|
|
Role of Zinc-α2-glycoprotein in tumors
Kotvalová, Hanka ; Šmahel, Michal (advisor) ; Kubů, Martin (referee)
The Zinc-α2-glycoprotein (ZAG) encoded by the AZGP1 gene particularly contributes to the regulation of lipid and glucose metabolism. In different types of tumors, its altered production was found and the association of the ZAG level with the patient's prognosis was suggested. However, the role of ZAG in tumor progression can differ in individual malignancy types and mechanisms of ZAG function are not sufficiently identified. The objectives of the bachelor's thesis are a description of the structure of the ZAG protein and the regulation of AZGP1 expression, a summary of the identified ZAG functions in nonmalignant diseases, and a focus on the role of ZAG in tumors, particularly on the mechanisms of its action and its potential use as a biomarker.
|
|
|
Adhesion, growth and differentiation of osteoblasts and mesenchymal stromal cells on biocompatible nanomaterial surfaces
Brož, Antonín ; Hubálek Kalbáčová, Marie (advisor) ; Černý, Jan (referee) ; Kylián, Ondřej (referee)
The thesis is based on articles describing the fundamental research of carbon based nanomaterials for their possible utilization in biomedicine. The aim of this thesis was to describe the way how human osteoblasts (SAOS-2 cell line) and primary human mesenchymal stem cells (hMSC) adhere, grow and behave on surfaces made of several carbon allotropes - nanocrystalline diamond (NCD), single walled carbon nanotubes (SWCNTs) films and graphene. The utilization of carbon as the basic material promised good biocompatibility and possibility of useful surface modifications. The NCD had modified surface nanotopography (nanoroughness and nanostructuring prepared by dry ion etching). All the materials had modified surface atomic termination with oxygen and hydrogen which changes the surface electrical conductivity, surface charge and wettability. It was hypothesized that the surface termination can also influence the cell adhesion and growth. It turned out that all the studied materials were suitable as substrates for cultivation of mentioned cell types. Various nanoroughnesses of NCD surface had different effect on the cell adhesion and cell metabolic activity. Nanostructuring of the NCD influenced the formation of focal adhesions. The surface terminations of NCD and the other studied nanomaterials in...
|
|
|
Analysis of the effects of Src kinase inhibitors on adhesion signaling in human hematopoietic cells
Obr, Adam ; Kuželová, Kateřina (advisor) ; Jiroušková, Markéta (referee)
Adhesion of hematopoietic cells to the bone marrow microenvironment is important for their proper development. It is proven that Src-family kinases (SFK) regulate cell adhesion, although their exact role in the regulation of adhesion signaling remains unclear. Since adhesion processes are investigated mainly in adherent cell types, far less is known about hematopoietic cells. However, defects in the cell adhesion accompany a number of hematological diseases, like chronic myeloid leukaemia (CML). SFK overexpression is one of the proposed mechanisms of resistance to the first-line CML treatment, imatinib mesylate. Second generation drugs (e. g. dasatinib) inhibit SFK together with Bcr-Abl. Additionally, SFK-specific inhibitors (PP2, Src inhibitor-1) are also available, but there are no studies about effects of these drugs on cellular adhesivity of hematopoietic precursors. To explore the dynamics of hematopoietic cell adhesion to the extracellular matrix, we introduced a new approach using the RTCA xCELLigence DP system along with the well-established method of fluorimetric detection of adherent cell fraction. Our general observation is that various drugs (dasatinib, imatinib, PP2, Src inhibitor-1) induce pro-adhesive effects in several leukemic cell lines. Direct comparison of the kinetics of...
|
|
|
Adhesion, growth and differentiation of osteoblasts and mesenchymal stromal cells on biocompatible nanomaterial surfaces
Brož, Antonín ; Hubálek Kalbáčová, Marie (advisor) ; Černý, Jan (referee) ; Kylián, Ondřej (referee)
The thesis is based on articles describing the fundamental research of carbon based nanomaterials for their possible utilization in biomedicine. The aim of this thesis was to describe the way how human osteoblasts (SAOS-2 cell line) and primary human mesenchymal stem cells (hMSC) adhere, grow and behave on surfaces made of several carbon allotropes - nanocrystalline diamond (NCD), single walled carbon nanotubes (SWCNTs) films and graphene. The utilization of carbon as the basic material promised good biocompatibility and possibility of useful surface modifications. The NCD had modified surface nanotopography (nanoroughness and nanostructuring prepared by dry ion etching). All the materials had modified surface atomic termination with oxygen and hydrogen which changes the surface electrical conductivity, surface charge and wettability. It was hypothesized that the surface termination can also influence the cell adhesion and growth. It turned out that all the studied materials were suitable as substrates for cultivation of mentioned cell types. Various nanoroughnesses of NCD surface had different effect on the cell adhesion and cell metabolic activity. Nanostructuring of the NCD influenced the formation of focal adhesions. The surface terminations of NCD and the other studied nanomaterials in...
|
|
| |
|
|
Analysis of dynamical interactions of axon shafts and their biopysical modelling.
