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)

In a group of four human tumor cell lines comprising one melanoma, one glioma, one teratocarcinoma and one neuroblastoma, the expression of the intercellular adhesion molecule-1 (ICAM-1) was found to be significantly increased following treatment with 10 microM of all-trans retinoic acid. In the melanoma and glioma cell lines HS 294T and HS 683, greater than 90% of the cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) CL203.4 in the absence of treatment. Retinoic acid increased the cell surface expression of the molecule by 2-fold. In the teratocarcinoma and neuroblastoma cell lines, TERA-2 and SK-N-SH, the constitutive expression of ICAM-1 was weak, the percentage of cells stained above the background being less than 25%. Retinoic acid induced ICAM-1 expression in greater than 80% of the cells and increased the levels of expression by 2.5 to 3-fold. Immunoprecipitation studies in biosynthetically labeled cells as well as RNase protection analysis confirmed that retinoic acid treatment increased the amount of ICAM-1 at both the protein and mRNA level. The induction or stimulation occurred within 24 h, was maximal after 4 days and reversible.
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PMID:Regulation by retinoic acid of ICAM-1 expression on human tumor cell lines. 168 Mar 99

Cultured rat glioma (ASK) cells are morphologically converted from a spindle to an astrocyte form when treated with dibutyryl cAMP. This morphologic transformation is discernible by light microscopy and can be visually quantitated. As described herein, dose-dependent astrocyte generation was demonstrated by treatment of confluent monolayers with forskolin [1], a compound known to activate adenylate cyclase, and the potency of four forskolin derivatives was found to correlate with previously established biologic potential. Neither a crude ginseng extract nor purified ginsenosides were active in the process, but supplementation of the otherwise inactive ginseng extract with 1 demonstrated 50% of the cells were morphologically converted to the astrocyte form at a concentration of approximately 0.0008%. Retinoic acid was also active in this test system; the morphologic transformation was reversed on treatment with colchicine, and intracellular cAMP concentration was elevated approximately 10-fold. Evaluation of 15 retinoids established a general correlation between the activity in this system and other systems reported in the literature. Thus, the astrocyte formation assay appears to provide several advantages that make it attractive as a screen for the detection or evaluation of substances capable of elevating intracellular cAMP concentration. In addition to technical ease, the procedure is rapid, sensitive, and relatively inexpensive.
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PMID:A rapid and sensitive bioassay involving cultured rat glioma cells to screen for substances capable of elevating intracellular cyclic AMP concentration. 284 41

Retinoic acid (RA) inhibited the growth and induced morphological changes in C6 rat glioma cells. The effects of RA on growth rate became apparent after 48 hr and were concentration-dependent and reversible. There was a 60% inhibition of growth using 10(-5) RA, which increased at low serum concentration to over 90% inhibition and was minimized at high concentration of serum. RA did not change the saturation density of the cells. The morphology of C6 cells, was altered from its normal pattern of randomly oriented spindle shaped cells, to cells which aligned to form palisades of fibroblast-like cells. Biochemical analysis of the cells showed no significant change in the activities of several lysosomal hydrolyses or the level of total protein in RA-treated cells compared to control cells. There was, however, a significant decrease in the activity of ornithine decarboxylase early during the treatment with RA, and an increase in the levels of fibronectin secreted into the media by the RA-treated cell. These results suggest that RA can suppress the expression of the transformed phenotype of glioma cells.
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PMID:Effects of retinoic acid on expression of the transformed phenotype in C6 glioma cells. 360 Jan 88

The proteolipid protein (PLP) gene codes for the major central nervous system myelin protein. We have studied the effects of different agents on the expression of the PLP gene in C6 glioma cells. Retinoic acid (RA), but not dexamethasone, estradiol, insulin, growth hormone, or vitamin D3, had a drastic effect, increasing 10-20-fold the level of PLP mRNA. Concomitantly, RA also induced the appearance of the corresponding immunoreactive protein. The increase in PLP RNA level showed a slow kinetics and was blocked by cycloheximide, suggesting a posttranscriptional regulation by RA. Nuclear run-on assays confirmed that the rate of PLP gene transcription was unchanged by RA. In contrast, we found that retinoic acid augmented PLP mRNA stability, causing a substantial increase in its half-life. RA action was independent of cell density, serum, or PDGF but was partially inhibited by bFGF. On the other hand, thyroid hormone caused a moderate increase in PLP mRNA levels in C6 cells but only when the low numbers of thyroid receptors in these cells were increased by retrovirally mediated expression of an exogenous c-erbA/TR alpha-1 gene. Our results indicate that RA specifically up-regulates PLP expression in glioma C6 cells at a posttranscriptional level by increasing PLP RNA half-life.
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PMID:Retinoic acid posttranscriptionally up-regulates proteolipid protein gene expression in C6 glioma cells. 750 83

