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Molecular genetic analysis of thyroid carcinomas in pediatric and adolescent patients
Bulanová, Barbora ; Kuklíková, Vlasta (advisor) ; Ludvíková, Marie (referee) ; Vícha, Aleš (referee)
Thyroid nodules are rare in pediatric and adolescent patients, but they are at greater risk of malignancy than adult patients. Thyroid carcinomas are the most common endocrine malignancy and their incidence is increasing. Although there are several types of thyroid carcinoma, 90% of cases in pediatric and adolescent patients are papillary thyroid carcinomas (PTCs). The aim of this study was to analyze a large cohort of PTCs from pediatric and adolescent patients, determine their genetic cause, and correlate the findings with clinical pathological data. Another aim was to characterize the most frequent findings and compare them with a cohort of adult patients with thyroid carcinoma positive for the same mutation. The final objective was to optimize a suitable methodology for detecting the most common findings in pediatric and adolescent patients for routine use. Thyroid tumor tissue samples were examined using molecular genetic methods, mostly using next-generation sequencing and real-time PCR analysis. We found that fusion genes were the most common cause of PTC in pediatric and adolescent patients, detected in 56% of patients. In total, 20 different types of fusion genes were identified, some of which have not been previously described in the literature. The fusion genes included the oncogenes...
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The role of nurse in pain management after major orthopedic surgery
LUDVÍKOVÁ, Marie
This thesis is concerned with the role of the nurse in pain management after major orthopaedic surgeries. The thesis covers the topic of pain and its division and describes the role of the nurse in pain history and pain assessment as well as their role in postoperative pain management. Last but not least, the thesis focuses on the topic of alloplasty of large joints and anaesthesiology, namely the types of anaesthesia. The three main objectives set prior to the research were to map the role of the nurse in the management of postoperative analgesia after major orthopaedic surgeries, to assess the effect of different types of anaesthesia during surgery on postoperative pain intensity and the subsequent analgesic consumption, and to map the usefulness of epidural catheters in pain management in patients after major orthopaedic surgeries. Based on the stated objectives, the research question was established: What is the role of the nurse in the management of postoperative analgesia after major orthopaedic surgeries? This research was conducted using semi-structured interviews with nurses working in orthopaedic ICUs. The quantitative part of the research was conducted using two questionnaires to test hypotheses regarding whether there is a difference in postoperative pain intensity and subsequent analgesic consumption related to the type of anaesthesia used and whether pain is better managed in patients after major orthopaedic surgeries who have an epidural catheter in place. The first questionnaire was completed by nurses working in the orthopaedic ICU, but it was aimed at collecting the patient data so the patients' nursing records were needed for completion. The second questionnaire collected data from nurses working in orthopaedic ICUs and standard beds.
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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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Study of Metastatic Processes and Response to Chemotherapy in Primary Cultures Obtained from Colorectal Carcinoma and Lymph Node Metastases
Krbal, Lukáš ; Šteiner, Ivo (advisor) ; Ludvíková, Marie (referee) ; Němejcová, Kristýna (referee)
Study of metastatic processes and response to chemotherapy in primary cultures obtained from colorectal carcinoma and lymph node metastases Colorectal carcinoma is one of the most common malignant diseases in the Czech Republic. Despite an implementation of primary population screening to detect premalignant lesions, the incidence and the mortality of the disease do not appear to decrease significantly. A significant percentage of patients still manifest with late (metastatic) stage of the disease. Isolation of primary cell cultures of colorectal carcinoma is a method in which a large number of tumour cells is obtained relatively rapidly under "in vitro" conditions. With a low number of passages the cells can retain most of the characteristics of the original cells "in vivo". Therefore, cell cultures are an ideal model for studying the efficacy of chemotherapeutics and chemoresistance, as well as markers involved in carcinogenesis and metastasis of colorectal carcinoma. Overall, samples from 60 patients with colon adenocarcinoma were obtained. Our intention was to take one sample from the primary tumour and another sample from the lymph node from each patient. From the primary tumours we successfully obtained 26 primocultures with a success rate of 45 % (26/58); from the collected lymph nodes we...
