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Raman spectroscopy of biologically active species and antitumor drugs
Třeštíková, Liběna ; Vetterl,, Vladimír (referee) ; Vrána, Oldřich (advisor)
SERRS spektra of biological materials are very komplex, because they consist of signals from all molecules present in cells. In this text are presented SERRS spektra of antitumor drugs and its komplex with DNA. Experimental are rated on doxorubicin and another antitumor druha and on study of theirs potential by treatment for tumors. Doxorubicin belong to clase antracycline antibiotics and is used for stop of tumor cells reproduction. Scientists found still new ways, new drugs. SERRS is one of possibilities for study of this drugs and theirs interaction with DNA.
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Effect of selected antineoplastic drugs on the gene expression of DNA repair proteins
Klčová, Silvia ; Jirkovská, Anna (advisor) ; Suchá, Simona (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Silvia Klčová Supervisor: PharmDr. Anna Jirkovská, Ph.D. Title of diploma thesis: Effect of selected antineoplastic drugs on the gene expression of DNA repair proteins. Every single cell of the human body is continuously exposed to a wide range of stress factors, with the consequence of damage to the DNA molecule. The resulting changes represent variety of alterations - from simple alkylation modifications of bases to the most unfavorable double-strand breaks (DSBs). However, the effect of cellular stress and subsequent genotoxic DNA damage is a double-edged sword. On the one hand, typical alterations in the genome can be triggered by mutagenic agents (such as components of tobacco smoke or ionizing radiation). Consequences of their action can accumulate and trigger loss of control over various steps of the cell cycle, which results in tumor cell transformation. On the other hand, however, inducing detrimental impact affecting the genome of tumor cells is one of the fundamental approaches in cytostatic treatment of cancer. Therefore, we focused our research on several antineoplastic drugs widely used in clinical practice (etoposide, daunorubicin, dexrazoxane) or undergoing clinical...
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Preparation of mitotic inhibitors in the form of nanotransporters
Meskařová, Veronika ; Indra, Radek (advisor) ; Hýsková, Veronika (referee)
Cancer is one of the most widespread diseases that every third person will encounter it. It is a disease arising from the sudden growth and rapid division of own cells. Despite progress in treatment, an effectiveness is not sufficient, and cancer is the second most common cause of death. In addition, the treatment is associated with several side effects. Currently nanomedicine uses nanomaterials for transport drugs in cancer treatment. It is possible to deliver the drug to the target site, but also to reduce the systemic toxicity of the drug by binding the drug to a suitable nanotransporter. This diploma thesis deals with seeking the appropriate mass ratio of antitumor drugs, colchicine and docetaxel, and the nanotransporter apoferritin. The aim was to find suitable in vitro conditions for high drugs encapsulation into the nanotransporter. Drugs encapsulation took place under active and passive conditions. Active encapsulation was under way on opening and closing nanotransporter by changing pH environment in test tube. Drugs were dissolved in DMSO or water with addition of HCl to charge the drug molecules and improve the binding of the drug into nanotransporter. As part of passive encapsulation, drugs were incubated in surroundings of urea or bivalent metal ions. Overall, it can be concluded that...
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The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta ; Stiborová, Marie (advisor) ; Martínková, Markéta (referee)
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
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Metabolism of cabozantinib by enzymes of first phase of biotransformation
Jurečka, Tomáš ; Indra, Radek (advisor) ; Kubíčková, Božena (referee)
Cabozantinib is an anticancer drug that inhibit tyrosine kinases which allow signal pathways important for growth and development of tumors. It is used for treatment of medullary thyroid cancer, hepatocellular carcinoma and kidney cancer. The major enzymes of the first phase of biotransformation that metabolize cabozantinib are cytochromes P450. In this thesis it was studied metabolism of cabozantinib and cytochromes P450 that participated on this metabolism. Hepatic microsomes of rat, mouse and rabbit were used for studying metabolism of cabozantinib in this thesis. It was also focused on the impact of particular isoforms of cytochromes P450 on metabolism of cabozantinib in rat microsomes. Time dependence of cabozantinib conversion in hepatic rat microsomes was also studied. Enzyme kinetics of metabolism of cabozantinib in hepatic rat microsomes, as well as impact of cytochromes P450 inhibitors on the metabolism were included. Metabolites were analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. Formation of metabolites of cabozantinib increased over time to 30 minutes of incubation and with some others to 40 minutes of incubation. Up to five different metabolites were detected in experiments (M1, desmethyl cabozantinib, M3, monohydroxy cabozantinib and cabozantinib...
