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Interaction of mesenchymal stem cells with immune system and their use in cancer therapy
Sivák, Ladislav ; Kovář, Marek (advisor) ; Paňková, Daniela (referee)
Mesenchymal stem cells (MSC) are multipotent progenitor cells with the ability to differentiate into ectodermal, mesodermal and endodermal cell line. They interact with innate and adaptive immunity and modulate their effector functions. Immunoregulatory effect of MSC results in suppression of inflammatory immune response and induces anti-inflammatory immune response. In addition, MSC have the ability to migrate into tumor site trough soluble factors produced by tumor cells and contribute to tumor growth and metastasis. Preferential homing to site of cancer growth and regulation of immune system make the MSC a promising tool for cancer therapy. Key words: mesenchymal stem cells, immunoregulation, tumors, cancer gene therapy
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Formation of blastema during limb regeneration in Amphibia
Paušlyová, Lucia ; Tlapáková, Tereza (advisor) ; Paňková, Daniela (referee)
Total limb regeneration among vertebrates is basically restricted to some amphibians. Urodeles have the ability to regenerate amputated limbs through their life span. Anurans have the ability of complete regeneration of amputated limbs only in their larval stage. The key process of the limb regeneration is the formation of undifferentiated cell group which is called blastema. There are many cell types that contribute to formation of the blastema while the most important part in this process belongs to the skeleton muscle tissue and dermal fibroblasts. Another critical factor in formation of the blastema and its growth are the nerves in the area of wound and neurotrophic factors produced by them. In the last 20 years it has been great improvement in using different markers for tracking the fate of blastema cells.
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Molecular mechanisms of amoeboid invasion of cancer cells
Paňková, Daniela ; Brábek, Jan (advisor) ; Dvořák, Michal (referee) ; Vomastek, Tomáš (referee)
Tumour cell invasion is one of the most critical steps in malignant progression. It includes a broad spectrum of mechanisms, including both individual and collective cell migration, which enables them to spread towards adjacent tissue, and form new metastases. Understanding the mechanisms of cell spreading, and invasion, is crucial for effective anticancer therapy. Two modes of individual migration of tumour cells have been established in a three-dimensional environment. Mesenchymally migrating cells use proteases to cleave collagen bundles, and thus overcome the ECM barriers. Recently described protease-independent amoeboid mode of invasion has been discovered in studies of cancer cells with protease inhibitors. During my PhD study, I have focused on determining the molecular mechanisms involved in amoeboid invasion of tumour cells. We have examined invasive abilities in non-metastatic K2 and highly metastatic A3 rat sarcoma cell lines. We have shown that even though highly metastatic A3 rat sarcoma cells are of mesenchymal origin, they have upregulated Rho/ROCK signalling pathway. Moreover, A3 cells generate actomyosin-based mechanical forces at their leading edges to physically squeeze through the collagen fibrils by adopting an amoeboid phenotype. Amoeboid invasiveness is also less dependent on...
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Matrix metalloproteinases in anterior eye segment
Paračková, Zuzana ; Ardan, Taras (advisor) ; Paňková, Daniela (referee)
Matrix metalloproteinases belong to the group of proteases which in normal tissue are responsible for degradation a and remodeling of extracellular matrix components and their activity is regulated by endogenous inhibitors. However, many patological conditions of the anterior eye segment are characterized by increased activity of matrix metalloproteinases and conversely decreased activity of their tissue inhibitors.The imbalance between matrix metalloproteinases and their inhibitors can lead to destructive proteolytic tissue damage anterior eye segment, including blindness. Key words: matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, extracellular matrix
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Role of cAMP signaling in phagocyte migration
Dáňová, Klára ; Kamanová, Jana (advisor) ; Paňková, Daniela (referee)
Cell migration plays a key role in a wide diversity of biological processes. Migration enables phagocytic cells to localize into the site of inflammation and to lymph nodes, thereby leading to initiation of innate and adaptive immune responses, respectively. The signal transduction that coordinates phagocyte migration consist of diverse signaling proteins, being often under control of 3'-5'-cyclic adenosine monophosphate (cAMP) and its two effectors, protein kinase A (PKA) and Epac (exchange protein activated by cAMP). Small GTPase Rap is activated by Epac and controls phagocyte migration via activation of RAPL and RIAM proteins. On the other hand, PKA regulates cell migration via modulation of activity of other proteins, which comprise actin, integrins, small GTPases Rho, Rac, Cdc42 as well as protein VASP. A prominent feature of cAMP signalization is its spatio-temporal organization. Therefore, besides description of cAMP-regulated signaling cascades in cell migration, this bachelor thesis also depicts how changes of activity of cAMP effectors in time and place are involved in regulation of cell movement.
