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The role of biotransformation enzymes in the resistance of cancer cells against standard cytostatics
Giannitsi, Anna ; Hofman, Jakub (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Giannitsi Supervisor: RNDr. Jakub Hofman, Ph.D Title of diploma thesis: The role of biotransformation enzymes in the resistance of cancer cells against standard cytostatics Drug resistance is currently one of the major problems of chemotherapy. Tumor cells are able to defend themselves against the effect of cytostatic drugs due to various mechanisms which leads to a failure of anticancer therapy. The effort to describe new mechanisms of resistance and to develop new therapeutic methods, which would limit this therapeutic obstacle, is logically the subject of many studies. The activity of drug metabolizing enzymes and the subsequent decrease of intercellular concentration of anticancer drugs belongs to one of the possible mechanisms of pharmacokinetic resistance. Enzymes of I. and II. phase of biotransformation participate in this phenomenon. Cytochromes P450, main enzymes of the I. phase, play a major role in the metabolism of many cytostatic agents producing either pharmacologically active or inactive metabolites. Increased expression in tumors and the involvement of individual isoforms into the overall metabolism of cytostatic, which is deactivated by their activity, seems to be one of the...
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Trends in Medicines Usage in ATC Group L01
Weber, Jakub ; Lešetický, Ondřej (advisor) ; Kostřiba, Jan (referee)
The work analyzes trends in medicines used in specialized medical centers from ATC (Anatomical-Therapeutic-Chemical Classification System) L01 in Czech Republic from perspective of the State Institute of Drug Control (SUKL) and of Czech Health Insurance Companies (Vseobecna zdravotni pojistovna Ceske republiky as the biggest one, and rest joined in Svaz zdravotnich pojišťoven Ceske republiky). SUKL perspective considers medicines delivered to healthcare facilities and the other side providing information regarding payments for L01 medicines between years 2012-2015. Conclusions presented show slightly decreasing trend in terms of number of packages delivered (935 ths. in 2012 and 931 ths. in 2015). On the other hand, value of medicines has increased from 5 067 mil. CZK in 2012 to 6 568 mil. CZK in 2015. The increase in value and decrease in volume in the same time (while prices remain stable or decreasing) indicates trend in increasing size of packaging or entry of new strength (with more active ingredient and therefore more expensive) e.g. entry of Herceptin 600 mg in 2014. This paper further identifies the most expensive medicines in ATC L01 group and starts a discussion about possible reasons of discrepancies between different sources of data which are for the most expensive medicines in hundreds of mil. CZK in value and ths. of packages in terms of volume (e.g. Avastin in 2014: difference 104 mil. CZK and 5 598 packages).
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Hydrophilic interaction liquid chromatography for separation of cytostatically active compounds
Voborná, Markéta ; Kalíková, Květa (advisor) ; Kozlík, Petr (referee)
This diploma thesis deals with optimization of separation conditions for the four groups of analytes related to 7-deazaadenosine (each group was composed of four derivatized nucleosides) using hydrophilic interaction liquid chromatography. All the sixteen analytes were synthesized as potentially cytostatically active compounds. The effect of the type of stationary phase in the chromatographic column, the ratio of organic and aqueous parts of the mobile phase, pH of the buffer used as the mobile phase component and the concentration of ammonium acetate in the buffer in the range of 5-50 mM were tested during the optimization process. Three stationary phases were tested - bare silica (Spherisorb® Silica column), silica- bonded amide (TSKgel Amide-80 column) and silica-bonded native cyclofructan 6 (Frulic-N column). The dimensions of all columns were 2504.6 mm i.d.; particle size 5 µm. During the optimization of separation the mechanism of HILIC was studied. It was found that the distribution of analytes between the aqueous layer partially coated on the surface of the stationary phase and the mobile phase and also the adsorption of analytes on the stationary phase participated in the retention and separation mechanism in all tested chromatographic systems. The three groups of analytes (SK1, SK3, SK4)...
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