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Utilization of mass spectrometry for analysis of biologically active compounds
Kaliba, David
This PhD thesis provides a commented set of four publications. These publications are focused on capillary electrophoresis, liquid chromatography, and UV/Vis spectrometry used to study complexes of rhenium with aromatic ligands. The methods of mass spectrometry with soft ionization techniques, 1 H and 13 C nuclear magnetic resonance, and infrared spectrometry were used for structural characterization of the individual complexes. The complexes were synthetized in reactions of the rhenium precursor tetrabutylammonium tetrachlorooxorhenate with the corresponding ligand under both aerobic and anaerobic conditions. In the course of the research, it was revealed that the prepared complexes (with Re in the oxidation number +V and +VI) are unstable and their oxidation numbers change to another more stable form (Re+VII ). Sub-projects which were successfully implemented during the research were as follows: Design and successful realization of the process of synthesis of selected rhenium complexes with aromatic ligands 1,2-dihydroxybenzene, 1,2,3-trihydroxybenzene, and 2,3-dihydroxynaphthalene in reactions with and without air access, and their structural characterization by ESI-MS, APPI- MS, LDI-MS, ESI-MS/MS, NMR, and IR. ESI-MS SRM and UV/Vis time studies of the behaviour of primary rhenium complexes...
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The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
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Anticancer drugs in forms of nanoparticles and mechanisms potentiating their anticancer efficiency
Meskařová, Veronika ; Indra, Radek (advisor) ; Bělonožníková, Kateřina (referee)
Cancer has been one of the most common diseases of civilization for centuries. In the 18th century, some cancers were described and the first treatments were proposed. Currently, oncosurgery, chemotherapy, radiotherapy, immunotherapy and hormonal treatment are used to treat cancer. At the same time, efforts are being made to find new anticancer drugs that target tumor cells more selectively. Recently, nanomedicine has also started to be used. This bachelor thesis deals with minimizing the binding of the amount of cytostatic ellipticine to the surface of the nanotransporter apoferritin and achieving higher encapsulation efficiency. Two types of apoferritins at different weight ratios to ellipticine were studied. It has been found that by finding a suitable weight ratio of the two molecules, binding can be minimized, and encapsulation efficiency can be increased. When working with commercial apoferritin, there was a higher encapsulation and a lower binding of ellipticine to the surface at the weight ratio of 1:10. In contrast, when working with recombinant apoferritin, the encapsulation is higher and ellipticine binding are lower at the lower ratio of 1: 2,5. Key words: oncological diseases, anticancer drugs, nanomedicine, cytostatic, nanotransporter, ellipticine, apoferritin [IN CZECH]
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Preparation of anticancer drugs bound in apoferritin
Fürbacherová, Pavlína ; Indra, Radek (advisor) ; Koblihová, Jitka (referee)
Cancer is one of the most serious problems, which modern medicine faces. In recent years, nanotechnologies and their use in medicine, has developed greatly. The aim is to make drug administration more effective and help to improve treatment of cancer illnesses. Incorporation of chemical substance into a nanoparticle can solve the problem with low stability of the drug, and/or it help to eliminate side effects. Nanoparticle apoferritin, which was studied in this thesis, is a form of commonly occurring protein ferritin. Its structure contains cavity, that can be used for incorporation of drug. Its chemical structure (high temperature stability and stability at wide pH range, easy manipulation by changing pH) and its biocompatibility makes apoferritin a potentionally suitable transporter. Presented thesis studied apoferritin's ability to incorporate anticancer drug cabozantinib into its structure. Cabozantinib is tyrosine kinase inhibitor which is used for treatment of thyroid cancer, renal cell carcinoma and hepatocellular carcinoma. The effect of final pH to the formation of the complex of apoferritin with cabozantinib, and stability of this complex was also studied in this thesis. Considering the results we can say that apoferritin is able to encapsulate cabozantinib into its inner structure. As we...
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The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
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