Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Activity of several enzymes of the glycogen and carbohydrate metabolism is studied in HT 29 colon adenocarcinoma cell line and in HT 29 tumors developed in nude mice, by reference to the normal human colon mucosa. Activity of glycogen synthase, glycogen phosphorylase, pyruvate kinase, fructose-1,6-diphosphatase, glucose-6-phosphate dehydrogenase and lactate dehydrogenase is found to be increased in both the cultured cells and the tumors. It indicates that the biochemical strategy of malignant cells, due to the neoplastic transformation process, involves specific changes in the carbohydrate metabolism of tumor as well as in vitro growing correspondent cell line.
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PMID:Activity of enzymes related to carbohydrate metabolism in the HT 29 colon adenocarcinoma cell line and tumor. 669 92

Ehrlich ascites tumor cells from mice were damaged during in vitro incubation with a cytotoxin from Pseudomonas aeruginosa at concentrations of greater than 1 microgram/ml. After a short time the cells started to lose potassium whereas their sodium content increased. When the protein concentration of the incubation medium was adjusted to the protein concentration inside the cells, swelling and release of glucose-6-phosphate dehydrogenase was avoided. However, lysis of the cells still took place. Preincubation of cells with tetrodotoxin, 4-aminopyridine or tetraethylammonium did not influence damage to the cells. The cells showed a steep increase in toxin response between 17 degrees and 27 degrees C ranging from insensitivity to full sensitivity. An increase in electrical conductance was measured during incubation of cholesterol bilayer membranes with a cytotoxin concentration of 1 microgram/ml. The conductance was increased by a factor of ten within 30 min at 25 degrees C which indicates the involvement of membrane lipids in the cytotoxin action.
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PMID:Permeability changes of Ehrlich mouse ascites tumor cells induced by a cytotoxin from Pseudomonas aeruginosa. 681 57

1. Isotope and non-isotope methods were used to study hepatic metabolism of glucose in tumor-host livers. 2. Glycogen synthase, phosphofructokinase activities (Vmax) were decreased, while glucose-6-phosphate dehydrogenase and lactate dehydrogenase activities were increased in tumor-host livers. 3. Glycogen phosphorylase, glucokinase and several mitochondrial enzymes, had normal maximum activity in tumor-host livers. Net flux of glucose was decreased in the Embden-Meyerhof and the pentose phosphate pathway in tumor animals. 4. The hepatic cycling of glucose-carbons in tumor animals was significantly decreased as shown by different [14C] [3H] ratios of radioactivity in RNA and lactate, determined from simultaneous incorporation of [U-14C]glucose and [2-3H]glucose. 5. This study demonstrates that previous reports of increased activities of rate limiting enzymes of glucose metabolism in tumor-host livers do not represent a general finding of high glucose metabolism in tumor-host livers.
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PMID:Activities of key enzymes in relation to glucose flux in tumor-host livers. 682 4

A cell line, designated OKK, has been established from a human maxillary carcinoma in a Japanese man. The cultured cells were inoculated into nude mice, with the subsequent establishment of tumors. Alkaline phosphatases were extracted from these tumors and partially purified by chromatography. The electrophoretically fastest moving isoenzyme, designated tentatively as OKK T isoenzyme, was biochemically and immunologically investigated by comparing it with the Kasahara isoenzyme purified partially from the tumor, which originated from FL cells inoculated into a nude mouse. The properties of the OKK T isoenzyme were identical to those of the Kasahara isoenzyme. Thus, the enzymes showed a similar inhibition by amino acids (L-phenylalanine and L-leucine), the same behavior with respect to other properties, including heat stability, immunological character and molecular weight. The genetic phenotype of the glucose-6-phosphate dehydrogenase of this established cell line was proved not to be identical to that of a HeLa cell line.
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PMID:Production of Kasahara isoenzyme by OKK cell line established from a human maxillary carcinoma. 683 48

A fraction of tumour cells in the state of proliferative rest was prepared by sedimentation from aged Ehrlich tumor and lymphoma NK/Ly. These cells do not incorporate [3H]-thymidine and contain fewer proteins and RNAs than the proliferating cells. The incorporation of [3H]-uridine by these cells makes up to 3.5-10% of the maximal incorporation by proliferating cells at the S-phase. The resting cells have a low rate of glycolysis and a high rate of respiration. The activity of lactate dehydrogenase, glucose-6-phosphate dehydrogenase and malate dehydrogenase in these cells is considerably reduced. The resting cell nuclei were found to contain a low molecular weight protein with molecular weight of 9000 +/- 500 (protein P-9) absent in proliferating cell nuclei. Using acetone fractionation and a subsequent preparative electrophoresis in a phenol solution, protein P-9 was isolated from the nuclei of lymphoma NK/Ly and Gerene carcinoma in a pure state. The physico-chemical properties of the protein from various sources were found to be similar. Thus, protein P-9 can be attributed to low molecular weight non-histone proteins with pI at the weakly alkaline region of pH.
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PMID:[Isolation and physico-chemical properties of P-9 protein, marker for the resting cells of lymphoma NK/Ly and Gerene carcinoma]. 729 22

