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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

31P-NMR spectroscopy has been used to study the energy metabolism and the NMR visibility of ATP and intracellular Pi of the C6 glioma cell line and rat astrocyte grown on microcarrier beads with the following results. 1. In vivo NMR spectra of C6 glioma cells and rat astrocytes indicate that these cells were able to maintain their level of ATP resonances during a long anoxic period (more than an hour). Both cell types were sensitive to ischemia which induced a loss of ATP resonances within 40 min. Glucose starvation induced by 40% decrease in ATP resonances correlated to a 50% increase in the intensity of the Pi signal. These changes corresponded to a new steady state which could be reversed by reperfusing the cells with a glucose-containing medium. 2. In contrast to in vivo data, 31P-NMR analyses of perchloric acid extracts of cells incubated in a glucose-free medium showed that their ATP and Pi contents were unchanged during starvation. The changes of NMR visibility of the metabolites in living C6 cells were correlated to modifications of their macroscopic longitudinal relaxation times, evolving from 0.30 +/- 0.08 s and 6.6 +/- 1.5 s in the presence of glucose to 0.68 +/- 0.26 s and 3.2 +/- 0.9 s in the absence of glucose for ATP and Pi, respectively. The changes of the NMR detectability of ATP and Pi indicate that changes in their microenvironment occur during glucose starvation, suggesting the existence of different pools of these metabolites within the cells. 3. Under various experimental conditions, i.e. anoxia, ischemia and glucose starvation, rat astrocytes in primary culture showed a very similar behavior to that of C6 cells, suggesting a similar adaptability to the nature of the energy supply for both the normal and the malignant cell.
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PMID:Phosphorus-31 nuclear magnetic resonance of C6 glioma cells and rat astrocytes. Evidence for a modification of the longitudinal relaxation time of ATP and Pi during glucose starvation. 199 80

The occurrence of the endogenous regulatory response to high rates of 2-deoxyglucose (2-DG) uptake, as previously described for C6 glioma cells during incubation with 2 mM 2-DG (Lange et al.: J. Cell. Physiol., 1989), was studied in 3T3-L1 preadipocytes and adipocytes, and the influence of insulin on this endogenous uptake regulation was examined. In contrast to 3T3-L1 preadipocytes, insulin-sensitive differentiated 3T3-L1 adipocytes displayed the time-dependent cyclic pattern of 2-DG uptake rates characteristic of the membrane-limited and endogenously regulated cellular state of hexose utilization. Although insulin induced a threefold stimulation of 2-DG tracer uptake in adipocytes, the hormone did not additionally stimulate the uptake rates or affect the periodic response: maximum and minimum levels of uptake remained unchanged. Scanning electron microscopy (SEM) revealed that the acquirement of the differentiated state is accompanied by a conspicuous transformation of the smooth surface of undifferentiated 3T3-L1 cells into a surface covered by numerous microvilli of uniform size and appearance. Treatment with insulin (10 mU/ml; 10 minutes) converted these microvilli into voluminous saccular membrane protrusions of the same type as had been formed during incubation of 3T3-L1 adipocytes with 2 mM 2-DG, and which have previously been shown to be involved in the endogenous uptake regulation of C6 glioma cells (Lange et al.: J. Cell. Physiol., 1989). These insulin-induced saccated membrane areas appeared to become integrated into the cell surface. Accordingly, insulin treatment caused a twofold increase of the intracellular distribution space of 3-O-methylglucose (3-OMG) in 3T3-L1 adipocytes. This insulin-induced increase of the 3-OMG distribution space exhibited the same time (t1/2 = 2-2.5 minutes) and dose dependence (EC50 = 20 nM) as the insulin-induced stimulation of 3-OMG transport. Glucose deprivation during the differentiation period inhibited the outgrowth of microvilli from the cell surface. Glucose starvation (18 hours at less than 0.5 mM) induced a conspicuous reduction of the length of microvilli on differentiated 3T3-L1 cells. In this state, the stalks of the microvilli are almost invisible and the enlarged spherical tips of the microvilli (with an average diameter of 370 nm compared to 230 nm of fed cells) appeared to protrude directly out of the cell surface. Starvation-induced shortening of microvilli was accompanied by a threefold increase of the basal 3-OMG transport rate and a greater than twofold increase of the intracellular 3-OMG distribution space as compared to fed cells (10 mM; 18 hours).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationship between insulin stimulation and endogenous regulation of 2-deoxyglucose uptake in 3T3-L1 adipocytes. 240 95

