Kateřina Míčová

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Association of trough imatinib plasma levels (IPL) with cytogenetic or molecular response to treatment in patients with chronic myeloid leukemia (CML) was repeatedly reported. We analyzed their value in the routine clinical setting in 131 patients with chronic phase CML in whom imatinib was applied as first- or second-line treatment. A total of 1,118(More)
Modern high resolution mass spectrometry offers unique identification capability in drug metabolism studies. In this work detailed imatinib metabolization in the plasma of patients with chronic myeloid leukemia is presented. The metabolites were separated by liquid chromatography on a C18 column with mass spectrometry detection via an Orbitrap Elite(More)
BACKGROUND The aim of this study was to develop, validate and compare flow injection analysis (FIA) and ultra-high-performance liquid chromatography (LC)/tandem mass spectrometry methods for the determination of imatinib in plasma from patients with chronic myeloid leukemia. METHODS The plasma for analysis by both methods was deproteinated by methanol(More)
Despite the prognostic value of trough imatinib plasma levels (IPL) identified in some studies, no recommendations for the use of IPL results in routine management of CML patients have been issued. We report two patients in whom daily imatinib dose was increased from 400 to 600 or 800 mg because of low IPL found at various intervals from the beginning of(More)
The discovery of tyrosine kinase inhibitors (TKIs) brought a major breakthrough in the treatment of patients with chronic myeloid leukemia (CML). Pathogenetic CML events are closely linked with the Bcr-Abl protein with tyrosine kinase activity. TKIs block the ATP-binding site; therefore, the signal pathways leading to malignant transformation are no longer(More)
1. Reactivity of benzene oxide (BO), a reactive metabolite of benzene, was studied in model reactions with biologically relevant S- and N-nucleophiles by LC-ESI-MS. 2. Reaction with N-acetylcysteine (NAC) in aqueous buffer solutions gave N-acetyl-S-(6-hydroxycyclohexa-2,4-dien-1-yl)cysteine (pre-phenylmercapturic acid, PPhMA), which was easily dehydrated in(More)
BACKGROUND Therapeutic drug monitoring is recommended for the optimal management of patients with several malignant diseases. The aim of this study was to develop and validate an isotope dilution direct injection mass spectrometry method for the high throughput determination of tyrosine kinase inhibitors in plasma from leukemic and cancer patients. (More)
Tauopathies represent heterogeneous groups of neurodegenerative diseases that are characterised by abnormal deposition of the microtubule-associated protein tau. Alzheimer’s disease is the most prevalent tauopathy, affecting more than 35 million people worldwide. In this study we investigated changes in metabolic pathways associated with tau-induced(More)
5-Ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC) are mainly used as markers of cellular replicational activity. Although EdU is employed as a replicational marker more frequently than EdC, its cytotoxicity is commonly much higher than the toxicity of EdC. To reveal the reason of the lower cytotoxicity of EdC, we performed a DNA analysis(More)
Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups(More)