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Glucose Analog (glucose + analog)
Selected AbstractsEffect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2006Ursula Banning Abstract:,Background:,In Hodgkin's lymphoma, F-18-fluoro-deoxy- d -glucose positron emission tomography (FDG-PET) is used for staging and response evaluation after chemotherapy. However, drug-mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG-PET. Methods:,We analyzed the effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy- d -glucose or the glucose analog 2-[N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in vitro. Results:,Etoposide induced a dose-dependent cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was mainly mediated via caspase-dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase-independent mechanisms. Conclusion:,Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false-negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in Hodgkin's lymphoma patients. [source] Adjusted Scaling of FDG Positron Emission Tomography Images for Statistical Evaluation in Patients With Suspected Alzheimer's DiseaseJOURNAL OF NEUROIMAGING, Issue 4 2005Ralph Buchert PhD ABSTRACT Background and Purpose. Statistical parametric mapping (SPM) gained increasing acceptance for the voxel-based statistical evaluation of brain positron emission tomography (PET) with the glucose analog 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) in patients with suspected Alzheimer's disease (AD). To increase the sensitivity for detection of local changes, individual differences of total brain FDG uptake are usually compensated for by proportional scaling. However, in cases of extensive hypometabolic areas, proportional scaling overestimates scaled uptake. This may cause significant underestimation of the extent of hypometabolic areas by the statistical test. Methods. To detect this problem, the authors tested for hyper metabolism. In patients with no visual evidence of true focal hypermetabolism, significant clusters of hypermetabolism in the presence of extended hypometabolism were interpreted as false-positive findings, indicating relevant overestimation of scaled uptake. In this case, scaled uptake was reduced step by step until there were no more significant clusters of hypermetabolism. Results. In 22 consecutive patients with suspected AD, proportional scaling resulted in relevant overestimation of scaled uptake in 9 patients. Scaled uptake had to be reduced by 11.1%± 5.3% in these cases to eliminate the artifacts. Adjusted scaling resulted in extension of existing and appearance of new clusters of hypometabolism. Total volume of the additional voxels with significant hypometabolism depended linearly on the extent of the additional scaling and was 202 ± 118 mL on average. Conclusions. Adjusted scaling helps to identify characteristic metabolic patterns in patients with suspected AD. It is expected to increase specificity of FDGPET in this group of patients. [source] Hypothalamic Function in Response to 2-Deoxy- d -Glucose in Long-Term Abstinent AlcoholicsALCOHOLISM, Issue 5 2001John C. Umhau Background: The body adapts to diverse stressful stimuli with a response characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Chronic alcohol consumption can cause changes in the function of this neuroendocrine system. Although many studies have examined this phenomenon in drinking and recently sober alcoholics, few studies have examined HPA axis function in long-term sober alcoholics. Methods: To characterize HPA axis function in long-term sober alcoholics, we used a challenge paradigm with 2-deoxy-d-glucose (2-DG). An infusion of 2-DG (a nonmetabolizable glucose analog) induces a well-characterized stress response. In a previous study, our laboratory found an exaggerated corticotropin and cortisol response in alcoholics abstinent 3 weeks; in this investigation we compared the effects of an infusion of 2-DG on 19 healthy volunteers and 20 community-living alcoholics who had been abstinent more than 6 months. Results: In contrast to the previous study, long-term sober alcoholics did not have an exaggerated corticotropin and cortisol response after 2-DG. Conclusions: Previously observed abnormalities in cortisol regulation in 3-week-sober alcoholics may be related to the acute effects of recent alcohol consumption and withdrawal. Future investigations into the metabolic function of alcoholics, particularly investigations involving the HPA system, should consider the possibility that normalization may not occur until long-term abstinence has been achieved. [source] Psicose inhibits lettuce root growth via a hexokinase-independent pathwayPHYSIOLOGIA PLANTARUM, Issue 3 2005Hisashi Kato-Noguchi Fructose analog, psicose, and glucose analog, mannose, inhibited root growth of lettuce seedlings. Psicose is phosphorylated by hexokinase and fructokinase (EC 2.7.1.4) to psicose-6-phosphate with no known capacity for further metabolism. Mannose is phosphorylated by hexokinase (EC 2.7.1.1) to mannose-6-phosphate which is further metabolized very slowly. Hexokinase is known to have a sugar-sensing function and possibly triggers a signal cascade resulting in changes of several gene expressions. It was determined, compared with the behaviour of mannose, whether psicose inhibits the root growth through this system. The addition of phosphate into the growth medium of lettuce seedlings did not affect the inhibition by psicose and mannose, and both sugars did not reduce adenosine triphosphate (ATP) level in the roots, suggesting that the inhibition is not due to phosphate starvation and ATP depletion. The inhibiting effects of psicose and mannose were overcome by adding sucrose into the medium, which suggests that the inhibition is not caused by accumulation of psicose-6-phosphate or mannose-6-phosphate in the seedlings. Mannoheptulose, a specific competitive inhibitor of hexokinase, defeated the mannose-induced inhibiting but was not able to relieve the psicose-induced inhibition. Thus, the phosphorylation of mannose by hexokinase may trigger a signal cascade resulting in the growth inhibition of lettuce roots, which is consistent with the hypothesis established in Arabidopsis. However, psicose cannot inhibit the growth of lettuce roots via a hexokinase-mediated pathway, and the phosphorylation of psicose by fructokinase might trigger a hexokinase-independent signal cascade resulting in the growth inhibition. [source] Synthesis and Antitumor Activity of Novel Dibutyltin Carboxylates of Aminoglucosyl DerivativesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2009Wei Li In this study, di-n-butyltin(IV) oxide was reacted with the amino glucose analog, cis -4-[N -(1,,3,,4,,6,-tetra- O -benzoyl-2-deoxy-glucopyranosyl)imido]-4-oxo-2-butenoic acid (1a) and o -[N -(1,,3,,4,,6,-tetra- O -benzoyl-2-deoxy-glucopyranosyl) carbamoyl] benzoic acid (2a) to give the complexes bis-{cis -4-[N -(1,,3,,4,,6,-tetra- O -benzoyl-2-deoxy-glucopyranosyl)imido-4-oxo-2-butenoic acid]-di-n-butyltin} carboxylate (1) and bis-{o -[N -(1,,3,,4,,6,-tetra- O -benzoyl-2-deoxy-glucopyranosyl) carbamoyl-benzoic acid]-di-n-butyltin}carboxylate (2). These two compounds were then characterized by IR, NMR and MS. In vitro tests showed that both compounds have high cytotoxicity in four tumor cell lines (P388, HL-60, A549 and BEL-7402). Clonogenic assays demonstrated that both compounds 1 and 2 have hematopoietic cell toxicity at 10,6 m. [source] | |||||||||||||