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Invoice Issue and Validation Process in Large Organisation
Smejkal, Milan ; Neužil, Jiří (referee) ; Videcká, Zdeňka (advisor)
The Assessment of the Current State of the Circulation of Selected Parts of Documents in a Large Organisation, Particularly Issuing an Invoice. The analysis deals mainly with large organisations, where an invoice is issued by the chief accounting office on the basis of information supplied by particular organisation units. A worker in an organisation unit creates a requirement for an invoice that is sent to the chief accounting office after having been approved. Here an accountant issues an invoice or sends the requirement back to be completed if some information is missing. Process Description, Introducing the Process into the Information System of an Organisation The analysis aims at making processes in large organisations efficient through information systems, exploiting information and speeding up the circulation of documents.
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Alemat s.r.o. headquarters and warehouse
Petr, Lukáš ; Neužil, Jiří (referee) ; Müller, Jan (advisor)
This diploma thesis deals with design of office building with warehouse. The buildings are situated on slightly sloping terrain in cadastre unit of Sudoměřice u Tábora. Both buildings have rectangular shape and are connected with two sides. The Alemat s.r.o. company is internet shop, predominately with electronics. In the office building is also showroom where are some products will be shown. The warehouse will serve for receipt and issue of goods and to store them. The perimeter walls of office building is designed from ceramic block thickness of 250mm, for example Heluz Family 25. The walls will be insulated with 200mm of expanded polystyrene. The foundation construction is designed as foundation strips from plain concrete and permanent formwork brick filled with concrete and reinforced with steel. The ceiling construction is designed as prestressed panels thickness of 250mm. The roof is flat with main hydro isolation made of plasticized PVC foil loaded with pea gravel. The main construction of warehouse will be made of steel frames. The exterior skin of the warehouse will form panels Kingspan thickness of 140mm. The foundation construction is designed as monolithic foundation pads. Between the pads will be monolith grade beams. The roof is designed also from Kingspan panels. To the panel will be mechanically fastened plasticized PVC foil. Roof drainage is designed to rain gutters.
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The role of erbB-2 oncogene in the biology of cancer stem-like cells
Prokopová, Kateřina ; Neužil, Jiří (advisor) ; Anděra, Ladislav (referee)
Recent studies indicate the existence of a subpopulation of cells within tumours with stem cell-like characteristics. These "cancer stem-like cells" (CSCs) are relatively resistant to established therapies, usually targeting differentiated and fast proliferating cells. Therefore, CSCs may be a reason for the relapse of neoplastic diseases. CSCs can be characterised by a specific gene expression profile and deregulated signalling pathways. Of these, upregulation of the erbB-2 (HER2) receptor, a hallmark of ~25-30% breast cancer patients, is related to dismal prognosis, elevated proliferation potential and resistance to chemotherapy. Recent evidence has suggested that upregulation of erbB-2 leads to increase in the pool of CSCs. In our study we used mammospheres, cells grown in the absence of serum, an in vitro model of breast CSCs, which were prepared by "weaning" breast cancer MCF7 cells to a special medium. These cells were CD44high and showed increased expression of ABCG-2, Sox-2, Vimentin as well as high levels of erbB-2. Next, we prepared a stable line of MCF7 cells with low levels of erbB-2 by shRNA. ErbB-2low cells were characterised for expression of set of CSCs markers and tested for tumour forming efficacy in nude mice using ultrasound imaging. Keywords Cancer stem-like cells, erbB-2,...
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Targeting mitochondria to overcome resistance of breast cancer to therapy
Rohlenová, Kateřina ; Neužil, Jiří (advisor) ; Špíšek, Radek (referee) ; Vítek, Libor (referee)
(EN) Tumours are heterogeneous and consist of multiple populations of cells. The population of cells with tumour-initiating capability is known as cancer stem cells (CSC). Cells with increased stemness properties and elevated resistance to anti-cancer treatment have been shown to be highly affected upon decline of mitochondrial respiration, linking the concept of CSCs to deregulated bioenergetics. Consistently, functional electron transport chain (ETC) is crucial in tumorigenesis. Expression of HER2 oncogene, associated with resistance to treatment in breast cancer, has been connected with regulation of mitochondrial function. We therefore investigated the possibility that manipulation of mitochondrial bioenergetics via disruption of ETC eliminates the conventional therapy-resistant populations of tumour, such as CSCs and HER2high cells. We demonstrate that HER2high cells and tumours have increased complex I-driven respiration and increased assembly of respiratory supercomplexes (SC). These cells are highly sensitive to MitoTam, a novel mitochondria-targeted derivative of tamoxifen, acting as a CI inhibitor and SC disruptor. MitoTam was able to overcome resistance to tamoxifen, and to reduce the metastatic potential of HER2high cells. Higher sensitivity of HER2high cells to MitoTam is dependent on...
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TRAIL-induced Apoptosis in Populations of Colon Cancer Cell Lines under Various Cultivation Conditions
Nevařil, Leonard ; Anděra, Ladislav (advisor) ; Neužil, Jiří (referee)
Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) is a cytokine of TNF family, which participates in the non-exclusive regulation of survival and proliferation of mainly hematopoietic cells. Shortly after its discovery it also brought significant attention as specific and potent inducer of apoptosis of cancer cells of various origins, and since then it has been investigated as a potential novel anti-tumor therapeutics. Recently, cancer stem cells (CSCs) were suggested to be a distinct subset of tumor cells that could be responsible at least in some tumors for their sustainment, recurrence and drug resistance. These cells in the "hierarchic" model of tumorigenesis thus represent an important and attractive target for efficient tumor therapy. In this study we use several colorectal adenocarcinoma cell lines as an experimental model for the analysis of CSC-prone cultivation conditions on TRAIL-induced apoptosis of these cells. For enrichment of eventual cancer stem cells we cultivated cell lines in a serum-free medium, originally developed for cultivation of neural stem cells, and assessed the expression of putative CSC markers CD133 and ABCG2 by flow cytometry (FACS). Simultaneously, we tested the expression of TRAIL receptors and susceptibility to TRAIL-induced apoptosis in these cells. We...
