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)

Human glioma cells (12-18) and fetal neural cells (CH II) in culture were exposed for 20 hr to [14C]glucosamine to determine the level and distribution of radiolabel incorporated into gangliosides. Cells of identical passage levels at two stages of growth, preconfluent and confluent, were preincubated for 0 to 60 hr in serum-free medium (SFM). Both higher cell densities and longer incubations in SFM caused a change in the amounts and patterns of radiolabeled gangliosides. Preincubation for 60 hr in SFM caused an increase (P less than 0.05) in the percent of total recovered ganglioside radiolabel in GM1 of CH II cells, from 10.5 to 16.7% in preconfluent cells and from 14.1 to 31.9% in confluent cells. Conversely, the proportion of radiolabel in GM3 and GM2 decreased with longer preincubations in SFM. A similar preincubation of glioma cells caused an increase in the proportion of label into GD1a of both preconfluent and confluent cells (P less than 0.02) from 4 to 11% of the total ganglioside radioactivity. Higher cell densities also resulted in consistently higher percent (of total ganglioside) incorporation into GD1a of 12-18 cells (P less than 0.05) and GM1 of CH II (P less than 0.01). These results show that there is a shift in the incorporation of precursor label into more complex gangliosides under conditions associated with the arrest of cell division. These phenomena may represent a regulatory response of the ganglioside biosynthetic apparatus to changes in extracellular environment and cell contact.
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PMID:Effects of human brain cell culture conditions on [14C]glucosamine radioactivity incorporation into gangliosides. 687 78

D-Glucosamine is toxic to several malignant cell lines and in vivo tumors at concentrations that have little effect upon normal host tissues. Evidence is presented to support the hypothesis that cellular membranes may be the primary targets of glucosamine's tumoricidal activity. Treatment of rat C6 glioma cells with a cytotoxic concentration of glucosamine (20 mM) caused fragmentation of rough endoplasmic reticulum, proliferation of Golgi complexes, evagination of outer nuclear and mitochondrial membranes, and the accumulation of membranous vacuoles and lipid droplets in the cytoplasm. These changes were detected within the first 3 hr after treatment of cultures with glucosamine and became increasingly severe until cell lysis occurred between 24 and 48 hr of treatment. The cytotoxicity of glucosamine was potentiated by the local anesthetic lidocaine, and by other membrane-active drugs, at concentrations that were growth inhibitory but nonlytic. Most of these drugs possessed local anesthetic activity and inhibited glioma sterol synthesis. Within the same period of time required for ultrastructural changes in cellular membranes, glucosamine inhibited the incorporation of [2-(14)C]acetate into sterols and into an unidentified 400-dalton lipid that migrated close to sterols on thin-layer chromatograms. This inhibition was potentiated by lidocaine and increased over the same range of D-glucosamine concentrations that led to increased cell toxicity after a 48-hr treatment. These findings suggest that the effects of glucosamine upon cellular membranes may be central to its tumoricidal activity and that glucosamine, in combination with membrane-active drugs, may be useful in the treatment of certain types of tumors, particularly those of the central nervous system.
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PMID:Membrane-active drugs potentiate the killing of tumor cells by D-glucosamine. 692 67

A detailed analysis of mammalian cell surface proteins is described by a new two-dimensional polyacrylamide gel electrophoresis technique. The first dimension gel contains 2% acrylamide, 0.1% sodium dodecyl sulfate, 0.3% Triton CF10 and 9 M urea. A combination of the detergents and urea permits the separation of poorly soluble, hydrophobic cell surface proteins. Under these conditions, the molecular size of proteins has a limited contribution to the fianl separation due to a low acrylamide concentration. Differences in charge properties, hydrophobicity, and glycosylation are the elements determining the resolution. In the second dimension, the proteins are separated primarily according to molecular weights, by a conventional polyacrylamide gel system in the presence of 0.1% sodium dodecyl sulfate. In this study, proteins of C6 rat glioma cell line are characterized. Cell surface proteins are specifically radio-labeled with 125I by a lactoperoxidase method, and compared with presumptive integral surface proteins which are resistant to extraction with 0.1 M NaOH. Also studied are total cellular proteins, fucose- and glucosamine-containing glycoproteins, and protein species with variable susceptibility to weak trypsin digestion. The electrophoresis system allows an unambiguous identification of each protein species.
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PMID:A two-dimensional polyacrylamide gel electrophoresis system for the analysis of mammalian cell surface proteins. 700 22

