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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana ; Anděra, Ladislav (advisor) ; Rudolf, Emil (referee) ; Vondráček, Jan (referee)
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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Immune cells infiltrating premalignant lesions and invasive carcinomas associated with HPV infection
Dalewská, Natálie ; Tachezy, Ruth (advisor) ; Španielová, Hana (referee)
The immune system participates in many defence mechanisms of the body which in- volve the action of different types of immune cells. Immune cells play an important role in tumour development and progression. They infiltrate tumours and contribute to the tumour microenvironment. They are also implicated in diseases associated with human papillomavi- rus infection. Human papillomaviruses are viruses with oncogenic potential which cause in- fection in a number of anatomical locations of the human body. Such infection can lead to benign lesions, pre-invasive lesions, and invasive tumours. Pre-invasive lesions often re- gress spontaneously, but at advanced stages of the disease, progression to malignancy can occur. The tendency to regress or progress varies depending on the HPV genotype involved in the lesion and the quantity, type, and location of infiltrating immune cells. The synergy of these factors influences the prognosis and treatment of the disease, and, therefore, deter- mining the immunological score as an important diagnostic parameter becomes of utmost relevance. The knowledge of the effect of immune cells on tumour cells is useful in immunotherapy, which is based on the activation of the patient's own anti-tumour immune mechanisms. Immunotherapy is used in combination with systemic therapy...
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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana ; Anděra, Ladislav (advisor) ; Rudolf, Emil (referee) ; Vondráček, Jan (referee)
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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Spatio-temporal PM2.5 variability in village during winter.
Štědrá, Karolína ; Hovorka, Jan (advisor) ; Bendl, Jan (referee)
This thesis evaluates the spatial variability of PM2.5 concentrations during two winter months in the small village Lbín close to Teplice at the turn of the year 2017/2018. The PM2.5 concentrations were monitored through a dedicated monitoring network using a total of eight DustTrak laser nephelometers (Model 8520). Six DustTraks were located directly in the village in the valley, one of them was located on the hill above the valley and the last one was located approximately in the half of the hill. Using a network measurements, we tried to determine that the household heatings are the main sources of air pollution in the village. The basic meteorological parameters - wind speed and direction, temperature and air humidity were monitored together with PM2.5 concentrations. It was observed statistically significant difference between the measuring stations, which points to the unevenly distribution of pollution sources. The particle concentrations typically reach peak values in the morning and in the evening. The maximum peak values were 2607 μg·m-3 in December and 4347 μg·m-3 in January. The lowest maximum values were 223 μg·m-3 and 177 μg·m-3 for devices located above the village. An important factor contributing to the current situation was wind speed. If the wind speed was higher than 1,29 m·s-1...
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Immune cells infiltrating premalignant lesions and invasive carcinomas associated with HPV infection
Dalewská, Natálie ; Tachezy, Ruth (advisor) ; Španielová, Hana (referee)
The immune system participates in many defence mechanisms of the body which in- volve the action of different types of immune cells. Immune cells play an important role in tumour development and progression. They infiltrate tumours and contribute to the tumour microenvironment. They are also implicated in diseases associated with human papillomavi- rus infection. Human papillomaviruses are viruses with oncogenic potential which cause in- fection in a number of anatomical locations of the human body. Such infection can lead to benign lesions, pre-invasive lesions, and invasive tumours. Pre-invasive lesions often re- gress spontaneously, but at advanced stages of the disease, progression to malignancy can occur. The tendency to regress or progress varies depending on the HPV genotype involved in the lesion and the quantity, type, and location of infiltrating immune cells. The synergy of these factors influences the prognosis and treatment of the disease, and, therefore, deter- mining the immunological score as an important diagnostic parameter becomes of utmost relevance. The knowledge of the effect of immune cells on tumour cells is useful in immunotherapy, which is based on the activation of the patient's own anti-tumour immune mechanisms. Immunotherapy is used in combination with systemic therapy...
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Link between inflammation and cancer
Schierl, Jaroslav ; Poljaková, Jitka (advisor) ; Miarková, Eva (referee)
Chronic inflammation caused by many initiators can lead to a development of a tumor disease. Among these initiators, we found chronic infections as well as other biological, chemical or physical factors which have endogenous and exogenous origins as for example tobacco smoke, alcohol, radiation, obesity and others. The inflammatory response is orchestrated by immune system cells which contribute to a tumorigenesis by producing reactive oxygen and nitrogen species which harm cell structures, and by releasing cytokines - important mediators of inflammation - which increase cell proliferation and angiogenesis. But apart from higher risk of tumourigenesis due to chronic inflammation, the immune system cells also participate in tumor microenvironment formation. The main contributors are tumor associated macrophages, dendritic cells and T-cells. Besides other things, the complex tumor microenvironment is characterized by the presence of many inflammation mediators which assist in malignant cell proliferation, tumour progression and metastasis and angiogenesis. This bachelor thesis describes the key protumor and antitumor factors which are also involved in the inflammation process. These factors include proinflammatory cytokines, enzymes and transcription factors. The transcription factor NF-κB plays an...
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Ekonomická analýza odvětví vinařství České republiky
Havlínová, Sabina
This Master's Thesis aims to review current wine grape production in the Czech Republic. External and competitive environment analyses and other methods from financial analysis are used here. A theoretical part of the thesis contains definition of strategy and strategic management. Beside that there are defined base tools used for macro-environment and micro-environment analyses. A practical part of the thesis is focused on PEST analysis, a delimitation of current wine grape production and competitive market. The practical part also covers main obstructions in entering to the wine industry. Last two parts of the thesis assess situation of wine grape production in the Czech Republic. SWOT analysis for the future evolution of this industry are included.
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Marketing analysis of Lidová jídelna Těšnov
Svoboda, Lukáš ; Vávra, Oldřich (advisor) ; Škranc, Oldřich (referee)
The main goal of this Bachelor´s Thesis is a marketing analysis of Lidová jídelna Těšnov and a proposal for a possible strategy of a new product, which is providing dinners. For the analysis, I will explore the macro environment using PEST analysis and the micro environment thanks to Porter's five forces analysis. Then I will look at the marketing mix and SWOT analysis of this company. Using these tools, I will compare an existing business strategy with a testing strategy of selling a new product (dinners), including promotion and communication with public. I will use also knowledge from questionnaires and detailed information from business owner. In conclusion, I will write some recommendations and suggestions for the new business strategy of selling dinners, including its promotion and communication.
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