Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma cells were used to analyze the effect of elevated glucose levels on myo-inositol metabolism and Na+/K+-pump activity. The activity of the Na+/K+ pump in neuroblastoma cells is almost totally sensitive to ouabain inhibition. Culturing neuroblastoma cells in 30 mM glucose caused a significant decrease in Na+/K+-pump activity, myo-inositol metabolism, and myo-inositol content, compared to cells grown in the presence of 30 mM fructose. Glucose supplementation also caused a large intracellular accumulation of sorbitol. The aldose reductase inhibitor sorbinil prevented the abnormalities in myo-inositol metabolism and partially restored Na+/K+-pump activity in neuroblastoma cells cultured in the presence of elevated glucose levels. These results suggest that the accumulation of sorbitol by neuroblastoma cells exposed to elevated concentrations of extracellular glucose causes a decrease in myo-inositol metabolism and these abnormalities are associated with a reduction in Na+/K+-pump activity.
 ...
PMID:Effect of increased glucose levels on Na+/K+-pump activity in cultured neuroblastoma cells. 283 22

The T3 concentration in brain predominantly reflects local production from T4 rather than T3 uptake from the circulating pool. We recently demonstrated that rat brain T3 content is increased by glucose feeding compared to chow feeding. One possible mechanism for this effect is an increase in brain T4 5'-deiodinase (5'-D) activity. Our recent preliminary studies of neuroblastoma (NB) cells demonstrate that renewal of RPMI-1640 medium stimulates T4 5'-D type II (NB T4 5'-D II) activity in these cells. The present studies were performed to determine the mechanism of this response. Studies were performed on NB cells supported in thyroid hormone-depleted (deficient) medium. This approach increased NB T4 5'-DII activity 4-fold compared to that in thyroid hormone-replete medium. Medium renewal further stimulated enzyme activity (7- to 9-fold; maximum at 6 h) in each group. The difference between the hypothyroid group and control was sustained over a 24-h period. Subsequent studies demonstrated that glucose (11 mM) was the specific medium ingredient mediating the medium renewal response. A progressive increase in NB T4 5'-DII activity was noted over 8 h during RPMI-1640 salt plus glucose (11 mM) incubation. This was equivalent to the effect of complete medium containing glucose (11 mM). Coincubation with insulin (10(-7)-10(-9) M) did not modify the enzyme response to glucose. In addition, fructose (10 mM) had a similar effect on enzyme activity. Glycerol and essential and nonessential amino acids also modestly increased NB T4 5'-DII activity compared to that in the control group (P less than 0.01). Actinomycin-D (1 microM), cycloheximide (100 microM), and puromycin (100 microM) significantly (P less than 0.001) decreased the glucose effect on T4 5'-DII by 5-, 9-, and 17-fold, respectively, after 6 h of incubation. In addition, puromycin (10-200 microM) inhibited both NB T4 5'-DII activity and [3H]amino acid incorporation during incubation in glucose. There was a significant correlation between these parameters (r = 0.8; P less than 0.001). The enzyme activity decay curves in the glucose-activated and control groups subsequent to puromycin (100 microM) addition at 8 h were parallel. The fractional turnover rate was 13%/h in the controls and 11%/h in the glucose groups. The calculated enzyme production rate was significantly higher (P less than 0.005) in the glucose group compared to that in the control group (17.4 vs. 6.8 fmol/mg protein.h).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Carbohydrate reactivation of thyroxine 5'-deiodinase (type II) in cultured mouse neuroblastoma cells is dependent upon new protein synthesis. 291 91

Neuroblastoma cells were used to determine the effect of high carbohydrate and polyol levels on myo-inositol metabolism. The presence of elevated concentrations of glucose or sorbitol caused a significant decrease in both inositol accumulation and incorporation into phospholipid. These conditions, however, did not alter the accumulation of the other phospholipid head groups or the growth rate and water content of the cells. Two weeks of growth in either of the modified conditions was necessary to obtain a maximal effect on inositol incorporation. In contrast, growth in elevated concentrations of fructose, mannitol, or dulcitol had no effect on inositol metabolism. The reduced inositol accumulation and incorporation into lipids seen with glucose or sorbitol supplementation resulted in a decrease in the total phosphatidylinositol content of the cell without changing the levels of the other phospholipids. Kinetic analysis of cells grown in the presence of elevated glucose indicated that V'max for inositol uptake was significantly decreased with little change in the K'm. These data suggest that glucose decreases myo-inositol uptake in this system by noncompetitive inhibition. Cells grown in the presence of increased glucose also had elevated levels of intracellular sorbitol and decreased levels of myo-inositol. These results suggest that the high levels of glucose and sorbitol which exist in poorly regulated diabetes may be at least partially responsible for diabetic neuropathy via a reduction in the cellular content of myo-inositol and phosphatidylinositol. This system may be a useful model to determine the effect of reduced inositol phospholipid levels on neural cell function.
 ...
PMID:myo-Inositol metabolism in 41A3 neuroblastoma cells: effects of high glucose and sorbitol levels. 309 18