Effects of various differentiating agents and DNA demethylating agents on the expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), marker enzymes for cholinergic and adrenergic differentiation, respectively, were examined in N-18 neuroblastoma cells. Retinoic acid (RA) and a medium conditioned over C6-glioma cells (GCM), which have been shown to enhance the ChAT activity of PC12 cells, NG108-15 cells and fetal rat brain cells, did not induce ChAT activity of N-18 cells. Treatment of the cells with the DNA demethylating agents alone also did not affect ChAT activity. But after pretreatment of the cells with the DNA demethylating agents, ChAT activity of N-18 cells was greatly increased by either RA or GCM. TH activity of N-18 cells was enhanced by forskolin, an activator of adenylate cyclase. The pretreatment of the cells with the DNA demethylating agents greatly enhanced the induction of TH activity by forskolin. Levels of ChAT and TH messenger RNA were altered in accordance with changes in ChAT and TH activities. Possible mechanisms of the actions of the demethylating agents on cholinergic and adrenergic differentiation are discussed.
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PMID:Induction of cholinergic and adrenergic differentiation in N-18 cells by differentiation agents and DNA demethylating agents. 750 29

Retinoic acid (RA) and nerve growth factor (NGF) are both differentiation factors for central nervous system tumours. Mouse-derived NGF inhibits proliferation of C6 glioma cells in vivo in the absence of serum. Retinoic acid inhibits in vivo growth of C6 gliomas in the subcutaneous tissue of rats. This study evaluated the response of C6 cells implanted in the rat cortex to NGF, RA, or a combination of the two in 89 rats. Tumour size, cellular density and morphology were analysed using light microscopy. Treatment with RA alone resulted in tumour volumes that were 38% of control and 48% of NGF-treated groups. There was no significant difference in the tumour volumes or in cell morphology in C6 cells treated with NGF alone compared to controls. Tumours treated with a combination of RA and NGF were larger however, than tumours treated with RA alone. This suggests that despite the growth inhibitory effects of NGF in vitro, NGF acts to prevent the growth inhibitory effect of RA in vivo.
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PMID:Trans retinoic acid inhibits in vivo tumour growth of C6 glioma in rats: effect negatively influenced by nerve growth factor. 793 86

Thyroid hormone (triiodothyronine; T3) has been shown to control the expression of beta 1-adrenergic receptors (beta 1-AR) in cardiac myocytes, but not in C6 glioma cells. This cell specificity has been attributed to low expression of T3 receptors and high expression of the c-erbA alpha 2 splice variant that interferes with the action of T3. To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) alpha 1 gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TR alpha 1, but not wild-type cells, were responsive to T3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3 had no effect on beta 1-AR gene expression in either set of cells. The beta 1-AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of beta 1-AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the beta 1-AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of beta 1-AR expression in C6 cells is also exerted at the translational level, because there was no correlation between mRNA and protein induction, as determined by radioligand binding studies. We conclude that lack of responsiveness of the beta 1-AR gene in C6 cells to T3 is not due to high expression of c-erbA alpha 2 but to undefined cell-specific factors.
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PMID:Post-transcriptional induction of beta 1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors. 902 5

