National Repository of Grey Literature 11 records found  1 - 10next  jump to record: Search took 0.01 seconds. 
The impact of selected sesquiterpenes on the effectiveness of anticancer therapy in MDA-MB-231 cell line
Tůmová, Veronika ; Svobodová, Hana (advisor) ; Malátková, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Title, Name, Surname of candidate: Veronika Tůmová Title, Name, Surname of tutor: PharmDr. Hana Bártíková, Ph.D Title of a diploma work: The influence of selected sesquiterpenes on the effect of cytostatics for the cell line MDA-MB-231 Breast cancer is one of the most common forms of cancer. It makes up approximately one quarter of cancer cases amongst women. The rise in the incidence of this disease in western countries has, over recent years, been linked to a lifestyle that characteristically involves a sedentary way of life and a diet rich in animal fats. There are currently many therapeutic regimes available for the treatment of breast cancer which are increasingly adapted to the individual needs of the patient and their specific tumor subtype. In spite of the wide range of treatments with a variety of mechanisms of effects on cancer tissues, current treatments are limited by inadequate effectiveness, serious undesirable side effects or the occurrence of resistance. Scientists have therefore been attempting to uncover ways to prevent these undesired effects. Sesquiterpenes α humulene and trans-nerolidol are naturally-occuring substances that, through their biochemical effects, act cytotoxically...
Construction of promoter-luciferase constructs for DHRS3 gene
Voborová, Lucie ; Malátková, Petra (advisor) ; Matoušková, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Voborová Supervisor: PharmDr. Petra Malátková, Ph.D. Title of diploma thesis: Construction of promoter-luciferase constructs for DHRS3 gene Membrane-bound reductases, which include DHRS3, are still under-researched area. It is assumed that DHRS3 plays a role in the metabolism of retinoids, which contributes to maintaining the balance of all-trans-retinoic acid (ATRA) signaling and thereby regulates the formation of body axis. Gene regulation of DHRS3 by retinoids has not been described yet. Therefore, we decided to examine the gene regulation of DHRS3. The clarification of gene regulation may tell more about DHRS3 function. In order to perform the analysis of the promoter it was necessary to prepare luciferase constructs containing varying lengths of the promoter region of DHRS3. The preparation of the constructs involved amplification, restriction, ligation, transformation, colony PCR, restriction analysis and sequencing. The individual steps were optimized for specific constructs so as to achieve their correct assembly. Thanks to appropriate procedures and optimization constructs were created in sufficient quantity and quality, and can thus be used in the analysis of the promoter...
Characterization of human warfarin reductase
Sokolová, Simona ; Malátková, Petra (advisor) ; Skarka, Adam (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Simona Sokolová Supervisor: PharmDr. Petra Malátková, Ph.D. Title of diploma thesis: Characterization of human warfarin reductase Warfarin is widely used anticoagulant drug. Considering the narrow therapeutic window of warfarin, it is important to fully understand its metabolism in human body. Oxidative, reductive and conjugation reactions are involved in warfarin metabolism. However, the reductive metabolism of warfarin has not been studied in details until now. The reduced metabolite of warfarin, i.e. warfarin-alcohol, is produced by the conversion of the carbonyl group of the side chain. It is known that human liver cytosolic and microsomal fractions exhibit warfarin reductase activity but the specific enzymes catalysing the reduction of warfarin are not known yet. The aim of this study was to identify the enzyme(s) participating in reduction of warfarin and to describe enzyme kinetics. Human liver cytosolic and microsomal fractions and recombinant enzymes AKR1A1, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, AKR1C4, CBR1 and CBR3 were incubated with warfarin at various concentrations. The produced warfarin-alcohol was quantified by UHPLC and the specific activities of enzymes and...
Significance of genetic factors for prognosis and prediction of cancer therapy outcome.
Šůsová, Karolína ; Wsól, Vladimír (advisor) ; Malátková, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Karolína Šůsová Supervisor: Prof. Ing. Vladimír Wsól, Ph.D. Title of diploma thesis: Significance of genetic factors for prognosis and prediction of cancer therapy outcome Colorectal cancer (CRC) is one of the most common cancers in the world and also in the Czech Republic. There are many reasons for such a high prevalence and mortality. In general, we can say, that the level of awareness of risk factors and primary prevention is very low. For example, the inoperability of the tumor, caused by the diagnosis of CRC at a late stage, makes therapy of patients difficult and reduces survival. 5 - Fluorouracil and leucovorin are the gold standard in the treatment of CRC. The targeted therapy has a great success in the palliative therapy and prolongs survival. However, many patients do not respond to adjuvant and palliative therapy well. This failure is often caused by drug resistance. Efflux of cytotoxic drugs out of cells caused by transport proteins of cancer cells. ABC transporters remain among the many elements of drug resistance. Deregulation of gene expression of ABC transporters in tumor cells was discovered in connection with other types of cancer. The aim of this study is to find...
In vitro biotransformation study of fenofibric acid
Kanavi, Matthildi ; Malátková, Petra (advisor) ; Štambergová, Hana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Student: Matthildi Kanavi Supervisor: PharmDr. Petra Malátková Title of diploma thesis: In vitro biotransformation study of fenofibric acid Fenofibric acid is a hypolipidemic agent that acts through PPARα and contributes to treatment of many types of dyslipidemias. It is the active metabolite of fenofibrate, but can be also administrated by itself. Concerning its metabolism, the majority of fenofibric acid is conjugated with glucuronic acid, while a minor amount yields a reduced metabolite. Reduced fenofibric acid is also an active substance. The identity of the enzymes participating in the reducing metabolic process has not been revealed yet. The current study investigated this carbonyl reduction in human liver subcellular fractions and by the use of nine recombinant cytosolic carbonyl-reducing enzymes of the AKR and SDR superfamilies. Enzymatic activity toward fenofibric acid reduction appeared in both cytosol and microsomes and was found that affinity of cytosol is greater while velocity in microsomes is higher. Of the nine tested enzymes, five reductases were identified to play role in the reduction of fenofibric acid. The highest activity was exhibited by CBR1, followed by AKR1C3, AKR1C2,...
