Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A specific antibody against nerve growth factor (NGF) and indirect immunofluorescence microscopy have been used to follow the in vitro binding of NGF to cells made permeable to large molecules. All cells tested, both target (sensory neurons and PCI2 cells) and nontarget (3T3, BKH 2I, C6 glioma cells), revealed a decoration of cytoskeletal structures which on the basis of their form, reactivity with antibodies, and sensitivity to specific drugs may be identified as microtubules (MTs) and microfilaments (MFs). The decoration of either structure depends on the fixation and permeabilization conditions: MFs, in the form of stress fibers, are stained by NGF when the plasma membrane is permeabilized with methanol/acetone; MTs become intensely stained when the plasma membrane is solubilized with a nonionic detergent in the presence of a MT-stabilizing medium. The two procedures do not affect the staining of these structures with specific antibodies. Binding of 125I-labeled NGF to PCI2 cells was not competitively inhibited by a 100-fold excess of several positively charged proteins but it was markedly decreased in the presence of DNase I. 125I-Labeled NGF interacted with MTs and F-actin (fixed with paraformaldehyde) in a range of concentrations similar to that used for their cellular localization with NGF-anti-NGF. Our studies show that the specificity and affinity of NGF binding to MTs and MFs is in the range of that of antibodies against tubulin and actin. The possible relevance of these findings to the mechanism of action of NGF in target cells is discussed.
 ...
PMID:Microtubules and microfilaments in fixed and permeabilized cells are selectively decorated by nerve growth factor. 703 86

Butyrate treatment results in the rapid formation of processes on F98 anaplastic glioma cells. The morphological differentiation occurs more rapidly and to a greater extent than that induced by nerve growth factor (NGF). The incorporation of [3H]thymidine is virtually stopped 1 day after treatment of F98 cells with sodium butyrate. Butyrate also caused a large increase in ornithine decarboxylase activity in F98 cells between 6 and 12 h after treatment. This was inhibited by both cycloheximide and actinomycin-D. NGF did not cause these effects. Butyrate also caused an increase in neuron-specific enolase (NSE) content in F98 cells. This effect appeared to be specific for butyrate. Since NSE induction is characteristic only of neurons and neuroendocrine cells, this finding indicates that butyrate is capable of inducing biochemical differentiation along neuronal lines in undifferentiated glioma cells.
 ...
PMID:Butyrate-induced increase in neuron-specific enolase and ornithine decarboxylase in anaplastic glioma cells. 713 40

Peripheral autonomic and sensory neurones derived from the neural crest will survive in vitro only if the culture medium is supplemented with specific factors (for review see ref. 1). For example, the nerve growth factor (NGF), although supporting the survival of sympathetic and spinal sensory neurons, is ineffective on parasympathetic neurones, whereas medium conditioned by chick heart cells (HCM) supports the survival of all three neuronal types. We showed previously that the requirements of cultured spinal sensory ganglion neurones for survival factors changed during development, and so provided a basis for the classification of such factors. We now demonstrate that cultured post-mitotic neurones from chick paravertebral sympathetic ganglia respond differentially to NGF, HCM and medium conditioned by C6 glioma cells (GCM). Thus, there three survival factors are functionally distinct in that they support the survival in culture of discrete subpopulations of sympathetic neurones. Those subpopulations responding to HCM and NGF are shown to differ not only in their requirements for survival factors but also in their contents of the cholinergic and adrenergic marker enzymes choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH).
 ...
PMID:Subpopulations of cultured chick sympathetic neurones differ in their requirements for survival factors. 745 24

Fas/APO-1 is a transmembrane protein of the nerve growth factor/TNF alpha receptor family which signals apoptotic cell death in susceptible target cells. We have investigated the susceptibility of seven human malignant glioma cell lines to Fas/APO-1-dependent apoptosis. Sensitivity to Fas/APO-1 antibody-mediated cell killing correlated with cell surface expression of Fas/APO-1. Expression of Fas/APO-1 as well as Fas/APO-1-dependent cytotoxicity were augmented by preexposure of human malignant glioma cells to IFN gamma and TNF alpha. Further, pretreatment with TGF beta 2, IL1 and IL8 enhanced Fas/APO-1 antibody-induced glioma cell apoptosis whereas other cytokines including TNF beta, IL6, macrophage colony-stimulating factor, IL10 and IL13 had no such effect. None of the human malignant glioma cell lines was susceptible to TNF alpha-induced cytotoxicity. Fas/APO-1 antibody-sensitive glioma cell lines (n = 5), but not Fas/APO-1 antibody-resistant glioma cell lines (n = 2), became sensitive to TNF alpha when co-treated with inhibitors of RNA and protein synthesis. Resistance of human glioma cells to Fas/APO-1 antibody-mediated apoptosis was mainly related to low level expression of Fas/APO-1 and appeared not to be linked to overexpression of the anti-apoptotic protooncogene, bcl-2. Given the resistance of human malignant glioma to surgery, irradiation, chemotherapy and immunotherapy, we propose that Fas/APO-1 may be a promising target for a novel locoregionary approach to human malignant glioma. This strategy gains support from the demonstration of Fas/APO-1 expression in ex vivo human malignant glioma specimens and from the absence of Fas/APO-1 in normal human brain parenchyma.
 ...
PMID:Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. 752 90

