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The study of activation and detoxication metabolism of the anticancer drug ellipticine by the cytochrome P450 system in vitro and in vivo…
Kotrbová, Věra ; Stiborová, Marie (advisor) ; Hansíková, Hana (referee) ; Souček, Pavel (referee)
Gen. Physiol. Biophys. (2006), 25, 245-261 245 Oxidation Pattern of the Anticancer Drug Ellipticine by Hepatic Microsomes - Similarity Between Human and Rat Systems M. Stiborová1 , L. Bořek-Dohalská1 , D. Aimová1 , V. Kotrbová1 , K. Kukačková1 , K. Janouchová1 , M. Rupertová1 , H. Ryšlavá1 , J. Hudeček1 and E. Frei2 1 Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic 2 Division of Molecular Toxicology, German Cancer Research Center, Heidelberg, Germany Abstract. Ellipticine is an antineoplastic agent, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerase II and formation of DNA adducts mediated by cytochrome P450 (CYP). We investigated the ability of CYP enzymes in rat, rabbit and human hepatic microsomes to oxidize ellip- ticine and evaluated suitable animal models mimicking its oxidation in humans. Ellipticine is oxidized by microsomes of all species to 7-hydroxy-, 9-hydroxy-, 12- hydroxy-, 13-hydroxyellipticine and ellipticine N2 -oxide. However, only rat micro- somes generated the pattern of ellipticine metabolites reproducing that formed by human microsomes. While rabbit microsomes favored the production of ellipticine N2 -oxide, human and rat microsomes predominantly formed 13-hydroxyellipticine. The species difference in...
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The role of glycoconjugates in cell signalling - CEACAM1 and Fc ε RI
Dudková, Lenka ; Šmíd, František (advisor) ; Stiborová, Marie (referee) ; Bílková, Zuzana (referee)
Carcinoembryonic cell adhesion molecule 1 (CEACAM1) is human membrane glycoprotein. The purpose of the first part of this thesis was to isolate CEACAM1 glycoprotein from bile and characterise its purity and recovery that have not been described before. Affinity chromatography of CEACAM1 on hydrazide-activated cellulose with immobilized monoclonal anti-CEA F34-187 antibodies is described. The method is based on the oxidation of the immunoglobulin carbohydrate component located on the Fc fragment of antibody by periodate and oriented bounding to hydrazide-activated matrix. Crude protein fraction from bile was applied onto the affinity column and CEACAM1 was eluted with 6 M guanidine-HCl. A single immunopositive 85 kDa band of CEACAM1 was detected on the western blot with anti-CEA antibody. Probably due to the high glycosylation of CEACAM1 any common method of protein staining was not applicable except staining with lectin.
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The effects of zinc ions on breast tissue cancerogenesis
Kratochvílová, Monika ; Stiborová, Marie (referee)
The concept of breast cancer describes a wide range of serious diseases. It is one of the most common cancer diseases among women worldwide. The most difficult and problematic subtype is the triple negative breast cancer. This subtype is characteristic by the loss of expression of hormon receptors and HER-2, which makes it unresponsive to available targeted therapy. The breast cancer, as well as other malignancies, has a relationship withzinc ions. Zinc is an essencial element and it is involved in many of important cellular processes and thus it is able to directlyor indirectly affect the cancerogenesis. Increased levels of zinc ions in malignant breast cancer tissue compared to healthy tissue were well described. However, zinc has documented anticancer properties. The aim of this study was to determine if excessive suplementation with zinc ions has an effect on breast cancer development in vivo. The cell line 4T1 was chosen as a model of the triple negative subtype in mus musculus. The mouse strain BALB/c was used as an animal model. A total dose of zinc sulphate per one gram of mouse weight used in the experiment was 0.15 mg. We determined not only the growth of primary tumour, but also an expression levels of selected genes and antioxidant capacity of the whole organism. The volume of primary...
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