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Diversity in the beauty industry and its perception in Czech environment
Kuželová, Kateřina ; Rosenfeldová, Jana (advisor) ; Ježková, Tereza (referee)
This bachelor thesis focuses on diversity in the beauty industry and its perception in Czech environment. Firstly, the theoretical framework introduces the concept of diversity marketing and describes how brands can include different underrepresented groups in their marketing strategies. For the purpose of this thesis, we recognize five such groups, namely: racial and ethnic minorities, people over the age of 50, people with various body shapes and sizes, members of the LGBTQ+ community and people with disabilities. So we focus on multicultural marketing, age-agnostic marketing, body-positive marketing, LGBTQ+ marketing and marketing strategies that include people with disabilities. Subsequently, we provide a few examples of several diverse cosmetic brands and we show that the inclusion of neglected groups can have a positive effect on consumer satisfaction and company's success. A review of previous research on diversity and its perception is then presented. In the practical part, we examine the perception of diversity in the Czech Republic. Our focus is Generation Z. The data is collected through a questionnaire. We find out how Czech Generation Z consumers perceive diversity in the cosmetics industry in general, how the inclusion of individual neglected groups is perceived, and whether and how...
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The role of mTOR complexes in immunophenotype of leukemia cells
Kořánová, Tereza ; Kuželová, Kateřina (advisor) ; Krulová, Magdaléna (referee)
Acute myeloid leukemia (AML) is a cancerous disease of hematopoiesis characterised by accumulation of immature cells (blasts) of the myeloid lineage. AML blasts utilise a range of mechanisms to escape the immune system including alteration of their metabolism or expression of inhibitory molecules. Activation of these mechanisms is not yet fully understood. One of the pathways used to regulate a great number of cellular processes is the mammalian target of rapamycin (mTOR) pathway. mTOR kinase forms two complexes, mTORC1 and mTORC2, each regulating different substrates and cellular functions. The aim of this thesis was to analyze the influence of inhibition of each of the mTOR complexes on the metabolism (oxidative phosphorylation and glycolysis) and expression of immune escape markers (HLA-I, HLA-DR, CLIP, PD-L1, TIM-3) was analysed. The inhibitor JR-AB2-011 (an mTORC2 inhibitor) reduced the mitochondrial respiration rate in the majority of the cell lines, but its impact on the cell immunophenotype was only weak. Importantly, we found that the effect on the cell metabolism did not stem from the inhibition of mTORC2. Rapamycin (an mTORC1 inhibitor) decreased both metabolic rates, as well as glucose uptake. At the same time, CLIP, PD-L1, and TIM-3 expression was reduced in all the studied cell lines,...
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Selected aspects of redox metabolism in leukemogenesis
Myšáková, Michaela ; Pimková, Kristýna (advisor) ; Kuželová, Kateřina (referee)
Blood cancers are caused by the accumulation of mutations in haematopoietic stem cells. This creates a malignant clone that has a selection advantage due to improved survival and unrestricted proliferation, a process of leukaemia development called leukemogenesis. Leukemogenesis is a complex process and it is difficult to identify a single mutation that is responsible for the transformation of haematopoietic cells. In addition to transcriptional deregulation caused by oncogenic fusion proteins, mutations in specific genes that regulate critical signaling pathways play a critical role in leukemogenesis. Examples of such genes include mutations in the isocitrate dehydrogenase 1 and 2 genes (mutIDH1/2). These genes are thought to play an important role in the development of leukaemia, as indicated by their increasing frequency in the progression of myelodysplastic syndrome to acute myeloid leukaemia. The functions of mutIDH1/2 include epigenetic regulation, changes in metabolism and redox homeostasis. It has been shown that regulation of reactive oxygen species (ROS) production and elimination, so-called redox homeostasis, is important for the proper function of haematopoietic stem cells and its disruption is a frequent phenomenon accompanying malignant transformation of these cells. Some mutations,...
