|
|
Creating a knowledge base for the diagnosing of diseases
Macháček, Daniel ; Steinerová, Kateřina (referee) ; Jirsík, Václav (advisor)
This bachelor thesis is focused on problematic of creation knowledge base. It is describing basics of expert systems, their function and possible usage in modern world. In result of this thesis is knowlenge base in web aplication NPS able to diagnose diseases of hematology-oncology and that is proving possibility for use in real life. Knowledge base was created in cooperation with experts in the medical field and contains real data.
|
|
| |
|
|
The role of asparagine synthetase in leukemic cells
Šafrhansová, Lucie ; Starková, Júlia (advisor) ; Čuřík, Nikola (referee)
This thesis focuses on the detection of mutations in the enzyme asparagine synthetase on leukemia cell metabolism and the role of this enzyme in the context of L-asparaginase- based chemotherapy. The experimental part of the work is divided into two separate sections. Given the lack of asparagine synthetase gene sequencing data in leukemias, the first objective was to determine whether mutations are present in the leukemia cell line that could affect ASNS function and thus play a role in the resistance of leukemia cells to ASNase therapy. No mutations that could affect the activity of the enzyme were detected by next-generation sequencing. In the second part, a model of RS4;11 that expresses ASNS was established. The effect of ASNS on glycolysis was then studied to sensitize these cells to the effects of L-asparaginase and to the depletion of asparagine and glutamine. It was observed that ASNS expression increased the level of glycolysis and increased the resistance of these cells to asparagine and glutamine depletion and their resistance to asparaginase. Key words: ASNS, aspragine, leukemia, L-asparaginase, chemotherapy, drug resistance
|
|
|
Novel methods of treatment of B cell malignancies based on immunotherapy with genetically modified T cells
Novotná, Natálie ; Otáhal, Pavel (advisor) ; Šmahel, Michal (referee)
CAR T cell therapy represents a promising method in treatment of hematological malignancies. Gene immunotherapy uses modified T cells that express a chimeric antigen receptor (CAR) on their surface. Modified T lymphocytes are able to recognize and destroy target cells based on specific surface markers. Although CAR T cell therapy is used in clinical practice, there is a number of limitations that reduce its effectiveness. The aim of this thesis is to explore new possibilities of making the entire therapy more efficient through endogenous secretion of interleukins (IL-7, IL-15, IL-21) under the control of inducible promoters, and thus to strengthen the persistence and expansion of CAR T cells in vivo. For this purpose, inducible expression systems containing the gene for CAR19 receptor specifically recognizing the CD19 molecule and the interleukin gene located under inducible NFAT or NR4A promoters, were constructed. The assembled vectors were electroporated into PBMC cells using the PiggyBac transposon system to achieve stable expression in T lymphocytes. After co-cultivation with RAMOS cell line, data were obtained by measurement on a flow cytometer and the ELISA method. Based on the results, it is evident that stimulated CAR T cells are able to generate higher concentrations of interleukins,...
|
|
|
Age-specific analysis of leukemia incidence and mortality
Soukupová, Alžběta ; Kulhánová, Ivana (advisor) ; Altová, Anna (referee)
The purpose of this bachelor's thesis is to analyze the trends in incidence and mortality from leukemia in Czechia with special focus on the trends by gender and age. The analysis of the incidence of leukemia was conducted between 1980 and 2018 and the analysis of mortality in the period between 2003 to 2020. The period for mortality had to be shortened due to the availability of the necessary data. For both analyses, standardized rates were calculated. Due to the low number of deaths, the standardized death rates were divided into larger age groups and combined into six-year periods. Based on the results, it was found that the incidence of leukemia is increasing in Czechia. The number of new cases of disease and death increases with age and is higher in men than in women. The trends in mortality in women is more stable than in men. Acute forms of leukemia dominate in childhood and cases of chronic leukemia begin to appear with age. In senior age, both types are represented equally. The largest number of people die each year from the acute myeloid leukemia (AML) and the least from the acute lymphoblastic leukemia (ALL). In the chronic types of this disease, such as chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML), there are frequent fluctuations over time and their development...
