|
|
Resenzitalizace leukemických a lymfomavých buněk k trailerem indukované apoptóze
Molinský, Jan ; Klener, Pavel (advisor) ; Hyršlová Vaculová, Alena (referee) ; Vyoral, Daniel (referee)
Apoptosis serves as a natural barrier to cancer development, and the resistance to apoptosis represents one of the key capabilities acquired during tumor development or progression. Impairment of the intrinsic apoptotic pathway exemplifies one of the established mechanisms of constitutive or acquired drug resistance. As most of the currently used cytotoxic drugs initiate tumor cell death by direct or indirect triggering of the intrinsic apoptotic pathway, impairment of the intrinsic pathway is associated with therapy failure. Targeting of the death receptors, however, enables induction of apoptosis even in the chemotherapy resistant cancer cells. TRAIL is a death ligand belonging to the TNFα superfamily that specifically kills tumor cells while sparing healthy tissues. Much enthusiasm has been generated for TRAIL as a highly promising targeted anti-cancer agent. However, many primary tumors have been shown to be TRAIL resistant. In attempt to overcome such an intrinsic TRAIL resistance a wide array of agents have been shown to sensitize tumor cells to TRAIL. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. In this study we analyzed the sensitivity of diverse hematologic malignancies to TRAIL-induced apoptosis and measured the...
|
|
|
Delineating aggressiveness of acute myeloid leukemia in a mouse model carrying mutations of Spil (PU.1) and Trp53.
Bašová, Petra ; Stopka, Tomáš (advisor) ; Machová Poláková, Kateřina (referee) ; Zuna, Jan (referee)
PU.1 downregulation within haematopoietic stem and progenitor cells (HSPCs) is the primary mechanism for the development of acute myeloid leukaemia (AML) in mice with homozygous deletion of the upstream regulatory element (URE) of PU.1 gene. p53 is a well known tumor suppressor that is often mutated in human haematologic malignancies including AML and adds to their aggressiveness; however its genetic deletion does not cause AML in mouse. Deletion of p53 in the PU.1ure/ure mice (PU.1ure/ure p53-/- ) results in more aggressive AML with shortened overall survival. PU.1ure/ure p53-/- progenitors express significantly lower PU.1 levels. In addition to URE deletion we searched for other mechanisms that in absence of p53 contribute to decreased PU.1 levels in PU.1ure/ure p53-/- mice. We found involvement of Myb and miR-155 in downregulation of PU.1 in aggressive murine AML. Upon inhibition of either Myb or miR-155 in vitro the AML progenitors restore PU.1 levels and lose leukaemic cell growth similarly to PU.1 rescue. The MYB/miR-155/PU.1 axis is a target of p53 and is activated early after p53 loss as indicated by transient p53 knockdown. Furthermore, deregulation of both MYB and miR-155 coupled with PU.1 downregulation was observed in human AML, suggesting that MYB/miR-155/PU.1 mechanism may be involved...
|
|
|
Regulation of DLX1 gene expression through AP-1 binding site
Rejlová, Kateřina ; Starková, Júlia (advisor) ; Machová Poláková, Kateřina (referee)
Regulation of expression DLX1 gene, whose elevated levels are detected in patients with acute myeloid leukemia with FLT3-ITD mutations, is not still completely explored topic. The first aim of this study was to determine which selected signaling pathways regulate gene expression of DLX1. ERK a JNK pathways were selected by using qRT-PCR and western blot. These pathways cause activation of the transcription factor AP-1 subunits, the AP-1 putative promoter binding site was identified also in the promoter of the DLX1 gene. The second aim of this study was to test the hypothesis on the regulation of gene expression of DLX1 (via ERK/JNK pathway) through AP-1 binding site on the promoter. Dual luciferase assay using luminescent luciferase activity was performed to test this hypothesis. Gene of the luciferase is contained in the used luciferase vector. The short and the long part of the DLX1 promoter (around AP-1 site) were inserted before the gene of the luciferase in the constructs used in this method. The results of this study indicate that the regulation of gene expression through AP-1 promoter binding site is important but not sufficient part of the regulatory cascade running through ERK and JNK pathway. There must be another transcription factors activated by ERK1/2 kinase which are probably also involved in...