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The role of NG2 glycoprotein in regulation of Rho/ROCK signaling
Kratochvílová, Magdalena ; Rösel, Daniel (advisor) ; Kuželová, Kateřina (referee)
NG2 is a transmembrane glycoprotein, which takes part in cellular processes such as adhesion, migration or invasivity, i.e., in processes important in tissue development but also in tumor and metastasis formation. Among other things, NG2 leads to an inhibition of neurite growth, and probably plays an important role in amoeboid type of cell invasion. These processes are in many respects similar. Both in inhibition of neurite growth and in mesenchymal-amoeboid transition occur morphological changes which lead to a loss of cell protrusions and a transition to a rounded shape. In both of these processes Rho/ROCK signaling also plays a crucial role. Connection between NG2 and the Rho/ROCK signaling pathway has been indicated in the process of inhibition of neurite growth. The mechanism of Rho/ROCK signaling regulation by NG2 glycoprotein is, however, still unknown. In this thesis is proposed a molecular mechanism of Rho/ROCK pathway activation by glycoprotein NG2 which relies on the NG2/MUPP1/Syx signaling complex where the scaffold protein MUPP1, bound to activated NG2, enables binding and activation of the Syx protein. Syx then as RhoGEF activates Rho/ROCK signaling, and the activated Rho/ROCK pathway leads to inhibition of neurite growth, increased cell contractility and traction forces. These processes are...
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Adhesion structures of leukemia cells and their regulation by Src family kinases
Obr, Adam ; Kuželová, Kateřina (advisor) ; Brdička, Tomáš (referee) ; Brábek, Jan (referee)
Adhesion signaling is a field of cell biology studied mostly on adherent cell types. However, hematopoietic cells grow in suspension, and use adhesion to the extracellular matrix (ECM) only in their early development, or - in case of differentiated cells - to perform the tasks they are specialized for. Peripheral leukemic cells are derived from more or less immature hematopoietic precursors that have, among other alterations, defects in adhesion to the bone marrow microenvironment. On the other hand, leukemic stem cells (LSC) use adhesion to the bone marrow ECM as a mean to evade chemotherapy, and are a source of the minimal residual disease, and of the disease relapses. Kinases of the Src family (SFK) are known regulators of adhesion signaling in adherent cell types, and their overexpression and/or hyperactivation is often seen in malignant diseases. They are also involved in hematooncologic disease progression and resistance to therapy, particularly in several types of leukemias. In the present work, we used a variety of methods including microimpedance measurement, fluorimetric measurement of adhered cell fraction, immunoblotting, confocal microscopy, and interference reflection microscopy. Our results indicate that active Lyn kinase, a hematopoietic SFK, is present in adhesion structures of...
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Analysis of the effects of Src kinase inhibitors on adhesion signaling in human hematopoietic cells
Obr, Adam ; Kuželová, Kateřina (advisor) ; Jiroušková, Markéta (referee)
Adhesion of hematopoietic cells to the bone marrow microenvironment is important for their proper development. It is proven that Src-family kinases (SFK) regulate cell adhesion, although their exact role in the regulation of adhesion signaling remains unclear. Since adhesion processes are investigated mainly in adherent cell types, far less is known about hematopoietic cells. However, defects in the cell adhesion accompany a number of hematological diseases, like chronic myeloid leukaemia (CML). SFK overexpression is one of the proposed mechanisms of resistance to the first-line CML treatment, imatinib mesylate. Second generation drugs (e. g. dasatinib) inhibit SFK together with Bcr-Abl. Additionally, SFK-specific inhibitors (PP2, Src inhibitor-1) are also available, but there are no studies about effects of these drugs on cellular adhesivity of hematopoietic precursors. To explore the dynamics of hematopoietic cell adhesion to the extracellular matrix, we introduced a new approach using the RTCA xCELLigence DP system along with the well-established method of fluorimetric detection of adherent cell fraction. Our general observation is that various drugs (dasatinib, imatinib, PP2, Src inhibitor-1) induce pro-adhesive effects in several leukemic cell lines. Direct comparison of the kinetics of...
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Molecular mechanisms of apoptosis induced by photodynamic activation in cancer cells
Moserová, Irena ; Králová, Jarmila (advisor) ; Kuželová, Kateřina (referee) ; Kovář, Jan (referee)
Photodynamic therapy (PDT) is a treatment modality for cancer. It combines selective accumulation of chemical compounds, called photosensitizers (PS), with light to irreversibly damage cancer cells via oxidative stress. The main goal of this thesis was to study photosensitizers represented by a unique group of newly synthesized porphyrin derivatives with glycol chain substitution. Glycol-functionalized porphyrins containing one to four low molecular weight glycol chains that are linked via ether bonds to the meta-phenyl positions of meso-tetraphenylporphyrin (mTPP(EG)1-4) were compared with fluorinated (pTPPF(EG)4) and nonfluorinated (TPP(EG)4) derivatives having glycol chains in para-phenyl positions. The cellular uptake and photodynamic activity was significantly dependent on terminal groups of the glycol substituent. Hydroxy glycol porphyrins, in contrast with methoxy glycol porphyrins, exhibited efficient intracellular transport and high induction of apoptosis in tumor cell lines in vitro. After initial testing effective prototype hydroxy ethylene glycol derivatives were selected and analyzed in detail. Para derivatives pTPP(EG)4 and pTPPF(EG)4 accumulated mainly in lysosomes whereas meta derivatives mTPP(EG)1-4 in the endoplasmic reticulum (ER). Position of ethylene glycol chain on the...
