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Complex morphological, immunohistochemical, molecular genetic and clinical pathological analysis of rare types of ovarian cancers
Galko, Kamila ; Nachtigal, Petr (advisor) ; Němečková, Ivana (referee)
Ovarian carcinomas are heterogenous group of diseases comprising various histotypes. Ovarian carcinomas as a whole are associated with the highest lethality among the female genital tumors. Currently, 5 main types of carcinomas are recognized: high grade serous carcinoma, low grade serous carcinoma, endometroid carcinoma, clear cell carcinoma and mucinous carcinoma. Other types, e.g. Brenner tumors, are very rare. Ovarian carcinomas are very diverse group with various precursors, morphology, genetic aberrations, epidemiologic and clinical, features, therapy and prognosis. The most studied and understood is high grade serous carcinoma with high incidence (up to 70 % of ovarian carcinomas). The number of studies dedicated to this tumor is still increasing. Other types of carcinomas are much less frequent, therefore related studies are rarer. Due to the rapid development of targeted therapy, it is necessary to evaluate the tumors not only morphologically but also on immunohistochemical and genetic level. Detection of neoantigens may indicate the mutation load of a tumor, it is also possible to evaluate status of mismatch repair (MMR) proteins and other features leading to chromosomal aberrations. In contrast to the high grade serous carcinoma, as for other types of carcinomas, knowledge about their...
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Soluble endoglin: effect on bile acids and cholesterol transport in livers
Grešková, Mária ; Nachtigal, Petr (advisor) ; Němečková, Ivana (referee)
Maria Greskova Soluble endoglin: effect on bile acids and cholesterol transport in livers Diplomathesis Charles University in Prague, Faculty of Pharmacy in Hradec Kralové Pharmacy Background: Increased plasma levels of soluble endoglin (sEng) have been shown in patients with acute heart failure, hypertension, diabetes mellitus type 2, and other metabolic and cardiovascular diseases such as e.g. hypercholesterolemia, atherosclerosis and cystic fibrosis, which influence as well liver functions. As there are no available data showing effect of sEng on the transport of cholesterol and bile acids, the aim ofthis diplomathesis wasto describe them. Methods: In this study were used six months-old female mice with high level of sEng on CBAxC57BL/6J background and control mice (n = 8, in each group) fed with chow diet for three months. /n vivo study was performed to analyze bile flow. mRNA expression of proteins responsible for cholesterol and bile acids transport and metabolism in the liver was performed by qRT-PCR. Results: sEng did not lead to changes neither in the bile flow nor in the concentration of cholesterol in plasma and liver. There were found no changes in the mRNAexpression of Sr-b1, Hmgcr, Abcg5, Abcg$, Acat2, Abcb4, Abcb11, Abcc2. sEng led to decrease in mRNAexpression of Cyp7al. Conclusion:...
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Morphological characteristics of steatosis development in precision cut liver slices and the possibility of its modification
Přibáňová, Petra ; Němečková, Ivana (advisor) ; Nachtigal, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Biological and Medical Sciences Study program: Laboratory diagnostics in healthcare Author: Petra Přibáňová Supervisor: RNDr. Ivana Němečková, Ph.D. Title of the thesis: Morphological characteristics of steatosis development in precision cut liver slices and the possibility of its modification Background and the aim of the thesis: Non-alcoholic hepatic steatosis is one of the most common causes of chronic liver disease. It is considered to be a manifestation of a metabolic syndrome associated with obesity, dyslipidaemia and type II diabetes mellitus. The aim of the bachelor thesis was to describe the anatomy and histology of the liver and hepatic steatosis, as well as to prepare histological slides, their subsequent staining and observation of the influence of different substances on the development of steatosis in liver tissue. Methods: Mouse liver was used to prepare precision cut liver slices (PCLS). The slices were then fixed and incubated in different media. Paraffine slides stained with hematoxylin- eosin or oil red were observed under a microscope. Results and conclusion: When comparing control PCLS without incubation with slices incubated for 36 hours in basic Williams' medium, we found that necrosis...
