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)

Astrocytes are characterized by extensive gap junctional intercellular communication (GJIC) mediated by channels composed primarily of connexin43. To examine some of the functions of this intercellular communication in glial cells, we have used three approaches. The first involves transfection of glioma cells, which are deficient in connexin expression and gap junctional communication, with connexin cDNAs to examine changes in cellular phenotype following increased gap junctional communication. Using differential display, we have identified several genes which appear to be regulated by GJIC. The second is to study astrocytes cultured from embryonic mice with a null mutation in the connexin43 gene. These homozygous null astrocytes are devoid of connexin43 and also deficient in intercellular dye transfer. Markers of glial differentiation appear similar in all genotypes. Measurement of intercellular calcium concentration following mechanical stimulation of confluent astrocytes revealed that the number of cells affected by a rise in intracellular calcium was reduced in homozygous cultures compared to wild type. The growth rate of astrocytes lacking connexin43 was reduced compared to wild-type astrocytes. The third approach employs the use of gap junction blockers in a model of neuronal and glial differentiation, namely P19 mouse embryonal carcinoma cells treated with retinoic acid. In this case, blocking GJIC during the differentiation protocol prevents the appearance of neuronal and astrocytic phenotypes. Taken together, these data suggest an important role for GJIC in glial function and differentiation.
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PMID:Consequences of impaired gap junctional communication in glial cells. 1063 43

Neuron-restrictive silencer factor (NRSF, also termed REST) has been proposed to restrict expression of a set of genes to neurons by blocking their transcription in nonneuronal cells. The N-methyl-D-aspartate (NMDA) receptor subunit type I (NR1) gene contains a consensus sequence for the NRSF/REST binding site (NRSE/RE1). In this study, we evaluated the contribution of NRSF/REST to neuronal specificity of the NR1 gene. NR1 mRNA expression correlates with the absence of NRSF/REST binding activity, rather than expression of NRSF/REST protein, in several cell lines, suggesting that the absence of NRSF/REST-binding activity is necessary for the expression of the NR1 gene. HeLa cells, which do not express the NR1 gene, have NRSF/REST binding activity to the NR1 NRSE/RE1, resulting in inhibition of NR1 promoter activity. However, we also found that two nonneuronal cell lines (C6 glioma and P19 embryonal carcinoma) that lack NRSF/REST-binding activity, manifest only small amounts of NR1 mRNA compared to neuronal cell lines (PC12 pheochromocytoma and neuronally differentiated P19 cells). The enhancement of NR1 mRNA levels during neuronal differentiation of P19 cells is accompanied by an increase in NR1 promoter activity in an NRSF/REST-binding independent manner. Our results suggest therefore that the absence of NRSF/REST-binding activity is necessary but not sufficient for robust NR1 transcription in neuronal cells.
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PMID:Absence of binding activity of neuron-restrictive silencer factor is necessary, but not sufficient for transcription of NMDA receptor subunit type 1 in neuronal cells. 1064 Jun 75

IGF-I antisense gene therapy has been applied successfully to animal models of glioma, hepatoma and teratocarcinoma. The antisense strategy has shown that tumor cells transfected with vectors encoding IGF-I antisense RNA lose tumorigenicity, become immunogenic and are associated with tumor specific immune response involving CD8+ lymphocytes. An IGF-I triple helix approach to gene therapy for glioma was recently described. The approach we have taken is to establish parameters of change using the IGF-I triple helix strategy. PCC-3 embryonal carcinoma cells derived from murine teratocarcinoma which express IGF-I were used as a model. The cells were transfected with vector which encodes an oligoribonucleotide that forms RNA-IGF-I DNA triple-helix structure. The triple-helix stops the production of IGF-I. Cells transfected in this manner underwent changes in phenotype and an increase in MHC-I and B-7 cell surface molecules. They also showed enhancement in the production of apoptotic cells (60-70%). The "triple helix" transfected cells lost the ability to induce tumor when injected subcutaneously in syngeneic 129 Sv mice. When co-transfected in vitro with expression vectors encoding both MHC-I and B-7 cDNA in antisense orientation, the "triple-helix" transfected cells were down-regulated in expression of MHC-I and B-7 and the number of apoptotic cells was significantly decreased. Injection of the doubly co-transfected cells into 129 Sv mice was associated with induction of teratocarcinoma. Comparison between antisense and triple-helix transfected cells strategies showed similar immunogenic and apoptotic changes. The findings suggest that triple-helix technology may offer a new clinical approach to treatement of tumors expressing IGF-I.
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PMID:Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis. 1119 46

