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)

High-resolution 31P nuclear magnetic resonance spectra at 145.7 MHz are reported for intact Ehrlich ascites tumor cells and their perchloric acid extracts. In the extracts it was possible to assign resonances to fructose 1,6-bisphosphates, dihydroxyacetone phosphate, ATP, ADP, AMP, Pi, NAD+, phosphorylcholine, glycero-3-phosphorylcholine, glycero-3-phosphorylethanolamine, and glyceraldehyde 3-phosphate from their chemical shifts, pH behavior, and spin couplings. All but glyceraldehyde 3-phosphate were observed and assigned in the intact cells. It was possible to show that the hydrolysis of fructose 1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate is in equilibrium, that the dihydroxyacetone phosphate leads to glyceraldehyde 3-phosphate reaction is not, and that in the intact cell without added oxygen or glucose the reaction 2ADP in equilibrium ATP + AMP is in equilibrium. From the known pH dependence of the Pi resonance it was possible to show that during aerobic or anerobic glycolysis the difference between intracellular and extracellular pH values was less than 0.2 pH units. Upon oxygenation the ATP concentration increased while the ADP concentration fell. Introducing deoxyglucose depleted the ATP and resulted in an AMP signal and one from deoxyglucose 6-phosphate, which is transported and phosphorylated but not catabolized.
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PMID:31P nuclear magnetic resonance studies of Ehrlich ascites tumor cells. 1 72

Colony formation of JB-1-E tumor cells was studied after hyperthermic treatment (42.5 degrees C) at a pH of 6.4 or 7.2 under hypoxic and euoxic conditions. At a pH of 7.2 and normal oxygen tension, there was a moderate decrease in colony formation with increasing duration of hyperthermic treatment (To = 65 min.). This effect was slightly enhanced under hypoxic conditions (To = 36 min.). The hyperthermic effect was enhanced to a considerably greater degree when treatment was performed at a pH of 6.4 (To = 19 min.), with no observable difference between hypoxia and euoxia. These findings indicate that environmental acidity is a determining factor in the hyperthermic effect. The hypoxic effect at a pH of 7.2 is probably due to a slight decrease in the intracellular pH caused by increased production of lactic acid.
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PMID:The influence of hypoxia and acidity on the hyperthermic response of malignant cells in vitro. 1

Several anticancer chemicals containing a quinone group were found to stimulate the aerobic oxidation of NADPH by liver microsomes. The enzyme responsible for the above reaction was identified as NADPH-cytochrome c reductase (EC 1.6.2.4), one of the microsomal flavoproteins. The fact that a catalytic amount (20 micronM) of these anticancer chemicals was sufficient to oxidize all the NADPH (100 micronM) indicates that they function as electron carries from the flavoprotein to molecular oxygen. As a corollary, Mitomycin-C and Carbazilquinone stimulated oxygen uptake by Ehrlich ascites tumor cells in the presence of glucose that Daunomycin and Adriamycin failed to do so, although the reason for it remains to be elucidated. Carbazilquinone, in contrast to others, also stimulated the microsomal NADH oxidation.
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PMID:Stimulation of microsomal NADPH oxidation by quinone group-containing anticancer chemicals. 1 20

The mode of generation of free radicals of daunomycin, adriamycin, and carboquone in the NADPH-rat liver microsome system was studied at room temperature by electron spin resonance (ESR) spectroscopy. ESR signals of all these quinoid anticancer chemicals were detected when dissolved oxygen in the reaction mixture was consumed since the radicals are easilyaut oxidizable. All the radicals had an appreciable lifetime under anaerobic conditions. However, there were differences in the mode of their generation between daunomycin and adriamycin, on the one hand, and carboquone, on the other, with respect to the lag time and the effect of the amount of chemicals, pH of the medium, kind of electron donors, NADPH and NADH, and the presence of excess of DNA. Especially, ESR signal reappeared after the first signal had decreased considerably, in the case of daunomycin and adriamycin but not in carboquone. Intact Ehrlich ascites tumor cells also gave rise to an ESR signal of adriamycin and carboquone, but the former signal was prevented from appearing in the presence of glucose.
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PMID:Electron spin resonance study on the mode of generation of free radicals of daunomycin, adriamycin, and carboquone in NAD(P)H-microsome system. 2 73

Dehydroascorbate, an electron affinic metabolite of vitamin C, sensitized Ehrlich ascites tumor cells, in vivo, to radiation and was selectively toxic to V79 Chinese hamster lung cells under hypoxic conditions (without radiation). The radiosensitization may involve both the electron affinic nature of dehydroascorbate as well as its ability to oxidize the intracellular NAD(P)H and non-protein sulfhydryl. Dehydroascorbate's oxidation of NAD(P)H required higher concentrations than other sulfhydryl oxidants such as N-ethylmaleimide and diamide. The oxidation of NAD(P)H by dehydroascorbate could be reversed by glucose. Hypoxic cell radiosensitization of V79 cells in tissue culture by dehydroascorbate could not be easily demonstrated because of the rapid breakdown and appreciable cytotoxicity of the drug at high concentration. The cytotoxicity was found to occur with both high and low densities of V79 cells. With low cell densities small amounts of oxygen did not reduce the cytotoxicity of dehydroascorbate, but virtually eliminated the cytotoxicity of nitroaromatic electron affinic compounds (metronidazole and Ro-07-0582). The cytotoxicity to dense cell suspensions was found to depend upon the type of buffer included in the reaction medium. The maximum cytotoxicity was obtained in buffer free saline. The reduced form of dehydroascorbate, vitamin C, was found to be toxic only under aerobic conditions. The aerobic cytotoxicity could be prevented by the addition of catalase to the growth medium or by an increase in cell density, suggesting it was caused entirely by the production of H2O2 from the oxidation of vitamin C.
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PMID:Toxicity, radiation sensitivity modification, and metabolic effects of dehydroascorbate and ascorbate in mammalian cells. 2 85

Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport.
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PMID:Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides. 2 36

We have established a clonal cell line, PC-G2, from an experimentally induced rat pheochromocytoma. Administration of nerve growth factor to PC-G2 causes a 4- to 8-fold induction in the specific activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase(3-hydroxylating); EC 1.14.16.2]. The response is elicited in a dose-dependent fashion, at concentrations above 0.1 microgram/ml. Antiserum to nerve growth factor inhibited the induction of tyrosine hydroxylase. Dexamethasone enhances the nerve growth factor-mediated elevation of tyrosine hydroxylase. After 3--4 days of exposure to nerve growth factor the maximal induction of tyrosine hydroxylase is seen, although a significant increase can be observed after 24 hr. In contrast to the PC-12 cell line (derived from the same tumor), in which neurite outgrowth occurs in response to nerve growth factor, there is no morphological change or alteration in growth rate of PC-G2 cells after exposure to nerve growth factor.
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PMID:Nerve growth factor-mediated induction of tyrosine hydroxylase in a clonal pheochromocytoma cell line. 3 87

Initial rate measurements of the stoichiometric relationships between H+ ejection, K+ and Ca2+ uptake, and electron transport were carried out on mitochondria from Ehrlich ascites tumor cells grown in mice. With succinate as substrate and N-ethylmaleimide to prevent interfering H+ reuptake via the phosphate carrier, close to 8 H+ were ejected per oxygen atom reduced (H+/O ejection ratio = 8.0); with the NAD-linked substrates pyruvate or pyruvate + malate, the H+/O ejection ratio was close to 12. The average H+/site ratio (H+ ejected/2e-/energy-conserving site) was thus close to 4. The simultaneous uptake of charge-compensating cations, either K+ (in the presence of valinomycin) or Ca2+, was also measured, yielding average K+/site uptake ratios of very close to 4 and Ca2+/site ratios close to 2. It was also demonstrated that each calcium ion enters the respiring tumor mitochondria carrying two positive electric charges. These stoichiometric data observed in mitochondria from Ehrlich ascites tumor cells thus are in complete agreement with similar data on normal rat liver and rat heart mitochondria and suggest that the H+/site ratio of mitochondrial electron transport may be 4 generally. It was also observed that the rate of deltaH+ back-decay in anaerobic tumor mitochondria following oxygen pulses is some 6- to 8-fold greater than in rat liver mitochondria tested at equal amounts of mitochondrial protein.
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PMID:The proton stoichiometry of electron transport in Ehrlich ascites tumor mitochondria. 3 36

Experiments were done to determine 1) whether the respiratory burst of superoxide anion (O2-) production in polymorphonuclear leukocytes (PMN) is triggered during antibody-dependent killing of tumor cells and 2) whether O2- production is essential for cytotoxicity. Three parameters of the respiratory burst (1-14C-glucose oxidation, oxygen consumption, and O2- release) were increased 2.5- to 7.3-fold during killing of antibody-primed tumor cells by human PMN. Added catalase and superoxide dismutase did not inhibit lysis, possibly because these enzymes were unable to diffuse into the inter-plasma-membrane space between killer and target cells. Evidence for an O2- requirement for cytotoxicity was the fact that concentrations of amobarbital or phenylbutazone sufficient to inhibit the cyanide-insensitive respiration of PMN also inhibited cytotoxicity. Also, hypoxic conditions inhibited cytotoxicity from 29 to 73%. The requirement for oxygen was most likely related to O2- generation and not mitochondrial respiration since cyanide and azide, which inhibit mitochondrial respiration, increased cytotoxicity.
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PMID:Polymorphonuclear leukocyte-mediated, antibody-dependent, cellular cytotoxicity against tumor cells: dependence on oxygen and the respiratory burst. 3 34

In hematoxylin-eosin stained quatorial sections of 14 human bronchial tumors, the relative proportions of different tissue elements were determined in two perpendicular planes, 500 and 200 mu wide, using the target principle. Data characterizing the level of necrotization of these tumors have revealed a poor supply of oxygen and nutritive substances to tumors in which large stroma areas were alternating with large fields of tumor parenchyma. As anticipated, necrotization increases with increasing size of the tumor. A network of narrow stroma strips in the tumor affords a more favourable supply of the cells. The proportions of necrotic, hypoxic and GO areas were calculated.
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PMID:[Possible quantification of vascularization and of non-proliferating, hypoxic and nerotic proportions of lung cancer in man (author's transl)]. 5 Aug 32


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