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Establishment of new methods for detection of selected polymorphisms in patients with chronic myeloid leukemia treated with imatinib mesylate
Kupčová, Markéta ; Pecka, Miroslav (advisor) ; Fátorová, Ilona (referee)
CHARLES UNIVERSITY IN PRAGUE Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Bc. Markéta Kupčová Supervisor: Doc. RNDr. Miroslav Pecka CSc. Consultant: Mgr. Filip Vrbacký Title of diploma thesis: The introduction of new methods for detection of selected polymorphisms in patients with chronic myeloid leukemia treated with Imatinib mesylate. Chronic myelogenous leukemia is a hematopoetic cancer characterized by the presence BCR / ABL fusion gene with pathological tyrosine kinase activity which causes uncontrolled proliferation of cells primarily granulocytic line. Revolution in the treatment of this disease, but also in the forecast, recorded discovery of inhibitors of tyrosine kinases, which in recent years has used with great success. The first inhibitor was Imatinib mesylate, which inhibit the activity of tyrosine kinases, however in some patients could arise resistance and treatment failure, which can be caused by many factors, which include the polymorphisms in the genes responsible for the transport and metabolism of the substance. For the thesis were selected genes whose products are involved in the transport and biotransformation Imatinib mesylate. Genes ABCB1, ABCG2, SLC22A1 and CYP3A5. These genes were genotyped chosen SNP by allelic...
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Laboratory diagnostic of the thrombofilic diseases.
Studená, Šárka ; Pecka, Miroslav (advisor) ; Blažek, Martin (referee)
The thesis describes the occurance of trombophilic attacs and about their diagnostic possibilities in women with recurent spontaneous abortions. In the study, the sample of women tested were the ones who subscribed for treatment in the 2nd internal disease clinic - Department of clinical hematology of Faculty hospital and Medical faculty Univerzity Karlovy in Hradec Kralove in years 1995-2007. I have also used the materials from archive whilst investigating some samples from past. I was actively involved in this investigation in last couple of years. During writing conclusion of the knowledge gained, following criteria from the literature of our choice and search were used based on the described importance of trombophylic attacs with rising incidence of is capture: age - in this part we used the median of age from the observed sample number of undertaken abortions - this parameter has a great significancy, however it is needed to overview whole period of pregnancy, afterwhich the abortions arose (in first trimester is crucial third abortion and in second trimester the second abortion has been under the count) number of newborn children - the risk of spontaneous abortion is rising with every child the period of using contraception - the usage of contraceptives can in an early stage show the...
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Prognostic importance of angiopoietin-2 gene transcription in chronic lymphocytic leukemia.
Gradošová, Iveta ; Pecka, Miroslav (advisor) ; Smolej, Lukáš (referee)
Chronic lymphocytic leukemia (CCL) is the most common leukemia, which is characterised by a high variable progress. According to scientific evidence acquired during several last years, angiogenesis has been proven to play an important role in pathogenesis of CLL. One of the very important cytokines playing role in this process is angiopoietin-2 (Ang-2). Elevated expression of Ang-2 has been reported in several hematological malignancies; however, data regarding Ang-2 in CLL are very limited. I measured Ang-2 transcript levels in purified mononuclear cels of 24 untreated patients with CLL by quantitative real-time PCR and normalized them for differences in RNA concentration in each sample by quantitation of transcript of Abl1 housekeeping gene. Elevated Ang-2 mRNA concentrations were detected in 10 cases (Ang-2 to Abl1 expression ratio > 5x10-3). On the other hand, 14 patients had very low or undetectable levels of Ang-2 mRNA (Ang-2 to Abl1 expression ratio < 5x10-3 or Ang-2 Cp > 35). The association between Ang-2 expression and other prognostic factors, clinical stage according to Rai and clinical course of CLL was evaluated by Chi-Square method. There was a significant association between high Ang-2 mRNA levels and unmutated IgVH genes (n= 21, p = 0.012), but not with CD38 (p = 0.057), ZAP-70 expression (p...
