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

When tested in a poly(U)-dependent polyphenylalanine synthesizing system and in a postnuclear supernatant, both derived from Ehrlich ascites tumor cells, 2'(3'),5'-ADP did not affect chain elongation of polypeptide synthesis. In a cell-free system which was dependent on initiation and programmed by natural mRNA, however, the amino acid incorporating activity was suppressed to about 10% of the control in the presence of 1 mM 2'(3'),5'-ADP. The inhibitor was shown not to interfere with the attachment of poly(U) to the small ribosomal subunit and with the formation of mRNA-80S ribosome complexes in a complete protein synthesizing system. The subsequent attachment of a 40S ribosomal subunit to the mRNA-80S ribosome complex and the formation of polysomes, however, was depressed by the inhibitor. The experimental results suggest that 2',(3'),5'-ADP inhibits initiation-dependent protein synthesis between monosome formation and the formation of the first peptide bond(s).
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PMID:2'(3'),5'-ADP inhibits initiation-dependent protein synthesis in a cell-free system from Ehrlich ascites tumor cells. 56 Jun 26

The addition of glucose to ELD and ELT/B1 mouse ascites tumor cell suspensions caused a 2.3-fold increase in the phosphorylation state ratio, (ATP)/(ADP) (Pi), because of a decrease in the intracellular Pi concentration. The addition of glucose to these cell suspensions has been reported by Chance and Hess ('59) to cause an increase in the study state reduction of cytochrome b and an increase in the steady state oxidation of cytochrome c. On a quantitative basis these two independent measurements suggest that a near equilibrium exists between the oxidation-reduction state of the mitochondrial electron carriers and the reactions of ATP synthesis (as expressed by the phosphorylation state ratio) both before and after glucose addition. We conclude that the mechanism of the inhibition of respiration by glycolysis (the Crabtree effect) is a decrease in the rate of electron transport caused by the mass action effect of the elevated phosphorylation state ratio.
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PMID:On the mechanism of the Crabtree effect in mouse ascites tumor cells. 56 9

A regulatory function of the cell membrane in controlling the cytoplasmic level of Pi has been proposed, and in Ehrlich ascites tumor cells an active influx of primary phosphate has been reported in the literature. In the present study, Ehrlich cells were incubated at 1.5--50 mM extracellular Pi at pH 7.4 (Pi mainly secondary phosphate) and at pH 6.0 (mainly primary phosphate), and the measured cell Pi was compared with the value expected from a passive distribution of Pi. At a low extracellular Pi concentration the cell Pi was 3--6 mumol/g or even more. It is suggested that a major part of this cell Pi can be accounted for by enzymic release of Pi during the sampling procedure. If this interpretation is correct, the present results show that both ionic species of Pi are in electrochemical equilibrium across the cell membrane at steady state. Moreover, in vivo the concentration of free Pi in the cytosol will presumably be maintained at a steady-state level of about 0.4 mM, one order of magnitude below the directly measured values. This implies that the ratio [ATP]/[ADP][Pi] which is important in the regulation of energy metabolism, is higher than reported in the literature.
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PMID:Inorganic phosphate in Ehrlich ascites tumor cells and its distribution across the cell membrane. 56 66

Values of serum and plasma LDH in rats were comparatively studied, and the following results were obtained: 1) The activity of LDH increased in serum with time during clotting, but no changes of LDH activity were found in plasma. 2) When platelet rich plasma (PRP) was recalcified and allowed to clot, LDH-release from platelets with a corresponding increase of serum LDH was observed, but addition of ADP or thrombin to PRP did not have an effect on LDH-release. 3) LDH-release from platelets by calcium was not inhibited by aspirin, and it was influenced by the quality of the test tube. 4) Values of serum and plasma LDH on experimentally induced liver-damaged or kidney-damaged rats and tumor-bearing rats were examined in relation to their tissue damages, revealing that plasma LDH activity represents the condition of a disease better than serum LDH activity.
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PMID:[Comparative studies on lactate dehydrogenase in serum and plasma of rats (author's transl)]. 66 15

