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)

The R3230AC mammary adenocarcinoma was not dependent on insulin; tumor growth was equal to or greater in diabetic rats than in intact animals. However, tumor growth was reduced when daily doses of insulin were administered. Treatment with estrogen inhibited growth of the R3230AC carcinoma, either in diabetic rats or in intact animals simultaneously treated with insulin. The effects of insulin plus estrogen treatment appeared to be additive in causing inhibition of tumor growth. Tumors from diabetic rats showed few metabolic alterations as reflected by little or no changes in the activities of selected glycolytic enzymes, pyruvate kinase, phosphofructokinase, and hexokinase, nor any striking changes in the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, representing the pentose phosphate pathway. A modest reduction in the ratio of utilization of (1-14C)glucose: (6-14C)glucose was seen in vitro by tumors from diabetic rats. It was concluded that insulin, along with estrogen and prolactin, should be considered as a hormonal factor that influences growth of this automonous, hormone-responsive adenocarcinoma.
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PMID:Influence of insulin on estrogen-induced responses in the r3230ac mammary carcinoma. 12 68

The mitochondrial-bound hexokinases (adenosine triphosphate:D-hexose 6-phosphotransferase) of mammary adenocarcinoma and of normal gland were compared in lactating C3H mice. Treatment of mitochondria isolated from both the normal and neoplastic tissue with 0.5 m NaCl or 0.1 mM glucose 0-phosphate effected the release of about 50% of the bound hexokinase. In the presence of magnesium ion, enzyme from either source attached to mitochondria from either tissue and in all combinations to the same extent. Identification of the isoenzyme complement in the mitochondrial extract by diethylaminoethylcellulose chromatography revealed only types I and II. In the tumor, the hexokinase activity in both the cytosol and the fraction solubilized from mitochondria was predominantly in the form of type I ( 60%). In contrast, the activity released from mitochondria isolated from normal gland was predominately type II, while the cytosol contained almost equivalent amounts of types I and II. While this difference does not explain differences in glucose utilization between the normal and neoplastic tissue, it may provide a means of distinguishing between the two.
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PMID:Identity, release, and binding of mitochondrial-bound hexokinases in mammary glands and adenocarcinomas of lactating mice. 116 11

1. Solubilization of mitochondrial bound hexokinase (HK), which represents 75-80% of the total enzyme activity in the cells, was investigated in freshly isolated mitochondria from undifferentiated (Glc+) or differentiated (Glc-) HT29 adenocarcinoma cells. In both models, the bound HK is almost completely released in vitro by 100 microM glucose 6-P (G 6-P). 2. Free ATP (5 mM) or palmitate (800 microM) produce a partial solubilization of bound HK, more markedly in the case of Glc- mitochondria. 3. Glucose or glucose 1-P are found unable to solubilize bound HK. Glucose 1,6-P2, 2-deoxyglucose 6-P or glucosamine 6-P can solubilize the enzyme but are less efficient than G 6-P. 4. Mg2+ and Pi are found to counteract the glucose 6-P induced solubilization of HK in both types of mitochondria. Taking into account the intracellular concentrations of these ions, this could in part explain why, in HT29 cells, HK is predominantly bound to the mitochondria.
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PMID:Mitochondrial hexokinase from differentiated and undifferentiated HT29 colon cancer cells: effect of some metabolites on the bound/soluble equilibrium. 233 66

A study of hexokinase isozymic pattern and age dependence of the enzyme was carried out on erythrocytes of 4 patients with adenocarcinoma of the gastrointestinal tract. On the basis of our results, we think that the increase in hexokinase activity previously reported and the increase in both subtypes (Ia and Ib) of the enzyme herein described are not due to a mean younger red cell population caused by secondary anemia, which is frequently present in cancer patients.
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PMID:Relationship between erythrocyte hexokinase in cancer patients and red cell age. 667 38

In the present work we have considered the following erythrocyte enzymatic activities; hexokinase (HK), pyruvate kinase (PK), glucose-6-phosphate-dehydrogenase (G6PD), 6-phosphogluconate-dehydrogenase (6PGD), glicero phosphate-isomerase (PHI) and glutathione-reductase (GR) in the red blood cells of 130 subjects of which 55 were healthy or with non cancerous pathology and 75 with malignant tumors. Evident modification has been shown only for the HK which together with fructose-6-phosphate-kinase (PFK) and PK are limiting steps of glycolysis. The increased HK activity value resulted particularly significant in red blood cells of patients affected by well differentiated adenocarcinoma.
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PMID:[Hexokinase activity of erythrocytes in cancer patients]. 734 23

