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)

We have explored the potential for cloning novel neurotrophic factor cDNAs via assay of neurotrophic activities following expression in Xenopus oocytes. In this report, we describe the successful application of the method to tract rat ciliary neurotrophic factor (CNTF) activity from mRNA purified from cultured cells and from mRNA synthesized by in vitro transcription of a cDNA library. Rat C6 glioma cells, which had been previously shown to have CNTF-like activity (Westermann et al., 1988), were used as source material. We tested protein extracts of C6 cells using an in vitro assay of primary neurons from the chick ciliary ganglion (CCG assay) and detected a CNTF-like activity. RNA isolated from C6 cells was shown to direct the synthesis of the activity following microinjection into Xenopus oocytes and one-step fractionation of Xenopus extract. C6 mRNA was size-fractionated, and fractions encoding CNTF-like activity were cloned into a lambda phage vector at a site distal to a T7 promoter. Synthetic RNA transcribed from total library DNA was injected into Xenopus oocytes, and a CNTF-like activity in the oocyte extract was detected by the CCG assay. Further fractionation of library clones narrowed the presence of the clone encoding the CNTF-like activity to a pool containing 20,000 members. The presence of a full-length CNTF cDNA clone in this pool and partial clones in other pools was confirmed by Polymerase Chain Reaction (PCR) using oligonucleotides from the rabbit CNTF cDNA (Lin et al., 1989) as primers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression cloning of neurotrophic factors using Xenopus oocytes. 162 43

Two kinds of novel neural trophic factors were currently detected in von Recklinghausen neurofibroma (NF1) extracts. One of the two was a growth factor, neuroblastoma growth factor (Mr less than 5 kDa), which promotes the proliferation of human neuroblastoma cell and survival and neurite-extension of rat cortical neurons, but differently from nerve growth factor (NGF) or NGF-like factors. The other one was a glial growth inhibitor (Mr = 100 kDa), which suppresses the growth of glioma cell lines, astrocytoma, glioblastoma, oligodendroglioma and Schwannoma. These factors do not appear to be previously identified cytokines or growth factors such as interleukins, granulocyte colony-stimulating factor, NGF and fibroblast growth factor. There was also detectable ciliary neurotrophic factor-like activity in the extracts. The primary cause of high contents of these factors in NF1 is not known, but may relate to fundamental mechanisms controlling growth and differentiation of neurons and glias during development of nervous system.
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PMID:von Recklinghausen neurofibroma produces neuronal and glial growth-modulating factors. 193 68

The effect of ciliary neurotrophic factor (CNTF) on beta-amyloid precursor protein (APP) gene expression was investigated in cultured rat C6 glioma cells and human SH-SY5Y neuroblastoma cells. CNTF increased APP mRNA abundance in C6 glioma cells in a dose-dependent manner, with an approximately 3-fold increase in maximum observed after 24 h with a concentration of 1 ng/ml. However, no significant differences in the splicing pattern of the three major isoforms of APP mRNA were apparent between control and CNTF-treated C6 glioma cells. CNTF had no effect on APP mRNA abundance in SH-SY5Y neuroblastoma cells. These findings suggest that CNTF can modulate APP mRNA expression and might affect amyloidogenesis in Alzheimer's disease.
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PMID:Ciliary neurotrophic factor induced-increase in beta-amyloid precursor protein mRNA in rat C6 glioma cells. 794 86

Survival and differentiation of a sympathoadrenal progenitor cell line (termed MAH), transduced with a v-myc oncogene, was studied subsequent to transplantation in the peripheral and central nervous system of adult rats. In the brain, MAH cell survival depended on the secretion of ciliary neurotrophic factor (CNTF) by co-grafts of genetically modified glioma cells. No trophic factor supplement was required for development of the MAH cells in the peripheral nerve environment. Transplanted progenitor cells withdrew from the cell cycle within 48 h and differentiated into a prominent population of large sympathetic-like neurons. The neurons expressed the alpha subunit of the CNTF receptor and appropriate spatial distributions of cytoskeletal proteins and catecholamine related enzymes. The results identify a role for CNTF in the development of the sympathoadrenal cell lineage and support the concept of immortalized progenitor cells as alternatives to primary cells for cell replacement strategies in the nervous system.
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PMID:Ciliary neurotrophic factor promotes the terminal differentiation of v-myc immortalized sympathoadrenal progenitor cells in vivo. 857 93

The authors have shown previously that in addition to its survival effects on neurons and glia, ciliary neurotrophic factor (CNTF) induced potent cachectic effects and acute phase proteins when present in the peripheral circulation at concentrations of < or = 10 ng/ml. These effects did not depend upon the induction of other cytokine family members. Described here are the specific physiological effects which systemic administration of CNTF can induce in somatic tissue. Mice implanted with C6 glioma cells, genetically modified to secrete CNTF, exhibited rapid catabolism of adipose tissue and skeletal muscle, depressed steady-state levels of glucose and triglycerides, elevations in red blood cell content, gall bladder hypertrophy and thymic atrophy, with a disproportionate loss of CD4+/CD8+ T cells. This cachectic wasting resulted in death over a period of 7-10 days. Implantation of the parental C6 line, or C6 cells which express a non-secreted form of CNTF, did not result in overt effects over this time period. These findings have implications both for the biology of CNTF family members, and the therapeutic use of factors such as CNTF in vivo.
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PMID:Physiological effects of CNTF-induced wasting. 898 Aug 80

