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The role of caspase-3 in apoptosis
Kolářová, Karolína ; Tlapáková, Tereza (advisor) ; Anděra, Ladislav (referee)
Caspases provide anti-inflammatory, apoptotic and developmental processes in organisms. They are enzymes with a wide range of activities in all cells, and various pathogeneses can occur if their proper function is disturbed. Since the 1990s, caspases have been a topic of interest for scientists, as their direct link to the triggering of apoptotic processes is a promising possibility for the therapy of diseases related to apoptosis, such as cancer, neurodegenerative diseases, but also cardiac ischemia and diabetes. The cascade of apoptotic processes is controlled by the aforementioned caspases, which are located in the caspase cascade. When the cascade is triggered in a cell, it is due to the presence of a "danger" signal, which can be very different. The most well-known triggers of the apoptotic cascade include activated Fas receptor and FasL ligand, cytochrome c present in the cytoplasm, an imbalance of IAPs in the cell, damaged DNA, and many others. Upon receipt of a signal, initiator caspase-2, caspase-8, and caspase-9 are activated, which in turn activate effector caspases-3, caspase-6, and caspase- 7, cleaving many substrates to promote apoptosis. Thus, caspase-3 is the effector enzyme responsible for the actual execution of apoptosis. However, caspase-3 properties are not only apoptotic, it...
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Transcriptomic analysis of Mesocestoides corti
Korená, Lucie ; Leontovyč, Roman (advisor) ; Převorovský, Martin (referee)
Some species of parasites, including helminths, can inhibit carcinogenesis in their hosts. The antitumoral effect has been discovered in the tapeworms Taenia crassiceps and Echinococcus granulosus, which genes associated with cancer regression have been identified. The effect of melanoma suppression has also been observed in tapeworm Mesocestoides corti by the Laboratory of Helminthology, Department of Parasitology, Faculty of Science, Charles University, however the mechanism-of-action, remains unknown. For the upcoming research it was essential to have the complex molecular data such as transcriptome of the developmental stage s of M. corti. This work is focused on the transcriptomic profiling of the tapeworm M. corti and the differential gene expression in two different strains of murine hosts (inbred and outbred) using the RNA-Seq. The main goal was to identify upregulated transcripts in the tapeworms from the murine hosts that could have a potential effect on cancer regression. Differential gene expression analysis was performed, and the results showed that tapeworms in murine hosts (regardless of strain) had more upregulated transcripts than tapeworms cultured in vitro. Analysis of highly upregulated transcripts in the tapeworms that were grown in the murine hosts identified several...
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Metabolism of the mitotic inhibitor BTB-1 by first phase biotransformation enzymes
Vančurová, Kateřina ; Indra, Radek (advisor) ; Martináková, Lenka (referee)
Cancer is still one of the most common deaths in the world and therefore new drugs are needed to be developed to stop or slow down this disease. Recently, there has been a huge expansion in drug development. Cytostatics that are still widely used include a group of mitotic inhibitors aimed at inhibiting mitosis. A representative of a mitotic inhibitor is the small newly discovered molecule BTB-1. This molecule mediates reversible inhibition of the molecular motor Kif18A, which plays an important role in cell division. In the first part of this presented bachelor thesis, a suitable method for the determination of BTB-1 using high performance liquid chromatography was developed and subsequently its sensitivity was verified. Furthermore, a suitable extracting reagent was found. In the second part of the bachelor thesis, the metabolism of BTB-1 was studied by the microsomal system of non-premedicated rats and rats premedicated with various cytochrome P450 inducers. Subsequently, the time dependence of BTB-1 conversion was studied by the microsomal system of premedicated rats. The effect of different concentrations of BTB-1 on its metabolism was also studied using the microsomal system of premedicated rats. Furthermore, the metabolism of this new molecule was studied using cytosolar systems isolated...
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Targeting IRAK4 kinase in autoimmune diseases and cancer
Synáčková, Alžběta ; Dráber, Peter (advisor) ; Brdička, Tomáš (referee)
Immune system provides host protection against invading pathogens. However, aberrant activation can lead to development of autoimmune diseases or cancer. Understanding the mechanisms of inflammation and immune responses is crucial for treatment of such conditions and reestablishing immune balance. Toll-like receptors and interleukin-1 family receptors are a key component of the innate immune system. Their downstream molecules, MyD88 and IRAK4, are essential for receptor signaling as their deficiency causes host susceptibility to infection. On the other hand, overactivation of this pathway was shown to be able to promote autoimmunity and cancer. The main focus of this text will be to summarize current knowledge about the mechanism of IRAK4 signaling and how it can be exploited in the development of therapeutics. Keywords IRAK4, MyD88, Toll-like receptors, IL-1 receptor, cytokines, autoimmunity, cancer
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Role of Exosomes in the Progression, Diagnosis, and Treatment of Brain Tumors
Vaníková, Lucie ; Zíková, Martina (advisor) ; Lacina, Lukáš (referee)
Recent studies have confirmed the importance of extracellular vesicles, particularly exosomes, in the development of brain tumors. Considerable attention has been paid mainly to the influence of exosomes on biological processes in brain tumors. Exosomes mediate intercellular communication in the tumor microenvironment by transporting biomolecules. Most often they transmit various types of ribonucleic acids, specifically microRNAs, which affect the signalling pathways related to tumour growth in target cells. Thus, exosomes play an important role in tumor cell proliferation and differentiation, metastasis, and tumor resistance to chemotherapy or radiation. Due to their small size, exosomes can cross the blood-brain barrier and thus promote tumor progression. The topic of the bachelor thesis is a summary of the current knowledge on the role of exosomes in brain tumor progression, diagnosis and treatment.
