National Repository of Grey Literature 33 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
The Question of Succession of James, Duke of York, during the Reign of Charles II
Chmelíková, Pavla ; Valkoun, Jaroslav (advisor) ; Vodička, Pavel (referee)
This diploma thesis deals with 70s and 80s in 17the century in England. During this period of the reign of Charles II Stuart comes to the forefront the question of succession, which culminated in the so-called exclusion crisis (1679-1681). The thesis will try to outline in seven chapters, including the introduction and conclusion, the development of the crisis of succession associated with the person of James, Duke of York. The first part of the work will focus on the period before the exclusion crisis and will highlight important moments such as the approval of the Test Act or the Popish Plot. Another part of the thesis will deal with the period of crisis itself until the dissolution of the last Exclusion Parliament in Oxford in 1681 and the defeat the Whig party. The last chapter will close the whole question of succession in 1685, the death of Charles II Stuart and the advent of James II to the English throne.
Clinical classification of sequence variants in non-coding regulatory regions in breast cancer susceptibility genes.
Bubáková, Eliška ; Ševčík, Jan (advisor) ; Vodička, Pavel (referee)
Inactivation of tumor supressor gene BRCA1 causes a life-long risk of breast carcinoma development. Genetic screenings of indicated individuals from high-risk families help to identify large number of sequence variants in known predisposing genes. Majority of discovered variants doesn't have clinical significance yet which causes a big problem for diagnostics. Some of these variants are found within regulatory non-coding regions of gene. A part of the clinical classification of variants is their functional characterization. The goal of this thesis was to create a model system for functional characterization of variants in non-coding regions and to verify its function. Model system was based on targeted gene manipulation by co-transfecting CRISPR-Cas9 construct and donor construct that contained a portion of BRCA1 gene sequence with analyzed modifications, into U2 OS cells. The cells have stably integrated DR-GFP system which allows the activity of homologous recombination (HR) to be determined. Monoallelic modifications were induced into U2 OS cells. These modifications were in a Kozak sequence region of BRCA1 gene. Expression level of BRCA1 mRNA was determined by qRT-PCR, which showed the same levels of mRNA in all cells with analyzed alterations. Next, expression level of BRCA1 protein was...
Chromosomal damage and shortening of telomeres in cancer patients and healthy subjects
Kroupa, Michal ; Vodička, Pavel (advisor) ; Kmoníčková, Eva (referee) ; Rössner, Pavel (referee)
Impaired chromosome segregation during mitosis, inaccurate DNA damage response and excessive telomere shortening may all modulate the frequency of chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL). There is evidence that increased frequency of structural CAs in PBL may be considered as a marker of enhanced cancer risk. In the present Thesis, an effect of variants in genes involved in mitotic checkpoint and DNA damage response on the inter-individual differences in CAs frequency in PBL was investigated. Considering the importance of disrupted telomere structure and its function in cancer biology, a link between telomere length and clinicopathological and molecular features of cancer patients was analysed. Furthermore, the relevance of telomere length and CAs frequency as markers of patients' survival was examined. The major outcomes of the Thesis, fully reported in detail in seven attached Manuscripts, are: I) Increased frequency of structural CAs and/or disrupted telomere length in PBL may be considered as risk factors for the different types of solid cancer; II) Telomere shortening in PBL of healthy subjects increased the frequency of structural CAs; III) Binary interactions of gene variants in mitotic checkpoint and DNA repair pathways may modulate the frequency of structural...
