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Study on interactions of selected targeted drugs with ABC drug transporters
Svobodová, Markéta ; Hofman, Jakub (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Markéta Svobodová Supervisor: doc. RNDr. Jakub Hofman, Ph.D. Title od diploma thesis: Study on interactions of selected targeted drugs with ABC drug transporters Cancer is one of the most common causes of death and its incidence is constantly increasing. Treatment mainly includes a combination of drug therapy, surgery and radiotherapy. A new approach, with huge potential, is the use of targeted anti-tumor therapy. This approach is based on specific interaction with tumor cells that reduces the negative effects occuring in conventional chemotherapy. Despite intensive research, we still face insufficient response to treatment. The main cause of therapy failure is the emergence of multidrug resistance (MDR) and the formation of metastases. The MDR phenomenon is most often associated with the overexpression of ATP binding cassette (ABC) transporters. These are responsible not only for the excessive efflux of anticancer drugs from cells, but also mainly affect their pharmacokinetics. Inhibition of these transporters increases the intracellular concentration of the cytostatic and provide the ability to modulate MDR. Therefore, one of the aims of this work was to investigate the inhibitory activity of...
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Study on the role of selected cytochrome P450 isoforms in cytostatic resistance at apoptosis level
Moriová, Magdalena ; Hofman, Jakub (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradci Králové Departement of Pharmacology & Toxicology Student: Magdalena Moriová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on the role of selected cytochrome P450 isoforms in cytostatic resistance at apoptosis level Cytostatic resistance is one of the most problematic obstacles in oncological treatment. Beside pharmacodynamic mechanisms, pharmacokinetic factors play an important role in drug resistance as well. Enzymatic transformation of active substance to inactive metabolite in tumor cells probably belongs to these mechanisms, however, evidences concerning the relevance of this phenomenon are predominantly either indirect and/or affected by interference elements. Using comparative experiments with HepG2 cell lines with/without CYP3A4 overexpression, we focused on the evaluation of the role of this clinically important enzyme in the resistance against docetaxel. Methodologically, it was the assessment of apoptosis induction (activation of caspases 3/7, 8 and 9) using commercial luminescent kits. Our results suggest significant participation of CYP3A4 enzyme on the reduction of docetaxel anticancer efficacy after 48 h from treatment, whereas this effect was not recorded in earlier intervals. These findings perfectly correlate...
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Study on interactions of PARP inhibitors with ABC drug efflux transporters
Dziaková, Lucia ; Hofman, Jakub (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucia Dziaková Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on interactions of PARP inhibitors with ABC drug efflux transporters. ATP-binding cassette (ABC) transporters are integral membrane proteins that use the energy obtained from ATP to carry transport of numerous endogenous substrances out of the cells, but attention is drawn primarily to the fact that they transfer also xenobiotics. Their overexpression in tumor tissue contributes to multidrug resistance (MDR), which in most cases leads to therapy failure. Poly(ADP-ribose)polymerase inhibitors (PARPi) represent a promising therapeutic approach in the treatment of cancers that exhibit defects in homologous recombination (HR). This work focuses on four selected PARPi (olaparib, rucaparib, niraparib, veliparib) and their interaction potential towards ABC drug efflux transporters (ABCB, ABCC1, ABCG2). In our work, we worked with MDCKII cells (parent, transduced by the transporters of interest) and utilized the principle of accumulation studies based on the measurement of fluorescence intensity of specific model substrates (hoechst33342, calcein AM, daunorubicin, mitoxantrone). We used established inhibitors of studied...
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Comparison of platelet aggregation in healthy population.
Minarovičová, Júlia ; Mladěnka, Přemysl (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Júlia Minarovičová Supervisor: prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Comparison of platelet aggregation in healthy population Platelets have an irreplaceable role in the process of aggregation. Nevertheless, their increased activity is associated with the development of many cardiovascular diseases. This process can be influenced by clinical used substances from the group of antiplatelet drugs, which differ in their effectiveness within the population. Within this study, platelet aggregation was tested using impedance aggregometry, whose principle is the change in electrical impedance between electrodes caused by the adhesion of activated platelets. Firstly, whole blood was incubated with clinically used antiplatelet drugs (ticagrelor, vorapaxar, and acetylsalicylic acid) and a flavonoid metabolite, 4-methylcatechol. Subsequently, a platelet aggregation inducer (ADP, thrombin receptor activating peptide 6 /TRAP/, collagen, arachidonic acid, ristocetin, U-46619, and platelet-activating factor /PAF/) was added, and the process was monitored for 6 minutes. The most potent inhibitor of the aggregation induced by arachidonic acid was acetylsalicylic acid in a concentration of 70 μM...
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Information System Assessment and Proposal for ICT Modification
Slezák, Tomáš ; Hofman, Jan (referee) ; Koch, Miloš (advisor)
This diploma work is focused on the analysis of the information system of the firm and then there is a suggestion of how to change the system. The first part of the work includes the terms which are used in the work and also describes the theory of the information system, what is neccesary for the understanding of the whole work. In the next chapter there are basic information about the firm and the analysis of its information system. According to this analysis a new information system, which improves its efficiency, is designed
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Measuring system of photovoltaic panels efficiency
Hofman, Jiří ; Háze, Jiří (referee) ; Vaněk, Jiří (advisor)
This diploma thesis is focused on development and initial run of a measurement system whose aim is to measure photovoltaic panel efficiency. Experimental photovoltaic panel is installed outside the laboratory. Measurement system consists of the solar radiation measurement module (pyranometer), photovoltaic panel load module (panel power measurement) and panel climate measurement module. Data from measurement module is being captured via control computer for subsequent analysis of panel efficiency and climatic impacts on it.
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Web sites concept
Hofman, Jan ; Bureš, Josef (referee) ; Koch, Miloš (advisor)
My project put mind to complete web sites concept. Content of project consist in first analyse of all functions, webdesign concept and technical implementation through the use of web programming languages, too. Another part of project is description of the first web initialization, elimination of mistakes, follow-up administration and updating programmed code or text.
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Company Internet Sites and E-commerce
Hofman, Jan ; Bureš, Josef (referee) ; Koch, Miloš (advisor)
Thesis deal with complete proposition of internet sites and e-commerce. Thesis includes first analyse of all web functions, scheme of e-commerce, scheme of graphic layout, e-commerce implementation by the help of web programming languages and databases. Part of thesis is first initiation of internet sites, debugging, administration systém, technical and content updating. There is also economical evaluation, influence on the company, service of e-commerce and off-set evaluation whole system.
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Global Positioning System Signal Emulator
Hofman, Jan ; Zamazal, Michal (referee) ; Povalač, Aleš (advisor)
Thesis is adressed to the principals of a satellite navigation. It is focused on a determination of a longitude, latitude and altitude of a single point on the surface of the Earth. It contains analysis of navigation messages and a manner of processing of navigation signals in GPS receivers. Realization of an emulator of the navigation signal of GPS system in Matlab is also described. The purpose of this emulator is a generation of navigation messages, which could be transmitted by universal software radio. The last part of thesis contains the analysis of these signals, which were captured by second software radio.
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