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Studies of intercellular interactions in tumours
Jechová, Alžběta ; Smetana, Karel (advisor) ; Skalníková, Helena (referee) ; Masařík, Michal (referee)
Beside tumor cells themselves, tumors consist of many non-malignantly transformed cellular elements and an extracellular matrix. This so-called tumor microenvironment, or stroma, significantly influences the biological properties of the tumor through intercellular interactions. In this thesis I have focused on the study of tumor-associated fibroblasts in squamous cell carcinomas of the head and neck, malignant melanoma and glioblastoma. The data show the presence of cells with mesenchymal characteristics, present even in the glioblastoma stroma, which could potentially have a positive effect on proliferative activity and invasiveness of glioblastoma cells. In malignant melanoma, the presence of keratinocytes should also be considered, as they are the major cells of the epidermis influencing tumor melanocytes. The conditioned medium from UVB irradiated keratinocytes and non-irradiated fibroblasts stimulates the invasion of malignant melanoma cells. Targeting the tumor stroma may be a new direction in oncological therapy, so we have focused on the influence of synthetic polyamine on the formation of myofibroblasts, which are an active part of the population of tumor-associated fibroblasts. The tested polyamine prevents the formation of myofibroblasts but has no effect on those already formed nor on...
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Complex Preoperative Brain Tumor Imaging
Tupý, Radek ; Ferda, Jiří (advisor) ; Vymazal, Josef (referee) ; Tüdös, Zbyněk (referee)
Title Complex preoperative brain tumor imaging Abstract The differentiation of glioblastoma, metastases and brain lymphoma using modern diagnostic imaging methods has a major impact on the strategy of further diagnostic examinations and treatment. In a group of 67 patients with glioblastoma and 31 with cerebral metastasis, the ability to differentiate them according to the evaluation of perfusion parameters changes in peritumoral white matter by T1 dynamic post-contrast magnetic resonance imaging was verified, with the positive predictive value in glioblastoma detection up to 91%. In a group of 36 brain lymphoma patients the importance of imaging submodalities and contribution of a complex magnetic resonance imaging protocol to detect lymphoma up to 80% were evaluated. Key words brain, glioblastoma, lymphoma, magnetic resonance imaging, neoplasm metastasis
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Cytogenetic and molecular characterization of astrocytic tumors
Čurnová, Lenka ; Vícha, Aleš (advisor) ; Gemperle, Jakub (referee)
Astrocytic tumours include a heterogeneous group of tumours with different histological features. Their diagnostics and classification could be difficult in some cases. Besides histological features of the neoplastic tissue genetic mutations in the tumour cells are important for the basic characteristic of the tumours. According to the histological and clinical characters tumours of the central nervous system are divided into several malignancy grades. Low-grade astrocytomas are the most common solid tumours of children. More malignant forms (mainly glioblastomas) represent a significant group of tumours of CNS of adult patients. IDH1, TP53, EGFR, PTEN typically belong among genes which carry mutations in the cells of astrocytic tumours. Mostly pilocytic astrocytomas are often connected with mutations of the BRAF gene which is a part of the mitogen activated protein kinase (MAPK) pathway. Many modern methods are used for the investigation of the mutations in the genome of the neoplastic tissue. PCR, real-time PCR and sequencing are the most important molecular methods. The most often used cytogenetic methods which are based on the hybridization of the DNA are FISH and microarray techniques. In some cases also immunological methods could be used. The correct diagnostics of the tumour and its...
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Definition of the expression pattern of DASH system in transformed glial cells, the coupled expression of fibroblast activation protein and dipeptidyl peptidase-IV.
Balážiová, Eva ; Šedo, Aleksi (advisor) ; Borovanský, Jan (referee) ; Mareš, Vladislav (referee)
Dipeptidyl peptidase-IV (DPP-IV) is a multifunctional transmembrane glycoprotein removing X-Pro dipeptide from the amino-terminus of the peptide chain. This evolutionary conserved sequence protects a number of biologically active peptides against the unspecific proteolytic cleavage. DPP-IV belongs into the group of "Dipeptidyl peptidase-IV Activity and/or Structure Homologues" (DASH), which, except the canonical DPP-IV, comprises fibroblast activation protein-α/seprase (FAP), and several other molecules. However several of DASH molecules are the enzymes, they execute at least some of their biological functions by non-proteolytic protein-protein interactions. DASH molecules, their substrates and binding partners are parts of "DASH system" which is affected in several pathological process including a cancer. Specifically DPP-IV and its closest structural relative FAP are among others expected to be involved in the development and progression of malignant glioma. In this study we showed the expression and colocalization of DPP-IV and FAP in glioma cells in vitro and in human high grade gliomas. In addition to the DPP-IV/FAP double positive transformed glial cells, we also identified a subpopulation of FAP positive mesenchymal cells located in the perivascular compartment. Moreover we described the...
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Tubuline isotypes in cancerogenesis
Hořejší, Barbora ; Dráber, Pavel (advisor) ; Binarová, Pavla (referee) ; Opatrný, Zdeněk (referee)
The long-term goal of the Laboratory of Biology of Cytoskeleton is to explain in molecular terms the role of microtubules in cellular processes and to characterize proteins associated with microtubules and its organizing centers (MTOCs). The main attention of our research is focused on -tubulin and its role in microtubule nucleation. We have shown previously that besides its localization on centrosomes, -tubulin is found on celullar membranes (Macůrek et al., 2008), plant kinetochores (Dryková et al., 2003) and marginal bend of embryonal chicken erytrocytes (Linhartová et al., 2002). g-Tubulin also interacts with protein tyrosine kinases, that can regulate microtubule nucleation (Sulimenko et al., 2006; Macůrek et al. 2008). There are growing evidence that centrosomal proteins can affect genetic stability of the cell. g-Tubulin is involved in the regulation of the cell cycle (Vardy et al., 2002) and can participate in activation of checkpoint mechanism controlling the integrity of DNA. Recently, it has been proved its interaction with nuclear protein ATR (Zhang et al., 2007) and Rad51 (Lesca et al., 2005). That's why g-tubulin has been connected with the process of cancerogenesis. Cancer cells also display the changes in expression of b-tubulin isotypes (Katsetos et al., 2003). Moreover, increased level of...
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Role fibroblastového aktivačního proteinu v růstu a invazivitě gliomových buněk
Fejfarová, Edita ; Bušek, Petr (advisor) ; Szabo, Pavol (referee)
High grade astrocytomas are very progressive brain tumors. Glioblastoma multiforme is the most frequent and the most malignant type with very infiltrative phenotype of the tumor cells. Fibroblast activation protein FAP is a predominantly membrane bound prolyl peptidase bearing exo- and endopeptidase hydrolytic activities. FAP is known to play a role in wound healing, cell migration and invasion and its expression is linked to the pathogenesis of several malignancies. mRNA expression of FAP is upregulated in 48% of glioblastomas according to The Cancer Genome Atlas microarray data. The involvement of FAP in the pathogenesis of astrocytic tumors is largely unknown. The aims of this work are to analyse the expression of FAP in primary cell cultures derived from high grade gliomas and to analyse the influence of FAP on the growth, migration and invasion of glioma cells. Our ELISA and western blot results showed heterogenous expression of FAP in the studied glioma primary cell cultures and cell lines. Both enzymatic activities characteristic of FAP were detected in the primary glioma cell culture P11 with high expression of FAP. In these cells, FAP was present not only in the typical plasma membrane localization, but also in the cytoplasm as demonstrated by immunofluorescence staining. The P11 cells...
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