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)

Preliminary studies of 13 enzymes subserving various metabolic pathways were undertaken in tumor-free liver biopsy samples from cancer patients and control subjects. The observations indicate that as a result of nonhepatic neoplasms, with (7 cases) or without (6 cases) hepatic involvement, the biochemical composition of the liver becomes partially undifferentiated. Quantification of appropriate enzymes in histologically normal liver samples could thus distinguish clearly between cancer hosts and controls. The best discriminators include two hepatic enzymes whose concentrations were decreased to less than 30% of normal (soluble glutamate dehydrogenase and the cold stable pyrroline-5-carboxylate reductase) and three for which it was elevated two to four-fold (hexokinase, peptidyl proline hydroxylase and thymidine kinase) in response to distant neoplasms. The same alterations in hepatic enzyme pattern were not seen in any cancer-free patients with or without morphologic liver damage.
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PMID:Enzyme pathology of the liver in patients with and without nonhepatic cancer. 737 35

Mitogenic stimulation of quiescent cells not only triggers the cell division cycle but also induces an increase in cell volume, associated with an activation of cellular metabolism. It is therefore likely that genes encoding enzymes and other proteins involved in energy metabolism and biosynthetic pathways represent a major class of mitogen-induced genes. In the present study, we investigated in the non-established human fibroblast line WI-38 the induction by mitogens of 17 genes whose products play a role in different metabolic processes. We show that these genes fall into 4 different categories, i.e. non-induced genes, immediate early (IE) primary genes, delayed early (DE) secondary genes and late genes reaching peak levels in S-phase. In addition, we have analysed the regulation of these genes during normal cell cycle progression, using HL-60 cells separated by counterflow elutriation. A clear cell cycle regulation was seen with those genes that are induced in S-phase, i.e. thymidine kinase, thymidylate synthase and dihydrofolate reductase. In addition, two DE genes showed a cell cycle dependent expression. Ornithine decarboxylase mRNA increased around mid-G1, reaching maximum levels in S/G2, while hexokinase mRNA expression was highest in early G1. In contrast, the expression of other DE and IE genes did not fluctuate during the cell cycle, a result that was confirmed with elutriated WI-38 and serum-stimulated HL-60 cells. These observations suggest that G0-->S and G1-->S transition are distinct processes, exhibiting characteristic programmes of gene regulation, and merging around S-phase entry.
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PMID:Differential induction of 'metabolic genes' after mitogen stimulation and during normal cell cycle progression. 751 13

Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level using remote imaging detectors. One underlying premise of molecular imaging is that this emerging field is not defined by the imaging technologies that underpin acquisition of the final image per se, but rather is driven by the underlying biological questions. In practice, the choice of imaging modality and probe is usually reduced to choosing between high spatial resolution and high sensitivity to address a given biological system. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) inherently use image-enhancing agents (radiopharmaceuticals) that are synthesized at sufficiently high specific activity to enable use of tracer concentrations of the compound (picomolar to nanomolar) for detecting molecular signals while providing the desired levels of image contrast. The tracer technologies strategically provide high sensitivity for imaging small-capacity molecular systems in vivo (receptors, enzymes, transporters) at a cost of lower spatial resolution than other technologies. We review several significant PET and SPECT advances in imaging receptors (somatostatin receptor subtypes, neurotensin receptor subtypes, alpha(v)beta(3) integrin), enzymes (hexokinase, thymidine kinase), transporters (MDR1 P-glycoprotein, sodium-iodide symporter), and permeation peptides (human immunodeficiency virus type 1 (HIV-1) Tat conjugates), as well as innovative reporter gene constructs (herpes simplex virus 1 thymidine kinase, somatostatin receptor subtype 2, cytosine deaminase) for imaging gene promoter activation and repression, signal transduction pathways, and protein-protein interactions in vivo.
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PMID:Molecular imaging of gene expression and protein function in vivo with PET and SPECT. 1235 50

