|
|
Histopathologic and molecular diagnostics of lung and pleural neoplasms
Čapková, Linda ; Kodet, Roman (advisor) ; Matěj, Radoslav (referee) ; Skřičková, Jana (referee)
The aim of the presented thesis is to introduce modern molecular methods that may contribute to deepening our knowledge of pulmonary carcinogenesis. Furthermore, we would like to point out the significance of immunohistochemistry in differential diagnostics of the most common primary pulmonary and pleural neoplasms. Lung carcinoma of all histological subtypes is a result of stepwise accumulation of genetic and epigenetic changes, including allelic losses (LOH), chromosomal instability and imbalance, oncogene and tumor suppressor gene mutations, epigenetic silencing by promotor hypermethylation or aberrant gene expression guidinig cell proliferation. In our study, certain genetic changes were detected in squamous cell carcinomas (SCC) of the lung, their precancerous lesions as well as in normal bronchial mucosa in a selected group of heavy smokers with limited ventilation. We investigated the relation between molecular changes of LOH type in chromosomal regions harbouring mismatch repair genes and cell cycle regulators and human telomerase reverse transcriptase (hTERT) mRNA expression. We also evaluated the relation between these molecular changes and histologic pattern in bronchial mucosa in this patient group. hTERT mRNA expression analysis in correlation with LOH in bronchial mucosa of heavy...
|
|
|
The characterization of blood platelet cellular prion protein
Broučková, Adéla ; Holada, Karel (advisor) ; Matěj, Radoslav (referee) ; Suttnar, Jiří (referee)
The conformational conversion of the cellular prion protein (PrPc) to the misfolded isoform (PrPsc) is the central pathogenic event in the transmissible neurodegenerative prion diseases. The recently shown transmissibility of variant Creutzfeldt-Jakob disease by blood transfusion emphasizes the need for better understanding of the PrPc in blood. In the current thesis, we focused on blood platelet PrPc, which has not been very well described so far. In the first part of the thesis, platelet PrPc was characterized as glycosylphosphatidylinositol- anchored glycoprotein with dominant diglycosylated form. Platelet PrPc was shown to be sensitive to cleavage with proteinase K, which is a feature discriminating between cellular and pathological prion protein. We have confirmed that platelet PrPc binds copper ions by its N- terminal octapeptide repeat region. Regarding quantity of PrPc molecules expressed on blood elements we have proved that both platelets and red blood cells express considerable amount of PrPc and thus can not be neglected in the problematic of prions transmission by blood transfusion. The detailed study regarding PrPc localization in blood platelets is presented in the second part of the thesis. PrPc was shown to be expressed in -granules as well as on the cytoplasmic membrane of...
|
|
| |
|
|
The role of proteinases-activatable receptor - 2 (PAR-2) in pathogenesis of human disease
Matěj, Radoslav ; Mandys, Václav (advisor) ; Fakan, František (referee) ; Ehrmann, Jiří (referee) ; Rudolf, Emil (referee)
It was presented that one of the pancreatic enzymes, trypsin, modulates many biological processes by acting on specific proteinase-activated receptor 2 (PAR-2). PAR-2 belongs to a family of G protein coupled receptors activated by tethered ligand sequences within the N-terminal, which is made accessible after the site-specific cleavage of the protein. Trypsin activates PAR-2 by the mediation of a unique process inhering in the recognition of the receptor by enzyme, subsequent c1eavage at the specific site ofNH2-terminal and presentation of a new NH2 terminal, which behaves as a tethered ligand. This ligand interacts with the extracellular doma in of receptor molecule. Thus, P AR-2 is a receptor, whose I igand is a physical part of the receptor molecule. This receptor was previously described on norma I as well as ma lignant immunocompetent cells, on endothelial and muscle cells of major as well as minor vessels. Its presence was also immunohistochemically demonstrated on intestinal epithelial cells, epithcl ial cells of exocrine organs, keratinocytes, fibroblasts and other cell types in stomach, small intestine, colon, liver and kidney. PAR-2 is expressed on various cells with a wide spectrum of cellular responses after activation. ln the firs t part of th is work we focused on the role of PAR-2 dUl·ing the...
|
|
| |
guest ::
