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

Three cell lines established from human gliomas were found to differ in the capacity to phosphorylate the glycolytic enzyme pyruvate kinase in vitro. Phosphorylation in the glioblastoma cell line U-138 was more pronounced than in the glioma cell line Hs 683 and in the glioblastoma cell line A-172. All 3 cell lines showed similar pyruvate kinase isozyme patterns and expressed about 90% K-type and 10% M-type subunits. So, differences in pyruvate kinase phosphorylation could not be explained by differences in the availability of the appropriate substrate, being pyruvate kinase type K. As in gliomas, phosphorylation could specifically and almost completely be inhibited by fructose-1,6-bisphosphate. In order to investigate a potential physiological significance of the phosphorylation of pyruvate kinase, we have characterized these cell lines for several glycolytic parameters. In U-138 cells, the production of lactate appeared to be 2 times higher as compared with A-172 and Hs 683 cells under normal growth conditions and even 4 times higher under low glucose culture regime. The efflux of lactate correlated with the pyruvate kinase phosphorylation pattern in the cell lines. In none of the cell lines could the lactate production be stimulated by glutamine as additional energy source under low glucose culture conditions. The higher glycolytic flux in U-138 cells was not accompanied by higher glycolytic enzyme activities. The isozyme patterns of hexokinase, pyruvate kinase, aldolase, enolase and lactate dehydrogenase in the cell lines were nearly identical and resembled the patterns previously described for solid gliomas. However, the isozyme composition of phosphofructokinase in the cell lines differed from the situation in gliomas. While in gliomas the expression of L-type phosphofructokinase is favored, in the glioma cell lines, we found an increase in the expression of C-type subunits.
 ...
PMID:Phosphorylation of pyruvate kinase and glycolytic metabolism in three human glioma cell lines. 179 9

Glioma are often histologically heterogenous. As many of these tumors are not removable in toto, due to their localisation, the most malignant part of the tumor may be missed and information for optimum therapeutic management is incomplete. Furthermore, low grade gliomas tend to become more malignant in their development; additional surgical intervention is often not possible. Non-invasive measurement of tumor glucose metabolism with (F-18)-2-fluoro-2-deoxyglucose (FDG) and positron-emission-tomography (PET) may be used to evaluate tumor malignancy. Malignant gliomas (astrocytoma III degree and glioblastoma) frequently showed increased peak metabolic rates (in comparison with normal white matter) and uncoupling of FDG transport and phosphorylation. Preliminary experiences with image-guided localized phosphorus-31 MR spectroscopy (P-31 MRS) demonstrated a decrease of phosphodiesters in malignant gliomas, whereas the phosphomonoesters showed an increase in several cases. The phosphocreatine peak was often reduced. A more active therapy of low grade gliomas might be indicated when signs of hypermetabolism in FDG-PET and alteration of energy-rich phosphates or membrane-phosphates in P-31 MRS are found.
 ...
PMID:[Metabolic studies of gliomas with positron emission tomography and phosphorus 31 MR spectroscopy in diagnosis and treatment planning]. 268 95

In order to investigate whether cerebrospinal fluid (CSF) polyols are consumed by brain tissue, the concentration of seven polyols in the CSF and the serum of 30 patients with intracranial tumor and 17 control individuals was measured by gas chromatography. The mean polyol content in the control samples showed that the fructose, inositol, and glucitol levels were significantly greater in CSF than in serum. A comparison of the lumbar CSF from control subjects and 11 patients with malignant tumors exposed to the CSF showed the fructose and inositol levels to be significantly lower (54% and 45%, respectively) and the glucose content to be slightly higher (110%) in the tumor cases. These differences were markedly greater in the ventricular than in the lumbar CSF and greater in patients with tumors exposed to the CSF space than in those with tumors buried in the brain tissue. In ventricular CSF obtained from seven patients with malignant brain tumors before and after radio- and/or chemotherapy, significant increases in fructose (34%) and glucitol (48%) levels were found, but the other polyols did not change significantly. In culture, the human glioblastoma cell growth rate was higher in the medium containing fructose and glucose than in that containing glucose alone. A notable amount of fructose and glucose was consumed by cultured glioblastoma cells. The roles of polyols contained in CSF and the effects of fructose on the growth of cultured glioblastoma cells are discussed in light of these findings and of previous reports.
 ...
PMID:Polyol content of cerebrospinal fluid in brain-tumor patients. 291 16

