|
|
Expression of ABC transporters in cell cultures of non-small cell lung cancer: effect of selected targeted drugs
Žofajová, Barbora ; Hofman, Jakub (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Barbora Žofajová Supervisor: doc. RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Expression of ABC transporters in non-small cell lung carcinoma cell cultures: effect of selected targeted drugs ABC transporters form a special family of transmembrane proteins, their function is the active efflux of substrates into the extracellular environment. These transporters are expressed in normal tissues and tumor cells. Thus, they influence drug pharmacokinetics and play a role in the development of multidrug resistance (MDR). Tyrosine kinases have essential functions ranging from proliferation to differentiation and cell death, their mutation can cause carcinogenesis. Finding, exploring, and inhibiting the functions of these targets is a promising strategy to treat cancer. This work aimed to determine whether the selected drugs are involved in pharmacokinetic interactions that are based on inductions of ABC efflux transporter genes and whether they have the potential to affect MDR phenotype of tumor cells. The drugs, which we studied, were three targeted anticancer drugs (capmatinib, pralsetinib, and tazemetostat) and two well- known chemotherapeutic drugs (pemetrexed and methotrexate). First, we...
|
|
|
New strategies in pharmacotherapy and prevention of migraine
Kovaříková, Gabriela ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Gabriela Kovaříková Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: New strategies for the treatment and prevention of migraine Abstract: Migraine is a severe neurological disease, which has many subtypes. Migraine affects patient's physical and mental well-being and also work and family relationships. Migraine manifests as characteristic pain accompanied by vomiting and nausea or other symptoms. The first part of this paper deals with the current knowledge on pathophysiology of migraine, factors which affect migraine, degree of heritability, and specifics of chronic migraine. Diagnosis of migraine is also included and that based on MIDAS questionnaire are addressed in the diploma thesis. The second part is devoted to the therapy of acute attacks and prophylaxis of migraine, describes drugs used in these indications, characterizes them in more detail and lists their limitations. This section also outlines new pathophysiological findings and molecules that may receive future attention. New biological therapies and progress in terms of monoclonal antibody registration are also described. Nonpharmacological strategies for migraine treatment are mentioned as well. In addition, the...
|
|
|
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...
|
|
|
Interindividual variability in expression of selected membrane transporters; their impact on prognosis and therapy of patients with acute myeloid leukemia
Nálevková, Karolína ; Čečková, Martina (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Karolína Nálevková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultant: PharmDr. Aleš Šorf, Ph.D. Title of diploma thesis: Interindividual variability in expression of selected membrane transporters; their impact on prognosis and therapy of patients with acute myeloid leukaemia. Acute myeloid leukaemia (AML) is a malignant disease of hematopoietic system. Available treatment does not produce suitable results, as the 5-year survival is only about 30%. The primary induction therapy has remained the same for many years - combination of cytarabine and anthracycline, known as "7+3". By karyotyping and immunophenotyping of patients in the last few years, heterogeneity of the disease was confirmed, which also led to the development of targeted drugs. Other factors such as transporters that play a role in drug transport across plasma membranes may affect the treatment outcome. In my diploma thesis, I therefore focused on the effect of selected membrane transporters OCTN1, OCTN2 and ABCC4 on the prognosis and therapy of AML patients. First, we specified the number of transcripts of studied genes using the RT-PCR and ddPCR methods in samples isolated from mononuclear cells of the blood of de...
|
|
|
Study of adenosine effects on proliferation of BeWo cell line
Papírník, Josef ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Josef Papírník Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Studium of adenosine on proiferation activity in BeWo cell line The placenta is a rapidly developing organ that provides nutrition, protection and environment for the growing fetus. Fetal development is dependent on the supply of nutrients from the mother's blood either by passive diffusion or mediated by transporters. One of the essential nutrients are nucleosides, which are known to promote DNA synthesis and thus the growth of certain tissues. In order to pass across the plasma membrane they need nukleoside transporters (NTs) because of its hydrophilic feature. Additionally Ado takes part in cell signaling. Its wide- ranging effects, including influencing proliferation, are mediated by its binding to adenosine receptors (ARs). The placenta expresses NTs and ARs, which means that it is equipped to uptake nucleosides from maternal blood and has ability to receive signals from the external environment via the adenosine molecule. However, the importance of nucleosides for placental growth has not been investigated yet. The aim of this thesis is to test the effect of nucleosides on the proliferation of...
