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)

This paper describes the first phase of the development of a Protocol based Decision Support System (PDSS) that will be linked to an Electronic Patient Record system (EPR system). The protocol system will be pro-active: the physician will be automatically prompted from the EPR of a particular patient if the protocol that applies for that patient defines it necessary. The PropeR project studies the impact of a PDSS that is linked to an EPR on daily care processes. There are two areas of research: hospital and home care. This paper describes the application in the hospital. The protocol that is being computerized is a treatment protocol for Acute Myelogenous Leukaemia (AML) that also studies treatment alternatives (conventional versus experimental treatment). This paper based AML protocol has been translated into a formal representation. The KA-tool Gaston is used to make this representation. Twenty-eight subprotocols have been organized in a hierarchical structure with three levels. One of the aims of the project is to make a representation of the AML protocol that can be used in other organizations as well. The main problem we encountered is that the representation not only contains the content of the protocol, but also aspects of application of that protocol in daily care of the hospital and aspects of support. The solution to this problem is the creation of two layers of representation: the first layer is an exact copy of the protocol and thus sharable and the second layer focuses on the support of the protocol in the daily working processes and is mainly domain specific: for the University Hospital Maastricht. At the moment, this division into two layers is being discussed.
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PMID:The PropeR way to support medical doctors in daily practice. Developing the protocol based DSS. 1466 10

Acetaminophen, a common analgesic and antipyretic drug, is frequently administered to individuals undergoing anthracycline chemotherapy. Here, the effect of acetaminophen on the metabolism of daunorubicin and doxorubicin by isolated enzymes lactoperoxidase and myeloperoxidase, and by myeloperoxidase-containing human leukemia HL-60 cells was investigated using spectrophotometric and EPR techniques. We report that at pharmacological concentrations acetaminophen strongly stimulates oxidation of the anthracyclines by lactoperoxidase and myeloperoxidase systems, which results in irreversibly altered (colorless) products. The initial rate and efficacy of daunorubicin oxidation depends on pH. While at pH approximately 7 the oxidation is rapid and extensive, almost no oxidation occurs at pH approximately 5. In the absence of daunorubicin, oxidation of acetaminophen by lactoperoxidase/hydrogen peroxide is only weakly dependent on pH, however, at pH 7.4 it strongly depends on [daunorubicin]. Ascorbate and reduced glutathione strongly inhibited oxidation of anthracyclines by lactoperoxidase and HL-60 systems. Using EPR, a daunorubicin-derived radical was detected in a daunorubicin/acetaminophen/peroxidase/hydrogen peroxide system as a narrow single line (0.175 mT) with g = 2.0047. When daunorubicin was omitted, only an acetaminophen-melanin EPR signal was detected (g = 2.0043, line width approximately 0.5 mT). Similar results were obtained with doxorubicin. We suggest that the stimulation by acetaminophen is primarily due to its preferential oxidation by peroxidases to the corresponding phenoxyl radical, which subsequently reacts with daunorubicin (doxorubicin). Because biological properties of oxidatively transformed anthracyclines will certainly be different from those of their parent compounds, the possible acetaminophen-enhanced degradation of the anthracyclines in vivo is likely to interfere with anticancer and/or cardiotoxic activities of these agents.
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PMID:Acetaminophen stimulates the peroxidative metabolism of anthracyclines. 1517 84

