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Tumor markers in diagnostics and therapy monitoring with a focus on pediatric oncology
Votava, Tomáš ; Topolčan, Ondřej (advisor) ; Šafarčík, Kristian (referee) ; Ludvíková, Marie (referee) ; Sumerauer, David (referee)
Background: Thymidine kinase (TK) is involved in nucleic acid synthesis and is therefore considered to be an important proliferation tumor marker. Our main goal was to determine significance of elevated TK levels in the context of prognosis, differential diagnosis, monitoring after treatment and relapse marker during follow up in children suffering from acute leukemia and lymphoma. Another marker beta(2)-microglobulin (2MG) was studied for the same purpose. Patients and Methods: TK and 2MG serum levels in 58 children with acute leukemia and 14 children with lymphoma were determined using radio-receptor analysis (TK) and ELISA assay (2MG). Control group included 109 patients with benign disease for leukemia group and 35 patients with benign lymphadenitis for lymphoma group. Results: Our results showed that especially TK serum levels at the time of diagnosis of acute leukemia were extremely elevated (median - 409 U/l ) as well as 2MG (median - 1,96 mg/l). Both markers clearly discriminated acute leukemia from benign diseases (p<0.0001). In the term of prognosis, none of the markers reached significant p-value. During relapse of acute leukemia (7 cases), the marker levels increased considerably above the individual remission level and were statistically significant p < 0.02535 (TK) and p < 0.04551 (2MG). These...
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Vascular Calcification and Bone Demineralization in Patiens with Chronic Renal Failure
Mareš, Jan ; Opatrná, Sylvie (advisor) ; Topolčan, Ondřej (referee) ; Spustová, Viera (referee) ; Štěpán, Jan (referee)
Background: Patients treated with chronic dialysis show extreme mortality, particularly due to cardiovascular disease. Renal failure is associated with different risk factors of cardiovascular complications than those defined for non-renal population. One of these factors, currently considered most important, are vascular calcifications. At the same time, patients on dialysis regularly suffer from derrangements of calcium-phosphate metabolism, including skeletal demineralization. As a consequence, both incidence and prevalence of bone fractures are high. Aims: This study therefore investigates vascular calcifications and skeletal demineralization, their clinical implications and associations in patients treated with long-term dialysis. Methods: Two groups of patients were examined in a prospective manner (follow-up > 1 year); 32 patients treated with peritoneal dialysis and 72 treated with regular hemdodialysis. Treatment parameters and biochemical markers of calcium-phosphate metabolism were monitored throughout the study. Bone mineral density of lumbar spine (together with vertebral fractures) as well as coronary artery, valvular and aortic calcifcations were determined repeatedly. All radiological parameters were measured during one computed-tomography scanning session. Results: A significant...
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Insulin like and other growth factors and tumors
Kučera, Radek ; Topolčan, Ondřej (advisor) ; Klimeš, Jiří (referee) ; Šafarčík, Kristian (referee)
Inzulinu podobné a jiné růstové faktory a nádory Insulin like and other growth factors and tumors Disertační práce Plzeň 2011 Mgr. Radek Kučera Summary The interaction between growth factors and cancer incidence and development has been discussed recently. First works suggesting possible connection between increased production of insulin like growth factors with an increased incidence of tumors came already from early 80s of the last century. The aim of my work was focused on evaluation of possible relation between insulin like growth factors or their binding proteins and tumors from different perspectives, to assess their significance and try to determine what role the IGFs and IGFBPs may play in the current tumor diagnostics. The work itself is divided into two parts, the theoretical and practical ones. In the theoretical part, I summarized the action of IGF in human body and also focused on previous findings on the role of IGF system in cancer diagnoses. In the practical part, divided into three subsections, I focused on investigation of relations in a large set of patients with different cancer diagnoses, in a group of women with breast cancer and, finally, I focused on changes of IGF1 levels during follow-up. Theoretical part Insulin-like growth factors (IGF) are peptides, that participate on growth...
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The clinical relevance of biomarkers for aggression assessment and prognosis in non-small cell lung cancer
Pražáková, Markéta ; Topolčan, Ondřej (advisor) ; Ludvíková, Marie (referee) ; Molino, Rafael (referee)
Aim: The aim of this thesis was to measure a large spectrum of biomarkers in serum or plasma of patients with operable stage of NSCLC and to evaluate and compare the clinical utility of these biomarkers in the three most important clinical applications for NSCLC: diagnosis, prognosis and postsurgery follow up care. Patients and methods: Total of 22 biomarkers with the most promising profiles were monitored: 8 standard tumor markers (cytokeratines Cyfra 21-1, TPA, TPS, and MonoTotal, CEA, SCC, TK, Chromogranin A) and 14 potential useful biomarkers including pro-inflammatory cytokines IL-6, IL-8, MCP-1, pro-angiogenic cytokine VEGF, matrix metaloproteinases MMP-1, MMP-2, MMP-7, MMP-9 and their inhibitors TIMP-1 and TIMP-2, adhesion molecules ICAM-1, VCAM-1, growth factor IGF-1, and PAI-1 stimulating tumor growth and angiogenesis. With a view of evaluating the clinical relevance of these markers for NSCLC we measured serum or plasma levels of these 22 markers in group of 93 patients with NSCLC undergoing radical surgery and in group of 20 patients with benign lung disease. For biomarker measurement were used conventional immunoanalytic routine methods (IRMA, REA, CLIA, MEIA, TRACE, ELISA) and multiplex immunoanalytic method. Results: Cyfra 21-1, MonoTotal, TPA, TPS, CEA, SCC, Chromogranin A, TIMP-1, MMP-1,...