Walker 256 carcinoma cells form irreversible aggregates with rat platelets activated by ADP or serotonin. Since serotonin induces platelet shape change but not platelet aggregation the degree of activation indicated by the disc-sphere transformation is sufficient for platelets to interact with these tumor cells. This is confirmed by experiments with spheroid washed platelets which form irreversible mixed aggregates with Walker 256 carcinoma cells without a stimulus being required. This type of tumor cells could react with platelets in vivo, provided the platelets are activated by disturbed blood flow or contact with subendothelium. Our observations can explain why other authors found no interaction between Walker 256 carcinoma cells and non-activated platelets in vitro even though platelets contributed to the formation of bloodborne metastases of this tumor.
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PMID:Aggregation of activated platelets with Walker 256 carcinoma cells. 75 60

Periodate-oxidized inosine (Inox; NSC 118994) and periodate-oxidized 5'-inosinic acid (PI-IMP) were prepared and studied for their effects on ribonucleotide reductase activity in partially purified extracts from Ehrlich tumor cells and on nucleic acid synthesis in intact tumor cells in culture. Ribonucleotide reductase activity in cell-free extracts from Ehrlich tumor cells was inhibited by Inox and PI-IMP. PI-IMP was more inhibitory to the reductase activity than was Inox. Furthermore, the inhibition of ribonucleotide reductase activity by Inox and PI-IMP was greater for cytidine-5'-diphosphate reductase activity than for adenosine-5'-diphosphate reductase activity. The ribonucleotide reductase activity in cell-free extracts prepared from Ehrlich tumor cells treated with Inox or PI-IMP in culture was decreased compared with the activity in the extracts from untreated cells. Incorporation of labeled cytidine into the RNA and DNA of Ehrlich tumor cells in culture was inhibited by both Inox and PI-IMP. The conversion of cytidine to deoxycytidine nucleotides in the acid-soluble pool was likewise inhibited. These data indicate that Inox and PI-IMP inhibit the ribonucleotide reductase step as one of the sites of action of these compounds. However, the inhibition of RNA synthesis indicates that there must be additional sites of action of these nucleoside analogs.
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PMID:Inhibition of ribonucleotide reductase activity and nucleic acid synthesis in tumor cells by the dialdehyde derivatives of inosine (NSC 118994) and inosinic acid. 98 50

1. The regulatory properties of two interconvertible kinetic forms of class A pyruvate kinase from Ehrlich ascites tumor cells have been studied with a partially purified enzyme preparation free of interfering enzymatic activities. 2. The hyperbolic form shows Michaelis-Menten kinetics for P-pyruvate, with high affinity for this substrate and low affinity for the inhibitory amino acids alanine and phenylalanine. The sigmoidal form displays positive cooperativity respect to P-pyruvate (n=1.4), with lower affinity for this substrate and higher affinity for the inhibitory amino acids. 3. The equilibrium between the hyperbolic and the sigmoidal forms of the enzyme is affected by substraetes and effectors. P-pyruvate, ADP and Fru-P2 shift the equilibrium to the hyperbolic form while ATP, alanine and phenylalanine stabilize the sigmoidal form. 4. Effector metabolites affect the molecular weight of the protein, acting on an equilibrium between dimers and tetramers. P-pyruvate and ADP associate the enzyme to a tetramer while ATP, alanine and phenylalanine favor the occurrence as a dimer. The positive modifier Fru-P2 did not associate the enzyme to the tetramer, even at 1 mM concentration. 5. A tentative molecular model for pyruvate kinase A on the basis of the kinetic and aggregation interconversion is proposed.
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PMID:Interconversion phenomena between two kinetic forms of class a pyruvate kinase from Ehrlich ascites tumor cells. 100 94

