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The Earliest Graves in Saint Vitus Cathedral and Their Dating Issue
Vrána, David
During the years 1995–2018, inspection research was carried out for graves K1 and K2 discovered under the Saint Wenceslas Chapel floor in Saint Vitus Cathedral, on the site of the former rotunda with the same consecration. The results of radiocarbon dating of the human remains and the wooden structure, as well as other findings, indicate an origin in the 9th century, however, putative stratigraphic problems obstruct the acceptation of these results. A belief prevails that the graves were dug only after the rotunda’s erection, or rather after the building of the alleged later annex for the south apse that contains the grave of Saint Wenceslas. This opinion is based on the finding of masonry inside the apse that was detected under the later Gothic altar and that was interpreted as the remains of the demolished foundation of the rotunda nave. Based on the latest evaluation, it seems more likely that the relics under the Gothic altar are connected with the earliest stage of the altar and the foundation altar step (gradus altaris). Covering the dead in grave K1 with lime or mortar was also identified as a stratigraphic issue, nevertheless, it must have been done after the deceased was placed in the grave. Similarly, the findings of marlstone and mortar fragments in the corner of grave K1 during the archaeological inspection in 1995 provide no evidence that the grave was dug only after the erection of the rotunda because it is most likely only secondary contamination. The identification of the deceased persons remains uncertain, but morphology features and the blood group of the man in grave K1 suggest his affiliation with the House of Přemyslid. Based on current findings, the hypothesis of E. Vlček about the identification of the dead from grave K1 with Prince Bořivoj I (†890) cannot be ruled out, yet the buried woman in the neighbouring grave K2 indicates the need to search for another explication that only a new successfully conducted DNA analysis would confirm.
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Pharmacogenetic prediction of tamoxifen efficiacy and adverse effects in hormonal dependent breast karcinoma patients.
Argalácsová, Soňa ; Slanař, Ondřej (advisor) ; Vrána, David (referee) ; Paluch, Zoltán (referee)
ABSTRACT/SUMMARY Background: The clinical efficacy of tamoxifen therapy may be modified by the drug-metabolizing enzymes and transporting molecules involved into the pharmacokinetics of tamoxifen. The aim of this study was to evaluate the association of CYP2D6, ABCB1 polymorhisms and comedication with efficacy and safety of tamoxifen treatment. Methods: Totally 258 women with hormonal positive breast carcinoma were retrospectively evaluated in relation to CYP2D6, ABCB1 polymorphisms and comedication. Results: CYP2D6 polymorphisms or co-medication affecting CYP2D6 activity demonstrated no statistically significant effect on the efficacy of tamoxifen therapy or adverse event incidence; there was only a trend towards shortening the time to event (TTE) in CYP2D6 poor metabolizers. ABCB1 polymorphism rs2032582 was not associated with clinical outcomes, while a trend towards an increase of TTE in variant allele carriers was noted. The ABCB1 polymorphism rs1045642 demonstrated statistical significance in premenopausal patients (p = 0.0012, HR 0.69 (95% CI 0.21 to 2.31), and its significant association was noted with gynaecological /vasomotor adverse events (p = 0.0221, HR = 1.0588), with no evidence of the influence on the incidence and onset of venous complications. Conclusions: Although this work did not show...
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The Changes of the Tumor Vascular Endothelial Growth Factor Expression and the Density CD8+ Tumor Infiltrating Lymphocytes after Neoadjuvant Chemoradiation in Patients with Rectal Adenocarcinoma
Buka, David ; Petera, Jiří (advisor) ; Vrána, David (referee) ; Mohelníková Duchoňová, Beatrice (referee)
Rectum adenocarcinoma is one of the most frequent tumour diseases in the Czech Republic. Therefore any progress in therapy or prevention of this disease can have a significant impact on mortality and morbidity of major amount of oncological patients. Within therapy the neoadjuvant concomitant radiochemotherapy or the sole radiotherapy is used before surgical resection in one third to half of all newly diagnosed cases. The goal is to achieve tumor downstaging and local relaps probability decrease. There is a large amount of processes on molecular and cellular level in organism reaction to neoplasia genesis, whose understanding can have a substantial impact on therapy's success rate or on therapy's efficiency prediction. One of these processes is angiogenesis induced by high production of vascular endothelial growth factor (VEGF). As per immunohistochemical studies VEGF is not expressed in typical colorectum mucous membrane. However it is strongly expressed in case of adenocarcinoma. Another important process of organism's malignancy response is tumour tissue infiltration by CD8+ T lymphocytes (TIL), which are one of the important components of cellular immunity against tumour and which significantly contribute to tumour cells elimination. Potential of CD8+ T lymphocytes is considerable not just in...
