National Repository of Grey Literature 10 records found  Search took 0.01 seconds. 
Investigation of compouds affecting the neoplastic cell changes
Andrš, Martin ; Jun, Daniel (advisor) ; Šinkorová, Zuzana (referee) ; Vávrová, Jiřina (referee)
Radiation and genotoxic drugs after more than 70 years since their discovery still belong to the cornerstones of cancer treatment. However, these types of therapy often suffer from severe adverse effects and resistance caused by DNA repair mechanisms. The basic feature of cancer cells is genome instability, leading to various mutations and upregulated or otherwise defective DNA repair, making the cancer cells vulnerable to additional interference with the DNA damage response (DDR) mechanisms. This is the fundamental idea behind the DDR targeted therapy, which has been thoroughly studied for almost two decades. The main goals of this therapy is an improvement of the efficacy of DNA damaging treatments leading to lesser doses and adverse effects but also enabling selective targeting of defective cancer cells. The development of this area of research was very slow at the onset, but last few years it finally brought the first compound into therapy and several others into clinical trials. Among the plethora of signal and effector proteins involved in DDR, three related kinases ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related) and DNA-PK (DNA- dependent protein kinase) play the principal roles in initiation and regulation of signaling pathways in response to DNA double and single strand...
Effects of valproic acid and its combinations with cytostatic agents on tumor cells in vitro
Hinďoš Hřebačková, Jana ; Dyr, Jan (advisor) ; Vávrová, Jiřina (referee) ; Entlicher, Gustav (referee)
Cancer is one of the most challenging problems the modern medicine is facing today. An increasing incidence and a great variability of tumor cells are the main reasons those drive the research to develop better diagnostics and therapeutic protocols. Histone deacetylase inhibitors, a group of epigenetic chemotherapeutics, are able to improve the performance of currently used anticancer agents. Vaplroic acid that is commonly used as antiepileptic drug exhibits a remarkable anticancer activity by itself as well as it is capable of therapy potentiation based on other therapeutic agents. Its effect to inhibit growth of tumor cells and induce apoptotic cell death seems to be even greater under hypoxic conditions (<1% O2). This study is focused on effect of valproic acid on neuroblastoma cell lines in vitro under normoxic and hypoxic conditions. We observed significantly greater efficacy of valproic acid in hypoxia compared to normoxia. The mechanism of induction of apoptotic cell death is based on disruption of the balance between pro- and antiapoptoic proteins. Intrinsic apoptotic pathway is probably initiated by the action of 19 kDa variant of proapoptotic protein Bax on mitochondrial membrane. Moreover, we examined the efficiency of a combined treatment of neuroblastoma cells with valproic acid and...
The molecular mechanisms of stem cells response to cytostatic treatment
Seifrtová, Martina ; Řezáčová, Martina (advisor) ; Vávrová, Jiřina (referee) ; Skálová, Lenka (referee)
The molecular mechanisms of stem cells response to cytostatic treatment Apoptosis has been suggested as a common mechanism by which the cells are eradicated during chemotherapy. Most studies have focused on the reaction to DNA damage in tumor cell lines, but it is obvious that not only the tumour cells, but also normal cells are exposed to DNA-damage inducing agents during an anticancer treatment. Within this study we focus on the reaction of stem cells which are an important component of tissues and represent promising tool for a tissue engineering. Before their use, however, their reaction to the DNA damage caused by various genotoxic stressors requires elucidation and characterization of these cells under genotoxic stress contributes to the evaluation of their safety usage. In this study we assessed the effects of the frequently used chemotherapeutic agents mitoxantrone (MTX) and cisplatin (CP) on mesenchymal stem cells isolated from a dental pulp (DPSCs) and compared it with the response of human dermal fibroblasts (HDFs). Our data indicate that both cell types react to MTX and CP by the induction of apoptosis as well as by a cell cycle arrest in a dose-dependent manner. DPSCs and HDFs treated with clinically relevant concentrations of MTX underwent a permanent cell cycle arrest called...
Changes in cell immune parameterswith focus on NK cells in patients with pancreatic cancer in relation to therapy and depression
Kopecký, Jindřich ; Filip, Stanislav (advisor) ; Vávrová, Jiřina (referee) ; Ćwiertka, Karel (referee)
Changes in cell immune parameters with focus on NK cells in patients with pancreatic cancer in relation to therapy and depression Pancreatic cancer (further PC) is one of the diseases with the greatest malignant potential. Most of patients die within 1 year from diagnosis, and only 2-5 % of patients survive more than 5 years. A major cause of late diagnosis of PC and so his insufficient therapeutic management is due to the late clinical signs of PC. Despite of progress in understanding of the molecular and biological basis of tumor genesis, the prognosis of patients with PC stays during the years unchanged. One of the often clinical signs related with PC is the presence of depressive symptoms or already developed clinically depression. The association of depression and cancer constitutes an important factor affecting the quality of life and can lead to increased morbidity. Even when the relationship between the function of subcortical centers of the brain, immune and endocrine system is known, the role of long-term stress and depression in the homeostasis is often overlooked. The mental health has a great importance for the proper functioning of the immune system from the long term. During the tumor genesis there are activated cytotoxic cells (cytotoxic T lymphocytes and NK cells) and other cell...
