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Kvantitativní uvolňování a riziko růstu inflace v USA
Jarošová, Marie
The thesis is focused on quantitative easing, which used the U.S. central bank for the third time in a few years, to deepen the expansionary monetary policy. There is examining the relationship between quantitative easing and inflation, as the sharp rise in inflation is considered a major risk associated with quantitative release an. Relationship between quantitative easing and inflation is observed by means of simple regress analysis (using the OLS) and the moving correlation (rolling correlation) between each wheel QE with regard to the development of mortgage, financial and debt crisis.
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Unbalanced changes in cancer cells genome and its role in cancer pathogenesis
Lhotská, Halka ; Zemanová, Zuzana (advisor) ; Jarošová, Marie (referee) ; Kuglík, Petr (referee)
Malignant transformation of cell is characterized by genomic instability that involves unbalanced changes besides other things. We analyzed genomic aberrations, promoter methylation and mutations of several clinically relevant genes using I-FISH, mFISH, mBAND, CGH array, SNP array, MLPA, MS-MLPA and MS-PCR methods. We focused on two groups of patients well known for frequent appearance of unbalanced changes - patients with malignant brain tumors (gliomas) and patients with myelodyspastic syndromes (MDS). In patients with low grade glioma (WHO grade I - II), the codeletion of 1p/19q (82,6% oligodendrogliomas and oligoastrocytomas), mutation of IDH1/IDH2 genes (87% WHO grade I-II gliomas), copy neutral loss of heterozygozyty of 17p (72,2% astrocytomas) and higher presence of unbalanced aberration in astrocytomas belongs to the most frequent findings. We described yet unpublished methylation of MLH3 gene promoter in 60,9% oligodendrogliomas and in 27,3% astrocytomas. We also observed clonal evolution in patients with recurrent tumors. We studied secondary rearrangements of deleted chromosome 5 in patients with MDS and complex karyotype and we described its most recurrent translocation partners and breakpoints. We observed chromothripsis in 49% of these patients and it was frequently associated with...
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Gene expression analysis in patients with myelodysplastic syndrome
Vašíková, Alžběta ; Votavová, Hana (advisor) ; Neuwirtová, Radana (referee) ; Jarošová, Marie (referee)
Myelodysplastic syndrome (MDS) is a clonal disorder affecting maturation and differentiation of hematopoietic stem cells. MDS is characterized by ineffective hematopoiesis resulting in peripheral blood cytopenia in at least one lineage, and increased risk of development of acute myeloid leukemia (AML). This disorder mostly affects the elderly, with the incidence of 10-50/100000 people per year. Heterogeneity of MDS is further underlined by the presence of both idiopathic primary and secondary therapy-related forms, which arise from accumulation of mutational events induced by cytotoxic therapy (exposure to alkylating agents or after therapy with topoisomerase II inhibitors). In this thesis, we focused on determination of differential gene expression between MDS patients and control subjects using different microarray platforms. Using nylon membranes, we detected 4 genes (ERCC1, FLT1, NME4, PCNA) with increasing expression pattern in advanced MDS stages, which correlated with disease progression. Their strong up- regulation was also observed in patients with de novo AML, suggesting their involvement in the leukemic transformation of MDS. Comparison of gene expression profiles of early and advanced MDS obtained by Agilent microarrays resulted in the set of differentially expressed genes, which might...
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The use of novel technologies in the identification of unique molecular markers for minimal residual disease assessment in acute leukemia patients
Jančušková, Tereza ; Peková, Soňa (advisor) ; Jarošová, Marie (referee) ; Lysák, Daniel (referee)
Acute leukemias (AL) comprise a heterogeneous group of hematologic malignancies, and individual patient responses to treatment can be difficult to predict. Monitoring of minimal residual disease (MRD) is thus very important and holds great potential for improving treatment strategies. Common MRD targets include immunoglobulin heavy chain or T-cell receptor gene rearrangements, recurrent cytogenetic abnormalities and mutations in important hematological genes. Whereas in the majority of adult acute lymphoblastic leukemia patients a suitable MRD target can be identified, in adult acute myeloid leukemia patients well-characterized targets are found in only half of cases. The identification of new specific molecular markers of leukemic blasts for MRD assessment, particularly in AML patients, is therefore highly desirable. Our aim was to develop a flexible strategy for mapping of cytogenetically identified unique clone-specific abnormalities down to the single nucleotide level and, based on the sequence, design a specific real-time PCR assay for MRD assessment in AL patients without any previously described MRD marker. Using a combination of cytogenetic (chromosome banding, chromosome microdissection), molecular cytogenetic (mFISH, mBAND) and molecular biological (next- generation sequencing, long-range...
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Pathogenesis of childhood leukemia
Hovorková, Lenka ; Zuna, Jan (advisor) ; Kolenová, Alexandra (referee) ; Jarošová, Marie (referee)
BCR-ABL1 fusion gene is a hallmark of chronic myeloid leukaemia (CML), but can be found also in patients with acute lymphoblastic leukaemia (ALL). In BCR-ABL1-positive ALL, two principal approaches for treatment response and minimal residual disease (MRD) monitoring are routinely used - quantification of genomic clonal rearrangements of immunoglobulin/T-cell receptor genes (Ig/TCR) and BCR-ABL1 expression. We established methods for determination of BCR-ABL1 genomic fusion and used the intronic breakpoints to measure MRD levels also at the BCR-ABL1 DNA level. Comparison of MRD based on Ig/TCR and genomic BCR-ABL1 in 47 consecutive childhood patients showed poor correlation in about 25 % cases with significantly higher BCR-ABL1 levels. In those patients, we found the BCR-ABL1 not only in ALL-blasts, but also in other cell subtypes (T-cells, myeloid cells) negative for clonal Ig/TCR rearrangements. For the similarity with CML we assigned this new leukaemia subtype with multilineage BCR- ABL1 involvement "CML-like" leukaemia. Our ongoing study is focused on the prognostic implications of discordant MRD results. As we characterized the genomic BCR-ABL1 fusion in 428 patients (which is to our knowledge the largest cohort described so far), we also analysed the origin of the breakpoints. Our data suggest...
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Unbalanced changes in cancer cells genome and its role in cancer pathogenesis
Lhotská, Halka ; Zemanová, Zuzana (advisor) ; Jarošová, Marie (referee) ; Kuglík, Petr (referee)
Malignant transformation of cell is characterized by genomic instability that involves unbalanced changes besides other things. We analyzed genomic aberrations, promoter methylation and mutations of several clinically relevant genes using I-FISH, mFISH, mBAND, CGH array, SNP array, MLPA, MS-MLPA and MS-PCR methods. We focused on two groups of patients well known for frequent appearance of unbalanced changes - patients with malignant brain tumors (gliomas) and patients with myelodyspastic syndromes (MDS). In patients with low grade glioma (WHO grade I - II), the codeletion of 1p/19q (82,6% oligodendrogliomas and oligoastrocytomas), mutation of IDH1/IDH2 genes (87% WHO grade I-II gliomas), copy neutral loss of heterozygozyty of 17p (72,2% astrocytomas) and higher presence of unbalanced aberration in astrocytomas belongs to the most frequent findings. We described yet unpublished methylation of MLH3 gene promoter in 60,9% oligodendrogliomas and in 27,3% astrocytomas. We also observed clonal evolution in patients with recurrent tumors. We studied secondary rearrangements of deleted chromosome 5 in patients with MDS and complex karyotype and we described its most recurrent translocation partners and breakpoints. We observed chromothripsis in 49% of these patients and it was frequently associated with...
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