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  • Artikel: DFG Deutsche Nationallizenzen  (3)
  • AML  (2)
  • 05 B 35  (1)
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  • Artikel: DFG Deutsche Nationallizenzen  (3)
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  • 1
    ISSN: 1432-0584
    Schlagwort(e): Key words Cytidine deaminase ; AraC ; AML ; Pharmacokinetics ; Pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The clinical effects of cytosine arabinoside (AraC) are highly dependent on schedule and dose. Many regimens administered to patients are derived from artificial model systems involving permanent leukemic cell lines. The differences in pharmacokinetics between the in vivo situation and such cell lines are largely neglected. However, cytidine deaminase activity in particular has a major impact on AraC pharmacokinetics by degrading AraC to its inactive metabolite AraU, and it has been shown to be of prognostic relevance in the treatment of acute myeloid leukemia. This study therefore investigated cytidine deaminase activities and AraC deamination in a variety of the most commonly used leukemic cell lines and fresh blasts and their impact on the results of an in vitro model system. It was found that cells from different cell lines (BLIN, CEM, HL60, K562, RAJI, REH, U937) vary greatly in cytidine deaminase activity (e.g., 1.89 nmol per min/mg in K562 versus 0.01 in BLIN cells) and degrade between 18.5 (BLIN) and 96.5% (REH) of AraC to AraU in the incubation medium. This degradation results in highly different AraC exposures for different cells (e.g., AUC of 960 ng per h/ml in REH versus 4048 ng per h/ml in BLIN cells) in spite of identical starting concentrations of the drug. Formation of AraCTP as the main cytotoxic metabolite of AraC is significantly influenced by the differences in cell type-dependent cytidine deaminase activity (e.g., 35.6 ng/107 cells in REH versus 180.2 ng/107 cells in BLIN cells). In contrast to permanent cell lines, fresh leukemic blasts and normal bone marrow mononuclear cells featured low AraC degradation in the model system.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0584
    Schlagwort(e): Key words G-CSF ; AML ; Cytosine arabinoside ; Refractory disease ; Salvage therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Patients with primary refractory or relapsed acute myeloid leukemia (AML) who undergo intensive salvage chemotherapy carry a high risk of treatment failure due to infectious complications and early relapses. The study presented here assessed the effect of granulocyte colony-stimulating factor (G-CSF) on the duration of post-treatment neutropenia, the incidence of infection-related deaths, and the disease-free and overall survival. Sixty-eight evaluable patients with relapsed and refractory AML received G-CSF 5 μg/kg per day subcutaneously starting 2 days after the completion of salvage treatment with the S-HAM regimen, consisting of high-dose cytosine arabinoside twice daily on days 1, 2, 8, and 9 and mitoxantrone on days 3, 4, 10, and 11. Ninety-one patients who were treated with the identical S-HAM regimen but without G-CSF support during a preceding study served as controls. The application of G-CSF resulted in a significant shortening of critical neutropenia of less than 500 μl (36 vs. 40 days;p=0.008), which translated into a trend towards a lower early death rate (21% vs. 30%) and an increase of complete remissions (56% vs. 47%, p=0.11). In patients younger than 60 years a significant prolongation of time to treatment failure (159 vs. 93 days, p=0.038) and of duration of disease-free survival (203 vs. 97 days, p=0.003) was observed. These results indicate a beneficial effect of G-CSF on early mortality as well as on long-term outcome when administered after S-HAM salvage therapy for advanced AML.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Combinatorica 9 (1989), S. 145-152 
    ISSN: 1439-6912
    Schlagwort(e): 05 B 35
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Mathematik
    Notizen: Abstract The matroid matching problem (also known as matroid parity problem) has been intensively studied by several authors. Starting from very special problems, in particular the matching problem and the matroid intersection problem, good characterizations have been obtained for more and more general classes of matroids. The two most recent ones are the class of representable matroids and, later on, the class of algebraic matroids (cf. [4] and [2]). We present a further step of generalization, showing that a good characterization can also be obtained for the class of socalled pseudomodular matroids, introduced by Björner and Lovász (cf. [1]). A small counterexample is included to show that pseudomodularity still does not cover all matroids that behave well with respect to matroid matching.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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