Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiation survival and recovery from potentially lethal damage has been measured in human glioblastoma cells as they progressed from an exponential to an extended plateau growth phase. Immediate plating (IP) survival following 7.5 Gy 60Co irradiation decreased from 2.3% for cells in exponential growth phase to 0.11% for cells held in an extended plateau growth phase with no change or adjustments made to the medium. Delayed plating (DP) survival decreased from 10% to 2.5%, respectively. Under these conditions, medium pH, rate of glycolysis, and proliferation status were monitored. IP survival was found to be sensitive to both proliferation status and the amount of time the cells spent in a metabolically quiescent state. Recovery ratios (DP surv./IP surv.) increased from 4.3 to 23, primarily due to IP survival decreasing at a greater rate than DP survival. Aerobic glycolysis was found to be responsible for approximately 42% of the glucose utilization. Metabolic activity (glycolysis) was increased by increasing the pH of the existing medium. Survival was measured 3 days after each pH adjustment to allow a new metabolic equilibrium to establish with a pH and rate of glycolysis comparable to that in control experiments that had no pH adjustments. Both IP and DP survival showed only slight decreases compared to control experiments, while the recovery ratio at the end of a 6-day plateau period remained the same as in control experiments. No additional cell growth or redistribution of cells within the cell cycle occurred. Thus a period of increased metabolic activity prior to irradiation is advantageous for both IP and DP survival as compared to a period of low metabolic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in survival and potentially lethal damage recovery following periods of high and low metabolic activity in human glioma cells. 808 69

The expression of facilitative glucose transporter (GLUT) isoforms in human astrocytic tumors was examined. Reverse transcriptase-polymerase chain reaction of a surgically biopsied glioblastoma was carried out using the degenerative oligonucleotide primers corresponding to the sequences of the human facilitative glucose transporter family, and polymerase chain reaction products were hybridized with human GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5 cDNA probes. The results showed that a biopsied glioblastoma expressed GLUT1, GLUT3, and GLUT4 glucose transporter genes. Northern blot analysis of total RNA (10 micrograms) from a biopsied glioblastoma showed the transcripts of only GLUT1 and GLUT3, suggesting that the expression of insulin-responsive glucose transporter GLUT4 mRNA is relatively low. Immunoblot analysis of biopsied glioblastoma tissues by polyclonal antibodies against the C-terminal synthetic peptides of GLUT1, GLUT3, and GLUT4 showed a single band of each polypeptide. However, elevated expression of GLUT1 and GLUT3 glucose transporters was not observed in the glioblastoma. Astrocytic tumor tissues (n = 14) were also examined immunohistochemically. Reactive products for GLUT1 were observed in the luminal surface of capillaries in all cases, whereas tumor cells were positive for GLUT1 in only two of 14 cases. GLUT3 was positive in astrocytic tumor cells in all cases. Three of 14 cases expressed the GLUT4 protein, which was localized in the cytoplasm of tumor cells. These results suggest that the facilitative glucose transport may be altered in astrocytic tumor cells and thus display a significant change in glucose metabolism.
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PMID:Expression of facilitative glucose transporter isoforms in human brain tumors. 824 60

Radionuclides are applied in oncology for diagnosis and therapy. The former demands gamma--emitting radionuclides for labeling specific substrates for localizing malignant tissue and for analyzing tumor metabolism in vivo. Here, positron emission tomography (PET) may register in vivo the metabolism, for example, of glucose, amino acids, and receptors and of potentially useful cytotoxic agents. The advantage of the positron emitting radionuclides of carbon, nitrogen and fluorine is the labeling of substrates without changing substrate specificity within the metabolic reaction chain; also, substrate concentration in situ may be quantified. With regard to therapy radionuclides that emit beta- and alpha-particles or decay by electron capture with the Auger effect, are administered in ionic form or with tumor seeking substrates. Examples are radioiodine for treating thyroid malignancy and radiophosphorus for myeloproliferative diseases. Organically bound radionuclides are given as labeled ligands for specific receptors, such as meta-iodo-benzylguanidine (MIBG) for treating the catecholamine producing tumors phaeochromocytoma and neuroblastoma and labeled monoclonal antibodies for tumors specific receptors. Highly localized energy depositions come from Auger emitters such as 125I and by the neutron capture therapy, where boron-10 in the tumor cell is exposed to thermal neutrons for initiating the B10 (n; alpha) Li7 reaction, especially for treating neuro- and glioblastoma and melanoma. Endogenous radiotherapy with radionuclides rely on the success of delivering a proper amount of energy into individual tumor cells with optimal protection of normal tissue. The inevitable heterogeneity of energy deposition events from such approaches demands careful dosimetric assessment for which the classical methods of dosimetry for percutaneous radiotherapy are not applicable.
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PMID:Contributions of nuclear medicine to the therapy of malignant tumors. 844 68

