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Refinement of tissue diagnostics in the transplant program
Balko, Jan ; Zámečník, Josef (advisor) ; Škarda, Jozef (referee) ; Němejcová, Kristýna (referee)
Refinement of tissue diagnostics in the transplant program Abstract The thesis describes tissue diagnostics of organ transplants of the donor as well as recipient. In case of donated organs (grafts), it aims to improve the provisional scoring system of graft rejection after uterine transplantation. Using histopathological methods including immunohistochemistry, it compares lymphocytic population classified in the scoring system with histopathological findings within the resected uteri of women who underwent hysterectomy for benign reasons. The aim was to validate the necessity of the category of so called borderline changes, whose morphology was proven to overlap with physiological finding within healthy uterine cervix. Therefore, there is no need for immunosuppressive therapy in such cases. In case of recipients, the thesis investigates the role of pulmonary megakaryocytes in explanted lungs after transplantation. The idea was to elucidate pathogenesis of the diseases leading to the need of transplantation itself. Pulmonary megakaryocytes within explanted lungs of various recipients were mapped using histopathological methods and immunohistochemistry. The strikingly increased number of such cells was detected among vascular disorders, especially idiopathic pulmonary hypertension. This finding could...
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Role of PARs and other biomarkers in the diagnosis of lung and neurodegenerative diseases
Brůžová, Magdalena ; Matěj, Radoslav (advisor) ; Němejcová, Kristýna (referee) ; Škarda, Jozef (referee)
1 SUMMARY In recent years, biomarker research has been the subject of many studies that address the etiopathogenetic processes of various diseases. Finding a biomarker that reflects the pathological processes of the disease with high sensitivity and specificity and was easily available and stable, would greatly facilitate the diagnosis of those diseases that are not easy to distinguish by conventional screening methods. Interstitial lung diseases (ILDs) include a heterogeneous group of disorders mostly of inflammatory nature. The resulting damage of the lung parenchyma can lead to its remodeling and fibrotization. The fibroproliferative process in different types of ILDs can result in similar clinical manifestations and findings on radiological images and biopsy specimens, which makes differential diagnosis difficult. Therefore, research in this area focuses on the presence of biomarkers in bronchoalveolar lavage fluid (BALF) to determine biomarker levels specific to individual ILDs. BALF analysis is used for differential diagnosis of patients with ILDs, but it can also be used to monitor the course of the disease, or response to the treatment. In our first study, we compared the levels of biomarkers in BALF in patients with sarcoidosis and hypersensitivity pneumonia (HP). From the results of the study, it...
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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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Significance of HNF-1B in different types of carcinomas and non-neoplastic lesions of the female genital system at the level of protein expression, epigenetic and genetic changes
Němejcová, Kristýna ; Dundr, Pavel (advisor) ; Zámečník, Josef (referee) ; Nenutil, Rudolf (referee)
Introduction HNF-1β is a transcription factor that plays a crucial role in the ontogenesis, regulates expression of multiple genes involved in cell cycle modulation and seems to be involved in cancerogenesis of various tumors. HNF-1β protein is coded by the HNF1B gene. Genetic and epigenetic changes of HNF1B play role in tumorigenesis and these changes can be accompanied by loss of expression or increased protein expression as detected by immunohistochemistry. In gynecopathology, expression of HNF-1β was considered as specific marker of clear cell carcinomas of the ovary and endometrium. However, more recent studies described HNF-1β expression also in tumors of other histogenesis. Aims: Our study focused on the immunohistochemical and molecular analysis of HNF1B in the normal tissue, various types of tumors and non-neoplastic lesions of the female genital tract. The goals of our study were: 1. Analysis of HNF-1β expression in cervical carcinomas. 2 Analysis of HNF-1β expression in endometrial carcinomas and non-neoplastic tissues of the female genital tract. 3. Analysis of epigenetic and genetic changes of HNF1B in endometrioid carcinomas and ovarian clear cell carcinomas. 4. Comprehensive analysis of atypical polypoid adenomyomas. Material and methods: A total of 574 samples including 399...
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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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Significance of HNF-1B in different types of carcinomas and non-neoplastic lesions of the female genital system at the level of protein expression, epigenetic and genetic changes
Němejcová, Kristýna ; Dundr, Pavel (advisor) ; Zámečník, Josef (referee) ; Nenutil, Rudolf (referee)
Introduction HNF-1β is a transcription factor that plays a crucial role in the ontogenesis, regulates expression of multiple genes involved in cell cycle modulation and seems to be involved in cancerogenesis of various tumors. HNF-1β protein is coded by the HNF1B gene. Genetic and epigenetic changes of HNF1B play role in tumorigenesis and these changes can be accompanied by loss of expression or increased protein expression as detected by immunohistochemistry. In gynecopathology, expression of HNF-1β was considered as specific marker of clear cell carcinomas of the ovary and endometrium. However, more recent studies described HNF-1β expression also in tumors of other histogenesis. Aims: Our study focused on the immunohistochemical and molecular analysis of HNF1B in the normal tissue, various types of tumors and non-neoplastic lesions of the female genital tract. The goals of our study were: 1. Analysis of HNF-1β expression in cervical carcinomas. 2 Analysis of HNF-1β expression in endometrial carcinomas and non-neoplastic tissues of the female genital tract. 3. Analysis of epigenetic and genetic changes of HNF1B in endometrioid carcinomas and ovarian clear cell carcinomas. 4. Comprehensive analysis of atypical polypoid adenomyomas. Material and methods: A total of 574 samples including 399...
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