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Establishment of new methods for detection of selected polymorphisms in patients with chronic myeloid leukemia treated with imatinib mesylate
Kupčová, Markéta ; Pecka, Miroslav (advisor) ; Fátorová, Ilona (referee)
CHARLES UNIVERSITY IN PRAGUE Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Bc. Markéta Kupčová Supervisor: Doc. RNDr. Miroslav Pecka CSc. Consultant: Mgr. Filip Vrbacký Title of diploma thesis: The introduction of new methods for detection of selected polymorphisms in patients with chronic myeloid leukemia treated with Imatinib mesylate. Chronic myelogenous leukemia is a hematopoetic cancer characterized by the presence BCR / ABL fusion gene with pathological tyrosine kinase activity which causes uncontrolled proliferation of cells primarily granulocytic line. Revolution in the treatment of this disease, but also in the forecast, recorded discovery of inhibitors of tyrosine kinases, which in recent years has used with great success. The first inhibitor was Imatinib mesylate, which inhibit the activity of tyrosine kinases, however in some patients could arise resistance and treatment failure, which can be caused by many factors, which include the polymorphisms in the genes responsible for the transport and metabolism of the substance. For the thesis were selected genes whose products are involved in the transport and biotransformation Imatinib mesylate. Genes ABCB1, ABCG2, SLC22A1 and CYP3A5. These genes were genotyped chosen SNP by allelic...
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|
|
Laboratory diagnostic of the thrombofilic diseases.
Studená, Šárka ; Blažek, Martin (referee) ; Pecka, Miroslav (advisor)
The thesis describes the occurance of trombophilic attacs and about their diagnostic possibilities in women with recurent spontaneous abortions. In the study, the sample of women tested were the ones who subscribed for treatment in the 2nd internal disease clinic - Department of clinical hematology of Faculty hospital and Medical faculty Univerzity Karlovy in Hradec Kralove in years 1995-2007. I have also used the materials from archive whilst investigating some samples from past. I was actively involved in this investigation in last couple of years. During writing conclusion of the knowledge gained, following criteria from the literature of our choice and search were used based on the described importance of trombophylic attacs with rising incidence of is capture: age - in this part we used the median of age from the observed sample number of undertaken abortions - this parameter has a great significancy, however it is needed to overview whole period of pregnancy, afterwhich the abortions arose (in first trimester is crucial third abortion and in second trimester the second abortion has been under the count) number of newborn children - the risk of spontaneous abortion is rising with every child the period of using contraception - the usage of contraceptives can in an early stage show the...
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Prognostic importance of angiopoietin-2 gene transcription in chronic lymphocytic leukemia.
Gradošová, Iveta ; Pecka, Miroslav (advisor) ; Smolej, Lukáš (referee)
Chronic lymphocytic leukemia (CCL) is the most common leukemia, which is characterised by a high variable progress. According to scientific evidence acquired during several last years, angiogenesis has been proven to play an important role in pathogenesis of CLL. One of the very important cytokines playing role in this process is angiopoietin-2 (Ang-2). Elevated expression of Ang-2 has been reported in several hematological malignancies; however, data regarding Ang-2 in CLL are very limited. I measured Ang-2 transcript levels in purified mononuclear cels of 24 untreated patients with CLL by quantitative real-time PCR and normalized them for differences in RNA concentration in each sample by quantitation of transcript of Abl1 housekeeping gene. Elevated Ang-2 mRNA concentrations were detected in 10 cases (Ang-2 to Abl1 expression ratio > 5x10-3). On the other hand, 14 patients had very low or undetectable levels of Ang-2 mRNA (Ang-2 to Abl1 expression ratio < 5x10-3 or Ang-2 Cp > 35). The association between Ang-2 expression and other prognostic factors, clinical stage according to Rai and clinical course of CLL was evaluated by Chi-Square method. There was a significant association between high Ang-2 mRNA levels and unmutated IgVH genes (n= 21, p = 0.012), but not with CD38 (p = 0.057), ZAP-70 expression (p...
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