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)

Considerable thymidine kinase and pyrroline-5-carboxylate reductase activities were found in the plasma of rats bearing a transplanted lymphoma; neither activity was detected in plasma of hosts carrying hepatic, renal, mammary, or submaxillary gland tumors. All host livers exhibited signs of biochemical immaturity as indicated by the appropriate increases or decreases in the concentrations of the nine enzymes measured. The extent and time schedule of the changes in host liver varied with the enzyme and with the tumor that caused them. The hepatic concentrations of ornithine aminotransferase, arginase, pyrroline-5-carboxylate reductase, and glucokinase (all diminished), and of peptidyl proline hydroxylase and hexokinase (increased) were sensitive indicators of tumor growth in general. The concentration of ornithine aminotransferase decreased before the tumors became palpable. At more advanced stages, the high hepatic thymidine kinase activity distinguished the presence of hepatoma and lymphoma from those of all other equally fast-growing tumors. However, only in lymphoma-bearing rats did a fivefold elevation of hepatic thymidine kinase occur as early as 4 days after implantation. Additional observations on the lymphoma itself, on blood cells, and on the involuting thymus of normal rats indicate that the striking systemic effects of this tumor cannot be explained by a release of enzymes from the thymus or by the increased number of lymphoma cells present in blood or liver.
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PMID:The effect of lymphoma and other neoplasms on hepatic and plasma enzymes of the host rat. 18 34

Activities of certain cytoplasmic enzymes were measured in bovine T lymphoma (BTL-PC3 cells). The activities of hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase in PC3 cells were elevated as much as 2 or 3-fold of those in bovine thymocyte. The high activities of these enzymes derived from activation of glucose metabolism may reflect the high growth potential of PC3 cells.
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PMID:Activities of certain cytoplasmic enzymes in bovine T lymphoma. 142 May 55

Glucocorticoids induce apoptosis in lymphocytes by causing the release of cytochrome c into the cytosol; however, the events in the signaling phase between translocation of the steroid-receptor complex to the nucleus and the release of cytochrome c have not been elucidated. Previously, we found that, in response to steroid treatment, WEHI7.2 mouse thymic lymphoma cells overexpressing catalase (CAT38) show delayed apoptosis (delayed cytochrome c release) compared to the parental cells, while Bcl-2 overexpressing cells (Hb12) are protected from steroid-induced apoptosis. In lymphocytes, glucocorticoid treatment decreases glucose uptake. Both glucose deprivation and the attendant ATP drop are known inducers of apoptosis. Therefore, we used (31)P and (1)H NMR spectroscopy to compare metabolic profiles of WEHI7.2, CAT38 and Hb12 cells in the presence and absence of dexamethasone to determine: (1) whether glucocorticoid effects on glucose metabolism contribute to the mechanism of steroid-induced apoptosis; and (2) whether catalase or Bcl-2 overexpression altered metabolism thereby providing a mechanism of steroid resistance. Loss of mitochondrial hexokinase activity was correlated to the induction of apoptosis in WEHI7.2 and CAT38 cells. CAT38 and Hb12 cells have an altered basal metabolism which includes increases in hexokinase activity, lactate production when subcultured into new medium, use of mitochondria for ATP production and potentially increased glutaminolysis. These data suggest that: (1) glucocorticoid effects on glucose metabolism may contribute to the mechanism of steroid-induced lymphocyte apoptosis; and (2) the altered metabolism seen in catalase and Bcl-2 overexpressing cells may contribute to both the steroid resistance and increased tumorigenicity of these variants.
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PMID:Overexpression of catalase or Bcl-2 alters glucose and energy metabolism concomitant with dexamethasone resistance. 1527 25

A 62-year-old woman experienced headache and rapidly progressive left hemiparesis over 2 weeks. Diffusion-weighted and fluid-attenuated inversion recovery MR images of the head showed increased signal intensity in the right basal ganglia, periventricular white matter and the brain stem. Enhancement was not observed on a T1-weighted spin-echo MR image after the administration of a contrast material. An 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) study with kinetic analysis showed decreased FDG transport and increased hexokinase activity in the lesions compared with the contralateral hemisphere. The diagnosis was made by biopsy of the right caudate head and pathologic specimens were positive for malignant large-cell lymphoma, B-cell phenotype. The patient received high-dose methotrexate with CHOP chemotherapy, and an [18F]FDG-PET study with kinetic analysis showed decreased hexokinase activity after the first chemotherapy. Kinetic [18F]FDG-PET analysis may be useful to diagnose and monitor the treatment effect in non-enhancing primary central nervous system lymphoma.
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PMID:Usefulness of [18F]FDG-PET kinetic analysis in non-enhancing primary central nervous system lymphoma: case report. 1616

