Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To estimate proliferating activity of central neurocytoma, we measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGI) using dynamic positron emission tomography (PET), as well as autoradiographic rCMRG1 (arg-rCMRG1), in patients with histologically verified central neurocytoma. The subject included five patients, four males and one female, aged from 23 to 53 years with a mean age of 41 years old. All tumors were located in the lateral ventricle and two extended into the third ventricle through the forearm of Monro. Tumor lesion on the PET images was determined using CT or MRI, which was performed at levels equivalent to those for the PET scans. 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 18F-fluorodeoxyglucose (FDG) model. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter. Tumor k1 and k2 values were similar to or higher than those of the contralateral gray matter, suggesting high permeability due to lack of blood-brain barrier. Tumor k3 value, an indicator of hexokinase activity, and kinetic-rCMRG1 were exceedingly lower in three of five patients. These three patients have been free from tumor recurrence or regrowth, postoperatively. The other two patients, tumor kinetic-rCMRG1 was similar to or higher than that of the contralateral gray matter. One patient suffered from tumor regrowth shortly after resection, and the other has been followed up postoperatively. Thus, k3 and kinetic-rCMRG1 are indicative parameters of proliferative activity in central neurocytoma.
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PMID:[Kinetics of glucose metabolism in central neurocytomas]. 757 44

To estimate hemocirculation and proliferating activity of intraventricular tumor, we measured kinetic rate constants (k1, k2, k3) 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 intraventricular tumor. The subjects included ten patients, five males and five females, aged from 13 to 53 years with a mean age of 32 years old. Eight tumors were located in the lateral ventricle and two extended into the third ventricle through the foramen of Monro. Another two tumors were located in the fourth ventricle. Histological diagnosis was as follows: five cases of central neurocytoma, one subependymal giant cell astrocytoma, one ependymoma, one choroid plexus carcinoma, one subependymoma, and one meningioma. Tumor lesion on the PET images was determined using CT or MRI, which was performed at levels equivalent to those for the PET scans. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter. Hemocirculation (rCBF, rCBV) of the tumor was similar to or higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Oxygen metabolic parameters (rOEF, rCMRO2) were significantly lower than those of the contralateral gray matter. Especially, low rOEF resulted in an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl), as compared with that of meningiomas or malignant gliomas, suggested aerobic glycolysis. 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 (18FDG). Tumor k1 and k2 values were similar to or higher than those of the contralateral gray matter, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply. Tumor k3 value, an indicator of hexokinase activity, and kinetic-rCMRGl were lower in six of eight patients. These six patients have been free from tumor recurrence or regrowth, postoperatively. In the other two patients, tumor kinetic-rCMRGl was similar to or higher than that of the contralateral gray matter, suggesting high activity of proliferation. However, one patient received irradiation and has been followed up, and the other received total resection and has shown no recurrence. Functional information concerning intraventricular tumor is obtained by PET analysis, and kinetic analysis of the rate constants is useful for interpreting a detailed metabolic process of glucose, and provides additional information on intraventricular tumor aggressiveness.
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PMID:[Hemocirculation and metabolism in intraventricular tumors: kinetic analysis of glucose metabolism]. 885 49

The aim of this study was to determine whether the apparent loss of overall gray-white matter contrast (GM/WM) seen on FDG-PET imaging reflects the differential changes of glucose metabolic rate (CMRglc) in cortical gray mater (GM) and subcortical white mater (WM) following TBI. The clinical significance of the CMRglc GM-to-WM ratio was also evaluated. Nineteen normal volunteers and 14 TBI patients were studied. Each subject had a quantitative FDG-PET, a quantitative H215O-PET and a MR scan acutely following TBI. Stabilities of the global and regional FDG lumped constants (LC) were studied. Parametric images (pixel unit: mg/min/100g) of FDG uptake rate (CURFDG) and CMRglc were generated. The changes of CMR(glc) in whole brain, GM and WM were studied separately by using a MRI-segmentation-based technique. The GM-to-WM ratios of both CURFDG and CMRglc images were significantly (p < 0.001) decreased (>31%) in TBI patients. The global LC value reduced significantly (p < 0.01) in TBI patients. The CMRglc decreased significantly (p < 0.001) in GM but not in WM (p > 0.1). Kinetic analysis revealed significant (p < 0.001) decrease of GM hexokinase activity in TBI patients. The GM-to-WM ratios of CMRglc correlated (r = 0.64) with the initial Glasgow Coma Score (GCS) of TBI patients. The patients with higher CMRglc GM-to-WM ratios (>1.54) showed good recovery 12 months after TBI. There was a selective CMRglc reduction in cortical GM following TBI. The pathophysiological basis for the reduction in GM-to-WM CMRglc ratio seen on FDG-PET imaging following TBI remains to be determined.
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PMID:Selective metabolic reduction in gray matter acutely following human traumatic brain injury. 1500 Jul 56

A 44-year-old man with a history of sudden onset short-term disorientation was admitted to our hospital. T2-weighted fast spin-echo MR images of the head showed increased signal intensity in the bilateral frontal and parietal white matter. Gadolinium-enhanced T1-weighted spin-echo images showed multiple areas with punctate and linear enhancement scattered in the bilateral frontal and parietal white matter. Although 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) did not display a significant increase in FDG accumulation in the bilateral frontal and parietal white matter, kinetic analysis of this scan showed increased hexokinase activity in the lesions compared to the unaffected occipital white matter. Diagnosis was made by open biopsy of the right frontal lobe and pathologic specimen was positive for lymphomatoid granulomatosis (LYG). The patient received high-dose methotrexate with CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone) chemotherapy and follow-up MRI showed improvement of the lesions. [18F]FDG-PET study with kinetic analysis may be useful to diagnose LYG in the central nervous system.
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PMID:FDG-PET findings of the brain in lymphomatoid granulomatosis. 1738 7

Molecular imaging using PET or hyperpolarized MRI can characterize tumor phenotypes by assessing the related metabolism of certain substrates. However, the interpretation of the substrate turnover in terms of a pathophysiological understanding is not straightforward and only semiquantitative. The metabolism of imaging probes is influenced by a number of factors, such as the microvascular structure or the expression of key enzymes. This study aims to use computational simulation to investigate the relationship between the metabolism behind molecular imaging and the underlying tumor phenotype. The study focused on the pathways of glucose metabolism and lactate oxidation in order to establish the quantitative relationship between the expression of several transporters (GLUT, MCT1 and MCT4), expression of the enzyme hexokinase (HK), microvasculature and the metabolism of glucose or lactate and the extracellular pH distribution. A computational model for a 2D tumor tissue phantom was constructed and the spatio-temporal evolution of related species (e.g. oxygen, glucose, lactate, protons, bicarbonate ions) was estimated by solving reaction-diffusion equations. The proposed model was tested by the verification of the simulation results using in vivo and in vitro literature data. The influences of different expression levels of GLUT, MCT1, MCT4, HK and microvessel distribution on substrate concentrations were analyzed. The major results are consistent with experimental data (e.g. GLUT is more influential to glycolytic flux than HK; extracellular pH is not correlated with MCT expressions) and provide theoretical interpretation of the co-influence of multiple factors of the tumor microenvironment. This computational simulation may assist the generation of hypotheses to bridge the discrepancy between tumor metabolism and the functions of transporters and enzymes. It has the potential to accelerate the development of multi-modal imaging strategies for assessment of tumor phenotypes.
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PMID:Exploring the quantitative relationship between metabolism and enzymatic phenotype by physiological modeling of glucose metabolism and lactate oxidation in solid tumors. 2576 4