National Repository of Grey Literature 124 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Effect of abacavir on the expression of nucleoside transporters, adenosine receptors, and enzymes involved in adenosine synthesis and biodegradation in trophoblasts
Gala, Viktor ; Červený, Lukáš (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Viktor Gala Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Effect of abacavir on the expression of nucleoside transporters, adenosine receptors, and enzymes involved in adenosine synthesis and biodegradation in trophoblasts The nucleoside reverse transcriptase inhibitor (NRTI) abacavir (ABC) is now the mainstay of combination antiretroviral therapy (cART) for HIV in pregnant women. The introduction of cART, along with several other measures, has reduced mother-to-fetus transmission of HIV to less than 1% in recent years. The placenta is a key organ for the health of both the fetus and the mother. Imbalances in placental development can result in adaptive changes and fetal programming errors. cART recommended in pregnancy is known for its good safety profile, but some epidemiological studies suggest a higher risk of reduced fetal weight, preterm birth, etc. The placenta is a rapidly growing organ dependent on the supply of building materials that resembles tumor growth in certain aspects. Nucleosides are promoters of tumor proliferation and are involved in the development of immunotolerance. The placenta is complexly equipped for nucleoside synthesis, uptake,...
Resistance mechanisms in therapy of acute myeloid leukemia
Suchá, Simona ; Čečková, Martina (advisor) ; Žák, Pavel (referee) ; Matoušková, Petra (referee)
IN ENGLISH LANGUAGE Candidate: Mgr. Simona Suchá Supervisor: Assoc. Prof. PharmDr. Martina Čečková, PhD. Title of the doctoral thesis: Resistance mechanisms in therapy of acute myeloid leukemia Acute myeloid leukemia (AML) is a hematologic cancer known for its extensive heterogeneity, poor treatment outcomes and high relapse rate. Therapy outcome is often compromised by highly resistant leukemic clones present at diagnosis, which evade chemotherapy and continue to spread the disease. Identification of their cellular features is, therefore, a key in successful targeting and eliminating of these resistant leukemic cells. AML cells can, however, develop drug resistance even overtime due to prolonged drug exposure. Extremely high adaptability of leukemic cells enables them to survive whenever therapeutic stress stimuli occur. Uncovering molecular mechanisms that cells utilize to activate their survival mode is crucial in selection of treatment leading to maximal efficacy. Based on these grounds, two main aims of this thesis were set. First, to determine clinical relevance of ABC efflux transporters in AML and to evaluate the effect of targeted agents on chemotherapy. The focus was put on agents belonging to either FLT3 inhibitors (midostaurin) or CDK4/6 inhibitors (abemaciclib, palbociclib,...
CHARACTERIZATION OF GILTERITINIB-RESISTANT LEUKEMIC CELL LINE
Zlesáková, Lucie ; Čečková, Martina (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucie Zlesáková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Suchá, Ph.D. Title of diploma thesis: Characterization of gilteritinib-resistant leukemic cell line Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis for which therapy failure is often responsible. Development of drug resistance is among the most common causes of treatment failure. The exact mechanisms leading to the resistance are not known, especially for drugs recently introduced into the clinical practice such as gilteritinib. Therefore, the gilteritinib-resistant leukemic cell line (referred to as HL-60 g75) has been established in our lab and further characterized. The aim of this study was to evaluate the sensitivity of HL-60 g75 cells to gilteritinib and to clarify the stability of acquired resistance. We revealed that the resistance of HL-60 g75 cells is transient, since only after 4 weeks of gilteritinib-free cell culture, sensitivity of these cells was restored. While gilteritinib induced apoptosis similarly in both gilteritinib-sensitive (HL-60 wt) and -resistant cells, cell cycle analysis revealed lower responsiveness of HL-60 g75 to gilteritinib than HL-60 wt....
Evaluation of gene expression of selected ABC and SLC transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines
Pokorná, Petra ; Čečková, Martina (advisor) ; Mladěnka, Přemysl (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petra Pokorná Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Dudičová Title of diploma thesis: Evaluation of gene expression of selected ABC and OATP transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines Placenta is the first and the largest fetal organ that gradually develops during pregnancy and plays an essential role in the development of the fetus. It fulfills the entire spectrum of functions, ensures the transport of nutrients to the fetus and the removal of waste substances back into the maternal circulation, protects the fetus from toxins, and at the same time fulfills a certain mechanical and especially immunological barrier between mother and fetus. One of the main functions of the placenta is the transport function which is made possible by membrane transporters present mainly in the syncytiotrophoblast layer of the placenta. Transporters in the human placenta can be divided into two families, SLC and ABC which are further divided into several subfamilies. The expression of transporters changes physiologically during pregnancy, but pathological conditions such as inflammation can also influence the expression....
The influence of LDL-apheresis on aggregation of blood platelets, blood coagulation, and the effect of standard drugs.
