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)

The influence of valproate on in vitro glycosylation events in C6 glioma has been investigated, as this major human teratogen restricts proliferation in the mid-G1 phase of the cycle and alters the prevalence and/or glycosylation state of cell surface glycoproteins with the potential to mediate cell-cell and cell matrix interactions critical to development. C6 glioma cultured continuously in the presence of 1 mM valproate exhibited a significant depression of exponential growth but attained confluency one day later, when the majority of cells entered the G1 phase of the cycle. Glycoprotein sialyltransferase, which exhibited a four-fold increase during exponential growth and a small decrease at confluency, was markedly attenuated in valproate-exposed cells in a manner which was indirect. This was associated with an inhibition of transient alpha2,3 sialylation of a 65 kDa glycoprotein expressed maximally at 4 hr into the G1 phase of the cell cycle. This effect was cell-cycle phase-specific, as exposure of synchronized cells to valproate inhibited transient sialylation at 4 and 5 hr into the G1 phase. Inhibition of the 65 kDa glycoprotein sialylation by valproate is suggested to arise from impaired signal transduction preceding the eventual arrest by the drug at a 5-6 hr G1 phase restriction point.
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PMID:Valproic acid suppresses G1 phase-dependent sialylation of a 65kDa glycoprotein in the C6 glioma cell cycle. 940 28

Major depression, opioid addiction, neurodegenerative diseases, and glial tumors are associated with disturbances of imidazoline receptors (IR) in the human brain. In depression, the level of a 45-kD IR protein (putative I1-IR) is increased in the brain of suicide victims (51%) and in platelets of depressed patients (40%). The density of platelet I1-IR ([125I]-p-iodoclonidine binding) is also increased in depression (135%). The 29/30-kD IR protein (putative I2B-IR) is downregulated (19%) in suicide victims in parallel with a reduction (40%) in the density of I2B-IR ([3H]idazoxan binding). Antidepressant drugs induce downregulation of 45-kD IR protein and I1-sites in platelets of depressed patients and upregulation of I2-sites in rat brain. The densities of I2B-IR and the related 29/30-kD IR protein are decreased (39% and 28%) in the brain of heroin addicts. The density of I2B-IR is increased in Alzheimer's disease (63%) and decreased in Huntington's disease (56%). Brain I2B-IR is not altered in Parkinson's disease. The level of I2-IR in glial tumors is increased (two-fivefold) in parallel with the abundance of the related 29/30-kD IR protein (39%), whereas the level of 45-kD IR protein is decreased (39%). The possible functional relevance of these findings in the context of the pathogenesis of these disorders remains to be elucidated.
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PMID:Imidazoline receptors and human brain disorders. 1041 44

Some of the psychotropic agents widely used for the amelioration of anxiety, depression, and psychosis also show an effect at the cellular proliferation level. Surprisingly little research, however, has been directed to the antitumoral potential of these drugs, alone or in combination with established cancer treatments. Our review of the literature to date has yielded some promising early findings. Ligands active at the benzodiazepine (BZ) receptors have been studied the most extensively and were found to have differential, concentration-dependent effects on the growth and proliferation of both normal and cancer cells. Of the phenothiazines tested, chlorpromazine (CPZ) and perphenazine (PPZ) had the most potent cytotoxic action on fibroblasts and glioma cells. Antiproliferative effects also were noted by these and other agents in leukemic and breast cancer cell lines. Additional psychotropic drugs studied include the atypical antipsychotics, antidepressants, and mood stabilizers, especially lithium. Most of the reported activities were observed in in vitro studies and were achieved at high pharmacological concentrations. Further in vivo studies in well-designed animal models are warranted to determine whether these well-tolerated, relatively inexpensive, and widely available drugs or their derivatives may be added in the future to the armamentarium of cancer pharmacotherapy.
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PMID:Effects of psychotropic drugs on cell proliferation and differentiation. 1048 24

The frequency of mood disorder was studied in a cohort of patients with treated intracranial glioma or meningioma, where psychological morbidity was related to physical and neuropsychological functioning and to the patients' knowledge of their disease. Forty patients were assessed on a range of physical, psychological and neuropsychological measures, with additional interview of a relative to obtain supplementary information regarding each patients' knowledge of their disease. Two (5%) of the 40 patients had clinically significant levels of anxiety, six (15%) clinically significant levels of depression and 92% full or intermediate knowledge about their prognosis. Psychological morbidity was associated with high levels of physical disability and also with cognitive dysfunction, but was not related to the grade of the patient's tumour or the extent to which the patient was aware of the nature of his or her disease. A proportion of patients with intracranial tumours suffer levels of psychological distress sufficient to warrant psychological and/or pharmacological intervention.
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PMID:Mood disorders in patients after treatment for primary intracranial tumours. 1062 79