The neutral mononuclear copper complex with the quinolone antibacterial drug N-propyl-protected norfloxacin, Hpr-norfloxacin, in the presence of the nitrogen donor heterocyclic ligand 2,2'-bipyridine has been prepared and characterized. The crystal structure of (chloro)(2,2'-bipyridine)(pr-norfloxacinato)copper(II), 1, has been determined and refined with X-ray crystallography. X-band electron paramagnetic resonance (=EPR) spectroscopy at liquid helium temperatures from powdered samples indicates the presence of dimeric units in consistency with the crystal structure. In aqueous solutions of 1 the EPR behavior indicates mixture of dimeric and monomeric species. The antimicrobial activity of the complex has been tested on three different microorganisms and the best inhibition (MIC=0.25mugmL(-1)) has been exhibited against Escherichia coli. The study of the interaction of the complex with calf-thymus DNA has been performed with diverse spectroscopic techniques and has shown that complex 1 is bound to calf-thymus DNA by the intercalative mode. Potential anticancer cytostatic and cytotoxic effects of complex 1 on human promyelocytic leukemia HL-60 and human chronic myelogenous leukemia K562 cell lines have been investigated. Complex 1 shows an increased antiproliferative and necrotic effect on both HL-60 and K562 human leukemia cells in comparison to the free pr-norfloxacin.
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PMID:Structure and biological properties of the copper(II) complex with the quinolone antibacterial drug N-propyl-norfloxacin and 2,2'-bipyridine. 1702 85

In the Moloney murine leukemia virus (MoMuLV) envelope glycoprotein (Env) we identified a membrane-proximal cytoplasmic domain (residues 598-616) that facilitates the Env incorporation into virions and Env-mediated fusion [Rozenberg, Y., Conner, J., Aguilar-Carreno, H., Chakraborti, S., Dimiter, D.S., Anderson, W.F., 2008. Viral entry: membrane-proximal cytoplasmic domain of MoMuLV envelope tail facilitates fusion. In the same issue. (accompanying paper)]. By biophysical methods (CD, EPR) a corresponding peptide (membrane-proximal peptide, 598-616) was demonstrated to form a membrane-parallel amphiphilic alpha-helix in the presence of membranes. Electrophysiological studies with planar bilayers and liposomes indicate that the membrane-proximal peptide is membrane destabilizing. This peptide and the fusion peptide from the MoMuLV transmembrane (TM) ectodomain were tested for their effect on the bilayer for hexagonal phase transition temperature of dipalmitoleoylphosphatidylethanolamine (T(H)). Importantly, the external fusion peptide and the internal membrane-proximal peptides of MoMuLV env exert opposite effects on membrane curvature. The fusion peptide lowers T(H) while the membrane proximal peptide raises it. These effects on T(H) correlate with the ability of these peptides to induce lipid mixing in large unilamellar vesicles composed of dioleoylphosphatidylethanolamine: dioleoylphosphatidylcholine:cholesterol (1:1:1 mol). When added externally to preformed liposomes, the N-terminal fusion peptide promotes lipid mixing while the cytoplasmic membrane-proximal peptide inhibits this effect. These finding indicate a possible mechanism by which the membrane-proximal domain in MoMuLV Env may affect the formation of membrane fusion intermediates.
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PMID:Membrane activity of an amphiphilic alpha-helical membrane-proximal cytoplasmic domain of the MoMuLV envelope glycoprotein. 1820 41

Three novel stable Pt(III) complexes with distorted octahedral structure and (dz2)1 ground state have been obtained in the course of Pt(II)-hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) interaction in alkaline aqueous medium and aerobic conditions. A redox interaction also takes place together with the complexation process leading to the formation of Pt(III) species and organic radicals. The processes in the reaction system and the structure of the complexes formed cis-[Pt(III)(NH3)2(Hp-3H)(H2O)2]H2O1, [Pt(III)(Hp-3H)(H2O)2]H2O2, and [Pt((O,O)Hp-2H)Cl(H2O)3] 3, were studied by UV-Vis, IR, EPR and XPS spectra, thermal (TGS, DSC), potentiometric and magnetic methods. The newly synthesized complexes show promising cytotoxic activity comparable with that of cis-platin in in vitro tests against a panel of human leukemia cell lines. The observed cytotoxicity of the complex 2 against SKW-3 cells (KE-37 derivative) is due to induction of cell death through apoptosis.
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PMID:Synthesis, Structural Characterization, and Cytotoxic Activity of Novel Paramagnetic Platinum Hematoporphyrin IX Complexes: Potent Antitumor Agents. 1830 70

