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Influence of microchimeric cells on tumor growth
Šimková, Lucie ; Tlapáková, Tereza (advisor) ; Peltanová, Barbora (referee)
Microchimerism is caused by the presence of few genetically different cells in the human body. Microchimerism can arise, for example, during pregnancy, during which the bilateral cell migration occurs. The maternal cells that the child acquires during pregnancy and subsequent breastfeeding help to shape its immune system, for example. Blood transfusion or transplantation is another possibility for microchimerism. Microchimeric cells can be stored in an individual's body for decades and can thus also affect their health. These cells have stem cell-like attributes that allow them to incorporate into the damaged tissue. As a result, they can have a positive effect on tissue repair, but they can also cause autoimmune diseases or influence the development or suppression of cancer.
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The longevity in mole rat.
Jelínková, Alena ; Schierová, Michaela (advisor) ; Španielová, Hana (referee)
Naked mole rat and blind mole rat are useful model organisms for human age-associated diaseases studies. Unlike human, their long lifespan is not accompanied by physical health impairment. In both species, the genes involved in aging process or carcinogenesis are under positive selection or their regulation differs from the regulatory pattern known in other rodents or human. Some genes are present in higher number of copies, missing or entirely new and not observed in other organisms. In naked mole rat, the degenerative development is reduced by elevated level of proteins which prevent amyloid β aggregation and contribute to oxidative damage tolerance. Their healthy aging is also caused by effective elimination of damaged proteins, natural caloric restriction or angiogenesis enhancement. High level of α-2-macroglobulin in blood, which is able to inhibit signal pathways required for tumor growth and malignancy, as well as the early contact inhibition repress tumorigenesis in naked mole rat. Many different mechanisms are involved in prolonged lifespan in both naked and blind mole rat species. The aim of this thesis is to present the most important genome and proteome differences contributing to their long lifespan. Key words: naked mole rat, blind mole rat, tumorigenesis resistance, senescence,...
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Oncoretroviruses: tumor transformation mechanisms of hematopoietic cells resulting in leukaemia
Gašpareková, Mária ; Bendová, Michaela (advisor) ; Mrvová, Silvia (referee)
HTLV-1 and FeLV are retroviruses, which are able to transform host cells and cause cancer, mostly leukemia, in infected organism. Belonging to Retroviridae family and both using very similar genome, these viruses developed different ways to reach transformation of infected cells. While FeLV uses insertional activation close to cellular proto-oncogenes in order to regulate transcription of these genes or carries cellular oncogene in its genome, HTLV-1 codes viral proteins which are able to regulate many processes of the cell. One of these proteins is Tax, which regulates many events in the cell, such as signalization, cell cycle, apoptosis and others. Another protein responsible for oncogenesis is HBZ, which is transcribed from antisense strand of proviral DNA. In the end HTLV-1 and FeLV strategies causing cancer are compared with some other leukemic retroviruses in order to show, that molecular strategies described on examples of HTLV-1 and FeLV are more or less common also for other oncogenic retroviruses. Key words: HTLV-1, FeLV, transformation, leukaemia, tumor, oncogene
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MicroRNAs in Human Cancers Associated with Viral Infections
Dvořáková, Lucie ; Tachezy, Ruth (advisor) ; Drda Morávková, Alena (referee)
MicroRNA (miRNA) are short single-stranded RNAs that do not encode proteins. Their main function is the regulation of the gene expression on the level of translation. This regulation is mediated by the binding of miRNA to the partially complementary segments of mRNA, both cellular or viral. It is estimated that miRNAs affect expression of at least one third of human genes and thereby influence regulation of cellular growth, differentation and apoptosis of cells. Recently the miRNAs encoded mainly by DNA viruses were discovered. These miRNAs enhance the persistence of viral infection in the host and can contribute to malignant transformation. However, the oncogenesis is also significantly affected by the regulation of cellular miRNAs expression by viral proteins. The miRNA research is topical. MiRNAs are considered as potential biomarkers and their utilization as a cancer therapy is being intensely explored. In this thesis, I'm describing the biogenesis and regulatory functions of miRNAs. I'm also presenting an overview of viral miRNAs focusing on human oncogenic viruses which do not only code their own miRNAs but also influence the expression of the host miRNAs. Finally, I am focusing on current clinical applications of miRNA. Key words: viral miRNA, cellular miRNA, oncogenesis, viral infections,...
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The effect of Crk SH3domain inhibition in invasiveness of cells
Tomášová, Lea ; Rösel, Daniel (advisor) ; Vomastek, Tomáš (referee)
Protooncogene Crk was found to be upregulated in tumours with aggressive and invasive potential. The adaptor protein Crk has an important role in cell signaling: it integrates signals from activated integrins and growth factors receptors via its SH2 domain and transmits the signal to its SH3 domain binding partners that activate the small GTPases Rac1, Rap1 and Ras. This leads to regulation of cell migration, proliferation and survival. The aim of this thesis project was to inhibit the Crk dependent signaling by a competitive inhibition of the Crk SH3 domain, using a high affinity CrkSH3 binding peptoid. Binding of the inhibitor to the Crk SH3 domain prevents binding of cellular Crk SH3 interaction partners and the corresponding signal transmission is impaired. In this thesis project the effect of the Crk SH3 inhibition on the invasiveness of cancer cells was analyzed. The observed inhibitory effect on cell invasion as well as on anchorage independent growth provides a proof of therapeutical relevance of targeting CrkSH3N domain by peptoide-based inhibitors. Powered by TCPDF (www.tcpdf.org)
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