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 major route of phosphatidylcholine (PtdCho) biosynthesis in mammalian cells is the sequence: choline (Cho)----phosphocholine (PCho)----cytidinediphosphate choline (CDP-Cho)----PtdCho. Recently, we have found that intermediates of this pathway are not freely diffusible in cultured rat glioma (C6) cells but are channeled towards PtdCho biosynthesis (George et al. (1989). Biochim. Biophys. Acta. 1004, 283-291). Channeling of intermediates in other mammalian systems is thought to be mediated through adsorption of enzymes to membranes and cytoskeletal elements to form multienzyme complexes. In this study, agents which perturb the structure and function of cytoskeletal elements were tested for effects on phospholipid metabolism in glioma cells. The filament-disrupting agent cytochalasin B (CB), but not other cytochalasins or the microtubule depolymerizer colchicine inhibited PtdCho and phosphatidylethanolamine (PtdEtn) biosynthesis as judged by dose-dependent reduction of labeling from [3H]Cho and [14C]ethanolamine (Etn). 32Pi pulse-labeling indicated that CB selectively decreased PtdCho and PtdEtn biosynthesis without affecting synthesis of other phospholipids. Synthesis of water-soluble intermediates of PtdCho metabolism was unaffected but the conversion of phosphoethanolamine to CDP-ethanolamine was reduced by CB. Effects of CB on phospholipid biosynthesis were not due to inhibition of glucose uptake as shown by experiments with 2-deoxyglucose, glucose-starved cells and other cytochalasins. Experiments with Ca(2+)-EGTA buffers and digitonin-permeabilized cells, and the Ca(2+)-channel blocker verapamil suggest that effects of CB on PtdCho and PtdEtn biosynthesis are due to alteration of intracellular Ca2+. Taken together, these results suggest that CB acts at sites distinct from glucose transport and cellular microfilaments to specifically inhibit PtdCho and PtdEtn biosynthesis by mechanisms dependent on intracellular Ca2+.
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PMID:Inhibition of phosphatidylcholine and phosphatidylethanolamine biosynthesis by cytochalasin B in cultured glioma cells: potential regulation of biosynthesis by Ca(2+)-dependent mechanisms. 185 4

Hyperthermia increases the cytotoxicity of the nitrosourea BCNU (carmustine). Glucose given before treatment may further increase the value of thermochemotherapy, presumably by lowering tumour pH through blood flow reduction. The water-soluble ACNU (nimustine) is an alternative to other nitrosoureas in the treatment of gliomas. The drug is soluble without use of ethanol, and the eye complications when given intra-arterially are reduced compared with similar use of BCNU. The influence of simultaneous hyperthermia on treatment with ACNU, and the value of glucose administered before thermochemotherapy therefore were investigated in the malignant rat glioma BT4An. BD IX rats with subcutaneous BT4An tumours on the hind leg were treated with ACNU (i.p.), or ACNU and locally applied waterbath hyperthermia (44 degrees C for 45 min), with or without previous glucose (6 g/kg i.p. 2 hours before treatment). ACNU (10 or 20 mg/kg) alone and ACNU (20 mg/kg) after previous glucose did not influence tumour growth, compared to the controls. Simultaneous ACNU (10 mg/kg) and hyperthermia clearly was more effective than treatment with hyperthermia alone. Glucose load before treatment further enhanced the effect of combined ACNU and hyperthermia. Glucose before treatment did not change local toxicity or weight profiles of treatment with ACNU alone, or simultaneous ACNU and hyperthermia. Glucose load therefore represented a therapeutic gain when administered before thermochemotherapy with ACNU.
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PMID:Thermal enhancement of ACNU and potentiation of thermochemotherapy with ACNU by hypertonic glucose in the BT4An rat glioma. 189 66

Little is known about the sensitivity of human glioblastoma cells to hyperthermia alone and in combination with other therapies. We carried out in vitro cell survival studies on the human glioblastoma cell line U-87MG and our model canine glioma canine brain tumor (CBT) cells after multimodality treatment. Ionizing radiation was administered to flasks of cells in logarithmic growth at 500 rads (5 Gy) with consecutive treatment by hyperthermia, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), or cisplatin. Cells were treated with single doses of BCNU at 5 microM with sequentially added radiation or hyperthermia and at 1 to 2 micrograms/ml of cisplatin with hyperthermia. Hyperthermia was administered in a precision controlled water bath at 44 degrees C for 30 minutes in combination with chemotherapy or radiation. In general, the sensitivity of U-87MG and CBT cells was similar for all test regimens. For example, colony formation efficiency decreased by 64% in CBT cells and by 64.4% in U-87MG cells after hyperthermia alone at 44 degrees C for 60 minutes. All combinations of BCNU, hyperthermia, and radiation administered in vitro produced enhanced cell killing, but the effects of multiple modalities were generally additive in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro response of human glioblastoma and canine glioma cells to hyperthermia, radiation, and chemotherapy. 194 32

