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S Kasimir-Bauer

Publications and source records attributed to S Kasimir-Bauer.

6 recordsLinked to original sources
PubMed1998

Chronic myelogenous leukemia: effect of interferon-alpha treatment on phagocytic activity and capacity of circulating neutrophils.

This study focuses on the effect of interferon (IFN)-alpha on phagocytosis of FITC-labeled Escherichia coli by polymorphonuclear neutrophils (PMNs) in chronic myelogenous leukemia (CML). The phagocytic activity and capacity of PMNs from IFN-alpha treated patients (n = 17), untreated CML patients (n = 9) and from healthy donors (n = 20) were compared using flow cytometry. Both parameters of PMN phagocytosis were reduced in untreated CML and in IFN-alpha treated CML with Ph1 chromosome persistence but normal in IFN-alpha treated CML with Ph1 conversion. Thus, the phagocytic performance of PMNs in patients with chronic phase CML is significantly improved after successful treatment with IFN-alpha.

Adolescent↗
PubMed1998

In acute myeloid leukemia, coexpression of at least two proteins, including P-glycoprotein, the multidrug resistance-related protein, bcl-2, mutant p53, and heat-shock protein 27, is predictive of the response to induction chemotherapy.

To identify prognostic factors alternative or additional to P-glycoprotein (Pgp), we studied the impact of the multidrug resistance-related protein (MRP), bcl-2 (flow cytometry), mutant p53 (single-strand conformation polymorphism), and heat-shock protein 27 (HSP27, Western blotting) in myeloid blasts obtained at the time of diagnosis in patients with de novo acute myeloid leukemia (AML). We collected bone marrow samples from untreated AML patients, prepared the cells as well as the cellular protein, and froze all the material. We then analyzed 20 patients who responded with complete remission (CR) and 20 patients who had blast persistence (BP). The purpose of the study was to determine whether leukemic blasts from patients with BP were more resistant to chemotherapy than those from patients with CR. There was no significant correlation between the expression of any of these proteins alone and treatment outcome in both groups studied. In contrast, there was a significant correlation between the coexpression of at least two of these proteins and response (p = 0.0298), which turned out to be a significant independent prognostic factor for treatment failure (p = 0.0329, relative risk = 1.5) according to multivariate analysis. We conclude that drug resistance in AML is multifactorial. Thus, coexpression of different resistance mechanisms may be responsible for the primary drug resistance in de novo AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Down-regulation of topoisomerase II by camptothecin does not prevent additive activity of the topoisomerase II inhibitor etoposide in vitro.

Topoisomerases (Topo) I and II are cellular enzymes that catalyze the relaxation of topologically strained DNA and that are involved in a number of DNA-related processes. Their complete inhibition by Topo I and II inhibitors gives promise for improvements in the treatment of malignant diseases. However, preclinical studies showed down-regulation of Topo II protein expression by Topo I inhibitors, which may preclude the useful application of combined topoisomerase inhibition in the clinic. We investigated the efficacy of the combination of etoposide (ETP) and camptothecin (CPT) in human gastric and lung cancer cell lines with different sensitivity towards ETP. The cytotoxicity of different drugs was assessed by the sulforhodamine B assay. Drug interactions were evaluated by isobologram analysis. The polymerase chain reaction and flow cytometry were employed for examination of the mdr1 (multidrug resistance type 1) phenotype. As reported by others, incubation of the P glycoprotein (P-gp)-negative tumor cell lines with the Topo I inhibitor CPT resulted in a significant down-regulation of Topo II protein expression. This was obviously due to changes in the cell cycle distribution of the cells induced by the treatment, with a marked increase of cells in G2/M phase and a consecutive decrease of S phase cells. Despite these biochemical changes, isobologram analysis showed additive cytotoxic activity of CPT and ETP in all the cell lines, independent of whether the drug incubation was performed simultaneously or sequentially. These data indicate that down-regulation of Topo II protein by CPT does not prevent additive activity of CPT and ETP in vitro, and therefore combined Topo I and II inhibition may be useful for investigation in clinical trials.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Modulation of multidrug resistance by BIBW22BS in blasts of de novo or relapsed or persistent acute myeloid leukemia ex vivo.

The phenylpteridine derivative BIBW22BS (BIBW22) is a potent modulator of multidrug resistance (MDR). We investigated BIBW22 in comparison to dexniguldipine and verapamil as modifier of MDR in blasts of de novo, relapsed or persistent acute myeloid leukemia (AML) in vitro. All patients with relapsed or persistent AML had been pretreated with idarubicin and cytosine arabinoside. The degree of MDR was determined by efflux kinetics of rhodamine 123 (R123), daunorubicin, and idarubicin measured by flow cytometry (FACS). A total of 51 patients with AML, 25 de novo and 26 relapsed or persistent, were investigated. While only 6 out of 25 de novo AML blast populations showed moderate efflux of R123 and daunorubicin, 17 out of 26 blast populations of relapsed or persistent AML had an efflux between 20% and 44% within 15 min ex vivo. This efflux could be significantly inhibited by 1 microM BIBW22, 1 microM dexniguldipine, or 10 microM verapamil. For idarubicin we found an effusion of 40+/-9% within 15 min in all blast populations that could not be inhibited by the modulators. Clinically achievable drug concentrations causing only moderate side-effects are in the range of 0.5 microM dexniguldipine and 3 microM verapamil. Up to now, BIBW22 has not been investigated clinically. Thus the potential toxicity of concentrations of 0.5-1 microM BIBW22, sufficient for an optimal efflux inhibition ex vivo, is not known yet. We conclude from our ex vivo investigations in blast populations of de novo, relapsed or persistent AML that BIBW22 is a potent modulator of MDR.

Antigens, CD34↗
PubMed1994

Philadelphia chromosome-positive chronic myelogenous leukemia: functional defects in circulating mature neutrophils of untreated and interferon-alpha-treated patients.

This study focuses on possible functional defects of circulating mature neutrophils in chronic phase chronic myelogenous leukemia (CML) and their modulation by interferon-alpha (IFN-alpha). Polymorphonuclear cells (PMN) of seven untreated and nine IFN-alpha-treated patients were evaluated for the following parameters by the following methods: generation of oxygen species, by luminol-dependent chemiluminescence; leukotriene B4 (LTB4) generation, by high-performance liquid chromatography (HPLC); expression of LTB4 and formylmethionyl-leucyl phenylalanine (FMLP) receptor sites, by 3H-binding assay; and GTPase activity, by 32P-gamma-GTP. Compared to normal controls, reduced values were obtained in treated and untreated CML for most parameters studied. Therapy with IFN-alpha resulted in significantly diminished values for oxygen species (NaF stimulation) and LTB4 (FMLP stimulation) generation, as well as FMLP receptor expression as compared to untreated CML. We conclude that alterations at the level of oxygen species production, mediator generation, receptor expression, and transmembrane signaling are involved in functional defects of circulating mature neutrophils from CML patients. IFN-alpha seems to enhance some of these functional defects, but the clinical relevance of these findings has be elucidated.

Adult↗