Černotová, Veronika ; Mladěnka, Přemysl (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Černotová Supervisor: prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Lukáš Konečný, MSc. Title of diploma thesis: The influence of LDL-apheresis on aggregation of blood platelets, blood coagulation and the effect of standard drugs LDL-apheresis is a method that removes LDL-cholesterol (LDL-C) from the blood. It is used to treat familial hypercholesterolemia (FH), a genetic disorder causing high LDL-C levels and an early development of cardiovascular diseases. Blood platelets and coagulation system play an important role in these diseases and their activity is also affected by lipids. The aim of this thesis was to analyze possible differences in platelet aggregation and blood coagulation in patients suffering from FH. Two methods of treatment in this group were compared - lipid apheresis and PCSK9Ab (proprotein convertase subtilisin/kexin type 9 monoclonal antibodies). The observed parameters were also compared with age-matched healthy volunteers. Our cohort consisted of 15 patients and 15 healthy donors. Six patients were treated with lipid apheresis and also PCSK9Ab, six subjects only with PCSK9Ab. Platelet aggregation was measured with an impedance aggregometer using 7 different...
Resistance mechanisms in therapy of acute myeloid leukemia
Suchá, Simona ; Čečková, Martina (advisor) ; Žák, Pavel (referee) ; Matoušková, Petra (referee)
IN ENGLISH LANGUAGE Candidate: Mgr. Simona Suchá Supervisor: Assoc. Prof. PharmDr. Martina Čečková, PhD. Title of the doctoral thesis: Resistance mechanisms in therapy of acute myeloid leukemia Acute myeloid leukemia (AML) is a hematologic cancer known for its extensive heterogeneity, poor treatment outcomes and high relapse rate. Therapy outcome is often compromised by highly resistant leukemic clones present at diagnosis, which evade chemotherapy and continue to spread the disease. Identification of their cellular features is, therefore, a key in successful targeting and eliminating of these resistant leukemic cells. AML cells can, however, develop drug resistance even overtime due to prolonged drug exposure. Extremely high adaptability of leukemic cells enables them to survive whenever therapeutic stress stimuli occur. Uncovering molecular mechanisms that cells utilize to activate their survival mode is crucial in selection of treatment leading to maximal efficacy. Based on these grounds, two main aims of this thesis were set. First, to determine clinical relevance of ABC efflux transporters in AML and to evaluate the effect of targeted agents on chemotherapy. The focus was put on agents belonging to either FLT3 inhibitors (midostaurin) or CDK4/6 inhibitors (abemaciclib, palbociclib,...
Impact of new FLT3 inhibitors on daunorubicin accumulation in ABCB1-expressing leukemic cells
Králová, Adéla ; Čečková, Martina (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Adéla Králová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Suchá Title of Diploma thesis: Impact of new FLT3 inhibitors on daunorubicin accumulation in ABCB1-expressing leukemic cells Fms-like tyrosine kinase 3 (FLT3) inhibitors represent a new generation of drugs in the treatment of acute myeloid leukemia (AML). Standard therapeutic regimen of AML is initiated with induction therapy consisting of cytarabine and anthracyclines. The disadvantage of this combination is emerging resistance often caused by the ABCB1-mediated efflux. Therefore, simultaneous inhibition of FLT3 and ABCB1, which is inhibited by FLT3 inhibitors used in clinical practice, appears to be a beneficial approach to therapy. However, their effectiveness is declining hence the effort to develop new FLT3-inhibiting molecules. The aim of our work was to evaluate whether our two promising new FLT3-inhibiting compounds would inhibit ABCB1 as well. Promyelocyte cells overexpressing ABCB1 (HL60-ABCB1) and parent HL60-par were used in this study alongside AML-derived cell lines (MOLM-13, THP-1, Kasumi-1). Employing accumulation studies on HL60-ABCB1, strong inhibitory effect towards ABCB1 was demonstrated...
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...
The effect of in vitro and ex vivo placental cells stimulation on expression of selected ABC and OATP transporters
Dudičová, Simona ; Čečková, Martina (advisor) ; Jirkovská, Anna (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Simona Dudičová Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: The effect of in vitro and ex vivo placental cells stimulation on expression of selected ABC and OATP transporters The placenta is an organ that plays a key role throughout pregnancy for proper fetal development. One of the important functions provided by the placenta is the transport of substances between the mother and the fetus. This transfer of substances enabled mainly by membrane transporters, which are located on the apical and basal membranes of the syncytiotrophoblast. During various physiological or pathological changes in the human body, their expression and amount can vary significantly. Inflammatory reactions that may occur during pregnancy are also related to these changes, and therefore we have addressed this issue and believed that this condition may alter the expression of placental transporters. The aim of this work was to investigate the changes in the expression of membrane transporters using placental cells on BeWo cell lines and placental villous explants that were stimulated by pro-inflammatory mediators. The change in the expression of individual ATP-binding cassettes,...
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...

National Repository of Grey Literature : 124 records found   1 - 10nextend  jump to record:
Interested in being notified about new results for this query?
Subscribe to the RSS feed.