The aim of this study was to investigate correlations between the standardized uptake value of the biopsy site (BSUVmax) and levels of glucose transporter (GLUT)-1, GLUT-3 and hexokinase-II (HK-II), between BSUVmax and the Ki-67 proliferation index (MIB-1), and between BSUVmax and clinicopathological factors. Sixty-eight patients with diffuse large B-cell lymphoma (DLBCL) were included in this study. BSUVmax was significantly correlated with GLUT-1, GLUT-3 and the International Prognostic Index (IPI) (GLUT-1: r = 0.584, IPI: r = 0.363, p < 0.001; GLUT-3: r = 0.369, p = 0.009; IPI: r = 0.363, p = 0.004), but not with MIB-1 and HK-II. A statistically significant correlation was observed between GLUT-3 expression and each of IPI and gene expression profiling (GEP) (IPI: p = 0.0186; GEP: p = 0.0179). 2-Deoxy-2-[(18)F]-fluoro-d-glucose (FDG) uptake was significantly correlated with the levels of GLUT-1 and GLUT-3 and with IPI. The results indicated that GLUT-3 expression is related to GEP and IPI, and that BSUVmax and GLUT-3 may have a relationship with the prognosis of DLBCL.
Leuk Lymphoma 2014 Mar
PMID:Relationship between 2-deoxy-2-[(18)F]-fluoro-d-glucose uptake and clinicopathological factors in patients with diffuse large B-cell lymphoma. 2370 Nov 33

Extranodal nasal-type natural killer/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV) associated lymphoma that progresses rapidly and relapses frequently. Advanced ENKTL is multidrug chemoresistant and has a poor prognosis. In this study, we aim to develop a novel hexokinase domain component 1 (HKDC1)-based antitumor target for ENKTL that is involved with the antimetabolic signaling pathway, EBV replication, and P-glycoprotein (P-gp) expression. We showed that HKDC1 is highly upregulated in ENKTL cells and HKDC1 knockdown significantly suppresses ENKTL tumor growth. In addition, HKDC1 is highly identical with four other hexokinase isoforms, with the only difference being in the last eight amino acids (aa) at the C-terminal. Further investigation showed that peptide delivery of the last eight aa of HKDC1 at the C-terminal (HKC8) with D-configuration using transferrin (Tf) receptor internalization sequence (Tf-D-HKC8) inhibits HKDC1 association with vascular endothelial growth factor 1 (VDAC1), resulting in mitochondrial dysfunction and reactive oxygen species (ROS) overgeneration and subsequently suppressing EBV replication and P-gp expression, making it very effective in killing EBV-positive ENKTL cells. Further in vivo experiments showed that local injection of Tf-D-HKC8 peptide significantly suppresses ENKTL tumor growth and EBV replication in ENKTL xenograft mouse models. We conclude that HKDC1 C-terminal-based peptides inhibit ENKTL by modulation of mitochondrial function and EBV suppression.
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PMID:HKDC1 C-terminal based peptides inhibit extranodal natural killer/T-cell lymphoma by modulation of mitochondrial function and EBV suppression. 3220 47

The usefulness of whole-body 18-fluoro-2-deoxyglucose (FDG)-fluorodeoxyglucose positron emission (PET)/computed tomography (CT) is established for assessment of disease staging, detection of early disease recurrence, therapeutic evaluation, and predicting prognosis in various malignancies; and for evaluating the spread of inflammation. However, the role of FDG-PET/CT for the liver is limited because CT and magnetic resonance imaging (MRI) can provide an accurate diagnosis of most tumors. In addition, in other potentially useful roles there are several pitfalls in the interpretation of FDG uptake in PET/CT imaging. Accurate evaluation demands knowledge of the FDG uptake of each lesion, including potential negative and positive uptakes, and requires an understanding of the underlying background of the molecular mechanisms. The degree of FDG uptake is dependent on cellular metabolic rate and the expression of glucose transporter, hexokinase, and glucose-6-phosphatase, which in turn are closely affected by biological characteristics such as pathological category (e.g., adenocarcinoma, squamous cell carcinoma, small cell cancer, transitional cell cancer, neuroendocrine tumor, sarcoma, lymphoma), tumor differentiation, histological behavior (e.g., solid, cystic, mucinous), and intratumoral alterations (e.g., necrosis, degeneration, hemorrhage). Correlation with the CT and MRI findings, which also precisely depict the pathological findings, is important to avoid misdiagnosis.
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PMID:FDG-PET/CT imaging findings of hepatic tumors and tumor-like lesions based on molecular background. 3224 50