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Design, preparation and structural studies of biologically relevant protein variants of cancer-related Carbonic Anhydrase IX
Fejfarová, Adéla ; Maloy Řezáčová, Pavlína (advisor) ; Novotný, Marian (referee)
3 Abstract Carbonic anhydrase IX (CA IX) represents an attractive target for the development of anticancer drugs as it is overexpressed in various types of solid tumors. By its catalytic activity, CA IX assists the cancer cells to maintain the optimal intracellular pH and to acidify the extracellular milieu promoting tumor development. There are twelve enzymatically active carbonic anhydrases (CAs) present in human body, all sharing a high sequence identity and a typical β-sheet structural fold of the well-studied catalytic domain. Although, the activity of CAs is efficiently inhibited by sulfonamide-containing compounds, the design of inhibitor selective to the cancer-related CA IX has been hampered by the high sequence conservation. CA IX has several unique features compared to other members of the family, which investigation may help in the development of selective drug compounds. Namely, it is a type I transmembrane dimeric protein with unique N-terminal proteoglycan-like (PG) domain, extracellular catalytic domain, and short cytoplasmic C-terminal segment. The above denoted traits make CA IX subject of structure-based drug design efforts. However, the expression and purification in high yield as well as crystallization experiments has been challenging. Therefore, protein variant bearing six amino acid...
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The role of book influencers in realation to the publishers, booksellers and readers
Fejfarová, Adéla ; Halada, Jan (advisor) ; Zavřelová, Monika (referee)
The diploma thesis deals with book influencers and their use by publishers and booksellers as a marketing tool. The thesis presents this modern phenomenon, its characteristics, principles, the most important book influencers in the Czech Republic and the online environment where book influencers operate. The aim was to find out the principles and conditions of cooperation between book influencers, publishers and booksellers, their relationships and the effect of the online content of book influencers on readers. The evaluation was carried out on the basis of a questionnaire survey with six book influencers, eight publishers, two booksellers and 662 readers. The research part shows us how these cooperations work in practice, whether it is a key marketing tool for publishers and booksellers, how it will develop in the future and what are the attitudes of all three examined groups to this phenomenon. At the same time, the research outlines the issue of blurring the differences between book influencers and literary critics, where we can notice considerable misunderstandings on the part of literary critics and rivalry. At the end of the thesis, there are formulated specific assumptions for future development, current trends and shortcomings which should be improved or eliminated both by book influencers...
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Immunogenic cell death in tumor specimens in the clinics
Fejfarová, Adéla ; Drbal, Karel (advisor) ; Büchler, Tomáš (referee)
Tumor development and growth are under the control of the immune system in the human body. Danger-associated molecular pattern (DAMP) molecules trigger the anti-tumor response by binding to pattern recognition receptor (PRR) on myeloid cells which in turn activate an adaptive immune system. DAMP molecules are released from cancer cells during a process of immunogenic cell death (ICD) which is a form of regulated cell death (RCD). ICD is induced by a variety of treatments in experimental settings as well as by therapeutic modalities commonly used in medicine. A typical DAMP marker of ICD is calreticulin which is translocated from the endoplasmatic reticulum to the plasma membrane attached to the CD91 receptor. Another marker is the nuclear protein HMGB1 which is released into the tumor environment at the later stage of ICD. This bachelor thesis describes a variety of detection methods and the results of DAMP externalization after ICD induction in vitro in cancer cell lines and in tumor specimens from cancer patiens. Moreover, the link between DAMP molecules and cancer patient survival is discussed. Last, it also summarizes the current status of clinical trials concerning ICD. Keywords tumor, antitumor immunity, cell death, adjuvans, DAMP, chemotherapeutics, immunogenic cell death, clinical trials
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Strategie rozvoje firmy
Fejfarová, Adéla Bc. ; Kovář, František (advisor) ; Dvořák, Jiří (referee)
Cílem práce je zjistit možný potenciál firmy do budoucnosti a to s produktem, který nabízí. Firma je značně ovlivněna externím prostředím a mým cílem je zjistit, do jaké míry mají externí vlivy dopad na samotnou existenci firmy. Okrajově se také zabývám myšlenkou expanze společnosti a nápady na rozvoj produktu.
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