Cloning, epression and purification of mycobacterial dihydrofolate reductase
Šedivá, Kateřina ; Novotná, Eva (advisor) ; Malátková, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Šedivá Supervisor: Mgr. Eva Novotná, Ph.D. Title of diploma thesis: Cloning, expression and purification of mycobacterial dihydrofolate reductase Dihydrofolate reductase is an enzyme essential for the metabolism of folic acid - it catalyzes the reduction of dihydrofolate to tetrahydrofolate. Tetrahydrofolate is an important cofactor involved in one-cabron transfer reactions. Dihydrofolate reductase plays a key role in the synthesis of DNA, RNA and proteins. Dihydrofolate reductase was also found in M. tuberculosis. This bacterium is the most common causative agent of tuberculosis in humans. Thus dihydrofolate reductase could be a potential target for the design of new antituberculotics. The recombinant protein dihydrofolate reductase was prepared in several steps. The coding sequence of the protein was first amplified by polymerase chain reaction. A recombinant plasmid, obtained by the ligation of an amplified segment of DNA with plasmid pET-28b(+), was transformed into competent cells E. coli strain BH101 by the heat shock method. Cells E. coli strain BL21(DE3) were used for the protein expression. The expression was induced by the addition of isopropyl-β-D-...
Characterization of human warfarin reductase
Sokolová, Simona ; Malátková, Petra (advisor) ; Skarka, Adam (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Simona Sokolová Supervisor: PharmDr. Petra Malátková, Ph.D. Title of diploma thesis: Characterization of human warfarin reductase Warfarin is widely used anticoagulant drug. Considering the narrow therapeutic window of warfarin, it is important to fully understand its metabolism in human body. Oxidative, reductive and conjugation reactions are involved in warfarin metabolism. However, the reductive metabolism of warfarin has not been studied in details until now. The reduced metabolite of warfarin, i.e. warfarin-alcohol, is produced by the conversion of the carbonyl group of the side chain. It is known that human liver cytosolic and microsomal fractions exhibit warfarin reductase activity but the specific enzymes catalysing the reduction of warfarin are not known yet. The aim of this study was to identify the enzyme(s) participating in reduction of warfarin and to describe enzyme kinetics. Human liver cytosolic and microsomal fractions and recombinant enzymes AKR1A1, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, AKR1C4, CBR1 and CBR3 were incubated with warfarin at various concentrations. The produced warfarin-alcohol was quantified by UHPLC and the specific activities of enzymes and...
Carbonyl Reductases Role in the Biotransformation of Drug Bupropion
Tomanová, Radana ; Zemanová, Lucie (advisor) ; Malátková, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Radana Tomanová Supervisor: RNDr. Lucie Škarydová, Ph.D. Title of thesis: Carbonyl reductases role in the biotransformation of drug bupropion Bupropion is a second-generation antidepressant that is also used at lower doses for smoking cessation. Structurally it is a monocyclic aminoketone, which is metabolized in human liver to three major pharmacologically active metabolites. Bupropion is hydroxylated to hydroxybupropion, reduction leads to formation of threohydrobupropion and also minor metabolite erythrohydrobupropion. The aim of this study was to determine in vitro the activity of human liver subcellular fractions and human carbonyl-reducing enzymes with bupropion and to discover the participation of enzymes in the liver metabolism of bupropion. Initially the role of subcellular fractions and recombinant carbonyl-reducing enzymes belonging to the superfamily AKR, family CBR and 11β-HSD 1 in in vitro biotransformation of bupropion was examined. Determination of formed metabolites was shown that all liver subcellular fractions and also 11β-HSD 1, AKR1C1, AKR1C2, AKR1C3 and CBR1 enzymes are active in the reduction of bupropion. The major in vitro liver metabolite was...
Regulation of Human Carbonyl Reductase 3 (CBR3) Expression
Malátková, Petra ; Wsól, Vladimír (advisor) ; Pávek, Petr (referee) ; Machala, Miroslav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Petra Malátková Supervisor Prof. Ing. Vladimír Wsól, Ph.D. Title of Doctoral Thesis Regulation of Human Carbonyl Reductase 3 (CBR3) Expression The regulation of human carbonyl reductase 3 (CBR3) expression has been complete mystery until recently and is still not well understood. Because the transcriptional regulation of a gene is closely related to the function of encoded protein, the elucidation of the regulation of CBR3 might help to understand its physiological role which has not been elucidated up to the present. The promoter of CBR3 has been described in 2009. The CBR3 promoter contains several putative binding sites for various transcription factors. In 2010, we have shown that CBR3 is regulated via the Nrf2/ARE signaling pathway. This was the first study about the transcriptional regulation of CBR3. The involvement of Nrf2 in the regulation of CBR3 has been recently confirmed by another research group. The functional antioxidant response element (ARE) is located at 2698 bp upstream of the translation initiation codon of CBR3 (−2698ARE). However, the analysis of CBR3 promoter encompassing 2500 bp indicated the presence of cis regulatory upstream element in sequence between...

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