|
|
Mechanisms of anticancer drug action in neuroblastomas
Groh, Tomáš ; Stiborová, Marie (advisor) ; Levová, Kateřina (referee) ; Vališ, Karel (referee)
Cancer cells are able to adapt to different stress factors such as hypoxia, which is caused by insufficient tumor vascularization. An increased acetylation status of histones H3 and H4 in UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines was found to be a mechanism of adaptation of these cells to hypoxia. An increase in acetylation of histones H3 and H4 is suggested to cause changes in the structure of chromatin that lead to activation of gene transcription. In addition, cultivation of tested neuroblastoma cells under hypoxic conditions changes expression of proteins of a transcription factor N-myc, which is essential for development of neuroblastomas. This transcription factor is also responsible for a metabolic adaptation of neuroblastoma cells, increases their aggressiveness and its expression leads to a worse prognosis of the disease. Inhibitors of histone deacetylases (HDAC) are suggested to be the promising agents exhibiting various anticancer effects. They can induce cell cycle arrest, differentiation or programmed cell death in sensitive tumors. In this study, the effect of one of inhibitors of HDACs, valproate, on expression of proteins of transcription factors N-myc and hypoxia inducible factor 1α (HIF-1α) was investigated. Valproate decreases protein levels of both transcription factors in...
|
|
|
Molecular mechanism of carcinogenicity of aristolochic acid
Levová, Kateřina ; Stiborová, Marie (advisor) ; Ryšlavá, Helena (referee) ; Souček, Pavel (referee)
Aristolochic acids (AA) are carcinogenic and nephrotoxic alkaloids from Aristolochia species. Aristolochic acid I (AAI), the major component of AA, causes the development of Aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN). These two diseases cause total renal failure and urothelial malignancies. The fact that these diseases have not been developed in all persons, who have been exposed to their action, might be causd by different activities and protein levels of the enzymes metabolizing AAI. Thus, the identification of enzymes involved in the metabolism, and detailed knowledge of their expression and catalytic specifities is a major importance. Aristolochic acid I (AAI) can be metabolized by several types of reactions. Like most nitroaromatics, the main activation pathway of AAI is reduction of its nitro group to form a cyclic acylnitrenium ion, which can bind to the purine bases, thereby forming AAI-DNA adducts. The detoxication pathway of AAI is its oxidative demethylation by cytochromes P450 forming detoxication metabolite 8-hydroxyaristolochic acid Ia (AAIa). In the present thesis, using rat and human enzymes and as well as several mice models, the metabolism of AAI in vitro and in vivo was investigated. The first model has deleted gene for NADPH:cytochrome P450...
|
|
|
The Process of Education in nursery school in France
Levová, Kateřina ; Klinka, Tomáš (advisor) ; Machleidtová, Silva (referee)
Title of the thesis: The process of education in nursery school in France This thesis deals with the process of education in nursery school in France. This topic concerns all pedagogic influence on the child while attending the school. The preparation of the work is based on the literary and the practical research. The practical research we chose is an observation of the teaching proces in nursery school and an interview with the teachers of these schools. The content of the thesis is divided into five essential domains. The first is the introduction to the theme of the process of education in nursery school. This part focuses on the objectives of the education and limits the period spent in nursery school. The second domain presents the conditions and organisitional factors of education. The third domain analyses the educational activities - their characteristic, classification and their connection with domains of progression from the national curriculum. The fourth domain deals with concrete examples of the activities. The last domain talks about the evaluation and by this conclude the theme of process of education. Keywords : education in nursery school, national curriculum, factors of education, organization of education, activities in nursery school, nursery school in France
|
|
|
Metabolic detoxication of carcinogenic aristolochic acids by cytochromes P450
Levová, Kateřina
Aristolochic acids (AA) are the major alkaloid of Aristolochia species. Carcinogenic and nephrotoxic plant alkaloid aristolochic acid I (AAI), the major toxic component of AA, causes the development of Aristolochic acid nephropathy (AAN). It is a unique type of rapidly progressive renal fibrosis which leads to a total renal failure. AAI also causes a similar type of kidney fibrosis with malignant transformation of the urothelium, Balkan endemic nephropathy (BEN). One of the common features of AAN and BEN is that not all individuals exposed to AA suffer from nephropathy and tumor development. One possible explanation for these different responses could be individual differences in the activities of the enzymes catalyzing the biotransformation of AAI. Thus, the identification of enzymes principally involved in the metabolism of AAI, and detailed knowledge of their catalytic specificities is of a major importace. Aristolochic acid I is oxidized by demethylation to form AAIa. This metabolic pathway is known as detoxication. AAI metabolite AAIa was separated from AAI by HPLC. Therefore, the present study has been designed to evaluate the cytochrome P450 (CYP)-mediated oxidative detoxification of AAI in rat and human liver. The efficiency of human recombinant CYPs to oxidize AAI was also tested. To find...
|
|
| |
|
|
How business cycle affects attendance of czech cinemas between 1993 -2013?
Levová, Kateřina ; Pikhart, Zdeněk (advisor) ; Zeman, Karel (referee)
The basic question of this thesis was the relationship between the business cycle and the cinema attendance in the Czech Republic. Other questions are the effect of technological advances, household income and the impact of substitutes and complements to attendance. Similar questions have already examined several papers in different countries, but the results are not identical. The benefit of this work is examining the Czech industry, which from an economic point of view is not analyzed too often. The first part describes the relevant theories: the theory of the business cycle theory, theory of the consumer and demand. Another part contains a description of the analyzed sector, its historical development and an overview of studies that have worked on this issue. Following are two models: the first examining a total annual cinema attendance (1993 - 2013) and the second model focused on the average attendance per projection). In both models was studied cinema attendance dependence on the cyclical component of the unemployment rate and other variables. In both cases, the results suggest that attendance is procyclical. The amount of real wages has a positive impact on attendance. The impact of technological advances on the contrary negative.
|
guest ::