CNG channels are cyclic nucleotide-gated Ca(2+)-permeable channels that are suggested to be involved in the activity-dependent alterations of synaptic strength that are thought to underlie information storage in the CNS. In this study, we isolated an endogenous RNA transcript antisense to CNG(alpha)1 mRNA. This transcript was capable of down-regulating the expression of sense CNG(alpha)1 in the Xenopus oocyte expression system. RT-PCR, Northern blot, and in situ hybridization analyses showed that the transcript was coexpressed with CNG(alpha)1 mRNA in many regions of human brain, notably in those regions that were involved in long-term potentiation and long-term depression, such as hippocampal CA1 and CA3, dentate gyrus, and cerebellar Purkinje layer. Comparison of expression patterns between adult and fetal cerebral cortex revealed that there were concurrent developmental changes in the expression levels of anti-CNG1 and CNG(alpha)1. Treatment of human glioma cell T98 with thyroid hormone T(3) caused a significant increase in anti-CNG1 expression and a parallel decrease in sense CNG(alpha)1 expression. These data suggest that the suppression of CNG(alpha)1 expression by anti-CNG1 may play an important role in neuronal functions, especially in synaptic plasticity and cortical development. Endogenous antisense RNA-mediated regulation may represent a new mechanism through which the activity of ion channels can be regulated in the human CNS.
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PMID:An endogenous RNA transcript antisense to CNG(alpha)1 cation channel mRNA. 1238 67

Poly(A(+)) RNA was extracted from the temporal lobe (TL) of medically intractable epileptic patients which underwent surgical TL resection. Injection of this mRNA into Xenopus oocytes led to the expression of ionotropic receptors for gamma-aminobutyric acid (GABA), kainate (KAI) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Membrane currents elicited by GABA inverted polarity at -15 mV, close to the oocyte's chloride equilibrium potential, were inhibited by bicuculline, and were potentiated by pentobarbital and flunitrazepam. These basic characteristics were also displayed by GABA currents elicited in oocytes injected with mRNAs isolated from human TL glioma (TLG) or from mouse TL. However, the GABA receptors expressed by the epileptic TL mRNA exhibited some unusual properties, consisting in a rapid current run-down after repetitive GABA applications and a large EC(50) (125 microM). AMPA alone evoked very small or nil currents, whereas KAI induced larger currents. Nevertheless, upon cyclothiazide treatment, AMPA elicited substantial currents that, like the KAI currents, were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore, the glutamate receptor 5 (GluR5) agonist, ATPA, failed to evoke an obvious current although both RT-PCR and Western blot analyses showed GluR5 expression in the epileptic TL. Oocytes injected with mouse TL or human TLG mRNAs generated KAI and AMPA currents similar to those evoked in oocytes injected with epileptic TL mRNA but, in contrast to these, the mouse TL and human TLG oocytes were also responsive to ATPA. Our findings are in accord with the concept that both a depression of GABA inhibition and a dysfunction of the KAI-receptor system maintain a high neuronal excitability that results in epileptic seizures.
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PMID:Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy. 1240 14

Three variants of murine serotonin transporter (5-HTT) mRNA, which consist of a different exon-one (exon 1a, exon 1b or exon 1c) and the same exon-two to exon-five, were identified. The promoter region for each exon 1 (p1a, p1b and p1c, respectively), ligated to pGL-3 enhancer vector, had activities significantly higher than the empty vector in all cell lines tested except p1c in PC-12, whereas the activity of p1c was significantly lower than the others. Effects of the treatment of dibutyryl-cyclic AMP, human interferon-alpha or mouse interferon-gamma have different profiles among COS-7, PC-12, C6 glioma and immortalized rat serotonergic raphe neurons, RN46A. These three promoter regions may play a role in the transcription of the 5-HTT and could offer a model of the regulation of 5-HTT production in humans and further the pathogenesis of depression.
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PMID:Novel variants of murine serotonin transporter mRNA and the promoter activity of its upstream site. 1275 93