A subline of rat C6 glioma cells, C6-10A cells, in which epinephrine can induce nerve growth factor (NGF) synthesis/secretion, was isolated. C6-10A cells have retained their sensitivity to epinephrine for more than 2 years in a medium containing 0.5% fetal calf serum (FCS) but easily lose it in 10% FCS. C6-10A cells are S-100- and glial fibrillary acidic protein-positive, and the doubling time is about 60 h in the medium containing 0.5% FCS and about 20 h in 10% FCS. Epinephrine induced NGF synthesis/secretion prominently in serum-free cultures of C6-10A cells and in cultures with a high cell density, but not in serum-containing cultures. The induction did not occur with parent C6 cells under the appropriate conditions in C6-10A cells. NGF secretion was induced by catecholaminergic compounds in the following order isoproterenol > epinephrine = norepinephrine >> dopamine. The induction caused by epinephrine was blocked by propranolol (beta-blocker) but not by phentolamine (alpha-blocker). Various compounds that activate the adenylate cyclase system also induced NGF synthesis/secretion. These results indicate that C6-10A cells are astrocytes that are highly responsive to beta-adrenergic receptor agonists, which stimulate NGF synthesis/secretion via receptors coupled with adenylate cyclase machinery. These cells may be a useful aid in studying the mechanism of NGF synthesis/secretion.
 ...
PMID:Characterization of C6-10A glioma cells highly responsive to beta-adrenergic receptor agonist-induced NGF synthesis/secretion. 753 21

Human malignant glioma cells are susceptible to apoptosis induced by antibodies to Fas/APO-1, a cytokine receptor protein of the nerve growth factor/tumor necrosis factor receptor superfamily. Here we show that a critical level of cell surface expression of Fas/APO-1 is a prerequisite for induction of glioma cell apoptosis via Fas/APO-1. Although Fas/APO-1 mRNA was expressed in three Fas/APO-1 antibody-resistant glioma cell lines, these cells expressed either little Fas/APO-1 protein (LN-319 and LN-405) or an abnormal Fas/APO-1 protein that was not translocated to the cell membrane and therefore functionally inactive (LN-308). Although all glioma cell lines expressed mRNA for Fas/APO-1-delta TM, a soluble form of Fas/APO-1 lacking the transmembrane domain, none of the cell lines released detectable amounts of soluble Fas/APO-1, a potential endogenous antagonist of Fas/APO-1-mediated glioma cell apoptosis. Stable transfection of three resistant glioma cell lines with a human Fas/APO-1 cDNA expression vector dramatically enhanced cell surface expression of Fas/APO-1 and induced susceptibility to Fas/APO-1 antibody-mediated apoptosis. These data indicate that malignant glioma cells, unlike other tumor cells, uniformly harbor the intracellular cascade required for Fas/APO-1-mediated apoptosis. Low level of Fas/APO-1 expression results from inefficient transcription and translation of the Fas/APO-1 gene or the synthesis of mutant Fas/APO-1 proteins. gamma-Interferon, tumor necrosis factor-alpha, and interleukin 1 beta augmented Fas/APO-1-mediated apoptosis of Fas/APO-1-transfected glioma cells by acting on the subcellular suicidal cascade triggered by Fas/APO-1 activation. Dexamethasone attenuated Fas/APO-1 antibody-induced apoptosis, not only of constitutively Fas/APO-1-positive glioma cells, but also of Fas/APO-1-transfected glioma cells. The antiapoptotic effect of dexamethasone could be overcome by preexposure of the glioma cells to gamma-interferon or by coexposure to Fas/APO-1 antibodies and cycloheximide. Thus, Fas/APO-1 gene transfer and combined immunotherapy using Fas/APO-1 antibodies and cytokines may overcome Fas/APO-1 antibody resistance of Fas/APO-1-negative human malignant glioma cells, which may represent subpopulations within single gliomas or form a separate subgroup of human malignant gliomas.
 ...
PMID:Fas/APO-1 gene transfer for human malignant glioma. 754 Sep 53

