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</o:shapelayout></xml><![endif]--></head><body lang=SL link=blue vlink=purple><div class=WordSection1><p class=MsoTitle style='margin:0cm;margin-bottom:.0001pt'><span style='font-size:8.0pt;font-family:"Verdana","sans-serif";color:black'><o:p> </o:p></span></p><p class=MsoTitle align=center style='margin:0cm;margin-bottom:.0001pt;text-align:center'><span style='font-size:18.0pt;font-family:"Verdana","sans-serif";color:black'>VABILO NA PREGLOV KOLOKVIJ <o:p></o:p></span></p><p class=MsoNormal><b><span style='font-size:8.0pt;font-family:"Verdana","sans-serif"'><o:p> </o:p></span></b></p><p class=MsoNormal align=center style='text-align:center;line-height:150%'><b><span style='font-size:18.0pt;line-height:150%;font-family:"Verdana","sans-serif"'>Dr. Nataša Obermajer</span></b><b><i><span lang=FR><o:p></o:p></span></i></b></p><p class=MsoNormal align=center style='text-align:center;line-height:150%'><i><span lang=FR>Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Hillman Cancer Center, Pittsburgh, PA, 15213 ZDA.<o:p></o:p></span></i></p><p class=MsoNormal align=center style='text-align:center'><span lang=IT style='font-size:8.0pt;font-family:"Arial","sans-serif"'><o:p> </o:p></span></p><p class=MsoNormal align=center style='text-align:center;line-height:150%'><b><span style='font-size:16.0pt;line-height:150%;font-family:"Verdana","sans-serif"'>Četrtek, 1. 09. 2011, ob 13:00<o:p></o:p></span></b></p><h6 align=center style='margin-bottom:6.0pt;text-align:center'><span lang=FR style='font-size:12.0pt;font-family:"Verdana","sans-serif"'>Velika predavalnica Kemijskega inštituta <o:p></o:p></span></h6><p class=MsoNormal style='mso-margin-top-alt:6.0pt;margin-right:0cm;margin-bottom:6.0pt;margin-left:0cm;text-align:justify'><b><span lang=EN-GB style='font-size:8.0pt;font-family:"Verdana","sans-serif";color:#993366'><o:p> </o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span lang=EN-GB style='font-size:16.0pt;font-family:"Verdana","sans-serif";color:#993366'>Ključna vloga COX2/PGE<sub>2</sub> pri nastanku in regulaciji tumorskega imunskega odziva- pomen inhibicije PGE<sub>2</sub> pri protitumorski imunoterapiji<o:p></o:p></span></b></p><p class=MsoNormal style='text-align:justify;line-height:150%'><i><span lang=FR style='font-size:8.0pt;line-height:150%;font-family:"Verdana","sans-serif"'><o:p> </o:p></span></i></p><p class=MsoNormal style='text-align:justify;line-height:150%'><span lang=FR style='font-size:10.0pt;line-height:150%;font-family:"Arial Narrow","sans-serif"'>Kronično vnetje, ki je povezano z nastankom in razvojem številnih rakavih obolenj, služi dvema različnima nasprotujočima funkcijama: promociji rasti tumorja in protitumorskem imunskem odzivu. Učinkovit protitumorski imunski odziv je odvisen primarno od celic T. Medtem ko IFN-γ-producirajoče celice Th1 in citotoksični limfociti T (CTL) posredujejo protitumorski imunski odziv, drugi tipi celic T, kot so FoxP3-izrazujoče regulatorne celice T (T<sub>reg</sub>) in IL-10 regulatorni tip 1 celic (Tr1) zavirajo imunski odziv proti s tumorjem povezanim antigenom in predstavljajo glavno breme pri uspešni protitumorski imunoterapiji. Hkrati IL-17-producirajoče Th17 celice promovirajo tumorsko rast in tudi tumorsko regresijo. Poleg celic T igrajo pomembno vlogo pri tumorskem imunskem odzivu mieloidne celice. V nasprotju z dendritičnimi celicami (DC), mieloidne supresorske celice (MDSC) zavirajo učinkovite protitumorkse imunske odzive CTL. <o:p></o:p></span></p><p class=MsoNormal style='text-align:justify;text-indent:36.0pt;line-height:150%'><span lang=FR style='font-size:10.0pt;line-height:150%;font-family:"Arial Narrow","sans-serif"'>PGE<sub>2</sub> je s tumorjem povezani vnetni dejavnik, ki je vpleten v nastanek in regulacijo imunskega odziva v tumorskem okolju. PGE<sub>2</sub> vpliva na mieloidne celice, in sicer akumulacijo in funkcijo teh celic. S tumorjem-povezni PGE<sub>2</sub> povzroči nastanek COX2/PGE<sub>2</sub> pozitivne povratne zanke v mieloidnih prekurzorskih celicah, ki vodi v indukcijo in akumulacijo imunosupresorskih mieloidnih celic, MDSC. Akumulacija je posledica COX2/PGE<sub>2</sub>–reguliranega vztrajnega izražanja imunosupresorskih dejavnikov IL-10, NOS2, IDO1, ARG1, IL-4R</span><span lang=FR style='font-size:10.0pt;line-height:150%;font-family:Symbol'>a</span><span lang=FR style='font-size:10.0pt;line-height:150%;font-family:"Arial Narrow","sans-serif"'> ter CXCR4-CXCL12-odvisnega zadrževanja MDSC v tumorskem okolju. Supresorski dejavniki, ki so pod nadzorom COX2/PGE<sub>2</sub> povratne zanke v MDSC, močno zavirajo CTL imunske odzive. Hkrati COX2/PGE<sub>2</sub> v MDSC promovira produkcijo citokinov IL-1</span><span lang=FR style='font-size:10.0pt;line-height:150%;font-family:Symbol'>b</span><span lang=FR style='font-size:10.0pt;line-height:150%;font-family:"Arial Narrow","sans-serif"'>, IL-6 in IL-23 v MDSC in z njimi sinergistično promovira Th17 imunski odziv. Inhibicija COX2/PGE<sub>2</sub> povratne zanke s COX2 inhibitorjem Celecoxibom ali EP2 in EP4 antagonisti uspešno zavre izražanje imunosupresorskih dejavnikov in supresijo CTL ter migracijsko afiniteto MDSC v tumorsko okolje. Poleg tega je močno zavrt tudi Th17 imunski odziv. Čeprav PGE<sub>2</sub> ne inducira CTL imunosupresivnih funkcij v diferenciranih oblikah mieloidnih celic, kot so nezrele DC, pa zavira produkcijo IL-12 v DC in s tem nastanek tipa-1 imunskega odziva, ki je bistven za učinkovit protitumorski imunski odziv. <o:p></o:p></span></p><p class=MsoNormal style='text-align:justify;text-indent:36.0pt;line-height:150%'><span lang=FR style='font-size:10.0pt;line-height:150%;font-family:"Arial Narrow","sans-serif"'>Navedena dejstva nakazujejo na velik smisel inhibicije COX2/PGE<sub>2</sub> povratne zanke pri terapiji rakavih obolenj. <o:p></o:p></span></p><p class=MsoNormal align=center style='text-align:center;line-height:150%'><span lang=EN-US style='font-size:8.0pt;line-height:150%;font-family:"Arial","sans-serif"'><o:p> </o:p></span></p><p class=MsoNormal align=center style='text-align:center;line-height:150%'><span lang=EN-US style='font-family:"Arial","sans-serif"'>Vljudno vabljeni! <o:p></o:p></span></p><p> <o:p></o:p></p></div></body></html>