The uptake of the fluorescent, lysosomotropic weak base acridine orange (AO) by living cells in culture was studied by flow cytofluorometry. A mouse myeloma cell line (SP 2/0), growing in suspension, and an anchorage-dependent human malignant glioma cell line (U-251 MG), brought into suspension by trypsinization, were used. The consequences of trypsinization were also studied using static cytofluorometry. The lysosomal accumulation of AO by myeloma cells growing in suspension was found to be only moderately affected by starvation (i.e. incubation without medium change) for a period of up to five days. Trypsinization of the glioma cells after staining with AO caused pronounced release of the fluorescent dye while trypsinization before staining with AO did not significantly change the average lysosomal concentration of AO. We did, however, notice certain side effects of trypsinization in the form of both increased cellular green fluorescence and greater intercellular variability that reduce the validity of data obtained from cells detached by routine trypsinization. In conclusion, the condition of the lysosomal vacuome of living cultured cells growing in suspension may be studied by flow cytofluorometry after vital staining with the lysosomotropic weak base AO. Anchorage-dependent trypsinized cells, however, yield unsatisfactory results when examined in a flow cytofluorometer system and are better studied while still attached to their substratum, using static cytofluorometry.
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PMID:Flow cytofluorometry of lysosomal acridine orange uptake by living cultured cells. Effect of trypsinization and starvation. 361 27

Perfusion insufficiency, and the resultant hypoxia, often induces a compensatory neovascularization to satisfy the needs of the tissue. We have used multicellular tumor spheroids, simulating avascular microenvironments within a clonal population of glioma tumor cells, in conjunction with in situ analysis of gene expression, to study stress inducibility of candidate angiogenic factors. We show that expression of vascular endothelial growth factor (VEGF) is upregulated in chronically hypoxic niches (inner layers) of the spheroid and that expression is reversed when hypoxia is relieved by hyperoxygenation. Acute glucose deprivation--another consequence of vascular insufficiency--also activates VEGF expression. Notably, glioma cells in two distinct regions of the spheroid upregulated VEGF expression in response to hypoxia and to glucose starvation. Experiments carried out in cell monolayers established that VEGF is independently induced by these two deficiencies. Upon implantation in nude mice, spheroids were efficiently neovascularized. Concomitant with invasion of blood vessels and restoration of normoxia to the spheroid core, VEGF expression was gradually downregulated to a constitutive low level of expression, representing the output of nonstressed glioma cells. These findings show that stress-induced VEGF activity may compound angiogenic activities generated through the tumor "angiogenic switch" and suggest that stress-induced VEGF should be taken into account in any attempt to target tumor angiogenesis.
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PMID:Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. 753 42

The Id2 gene is one of several "Id-like" genes which encode helix-loop-helix proteins which dimerize with basic helix-loop-helix proteins and inhibit binding to the DNA enhancer element known as an E box. By repressing the DNA binding activity of basic helix-loop-helix proteins, Id proteins inhibit transcription of tissue-specific genes in myoblasts, hematopoietic precursor cells, and other types of undifferentiated cells. Serum starvation results in the disappearance of Id gene transcripts in most types of cultured cells, and often induces differentiation of these cells. In order to gain some insight into this process, we have analyzed Id2 promoter function in the glioma cell line U87Y. We have isolated 300 base pairs of Id2 promoter sequence which is sufficient to repress the activity of a reporter gene in serum-starved U87Y cells, but induces the activity of the reporter gene when the cells are stimulated with fresh serum. Two regions within this 300 base pair sequence contain repressor elements; deletion of either region results in increased promoter activity. Both repressor regions serve as binding sites for a protein present in extracts from serum-starved U87Y cells but not in serum-stimulated cells.
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PMID:Repression of the Id2 (inhibitor of differentiation) gene promoter during exit from the cell cycle. 762 74

Trapidil is a PDGF antagonist that can inhibit the proliferation of the PDGF-producing glioma cells, U251MG. As the mechanism of growth-regulation by trapidil remains unclear, we studied its effect on the growth of U251MG cells. We performed a cell cycle analysis and examined the intracellular transduction pathway and oncogene expression in serum-stimulated glioma cells with or without trapidil. After the serum starvation for 3 days, glioma cell proliferation was stimulated by the addition of serum. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G0-G1 to S phase, suggesting that some metabolic event is required for progress through the G0-G1 phase and that this event is sensitive to trapidil. Internal signal transduction mechanisms are central in the molecular control of cell growth. One such regulator is the protein kinase C(PKC) system and the c-fos gene is likely to be a direct target of intracellular signal transduction pathways. Therefore, we hypothesize that the intracellular PKC activity and c-fos expression of the trapidil-treated cells are suppressed. We posit that trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression in cells stimulated with serum containing growth factors.
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PMID:The mechanism of growth-regulation of glioma cells by trapidil. 767 82