We recently reported that tyrphostin 23 (3,4-dihydroxybenzylidene malononitrile) is unstable in solution and that some of the degradation products are better inhibitors of the tyrosine kinase activity of Src and the EGF-receptor kinase than the parent compound itself (Ramdas et al., Cancer Res. 54, 867-868, 1994). In this study, the tyrphostin 23-derived compound designated P3, which is a more stable and potent protein tyrosine kinase inhibitor, was isolated. P3 was purified from oxidized tyrphostin 23 by solvent extraction, silica-gel flash chromatography, and reverse-phase high-pressure liquid chromatography. The physical characteristics of the isolated compound were determined and its chemical structure elucidated by 1H and 13C NMR spectroscopy. The proposed structure of this new inhibitor is that of a tyrphostin 23 dimer joined at the benzylidene carbon. P3 was evaluated in vitro as an inhibitor of four different protein tyrosine kinases (Src, Csk, EGF-receptor, and FGF-receptor) and two protein serine kinases (PK-A and PK-C). This compound exhibited the most inhibitory activity against Src with a Ki value of 6 microM and was less inhibitory toward the other protein kinases with Ki values ranging from 35 to 300 microM. P3 did not inhibit other nucleotide-utilizing enzymes such as lactate dehydrogenase and hexokinase. The growth and colony formation of HT-29 colon adenocarcinoma cells that contain activated Src was inhibited by P3 with an IC50 value of approximately 10 microM.
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PMID:A tyrphostin-derived inhibitor of protein tyrosine kinases: isolation and characterization. 748 83

The activities of D-glucose transport (D-GT) and cytosolic enzymes were significantly higher in mammary adenocarcinoma of dogs than in mammary gland from normal dogs. The activities of D-GT in adenocarcinoma were over three-and-a-half times higher than in the controls. The K(m) value of the D-GT activity for glucose in both the adenocarcinoma and normal mammary gland was approximately 0.9 mM. The activities of the key glycolytic enzymes, hexokinase and pyruvate kinase, in the adenocarcinoma were also more than three-and-a-half times higher than in the controls. The increased activities of D-GT are considered to be accompanied by an acceleration of glucose utilisation in the adenocarcinoma of dogs.
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PMID:Changes in glucose transport activities in mammary adenocarcinoma of dogs. 916 Apr 33

The transient change in uptake of deoxyglucose (DG) and expression of glycolysis-associated gene products in cultured tumor cells (LS180 human colon adenocarcinoma cells) immediately after single-dose X irradiation were examined to acquire basic data for use in the early assessment of tumor responses to radiation treatment by position emission tomography. An increase in accumulation of DG was found 3-5 h postirradiation. Inhibitors of both mRNA and protein synthesis and glycoprotein transport suppressed the increase in accumulation of DG to the control level. Both the glucose transporter-1 mRNA expression and the enzymatic activity of hexokinase in the cells were significantly elevated in conjunction with high DG accumulation. These findings indicate that the transiently elevated glucose metabolism occurred via processes at the levels of gene expression. These transient tumor cell responses might be useful for the early assessment of radiation damage.
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PMID:Transient increase in glycolytic metabolism in cultured tumor cells immediately after exposure to ionizing radiation: from gene expression to deoxyglucose uptake. 918 72

To determine the influence of tumor cell proliferation and changes in the genetic program in malignant cells on the fluorodeoxyglucose (FDG) uptake we performed PET studies in several animal tumors: spontaneous mammary fibroadenoma, chemically-induced mammary adenocarcinoma and Dunning prostate adenocarcinoma. The expression of the glucose transporter (GLUT1) and of hexokinase (Hk) was measured using 32P-labeled cDNA probes and densitometry. Furthermore the proliferative activity was determined with one-dimensional flow cytometry. The FDG uptake and the proliferation parameters were not correlated. The normalized amounts of GLUT and Hk mRNA were lower in spontaneous fibroadenomas and prostate tumors than in chemically induced mammary. The FDG uptake was correlated to GLUT1 expression with r = 0.83 and to Hk expression with r = 0.77. Multiple regression analysis revealed a relation of FDG uptake to GLUT1 and HK with r = 0.87. Our results show that the FDG uptake in our study was related not to differences in proliferation, but rather to differences in the transcription of glycolysis associated genes.
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PMID:FDG uptake, tumor proliferation and expression of glycolysis associated genes in animal tumor models. 923 32

Decreased tumour [(18)F]2-fluoro-2-deoxy-D-glucose ((18)FDG) incorporation is related to response however its significance at the cell level in gastro-oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD(10) and LD(50)), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. (18)FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V-PE binding (a measure of apoptosis). Treatment of cells for 48 and 72 h with LD(50) doses of cisplatin resulted in reductions in (18)FDG incorporation of 27 and 25% respectively and of 5-fluorouracil reduced (18)FDG incorporation by 34 and 33% respectively: epirubicin treatment reduced incorporation by 30 and 69% respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with (18)FDG incorporation before the recovery period allowed an assessment of the predictive ability of (18)FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in (18)FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between (18)FDG incorporation and cell cycle distribution. Our results show that at the tumour cell level in gastric tumour cells, decreased (18)FDG incorporation and glucose transport, accompanies therapeutic growth inhibition. (18)FDG incorporation is particularly diminished in cells exhibiting apoptosis.
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PMID:[18F]2-fluoro-2-deoxy-D-glucose incorporation by AGS gastric adenocarcinoma cells in vitro during response to epirubicin, cisplatin and 5-fluorouracil. 1784 47


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