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Analysis of dietary intake and major dietary sources of omega-3 fatty acids in cancer patients.
Balušková, Denisa ; Gojda, Jan (advisor) ; Těšínský, Pavel (referee)
Introduction: nutrition of cancer patients is a frequently discussed topic. Tumor growth is conditioned by the production of pro-inflammatory cytokines in the body, which leads to metabolic changes and the development of tumor cachexia syndrome. Immunomodulatory nutrition and efforts to at least partially control inflammation are essential in cancer. Aim of the study: The aim of the study was to evaluate the dietary intake of omega-3 fatty acids in the diet of cancer patients and to analyse the main dietary sources of these polyunsaturated acids. Research Methods: In this observational and questionnaire-based non-interventional study, 10 respondents who had not shown signs of cancer for more than a year, were older than 18 years and according to the highest frequency of cancer incidence were selected. Results: The average daily intake of omega-3 FAs in the study group was 1.59 g/day for both sexes, which represents 53% of the recommended therapeutic dose of 3 g/day (DLD). In contrast, the average daily intake of omega-3 FAs in men was found to be 1.47 g/day, corresponding to 49 % of the DLD. Conclusion: Analysis of the dietary intake of cancer patients in remission suggested that their intake of omega 3 fatty acids is minimal and does not even reach the recommended values for the general...
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Analysis of Cancer-Associated Protein Mutations
Borko, Simeon ; Martínek, Tomáš (referee) ; Musil, Miloš (advisor)
PredictSNP ONCO is a web tool that analyses the impact of protein mutations on the development of oncological diseases. The tool integrates several bioinformatics tools and provides the result of its own predictor, which classifies mutations as oncogenic or benign. Apart from that, PredictSNP ONCO provides the results of a virtual screening of drugs that could inhibit the function of affected proteins. The web interface is freely available at https://loschmidt.chemi.muni.cz/predictsnp-onco/.
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Small Molecules as Immune Modulators in Anticancer Therapy
Pavlovová, Anna ; Míšek, Jiří (advisor) ; Smrček, Stanislav (referee)
The aim of this bachelor thesis was to summarize knowledge about several selected therapeutic targets used for cancer immunotherapy and small molecules that can have an immunomodulatory effect on these targets. This is a relatively new and attractive topic in the field of biomedical sciences, which is constantly evolving. Some small molecules have already been approved for treatment of specific cancer diseases, and many more are currently undergoing various stages of clinical trials. This work should provide the reader with an overview of possible approaches to modulate the immune system using small molecules. Key words: small molecules, immunotherapy, cancer, checkpoint inhibitors, tumor microenvironment
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Production and characterisation of therapeutical antibody Farletuzumab - Thiomab E154C S378C
Mochánová, Michaela ; Brynda, Jiří (advisor) ; Dračínská, Helena (referee)
5 Abstract The human folate receptor α (FRα) is a receptor that binds folic acid, which as one of the vitamins is required for basic cellular processes, cellular growth, and differentiation. FRα's expression is strictly regulated in healthy tissue but is highly overexpressed in some tumor types. A humanized monoclonal antibody against folate receptor α called Farletuzumab has been developed. Binding of Farletuzumab to FRα leads to the activation of the immune system via antibody-dependent cytotoxicity and complement-dependent cytotoxicity. To enhance the antitumor effect, selected amino acids in the Farletuzumab antibody molecule were mutated to cysteines, allowing the subsequent use of THIOMAB technology. These cysteines are used to specifically conjugate the antibody to an artificial effector molecule that triggers the cGAS-STING (cyclic GMP-AMP synthase - stimulator of interferon genes) signaling pathway. The combination of the antibody's own anti-tumor effect and the triggering of the immune response to the cGAS-STING signaling pathway maximizes the immune response against cancer cells. Therefore, the aim of my work was to express the antibody in a suitable eukaryotic cell system and then to do a basic characterization of the protein. The Farletuzumab Thiomab antibody was prepared by heterologous...
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Role of NAV3 in glioblastoma cells invasiveness
Legátová, Anna ; Brábek, Jan (advisor) ; Libusová, Lenka (referee)
The invasion of tumor cells from the primary lesion and the formation of metastases are the main reasons for the severe impact of cancer diseases. An option for dealing with this poor impact is the development of drugs (so-called migrastatics) that would target these processes and thus limit the spread of tumor cells from the site of the primary tumor. However, to develop such drugs, it is essential to clarify the molecular mechanisms that control or promote cell migration. One of the possible strategies for migrastatics development is the targeting of cytoskeletal structures, which play an indispensable role in cell migration. This work is focused on Neuron navigator 3 (NAV3), a protein that binds to + ends of microtubules (MTs), participates in their stabilization, and is able to mediate crosstalk between MTs and the actin network. The function of NAV3 is important for directing MTs into growing axons and proper neurite outgrowth, which is necessary for brain development. The results of this thesis suggest that NAV3 could act as a pro-tumor factor, which localizes not only to the + ends of MTs, but also to the cell protrusions, and whose presence supports the cell expansion and increases the invasive potential of glioblastoma cell lines. Key words: neuron navigator 3, microtubules, cancer,...
