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Checkpoint blockade in cancer immunotherapy
Vacková, Julie ; Šmahel, Michal (advisor) ; Černý, Jan (referee) ; Říhová, Blanka (referee)
The immune checkpoint blockade is a novel approach of cancer therapy, which markedly enhanced treatment efficacy of several cancer types. However, the frequency of cancer patients non-responding to this treatment is high. Establishment of predictive markers to distinguish patients suitable for the immune checkpoint blockade would enhance the number of patients receiving benefit from the therapy. This dissertation thesis focuses on the enhancement of efficacy of immune checkpoint inhibitors (ICIs) and predictive markers in experimental models of mouse tumours induced by TC-1 and TC-1/A9 cell lines and its clones with deactivation of interferon (IFN)-γ signalling (TC-1/dIfngr1 and TC-1/A9/dIfngr1), or CD80 molecule (TC-1/dCD80-1). IFN-γ is presumed to be the main inducer of programmed death ligand 1 (PD-L1) and a major histocompatibility complex I (MHC-I). Moreover, PD-L1 expression may predict sensitivity to PD-1/PD-L1 blockade. Non-functional IFN-γ signalling or downregulated MHC-I expression has been associated with resistance to ICIs in some patients. We found that IFNs type I (IFN-α and IFN-β) induced the expression of PD-L1 and MHC-I on TC-1/A9/dIfngr1 tumour cells with reversible downregulation of both molecules. We also showed that deactivation of IFN-γ signalling in TC-1/A9 cells was not a...
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The cooperation between professional fire unit of central Bohemia region and volutary fire unit with predisposition to traffic accidents.
VACKOVÁ, Eliška Julie
In the diploma thesis "Cooperation of Fire Rescue Brigade of Central Bohemia Region and Voluntary Fire Brigade Corps Units of Municipalities with Predestination for Traffic Accident Interventions", the author dealt with the evaluation of possibilities of cooperation in traffic accidents between fire brigade units of Central Bohemia and voluntary fire brigade units of municipalities destined for rescue and liquidation accidents. In the theoretical part of the thesis there are given the basic terms from the area of rescue of injured persons from crashed vehicles, legal and internal regulations dealing with this issue and criteria for fulfillment of predetermination for rescue work in traffic accidents - professional training, numbers and equipment with mobile fire equipment and material means fire protection for rescue. The next chapter in the theoretical part is the concrete activities of fire protection units in the type of traffic accident. The conclusion of the theoretical part consists of the existing situation in the Central Bohemian Region - description of transport infrastructure, area coverage of the region by fire protection units destined for rescue work in traffic accidents and statistics of accident rate on roads for 2018, in which the fire brigade of the Central Bohemia Region and units of voluntary fire brigade units of municipalities intervened predestined for rescue work in traffic accidents. The practical part presents the results of the questionnaire survey. For this questionnaire survey, the first representative sample of the survey was selected by the commanders of voluntary fire brigade units of municipalities of the Central Bohemian Region destined for rescue operations in traffic accidents. The second representative sample of the survey was selected by guarantors for individual territorial departments of the Central Bohemian Fire Rescue Service for rescue together with instructors for rescuing injured persons in road accidents at individual stations of the Fire Rescue Service of the Central Bohemia Region. The survey was carried out for a defined set in the form of a semi-structured questionnaire. Individual questionnaires were evaluated on the basis of the survey in Chapter 3. Discussion. This evaluation found that no one is a clear opponent of volunteer fire brigade units in municipalities destined for rescue operations in traffic accidents and their traffic accidents are desirable, but there is still plenty of room for improvement. As a measure to increase the efficiency of cooperation between the fire brigade units of the Central Bohemian Region by voluntary fire brigade units of municipalities with a predestination for rescue work in traffic accidents, it was recommended to newly determine the units of voluntary fire brigades of municipalities for rescue work in road accidents in the Central Bohemian Region where unit of Fire Rescue Brigade of Central Bohemia Region has a long range. Furthermore, it was recommended to create internal regulations regulating the minimum equipment of mobile fire fighting equipment and material fire protection equipment for rescue of volunteer fire brigade units of municipalities destined for rescue work in traffic accidents and to develop a new internal regulation regulating the requirements of training fire brigade units as they are confusing.
