Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of 14C-lysine by leukaemic cells in acute myeloblastic, myelomonocytic, lymphoblastic and chronic myeloid leukaemia with blast crisis was studied. The investigations included lysine metabolism to CO2, lipids, organic acids and nucleotides and its incorporation into cellular proteins. The obtained results were compared with determinations carried out in granulocytes and lymphocytes of healthy subjects. Cells in acute leukaemias metabolized 14C-lysine in a similar range. In relation to normal cells the range of lysine metabolism to lipids in the leukaemic cells was significantly higher (p less than 0.01), while that of organic acids was significantly lower (p less than 0.05). The activity of 14C-lysine metabolism depended on the number of blast cells in the sample and the type of acute leukaemia. Neoplastic cells in blast crisis and in acute myeloblastic leukaemia incorporated more actively 14C-lysine into proteins than cells in acute myelomonocytic and acute lymphoblastic leukaemia (p less than 0.05). Similar differences in lysine metabolism were observed between myelomonocytes and blast cells from acute lymphoblastic leukaemia (p less than 0.05).
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PMID:[Lysine metabolism in acute leukemia]. 29 72

L1210 murine leukemia cells grow in an ascites plasma that contains lipids, including 0.62 +/- 0.046 (S.E.) MICRONEq free fatty acid per ml. in vitro incubations demonstrated that isolated L1210 cells readily utilize free fatty acid that is added to the incubation medium. When the cells were incubated with albumin-bound [1-14C]palmitate, about 12 times more radioactivity was incorporated into cell lipids than was oxidized to CO2. Triacylglycerols contained 1.5 to 4 times more radioactivity than phospholipids, and from 48 to 69% of the phospholipid radioactivity was recovered in the choline phosphoglycerides. [1-14C]Palmitate utilization increased as the fatty acid concentration of the medium was raised, the largest increase occurring in the triacylglycerol fraction. Palmitate utilization also was increased by the presence of carbohydrates in the medium, their effectiveness (in descending order) being glucose, mannose, galactose, fructose, and glycerol. By contrast, ribose did not produce any stimulatory effect. During a 1-hr incubation, between 82 and 87% of the [1-14C]palmitate that was taken up remained as palmitic acid. From 8 to 15% was elongated to stearate, and only 2 to 3% was desaturated to palmitoleate and oleate. Based upon the lipid content, growth rate, and palmitate utilization rate of the cells, it appears that a major portion of the lipid requirements of the L1210 cell may be supplied by the fatty acid contained in the ascites plasma. In addition, our results suggest that most of the saturated fatty acid taken up is incorporated into cell lipids without structural modification.
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PMID:Fatty acid utilization by L1210 murine leukemia cells. 55 21

P388 (murine) and CEM (human) leukemia cells were exposed in vitro to a serine-deprived medium. Cultivation was carried out at 37 degrees C, 5% CO2. Proliferation assay was conducted with a RPMI 1640 medium (control) and a serine-deprived medium for 3 days. The deprivation of serine reduced the proliferation of both cells, and the necessity of serine for the cell proliferation was thus recognized. The effects of the substance on the level and pattern of intracellular amino acids were observed. P388 cells exposed to serine-deprived medium for 3 h were then transferred to the control medium. The cellular amino acid levels were determined at the time of medium change and 1, 2, 3 h thereafter. Serine-deprivation improved intracellular amino acids in comparison with those from control, and the medium change to control reduced their levels. Therefore, extracellular serine appeared to regulate the efflux of amino acids from cells. This suggests that serine-deprivation may be useful for anticancer drug retention in the cells.
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PMID:Stimulation of amino acid efflux from cells by extracellular serine. 134 49