|
|
|
Identification and characterization of novel regulators of hematopoietic stem cell function
Grušanović, Srđan ; Alberich Jorda, Meritxell (advisor) ; Balounová, Jana (referee) ; Froňková, Eva (referee)
Hematopoietic stem cells (HSCs) are sitting atop a carefully orchestrated system, called the hematopoietic system. HSCs maintain the constant production of mature blood cells throughout our life, and dysregulated HSC function may lead to severe health problems including bone marrow aplasia and leukemia. Thus, HSC activity needs to be tightly controlled by a complex network of cell intrinsic and cell extrinsic factors. In this thesis, we focus on two previously uncharacterized extrinsic mechanisms that might be involved in the regulation of HSC function. A common aspect of these mechanisms is the production of pro-inflammatory cytokines. First, we investigated the impact of donor NK cells on donor HSC function upon bone marrow transplantation, a frequent clinical intervention. We observed that NK cells negatively affect HSC engraftment and reconstitution during transplantation. To address the potential mechanism, we employed Cebpg knockout mice, which produce non-functional NK cells, and determined that NK cells affect HSC activity through the production of IFNγ. Remarkably, IFNγ-blocking antibodies improved murine and human HSC activity upon bone marrow transplantation. Altogether, we concluded that suppression of inflammatory signals generated by donor innate immune cells can have a significant...
|
|
|
Use of radiotherapy in treatment of children with leukemia
PAVLIŠTÍKOVÁ, Veronika
This bachelor thesis deals with the use of radiotherapy in childhood leukemias and is divided into a theoretical part and a part of practical patients. The theoretical part generally describes the introduction to the physiology of blood, it also deals with the issue of hematological diseases treated before transplantation of blood cells in hematopoiesis, which include myelodyplastic syndrome and leukemia. It also describes the types of leukemia that occur in pediatric patients. The chapter dealing with the diagnosis of the disease describes the physical and biochemical examination, blood count and differential budget of white blood cells, bone marrow examination, immunological and molecular biological examination. A large part of the theoretical part deals with the treatment of the disease, which describes the available treatment methods, such as cytostatic treatment or chemotherapy, the principle of blood stem cell transplantation and its distribution, not least radiotherapy, which describes the technique of total body irradiation and prophylactic irradiation of the cerebellum. The last-mentioned treatment methods include alternative treatment and supportive treatment, which deals with transfusion of blood derivatives, prevention and treatment of infectious complications, nutrition and rehabilitation. It also describes the side effects of treatment and their therapy. Finally, the theoretical part focuses on psychological and social issues. In the practical part, the data concerning patients with leukemia are processed using the NIS system at the Department of Pediatric Hematology and Oncology in Prague at the Motol University Hospital. The results of the work are summarized in the discussion and conclusion. The aim of the bachelor thesis was to describe the treatment of leukemia in pediatric patients and to analyze the severity of side effects of radiotherapy treatment.
|
|
|
Tumor Specific Signaling in T-Cell Lymphoma
Kulinich, Viktoriia ; Havránek, Ondřej (advisor) ; Kužílková, Daniela (referee)
T lymphomas are malignant tumors arising from T cells; they represent a rare variant of non-Hodgkin's lymphomas. As in other cancers, tumor T cells need to modify their signaling to support their growth and survival. T-lymphoma tumor cells are capable to adapt various signaling cascades important also in normal healthy T cells to their benefit. The aim of this work is to summarize tumor-specific signaling typical for different types of T-cell lymphomas; both, identical to the signaling of normal T lymphocytes and altered by tumor specific somatic mutations. Detailed focus is on T lymphoma most frequent and important alterations and signaling pathways. These are specifically alterations of signaling pathways associated with T-cell receptor, JAK/STAT cytokine signaling, and Notch signaling. These pathways are particularly important for the differentiation and growth of T lymphocytes in general, therefore, it is not surprising that these pathways are also often pathologically activated or deactivated in tumor cells. Keywords: lymphocytes, non-Hodgkin lymphomas, T-cell receptor, leukemia, JAK/STAT signaling, Notch signaling, oncogenic signaling pathways
|
|
|
Adhesion structures of leukemia cells and their regulation by Src family kinases
Obr, Adam
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...
|
|
|
The role of HOXA9 gene in leukemogenesis
Rejlová, Kateřina ; Starková, Júlia (advisor) ; Fraiberk, Martin (referee)
The evolutionarily conserved family of homeobox genes plays an important role in the development of the anterior-posterior body axis of vertebrates. These genes significantly affect hematopoiesis, the development of blood cells. Extensive studies on homeobox genes in normal hematopoiesis confirmed their role also in leukemogenesis. Since the neoplastic transformation of blood cells, i.e. leukemia, is the most frequent malignancy in children, it has become a major subject of research for many scientists. Precisely in what stage of the malignant transformation the homeobox genes take part has not been shown yet. Neither is it known whether HOX genes are crucial in pathogenesis or whether their deregulation is only a side effect of leukemogenesis. The most studied homeobox gene in leukemogenesis is the HOXA9 gene, which showed correlation with the prognosis of patients with certain leukemias. Many studies describe the effect of HOXA9 in leukemic cell transformation, suggesting this gene could be a promising future target in leukemia therapy. This work is focused on the HOXA9 gene and its association with leukemic transformation of blood cells.
|
guest ::