Inhibitors of astrocyte cell division, immunologically related to the sugar moiety of epidermal growth factor receptor and to blood group antigens, have been purified from mammalian brain extracts. Mass spectra, high resolution proton magnetic resonance spectra, and chemical and enzymic analysis of the purified fraction indicated that the compounds isolated were glycosphingolipids, although signals compatible with the presence of aminoacid residues were also observed. Lectin binding indicated the presence of NAc-Neuraminic acid, NAc-glucosamine, fucose, galactose, and glucose. The inhibitor was cytostatic for astrocytes, C6 glioma cells, and endothelial cells, with approximate ID50 of 250 nM. Primary cultures of fibroblasts or 3T3 cells were not affected up to concentrations of 800 nM. Concentrations of the inhibitor of 800 nM or higher, caused non-specific cytotoxicity. The biological and immunological properties of this brain inhibitor were identical to those of the EGF receptor-related inhibitor previously described with the acronym ERI. Because of its source and cytostatic action, the glial inhibitor has been renamed neurostatin. Rabbit antibodies to neurostatin immunostained astrocytes and neurons, both in culture and in tissue sections.
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PMID:Control of glial number: purification from mammalian brain extracts of an inhibitor of astrocyte division. 960 Mar 84

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

Sphingosine 1-phosphate (S1P) induced the inhibition of glioma cell migration. Here, we characterized the signaling mechanisms involved in the inhibitory action by S1P. In human GNS-3314 glioblastoma cells, the S1P-induced inhibition of cell migration was associated with activation of RhoA and suppression of Rac1. The inhibitory action of S1P was recovered by a small interference RNA specific to S1P(2) receptor, a carboxyl-terminal region of Galpha12 or Galpha13, an RGS domain of p115RhoGEF, and a dominant-negative mutant of RhoA. The inhibitory action of S1P through S1P(2) receptors was also observed in both U87MG glioblastoma and 1321N1 astrocytoma cells, which have no protein expression of a phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These results suggest that S1P(2) receptors/G(12/13)-proteins/Rho signaling pathways mediate S1P-induced inhibition of glioma cell migration. However, PTEN, recently postulated as an indispensable molecule for the inhibition of cell migration, may not be critical for the S1P(2) receptor-mediated action in glioma cells.
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PMID:S1P(2) receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN. 1808

Therapeutic benefit in glial tumors is often limited due to low permeability of delivery systems across the blood-brain barrier (BBB), drug resistance, and poor penetration into the tumor tissue. In an attempt to overcome these hurdles, polyether-copolyester (PEPE) dendrimers were evaluated as drug carriers for the treatment of gliomas. Dendrimers were conjugated to d-glucosamine as the ligand for enhancing BBB permeability and tumor targeting. The efficacy of methotrexate (MTX)-loaded dendrimers was established against U87 MG and U 343 MGa cells. Permeability of rhodamine-labeled dendrimers and MTX-loaded dendrimers across the in vitro BBB model and their distribution into avascular human glioma tumor spheroids was also studied. Glucosylated dendrimers were found to be endocytosed in significantly higher amounts than nonglucosylated dendrimers by both the cell lines. IC 50 of MTX after loading in dendrimers was lower than that of the free MTX, suggesting that loading MTX in PEPE dendrimers increased its potency. Similar higher activity of MTX-loaded glucosylated and nonglucosylated dendrimers was found in the reduction of tumor spheroid size. These MTX-loaded dendrimers were able to kill even MTX-resistant cells highlighting their ability to overcome MTX resistance. In addition, the amount of MTX-transported across BBB was three to five times more after loading in the dendrimers. Glucosylation further increased the cumulative permeation of dendrimers across BBB and hence increased the amount of MTX available across it. Glucosylated dendrimers distributed through out the avascular tumor spheroids within 6 h, while nonglucosylated dendrimers could do so in 12 h. The results show that glucosamine can be used as an effective ligand not only for targeting glial tumors but also for enhanced permeability across BBB. Thus, glucosylated PEPE dendrimers can serve as potential delivery system for the treatment of gliomas.
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PMID:Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability. 1817 Oct 13

