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The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells.
Čermáková, Lucie ; Novotná, Eva (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Lucie Čermáková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells Leukemia presents malignant diseases of hematopoiesis, which essence is the malignant transformation of a hematopoietic stem cell at various levels of maturation and increased proliferative activity. Chemotherapy is the gold standard in the treatment of leukemia. One of the many treatments is the use of anthracycline chemotherapeutics, especially daunorubicin (DAU). Anthracyclines are widely used in clinical practice but have high cardiotoxic effects that limit their dosage. One of the main causes of side effects is the reduction of an anthracycline chemotherapeutic to the appropriate toxic metabolite, which accumulates in the heart. Carbonyl, reducing enzymes from the superfamily aldo-ketoreductase (AKR), and short-chain dehydrogenase/reductase (SDR) are involved in this reduction. At the same time, carbonyl reducing enzymes, has been shown to be involved in the mechanisms that cause tumor cells to be resistant to anthracyclines, thereby reducing the inhibition of the growth of these cells. In the diploma thesis we found that...
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