Human cytomegalovirus glycoprotein B (gB) plays a role in the fusion of the virion envelope with the host cell membrane and in syncytium formation in infected cells. Hydrophobic sequences at the carboxyl terminus, amino acids (aa) 714 to 771, anchor gB in the lipid bilayer, but the unusual length of this domain suggests that it may serve another role in gB structure. To explore the function(s) of this region, we deleted aa 717 to 747 (gB deltaI mutation), aa 751 to 771 (gB deltaII mutation), and aa 717 to 772 (gB deltaI-II mutation) and constructed a substitution mutation, Lys-748 to Val (Lys748Val)-Asn749Ala-Pro750Ile (gB KNPm). Mutated forms of gB were expressed in U373 glioblastoma cells and subjected to analysis by flow cytometry, confocal microscopy, and immunoprecipitation. Mutations gB deltaI-II and gB deltaII alone caused secretion of gB into the medium, confirming that aa 751 to 771 function as a membrane anchor. In contrast, mutations gB deltaI and gB KNPm blocked cell surface expression and arrested gB transport in the endoplasmic reticulum (ER). Detailed examination of gB deltaI and gB KNPm with a panel of monoclonal antibodies showed that the mutated forms were indistinguishable from wild-type gB in conformation and formed oligomers; however, they remained sensitive to endoglycosidase H and did not undergo endoproteolytic cleavage. Analysis of protein complexes formed by gB and molecular chaperones in the ER showed that calnexin and calreticulin, lectin-like chaperones, bound equal amounts of uncleaved wild-type gB, gB deltaI, and gB KNPm, but the glucose-regulated proteins 78 (BiP) and 94 formed stable complexes only with the mutated forms, causing their retention in the ER. Our studies show that aa 714 to 750 are key residues in the architecture of gB molecules and that the ER chaperones, which facilitate gB folding and monitor the quality of glycoproteins, detect subtle changes in folding intermediates that are conferred by mutations in this region.
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PMID:Mutations in the carboxyl-terminal hydrophobic sequence of human cytomegalovirus glycoprotein B alter transport and protein chaperone binding. 889 27

In order to investigate early changes in the glucose metabolism of irradiated tumours, tumour uptake of 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) was studied in human tumour xenografts. Three human tumour lines [ependymoblastoma (NNE), small cell lung cancer (GLS), and glioblastoma (KYG)] showing different radiosensitivities and incidences of radiation-induced apoptosis were subcutaneously transplanted into nude mice, and were irradiated at a single dose of 10 Gy. Then 0.5 mCi of 18FDG was intravenously administered 1 h before sacrifice. The animals were sacrificed at 2, 4 and 6 h following irradiation, and 18FDG accumulation in the tumours was examined. Before irradiation, GLS and KYG tumours showed significantly higher rates of 18FDG accumulation compared with NNE tumours (P <0.004 and P <0.001, respectively). NNE (the most radiosensitive tumour with the highest incidence of radiation-induced apoptosis), however, displayed a 2.3-fold higher rate of 18FDG accumulation at 2 h following irradiation compared with a non-irradiated group (P <0.01), and thereafter showed a plateau up to 6 h. The accumulation did not increase significantly in the other tumours with lower radiosensitivity and much less radiation-induced apoptosis. The rapidity of the increase in 18FDG accumulation in the most radiosensitive tumour line, occurring as early as 2 h following irradiation, suggests that the increase was independent of recovery phenomena following radiation damage.
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PMID:Rapid rise in FDG uptake in an irradiated human tumour xenograft. 909 96

