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)

Several neural cell lines were examined for their ability to synthesize sulfatide and 2',3'-cyclic nucleotide phosphohydrolase, biochemical components characteristic of myelin. The mouse glioma G26 and the rat schwannoma TRM6B actively produced sulfatide, while the rat glioma C6 was inactive, supporting the probable oligodendroglial origin of the G26. In contrast, the C6 cell line had a high level of 2'-3'-cyclic nucleotide phosphohydrolase activity, while TRM6B showed 30% and the G26 75% lower activities. Thus, these two activities appear to be independently regulated.
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PMID:Sulfatide synthesis by neural cell lines. 23 75

Specific activity of the myelin enzyme, 2':3'-cyclic-nucleotide 3'-phosphohydrolase (EC 3.1.4.37), increases 2- to 10-fold when sparsely inoculated cultures of C6 rat glioma cells are allowed to grow to high cell density. Cyclic-nucleotide phosphohydrolase specific activity is also induced in C6 cells and in oligodendrocytes by dibutyryl cyclic AMP or by agents that elevate intracellular cyclic AMP. In this report, we have compared the density-dependent induction of cyclic-nucleotide phosphohydrolase activity with the cyclic AMP-dependent induction. Dibutyryl cyclic AMP induced cyclic-nucleotide phosphohydrolase specific activity in both sparse and dense cultures which had very different density-dependent cyclic-nucleotide phosphohydrolase activities. Induction of both cyclic-nucleotide phosphohydrolase specific activity and intracellular cyclic AMP content by norepinephrine also occurred to a similar degree in sparse and dense cultures. Similar results were obtained for several clones of C6 cells, and for a clone of oligodendrocyte x C6 cell hybrids. Induction of cyclic-nucleotide phosphohydrolase by norepinephrine or dibutyryl cyclic AMP was not due to a change in cell density or rate of cell proliferation, nor did cell density have any appreciable effect on cyclic AMP content of the cells. These results show that regulation of cyclic-nucleotide phosphohydrolase activity in C6 cells involves two distinct mechanisms.
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PMID:Two independent mechanisms of induction of 2':3'-cyclic-nucleotide 3'-phosphohydrolase in glioma cells by cyclic AMP and high cell density. 630 88

1. Extracellularly added P(1),P(3)-di(adenosine-5') triphosphate (Ap(3)A), P(1),P(4)-di(adenosine-5') tetraphosphate (Ap(4)A), ATP, ADP, AMP and adenosine are growth inhibitory for rat C6 glioma cells. Analysis of nucleotide hydrolysis and the use of nucleotidase inhibitors demonstrated that the latter inhibition is due to hydrolysis of the nucleotides to adenosine. 2. Agonists of the P2Y(AC)(-)-receptor enhance the growth of C6 cells if their hydrolysis to adenosine is inhibited by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). In these conditions, the potency to stimulate cell growth parallels the ranking of the receptor agonists, i.e. 2-methylthioadenosine-5'-diphosphate (2MeSADP)>Ap(3)A>Ap(4)A. ATP and ADP are still hydrolysed in the presence of PPADS and have no proliferative effect on C6 cells. 3. The enhanced growth is due to a P2Y(AC)(-)-receptor-mediated activation of p42/44 mitogen-activated protein kinase (MAPK) as shown by immunoblotting and protein kinase assays for active MAPK and the use of the MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059. 4. The UTP-induced enhancement of the growth of C6 cells is due to activation of MAPK by a PPADS sensitive nucleotide receptor. 5. In conclusion, the effect of nucleotides on the growth of C6 cells is determined by ecto-nucleotidases and by activation of nucleotide receptors. Hydrolysis of nucleotides to adenosine induces growth inhibition while inhibition of the hydrolysis of agonists of the P2Y(AC)(-)-receptor enhances cell growth by activation of MAPK.
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PMID:P2Y(AC)(-)-receptor agonists enhance the proliferation of rat C6 glioma cells through activation of the p42/44 mitogen-activated protein kinase. 1156 59

