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Immuno-biological Aspects of Head and Neck Squamous Cell Carcinoma
Bouček, Jan ; Říhová, Blanka (advisor) ; Fučíková, Terezie (referee) ; Šlapák, Ivo (referee)
The process of tumorigenesis is conditioned by change or the series of changes at a gene level. The development of cancer is largely pre-ordained by this change, but very important role is played by other factors. In case of solid tumors it is mainly a tumor microenvironment, where the tumor cells are in contact with stromal cells, especially fibroblasts, and immune cells. Tumor microenvironment can also critically modify the nature and intensity of anti- tumor immune response. Squamous cell carcinomas of the head and neck are the sixth most common cancer, which affect each year more than half a million patients worldwide. Despite advances and improvements in all treatment modalities, achieved therapeutic results even in Western countries are not satisfactory and remain at approximately the same values for several decades. At prezent, the 5 years survival rate, regardless of the location and stage of disease, is approximately only 40%. In the prezented work the immunological and biological aspects of squamous cell carcinoma of the head and neck are discussed. It summarizes the recent findings on the molecular basis of the behavior of tumor cells and the influence and significance of regulation of the immune system for the clinical course of disease and the modern therapeutic approaches.
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Immunogenic cell death and its application in imunotherapy protocols
Fučíková, Jitka ; Špíšek, Radek (advisor) ; Říhová, Blanka (referee) ; Reiniš, Milan (referee)
Treatment of tumors by protocols based on combination of surgery, radiotherapy and systemic chemotherapy resulted in the improved prognosis of many human cancers. Despite the continuous introduction of new drugs and further improvements of chemotherapy protocols, it's likely that at some point chemotherapy will reach its limits and clinical efficacy will plateau. Immunotherapy has emerged as another treatment modality with the potential to contribute to further improvements in the survival. The products of advanced cellular terapies must be generated using GMP-approved reagents and number of studies have addressed the need to generate large numbers of DCs for clinical trials according to regulatory authorities and to current legislation. The rising knowledge about dendritic cells (DCs) in the immune response against tumors and the ability to prepaire DCs in vitro leaded to the establishment of immunotherapy protocols. Breakthrough studies that identified markers of immunogenic tumor cell death after chemotherapy treatment challenge the long-time perception of chemotherapy and immunotherapy as opposing and incompatible treatment modalities. My PhD thesis is a contributiont to this topic. In the first paper we identified monocyte-derived DCs that were generated in CellGro and activated using PolyI:C as the...
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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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