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Local steroidogenesis in peripheral tissues and its regulation
Langová, Veronika ; Ergang, Peter (advisor) ; Hudcovic, Tomáš (referee)
The innate and adaptive immune processes are modulated by hormones including glucocorticoids and by microbiota. The exact mechanisms underlying the microbial and hormonal contributions to this control are not completely clear. Present study is therefore focused to crosstalk between microbiota and de novo biogenesis or local regeneration of glucocorticoids. In particular, the study analysed the effect of commensal microbiota on expression of genes encoding steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp21a1, Cyp11b1) and regeneration of glucocorticoids (Hsd11b1) in adrenal glands, colon, spleen and mesenteric lymph nodes using conventional and germ-free mice. The expression of all 5 components of steroidogenesis was identified only in the adrenal gland and colon, whereas the lymphoid organs expressed predominantly Star, Cyp11a1 and Hsd3b1 indicating the ability to produce only progesterone but not corticosterone. Microbiota decreased the expression of Star in all studied tissues but the expression of other genes was insensitive to microbiota or did not respond homogenously depending on the tissue and gene. Hsd11b1 expression was upregulated by microbiota in the spleen but not in other tissues. Similarly, the in vitro treatment of immune cells isolated from mesenteric lymph nodes by microbial...
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Sex-specific analysis of mortality for malignant neoplasms in the Czech Republic in the years 1994-2013
Maláková, Kateřina ; Hulíková Tesárková, Klára (advisor) ; Kohoutová, Barbora (referee)
Sex-specific analysis of mortality for malignant neoplasms in the Czech Republic in the years 1994-2013 Abstract The aim of this bachelor thesis is to analyze and describe the evolution of mortality due to malignant neoplasms in the Czech Republic from 1994 to 2013 and to study mortality of malignant neoplasms by sexes in detail in the chosen spatial and temporal distribution for the purpose of identifying possible factors which can have an influence on differences between men and women. This thesis deals with mortality from selected causes of death in the malignant neoplasms in addition to the analysis of mortality for the whole group of malignant tumours. There was used standardized mortality rate as the main indicator of mortality and the probability of death by age and decomposition of the difference in life expectancy at birth by cause of death and age between 1994 and 2013 were also used as a more detailed analysis of mortality. During the reported period standardized mortality rate decreased for the whole group of malignant neoplasms and for most particular causes of death for both sexes. It was also found that the differences between men and women are rather decreasing, but for some causes of death such as malignant neoplasm of colon, malignant neoplasm of bronchus and lungs, and malignant neoplasm...
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Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
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CIrcadian regulation of miRNA and clock-controlled genes in tumorigenesis
Balounová, Kateřina ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee)
The circadian clock generates circadian rhythms, which participate on regulation of a number of signalling pathways. Disruption of the circadian regulatory mechanism is linked to a development and a progression of certain types of cancer including colorectal tumorigenesis. Progression of tumorigenesis depends on the cell cycle machinery related to cell proliferation and apoptosis. MiRNAs play a role in initiation and progression of tumorigenesis because they interfere in regulatory pathways associated with tumorigenesis. The aim of the thesis was to determinate existence of circadian rhytms in clock controlled genes (Tef, Dbp), miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-155-5p, miR-192-3p) and genes of the cell cycle machinery (Ccnd1, Ccne1, Ccna1, Ccnb1) and apoptosis (Casp3, Bcl2, Bad). Further, to compare detected circadian rhythms during aging and neoplastic transformation of colon by quantitative RT-PCR. We have observed circadian expression of Tef, Dbp, Ccne1, Ccna1, Ccnb1, Casp3 and Bcl2 in young mice colon, Tef, Dbp, miR-1-3p, Ccne1, Ccna1 in old mice colon and Tef and Dbp in colorectal tumors. In summary, circadian expression of clock controlled genes varied but was maintained in mice colorectal tumors. In aging we demonstrated weakening of circadian rhythms of the genes of the cell...
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Treatment of client suffering from Crohn's disease
Krejčí, Šárka ; Hejtmánková, Lenka (advisor) ; Lukášová Jeřábková, Lenka (referee)
The topic I chose for my bachelor thesis is the treatment of a client suffering from Crohn's disease. It consists of a theoretical and an empirical part. The theoretical part describes Crohns's disease including its history, occurrence, symptoms, treatment, impact on fertility and new findings connected to its treatment. The empirical part contains qualitative research in the form of a case study. The aim of the bachelor thesis was understanding the individual needs of a patient suffering from Crohns's disease. The case study describes the life of a woman from when the first symptoms were found till the present day. I found that the disease affects not only the physical but also the psycho-social aspect of the patients, which is often forgotten. Key words Crohn's disease, chronic inflammatory diseases, small intestine, large intestine
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Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee) ; Herichová, Iveta (referee)
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
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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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Microarray Data Interpretation
Ludwig, Petr ; Šilhavá, Jana (referee) ; Smrž, Pavel (advisor)
This Bachelor thesis explains the basics of biochip or microarray data interpretation, starting with short introduction to genetics, especially genetic information significance evaluating. The focus was set mainly on the set of scripts transforming and analyzing the sample data. The data used in this thesis are a result of biochip analysis of the Colon Tumor tissues. The secondary result represents disclosing the main marker for this particular type of cancer, the primary result is evaluation of marker significance in the context of signaling pathways. The resulting pathways are sorted by relevance.
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