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)

Rho-like GTPases, including Cdc42, Rac1 and RhoA, regulate distinct actin cytoskeleton changes required for cell adhesion, migration and invasion. In the present study, we examined the role of Rac signaling in inherent migration, as well as radiation-induced migration, of rat glioma cells. Stable overexpression of dominant-negative Rac1N17 in a C6 rat glioma cell line (C6-RacN17) promoted cell migration, and ionizing radiation further increased this migration. Migration was accompanied by decreased expression of the focal adhesion molecules FAK and paxillin. Focal contacts and actin stress fibers were also reduced in C6-RacN17 cells. Downstream effectors of Rac include JNK and p38 MAP kinases. Irradiation transiently activated p38, JNK and ERK1/2 MAP kinases in C6-RacN17 cells, while p38 and JNK were constitutively activated in C6 control cells. Blocking JNK activity with JNK inhibitor SP600125 inhibited migration, suggesting that the JNK pathway may regulate radiation-induced, as well as inherent, migration of C6-RacN17 cells. Additionally, the radiation-induced migration increase was also inhibited by SB203580, a specific inhibitor of p38 MAP kinase. However, PD98059, a MEK kinase 1 inhibitor, failed to influence migration. This is the first evidence that suppression of Rac signaling may be involved in invasion or metastasis of glioma cells before and/or after radiotherapy. These data further suggest that radiotherapy for malignant glioma needs to be used with caution because of the potential for therapy-induced cell migration or invasion and that pharmacological inhibition of cell migration and invasion through targeting the Rac signaling pathway may represent a new approach for improving the therapeutic efficacy of radiotherapy for malignant glioma.
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PMID:Dominant-negative Rac increases both inherent and ionizing radiation-induced cell migration in C6 rat glioma cells. 1628 69

In the present study, we have used the gene expression data available in the SAGE database in an attempt to identify glioblastoma molecular markers. Of 129 genes with more than 5-fold difference found by comparison of nine glioblastoma with five normal brain SAGE libraries, 44 increased their expression in glioblastomas. Most corresponding proteins were involved in angiogenesis, host-tumor immune interplay, multidrug resistance, extracellular matrix (ECM) formation, IGF-signalling, or MAP-kinase pathway. Among them, 16 genes had a high expression both in glioblastomas and in glioblastoma cell lines suggesting their expression in transformed cells. Other 28 genes had an increased expression only in glioblastomas, not in glioblastoma cell lines suggesting an expression possibly originated from host cells. Many of these genes are among the top transcripts in activated macrophages, and involved in immune response and angiogenesis. This altered pattern of gene expression in both host and tumor cells, can be viewed as a molecular marker in the analysis of malignant progression of astrocytic tumors, and as possible clues for the mechanism of disease. Moreover, several genes overexpressed in glioblastomas produce extracellular proteins, thereby providing possible therapeutic targets. Further characterization of these genes will thus allow them to be exploited in molecular classification of glial tumors, diagnosis, prognosis, and anticancer therapy.
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PMID:Characterization of genes with increased expression in human glioblastomas. 1639 19

This study examines the influence of insoluble matrix components of glioma (astrocytoma) cells on LPS-mediated inducible nitric oxide (NO)/NO synthase (iNOS) induction in microglia cells. Insoluble matrix components prepared from C6 rat glioma cells strongly suppressed iNOS induction and subsequent NO release induced by LPS. Matrices prepared from several glioma cell lines displayed similar inhibitory effects on LPS-induced NO/iNOS induction, whereas matrices from primary cultured rat astrocytes had a minimal influence. Of the various purified ECM materials examined, collagen suppressed LPS-mediated iNOS/NO induction in microglia. C6 matrices potentiated LPS-induced NF-kappaB DNA binding/transcriptional activity, suggesting that the suppression of LPS-induced iNOS by C6 matrices is NF-kappaB independent. C6 matrices inhibited LPS-mediated activation of p38 and JNK MAP kinases. This study shows that non-diffusible factors derived from astrocytoma cells in the brain are critically involved in the suppression of microglial cell activation. Our results indicate that activation of microglia can be regulated by various cellular and pathological environmental conditions, not only through cell-cell contact or soluble factors, but also via insoluble matrix components.
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PMID:Insoluble matrix components of glioma cells suppress LPS-mediated iNOS/NO induction in microglia. 1684 40

