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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes the isozyme composition and regulatory properties of pyruvate kinase (PK) from well-differentiated (DMTC) and undifferentiated (AMTC) medullary thyroid carcinomas of the rat. These tumors were chosen as an animal model for human (neuro-)entodermal neoplasms differing in their degree of differentiation. The results were compared with human medullary thyroid carcinomas (MTC) and phaeochromocytomas. AMTC were characterized by increased PK activity, a higher apparent S0.5 for phosphoenolpyruvate, enhanced inhibition by alanine, presence of predominantly M2-type isozyme and loss of M1-type-containing hybrids as compared to DMTC. The alterations in PK isozyme expression and hence kinetic behaviour could not be demonstrated in human MTC or phaeochromocytomas due to the apparently well-differentiated nature of these tumors and the presence of M2-type isozymes. These results are discussed with reference to the nature and significance of PK isozyme shifts found in other tumors. It is suggested that the determination of PK isozyme composition might prove useful in the diagnosis of nueroectodermal neoplasms originating from tissues not primarily expressing M2-type isozyme(s).
Tumour Biol 1985
PMID:Pyruvate kinase isozymes and dedifferentiation of (neuro-)ectodermal tumors. 402 64

The activities of selected glycolytic enzymes in breast tumor tissues were examined based on earlier studies showing a relationship between therapy and/or prognosis of breast cancer and tissue enzyme. In the present study, five glycolytic enzymatic activities (pyruvate kinase [PK], glucose-6-phosphate dehydrogenase [G6PD], phosphohexose-isomerase [PHI], lactate dehydrogenase [LDH], and 6-phospho-glucocate dehydrogenase [6PGD]) were measured in the cytosol (105,000 g) of 57 breast carcinomas and 22 benign breast lesions. Nucleic acids and DNA were also determined. The results were related to the wet weight of the tissue, to total and tissue cytosol proteins, and to DNA. The various means of expressing the results were compared. The correlations were satisfactory except for PHI and LDH. In these cases, this might have been due to blood contamination. The enzyme activities content was lower in the benign breast lesions than in the breast carcinomas irrespective of the way the results were expressed.
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PMID:Glycolytic enzymes in human breast carcinoma cytosols: the influence of commonly used reference parameters. 406 53

Metabolic studies in tumor cells have indicated that bioenergetic regulatory mechanisms geared to acute changes in oxygen availability are abnormal. In the present studies we have examined bioenergetic adaptations to chronic oxygen depletion in culture maintained tumor cells in comparison to normal cell lines. Activities of two key glycolytic enzymes (pyruvate kinase (PyKI) and phosphofructokinase (PFK)) were measured in two tumor cell lines (fibrosarcoma (FS) and Hela) and two normal cell lines (rat lung fibroblasts (RLF) and WI-38) maintained in culture for up to 96 hours under aerobic (PO2 approximately 140) and hypoxic PO2 approximately 15) conditions. Exposure to low O2 tensions for 96 hours resulted in significant increases in PyKi and PFK in both RLF and WI-38, ut did not alter activities of these enzymes in either FS or HeLa cell systems. Activities of two enzymes involved in O2 metabolism (cytochrome oxidase (CyOx) and superoxide dismutase (SOD) were also measured in the two tumor cell lines and in RLF. chronic hypoxia significantly decreased the activities of CyOx and SOD in RLF cell systems but did not alter the activities of these enzymes in the tumor cells. In these studies, the tumor-derived cell lines do not demonstrate specific enzymatic responses to sustained oxygen depletion in vitro noted in normal cell systems, suggesting significant abnormalities in regulatory mechanisms geared to chronic changes in molecular O2.
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PMID:Differences in oxygen-dependent regulation of enzymes between tumor and normal cell systems in culture. 627 Jan 67

The effect of a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), on differentiation marker expression in skeletal myotubes and their immediate progenitors, presumptive myoblasts (PMbs), was investigated. The markers employed included the K-isozyme of pyruvate kinase (PK-K) and a newly characterized phosphoprotein (pp(65;4.5)), which are both normally concentrated in PMbs, and the M-isozyme of pyruvate kinase (PK-M) and phosphorylated derivatives of alpha- and beta-tropomyosin (pT), which are normally concentrated in myotubes. PMbs treated with TPA for 3, 6 or 10 days continued to express PK-K and pp(65;4.5), and did not express PK-M or pT at detectable levels. Myotubes which were treated for 3 or 6 days were inhibited in their expression of PK-M and pT, but were not stimulated in their expression of PK-K or pp(65;4.5). The effects of TPA were reversible upon discontinuation of treatment. In parallel experiments, where pp(65;4.5) and pT were monitored, infection with Rous sarcoma virus (RSV) had similar effects. The data suggest that TPA treatment and RSV transformation do not alter the state of differentiation of target cells per se but, in the case of myotubes, do suppress the expression of that state.
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PMID:The comparative effects of tumor-related agents on developmental marker expression in presumptive myoblasts and myotubes. 630 63

