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Mechanisms of the induction of taxane resistance in breast cancer cells
Daniel, Petr ; Kovář, Jan (advisor) ; Vodička, Pavel (referee) ; Macůrek, Libor (referee)
About 1 in 3 humans will experience cancer during their lifetime, and about 1 in 6 humans will die of cancer disease. Breast cancer is currently the most diagnosed neoplasm in women, with 2.2 million cases and 685 thousand of deaths worldwide. Despite significant advances in diagnostics, molecular biology and drug development toward the goal of patient-tailored therapy, the mortality rate stagnates. Patients become unrespon- sive to treatment due to drug resistance occurs. Generally, cancer can be naturally insensitive to primary treatment (innate resistance) or manifest resistant phenotype after a prolonged period (acquired resistance). This PhD thesis concerns acquired drug resistance to taxanes in breast cancer cells. We aimed to put light on mechanisms involved in paclitaxel and Stony Brook Taxane 0035 resistance and how we can overcome them. We found several suspect genes with changed expression at the protein level between taxane-sensitive and taxane-resistant breast cancer cells. Among them, ABCB1 gene codes for a versatile multidrug transporter P-glycoprotein was pivotal for resistance to paclitaxel and Stony Brook Taxane 0035. Other genes with altered expression were localized primarily on the q arm of chro- mosome 7, exemplified by thyroid hormone receptor interactor 6 (TRIP6). A combination of...
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Outcome of patients after acute ischemic stroke treated with mechanical thrombectomy.
Křivánková, Jana ; Widimský, Petr (advisor) ; Kováč, Jan (referee) ; Procházka, Václav (referee)
Outcome of patients after acute ischemic stroke treated with mechanical thrombectomy. Background. Thrombectomy is an effective treatment for acute ischaemic stroke (AIS). Aims. The study aimed to compare the clinical results of patients with different types of large cerebral artery occlusion who underwent mechanical thrombectomy at the Cardiocenter of the Faculty Hospital of Královské Vinohrady. Methods. This was a single-center, prospective registry of 214 consecutive patients with AIS enrolled between 2012 and 2018. All thrombectomy procedures were performed in a cardiology cath lab with stent retrievers or aspiration systems. The functional outcome was assessed by the modified Rankin Scale (mRS) after three months. Results. Ninety-three patients (44%) had middle cerebral artery (MCA) occlusion, 28 patients (13%) had proximal internal carotid artery (ICA) occlusion, 27 patients (13%) had tandem (ICA+MCA) occlusion, 39 patients (18%) had terminal ICA (T-type) occlusion, and 26 patients (12%) had vertebrobasilar (VB) stroke. Favorable clinical outcome (mRS ≤2) was reached in 58% of MCA occlusions and 56% of isolated ICA occlusions, but in only 31% of T-type occlusions and 27% of VB stroke. Poor clinical outcome in T-type occlusions and VB strokes was influenced by the lower recanalization success...
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The role of oxysterol signaling pathway in the development of solid tumors
Spálenková, Alžběta ; Souček, Pavel (advisor) ; Hodek, Petr (referee) ; Vondráček, Jan (referee)
Oxysterols are oxidized derivatives of cholesterol that play an important role in the pathogenesis of many diseases, including cancer. They affect processes such as cell proliferation, apoptosis, and cell migration and may also influence the efficacy of some anticancer drugs. Their levels may also be associated with the prognosis of cancer patients. The present thesis summarizes studies that expand the knowledge on the importance of oxysterols in breast cancer at different levels. In the first study, we analyzed gene expression of key factors of the oxysterol signaling pathway on the prognosis of patients with estrogen receptor (ER)-positive breast cancer. The results of this analysis revealed the association of the expression of some genes with clinico- pathological data of patients, such as tumor stage (according to TNM classification) or the tumor grade. Furthermore, we revealed an association between ABCG2 gene expression and disease free survival of patients. However, for other genes, the prognostic potential will require validation in a larger cohort of patients. The second study was designed to determine plasma levels of seven oxysterols in patients with ER-positive breast cancer. This study resulted in an association of the levels of different oxysterols with tumor size or stage. Higher...
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Mapping of packet processing from P4 Language to FPGA Technology
Kekely, Michal ; Fišer, Petr (referee) ; Zilberman, Noa (referee) ; Kořenek, Jan (advisor)
Táto dizertačná práca sa zaoberá návrhom nových hardvérových architektúr na klasifikáciu paketov. Hlavným cieľom je navrhnúť všeobecné a flexibilné hardvérové prístupy, ktoré sú schopné klasifikovať pakety na vysokorýchlostných počítačových sieťach. Prístupy musia byť konfigurovateľné pomocou popisu v jazyku P4 a musia byť škálovateľné na siete s rýchlosťou 100 Gb/s a viac. Práca začína analýzou aktuálneho stavu poznania v oblasti klasifikácie paketov. Na základe tejto analýzy sú navrhnuté nové architektúry pre klasifikáciu paketov. Pri návrhu sa dbá na škálovateľnosť, flexibilitu a pamäťovú efektivitu. Cieľom je dosiahnuť vysokú priepustnosť a zároveň udržať programovateľnosť pomocou P4 a schopnosť vykonať všeobecnú klasifikáciu paketov. Navrhnuté prístupy sú optimalizované a rozšírené, aby boli čo najefektívnejšie. Prvá architektúra využíva algoritmus DCFL rozšírený o paralelnú pamäť typu TCAM, duplikáciu pamätí a analýzu množiny pravidiel. Cieľom je dosiahnutie všeobecnej klasifikácie paketov, ktorá má nízke pamäťové nároky a ponúka možnosť škálovať priepustnosť za cenu zvýšených zdrojov. Druhý navrhnutý prístup je špecializovanejší. Optimalizuje klasifikáciu paketov založenú na úplnej zhode. Toto je dosiahnuté využitím distribuovaných pamätí na čipe FPGA na zrýchlenie algoritmu kukučieho hešovania. Hlavným cieľom je dosiahnuť veľmi vysokú priepustnosť efektívne. Architektúry sú ďalej rozšírené navrhnutím mechanizmu vyrovnávacej pamäte, ktorá dovoľuje efektívne použiť externé pamäťové bloky. Nakoniec sú tieto architektúry vyhodnotené na skutočných sieťových dátach a sú ukázané dosiahnuté výsledky.