Malignant gliomas account for more than 60% of all primary brain tumors in adults. Adjuvant chemotherapy in addition to radical surgery and radiation therapy has provided only a modest increase in survival. Retinoic acid has been shown to have growth-inhibitory activity against glioma cells in culture. This provides the rationale for a Phase II study using 13-cis-retinoic acid (CRA) in patients with recurrent malignant brain tumors. The objective of this study was to determine the clinical activity of CRA in patients with a histologically proven diagnosis of malignant brain tumor and documented progressive or recurrent disease after radiation and chemotherapy. Fifty patients with documented recurrent disease were treated with CRA as a single agent p.o. at a dose of 60-100 mg/m2 per day. Three weeks of treatment were followed by 1 week of rest. Of the 43 patients who received more than 4 weeks of therapy, 3 (7%) achieved partial response, 7 (16%) achieved minor response, 13 (30%) remained stable, and 20 (47%) had disease progression. The median time from onset of treatment to disease progression for the whole group of 43 patients was 16 weeks (19 weeks for glioblastomas and 11 weeks for anaplastic glioma), whereas that for the 23 patients with partial response and minor response and who remained stable was 66 weeks, and that for the 20 patients with progressive disease was only 8 weeks. The median survival time for glioblastoma was 58 weeks, and 34 weeks for anaplastic astrocytoma. Toxicity was mainly dermatological, with dry skin and cheilitis. These preliminary results suggest that 13-cis-retinoic acid is active against malignant gliomas and is very well tolerated.
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PMID:Treatment of recurrent malignant gliomas with high-dose 13-cis-retinoic acid. 981 51

Confluent cell monolayers of brain capillary endothelial cells (BCEC) are used widely as an in vitro cell culture model of the blood-brain barrier. The present study describes the influence of cell-culture conditions on tight junctions, filamentous-actin cytoskeleton, and expression of ATP-binding cassette (ABC) transporters in primary cell cultures of porcine BCEC. Astrocyte as well as C6 glioma-conditioned cell culture medium was used in combination with retinoic acid, dexamethasone, cyclic adenosine monophosphate (cAMP) analogs, or 1,25-dihydroxyvitamin D3. It was shown that C6-conditioned medium led to a reorganization of filamentous actin and to an improved staining of zonula occludens-associated protein-1 (ZO-1). Further optimization of these culture conditions was achieved with cAMP analogs and dexamethasone. Retinoic acid, as well as 1,25-dihydroxyvitamin D3, did not improve cellular tight junctions as judged by filamentous actin, ZO-1 rearrangement, and transcellular electrical resistance (TER) measurements. However, these morphological changes did not influence the paracellular permeability of the extracellular marker sucrose. Expression of ABC transporters such as P-glycoprotein, multidrug resistance-associated protein-1(MRP1), and MRP2 were compared by measuring messenger RNA (mRNA) levels in whole-brain tissue, isolated brain capillaries, and cultured cells. In freshly isolated BCEC, mRNA levels of MRP2 and P-glycoprotein dropped by two- to sevenfold, respectively, whereas MRP1 mRNA levels were slightly increased. During cell culture, mRNA levels of MRP1 and MRP2 decreased by up to fivefold, while P-glycoprotein levels remained constant. These results were unaltered by different cell-culture conditions. In conclusion, the present study suggests that paracellular permeability, as well as mRNA expression of the studied ABC transporters in primary cultures, of porcine BCEC are insensitive toward changes in cell-culture conditions.
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PMID:Modulation of transendothelial permeability and expression of ATP-binding cassette transporters in cultured brain capillary endothelial cells by astrocytic factors and cell-culture conditions. 1461 Jun 30

Retinoic acid (RA) is a major chemopreventive agent which exerts strong anti-tumor activity partly by trans-repressing the Wnt/beta-catenin signaling pathway in some tumor cell lines. However, the definite mechanism of RA trans-repression of the Wnt/beta-catenin signaling pathway has not been elucidated clearly. In this work, we found that all-trans retinoic acid (ATRA) significantly inhibited proliferation of glioma cells, accompanied by up-regulation of expression of Axin and altered subcellular distribution of beta-catenin. Transfecting C6 cells with rAxin further confirmed that increased expression of Axin is obligate for inhibition of proliferation and the increase of the cytoplasmic beta-catenin. Our results suggested that Axin might play an important role in RA-mediated anti-proliferative effects of glioma cell lines.
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PMID:ATRA-inhibited proliferation in glioma cells is associated with subcellular redistribution of beta-catenin via up-regulation of Axin. 1821 12


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