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Cardiotoxic effects of anthracyclines in oncological treatment
Tekáčová, Kateřina ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Anthracyclines are antitumor antibiotics used during chemotherapy in cancer patients. Treatment with anthracyclines has good results but a side effect is significant cardiotoxicity. This bachelor thesis describes the mechanisms of action of anthracyclines which are essential in cancer therapy and may be risky for patients. The thesis also defines the term of cardiotoxicity and summarizes factors that may increase the risk of cardiotoxicity. The most commonly used agents in the anthracycline series are briefly described. Cardiotoxicity can be detected by cardiac markers, especially particular troponin and diagnostic methods. The last chapter describes the groups of substances that reduce the cardiotoxic effects of anthracyclines. Key words: heart, anthracyclines, cardiotoxicity, chemotherapy, onkology treatment
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In vitro study of newly synthesized potential cardioprotective drugs
Liptáková, Lucie ; Hašková, Pavlína (advisor) ; Macháček, Miloslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Liptáková Supervisor: RNDr. Pavlína Hašková, Ph.D. Title of master thesis: In vitro study of newly synthesized potential cardioprotective drugs Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are in an organism generated under normal or pathological conditions. There are antioxidant mechanisms, which protects the organism from their harmful effect. In case of imbalance between ROS/RNS production and antioxidant mechanisms, an oxidative stress is initiated. The oxidative stress is involved in the pathogenesis of many diseases, including cardiovascular desease. In consequence of higher presence of mitochondria and lower presence of antioxidants cardiomyocytes are more sensitive to the oxidative stress. Iron, by catalysing radical's reactions, significantly participates on formation and development of oxidative stress. Elimination of the free iron by iron chelators is one option how to prevent or moderate oxidative stress. The aim of this master theses was to study cardioprotective effect in presence of H2O2 and own toxicity of newly synthetized aroylhydrazone iron chelators (H21, H22, H23, H24, H25 and H26) on rat embryotic cardiomyoblasts H9c2. Protective and toxic...
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Antiproliferative and cardioprotective potential of the newly synthetised analogues of dexrazoxane.
Gavurová, Lucie ; Jirkovská, Anna (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Gavurová Supervisor: PharmDr. Anna Jirkovská, PhD. Title of diploma thesis: Antiproliferative and cardioprotective activity of novel dexrazoxane analogues Anthracycline antibiotics (such as daunorubicin, doxorubicin or epirubicin) forms the basis of anticancer therapy in many hematological malignancies and solid tumors. However, their clinical use is limited by adverse effects. The most serious of these effects is chronic form of anthracycline-induced cardiotoxicity. Dexrazoxane is the only one clinically approved cardioprotective agent against anthracycline cardiotoxicity so far. Despite its well-evidenced cardioprotective effects, dexrazoxane use is very limited due to its possible adverse effects. The the synthesis of novel analogs of might contribute to understanding of the relationship between structure and effects of dexrazoxane. Finally, this approach could lead to the synthesis of structure with better pharmacological properties. The aim of this diploma thesis was to assess the antiproliferative activity of novel analogues of dexrazoxane (JR-281B, JR-311, JR-306A, JR-306B, JR-232 and JR-312B), and the study of the influence on the antiproliferative effect of anthracyclines....
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Antiproliferative activity of novel dexrazoxane analogues and their effect on antitumor effectiveness of anthracyclines
Martinková, Pavla ; Jirkovská, Anna (advisor) ; Pohanka, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Pavla Martinková Supervisor: PharmDr. Anna Jirkovská, PhD. Title of diploma thesis: Antiproliferative activity of novel dexrazoxane analogues and their effect on antitumor effectiveness of anthracyclines Athracycline antibiotics (such as daunorubicin, doxorubicin or epirubicin) belong to the most common terapeutics of both solid tumors and hematological malignities. Unfortunately the serious and life-threatening adverse effect cardiotoxicity compromises their clinical usefulness. The only approved protection against anthracycline cardiotoxicity so far is dexrazoxane. Despite the outstanding cardioprotective ability, dexrazoxane use is very limited mainly due to its possible side effects. So we were directed towards synthesis of dexrazoxane analogues with better pharmacological properties. The aim of this diploma thesis was to assess the antiproliferative activity of novel analogues of both dexrazoxane (MK-15 and ES-5) and ADR-925 (JR-159 and KH- TA4) and their influence on the antiproliferative effectiveness of anthracyclines. Moreover, we aimed to study their chelating properties and their inhibition of the topoisomerase II in solution. We tested the antiproliferative activity of...