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Prognostic factors in malignant melanoma
Třešková, Inka ; Topolčan, Ondřej (advisor) ; Pizinger, Karel (referee) ; Nekulová, Miroslava (referee)
Background: Malignant melanoma is one of the most malignant types of skin cancer. Incidences are on the rise worldwide and in the Czech Republic an increase of 5% in diagnosed cases is noted each year. Early detection and early surgical removal are associated with reduced mortality. The strong aggressiveness of this malignant disease is caused by its local invasive growth and tendency to metastasize early. Aim of the study: The malignant melanoma is highly metabolically active tumor that releases a number of enzymes, cytokines, growth hormones and other molecules. The aim of this work was to determine the usability of preoperative and postoperative serum and plasma levels of biomarkers in primary diagnosis of tumor activity and in the postoperative follow-up care. These findings would be of clinical relevance for the patient's prognosis, modification of multimodal treatment and follow-up of patients with malignant melanoma. Methods: We measured circulating levels of several biomarkers in a group of 77 patients with malignant melanoma and cohort of 34 patients without cancer as a control group. Using routine immunoassays and novel multiplex xMAP technology, we measured: thymidine kinase, tissue polypeptide specific antigen, protein S100A, osteoprotegerin, osteopontin , insulin-like growth factor 1...
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Interpretation of Common Used Tumor Markers Affectedy by Systemic and Inflammatory Diseases
Čásová, Miroslava ; Topolčan, Ondřej (advisor) ; Ludvíková, Marie (referee) ; Šafarčík, Kristian (referee)
Interpretation of Common Used Tumor Markers Affected by Systemic and Inflammatory Diseases Introduction: An examination of tumor markers is often made as a basis for the successful diagnosis and follow-up treatment of patients with malignant tumors. However, are tumor markers truly significant by themselves, or are they just a baseline quantitative expression of value that we use to diagnose a patient as better or worse based on it increasing or decreasing value? Objective: This paper attempts to answer the question of what factors can affect serum protein and mucin markers and thus lead to a misinterpretation of their results. Methods: Tumor markers were determined by isotopic and non-isotopic laboratory analysis methods, using operational protocols of the immunoanalytic laboratory. All methods were checked using internal quality control, and four times a year using an external quality control. Additionally, 16 236 samples were analysed using 3180 probands during the period 2008-2014. Results: We discovered that in premenopausal women, the markers AFP, CA 125 and HE 4 rise during ovulation peak periods while other markers changed minimally or not at all. However, in postmenopausal women, we proved the incidence of a false positivity marker. With women in the 1st and 2nd trimester of pregnancy, the...
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The incidence of thyroid in selected regions of the Czech Republic in terms of saturation with iodine
Dvořáková, Marcela ; Zamrazil, Václav (advisor) ; Topolčan, Ondřej (referee) ; Stárka, Luboslav (referee) ; Čáp, Jan (referee)
24 9. SUMMARY 1. Natural sources such as water or soil contain iodine in low amounts in the Czech Republic. 2. Clinical manifestations of iodopenia were severe and occured in certain geographical areas in the past. 3. Iodization of table salt started in the fifties of the last century as a result of extensive epidemiological research and since then it has significantly improved iodine saturation in general. 4. Further steps in iodine prophylaxis in the mid-nineties of the 20th century have improved iodine saturation according to ICCIDD/WHO criteria. 5. Resolution of iodine deficiency does not represent, however, a closed chapter. 6. Individuals at risk, such as pregnant or breastfeeding women and patients on a salt- restricted diet, are worthy of public health concern. 7. There needs to be increased awareness of chronic excess of iodine with respect to an increasing prevalence of autoimmune thyroid disorders. 8. There is a need to continue education of the general population focused on adequate iodine intake from various foods (see products, milk) and to maintain a daily iodine intake in the "optimal ranges". Based on the international criteria, the Czech Republic is iodine sufficient country. This happened due to a multidisciplinary collaboration coordinated by the Regional Iodine Deficiency Council...
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Assessment of Biological Activity of Colorectal Carcinoma using RT REAL-TIME PCR
Pešta, Martin ; Topolčan, Ondřej (advisor) ; Pešek, Miloš (referee) ; Pecen, Ladislav (referee)
The author in his doctoral thesis, proposed primers and conditions optimized design Quantitative PCR for determining the gene expression of MMP-7, TIMP-1, MMP-2 and TIMP- second Revealed the presence of gene expression of GAPDH TIMP-1 and TIMP-2 in cancer line HT-29 SW480 and SW620. Noted the high level expression of MMP-7 in line HT-29th Expression of the 2-3 orders of magnitude higher than the lines SW480 and SW620. MRNA expression of MMP-2 in line HT-29 noticed. MRNA expression of MMP-2 by the detected lines SW480 and SW620. He found that determining absolute and relative expression in tumor lines is ekvivalentní. significantly higher mRNA expression of MMP-7, TIMP-1, MMP-2 and TIMP-2 in tumor tissue compared to normal tissue. It can be used in therapy. Noticed the presence of correlation of gene expression MMP-7, TIMP-1, MMP-2 and TIMP-2 with survival and DFI. He showed that a higher stage cancer correlated with a higher median momery MMP-2/TIMP-2. 7, Noticed the difference in gene expression between TS, TP and DPD in control and tumor tissue. Scored marginally significant increase in TS expression in colon tumors compared to tumors rectosigmoid and rectum. This finding can be used in treatment decisions. scored marginally significant correlation between the expression of TS and DPD. This finding can be...
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