We studied the antitumor properties of the dinuclear copper(II) complex of l-carnitine [Cu 2( l-carnitine) 2Cl 2(H 2O) 2]Cl 2, as well as those of l-carnitine and copper chloride dihydrate, in human leukemic cells. The complex was synthesized and characterized using EPR, (1)H NMR, (13)C NMR, IR, and UV-vis analyses. Its cytotoxic effect on the human leukemia cell lines HL-60 and K562 was studied by assessing the metabolic activity of cells (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT method), the structural integrity of cell membrane using Trypan blue assay, and the proliferation capacity of cells studying growth curves. Both leukemia cell lines showed a concentration-specific increased cytotoxicity of the complex, compared to l-carnitine or copper chloride dihydrate, with distinct underlying mechanisms, which were decreased proliferation efficiency for HL-60 cells and increased necrotic phenomena for K562 cells. Our results are indicative of a concentration-specific enhanced antileukemic effect of the complex, implying its value as a tool in the implementation of leukemia.
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PMID:Enhanced concentration-dependent cytotoxic effect of the dinuclear copper(II) complex of L-carnitine [Cu2(L-carnitine)2Cl2(H2O)2]Cl2, compared to L-carnitine or copper chloride dihydrate, in human leukemic cell lines. 1852 42

In the search for new metal-based drugs for the treatment of tumoral and parasitic diseases a vanadyl complex, [V(IV)O(SO(4))(H2O)(2)(dppz)].2H(2)O, that includes the bidentate polypyridyl DNA intercalator dipyrido[3,2-a:2',3'-c]phenazine (dppz), was synthesized, characterized by a combination of techniques, and in vitro evaluated on the human acute promyelocytic leukemia cell line HL-60 and against Dm28c strain epimastigotes of the parasite Trypanosoma cruzi, causative agent of Chagas' disease. EPR spectroscopy suggests a distorted octahedral geometry for the complex with the dppz ligand acting as bidentate, binding through both nitrogen donor atoms in an axial-equatorial mode. An oxo group, two water molecules and a sulphate donor occupy the remainder coordination positions. The complex, as well as the anti-trypanosomal reference drug Nifurtimox, showed IC(50) values in the muM range against T. cruzi Dm28c strain. In addition the complex exhibited excellent in vitro anti-tumor activity against leukemia (HL-60 cell line) comparable to that of cisplatin, inducing cell death by apoptosis with IC(50) values in the micromolar range. Data from gel electrophoresis and atomic force microscopy indicate that the complex interacts with DNA, suggesting that its mechanism of action may include DNA as a target. EPR and (51)V NMR experiments were also carried out with aged aerated solutions of the complex to get insight into the stability of the complex in solution and the species responsible for the in vitro activities observed.
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PMID:A novel vanadyl complex with a polypyridyl DNA intercalator as ligand: a potential anti-protozoa and anti-tumor agent. 1969 8

The paper presents the synthesis of complex combinations of Cu(II), V(IV) and Ni(II) with Schiff bases obtained through the condensation of 4-amino-1,5-dimethyl-2-phenyl-1H-3-pyrazol-3(2H)-one (antipyrine) with 2-hydroxybenzaldehyde, 4-hydroxy-5-methoxyisophthalaldehyde and 4,5-dihydroxyisophalaldehyde respectively. The characterization of newly formed complexes was done by (1)H NMR, (13)C NMR, UV-VIS, IR, EPR spectroscopies and molar electric conductibility studies. The effect of these complexes on proliferation of human leukemia cells (HL-60) and their antibacterial activity against Staphylococcus aureus var. Oxford 6538, Escherichia coli ATCC 10536 and Candida albicans ATCC 10231strains were studied and compared with those of free ligands.
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PMID:Metal-based biologically active agents: Synthesis, characterization, antibacterial and antileukemia activity evaluation of Cu(II), V(IV) and Ni(II) complexes with antipyrine-derived compounds. 1994 98