Triptolide (Tri) is a diterpenoid triepoxide isolated from Tripterygium wilfordii Hook F. The effects of Tri on the colony formation of breast cancer cell lines MCF-7 and BT-20, stomach cancer cell lines MKN-45, MKN-7, and KATO-III, and promyelocytic leukemia cell line HL-60 were reported. Using Hamburger-Salmon's double layer agar technique with certain modifications, cancer cells were cultured in 0.3% agar in a highly humidified atmosphere of 5% CO2 at 37 degrees C for 14-21 d. Colonies were counted on d 14 (occasionally d 21) with the colony analyzer system CA-7A. Of the 5 solid tumor cell lines tested, 4 showed diminished colony formation in soft agar by greater than 70% of control value in Tri 10(-8) mol.L-1 (continuous exposure). The magnitudes of the inhibitory effect of Tri on most breast and stomach cancer cell lines were similar to that on the leukemia cell line HL-60. IC50 were 0.504-1.22 micrograms.L-1. The clinically achievable peak plasma concentration (PPC) of Tri was estimated as 0.15 mg.L-1, being 72-126 times higher than the IC70 of the cancer cell lines except KATO-III. The results suggest that Tri might have a potential therapeutic effect on some types of solid tumors, e.g., breast and stomach cancers.
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PMID:Inhibitory effect of triptolide on colony formation of breast and stomach cancer cell lines. 181 94

The PO2 measured in a sample of blood can be misleadingly low, owing to consumption of oxygen in vitro in patients with leukemia. The purpose of this study was to determine whether a rise in PCO2 in such blood could be a useful indication of consumption of oxygen in vitro. Because of the non-bocarbonate buffer capacity of blood and the carriage of CO2, mainly as bicarbonate, we reasoned that the rise in PCO2 would be too small to be helpful. Hence the quantitative relationship between the consumption of oxygen and the production of CO2 in blood was determined. Other reactions yielding CO2 (the titration of lactic acid) were monitored. Consumption of oxygen was stimulated in blood of normals in vitro by adding methylene blue (100 mumol/L); in addition, blood from four patients with leukemia was studied without additions. The rate of consumption of oxygen at 22 degrees C was linear over 60 min; the respiratory quotient was close to unity. The rise in PCO2 was small even when the fall in PO2 was 60 mmHg. We conclude that a rise in PCO2 is not a reliable way to diagnose consumption of oxygen in blood in vitro as patients may hyperventilate, making it very difficult to recognize a small rise in PCO2.
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PMID:Can oxygen consumption in blood in vitro be detected by a change in PCO2? 190 1

A eukaryotic growth medium (Program Development Research Group Basal Growth Medium) was developed for CO2-independent maintenance and propagation of human and nonhuman tumor cell lines representing diverse histologies (e.g., cancers of the brain, colon, lung, ovary, and kidney, as well as leukemia and melanoma). It was also shown to be suitable for the maintenance and propagation of nontumor cells of human and nonhuman derivation. The medium derives its buffering capacity primarily from beta-glycerophosphate, exhibits a stable physiologic pH of 7.3-7.4, and is optimized to facilitate growth in atmospheric CO2. It is also useful in cellular growth and cytotoxicity assays based on either the metabolic reduction of tetrazolium reagents or protein staining. The 50% inhibitory concentration values obtained with carmustine, doxorubicin, and tamoxifen in cell lines maintained in the new medium under atmospheric CO2 were closely comparable to those obtained with these drugs against cells maintained in RPMI-1640 under a 5% CO2 environment.
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PMID:New carbon dioxide-independent basal growth medium for culture of diverse tumor and nontumor cells of human and nonhuman origin. 211