The effects of cell injury on Ehrlich ascites tumor cell mitochondria were studied using two model injuries: (1) interference with cell membrane function and (2) inhibition of ATP synthesis with specific mitochondrial inhibitors. These studies indicate a good correlation between level of ATP and number of swollen mitochondria and between swollen mitochondria and occurrence of flocculent densities. No correlation existed between total ADP level and percentage of condensed mitochondria if all ADP values were considered, although a biphasic relationship appeared to exist between the number of condensed mitochondria and the levels of ATP. The study suggests a reproducible sequence of mitochondrial events following either inhibition of ATP synthesis or induction of cell membrane permeability with the nonpenetrating, membrane-damaging agent p-chloromercuribenzene sulfonic acid. These include the rapid appearance of condensed mitochondria, the reinflation of these to resemble orthodox mitochondria, and the occurrence of high amplitude swelling followed by flocculent densities or calcification, or both. Calcification did not occur when ATP synthesis was inhibited but did occur when the cell membrane was damaged with p-chloromercuribenzene sulfonic acid. It is suggested that the early mitochondrial condensation is related to loss of ions and water from the mitochondrial inner compartment following inhibition of active accumulation systems. It is furthermore suggested that the appearance of the condensed mitochondrial state can be taken as evidence of the intactness of the mitochondrial respiratory chain. The occurrence of swelling indicates structural changes in the mitochondrial inner membrane which occur following loss of ability for ATP synthesis.
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PMID:Studies on the pathogenesis of cell injury: effects of inhibitors of metabolism and membrane function on the mitochondria of Ehrlich ascites tumor cells. 111 9

In a model system consisting of highly coupled rat liver mitochondria respiring in the presence of substrate, pyruvate kinase, phosphoenolpyruvate, ATP, hexokinase and glucose, the increase in the mitochondrial concentration results in a progressive decrease in the activity of pyruvate kinase. These results are in accord with a role of pyruvate kinase as a determinant of glycolytic activity by competing with mitochondrial oxidative phosphorylation for the available ADP. The addition of adequate amounts of the amino acids, cysteine, alanine and phenylalanine, known as inhibitors of pyruvate kinase, to living Ehrlich ascites tumor cell suspensions results in a stimulation of the respiratory rate and in a decrease of the glycolytic rate of the cells. Concomitant with these changes, there is an accumulation of intracellular phosphoenolpyruvate and ADP, and a decrease in pyruvate and ATP. These results provide additional evidence for paying attention to pyruvate kinase as another key enzyme whose properties and activities may be major determinants for the control of glycolysis and the Crabtree and Pasteur effects of tumor cells.
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PMID:Stimulation of tumor-cell respiration by inhibitors of pyruvate kinase. 117 5

We have investigated the modulation of tumor necrosis factor (TNF)-mediated tumor cell lysis by cAMP. Among a panel of human breast tumor cell lines, MCF7 and MDA MB 231 were shown to be, respectively, sensitive and resistant to TNF-mediated cell lysis in vitro. 125I-labeled TNF-binding experiments demonstrated that both cell lines bind TNF, indicating that the differential sensitivity to TNF was not related to TNF receptor expression. To study the relationship between TNF-mediated cell lysis and cAMP accumulation, cAMP measurement was performed following TNF treatment. Our data show that TNF alone did not induce an enhancement of intracellular cAMP accumulation either in the TNF-sensitive or in the TNF-resistant cell line. Experiments in which cells were exposed to forskolin revealed that this cAMP elevating drug was efficient in enhancing the sensitivity to TNF of MCF7 cell line. This potentiating effect of forskolin was maximal for suboptimal concentrations of TNF (10 ng/ml), reaching up to 100% when forskolin was added at 100 microM. However, co-stimulating with forskolin of either MDA MB 231 or a TNF-resistant MCF7 clone (MCF7-R-A1) did not induce any reversal of resistance to TNF. We further assessed the interaction of TNF with transmembrane signalling and the possible involvement of guanine nucleotide-binding proteins (G-proteins). Bacterial toxin-catalyzed ADP ribosylation of MCF7 and MDA MB 231 membranes was, therefore, performed. Using cholera toxin, we demonstrate that TNF treatment did not quantitatively alter the activity of stimulatory G-proteins either in MCF7 or MDA MB 231 cell line. In contrast, pertussis toxin-catalyzed ADP ribosylation experiments suggest a functional coupling of TNF receptors to a 40-kDa pertussis toxin-sensitive G-protein in the TNF-sensitive MCF78 cell line but not in the TNF-resistant MDA MB 231 cell line. Taken together, these data indicate that cAMP might play a role in TNF-mediated cell lysis and are in support of the involvement of a pertussis toxin-sensitive G-protein in TNF-mediated MCF7 cells lysis.
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PMID:Tumor necrosis factor-mediated cell lysis in vitro: relationship to cAMP accumulation and guanine nucleotide-binding proteins. 131 37


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