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Visualizations history of changes in cadastral map
Klecanda, Vojtěch ; Čábelka, Miroslav (advisor) ; Souček, Petr (referee)
The goal of this master thesis is to suggest a methodology for a visualization history of changes in cadastral maps. The suggested methodology takes into account a selection of original historical and contemporary data, processing workflow and follow-up visualization using existing open source web technologies. The greatest contribution of this thesis is in the design of the spatio-temporal database, because currently there does not exist workable editor similar to it, which could be used for creating such data. The suggested procedure is based on database updating method of ISKN database utilizing amendment records. However this method is significantly simplified with the use of PostgreSQL/PostGIS geospatial functions. The available literature and other informational sources to the topic are overviewed in the first part of the master thesis. The term "spatio-temporal data" is thoroughly defined and also the ways of integrating temporal features into spatial data, methods of visualization of spatio-temporal data and recent state of their implementations into desktop platforms and web applications are noted. Furthermore historical and current data sources and their usability for the master thesis are described. The full methodology of pre-processing and processing of data and a subsequent visualization using...
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Biomarkers of prognosis and therapy efficacy in ovarian carcinoma
Cerovská, Ela ; Souček, Pavel (advisor) ; Schierová, Michaela (referee)
Ovarian carcinoma is a serious illness with the highest mortality rate among all female cancers. No suitable methods for early diagnosis, precise determination of prognosis or prediction of therapy efficacy are currently available, which leads to diagnosis in advanced stages of disease and therapy efficacy limitation. Consequently, the development of chemoresistance to conventional drugs and frequent relapse of the disease pose a fundamental complication too. The main goal of the current study was identification of new putative prognostic and therapeutic biomarkers, whose introduction into clinical practice could help to improve the dismal outcome of ovarian carcinoma patients. The present master thesis provides results of expression analysis of genes whose products take part in the transport, metabolism and mechanism of action of platinum based drugs and taxanes, and also the regulation of cell cycle and signaling. Transcript levels of these genes have been assessed in series of tumor and control ovarian tissue samples and the difference between both tissue types was evaluated. Gene expression level in tumors was then compared with patient's clinical data and candidate genes, ABCA2 and PRC1, were selected from the obtained results for more detailed analysis. The protein level of candidate genes...
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Mechanism of enzymatic activation of carcinogens and drugs by the system of cytochrome P450
Indra, Radek ; Stiborová, Marie (advisor) ; Souček, Pavel (referee) ; Koblihová, Jitka (referee)
13 Abstract An environmental pollutant and a human carcinogen benzo[a]pyrene (BaP) is after its activation with cytochrome P450 (CYP) able to covalently bind to DNA. In the thesis, one of the target was to investigate an influence of individual components of mixed function monooxygenase (MFO) system on metabolism of benzo[a]pyrene and generation of adducts of activated BaP with DNA. The study was particularly focused to increase our knowledge on the effect of cyt b5 on metabolism of BaP by cytochrome P450 1A1 (CYP1A1) and its potential to serve as a donor of electrons during the reaction cycle of this cytochrome P450. The effect of cyt b5 on generation of BaP metabolites and adducts of BaP with DNA was investigated. In addition the effect of two different expression systems for cytochrome P450 1A1 (prokaryotic and eukaryotic) was also studied. The influence of cyt b5 on oxidation another xenobiotic compound, a plant alkaloid ellipticine that exhibit antitumor activities, was also investigated. Its pharmacological efficiency, as well as side effects depends on its metabolic activation by cytochrome P450. CYP3A4 is very important for ellipticine activation and therefore this enzyme was used in our experiments. Furthermore, a suitability of rat as a model organism mimicking the metabolic fate of BaP...
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Gene expression study of oxysterol signal pathway in breast cancer patients
Kloudová, Alžběta ; Souček, Pavel (advisor) ; Vopálenský, Václav (referee)
Hormonal therapy is a common part of breast carcinoma treatment in patients whose tumors express estrogen and progesterone receptors. The aim of hormonal therapy is to prevent proliferative effect of hormones througt their receptor proteins in order to inhibit tumor growth. However, certain number of tumors is resistant to hormonal therapy despite expression of hormonal receptors. Presently, the reasons of this resistance are not fully understood. Oxysterols are hydroxylated cholesterol derivates, which may play some role in development of the resistance. They may interfere with hormonal therapy effect and influence some signal pathways leading to cancer progression. This study comes with results of gene expression of proteins influenced by oxysterol action, metabolic and transport proteins, transcription factors and members of signaling pathways that may be related to oxysterol effect. This thesis identifies some candidate genes for future analysis on the basis of comparison of gene expression between estrogen receptor positive and negative tumors and correlation with clinopathological data. The final goal should lead to discovery of new diagnostic markers for breast cancer therapy. Powered by TCPDF (www.tcpdf.org)
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Influence of biotransformation and transport to the effects of chemotherapy and prognosis of breast cancer
Hubáčková, Miluše ; Souček, Pavel (advisor) ; Pávek, Petr (referee) ; Janatová, Markéta (referee)
Influence of biotransformation and transport to the effects of chemotherapy and prognosis of breast cancer Abstract: Introduction: The aim of this study was to evaluate the influence of biotransformation enzymes and enzymes of multidrug resistance for the prognosis and effects of chemotherapy of breast cancer patients. The first part dealed with the genetic factors and the influence of genetic polymorphisms in selected biotransformation genes and in ABCB1 gene and their influence in the formation and prognosis of breast cancer. In the second part, the expression profiles of these genes were analyzed as potential prognostic and predictive properties of a treatment's outcome. Materials and methods: Polymorphisms of biotransformation genes were determined using real-time PCR and polymorphisms of ABCB1 gene were determined using NanoChip Assay, which was performed in our cooperated department. In both cases, the polymorphisms were detected in DNA obtained from the blood of patients. The expression of genes was determined using quantitative real-time PCR in paired tumor and adjacent non-tumor tissue of breast cancer samples. The expression of NQO1 and p53 protein was assesed by immunohistochemistry in the tumor breast tissues. Results: The frequencies of the studied SNPs did not differ from the previous...