To investigate whether brain tumors secrete a factor(s) responsible for peritumoral brain edema, we studied the effect of conditioned medium from cultured C6 glioma cells on rat brain capillary permeability. Three different fractions of conditioned medium were obtained. SUP-N was a culture supernatant incubated 4 hours in serum-free medium. SUP-C was the 60-100 fold concentrated fraction obtained by dialysis-concentration of SUP-N; it contained 950 micrograms/ml of protein greater than 10 k-daltons from 3 x 10(8) cells. SUP-L was a water-dispersible lipid fraction from SUP-N; the major components of SUP-L were neutral lipids and free fatty acids. The supernatant fractions and their corresponding control solutions were infused into normal rat brain, and capillary permeability was determined using quantitative autoradiography by measuring the unidirectional entry constant, K (micrograms l/g.min), of 14C-alpha-aminoisobutyric acid (14C-AIB) into brain tissue. SUP-C and SUP-L significantly increased capillary permeability of normal brain; the effect of SUP-C was more intense and extensive than that of SUP-L. The highest mean K value (Kmax) of SUP-C was 10.83 +/- 0.99 and that of the control was 2.53 +/- 0.22 (p less than 0.001). The Kmax of SUP-L was 5.61 +/- 0.23 and that of the control was 2.67 +/- 0.36 (p less than 0.01). A time-course study after infusion of SUP-C demonstrated that more than 1.5 hours is required for the supernatant fraction to open the barrier and that the effect of SUP-C was reversible. The increase of capillary permeability induced by SUP-C was significantly inhibited by pretreatment of rats with dexamethasone (10 mg/kg, ip) 1 hour before intracerebral infusion of SUP-C (Kmax (untreated): 8.30 +/- 0.82, Kmax (treated): 1.33 +/- 0.64, p less than 0.001). These results indicate that experimental brain tumors secrete at least two different diffusible factors responsible for capillary endothelial leakage in normal brain. One is a protein of molecular weight greater than 10 k-daltons, whose effect is inhibited by glucocorticoids, and the other is a waterdispersible lipid.
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PMID:Increased capillary permeability in rat brain induced by factors secreted by cultured C6 glioma cells: role in peritumoral brain edema. 202 71

Preparing cellular structures for visualization by high-resolution scanning electron microscopy (SEM) is a multi-step process which includes fixation, dehydration, drying and metal coating. Drying and metal coating are limiting for high-resolution work. Commonly, the dried samples are exposed to the air before they are inserted into a metal coating apparatus, thereby exposing them to moisture and the accompanying risk of rehydration, which may cause changes in the supramolecular structure. We have modified a freeze-dryer to accommodate a magnetron sputtering head, in order to sputter-coat the frozen-dried samples while still in the drying chamber in the cold, a process we call cryosputtering. A layer of 1.5 nm of tungsten was cryosputtered onto whole mounts of cytoskeletons from detergent-extracted human glioma cells or fibroblasts and the specimens were examined by high-resolution SEM and transmission electron microscopy (TEM). To reduce the effects of backstreaming oil from the vacuum system, a turbomolecular pump backed by a two-stage rotary vane pump was connected to the drying-coating chamber. This pump system provides a high vacuum, making it possible to dry the specimens at -90 degrees C/183 K, thus reducing the risk for recrystallization of water. Furthermore, the high vacuum minimizes the negative effects of contaminants, which can be deposited onto the specimen surface and affect the quality of the metal coat formed during sputtering.
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PMID:Cryosputtering--a combined freeze-drying and sputtering method for high-resolution electron microscopy. 203 32

Melphalan-induced toxicity in nude mice following pretreatment with a regimen of L-buthionine sulfoximine (BSO), previously shown to enhance the activity of this alkylating agent against rhabdomyosarcoma and glioma xenografts, was examined. Mice were pretreated with i.p. BSO (2.5 mmol/kg x 7 doses at 12-h intervals plus concomitant availability of a 20-mM solution in the drinking water) or vehicle prior to a single i.p. injection of melphalan (35.65 mg/m2). As compared with control animals who received no BSO pretreatment, mice pretreated with BSO lost weight prior to therapy with melphalan (6.9% weight loss vs 0.3% weight gain; P less than 0.005) and showed a greater mean nadir weight loss after melphalan (3.8% vs. 2.1%; P = 0.049). Treatment with melphalan was associated with histologic evidence of reversible gastrointestinal toxicity, reversible myelosuppression, and histologic evidence of acute renal tubular necrosis, with no differences being observed between mice that had been pretreated with BSO and those that had been pretreated with vehicle. No evidence of cardiac, hepatic, or skeletal muscle toxicity was found in melphalan-treated animals. These results suggest that treatment of nude mice with melphalan following BSO-mediated depletion of glutathione does not result in enhanced organ toxicity despite an increase in the antineoplastic activity of this alkylating agent.
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PMID:Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine. 204 29

