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Mechanisms of phenotypic plasticity induced by genotoxic stress
Přibyl, Miroslav ; Hodný, Zdeněk (advisor) ; Remešová, Hana (referee) ; Vomastek, Tomáš (referee)
Therapy resistance of malignant cells represents the main reason responsible for the failure of cancer therapy. The growth of malignant cells at primary tumour sites but most importantly the dissemination of tumour cells and their growth at secondary sites, are the main reasons why patients eventually succumb to the disease. Even novel immune-based therapies find their limitation in most tumour types. The therapy resistance is mediated by the tumour cells but also by other cellular components of the tumour microenvironment. Understanding the tumour cells mechanisms and the tumour microenvironment features responsible for therapy resistance enables the development of novel therapeutic strategies. Here, we show that ionizing irradiation, 5-azacytidine, and IFNγ treatments induced expression of suprabasin (SBSN) and therapy-resistant low-adherent phenotype in cancer cells. Knockdown of SBSN resulted in suppression of the phenotype. Next, we identified aberrantly elevated SBSN in the bone marrow of a subgroup of myelodysplastic syndromes (MDS) patients. SBSN was expressed by myeloid-derived suppressor cells (MDSCs) and showed significant anti-correlation with T cell abundance and CCL2 levels, hence promises a prognostic value in clinical use. We compiled the most of the relevant knowledge of SBSN...
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Mechanisms of phenotypic plasticity induced by genotoxic stress
Přibyl, Miroslav ; Hodný, Zdeněk (advisor) ; Remešová, Hana (referee) ; Vomastek, Tomáš (referee)
Therapy resistance of malignant cells represents the main reason responsible for the failure of cancer therapy. The growth of malignant cells at primary tumour sites but most importantly the dissemination of tumour cells and their growth at secondary sites, are the main reasons why patients eventually succumb to the disease. Even novel immune-based therapies find their limitation in most tumour types. The therapy resistance is mediated by the tumour cells but also by other cellular components of the tumour microenvironment. Understanding the tumour cells mechanisms and the tumour microenvironment features responsible for therapy resistance enables the development of novel therapeutic strategies. Here, we show that ionizing irradiation, 5-azacytidine, and IFNγ treatments induced expression of suprabasin (SBSN) and therapy-resistant low-adherent phenotype in cancer cells. Knockdown of SBSN resulted in suppression of the phenotype. Next, we identified aberrantly elevated SBSN in the bone marrow of a subgroup of myelodysplastic syndromes (MDS) patients. SBSN was expressed by myeloid-derived suppressor cells (MDSCs) and showed significant anti-correlation with T cell abundance and CCL2 levels, hence promises a prognostic value in clinical use. We compiled the most of the relevant knowledge of SBSN...
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Přesnost nakládky do závěsného horizontálního krmného míchacího vozu
PŘIBYL, Miroslav
The theoretical part of the thesis entitled "Accuracy of loading into a hanging horizontal feed wagon" deals with the historical development of feed administration of cattle and currently used trends in feeding. The diploma part also describes the basic technology of production of bulky and fodder fodder, there is also a modern technology for their distribution, characteristics and the way of loading individual components of the ration, which also includes the evaluation of loading of individual components. The thesis also deals with the choice of mixing feed wagon. The practical part is focused on the evaluation of loading accuracy into the hanging horizontal feed wagon.
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Elucidation of ERK1 and ERK2 protein kinases effect on cap-independent translation initiation
Přibyl, Miroslav ; Vopálenský, Václav (advisor) ; Vomastek, Tomáš (referee)
Protein kinases ERK1 and ERK2 are one of the most studied proteins in cell signalling. Both proteins are involved in a plethora of processes, such as phosphorylation and activation of kinases as part of signalling pathways. Enzymes ERK1 and ERK2 are part of MAPK/ERK signalling cascade, connected to many cellular including cell proliferation, cell growth or differentiation. The MAPK/ERK signalling cascade is often activated in different types of tumors, making it a candidate for developing new chemical inhibitors. One of the important questions in fundamental research of ERK1 and ERK2 protein kinases is the search for difference between these proteins. Current knowledge points to redundancy of both proteins, howver several examples suggest otherwise. Recently, the work presented in Casanova et al. 2012 indirectly suggests divergent effect of ERK1 and ERK2 on cap-independent translation initiation. In the Laboratory of RNA biochemistry we focus on HCV IRES (Hepatitis C Virus Internal Ribosome Entry Site) dependent translation initiation. This diploma thesis lead to establish RNA interference method in our laboratory and to establish reporter system to study ERK1 and ERK2 effect on HCV IRES dependent translation initiation. Based on our data acquired during our research, we present in this work...
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ERK1/2 MAP kinase - Structure and Interaction Partners
Přibyl, Miroslav ; Vopálenský, Václav (advisor) ; Žíla, Vojtěch (referee)
Extracellular signal molecules are recognized by membrane receptors on the surface of eukaryotic cells. Receptors transmit the signal into the intracellular space where activation of the concrete enzymes occurs. Activated enzymes may be protein kinases that phosphorylate the substrate proteins corresponding to the requirements for specific recognition by a protein kinase. Substrate proteins may be structural proteins and enzymes, which in turn transmit the signal or directly affect the physiological processes of the cell. The protein kinase family accounts for ERK1 and ERK2 (Extracellular signal-regulated kinase 1 and 2), enzymes which affect cell growth, cell cycle and numerous other physiological processes of the cell. Protein kinases are dynamic molecules, which undergo a series of conformational changes during their catalytic cycle and whose stability and function are affected by conformational changes. Conserved amino acid residues carry out the function of protein kinases. These factors are also involved in interactions with protein substrates and regulatory proteins, and are responsible for specific function of protein kinase.
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Srovnání výkonnosti teleskopických nakladačů při rozdílných pracovních operacích
PŘIBYL, Miroslav
Thesis on Comparison of the performance telescopic loaders at different working operations analyzes of machines, the factors that affect performance loaders in construction, agriculture and the implementation of the work operations. There is also mentioned the analysis of technical parameters and binding on the size category. The second part deals with the evaluation results of the collection of data to determine the actual times loader cycles, depending on the job. The work also included the actual performance of feeders depending on opera- tions. The conclusion set out proposals for optimum machine availability on site.
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