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)

Ciliary neurotrophic factor (CNTF) has been shown to modulate the in vitro and in vivo survival, proliferation and differentiation of many neuronal cell types. Evidence indicates that it produces most if not all these effects by binding to a receptor subunit referred to as the CNTF receptor alpha component (CNTFR alpha). We cloned a cDNA encoding part of the rat CNTFR alpha and used it in Northern analyses to study CNTFR alpha mRNA expression. Examination of various tissues of embryonic day 18 and postnatal day 14 rats indicated that CNTFR alpha mRNA is primarily but not exclusively expressed in brain at these stages of development. Further studies revealed that the CNTFR alpha transcripts are present throughout brain development from embryonic day 12 to adulthood and display a widespread distribution in the adult brain. A survey of rodent cell lines detected highest CNTFR alpha mRNA concentrations in neuronal lines and a low concentration in a Schwann cell derived line. CNTFR alpha mRNA was not detected in fibroblast lines and a glioma line. Finally, nerve growth factor treatment decreased CNTFR alpha mRNA levels in PC12 cells. This result demonstrates that signal transduction processes activated by a neurotrophin can influence CNTF activated signal transduction processes. Such cross-talk may play an important in vivo role in the development and maintenance of the many neuronal cell types that are responsive to both neurotrophins and CNTF.
 ...
PMID:CNTF receptor alpha mRNA expression in rodent cell lines and developing rat. 780 24

Regulation of CNTF mRNA was investigated in primary cortical astrocytes cultured from newborn rats and in C6 glioma cells. Northern blot analysis indicated that semi-confluent astrocyte cell cultures. CNTF added to confluent astrocyte cultures down-regulated CNTF message in a dose-dependent fashion. In contrast, when CNTF was given to semi-confluent astrocyte cultures the level of CNTF mRNA was up-regulated. C6 glioma cells also showed a cell density-dependent expression of CNTF: cells from confluent cultures expressed detectable amounts of CNTF mRNA whereas those from semi-confluent cultures did not. Thus, CNTF mRNA expression by astroglial and glioma cells is regulated by cell contact and exogenous CNTF in vitro.
 ...
PMID:Cell density and exogenous CNTF affect CNTF mRNA levels in glial cell cultures. 784 80

Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra-neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting in death over a period of 7-10 d. This weight loss could not be explained by a reduction in food intake and involved losses of both fat and skeletal muscle. CNTF also induced the synthesis of acute phase proteins such as haptoglobin. Implantation of C6 lines expressing a nonsecreted form of CNTF, or the parental C6 line itself, did not result in wasting effects. Analysis of this CNTF-induced wasting indicates similarities with the previously described cachectins, tumor necrosis factor, interleukin 6, and leukemia inhibitory factor, but does not involve the induction of these cytokines.
 ...
PMID:Systemic administration of ciliary neurotrophic factor induces cachexia in rodents. 820 Oct 2

Oligodendrocytes (OLs) and their myelin membranes are the apparent injury targets in the putative human autoimmune disease multiple sclerosis. The basis for this selective injury remains to be defined. OLs in vitro have been shown to be susceptible to both tumor necrosis factor (TNF) and non-TNF-dependent immune effector mechanisms. The former involves initial nuclear injury (apoptosis); the latter, when mediated by activated T cells, involves initial cell membrane injury (lysis). In the current study, we determined whether human adult CNS-derived OLs could be protected from the above immune effector mechanisms by selected neurotrophic factors (CNTF, BDNF, NGF, NT-3, and NT-4/5) or cytokines demonstrated to protect from human or experimental autoimmune demyelinating diseases (beta-interferon [IFN], IL-10, and TGF-beta). Nuclear injury was assessed in terms of DNA fragmentation using a DNA nick-end-labelling technique; cell membrane injury was assessed by lactate dehydrogenase or chromium 51 release. MTT and cell counting assays were used to assess cell viability and cell loss, respectively. Amongst the neurotrophic factors and cytokines tested, only CNTF significantly protected the OLs from TNF-mediated injury. CNTF also protected the OLs from serum deprivation-induced apoptosis. CNTF, however, did not protect the OLs from injury induced by activated CD4+ T cells. CNTF also did not protect human fetal cortical neurons from serum deprivation or TNF-induced DNA fragmentation, nor did it protect the U251 human glioma cell line from DNA fragmentation induced by a combination of TNF and reduced serum concentration in the culture media. Our results indicate that potential protective effects of neurotrophic factors or cytokines on neural cell populations can be selective both for cell type involved and mechanism of immune-mediated injury. CNTF is the protective factor selective for nuclear-directed injury of OLs.
 ...
PMID:Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factor-mediated injury. 871 18

