|
|
Diagnostic and prognostic markers in the era of targeted treatment of CRC.
Veškrňová, Veronika ; Büchler, Tomáš (advisor) ; Mohelníková Duchoňová, Beatrice (referee) ; Valík, Dalibor (referee)
Introduction: Colorectal cancer (CRC) is the most common malignant tumor in both sexes in the Czech Republic. Prognostic factors in CRC can be classified as clinical (stage at the time of diagnosis, histological type of tumor), genetic (RAS, BRAF), immunological (Immunoscore)and biochemical (CEA, CA 19-9, miRNA). MicroRNAs (miRNAs) regulate the expression of oncogenes and tumor suppressors. The regulatory function of miRNAs is influenced by single nucleotide polymorphisms (SNPs) of target miRNA binding sites (miRSNPs). Aims: To evaluate the currently available prognostic factors for CRC patients treated using targeted therapies and assess the role of novel ones, including miRNA. Methods: The thesis includes clinical works focused on targeted treatment of colorectal cancer, original work focused on the role of miRNA in colorectal cancer pathogenesis and especially as a prognostic and predictive marker, work focused on functional polymorphisms of DNA repair genes and a review article summarizing biochemical factors influencing the effect of fluoropyrimidine cytostatics in the treatment of colorectal cancer. Results: We have identified miR-17/92 as a non-invasive biomarker for predicting post-treatment prognosis in patients with a higher risk of relapse, as well as miRSNPs rs8679 polymorphisms as a...
|
|
|
A pathogenity of adenylosuccinate lyase deficiency
Zikánová, Marie ; Kmoch, Stanislav (advisor) ; Adam, Tomáš (referee) ; Valík, Dalibor (referee)
Adenylosuccinate lyase (ADSL) is an enzyme acting in two pathways of purine nucleotide metabolism. Mutations in ADSL gene compromising the enzyme activity lead to an inherited metabolic disease with severe neurological involvement - ADSL deficiency. Three distinct clinical phenotypes can be distinguished based on onset and severity of symptoms. The pathogenic mechanisms leading to the development of symptoms and underlying the phenotypic heterogeneity are unclear. The main pathogenic effect is attributed to the toxic effects of accumulating succinylpurines (SAdo, SAICAr). Their concentrations in cerebrospinal fluid, particularly diverse SAdo/SAICAr ratio, do correspond with the phenotypic groups. It is hypothesized that it may result from a mutation specific and thus structural related non-parallel loss (or gain) of enzyme activity towards one of its substrates. The main goal of the thesis is to seek for biochemical and structural basis of the diverse SAdo/SAICAr ratios and thus explain a pathogenetic mechanism of ADSL deficiency.
|
|
| |
|
| |
|
| |
guest ::