The parallel effects of simvastatin on cell cycle and PKC activity in rat C6 glioma cells were investigated. Simvastatin, 2.5 microM, for 24 h resulted in cell growth arrest in early G1 phase of the cell cycle and in a significant increase of total PKC activity (283 +/- 42 vs 470 +/- 61 pmoles/min/mg protein p = 0.002 for control cells and simvastatin-treated cells, respectively). The effect of simvastatin was fully prevented by mevalonate. A time dependent increase of PKC activity was observed in control exponentially free-growing C6 cells approaching confluency: a highly significant negative correlation (r = -0.91 p < 0.0001) between PKC activity and growth rate was calculated. PKC activity was high in cells arrested in G0 by serum starvation (0.4%). Following addition of complete medium (17.5% serum) the PKC activity progressively decreased and reached a minimum when cells traversed the G2/M phase, as determined by DNA analysis distribution. PKC activity dropped 30% in simvastatin-arrested early G1 cells; 44% in hydroxyurea-arrested cells at the G1/S boundary; and 73% in Colcemid mitosis-blocked cells. The results show that C6 glioma cell PKC activity is maximal in a G0 quiescent state and varies at different points of the cell cycle.
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PMID:PKC activity in rat C6 glioma cells: changes associated with cell cycle and simvastatin treatment. 817 95

Insulin has a wide variety of biological effects. One of them is a mitogen-like activity whereby cell proliferation is stimulated. In this study we found a heretofore unreported insulin-elicited transient apoptosis of glioma cells. When serum-starved glioma cells were fed with a fresh regular medium, in the 6- to 12-h post-starvation period, the growth rate as determined by cell number was significantly suppressed by insulin, although cell cycle progression and DNA synthesis were actually accelerated. Increase in apoptosis in those growth-retarded cultures was demonstrable by Hoechst staining, detection of histone-associated DNA fragment, and in situ cell death detection. Apoptosis occurred among cells in all stages of cell cycle. After 24 h post-starvation, insulin increased the total cell number like a typical growth-promoting mitogen. In this regard, IGF-1, but not EGF nor TGF-beta 1, behaved like insulin.
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PMID:Transient induction of apoptosis in serum-starved glioma cells by insulin and IGF-1. 897 21

Growth of numerous malignant tumors depends on an exogenous methionine (MET) supply, while endogenously synthesized MET supports normal cell proliferation. Because an antitumor effect should be obtained by aggravating the altered MET metabolism in gliomas, MET dependency of human xenografted gliomas was evaluated and a therapeutic approach using MET deprivation or MET analogs to induce MET starvation was applied. In vitro proliferation inhibition of glioma cell lines by MET deprivation and two MET analogs, ethionine (ETH) and trifluoromethylhomocysteine (TFH), was measured. Proliferation of 7 human glioma cell lines tested was inhibited in MET-free medium, and was poorly or not reversed by homocysteine (HCY). ETH or TFH (concentration range: 0.005-2 mg/ml) inhibited proliferation of all cell lines tested. MET analog-induced inhibition was abolished by MET and enhanced by HCY. Cell-cycle alterations due to MET deprivation were optimally assessed after 30 h of culture and bromodeoxyuridine incorporation. In MET- medium, cells were arrested in the G1-phase. ETH induced a dramatic accumulation of cells in the G2-phase. ATP contents were reduced by MET analogs only in HCY+ medium, suggesting complementary effects of MET analogs and HCY. Human glioma bearing nude mice were fed an amino acid-substituted MET- HCY-supplemented diet (MET-HCY+) and/or treated with MET analogs, injected intraperitoneally daily. Using two human xenografted tumors derived from gliomas, antitumor effects were obtained by subjecting tumor-bearing nude mice to MET starvation. TG-1-MA was more sensitive to MET depletion (40% of growth inhibition, P < 0.10) than TG-8-OZ (no growth inhibition). Antitumor effects of a MET-HCY+ diet and 200 mg/kg of ETH were potentiated when co-administered to glioma-bearing mice (77% GI, P < 0.025 and 67%, P < 0.0057 to TG-1-MA and TG-8-OZ respectively). A dose-response effect with no toxicity was obtained when the ETH dose was increased 10 fold. Potentiation of the effects of ETH and a MET-free diet indicates that they probably act on the same pathway but not the same target. In conclusion, experimentally induced MET deprivation and MET-analog treatment retarded the growth of human gliomas. Combination of MET-analog therapy with MET substitution by HCY enhanced their respective effects.
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PMID:Methionine deprivation and methionine analogs inhibit cell proliferation and growth of human xenografted gliomas. 906 Oct 49

The induction of glutamine starvation has been suggested as a potential target for antitumoral treatment using inhibitors of amidotransferase, an enzyme which mediates the conversion of glutamate to glutamine. Using multicellular aggregates from tumor cell lines, the effect of treatment with a suggested glutamine antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of treatment response, three different parameters were measured: aggregate size, uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the carcinoid cell line BON. In this cell line the maximum effect was reached already at 10 microM concentration. DON induced marked growth inhibition in the BON aggregates which lasted 3-4 weeks after which regrowth started. During this period the secretion of chromogranin and methionine uptake was also inhibited. These studies suggest that the neuroendocrine cell line BON is especially vulnerable to treatment by DON and show that strong inhibitory effects are found at concentrations lower than that achieved in patient blood in previous clinical trials.
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PMID:Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell aggregates. 925 48


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