We have recently shown that VEGF functions as a survival factor for newly formed vessels during developmental neovascularization, but is not required for maintenance of mature vessels. Reasoning that expanding tumors contain a significant fraction of newly formed and remodeling vessels, we examined whether abrupt withdrawal of VEGF will result in regression of preformed tumor vessels. Using a tetracycline-regulated VEGF expression system in xenografted C6 glioma cells, we showed that shutting off VEGF production leads to detachment of endothelial cells from the walls of preformed vessels and their subsequent death by apoptosis. Vascular collapse then leads to hemorrhages and extensive tumor necrosis. These results suggest that enforced withdrawal of vascular survival factors can be applied to target preformed tumor vasculature in established tumors. The system was also used to examine phenotypes resulting from over-expression of VEGF. When expression of the transfected VEGF cDNA was continuously "on," tumors became hyper-vascularized with abnormally large vessels, presumably arising from excessive fusions. Tumors were significantly less necrotic, suggesting that necrosis in these tumors is the result of insufficient angiogenesis.
 ...
PMID:Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. 923 51

It has become clear that disruptions in the genome of somatic cells play a causative role in tumour development. We know that the ultimate formation of a malignancy is the result of a multistep process in which the functional loss and/or the altered or increased expression of genes play important roles. One such family of genes are the oncogenes, encoding protein products with mainly growth stimulating effects. Platelet-derived growth factor (PDGF) belongs to the family of oncogenes. It is likely that PDGF plays an essential role in the development of at least a subgroup of malignant astrocytic tumours that do not contain amplification of the EGF-receptor. The expression of PDGF alpha-receptors is related to tumour progression in these tumours, and some of the most malignant tumours were shown to contain amplification of the PDGF alpha-receptor. It is also clear now from several experimental studies that PDGF can drive the transformed phenotype, and that PDGF antagonists, by blocking the PDGF autocrine pathway revert the transformed phenotype of certain tumour cells. Because of the findings that receptor protein tyrosine kinases such as the EGF- and the PDGF-receptor play a crucial role in the development of gliomas, it is possible that inhibitors of the phosphorylation of the protein tyrosine kinases will be future candidates for glioma therapy. They might be able to at least delay the development of a fully malignant glioma. The role of PDGF in other tumours of neuroglial origin in the central nervous system has not been studied as extensively as its role in gliomas. Recent data suggest that also for the primitive neuroectodermal tumours overexpression of the PDGF alpha-receptor is related to malignancy of the tumours. For other tumours, such as neuroblastomas, PDGF exerts a differentiating rather than a mitogenic function and is an important survival factor. Further studies are needed to elucidate the role of PDGF in these non-glial primary brain tumours. Moreover, for a complete understanding of the role of PDGF in malignancies of the CNS, it is important to explore its function in the development of the normal CNS further.
 ...
PMID:Platelet-derived growth factor (PDGF) in primary brain tumours of neuroglial origin. 958 5

