National Repository of Grey Literature 154 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
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...
The effect of alisertib and brigatinib on the activity of selected human carbonyl reducing enzymes.
Lakomá, Petra ; Novotná, Eva (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Petra Lakomá Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: The effect of alisertib and brigatinib on the activity of selected human carbonyl reducing enzymes Key words: brigatinib, alisertib, daunorubicin, inhibition, carbonyl-reducing enzymes Protein kinases are enzymes, whose main function is based on a transfer of phosphate group from ATP to protein substrate. This common posttranslational modification is involved in the regulation of intracellular processes and cell signaling. Altered expression of protein kinases is often coupled with a development of cancer. Inhibition of protein kinases may prevent cancer cell proliferation and induce their cell death. The main aim of the diploma thesis was to measure inhibition potential of protein kinase inhibitors, alisertib and brigatinib, against carbonyl-reducing enzymes. Overexpression of carbonyl-reducing enzymes in cancer cells may cause resistance to drugs followed by failure of chemotherapeutic therapy. In case of antracyclin chemotherapeutic daunorubicin, carbonyl-reducing enzymes reduce the carbonyl in C-13 giving rise a primary metabolite daunorubicinol, which has lower cytotoxic effect but higher cardiotoxicity. The effort to...
The detection of protein covalent complexes with DNA using fluorescent microscopy
Melicharová, Růžena ; Jirkovská, Anna (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department od Biochemical Sciences Candidate: Růžena Melicharová Supervisor: PharmDr. Anna Jirkovská, Ph.D. Title of thesis: The detection of protein covalent complexes with DNA using fluorescent microscopy Anthracycline antibiotics are present one of the most potent antineoplastic drugs. The mechanism of their action is complex. They are reported to intercalate to DNA, form DNA adducts and interact with topoisomerase II (TopII) as its poisons. Catalytic cycle of TopII is interrupted when anthracyclines stabilize the covalent complex of DNA and TopII and that causes cell damage. However, using of anthracyclines is limited by several adverse effects e. g. myelotoxicity and cardiotoxicity. The mechanism of cardiotoxicity is still unclear but may be associated with poisoning of the TopIIβ isoform. Unlike the TopIIα, TopIIβ is present mostly in quiescent cells as cardiomyocytes. Furthermore, the only clinically approved cardioprotective drug dexrazoxane belongs to TopII catalytic inhibitors. Nevertheless, the details of the dexrazoxane-afforded protection are unclear. This thesis was aimed to optimize the TARDIS (trapped in agarose DNA immunostaining) assay to detect and quantify covalent cleavage complexes, compare different ways for analysis of...
Evaluation of Efficiency and Risks of Private Construction Project
Čičmanec, Juraj ; Novotná, Eva (referee) ; Hromádka, Vít (advisor)
The diploma thesis deals with the evaluation of the effectiveness and risks of a private construction project. This work is divided into two parts. The first part is a theoretical part, which defines the basic concepts associated with investment as such, but also directly with investment in real estate and construction investment. In the second part, this work deals with risk assessment, determination of their size and finally risk management. The end of the theoretical part is the elaboration of methodology for the practical part. The beginning of the practical part the work is devoted to the description of the construction area and specification of the building itself. In the next part are set investment costs, operating income and expenses. Operating income consists of the lease itself. This was determined on the basis of similar investments in the area. Operating expenses are divided into fixed and variable where only fixed are included in the evaluation. Subsequently, the work establishes the profit and loss statement and therefrom the cash flows. The second part defines the risks associated with the construction of the project. The switching value is then calculated for critical project risks. The end of the practical part is devoted to risk management. The conclusion summarizes the results of individual parts of the thesis and a written recommendation for the investor whether to realize the project or not.
Effect of selected tyrosine kinase inhibitors on the activity of human carbonyl reducing enzymes
Tomanová, Alžbeta ; Novotná, Eva (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Alžbeta Tomanová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Effect of selected tyrosine kinase inhibitors on the activity of human carbonyl reducing enzymes Key words: tyrosin kinases, screening, carbonyl, daunorubicin, inhibition Tyrosine kinases are a subclass of protein kinases, catalysing the transfer of ATP phosphate residue to a protein, thereby playing an important role in cellular signaling. Abnormal tyrosine kinase activity is present in various malignancies. In certain cases, inhibition of their function can prevent tumor cell proliferation and eventually induce apoptosis. At the same time, some tyrosine kinase inhibitors have demonstrated the ability to inhibit efflux transporters, which are often involved in the development of resistance to anticancer treatment. In this diploma thesis, the inhibitory effect of imatinib, nilotinib, dasatinib and acalabrutinib (tyrosine kinase inhibitors) has been studied on carbonyl reducing enzymes, whose overexpression by tumor cells may lead to resistance to chemotherapy. In particular, in the case of anthracyclines, the reduction of carbonyl group on C-13 results in not only lower cytotoxic activity, but also increased...
