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)

Swelling of glial and nerve cells is characteristic of brain damage in cerebral ischemia or trauma. The therapeutical efficiency of inhibition of Cl(-)-transport by a novel antagonist, the diuretic torasemide, on cytotoxic swelling of glial cells from lactacidosis, or glutamate was analyzed. Lactacidosis and the interstitial accumulation of glutamate are hallmarks of the pathophysiological alterations in ischemic or traumatic brain tissue. C6 glioma cells harvested from culture and suspended in a physiological medium were either exposed to pH 6.2, or 5.0 by lactic acid, or exposed to 1 mM glutamate at normal pH. Cell swelling and viability were quantified by flow cytometry. Lactacidosis of pH 6.2 led to an increase in cell volume to 117.9 +/- 0.7% within 60 min. Torasemide (1 mM) inhibited the swelling response by 50% (P < 0.01). Cell swelling at pH 5.0, although more severe, was again attenuated by torasemide (P < 0.01). No effect was seen on the decrease in cell viability at this level of acidosis. Addition of glutamate led to a steady increase in cell volume which, contrary to cell swelling from lactacidosis, was not inhibited by torasemide. Inhibition of cell swelling from acidosis by this diuretic may be attributed to blocking of Cl-/HCO3- exchange mechanisms activated by acidosis. The lack of effect by torasemide in glial cell swelling from glutamate indicates operation of a different mechanism inducing cell swelling, for example cellular accumulation of the amino acid together with Na+ and water.
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PMID:Swelling of glial cells in lactacidosis and by glutamate: significance of Cl(-)-transport. 768 80

Water-soluble metabolites extracted from 20 astrocytic tumors (11 glioblastomas, 3 anaplastic astrocytomas, and 6 low-grade astrocytomas) and four normal brains were measured qualitatively and quantitatively using in vitro high-resolution proton magnetic resonance (1H-MR) spectroscopy. MR spectra from tumors exhibited characteristic patterns according to malignancy, presumably reflecting the metabolism of gliomas. Concentrations of choline-containing compounds, inositol, alanine, and glycine increased according to the malignancy, while that of total creatine decreased. In particular, glycine concentration was very high in glioblastoma, and an immunohistochemical study using anti-glycine antibody demonstrated that glycine was mainly distributed in glioma cells, not in proliferative endothelial cells. The ratios of choline-containing compounds and glycine to total creatine are useful parameters for grading gliomas, and the ratio of glycine to total creatine is useful for the differential diagnosis of glioblastoma from metastatic tumor. Such indications appearing in in vivo 1H-MR spectroscopy might provide clinically useful information on tumor metabolism and malignancy, and help assess the effects of radiation therapy and chemotherapy on gliomas.
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PMID:Proton magnetic resonance spectroscopy of astrocytic tumors: an in vitro study. 768 80

These experiments investigate the biodistribution of radiolabelled MAb in a human glioma xenograft model after 4 h of local hyperthermia (HT) with a twofold purpose: to maximize the ratio of cumulative isotope activity in tumour relative to normal tissues, and to examine the temperature dependence of the effect. Restrained, unanaesthetized athymic nude mice bearing 150-200 mm3 s.c. human glioma xenografts (D-54 MG) were given 5 micrograms 125I-labelled specific and 131I-labelled non-specific MAb immediately prior to HT (water bath) for 4 h. Cohorts of five animals were killed at 0, 4, 8, 12 and 24 h after HT, and normal and tumour tissues were analysed for activity of each isotope. MAb uptake in tumour was greater with HT than with controls, and greater for specific MAb than for non-specific MAb. Uptake in thyroid was not significantly affected by tumour HT, suggesting that HT does not increase the rate of dehalogenation. Uptake in several other normal tissues away from the heated site was significantly increased (as were reported previously in mice anaesthetized with pentobarbital sodium during treatment; Cope et al. 1990), but the temporal pattern was different from that observed in tumour, suggesting that short-lived isotopes might lead to preferential dose deposition in heated tumour. Doses to various tissues were calculated for isotopes having a range of half-lives; the results clearly indicated that maximum differential in uptake between tumour and normal tissues would occur for isotopes with half-lives < 3 days. A separate series of experiments compared tumour uptake for 40, 42 and 44 degrees C HT. These results demonstrated that 42 and 44 degrees C HT created maximum enhancement in specific antibody uptake over controls. Specific MAb was retained over time in 42 degrees C-heated tumours, whereas significant washout occurred for non-specific MAb, which indicates that MAb retention was due to increased specific binding at this temperature and not vascular damage with antibody trapping. Retention of both specific and non-specific MAb was seen at 44 degrees C, suggesting that vascular damage becomes an important non-specific mechanism for antibody retention at higher temperatures.
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PMID:Hyperthermic modulation of radiolabelled antibody uptake in a human glioma xenograft and normal tissues. 771 71

