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The Role of Dipeptidyl Peptidase-IV in Glioma Cell Growth
Bušek, Petr ; Šedo, Aleksi (advisor) ; Trka, Jan (referee) ; Konvalinka, Jan (referee)
Dipeptidyl peptidase-IV (DPP-IV, CD26, EC 3.4.14.5) is a widely expressed serine protease that by limited proteolysis regulates a number of biologically active peptides including a number of mitogenic peptides involved in cancer development. Deranged DPP-IV expression and/or enzymatic activity has been reported in a number of tumors, and could lead to altered signaling and biological function of its substrates. Changes in DPP-IV expression were observed in glioma cell lines in association with differentiation, and recently also in malignant gliomas in vivo. In addition, DPP-IV substrates substance P (SP) and stromal cell derived factor-1 (SDF-1) that trigger growth promoting intracellular signaling cascades in glioma cells have strongly been implicated in the pathogenesis of gliomas. The aim of this study was (i) to investigate the effects of DPP-IV on the signaling of its biologically active substrates that promote the malignant phenotype of glioma cells, and (ii) to assess the effects of DPP-IV on the growth, migration and adhesion of human glioma cells. Using transfected glioma cell lines (U373CD26, T98GCD26, U87CD26) with mifepristone-inducible DPP-IV expression, we demonstrate that DPP-IV overexpressing T98GCD26 cells can cleave SP and thus abrogate its ability to trigger calcium signaling in U373...
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TEL/AML1, BCR/ABL and TEL/ABL Fusion genes in childhood acute lymphoblastic leukemia
Žaliová, Markéta ; Trka, Jan (advisor) ; Machová Poláková, Kateřina (referee) ; Pospíšilová, Dagmar (referee)
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. It represents a group of clinically and biologically heterogenous malignancies that can be subclasified into several subtypes according to the presence of recurrent genetic aberrations. The typical genetic aberrations in childhood ALL are chromosomal translocation, that often result in creation of fusion genes encoding either chimeric kinases or chimeric transcription factors. These recurrent genetic aberations are aquired lesions, they are supposed to be the initial hits (that may arise even prenataly) with a causal role in the process of leukemogenesis, which is, however, in the majority of them not yet fully understood. They further represent specific markes used for the detection of leukemic cells and some of them have also prognostic significance and belong among the factors used for risk group stratification in treatment protocols. Risk group stratification and subsequent risk-adapted therapy together with introduction of new therapeutic approaches (intensive chemotherapeutic regimens involving intrathecal application, hematopoetic stem cell transplantation (HSCT), supportive therapy) account for the significant improvement of the treatment outcomes of childhood ALL in the last decades. In addition to genotype, several...
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The alterations of MLL (mixed-lineage leukemia) gene and their clinical importance in pediatric patients with acute leukemia
Řezníčková, Leona ; Trka, Jan (advisor) ; Sedláček, Zdeněk (referee)
Presence of the MLL gene rearrangement at 11q23 is an important prognostic feature. Moreover, the rearrangements represent a suitable target for the minimal residual disease (MRD) monitoring in some subtypes of childhood acute leukaemias (AL). Currently more than 80 different translocations involving the MLL gene and more than 50 of those are characterised at the molecular leve\. Using multiplex-reverse transcriptase polymerase chain reaction (multiplex RT -PCR) and - in some cases - its combination with DNA analysis of the translocation breakpoint we examined a group of infants «1 year of age) diagnosed with acute lymphoblastic leukaemia (ALL), children with M4 and M5 subtypes of acute myeloid leukaemia (AML) and patients with secondary leukaemias. Moreover, we exaITŮned children with B-cell precursor fulfilling at least one of the ťollowing criteria: proB immunophenotype, cytogenetically confirmed MLL rearrangement and/or expression oťNG2 molecule shown by f10w cytometry. MultiplexRT PCR technique enables fast detection of the most frequent fusion partners of the :MLL gene (AF4, AF6, AF9, AFlO, ENL a ELL). We screened almost 80 patients diagnosed and treated in the Czech Republic between 1997 and 2007 and we found an MLL-fusion gene in 51 of them. Vast majority of rearrangements (92%) was detected by the...
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The Role of WT1 gene in normal hematopoiesis and leukemogenesis
Kramarzová, Karolina ; Trka, Jan (advisor) ; Zadražil, Stanislav (referee)
6 Abstract The Wilms' tumor gene is highly expressed in a large proportion of human acute leukemias and other hematological malignancies. It is thought to play an important role in human hematpoiesis and leukemogenesis. Despite the large number of studies, WT1 expression patterns and its clinical significance in acute myeloid leukemia remain still controversial. To investigate the prognostic relevance of initial WT1 expression and its usefulness as a marker for minimal residual disease, we have analysed 66 bone marrow samples from newly diagnosed AML patients. RQ-RT-PCR for absolute quantification of total WT1 was designed according to Europe Against Cancer Program. In 82 % of samples we detected a higher expression of WT1 compared to normal healthy donors or patients with acute lymphoblastic leukemia (p<0.0001). We did not find any correlation between initial WT1 expression level and age or sex. Patients with FAB M3 subtype showed significantly higher WT1 levels than other subtypes, especially M5 (p<0.001). We found a strikingly high WT1 expression in standard risk group patients compared to high risk group (p<0.0007). Children with FAB/cytogenetical favorable prognostic factors have high WT1 expression, while there was no relation between WT1 levels at diagnosis and day 15 BM response. We did not find any...
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Evaluation of the Financial Situation of the Company and Proposals to its Improvement
Hurytová, Kristýna ; Trka, Jan (referee) ; Pernica, Martin (advisor)
This bachelor thesis focuses on the evaluation of financial situation of the company ADC Czech Republic in fiscal years 2010 - 2014. In the first part there are theoretical foundations of the defined indicators which will be later calculated in the practical part of thesis. Second part is practical, where the analysed company is introduced. Financial indicators will be calculated based on theoretical part of the thesis and results commented. The last part of thesis are recommendations. Measures will be proposed in order to improve current financial situation of the analyzed company.
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