The chemopreventive efficacy of dehydroepiandrosterone (DHEA) and indomethacin (IM) alone or in combination was investigated in a rat multiorgan carcinogenesis model. These two chemicals were selected as chemopreventive agents with different functions. Animals were sequentially given five carcinogens with different organ target sites in the first 4-week initiation period. One week after its completion, the rats received 0.3% DHEA in the diet, 20 ppm IM in the drinking water, or 0.3% DHEA + 20 ppm IM until experimental week 28. DHEA enhanced hepatocarcinogenesis, but concurrent treatment with IM suppressed tumor development as compared to the DHEA group. DHEA inhibited tumor development in the thyroid, with a similar tendency observed for the small intestine. In addition, treatment with this hormone decreased occurrences of preneoplasias in the urinary bladder and seminal vesicles. Treatment with IM clearly suppressed development of preneoplasias or neoplasias in the lung and small and large intestines. In the urinary bladder, treatment with IM tended to decrease preneoplastic lesion development. Analysis of multiplicity of total tumors of any category revealed comparable values for DHEA and control groups, while the IM group showed a significant reduction. IM in combination with DHEA caused suppression as compared to DHEA alone. In a separate 8-week experiment, DHEA or IM were administered for 4 weeks after prior carcinogen application, and biochemical responses in the target organs were investigated. DHEA increased glucose-6-phosphate dehydrogenase levels in the liver but caused a decrease in the small intestine. In addition, DHEA decreased serum T4 but not T3. IM decreased prostaglandin E2 content in the small intestine. In conclusion, although DHEA or IM exert significant chemopreventive effects in multiorgans with the exception of the DHEA-treated liver case, treatment in combination did not result in amplification of their beneficial influence. Our results suggest the possible application of IM for chemoprevention in high-risk individuals, but the question of effects of DHEA in the liver must be answered before this hormone can be considered for use in humans.
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PMID:Chemoprevention by dehydroepiandrosterone and indomethacin in a rat multiorgan carcinogenesis model. 758 22

Fe-NTA is a known renal carcinogen. However, little is known about its carcinogenic potential in liver. In this study we for the first time show that Fe-NTA is a potent hepatic tumor promoter. Fe-NTA administration induced dose dependently the hepatic ornithine decarboxylase (ODC) activity several folds as compared to its activity in the saline-treated rats. Similarly, hepatic DNA synthesis which is measured as [3H]thymidine incorporation in DNA is also increased following Fe-NTA treatment. The effects of Fe-NTA were similar to other tumor promoters not only with respect to inducing ODC activity and [3H]thymidine incorporation in DNA but also in depleting antioxidant armory of the tissue. Fe-NTA depleted levels of glutathione to about 35% of the saline-treated control and activities of antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase decreased significantly (45-55% of saline-treated control). Concomitant with the depletion in antioxidant armory, Fe-NTA augmented hepatic microsomal lipid peroxidation more than three folds. The pretreatment of rats with antioxidants BHA or BHT diminished the observed effects of Fe-NTA. Our data indicate that Fe-NTA is a potent hepatic tumor promoter and acts through a mechanism involving oxidative stress.
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PMID:Ferric nitrilotriacetate (Fe-NTA) is a potent hepatic tumor promoter and acts through the generation of oxidative stress. 762 70

A phase I study of mitomycin C with menadione (2-methyl-1,4-naphthoquinone, a vitamin K analogue which lowers intracellular pools of reduced glutathione) was designed as an approach to overcoming tumor cell resistance to alkylating agent chemotherapy. Patients with refractory solid tumors (n = 51) were treated with a 48-h continuous intravenous infusion of menadione followed by a bolus intravenous dose of mitomycin C at the completion of the menadione infusion. Initial menadione doses of 8.0 and 4.0 g/m2 over 48 h were associated with hemolysis, so subsequent dose levels of menadione ranged from 1.0 to 3.0 g/m2 with mitomycin C from 5 to 20 mg/m2. All three patients treated with menadione at 8.0 g/m2 and the single patient treated at 4.0 g/m2 with mitomycin C at 5 mg/m2 developed clinically significant hemolysis despite the presence of red blood cell glucose-6-phosphate dehydrogenase. Subsequently, a revised escalation scheme for menadione was used, and all patients tolerated menadione doses of 1-2.5 g/m2 over 48 h with mitomycin C doses up to 20 mg/m2. Since the 3.0 g/m2 dose of menadione was associated with mild hemolysis in three of four patients, the maximum tolerated dose of menadione was established at 2.5 g/m2. All of the mitomycin dose levels were tolerated without unexpected toxicities attributable to the combination. Prolonged infusions of menadione at doses which have been associated with lowering of intracellular glutathione pools in short-term exposure are limited by dose-dependent hemolysis, probably due to depletion of erythrocyte glutathione by menadione-related redox cycling. There was no detectable deleterious effect of pre-exposure to menadione on mitomycin C tolerance. We recommend a combination of menadione at 2.5 g/m2 as a continuous intravenous infusion and mitomycin C at 15 mg/m2 for further study in solid tumors, for which treatment with single-agent mitomycin C is appropriate.
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PMID:Phase I study of mitomycin C and menadione in advanced solid tumors. 762 48

In this work comprehensive data of antioxidant enzymes are reviewed and their role in carcinogenesis is discussed. When compared to their normal tissue counterparts, more of the tumor tissues were low in Cu, Zn-SOD and catalase activity and in some cases in Mn-SOD. It is probably characteristic for tumor tissues. Glutathione peroxidase, and glutathione reductase and glucose-6-phosphate dehydrogenase activities are highly variable. The reason why cancerous cells exhibit abnormal levels and activities of antioxidant enzymes is unknown. It was hypothesized, that during formation of the tumor, by certain obscure mechanism, cells with imbalance of antioxidant enzymes profile were selected over normal cells. It is not known whether the changes in antioxidant defence observed in cancerous tissues play a role in carcinogenesis, or are formed as a results of the disease.
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PMID:[Activity of antioxidant enzymes in cancer diseases]. 763 95


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