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Molecular mechanisms of coronary vasculature development
Neffeová, Kristýna ; Kolesová, Hana (advisor) ; Neckář, Jan (referee)
The cardiovascular system is the first functional system that develops in vertebrates during embryonic development. Its irreplaceable function is the transport of nutrients and the removal of waste products. During the development the heart not only grows, but also acts as a pump that drives the blood circulation of the embryo. With advancing development, it is necessary to ensure an adequate supply of oxygen to the heart, for that reason coronary arteries are formed. Each cardiomyocyte is surrounded by at least one capillary, therefore the interaction between cardiomyocytes and endothelial cells plays an indispensable role in the proper functioning of the heart. Understanding, how cardiomyocytes and endothelial cells communicate, is essential for medical research in cardiac tissue regeneration. A number of factors involved in coronary development are described in the literature. However, these factors are described as separate signaling pathways, not as a system of mutually interacting mechanisms. The main goal of my bachelor thesis is to connect individual signaling cascades important in cardiomyocyte-endothelial cell communication and describe their interactions. The main factors overviewed are VEGF, Notch, PDGF, Angiopoietin and others. Factors function and signalization is reviewed in details....
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Renal carcinoma bological therapy and the role of cell signaling checkpoints
Černá, Kristýna ; Otavová, Katarína (advisor) ; Tolde, Ondřej (referee)
Principles of targeted biological treatment of metastatic renal cell carcinoma include mainly inhibitors of the tyrosine kinase receptors VEGFR and inhibitors of intracellular mTOR kinase. Across the new healing regimes there are the blockades of immune checkpoints of the immune system cell. Detailed molecular characterization of tumor is necessary not for only aplication of medicaments, but also for the development of drugs that target specific molecular pathway of cell signalization of the carcinoma cells. The work is focused on the description of the signaling pathway mTOR and VEGF in metastatic renal cell carcinoma. It summarizes all validated clinical biomarkers which are used to diagnose and stratify patients for the treatment of mRCC. It also offers insight into the present experiments that are finding new specific molecular markers. That may be the future solution for customized approach in the treatment of renal carcinoma an tumors in general.
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Changes in placental angiogenesis and their impact on fetal intrauterine growth restriction
Kudějová, Alena ; Švandová, Ivana (advisor) ; Magner, Martin (referee)
Any pathological interference with normal vascular development of placenta may have a critical impact on fetal growth and development. The proliferation and differentiation of several cell types play a very important role in the vascular system of placenta. The main factors taking part in the vascular development of placenta include cell elements (e.g. trofoblast, stromal chorion cells, haemangiogenic progenitors), the extracellular matrix, growth factors and cytokines (e.g. VEGF, PlGF, Ang-1,2 and bFGF). The extrinsic factors may also influence the partial oxygen pressure, nutritients availability, and/or the blood perfusion in placenta. Placental ischaemia leading to the worsening of uteroplacentar perfusion is the most common cause of the intrauterine growth retardation (IUGR). The IUGR development is then the result of insufficient prolongation, branching, and dilatation of capillary loops during the formation of terminal villi. Published studies focusing on growth factors in placentas from physiological pregnancies and pregnancies with IUGR do not give clear results. This BSc. Thesis is a review focused on up-to-date-known data concerning changes in placental angiogenesis and their impact on IUGR. Key words: placenta, angiogenesis, IUGR, pregnancy
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Molecular genetic characterization of the rare tumours of the urogenital tract.