|
|
|
Study of adenosine effects on proliferation of JEG-3 cell line
Nguyen, Ngoc Duong ; Červený, Lukáš (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Nguyen Ngoc Duong Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Effect of adenosine on the proliferation of JEG-3 cell line Adenosine is a purinergic signaling molecule that is used in nucleic acid synthesis. Transport of hydrophilic nucleosides through the plasma and/or organelle membranes is provided by equilibrative nucleoside transporters (ENTs), members of the SLC29A transporter family, and concentrative nucleoside transporters (CNTs), members of the SLC28A transporter family. The placenta is a complex and rapidly growing organ. It shows some patterns similar to tumors except for the fact that the placenta's growth is fully controlled. It was found that extracellular nucleosides support the proliferation of cancerous and some non-cancerous cells. The placenta expresses high levels of NTs which indicates the placenta's ability to take up the nucleosides from circulation, however, the contribution of this process to placental growth is known. The diploma thesis aims to test the effect of adenosine and other nucleosides on trophoblast proliferation. We evaluated whether adenosine and other nucleosides increase the proliferation of the choriocarcinoma-derived JEG-3 cell...
|
|
|
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...
|
|
|
Interindividual variability in expression of selected membrane transporters; their impact on prognosis and therapy of patients with acute myeloid leukemia
Nálevková, Karolína ; Čečková, Martina (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Karolína Nálevková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultant: PharmDr. Aleš Šorf, Ph.D. Title of diploma thesis: Interindividual variability in expression of selected membrane transporters; their impact on prognosis and therapy of patients with acute myeloid leukaemia. Acute myeloid leukaemia (AML) is a malignant disease of hematopoietic system. Available treatment does not produce suitable results, as the 5-year survival is only about 30%. The primary induction therapy has remained the same for many years - combination of cytarabine and anthracycline, known as "7+3". By karyotyping and immunophenotyping of patients in the last few years, heterogeneity of the disease was confirmed, which also led to the development of targeted drugs. Other factors such as transporters that play a role in drug transport across plasma membranes may affect the treatment outcome. In my diploma thesis, I therefore focused on the effect of selected membrane transporters OCTN1, OCTN2 and ABCC4 on the prognosis and therapy of AML patients. First, we specified the number of transcripts of studied genes using the RT-PCR and ddPCR methods in samples isolated from mononuclear cells of the blood of de...
|
|
|
Migraine and its treatment
Petríková, Andrea ; Jirkovský, Eduard (advisor) ; Červený, Lukáš (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmacology and Toxicology Supervisor: PharmDr. Eduard Jirkovský, Ph.D. Author: Andrea Petríková Title of Diploma Thesis: Migraine and its treatment Migraine is one of the primary headaches, manifested in repeated attacks of severe one-sided and throbbing headaches, usually lasting 4-72 hours. They are accompanied by one of the following symptoms: photophobia, phonophobia, odorophobia, nausea, vomiting. From one seizure to the next, the patient feels like a healthy patient. In my work I describe current pharmacotherapeutic procedures in the treatment of migraine. In the first part of the diploma thesis, I presented a literature review of migraines, which begins with the classification of headaches. I continue with the definition of migraine, history, classification of migraine, pathophysiology, prevalence and diagnostic criteria of migraine. In the second part I describe the different types of treatment with their procedures and the drugs that are used. Based on our knowledge of the pathophysiology of migraine, new drugs have been developed for the treatment of acute migraine attacks that target calcitonin gene-related peptide (CGRP) and serotonin 5-HT1F receptors. I describe their mechanism, which drugs have been...
|
|
|
The impact of SIRT1 inhibition on zebrafish morphology and behavior
Faustová, Zuzana ; Červený, Lukáš (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Zuzana Faustová Supervisor: Prof. Doutor Jorge Miguel de Ascenção Oliveira PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: The impact of SIRT1 inhibition on zebrafish morphology and behavior After discovery of connection between yeast Silent Information Regulator 2 (Sir2) and its ability to alter lifespan, Sir2 and its seven mammalian orthologs became very attractive therapeutic target. These so called sirtuins are members of a histone deacetylase family. They possess unique catalytic activity having nicotinamide adenine dinucleotide as a cofactor and their function can be influenced by environmental factors. The aim of this diploma thesis was to extend knowledge of Sirtuin 1 (SIRT1), which is from all mammalian sirtuins considered to have the closest relation to yeast Sir2. At first we tested the impact of SIRT1 inhibition on early developmental stages of zebrafish (Danio rerio) embryos and larvae, finding out that SIRT1 is important for normal development and SIRT1 inhibition or malfunction result in cardiovascular defects, delayed development, and death. Additionally, we tried to learn more about SIRT1 and its connection with Parkinson's disease by combining nontoxic doses...
|
guest ::
