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Gene expression study of oxysterol signal pathway in breast cancer patients
Kloudová, Alžběta ; Souček, Pavel (advisor) ; Vopálenský, Václav (referee)
Hormonal therapy is a common part of breast carcinoma treatment in patients whose tumors express estrogen and progesterone receptors. The aim of hormonal therapy is to prevent proliferative effect of hormones througt their receptor proteins in order to inhibit tumor growth. However, certain number of tumors is resistant to hormonal therapy despite expression of hormonal receptors. Presently, the reasons of this resistance are not fully understood. Oxysterols are hydroxylated cholesterol derivates, which may play some role in development of the resistance. They may interfere with hormonal therapy effect and influence some signal pathways leading to cancer progression. This study comes with results of gene expression of proteins influenced by oxysterol action, metabolic and transport proteins, transcription factors and members of signaling pathways that may be related to oxysterol effect. This thesis identifies some candidate genes for future analysis on the basis of comparison of gene expression between estrogen receptor positive and negative tumors and correlation with clinopathological data. The final goal should lead to discovery of new diagnostic markers for breast cancer therapy. Powered by TCPDF (www.tcpdf.org)
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Mechanisms of resistance and iron metabolism in cancer stem cells
Lettlová, Sandra
(EN) Analogously to normal stem cells within the tissues, cancer stem cells (CSCs) have been proposed to be responsible for maintenance and growth of tumours. CSCs represent a small fraction of cells within the tumour, which is characterised by self-renewal capacity and ability to give rise to a tumour when grafted into immunocompromised mice. Cells with increased stemness properties are believed to be responsible for tumour resistance, metastases formation and relapse after tumour treatment. The first part of this work concentrates on resistance of the tumours, which is often associated with increased expression of ATP-binding cassete (ABC) transporters pumping chemotherapeutics out of the cells. For the purposes of this study, we utilized an in vitro model of CSCs, based on cultivation of cells as 3D "spheres". Expression profiling demonstrates that our model of CSCs derived from breast and prostate cancer cell lines express higher mRNA level of ABC transporters, particularly ABCA1, ABCA3, ABCA5, ABCA12, ABCA13, ABCB7, ABCB9, ABCB10, ABCC1, ABCC2, ABCC3, ABCC5, ABCC8, ABCC10, ABCC11 and ABCG2 among the cell lines tested. The protein level of ABC transporters tested in breast CSCs showed higher expression of ABCB8, ABCC1, ABCC2, ABCC10 and ABCG2 but downregulation of ABCB10 and ABCF2 proteins....
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Role of estrogen signaling in breast carcinoma: implications for cell metabolism
Urbančoková, Alexandra ; Smolková, Katarína (advisor) ; Dibus, Michal (referee)
Cellular transformation leads to rapid cell proliferation that causes a global disease called cancer. Breast cancer is the second most frequent group that affects primarily women. Disease progression is stimulated by the female sex hormone estrogen. This hormone affects cells via estrogen receptor signalization, for example, by changes in proliferation, angiogenesis, apoptosis, and differentiation. The estrogen signaling pathway also alters breast cancer cell metabolism. The inhibition of estrogen signalization is commonly used in cancer treatment. Nonetheless, some tumors show resistance to the treatment and increase the need for new targets of therapy which can be found among the changes in breast cancer cells metabolism. This thesis introduces more closely the topic of breast cancer and the effect of estrogen receptors.
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Mechanisms of resistance and iron metabolism in cancer stem cells
Lettlová, Sandra
(EN) Analogously to normal stem cells within the tissues, cancer stem cells (CSCs) have been proposed to be responsible for maintenance and growth of tumours. CSCs represent a small fraction of cells within the tumour, which is characterised by self-renewal capacity and ability to give rise to a tumour when grafted into immunocompromised mice. Cells with increased stemness properties are believed to be responsible for tumour resistance, metastases formation and relapse after tumour treatment. The first part of this work concentrates on resistance of the tumours, which is often associated with increased expression of ATP-binding cassete (ABC) transporters pumping chemotherapeutics out of the cells. For the purposes of this study, we utilized an in vitro model of CSCs, based on cultivation of cells as 3D "spheres". Expression profiling demonstrates that our model of CSCs derived from breast and prostate cancer cell lines express higher mRNA level of ABC transporters, particularly ABCA1, ABCA3, ABCA5, ABCA12, ABCA13, ABCB7, ABCB9, ABCB10, ABCC1, ABCC2, ABCC3, ABCC5, ABCC8, ABCC10, ABCC11 and ABCG2 among the cell lines tested. The protein level of ABC transporters tested in breast CSCs showed higher expression of ABCB8, ABCC1, ABCC2, ABCC10 and ABCG2 but downregulation of ABCB10 and ABCF2 proteins....
