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Glycobiology of the head and neck cancer
Szabo, Pavol ; Smetana, Karel (advisor) ; Říhová, Blanka (referee) ; Brábek, Jan (referee)
Povrch buněk je bohatě pokryt oligosacharidy, které jsou v plazmalemě ukotvené pomocí proteinů a lipidů. Oligosacharidy zprostředkují vzájemnou vazbu mezi buňkami nebo vazbu buněk k složkám extracelulární matrix. Galektiny jsou živočišné lektinů které mají afinitu k oligosacharidům obsahujícím β-galaktózu. Jsou to multifaktoriální proteiny, které se účastňují řady reakcí v organizmu, jako jsou mezibuněčné interakce, interakce buněk s mezibuněčnou hmotou, proliferace i apoptóza a sestřih pre-mRNA. Proteiny po translaci procházejí různými strukturálnimy úpravami, které mají vliv na jejich funkci. Galektin-3 je možný prognostický ukazatel u nádorů vycházejících z vrstevnatých dlaždicových epitelů je fosforylován na N-konci. Prokázali jsme, že tato posttranslační modifikace nemá vliv na jeho vazebnou reaktivitu. Jiný endogenní lektin, galektin-1 je charakteristickou molekulou nádorového stromatu a granulační tkáně hojícího se poranění. Zjistili jsme, že galektin-1 indukuje na TGF-β nezávislý in vitro přechod normálních fibroblastů na myofibroblasty včetně produkce sítě extracelulární matrix bohaté fibronektinem a galektinem-1. Tento poznatek je využitelný v terapii hojení ran a v tkáňovém inženýrství. Dnes je jasné, že nádorové stroma ovlivňuje i biologické vlastnosti nádoru (lokální agresivita,...
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Immunoprotective character of polymer cytotoxic drugs
Šírová, Milada ; Říhová, Blanka (advisor) ; Turánek, Jaroslav (referee) ; Rabišková, Miloslava (referee)
18 I. INTRODUCTION Cancer is a serious health problem worldwide. In economically developed countries, it is a second most frequent cause of death after cardiovascular dis- eases, and the number of oncological patients continuously increases with the increasing age of population. The mainstay of cancer therapy is combination of surgery, radiation and chemotherapy. Whilst surgery and radiation are relatively precise and suitable to achieve a local control over the tumor, chemotherapy exerts a systemic ef- fect. These three modalities, when properly combined and sequenced, can cure a substantial number of hematological cancers and a smaller, but still significant subset of various solid tumors. Most cytostatic/cytotoxic drugs that are now in common use target the cells with high proliferation rate. The non-selective character of chemotherapy leads to increased toxicities towards normal rapidly proliferating cells. This means that the drugs have to be used at suboptimal doses, leading to development of (multi)drug resistance, metastatic disease and, eventually, to failure of the therapy. Innovative therapeutic strategies need to be developed in order to achieve better treatment outcome. For that purpose, several approaches are be- ing applied. First, sophisticated genomic and proteomic research could identify...
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Humoral response to heat shock proteins in patients with juvenile idiopathic arthritis and in relation to complications following transplantation of hematopoietic stem cells
Zlacká, Denisa ; Hromadníková, Ilona (advisor) ; Říhová, Blanka (referee) ; Posová, Helena (referee)
ln 0\If worlu w~ aimN to.rudy the ml~ of ll! H>p60. U bol'i< Hsp6) md .u=;- indocibl~ ll! Hsp70 in pathogmesis of juvmil~ idiopathi<: anhriti, (JlA) md !haom:ot<>id anhriti, (RA), ln tbe.rudy of hUlllOflll =pons.r ~gainsl ll! Hsp60, M. 00.1:. H'p65 md rh Hsp70 w= found sigoificml rl«.·atM l~..,ls of mTi~, against -iodurib~ Hsp70 in a tot:tl cohon ofp:lTi..u, "~Ih J1'. whm COII1pMM with br:ollhy indi\idWS. 1k pr~\':oIroc~ of mTi-Hsp70 antibodies is much high<f in JlA pati<n15 wbro COIllp:If~d "ith br:olthy controls suggesTing tbeir possiblr rol~ in patbological mrclwlism oftbe ~ ln Ibr study of ~ ~,ioo of ioduribl~ Hsp70 W~ dtt<-crN high mrrubrnJt a~,ion of Hsp70 00 fibrob1asl-liU .yn,,,"i:ol c~Us dtri"N ftom syno\i. aff..,Tnl by allloimmunr inflamm:llion. W~ 5Cfffnr<l tbe 1""""""" of Hsp =q>IOI'S 1ikr TI1t2 2I!d TI.R4. CDl4. CDM. CD40 :md CD91 :os w~U ., thriI associaTion "ith inducibl~ Hsp71l OD RA <krj\"N fibrobbst-hl:~ syno,-i:Il cdls. 80th .ynovi.>! cdl, 2I!d skin fibroblasts aprrsstd bigh ~",l, of cdl.ruďac~ CD9!. bo\\'~""-_ DO Ol lov, b",ls of otbrr rtttplOf1i W~ sprrul:IlN tIw indociblr &p70 rd~2Sr<I from infIamrd S)'OO''ia1 1~ mighl br c:tpturt<l 0010 tbe ""U ,UĎ""" of 'yn<l\ia! ""U, from tbe txtrac~llular sp:Ic~ \;" CD91 fm'Jlt()[ ln tbe ,rudy of htm10ral respon= agairul tbe brat sbock...
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The role of heat shock proteins in pathogenesis of leukaemia, graft versus host disease, juvenile idiopathic and rheumatoid arthritis"
Sedláčková, Lucie ; Hromadníková, Ilona (advisor) ; Říhová, Blanka (referee) ; Prokešová, Ludmila (referee)
The aims of the study: Heat shock proteins (Hsps) represent major immunodominant antigens in a wide spectrum of microbial pathogens and immune reactivity against different members of HSP families accompanies many infectious diseases. Known role of Hsps in antigen resentation could also suggest their potential role in the alloreactive process that leads to acute graft versus host disease (GvHD). sequence homology and cross-reactivity between microbial and human Hsps led to the concept that Hsps might be involved in the atiopathogenesis of autoimmune diseases such as juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA). The major groups of molecular chaperones have been implicated in cancer development as well and stress-inducible Hsp70 was found to be present on the plasma membrane of tumour cells but not on the corresponding normal tissues. On the basis of previous observations we focused our study on the role of Hsps, namely Hsp60 and Hsp70, in the pathogenesis of leukaemia, graft versus host disease, juvenil idiopathic arthritis and rheumatoid arthritis. Powered by TCPDF (www.tcpdf.org)
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Expanzi aktivovaných CD8+ t-lymfocytů lze výrazně zvýšit podáváním komplexů IL-2 a anit-IL-2protilátky
Tomala, Jakub ; Kovář, Marek ; Strohalm, Jiří ; Etrych, Tomáš ; Ulbrich, Karel ; Říhová, Blanka
By using the model of adoptively transferred transgenic CD8+ cells (OT-I) labeled by CFSE dye, we have measured clonal expansion, proliferation and expression of surface markers after various stimulation.We have studies prophylactic effect of complexes, alone or in combination with other cytokines, on various cancer cell lines in vivo. Our results indicate such approach is very promising and could be potent therapeutical tool in tratment of cancer
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