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Genetic polymorphism of biotransforming enzymes and risk of pancreatic cancer development in Czech Republic
Vrána, David ; Novotný, Jan (advisor) ; Holubec, Luboš (referee) ; Kološtová, Věra (referee)
Genetic polymorphism of biotransforming enzymes and risk of pancreatic cancer development in Czech Republic Objective: Pancreatic cancer represents one of the biggest challenges of present-day oncology. It effects mainly effects patients in sixth or higher decade of life and due to minimal symptoms in early stages, it is usually diagnosed in locally advanced or metastatic stage of the disease. The only modality which represents a possible chance for long term survival is radical surgical resection. Chemotherapy and possible targeted therapy have only a palliative role. Due to the above mentioned facts, it would be highly useful to identify genetic factors, which could play a role in pancreatic cancer development and create specific screening program which could identify early stages of the disease. We have focused our study on gene polymorphisms in biotransforming enzymes, which modify carcinogen and procarcinogen metabolism and may represent risk factors for pancreatic cancer. Methods: We have included 278 pancreatic cancer patients into this study. As a control group we have chosen healthy volunteers from general practicioner clinics and healthy blood donors. We have focused on gene polymorphisms in biotransforming enzymes CYP1B1, EPHX, NQO1 GSTP1, GSTT1, GSTM1. DNA was amplified by PCR,...
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Protection of the population and measures against weapons of mass destruction in former Czechoslovakia from 1950's until the 1970's
Vrána, David ; Parkan, František (advisor) ; Koura, Petr (referee)
Presented diploma thesis is pursued to the topic of conceptual evolution of civil protection in the last century's 50's to 70's period. This period of time, population safety was secured by so called Civil Defence. Noticeable atribute of all the Civil Defence measures impacting population was mainly protection against mass destruction weapons. That is why protection against mass destruction weapons is given the most attention in this diploma thesis. Target of the thesis is historical analyse concerning Civil Defence and its evolution in Czechoslovakia in noted period. Out of it the thesis sketches also general formation and evolution of civil protection in previous period. Diploma thesis is done based on study of available literature and mainly based on accessible sources from military archive in Prague. Thesis is divided to six chapters, chronologically describing the most important milestones in Civil Defence conceptual evolution. Emphasis is laid on description of its organisational structure and way of population protection against mass destruction weapons. During studies of these sources, the emphasis was laid also on military evaluation of country territory according to level of expected threat by aerial attack that time, or later by nuclear weapon of mass destruction in case of war conflict....
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Pharmacogenetic prediction of tamoxifen efficiacy and adverse effects in hormonal dependent breast karcinoma patients.
Argalácsová, Soňa ; Slanař, Ondřej (advisor) ; Vrána, David (referee) ; Paluch, Zoltán (referee)
ABSTRACT/SUMMARY Background: The clinical efficacy of tamoxifen therapy may be modified by the drug-metabolizing enzymes and transporting molecules involved into the pharmacokinetics of tamoxifen. The aim of this study was to evaluate the association of CYP2D6, ABCB1 polymorhisms and comedication with efficacy and safety of tamoxifen treatment. Methods: Totally 258 women with hormonal positive breast carcinoma were retrospectively evaluated in relation to CYP2D6, ABCB1 polymorphisms and comedication. Results: CYP2D6 polymorphisms or co-medication affecting CYP2D6 activity demonstrated no statistically significant effect on the efficacy of tamoxifen therapy or adverse event incidence; there was only a trend towards shortening the time to event (TTE) in CYP2D6 poor metabolizers. ABCB1 polymorphism rs2032582 was not associated with clinical outcomes, while a trend towards an increase of TTE in variant allele carriers was noted. The ABCB1 polymorphism rs1045642 demonstrated statistical significance in premenopausal patients (p = 0.0012, HR 0.69 (95% CI 0.21 to 2.31), and its significant association was noted with gynaecological /vasomotor adverse events (p = 0.0221, HR = 1.0588), with no evidence of the influence on the incidence and onset of venous complications. Conclusions: Although this work did not show...
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