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)

An in vivo model for correlative imaging studies of intracerebral glial tumors and peritumor brain edema has been developed. Adult male and female cats implanted with 1 x 10(6) or 5 x 10(5) 9L glioma cells had parietal tumors of 4 mm or greater in diameter and showed signs of increased intracranial pressure 13.7 +/- 1.9 days or 19.2 +/- 1.3 days after implantation. No immunosuppression was required and the success rate for tumor growth after implantation was 88%. Histologically, the tumor resembles a malignant astrocytoma. The tumor contained the highest water content (85.94%); peritumor white matter was more edematous (73.01%) than white matter in the contralateral hemisphere (69.04%), sham-operated (69.41%) and control brain (68.76%). There was no correlation between the size of the tumor and water content in tumor or white matter. Increased tissue albumin in peritumor white matter indicated blood-brain barrier dysfunction within the tumor and confirmed the vasogenic origin of the edema. Proton magnetic resonance imaging provided good spatial and contrast resolution with increased signal intensity in edematous white matter, decreasing with distance from the tumor. The large brain of this animal model allows the use of serial imaging and regional correlative biochemical measurements in a single animal. Other advantages of this model are its predictability and the short time required to produce tumors with marked peritumor edema.
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PMID:A feline model for experimental studies of peritumor brain edema. 322 Dec 63

The catabolism of phosphatidylcholine (PtdCho) has been studied in cultured murine neuroblastoma (N1E-115), C6 glioma, rat brain primary glia, and human fibroblast cells. Cells were pulse labelled for 96 h with [methyl-3H]choline followed by a chase for up to 24 h in medium containing 4 mM choline. Measurement of the radioactivity and mass of choline-containing compounds in these cells indicated that the major degradative pathway is PtdCho----lysophosphatidylcholine (lysoPtdCho)----glycerophosphocholine (GroPCho)----choline. At all times during the chase, PtdCho, sphingomyelin and lysoPtdCho comprised 72-92% of the cell-associated radioactivity; the remaining 10-30% was water-soluble and was chiefly GroPCho (30-80%) in all cell lines. In fibroblasts, however, phosphocholine (PCho) was also a major labelled water-soluble component (33-54%). The specific activity of GroPCho closely parallelled that of PtdCho in fibroblasts, but decreased faster than PtdCho in C6 and N1E-115 cells. We postulate that this may be due to distinct pools of PtdCho in the cell with differing rates of turnover. The changes in specific activity of PCho suggest that the major portion is formed by synthesis rather than as a degradative product. However, the inability to reduce the specific activity of this fraction to that of the intracellular choline suggests that a portion may be derived from either PtdCho or GroPCho.
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PMID:Phosphatidylcholine metabolism in cultured cells: catabolism via glycerophosphocholine. 339 Apr 56

Photoradiation therapy using the photosensitizing agent, hematoporphyrin derivative (HpD), and laser light has been currently employed as a new modality for the treatment of cancer. At present, however, the application of this therapy is limited to superficial tumors because of difficulties in achieving light penetration, whereas 13.56 MHz radiofrequency (RF) used in hyperthermia is capable to penetrate into deeper regions and elevate the temperature of brain tumors. In the present studies, the author evaluated an anti-tumor effect of hyperthermic treatment with HpD administration on experimental malignant brain tumors both in vitro and in vivo and, moreover, investigated the histological changes of subcutaneous tumors following water bath heating and the uptake of HpD into the brain and subcutaneous tumors. In vitro, C-6 and Rous sarcoma virus-induced mouse glioma cells (RSV glioma cells) were incubated in the medium containing HpD (0-125 micrograms/ml) for 24 hours. Hyperthermia was performed either in a water bath or by 13.56 MHz RF heating in the range of 37-43 degrees C. All procedures were carried out in the dark. The anti-tumor effect was evaluated by counting the viable glioma cells. HpD itself showed a growth inhibitory effect on C-6 and RSV glioma cells dose-dependently, while synergistic effect was observed in combination with hyperthermia. C-6 cells were more sensitive to this treatment than RSV glioma cells. The degree of response depended on the heating time and the temperature. In both cells, the effect of heating by water bath and 13.56 MHz RF was similar at each temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anti-tumor effect of hyperthermia plus hematoporphyrin derivative on malignant brain tumor]. 341 65

