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)

A microphysiometer was used to quantify the rate of extracellular acidification by C6 glioma cells and L fibroblasts expressing recombinant dopamine D2 receptors. The dopamine D2 receptor agonist, quinpirole, accelerated the rate of acidification of the medium by C6 cells expressing either the short or long form of D2 receptors, D2(415) and D2(444), but not by wild-type cells that were not transfected with a D2 receptor cDNA. The rate of acidification increased with increasing concentrations of quinpirole up to 100 nM. Inhibition of the response by the dopamine D2 antagonist, spiperone, provided additional evidence that the enhanced extracellular acidification resulted from stimulation of D2 receptors. To test the hypothesis that D2 receptor-stimulated extracellular acidification was due to transport of protons by a Na+/H+ antiporter and reflected intracellular alkalinization, the effect of two inhibitors of Na+/H+ exchange, amiloride and methyl-isobutyl-amiloride, was determined. Both compounds inhibited quinpirole-induced extracellular acidification at concentrations that did not alter D2 receptor-mediated inhibition of adenylylcyclase or radioligand binding to D2 receptors. In addition, quinpirole-induced extracellular acidification was greatly inhibited by removal of sodium from the extracellular medium, confirming the participation of Na+/H+ exchange in the extrusion of acid. Quinpirole (100 nM) also increased the rate of extracellular acidification by L cells expressing D2(415), LZR1 cells. Treatment with pertussis toxin (100 ng/ml for 18 h) had no effect on the quinpirole-induced acid extrusion by C6D2(415) and LZR1 cells, although the same pertussis toxin treatment regimen completely prevented inhibition of adenylylcyclase. We conclude that recombinant D2 receptors accelerate Na+/H+ exchange in C6 cells and L fibroblasts by a pathway that does not involve inhibition of adenylylcyclase or pertussis toxin-sensitive G proteins.
J Biol Chem 1992 Dec 25
PMID:Dopamine D2 receptor stimulation of Na+/H+ exchange assessed by quantification of extracellular acidification. 136 Nov 88

The effects of platelet-derived growth factor (PDGF) on phospholipase D (PLD) activity and deoxyribonucleic acid (DNA) synthesis in rat C6 glioma cells have been investigated. Pretreatment of serum-starved C6 cells with PDGF results in enhanced choline production and the phosphatidylethanol (PEt) formation in the presence of ethanol, indicating the activation of PLD acting on phosphatidylcholine (PC). The dose-response curve for choline generation and DNA synthesis were comparable. In addition, the effects of PDGF on both PEt formation and [3H]thymidine incorporation into acid-precipitable material was blocked by the potent protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) but not by N-(2-guanidinoethyl)-5-isoquinolinesulphonamide (HA1004), a relatively weak inhibitor of PKC, suggesting that PDGF plays an important role as a positive regulator of glioma cell growth via a PLD-mediated mitogenic signal transduction cascades, which depends largely on the activation of PKC.
Neurol Res 1992 Dec
PMID:Activation of phospholipase D by platelet-derived growth factor (PDGF) in rat C6 glioma cells: possible role in mitogenic signal transduction. 136 54

C6 rat glioma cells were utilized as a model system to probe the 'serotonin/norepinephrine link' at the level of preproenkephalin (PPE) gene expression. The beta adrenoceptor mediated increase in PPE mRNA was attenuated by the selective beta 1 adrenoceptor antagonist metoprolol which blocked the isoproterenol induced cyclic AMP generation by 97%. The subtype nonspecific antagonist propranolol blocked both the isoproterenol induced increase in cyclic AMP and the increase in the PPE mRNA steady-state levels. Serotonin (5-HT) had no effect on the density of beta adrenoceptors or their down-regulation by isoproterenol and did not alter the PPE gene expression in the absence of the beta signal. However, 5-HT significantly deamplified the beta signal mediated enhancement of the PPE mRNA thus indicating that the aminergic link occurs beyond the beta adrenoceptor.
Brain Res Mol Brain Res 1992 Dec
PMID:The 'serotonin/norepinephrine link' beyond the beta adrenoceptor. 136 25

In the period from Jan 1 1984 to Dec 31 1990 clinical and radiological evidence of brain glioma was found in 120 cases treated previously surgically. The group comprised 55 women (46%) and 65 men (54%). At the time of tumour diagnosis their age was ranged 40 to 60 years. All patients received non-radical surgical treatment, supplemented with Co60 radiation in 104 cases, in 3 cases Co60 treatment was given together with chemotherapy (CCNU) and 12 patients received no complementary treatment. Thirty four patients (28%) had reoperations, in two cases even twice. In 86 cases (72%) treatment was palliative. Three types of secondary tumour regrowth were discerned. Reoperation prolonged survival and its effectiveness was greatest in regrowth type I. The shortest survival till the appearance of regrowth signs and the shortest survival after recurrence were in type II of regrowth.
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PMID:[Diagnosis and treatment of recurrent brain glioma]. 140 84