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Mitochondria and their role in carcinogenesis
Bajzíková, Martina ; Neužil, Jiří (advisor) ; Masařík, Michal (referee) ; Mráček, Tomáš (referee)
(EN) Mitochondria are the principal intracellular organelles responsible for fuel generation; however, they are not just cell powerhouses but are involved in a range of other intracellular functions including cell metabolism, proliferation, death, and immune responses. Loss of function in mitochondria will result in oxidative stress, which is one of the underlying causal factors for a variety of diseases including cancer. Cancer cells can predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic behavior is known as the "Warburg Effect." Linked to this, cancer cell mitochondria can switch between glycolysis and oxidative phosphorylation (OXPHOS) for their energy requirements and survival. The electron transport chain (ETC) function is pivotal for mitochondrial respiration, which is also needed for dihydroorotate dehydrogenase (DHODH) activity that is essential for de novo pyrimidine synthesis. In our research, we have used respiration-deficient cancer cells to challenge the dogma that mitochondria with their DNA are constrained within cells in the body. Our results document that mitochondria move from normal cells within the tumor stroma to tumor cells without mitochondrial DNA (mtDNA), resulting in long-lasting recovery of mitochondrial functions and,...
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The role of mitochondrial complex II in cancer cell biology
Kraus, Michal ; Neužil, Jiří (advisor) ; Kašpárek, Petr (referee)
Mitochondria are essential organelles for most eukaryotic cells, containing intricate networks of numerous proteins. These include, among others, complexes I-IV of the electron transport chain. Being at the crossroads of the tricarboxylic acid cycle and the respiratory chain, mitochondrial complex II plays a key role in cellular metabolism. The protein complex, also known as succinate dehydrogenase, is capable of not only succinate oxidation and electron transfer but also contributes to the production of reactive oxygen species. Mitochondrial complex II consists of four subunits, SDHA-D, and four dedicated protein assembly factors SDHAF1-4 that participate in complex II biogenesis. Mutations and epigenetic modulations of genes coding for succinate dehydrogenase subunits or assembly factors are associated with pathological conditions such as neurodegenerative diseases, or may result in tumor formation. However, inborn complex-II-linked mitochondrial pathologies are rather understudied, compared to diseases with causative errors of other mitochondrial complexes, presumably due to the fact that none of complex II subunits is encoded in the mitochondrial genome. Recent studies have shown that impairment of mitochondrial complex II function or assembly leads to accumulation of alternative assembly forms...
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Signalling pathways in pancreatic cancer and its treatment by targeting of mitochondria
Ezrová, Zuzana ; Neužil, Jiří (advisor) ; Masařík, Michal (referee) ; Divoký, Vladimír (referee)
Pancreatic cancer is one of the deadliest types of malignant diseases. Asymptomatic early tumour stages, tumour heterogeneity, cancer cell plasticity and unusually dense pancreatic stroma are responsible for the poor prognosis attributed to late diagnosis and therapy resistance. Therefore, targeting of a pivotal element common for any cell type within the tumour, e.g. mitochondria, may bring significant improvement. In this work, we demonstrate mitochondrial targeting of metformin, an anti-diabetic drug associated with reduced risk of developing pancreatic cancer, substantially increases accumulation of the compound in mitochondria. In consequence, we show that mitochondrially targeted metformin, MitoMet, eliminates pancreatic cancer cells in more than 1000-fold lower concentration than used for its parental compound. Following interaction with respiratory complex I (CI), MitoMet inhibits mitochondrial respiration, activates AMP-activated protein kinase pathway and causes depolarization of mitochondrial membrane potential in pancreatic cancer cells. Moreover, MitoMet induces cell cycle arrest and apoptosis, which is partially mediated via increased level of reactive oxygen species (ROS), and suppresses pancreatic tumour growth in vivo. Interestingly, SMAD4-deficient pancreatic cancer cells manifest...
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Heme catabolic pathway in pathogenesis of liver diseases
Váňová, Kateřina ; Muchová, Lucie (advisor) ; Brůha, Radan (referee) ; Neužil, Jiří (referee)
This thesis focuses on the role of heme catabolic pathway in the pathogenesis of selected liver diseases. The aim was to clarify if the modulation of heme oxygenase (Hmox) and its catabolic products - especially carbon monoxide (CO) and bilirubin - affected the development and progression of liver diseases, focusing on inflammatory and cholestatic pathways. Firstly, we discovered that the induction of hmox1 prevented hepatocellular damage in endotoxin-induced inflammation. Furthermore, administration of CO in vivo in early-phase of endotoxin-induced cholestasis decreased the inflammatory cytokine production in the liver and simultaneously prevented downregulatory effect of cytokines on hepatocyte transporters resulting in hepatoprotection. For the first time, we characterized in vivo tissue distribution and elimination of inhaled CO in rats. In vitro experiments and the model of extrahepatic cholestasis revealed the significant role of intracellular bilirubin in hepatocellular protection against oxidative damage which accompanies cholestatic disorders. Last but not least, hmox1 induction by heme increased hepatocyte transporters expression and subsequently stimulated bile flow participating in conferring protection against estrogen-induced cholestasis. Presented results demonstrate that the heme...
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