Neonatal Fischer 344 rats were immunosuppressed with antithymocyte serum and later were given an injection intracerebrally of cells from the human glioma permanent line D-54MG. Symptomatic tumor-bearing rats were studied with double-label quantitative autoradiography to concurrently measure blood flow and a unidirectional blood-to-tissue transfer constant (K) for alpha-aminoisobutyric acid (AIB). A net extraction fraction (En) was calculated from the measured values for blood flow and K. Mean whole tumor blood flow was 53.5 +/- 4.9 ml/100 g/min (mean +/- SEM), which was significantly less than the blood flow to the tumor-free cortex (198 +/- 15.5 ml/100 g/min) but not significantly different from the blood flow in the tumor-free corpus callosum (50.6 +/- 4.3 ml/100 g/min). Mean whole tumor K-value for AIB was 5.8 +/- 0.5 ml/100 g/min, approximately 30 times the K-value for tumor-free brain. The calculated mean whole tumor En was 0.2 +/- 0.09, nearly 100 times the value for the tumor-free brain. Regionally, blood flow was lower in the tumor center and higher in its tumor periphery, although the difference was not significant. Both K- and En-values were significantly higher for the tumor center and decreased radially for the areas from center out. The values for K and En of AIB in the D-54MG gliomas are the highest of any experimental brain tumor model studied to date and indicate that in some tumor regions in this model, blood-to-tissue transport of the water-soluble compound AIB may be dependent on blood flow as well as on the permeability-surface area product of the tumor capillaries.
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PMID:Concurrent measurements of blood flow and transcapillary transport in xenotransplanted human gliomas in immunosuppressed rats. 347 39

The effects of the potent tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) on phosphatidylcholine (PtdCho) metabolism were investigated in the neuroblastoma X glioma hybrid cell line NG108-15. TPA (100 nM) stimulated by 150-200% the release into the medium of 3H radioactivity from cells that had been pre-labelled with [3H]choline. H.p.l.c. analysis of the medium revealed that TPA stimulated the release of only free [3H]choline (212 +/- 11% of control), without affecting such other labelled metabolites as [3H]phosphocholine and [3H]glycerophosphocholine. This effect was concentration-dependent, with a half-maximal effect obtained at 27.5 +/- 6.8 nM, and was observable as early as 5-10 min after exposure to TPA. The TPA-induced release of [3H]choline into the medium was accompanied by a small and variable decrease in cellular [3H]PtdCho (to 93 +/- 4% of control). However, the radioactivity associated with water-soluble cellular choline metabolites (mainly [3H]phosphocholine and [3H]glycerophosphocholine) remained unchanged. TPA also stimulated the release of [3H]choline derived from [3H]PtdCho that had been produced via the methylation pathway from [3H]methionine. These data suggest that phosphatidylcholine may serve as the source of free choline released from the cells in response to TPA. The possible enzymic mechanisms underlying this response are discussed.
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PMID:Stimulation of choline release from NG108-15 cells by 12-O-tetradecanoylphorbol 13-acetate. 356 13