The insulin receptor from human brain tumors of glial origin was examined for the first time using intact cells (from an established cultured human glioblastoma cell line) and partially purified solubilized membranes (from cultured cells and freshly isolated human brain tumors). The structure of the glial insulin receptor subunits was assessed by affinity cross-linking of 125I-insulin with the alpha-subunit of the receptor, neuraminidase treatment of the cross-linked receptor, behavior of the receptor on lectin columns, and electrophoretic mobility of the phosphorylated beta-subunit. The functions of the insulin receptor were examined by measuring specific 125I-insulin binding (receptor concentration, affinity, specificity, pH-, time-, and temperature dependence), insulin-induced down-regulation of the receptor, insulin-stimulated autophosphorylation of the beta-subunit, and phosphorylation of exogenous substrates as well as insulin-stimulated glucose uptake in glioblastoma cells. All of these properties were typical for the insulin receptor from target tissues for insulin action. The insulin receptor of the normal human brain showed the altered electrophoretic mobility and lack of neuraminidase sensitivity of its alpha-subunit previously reported for the rat brain receptor. There was no difference, however, in the functions of the receptor subunits (binding, phosphorylation) from the normal brain tissue and the eight human gliomal tumors. Since the glial elements compose a majority of the brain cells, the "normal" structure and function of their insulin receptor might provide a key to understanding the role of insulin in the carbohydrate metabolism of the human central nervous system.
 ...
PMID:Insulin receptor of human cerebral gliomas. Structure and function. 300 70

A pediatric case of multifocal glioblastoma is reported with special reference to positron emission tomography (PET) evaluations in the diagnosis and therapy. A PET scan employing 15O and 18F positron tracers disclosed a right thalamic lesion high in regional cerebral blood flow, cerebral blood volume and metabolic glucose rate, suggesting a malignant tumor. In contrast, a left frontal lesion with low regional cerebral blood flow, cerebral blood volume and metabolic glucose rate was presumed to be rather hypodynamic and hypometabolic. Histological examination of these isolated masses showed both to be glioblastomas, and, as predicted by the PET findings, there were minor histological distinctions. In repeated PET scans following postoperative combined radiochemotherapy, metabolic glucose rate values at the thalamic tumor decreased to about 50% the levels before therapy, although there was no distinguishable change in tumor size on the concurrent computerized tomography scans. This therapeutic efficacy on tumor metabolism was highly consistent with the period of clinical relief.
 ...
PMID:Positron emission tomographic evaluations in the diagnosis and therapy of multifocal glioblastoma. Report of a pediatric case. 303 75

Four cases with lesions suspected to be low-grade intracerebral tumours but later proved to be cavernous haemangiomas are described. The patients were examined with contrast enhanced CT and with positron emission tomography (PET). The lesions were partly calcified with a mild or no mass effect and a slight contrast enhancement at CT. There were signs of disrupture of the blood-lesion barrier also on radionuclide studies. PET with 11C-methionine and 11C-glucose showed a normal or decreased accumulation of the tracers. This combination of findings has not been encountered in intracranial tumours. As a comparison, one case of glioblastoma is described. In this patient, the CT findings suggested a cavernous haemangioma. However, PET showed a markedly increased accumulation of 11C-methionine, which is compatible with brain tumour but not with haemangioma.
 ...
PMID:Positron emission tomography of cavernous haemangiomas of the brain. 309 81