The role of adenosine 5'-triphosphate (ATP) and P2Y(1) nucleotide receptor in potentiating agrin-induced acetylcholine receptor (AChR) aggregation is being demonstrated in a co-culture system of NG108-15 cell, a mouse neuroblastoma X rat glioma hybrid cell line that resembles spinal motor neuron, with C2C12 myotube. In the co-cultures, antagonized P2Y(1) receptors showed a reduction in NG108-15 cell-induced AChR aggregation. Parallel to this observation, cultured NG108-15 cell secreted ATP into the conditioned medium in a time-dependent manner. Enhancement of ATP release from the cultured NG108-15 cells by overexpression of active mutants of small GTPases increased the aggregation of AChRs in co-culturing with C2C12 myotubes. In addition, ecto-nucleotidase was revealed in the co-culture, which rapidly degraded the applied ATP. These results support the notion that ATP has a role in directing the formation of post-synaptic apparatus in vertebrate neuromuscular junctions.
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PMID:ATP potentiates the formation of AChR aggregate in the co-culture of NG108-15 cells with C2C12 myotubes. 1584 90

Glioblastoma multiforme is the most common type of primary brain tumour and has the worst clinical outcome. Nucleotides represent an important class of extracellular molecules involved in cell proliferation, differentiation and apoptosis. Alterations in purinergic signalling have been implicated in pathological processes, such as cancer, and glioma cell lines are widely employed as a model to study the biology of brain tumours. Increasing evidence, however, suggests that glioma cell lines may not present all the phenotypic and genetic characteristics of the primary tumours. We have compared the biological characteristics of C6 rat glioma cells in culture and the same cells after their implantation in the rat brain and growth in culture (denominated as the C6 ex vivo culture model). Parameters evaluated included cell morphology, differentiation, angiogenic markers, purinergic receptors and ecto-nucleotidase mRNA profile/enzymatic activity. Analysis of the C6 glioma cell line and C6 ex vivo glioma cultures revealed distinct cell morphologies, although cell differentiation and angiogenic marker expressions were similar. Both glioma models co-expressed multiple P2X and P2Y receptor subtypes with some differences. In addition, the C6 glioma cell line and C6 ex vivo glioma cultures exhibited similar extracellular ATP metabolism and cell proliferation behaviour when exposed to cytotoxic ATP concentrations. Thus, the disruption of purinergic signalling is a feature shown not only by glioma cell lineages, but also by primary glioma cultures. Our results therefore suggest the participation of the purinergic system in glioma malignancy.
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PMID:A comparative study of ectonucleotidase and P2 receptor mRNA profiles in C6 cell line cultures and C6 ex vivo glioma model. 1902 97

Tumor dormancy has important implications for early detection and treatment of cancer. Lack of experimental models and limited clinical accessibility constitute major obstacles to the molecular characterization of dormant tumors. We have developed models in which human tumors remain dormant for a prolonged period of time (>120 days) until they switch to rapid growth and become strongly angiogenic. These angiogenic tumors retain their ability to grow fast once injected in new mice. We hypothesized that dormant tumors undergo a stable genetic reprogramming during their switch to the fast-growing phenotype. Genome-wide transcriptional analysis was done to dissect the molecular mechanisms underlying the switch of dormant breast carcinoma, glioblastoma, osteosarcoma, and liposarcoma tumors. A consensus expression signature distinguishing all four dormant versus switched fast-growing tumors was generated. In alignment with our phenotypic observation, the angiogenesis process was the most significantly affected functional gene category. The switch of dormant tumors was associated with down-regulation of angiogenesis inhibitor thrombospondin and decreased sensitivity of angiogenic tumors to angiostatin. The conversion of dormant tumors to exponentially growing tumors was also correlated with regulation and activation of pathways not hitherto linked to tumor dormancy process, such as endothelial cell-specific molecule-1, 5'-ecto-nucleotidase, tissue inhibitor of metalloproteinase-3, epidermal growth factor receptor, insulin-like growth factor receptor, and phosphatidylinositol 3-kinase signaling. Further, novel dormancy-specific biomarkers such as H2BK and Eph receptor A5 (EphA5) were discovered. EphA5 plasma levels in mice and mRNA levels in tumor specimens of glioma patients correlated with diseases stage. These data will be instrumental in identifying novel early cancer biomarkers and could provide a rationale for development of dormancy-promoting tumor therapy strategies.
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PMID:Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype. 1917 81

