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Regulation of transcription by proteins of the Early growth response and Myb families
Čermák, Vladimír ; Dvořák, Michal (advisor) ; Vomastek, Tomáš (referee) ; Elleder, Daniel (referee)
The regulation of transcription of tens of thousands of genes in a vertebrate organism is an enormously complex phenomenon which entails the participation of thousands of various regulatory proteins. The largest functional category of these regulators is accounted for by sequence-specific DNA-binding proteins known as transcription factors. Proteins of the EGR and Myb families of transcription factors are long-studied regulators of a variety of physiological processes including cellular proliferation and differentiation. The structural and physical aspects of their function have been well characterized. Their cell-type specific participation in complex gene-regulatory networks, on the other hand, is still incompletely understood and represents a major challenge in the respective research areas. Preliminary analysis of gene expression data from metastasizing PR9692 and non- metastasizing PR9692-E9 chicken sarcoma cell lines revealed that the transcription factor EGR1 is expressed at a higher level in metastasizing cells and can thus take part in the regulatory processes that underlie the differences between the two cell lines. Further investigation demonstrated that the introduction of exogenous EGR1 into PR9692-E9 cells restored their metastatic potential to a level indistinguishable from PR9692...
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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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Regulation of transcription by proteins of the Early growth response and Myb families
Čermák, Vladimír ; Dvořák, Michal (advisor) ; Vomastek, Tomáš (referee) ; Elleder, Daniel (referee)
The regulation of transcription of tens of thousands of genes in a vertebrate organism is an enormously complex phenomenon which entails the participation of thousands of various regulatory proteins. The largest functional category of these regulators is accounted for by sequence-specific DNA-binding proteins known as transcription factors. Proteins of the EGR and Myb families of transcription factors are long-studied regulators of a variety of physiological processes including cellular proliferation and differentiation. The structural and physical aspects of their function have been well characterized. Their cell-type specific participation in complex gene-regulatory networks, on the other hand, is still incompletely understood and represents a major challenge in the respective research areas. Preliminary analysis of gene expression data from metastasizing PR9692 and non- metastasizing PR9692-E9 chicken sarcoma cell lines revealed that the transcription factor EGR1 is expressed at a higher level in metastasizing cells and can thus take part in the regulatory processes that underlie the differences between the two cell lines. Further investigation demonstrated that the introduction of exogenous EGR1 into PR9692-E9 cells restored their metastatic potential to a level indistinguishable from PR9692...
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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 role of radiologist assistant in radioiodine diagnostics and treatment of thyroid cancer
Hrbek, Jaroslav ; Táborská, Kateřina (referee) ; Vlček, Petr (advisor)
The bachelors thesis on the task of a radiological assistant during radioiodine diagnostics and treatment of thyroid gland carcinomas deals with the issue of thyroid gland carcinomas in the Czech Republic. It contains a brief overview of the types of carcinomas that affect the thyroid gland, their classification, diagnostics and therapy, concentrating on utilisation of modern examination methods and therapeutic practices, including among others application of radioiodine. The thesis also contains cases of four patients with similar diagnoses, the comparison of the development of whose respective illnesses I found interesting. Last but not least, the thesis includes a number of annexes comprising among others tables with important instructions for patients before and after application of radioiodine, and photographs from the site where the radioiodine application takes place Powered by TCPDF (www.tcpdf.org)
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The role of immune cells in tumor growth and spontaneous regression in a rat sarcoma model
Kovalská, Jana ; Chmelíková, Eva (advisor) ; Anna, Anna (referee)
The aim of the thesis is to study differences between sexes of rats in tumour growth, the difference in immune response between rats with progressing and spontaneously regressing tumours compared to control rats and verification of immunological memory. We used Lewis rat model with subcutaneously inoculated sarcoma. Peripheral blood of males showed a higher number of red blood cells, a higher concentration of haemoglobin and higher haematocrit compared to females. Experimental females with inoculated sarcoma had higher levels of CD161 (NK) cells at the beginning of experiment in comparison with the experimental and control males and control females. A strong infiltration of NK cells was observed in tissue sections of spontaneously regressing sarcoma compared to progressing tumours tissue. Important factors that can influence if the animal will show tumour progression or spontaneous regression are neutrophil granulocytes (they can induce both tumour-supporting and anti-tumour response), vascularization and extent of necrosis in tumour tissue. We have verified immunological memory in a small group of females by the secondary inoculations of the same tumour cells after complete disappearance of primary, spontaneously regressing tumour. No sarcoma repeatedly evolved in any of the females. Results obtained in the present work brought new insights into the problems of tumour in the Lewis rat sarcoma model with inoculated sarcoma. These results may have significance also for area of clinical oncology due to similarities with the behaviour of some human cancers.
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