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Copper chelating potential of iron chelators from the group of aroylhydrazones
Kříž, Jakub ; Mladěnka, Přemysl (advisor) ; Bárta, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Farmacology and toxicology Candidate Mgr. Jakub Kříž Consultant Doc. PharmDr. Přemysl Mladěnka, Ph.D. Title of Thesis Copper chelating potential of iron chelators from the group of aroylhydrazones Copper is one of the essential trace elements. It is present in two oxidation-reduction forms Cu+ and Cu2+ in the human body. The ability of an easy transformation between this two forms is the crucial feature for the activity of copper enzymes, like superoxide dismutase and cytochrome c oxidase. Copper kinetics is quite complicated. The key organ which affects copper kinetics is the liver, but the small intestine plays an important regulatory role too. There are disorders, which are associated with both copper deficiency and accumulation. The best known disorder caused by copper excess is Wilson's disease. It is caused by a mutation in the ATP7B gene. It codes a transporter, which is responsible for elimination of copper. Excessive accumulation of copper causes several symptoms, mainly hepatic and neurological problems. Wilson's disease is treated by chelators, which bind the excess of metal ions in the organism. The aim of my thesis was to verify the copper-chelation efficiency of three selected iron chelators. The...
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Radiolabeling of ramucirumab followed with the study of its internalization in vitro
Gajdoš, Jakub ; Bárta, Pavel (advisor) ; Kuchařová, Monika (referee)
v anglickém jazyce Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Bc. Jakub Gajdoš Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: Radiolabeling of ramucirumab followed with the study of its internalization in vitro. The process of angiogenesis ensures the formation of the bloodstream at the site of its increased need. Therefore, it is not surprising that angiogenesis is often included in the tumor production process, because it provides the tumor cells nutrition supply and metabolite removal. The targeting of angiogenesis has become a key topic of some scientific research. The process of tumor blood supply formation provides a family of vascular endothelial factors (VEGFs) and their respective receptors, which have become the target of the angiogenesis attenuation in a cancer treatment. One of many therapeutics is the monoclonal antibody ramucirumab targeted against VEGF receptor type 2 (VEGFR-2). Radioactive labeling of ramucirumab with a suitable radionuclide could bring benefits in either radiotherapy or radiodiagnostics. The aim of this diploma thesis was the indirect radioactive labeling of monoclonal antibody ramucirumab using 99m Tc as radiodiagnostic nuclide via the chelation agent succinimidyl-6-...
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Study of transport of protein molecules across cell membranes
Hornová, Aneta ; Hyršová, Lucie (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Aneta Hornová Supervisor: PharmDr. Lucie Hyršová, Ph.D. Title of diploma thesis: Study of transport of protein molecules across cell membranes Kidney transporters are found mainly in the proximal tubules, they participate in the secretion and reabsorption of endogenous and exogenous substances. Plenty of kidney transporters have been identified, however this diploma thesis is focused on megalin. Specifically, we dealed with determination of transport of peptides via this renal transporter in HK-2 and JEG-3 cell lines. Megalin is a glycoprotein whose main function is tubular reabsorption of albumin filtered in glomerules and other high molecular weight substances. Another endogenous substrates of megalin are e.g. transcoblamine - vitamin B12, insulin or light chains of immunoglobulins. It is also able to transport some drugs like aminoglycoside and polypeptide antibiotics. Within this work, we investigated the influence of reduced expression of megalin on the transport of albumin and anti-VEGFR2 aptamer. Reduction of expression was achieved by transfection of cells with siRNA against the LRP2 gene. Lower expression of LRP2 led to reduction of transport of albumin and anti-VEGFR2 aptamer into...
