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Antigenome defines a selection of mutated tumor peptides driving tumor-specific T-cell response
Hadlová, Petra ; Drbal, Karel (advisor) ; Dibus, Michal (referee)
T cells, as an essential part of the adaptive immune system, play crucial role in eradication of tumor growth. T cells target, interact with and eventually annihilate the tumor cells in antigen- specific (Ag) manner. T cells interact with tumor cells via short epitopes bound to the major histocompatibility complex (MHC) molecules on the tumor cell surface. Tumor specific neoepitopes arise from random somatic mutations and constitute a part of the tumor antigenome. Antigenome comprises of two classes of antigens, tumor specific antigens (TSA) and tumor associated antigens (TAA). TSA are neoantigens carrying neoepitopes unique to each tumor. TAA are self-antigens presented by both tumor cells and non-transformed cells. Each tumor cell is able to develop numerous ways to evade the immune system consisting of T cells, NK cells, macrophages and other mechanisms employed. Despite that immunotherapy has shown a great potential in personalized medicine. The stratification of responsive patients is essential for effective and durable management of therapy in clinical practice. Methods are employed, which study existing reactive T cell clones, somatic mutations present in each patient, role of somatic mutations in tumor development and present neoepitopes. All these patient- specific features facilitate...
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HPLC-ED/UV for determination of vanillylmandelic acid in human urine after solid phase extraction
Němečková-Makrlíková, Anna ; Dejmková, H. ; Navrátil, Tomáš ; Barek, J. ; Vyskočil, V.
HPLC with electrochemical and spectrophotometric detection (ED/UV) after solid phase extraction (SPE) was used for determination of vanillylmandelic acid in human urine. HPLC-ED was performed at a glassy carbon electrode in a “wall-jet” arrangement in acetate-phosphate buffer at pH = 2.5 and gradient elution (increasing content of\nacetonitrile from 5 to 25% in 10 minutes) was used. Optimized parameters were following: flow rate of mobile phase 1 mL min−1, detection potential +1.1 V, detection wavelength 279 nm, injected volume 20 μL. Dependence of the peak current on the analyte concentration was linear in the concentration range from 10 to 150 μmol L−1, with obtained limits of detection 2.6 μmol L−1 (calculated from peak height) and 1.9 μmol L−1 (calculated from peak area) for HPLC-ED, and 11.0 μmol L−1 (calculated from peak height) and 9.8 μmol L−1 (calculated from peak area) for HPLC-UV.
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Somatic driver mutations during early differentiation of bladder carcinoma cell of origin
Brázdilová, Ludmila ; Drbal, Karel (advisor) ; Láníková, Lucie (referee)
A normal healthy cell traves through different routes to become a tumor cell, which according to the cell-of-origin theory initiates the whole tumor. Deregulation of cell processes by somatic mutations directs the cell into transformation. To this day, many mutations that cause a tumor phenotype, termed driver mutations, have been identified by genomic and targeted analyses. Not only for optimal therapy management but also for the prediction of disease progression the detection of driver mutations accumulating in the cell of origin of a specific tumor is very important. This thesis is focused on driver mutations of bladder carcinoma cell of origin, which is a tumor with a high mutation load. Bladder carcinomas compose a very heterogeneous group of tumors, having phenotype parallels in many other carcinomas, such as breast cancer. The driver mutations could be used as diagnostic and prognostic markers, but are not yet used in clinical practice. This thesis intends to summarize known findings about bladder carcinoma tumor initiation, based on understanding its cell of origin. Further characterisation of important driver mutations in bladder carcinoma and a comparison to other carcinomas is shown here, with respect to their molecular classification.
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Antigenome defines a selection of mutated tumor peptides driving tumor-specific T-cell response
Hadlová, Petra ; Drbal, Karel (advisor) ; Dibus, Michal (referee)
T cells, as an essential part of the adaptive immune system, play crucial role in eradication of tumor growth. T cells target, interact with and eventually annihilate the tumor cells in antigen- specific (Ag) manner. T cells interact with tumor cells via short epitopes bound to the major histocompatibility complex (MHC) molecules on the tumor cell surface. Tumor specific neoepitopes arise from random somatic mutations and constitute a part of the tumor antigenome. Antigenome comprises of two classes of antigens, tumor specific antigens (TSA) and tumor associated antigens (TAA). TSA are neoantigens carrying neoepitopes unique to each tumor. TAA are self-antigens presented by both tumor cells and non-transformed cells. Each tumor cell is able to develop numerous ways to evade the immune system consisting of T cells, NK cells, macrophages and other mechanisms employed. Despite that immunotherapy has shown a great potential in personalized medicine. The stratification of responsive patients is essential for effective and durable management of therapy in clinical practice. Methods are employed, which study existing reactive T cell clones, somatic mutations present in each patient, role of somatic mutations in tumor development and present neoepitopes. All these patient- specific features facilitate...
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