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In vitro study of newly synthesized potential cardioprotective drugs
Liptáková, Lucie ; Hašková, Pavlína (advisor) ; Macháček, Miloslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Liptáková Supervisor: RNDr. Pavlína Hašková, Ph.D. Title of master thesis: In vitro study of newly synthesized potential cardioprotective drugs Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are in an organism generated under normal or pathological conditions. There are antioxidant mechanisms, which protects the organism from their harmful effect. In case of imbalance between ROS/RNS production and antioxidant mechanisms, an oxidative stress is initiated. The oxidative stress is involved in the pathogenesis of many diseases, including cardiovascular desease. In consequence of higher presence of mitochondria and lower presence of antioxidants cardiomyocytes are more sensitive to the oxidative stress. Iron, by catalysing radical's reactions, significantly participates on formation and development of oxidative stress. Elimination of the free iron by iron chelators is one option how to prevent or moderate oxidative stress. The aim of this master theses was to study cardioprotective effect in presence of H2O2 and own toxicity of newly synthetized aroylhydrazone iron chelators (H21, H22, H23, H24, H25 and H26) on rat embryotic cardiomyoblasts H9c2. Protective and toxic...
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Antiproliferative activity of novel dexrazoxane analogues and their effect on antitumor effectiveness of anthracyclines
Martinková, Pavla ; Jirkovská, Anna (advisor) ; Pohanka, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Pavla Martinková Supervisor: PharmDr. Anna Jirkovská, PhD. Title of diploma thesis: Antiproliferative activity of novel dexrazoxane analogues and their effect on antitumor effectiveness of anthracyclines Athracycline antibiotics (such as daunorubicin, doxorubicin or epirubicin) belong to the most common terapeutics of both solid tumors and hematological malignities. Unfortunately the serious and life-threatening adverse effect cardiotoxicity compromises their clinical usefulness. The only approved protection against anthracycline cardiotoxicity so far is dexrazoxane. Despite the outstanding cardioprotective ability, dexrazoxane use is very limited mainly due to its possible side effects. So we were directed towards synthesis of dexrazoxane analogues with better pharmacological properties. The aim of this diploma thesis was to assess the antiproliferative activity of novel analogues of both dexrazoxane (MK-15 and ES-5) and ADR-925 (JR-159 and KH- TA4) and their influence on the antiproliferative effectiveness of anthracyclines. Moreover, we aimed to study their chelating properties and their inhibition of the topoisomerase II in solution. We tested the antiproliferative activity of...
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In vitro study of newly synthesized potential cardioprotective drugs
Liptáková, Lucie ; Hašková, Pavlína (advisor) ; Macháček, Miloslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Liptáková Supervisor: RNDr. Pavlína Hašková, Ph.D. Title of master thesis: In vitro study of newly synthesized potential cardioprotective drugs Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are in an organism generated under normal or pathological conditions. There are antioxidant mechanisms, which protects the organism from their harmful effect. In case of imbalance between ROS/RNS production and antioxidant mechanisms, an oxidative stress is initiated. The oxidative stress is involved in the pathogenesis of many diseases, including cardiovascular desease. In consequence of higher presence of mitochondria and lower presence of antioxidants cardiomyocytes are more sensitive to the oxidative stress. Iron, by catalysing radical's reactions, significantly participates on formation and development of oxidative stress. Elimination of the free iron by iron chelators is one option how to prevent or moderate oxidative stress. The aim of this master theses was to study cardioprotective effect in presence of H2O2 and own toxicity of newly synthetized aroylhydrazone iron chelators (H21, H22, H23, H24, H25 and H26) on rat embryotic cardiomyoblasts H9c2. Protective and toxic...
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Antiproliferative and cardioprotective potential of the newly synthetised analogues of dexrazoxane.
Gavurová, Lucie ; Jirkovská, Anna (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Gavurová Supervisor: PharmDr. Anna Jirkovská, PhD. Title of diploma thesis: Antiproliferative and cardioprotective activity of novel dexrazoxane analogues Anthracycline antibiotics (such as daunorubicin, doxorubicin or epirubicin) forms the basis of anticancer therapy in many hematological malignancies and solid tumors. However, their clinical use is limited by adverse effects. The most serious of these effects is chronic form of anthracycline-induced cardiotoxicity. Dexrazoxane is the only one clinically approved cardioprotective agent against anthracycline cardiotoxicity so far. Despite its well-evidenced cardioprotective effects, dexrazoxane use is very limited due to its possible adverse effects. The the synthesis of novel analogs of might contribute to understanding of the relationship between structure and effects of dexrazoxane. Finally, this approach could lead to the synthesis of structure with better pharmacological properties. The aim of this diploma thesis was to assess the antiproliferative activity of novel analogues of dexrazoxane (JR-281B, JR-311, JR-306A, JR-306B, JR-232 and JR-312B), and the study of the influence on the antiproliferative effect of anthracyclines....
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