Šmít, Daniel ; Zápotocký, Martin (advisor) ; Reingruber, Jūrgen (referee) ; Maršálek, Petr (referee)
in English While axon fasciculation plays a key role in the development of neural networks, very lit- tle is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behaviour that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments. We show that zippering arises from the competition of axon-axon adhesion and me- chanical tension in the axons. This is upheld on quantitative level by conforming change of network global structure in response to various pharmacological treatments, without active involvement of growth cones. The calibrated manipulations of interacting shafts provide qualitative support for the hypothesis, and also allow us to quantify the mechan- ical tension of axons in our system. Furthermore, we introduce a biophysical model of the zippering dynamics, which efficiently serves the purpose of estimating the magnitude of remaining involved...
|
|
|
Application of the stem cells in bone tissue engineering
Kročilová, Nikola ; Bačáková, Lucie (advisor) ; Eckhardt, Adam (referee)
Problems with musculoskeletal system, such as of developmental disorders, fractures or damage of the bone by age, inflammatory or tumor diseases, are still increasing in orthopaedics. Sometimes the bone tissue is not capable to completely regenerate to exert its physiological function in the organism. For this reason, using the bone replacements is necessary and common nowadays. Despite of an intensive research and testing of a wide range of the potential biomaterials and their combinations, the usage of metal materials for construction of the bone implants, still remains to be the gold standard. Ti-6Al-4V alloy is one of the commercialy used metal materials, which is known for the high mechanical and chemical resistance and a good biocompatibility. For a good biological response of the patient's organism for the bone implant, is an ability of osteointegration into the surrounding bone tissue, the key. This ability can be influenced in the case of the metals, by their surface structure. As it is known from earlier studies, the surface topography of the material is very important for the adhesion and proliferation of the bone cells, which are able to discriminate, very sensitively, between various stages of the material surface roughness. For this reason we have focused on studying of an influence...
|
|
|
The role of Ser/Thr phosphorylation of p130CAS in signaling
Dibus, Michal ; Rösel, Daniel (advisor) ; Macůrková, Marie (referee)
p130Cas is an important adaptor protein that plays an essential role in many intracellular signaling processes. Given the fact that p130Cas is a well-known substrate for wide spectrum of kinases, its function is regulated mostly by phosphorylation on tyrosine, threonine and serine residues. This work is focused on Serine/Threonine phosphorylation and its role in regulation of p130Cas signaling. Although it is known that Serine/Threonine phosphorylation of p130Cas is regulated by cell cycle, integrin-mediated cell adhesion and association with BCAR3, the mechanisms leading to the phosphorylation are still not well understood and the kinases involved in these processes are unknown. Being p130Cas an important regulator of cell migration and tumor invasiveness, understanding of these mechanisms should provide a useful tool in developing new strategies in aiming of anti-cancer drugs.
|
|
|
Analysis of the effects of Src kinase inhibitors on adhesion signaling in human hematopoietic cells
Obr, Adam ; Kuželová, Kateřina (advisor) ; Jiroušková, Markéta (referee)
Adhesion of hematopoietic cells to the bone marrow microenvironment is important for their proper development. It is proven that Src-family kinases (SFK) regulate cell adhesion, although their exact role in the regulation of adhesion signaling remains unclear. Since adhesion processes are investigated mainly in adherent cell types, far less is known about hematopoietic cells. However, defects in the cell adhesion accompany a number of hematological diseases, like chronic myeloid leukaemia (CML). SFK overexpression is one of the proposed mechanisms of resistance to the first-line CML treatment, imatinib mesylate. Second generation drugs (e. g. dasatinib) inhibit SFK together with Bcr-Abl. Additionally, SFK-specific inhibitors (PP2, Src inhibitor-1) are also available, but there are no studies about effects of these drugs on cellular adhesivity of hematopoietic precursors. To explore the dynamics of hematopoietic cell adhesion to the extracellular matrix, we introduced a new approach using the RTCA xCELLigence DP system along with the well-established method of fluorimetric detection of adherent cell fraction. Our general observation is that various drugs (dasatinib, imatinib, PP2, Src inhibitor-1) induce pro-adhesive effects in several leukemic cell lines. Direct comparison of the kinetics of...
|
|
| |
guest ::