In this work we studied the subcellular localization of ciliary neurotrophic factor (CNTF) in primary culture of rat cortical type I astrocytes and rat glioma C6 cells, transfected COS-7 cells and in the Xenopus oocytes. In all these models, morphological and biochemical evidence are provided for the nuclear localization of CNTF. In addition the nuclear translocation of CNTF is temperature-sensitive and thus strongly suggestive of a mechanism of facilitated transport.
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PMID:Nuclear localization of ciliary neurotrophic factor in glial cells. 1008 49

In this study we examine the activation of the latent Stat family of transcription factors by the gp130 family of cytokines in cell lines derived from human brain tumours. Of the cytokines tested, oncostatin M resulted in the most dramatic induction of Stat1 and Stat3 in all cell lines analysed, as assessed by the formation of protein/DNA complexes. Interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor also induced Stat complexes more selectively and to a lesser magnitude than oncostatin M. The kinetics of Stat1 and Stat3 activation was rapid and transient; the nuclear accumulation of DNA binding-proficient Stat protein was detected in the nucleus within minutes of cytokine induction. The transcriptional potential of the oncostatin M-activated Stat molecules was demonstrated in two glioma cell lines (U87-MG, SNB-19) by transient transfection experiments using a Stat-responsive reporter plasmid. Oncostatin M-dependent transcription from this reporter plasmid was reduced to uninduced levels by the inclusion of a dominant-negative Stat3 molecule, demonstrating that Stat molecules were responsible for the induction. These studies demonstrate that oncostatin M is the most potent activator of Stat molecules in a variety of brain tumour-derived cell lines, an observation that could have implications affecting the balance between proliferation/apoptosis of these cells.
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PMID:Activation of stat3 and stat1 DNA binding and transcriptional activity in human brain tumour cell lines by gp130 cytokines. 1070 21

Oncostatin M (OSM) and other members of the interleukin-6 cytokines, like ciliary neurotrophic factor and leukemia inhibitory factor, can induce differentiation of glial cells. We have recently described that OSM inhibited the growth of human glioma cells in vitro and induced a cell morphology resembling that of mature astrocytes. Using the glioblastoma cell line 86HG39, we demonstrated that treatment of the glioma cells with OSM also leads to a differentiation of the malignant glioma cells as judged by a strong increase in glial fibrillary acidic protein expression. The differentiation and the growth inhibition were not significantly blocked by expression of a dominant-negative (dn) signal transducer and activator of transcription (Stat) 3 protein. OSM exerted a reduction in DNA synthesis even in the presence of a high expression level of dnStat3. Moreover, inhibition of the ras-raf-mitogen-activated protein kinase (MAPK) pathway by the MAPK kinase 1 inhibitor PD98059 resulted in a synergistic enhancement of the OSM effect, indicating that the activation of this pathway counteracts the activity of the cytokine.
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PMID:Oncostatin M-mediated growth inhibition of human glioblastoma cells does not depend on stat3 or on mitogen-activated protein kinase activation. 1093 78

The loss of gap junctional intercellular communication has been proposedas playing a major role in the process of carcinogenesis. Most neoplastic cells, including C6 gliomas, express less connexins and have fewer gap junctions, reduced gap junctional intercellular communication, and increased growth rates compared with their nonneoplastic counterparts. The purpose of this study was to determine whether ciliary neurotrophic factor (CNTF) can be used to increase endogenous connexin43 levels, increase intercellular coupling, and retard the growth rate of C6 glioma cells. C6 cells were grown in serum-reduced medium (1% serum) and exposed to the following agents: vehicle (PBS), CNTF (20 ng/ml), CNTF soluble receptor (CNTFRalpha; 200 ng/ml), or Complex (CNTF + CNTFRalpha). Reverse transcription-PCR analysis indicated that C6 cells express CNTF mRNA but not CNTFRalpha mRNA. When cells were exposed to the above agents, only Complex caused an up-regulation of connexin43 protein (based on immunocytochemical and immunoblot analysis). Furthermore, Complex increased gap junctional coupling in C6 cells as noted by the passage of the gap junction permeable dye calcein. Finally, it was demonstrated that Complex-treatment reduces the growth rate of C6 cells compared with all of the other agents tested. Taken together, this study has demonstrated that CNTF in combination with its soluble receptor can increase connexin43 expression, increase gap junctional coupling, and reduce the in vitro proliferation of C6 glioma cells.
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PMID:Ciliary neurotrophic factor (CNTF) in combination with its soluble receptor (CNTFRalpha) increases connexin43 expression and suppresses growth of C6 glioma cells. 1206 2