National Repository of Grey Literature 97 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Development of methodology for detection of circulating nucleic acids in cancer patients
Kobrle, Lukáš ; Souček, Pavel (advisor) ; Valihrach, Lukáš (referee)
Cancer diagnosis represents one of the most common causes of death in the world, also linked to an ever-increasing incidence of even some more difficult-to-treat variants. One of the most common types of cancer in the world is colorectal cancer, which ranks second in terms of mortality. For these reasons, various methods have been developed for an early diagnosis of the disease. One of the modern and non-invasive methods is the so-called liquid biopsy, based on the detection of circulating DNA and RNA from the blood of patients. This method is also suitable for choosing a therapy, monitoring its effectiveness, and observing the relapse of the disease. In this work, a methodical workflow was created for the monitoring of circulating nucleic acids for its further use in a cohort of patients with colorectal cancer. Various commercial kits were used for the isolation of circulating nucleic acids from plasma of healthy controls, among which the best ones, in terms of quality and quantity, was chosen. The threshold for hemolysis detection by qPCR was also determined using samples from healthy donors. Everything was then applied to RNA samples extracted from plasma of cancer patients, from whichna library of short RNA molecules was prepared for subsequent sequencing. After processing the results, the...
Heme sensor proteins as potential biomarkers of cellular and oxidative stress processes induced by ionizing radiation
Vávra, Jakub ; Martínková, Markéta (advisor) ; Souček, Pavel (referee) ; Tichý, Aleš (referee)
[IN CZECH] Ionizing radiation is a potential inducer of the oxidative stress processes in cells. As a result, reactive radicals are formed in the intracellular space modifying the essential biomolecules. Ionizing radiation has either direct (radiation sickness) or indirect (malignant processes) effect on the organism. Therefore, a fast determination of the dose is required when suspected irradiation of the organism occurs. However, a method routinely applicable, fast enough and at the same time suitable for dose estimation based on biomarkers has not been developed so far. The aim of this thesis is to describe new properties of the selected heme sensor proteins and discuss their potential importance for the cellular adaptation to oxidative stress conditions. Specifically, the thesis is focused on two eukaryotic proteins, heme regulated inhibitor (HRI) and transcription factor p53. The study of functional regulation as well as the conformational changes of these proteins induced by heme is greatly emphasized. Besides, the optimization of the key experimental methods was conducted. Specifically, Phos-tag electrophoresis was applied for the kinetics study of HRI wild type and its Gly202Ser mutant form, which is a characteristics of lung cancer development. Unsurprisingly, for both HRI forms studied,...
The role of truncated PPM1D/Wip1 phosphatase in cancer
Martiníková, Andra-Stefania ; Macůrek, Libor (advisor) ; Souček, Pavel (referee) ; Mistrík, Martin (referee)
When encountering damage, the cells activate the DNA Damage Response (DDR) pathway and stop the cell cycle until the DNA is repaired. PPM1D/WIP1 phosphatase resumes the cell cycle after the damage has been repaired, by directly dephosphorylating DNA damage markers. The DDR pathway prevents genome instability or cancer development. Mutations in the Ppm1d gene encoding PPM1D result in an overstable and truncated protein observed both in cancer patients and in cancer cell lines. In this thesis, we used an "in-house" transgenic mouse model in which mutations in the exon 6 of the Ppm1d gene resulted in a truncated PPM1D protein. First, we observed high PPM1D levels and impaired DDR to gamma ionizing radiation (IR) in the mouse thymi having truncated PPM1D (Ppm1dT/+ ). We then bred the Ppm1dT/+ mice with the Trp53+/- heterozygote knock-out mice which are prone to thymic lymphoma. The Ppm1dT/+ Trp53+/- double-mutants had a higher frequency of developing IR-induced T-cell lymphomas, compared to the single Trp53+/- mutants. Moreover, truncated PPM1D leads to a defective cell cycle checkpoint activation in human non-transformed RPE cells (RPE1), which then proliferate despite the presence of DNA damage. RPE1 cells also display increased proliferation after replication stress. RPE1 or U2OS cells with...