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Mechanisms of resistance and iron metabolism in cancer stem cells
Lettlová, Sandra ; Truksa, Jaroslav (advisor) ; Kovář, Jan (referee) ; Brábek, Jan (referee)
(EN) Analogously to normal stem cells within the tissues, cancer stem cells (CSCs) have been proposed to be responsible for maintenance and growth of tumours. CSCs represent a small fraction of cells within the tumour, which is characterised by self-renewal capacity and ability to give rise to a tumour when grafted into immunocompromised mice. Cells with increased stemness properties are believed to be responsible for tumour resistance, metastases formation and relapse after tumour treatment. The first part of this work concentrates on resistance of the tumours, which is often associated with increased expression of ATP-binding cassete (ABC) transporters pumping chemotherapeutics out of the cells. For the purposes of this study, we utilized an in vitro model of CSCs, based on cultivation of cells as 3D "spheres". Expression profiling demonstrates that our model of CSCs derived from breast and prostate cancer cell lines express higher mRNA level of ABC transporters, particularly ABCA1, ABCA3, ABCA5, ABCA12, ABCA13, ABCB7, ABCB9, ABCB10, ABCC1, ABCC2, ABCC3, ABCC5, ABCC8, ABCC10, ABCC11 and ABCG2 among the cell lines tested. The protein level of ABC transporters tested in breast CSCs showed higher expression of ABCB8, ABCC1, ABCC2, ABCC10 and ABCG2 but downregulation of ABCB10 and ABCF2 proteins....
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Gene expression study of oxysterol signal pathway in breast cancer patients
Kloudová, Alžběta ; Souček, Pavel (advisor) ; Vopálenský, Václav (referee)
Hormonal therapy is a common part of breast carcinoma treatment in patients whose tumors express estrogen and progesterone receptors. The aim of hormonal therapy is to prevent proliferative effect of hormones througt their receptor proteins in order to inhibit tumor growth. However, certain number of tumors is resistant to hormonal therapy despite expression of hormonal receptors. Presently, the reasons of this resistance are not fully understood. Oxysterols are hydroxylated cholesterol derivates, which may play some role in development of the resistance. They may interfere with hormonal therapy effect and influence some signal pathways leading to cancer progression. This study comes with results of gene expression of proteins influenced by oxysterol action, metabolic and transport proteins, transcription factors and members of signaling pathways that may be related to oxysterol effect. This thesis identifies some candidate genes for future analysis on the basis of comparison of gene expression between estrogen receptor positive and negative tumors and correlation with clinopathological data. The final goal should lead to discovery of new diagnostic markers for breast cancer therapy. Powered by TCPDF (www.tcpdf.org)
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The role of estrogen receptors in prognosis and therapy outcome of breast cancer
Kloudová, Alžběta ; Souček, Pavel (advisor) ; Dračínská, Helena (referee)
Estrogen receptors (ER) are members of nuclear receptor family, which mediate distinct physiological functions after binding a steroid ligand. Apart from that they play a role in many diseases including breast cancer. ER is among proteins routinely evaluated in clinical practice and on the basis of ER expression, patients are treated by endocrine therapy. There are different opinions of the role of ER in cancer cells, but in the future, detection of ER and treatment by ER- and ER-selective ligands could contribute to improvement of cancer therapy. Isoforms, mutations and posttranslational modifications of ER present other important factors, which can influence estrogen signalization and endocrine therapy efficiency and deciphering of their importance for cancer cells could bring better understanding of ER signalization and improvement of the therapy.
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Importance of HSD17B1 gene amplification in breast cancer
MAŠOVÁ, Michaela
Breast cancer is the most common female tumour disease. Although, the incidence is constantly growing, mortality of this disease is decreasing. However, there are still occurrences, where the conventional therapy failed. One of the important therapeutic attribute is hormone dependence of breast cancer and status of growth factor receptor HER2 (Her-2/neu, c-erbB-2). Treatment of the breast cancer with higher expression of estrogene or progesterone receptors (ER or PR) could be targeted-into blockade of these receptors or in the case of HER2 we could blockade it´s function with monoclonal antibody trastuzumab or lapatinib. Because of aggression of HER2 positive tumour cells, this subtype of breast cancer belonged to the group of patients with the worst prognosis. Thanks to targeted (biological) therapy belongs this patients into the group with the best treatable breast cancer today. However, in some of the hormone-dependent breast cancer cases the treatment fails. One of the reasons could be the product of HSD17B1 gene that is involved in metabolism of these hormones. Moreover, this gene is localized on chromosome 17 (like HER2 gen) and therefore it´s aberration could be suspected. Because the FISH probe for HSD17B1 gene is not commercially available, we prepared it by using transgenic E. coli bacterial clones. The specifity was checked on chromosomal spreads. In this presented thesis, we investigated 50 patient´s breast cancer samples by using fluorescent in situ hybridization to determine the status of HSD17B1 gene. Amplification of the gene could be important in the treatment of breast cancer and in resistance to antihormonal therapy. Next, we tried to check, if the status of HSD17B1 gene could be dependent on status of HER2 gene or if it correlates for example with patient´s age at time of diagnosis etc. Although, the statistical important correlations were not found, it seems, that HSD17B1 gene is lightly increased in some cases. In the next phase the study will be extended of another patient samples and the clinical dates and analysis in relation to HSD17B1 will be done. This is a pilot project. The main goal was to prepare HSD17B1 gene probe intended for commercialization and check the probe on the set of patients with breast cancer.
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