|
|
Patient-derived xenograft models of human lymphomas for experimental immunotherapy
Jakša, Radek ; Klener, Pavel (advisor) ; Škarda, Jozef (referee) ; Kalinová, Markéta (referee)
Non-Hodgkin lymphomas (NHL) represent the most common hematologic malignancies. Patient-derived xenografts (PDX) are used for various aspects of translational research including preclinical in vivo validation of experimental treatment approaches. While it was repeatedly demonstrated that PDX keep majority of somatic mutations with the primary lymphoma samples, from which they were derived, the composition of PDX tumor microenvironment (TME) has not been extensively studied. We derived 15 PDX models from patients with various subtypes of aggressive lymphomas. We implemented complex genetic and immunohistochemical analysis of the established PDX models head-to-head with the patient's primary lymphoma cells, from which the PDXs were derived. We clearly confirmed that the established PDX cells shared majority of somatic mutations with the patient's primary cells, from which they were derived. Thus, from the genetic perspective the PDX models represent relevant tools for the study of lymphoma biology. Immunohistochemistry analysis of selected antigens revealed some differences between the PDXs and patients' primary cells. Importantly, the analysis demonstrated complete loss of non-malignant cellular components of the tumor microenvironment frequently observed in lymphoma infiltrated lymph nodes,...
|
|
|
Influences in the marketing environment for the selected company
HRUBEŠ, Marek
This bachelor's thesis deals with the analysis of the marketing environment of the selected company. In the practical part, the author analyses the marketing environment on the basis of the professional literature. The analysis is carried out by the selected financial indicators, the Porter´s Five Forces model and PEST analysis. In the next part of the thesis, the analytical methods applied by the company in practice are compared with those used by the author. On the basis of the outputs from the analyses and the comparison of the analytical methods, there are deduced recommendations for the company.
|
|
|
ANALYSIS OF MARKETING ENVIRONMENT IN VÝSTAVIŠTĚ ČESKÉ BUDĚJOVICE, A. S.
SUCHÁ, Veronika
Exhibitions and trade fairs have formed an integral part of the market in the Czech Republic. No matter whether its size is small, medium or large, every company becomes increasingly interested in knowledge of its environment (both internal and external). What is also important is correct assessment of internal conditions and their optimal connection with the external environment factors. The companies do not take up with the statement that there are strong and weak points, opportunities and risks. It is important to examine the factors, assess them and use the ascertained facts to increase prosperity. I used the analysis of the Porter{\crq}s Five Forces Model to ascertain the company micro-environment. I divided the collected information into two groups. The first group concerned the information about the company itself while the second one characterized the company environment (customers, suppliers and competitors). The first important group which forms a part of the company environment is the customers. The customers of the exhibition grounds in České Budějovice can be divided into two groups: the first group consists of exhibitors and traders, and the second one is the visitors. The company has various promotional and advertising printed materials elaborated by its suppliers. As far as the competitors in the Czech Republic are concerned, these are particularly the fair managements that organize fairs on the same or similar topics. As the macro-environment of the company, the whole of the Czech Republic can be defined, however, the most important part is the region of South Bohemia. In this region, the factors characteristic for the area, such as lower economic power, lower purchase power and considerable saving behaviour of the region population, have to be taken into account.
|
|
|
Phenotype of melanocytes under physiological and pathological conditions
Strnadová, Karolína ; Lacina, Lukáš (advisor) ; Mokrý, Jaroslav (referee) ; Balvan, Jan (referee)
In addition to the dominant keratinocytes and fibroblasts, melanocytes are also indispensable representatives of skin cell populations. Melanocytes are pigment cells whose primary function is to produce the pigment melanin, which is important for protecting keratinocytes from harmful ultraviolet radiation. Excessive exposure to this radiation is a risk factor for the development of skin tumours, including malignant melanoma of the skin, in which pathological transformation of melanocytes into melanoma cells occurs. The presented thesis focuses on 4 thematic areas associated mainly with malignant melanoma. In the first thematic area, the increasing incidence of malignant skin melanoma is associated with the ageing of the population. One of the reasons seems to be the more frequent occurrence of proinflammatory setting in the ageing organism. It prepares a suitable environment for tumour development. The second thematic area focuses on new approaches that could expand the range of diagnostic methods for the early detection of malignant melanoma. The first approach methodically uses the detection of proinflammatory molecules in the patient's serum. Higher serum levels of IL-6 and IL-8 correlate with an unfavourable patient prognosis. The second approach is based on the possibility of detecting a...
|
|
|
Marketing Plan for a Selected Company
Höklová, Kateřina ; Schüller, David (referee) ; Chlebovský, Vít (advisor)
Tato bakalářská práce se zabývá návrhem marketingového plánu zvolené společnosti. Hlavním cílem této práce je sestavení marketingového plánu vybrané společnosti. Teoretická část se zabývá popisem pojmů a metod, které přispívají k samostatné tvorbě marketingového plánu. Metodická část popisuje zvolenou strategii a metodiku, jak budou shromážděné informace zpracovány. V praktické části je provedena analýza okolí, konkurence a současná analýza marketingových aktivit. V poslední části najdeme návrh na úpravu a rozšíření marketingových aktivit, který je sestaven dle předchozí analýzy.
|
|
|
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...
|
|
|
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...
|
|
|
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...
|
|
|
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...
|
|
|
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...
|
guest ::
