National Repository of Grey Literature 11 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
Complex Evaluation of Immune Defects in Patients with Chronic Lymphocytic Leukemia
Vodárek, Pavel ; Belada, David (advisor) ; Doubek, Michael (referee) ; Papajík, Tomáš (referee)
Complex evaluation of immune defects in patients with chronic lymphocytic leukemia MUDr. Pavel Vodárek Abstract of dissertation thesis Chronic lymphocytic leukemia (CLL) is associated with significant combined immunodeficiency. Amongst most important immune defects are hypogammaglobulinemia and changes in relative and absolute counts of different lymphocyte populations and subsets. As consequence of these changes, there can be higher frequency of infections and progression of CLL itself. The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) levels and lymphocyte populations has not been extensively studied. In this dissertation thesis, we analysed Ig levels and lymphocyte populations (using flow cytometry) in 45 patients with indolent untreated CLL and 90 patients with progressive disease indicated for treatment. In 58 patients, we evaluated the impact of first-line CIT. For lymphocyte populations' analysis, we had also cohort of 34 healthy controls. Patients with progressive disease had significantly lower levels of all Ig classes and subclasses than patients with inactive disease: IgG, median 6.96 vs. 9.86 g/l, p=0.0001; IgA, median 0.63 vs. 1.53 g/l, p<0.0001; IgM, median 0.36 vs. 0.57 g/l, p=0.0035. After treatment, median IgA increased from 0.59 g/l to 0.74 g/l (p=0.0031). Other Ig classes and...
Incidence of hyperlipoproteinemia and atherosclerotic changes in long-term survivors of Hodgkin lymphoma in childhood or adolescence
Čepelová, Michaela ; Kraml, Pavel (advisor) ; Češka, Richard (referee) ; Papajík, Tomáš (referee)
The survival of children and adolescents with Hodgkin lymphoma has improved dramatically over the last decades, but even young adult long-term survivors are at increased risk of developing multiple cardiovascular late sequelae of previous treatment. We evaluated the presence of modifiable cardiovascular risk factors (hypertension, hyperlipoproteinemia, hyperinsulinemia, obesity) in young adult Hodgkin lymphoma survivors, who were disease- free for a minimum of 10 years after the end of their treatment, and in age- and gender- matched healthy volunteers. We assumed higher prevalence of modifiable cardiovascular risk factors together with earlier development of atherosclerotic changes in this specific population. All survivors and volunteers uderwent physical examination, duplex ultrasonography of both common carotid arteries, all participants completed questionnaire on their eating habits and physical activities We performed biochemical analyses, including lipid profile, fasting glucose and insulin levels, markers of inflammation, endothelial dysfunction and oxidative stress. The HL survivors showed unfavorable lipid profiles, markers of oxidative stress, endothelial dysfunction and inflammation compared to those of healthy controls. We found a higher prevalence of insulin resistance, metabolic syndrome and...
Current aspects of care patients with chronic lymphocytic leukemia
Šimkovič, Martin ; Smolej, Lukáš (advisor) ; Doubek, Michael (referee) ; Papajík, Tomáš (referee)
In recent years it has been an unprecedented development of knowledge of biology and treatment options of chronic lymphocytic leukemia (CLL). Survival of patients with CLL was improved by the introduction of the monoclonal antibodies (anti-CD20) and combined chemoimmunotherapy regimens. Despite this undeniable advance in the treatment of CLL and progress in knowledge of CLL biology and pathophysiology, many current aspects of care of these patients remain unresolved. In our work we focus on epidemiology of CLL, treatment of relapsing/refractory CLL patients, rituximab infusion-related adverse events and venous thromboembolism in CLL patients. Incidence of CLL in Hradec Králové district during period 1999-2013 was 8.2 patients per 100,000 persons per year. Trends in epidemiology were analyzed after splitting patients into two groups according to the period in which the diagnosis was made: n=92 in the period 1999- 2005 and n=108 in the period 2006-2013. Significant prolongation of survival (median OS not reached vs 86 months) was observed in patients treated during the period 2006-2013 in comparison to those treated in the period 1999-2005. However, the improvement of overall survival was achieved only in younger patients (≤ 70 years). Patients with refractory CLL have highly unfavourable prognosis....