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Mechanisms of immunosuppressive drug-mediated effect on mesenchymal stem cell properties
Vacková, Julie ; Krulová, Magdaléna (advisor) ; Grobárová, Valéria (referee)
Mesenchymal stem cells (MSC) defined as multipotent, nonhematopoietic stem cells have been shown to possess various immunosuppressive properties. Thus they can be used to attenuate transplant rejection and also for treatment of autoimmune diseases. But simultaneously with MSC patients take immunosuppressive drugs and there is no evidence how this medication affect MSC. The goal of this study is to elucidate how frequently used immunosuppressive drugs cyclosporineA, mycophenolate mofetil, rapamycin, dexamethasone and prednisone influence immune-related parameters of mice and human MSC. Here we show that MSC from various sources are affected differentialy after short-term exposure of the tested immunosuppressants. Only cyclosporine A does not change immune-related parameters of mice MSC in the comparison to other immunosuppressants. However, cyclosporine A, mycophenolate mofetil and rapamycin enhance human MSC expression of TSG-6, PD-L1 and TGF-β which are involved in inhibition of lymphocyte proliferation and effector function, inhibition of dendritic cell maturation and in support of tolerogenic phenotype of macrophages. Although glucocorticoid drugs promote survival of human MSC and expression of Fas-L they reduce expression of molecules that mediate immunosuppression. In this respect, the best...
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Effect of parasites on haematological traits in vertebrates
Vacková, Julie ; Vinkler, Michal (advisor) ; Svobodová, Jana (referee)
Deviation out of homeostasis is reflected by physiological stress and altered immunological activity leading to changes in blood composition. Haematological examination may reveal deflection from the long-term optimum-the state of health. Haematological changes associated with parasitism are in some cases so distinctive that they allow the estimation of the parasite type affecting the host health. I aim to summarise basic methods utilised in veterinary haematology and evaluate the influence of individual groups of parasites on haematological parameters related to red and white blood cells. In vertebrates the most significant haematological changes are caused by multicellular endoparasites. Typical is eosinophilia and increased total leucocyte count. Ectoparasites are usually responsible for decrease in erythrocytes and increase in leucocytes. Extracellular bacteria increase total neutrophil and lymphocyte counts while intracellular bacteria cause decrease in all blood cell types. Viruses often decrease number of erythrocytes and leucocytes and change neutrophil/lymphocyte ratio. Changes in the haematological parameters caused by protists are difficult to generalize and not much is presently known about the influence of fungi on the blood composition in vertebrates. Variation in the effect of...
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Basic knowledge of firefighters in the unit voluntary municipal fire brigade
VACKOVÁ, Eliška Julie
In my Bachelor Thesis "Basic knowledge of the firefighter in the unit of the voluntary fire brigade of the municipality" I dealt with the level of professional knowledge of members of the units of volunteer municipal fire brigades. To evaluate the level of expertise, three units of volunteer fire brigade were selected as a representative sample and subjected to the verification of their expertise in the form of a written test. All selected and tested units belong to the Mlada Boleslav Territorial Department and these are Category III Fire Units. On the basis of the tests carried out, after the evaluation of the tests, it was found that the level of expertise of the members of the voluntary municipal fire brigade units was insufficient. Only 30% of the members of the volunteer fire brigade units of the municipalities tested were "successful". Due to the unsatisfactory result of the testing and therefore the low level of expertise of the members of the municipal volunteer fire brigade units, it is proposed to amend the Guideline of the General Director of the Fire Brigade of the Czech Republic No. 3/2014 on the training and professional competence of members of Volunteer Fire Brigade of the municipality and Volunteer Fire Service of company. Units. The aim of the proposed modifications is to make the training more effective and thus to increase the level of expertise of members of the municipal volunteer church corps units. The theoretical part describes the history of professional competence and the implementation of training, the training of members of the Volunteer Municipal Firefighters' Units and its legal regulation. The difference between basic and regular training, including their solution and focus, is described. It also describes the training of commanders and engineers and specialized courses for members of the Volunteer Fire Brigade units of municipalities. At the end of the theoretical part is described the physical preparation of members and performing verification and tactical exercises.
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