The present study demonstrates photoinduced generation of superoxide radical anion and singlet oxygen upon UVA irradiation of ethyl 1,4-dihydro-8-nitro-4-oxoquinoline-3-carboxylate (DNQC), and its cytotoxic/phototoxic effects on murine leukemia L1210 cells. The formation of reactive oxygen species (ROS) was investigated by EPR spectroscopy using in situ spin trapping technique and 4-hydroxy-2,2,6,6-piperidine (TMP) for singlet oxygen ((1)O(2)) detection. The EPR spectra monitored upon photoexcitation of aerated solutions of DNQC in dimethylsulfoxide evidenced the efficient activation of molecular oxygen via Types I and II mechanisms. The cytotoxic/phototoxic effects of DNQC, analysis of cell cycle, induction of apoptosis/necrosis, DNA damage and molecular mechanism of apoptotic death of L1210 cells in dark and in the presence of UVA irradiation were compared. DNQC induced a different cytotoxic/phototoxic effect, which was concentration- and time-dependent. The four highest tested concentrations of non-photoactivated and photoactivated DNQC induced immediate cytotoxic/phototoxic effect after 24h cultivation of L1210 cells. This effect decreased with the time of treatment. The irradiation increased the sensitivity of leukemia cell line on DNQC, but the cell sensitivity decreased with time of processing. Quinolone derivative DNQC significantly induced direct DNA strand breaks in L1210 cells, which were increased with the irradiation of cells. The DNA damage generated by DNQC alone/with combination of UVA irradiation induced cell arrest in G(0)/G(1) and G(2)/M phases, decrease in the number of L1210 cells in Sphase and apoptotic cell death of certain part of cell population after 24 h of influence. DNQC alone/with combination of UVA irradiation induced apoptosis in L1210 cells through ROS-dependent mitochondrial pathway.
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PMID:Photochemical and phototoxic properties of ethyl 1,4-dihydro-8-nitro-4-oxoquinoline-3-carboxylate, a new quinoline derivative. 2096 43

Five 2,6-substituted 4-anilinoquinazolines were evaluated for their ability to generate superoxide radical anion and singlet oxygen upon UVA irradiation and to induce cytotoxic/phototoxic effects on cancer cell lines L1210, HeLa and HT-29. The formation of radical intermediates, especially reactive oxygen species, upon UVA photoexcitation of the studied derivatives was monitored by indirect techniques of EPR spectroscopy. For all 4-anilinoquinazolines the photoinduced generation of superoxide radical anion was evidenced using spin trapping agent 5,5-dimethyl-1-pyrroline N-oxide, and the presence of (1)O2 was detected by the oxidation of 4-hydroxy-2,2,6,6-tetramethylpiperidine to the paramagnetic species 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxyl. The confirmed photoinduced activation of molecular oxygen via both Type I and Type II photooxidation mechanisms indicates potential phototoxic responses in cells. Biological results showed that derivatives I-V initiated different cytotoxic/phototoxic effects dependent on their concentration, time of treatment and the character of the cell line. UVA irradiation increased the cytotoxic activity of all tested 4-anilinoquinazoline derivatives. The highest cytotoxicity/phototoxicity on all tested cancer cells was induced by N,2-diphenyl-quinazolin-4-amine (derivative III). This most effective derivative emerged as the potent photosensitizer, which possesses a significant antiproliferative activity and DNA damage in L1210 cells increased by UVA irradiation. In addition derivative III induced programmed cell death in leukemia cells through mitochondrial/caspase 9/caspase 3-dependent pathway.
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PMID:UVA-induced effects of 2,6-disubstituted 4-anilinoquinazolines on cancer cell lines. 2670 Apr 24


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