The effect of 2',3'-dideoxycytidine (ddC) treatment on two human glioblastoma cell lines was characterized. ddC treatment (10 nM-100 microM) of glioblastoma cells was associated with enlargement and shortening of processes within 2-3 days. Assessment of mitochondrial membrane potential showed an early decrease in the number of polarized mitochondria in the glioma cells, at between 16 to 84% of the untreated control. With chronic exposure to varying doses of ddC, the tumor cells underwent apoptosis within 5-32 days. This apoptosis was dramatic, with a complete loss of cell viability in < 6 hours after cells were noted to begin detaching from the tissue culture flask. Supplementation with uridine, pyruvate and glucose could delay cellular death at the lower doses of ddC (10 nM to 15 microM) but not at the higher doses. However, regardless of supplementation, all cells eventually underwent apoptosis. ddC is a potent inducer of apoptosis in human glioblastoma cells. Assessments of efficacy in in vivo models and clinical trials should be performed to determine the value of ddC in the treatment of malignant brain tumors.
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PMID:2',3'-Dideoxycytidine is a potent inducer of apoptosis in glioblastoma cells. 967 16

It was the aim of the study to compare the inhibition of 18F-2-Fluor-D-deoxy-glucose uptake (18F-FDG) in tumor cells by various concentrations of FDG carrier or D-glucose in an experimental model using tissue culture and positron emission tomography (PET). Glioblastoma cells in culture were incubated with 18F-FDG with and without added carrier or in presence of glucose concentrations in the range from 0-5 mmol/L. Cellular uptake of 18F-FDG was measured after 20 min. of incubation in PBS-buffer containing different sugar concentrations. The uptake was determined with a PET camera. The similarity of the kinetics of the FDG and glucose uptake are backing the hypothesis that both substrates use the same carrier system. The more intense inhibition of the 18F-uptake by FDG can be explained by the different intracellular metabolism of both substrates. The results explain the clinical experience that there is an optimal 18F-FDG uptake in the patient's tumor when the blood glucose level is as low as possible and the specific activity of 18F-FDG is very high.
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PMID:[Inhibition of 18F-FDG uptake in glioblastoma cells by FDG and glucose]. 1052 Mar 78

The human erythrocyte GLUT-1 is a transmembrane protein which facilitates transport of glucose in the cell in an energy-independent fashion. Neuroectodermal stem cells show strong membrane immunoreactivitry with this marker at early developmental stages in rodents. Membranous expression by undifferentiated neuroectodermal cells gradually decreases while GLUT-1 becomes confined to the endothelial cells, when these acquire blood-brain barrier function. We thus sought to determine whether GLUT-1 expression was limited to embryonal neoplasms of the central nervous system (CNS) which are presumably derived from developmentally arrested neuroectodermal stem cells. Archival material of 40 primary CNS neoplasms were examined for immunoreactivity with anti-GLUT-1. This included both non-embryonal neoplasms (18 astrocytic tumours, one ependymoma and three oligodendroglioma) and embryonal neoplasms (12 cerebellar medulloblastomas, four supratentorial PNETs and two atypical teratoid/rhabdoid tumours (AT/RhT)). In addition, cell lines and nude mice xenografts derived from both undifferentiated and differentiated tumours were assessed for GLUT-1 immunoreactivity by both immunohistochemistry and Western blotting. All embryonal tumours, MBs and PNET xenografts consistently showed GLUT-1 membrane staining. Non-embryonal neoplasms were negative except for vascular staining. Membrane protein fraction of embryonal tumours cell lines immunoreacted by immunoblot with GLUT-1, whereas the glioblastoma cell line was negative. Expression of GLUT-1 supports the stem cell nature of the cells of origin of MBs, supratentorial PNET and AT/RhTs. As a result, GLUT-1 is a useful marker to define the embryonal nature of CNS neoplasms.
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PMID:Membranous expression of glucose transporter-1 protein (GLUT-1) in embryonal neoplasms of the central nervous system. 1073 70