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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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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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Morphology and Functional Characteristics of Human Gametes - the Potencial Clinical Application
Čedíková, Miroslava ; Králíčková, Milena (advisor) ; Ludvíková, Marie (referee) ; Hubičková Heringová, Lucie (referee)
Reduced fertility is a growing problem trough the population in fertile age. It currently affects 10-15% of couples; any method of assisted reproduction cannot help 10% of them. The effort to identify new prognostic markers that would help to improve the effectiveness of treatments of infertility assumes increasing significance. The first part of this publication is focused on the study of levels of selected hormones and markers of oxidative stress in follicular fluid of women with diagnosis of infertility compared to healthy and fertile donors of oocytes. Levels of prolactin, free T3 and T4 hormone, homocysteine, malonydiladehyd, glutathione peroxidase and total antioxidant capacity and were analyzed. Next part is devoted to the difference between these parameters in women with normal body mass index (BMI) compared to women suffering from overweight. The second half of this work is focused on the male factor of infertility. The aim of our study was to determine comprehensively mitochondrial respiratory activity of sperm with normal and reduced motility and to evaluate the impact of propolis on human sperm motility. Respiratory activity of sperm was measured using oxygraph Oroboros. The results showed significantly higher levels of prolactin and free T4 hormone in follicular fluid of infertile...
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New trends in cell and molecular biology of the head and neck cancer
Fík, Zdeněk ; Chovanec, Martin (advisor) ; Komínek, Pavel (referee) ; Ludvíková, Marie (referee)
Head and neck squamous cell carcinomas are still challenging despite progress in the oncological treatment. Study of the molecular biology allows to deeply characterize tumor properties and to predict the prognosis for affected patients. Nowadays there are many drugs clinically tested in the group of targeted therapy medicine Experimental work comprised both in vitro and in situ assays, being performed thanks to the collaboration between a number of departments of the 1st Faculty of Medicine of the Charles University in Prague, Academy of Sciences of the Czech Republic, Institute of Hematology and Blood Transfusion and Faculty of Veterinary Medicine of the Ludwig-Maxmillian University Munich. Galectin-1 is important inductor of the myofibroblasts/cancer associated fibroblasts. These fibroblasts are regarded as negative prognostic markers thanks to their capability of invasive cancer cells induction. On the other hand, Galectin-9 is not present in the carcinoma and in the case of dysplasia, its expression indicate aberrant features together with aberrant expression of keratin 14 and 19. Except from galectins using as prognostic markers, we focused on the galectins as a therapeutics instruments as well. Presented work with mutant variants of galectin-2 proved their effect on both pharmacodynamics and...
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Histomorphological Changes in Normal and Pathological Cartilage Tissues and after their Experimental and Clinical Transplantation
Kaňa, Radim ; Nečas, Emanuel (advisor) ; Slípka, Jaroslav (referee) ; Ludvíková, Marie (referee)
1 Abstract Introduction Autologous transplants of the cartilage tissue from the pinna is commonly used in reconstructive surgery of the nasal skeleton. The present study used animal models to elucidate responses of the auricular cartilage to its damage or transplantation to ectopic sites. Histomorphological analysis of changes observed in auricular cartilage including immunohistochemical study of different isoforms of actin and S-100 proteins was performed. Human articular cartilage prepared by in vitro cultivation using artificial scaffolds was also studied after its transplantation. Aims of the study The aim was to study histological changes and expression of chondrocytic markers (α- SMA and S-100 proteins) in intact, artificially traumatised, or in a human auricular cartilage cultivated in culture medium. An attempt to grow human auricular cartilage chondrocytes implanted in vitro into various types of three dimensional scaffolds aimed at testing chondrocyte survival and phenotype both in the culture and after transplantation to immunodeficient mice. A human auricular cartilage transplanted into the nasal skeleton of patients during a reconstruction surgery should be submitted to a histomorphological examination. Research assumed also comparison of the auricular cartilage responses to a damage,...
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