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Centre for Prevention, Masaryk Oncology Institute in Brno
Buzová, Magdaléna ; Kraus, David (referee) ; Galeová, Nicol (advisor)
The objective of the diploma thesis is the new building of Cancer Prevention Centre, first of its kind in the Czech Republic. The site is located on steep terrain of the south hillside of Žlutý kopec in Brno, which is a part of Masaryk Oncological Hospital complex. The aim of the Cancer Prevention Centre is to attract the citizens’ attention and invite them to undergo a preventive medical check-up with the potential to save hundreds of lives every year. The project takes this fact in consideration and strives to find ways leading not only towards establishing new relationship between the building and the public, but also towards connecting the city centre and nearby by residential area with the hospital complex. The three volumes of the buildings create a dynamic composition and therefore complete the characteristic development of Masaryk Oncological Centre. The main concept however revolves around the motive of instability, balance and journey which are all linked to tumour diseases.
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P53 protein isoforms production and purification in the bacterial expression system
Vadovičová, Natália ; Obruča, Stanislav (referee) ; Brázda, Václav (advisor)
Apart from the p53 protein, the TP53 tumor-suppressor gene is expressed as another eleven protein isoforms with the use of alternative splicing, alternative promotors and alternative translational initiation sites. Abnormal expression of these isoforms has been observed in tumor tissues. The binding properties as well as the biological functions are also modulated, due to sequential and therefore structural differences from the p53 protein. p53 is regulated by these isoforms in both suppressive and supportive manner. Explanation of the p53 isoform regulation mechanism in cells could lead to desired alternative splicing of the chosen isoforms, and modulation of isoform expression could be used in cancer treatment based on p53 therapy. Basic information about p53 protein is summarised in the theoretical part of this master thesis, supplemented with recent advances in the field of p53 isoforms, as well as the Gateway cloning method. The main goal of the experimental part was p53 isoform production in a bacterial expression system. Prior to the protein production, DNA sequences coding twelve p53 isoforms were prepared using PCR and Gateway cloning. In total, twelve entry clones and eight expression clones were prepared by cloning the isoforms’ sequences. After the protein production and purification, the detection using SDS-PAGE and Western Blotting was performed with five p53 protein isoforms: p53, 40p53, 40p53 and 40p53. DNA binding properties of p53 protein isoforms will be tested in subsequent research.
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Hyaluronan for targeted drug delivery
Ureš, Tomáš ; Vávrová, Milada (referee) ; Pekař, Miloslav (advisor)
Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disacharide units containing N-acetyl-D-glucosamine and glucuronic acid. HA is present in almost all biological fluids and tissues. In many cancer cells there is an upregulation of CD44, a receptor that binds HA. The receptor CD44 collocates hyaluronan in the special way. The bioconjugates built-up from the cytotoxic substances and hyaluronan are called prodrugs. The prodrugs can be used for targeted drug delivery system. Their main advantage is there is no need to medicine so high doses of pharmaceuticals and their adverse side effects are minimized. Hyaluronan can be used as well as the intra-articulation injection by osteoarthritis. HA is also used as the nutrition of joints, by treatment for diverse dermatic lesions, the repair of scars and it can be the ingredient of eye drops and nasal sprays. The cosmetic manufactures add HA into anti-wrinkle creams and anti-aging care.
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Measurement of antioxidant markers at children with malignant tumours
Hořavová, Lenka ; Masařík, Michal (referee) ; Provazník, Ivo (advisor)
Tumour disease belongs to one of the most serious health problems of our time. Finding of new indicators to recognise the beginning of the illness is the key role for today‘s research. Oxidative stress is known to be related to the disharmony between the prooxidant concentration and antioxidant mechanisms. Moreover, it is shown that these changes are very important for patients. Further it appears that these changes are very significant with path physiologically critically ill patients. Direct measuring of the reactive oxygen radicals or oxidative stress’ markers is still very hard in clinical medicine. The oxidative stress’ level is watched as the change of the antioxidant activity or alternatively as the antioxidant status. Work is focused on the spectrophotometric fixing of the antioxidant activity and markers signalising the damage of organism. The automated photometric analyzer is going to be used to gain the experimental data. Data will be processed statically.
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Influence of liposomal platinum cytostatics on cancer cells – voltammetric study
Laníková, Petra ; Prášek, Jan (referee) ; Hynek, David (advisor)
Aim of this thesis is voltammetric study influence of liposomal platinum cytostatics on cancer cells. One of the goals is summarize available informations about influence of cisplatine on cancer cells, its encapsulation into liposome and affection of this cytostatic cisplatin encapsulated in liposome on cancer cell lines. In literary recherche is detail description of these issues. Than is there specification of voltammetric methods, which serve to electrochemical detection of cisplatin. Based on literary recherche was chosen the best method for detection and subsequently the method was optimalized and than was applied to measuring itself.
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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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