|
|
Study of molecular markers correlating with prognosis and result of therapy colorectal carcinoma.
Protivová, Martina ; Souček, Pavel (advisor) ; Hromadníková, Ilona (referee)
Colorectal cancer is one of the most common cancer in this country and abroad. A major problem in the treatment of this disease is interindividual variability in response to treatment, since a large proportion of patients show resistance or adverse toxicity to the drug. The cause of this variability can be an individual's genetic makeup. From this perspective a need to find molecular markers for prognosis of the disease and markers through which we can predict response to therapy is growing. The main aim of this study was to find differences in gene expression between healthy and tumor tissue from patients well and poorly responding to treatment based on 5-fluorouracil and compare the results to clinical data. This study aimed to evaluate gene expression of 14 potential molecular markers involved in 5-FU pathways involving metabolism, transport, and objectives of the drug. Patients selection for the study was based on 5-FU regimens treatement. Expression was evaluated in two independent sets consisting of patients with indicated palliative or adjuvant chemotherapy. For each patient malignant and paired nonmalignant tumor tissue was available. Gene expression in these samples was measured using real-time RT-PCR with relative quantification using the preamplified cDNA. In the first phase the gene...
|
|
|
Initial and permanent formation of permanent deacons in Brno diocese
Souček, Pavel ; Opatrný, Aleš (advisor) ; Kotas, Jan (referee)
Bibliographic citation: Initial and permanent formation of permanent deacons in Brno Diocese [manuscript]: Bachelor's thesis / Pavel Souček; Supervisore: Aleš Opatrný. - Prague, 2009.-xx s. Annotation The aim of this Bachelor thesis called "Initial and Permanent Formation of Permanent Deacons in Brno Diocese" is to describe and then evaluate the formation of permanent deacons, applicants and deacons already ordained in Brno Diocese in the time period of 2000 to 2010. The thesis consists of two parts. The first part describes the restitution of permanent deaconship after the II. Vatican Council, the general service of the permanent deaconship in the tradition of the Church and Church documents, which relate to this topic on a general level. The second part deals with the formation of permanent deacons including the initial formation for applicants for permanent deaconship and formation of permanent deacons after their ordination as it is implemented in Brno Diocese. The final part provides an analytical assessment of the formation. Key words Deaconship, permanent deacon, diaconate, service.
|
|
| |
|
|
Potenciální využití WIP1 fosfatasy v terapii nádorového onemocnění prsu
Pecháčková, Soňa ; Macůrek, Libor (advisor) ; Souček, Pavel (referee) ; Krejčí, Lumír (referee)
Cells in our body respond to genotoxic stress by activation of a conserved DNA damage response pathway (DDR). Depending on the level DNA damage, DDR signaling promotes temporary cell cycle arrest (checkpoint), permanent growth arrest (senescence) or programmed cell death (apoptosis). Checkpoints prevent progression through the cell cycle and facilitate repair of damaged DNA. DDR represents an intrinsic barrier preventing genome instability to protect cells against cancer development. WIP1 (encoded by PPM1D) phosphatase is a major negative regulator of DDR pathway and is essential for checkpoint recovery. This thesis contributed to the understanding of molecular mechanisms of WIP1 function and revealed how WIP1 can be involved in tumorigenesis. Firstly, we described that WIP1 protein levels decline during mitosis by APC-Cdc20 dependent proteasomal degradation. WIP1 is phosphorylated at multiple residues which inhibit its enzymatic activity. We propose that inhibition of WIP1 in mitosis allows sensing of low levels of DNA damage that appear during unperturbed mitosis. Further, we identified novel gain-of-function mutations of PPM1D which result in expression of C-terminally truncated WIP1. These truncated WIP1 variants are enzymatically active and exhibit increased protein stability. As result, cells...
|
|
|
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...
|
|
|
Metabolism of carcinogenic o-nitroanisol and its metabolite o-nitrophenol and two environmental pollutants 2-nitrobenzanthrone and 3-nitrobenzanthrone
Svobodová, Martina ; Stiborová, Marie (advisor) ; Entlicher, Gustav (referee) ; Souček, Pavel (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF SCIENCE DEPARTMENT OF BIOCHEMISTRY Metabolism of carcinogenic o-nitroanisole, its metabolite o-nitrophenol and environmental pollutants 2-nitrobenzanthrone and 3-nitrobenzanthrone Summary of PhD Thesis RNDr. Martina Svobodová Supervisor: Prof. RNDr. Marie Stiborová, DrSc. Prague 2010 RNDr. Martina Svobodová Introduction -1- INTRODUCTION 2-Nitroanisole 2-Nitroanisole (2-methoxynitrobenzene, 2-NA, figure 1) is an important industrial pollutant and a strong carcinogen for rodents causing neoplastic transformation in the urinary bladder and, to a lesser extent, in the spleen, liver and kidney [19, 30, 31] . 2-NA is also a toxic compound, causing anemia. 2-NA is used primarily as a precursor in the synthesis of o-anisidine (2-methoxyaniline), which is an intermediate in the production of many azo dyes. This compound is used in pharmaceutical industry as an intermediate in the synthesis of some medicaments [30, 31] . In spite of potent rodent carcinogenicity of 2-NA, this chemical is weakly mutagenic in the Ames test with the Salmonella typhimurium. This carcinogen also exhibits a low activity in cytogenetic tests. It induces a slight increase in chromosomal aberration and in sister chromatid exchanges, but only at high concentrations [31] . 2-nitroanisole may be...