Several anticancer drugs have recently been shown to induce cell death in a manner similar to programmed cell death or apoptosis. The purpose of this study is to explore the mode of cell death caused by ACNU, a water-soluble nitrosourea. Exposure of rat glioma cell line KEG-1 to ACNU for 2 hours resulted in oligonucleosomal DNA fragmentation, creating a 'ladder' on agarose gel electrophoresis. DNA fragmentation began 18 hours after ACNU treatment, and preceded loss of membrane integrity as evaluated by the trypan blue exclusion test. The extent of DNA fragmentation increased in a dose-dependent manner, and the cell survival rate decreased reciprocally. A translational inhibitor, cycloheximide, suppressed this DNA fragmentation and enhanced cell survival rate with partial inhibition of protein synthesis. However, a transcriptional inhibitor, actinomycin D, failed to inhibit DNA fragmentation or enhance cell survival. Cycloheximide-inhibitable DNA fragmentation was also found in the KEG-1 implanted in vivo rat model following the administration of ACNU. These findings suggest that ACNU induces cell death associates with DNA fragmentation and partially with protein synthesis.
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PMID:Cell death due to ACNU-induced DNA fragmentation: inhibition by cycloheximide. 771 48

Two aspects of cytokine therapy of intracerebral tumors are considered in this study: modulation of tumor growth in vivo and central nervous system toxicity. Coimplantation of RG-2 glioma cells and retroviral vector producer cell lines was performed to provide a local source of interleukin-2 (IL-2) or IFN-gamma within the tumor and coinitiate an antitumor immune response. We demonstrated that local intratumoral production of IL-2 and IFN-gamma generates a cell-mediated antitumor response in vivo. This response was manifest as a diffuse infiltration of monocytes/macrophages, CD4+ and CD8+ T cells, and activation of microglial OX42+ cells in intracerebral RG2 tumors. The cell-mediated antitumor immune response resulted in the early suppression of intracranial and subcutaneous tumor growth, but the effect was not sustained and there were no tumor regressions. The absence of increased survival of animals with intracranial tumors is explained in part by the severe central nervous system toxicity caused by local production of IL-2 and IFN-gamma. Central nervous system toxicity induced blood-brain barrier disruption, vasogenic brain edema, and dislocation of the brain midline structures, as observed by dynamic magnetic resonance imaging and direct measurements of tissue water content. The clinical application of IL-2 and IFN-gamma gene transfer therapy for intracerebral tumors must consider the potential for severe vasogenic brain edema associated with intracerebral production of these cytokines.
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PMID:RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. 772 57

Cyclocreatine, an analogue of creatine, inhibits tumor cell proliferation in vitro and in vivo. The effects of cyclocreatine in large C6 glioma multicellular spheroids were mapped here by magnetic resonance microscopy. Diffusion-weighted images of C6 glioma spheroids resolved the bright viable rim and the dark necrotic center. Sequential sets of diffusion images, following cyclocreatine administration, showed increasing self-diffusion coefficients of the intracellular water in the viable rim (0.49 x 10(-5) cm2/s for untreated spheroids, 0.62 x 10(-5) cm2/s after 48 h perfusion with 20 mM cyclocreatine). This fact correlated with cellular swelling apparent in histological sections. The radial distribution of cyclocreatine and soluble lipids across perfused C6 spheroids was measured by one-dimensional chemical shift imaging. Cyclocreatine accumulation was prominent throughout the viable cell layer, with no cyclocreatine accumulation in the necrotic center. In both cyclocreatine-treated and control spheroids the lipid signal was highest in the necrotic center and lower in the inner viable cell layer.
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PMID:Cyclocreatine accumulation leads to cellular swelling in C6 glioma multicellular spheroids: diffusion and one-dimensional chemical shift nuclear magnetic resonance microscopy. 780 26

Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P -0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.
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PMID:Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in dogs. 780 74

Resistance to chemotherapy in brain tumors is complex and may involve multiple mechanisms. For commonly used drugs, such as nitrosoureas and platinum compounds, major mechanisms may involve increaded DNA repair or removal of the drug-DNA adducts. For water soluble nitrosoureas and also for platinum compounds, other mechanisms, such as alteration in drug transport, may be important. Another major mechanism may involve glutathione and glutathione-S-transferase pathways. For vinca alkaloids and epipodophyllotoxins p-glycoprotein mediated MDR appears to be the major feature in drug resistance. In addition, alteration of tubulin and topoisomerase II have been described in resistance to vinca alkaloids and epipodophyllotoxins respectively. Recently, increased multidrug resistance associated protein gene expression has been found in glioma cells and brain tumor samples; its clinical significance requires further investigation.
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PMID:Drug resistance in brain tumors. 780 93

When a photochemically-induced infarct was produced in the right cortex of rats, tissue water content was increased markedly 4 and 24 h later (control: 79.00 +/- 0.08% ischaemia, 24 h: 82.96 +/- 0.15%). The left cortex was unaffected. Chlormethiazole (200 mg/kg i.p.) injection 5 min after onset of ischaemia decreased the oedema (ischaemia/chlormethiazole, 24 h: 82.16 +/- 0.21%, P < 0.01). At 24 h, ischaemic tissue Na+ content was increased (61%) and the K+ content decreased (9%). The Na+/K+ ratio therefore increased significantly (P < 0.001), a change that was diminished by chlormethiazole administration (P < 0.02). Chlormethiazole (1 mM), unlike furosemide (5 mM), did not reduce swelling of C6 glioma cells in hypotonic medium. The data suggest that chlormethiazole decreases oedema in this stroke model because of its neuroprotective properties and not because of an effect on anion transport.
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PMID:Attenuation by chlormethiazole of oedema following focal ischaemia in the cerebral cortex of the rat. 793 18

The effect of arachidonic acid (AA, 20:4) was analyzed in vitro by employment of C6 glioma cells and astrocytes from primary culture. The cells were suspended in an incubation chamber under continuous control of pH, pO2, and temperature. Cell swelling was quantified by flow cytometry. After a control period, the suspension was added with AA at concentrations of 0.01 to 1.0 mM. Administration of AA induced an immediate, dose dependent swelling in C6 glioma cells or astrocytes. AA-concentrations of 0.01 mM led to an increase of the glial cell volume to 103.0 +/- 1.0% of control, 0.1 mM to 110.0 +/- 1.5%, and 1.0 mM to 118.8 +/- 1.5% within 10 min. The swelling response to linoleic acid (18:2) was only about half of what was found when AA was administered at a concentration of 0.1 mM, whereas stearic acid (18:0) did not induce any cell volume changes. Inhibition of the cyclo- and lipoxygenase pathway by BW 755C did not prevent glial swelling from AA, whereas it was reduced by SOD, or almost completely abolished by the aminosteroid U-74389F, an antagonist of lipid peroxidation. Replacement of Na(+)- and Cl- -ions in the suspension medium by choline chloride was also associated with complete abolishment of cell swelling from AA. The results demonstrate an impressive efficacy of arachidonic acid to induce glial swelling which might be attributable to activation of lipid peroxidation by the fatty acid, leading to an increased Na(+)-permeability and subsequent influx of water into the cells.
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PMID:Mechanisms of glial swelling by arachidonic acid. 797 45


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