Autophagy can promote cell survival or death, but the molecular basis of its dual role in cancer is not well understood. Here, we report that glucosamine induces autophagic cell death through the stimulation of endoplasmic reticulum (ER) stress in U87MG human glioma cancer cells. Treatment with glucosamine reduced cell viability and increased the expression of LC3 II and GFP-LC3 fluorescence puncta, which are indicative of autophagic cell death. The glucosamine-mediated suppression of cell viability was reversed by treatment with an autophagy inhibitor, 3-MA, and interfering RNA against Atg5. Glucosamine-induced ER stress was manifested by the induction of BiP, IRE1alpha, and phospho-eIF2alpha expression. Chemical chaperon 4-PBA reduced ER stress and thereby inhibited glucosamine-induced autophagic cell death. Taken together, our data suggest that glucosamine induces autophagic cell death by inducing ER stress in U87MG glioma cancer cells and provide new insight into the potential anticancer properties of glucosamine.
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PMID:Glucosamine induces autophagic cell death through the stimulation of ER stress in human glioma cancer cells. 2064 3

The development of optimal culture methods for embryonic, tissue and cancer stem cells is a critical foundation for their application in drug screening. We previously described defined adherent culture conditions that enable expansion of human radial glia-like fetal NS (neural stem) cells as stable cell lines. Similar protocols proved effective in the establishment of tumour-initiating stem cell lines from the human brain tumour glioblastoma multiforme, which we termed GNS (glioma NS) cells. Others have also recently derived more primitive human NS cell lines with greater neuronal subtype differentiation potential than NS cells, which have similarities to the early neuroepithelium, named NES (neuroepithelial stem) cells. In the present paper, we discuss the utility of these cells for chemical screening, and describe methods for a simple high-content live-image-based platform. We report the effects of a panel of 160 kinase inhibitors (Inhibitor Select I and II; Calbiochem) on NES cells, identifying three inhibitors of ROCK (Rho-associated kinase) as promoting the expansion of NES cell cultures. For the GNS cells, we screened a panel of 1000 compounds and confirmed our previous finding of a cytotoxic effect of modulators of neurotransmitter signalling pathways. These studies provide a framework for future higher-throughput screens.
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PMID:Imaging-based chemical screens using normal and glioma-derived neural stem cells. 2065 5

High exposure to cadmium is a risk factor for many neuronal diseases. Overexpression of cyclooxygenase (COX)-2 is linked to many neuroinflammatory and neoplastic diseases. We, herein, investigated the effect of cadmium on the expression of COX-2 in C6 rat glioma cells. Treatment with cadmium sulfate (cadmium) increased the expression of COX-2 mRNA. Remarkably, cadmium treatment further increased expression of not only the N-glycosylated COX-2 protein of 72 kDa but also the unglycosylated COX-2 of 66 kDa, as assessed by the unglycosylated COX-2 induced by tunicamycin or glucosamine, known inhibitors of COX-2 N-glycosylation. Of note, when translation was blocked in the presence of cycloheximide (CHX), levels of both N-glycosylated and unglycosylated COX-2 proteins induced by cadmium rapidly declined but the decline was prevented by MG132, a 26S proteasomal inhibitor. However, in the absence of CHX, cadmium induced and maintained expression of the unglycosylated COX-2 proteins. Pharmacological inhibition studies importantly demonstrated that the cadmium-mediated COX-2 transcriptional upregulation in C6 cells was not shown by exogenous glutathione (GSH) supplementation or treatment with inhibitors of extracellular signal-regulated protein kinase-1/2 (ERK-1/2), p38 MAPK and c-Jun N-terminal protein kinase-1/2 (JNK-1/2), respectively. Expression of COX-2 was not noted in C6 cells exposed to other heavy metals (cobalt or manganese). These results demonstrate that cadmium specifically induces expression of COX-2 through both transcriptional and co-translational (N-glycosylation) regulation in C6 cells in which the cadmium-induced COX-2 transcriptional upregulation is closely related to oxidative stress-dependent activation of the family of MAPKs and the cadmium-induced expression of both N-glycosylated and unglycosylated COX-2 proteins is proteasome- and translation-dependent.
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PMID:Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells. 2276 15


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