The kinetic and structural properties of purified, homogeneous pyruvate kinase type M2 from chicken lung and tumors, including that from Rous sarcoma virus-transformed chicken fibroblasts, have been compared. The "tumor enzyme" is characterized by a low affinity for phosphoenolpyruvate, pronounced serine activation, and strong alanine inhibition as compared to the "lung type". In contrast to the rat lung enzyme, which is not affected by serine, the chicken lung enzyme is slightly activated by serine. The serine metabolites phosphoserine and glycine do not activate the "tumor type M2 pyruvate kinase", but L-alpha-glycerophosphorylcholine and phosphatidylserine do slightly activate at physiological concentrations. Studies with substances structurally related to serine reveal that the hydroxyl group of serine is a prerequisite for the activation and that the amino and carboxyl groups determine the affinity of the "tumor type M2 pyruvate kinase" for serine. Two different fragmentation methods (CNBr-cleavage and V-8 proteolysis) and two different methods for separation of the resulting peptide fragments (polyacrylamide gel isoelectric focussing and SDS-polyacrylamide electrophoresis) indicated a high degree of homology between the type M2 pyruvate kinases from lung and tumors as well the type M1 from muscle. Each type of pyruvate kinase, however, contains one or two unique protein fragments which are characteristic for its type. We have termed those fragments L (lung), M (muscle), and T (tumor).
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PMID:Structural and kinetic differences between the M2 type pyruvate kinases from lung and various tumors. 632 72

The requirements for in vitro mitochondrial protein synthesis have been studied using isolated mitochondria from cultured adrenal Y-1 tumor cells from mice. By reducing the reaction volume to 50 microliter we were able to assay in replicate the requirements for various reaction components using trichloroacetic acid (TCA)-precipitable counts for a quantitative evaluation with time of incubation. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis followed by autoradiography was also used for a qualitative and quantitative evaluation of the translation products. With the optimized system, 1 to 3% of added [35S]methionine was incorporated. The products of mitochondrial protein synthesis range from 70,000 to 5000 molecular weight. Major autoradiographic bands were observed at 38,000, 31,000, 23,000, 20,000, and 5600 molecular weight as separated on 10 to 20% gradient SDS-polyacrylamide gels; however, 20 to 30 protein products of various molecular weights were discernible. Mitochondrial concentrations of 0.8 to 1.4 mg/ml of incubation gave the better incorporation of [35S]methionine per milligram of protein. Total [35S]methionine incorporated into mitochondrial protein was greatest at 25 degrees C after 90 min. Chloramphenicol at 10 micrograms/ml inhibited mitochondrial protein synthesis by more than 50% and at 100 micrograms/ml inhibited incorporation by more than 95%. Cycloheximide had no effect on incorporation at less than 1.0 mg/ml. Magnesium and ATP in a molar ratio of one to one at 5 mM gave optimal incorporation. Other energy generating systems using oxidative phosphorylation to supply ATP for protein synthesis were not as effective as ATP and 5 mM phosphoenol pyruvate, 20 micrograms/ml pyruvate kinase and 5 mM a-ketoglutarate. In contrast to in vitro yeast mitochondrial protein synthesis, no enhancement of in vitro adrenal cell mitochondrial protein synthesis was found with GTP or its analogs. The buffers N,N-bis(2-hydroxyethyl)glycine, N-(tris(hydroxymethyl)methyl)glycine, and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid were superior to Tris-HCl for mitochondrial protein synthesis. Optimal pH for [35S]methionine incorporation into mitochondrial proteins was pH 7.0 to 7.6. Potassium at 50 to 90 mM gave the best incorporation of [35S]methionine, and the higher molecular weight products of translation were enhanced at these concentrations. Sodium at 10 to 40 mM had no effect; however, 100 mM sodium inhibited label incorporation by 30%. Calcium at 100 microM inhibited mitochondrial protein synthesis by approximately 50%, and at 1.0 mM little if any incorporation occurred.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Optimization of in vitro protein synthesis by isolated mouse adrenal mitochondria. 632 34