Many naturally occurring substances of plant origin ingested in human diet, exhibit anticarcinogenic and antimutagenic effects. One of the active phytochemical which shows the active anticarcinogenic role is Piper longum Linn. (Pl). Pl is widely used in ayurvedic industry due to its property in healing some of the bodily ailments. Despite being known for the antioxidant, antimicrobial and anticarcinogenic effects, its relation to brain and its tumour development is still scarce. Hence, the experimental glioma model was developed in rats using C6 glioma cells and the effect of Pl was evaluated in the brain tissue of experimental group of rats. From the study, the glioma induced animals showed an increased level of lipid peroxides (LPO), tissue marker enzymes lactate dehydrogenase (LDH), creatine kinase (CK), 5'nucleotidase (5'ND) and acetylcholine esterase (AChE). But Pl treatment (20 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in glioma induced rats. In addition, the anticarcinogenic effect of Pl was confirmed by microscopic analysis and the restoration of increased lipids and protein bound carbohydrates (PBCs) in the brain tissue of glioma induced rats. Hence our results implicate a major role for Pl in preventing the cancer development in the experimental glioma model.
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PMID:Studies on the neuroprotective role of Piper longum in C6 glioma induced rats. 1973 Jul 92

Glioblastomas are highly aggressive brain tumours and are characterised by substantial cellular heterogeneity within a single tumour. A sub-population of glioblastoma stem-like cells (GSCs) that shares properties with neural precursor cells has been described, exhibiting resistance to therapy and therefore being considered responsible for the high recurrence rate in glioblastoma. To elucidate the underlying cellular processes we investigated the role of phosphatases in the GSC phenotype, using an in vitro phosphatome-wide RNA interference screen. We identified a set of genes, the knockdown of which induces a significant decrease in the glioma stem cell marker CD133, indicating a role in the glioblastoma stem-like phenotype. Among these genes, the ecto-nucleotidase ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) was found to be highly expressed in GSCs compared with normal brain and neural stem cells. Knockdown of ENPP1 in cultured GSCs resulted in an overall downregulation of stem cell-associated genes, induction of differentiation into astrocytic cell lineage, impairment of sphere formation, in addition to increased cell death, accumulation of cells in G1/G0 cell cycle phase and sensitisation to chemotherapeutic treatment. Genome-wide gene expression analysis and nucleoside and nucleotide profiling revealed that knockdown of ENPP1 affects purine and pyrimidine metabolism, suggesting a link between ENPP1 expression and a balanced nucleoside-nucleotide pool in GSCs. The phenotypic changes in E-NPP1-deficient GSCs are assumed to be a consequence of decreased transcriptional function of E2F1. Together, these results reveal that E-NPP1, by acting upstream of E2F1, is indispensable for the maintenance of GSCs in vitro and hence required to keep GSCs in an undifferentiated, proliferative state.
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PMID:Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1. 2453 36

Canine glioma is considered a potential model for human glioma, with recent studies of occurrence, therapy, and reclassification supporting the value of the canine model. The current diagnosis of canine glioma is based on morphologic criteria and immunohistochemistry (IHC), including oligodendrocyte transcription factor 2 (Olig2), glial fibrillary acidic protein (GFAP), and 2', 3' cyclic nucleotide phosphatase (CNPase). Microtubule-associated protein 2 (MAP2) is a proven marker of human glioma and is used to complement the diagnosis and its specific immunoreactivity pattern contributes to the differentiation of astrocytomas from other glial tumors. The objective of this study was to evaluate whether canine gliomas express MAP2 and to explore differences in the pattern of immunolabeling between different gliomas. Seventy-eight cases of canine glioma were evaluated for MAP2 expression by immunohistochemistry. A glial origin was supported by Olig2 IHC in all cases. MAP2 immunolabeling was evaluated on a semi-quantitative basis, including the percentage of immunolabeled neoplastic cells, as well as the signal intensity, distribution, and pattern of immunolabeling. MAP2 was expressed in all cases, with significant correlation between diagnosis and signal intensity (P = 0.04). MAP2 immunolabeling distribution was dominated by diffuse (34/78; 44%), followed by patchy (20/78; 26%), multifocal to coalescing (16/78; 21%), and scattered (8/78; 10%). All oligodendrogliomas (53/53; 100%) and undefined gliomas (12/12; 100%) revealed a combination of perinuclear and cytoplasmic immunolabeling, and all but 3 astrocytomas had a combination of perinuclear and cytoplasmic processes immunolabeling (10/13; 77%). Significant correlation between immunolabeling pattern and diagnosis was obtained (P = 0.001). The study demonstrates that MAP2 is expressed in canine gliomas and the pattern of expression can also be applied to help distinguish astrocytomas from oligodendrogliomas and undefined gliomas.
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PMID:Microtubule-Associated Protein 2 Expression in Canine Glioma. 3180 65