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The analysis of plasticity of cancer cell invasiveness
Merta, Ladislav
The ability of cancer cells to adopt various invasive modes (the plasticity of cancer cell invasiveness) represents a significant obstacle in the treatment of cancer metastasis. Cancer invasiveness involves various modes of migration. Cells can move together (with the preserved intercellular junctions; collective invasiveness) or individually. Within individual invasiveness, we distinguish two principal invasive modes - mesenchymal and amoeboid. The mesenchymal mode of migration is characterized by an elongated shape, proteolytic degradation of the fibres of the extracellular matrix, and the formation of strong contacts with the extracellular matrix. The amoeboid mode of migration is not dependent on proteolytic activity, the cells are characterized by a round shape and increased contractility, which they use to squeeze themselves through the pores of the extracellular matrix. This thesis deals with the analysis of the plasticity of cancer cell invasiveness, specifically the transitions between individual amoeboid and mesenchymal migration modes, in the 3D environment of the collagen gel as a model of extracellular matrix. The work presents models of mesenchymal-to-amoeboid transition (MAT), which include BLM, HT1080 and MDA-MB-231 cell lines, in which MAT is induced by the expression of...
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The analysis of plasticity of cancer cell invasiveness
Merta, Ladislav
The ability of cancer cells to adopt various invasive modes (the plasticity of cancer cell invasiveness) represents a significant obstacle in the treatment of cancer metastasis. Cancer invasiveness involves various modes of migration. Cells can move together (with the preserved intercellular junctions; collective invasiveness) or individually. Within individual invasiveness, we distinguish two principal invasive modes - mesenchymal and amoeboid. The mesenchymal mode of migration is characterized by an elongated shape, proteolytic degradation of the fibres of the extracellular matrix, and the formation of strong contacts with the extracellular matrix. The amoeboid mode of migration is not dependent on proteolytic activity, the cells are characterized by a round shape and increased contractility, which they use to squeeze themselves through the pores of the extracellular matrix. This thesis deals with the analysis of the plasticity of cancer cell invasiveness, specifically the transitions between individual amoeboid and mesenchymal migration modes, in the 3D environment of the collagen gel as a model of extracellular matrix. The work presents models of mesenchymal-to-amoeboid transition (MAT), which include BLM, HT1080 and MDA-MB-231 cell lines, in which MAT is induced by the expression of...
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The analysis of plasticity of cancer cell invasiveness
Merta, Ladislav ; Brábek, Jan (advisor) ; Šindelka, Radek (referee) ; Staněk, David (referee)
The ability of cancer cells to adopt various invasive modes (the plasticity of cancer cell invasiveness) represents a significant obstacle in the treatment of cancer metastasis. Cancer invasiveness involves various modes of migration. Cells can move together (with the preserved intercellular junctions; collective invasiveness) or individually. Within individual invasiveness, we distinguish two principal invasive modes - mesenchymal and amoeboid. The mesenchymal mode of migration is characterized by an elongated shape, proteolytic degradation of the fibres of the extracellular matrix, and the formation of strong contacts with the extracellular matrix. The amoeboid mode of migration is not dependent on proteolytic activity, the cells are characterized by a round shape and increased contractility, which they use to squeeze themselves through the pores of the extracellular matrix. This thesis deals with the analysis of the plasticity of cancer cell invasiveness, specifically the transitions between individual amoeboid and mesenchymal migration modes, in the 3D environment of the collagen gel as a model of extracellular matrix. The work presents models of mesenchymal-to-amoeboid transition (MAT), which include BLM, HT1080 and MDA-MB-231 cell lines, in which MAT is induced by the expression of...
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Oxidative phosphorylation addiciton as a new approach to the therapy of neoplastic diseases
Růžičková, Anna ; Neužil, Jiří (advisor) ; Merta, Ladislav (referee)
Neoplastic diseases belong at present time among the most frequent causes of premature death in industrialized countries. Discovery of novel approaches to their therapy is highly warranted. Recent results point to the requirement of mitochondrial respiration for tumor progression. This is linked primarily to recent discovery of horizontal transfer of mitochondrial transfer from the host to cancer cells with damaged mitochondrial DNA. This is a needed for the recovery of mitochondrial respiration, a prerequisite for tumor progression. It has appeared that the rate of respiration necessary for tumor progression differs in individual types of tumors. This hypothesis, which is refer to as 'oxidative phosphorylation addiction', however, needs to be verified. It could serve as the basis for proposing of novel therapic strategy for neoplastic diseases, using compounds that directly affect mitochondrial respiratory complexes. Key words: mitochondria, oxidative phosphorylation, horizontal transfer of mitochondrial DNA, neoplastic pathologies, mitochondrially targeted anti-cancer agents
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Cell viability changes after interaction with TiO2 nanoparticules and anthracycline cytostatics
Kondělková, Regina ; Štenglová Netíková, Irena (advisor) ; Merta, Ladislav (referee)
The goal of this thesis is to conduct a literary research about cell viability changes after interaction with TiO2 nanoparticules and anthracycline cytostatics. Anthracycline cytotoxic agents are one of the most commonly used groups of antineoplastic drugs, particulary doxorubicin. A serious side effect of anthracyclines in para drug administration (extravasation) is necrosis of the surrounding tissue. Effective treatment for this side effect is not available as of yet. One possible way could be to use sorption and degradation characteristics of nanoparticles of TiO2, which are non-toxic to the human body. Anthracyclines are characterized by rapid adsorption to the surface of nanoparticles of TiO2 and subsequent degradation to non-toxic products. Therefore further I deal with the use of nanoparticles of TiO2, their unique chemical properties and the way they affect cell viability, especially keratinocyte cell lines in vitro. It has been shown that there is no reduction in cell viability when culturing keratinocytes together with TiO2 nanoparticles and thus it opens the door for further studies on the use of nanoparticles of TiO2 for the treatment of necrotizing anthracycline extravasation.
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Organization and mobility of G protein-coupled receptors in plasma membrane
Merta, Ladislav ; Svoboda, Petr (advisor) ; Sýkora, Jan (referee)
This diploma thesis deals with the analysis of structural and dynamic organization of thyrotropin releasing hormone receptor (TRH-R) and δ-opioid receptor (DOR) within plasma membrane (PM) in relation to the specific sub-compartments of PM denominated as domains or membrane rafts. Modern fluorescence microscopy techniques FLIM, FRAP and RICS were used for this purpose. The experiments were performed on the live cells derived from HEK293 cell line. To reach the main goal of this work, the integrity of PM structure was altered by depletion of cholesterol which was performed by incubation of cells with β cyclodextrin. Results clearly support our previously suggested idea that the vast majority of TRH-R is localized in non-raft regions of plasma membrane. This work also compared different modes of performance of FRAP and results obtained by FRAP and RICS because these methods are to some extent analogous. This is one of the first works that used the RICS approach to characterize the G protein-coupled receptors. In the second part of this work, the setup of transient transfection of the HEK293 cells with DOR-ECFP and DOR EYFP constructs was established. Simultaneously, the functionality of these constructs, i.e. the ability of DOR to activate the cognate G protein was determined. Powered by TCPDF (www.tcpdf.org)
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