National Repository of Grey Literature 2 records found  Search took 0.02 seconds. 
Analysis of the pathways responsible for the resistance of leukemic cells towards L-asparaginase
Šimčíková, Markéta ; Konvalinka, Jan (advisor) ; Poljaková, Jitka (referee)
Acute lymphoblastic leukaemia (ALL) is the most frequent malignancy in childhood. Despite the very successful ALL therapy, relapses occur to 15-20 % of children. One of the possible relaps causes is the resistance to therapeutics. ALL is treated with combined chemotherapy in which cytostatic agent L-asparaginase plays the essen- tial role. L-asparaginase depletes extracellular asparagine and glutamine. Antagonist of the L-asparaginase is asparagine synthetase enzyme, which synthesizes the cellular asparagine. The specific antileukaemic effect of L-asparaginase is believed to be thanks to lower activity of the asparagine synthetase in leukaemic cells comparing to the healthy cells. The asparagine and glutamine deficiency harms the cellular proteosyn- thesis and induces apoptosis. Mechanism of the L-asparaginase cytotoxic effect and mechanism of corresponding resistance is still not fully explained. This bachelor thesis is a part of a project studying mechanisms of leukaemic cells resistance to L-aparaginase. In the model leukaemic REH cell line a deletion del(5)(q34) was discovered, which cannot be found in the resistant clone of these cells. This thesis focuses on proving different sensitivity of leukaemic cells, with or without the deletion, to L-asparaginase. The limiting dilution was used to obtain...
Analysis of the pathways responsible for the resistance of leukemic cells towards L-asparaginase
Šimčíková, Markéta ; Konvalinka, Jan (advisor) ; Poljaková, Jitka (referee)
Acute lymphoblastic leukaemia (ALL) is the most frequent malignancy in childhood. Despite the very successful ALL therapy, relapses occur to 15-20 % of children. One of the possible relaps causes is the resistance to therapeutics. ALL is treated with combined chemotherapy in which cytostatic agent L-asparaginase plays the essen- tial role. L-asparaginase depletes extracellular asparagine and glutamine. Antagonist of the L-asparaginase is asparagine synthetase enzyme, which synthesizes the cellular asparagine. The specific antileukaemic effect of L-asparaginase is believed to be thanks to lower activity of the asparagine synthetase in leukaemic cells comparing to the healthy cells. The asparagine and glutamine deficiency harms the cellular proteosyn- thesis and induces apoptosis. Mechanism of the L-asparaginase cytotoxic effect and mechanism of corresponding resistance is still not fully explained. This bachelor thesis is a part of a project studying mechanisms of leukaemic cells resistance to L-aparaginase. In the model leukaemic REH cell line a deletion del(5)(q34) was discovered, which cannot be found in the resistant clone of these cells. This thesis focuses on proving different sensitivity of leukaemic cells, with or without the deletion, to L-asparaginase. The limiting dilution was used to obtain...

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