Strategic development of the territory in the context of EU policy
Pospíšilová, Radka ; Novotná, Eva (referee) ; Vaňková, Lucie (advisor)
The bachelor thesis deals with territorial development in the context of EU policy. The subject of the theoretical part of the thesis is the sphere of investment and their financing, management of municipalities, EU policy and subsidy programs in the period 2014 – 2020. The practical part analysis the investment in the reconstruction of the transport terminal in the town Holešov. It also includes alternatives to investment financing. Finally, an effect of the investment on the development of the territory is summarized.
Economic and Financial Evaluation of Project Carried out on Municipal Level
Khaliliya, Shirin ; Novotná, Eva (referee) ; Hromádka, Vít (advisor)
The bachelor thesis deals with the evaluation of the effectiveness of public investment, which is implemented at the municipal level. A cycle path is chosen as a specific public investment.
Inhibitors of human enzyme akr1C3 of plant origin
Lojdová, Kateřina ; Novotná, Eva (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Kateřina Lojdová Supervisor: RNDr. Eva Novotná, Ph.D. Consultant: RNDr. Lucie Zemanová, Ph.D. Title of thesis: Inhibitors of human enzyme AKR1C3 of plant origin Enzyme AKR1C3 is a part of large superfamily of aldo-keto reductases. It is a hydroxysteriod dehydrogenase, in human body it participates among others in steroid hormone metabolism but also in activation and deactivation of some drugs. Increased expression of this enzyme is linked to higher aggressivity of some neoplastic diseases and poor prognosis of the treatment, e.g. prostate cancer. This makes AKR1C3 an interesting target for farmaceutical and medical research. Discovery of strong and selective AKR1C3 inhibitor is the first step in finding a drug, that could affect tumor metabolism and restore its sensitivity to treatment. There were 32 naturally occuring compounds from flavonoid and alkaloid groups tested in this study. Its goal was to determine inhibiton efficacy of selected compounds to enzyme AKR1C3. Reduction of a potential anticancer drug oracin to dihydrooracin was used for the measurement, the results were evaluated using an HPLC analysis. IC50 was determined for compounds with significant inhibitory effect.
Study of protein-protein interaction of DHRS7 enzyme by pull-down assay
Hermanová, Kateřina ; Novotná, Eva (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biochemical Sciences Candidate: Kateřina Káchová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Study of protein-protein interaction of DHRS7 enzyme by pull-down assay Dehydrogenase/reductase (SDR family) member 7 (DHRS7) is one of the less studied enzymes of SDR superfamily. It has been proven that this enzyme is in vitro involved in reductive metabolism of various compounds, such as steroids, retinoids and xenobiotics. Recently results pointing out to possible role of this enzyme in the pathogenesis of prostate cancer or other diseases has been published. It would be suitable to better characterize this enzyme to clarifying its patho/physiological role in the organism. Because protein-protein interactions seem to be important for the function of proteins, the aim of this study was to identify interaction partners of the DHRS7, and thus contribute to the improvement of understanding of this enzyme. For our experiments, pull-down assay, in vitro method was utilized. The first step was immobilization of DHRS7 enzyme (bait protein) to suitable carrier (His Mag Sepharose Ni particles and nonmagnetic Protino Ni-IDA particles). Subsequently, the carrier with immobilized DHRS7 was incubated with the lysate of Hep G2...
Effect of selected cytostatics for the treatment of leukemia on the activity of human carbonyl reducing enzymes
Šmídlová, Monika ; Novotná, Eva (advisor) ; Wsól, Vladimír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical sciences Candidate: Bc. Monika Šmídlová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Effect of selected cytostatics for the treatment of leukemia on the activity of human carbonyl reducing enzymes Key words: reductases, leukemia, cytostatics, inhibition Anthracycline antibiotics, especially daunorubicin, are widely used for the treatment of acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Although the efficacy of these drugs is high, treatment is still limited due to cardiotoxicity and tumor cell resistance to anthracyclines. Mechanisms that contribute to the formation of anthracycline resistance include metabolic biotransformation (reduction) to less efficient secondary alcohols. The reduction is calatyzed by carbonyl reducing enzymes belonging to aldo-keto reductase (AKR) and short chain dehydrogenase/reductase (SDR) superfamilies. The discovery of AKR and SDR inhibitors could help to overcome anthracycline resistance and also reduce cardiotoxicity caused by these drugs. The aim of the diploma thesis was to find out whether all-trans-retinoic acid, cyclophosphamide, cytarabine, cladribine and prednisolone are able to inhibit anthracycline reductases AKR1A1, AKR1B10, AKR1C3, AKR7A2...

National Repository of Grey Literature : 154 records found   1 - 10nextend  jump to record:
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