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Radiolabelled antibodies - the perspective for diagnosis and therapy
Mejtská, Jana ; Bárta, Pavel (advisor) ; Ramos Mandíková, Jana (referee)
1 CHARLES UNIVERSITY FAKULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF BIOPHYSICS AND PHYSICAL CHEMISTRY DISSERTATION THESIS RADIOLABELED ANTIBODIES - THE PERSPECTIVE FOR DIAGNOSIS AND THERAPY Supervizor: Mgr. PAVEL BÁRTA, Ph.D. HRADEC KRÁLOVÉ, 2017 Bc. JANA MEJTSKÁ 2 ABSTRACT EN Different types of tissues have a characteristic cell morphology. Each cell has typical molecules on its surface, which may be either of physiological or pathological type. The presence of these surface structures can be interesting for possible modulation of specific cell populations from neighboring cells. Utilization of this property is then essential particularly in a case of tumor cells. Targeting on tumor specific cell structures involves the use of receptor specific peptides or monoclonal antibodies. The discovery of the preparation of monoclonal antibodies has opened a new chapter in the treatment and diagnosis not only tumor diseases. The advantage of monoclonal antibodies is their specificity and also high affinity to the type of the target cell structures. This study is focused on the summary of monoclonal antibodies which are currently being applied on the treatment or diagnosis of a particular cancer. Furthermore, this work also includes antibodies which are under development for intended medical applications with...
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Study of renal transport mechanisms of radiolabeled antibodies
Karasová, Jana ; Trejtnar, František (advisor) ; Bárta, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmacology and Toxicology Candidate: Mgr. Jana Kanokova Supervisor: Doc. PharmDr. Frantisek Trejtnar, CSc. Title of rigorous thesis: Study of renal transport mechanisms of radiolabeled antibodies Utilization of monoclonal antibodies belongs to one of the important strategies in the treatment of oncological diseases. This treatment has a great advantage in precise focusing on the target structure with minimal damage to surrounding non-target tissue. The antibodies against the receptor for epidermal growth factor (EGFR) expressed in higher rate by variety of tumor types represent one of the important group. Nowadays oncology utilizes both unconjugated antibodies, and the ones conjugated with other effector components, e.g. cytostatic agents, radionuclides, toxins. One of the important limits for the antibodies conjugated with radionuclides appears to be their potential accumulation in kidneys with subsequent radiotoxic damage to the kidney tissue. The aim of this experimental study was to investigate the accumulation of three 131 I- labeled anti-EGFR antibodies - panitumumab, cetuximab and nimotuzumab using a kidney model in vitro, and compare it with renal uptake of the natural peptide ligand EGFR which was...
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Role of disulphide bonds in hA2A subtype adenosine receptor
Zappe, Lukáš ; Matoušková, Petra (advisor) ; Bárta, Pavel (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lukáš Zappe Supervisor: Ing. Petra Matoušková Ph.D., PD Dr. Anke C. Schiedel Title of diploma thesis: Role of disulphide bonds in hA2A subtype adenosine receptor The adenosine A2A receptor belongs to the G protein coupled receptor family (GPCR). GPCRs are the targets of almost 40% of the drugs on the market. GPCRs are characterized by seven transmembrane helices, which are linked by three extracellular and three intracellular loops (ECL and ICL). The structure of the receptor has been revealed by crystallography, hence we know that ECL1 and ECL2 are connected by several disulphide bonds. The ECL2 is believed to be involved in ligand binding and recognition. In order to understand the relevance of those disulphide bonds involved in this process, four adenosine A2A receptor mutants were generated by one-site direct mutagenesis, in which the cysteine residues were replaced with serine residues (C146S, C159S, C166S and C146S- C159S). These receptor mutants were expressed in the mammalian cell line, CHO K1(Chinese Hamster Ovary) and the receptor expression was tested with ELISA (Enzyme- linked immunosorbent assay). The determination of ligand binding has been carried out by radioligand...