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Current trends in dyslipidemia therapy
Krupová, Tatiana ; Nachtigal, Petr (advisor) ; Tripská, Katarína (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Current trends in dyslipidemia therapy Author: Tatiana Krupová Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D Background: The purpose of this diploma thesis is to describe therapeutic options of different types of dyslipidemia with focus on current trends and new discoveries regarding this matter. Main findings: This diploma thesis emphasizes the importance of correct treatment of dyslipidemia using well-known drugs, as well as new groups of medications to enable the prevention of cardiovascular diseases, the main cause of mortality worldwide. Conclusion: The information gathered for this diploma thesis confirms significant progress in the development of new types of treatment, which consequently makes it possible to better prevent complications that are mainly manifested by the development of cardiovascular diseases. Keywords: cholesterol, lipids, lipoproteins, dyslipidemia, coronary heart disease, statins, fibrates, sequestrants, ezetimibe, niacin, omega-3 fatty acids, phytosterols, fiber, PCSK9 inhibitors, bempedoic acid, mipomersen, volanesorsen, lomitapide, evinacumab, inclisiran, LXR agonists
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Carotuximab effects on endoglin expression and signaling in liver fibrosis
Mohammadi, SeyedehNiloufar ; Nachtigal, Petr (advisor) ; Rathouská, Jana (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Biological and Medical science Carotuximab effect on endoglin expression and signaling in liver fibrosis Diploma thesis Seyedehniloufar Mohammadi Hradec Králové 2022 Supervisor: Prof. PharmDr. Petr Nachtigal, Ph.D. Consultant: M.Sc. Samira Eissazadeh Abstract Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Supervisor: Prof. PharmDr. Petr Nachtigal, Ph.D Student: Seyedehniloufar Mohammadi Title of the thesis: Carotuximab effects on endoglin expression and signaling in liver fibrosis Objective of the thesis Endoglin is a 180 kDa transmembrane glycoprotein that acts as a coreceptor for binding to the Transforming growth factor β (TGFβ) superfamily and is found in two forms in the blood: membrane endoglin (Eng) and soluble endoglin (sEng) circulating in the blood. It has been demonstrated that Eng might play an important role in the process of liver fibrosis, inflammation, and endothelial dysfunction. According to different studies, Eng can have prefibrotic or antifibrotic activity. The precise impact of Eng expression and signalling changes, and sEng levels during liver disorders are still unknown. Carotuximab, TRC105 (chimeric IgG1), is a therapeutic monoclonal antibody that binds to...
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Immunohistochemical analysis of endoglin expression and biomarkers of inflammation during liver fibrosis after Carotuximab administration
Široká, Veronika ; Nachtigal, Petr (advisor) ; Vitverová, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Immunohistochemical analysis of endoglin expression and biomarkers of inflammation during liver fibrosis after Carotuximab administration Author: Veronika Široká Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D. Background: The aim of this diploma thesis was to analyze changes in the expression of endoglin and markers of inflammation VCAM-1 and ICAM-1 in liver in an experimental mouse model of liver fibrosis, which was induced by administration of a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC). Another aim was to elucidate the effect of carotuximab administration on the expression of these markers after fibrosis induction, and to determine whether carotuximab administration effects the process of liver fibrosis by endoglin inhibition. Methods: The experimental mice were divided into three groups - the control group, which was fed a standard (chow) diet, the DDC group, which was fed a DDC-supplemented diet, and the DDC/TRC105 group, which was administrated by carotuximab along with the DDC diet. Liver tissue samples from all three groups were subjected to histochemical staining to detect steatosis (light microscopy) and indirect...
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Modulation of cholesterol and bile acid metabolism via soluble endoglin and pharmacotherapy
Igreja e Sá, Ivone Cristina ; Nachtigal, Petr (advisor) ; Vítek, Libor (referee) ; Červený, Lukáš (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Biological and Medical Sciences Doctoral Degree Program Pharmacology and Toxicology Candidate M.Sc. Ivone Cristina Igreja e Sá Supervisor prof. PharmD. Petr Nachtigal, Ph.D. Advisor Title of Doctoral Thesis Modulation of cholesterol and bile acid metabolism via soluble endoglin and pharmacotherapy Endoglin (Eng, CD105) is a transmembrane glycoprotein and co-receptor of the Transforming growth factor-β (TGFβ) receptor complex. Upregulated expression of Eng has been implicated in endothelial dysfunction, liver impairment, and hepatic fibrosis development. When Eng is cleaved by the matrix metalloproteinase-14 (MMP14), its soluble form termed soluble endoglin (sEng, sCD105) is released into the circulation. Increased plasma levels of sEng have not only been observed in patients with cardiovascular and metabolic diseases associated with hypercholesterolemia (e.g., atherosclerosis) but have also been reported to promote conditions of the metabolic syndrome (e.g., hypertension). However, the direct role of sEng in the modulation of hepatic metabolism and liver functions under physiologic or pathological conditions has not been previously explored. Therefore, this doctoral thesis aimed to test the hypothesis that...
