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Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05
Douděrová, Aneta ; Macháček, Miloslav (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Aneta Douděrová Supervisor: RNDr. Miloslav Macháček, PhD. Consultants: pplk. doc. PharmDr. Aleš Tichý, PhD. Title of diploma thesis: Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05 Nowadays, tumor diseases belong to the world's main causes of death. Research in the area of tumor treatment deals with the development of new methods that improve the health of patients. The aim of my diploma thesis was to find out if the usage of autophagy inhibitors in combination with ionizing radiation (IR) contributed to radiosensitization of non-small cell lung cancer cells H1299. It was based on an assumption that autophagy was a cytoprotective mechanism leading to a cell survival during stress conditions such as IR. In order to examine qualitative changes of H1299 cells pre-treated by the new autophagy inhibitor Lys05 or well known autophagy inhibitor Bafilomycin A1 we used fluorescence microscopy in combination with green staining by LysoSensor green DND-189. The intensity of fluorescence was quantified by flow cytometry. The results have shown that pre-treatment by autophagy inhibitors in combination with IR led to morphological changes of cells and to...
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Co2+ loaded block copolymer micelles: Preparation and their uptake into macrophages
Měrková, Veronika ; Jansová, Hana (advisor) ; Raisová Stuchlíková, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Friedrich Schiller University Jena Faculty of Chemistry and Earth Sciences Institute for Organic and Macromolecular Chemistry Candidate: Veronika Měrková Supervisors: PharmDr. Hana Jansová, Ph.D., Prof. Dr. Felix H. Schacher Title of diploma thesis: Co2+ loaded block copolymer micelles: Preparation and their uptake into macrophages Since lots of patients suffer from post-operative infections resulting in sepsis, there were attempts to modulate immune system response in order to treat this pathological state. Cobalt is a biogenic trace element, however its direct administration may cause immunological reactions. The immune response can be inflammatory or anti- inflammatory mediated by macrophages (MΦ). Both are responsible for specific actions, regarding MΦ activation and cytokine release. The aim of this study was to provoke such response in MΦ and therefore to possibly control the inflammatory process. Nevertheless, free cobalt ions are toxic. In order to find a suitable and safe way of cobalt administration, the triblock terpolymer PEO-b-PAGECOOH-b-PtBGE was synthesized and assembled into micelles in aqueous solution. Eventually the micelles were loaded with cobalt chloride to facilitate the detection in a...
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The impact of selected sesquiterpenes on antioxidant enzymes in HT-29 cell line
Junková, Martina ; Raisová Stuchlíková, Lucie (advisor) ; Jansová, Hana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Martina Junková Tutor: RNDr. Lucie Raisová Stuchlíková, Ph.D. Title: Effect of selected sesquiterpenes on antioxidant enzymes in the HT-29 cell line Colorectal cancer is one of the most common cancer type in Czech republic. The oncological treatment causes frequent side effects, what result in hard accepting by patients. There is also emerging resistance to classical chemotherapy (5-fluorouracil). During searching new alternatives, some promising natural substances became a subject of researches. The subtropical tree Myrica rubra and its extracts contain many biologically active substances, which are studied among others for their anti-cancer and antiproliferative effects. β-caryophyllene (BCP), β-caryophyllenoxid (CAO), α- humulene (HUM), trans-nerolidol (NER) and valencen (Val) belong to main sesquiterpenes in this essential oil Myrica rubra. In our study, effect of essential oil Myrica rubra, HUM and NER, in concentrations of 25 and 50 μg/ml, were examined after a 24-hours incubation of the HT-29 cell line on the activity of antioxidant enzymes, their transcription and amount of proteins. Monitored enzymes were glutathione peroxidase (GPx), glutathione reductase (GR),...
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Co2+ loaded block copolymer micelles: Preparation and their uptake into macrophages
Měrková, Veronika ; Jansová, Hana (advisor) ; Raisová Stuchlíková, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Friedrich Schiller University Jena Faculty of Chemistry and Earth Sciences Institute for Organic and Macromolecular Chemistry Candidate: Veronika Měrková Supervisors: PharmDr. Hana Jansová, Ph.D., Prof. Dr. Felix H. Schacher Title of diploma thesis: Co2+ loaded block copolymer micelles: Preparation and their uptake into macrophages Since lots of patients suffer from post-operative infections resulting in sepsis, there were attempts to modulate immune system response in order to treat this pathological state. Cobalt is a biogenic trace element, however its direct administration may cause immunological reactions. The immune response can be inflammatory or anti- inflammatory mediated by macrophages (MΦ). Both are responsible for specific actions, regarding MΦ activation and cytokine release. The aim of this study was to provoke such response in MΦ and therefore to possibly control the inflammatory process. Nevertheless, free cobalt ions are toxic. In order to find a suitable and safe way of cobalt administration, the triblock terpolymer PEO-b-PAGECOOH-b-PtBGE was synthesized and assembled into micelles in aqueous solution. Eventually the micelles were loaded with cobalt chloride to facilitate the detection in a...
