National Repository of Grey Literature 8 records found  Search took 0.00 seconds. 
Biological Characteristics of Colon Cancer Cells in In Vitro Models and its Use for Individualization of Therapy
John, Stanislav ; Rudolf, Emil (advisor) ; Ćwiertka, Karel (referee) ; Kiss, Igor (referee)
Malignant tumours are the second most common cause of death worldwide right behind the cardiovascular diseases. This tendency is by the opinion of the World Health Organisation increasing especially in well developed countries. (Ferlay 2012) Because cancer has become in 20th century serious social and economic problem, research on it is for WHO and IARC (International Agency for Research on Cancer) the top priority. (Mendis 2014) Relative and absolute incidence is also rising. The reason, besides others, is aging of population. Because age is one of the main prognostic factors for cancer, people are more likely to "survive" till the onset of it. However, diagnostic options are improved and many tumours are detected in early stage which in turn boosts the ability and effectiveness of treatment. Screening programmes are introduced into routine medical practice (e.g. mammography, prostate-specific antigene, occult blood testing or colonoscopy) inducing awareness in the general population. (Dušek et al. 2005; Mendis 2014) Last but not least, the treatment itself has developed considerably over the last 15 to 20 years, with the focus on patient "tailor-made" therapy. It includes new mini-invasive or robot-assisted surgical techniques, new radiation techniques (IG-IMRT - Image-Guided Intensity-Modulated...
Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana ; Anděra, Ladislav (advisor) ; Rudolf, Emil (referee) ; Vondráček, Jan (referee)
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
Analysis of Growth-inhibitory Mechanism of Flubendazole in Malignant Melanoma Cells
Čáňová, Kristýna ; Rudolf, Emil (advisor) ; Slaninová, Iva (referee) ; Mandys, Václav (referee)
Analysis of growth-inhibitory mechanisms of flubendazole in malignant melanoma cells Malignant skin melanoma is at its advanced stage highly aggressive and chemoresistant to almost all currently available therapies. Moderns efforts are thus aimed to identify new targets in melanoma cells or to take advantage of novel indications of already approved drugs - a process called drug repurposing. This work was focused on evaluation of cell growth inhibitory properties of one such drug - flubendazole (FLU) - a widely used anthelmintic compound belonging to benzimidazole family. This drug specifically interacts with β-tubulin, which results in disruption of microtubule structure and function in the exposed cells. Several members of the benzimidazole family (including FLU) have already shown the growth inhibitory potential in tumor cells derived from breast, colon, blood and nervous system malignancies. Still, the specific activity of FLU in malignant melanoma has not been tested to the date. Cytotoxicity of FLU was tested in three malignant melanoma cell lines representing diverse melanoma molecular types (A-375, BOWES and RPMI-7951) during up to 72 hours using WST-1 and x-CELLigence assays. Based on achieved IC50 from individual cell lines, the 1 µM FLU concentration was selected for further testing. While...
Srovnání indukce a regulace autofagocytózy v proliferujících a senescentních nádorových buňkách
Pešina, František ; Anděra, Ladislav (advisor) ; Rudolf, Emil (referee)
Autophagy, senescence and apoptosis are tightly linked processes which together determine the fate of cells in response to various stresses. There is ample evidence supporting the notion that senescent cells are highly dependent on autophagy and this process is here much more intensive than in nonsenescent cells. Autophagy may to some extent compensate increased energetic and metabolic demands of senescent cells and also helps with removal of toxic products such as oxidized proteins, protein aggregates and damaged organelles resulting from an overloaded metabolism of some senescent cells. In addition, some studies reported the need of autophagy for the adoption of senescent phenotype. However, there are also studies with seemingly contradictory results claiming that increased autophagy prevents or delays cellular senescence. Relationship of autophagy to apoptosis is similarly ambivalent. Whereas intact autophagy is necessary for the cell, while slightly increased autophagy still has a rather positive impact, excessive autophagy may lead to degradation of critical components necessary for cell function and survival and can trigger one of the modes of programmed cell death. In the first part of this work, we focused on the analysis of autophagic response in senescent and proliferating pancreatic...
