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 organelle pathology of neutrophils in chronic granulocytic leukaemia (CGL) was investigated by analytical subcellular fractionation. There were minor reductions in activity of some granule enzymes with an abnormal distribution in sucrose density gradients of the specific granules. There was a marked reduction of 5'-nucleotidase activity but this is probably related to the relative reduction of the mononuclear cell contamination of the neutrophils isolated from leukaemic patients compared with controls. Another plasma membrane enzyme, NADH-nitroblue tetrazolium reductase, which has a microbicidal role, had increased activity. Neutrophils from patients with CGL had 13% the alkaline phosphatase activity of controls and were compared with neutrophils from women in the third trimester of pregnancy when the activity was increased to 8 times the control level. The latent activity, per cent inhibition by Levamisole, kinetic constants and subcellular distribution of alkaline phosphatase were similar in the three groups. It is suggested that the properties and intracellular localization of alkaline phosphatase are normal in CGL and that there is a quantitative lack of enzyme.
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PMID:Studies on the subcellular organelles of neutrophils in chronic granulocytic leukaemia with special reference to alkaline phosphatase. 28 20

The activity of some of the clinically important enzymes was investigated in leukemic sera at 37 degrees, using the Beckman Enzyme Activity Analyzer were found to be slightly elevated in some untreated cases of leukemia (1.), while ALP was found to be frequently elevated. Untreated patients with l. had normal or below normal SCPK activity. The most characteristic and significant rise in activity, was found to be associated with SLDH and SHBDH in most cases of acute l. (86%) and in CML, while any elevation observed in CLL, was very slight. The general kinetic parameters of SLDH and SHBDH, were investigated at 37 degrees in acute leukemic patients. These included optimum substrate concentrations (NADH, pyruvate, and 2-oxobutyrate), the rate of pyruvate and 2-oxobutyrate reduction, substrate-velocity relationship, Km (pyruvate), Km (NADH), Km (2-oxobutyrate) as well as the effect of temperature and pH on the kinetics of the reaction. These kinetic characteristics were found to be differently affected by the leukemic process.
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PMID:Kinetics of lactate dehydrogenase and other enzyme studies in human serum in leukemia. 29 68

MTT reduction is usually analysed by colorimetric assay to study mitochondrial dehydrogenase activity as a test of cytotoxicity. This enzymatic reaction produces dark-blue granules of formazan, which increase cell refringency. In this work, we define the conditions for MTT use in quantitative flow cytometric analysis. MTT reduction provides a non-fluorescent dye usable by this technique to study an intracellular NADH-dependent dehydrogenase activity in vital cells. We observe that formazan production increases asymptotically with cell concentration and that this temperature-dependent Michaelis enzymatic reduction is produced essentially by mitochondrial dehydrogenases. In isolated mitochondria from rat hepatocytes and in whole L1210 murine leukemia cells, the Michaelis constants (KM) observed in the presence of respiratory substrates were, respectively, 10 microM and 500 microM. The inhibition of mitochondrial protein synthesis by chloramphenicol, which induces a rise of MTT reduction due to the correlative stimulation of glycolysis (Pasteur effect), is a limit of the MTT assay as a cytotoxicity test.
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PMID:NADH-dependent dehydrogenase activity estimation by flow cytometric analysis of 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. 163 32

In order to synthesize bifunctional antitumor compounds, the interactions of adriamycin with metallocene dichlorides, Cp2MCl2, where M = Zr, Ti, V, have been studied. Using absorption, fluorescence, and circular dichroism measurements, we have shown that adriamycin is able to coordinate to the three metal ions. The interaction of Cp2ZrCl2 and Cp2VCl2 with adriamycin leads to compounds of 1:2 metal:drug stoichiometry, whereas the interaction of Cp2TiCl2 with adriamycin leads to two types of compounds of 1:2 and 1:1 stoichiometry. The Zr-adriamycin complex, which is unable to dissociate, even at a pH lower than 1, does not display antitumor activity against P-388 leukemia. However Ti-adriamycin complexes, which are more susceptible to dissociation in acidic media, exhibit antitumor activity that compares with that of the free drug. These complexes, unlike adriamycin, do not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. In addition, the presence of metal ions promote the binding of the drug to DNA and erythrocyte ghosts.
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PMID:Bifunctional antitumor compounds: interaction of adriamycin with metallocene dichlorides. 253 37