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Study of potential pharmacological protection of cardiac cells against oxidative stress and antracycline anticancer drugs
Jansová, Hana ; Šimůnek, Tomáš (advisor) ; Hrdina, Radomír (referee) ; Jun, Daniel (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF BIOCHEMICAL SCIENCES Candidate: Mgr. Hana Jansová Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis: STUDY OF POTENTIAL PHARMACOLOGICAL PROTECTION OF CARDIAC CELLS AGAINST OXIDATIVE STRESS AND ANTRACYCLINE ANTICANCER DRUGS Development of cardiovascular disorders is associated with various risk factors and oxidative stress plays an important role in many of them. Iron-catalysed production of highly toxic and reactive hydroxyl radicals may contribute to oxidative stress. Chelation of free iron seems to be a promising strategy to prevent the propagation of oxidative stress. However, the use of classic iron chelators in pathological conditions without iron overload is associated with the risk of toxicity due to the iron depletion. Hence, this study deals with cardioprotective properties of iron chelators as well as prochelators derived from them. We focused on prochelators with almost no affinity for iron ions until they are activated under disease-specific oxidative stress conditions. For a long time, it has been assumed that oxidative stress is also the main denominator in an anthracycline-induced cardiotoxicity. However, the previous studies suggested alternative mechanism(s). Therefore in the...
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In vitro study of antiproliferative effects of selected topoisomerase II inhibitors
Jansová, Hana ; Šimůnek, Tomáš (advisor) ; Kvasničková, Eva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Hana Jansová Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: In vitro study of antiproliferative effects of selected topoisomerase II inhibitors. Anthracycline antibiotics (such as doxorubicin or daunorubicin) are antineoplastics which act as the topoisomerase II poisons. They stabilize a reaction intermediate in which DNA strands are cut and covalently linked to tyrosine residues of topoisomerase II, eventually impeding DNA resealing. Failure of relaxing the supercoiled DNA results in block of DNA replication and transcription. Doxorubicin is used for the treatment of solid tumours as well as haematologic malignancies, while daunorubicin can be used to treat specific types of leukaemia. Unfortunately, cardiotoxicity represents serious side effect of these drugs. Therefore, combinations of anthracyclines with cardioprotective agent dexrazoxane are sometimes used. The proposed mechanism of dexrazoxane cardioprotective action is chelation of the iron ions which decrease the production of reactive oxygen species. Dexrazoxane is also a catalytic inhibitor of the topoisomerase II and there are doubts, whether it may compromise the antitumour effectiveness of the...
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STUDY OF POTENTIAL PHARMACOLOGICAL PROTECTION OF CARDIAC CELLS AGAINST OXIDATIVE STRESS AND ANTRACYCLINE ANTICANCER DRUGS
Jansová, Hana ; Šimůnek, Tomáš (advisor) ; Hrdina, Radomír (referee) ; Jun, Daniel (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF BIOCHEMICAL SCIENCES Candidate: Mgr. Hana Jansová Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis: STUDY OF POTENTIAL PHARMACOLOGICAL PROTECTION OF CARDIAC CELLS AGAINST OXIDATIVE STRESS AND ANTRACYCLINE ANTICANCER DRUGS Development of cardiovascular disorders is associated with various risk factors and oxidative stress plays an important role in many of them. Iron-catalysed production of highly toxic and reactive hydroxyl radicals may contribute to oxidative stress. Chelation of free iron seems to be a promising strategy to prevent the propagation of oxidative stress. However, the use of classic iron chelators in pathological conditions without iron overload is associated with the risk of toxicity due to the iron depletion. Hence, this study deals with cardioprotective properties of iron chelators as well as prochelators derived from them. We focused on prochelators with almost no affinity for iron ions until they are activated under disease-specific oxidative stress conditions. For a long time, it has been assumed that oxidative stress is also the main denominator in an anthracycline-induced cardiotoxicity. However, the previous studies suggested alternative mechanism(s). Therefore in the...
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Ethical education at the Curie´s Primary School in Prague
Jansová, Hana ; Machková, Eva (advisor) ; Vacek, Pavel (referee)
The master thesis concerns itself with theoretical and practical aspects of ethical education. Further, it describes the project of ethical education as implemented at the primary school Curieových in Prague in relation to individual theoretical concepts, which are used in this project, in particular the concept of ethical education according to R. R. Olivar and L. Lencz and drama in education. Part of the thesis is also the reflection of the specific features of the project and its consequences. The thesis raises the question what is the long-term effect of realization of the project on the climate of the school and the behaviour of the children. Part of the thesis is extensive annexes, which contain in particular records of programs of ethical education lessons, photo-documentaion and interviews with teachers.
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