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Tumours in historical and social context in the modern period
Hrudka, Jan ; Komárek, Stanislav (advisor) ; Tinková, Daniela (referee) ; Stingl, Josef (referee)
Univerzita Karlova v Praze Přírodovědecká fakulta Studijní program: Filosofie a dějiny přírodních věd MUDr. Jan Hrudka Nádory v dějinném a kulturním kontextu v novověku Tumours in historical and social context in the modern period Disertační práce Školitel / Supervisor: Prof. RNDr. Stanislav Komárek, Dr. Praha, 2017 SUMMARY: The PhD thesis called Tumours in historical and social context in the modern period is an attempt to describe a change of medical thinking in modern period; science and medicine turns from antique humoral pathology, explaining all diseases as an imbalance of the four body humours, to pathological anatomy and experimental physiology. In the point of view of pathological anatomy, the viscera of diseased person are no more "screen" or "mirror" of the disease, but it becomes directly the "stage" or "theatre" of the acting disease. This shift in the thought may be labelled as movement from humoralism to localism or ontologism; the disease isn't just abnormal amount of some natural juice any more, but becomes new original entity. This change undergoes the understanding of tumours and cancerous disease as well. Instead of antique understanding tumours as precipitates of black bile, the cell theory occurs in the 19th century. This theory explains tumours as a mass of cells undergoing excessive...
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Vliv chemoterapie a genotoxického stresu na imunologické vlastnosti nádorových buněk.
Horňáková, Michaela ; Reiniš, Milan (advisor) ; Drbal, Karel (referee)
Cancer treatment includes the use of chemotherapeutic agents, which have various effects on tumour cells, such as direct toxicity to cancer cells, immunogenic cell death induction and changes in cancer cells phenotype. Throughout the last decade many researchers have been focusing on the induction of genotoxic stress and cellular senescence, which chemotherapy can trigger. Even though induction of senescence in cancer cells represents an important mechanism for tumour suppression, there has been increasing evidence that shifting cancer cells into a senescent state by chemotherapy is not always beneficial. Senescent cells are associated with a specific secretory phenotype, which allows such cells to alter their microenvironment, modulate anti-tumour immunity, induce tumour suppression and even promote cancer development. Therefore, senescent cells elimination by innate or specific immunity, which can be boosted by immunotherapy, can be an important barrier preventing tumour growth. Powered by TCPDF (www.tcpdf.org)
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Mechanism of tumor development and its influencing by ellipticine
Parisová, Martina ; Stiborová, Marie (advisor) ; Moserová, Michaela (referee)
Ellipticine (5.11-dimethyl-6H-pyridate [4,3-b] carbazole) is a powerful anti-cancer agent, exhibiting multiple mechanisms of action. This work describes the causes of cancer processes and summarizes the main pharmacological mechanisms and cytotoxic effects of ellipticine together with the results found in our laboratory indicating, a new mechanism of ellipticine action. Cytotoxic and mutagenic activity of ellipticine is attributed to its two mechanisms of activity ellipticine intercalation into DNA and its effectivity to inhibit topoisomerase II. Ellipticine also forms covalent DNA adducts after its oxidation with cytochromes P450 and peroxidases. Cytochromes P450 oxidize ellipticine up to five metabolites, of which 13- hydroxyellipticin, 12-hydroxyellipticin and N(2)-oxide of ellipticine are responsible for formation of two major DNA adducts. In the case of peroxidases, ellipticine is oxidized to a radical producing the ellipticine dimer and a minor ellipticine metabolite, the N(2)-oxide of ellipticine. Because of the high efficiency of ellipticine and its derivatives against various types of cancer, this coumpound is studied in detail. Its utilization for drug tangeting is a challenge for further study.
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Obesity its causes and cosequences
Ondráčková, Anna ; Vybíral, Stanislav (advisor) ; Kuda, Ondřej (referee)
Obesity is one of the most common health problems in the Word. Over 500 million adults and over 40 million children are obese. The aim of this work is to summarize findings of causes and consequences of this health problem. Even though in some cases only genetic mutations are responsible for obesity for example mutation in ob gene or Prader-Willi syndrome most cases are caused by lifestyle of people -excessive food intake and insufficient physical activity. There are many health problems accompanying obesity. The most serious problems are metabolic syndrome, diabetes mellitus, cardiovascular diseases and cancer. The consequences of obesity are, however, not confined only to health. We can also observe the economic consequences. Financial cost of treatment of obesity and related diseases are estimated in billions of dollars. Pharmacological treatment has so far proved to be ineffective. If drugs are effective, the side effects are so severe that their use is not possible. So far, the adipose tissue hormones that regulate food intake provide the best hope.
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The communication Strategy of Nonprofit Organization Movember Foundation in the Czech Republic
Steinbergerová, Zuzana ; Shavit, Anna (advisor) ; Klimeš, David (referee)
The bachelor thesis Communication Strategy of Nonprofit Organization Movember Foundation in the Czech Republic presents international nonprofit organization which focuses on men's health. The first part of thesis focuses on history of the organization and its missions. The thesis continues with a chapter in which is explained the role of marketing in nonprofit organizations then marketing goals in the organization are defined. The next part of the thesis is concentrated on communication strategy of the organization in the Czech Republic. This part also analyzes who are target audiences and defines competitors among other nonprofit organizations within the same area of interest. Furthermore this chapter presents communication activities in two time periods: 2009- 2012 and 2013-2015 and analyses them. The next part concerns author's own research, which will reveal awareness of the organization in the Czech Republic. Moreover research will show if Czechs consider the organization as trustworthy institution or not. In addition to that, research will disclose if the organization was successful in terms of increasing the awareness of male's cancer during the 7- year-period of its presence in the Czech Republic. The last chapter of the thesis recommends how Movember Foundation can improve its...
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