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Construction and characterization of chimeric antigen receptors
Ptáčková, Pavlína ; Otáhal, Pavel (advisor) ; Kuželová, Kateřina (referee) ; Havránek, Ondřej (referee)
Background: The CD19 chimeric antigen receptor (CAR) adoptive T-cell therapy for B-cell leukemia is a promising treatment for relapsed or refractory malignities. The overall response rate of CD19 CAR-T cells in clinical trials was greater than 80% for patients with B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin's lymphoma (NHL). However, CAR-T cell therapy of leukemias and solid tumors has been limited by a lot of factors such as antigen loss of tumor escape variants, reduced proliferation, persistence and tumor-infiltration of CAR-T cells in vivo, immunosuppressive tumor environment, absence of ideal antigens and on-target, off-tumor toxicities. Therefore, new strategies improving the safety and efficacy of CAR-T cells, including further T-cell modification to overcome the immune suppression, are tested. Aims: (i) Bispecific CARs designed to express two antigen-binding domains prevent of antigen escape. (ii) T-cells were genetically modified to express CAR along with an inducible IL-21 gene cassette driven by NFAT-responsive promoter. IL-21 directly enhances CAR-T cell activity and anti-tumor effects. (iii) Applying suicide epitope modification in CAR enables significantly increasing the therapeutic safety of CAR-T cells. Methods: CARs were constructed by using molecular biology...
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Significance of Tim-3 protein expression on the surface of acute myeloid leukemia cells
Kořánová, Tereza ; Kuželová, Kateřina (advisor) ; Brdička, Tomáš (referee)
Acute myeloid leukemia (AML) is a cancer disorder of hematopoiesis, characterised by production of dysfunctional progenitor cells of myeloid cell lineage. Mutations provide malignant cells with the ability to proliferate independently of growth factors and to resist to cell death induction. In addition, transformed cells are often capable of escaping the immune system. T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was originally discovered on the surface of immune cells, where it acts as an inhibitory receptor. Later, Tim- 3 was also found on leukemia cells, but its function on this cell type is much less clear. Upon ligation with galectin-9 (Gal-9), Tim-3 acts on AML blasts as an activating receptor. The Tim- 3/Gal-9 complex signalization stimulates NF-κB, β-catenin, HIF-1, PKC and mTOR pathways, which substitute to some extent the function of growth factors. They support continuous regeneration of leukemic cells, provide stimulatory signals, and further increase the production and secretion of Tim-3 and Gal-9 in a positive feedback loop. An important function of Tim-3 is the transport and localization of Gal-9, which blocks the activation of T lymphocytes by interacting with Tim-3 on their surface, inhibits formation of immunological synapse and execution of effector...
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Adhesion structures of leukemia cells and their regulation by Src family kinases
Obr, Adam ; Kuželová, Kateřina (advisor) ; Brdička, Tomáš (referee) ; Brábek, Jan (referee)
Adhesion signaling is a field of cell biology studied mostly on adherent cell types. However, hematopoietic cells grow in suspension, and use adhesion to the extracellular matrix (ECM) only in their early development, or - in case of differentiated cells - to perform the tasks they are specialized for. Peripheral leukemic cells are derived from more or less immature hematopoietic precursors that have, among other alterations, defects in adhesion to the bone marrow microenvironment. On the other hand, leukemic stem cells (LSC) use adhesion to the bone marrow ECM as a mean to evade chemotherapy, and are a source of the minimal residual disease, and of the disease relapses. Kinases of the Src family (SFK) are known regulators of adhesion signaling in adherent cell types, and their overexpression and/or hyperactivation is often seen in malignant diseases. They are also involved in hematooncologic disease progression and resistance to therapy, particularly in several types of leukemias. In the present work, we used a variety of methods including microimpedance measurement, fluorimetric measurement of adhered cell fraction, immunoblotting, confocal microscopy, and interference reflection microscopy. Our results indicate that active Lyn kinase, a hematopoietic SFK, is present in adhesion structures of...
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