|
|
|
The position of creditors in reorganization
Souček, Petr ; Smolík, Petr (advisor) ; Zoulík, František (referee)
Act No. 182/2006 Coll., the Insolvency Act, represented big changes on the field of the Czech bankruptcy law. One of these changes was introduction of a new way of dealing with bankruptcy - the reorganization. It provides the debtor, who is in a difficult financial situation, with a chance to save his business. Reorganization represents a sanation form of bankruptcy proceedings and it is thus an alternative to a typical liquidation form of dealing with bankruptcy. The Insolvency Act strengthened the position of creditors in the bankruptcy proceedings. They have new powers and a greater influence on the ongoing proceedings. This thesis deals with the position of creditors in the reorganization. It analyzes their rights and obligations through the whole process of reorganization. The thesis begins with a definition of creditors and special creditors' bodies in general and defines basic terminology used in the thesis. This is followed by a description of the process of reorganization itself in chapter two. The foreign legislation as an inspiration of the Czech legislature is placed at the beginning of this part. A number of conditions have to be met that the court may authorize the reorganization. A bankruptcy of a debtor is a basic prerequisite. In chapter three, the attention is paid to the creditor...
|
|
|
Possibilities to Increase the Effectiveness of Selected Cytostatics
Hanušová, Veronika ; Skálová, Lenka (advisor) ; Hodek, Petr (referee) ; Souček, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Katedra biochemických věd Candidate Mgr. Veronika Hanušová Supervisor Prof. RNDr. Lenka Skálová, Ph.D. Title of Doctoral Thesis POSSIBILITIES TO INCREASE THE EFFECTIVENESS OF SELECTED CYTOSTATICS Cancer belongs among the most serious diseases and one of the most common causes of death in civilized countries. Many cancers can be cured by surgery, radiotherapy or chemotherapy, especially if they are detected early. The efficacy of anticancer treatments is frequently insufficient; the use of higher doses is limited by the development of systemic or organ toxicity. Recently, new strategies how to improve efficacy of cytostatics in cancer cells and decrease their toxicity in normal healthy cells have been intensively investigated. The aim of present thesis was to search and test the new possibilities, how to increase effectiveness of anticancer drugs. To achieve our goals, in vitro experiments (various cell culture, subcellular fractions of homogenate from cells, rats and mice) and in vivo experiments (tumor bearing mice) were performed. First tested approach was based on the inhibition of doxorubicin deactivation (DOX), which belongs among the most important antineoplastic drugs used in cancer therapy. DOX is metabolized...
|
|
|
Study of nucleic acids by means of drop coating deposition Raman microspectroscopy (DCDR)
Souček, Pavel ; Kopecký, Vladimír (advisor) ; Mojzeš, Peter (referee)
The work was focused on possibilities of the new technique of nonresonance Raman spectroscopy - drop coating deposition Raman (DCDR) spectroscopy upon study of nucleic acids. DCDR spectroscopy is based on deposition of a small droplet of the studied sample on a hydrophobic surface, where after evaporation of the solvent, ring of the studied material in glass phase is formed. That way the material is concentrated and upon measurements by means of Raman microspectrometry the increase of signal of several orders of magnitude is observed with respect to the standard technique of sample measurements in solvent. In this work we studied behavior of DNA 12-mer and DNA with 3000 base pairs. Our research showed that DCDR spectra of DNA dissolved in deionized water can be measured up to concentration of 30 M per base. The DCDR spectra are similar to those measured from solvents. Nevertheless, the deposited sample never forms a ring. It was shown that the size of nucleic acids didn't play dominant role upon ring formation but their charge which lead to repulsion of the molecules. After adding of sodium ions and subsequently also magnesium ions the ring formation was observed. Factor analysis of spectral maps demonstrated that formed rings are not fully homogenous and that upon their origin condensation of DNA could...
|
|
|
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)
|
guest ::
RSS feed.