Aquaporin-4 (AQP4), a mercury-insensitive water channel protein, is abundant in the central nervous system and is localized in astrocytes and ependymal cells. AQP4 is speculated to maintain the homeostasis of intracellular and extracellular water in the brain, but little is known about the mechanism of induction of its expression. To investigate the expressional regulation of AQP4, we analyzed changes in its expression during chemically induced differentiation of embryonal carcinoma cells (P19) to neuronal and astrocytic cells, and during the cell cycle of glioma cells. After exposure to retinoic acid for 4 days AQP4 mRNA expression started at the initiation of astrocytic differentiation of P19 cells at 6 days, and increased markedly by 21 days. AQP4 expression was parallel to that of GFAP, a marker intermediate filament of astrocytes. In glioma cell lines, AQP4 mRNA was not detected in the growing phase, but was induced when the cell cycle was arrested at G0/G1 by transient expression of p21. Although quiescent astrocytes in the G0/G1-phase cultured under the serum-free condition exhibited a high expression of AQP4, serum supplement moved them to the S-phase and markedly decreased the AQP expression. These results suggest that AQP4 expression may be induced not only at the initiation of astrocytic differentiation of neural stem cells, but also at the G0/G1-phase during the cell cycle of astrocytes.
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PMID:Regulation of aquaporin-4 expression in astrocytes. 1131 79

In this study, we present statistical analyses of pineal tumors based on the data from Brain Tumor Registry of Japan. The most frequent tumor in the pineal region was germinoma, and it accounted for 49.2% of all pineal tumors; it was followed by pineocytoma (8.5%), glioma (6.5%), pineoblastoma (5.1%), malignant teratoma (5.2%) and teratoma (5.1%). Germinoma is most frequent among patients between 10 and 19 years of age, and there are some patients aged >30 years; however, there are few patients with choriocarcinoma, embryonal carcinoma, and yolk sac tumor who are aged >30 years. Pineoblastoma is most frequent among patients under 5 years of age, while pineocytoma is evenly distributed in patients between 10 and 60 years of age. The 5-year survival rate of germinoma was 89.4%, while those of embryonal carcinoma, yolk sac tumor and choriocarcinoma were 35.3, 37.3 and 58.1%, respectively.
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PMID:Statistical analysis of pineal tumors based on the data of Brain Tumor Registry of Japan. 1932 57

Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ingredient of Asian foods. Curcumin has revealed its strong activities of anti-inflammatory, antioxidant, and anticancer. The efficient amount of curcumin could induce differentiation of stem cells and promoted the differentiation of glioma-initiating cells; however, the mechanisms underlying neural induction of curcumin have not yet been revealed. In this study, neural-inducing ability of curcumin was explored by using human pluripotent embryonal carcinoma cells, NTERA2 cells. The cells were induced toward neural lineage with curcumin and were compared with a standard neutralizing agent (retinoic acid). It was found that, after 14 days of the induction by curcumin, NTERA2 cells showed neuronal morphology and expressed neural-specific genes, including NeuroD, TUJ1, and PAX6. Importantly, curcumin activated neurogenesis of NTERA2 cells via the activation of autophagy, since autophagy-related genes, such as LC3, LAMP1, and ATG5, were upregulated along with the expression of neural genes. The inhibition of autophagy by chloroquine suppressed both autophagy and neural differentiation, highlighting the positive role of autophagy during neural differentiation. This autophagy-mediated neural differentiation of curcumin was found to be an ROS-dependent manner; curcumin induced ROS generation and suppressed antioxidant gene expression. Altogether, this study proposed the neural-inducing activity of curcumin via the regulation of autophagy within NTERA2 cells and underscored the health beneficial effects of curcumin for neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.
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PMID:Curcumin Induces Neural Differentiation of Human Pluripotent Embryonal Carcinoma Cells through the Activation of Autophagy. 3080 Jun 69


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