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Mannan-BAM, TLR ligands, and anti-CD40 immunotherapy in established murine pancreatic adenocarcinoma: understanding therapeutic potentials and limitations
VENHAUEROVÁ, Anna
The aim of this RNDr. Thesis is focused on understanding therapeutic potentials and limitations of the antitumor MBTA immunotherapy which is based on synergy of TLR agonists, anti-CD40, and phagocytosis stimulating ligands anchored into the tumor cell membranes. In this study, immunotherapy was tested in murine pancreatic adenocarcinoma Panc02 model. Firstly, the short-term and long-term efficacy of MBTA therapy was tested using established subcutaneous Panc02 tumors two times larger than in previous study. Secondly, the work is devoted to better understanding of the adaptive immunity involvement focusing on CD4+ and CD8+ T lymphocytes during the therapy and their effect on tumor volume reduction, long-term survival and resistance against tumor rechallenge. Subsequently, the ability of immunological memory to cross over the blood-brain barrier confirming its potential applicability in metastatic brain tumors was examined. Moreover, the antigen specificity of the immunological memory was evaluated. Finally, the potential of MBTA therapy to cure metastatic disease, represented by bilateral Panc02 mouse model, was studied. In this case, the MBTA therapy manifested a lower therapeutic response. Therefore, it was combined with diverse therapeutic approaches, such as intratumoral application of anti-CTLA-4 antibody, heat-killed Listeria monocytogenes, chemoablation using EtOH, targeting the tumor microenvironment by hyaluronidase, simultaneous injections of MBTA therapy in primary and secondary distant tumors, and its combination with RT. Despite all these combinations, our results showed that only simultaneous application of MBTA therapy into both tumors has potential for the treatment of the bilateral Panc02.
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Study of the substrate specificity of the LACTB tumour suppressor enzyme
Baudyšová, Alžběta ; Kečkéšová, Zuzana (advisor) ; Janečková, Lucie (referee)
Serine beta-lactamase-like protein (LACTB) is a tumour suppressor that modulates mitochondrial lipid metabolism and induces differentiation of breast cancer cells. This is achieved by the LACTB-dependent downregulation of phosphatidylserine- decarboxylase (PISD) which subsequently leads to decreases in the amounts of phosphatidylethanolamines and lysophosphatidylethanolamines in mitochondrial membranes. However, PISD was shown to not be a direct substrate of the LACTB enzyme what leaves the identity of the LACTB substrate an open question. To fill this important gap in the mechanism of the LACTB tumour suppressive pathway, this diploma thesis was focused on finding a physiological substrate of LACTB via Proteomic Identification of protease Cleavage Sites (PICS) assay. For this purpose, the other sub-aims of this project were to isolate recombinant wild-type LACTB and its catalytic mutant, to reveal ideal in vitro conditions for LACTB activity and to find out the requirements needed for LACTB multimerization. My results show that in vitro activity of LACTB is increased in the presence of higher pH and calcium ions. I also show that higher LACTB multimeric forms are bound together via disulfide bonds as they disintegrate after treatment with dithiothreitol. Furthermore, and most importantly, I show...
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Radiotherapy and skin care
NOVÁKOVÁ, Karolína
The bachelor thesis on the topic "Radiotherapy and skin care" deals with the adverse effects of ionizing radiation on the skin in the context of radiotherapy and how to care for the irradiated skin in terms of prevention of these adverse effects. The aim of the thesis was to describe the principle of radiotherapy and its effect on the human body, especially on irradiated areas of the skin, which may be more susceptible to adverse effects. The thesis is divided into theoretical and practical parts and is divided into 6 chapters. The theoretical part focuses on the principles of radiotherapy, the adverse effects of ionizing radiation, specifically the adverse effects on irradiated skin and the possibilities of skin care. The practical part of the thesis deals with a questionnaire survey. The research design of the thesis was carried out by means of a questionnaire survey among cancer patients. The questionnaire was designed in a semi-structured form and then statistically processed. The results obtained from the questionnaire survey provide information on the level of awareness of cancer patients about the side effects of radiotherapy, their correct or sufficient instruction about the side effects, and their knowledge of proper care of irradiated skin to prevent radiation damage or to mitigate the effects of adverse effects on irradiated skin. The results of this work can be used as study material for radiology assistants and medical students to add to their professional knowledge of the effects of radiotherapy on the skin, or can also serve to streamline the process of providing information on the care of irradiated skin.
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