Several aspects of the regulation of the pentose phosphate pathway were examined in cultured normal human cortical astrocytes and gliomas of pathological grades I-IV. The generation of radiolabeled CO2 from [1-14C]glucose by the oxidative arm of the pentose phosphate pathway is a saturable process and has a maximum flux rate of 8-9 nmol/hr/mg cell protein. The flux can be blocked by the glycolytic inhibitor iodoacetamide but is unaffected by agents which inhibit oxidative phosphorylation. The magnitude of the pentose phosphate flux is directly related to the glioma grade. Grade IV gliomas (glioblastoma) show a pentose phosphate flux rate of approximately 4% of the total glucose flux. The flux rate can be increased by pharmacological agents which decrease the NADPH/NADP+ ratio. Both the activity and the regulation of glioma glucose-6-phosphate dehydrogenase (G6PDH) are altered in high-grade gliomas. While the affinity constants for cofactors in whole homogenates were not significantly different in glioma or normal astrocyte homogenates, normal astrocytes have a lower Km for glucose-6-phosphate and a G6PDH activity which is 10-fold greater than that of gliomas. NADPH is a powerful regulator of G6PDH activity in the normal astrocytes and in gliomas. At a NADPH/NADP+ ratio of 7:1 the normal astrocyte G6PDH is entirely inhibited, while the glioma enzyme is only 70% inhibited even at a ratio of 20:1. Increased metabolic flux through the oxidative arm of the pentose phosphate pathway is apparently due to an altered form of G6PDH.
 ...
PMID:Regulation of the pentose phosphate pathway in human astrocytes and gliomas. 350 33

The addition of norepinephrine to cultured glioblastoma cells results in an inhibition of uptake of radioactivity from D-[2-(3)H]glucose, D-[1-(14)C]glucose, D-[2-(14)C]glucose, and D-[6-(14)C]glucose. In addition, if the glioblastoma cells are previously labeled with these substrates, norepinephrine causes an increase in the release of radioactivity. These effects were not observed with cultured neuroblastoma cells. It is suggested that the breakdown of glycogen is activated by norepinephrine as a result of an increase in 3':5'-cyclic AMP.
 ...
PMID:Effect of norepinephrine on glucose metabolism in glioblastoma and neuroblastoma cells in cell culture. 434 Jan 54

We measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with meningioma. Ten patients including one recurrent case, two males and eight females aged from 44 to 71 years with a mean age of 54 years old, were studied prior to surgical interventions. Histological diagnosis was as follows: seven cases of meningothelial type, two cases of angiomatous type and one fibrous type. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter in comparison with eight cases with malignant gliomas (five cases of malignant astrocytoma and three cases of glioblastoma, aged from 14 to 70 years with a mean age of 41 years old). Hemocirculation of the tumor was exceedingly higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Low rOEF implicated an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl) suggested rather aerobic glycolysis as compared with malignant gliomas. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three compartment model of 18F-fluorodeoxyglucose (FDG). Tumor k1 and k2 values markedly increased in all examined cases, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Kinetic analysis of glucose metabolism in meningiomas--comparison with malignant gliomas]. 760 82

Recovery from potentially lethal damage (PLD) has been measured in plateau growth phase human glioblastoma cells (U-87MG) under four postirradiation medium conditions. Recovery was maximal in depleted medium at an acidic pH, conditions which inhibit cellular proliferation. Compared with this control, PLD recovery (PLDR) was increasingly inhibited by alkalization of the existing medium (to pH 7.4), exchanging the old medium with fresh medium-pH acidified (to pH 6.8), and exchanging the old medium with fresh medium-pH unaltered (pH 7.4), respectively. These three medium adjustments were made at the time of irradiation. Increased glucose utilization (glycolysis) was detected postirradiation in all three cases, while increased proliferation was detected only when fresh medium was exchanged for old medium. Thus inhibition of PLDR has been correlated with increased glycolysis and increased proliferation during the recovery period. When acting together, these two processes provided almost complete inhibition. This study was revealed that the degree of inhibition may be related to the amount of glycolysis and/or proliferation occurring during the recovery period. Examining, in vitro, the range of PLDR achieved by postirradiation manipulation of medium pH may provide some indication of the range in PLDR that may be expected in vivo. Our study demonstrates that the effect of pH on glycolysis and proliferation may be important when determining the ability of a particular cell type to recover from PLD.
 ...
PMID:Inhibition of potentially lethal damage recovery by altered pH, glucose utilization and proliferation in plateau growth phase human glioma cells. 802 11


1 2 3 4 5 6 7 8 9 10 Next >>