The overall goal of this study was to analyze the effect and mechanism of radiation in combination with vaccinia viruses (VV) carrying the p53 gene against glioma. Comparison of two alternative treatments of cultured C6 (p53(+)) and 9L (p53(-)) rat glioma cells showed significantly reduced survival for both cell lines, especially 9L, when radiation was applied prior to virus versus radiation alone. High p53 protein expression mediated by VV-TK-p53 was measured in infected cells. Single modality treatment of C6 cells with psoralen and UV (PUV)-inactivated VV-TK-p53 (PUV-VV-TK-53) or radiation significantly decreased survival compared with PUV-inactivated L-15 (PUV-L-15) control virus. However, no difference was observed between radiation and combination treatments of C6 cells. In contrast, radiation followed by PUV-VV-TK-53 resulted in dramatic reduction of 9L cell viability, compared to single modality treatment. Flow cytometry analysis of Annexin-V-stained 9L cells showed that radiation and PUV-VV-TK-53 caused a significant decrease in live cells (17.2%) as compared to other treatments and control (61.6-98.3%). Apoptosis was observed in 37.2% of cells, while the range was 0.7-7.8% in other treatment groups; maximal p53 level was measured on day 7 post-infection. In athymic mice bearing C6 tumors, VV-TK-53 plus radiation in both single and multiple therapies resulted in significantly smaller tumors by day 30 compared to the agents given only once. Immunohistochemical analysis of tumor sections demonstrated p53 protein expression over 20 days after VV-TK-53 treatment. Analysis of blood and spleen cells of mice given multiple combination treatments showed significant splenomegaly, leukocytosis, and increased DNA synthesis and response to mitogen. Multiple combination treatments were also associated with significantly elevated natural killer and B cells in the spleen. There were no overt toxicities, although depression in red blood cell and thrombocyte parameters was noted. Collectively, the data demonstrate that radiation significantly improves the efficacy of VV-mediated tumor suppressor p53 therapy and may be a promising strategy for glioma treatment. Furthermore, the results support the conclusion that the mechanisms underlying the enhanced anti-tumor effect of combination treatment include apoptosis/necrosis and upregulation of innate immune defenses.
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PMID:Radiation enhances the anti-tumor effects of vaccinia-p53 gene therapy in glioma. 1277 53

Soluble form of intercellular adhesion molecules (sICAM) are increased in serum of many inflammatory diseases and tumours: the expression of such molecules is regulated by cytokines. In the present paper serum levels of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R) and sICAM-1 were evaluated in patients with glioma compared with different tumours (lung and kidney carcinoma) in order to investigate the compromise of the immune system in these malignancies and to understand the host defence mechanisms. 14 cases of astrocytomas (WHO grade II, III), 20 cases of glioblastomas (GBL, WHO grade IV), 5 cases of lung carcinoma and 6 cases of kidney carcinoma were studied; the results were compared with 15 healthy controls. IL-2, sIL-2R, sICAM-1 concentrations were assessed by an enzyme-linked immunosorbent assay (ELISA) technique. The results were analyzed by Student's t test. Our findings showed that serum levels of IL-2 and sIL-2R were increased in all cancer patients; on the contrary, sICAM-1 serum levels were not significantly increased in GBL and astrocytoma patients. The increased values of IL-2 and sIL-2R are in agreement with a depression of the immune reactivity in patients with glioblastoma and astrocytoma, as reported in literature. On the contrary the levels of sICAM-1 are unchanged in astrocytic tumours while patients with kidney carcinoma presented the higher levels and an unfavourable prognosis.
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PMID:Evaluation of serum levels of cytokines and intercellular adhesion molecule-1 (ICAM-1) in astrocytic tumours. 1289 44

We investigated the ability of N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide (AC-5216), a novel mitochondrial benzodiazepine receptor (MBR) ligand, to produce anti-anxiety and antidepressant-like effects in various animal models. AC-5216 showed high affinity for MBRs prepared from rat whole brain (Ki 0.297 nm), rat glioma cells (IC50 3.04 nm) and human glioma cells (IC50 2.73 nm), but only negligible affinity for the other main receptors including central benzodiazepine receptors. AC-5216 produced anti-anxiety effects in the Vogel-type conflict test in rats, and in the light/dark box and social interaction tests in mice at 0.1-3, 0.003-0.01 and 0.01-0.3 mg kg(-1), p.o., respectively. These effects of AC-5216 were antagonized by PK11195, an MBR antagonist. In the forced swimming test in rats, AC-5216 (3-30 mg kg(-1), p.o.) reduced the immobility time, and this effect was blocked by PK11195. AC-5216 had no myorelaxant effects, did not affect the memory or prolong hexobarbitone-induced sleep in mice, even at doses as high as 1000 mg kg(-1), p.o. Although it did slightly prolong the ethanol-induced sleep time at 1000 mg kg(-1), AC-5216 (1-100 mg kg(-1), p.o.) produced no distinct change in the rat electroencephalogram. These results indicate that AC-5216 produces anti-anxiety and antidepressant-like effects that are mediated by MBR, but does not cause the side effects normally associated with conventional benzodiazepines. Hence, AC-5216 shows potential for the treatment of stress-related disorders including anxiety and depression.
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PMID:Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. 1524 20


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