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  • 1
    ISSN: 1432-1335
    Keywords: Key words Acute lymphoblastic leukemia ; Methotrexate polyglutamates ; Thymidylate synthase ; Salvage pathway ; Relapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: In about 25% of patients suffering from acute lymphoblastic leukemia (ALL) treatment failures occur that are most likely due to development of resistance to methotrexate (MTX). Blasts from patients with ALL were evaluated for MTX uptake, formation of long-chain MTX polyglutamates (MTX-Glu5+6), cytotoxicity and thymidylate synthase inhibition by MTX and compared to blasts from patients with acute myelogenous leukemia (AML). Methods: Radioactively labeled MTX-Glu n were analyzed by means of HPLC. Thymidylate synthase activity was measured by a tritium-release assay. Cytotoxicity was determined by trypan blue exclusion. Results: In most ALL blasts (n = 9) large amounts of MTX-Glu5+6 (1.06–7.03 pmol/107cells) and high cytotoxicity (43.5%–92.7%) were found, while in others small amounts of MTX-Glu5+6 (0.0–0.39 pmol/107cells) caused only weak cytotoxicity (6.0%–27.9%) (n = 5, 2 relapsed patients). Resistance to MTX in blasts from AML patients (n = 5) was also caused by reduced synthesis of MTX-Glu5+6 (0.0–0.42 pmol/107cells). In contrast, some ALL blasts (n = 7, 4 relapsed patients) were able to survive MTX treatment despite large amounts of MTX-Glu5+6 (1.5–5.05 pmol/107cells) and extensive thymidylate synthase inhibition. Conclusions: Since the majority of ALL patients were examined at first diagnosis, an inherent mechanism of resistance seems most likely. We propose a mechanism based on the switch of thymidylate synthesis to the salvage pathway.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Key words Acute lymphoblastic leukemia ; Methotrexate polyglutamates ; Lymphoblast preparation ; Red blood cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Blasts isolated from bone marrow aspirates or blood samples of patients with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) were compared for uptake of methotrexate (MTX) and formation of MTX polyglutamates (MTX-Glu n ). Red blood cells (RBC) from the same patient samples were also analyzed. Methods: Blasts were isolated by standard density centrifugation. RBC were prepared from the pellet of the same centrifugation. MTX-Glu n were analyzed by means of HPLC and radiochemical quantification. Results: In lymphoblasts isolated from blood, the distribution patterns of MTX-Glu n were the same as in bone marrow lymphoblasts, but the total amount of MTX-Glu n accumulated in blood lymphoblasts was reduced by 41%–51% when compared to the same number of bone marrow lymphoblasts of the same patient. RBC accumulated MTX but no formation of MTX-Glu n occurred. Conclusions: The determination of MTX and MTX-Glu n in lymphoblasts isolated from blood samples of patients with common ALL provides qualitative information on the capacity of the blasts to form MTX-Glu n since distribution patterns of MTX and MTX-Glu n parallel that of bone marrow lymphoblasts. The amounts of MTX-Glu n accumulated, however, were much lower in blood lymphoblasts. Blood lymphoblasts are therefore not useful for a quantitative analysis of MTX-Glu n . The contribution of RBC to MTX and MTX-Glu n in vitro is only marginal and residual RBC in lymphoblast preparations from bone marrow can therefore be ignored.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0044-2313
    Keywords: Pentacarbonyl(diorganostibine)chromium, -molybdenum, -tungsten complexes ; Tetracarbonyl(diorganostibine)chromium and -molybdenum complexes ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Tetra- and Pentacarbonyl Compounds of Chromium, Molybdenum and Tungsten with Oxygen- and Sulfurbridged Distibines and with Chlorodiphenylstibine as Complex LigandsThe penta- and tetracarbonyl complexes of chromium, molybdenum and tungsten with the stibines Ph2SbCl and (Ph2Sb)2X (X = O and S) are obtained by photochemical reaction of the hexacarbonyls in thf and by thermic ligand substitution of (η4-C7H8)M(CO)4 (M = Cr, Mo) with stibines.In the case of (Ph2Sb)2X monodentate or bidentate coordination is possible.
    Notes: Die Synthese von Penta- und Tetracarbonylen der Metalle der 6. Nebengruppe mit Antimonliganden des Typs Ph2SbCl und (Ph2Sb)2X (X = O und S) erfolgt durch photochemische Umsetzung der Metallhexacarbonyle in THF bzw. durch thermische Ligandsubstitution aus (η4-C7H8)M(CO)4 (M = Cr, Mo) mit den Antimonliganden.Bei Verwendung der Chelatstibane (Ph2Sb)2X läßt sich sowohl eine monodentate als auch eine bidentate Koordination verwirklichen.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 619 (1993), S. 2061-2065 
    ISSN: 0044-2313
    Keywords: Dicarbonylbis(triphenylphosphite)(stibine)iron complexes ; Bis[dicarbonylbis(triphenylphosphite)iron](stibine) complexes ; Dicarbonyl(η5-methylcyclopentadienyl)(stibine)manganese complexes ; Bis[dicarbonyl(η5-methylcyclopentadienyl)manganese](stibine) complexes ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Complexes of Iron and Manganese with Oxygen-, Sulfur-, and Methylene-bridged Distibines and with Chlorodiphenylstibine as LigandsThe photochemical reaction of CO3Fe[P(OPh)3]2 and of MeCpMn(CO)3 with the stibines Ph2SbCl and (Ph2Sb)2X (X = O, S and CH2) yields mononuclear complexes (CO)2[P(OPh)3]2FeL and °Cp(CO)2MnL (L = Ph2SbCl, (Ph2Sb)2X) and the stibine bridged binuclear complexes °CO)2[P(OPh)3]2Fe{(Ph2Sb)2X}Fe(CO)2[P(OPh)3]2 and °Cp(CO)2Mn{(Ph2Sb)2X}Mn(CO)2MeCp.
    Notes: Durch photochemische Umsetzung von (CO)3Fe[P(OPh)3]2 und von MeCpMn(CO)3 mit Anti-monliganden des Typs Ph2SbCl und (Ph2Sb)2X (X = O, S und CH2) können Einkernverbindungen (CO)2[P(OPh)3]2FeL und MeCp(CO)2MnL (L = Ph2SbCl, (Ph2Sb)2X sowie die über Distibanliganden verbrückten Zweikernverbindungen (CO)2[P(OPh)3]2Fe{(Ph2Sb)2X}Fe(CO)2[P(OPh)3]2 und MeCp(CO)2Mn{(Ph2Sb)2X}Mn(CO)2MeCp synthetisiert werden.
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
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