Genetic factors in lymphoproliferative malignancies Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors
Havránek, Ondřej ; Trněný, Marek (advisor) ; Papajik, Tomáš (referee) ; Veselý, Pavel (referee)
Genetic factors in lymphoproliferative malignancies. Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors. MUDr. Ondřej Havránek Summary of PhD thesis: Background: The checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway that among others interacts with the p53 protein. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in non- Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is not clear. The most frequent TP53 gene R72P polymorphism was analyzed in several studies in NHL but not in HL. Methods: We have performed mutation analysis of the whole CHEK2 gene coding sequence in 340 NHL patients and the segment coding for CHEK2 forkhead-associated (FHA) domain in 298 HL patients and compared the results with our analyses of CHEK2 in breast, colorectal and pancreatic cancers. The TP53 R75P genotype was assessed in the same lymphoma populations. Both genes were analyzed using denaturing high-performance liquid chromatography. Results: The overall frequency of CHEK2 alterations within FHA-coding region was significantly higher in NHL and HL patients (19/340 - 5.6%; 17/298 - 5.7%, respectively) compared to non-cancer controls (19/683 - 2.8%; p = 0.03 and 0.04, respectively). These alterations were associated with...
Distinguishing of primary mediastinal B-cell lymphoma and diffuse large B-cell lymphoma with real-time quantitative polymerase chain reaction
Votavová, Hana ; Trněný, Marek (advisor) ; Papajik, Tomáš (referee) ; Kozák, Tomáš (referee)
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. It is a molecular and prognostic heterogeneous disease. Three main genetic subtypes are called germinal center-like DLBCL (GC-like DLBCL), non-germinal center-like DLBCL (nonGC-like DLBCL) and primary mediastinal B-cell lymphoma (PMBL). These subtypes can be reliably distinguished only with usage of gene expression profiling (GEP). The GEP method can be applied only when fresh frozen tissue is available. The method is technically difficult and expensive. Thus, it is not used routinely. Since the DLBCL subtypes differ in prognosis, it is extremely important to be able to distinguish them. The presented thesis is focused on distinguishing of PMBL diagnosis in the group of DLBCL. Easily stored formalin-fixed, paraffin-embedded tissue (FFPE) and gene expression analysis using real-time quantitative polymerase chain reaction (RTqPCR) are used. In the first step, PMBL and DLBCL cases were distinguished with an internationally accepted clinical-pathological method. The agreement between clinical-pathological diagnosis and GEP is only 76%. In the presented text a genetic algorithm for PMBL/DLBCL distinguishing is suggested. It uses three carefully chosen genes and their expression is measured with RTqPCR. Both, the...
Current aspects of care patients with chronic lymphocytic leukemia
Šimkovič, Martin ; Smolej, Lukáš (advisor) ; Doubek, Michael (referee) ; Papajík, Tomáš (referee)
In recent years it has been an unprecedented development of knowledge of biology and treatment options of chronic lymphocytic leukemia (CLL). Survival of patients with CLL was improved by the introduction of the monoclonal antibodies (anti-CD20) and combined chemoimmunotherapy regimens. Despite this undeniable advance in the treatment of CLL and progress in knowledge of CLL biology and pathophysiology, many current aspects of care of these patients remain unresolved. In our work we focus on epidemiology of CLL, treatment of relapsing/refractory CLL patients, rituximab infusion-related adverse events and venous thromboembolism in CLL patients. Incidence of CLL in Hradec Králové district during period 1999-2013 was 8.2 patients per 100,000 persons per year. Trends in epidemiology were analyzed after splitting patients into two groups according to the period in which the diagnosis was made: n=92 in the period 1999- 2005 and n=108 in the period 2006-2013. Significant prolongation of survival (median OS not reached vs 86 months) was observed in patients treated during the period 2006-2013 in comparison to those treated in the period 1999-2005. However, the improvement of overall survival was achieved only in younger patients (≤ 70 years). Patients with refractory CLL have highly unfavourable prognosis....