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The determination of fatty acid levels in the tissues of healthy, suddenly deceased persons and polymorbid patients
Novotná, Monika ; Kuchařová, Monika (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate: Monika Novotná Supervisor of Diploma Thesis: Mgr. Monika Kuchařová, Ph.D. Title of Diploma Thesis: The determination of fatty acid levels in the tissues of healthy, suddenly deceased persons and polymorbid patients The aim of the thesis was to determine the levels of 14 fatty acids in tissues of suddenly deceased, otherwise healthy individuals and in the group of polymorbid, chronic patients. It was a comparison of fatty acid levels in seven tissues of the human body: subendocardial left ventricular tissue, liver parenchyma tissue, kidney cortex, adrenal tissue, skeletal muscle, abdominal subcutaneous adipose tissue, and brain tissue. Each group included 10 deceased patients. The theoretical part incudes fatty acids as the main component of lipids. It deals mainly with the group of polyunsaturated fatty acids and their relation to pathologies in the human body. Gas chromatography, thanks to which we analyzed the fatty acid spectrum, is also described. The experimental part consists of the basic characteristics of the research groups, the description of the workflow and the results. Statistically processed data are divided into categories by individual fatty acids and other monitored...
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In vitro saturation study of 99mTc-HYNIC-ramucirumab on PC-3 cell line
Lach, František ; Bárta, Pavel (advisor) ; Smutná, Lucie (referee)
v anglickom jazyku Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: František Lach Supervisor: Mgr. Pavel Bárta, PhD Consultant: Mgr. Lucie Hyršová Title of diploma thesis: In vitro saturation study of 99m Tc-HYNIC-ramucirumab on PC-3 cell line The number of malignant tumours in the population has increased in recent years. Due to the frequent serious sides effects of chemotherapeutic drugs on the whole organism, targeted antitumor therapy is at the forefront. Due to its specific effect on the regulatory and signal pathways of protein structures, monoclonal antibodies are used for the target anti-tumour therapy. The basic properties of the growing tumour include vasculogenesis (the ability to build new blood vessels from the endothelial precursors) and angiogenesis (the process of self-inducing formation of blood vessels). Endothelial tumour progenitors include vascular endothelial growth factor (VEGF). VEGF activates its biological activity by binding to its transmembrane tyrosine-kinase receptors VEGFR. Indeed, the inhibition of the vascular endothelial factor receptors is the target of some monoclonal antibodies. Ramucirumab is a monoclonal antibody that selectively inhibits VEGF receptor type 2 (VEGFR-2) and thereby...
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Radiolabelled receprot-specific peptides for cancer diagnosis and therapy
Parýzková, Barbora ; Bárta, Pavel (advisor) ; Trejtnar, František (referee)
Charles University Fakulty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate: Bc. Barbora Parýzková Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: Radiolabelled receptor-specific peptides for cancer diagnosis and therapy. The presented diploma thesis is based on literature review and it deals with receptor- specific radioactive labeled peptides and their usage in the cancer diagnostic and treatment. It focuses on general knowledge about radiopharmaceuticals, further on the descriptions of either diagnostic or therapeutic radionuclides as well as on currently used chelating agents. The particular attention is paid to peptides like somatostatin and cholecystokinin and their usability in Nuclear Medicine for the imaging and treatment of certain malignancies. The other stated peptides in this diploma thesis are bombesin, vasoactive intestinal peptide and alpha melanocyte stimulating hormone. Keywords: receptor-specific peptides, radiolabelling, radionuclides for diagnosis and therapy, radiotherapy, radiodiagnostics, octreotide.
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Radiolabeling of ramucirumab followed with the study of its internalization in vitro
Gajdoš, Jakub ; Bárta, Pavel (advisor) ; Kuchařová, Monika (referee)
v anglickém jazyce Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Bc. Jakub Gajdoš Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: Radiolabeling of ramucirumab followed with the study of its internalization in vitro. The process of angiogenesis ensures the formation of the bloodstream at the site of its increased need. Therefore, it is not surprising that angiogenesis is often included in the tumor production process, because it provides the tumor cells nutrition supply and metabolite removal. The targeting of angiogenesis has become a key topic of some scientific research. The process of tumor blood supply formation provides a family of vascular endothelial factors (VEGFs) and their respective receptors, which have become the target of the angiogenesis attenuation in a cancer treatment. One of many therapeutics is the monoclonal antibody ramucirumab targeted against VEGF receptor type 2 (VEGFR-2). Radioactive labeling of ramucirumab with a suitable radionuclide could bring benefits in either radiotherapy or radiodiagnostics. The aim of this diploma thesis was the indirect radioactive labeling of monoclonal antibody ramucirumab using 99m Tc as radiodiagnostic nuclide via the chelation agent succinimidyl-6-...
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