The authors have previously shown that medroxyprogesterone acetate (MPA) inhibits growth and increases drug sensitivity in C6 glioma with myeloid bodies. Myeloid bodies can occur in cells either due to robust toxicity with mitochondrial membrane disruption or due to milder events such as seen in lysosomal-phospholipidosis. Exact patterns of myelinosis accompanying to MPA chemo-sensitization is important, because uncoupling of nuclear versus mitochondrial toxicity of anti-neoplastics by MPA would lead to safer employment of glioma chemotherapy with reduced neurotoxicity. By monitoring and comparing cell kinetics with fine structural features of cell death, the authors estimated subcellular effects accompanying growth-inhibitory drug actions in C6 glioma. The analysis revealed that MPA induced mainly lysosomal phospholipidosis, while inhibiting clonogenicity alone and augmenting procarbazine efficacy. It induced apoptosis in combination with cisplatin. It reduced mitochondrial-damage-based early cytotoxicity of methotrexate, yet it did not hinder its anti-clonogenic efficacy. Progesterone analogues - similar to antidepressants - inhibit cholesterol esterification, and this efficacy relates with their P-glycoprotein inhibition. Reducing esterification and plasma-membrane localization of cholesterol may lead MPA induction of lysosomal phospholipidosis, growth indolency, and drug sensitization in glioma.
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PMID:Medroxyprogesterone acetate induces c6 glioma chemosensitization via antidepressant-like lysosomal phospholipidosis/myelinosis in vitro. 1772 57

Tachykinins are excitatory neuropeptides synthesised in neuronal and glial cells of the human central and peripheral nervous system. They participate in both physiological and certain pathological conditions, i.e. synaptic transmission, nociception and neuroimmunomodulation. Tachykinins act as excitatory neurotransmitters and/or neuromodulators and induce DNA synthesis leading to stimulation of cell division and proliferation. Their biological responses are triggered via the well-established tachykinin receptors NK1, NK2 and NK3 that belong to the G protein-coupled receptor family (GPCRs). Substance P is the most important member of the tachykinin family that constitutes the major endogenous ligand for the NK1 receptor type. The presence of functional NK1 receptors has been documented in malignant brain tumours of glial origin. It has been evidenced that SP-NK1 receptor communication is involved in glioma development and progression. It is possible because the tumour cells display SP-mediated autocrine activity, the ability of cytokines stimulation and MAP kinases activation. It has been suggested that SP receptor antagonists application might be useful in attempts directed at anti-cancer therapy.
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PMID:Substance P and its receptors -- a potential target for novel medicines in malignant brain tumour therapies (mini-review). 1784 59

Tricyclic antidepressants and selective serotonin reuptake inhibitors are considered in theory to induce the outflow of neurotransmitters, norepinephrine, and serotonin from the synapses as a consequence of inhibiting their reuptake into the nerve terminals, resulting in the stimulation of glial cells surrounding the synapses in the brain. Then, we have investigated the direct actions of neurotransmitters on glial cell metabolism and function using rat C6 glioma cells as an in vitro model system and suggested that these neurotransmitters induce their differentiation probably through the production of 5alpha-reduced neurosteroids. On the other hand, the stimulation of the glioma cells with serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) gene expression, which may be closely related to the beneficial effects of antidepressant drugs. In the present study, to evaluate BDNF expression in differentiated glial cells, the glioma cells were pretreated with progesterone, and the effect of serotonin on BDNF messenger RNA levels in these cells was examined. Progesterone pretreatment enhanced the stimulatory action of serotonin on BDNF gene expression, and the enhancement of serotonin action observed in the cells pretreated with progesterone was almost completely abolished by finasteride, an inhibitor of the enzyme involved in the production of 5alpha-reduced neurosteroids. These findings propose the possibility that neurosteroid-mediated glial cell differentiation may result in the enhancement of serotonin-stimulated BDNF gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain, and hence, leading to the improvement of mood disorders and other symptoms in depressive patients.
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PMID:Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in rat c6 glioma cells through production of 5alpha-reduced neurosteroids. 1821 47