Prognostic factors in chronic lymphocytic leukemia
Motyčková, Monika ; Žák, Pavel (advisor) ; Doubek, Michael (referee) ; Papajík, Tomáš (referee)
Prognostic factors in chronic lymphocytic leukemia Introduction: Search for new prognostic markers in order to improve prognostic accuracy and predict clinical outcome at the time of diagnosis has recently become one of the major trends in chronic lymphocytic leukemia (CLL). Aims of the project: Assessment of selected markers of apoptosis and angiogenesis and their potential as new prognostic factors and correlation with conventional and modern prognostic factors and clinical course. Patients and Methods: We evaluated serum levels of tumor necrosis factor alpha (TNF-α), transforming growth factor beta-1 (TGF-ß1) and fibroblast growth factor-2 (FGF-2) using comercially available enzyme-linked immunosorbent assay; furthemore, we quantified expression of type II receptor for transforming growth factor beta (TGFßRII) and type 2 receptor for FGF-2 (FGFR2) on CLL cells using flow cytometry analysis in 75 previously untreated patients with CLL (47 males and 28 females, median age, 65 years, range, 38-82) and healthy donors. Results: We found significantly elevated TNF-α in patients with CLL compared to the control group (p<0.0001); high expression of TNF-α was associated with unfavourable prognosis: significantly higher TNF-α was present in patients with Rai high-risk group compared to low- and...
Genetic factors in lymphoproliferative malignancies Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors
Havránek, Ondřej ; Trněný, Marek (advisor) ; Papajik, Tomáš (referee) ; Veselý, Pavel (referee)
Genetic factors in lymphoproliferative malignancies. Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors. MUDr. Ondřej Havránek Summary of PhD thesis: Background: The checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway that among others interacts with the p53 protein. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in non- Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is not clear. The most frequent TP53 gene R72P polymorphism was analyzed in several studies in NHL but not in HL. Methods: We have performed mutation analysis of the whole CHEK2 gene coding sequence in 340 NHL patients and the segment coding for CHEK2 forkhead-associated (FHA) domain in 298 HL patients and compared the results with our analyses of CHEK2 in breast, colorectal and pancreatic cancers. The TP53 R75P genotype was assessed in the same lymphoma populations. Both genes were analyzed using denaturing high-performance liquid chromatography. Results: The overall frequency of CHEK2 alterations within FHA-coding region was significantly higher in NHL and HL patients (19/340 - 5.6%; 17/298 - 5.7%, respectively) compared to non-cancer controls (19/683 - 2.8%; p = 0.03 and 0.04, respectively). These alterations were associated with...
Distinguishing of primary mediastinal B-cell lymphoma and diffuse large B-cell lymphoma with real-time quantitative polymerase chain reaction
Votavová, Hana ; Trněný, Marek (advisor) ; Papajik, Tomáš (referee) ; Kozák, Tomáš (referee)
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. It is a molecular and prognostic heterogeneous disease. Three main genetic subtypes are called germinal center-like DLBCL (GC-like DLBCL), non-germinal center-like DLBCL (nonGC-like DLBCL) and primary mediastinal B-cell lymphoma (PMBL). These subtypes can be reliably distinguished only with usage of gene expression profiling (GEP). The GEP method can be applied only when fresh frozen tissue is available. The method is technically difficult and expensive. Thus, it is not used routinely. Since the DLBCL subtypes differ in prognosis, it is extremely important to be able to distinguish them. The presented thesis is focused on distinguishing of PMBL diagnosis in the group of DLBCL. Easily stored formalin-fixed, paraffin-embedded tissue (FFPE) and gene expression analysis using real-time quantitative polymerase chain reaction (RTqPCR) are used. In the first step, PMBL and DLBCL cases were distinguished with an internationally accepted clinical-pathological method. The agreement between clinical-pathological diagnosis and GEP is only 76%. In the presented text a genetic algorithm for PMBL/DLBCL distinguishing is suggested. It uses three carefully chosen genes and their expression is measured with RTqPCR. Both, the...

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