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Colorectal cancer - ways to prevention and early detection
Moravec, Martin ; Kment, Milan (advisor)
P? Ed? ASEM I got p? Íležitost closer insight into the work of one Laboratory? e AV? R. One of the p? Objects? T? the local research was colorectal carcinoma pathogenetic pathways and identification of its origin.When I m? L for? beginning of the fifth ro? exchanger choose his thesis topic, it seemed advisable to select you n what related rights? with this cancer. Its preventive employees? Measurement then related to p? SPECIFICALLY with the whole concept of our theses, which are show? conclusions of part state? re? No preventive work of doctors? Community. Colorectal cancer is a typical civilized? Her disease? It. The incidence is significant? higher in our Western, rich Euro-American population than in poor t countries? St. etího? and that significant? related to our lifestyle.V?'s New disease? for the year due to the total? the population? R is our land? to first place? St? tových statistics. This is alarming and given the great potential for primary prevention (lifestyle modifications) as well as secondary prevention (In? Same time the detection of disease? Kurabilním stage it in an appropriate screening population), this ratio becomes a topic? rn? significant. In my work I try to give an introduction to the topic of this disease? her, the knowledge of its origin and risk factors. Thus I gradually? HE...
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Peripheral metabolism of glucocorticoids in hypertensive rats
Vagnerová, Karla ; Pelouch, Václav (advisor) ; Kment, Milan (referee) ; Hampl, Richard (referee)
Klíčovým článkem periferního metabolismu glukokortikoidů Je llβ- hydroxysteroiddehydrogenasa (lI RSD), která katalyzuje přeměnu glukokortikoidů na jejich méně účinné ll-oxo deriváty a naopak a může tak ovlivnit koncentraci těchto hormonů přímo v tkáni. Existují dva isoenzymy 11HSD. llHSD2 je -schopna pouze snížit hladinu glukokortikoidů a je exprimovaná nejen v mi neralokortikoidně cílových tkáních ale i např. v p l acentě. Naproti tomu llRSDl in vivo převážně zvyšuje lokální koncentraci glukokortikoidů a je exprimovaná v nejrů znějšíc h tkáních. Přítomnost těchto isoenzymů v tkáni má obrovský význam při zprostředkování jak mineralokortikoidního tak glukokortikoidního signálu. Je známo, že mineralokortikoidy (aldosteron) glukokortikoidy (kortisol, kortikosteron) mají přibližně stejnou afinitu k mineralokortikoidnímu receptoru (MR) in vitro a navíc plazmatická hladina glukokortikodů je přibližně 1000x vyšší nežli mineralokortikoidů. In vivo dochází ovšem k specifické vazb ě aldosteronu na MR. Tato selektivní vazba je umožněna díky llHSD2, která konvertuje glukokortikoidy na méně účinné ll-oxo deriváty. Nedostatečná funkce tohoto isoenzymu vede k nadměrné aktivaci MR glukokortikoidem a tím k rozvoji hypertenze. Poslední dobou se uvažuje o tom, že v srdci a mozku, kde jsou exprimované MR a v malé míře lIRSD2,...
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Inflammation and peripheral metabolism of glucocorticoids
Leden, Pavel ; Kment, Milan (advisor) ; Hampl, Richard (referee) ; Kršek, Michal (referee)
10 Abstract Glucocorticoids play an important role in regulation of inflammation and their immunosuppressive effect is widely used for treatment of inflammatory diseases. The biological activity of glucocorticoids depends not only on their plasma concentrations, the number of receptors and the responsiveness of the target cells but also on the local metabolism of glucocorticoids that is predominated by 11β-hydroxysteroid dehydrogenase (11HSD). Two isoforms of 11HSD are known. The isoform 11HSD1 operates in vivo predominantly as a reductase that increases the local concentrations of glucocorticoids by reduction of their 11-oxo derivatives. The isoform 11HSD2 is a pure dehydrogenase that inactivates biologically active glucocorticoids to their inactive 11-oxo derivatives. The published data concerning peripheral metabolism of glucocorticoids during inflammation were obtained mostly in in-vitro studies. The aim of the thesis therefore was: (1) to study peripheral metabolism of glucocorticoids during trinitrobenzensulfonic acid (TNBS) induced colitis in rat. (2) to study peripheral metabolism of glucocorticoids in biopsies from human ulcerative colitis (3) to examine peripheral metabolism of glucocorticoids during dextran sodium sulphate (DSS) induced colitis in rat and (4) to study peripheral metabolism of...
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New markers of colon cancer evolution in ulcerative colitis
Švec, Jiří ; Kment, Milan (advisor) ; Keil, Radan (referee) ; Hampl, Aleš (referee)
Background: Long-standing ulcerative colitis (UC) has an increased risk of evolving into colorectal cancer (CRC) and upregulated expression of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK) and transcription factors c- MYB and TCF-4, has been implicated in the development and progression of sporadic colorectal cancer. Nevertheless much less is known about their role in the process of UC-associated colon carcinogenesis. Methods: We analyzed the gene expression of these markers during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry, and compared the expression profiles of this gene panel in samples of patients with CRC and in human tumor xenografts of SW620 malignant colonic cells. Additionally, we determined the expression of these genes in mouse models of sporadic and colitis-associated CRC in A/J and ICR mouse strains using quantitative RT-PCR and laser microdissection. Results: The transcript levels of survivin, c-MYB, COX-2, iNOS, and TCF-4 showed statistically significant increase during neoplastic transformation of UC-patient colonic mucosa, whereas TERT and ILK...