Children undergoing ABMT, a procedure which entails massive doses of chemotherapy along with total-body irradiation, are candidate to develop severe gastrointestinal toxicity and prolonged anorexia requiring administration of Parenteral Nutrition (PN) for variable periods. We report a series of 35 consecutive children affected by malignancies who underwent 37 courses of PN after ablative therapy followed by ABMT. Age ranged from 8 months to 17 years; 16 were females, 19 males. There were 23 cases of neuroblastoma, 5 of Wilms' tumor, 3 of acute myelogenous leukemia, 2 of Ewing's sarcoma, 1 case each of rhabdomyosarcoma and acute lymphoblastic leukemia. All patients developed severe neutropenia for 9-42 days (median 18 d). Fever occurred in all patients; sepsis was documented in 10. Duration of PN ranged from 10 to 64 days (23 +/- 9; mean +/- SD). PN solution, containing crystalline L-Aminoacids (8.5%) mixed with 33% glucose, minerals, trace elements and vitamins provided for children a caloric intake of 49.8 +/- 17.3 Kcal/Kg/day with a nitrogen intake of 0.26 +/- 0.27 g/Kg/day. Nutritional assessment, utilizing percent ideal body weight, serum protein electrophoresis, C3, pseudocholinesterase and fibrinogen, was performed at the beginning and at the completion of each course of PN. Mean percent ideal body weight was 95.8 before PN, 98.5 on last day of PN (p less than 0.0005). Other parameters did not change significantly. No metabolic complication nor severe electrolyte imbalance were observed except for 5 patients who developed hypokalemia in coincidence with administration of Amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Autologous bone marrow transplantation in children. Use of parenteral nutrition]. 311 38

A large-sized glucose polymer was isolated by pronase digestion from line PC12 pheochromocytoma cells metabolically labeled with [1-3H]galactose. The polymer was included on a column of concanavalin A-Sepharose and could be eluted with 10 mM methyl-alpha-mannoside. Its slight retention in a column of Bio-Gel A-5m suggested that its molecular weight was in the several millions. Glucose was the component monosaccharide and there were two minor lipophilic components present. The polymer was digested with alpha-amylase into a series of oligosaccharides and was cleaved by glucoamylase into glucose residues. The disaccharide obtained by digestion with alpha-amylase was identified as maltose in several HPLC systems and by NMR spectroscopy. NMR measurement revealed the trisaccharide to be maltotriose. Susceptibility of the polymer molecule to alpha-amylase, and the digestion products obtained, indicated a resemblance to glycogen. An analysis for saccharide compositions before and after reduction of the polymer suggested the presence of an aglycon part. Contrary to expectations based on the presence of this moiety, the polymer displayed good solubility in neutral organic solvents. Two-thirds of the glucose polymer was also soluble in 10% TCA. A similar glucose polymer was isolated from neuronal cells of rat embryos metabolically labeled with [1-3H]galactose. Mouse neuroblastoma cells did not synthesize the polymer.
 ...
PMID:Characterization of a glucose polymer from PC12 cells and neuronal cells of rat embryo. 314 16

This improved isotope-dilution gas chromatographic/mass spectrometric (GC/MS) method, in which [13C]glucose is the internal standard, meets the requirements of a Definitive Method. In a first study with five reconstituted lyophilized sera, a nested analysis of variance of GC/MS values indicated considerable among-vial variation. The CV for 32 measurements per serum ranged from 0.5 to 0.9%. However, concentration and uncertainty values (mmol/L per gram of serum) assigned to one serum by the NBS Definitive Method (7.56 +/- 0.28) were practically identical to those obtained with the proposed method (7.57 +/- 0.20). In the second study, we used twice more [13C]glucose diluent to assay four serum pools and two lyophilized sera. The CV ranged from 0.26 to 0.5% for the serum pools and from 0.28 to 0.59% for the lyophilized sera. In comparison, results by the hexokinase/glucose-6-phosphate dehydrogenase reference method agreed within acceptable limits with those by the Definitive Method but tended to be slightly higher (up to 3%) for lyophilized serum samples or slightly lower (up to 2.5%) for serum pools.
 ...
PMID:Precision of glucose measurements in control sera by isotope dilution/mass spectrometry: proposed definitive method compared with a reference method. 330 Oct 68

Neuroblastoma cells were used to determine the effect of sorbinil on myo-inositol metabolism in cells exposed to elevated levels of glucose in culture. Exposing cells to elevated levels of glucose led to an increase in levels of intracellular sorbitol. The increase in sorbitol levels was dependent on the extracellular glucose concentration. In contrast, the myo-inositol content of cells was decreased in the presence of increasing concentrations of extracellular glucose. Increasing the concentration of glucose in the culture medium caused a decrease in myo-inositol uptake and in the incorporation of extracellular myo-inositol into phospholipid. The effect of elevated glucose levels on myo-inositol metabolism and sorbitol accumulation was blocked by addition of 0.4 mM sorbinil. The ability of sorbinil to block the decrease in myo-inositol metabolism and sorbitol accumulation caused by 30 mM extracellular glucose was dependent on its concentration. Maximal effects were obtained with 0.4 mM sorbinil. However, there was some variation in the degree of effectiveness among batches of sorbinil. These results at the cellular level suggest that the intracellular accumulation of sorbitol is responsible for the alteration of myo-inositol metabolism observed in neuroblastoma cells exposed to elevated glucose concentrations.
 ...
PMID:Effect of sorbinil on myo-inositol metabolism in cultured neuroblastoma cells exposed to increased glucose levels. 339 31

