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Role of genetic factors in the prognosis and prediction of efficacy of chemotherapy in breast carcinoma patients
Brynychová, Veronika ; Souček, Pavel (advisor) ; Macůrek, Libor (referee) ; Stružinská, Ivana (referee)
Changes in the regulation of apoptosis and cell cycle are involved in tumor development, progression, and resistance to antitumor therapy. The aim of this work was to evaluate the importance of apoptotic caspases and regulators of cytokineses as possible prognostic and predictive markers in breast carcinoma patients. In addition to determining the transcript levels of selected genes in tumor and control tissues obtained from breast carcinoma patients, we have also focused on the importance of alternative splice variants of caspases and their potential genetially determined regulation. We analysed the obtained data in relation to the clinical-pathological characteristics of the tumors, the progression-free survival of patients and to the response of the patients to the neoadjuvant chemotherapeutic treatment. Part of the work was determination of protein expression levels and verification of the importance of selected candidates for the effect of chemotherapy by functional study. The transcript levels of caspase 2, 3, 7, 8, 9, 10, the specifically detected splice variants caspase 2S, 2L, 3A and B, 3S, 9A, 9B, 8L, and the transcript levels of KIF14 and CIT in breast carcinomas were unrelated to the progression-free survival of patients, or to the response of patients to neoadjuvant treatment. The...
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Comparison of apo- and holoforms of the transcription factor "Bach1"
Vávra, Jakub ; Martínková, Markéta (advisor) ; Brynychová, Veronika (referee)
Hemoproteins represent very important components of many living organisms. Participation in the processes of oxygen transport and storage, electron transport or enzymatic catalysis of reactions involving oxygen or hydrogen peroxide are commonly known functions of hemoproteins. Recently, there has been discovered a new group of hemoproteins. The main feature of this new group of proteins is their ability to detect changes in heme concentration (heme-responsive proteins) or changes in diatomic gas concentration (gas-responsive heme-containing sensor proteins) in their vicinity. Detection of these concentration changes generates signals that induce structural changes of the respective sensor proteins. Finally, the structural changes of the respective sensor proteins affect their functions or activities. The subject of this diploma thesis is the preparation and characterization of the eukaryotic heme sensor Bach1. We especially focused on the ability of Bach1 to bind heme molecules and on the comparison of various Bach1 properties in its apoform and holoform. Determination of the exact amount of heme molecules that specifically interact with heme sensor Bach1 represents very important part of this thesis. We also studied the effect of different redox states of heme iron and the presence of interaction...
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Analysis of genetic factors of breast cancer
Chmelařová, Žaneta ; Kleiblová, Petra (advisor) ; Brynychová, Veronika (referee)
The thesis The analysis of genetic factors of breast cancer by NGS deals with the current serious problematics of breast cancer from the perspective of genetic predisposition. Breast cancer is one of the most common tumors in women. Every year more than 7000 women are diagnosed with this disease and the mortality rate in the Czech Republic is nearly 2000 cases. Of the total number of patients diagnosed with breast cancer, approximately ten percent of patients have congenital mutations in one of the predisposing genes that cause a significantly increased risk of developing a cancer. More than half of these mutations occur in germline mutations of the BRCA1 or BRCA2 genes, others include a number of other genes, eg tp53, CDH1, PTEN, STK11, ATM, PALB2, CHEK2.Early diagnosis and identification of persons with increased risk of developing breast cancer is of key importance for their inclusion in preventive programs. Therefore, the thesis aims to testing genes that can cause a breast cancer. In the thesis, 219 known and candidate predisposition genes were analyzed in a group of 263 non-selected breast cancer patients using a targeted panel NGS, the Illumina platform. Selected identified suspect variants were further confirmed by Sanger sequencing. The aim of this work was also a mutational analysis of...
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Role of genetic factors in the prognosis and prediction of efficacy of chemotherapy in breast carcinoma patients
Brynychová, Veronika ; Souček, Pavel (advisor) ; Macůrek, Libor (referee) ; Stružinská, Ivana (referee)
Changes in the regulation of apoptosis and cell cycle are involved in tumor development, progression, and resistance to antitumor therapy. The aim of this work was to evaluate the importance of apoptotic caspases and regulators of cytokineses as possible prognostic and predictive markers in breast carcinoma patients. In addition to determining the transcript levels of selected genes in tumor and control tissues obtained from breast carcinoma patients, we have also focused on the importance of alternative splice variants of caspases and their potential genetially determined regulation. We analysed the obtained data in relation to the clinical-pathological characteristics of the tumors, the progression-free survival of patients and to the response of the patients to the neoadjuvant chemotherapeutic treatment. Part of the work was determination of protein expression levels and verification of the importance of selected candidates for the effect of chemotherapy by functional study. The transcript levels of caspase 2, 3, 7, 8, 9, 10, the specifically detected splice variants caspase 2S, 2L, 3A and B, 3S, 9A, 9B, 8L, and the transcript levels of KIF14 and CIT in breast carcinomas were unrelated to the progression-free survival of patients, or to the response of patients to neoadjuvant treatment. The...
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STR genotyping of Czech medieval population: archeologocal site in Mlekojedy (Litoměřice)
Brynychová, Veronika ; Hájek, Martin (advisor) ; Šimková, Halina (referee)
The aim of this diploma thesis was the initial genetic analysis of early mediaeval burial site from Mlekojedy polycultural locality (Litoměřice District, Czech Republic). Autosomal STR markers were chosen because of the following reasons. The high degree of polymorphism of these markers and the high extent of heterozygosity favor the use of STRs instead of mitochondrial DNA for the structural analysis of small populations. Usefulness of STR typing for validation purposes was demonstrated many times before. We used primers for miniSTRs to obtain the fullest results. Nuclear DNA was extracted from 35 % of bone samples and 91 % of teeth. We detected lower PCR amplification success rate of fragments longer than 150 bp and very high rate of allele drop-out which is sign of degraded DNA. Twelve reliable genotypes were determined for TH01 marker. Observed allele frequency and genetic diversity values were discussed in comparison with recent populations and other aDNA studies of burial sites. Keywords: ancient DNA, STR markers, miniSTR, early medieval burial site, Czech population
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