After radiotherapy, 20 patients, 18 with documented progression of malignant glioma and 2 with Grade II astrocytoma, received a total of 52 courses of intracarotid 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) at a dose of 150 mg/m2 dissolved in 5% dextrose in water. The patients were treated at 6-week intervals for a maximum of five courses of chemotherapy per patient. Response to treatment was analyzed on computed tomographic scans by measuring the volume of the enhancing tumor and any central low density. From these data, tumor doubling times ranging from 110 to 968 days were obtained. An 11 to 60% reduction in enhancing tumor volume was noted in 8 patients, 2 of whom had a greater than 50% decrease in tumor volume. One patient had no change in tumor volume 110 weeks after the initiation of BCNU chemotherapy. Four patients had tumor in more than one vascular territory; tumor growth was arrested in the perfused territory, but continued in the nonperfused area. In 1 of the 4 patients, tumor also grew along a shunt catheter tract and spread over the surface of the ipsilateral hemisphere. One patient developed clinically asymptomatic leukoencephalopathy after five courses of BCNU. Two patients had postradiation leukoencephalopathy before BCNU treatment. Seventeen patients had peritumoral low density with mass effect after BCNU; thus, the true incidence of BCNU-related leukoencephalopathy could not be determined. All patients experienced transient unilateral orbital pain during the infusion and scleral erythema that lasted for several hours afterward. Loss of vision was noted in 2 patients, although it seemed to be related to the therapy in only 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracarotid chemotherapy with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) in 5% dextrose in water in the treatment of malignant glioma. 358 50

We have examined the effects of phorbol esters on phosphatidylcholine (PtdCho) metabolism in the neuroblastoma-glioma hybrid cell line NG108-15. 12-O-Tetradecanoylphorbol-13-acetate (TPA), 100 nM, stimulated twofold the incorporation of [3H]choline into PtdCho during 2 h of incubation at 37 degrees C. This effect of TPA was concentration dependent, exhibiting an EC50 of 24.5 +/- 4.4 nM. The effect of TPA was also time dependent and became apparent only after a lag period of 15-30 min. TPA also decreased the incorporation of [3H]choline into water-soluble cellular constituents in a manner whose concentration and time-dependence paralleled the changes observed in PtdCho content. HPLC analysis of this pool revealed that the levels of its major (85-95%) constituent, [3H]phosphocholine, were decreased by 29 +/- 5%, whereas those of [3H]glycerophosphocholine (0.5-2% of the pool) were increased by 84 +/- 4%. PtdCho labeling was also stimulated when cells were pulse labeled with [3H]choline and chased in the presence of TPA. The incorporation of [3H]inositol, [14C]ethanolamine, or [14C]serine into phospholipids was not affected by TPA. The non-tumor-promoting compounds phorbol and 4 alpha-phorbol-12,13-didecanoate (at 100 nM) were completely ineffective in modulating choline incorporation, whereas the biologically active analogs 4 beta-phorbol-12,13-didecanoate and 4 beta-phorbol-12,13-dibutyrate were as effective as TPA. We conclude that tumor-promoting phorbol esters can modulate PtdCho metabolism in neural-derived cells. The mechanisms mediating this effect and the possible involvement of PtdCho metabolism in normal signal transduction events and in the biological actions of tumor promoters are discussed.
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PMID:Phosphatidylcholine biosynthesis in the neuroblastoma-glioma hybrid cell line NG108-15: stimulation by phorbol esters. 377 85

2-Chloroethyl nitrosocarbamoylcystamine or ICIG-1325 (CNCC) is a lipid-soluble isomeric mixture of nitrosoureas. Its dose-effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose-range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.c.) transplanted L1210 leukaemia and on six transplanted solid tumours, TM2 mammary carcinoma, M555 ovarian carcinoma, B16 melanoma, glioma 26, 3LL, Lewis lung carcinoma and colon 26 carcinoma. It was inactive on fibrosarcoma ICIG-Ci4. Its antitumour activity spectrum is wider than that of the related compounds 2-[3-(2-chloroethyl) 3-nitrosoureido]D-glucopyranose (CZT), (chloro-2-ethyl)-1(ribofuranosyl-isopropylidene-2'-3' paranitrobenzoate-5')-3 nitrosourea (RFCNU), and (chloro-2-ethyl)-1 (ribopyranosyl triacetate-2'-3'-4')-3 nitrosourea (RPCNU). A study of its metabolic disposition in animals has shown that CNCC undergoes extensive first-pass metabolism leading to the formation of four main plasma metabolites. These metabolites are water-soluble nitrosoureas that arose from the bioreduction of the disulphide bridge followed by the methylation and the oxidation of the thiol groups. Experimental screening was performed with these chemically synthesized metabolites. Both N'-(2-chloroethyl)-N-[2-(methylsulphinyl)ethyl]-N'-nitrosourea (CMSOEN2) and N'-(2-chloroethyl)-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (CMSO2EN2) are very active on L1210 leukaemia grafted intraperitoneally (i.p.) and i.c., L40 leukaemia, B16 melanoma, glioma 26 and Lewis lung carcinoma. Their effectiveness is better than that of the parent compound CNCC. In addition,the percentage of mice cured after CMSOEN2 or CMSO2EN2 treatment is increased especially on B16 melanoma and glioma 26. 6 Haematological toxicity of both active metabolites is lower than that of CNCC, particularly on platelets which is the main toxicity location due to nitrosoureas.
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PMID:Cytostatic action of two nitrosoureas derived from cysteamine. 380 87

