|
|
Tumor microenvironment modulation and the impact on cancer immunotherapy
Musil, Jan ; Němečková, Šárka (advisor) ; Mikyšková, Romana (referee) ; Otáhal, Pavel (referee)
Modulation of the tumor microenvironment represents a possible way to inhibit cancer growth and enhance anti-cancer immune responses. In the presented work we employ two strategies for tumor microenvironment modulation. Firstly, we have constructed rVACV co-expressing the tumor suppressor gene insulin-like growth factor-binding protein-3 (IGFBP- 3) and the fusion gene encoding the immunogen SigE7LAMP. The expression of IGFBP-3 was regulated either by the early vaccinia virus H5 promoter or by the synthetic early/late (E/L) promoter. We have shown that expression of IGFBP-3 regulated by the H5 promoter yielded higher amounts of IGFBP-3 protein when compared with the E/L promoter. Immunization with P13-SigE7LAMP-H5-IGFBP-3 was more effective in inhibiting the growth of TC-1 tumors in mice and elicited a higher T-cell response against VACV-encoded antigens than the control virus P13-SigE7LAMP-TK- . We found that high-level production of IGFBP-3 enhanced virus replication both in vitro and in vivo, resulting in profound antigen stimulation. Production of IGFBP-3 was associated with a higher adsorption rate of P13-SigE7LAMP-H5-IGFBP-3 to CV-1 cells when compared with P13-SigE7LAMP-TK- . We have identified two structural differences between the IMVs of the IGFBP-3 expressing virus P13-SigE7LAMP-H5-IGFBP-3...
|
|
|
Leukemia cell signaling and signaling of non-malignant B-cells
Kanderová, Veronika ; Kalina, Tomáš (advisor) ; Klener, Pavel (referee) ; Otáhal, Pavel (referee)
Acute leukemia (AL) is the most common pediatric cancer. Approximately 90 - 100 children is diagnosed every year in the Czech Republic. Acute leukemia is a complex disease that is pathologically manifested at the DNA, mRNA, protein and cellular level. Leukemic cells aberrantly express molecules that are found in other cell types under physiological conditions and their functional involvement in leukemic cells is unknow. We found that aberrantly expressed CEACAM6 increases the expression and affinity of integrins, increases the phosphorylation of intracellular kinases Akt, p38MAPK and p44/42 MAPK and triggers apoptosis in B-cell precursor acute lymphoblastic leukemia cells. Adaptor molecule NTAL, aberrantly expressed in T-cell acute lymphoblastic leukemia, signals through intracellular kinase p44/42 MAPK and potentiates corticosteroid induced apoptosis. Current leukemia research is focused mainly on monitoring of mutations at the DNA level, however, the functional consequences of these changes on cellular machineries are not straightforward. Since proteome analysis can provide link between gene sequence and cellular physiology, proteomics will contribute to elucidate mechanism of disease, prognosis and response to treatment. Protein microarrays technology is of major interest for basic proteomic research as...
|
|
|
Lineage plasticity in normal and malignant lymphocyte precursors
Rezková Řezníčková, Leona ; Froňková, Eva (advisor) ; Otáhal, Pavel (referee)
Klasické schéma vývoje hematopoetických buněk předpokládá časné oddělení lymfoidního a myeloidního prekurzoru. V poslední době jsou navrhovány složitější modely, které předpokládají větší flexibilitu hematopoezy a navrhují existenci progenitorů s lymfoidním i myeloidním potenciálem. Akutní hybridní leukémie jsou malignity, které podle různých kritérií nelze jednoznačně zařadit k lymfoidní nebo k myeloidní linii a jejichž chování spíše dává za pravdu novým modelům hematopoezy. Předkládaná práce se zabývala především výzkumem dětských leukémií s přesmykem z lymfoidní do myeloidní linie během indukční léčby. Jedná se o rozsáhlý projekt, v jehož rámci si diplomová práce si kladla za úkol určit liniové zařazení leukemických blastů pomocí detekce přestaveb genů pro imunoglobuliny a T-buněčné receptory (TCR). Potvrdili jsme, že myeloidní buňky derivované v průběhu léčby pochází u všech pacientů z původního lymfoidního klonu. Dále jsme u těchto případů zkoumali expresi vytipovaných genů ve srovnání s běžnými druhy leukémií. Třetí částí práce byl výzkum prognostického významu přítomnosti přestaveb TCR (a tedy příslušnosti k lymfoidní linii) u leukémií z T-lymfoidní řady.
|
|
|
The function of palmitoylation of membrane proteins in immune cells
Hanusová, Zdeňka ; Otáhal, Pavel (advisor) ; Pavlů, Barbora (referee)
Protein palmitoylation is a post-translation modification, which typically regulates the protein interaction with a membrane; apart from that, it can have various functions in protein regulation. Process of this modification covers covalent attachment of palmitate to an aminoacid residue in the target protein; identity of the aminoacid than determines the palmitoylation type. Most common is modification of a cystein residue - in that case we speak about so-called S-palmitoiyation. The exceptionality of this lipid modification type is in the reversibility of the whole process; this enables for example trafficking regulation of many proteins between various membrane compartments and ragulation of proteins' function. In vivo, palmitoylation of many proteins is mediated by enzymes protein acyltransferases, while depalmitoylation is mediated by enzymes acylprotein thioesterases. Palmitoylated proteins can be identified in wide spectrum of cellular types, also in immune cells. Palmitoylation plays here an important role, especially in interaction of signal proteins with lipid rafts and the related modulation of protein's function. Significance has palmitoylation also as a dynamic process, which mediates the right identification of protein's subcellular localization. This work is a review and it's aim is...
|
|
| |
|
| |
|
|
IT Infrastructure Enhancement through a Server Virtualization
Stančík, Michal ; Otáhal, Petr (referee) ; Ondrák, Viktor (advisor)
The thesis aims on a proposal of server infrastructure utilization within a particular organization based on a virtual environment. Analysis of current company’s IT infrastructure was chosen as a starting point for subsequent draft of suitable server consolidation solution that includes all necessary aspects from server configuration up to virtual environment conversion itself. Price calculation and benefits of proposed solution are listed at the end of the thesis.
|
|
| |
|
|
Variability of Aerosols and Chemical Composition of PM10, PM2.5 and PM1 on the Platform of the Prague Underground Metro
Cusack, Michael ; Talbot, Nicholas ; Ondráček, Jakub ; Minguillon, M.-C. ; Schwarz, Jaroslav ; Otáhal, P. ; Klouda, K. ; Ždímal, Vladimír
The aim of this study is to describe aerosol concentrations and variability, and chemically characterise PM sampled during a 24 hour period on a platform of the Prague underground metro system. To this end, PM and particle number concentration and size distribution are described, and the chemical composition of PM in various size fractions is discussed, both for periods when the metro was out of operation and operational.
Fulltext: content.csg -  PDF
Plný tet: SKMBT_C22014102013562 - PDF
|
|
|
A 19m Deep Well – a Downward Thermal Diffusion Cloud Chamber?
Holub, R.F. ; Hopke, P.K. ; Hovorka, J. ; Otahal, P. ; Ždímal, Vladimír
An unusual phenomenon, first observed on a clear summer day after several rainy days, were droplets constantly hitting the water surface in a 19 m deep and 2.4 m diameter water well. This droplet formation was occurring during the night as well. Since the droplet formation was near continuous, we called it “the eternal rain”. The water well is about 230 years old and located in the Benedictine monastery in Broumov, Czech Republic.
Fulltext: content.csg - PDF
Plný tet: SKMBT_C22013091713150 - PDF
|
guest ::
RSS feed.