|
|
|
Study of some markers of human leukemia
Pospíšilová, Klára ; Jílek, Petr (advisor) ; Skálová, Lenka (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study Field: zbioanalytical chemistry Candidate: Klára Pospíšilová Thesis Supervisor: PharmDr. P. Jílek, PharmDr. Consultant: RNDr. P. Řezáčová, MD., Ph.D., Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic Thesis Title: Study of some markers of human leukemia Abstract: Immunophenotyping of leukemia cells is an important part of leukemia diagnosis. Immunophenotype is determined by flow cytometry using monoclonal antibodies against antigens expressed by these cells. Antigen CD44 is one of many CD markers used in immunophenotyping of leukemias. Protein crystallography of a complex between CD44 antigen and its ligand, hyaluronate, bring more detailed information about the structure of the binding site, which may help develop strategies for influencing the binding and thus for potential therapeutic intervention.
|
|
|
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...
|
|
|
The role of HOXA9 gene in leukemogenesis
Rejlová, Kateřina ; Starková, Júlia (advisor) ; Fraiberk, Martin (referee)
The evolutionarily conserved family of homeobox genes plays an important role in the development of the anterior-posterior body axis of vertebrates. These genes significantly affect hematopoiesis, the development of blood cells. Extensive studies on homeobox genes in normal hematopoiesis confirmed their role also in leukemogenesis. Since the neoplastic transformation of blood cells, i.e. leukemia, is the most frequent malignancy in children, it has become a major subject of research for many scientists. Precisely in what stage of the malignant transformation the homeobox genes take part has not been shown yet. Neither is it known whether HOX genes are crucial in pathogenesis or whether their deregulation is only a side effect of leukemogenesis. The most studied homeobox gene in leukemogenesis is the HOXA9 gene, which showed correlation with the prognosis of patients with certain leukemias. Many studies describe the effect of HOXA9 in leukemic cell transformation, suggesting this gene could be a promising future target in leukemia therapy. This work is focused on the HOXA9 gene and its association with leukemic transformation of blood cells.
|
|
|
Signification of activatory and inhibitory ligands on leukemia cells to NK stimulations.
Imryšková, Zuzana ; Hromadníková, Ilona (advisor) ; Bezouška, Karel (referee)
In last decades, with expansion of immunological and biological methods are developed new diagnostical and treatment processes, which enable stratification of patients into sanative groups and trend to individual therapy. Absolutely transparent are effects relevant to leukemia. Present treatment procedures enable not only longer survivance of patients, but often their stable sanation. In present time is in progress intesive research imunotherapy NK cells, which could be able to finish minimal residual disease after chemotherapeutical treatment, which is evoke by persistant malignant cells. Next advantage of this treatment procedure is elimination of system disease in cosequence of exactly pointed cure. In this work he attended in vitro testing to possibility of utilization imunotherapeutic treatment by NK cells acute and chronic myeloid leukemia and chronic lymfoblastic leukemia. Using flow cytometry methods we detected activation and inhibitory ligands which are recognized by NK cells on the cell surface of leukemia blasts. These are members of MHC complex HLA-E, molecules derived from MHC class I (MICA, MICB), UL16-binding proteins (ULBP-1, ULBP -2, ULBP -3, ULBP -4) and also Hsp70 protein according to the newest observation. We also atended to detection of expression inducible heat shock...
|
|
| |
|
|
Nursing specifics in patients with leukemia
KAFKOVÁ, Zuzana
The topic of the essay was {\clq},Specific features of nursing patiens suffering from leukemia``. In the past the non-medical public understood the term onco-hematology to include one thing {--} leukemia. Qualitative research was used to prepare this essay; interviews and monitoring of processes in the internal medicine ward intermediary treatment in České Budějovice Hospital were applied in the process of data collection.
|
|
| |
guest ::
