 2 weeks from the initiation of treatment, and progressed over time. Four patients with a KPS of 10% improved their KPS to over 60%. This regimen was both well tolerated and logistically very convenient both for the patients and attending staff. Follow-up CT scans in three of 16 evaluable patients in the hypofractionated group showed complete tumor resolution. Median survival for Group IA was 7 months, for Group IB was 12 months, and overall was eight months. The Group II median survival was 9 months. This experience suggests that hypofractionated radiation in combination with C-DDP may offer rapid palliation with improvement in functional status in severely compromised patients with malignant glioma.
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PMID:Hypofractionated radiation therapy and concurrent cisplatin in malignant cerebral gliomas. Rapid palliation in low performance status patients. 247 66

Differential hybridization of a cDNA library from rat C6 glioma cells with cDNA probes from naive C6 glioma cells and from cells exposed to 17 beta-estradiol identified cDNAs of an mRNA stimulated by 17 beta-estradiol. This mRNA designated ESP1 mRNA, reached maximal levels after 8 h of treatment with 17 beta-estradiol. The stimulation was not suppressed by cycloheximide. Dexamethasone treatment of C6 glioma cells did not induce ESP1 mRNA. It codes for a 164 amino acids long peptide. The sequence is similar in part to that of CRIP protein, a probably member of the ferredoxin superfamily. The conservation of primary structure suggests a role of ESP1 peptide in oxygen consumption. ESP1 mRNA expression is sexually dimorphic in body tissue, whereas it is expressed to comparative levels in the brain of adult males and females. This suggests that 17 beta-estradiol stimulates the expression of the ESP1 gene in the brain of both gender.
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PMID:Characterization of an estradiol-stimulated mRNA in the brain of adult male rats. 274 28

We have compared the effects of norepinephrine, forskolin, and dibutyryl cyclic AMP (Bt2cAMP) on the regulation of the cytosolic enzyme glycerol phosphate dehydrogenase (GPDH) in the C6 rat glioma cell line. Forskolin and Bt2cAMP elicit a dose-dependent increase in the levels of the enzyme that was, however, unaffected by norepinephrine. The half-maximal effect of forskolin was obtained at 7-8 microM, and the effect was maximal at 30 microM. Dexamethasone at a 50 nM concentration produced a two- to sixfold induction of GPDH after 48 h. The combination of dexamethasone with forskolin or Bt2cAMP leads to an elevation in GPDH levels that is higher than that produced by one of the compounds alone. This potentiation is found when both agents are added together with or after the glucocorticoid. The increase in uninduced and dexamethasone-induced GPDH activity was blocked by cycloheximide and actinomycin D, indicating that de novo protein and RNA synthesis are required. The activity of cytosolic lactate dehydrogenase activity did not change after incubation with dexamethasone, but increased with forskolin or Bt2cAMP.
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PMID:Regulation of glycerol phosphate dehydrogenase and lactate dehydrogenase activity by forskolin and dibutyryl cyclic AMP in the C6 glial cells. 302 Jan 71

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

We have examined insulin receptor regulation by glucocorticoids in the C6 rat glioma cell line. Dexamethasone decreased insulin binding to intact cell monolayers in a dose and time-dependent fashion. The effect is maximal between 48 and 72 h with 50 nM dexamethasone that decreased binding by 40-60%. The natural steroid corticosterone produced a similar effect although it was less potent, and the antiglucocorticoid 17 alpha-methyltestosterone was ineffective in lowering the receptor and partially antagonized the effect of dexamethasone. Total number of binding sites was decreased by glucocorticoids, and when analyzed with a two-site model a 3-fold increase in the dissociation constant (Kd) of the low affinity site was also observed. In the absence of protein synthesis the receptor accumulates at the cell surface, since cycloheximide produced a large increase of insulin binding. Cycloheximide totally blocked the effect of dexamethasone when both compounds were added together to the cells suggesting that protein synthesis is necessary for the effect of the glucocorticoid. By contrast, in cells pretreated with dexamethasone, cycloheximide was unable to produce an increase in cell surface receptor, showing that glucocorticoids probably deplete not only membrane receptor but also total cellular receptor.
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PMID:Glucocorticoids regulate insulin binding in a rat glial cell line. 329 39


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