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Study of the expression and toxicity of catechol derivates in MCF-7 cell line
Kleplová, Dominika ; Carazo Fernández, Alejandro (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Dominika Kleplová Supervisor: PharmDr. Alejandro Carazo, PhD. Title of the Diploma thesis: Study of the expression and toxicity of catechol derivatives in MCF-7 cell line Estrogens perform many important functions in the human body. They act by binding to estrogen receptors (ER) and thus regulate reproduction, the menstrual cycle, bone density, cholesterol metabolism or brain function. They also play an important role in the development and onset of breast cancer, where the amount of ER expressed is used as a very important biomarker in patients suffering from this disease. Despite ongoing research, breast cancer is considered to have the highest mortality rate. Catechols are organic compounds. In the human body, they can occur as metabolites in the degradation of benzene and estrogens or other endogenous compounds such as neurotransmitters and their precursors. Catechols are known to be involved in redox processes in the body, to exert antioxidant and toxic effects, to interfere with protein function and to cause DNA strand breaks. Their positive effect on breast cancer therapy is the subject of research, but it has not yet been fully explored. The subject of this thesis is to study the...
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Study of the expression and toxicity of catechol derivates in breast cancer cell lines
Vyoralová, Tereza ; Carazo Fernández, Alejandro (advisor) ; Jirkovský, Eduard (referee)
Studium exprese a toxicity derivátů katecholu v prsních nádorových buněčných liniích, Tereza Vyoralová ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Tereza Vyoralová Supervisor: PharmDr. Alejandro Carazo Ph.D. Title of the diploma thesis: Study of the expression and toxicity of catechol derivates in breast cancer cell lines Estrogens have several important functions in the human organism and are also involved in the formation and development of breast cancer. These effects are mediated by binding to estrogen receptors (ER) and show complex spectrum of effects such as regulation of reproduction, menstrual cycle, brain function, bone density or mobilization of cholesterol. In addition the presence and quantification of ER in breast cancer is currently used as one of the most important predictive biomarkers in patients suffering from this disease. The occurence and activity of ER correlates with the response of breast cancer to hormonal treatment and with the patient's prognosis. Despite intensive research, breast cancer is still ranked among the cancers with the highest lethality. Catechols are organic compounds that are naturally present in food as pollutants, but also can be found in the human body, where they play an important role as...
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Study of the expression and toxicity of catechol derivates in breast cancer cell lines
Vyoralová, Tereza ; Carazo Fernández, Alejandro (advisor) ; Jirkovský, Eduard (referee)
Studium exprese a toxicity derivátů katecholu v prsních nádorových buněčných liniích, Tereza Vyoralová ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Tereza Vyoralová Supervisor: PharmDr. Alejandro Carazo Ph.D. Title of the diploma thesis: Study of the expression and toxicity of catechol derivates in breast cancer cell lines Estrogens have several important functions in the human organism and are also involved in the formation and development of breast cancer. These effects are mediated by binding to estrogen receptors (ER) and show complex spectrum of effects such as regulation of reproduction, menstrual cycle, brain function, bone density or mobilization of cholesterol. In addition the presence and quantification of ER in breast cancer is currently used as one of the most important predictive biomarkers in patients suffering from this disease. The occurence and activity of ER correlates with the response of breast cancer to hormonal treatment and with the patient's prognosis. Despite intensive research, breast cancer is still ranked among the cancers with the highest lethality. Catechols are organic compounds that are naturally present in food as pollutants, but also can be found in the human body, where they play an important role as...
