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)

Five cultured human glioma cell lines were investigated for their reaction to prostaglandin (PG) D2 and E2. In all cases a suppressive effect on DNA synthesis as assessed by 3H-thymidine incorporation was seen with all test substances as early as six hours after the addition of the compounds in doses of usually 10(-5) M. A dose response curve was generated in four cases and showed an estimated ED 50 of about 5 X 10(-6)M. The effect was most pronounced at 12 hours after which the cultures began to recover except those which had been incubated with PGD2. In those cultures which had been exposed to PGD2 virtually no thymidine incorporation was seen after 24 hours and as long as 72 hours. In another set of experiments, the effect of PGD 2, PGE 2, two synthetic PGD 2 analogues, with a chlorine substitution in position 9 (DACl) or with a fluoride substitution in position 9 (DAF) and a synthetic prostacyclin-analogue (Iloprost) was investigated after single and repeated addition of the compounds. A second administration after 12 hours of incubation did not result in a further decrease in 3H-thymidine incorporation like that observed during that first incubation period. In general the cells recovered after 24 hours total incubation time except those which had received PGD 2 or repeated doses of PGE 2. Only in those cells which had been treated with PGD 2, an almost complete blockade of 3H-thymidine incorporation was seen even after the single administration. Parallel evaluation of the cells by flow cytometry showed effects on cell cycle distribution at different times of the incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandins: antiproliferative effect of PGD 2 on cultured human glioma cells. 346 33

We studied the effect of intracarotid administration of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat C6 glioma by the hydrogen clearance method. Iloprost at doses of 0.1 and 0.5 micrograms/kg/min produced a selective increase of the regional cerebral blood flow in the tumour (17.8 +/- 5.6%, p < 0.05 and 27.3 +/- 10.3%, p < 0.05, respectively) without significant change of the regional cerebral blood flow in the ipsilateral hemisphere and the systemic arterial pressure. At a dose of 1 microgram/kg/min, iloprost produced a significant reduction of a systemic blood pressure, but did not change the regional cerebral blood flow significantly both in the tumour and the ipsilateral hemisphere. These results indicated that brain tumour vessels could respond to iloprost in a different fashion from the normal brain capillaries. The selective action of iloprost to the tumour vessels might contribute to the drug-delivery in malignant brain tumour.
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PMID:Effects of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat brain tumour. 751 Mar 71

Neuroblastoma x glioma hybrid NG108-15 cells endogenously express at least three receptors which activate adenylate cyclase via the intermediacy of the stimulatory G-protein, Gs. Sustained exposure of the cells to agonists at the IP prostanoid receptor results in a substantial decrease in cellular levels of the alpha-subunit of Gs (Gs alpha) [McKenzie and Milligan (1990) J. Biol. Chem. 265, 17084-17093; Adie, Mullaney, McKenzie and Milligan (1992) Biochem J. 285, 529-536]. By contrast, equivalent treatments of the cells with agonists at either the A2 adenosine receptor or the secretin receptor have no measurable effect on cellular amounts of Gs alpha. To examine whether this is a feature specific to the IP prostanoid receptor or is related to the level of expression of the individual receptors, NG108-15 cells were transfected with a construct containing a human beta 2-adrenoceptor cDNA under the control of the beta-actin promoter. Two clones of these cells were examined in detail, beta N22, which expressed some 4000 fmol/mg of membrane protein, and clone beta N17, which expressed approx. 300 fmol/mg of membrane protein of the receptor. Exposure of beta N22 cells to the beta-adrenergic agonist isoprenaline resulted maximally in some 55% decrease in membrane-associated levels of Gs alpha, without effect on membrane levels of Gi2 alpha, Gi3 alpha, G(o) alpha or Gq alpha/G11 alpha. Dose-response curves to isoprenaline in beta N22 cells indicated that half-maximal down-regulation of Gs alpha was produced by approx. 1 nM agonist. Equivalent exposure of beta N17 cells to isoprenaline did not significantly modify levels of any of the G-protein alpha subunits, including Gs alpha. In beta N22 cells the IP prostanoid receptor was expressed at similar levels to those in wild-type NG108-15 cells, and treatment with iloprost resulted in a similar down-regulation of cellular Gs alpha levels. Iloprost was also effective in causing down-regulation of Gs alpha levels in clone beta N17. Concurrent addition of both isoprenaline and iloprost to clone beta N22 resulted in less than additive down-regulation of Gs alpha. These results demonstrate that the phenomenon of agonist-induced specific G-protein down-regulation is determined by the levels of expression of the receptor.
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PMID:Agonist regulation of cellular Gs alpha-subunit levels in neuroblastoma x glioma hybrid NG108-15 cells transfected to express different levels of the human beta 2 adrenoceptor. 751 55