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Possible changes of endoglin expression in endothelial cells.
Tripská, Katarína ; Nachtigal, Petr (advisor) ; Mladěnka, Přemysl (referee) ; Vohnout, Branislav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Doctoral Degree Program: Pharmacology and Toxicology Candidate: Mgr. Katarína Tripská Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Possible changes of endoglin expression in endothelial cells Endoglin (Eng) is a co-receptor for ligands of the Transforming Growth Factor β superfamily. Multiple studies have demonstrated that Eng is associated with metabolic syndrome-related pathological conditions, such as hypercholesterolemia, hyperglycemia, hypertension, or obesity. However, the exact role of Eng in these pathologies is still unknown. Therefore, the main purpose of this thesis was to elucidate and summarize the role of membrane and soluble Eng in the selected pathologies associated with metabolic syndrome. We demonstrated that soluble Eng (sEng) levels, together with plasma lipids and markers of inflammation, were reduced after every lipoprotein apheresis in patients with familial hypercholesterolemia. This result, in combination with knowledge acquired by the review article, indicates that increased sEng levels are associated with cardiometabolic disorders. Regarding the role of membrane Eng, we showed that blockage of Eng expression by TRC105 results in a decrease...
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Possible changes of endoglin expression in endothelial cells.
Tripská, Katarína ; Nachtigal, Petr (advisor) ; Mladěnka, Přemysl (referee) ; Vohnout, Branislav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Doctoral Degree Program: Pharmacology and Toxicology Candidate: Mgr. Katarína Tripská Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Possible changes of endoglin expression in endothelial cells Endoglin (Eng) is a co-receptor for ligands of the Transforming Growth Factor β superfamily. Multiple studies have demonstrated that Eng is associated with metabolic syndrome-related pathological conditions, such as hypercholesterolemia, hyperglycemia, hypertension, or obesity. However, the exact role of Eng in these pathologies is still unknown. Therefore, the main purpose of this thesis was to elucidate and summarize the role of membrane and soluble Eng in the selected pathologies associated with metabolic syndrome. We demonstrated that soluble Eng (sEng) levels, together with plasma lipids and markers of inflammation, were reduced after every lipoprotein apheresis in patients with familial hypercholesterolemia. This result, in combination with knowledge acquired by the review article, indicates that increased sEng levels are associated with cardiometabolic disorders. Regarding the role of membrane Eng, we showed that blockage of Eng expression by TRC105 results in a decrease...
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Modulation of cholesterol and bile acid metabolism via soluble endoglin and pharmacotherapy
Igreja e Sá, Ivone Cristina ; Nachtigal, Petr (advisor) ; Vítek, Libor (referee) ; Červený, Lukáš (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Biological and Medical Sciences Doctoral Degree Program Pharmacology and Toxicology Candidate M.Sc. Ivone Cristina Igreja e Sá Supervisor prof. PharmD. Petr Nachtigal, Ph.D. Advisor Title of Doctoral Thesis Modulation of cholesterol and bile acid metabolism via soluble endoglin and pharmacotherapy Endoglin (Eng, CD105) is a transmembrane glycoprotein and co-receptor of the Transforming growth factor-β (TGFβ) receptor complex. Upregulated expression of Eng has been implicated in endothelial dysfunction, liver impairment, and hepatic fibrosis development. When Eng is cleaved by the matrix metalloproteinase-14 (MMP14), its soluble form termed soluble endoglin (sEng, sCD105) is released into the circulation. Increased plasma levels of sEng have not only been observed in patients with cardiovascular and metabolic diseases associated with hypercholesterolemia (e.g., atherosclerosis) but have also been reported to promote conditions of the metabolic syndrome (e.g., hypertension). However, the direct role of sEng in the modulation of hepatic metabolism and liver functions under physiologic or pathological conditions has not been previously explored. Therefore, this doctoral thesis aimed to test the hypothesis that...
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