We have established three new cell lines deriving from malignant human gliomas. The cell lines were described in terms of both morphology and growth characteristics. Most cells in all three cell lines expressed the neuroepithelial marker protein GFAP. In terms of growth characteristics, the cells showed only slight differences. The cell lines showed no expression of the neural form of the c-src gene, pp60c-srcN, but did express the ubiquitous form, pp60c-src. The established glioma cell lines were also examined for expression of members of the neuropoietic cytokine family, CNTF and LIF, and their respective receptor components CNTFRalpha, LIFRbeta and gp130. With the exception of CNTFRalpha both the ligands and their receptor components were expressed in similar amounts in all three cell lines. The presence of ligand and receptor prompted us to study the effects of exogenously supplied factors on the growth of the glioma cell lines. Whereas LIF induced a high c-fos expression, only low c-fos induction was observed upon CNTF treatment. Accordingly, CNTF did not have any noticeable effects on glioma cell growth in culture, while LIF mediated an inhibiting effect on the growth of the three glioma cell lines in culture.
 ...
PMID:Growth inhibition of newly established human glioma cell lines by leukemia inhibitory factor. 976 66

Ciliary neurotrophic factor (CNTF) promotes the survival of various neuronal cell populations. It is produced by astrocytes and influences the development and differentiation of glial cells. CNTF and related neuropoietic cytokines affect growth and differentiation of various neoplasms. Moreover, they induce the reactive transformation of astrocytes (gliosis) and influence growth and differentiation of neuroectodermal tumor cell lines in vitro. However, their role in gliomas is largely unknown. We studied the expression of CNTF and its receptor subunits in human astrocytomas and glioblastomas. In more than 95% of the tumors, CNTF transcripts were found by RNAase protection assay; in more than 80% of the cases, tumor cells were CNTF immunoreactive. CNTF receptor alpha (CNTFR alpha), the specific component of the tripartite CNTF receptor system, was detectable by Northern blot analysis in 80% of the cases. In situ hybridization revealed CNTFR alpha mRNA in the cytoplasm of neoplastic cells. Transcripts of the remaining two components of the CNTF receptor system, gp130 and LIFR beta, were found by Northern blotting in 83% and 70% of the tumors, respectively. Simultaneous expression of CNTF and all its receptor components was detected in approximately half of the tumors. These results indicate that CNTF and its receptor components are expressed by human glioma cells. The simultaneous expression of ligands and receptor subunits suggests that CNTF might act on human glioma cells via an auto- or paracrine mechanism.
 ...
PMID:CNTF and its receptor subunits in human gliomas. 1072 Feb 4

A growing body of evidence now suggests that programmed cell death (PCD) occurs via non-apoptotic mechanisms as well as by apoptosis. In contrast to apoptosis, however, the molecular mechanisms involved in the regulation of non-apoptotic PCD remain only poorly understood. Here we show that ceramide induces a non-apoptotic PCD with a necrotic-like morphology in human glioma cells. Characteristically, the cell death was not accompanied by loss of the mitochondrial transmembrane potential, cytosolic release of cytochrome c from mitochondria, or the activation of the caspase cascade. Consistent with these characteristics, this ceramide-induced cell death was inhibited neither by the overexpression of Bcl-xL nor by the pan-caspase inhibitor zVAD-fmk. However, strikingly, the ceramide-induced non-apoptotic cell death was inhibited by the activation of the Akt/protein kinase B pathway through the expression of a constitutively active version of Akt. The results for the first time indicate that the Akt kinase, known to play an essential role in survival factor-mediated inhibition of apoptotic cell death, is also involved in the regulation of non-apoptotic PCD.
 ...
PMID:Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide. 1170 21

The known effects of nerve growth factor (NGF) are induction of differentiation and promotion of survival. We analysed the effects of exogenously added NGF on rat C6 and 9L glioma cells and the rat pheochromocytoma cell line PC12. Cells were seeded into 96-well plates and exposed to different concentrations of FCS (10%, 5%, 1%, 0.5% and no FCS) supplemented with or without 50 ng/ml NGF for up to 120 hours. Cell survival was measured using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-assay. In this study we could clearly show two different effects: (1) proliferation was not influenced by NGF under high, medium or low serum and (2) survival rates increased under dramatic or complete serum deprivation, indicating that NGF acts as survival factor against cell death or cell cytostasis.
 ...
PMID:NGF increases cell survival rates under serum deprived conditions. 1172 57


1 2 Next >>