Experimental brain tumors were produced in cats by xenotransplantation of the rat glioma clone F98 into the white matter of the left hemisphere. One to 4 weeks after implantation, local adenosine triphosphate (ATP), glucose, lactate, and tissue pH were measured via imaging techniques in cryostat sections passing through the center of the tumor and correlated with changes in water and electrolyte content. The tumors exhibited a heterogeneous metabolic pattern, with a tendency for ATP to decrease and lactate to increase during tumor development. Tissue pH was above 7.5 in tumors with high ATP content but it sharply declined at low ATP levels. In peritumoral edema, ATP also decreased and lactate increased but, in contrast to tumor tissue, pH became more alkaline. Metabolic changes were associated with edema formation, as evidenced by the rise in water and sodium content. There was a distinct difference between tumor tissue and peritumoral edema: in tumor tissue, pH declined with increasing water content, whereas in peritumoral edema it increased. These observations are interpreted as follows: 1) in tumor tissue, "lactacidosis" and ATP depletion are attributed to disturbances in blood flow, resulting in metabolic failure and the intracellular "cytotoxic" accumulation of water; 2) in peritumoral edema, "lactalkalosis" is the result of an efflux of (alkaline) lactate salts from the tumor into the expanded extracellular compartment, and the decrease in ATP is the volumetric effect of extracellular "vasogenic" edema fluid and not the result of cellular energy failure. These findings are of importance for the interpretation of volume-selective magnetic resonance spectroscopy and may contribute to the establishment of spectroscopic criteria for the evaluation of therapeutical interventions.
J Neurosurg 1992 Dec
PMID:Regional metabolism in experimental brain tumors in cats: relationship with acid/base, water, and electrolyte homeostasis. 143 36

Brain tumor metabolism was studied with hydrogen-1 magnetic resonance spectroscopy and positron emission tomography with fluorine-18 fluorodeoxyglucose in 50 patients. N-acetylaspartate (NAA) was generally decreased in tumors and radiation necrosis but was somewhat preserved at neoplasm margins. Choline was increased in most solid tumors. Solid high-grade gliomas had higher normalized choline values than did solid low-grade gliomas (P < .02), but the normalized choline value was not a discriminator of tumor grade, since necrotic high-grade lesions had reduced choline values. Serial studies in one case showed an increase in choline as the glioma underwent malignant degeneration. Choline values were lower in chronic radiation necrosis than in solid anaplastic tumors (P < .001). In two cases studied before and after treatment, clinical improvement and a reduction in choline followed therapy. Lactate is more likely to be found in high-grade gliomas, but its presence is not a reliable indicator of malignancy.
Radiology 1992 Dec
PMID:Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance. 143 44

ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride], one of the chloroethylnitrosoureas (CENUs), is believed to be effective against malignant glioma when intravenously or intrathecally administered. A rat model with meningeal gliomatosis (MG) induced by an intracisternal inoculation of rat C6 or 9L glioma cells was intrathecally and intravenously treated with ACNU in order to test the feasibility of intrathecal chemotherapy with ACNU in the treatment of meningeal gliomatosis. The median survival time (MST) of the animals was significantly prolonged when ACNU was intrathecally administered at dosages of 0.5 to 1.5 mg kg-1 in the early stages of MG, i.e. within 3 days after the tumour inoculation, whereas intravenous therapy with ACNU at a dose of 15 mg kg-1 did not exhibit any efficacy in the rats inoculated with C6 glioma cells (C6-MG). Intrathecal ACNU, however, at dosages of up to 1.5 mg kg-1 failed to demonstrate any therapeutic effect in the late stage of MG, i.e. 5 days after the tumour inoculation, except in the rats inoculated with 9L brain tumour cells (9L-MG). Intravenous chemotherapy with ACNU at a dose of 15 mg kg-1 extended the MST of the 9L-MG rats more significantly in the late stage of MG than in its early stage. This points to the feasibility of intrathecal ACNU in the treatment of meningeal gliomatosis in its early stages, but not in its late stages in which intravenous ACNU might be more effective than intrathecal treatment against MG of which the parenchyma has already been deeply invaded by the tumour.
Br J Cancer 1992 Dec
PMID:Intrathecal chemotherapy with ACNU for meningeal gliomatosis. 145 69

Glial tumors remain challenging problems for the clinician and researcher. Despite more aggressive therapy, the majority of these tumors recur locally. This review will provide an update on the new strategies being developed to treat gliomas. Advances in our understanding of the biology of glial tumors will provide new targets at which to direct therapy.
Curr Opin Neurol Neurosurg 1992 Dec
PMID:Biology and therapy of glial tumors. 146 71

The principal non-glial tumors of the brain are meningiomas and acoustic schwannomas. Advances in the management of meningiomas have included endovascular techniques for embolization to reduce blood loss, radical surgical approaches, and the recognition of the high recurrence rate of these tumors. Advances in the management of acoustic tumors have been in preservation of VIIth nerve function, improved preservation of hearing, and the availability of stereotactic radiosurgical techniques as an alternative. There is still a substantial discussion concerning the route of surgery for acoustic tumors and not all agree that hearing preservation is a reasonable goal at present.
Curr Opin Neurol Neurosurg 1992 Dec
PMID:Non-glial tumors of the brain: tumors of the cerebellopontine angle and meningiomas. 146 72

The fungal metabolite brefeldin A (BFA) is known to disrupt the Golgi apparatus resulting in redistribution of Golgi proteins to the endoplasmic reticulum and inhibition of protein secretion. BFA was found to inhibit protein synthesis in rat glioma C6 cells by up to 70% between 0.1 and 1 microgram/ml. Inhibition was both time-dependent and reversible. BFA inhibited protein synthesis to varying degrees in a number of other cell lines but not in BFA-resistant marsupial kidney cells. The same concentrations of BFA which inhibited protein synthesis, also blocked the inhibitory effects of Pseudomonas exotoxin and ricin on BFA-sensitive cells. BFA, however, was unable to block the inhibition of protein synthesis by the toxins in the resistant marsupial kidney cells.
FEBS Lett 1992 Dec 21
PMID:Brefeldin A inhibits protein synthesis in cultured cells. 146 70


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