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The Theme of (Homo)Sexuality in the fiction of Michael Cunningham
Bárta, Pavel ; Chalupský, Petr (advisor) ; Ženíšek, Jakub (referee)
This bachelor thesis, The Theme of (Homo)Sexuality in the Fiction of Michael Cunningham, focuses on the approach to homosexuality in the United States of America and its position in American literature, particularly in the fiction of Michael Cunningham. The major part of the thesis deals with the theme of sexuality in three of Cunningham's novels, A Home at the End of the World, The Hours and By Nightfall, its impact on the protagonists and provides comparison among them. Key words Michael Cunningham, gay literature, sexuality, homosexuality, homoeroticism, AIDS, interpersonal relationships
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The Study of Receptor-specific Radiopharmaceuticals Interactions with Biological Systems at the Cellular Level
Bárta, Pavel ; Lázníček, Milan (advisor) ; Nachtigal, Petr (referee) ; Štětina, Rudolf (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Pavel Bárta Supervisor Prof. PharmDr. Ing Milan Lázníček, CSc. Title of Doctoral Thesis The study of receptor-specific radiopharmaceuticals interactions with biological systems at the cellular level The targeting of receptor specific peptides or antibodies is one important diagnostic and therapeutic tool in the fight against cancer diseases. Receptor specific peptides often have their origin from the human natural peptide hormones; hence they are commonly marked as peptide analogues. The peptide analogues contain in their amino acids sequence the binding site identical with the site of natural peptides, which they are originated from. This binding site is responsible for the interaction with the targeted receptor. The peptide analogues are employed instead of the natural peptides because their biological properties can be improved, for example facilitating distribution in the organism to their place of action, or protection from biological degradation. The peptide ligand binding itself on targeted receptors and its internalization into cells typically does not trigger a therapeutic effect. From this reason, peptide analogues carry active substances like cytotoxine or...
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Study of cytotoxicity of potential antituberculotics using selected methods on liver and kidney cell line
Katrnošková, Simona ; Ramos Mandíková, Jana (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Mgr. Simona Katrnošková Supervisor: PharmDr. Jana Ramos Mandíková, Ph.D. Title of Thesis: Study of cytotoxicity of potential antituberculotics using selected methods on liver and kidney cell line During pharmacologic therapy, tissues of liver and kidney are frequently exposed to high doses of xenobiotics. Via in vitro assays during preclinical testing, we are able to predict potential toxicity which helps to prevent the possible serious adverse drug reactions in clinical practice. The aim of this rigorous thesis was to state the cytotoxic profile of 4 potential antituberculotic drug candidates using appropriate cell models and in vitro assays. Another aim was to compare the cytotoxic effect of the tested compounds among themselves and to 4-aminosalicylic acid (PAS) which antituberculotic activity is known for many years. The tested substances were 3 salicylanilide diethyl phosphate-based derivatives and 4-(trifluormethyl)benzoic acid. For the cytotoxic potential assessment, we used the parameter half maximal inhibitory concentration IC50. We have used methods determining the cell metabolic activity, aminopeptidase activity, lactate dehydrogenase leakage and activity of 3/7 caspases in this...
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Study of interspecies differences in plasma protein binding of 18F-labeled radiopharmaceuticals
Nováková, Dana ; Lázníček, Milan (advisor) ; Bárta, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Dana Nováková Consultant: Prof. PharmDr. Ing. Milan Lázníček, CSc. Title of Thesis: Study of interspecies differences in plasma protein binding of 18 F-labeled radiopharmaceuticals In this thesis, the binding ability of three radiopharmaceuticals containing radionuclide 18 F to the plasma proteins was examined in bovine, pig, human and rat plasma, and the interspecies comparison was performed. Examined radiopharmaceuticals included 18 F-FDG, 18 F-fluorocholine and 18 F-thymidine. The two main methods used are equilibrium dialysis and ultrafiltration. These methods are based on separation of free ligand from the linked component. During the separation, semi-permeable membrane and special filters (AMICON and VIVASPIN) were used for equilibrium dialysis and ultrafiltration, respectively. Free fraction of drugs is considered to be an important parameter for the availability of the drug distribution into the tissues and cells, interaction with receptors, excretion and metabolism. All experiments were carried out at the physiological temperature of 37řC. Obtained results indicate low plasma protein binding of the three radiopharmaceuticals in all studied species, which suggests...
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Operational building of artificial lake
Bárta, Pavel ; Sedlák, Radek (referee) ; Beneš, Petr (advisor)
The object of this work is operational building of artificial lake, which is located in the cadastral area Loučky u Zátoru. The building is designed to provide the operation and safety of newly proposed water project. The building is detached, three floors and a partial basement, ground shape of a cross. The structural system is a brick, designed by the brick blocks HELUZ, based upon the strip foundation of plain concrete. Floors and stairs are made of reinforced concrete, gabled roof is covered up with concrete roofing BRAMAC.
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Family house with a design office
Bárta, Pavel ; Halla, Antonín (referee) ; Beneš, Petr (advisor)
The object of the bachelor's thesis is a family house with a design office, which is located in cadastral of township Jedovnice. The house is detached, L-shaped plan, two-floor, with no cellar, designed for 4-5-member family. Construction system is brick, made from ceramic blocks HELUZ based on strip foundations made from plain concrete. Ceilings are made from ceramic beams and blocks HELUZ, there is a prefabricated stair YTONG, a roof has gabled design with concrete roofing.
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