Transplantace kostní dřeně příjemcům s regenerující krvetvorbou: účinnost transplantace a stav regenerující kostní dřeně
Forgáčová, Katarína ; Nečas, Emanuel (advisor) ; Vávrová, Jiřina (referee) ; Hofer, Michal (referee)
Hematopoietic stem cells (HSCs) have the ability of both self-renewal and differentiation. After bone marrow damage, surviving host HSCs or transplanted donor HSCs are able to restore hematopoiesis and maintain it for a long time due to the self-renewal potential. HSCs reside in a specific microenvironment in the bone marrow, in stem cell niche, which supports their survival and controls their functioning. In this study, we investigated the impact of bone marrow damage induced by increasing doses of irradiation on engraftment efficiency of transplanted donor repopulating cells. Using the CD45.1/CD45.2 congenic mouse model, we developed a new approach enabling estimation of surviving HSCs in damaged hematopoietic tissue. Its principle is in measuring of the donor chimerism resulting from transplantation of a defined dose of normal congenic bone marrow cells. The transplanted donor cells contain repopulating cells, progenitors (STRCs) and HSCs (LTRCs) that give rise to blood cell production which proceeds in parallel with that present in the host hematopoietic tissue. We applied this approach to monitor spontaneous regeneration of repopulating cells, including HSCs, in mice irradiated with a sublethal dose of 6 Gy or by a lethal dose of 9 Gy and rescued by syngenic bone marrow cells. This was...
DNA methylation changes in ovarian cancer patients
Chmelařová, Marcela ; Palička, Vladimír (advisor) ; Vávrová, Jiřina (referee) ; Bouda, Jiří (referee)
DNA methylation changes in ovarian cancer patients. In our work we studied DNA methylation changes in ovarian cancer. Due to the aggressive nature of this disease, it is very important to obtain detailed mapping of molecular parameters including epigenetics. These parameters could potentially be used in the diagnostics and treatment of ovarian cancer. To begin with, we focused on establishing and optimizing techniques which are suitable for methylation analysis of DNA isolated from paraffin blocks. The next step was to analyze selected CpG loci primarily of tumor suppressor genes. Formalin-fixed, paraffin-embedded tissue samples from both ovarian adenocarcinomas and normal ovarian tissue were obtained from 109 women (69 patients with ovarian cancer, 40 patients with normal ovarium) treated at the Department of Obstetrics and Gynecology, University Hospital Hradec Kralove. The samples of normal ovary were obtained from patients surgically treated for non-malignant diagnosis. DNA was extracted using a Qiagen DNA extraction kit. We established and optimized two techniques - MSP (Methylation specific PCR) and MS-MLPA (Methylation Specific Multiplex Ligation-dependent Probe Amplification). We discovered that for methylation analysis of poor quality DNA isolated from paraffin blocks MS-MLPA is more...
The influence of magnetic field of power frequency on the adherence of leukocytes in patients with head and neck cancer
Čoček, Aleš ; Filip, Stanislav (advisor) ; Rosina, Jozef (referee) ; Vávrová, Jiřina (referee)
We know from research conducted to date that magnetic field of low-induction power frequency (50 Hz) increases the in vitro adherence capacity of T lymphocytes in patients with squamous cell larynx/pharynx cancer as well as that of T lymphocytes of voluntary blood donors (control group), towards the surface. The objective of this thesis was to find out if there is a difference between the impacts of low induction values, and to confirm or disconfirm the literary assumption that lower induction values have more pronounced influence on biological systems. At first, we carried out comparative tests of T lymphocyte adherence inhibition in the absence of magnetic field and in the presence of a field with a single set induction value (10mT (n=30), 1 mT ( n=30), 0.5 mT ( n=76), 0.1 mT (n=60), 0.05mT (n=69)). Blood samples from 265 patients were investigated in this way. The control group consisted of T lymphocytes of voluntary blood donors (n=316). As the next stage, T lymphocyte inhibition adherence tests were simultaneously carried out without the presence of magnetic field and with the presence of a field of comparable inductions so as to compare the T lymphocyte ability of one and the same patient (i.e. comparing the adherence capacity without field with that in the presence of a field of 0.1 mT, 0.05...
Chelating polymers for the therapy of Wilson's disease
Mattová, Jana ; Poučková, Pavla (advisor) ; Sedláková, Zdeňka (referee) ; Vávrová, Jiřina (referee)
Wilson's disease is a hereditary disorder of copper metabolism, which causes copper accumulation in organism, especially in the liver, kidneys and brain. Current treatment is based on using low-molecular weight copper chelators and high doses of zinc salts. Unfortunately, they can induce some severe side effects due to systemic action. The aim of this thesis is to improve the treatment of Wilson's disease by using of polymeric drug delivery systems. The size of polymer particles in tens of microns should provide non-resorbability of the drug after oral administration. Synthetic microparticles of poly(glycidyl methacrylate-co- ethylene dimethacrylate), natural microcrystalline cellulose and cross-linked chitosan were used as polymer matrices. N,N-di(2-pyridylmethyl)amine, triethylenetetraamine and 8-hydroxyquinoline were selected as specific copper chelators, which can complex copper cations with high efficiency. The principle of the proposed treatment is that the polymeric carrier-bound chelator complex copper directly from the food in digestive tract of the organism. Because of non-resorbability, the entire complex should be eliminated from the body together with stools. This virtually eliminates systemic side effects. The ability of adsorption of copper and the stability of polymer complex under...
Suggestions for Reduction of Unemployment in the District of Žďár nad Sázavou
Vávrová, Jiřina ; Mejzlíková, Kateřina (referee) ; Mikulec, Luděk (advisor)
Master´s thesis is specialized on unemployment in the Zdar nad Sazavou region. It contains analysis of factors affecting unemployment and structure of applicants for a job in different categories, deals with an active employment policy and includes proposed solution which should lead to reduction of unemployment rate in this region.

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