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Study of the influence of natural drugs on estrogen receptor and confirmation of their effect in cell cultures
Elbelová, Jana ; Carazo Fernández, Alejandro (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Jana Elbelová Supervisor: PharmDr. Alejandro Carazo, Ph.D. Title of the diploma thesis: Study of the influence of natural drugs on estrogen receptor and confirmation of their influence in cell culture Estrogens are one of the main reproductive hormones in women. Their function in the human organism is mediated by the estrogen receptor (ER). Estrogens are involved in important physiological processes such as reproduction, bone metabolism and cardiovascular function. Long term elevated levels of these hormones may also lead to breast cancer development. Phytoestrogens are natural ligands of estrogen receptor widely found in dietary products. These compounds have beneficial properties in treatment of menopausal symptoms thank to their estrogenic activities but are able to function as antiestrogenic agents too. In addition, they may play a role in the development of other illnesses (breast cancer etc.). Therefore, they can be considered as a potential pharmacological tool for the treatment of estrogen-related conditions. Within this master thesis, a total of six compounds, two phytoestrogens and four of their more relevant metabolites, were chosen (genistein, daidzein, S equol, O...
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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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Analysis of prognostic features in patients with breast cancer and colorectal cancer.
Vočka, Michal ; Petruželka, Luboš (advisor) ; Fínek, Jindřich (referee) ; Prausová, Jana (referee)
Cancers represent second the most common cause of death in the Czech Republic. The most common are breast and colorectal cancers. Identification of prognostic factors improving decision-making approaches for treatment optimization belongs to the key aims of clinical research in oncology. Carriers of mutation in cancer-susceptibility genes represent a small but clinically important group of high-risk patients. The implementation of NGS have accelerated predisposing genes analyses. The large extent of data about the presence of variants in predisposing genes is in striking contrast to only a very limited information available about clinico-pathological characteristics of mutation carriers. Determination of the risk of tumor development in carriers of rare mutations or variants of unclear significance in genes with incomplete penetrance represent substantial drawbacks of current NGS analyses. To address these issues, we have attempted i) to introduce a unified approach to NGS analysis in breast cancer patients, ii) to characterize importance of prognostic factors in BRCA1/BRCA2 mutation carriers, and iii) to identify the cancer risks in carriers of germline mutations in the CHEK2 gene. Colorectal cancer represents seemingly histologically homogeneous disease. However, at the molecular level it can be...
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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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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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Estrogen receptor beta (ERβ) in testicular cells and sperm
Dostálová, Pavla ; Žatecká, Eva ; Děd, Lukáš ; Dorosh, Andriy ; Postlerová, Pavla ; Jonáková, Věra ; Dvořáková-Hortová, Kateřina ; Pěknicová, Jana
Estrogen is a steroid hormone that plays an important role during sperm development in the male and female reproductive tract. Estrogen signalling is a complex process that depends on cell milieu and presence of receptors. Thanks to the steroid nature of estrogens, they can pass through the plasmatic membrane and bind to the intracellular estrogen receptors (ERs). Within the cell, there are several pools of ERs. One of them is localized to the cell nucleus and their activation leads to direct or indirect binding to DNA and ultimately to alternation in gene expression (genomic pathway). Other pools of ERs are associated with plasma membrane or are located in cytosol. Activation of membrane associated ERs leads to rapid non-genomic responses. Nowadays, two classical estrogen receptors are known – ERα and ERβ. Since ERβ is a predominant variant in testes, we focused our study on expression of ERβ variants in murine testes and sperm. We detected two variants of ERβ at mRNA level in both, testes and sperm. These variants differ in 54 nucleotids within the ligand binding domain and this variability results in different affinity to estrogen. We analyzed individual testicular cell types (spermatogonia, spermatocytes, spermatids, Sertoli cells) by RT-qPCR. Our results suggest that both ERβ variants are coexpressed in the same cell type and may therefore interact together. This may have consequences in mediating of estrogen signalling. Moreover, ERβ is expressed more in the later stages of spermatogenesis suggesting the role of ERβ in these stages or alternatively in spermatozoa alone. At the protein level, we detected ERβ in nuclear, membrane and cytosolic fraction prepared from testicular tissue suggesting the involvement of both, genomic and non-genomic, pathways of estrogen signaling in testes. In sperm, anti-ERβ antibodies localized ERβ in acrosome region and tail which is in accordance with the known role of estrogen on capacitation, acrosome reaction and motility.
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