Šteiner, Petr ; Vaněček, Tomáš (advisor) ; Španielová, Hana (referee)
The aim of this study was molecular characterization of four types of renal tumours (papillary renal cell carcinoma [PRCC], tubulocystic renal carcinoma [TCRC], pseudorossette forming renal carcinoma [PRRC] and unclassified renal carcinomas [URC]) and two types of rare tumours of the testes (Adult type of granulosa cell tumours [ATGCTs] and Incompletely differentiated sex cord stromal tumours [ISCSTs]). In case of TCRC the activity of signalling pathways involved in angiogenesis was studied. The aim was to determine the suitability of antiangiogenic agents for treatment of TCRC. Next, the methylation profile of 24 tumor suppressor genes was studied in TCRC and PRCC in order to analyze their similarity. Eventual differences could be helpful tool in differential diagnostics. Also, spectrum of chromosomal aberrations was analyzed by array-CGH in one case of PRRC and two cases of URC. Any unique aberration found would be useful in differential diagnostics of these tumors. Last, but not least, the specificity of mutation c.402C>G of FOXL2 gene for ovarian ATGCTs was verified by studying its occurrence in testicular ATGCTs and ISCSTs. Analysis of mRNA levels did not reveal any enhanced activity of the studied signalling pathways. Cluster analysis of methylation profiles showed close relationship between PRCC a...
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The use of CAM assay for characterization and study of cancer cell invasive properties
Vágnerová, Lenka ; Dvořák, Michal (advisor) ; Geryk, Josef (referee)
The chorioallantoic membrane (CAM) of chicken embryos belongs to the in vivo model systems frequently used for the study of angiogenesis and cell invasiveness. Using CAM assay we have tested selected chicken sarcoma cell lines characterized by different angiogenic properties and different ability to form metastasis. In addition to CAM assay, several other methods have been used to characterize the phenotype of these cell lines. We have selected a few proteins which could significantly influence the angiogenic and metastatic properties of investigated cell lines. We have established cell lines stably overexpressing these genes and compared their phenotypes with parental cell lines. We have shown that genes encoding ISL1, ARNT2, PROM1, HOXA11 proteins participate, in our experimental model, in activation of programes controlling angiogenesis and cell invasion.
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Příprava a charakterisace rekombinantního dermcidinu jako potenciálního proteinového partnera glutamátkarboxypeptidasy II
Tužil, Jan ; Konvalinka, Jan (advisor) ; Pavlíček, Jiří (referee)
A process of forming new blood vessels is necessary for tumour viability and expansion. Without vasculature, tumour stops growing at a size of millimeters. Some tumours, however, undergo an angiogenic switch and start to build up their own vascular architecture. The rate of apoptosis then decreases and the tumour becomes invasive. There are many factors that control the process of physiological angiogenesis. These might or might not relate to tumour tissue as well. Glutamate carboxypeptidase II (GCPII; EC 3.4.17.21) is a type II transmembrane glycoprotein with two known enzymatic activities. GCPII expression is upregulated in prostate cancer and also highly expressed in tumour-associated neovasculature even though none of these enzymatic functions was observed on the endothelium. Although numerous researches suggested that GCPII might serve as a receptor, no natural ligand has been identified yet. Preliminary experiments performed in our laboratory indicated some proteins to be possible natural ligands of GCPII. Therefore, we chose one of them- dermcidin, cloned and expressed this protein in mammalian cells. We investigated its possible interaction with GCPII introducing new detection system utilizing FLAG-tag however, we were not able to approve neither disapprove its interaction in vitro.
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Angiogenesis in cerebral ischemia border zone
Nulíčková, Radka ; Otáhal, Jakub (advisor) ; Brime, Tufikameni (referee)
Title of work: Angiogenesis in the border zones of cerebral ischemia The aims of work: The aim of this diploma thesis was to determinate the parameter of the angiogenesis after focal brain ischemia induced by photothrombosis in P7 rat pups. This thesis should answer the question, if there is some difference in vascular density according to the distance from the lesion and if there is some diference between the vascular density in normal brain and the brain with the lesion. Materials and Methods: Cerebral ischemia was induced in P7 rat pups with photothombic method. Intravenous administration of bengal rose dye was followed by illumination of beam of green laser over the cortex for 5 minutes at 0,5s on/off cycles. Bengal rose dye is potent photosensitive substance and the ilumination resulted in agregation of trombocytes and thrombosis. Cerebral ischemia evolved due to the thrombosis. After two months, the animals were overdosed with urethane and transcardially perfused. Then thein brain were cryoprotected and then cut into 50µm slices and prepaired for histological staining. The stained slices were the investigated under mikroskope. The microvessels in the cortex were counted and the density was estimated by stereological method. Results: Two brain with ischemic lesion and two control brain were...