Účinky seleničitanu sodného na buňky lidského kolorektálního karcinomu s odlišným p53 genotypem
Králová, Věra ; Rudolf, Emil (advisor) ; Skálová, Lenka (referee) ; Hofmanová, Jiřina (referee)
Effects of sodium selenite in human colon cancer cells with different p53 status Colorectal carcinoma (CRC) is one of the leading causes of cancer - associated mortality. Great effort is spent on the investigation of prevention possibilities by various types of environmental factors. Several epidemiological studies and clinical studies have shown an inverse association between selenium intake and the risk of different types cancer including CRC. Also in animal models and cell lines in vitro selenium compounds have shown ability to inhibit proliferation and induce cell death. The aim of this study was to assess the antiproliferative effects of sodium selenite in colorectal cancer cells in vitro, particularly in two model colorectal cancer cell lines HCT 116 differing in their p53 status. We have shown that sodium selenite in concentration range of 2.5 µM-10 µM inhibited proliferation and induced cell death in HCT 116 cells in a time- and concentration- dependent manner. Sodium selenite blocked the progression through the cell cycle in the S/G2-M phases, induced superoxide production in mitochondria, DNA damage and expression of p53 protein and activated cell death with involvement of caspases. Sodium selenite also increased the expression of autophagy markers. The HCT 116-p53KO cells, lacking...
The study of influence inositolhexaphosphate on proliferation and apoptosis in cells isolated out of colorectal cancer
Hašková, Pavlína ; Šimůnek, Tomáš (advisor) ; Rudolf, Emil (referee)
Introduction: Apoptosis - programmed cell death significantly participates in maintaining of tissue homeostasis. Its alteration is leading to cancer disease. Inositolhexaphosphate (IP6) is naturally occurring substance that is present in most legumes, cereals and seems. IP6 and its lower phosphorylated forms are also found in most mammalian cells, where they assist in regulatory a variety of important cellular function (including regulation of cell cycle). Methods: This work has been engaged in the study of influence IP6 on apoptosis in cells isolated out of colorectal cancer by in vitro quantification enzymatic activity of caspase 3 in cell extract. Results: It has proved by the Student's t-test that IP6 statistically significant influence apoptosis in cells isolated out of colorectal cancer.
The role of proteinases-activatable receptor - 2 (PAR-2) in pathogenesis of human disease
Matěj, Radoslav ; Mandys, Václav (advisor) ; Fakan, František (referee) ; Ehrmann, Jiří (referee) ; Rudolf, Emil (referee)
It was presented that one of the pancreatic enzymes, trypsin, modulates many biological processes by acting on specific proteinase-activated receptor 2 (PAR-2). PAR-2 belongs to a family of G protein coupled receptors activated by tethered ligand sequences within the N-terminal, which is made accessible after the site-specific cleavage of the protein. Trypsin activates PAR-2 by the mediation of a unique process inhering in the recognition of the receptor by enzyme, subsequent c1eavage at the specific site ofNH2-terminal and presentation of a new NH2 terminal, which behaves as a tethered ligand. This ligand interacts with the extracellular doma in of receptor molecule. Thus, P AR-2 is a receptor, whose I igand is a physical part of the receptor molecule. This receptor was previously described on norma I as well as ma lignant immunocompetent cells, on endothelial and muscle cells of major as well as minor vessels. Its presence was also immunohistochemically demonstrated on intestinal epithelial cells, epithcl ial cells of exocrine organs, keratinocytes, fibroblasts and other cell types in stomach, small intestine, colon, liver and kidney. PAR-2 is expressed on various cells with a wide spectrum of cellular responses after activation. ln the firs t part of th is work we focused on the role of PAR-2 dUl·ing the...

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