National Repository of Grey Literature 3 records found  Search took 0.01 seconds. 
Study of the effect of cyclin-dependent kinase inhibitors on the expression of selected AKR and CBR enzymes in human cell lines.
Kouklíková, Etela ; Novotná, Eva (advisor) ; Wsól, Vladimír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Etela Kouklíková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Study of the effect of cyclin-dependent kinase inhibitors on the expression of selected AKR and CBR enzymes in human cell lines Cyclin-dependent kinase inhibitors (CDKi) are considered as a suitable treatment especially in patients with wrong prognosis or advanced stage of cancer. It has only recently been discovered that CDKi are able to influence the activity of some enzymes from aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase (SDR) superfamilies. AKR and SDR enzymes belong to a group of carbonyl reducing enzymes that are involved in the metabolism of endobiotics and xenobiotics. An important group of drugs that are metabolized by these enzymes to less efficient compounds are anthracyclines. The aim of this diploma thesis was to find out whether purvalanol A, roscovitin, dinaciclib, AZD5438 and R547 can affect the expression of the most important anthracycline reductases (AKR1A1, AKR1B10, AKR1C3, AKR7A2 and CBR1) in human HepG2 and HL-60 cell lines. Expression of anthracycline reductases in cells exposed to CDKi was evaluated at mRNA level by RT-qPCR and at protein level by Western blotting. The...
Study of the effect of cyclin-dependent kinase inhibitors on the expression of selected AKR and CBR enzymes in human cell lines.
Kouklíková, Etela ; Novotná, Eva (advisor) ; Wsól, Vladimír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Etela Kouklíková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Study of the effect of cyclin-dependent kinase inhibitors on the expression of selected AKR and CBR enzymes in human cell lines Cyclin-dependent kinase inhibitors (CDKi) are considered as a suitable treatment especially in patients with wrong prognosis or advanced stage of cancer. It has only recently been discovered that CDKi are able to influence the activity of some enzymes from aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase (SDR) superfamilies. AKR and SDR enzymes belong to a group of carbonyl reducing enzymes that are involved in the metabolism of endobiotics and xenobiotics. An important group of drugs that are metabolized by these enzymes to less efficient compounds are anthracyclines. The aim of this diploma thesis was to find out whether purvalanol A, roscovitin, dinaciclib, AZD5438 and R547 can affect the expression of the most important anthracycline reductases (AKR1A1, AKR1B10, AKR1C3, AKR7A2 and CBR1) in human HepG2 and HL-60 cell lines. Expression of anthracycline reductases in cells exposed to CDKi was evaluated at mRNA level by RT-qPCR and at protein level by Western blotting. The...
Proteomika CDK inhibice v nádorových buňkách
Kovářová, Hana ; Skalníková, Helena ; Halada, Petr ; Strnad, M. ; Hajdúch, M.
In order to improve our understanding of the biochemical basis of the anti-cancer activity of olomoucine-derived synthetic cyclin-dependent kinase inhibitors (CDKIs) and to search for novel proteins associated with these biological effects we applied complex proteomic approaches. To analyse cellular responses to the CDKI we used two cancer models: the CEM T-lymphoblastic leukemia cell line representing hematological malignancy, and the A549 lung adenocarcinoma cell line as a solid tumor model. Cancer cells of these lines were cultured in both the presence and absence (controls) of the CDKI, bohemine (BOH). Cellular proteins of both of these lines were then extracted and fractionated using conventional two-dimensional gel electrophoresis (2-DE), and for the CEM T-lymphoblastic leukemia cell line we also used a 2-D liquid phase fractionation system ProteomeLab PF 2D ( Beckman Coulter). Computer-assisted data analysis of the resulting 2-D protein expression maps was applied to determine the similarity/dissimilarity of the maps and to select characteristic protein spots or bands based on the quantitative differences between BOH-treated and control cells. Many of these differentially expressed proteins were identified by mass spectrometry, since they represent candidate biomarkers of cancer cell responses to CDK inhibition and cellular pathways that are relevant to the anti-cancer activity of the CDKIs. Subsequently, we focused directly on these proteins in confirmatory studies using various techniques (including quantitative immunoblotting, immunocytochemistry and functional activity analyses) to demonstrate the validity of the proteomic results and extend our knowledge of the CDKI effects.

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