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ELISpot methodology and prediction of acute rejection after renal transplantation.
Rybáková, Kateřina ; Slavčev, Antonij (advisor) ; Mrázek, František (referee)
Transplantation is the best therapeutic solution for patients with chronic renal failure. Due to the great advances in immunosuppressive therapy in the last decades, graft and patient survival have improved significantly. On the other hand, immunosuppressive therapy has serious side effects - too strong immunosuppression may lead to infection or malignancies, conversely insufficient immunosuppression may lead to graft rejection. Due to the grave consequences of acute rejection, the main goal of cooperation of clinicians and transplant immunologists is to stratify patients into groups with low, moderate and high risk of rejection based on the evaluation of various immunologic risk factors. There are reports in the literature that the numbers (frequencies) of interferon gamma (IFNγ) producing cells before transplantation may be helpful to identify patients with high risk of acute cellular rejection and to predict long-term survival of the graft. In this retrospective study we determined the pre-transplant frequencies of activated donor specific T lymphocytes producing IFNγ after short stimulation (24 hrs) by ELISpot (Enzyme-linked immunosorbent spot assay). The results were correlated with the incidence of acute cellular (ACR) and antibody-mediated (AMR) rejection and with other risk factors. In our...
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Molecular mechanisms of fibroblastoid cell phenotype transitions:dedifferentiation of myofibroblasts and influencing of invasiveness and metastasis of sarcoma
Kosla, Jan
Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...
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Molecular mechanisms of fibroblastoid cell phenotype transitions:dedifferentiation of myofibroblasts and influencing of invasiveness and metastasis of sarcoma
Kosla, Jan
Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...
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ELISpot methodology and prediction of acute rejection after renal transplantation.
Rybáková, Kateřina ; Slavčev, Antonij (advisor) ; Mrázek, František (referee)
Transplantation is the best therapeutic solution for patients with chronic renal failure. Due to the great advances in immunosuppressive therapy in the last decades, graft and patient survival have improved significantly. On the other hand, immunosuppressive therapy has serious side effects - too strong immunosuppression may lead to infection or malignancies, conversely insufficient immunosuppression may lead to graft rejection. Due to the grave consequences of acute rejection, the main goal of cooperation of clinicians and transplant immunologists is to stratify patients into groups with low, moderate and high risk of rejection based on the evaluation of various immunologic risk factors. There are reports in the literature that the numbers (frequencies) of interferon gamma (IFNγ) producing cells before transplantation may be helpful to identify patients with high risk of acute cellular rejection and to predict long-term survival of the graft. In this retrospective study we determined the pre-transplant frequencies of activated donor specific T lymphocytes producing IFNγ after short stimulation (24 hrs) by ELISpot (Enzyme-linked immunosorbent spot assay). The results were correlated with the incidence of acute cellular (ACR) and antibody-mediated (AMR) rejection and with other risk factors. In our...
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Molecular mechanisms of fibroblastoid cell phenotype transitions:dedifferentiation of myofibroblasts and influencing of invasiveness and metastasis of sarcoma
Kosla, Jan ; Dvořák, Michal (advisor) ; Peková, Soňa (referee) ; Reiniš, Milan (referee)
Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...
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The effect IMRT technique by the head and neck tumors looking on the total dose in the organs at risk and the target volumes
WOLFOVÁ, Barbora
The effect IMRT technique by the head and neck tumors looking on the total dose in the organs at risk and the target volumes This work compares two techniques of planning radiotherapy in the head and neck areas. The technique used will be IMRT - Intensity Modulated Radiotherapy. The development of new technologies in radiotherapy equipment has also brought a wider range of methods of treating carcinomas. The IMRT technique represents a breakthrough in this process and that is why it is dealt with in this work as far as its advantages, as compared with conventional radiotherapy methods, are concerned. I have focused mainly on the distribution of doses in target volumes and critical organs, in particular in the salivary glands and the spinal chord. The region of the head and throat is an area containing the kinds of tissue with various sensitivity and tolerance to radiotherapy. The damage to such tissues has an enormous impact on the patient. That is why the region is a very suitable place for assessing the advantages of the IMRT as compared with conventional techniques. Ten plans from a set of patients suffering from tumour in the area of head and throat have been evaluated in this work by means of DVH (Dose Volume Histogram). The individual plans have been interpreted, conventional plans and IMRT ones separately. I have focused on comparing mean doses and the subsequent comparison of doses of 5 per cent and 95 per cent of the irradiated volume PTV, maximum doses on the spinal chord, and doses of 50 per cent of the irradiated volume of the salivary glands in the individual plans.
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