Molecular mechanisms involved in genotoxicity of industrially important monomers (styrene, 1,3-butadiene)
Kuricová, Miroslava ; Vodička, Pavel (advisor) ; Černá, Marie (referee) ; Machala, Miroslav (referee)
1 ABSTRACT The evaluation of individual health risk in workers occupationally exposed to industrial xenobiotics requires the use of a large number of parameters reflecting external exposure, internal exposure, biological effects and individual susceptibility. Environmental, occupational and life style-related exposure to mutagenic agents may contribute to cancer risk in humans. To prevent the potentially hazardous effects of such agents it is important to understand their mechanisms of action. Styrene is one of the most important monomer for producing polymers and copolymers in plastics, latex paints and together with 1,3-butadiene (BD) in the manufacture of synthetic rubbers. In this thesis, a large set of parameters, including markers of external and internal exposure and biomarkers of biological effects and susceptibility have been studied in relation to the occupational exposure to both styrene and BD. First part of the present study was focused on evaluating the role of various biomarkers to assess genotoxic effects of above mentioned xenobiotics. Biomarkers reflecting styrene- and BD-induced genotoxicity and mutagenicity: O6 -styrene guanine DNA adducts, haemoglobin adducts, single-strand breaks (SSBs), SSB Endo III sites, chromosomal aberrations (CA), hypoxanthine-guanine phosphoribosyltransferase...
Circulating microRNAs in rectal cancer
Červená, Klára ; Vodička, Pavel (advisor) ; Pitule, Pavel (referee)
Colorectal cancer (CRC) is the third most common cancer and one of the most common cause of cancer-related death worldwide. Early detection of colorectal cancer or precancerous lesion is a precondition for decreasing incidence and mortality CRC. Therefore, the search for new biomarkers to enable facilitate early diagnosis, prognosis and individualized treatment is particularly warranted. MicroRNA (miRNAs) are small non-coding RNA molecules involved in the post- transcriptional and translational regulation of gene expression. The discovery that miRNAs may act either as oncogenes or tumor suppressors has initiated extensive research. MiRNAs pose several advantages such as high stability, easy detection or presence in almost all body fluids. Due to these and other characteristics, circulating miRNAs aspirate to diagnostic, prognostic and predictive biomarkers of colorectal cancer. In our study, we analysed gene expression of fifteen selected miRNAs (miR-17, miR- 18a, miR-18b, miR-19a, miR-19b, miR-20a, miR-20b, miR-21, miR-103, miR-106a, miR- 133a, miR-143, miR-497, miR-564 and miR-6752) in the plasma of patients with rectal cancer and in the plasma of control group, which comprised by healthy donors of blood. In order to diminish tumour heterogeneity, we focused on rectal cancer. We discovered that...
The Role of DNA Repair in the Onset and Therapy of Ovarian Cancer
Tomášová, Kristýna ; Vodička, Pavel (advisor) ; Čáp, Michal (referee)
DNA repair and DNA damage response are very important biological systems, inevitable to maintain genomic stability and fidelity of the genetic information, for the onset of ovarian cancer. Further, DNA repair is also substantially involved in the response to the therapy, since many chemotherapeutics act as DNA damaging agents. This literary analysis is intended to survay the relevance of DNA repair to ovarian carcinogenesis. Special emphasis is placed on repair defects, as it is inextricably associated with the onset of cancer and treatment outcome. Apart from well-known alternations in ovarian cancer susceptibility genes, such as BRCA1 and BRCA2 involved in homologous recombination repair, ample space will be dedicated to less common gene mutations across different repair pathways. Research confirms that abnormalities in the proteins responsible for homologous recombination repair are the leading cause of ovarian cancer. The majority of authors also suggested that targeting DNA repair pathways, especially base excision repair, can improve chemotherapy efficiency in a synergic manner. The same applies to nucleotide excision repair, which repairs platinum-DNA adducts and thus contibutes to platinum drugs resistance emerging. By way of contrast, mismatch repair in ovarian cancer is rather poorly...
L01 DNA damage formation and DNA repair following an intervention of colorectal cell lines with ganoderma lucidum
Vodička, Pavel ; Opattová, Alena ; Čumová, Andrea ; Slíva, D.