Cytokines exert receptor-mediated control over glia. Up-regulation of receptor expression of cytokine production corresponds with the acquisition of a neoplastic phenotype. A modified radial dish assay was used to determine whether in vitro locomotion of glioma cells is modified by the epidermal growth factor, the basic fibroblast growth factor, the bb dimer of platelet-derived growth factor, the nerve growth factor, or the tumor necrosis factor alpha. Human glioma cells were plated in the center of a petri dish with one of these cytokines in 0.5 ml agar (50 ng/ml if the cytokine was distributed evenly throughout the dish) at one edge, and 0.5 ml plain agar at the opposite edge. After 24 hours, a central zone of cells was established; the agar was gelatinized. Feeding medium was added to the dish, and slow elution from the agar established a cytokine gradient. Cell counts were performed daily over 6 to 10 days at predetermined distances on both sides of the central zone to assess directional cellular movement with respect to the cytokine gradient and the plain agar. The epidermal growth factor caused continuous chemoattraction, whereas the tumor necrosis factor alpha caused slight chemorepulsion for 24 to 48 hours, followed by strong chemoattraction. The bb dimer of platelet-derived growth factor, the basic fibroblast growth factor, and the nerve growth factor all maintained chemorepulsion over the entire 6 to 10 days. Therefore, the cytokines did affect glioma cell motility in vitro, and the modified radial dish assay used in this study provided a useful in vitro model for assessing the impact of the cytokines on glioma cell locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modification of human glioma locomotion in vitro by cytokines EGF, bFGF, PDGFbb, NGF, and TNF alpha. 764 98

Our earlier investigations of the biology of the epidermal growth factor receptor (EGFR) in human gliomas demonstrated that the level of EGFR expression did not directly predict the glioma growth response to EGF, suggesting that the function of the EGFR in glioblastomas might not be limited to mediating the growth effects of EGF. We conducted the current studies to investigate the function(s) of the EGFR not related to growth control in human gliomas. These investigations show that the EGFR mediates the stimulative effects of EGF on glial process extension and glial fibrillary acidic protein (GFAP) expression. In addition, the level of EGFR expression correlates inversely with glioma cell responsiveness to differentiation promoting agents (for example, nerve growth factor and transforming growth factor-beta) that act through transmembrane tyrosine kinase receptors. Thus, glioma lines with a high level of EGFR expression (for example, T-98G cells) responded to fewer differentiation promoting factors than lines with a low level of EGFR expression (such as U-373MG cells). Our results suggest that the EGFR in gliomas may participate in mediating the process extension and GFAP stimulative effects of both EGF and other differentiation promoting agents. These properties represent components of the differentiated state in glia because their expression is stimulated by dibutyryl cyclic adenosine monophosphate in normal astrocytes. The involvement of the EGFR in the expression of these glial specific properties suggests that the EGFR may play an important role in glial differentiation.
 ...
PMID:The role of the epidermal growth factor receptor in human gliomas: II. The control of glial process extension and the expression of glial fibrillary acidic protein. 771 12

Prompted by the recent discovery that neurotrophins, which are known to be biologically active as noncovalently linked homodimers, can also be induced to form biologically active heterodimers in vitro, we have investigated the biosynthesis of neurotrophin heterodimers by transfected mammalian cells. When COS cells were cotransfected with expression plasmids for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-3 (NT-3), the appropriate heterodimers were detected in the conditioned medium by immunoprecipitation and, in the case of NGF.NT-3, using a two-site enzyme-linked immunosorbent assay. Heterodimer formation occurred predominantly intracellularly and did not require precursor cleavage, because heterodimers containing pro-NGF and pro-BDNF were detected in the conditioned medium. When rat C6 glioma cells or mouse AtT-20 neuroendocrine cells were cotransfected with expression plasmids for NGF and NT-3, NGF.NT-3 heterodimer was detected at levels comparable with those of homodimeric NGF and NT-3, indicating that heterodimer formation can occur at significant levels in a variety of cell types. These data provide evidence that NGF, BDNF, and NT-3 are capable of forming heterodimers when coexpressed in mammalian cells and suggest that such heterodimers are likely to be formed in vivo when a single cell expresses multiple neurotrophins.
 ...
PMID:The biosynthesis of neurotrophin heterodimers by transfected mammalian cells. 774 82

The monosialoganglioside GM1 has been shown to possess neurotrophic activity in vitro and in vivo and is now used as an experimental treatment for a variety of neurological disorders and trauma. Little is known about the mechanism of action used by GM1. Because GM1 appears to enhance nerve growth factor (NGF) activity, we have used C6trk+ cells, a derivative of C6-2B glioma cells that express the high-affinity receptor for NGF trkA, to determine whether the neurotrophic effects of GM1 occurs through induction of trkA activity. Exposure of C6trk+ cells to NGF (10-50 ng/ml) resulted in a five- to 10-fold increase in trkA tyrosine phosphorylation within 5 min. Incubation of cells with GM1 resulted in a threefold increase in trkA phosphorylation beginning within 1 h and peaking between 3 and 6 h. Optimal responses to GM1 were obtained using 80-100 microM concentrations. Moreover, tyrosine phosphorylation of known trkA target proteins, such as extracellular signal-regulated kinases, and suc-associated neurotrophic factor-induced tyrosine-phosphorylated target, were activated upon stimulation of C6trk+ cells with GM1. In addition, GM1 potentiated the NGF-mediated activation of tyrosine phosphorylation of trkA. GM1 failed to induce phosphorylation of trkA and target proteins in mock transfected cells. Thus, our data demonstrate that GM1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM1 may be attributed to its activation of trkA signal transduction.
 ...
PMID:GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. 779 Aug 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>