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Analýza vlivu inhibitorů Src kináz na adhezní signalizaci v lidských hematopoietických buňkách / Analysis of the effects of Src kinase inhibitors on adhesion signaling in human hematopoietic cells

Adhesion of hematopoietic cells to the bone marrow microenvironment is important for their proper development. It is proven that Src-family kinases (SFK) regulate cell adhesion, although their exact role in the regulation of adhesion signaling remains unclear. Since adhesion processes are investigated mainly in adherent cell types, far less is known about hematopoietic cells. However, defects in the cell adhesion accompany a number of hematological diseases, like chronic myeloid leukaemia (CML). SFK overexpression is one of the proposed mechanisms of resistance to the first-line CML treatment, imatinib mesylate. Second generation drugs (e. g. dasatinib) inhibit SFK together with Bcr-Abl. Additionally, SFK-specific inhibitors (PP2, Src inhibitor-1) are also available, but there are no studies about effects of these drugs on cellular adhesivity of hematopoietic precursors. To explore the dynamics of hematopoietic cell adhesion to the extracellular matrix, we introduced a new approach using the RTCA xCELLigence DP system along with the well-established method of fluorimetric detection of adherent cell fraction. Our general observation is that various drugs (dasatinib, imatinib, PP2, Src inhibitor-1) induce pro-adhesive effects in several leukemic cell lines. Direct comparison of the kinetics of...

Identiferoai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:310544
Date January 2012
CreatorsObr, Adam
ContributorsKuželová, Kateřina, Jiroušková, Markéta
Source SetsCzech ETDs
LanguageCzech
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/masterThesis
Rightsinfo:eu-repo/semantics/restrictedAccess

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