Gliomas are the most common types of brain tumors. Although sophisticated regimens of conventional therapies are being carried out to treat patients with gliomas, the disease invariably leads to death over months or years. Before new and potentially more effective treatment strategies, such as gene- and cell-based therapies, can be effectively implemented in the clinical application, certain prerequisites have to be established. First of all, the exact localization, extent, and metabolic activity of the glioma must be determined to identify the biologically active target tissue for a biological treatment regimen; this is usually performed by imaging the expression of up-regulated endogenous genes coding for glucose or amino acid transporters and cellular hexokinase and thymidine kinase genes, respectively. Second, neuronal function and functional changes within the surrounding brain tissue have to be assessed in order to save this tissue from therapy-induced damage. Third, pathognomonic genetic changes leading to disease have to be explored on the molecular level to serve as specific targets for patient-tailored therapies. Last, a concerted noninvasive analysis of both endogenous and exogenous gene expression in animal models as well as the clinical setting is desirable to effectively translate new treatment strategies from experimental into clinical application. All of these issues can be addressed by multi-modal radionuclide and magnetic resonance imaging techniques and fall into the exciting and fast growing field of molecular and functional imaging. Noninvasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging may reveal the assessment of the "location," "magnitude," and "duration" of therapeutic gene expression and its relation to the therapeutic effect. Detailed reviews on molecular imaging have been published from the perspective of radionuclide imaging (Gambhir et al., 2000; Blasberg and Tjuvajev, 2002) as well as magnetic resonance and optical imaging (Weissleder, 2002). The present review focuses on molecular imaging of gliomas with special reference on the status and perspectives of imaging of endogenous and exogenously introduced gene expression in order to develop improved diagnostics and more effective treatment strategies of gliomas and, in that, to eventually improve the grim prognosis of this devastating disease.
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PMID:Molecular imaging of gliomas. 1292 28

We have assessed the potential of [18F]fluorothymidine positron emission tomography ([18F]FLT-PET) to measure early cytostasis and cytotoxicity induced by cisplatin treatment of radiation-induced fibrosarcoma 1 (RIF-1) tumor-bearing mice. Cisplatin-mediated arrest of tumor cell growth and induction of tumor shrinkage at 24 and 48 hours, respectively, were detectable by [18F]FLT-PET. At 24 and 48 hours, the normalized uptake at 60 minutes (tumor/liver radioactivity ratio at 60 minutes after radiotracer injection; NUV60) for [18F]FLT was 0.76 +/- 0.08 (P = 0.03) and 0.51 +/- 0.08 (P = 0.03), respectively, compared with controls (1.02 +/- 0.12). The decrease in [18F]FLT uptake at 24 hours was associated with a decrease in cell proliferation assessed immunohistochemically (a decrease in proliferating cell nuclear antigen labeling index, LI(PCNA), from 14.0 +/- 2.0% to 6.2 +/- 1.0%; P = 0.001), despite the lack of a change in tumor size. There were G1-S and G2-M phase arrests after cisplatin treatment, as determined by cell cycle analysis. For the quantitative measurement of tumor cell proliferation, [18F]FLT-PET was found to be superior to [18F]fluorodeoxyglucose-PET (NUV60 versus LIPCNA: r = 0.89, P = 0.001 and r = 0.55, P = 0.06, respectively). At the biochemical level, we found that the changes in [18F]FLT and [18F]fluorodeoxyglucose uptake were due to changes in levels of thymidine kinase 1 protein, hexokinase, and ATP. This work supports the further development of [18F]FLT-PET as a generic pharmacodynamic readout for early quantitative imaging of drug-induced changes in cell proliferation in vivo.
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PMID:Early detection of tumor response to chemotherapy by 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo. 1589 11

Concordant expression of human hexokinase-1 and inorganic pyrophosphatase was established in somatic cell hybrids between thymidine kinase-deficient Chinese hamster cells and human fibroblasts carrying a translocation of the distal third of the long arm of chromosome 10 to chromosome 17. Neither human hexokinase-1 nor human inorganic pyrophosphatase expression segregated concordantly with human cytoplasmic glutamic-oxaloacetic transaminase expression.
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PMID:Localization of the structural genes for hexokinase-1 and inorganic pyrophosphatase on region (pter-->q24) of human chromosome 10. 1749 25


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