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The influence of xenobiotic metabolizing enzymes and transporters on the incidence of colorectal cancer and chemotherapy outcome
Krus, Ivona ; Souček, Pavel (advisor) ; Králíčková, Milena (referee) ; Hodis, Jiří (referee)
Introduction: Colorectal cancer (CRC) is one of the most frequent malignancies and affects approximately 5% of worldwide population. More than 75% of CRC cases represent sporadic forms. Susceptibility to nonhereditary CRC is significantly influenced by polymorphisms and mutations in low-penetrance genes. Variations in biotransformation and DNA repair genes may result in acumulation of toxins and DNA damage in cells leading to the development of cancer. Furthermore, different gene expression profiles of membrane transporters affecting the accumulation of anticancer drugs in tumour cells, e.g. ABC drug transporters, may largely influence inter-individual variability in drug response and chemotherapy outcome. The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal cancer. This study followed selected genetic alterations in xenobiotic-metabolizing enzymes (CYP1B1, GSTM1, GSTT1, GSTP1, NQO1 and EPHX1) and genes involved in response to DNA damage (CHEK2 and NBN), as potential CRC susceptibility factors. Another aim of this study was to investigate expression profile of all human ABC transporter genes to follow their prognostic and predictive potential in colorectal carcinoma. Materials and methods: The polymorphisms and other...
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Legal regulation of service in civil proceedings
Souček, Petr ; Pohl, Tomáš (advisor) ; Smolík, Petr (referee)
This thesis deals with the process of service of documents in civil proceedings. The thesis is based on an analysis of current legislation, which is in the introductory chapter supplemented for completeness with historical excursus to the development of this area of law in past. The thesis is for clarity divided according to the individual manners of service. Each of these methods of service of documents is subject to detailed analysis, and there is pointed out on shortcomings with respect to every manner of service. The aim is not only to analyze comprehensively the issue of service in civil proceedings, but also to point out the application problems that may arise today in connection with the contemporary legislation in practice. The author devotes considerable attention to data-boxes and their role in the process of service of documents, both in the direction from parties to the proceedings to the court and in the opposite direction. Besides electronic forms of service represented by data-boxes and e- mail, the thesis also deals with other methods of service, especially by means of a delivering body. In the seventh chapter is then analyzed institute regarding a declaration of an inefficiency of service, the purpose of which is to mitigate the adverse effects that the current system of service...
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Drug Interactions with Nuclear Receptors in the Regulation of Drug Metabolizing Enzymes and Drug Transporters
Nová, Alice ; Pávek, Petr (advisor) ; Skálová, Lenka (referee) ; Souček, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Pharmacology and Toxicology Candidate: Alice Nová, MSc Supervisor: Assoc. Prof. PharmDr. Petr pávek, Ph.D. Title of Doctoral Thesis: Drug interactions with nuclear receptors in the regulation of drug metabolizing enzymes and drug transporters Drug metabolizing enzymes play a key role in metabolism, elimination and detoxification of xenobiotics exposed to the body and protect the organism from potentially harmful effect of xenobiotics as well as certain endobiotics. Phase I and II drug metabolizing enzymes and drug transporters are expressed in most tissues in basal level or may be induced after exposure to xenobiotics. Affecting of expression or activity of drug metabolizing enzymes and drug transporters may result in unpredictable tissue and systemic drug distribution, to side effects or therapy failure. Up-regulation of drug metabolizing enzymes and drug transporters mediates mainly orphan nuclear receptors - pregnane X receptor (PXR) and constitutive androstane receptor (CAR) and transcription factor aryl hydrocarbon receptor (AhR). This doctoral thesis presents the results of three studies dealing with the gene regulation of drug metabolizing enzymes and drug transporters via nuclear receptors. In the first part of...
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The role of estrogen receptors in prognosis and therapy outcome of breast cancer
Kloudová, Alžběta ; Souček, Pavel (advisor) ; Dračínská, Helena (referee)
Estrogen receptors (ER) are members of nuclear receptor family, which mediate distinct physiological functions after binding a steroid ligand. Apart from that they play a role in many diseases including breast cancer. ER is among proteins routinely evaluated in clinical practice and on the basis of ER expression, patients are treated by endocrine therapy. There are different opinions of the role of ER in cancer cells, but in the future, detection of ER and treatment by ER- and ER-selective ligands could contribute to improvement of cancer therapy. Isoforms, mutations and posttranslational modifications of ER present other important factors, which can influence estrogen signalization and endocrine therapy efficiency and deciphering of their importance for cancer cells could bring better understanding of ER signalization and improvement of the therapy.
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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...
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