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Microarray Data Interpretation
Ludwig, Petr ; Šilhavá, Jana (referee) ; Smrž, Pavel (advisor)
This Bachelor thesis explains the basics of biochip or microarray data interpretation, starting with short introduction to genetics, especially genetic information significance evaluating. The focus was set mainly on the set of scripts transforming and analyzing the sample data. The data used in this thesis are a result of biochip analysis of the Colon Tumor tissues. The secondary result represents disclosing the main marker for this particular type of cancer, the primary result is evaluation of marker significance in the context of signaling pathways. The resulting pathways are sorted by relevance.
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Development of methodology for detection of circulating nucleic acids in cancer patients
Kobrle, Lukáš ; Souček, Pavel (advisor) ; Valihrach, Lukáš (referee)
Cancer diagnosis represents one of the most common causes of death in the world, also linked to an ever-increasing incidence of even some more difficult-to-treat variants. One of the most common types of cancer in the world is colorectal cancer, which ranks second in terms of mortality. For these reasons, various methods have been developed for an early diagnosis of the disease. One of the modern and non-invasive methods is the so-called liquid biopsy, based on the detection of circulating DNA and RNA from the blood of patients. This method is also suitable for choosing a therapy, monitoring its effectiveness, and observing the relapse of the disease. In this work, a methodical workflow was created for the monitoring of circulating nucleic acids for its further use in a cohort of patients with colorectal cancer. Various commercial kits were used for the isolation of circulating nucleic acids from plasma of healthy controls, among which the best ones, in terms of quality and quantity, was chosen. The threshold for hemolysis detection by qPCR was also determined using samples from healthy donors. Everything was then applied to RNA samples extracted from plasma of cancer patients, from whichna library of short RNA molecules was prepared for subsequent sequencing. After processing the results, the...
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Enzymy pro aktivaci protinádorových proléčiv
Kubináková, Nikol
The current issue of oncological therapy lies in its effectiveness and severe side effects. Despite the most modern devices available for treatment methods, cancer treatment is very challenging. Chemotherapy uses highly toxic substances, which results in side effects that can only aggravate the patient. These side effects very often limit the dose of the drug, so that it is not possible to achieve such a concentration that would completely eradicate the tumor in the body. The answer to the question of how to overcome or reduce the occurrence of side effects in cancer treatment is prodrug therapy, which includes less toxic substances/drugs. This therapy aims to target cytotoxic drugs to a non-toxic derivative or prodrug. Prodrugs are inactive and bioreversible derivatives of active drugs that function as a concept for improving active drugs. After administration of the prodrug, this prodrug is selectively activated by enzymes (Cytochromes P450), resulting in the regeneration of the toxic parent drug at the site of the tumor.
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Analysis of functional interaction between PKN3 kinase and CARMIL1 protein
Novotná, Petra ; Rösel, Daniel (advisor) ; Groušl, Tomáš (referee)
Cancer cell motility and cytoskeletal rearrangements are crucial for metastasis formation. These complex changes involve multiple cellular processes affected by many different proteins. One such protein is the Ser/Thr kinase PKN3. This kinase has been shown to be essential for metastasis formation in some aggressive types of breast and prostate cancer. Interestingly, the PKN3 kinase is not only important in malignant cancers but also in normal tissues. In endothelial cells, the PKN3 kinase can alter their adhesion, or in osteoclasts it helps to promote bone resorption. The effects of the PKN3 kinase on cancer malignancy and cell motility are well documented, but the mechanism behind these effects is still unclear. Therefore, our laboratory seeks to identify novel substrates and interaction partners of the PKN3 kinase. This work focuses on a novel potential substrate of the PKN3 kinase, CARMIL1. This protein is involved in actin cytoskeleton rearrangements by regulating actin polymerisation and thus cell motility. Here we provide evidence that the PKN3 kinase interacts with CARMIL1. Key words: PKN3, CARMIL1, actin cytoskeleton, cancer, invasion
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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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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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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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Kombinace nádorové imunoterapie s blokací inhibitorů apoptózy
HAVLOVÁ, Aneta
The aim of this thesis was to study the possibility of combination of cancer immunotherapy with blockade of inhibitors of apoptosis. I described structure, functions, and the effect of these inhibitors on cancer development. Special attention was paid to the ways which can be used to block inhibitors of apoptosis. Finally I suggested the combination of blockade of these inhibitors with MBTA immunotherapy.
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