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The application of functional tests to measure DNA repair capacity in molecular epidemiological studies
Slyšková, Jana ; Vodička, Pavel (advisor) ; Hampl, Aleš (referee) ; Kment, Milan (referee)
DNA repair is a vital process of a living organism. Inherited or acquired defects in DNA repair systems and cellular surveillance mechanisms are expected to be important, if not crucial factors in the development of human cancers. DNA repair is a multigene and multifactorial process which is most comprehensively characterized by the phenotypic evaluation of DNA repair capacity (DRC). DRC represents a complex marker with high informative value, as it comprises all genetic, epigenetic and non-genetic factors, by which it is modulated. Accordingly, DRC reflects the actual capability of the cell, tissue or organism to protect its DNA integrity. The present PhD study was focused on investigating DRC, which specifically involves base and nucleotide excision repair pathways, in human populations with different characteristics. The main aim was to answer substantial questions on the possible use of DRC as biomarkers in epidemiological studies. The study was in fact designed to understand the extent of physiological variability of DRC in a population, its modulation by genetic and non-genetic factors, tentative adaptability to high genotoxic stress and, finally, its involvement in cancer aetiology. In order to explore these issues, DRC, in respect to genetic and environmental variability, was investigated...
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Inflammation and peripheral metabolism of glucocorticoids
Leden, Pavel ; Kment, Milan (advisor) ; Hampl, Richard (referee) ; Kršek, Michal (referee)
10 Abstract Glucocorticoids play an important role in regulation of inflammation and their immunosuppressive effect is widely used for treatment of inflammatory diseases. The biological activity of glucocorticoids depends not only on their plasma concentrations, the number of receptors and the responsiveness of the target cells but also on the local metabolism of glucocorticoids that is predominated by 11β-hydroxysteroid dehydrogenase (11HSD). Two isoforms of 11HSD are known. The isoform 11HSD1 operates in vivo predominantly as a reductase that increases the local concentrations of glucocorticoids by reduction of their 11-oxo derivatives. The isoform 11HSD2 is a pure dehydrogenase that inactivates biologically active glucocorticoids to their inactive 11-oxo derivatives. The published data concerning peripheral metabolism of glucocorticoids during inflammation were obtained mostly in in-vitro studies. The aim of the thesis therefore was: (1) to study peripheral metabolism of glucocorticoids during trinitrobenzensulfonic acid (TNBS) induced colitis in rat. (2) to study peripheral metabolism of glucocorticoids in biopsies from human ulcerative colitis (3) to examine peripheral metabolism of glucocorticoids during dextran sodium sulphate (DSS) induced colitis in rat and (4) to study peripheral metabolism of...
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New markers of colon cancer evolution in ulcerative colitis
Švec, Jiří ; Kment, Milan (advisor) ; Keil, Radan (referee) ; Hampl, Aleš (referee)
Background: Long-standing ulcerative colitis (UC) has an increased risk of evolving into colorectal cancer (CRC) and upregulated expression of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK) and transcription factors c- MYB and TCF-4, has been implicated in the development and progression of sporadic colorectal cancer. Nevertheless much less is known about their role in the process of UC-associated colon carcinogenesis. Methods: We analyzed the gene expression of these markers during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry, and compared the expression profiles of this gene panel in samples of patients with CRC and in human tumor xenografts of SW620 malignant colonic cells. Additionally, we determined the expression of these genes in mouse models of sporadic and colitis-associated CRC in A/J and ICR mouse strains using quantitative RT-PCR and laser microdissection. Results: The transcript levels of survivin, c-MYB, COX-2, iNOS, and TCF-4 showed statistically significant increase during neoplastic transformation of UC-patient colonic mucosa, whereas TERT and ILK...
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The role of Aspirin in the prevention of Colorectal Cancer
Galas, Ron Eric ; Kment, Milan (advisor)
Non-steroidal Antiinflammatory Drugs have been shown to play an important role in the chemotherapeutic prevention of Colorectal Cancer. Their mechanism in doing so has been proven as far as scientific works today allow results and an understanding of this mechanism. Without a doubt, many aspects of this drug in terms of chemotherapy tailored to the treatment of Colorectal Cancer remain to be illuminated and are subject to further investigations. Whether a cyclooxygenase inhibitor can be used as a chemopreventive agent needs to be assessed in each case individually and the whole view of a patient must be taken into account considering his overall status of health and the exclusion of the potential harm of side effects. Given the fact that these drugs provide protection of Colorectal Cancer to a certain extent, their use will most probably increase in countries where they are easily accessable.
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