The activities of six different enzymes were compared in 29 normal, 34 dysplastic, and 80 cancerous (both primary and metastatic) human breast tissues; in MCF-7 cells; and in primary rat mammary tumors. Benign lesions generally showed enzyme activities similar to those of normal breast tissues. Malignant tumors had significantly increased activities of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), fructose-bisphosphate aldolase, hexokinase (HK), pyruvate kinase (PK), and creatine kinase. Enzyme activity in the malignant tumor was always higher than that in apparently normal or fibrocystic tissue from the same patient. Enzyme activities did not correlate with the levels of estrogen and progesterone receptors. LDH, MDH, and HK were elevated to a similar extent in all the tissues examined. Conversely, PK was elevated to a much greater extent in cancerous tissues, particularly in MCF-7 cells. The elevated activities of these enzymes may have diagnostic potential, especially when tumor tissue and apparently normal tissue from the same patient are compared.
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PMID:Enzyme activities in normal, dysplastic, and cancerous human breast tissues. 658 10

The histologic classification of mouse liver tumors, i.e., hepatic nodules type 1 and type 2 and hepatocellular carcinomas, was evaluated by a comparison of several biologic and biochemical markers that have been shown to be useful for the grading of tumor malignancy. The liver tumors were induced by N,N'-2,7-fluorenylenebisacetamide (CAS: 304-28-9; N,N'-fluoren-2,7-ylenebisacetamide) administration to male CD-1 mice. The ability to induce L-type pyruvate kinase activity in response to a high-carbohydrate diet disappeared in almost all the liver tumors. However, fairly good correlations were observed between the histologic classification and the relative weights of liver and intraperitoneal fat pads, between the histologic classification and the level of serum total cholesterol, and between the histologic classification and the K-type pyruvate kinase activity. The results suggest that the present histologic classification reflects the degree of tumor malignancy, and therefore, it would be useful for the classification of mouse liver tumors.
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PMID:Evaluation of a histologic classification of mouse liver tumors based on pyruvate kinase isozymes and status of host lipids. 659 42

Biopsies from 15 human gliomas, five meningiomas, four Schwannomas, one medulloblastoma, and four normal brain areas were analyzed for 12 enzymes of energy metabolism and 12 related metabolites and cofactors. Samples, 0.01-0.25 microgram dry weight, were dissected from freeze-dried microtome sections to permit all the assays on a given specimen to be made, as far as possible, on nonnecrotic pure tumor tissue from the same region. Great diversity was found with regard to both enzyme activities and metabolite levels among individual tumors, but the following generalities can be made. Activities of hexokinase, phosphorylase, phosphofructokinase, glycerophosphate dehydrogenase, citrate synthase, and malate dehydrogenase levels were usually lower than in brain; glycogen synthase and glucose-6-phosphate dehydrogenase were usually higher; and the averages for pyruvate kinase, lactate dehydrogenase, 6-phosphogluconate dehydrogenase, and beta-hydroxyacyl coenzyme A dehydrogenase were not greatly different from brain. Levels of eight of the 12 enzymes were distinctly lower among the Schwannomas than in the other two groups. Average levels of glucose-6-phosphate, lactate, pyruvate, and uridine diphosphoglucose were more than twice those of brain; 6-phosphogluconate and citrate were about 70% higher than in brain; glucose, glycogen, glycerol-1-phosphate, and malate averages ranged from 104% to 127% of brain; and fructose-1,6-bisphosphate and glucose-1,6-bisphosphate levels were on the average 50% and 70% those of brain, respectively.
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PMID:Diversity of metabolic patterns in human brain tumors: enzymes of energy metabolism and related metabolites and cofactors. 661 61

Isozyme patterns of 23 different enzymes were compared in normal, benign, and malignant breast tissues; in MCF-7 cells; and in organoids of normal human breast tissue. Benign lesions generally showed isozyme patterns similar to those of normal tissues. Lactate dehydrogenase isozyme 5 was significantly increased in malignant tumors; MCF-7 cells had only lactate dehydrogenase (L-lactate:NAD oxidoreductase; EC 1.1.1.27). The mitochondrial form of malate dehydrogenase was also significantly increased in human malignant tumors; this was especially evident when comparing tumor and apparently uninvolved breast tissue from the same patient. The K4 isozyme of pyruvate kinase was the major form in most malignant breast tumors, but in only 41% of normal tissues, 30% of fibrocystic disease specimens, and 46% of fibroadenomas. A more anodal band of pyruvate kinase, probably a K3M or K3Kpm hybrid, predominated in most normal and benign tissues, but in only 63% of primary and 56% of secondary tumors. All specimens had predominantly creatine kinase BB, aldolase A4, and hexokinase I. Traces of aldolase A3C and of hexokinase II were observed in some tumors. None of the tumors had the Regan variant of alkaline phosphatase. The isozymes of lactate and malate dehydrogenases and of pyruvate kinase appear to be the most promising as putative tumor markers.
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PMID:Isozyme patterns of normal, benign, and malignant human breast tissues. 664 May 38


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