NaHCO3 activated the folylpolyglutamate synthetase (FPGS) from rat liver and the human leukemia cell lines K562 and CCRF-CEM by 1.7- to 2.0-fold. Optimal activation was achieved by 10 mM NaHCO3 in all cases; NaCl, sodium formate, sodium acetate, NaN3, and Na2SO3 at 10 mM did not cause activation. Activation could be masked if assay solutions which had extensively absorbed atmospheric CO2 were used. Activation of the human CCRF-CEM FPGS was examined in detail. Km and Vmax values for pteroyl substrates (aminopterin or methotrexate) and L-glutamate increased proportionally in the presence of NaHCO3; there was thus no apparent change in the catalytic efficiency (Vmax/Km) of the FPGS reaction with these substrates. However, NaHCO3 increased the efficiency of the reaction with respect to ATP by decreasing its apparent Km while increasing the Vmax of the reaction. NaHCO3 also activated FPGS activity when folic acid, dihydrofolic acid and tetrahydrofolic acid were substrates. The relative distribution of products synthesized from methotrexate or tetrahydrofolate by FPGS was not altered by addition of NaHCO3. The potency of 5,8-dideazapteroylornithine, an FPGS-specific inhibitor, was not changed by the presence of NaHCO3 (IC50 = 0.4 microM). These results suggest that FPGS activity with folates and classical antifolates may be activated at physiological concentrations of NaHCO3. In addition, inadvertent contamination of assay solutions with bicarbonate from atmospheric CO2 may cause artifacts in the determination of activity levels and kinetic constants of FPGS.
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PMID:Activation of mammalian folylpolyglutamate synthetase by sodium bicarbonate. 216 55

Acute lymphatic leukemia (ALL) represents one of the most frequent malignancies in childhood. Central venous access ports or partly implanted silicone catheters are usually placed for high-dose chemotherapy in these children. We report two patients aged 7 and 3 years with acute lymphoblastic beta-cell leukemia (B-ALL), a less common subtype of ALL, which presented with hyperthermia (38.4 degrees C and 39 degrees C) during anesthesia with isoflurane for implantation of a central venous catheter. The hyperthermic reactions were accompanied by an increase in expired CO2 and acidosis as well as moderate elevation of heart rate and blood pressure. As in both patients the history and preoperative findings did not reveal signs of infection or other causes of fever, the observed alterations were interpreted as symptoms of malignant hyperthermia triggered either by succinylcholine or isoflurane, which were used in both children. In addition, the hyperthermia responded to administration of dantrolene sodium according to dose recommendations for treatment of malignant hyperthermia. In one of the patients, withdrawal of dantrolene during the initial postoperative hours was followed by a recurrent increase in body temperature, which once again could be suppressed by additional dantrolene infusion. According to the literature, malignant hyperthermia has occasionally been described in children with malignancies such as leukemia or Burkitt's lymphoma. Our observations indicate that children with B-ALL may be especially susceptible to malignant hyperthermia. Close monitoring of body temperature and expiratory CO2 are therefore indicated in these children, and dantrolene therapy should be started immediately in case of increased temperature during anesthesia.
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PMID:[Hyperthermic reaction in the perioperative phase in 2 children with acute lymphoblastic leukemia of B-cell type]. 292 70

Proliferation and differentiation are inversely related in many cell culture systems. The study of inducible systems is facilitated by optimal growth conditions in order that whatever differentiation is observed may be attributed to a specific effect of the inducer, rather than to a nonspecific effect of adverse growth conditions. To investigate the role of CO2 supply in an inducible system, the K562 human leukemia cell line inducible for hemoglobin synthesis was studied at 10%, 5% and 1.5% CO2 concentrations. The lower the CO2 concentration, the higher the percentage of benzidine-positive cells but the slower the growth rate. This increase in benzidine positivity reflected hemoglobin synthesis as indicated by incorporation of 3H-leucine into globin chains. If, in addition to reducing CO2 concentration, the complete medium was replaced by a bicarbonate-free medium, the percentage of benzidine-positive cells was further increased and growth further slowed. However, if endogenously produced CO2 was retained by sealing the culture vessel, these effects were mitigated. Since addition of ribosides blocked these effects, the mechanism for these effects appears to be inhibition of riboside biosynthesis due to the depletion of CO2 as a substrate. The implication of this work is that, for reproducibility in studies of inducible systems in which reduction of proliferation may itself increase the probability of differentiation, the CO2 tension, the bicarbonate concentration in the medium and the rate of egress of endogenously produced CO2 must be kept constant.
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PMID:Induction of hemoglobin synthesis in K562 cells by carbon dioxide deficiency. 310 85

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara-C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts greater than 70, were treated in an in vitro primary suspension culture with retinoic acid (10(-7) M), cytosine arabinoside (100 ng/ml) or both in combination. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA-LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37 degrees C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.
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PMID:Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells. 342 32


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