Tiazofurin through its active metabolite thiazole-4-carboxamide adenine dinucleotide (TAD) inhibits IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis. IMP dehydrogenase activity in human leukemic cell extracts (33.4 +/- 0.1 nmol/h/mg protein) was increased 11-fold compared to normal leukocytes (3.1 +/- 0.5). Km values for IMP and NAD+ of leukemic IMP dehydrogenase were 22.7 and 44.0 microM, respectively. XMP inhibited competitively with IMP and noncompetitively with NAD+. NADH exerted mixed type inhibition with respect to both IMP and NAD+. The inhibitory pattern of TAD was quite similar to that of NADH; however, the affinity of TAD to leukemic IMP dehydrogenase (Ki = 0.1 microM) was three orders of magnitude higher than the natural product NADH (Ki = 150 microM). These results contribute to an understanding of the mechanism of action of tiazofurin in the treatment of leukemia.
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PMID:IMP dehydrogenase: inhibition by the anti-leukemic drug, tiazofurin. 256 51

In order to synthesize bifunctional antitumor compounds, the interaction of streptonigrin with [AuCl4]- has been studied. Using absorption, circular dichroism, and fluorescence measurements, we have shown that streptonigrin forms with Au(III) a 1:1 Au(III)-streptonigrin complex. This complex is very stable as long as gold is in the trivalent state and is able to inhibit glutathione reductase activity. In the presence of biological agents such as NADH and reduced glutathione, Au(III) is slowly reduced to Au(I) and removed from its binding site to streptonigrin. Original streptonigrin is thus recovered. This complex exhibits antitumor activity against P-388 leukemia which compares with that of the free drug.
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PMID:Bifunctional antitumor compounds: synthesis and characterization of a Au(III)-streptonigrin complex with thiol-modulating properties. 273 77

Tiazofurin, an anti-cancer drug, which induces remissions in human leukemia, and ribavirin, an anti-viral agent, bind at separate sites (NADH and IMP-XMP sites, respectively) on the target enzyme, IMP dehydrogenase. Now we show that the binding to IMP dehydrogenase of these drugs at two separate sites is translated into synergistic inhibition of de novo guanylate biosynthesis and synergistic toxicity in rat hepatoma 3924A cells. These results may be utilized in the chemotherapy of neoplastic diseases and in the treatment of hepatitis virus infection and hepatocellular carcinoma.
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PMID:Synergistic cytotoxic effect of tiazofurin and ribavirin in hepatoma cells. 289 52

Fe(III) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric and spectroscopic measurements, we have shown that adriamycin and daunorubicin form two well-defined species with Fe(III), which can be formulated as respectively Fe(HAd)3 and Fe(HDr)3. In these formulas, HAd and HDr stand for adriamycin and daunorubicin in which the 1,4-dihydroxy-anthraquinone moiety is half-deprotonated. Both complexes are six-membered chelates. The stability constant is beta = (2.5 +/- 0.5) X 10(28) for both complexes. Interaction with DNA has been studied showing that, despite strong coordination to Fe(III), anthracyclines are able to intercalate between DNA bases pairs, releasing the metal. These complexes display antitumor activity against P 388 leukemia that compares with that of the free drug. Fe(HAd)3, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. Moreover, it is shown that the triferric adriamycin compound so called "quelamycin" is in fact a mixture of Fe(HAd)3 and polymeric ferric hydroxide.
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PMID:Iron(III)-adriamycin and Iron(III)-daunorubicin complexes: physicochemical characteristics, interaction with DNA, and antitumor activity. 298 53

Fe(III) complex of an antitumoral antibiotic carminomycin has been studied. Using potentiometric and spectroscopic measurements we have shown that carminomycin forms with Fe(III) a well-defined species in which three molecules of drug are chelated to one Fe(III) ion. This occurs with the release of one proton per molecule of drug. Magnetic susceptibility measurements suggest that six oxygen atoms are bound to iron. The stability constant is 3 X 10(34). The in vitro inhibition of P 388 leukemia cell growth by this complex compares with that of the free drug. This complex, unlike the free drug, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase.
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PMID:Physicochemical studies of the iron(III)-carminomycin complex and evidence of the lack of stimulated superoxide production by NADH dehydrogenase. 298 12

The adenine nucleotide profiles (AMP, ATP, NAD and NADH2) of peripheral blood lymphocytes isolated from patients with common variable hypogammaglobulinaemia (CVH) were similar to those in control cells. AMP and ATP levels were also similar in the lymphocytes of patients with chronic lymphatic leukaemia (CLL). Since CVH and CLL patients have reduced activity of plasma membrane ecto-5'-nucleotidase, our data suggests that this enzyme does not regulate the levels of intracellular adenine nucleotides, at least in "resting" cells.
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PMID:Adenine nucleotide concentrations in peripheral blood lymphocytes from patients with common variable hypogammaglobulinaemia and B-cell chronic lymphatic leukaemia. 318 62


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