The antiglioma activity of elliptinium (HME) was investigated in a human glioma clonogenic cell assay. Early passage cells of three human glioma cell lines (SF126, SF375, and SF407) were exposed to HME at the clinically achievable dose of 3 microM for 3 h. At this HME concentration, clonogenic cell survival was reduced by more than 3 logs in SF126 and SF375, and by 0.8 logs in SF407. A study of the kinetics of cell kill showed that whereas at moderate (less than or equal to 1.5 microM) HME doses cell kill increased with treatment time up to a maximum at approximately 3 h, cytotoxicity was more dose than time dependent at higher doses. Flash treatment of SF375 cells with 3 microM HME resulted in more than 2 logs clonogenic cell kill. Using high-pressure liquid chromatography, we investigated the in vitro decay kinetics of HME under our in vitro drug treatment conditions and observed a very rapid, protein nondependent 40% drop in HME concentration which was dose dependent and was probably due to HME adsorption on the surface of tissue culture plasticware. Subsequent decay of the drug was very slow, with a decay rate constant of 0.022/h and a half-life of 298 h. In order to determine whether HME crosses the blood-brain barrier, we measured the rat brain capillary permeability coefficient, P, of [3H]HME and [14C]HME. The mean P value of 2.2 X 10(-6) cm/s +/- 16% (SD) suggests that HME crosses the blood-brain barrier (t 1/2 = 46 min) consistent with its molecular size and octanol-water partition coefficient.
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PMID:Potential antiglioma activity of 9-hydroxy-2-N-methylellipticine as determined by pharmacological and human tumor clonogenic cell studies. 400 38

Using [14C]dimethyloxazolidinedione ([14C]-DMO) and quantitative autoradiography, we estimated tissue pH (pHt) and intracellular pH (pHi) in nine regions of the normal rat brain and in intracerebrally implanted RG-2 gliomas. Calculations of regional pHt, based on equilibrium tissue and arterial plasma [14C]DMO concentration, ranged from 6.83 to 6.94; pHi, calculated assuming an extracellular water volume of 0.15 ml/g for gray matter and 0.11 ml/g for white matter, ranged from 6.61 to 6.78. No consistent difference was found in pHt or pHi between white and gray matter regions. Tumor tissue water content was determined by drying to constant weight, and extracellular space water volume (Ve) was estimated with [14C]sucrose in nephrectomized rats using quantitative autoradiography. Tumor pHt ranged from 7.08 to 7.18. For Ve = 0.17 (measured), pHi was 6.94-7.06; for Ve = 0.30 (assumed), the corresponding range for pHi was 6.63-6.90. Thus, the RG-2 glioma is not more "acidic" than adjacent brain tissue and its "alkaline" pHt probably reflects a large extracellular water content and plasma-like extracellular pH.
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PMID:In vivo measurement of regional brain and tumor pH using [14C]dimethyloxazolidinedione and quantitative autoradiography. 403 Sep 15


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