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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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Rehabilitation care system for children with leukaemia in Czech Republic and selected countries of Europe
Dostálová, Markéta ; Jevič, Filip (advisor) ; Ptáková, Karolína (referee)
Leukemia is the most common cancer in childhood, making up 30-35% of all oncological diseases in children in the Czech Republic. The most frequent form of leukemia in pediatric patients is acute lymphoblastic leukemia (ALL). This form accounts for 80% of leukemia in children. Other types include acute myeloblastic leukemia (AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Treatment is based on the type and subtype of leukemia diagnosed and usually lasts 1-2 years, provided there is no relapse. Primary treatment involves many side effects, including on the musculoskeletal system, such as chemotherapy-induced polyneuropathy (CIPN) or muscle myopathy as an adverse effect of glucocorticoid therapy. Part of the comprehensive treatment is supportive treatment, which includes rehabilitation (RHB). The aim of this work is to find out and compare whether and under what conditions RHB in pediatric haemato-colongic patients is in the Czech Republic and selected countries of Europe, who and according to what patients RHB and whether clinics have any programs related to RHB in these patients. The general part introduces the issue of pediatric patients with leukemia including the possibilities and adverse effects of treatment. The special part is devoted to research based on...
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Oncoretroviruses: tumor transformation mechanisms of hematopoietic cells resulting in leukaemia
Gašpareková, Mária ; Bendová, Michaela (advisor) ; Mrvová, Silvia (referee)
HTLV-1 and FeLV are retroviruses, which are able to transform host cells and cause cancer, mostly leukemia, in infected organism. Belonging to Retroviridae family and both using very similar genome, these viruses developed different ways to reach transformation of infected cells. While FeLV uses insertional activation close to cellular proto-oncogenes in order to regulate transcription of these genes or carries cellular oncogene in its genome, HTLV-1 codes viral proteins which are able to regulate many processes of the cell. One of these proteins is Tax, which regulates many events in the cell, such as signalization, cell cycle, apoptosis and others. Another protein responsible for oncogenesis is HBZ, which is transcribed from antisense strand of proviral DNA. In the end HTLV-1 and FeLV strategies causing cancer are compared with some other leukemic retroviruses in order to show, that molecular strategies described on examples of HTLV-1 and FeLV are more or less common also for other oncogenic retroviruses. Key words: HTLV-1, FeLV, transformation, leukaemia, tumor, oncogene
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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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Study of translation initiation factors eIF3 and eIF4E in leukemic cell lines
Mrvová, Silvia ; Mašek, Tomáš (advisor) ; Haškovec, Cedrick (referee)
eIF3 and eIF4E are very important eukaryotic translation initiation factors. eIF3 is practically involved in every step of translation initiation, eIF4E is important mainly for its ability to bind the cap. Mammalian factor eIF3 consists of thirteen subunits, many subunits have a function apart from translation, such as in apoptosis and mitosis. It was proved that upregulated or downregulated expression of some subunits as well as upregulated expression of eIF4E is linked with different types of tumours and malignancies in human. In the first part of my work, I was examining the amount of transcripts of subunits eIF3a, b, d, e, f, g, h, i and j in cell lines which are used for study of acute lymphoblastic leukaemia. I tried to find if there is a difference in the amount of trancripts between lines or between lines and control line in these subunits. According to experiments and statistical analysis, I proved increased amount of mRNA for eIF3b subunit in control cell line NC-NC in comparison with other used leukaemic cell line except from line NALM6. Other differences were not statistically important. In the second part of my work, I was analysing 3' UTR region of transcripts of eIF4E1 and utilising of polyadenylation signals in this trancript. I used the leukeamic cell lines again. The experiments clearly...
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Impact of education on clients with leukemia.
DAVIDOVÁ, Adéla
The theoretical part of my bachelor thesis is focused on the description and characteristics of leukaemia, its diagnostics and treatment. Further, the theoretical part is focused on nursing care of clients suffering from leukaemia and meeting their bio-psycho-social needs. Last but not least, it deals with communication and the education process concerning leukaemia. The practical part of my bachelor thesis aims to find out the manner in which education is provided, the fields of the education conducted and how much clients suffering from leukaemia are contented with the education provided. To obtain data and process them, I used a qualitative research survey and the method of the semi-structured interview. I carried out anonymous interviews with two groups of respondents. The first group consisted of nurses working in a clinical haematology department, and the other were clients hospitalised in this department - clients with diagnosed leukaemia. The information that I obtained may help to improve communication between medical staff members and their clients, to improve the education of clients suffering from leukaemia, and, thanks to the correctly conducted education, to make dealing with the disease easier.
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