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Study of genetic factors modifying the risk of onset and progression of colorectal and pancreatic cancer
Mohelníková Duchoňová, Beatrice ; Souček, Pavel (advisor) ; Skálová, Lenka (referee) ; Macek, Milan (referee)
Introduction: The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal and pancreatic cancer. The first part deals with the etiological factors and the importance of polymorphisms in biotransformation enzymes and genetic alterations in the gene CHEK2 in the origin of these malignancies. In the second part, the ABC transporter genes were analyzed as potential prognostic and predictive markers of a treatment's outcome. Materials and methods: The polymorphisms and other genetic alterations were detected using real-time PCR, allelespecific PCR and PCR-RFLP methods in DNA which was extracted from the blood of patients. The frequency of polymorphisms was evaluated and their importance was assessed with regard to the available epidemiological data. Gene expressions were determined by qPCR in paired samples of tumor tissue and adjacent non-tumorous parenchyma. Results: A majority of the observed polymorphisms failed to show a relationship between their presence and the risk of any of these malignancies. CYP2A13 variant allele*7 coding inactive enzyme was found in 7 of 265 controls and in none of 235 pancreatic carcinoma patients. In contrast, GSTP1-codon 105 Val variant allele and GSTT1-null genotype were associated with an elevated...
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Analysis and characterization of BRCA1 splicing variants.
Hojný, Jan ; Kleibl, Zdeněk (advisor) ; Souček, Pavel (referee)
The Breast cancer gene 1 (BRCA1) codes for nuclear phosphoprotein with a key function in the regulation of DNA damage response. The BRCA1 protein contributes to the formation and regulation of protein supercomplexes that participates on the DNA double-strand break repair. These protein supercomplexes are formed by the protein-protein interactions between highly conservative protein motives in BRCA1 and its binding partners. Except to the wild type form of BRCA1 mRNA containing entire set of 22 exons coding for the 220 kD protein, numerous alternative splicing variants (ASVs) BRCA1 mRNA has been described. These ASVs code for BRCA1 isoforms lacking several critical functional domains. It has been proposed, that formation of BRCA1's ASVs represent a tool for regulation of BRCA1 function. Only poorly has been characterized a complex catalogue of in various human tissues and their expression. This study aims to address these questions. We optimized the identification of BRCA1's ASVs including those covering the entire transcripts of the wt BRCA1 mRNA with length exceeding 5.5 kb. In further analysis, we characterized 13 BRCA1's ASVs in RNA samples isolated from peripheral blood mononuclear cells (PBMNC) obtained from patients with breast cancer (BC) and control subjects. The majority of the identified...
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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.
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Genetic factors responsible for hereditary breast and ovarian cancer development Large rearrangements in BRCA1 and BRCA2 genes
Tichá, Ivana ; Pohlreich, Petr (advisor) ; Souček, Pavel (referee) ; Stiborová, Marie (referee)
2. Summary Background: A greatly increased risk for development of hereditary breast cancer is associated with germline mutations in several susceptibility genes. In this study we analyzed large genomic rearrangements (LGRs) in BRCA1/2 genes and we also focused on the role of CHEK2 and TP53 in tumorigenesis. Methods: A series of 586 high risk patients with breast/ovarian cancer that had previously been tested negatively for small mutations in BRCA1/2 was screened for LGRs by MLPA, LR-PCR and sequencing. Chromosome 17-specific aCGH was used to locate deletion breakpoints in regions flanking the BRCA1 gene. MLPA-analysis was also used to detect two frequently occurring mutations in CHEK2 (c.1100delC and a deletion of 5395 bp). The coding region of the TP53 gene was analyzed by sequencing. Results: We identified 9 different LGRs in the BRCA1 gene in 16 patients. Five alterations (deletion of exons 1-17, 5-10, 13-19, 18-22 and 21-24) were novel. Deletions of exons 1-17, 5-14 and 21-22 were identified repeatedly, and represented population specific (founder) mutations. LGRs accounted for 12.1% (16/132) of all detected pathogenic BRCA1 mutations. No LGRs were found in the BRCA2 gene. Pathogenic mutations in other tested genes were less frequent; 2 were detected in TP53 and 9 in CHEK2. Conclusions: In our...
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Modulation of metabolic activation of ellipticine by components of the mixed function monooxygenase system
Mrázová, Barbora ; Stiborová, Marie (advisor) ; Tichá, Marie (referee) ; Souček, Pavel (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF SCIENCE, DEPARTMENT OF BIOCHEMISTRY Modulation of metabolic activation of ellipticine by components of the mixed function monooxygenase system Summary of PhD Thesis RNDr. Barbora Mrázová Supervisor: Prof. RNDr. Marie Stiborová, DrSc. Praha 2010 RNDr. Barbora Mrázová Introduction 1 IINNTTRROODDUUCCTTIIOONN Ellipticine (5,11-dimethyl-6H-pyrido [4,3-b] carbazole, figure 1) and its more soluble derivates are alkaloids isolated from Apocyanaceae plants, which exhibit significant antitumor activities[15, 21, 24, 31] . Ellipticine was first isolated in 1959 from the leaves of the evergreen tree Ochrosia elliptica Labil[6] . Nevertheless, its pharmacological efficiencies (and efficiencies of some of its derivates) was found in 1967, when they were prepared by chemical syntheses[7] . Ellipticine and its more soluble derivates, 9-methoxy- ellipticine and 2-methyl-9-hydroxyellipticine in the form of acetate, have been utilized pharmacologically since 1970s. They are highly efficient against osteolytic breast cancer with metastases, acute myeloblastic leukemia, kidney sarcoma and thyroid carcinoma[1, 17, 18, 19, 23] . Ellipticines exhibit also significant anti-HIV activity because of their ability to inhibit retroviral integrase. This is the reason, why ellipticine is also...
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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...
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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...
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User oriented web portals
Souček, Petr ; Souček, Martin (advisor) ; Šidlichovská, Zuzana (referee)
My dissertation is focused on customer-oriented websites. It explains the basic principles of creating customer-targeted websites. It also deals with common suggestions to web design, web navigations and contents. I conclude my dissertation with application of the theoretically acquired knowledge on the analysis of business web presentation, including the e-shop.
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Combination of ellipticine chemotherapy and a5b1 integrin-targeted therapy in human glioblastoma
Martínková, Eva ; Stiborová, Marie (advisor) ; Souček, Pavel (referee) ; Eckschlager, Tomáš (referee) ; Barberi-Heyob, Muriel (referee)
Charles University Prague Faculty of Science Department of Biochemistry SUMMARY OF THE THESIS COMBINATION OF ELLIPTICINE CHEMOTHERAPY AND α5β1 INTEGRIN-TARGETED THERAPY IN HUMAN GLIOBLASTOMA by MARTÍNKOVÁ Eva Supervisors: Prof. RNDr. Marie STIBOROVÁ, DrSc. Dr. Monique DONTENWILL 2 Table
of
Contents INTRODUCTION............................................................................................................................... 3
AIMS
OF
THE
STUDY ...................................................................................................................... 5
RESULTS............................................................................................................................................. 6
PART
A ................................................................................................................................................................6
PART
B.................................................................................................................................................................6
DISCUSSION....................................................................................................................................... 8
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