Gliomas are the most common and lethal tumor type in the brain. The present study investigated the effect of oligomer procyanidins (F2) (F2, degree of polymerization 2-15), a natural fraction isolated from grape seeds on the biological behavior of glioblastoma cells. We found that F2 significantly inhibited the glioblastoma growth, with little cytotoxicity on normal cells, induced G2/M arrest and decreased mitochondrial membrane potential in U-87 cells. It also induced a non-apoptotic cell death phenotype resembling paraptosis in U-87 cells. In addition, it was found for the first time that F2 in non-cytotoxic concentrations selectively inhibited U-87 cell chemotaxis mediated by a G-protein coupled receptor formyl peptide receptor FPR, which is implicated in tumor cell invasion and metastasis. Further experiments indicated that F2 inhibited fMLF-induced U-87 cell calcium mobilization and MAP kinases ERK1/2 phosphorylation. Moreover, F2 attenuated the glioblastoma FPR expression, a new molecular target for glioma therapeutics, which has been shown to play important roles in glioma cells chemotaxis, proliferation and angiogenesis in addition to its promotion to tumor progression, but did not affect FPR mRNA expression in U-87 cells. Taken together, our results suggest that F2 may be a promising candidate for the development of novel anti-tumor therapeutics.
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PMID:Inhibition of U-87 human glioblastoma cell proliferation and formyl peptide receptor function by oligomer procyanidins (F2) isolated from grape seeds. 1916 69

Meningiomas are frequent intracranial, non-glial tumors of adults. We present the unusual left lateral ventricular localization of meningioma in a 51-year-old man. The magnetic resonance (MR) images showed well demarcated, large mass of the atrium of the left lateral ventricle with transependymal extension into the left temporal lobe. MR spectroscopy revealed the presence of "choline only" spectrum, typical for extra axial neoplasms. The mass was completely resected. The diagnosis of transitional type intraventricular meningioma, with psammoma bodies, histologic grade I was made. Progesterone and estrogen receptors were negative.
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PMID:MR and MRS characteristics of intraventricular meningioma. 1918 73

Progesterone treatment has previously been reported to promote the differentiation of glial cells probably through the production of 5alpha-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated brain-derived neurotrophic factor (BDNF) gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain and hence has been suggested to improve mood disorders and other symptoms in depressive patients. Based on these previous observations, the effects on glial cells of histone deacetylase (HDAC) inhibitors, which are known as agents promoting cell differentiation, were examined using rat C6 glioma cells as a model for in vitro studies. Consequently, trichostatin A (TSA), sodium butyrate (NaB), and valproic acid (VPA) stimulated glial fibrillary acidic protein (GFAP) gene expression, and their stimulatory effects on GFAP gene expression were inhibited by treatment of these cells with finasteride, an inhibitor of the enzyme producing 5alpha-reduced neurosteroids. In addition, HDAC inhibitors enhanced serotonin-stimulated BDNF gene expression, the enhancement of which could be abolished by the inhibition of 5alpha-reduced neurosteroid production in the glioma cells. These results suggest that HDAC inhibitors may be able to promote the differentiation of rat C6 glioma cells through the production of 5alpha-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated BDNF gene expression as a consequence of promoting their differentiation, indicating the possibility that differentiated glial cells may be implicated in preserving the integrity of neural networks as well as improving the function of neuronal cells in the brain.
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PMID:Histone deacetylase inhibitors promote neurosteroid-mediated cell differentiation and enhance serotonin-stimulated brain-derived neurotrophic factor gene expression in rat C6 glioma cells. 1936 Sep 4

Enzastaurin is an acyclic bisindolylmaleimide derived from staurosporine that acts as an ATP competitor, and interferes with the activity of protein kinase C (PKC) isoforms. Our previous studies have shown that clinically achievable concentrations of this agent induce apoptosis in many glioma cell lines. Our goal in this study was to expand on the previous results and to determine the signalling mechanisms responsible for enzastaurin-induced inhibition of cell growth and induction of apoptosis. To address these issues, cell cycle progression following enzastaurin treatment was analysed by fluorescence-activated cell sorting (FACS) in parallel with analyses of growth and apoptosis signalling pathways. Enzastaurin treatment activated H2AX and Chk2 phosphorylation, and enhanced phosphorylation of mitogen-activated protein kinase (MAPK) family kinases. Inhibition of MAP kinases by chemical inhibitors reduced H2AX and Chk2 phosphorylation and decreased apoptosis induced by enzastaurin. These data call attention to a novel signalling pathway (MAPK/H2AX) to regulate apoptosis in malignant glioma cells.
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PMID:Enzastaurin induces H2AX phosphorylation to regulate apoptosis via MAPK signalling in malignant glioma cells. 1991 8


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