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Inhibition of Thymidine Phosphorylase
Zákoucká, Eva ; Brynda, Jiří (advisor) ; Obšil, Tomáš (referee)
2. Abstract Thymidine phosphorylase (TPase), also known as gliostatin or Platelet-derived endothelial cell growth factor (PD-ECGF), is an enzyme with an important role in the nucleoside metabolism and is also involved in degradation and recycling of DNA. TPase catalyzes the reversible phosphorolysis of pyrimidine 2'-deoxynucleosides to 2-deoxy-D-ribose-1- phosphate and their respective bases, as well as the transfer of the deoxyribosyl moiety from one pyrimidine base to another. Thymidine phosphorylase is a therapeutic target of great importance because of its participation in angiogenesis especially in solid tumors of various tissues. Therefore, TPase stimulates tumor growth and progression, as well as metastasis. In addition to this, TPase inhibits apoptosis, particularly of tumor cells and causes degradation of several antiviral and anticancer drugs. Apart from the carcinoma tissues, thymidine phosphorylase is overexpressed in various other tissues affected by disorders characterized by proliferation of blood vessels including psoriasis, rheumatoid arthritis and atherosclerosis. Inhibiting the activity of TPase selectively in the tissues affected by the diseases listed above would be of great therapeutic significance. Therefore, many inhibitors, mainly substrate analogues, have been designed based on the...
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Model of dynamic contrast CT data for verification of registration algorithms
Kupková, Karolína ; Harabiš, Vratislav (referee) ; Walek, Petr (advisor)
This work is focused on the description of the dynamic contrast-enhanced CT examination and its contribution in the pneumooncology. It includes a program for creating a two-dimensional model of the scan from the thorax and for the perfuse examination simulation using the time-density curve. Real CT data are simulated more authentic using rigid geometric transformations and noise. The model will be used for the validation of registration algorithms that is used to suppress the spatial deformation generated by patient motions during the long time examination.
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CT laser mammography
BAČOVSKÁ, Michaela
According to the data from the Ministry of Health, malignant breast tumours rank in first place in terms of the most frequent malignant tumour disorders in women in the Czech Republic. Every year over 5500 new cases of breast carcinoma are diagnosed, with approximately 2000 women dying each year as a consequence of this disorder. In September 2002 blanket screening for breast cancer was officially launched in the Czech Republic. Its main task resides in identifying breast carcinoma in its early stages, and also in prolonging the survival of patiens due to more effective treatment of the initial stages of the disorder. After the introduction of screening there was logically also an increase in the recorded incidence, and at the same time there should be a reduction of mortality. The endeavour to scan breasts commenced with the development of X-ray examination methods and with the general development of new technologies in the last century diagnostic methods also came to the forefront. Progress was achieved primarily in the area of X-ray examination methods, whilst at the same time there was a parallel development of entirely new methods. Today computer tomography, magnetic resonance or emission computer tomography are entirely available. In terms of scanning breast glands the greatest progress was recorded by mammography, an in close linkage by ultrasound. In addition to these basic and proven methods, the latest development in mammodiagnostics enables us to use also new examination methods, which are used as supplementary methods. One of these is CT laser mammography (CTLM), which is used in several countries worldwide. In the Czech Republic the radiodiagnostice clinic of the Královské Vinohrady Teaching Hospital in Prague and the Masaryk Memorial Cancer Institute in Brno have access to a CTLM machine. As the name indicates, this concerns breast scanning using laser rays. CTLM displays the physiological vessel structure in the breast, as well as any angiogenesis if present.
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