Colorectal cancer (CRC) is the third most common malignancy in the world and second most common cause of cancer related deaths in Europe. CRC is complex disease that develops as consequence of environmental and health risk factors with involvement of suboptimal DNA repair, resulting in an accumulation of DNA damage. Reactive oxygen species (ROS) are highly reactive molecules strictly controlled by cellular antioxidant system. Disturbance in the prooxidation–antioxidation homeostasis increases an extent of ROS and consequently an accumulation of DNA damage as well as apoptosis. \nMany natural compounds possess anti-cancer activities tentatively mediated by the generation of ROS. Cancer cells are more sensitive to oxidative DNA damage than non-malignant ones. Modulation of oxidative DNA damage and its repair by natural compounds may lead to selective cancer cell-death and further sensitization of cancer cells to the treatment. Ganoderma Lucidum (GLC) (Reishi, Ling-Zhi), a mushroom used in Chinese medicine for thousands of years, represents an example of a natural compound with empirically recorded anti-cancer as well as anti-proliferative effects. \nThe aim of our study is to define effect of Ganoderma lucidum (GLC) extract on DNA damage and DNA repair system in colorectal cell lines with different genetic backgrounds.\nOur results suggest that GLC extract decreases activity of the cellular antioxidant system which leads to oxidative DNA damage. GLC extract increases genotoxic burden in colorectal cancer cell lines, highlighted by the suppressed base excision repair capacity. These data indicate that specific oxidative DNA damage caused by natural compounds may become a potential tool for the improvement of specific anti-cancer treatment.\n
Effects of natural substances on DNA damage and repair capacity in colorectal cell lines
Vodenková, Soňa ; Opattová, Alena ; Čumová, Andrea ; Slíva, D. ; Vodička, Pavel
Colorectal carcinoma)CRC) represents serious ilness with high incidence and mortality worldwide. Generaly, there is a lack of reliable predictive and prognostic biomarkers, implicated late diagnosis. The effectivity of treatment is rather low - about 50%. Main agent used in CRC treatment is 5 fluorouracil (5-FU), alone or in combination with other cytostatics. 5-FU is halogenated pyrimidine, which is or directly incorporated into DNA or disrupts thymidine synthesis in tumour cells. This damage is repaired by base excision repair (BBR) or mismatch repair. The aim of this study is to investigate the effect of 5FU together with extracts of Ganoderma lucidum (GL) and the role of BER in various lines of colorectal cancer cell lines. Results show increased oxidative damage after GL and 5FU+GL treatment and in the same time decrease of DNA repair in colorectal cell lines. This fact could contribute to improve of 5FU efficacy.
IL 57 - Sporadic colorectal cancer: From genetic make-up to complex phenotypic measurement, from risk determination to prognostic markers
Vodička, Pavel ; Slyšková, Jana ; Pardini, B. ; Naccarati, A. ; Souček, P. ; Vodičková, Ludmila ; Vymetálková, Veronika ; Svoboda, Miroslav ; Foersti, A. ; Hemminki, K.
Colorectal carcinogenesis (CRC), is a complex process, resulting in both genomic and chromosomal instabilities. The valid theories of carcinogenesis accent either the role of somatic mutation or the surrounding microenvironment, however neither of them explains all features of cancer. Uncontrolled proliferation and genomic instability point to the DNA damage response and repair as to the key players. In the present study, we will overview several biomarkers in mapping heterogeneous complex CRC disease and providing prognostic information.\nVariants in genes involved in important pathways, such as DNA repair, cell cycle control, folate metabolism and methylation, insulin resistance and obesity, ABC transporters, selenoprotein genes, genes involved in inflammatory/immune response have shown various degree of association with CRC risk. We present also the data on mutations in high risk genes involved in colorectal carcinogenesis. Gene expression levels were determined in relevant pathways and complemented with other important parameters (epigenetic regulators of transcription by methylation). Additionally, the role of post-transcriptional regulation via miRNA or lncRNA was investigated in relation to the risk of CRC and the efficacy of chemotherapy. We have discovered several genetic and epigenetic markers affecting independently the prognosis of CRC. Functional DNA repair tests (complex phenotype) have been implemented as markers of individual susceptibility to sporadic CRC and its prognosis.\nAn application of the whole set of various biomarkers is inevitable to define the phenotypic landscape of the disease and to delineate the individual response to the therapy.\n

National Repository of Grey Literature : 33 records found   1 - 10nextend  jump to record:
See also: similar author names
17 Vodička, Petr
1 Vodička, Přemysl
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