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Molecular mechanisms of amoeboid invasion of cancer cells
Paňková, Daniela ; Brábek, Jan (advisor) ; Dvořák, Michal (referee) ; Vomastek, Tomáš (referee)
Tumour cell invasion is one of the most critical steps in malignant progression. It includes a broad spectrum of mechanisms, including both individual and collective cell migration, which enables them to spread towards adjacent tissue, and form new metastases. Understanding the mechanisms of cell spreading, and invasion, is crucial for effective anticancer therapy. Two modes of individual migration of tumour cells have been established in a three-dimensional environment. Mesenchymally migrating cells use proteases to cleave collagen bundles, and thus overcome the ECM barriers. Recently described protease-independent amoeboid mode of invasion has been discovered in studies of cancer cells with protease inhibitors. During my PhD study, I have focused on determining the molecular mechanisms involved in amoeboid invasion of tumour cells. We have examined invasive abilities in non-metastatic K2 and highly metastatic A3 rat sarcoma cell lines. We have shown that even though highly metastatic A3 rat sarcoma cells are of mesenchymal origin, they have upregulated Rho/ROCK signalling pathway. Moreover, A3 cells generate actomyosin-based mechanical forces at their leading edges to physically squeeze through the collagen fibrils by adopting an amoeboid phenotype. Amoeboid invasiveness is also less dependent on...
|
|
|
Interaction of mesenchymal stem cells with immune system and their use in cancer therapy
Sivák, Ladislav ; Kovář, Marek (advisor) ; Paňková, Daniela (referee)
Mesenchymal stem cells (MSC) are multipotent progenitor cells with the ability to differentiate into ectodermal, mesodermal and endodermal cell line. They interact with innate and adaptive immunity and modulate their effector functions. Immunoregulatory effect of MSC results in suppression of inflammatory immune response and induces anti-inflammatory immune response. In addition, MSC have the ability to migrate into tumor site trough soluble factors produced by tumor cells and contribute to tumor growth and metastasis. Preferential homing to site of cancer growth and regulation of immune system make the MSC a promising tool for cancer therapy. Key words: mesenchymal stem cells, immunoregulation, tumors, cancer gene therapy
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Formation of blastema during limb regeneration in Amphibia
Paušlyová, Lucia ; Tlapáková, Tereza (advisor) ; Paňková, Daniela (referee)
Total limb regeneration among vertebrates is basically restricted to some amphibians. Urodeles have the ability to regenerate amputated limbs through their life span. Anurans have the ability of complete regeneration of amputated limbs only in their larval stage. The key process of the limb regeneration is the formation of undifferentiated cell group which is called blastema. There are many cell types that contribute to formation of the blastema while the most important part in this process belongs to the skeleton muscle tissue and dermal fibroblasts. Another critical factor in formation of the blastema and its growth are the nerves in the area of wound and neurotrophic factors produced by them. In the last 20 years it has been great improvement in using different markers for tracking the fate of blastema cells.
|
|
|
Matrix metalloproteinases in anterior eye segment
Paračková, Zuzana ; Ardan, Taras (advisor) ; Paňková, Daniela (referee)
Matrix metalloproteinases belong to the group of proteases which in normal tissue are responsible for degradation a and remodeling of extracellular matrix components and their activity is regulated by endogenous inhibitors. However, many patological conditions of the anterior eye segment are characterized by increased activity of matrix metalloproteinases and conversely decreased activity of their tissue inhibitors.The imbalance between matrix metalloproteinases and their inhibitors can lead to destructive proteolytic tissue damage anterior eye segment, including blindness. Key words: matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, extracellular matrix
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