Study of metabolism of tyrosine kinase inhibitors and mechanism of their anticancer effects
Vavrová, Katarína ; Indra, Radek (advisor) ; Souček, Pavel (referee) ; Ječmen, Tomáš (referee)
As inhibitors of tyrosine kinases have become more widely used in anticancer therapy, detailed understanding of their pharmacokinetic profile is increasingly essential for the improvement of treatment outcomes. Herein, the metabolism in liver microsomes in animal models and humans was studied. Clarification of which liver enzymes, specifically cytochromes P450 (CYP), are involved in the metabolism of vandetanib, cabozantinib and, lenvatinib, may play a key role in oncology practice, as these anticancer drugs are administrated in combination with other drugs. This co-administration may pose a risk of drug interactions, which may result in decreased efficacy or increased drug-related toxicity. To elucidate the metabolism of our selected anticancer drugs in human liver, the same approaches were gradually used- correlation analysis using human liver microsomes from 12 different donors, inhibition studies, and the use of recombinant CYP. In addition, an approach with animal liver microsomes that were premedicated with inducers of individual CYP was used to elucidate vandetanib metabolism in rat liver. Our first studied tyrosine kinase inhibitor was vandetanib. In the first paper, we studied its metabolism in humans through various approaches, and subsequently in another publication in rat. The...
Thermal stability of Ti/Ni multilayer thin films
Václavík, R. ; Zábranský, L. ; Souček, P. ; Sťahel, P. ; Buršík, Jiří ; Fořt, Tomáš ; Buršíková, V.
In this work, thermal stability and mechanical properties of Ti/Ni multilayer thin films were studied. The multilayer thin films were synthesised by alternately depositing Ti and Ni layers using magnetron sputtering. The thickness of constituent layers of Ti and Ni varied from 1.7 nm to 10 nm, and one coating was deposited by simultaneous sputtering of both targets. Single crystalline silicon was used as a substrate. The effects of thermal treatment on the mechanical properties were studied using nanoindentation and discussed in relation to microstructure evaluated by X-ray diffraction. Annealing was carried out under low-pressure conditions for 2 hours in the range of 100-800 degrees C.
Role of selected ABC transporters in breast cancer development
Perglerová, Karolína ; Souček, Pavel (advisor) ; Stiborová, Marie (referee)
Breast cancer is a leading cause of death among women in many countries. In the treatment of the breast cancer cytotoxic drugs (chemotherapy) are often used. Interindividual differences of drug response are an important cause of treatment failures. Bioavailability also depends on a major extent from the expression and activity of drug transport across biomembranes. In particular efflux transporters of the ATP-binding cassette family such as ABCB1, ABCC1 and ABCC2 have been identified as major determinants of chemoresistance in tumor cells. It was hypothesized that variance in the gene expression of membrane transporters and their genetic variance could explain at least in part interindividual differences of pharmacokinetics and clinical outcome of a variety of drugs. This thesis focuses on the functional significance of gene expression of ABCB1, ABCC1 and ABCC2 and single nucleotide polymorphisms in ABCC1 gene.
The study of the role of biotransformational enzymes in chemical carciogenesis
Kondrová, Eliška ; Souček, Pavel (advisor) ; Skálová, Lenka (referee) ; Vobořilová, Jana (referee) ; Bořek Dohalská, Lucie (referee)
In vitro biotransformation studies are an integral part of both toxicological research and drug development. They allow for a significant reduction of tests on human volunteers and provide detailed information about the metabolism of a given compound. Due to limited availability of human liver tissue, it is necessary to make use of alternative model systems and model animal species in the study of the interactions between biotransformation enzymes and xenobiotics. Since the activities of the most important human biotransformation enzymes are absent in the most commonly used laboratory species, rat, information gained in experiments with minipigs is very valuable. Recombinant human biotransformation enzymes expressed in bacteria can be used in biotransformation studies in the form of isolated bacterial membranes. These model systems provide information about the metabolism of a given xenobiotic by a defined enzyme and thein advantages compared to purified enzymes include low cost and quicker and easier preparation with lower loss of enzymatic activity during isolation. The aims of this study were: 1) To prepare a model system with recombinant human biotransformation enzymes expressed in bacterial membranes and to compare the properties of this system with minipig liver microsomes. To assess the usefulness of...
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.

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See also: similar author names
3 Souček, P.
11 Souček, Pavel
7 Souček, Petr
2 Souček, Prokop
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