Serum ferritin is present in two forms--a glycosylated form that results from active secretion by cells and a nonglycosylated form that is directly released by damaged cells. Glycosylated ferritin binds to concanavalin A (Con A) through the glucose and/or mannose residues of the molecule. Patients with neuroblastoma frequently present at diagnosis with abnormally elevated levels of serum ferritin. The ferritin levels will, however, return to normal with clinical remission, suggesting that the tumor is the origin of the elevated ferritin. With the use of a Con A binding assay, an investigation was made as to whether the increased levels of serum ferritin at diagnosis in neuroblastoma patients resulted from active secretion by the tumor or were the consequence of direct release of ferritin from damaged tissue. Serum samples were collected at diagnosis from 36 children with neuroblastoma and from 16 normal healthy subjects. Tissue ferritins were purified from normal human liver, placenta, HeLa cells, human neuroblastoma, and hepatoma cells grown in culture. Serum and tissue ferritins were measured before and after binding with Con A. Sixty-three percent of serum ferritin from neuroblastoma patients and 66% of serum ferritin from normal subjects were bound to Con A, suggesting that they were glycosylated and were likely to have been secreted. On the other hand, only 28% of tissue ferritin were bound to Con A. Furthermore, most patients showed abnormally elevated levels of serum ferritin, and 63% of these ferritins were bound to Con A. These results are compatible with the hypothesis that much of the elevated ferritin in sera of patients with neuroblastoma seen at diagnosis is the result of secretion of ferritin by the tumor.
 ...
PMID:Source of increased ferritin in neuroblastoma: studies with concanavalin A-sepharose binding. 345 40

Cultured neuroblastoma cells (clone neuro-2a) were used to demonstrate the influence of an anesthetic on energy metabolism by acting on the intracellular distribution of hexokinase activity. First of all, there was to be shown that a relationship between the intracellular hexokinase distribution and energy metabolism actually exists in neuroblastoma cells. Since glucose-6-phosphate could be assumed to be the main regulator of this enzyme distribution, experimental conditions were chosen where the glucose-6-phosphate level was changed significantly. A decrease in the glucose-6-phosphate level in the cells was achieved by deprivation of glucose and oxygen for 30 min. Under these conditions the glucose-6-phosphate level and the soluble hexokinase activity decreased significantly. The effect was reversible when glucose and oxygen were again added to the incubation medium of the cells. On the other hand, the antimetabolite 6-aminonicotinamide produced an accumulation of glucose-6-phosphate which caused an increase in the soluble hexokinase activity. These results brought evidence for a correlation of intracellular hexokinase distribution and energy metabolism. When alpha-(+/-)-5-allyl-1-methyl-5-(1-methyl-2-pentinyl) barbituric acid (methohexital) was added to the incubation medium of the neuroblastoma cells, a dose-dependent increase in soluble hexokinase activity was measurable, whereas the glucose-6-phosphate level was decreased at least within a therapeutically relevant dosage range of the anesthetic. This effect was reversible when methohexital was washed out from the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of methohexital on the relationship between hexokinase distribution and energy metabolism in neuroblastoma cells. 359 43

Because neuroblastoma cells in vitro are sensitive to changes in glucose levels in growth media, the effects of glucose levels and dietary carbohydrate on the sensitivity of neuroblastoma cells to chemotherapy were studied. In vitro, 20 microM bromoacetylcholine, 3mM 1,3-diaminopropane, and 5 mM 5-fluorouracil were added to the growth medium of strain N2a neuroblastoma cells cultured in Dulbecco's modified Eagle medium with high glucose (4.5 g/L, HG), normal glucose (1.0 g/L, NG), or low glucose (0.1 g/L, LG). Diaminopropane and 5-fluorouracil had some cytotoxic effect on cells in all media. Bromoacetylcholine killed cells in all media, but at a concentration of 20 microM was most effective in LG medium. Mice (A/Jax) were inoculated with neuroblastoma cells for in vivo studies. Mice could not tolerate a carbohydrate-free diet, while a high-carbohydrate diet caused no change in survival time. When mice on a high carbohydrate diet were treated with cyclophosphamide (100 mg/kg, ip) or 5-fluorouracil (125 mg/kg, ip) they died faster than drug-treated mice on a normal diet. Oral chlorpropamide or cimetidine did not prolong survival time. Analysis of blood glucose levels showed neuroblastoma significantly lowered blood glucose levels (p less than 0.05), while chlorpropamide had no significant effect. It is proposed that manipulation of plasma glucose to lower levels will not be effective in enhancing the chemotherapy of neuroblastoma.
 ...
PMID:Effects of glucose on neuroblastoma in vitro and in vivo. 365 98


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