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Materials characterization of mortar samples from the archaeological context of the Basilica of St. Wenceslas in Stará Boleslav.
Válek, Jan ; Kozlovcev, Petr ; Svorová Pawełkowicz, Sylwia ; Kotková, Kristýna
The mortar samples were characterized by optical microscopy and SEM-EDS. The aim of the study was to compare them with each other. All three samples have similar structure and material composition. The raw material for the lime was fine-grained sedimentary limestone with high CaCO3 content. The lime matrix has the character of air lime. In addition to the lime binder, there is also a mud-clay binder. This is separate from the lime binder. The sand grains are surrounded by the lime binder and there is a mud-clay filler in the intermediate space, indicating that this component was added as an admixture to the mortar only during use in construction. The sand used corresponds to the local conditions, both to aeolian sands (loess and loess sediments) dominated by worked quartz clasts and, in part, to sediments of fluvial origin (here mainly lithoclasts transported over a greater distance).
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Study on dynamics of spinning apparatus of some wolf spiders (Araneae: Lycosidae) during their life cycle
Dolejš, Petr ; Smrž, Jaroslav (advisor) ; Žďárek, Jan (referee) ; Hajer, Jaromír (referee)
Current knowledge of the spinning apparatus comes namely from studies on orb web spiders and their relatives, whereas that of wolf spiders were more or less neglected. Therefore, developmental changes of the spinning apparatus of four wolf spiders were studied throughout their life cycles. Each of these lycosids possesses stenochronous life cycle with similar number of instars (7-10) but of different length (1-3 years). There is only one period of reproduction in spring/summer in all four species. Sperms are being formed just after the final moult; diplotene in some species is peculiar. The courtship behaviour reflects the microhabitat occupied by the concrete spider species; the copulations are species specific. Ontogeny of the spinning apparatus of developing spiderlings was observed: The spinning apparatus initiate its function in the first instar. Secondary ampullate, all piriform and all but four aciniform glands are tartipore-accommodated; they do not moult in situ. The tartipores, vestigial structures corresponding to spigots of the previous instar, appear on the spinning field starting with the second instar. Tartipore-accommodated glands play roles also during proecdysis and their evolution corresponds with the way how do the spiders secure themselves when moulting. Hence, the not yet...
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Gene Expression Regulation of Biotransformation Enzymes and Transporters in Placental Barrier
Stejskalová, Lucie ; Pávek, Petr (advisor) ; Modrianský, Martin (referee) ; Vondráček, Jan (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxicology Candidate Mgr. Lucie Stejskalová Supervisor Doc. PharmDr. Petr Pávek, Ph.D. Title of Doctoral Thesis Gene expression regulation of biotransformation enzymes and transporters in placental barrier Placenta is a unique organ facilitating the communication between mother and fetus. It serves as a respiratory, excretory, endocrine and metabolic organ during intrauterine development of the fetus and is necessary for maintenance of pregnancy and for the fetal protection. Syncytiotrophoblast is a single layer that represents the critical morphological and metabolic component of the placental metabolic and exchange barrier. The placental trophoblast contains multiple drug transporters and metabolizing enzymes that form placental metabolic barrier. The levels of the enzymes are not stable and fluctuate throughout pregnancy. Most of the enzymes are expressed at very low mRNA levels, however, in some cases there is absence of any relevant detectable protein or catalytic activity. Cytochrome CYP1A1 is the only placental xenobiotic-metabolizing enzyme of the cytochrome P450 superfamily for which significant expression and catalytic activity have been conclusively demonstrated in placental trophoblasts...
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Synthesis of photoactive derivatives of phthalocyanines and study of their biological activity
Rychvalská, Lucia ; Zimčík, Petr (advisor) ; Vícha, Robert (referee) ; Zitko, Jan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Mgr. Lucia Rychvalská Supervisor: prof. PharmDr. Petr Zimčík, PhD. Doctoral Thesis: Synthesis of photoactive derivatives of phthalocyanines and study of their biological activity Phthalocyanines (Pc) are macrocyclic compounds with conjugated system of double bonds with absorption maximum around 650 - 750 nm. They are characterized by high singlet oxygen production which makes them suitable candidates for photosensitizers in photodynamic therapy. However, they form inactive aggregates in water environment because of their planar hydrophobic aromatic core. There are many strategies to solve this problem, and this thesis is focused on fighting aggregation of Pc by their supramolecular interactions with cucurbiturils (CB). Subphthalocyanines (SubPc) are similar macrocyclic compounds composed of only three (instead of four) isoindol units with boron as a central atom, which has also axial substituent. Because of their cone-shape and axial substituent they are less aggregated in water but usually not very soluble, which could also be solved by interaction with CB. First part of this thesis was focused on synthesis of Pc with aminoadamantyl substituents on...
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