Phosphatidylinositol 3-kinase (PI3-K) is a heterodimer of a regulatory subunit, p85, and a catalytic subunit, p110. A number of previous reports showed that PI3-K functions in diverse cellular phenomena such as cell proliferation, glucose catabolism, cell adhesion, and vesicle transport. It is also well known that a survival signal from the receptor tyrosine kinases utilizes Akt via PI3-K to protect cells from apoptosis. To examine the role of PI3-K in cellular sensitivity to genotoxic stresses such as cisplatin and ultraviolet (UV), we introduced deletion type p85 (Dp85) into two human glioblastoma cell lines (T98G and A172) and one melanoma cell line (G361). The Deltap85 works in a dominant-negative fashion on PI3-K activity by disrupting its p85 / p110 interaction. In all three transfected cell lines, the overexpression of Deltap85 rendered the cells markedly more sensitive to these DNA-damaging stresses than the cells transfected with the vector alone. Apoptosis was vigorously induced in cells overexpressing Dp85 following the treatment. The present results imply that PI3-K plays a critical role in determining cellular sensitivity to genotoxic stresses in human cancer cells, and that disruption of the p85 / p110 interaction of PI3-K may be a potential molecular target for developing a novel strategy for cancer treatment.
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PMID:Enhanced cell killing by overexpression of dominant-negative phosphatidylinositol 3-kinase subunit, Deltap85, following genotoxic stresses. 1112 31

Heat shock proteins (HSPs) are immediately expressed in neuronal and glial cells under various stressful conditions and play a protective role through molecular chaperones. We investigated the characteristics of the induction manner of heme oxygenase-1 (HO-1) and HSP70 in rat C6 glioblastoma cells. In heat treatment (42 degrees C for 30 min), C6 cells expressed high level of HO-1 and HSP70 mRNAs within 30-60 min, and their proteins at 3 hrs. Heat-induced expressions of HSPs mRNAs were completely inhibited with actinomycin D, suggesting the transcriptional regulation. Oxygen-glucose deprivation (OGD), cystine-free (inhibition of synthesis of glutathione), cyto-toxic (ethanol, sodium butyrate) treatments resulted in different expression manners between HO-1 and HSP70, which suggested that HO-1 and HSP70 play different protective roles against a variety kind of stressful conditions in glial cells. C6 cells can differentiate toward both astrocyte and oligodendrocyte directions. Treatment with dibutyryl cyclic AMP (cAMP) induces expression of glial fibrillary acidic protein (GFAP), a marker of astrocytes, and treatment with retinoic acid (RA) induces expression of myelin proteolipid protein (PLP), a marker of oligodendrocytes, respectively. Heat treatment before the initiation of differentiation by RA reduced the RA-induced expression of PLP mRNA profoundly, but not in GFAP mRNA level induced by cAMP. Heat treatment after the initiation of differentiation by cAMP or RA accelerated the expression of GFAP or PLP mRNAs. Astroglial differentiation by cAMP reduced the heat-induced expressions of HSPs mRNAs, but no change with RA pre-treatment. These results suggested that HSPs may modulate the glial differentiation in the developing brain. On the contrary, glial differentiation may give influence on the stress-induced HSPs expression. The timing of stressful damages, resulting in the expression of HSPs, on the developing brain is critically important for the pathogenesis of glial lesion. In the heat-treated C6 cells, the expression of platelet-derived growth factor (PDGF) receptor-alpha mRNA was significantly decreased. HSPs may have ability to induce the glial differentiation in part through down-regulation of the PDGF pathway.
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PMID:Induction of heat shock proteins and its effects on glial differentiation in rat C6 glioblastoma cells. 1159 26


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