The major route of phosphatidylcholine (Ptd-choline) biosynthesis in mammalian cells is the CDP-choline pathway which involves stepwise conversion of choline to phosphocholine (P-choline), cytidine diphosphate choline (CDP-choline), and Ptd-choline. Our previous studies with electropermeabilized (EP) rat glioma (C6) cells have indicated that the intermediates of this pathway are not freely diffusible in the cell but are channeled toward synthesis of Ptd-choline (George, T.P., Morash, S.C., Cook, H.W., Byers, D.M., Palmer, F. B. St.C., and Spence, M.W. (1989) Biochim. Biophys. Acta 1004, 283-291). In this study, Ca(2+)-[ethylene-bis(oxyethylenenitrilo)]tetraacetic acid buffers were used to investigate the role of intracellular free Ca2+ levels in functional organization of this pathway in EP glioma cells. In EP cells reduction of free Ca2+ in the medium from 1.8 mM to less than 200 nM resulted in 2-3-fold stimulation of exogenous [3H]choline and [14C]P-choline incorporation into Ptd-choline whereas incorporation of exogenous CDP-[14C]choline was augmented 100-fold; there was no uptake or incorporation of labeled P-choline or CDP-choline in intact cells. In EP cells incubated at 1.8 mM Ca2+ the water-soluble products of choline metabolism (choline, P-choline, CDP-choline, and glycerophosphocholine) were retained at 37 degrees C; in contrast, in the presence of 100 nM Ca2+ there was uniform leakage of these metabolites. Experiments with hemicholinium-3, an inhibitor of choline transport, and EP cells at 100 nM Ca2+ show that linkage of choline transport and Ptd-choline biosynthesis is also dependent on Ca2+. These results suggest that channeling of intermediates in the CDP-choline pathway of Ptd-choline biosynthesis in glioma cells is mediated by intracellular Ca2+ levels that may coordinately regulate the steps involved in conversion of choline to Ptd-choline.
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PMID:Channeling of intermediates in the CDP-choline pathway of phosphatidylcholine biosynthesis in cultured glioma cells is dependent on intracellular Ca2+. 206 17

The mechanical filtration coefficient (Lp) of the membrane of cultured glioma cells was determined from the rate of swelling of the cells. The swelling was induced by exposing the cells to distilled water. Assuming that cells swell in a symmetrical manner, Lp was 2.2 x 10(-8) cm/s.mmHg, or 1.7 x 10(-4) microns/s.cmH2O when calculated from changes of the cell diameter.
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PMID:The mechanical filtration coefficient (Lp) of the cell membrane of cultured glioma cells (C6). 208 73

Secondary mediator compounds are postulated to have a role in vasogenic oedematogenesis. They may also cause focal brain dysfunction due to their neuronal, axonal and glial modulating properties. Using the feline model of infusion brain oedema the effects of right frontal intracerebral infusion (200 microliters/hr for 3 hrs) of saline, bradykinin (10(-4) to 10(-6) M), arachidonic acid (10(-2) to 10(-3) M), 20% protein and four human glioma cyst fluids were evaluated. Somatosensory evoked potentials (SSEP), motor evoked potentials (MEPs), rCBF and rCBF CO2 reactivity (Hydrogen clearance). ICP, craniospinal compliance, local brain tissue water content (microgravimety), brain histology and BBB function (Evans Blue 2%) were measured. Brain water content increased locally from 69% to 79%, ICP increased (by mean 14 mmHg) and compliance decreased (mean 70%) and there were the histological features of brain oedema with all infusates. BBB opening occurred with Bradykinin (+), arachidonic acid (++), 20% protein ( ) and glioma cyst fluid (4+). Polymorphic and macrophage infiltrates were seen with all infusions but rCBF and MEPs remained normal. SSEPs changed with high dose bradykinin and some glioma cyst infusates whilst CBF CO2 reactivity was locally impaired by all infusates except saline and arachidonic acid. This study suggests that certain compounds in brain oedema fluid could mediate local brain dysfunction.
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PMID:The contribution of secondary mediators to the etiology and pathophysiology of brain oedema: studies using a feline infusion oedema model. 212 86

Glucocorticoids have been extensively used to treat brain oedema, but little is known on the mechanisms of steroids in the prevention and resolution of tumour-induced brain oedema. Recently, the mechanism of steroid action is thought to involve synthesis of proteins with antiphospholipase activity called lipocortins. In a previous study, we have demonstrated the efficacy of dexamethasone (DEX) in resolving peritumoural oedema in a rat glioma model. Using the same model, we studied the effect of recombinant human lipocortin I on the resolution of peritumoural oedema. Intracerebral tumours were produced in 6-week-old Wistar rats by implantation of rat glioma C6 cells. In comparison with sham-operated controls, the tumour-implanted animals showed significant increase in the cortical water content, which was reduced by DEX administration to the level in the sham-operated controls. The water content within the tumour was also significantly decreased by DEX treatment. On the other hand, there was no difference in water content between lipocortin-treated and non-treated animals. These findings suggest that tumour-induced brain oedema can be reduced by DEX treatment but not by lipocortin. In conclusion, it is doubtful whether glucocorticoids exert their action in resolving brain oedema by inducing PLA2 inhibitory proteins named lipocortins.
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PMID:Effect of recombinant human lipocortin I on brain oedema in a rat glioma model. 215 Oct 8


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