impact-assessment-repeated-exposure-organotypic-3d-bronchial-nasal

Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke

Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease ...

Philip Morris Products S.A.

La angiog&eacute;nesis es que una caracter&iacute;stica clave de la tumorig&eacute;nesis y su inhibici&oacute;n es una estrategia probada para el desarrollo de la novela terap&eacute;utica contra el c&aacute;ncer. Un aspecto importante de la angiog&eacute;nesis temprano es la migraci&oacute;n coordinada y la invasi&oacute;n de c&eacute;lulas endoteliales a trav&eacute;s del tejido del tumor hip&oacute;xico. Catepsina S se ha demostrado para desempe&ntilde;ar un papel importante en la angiog&eacute;nesis como factor de crecimiento endotelial vascular (VEGF). Intentamos evaluar el efecto antiangiog&eacute;nico de Fsn0503, un anticuerpo inhibidor de catepsina novela S, cuando se combina con anti-VEGF en el desarrollo vascular.

Anticuerpos dirigidos contra catepsina S inhibe la angiog&eacute;nesis y aumenta sin&eacute;rgicamente anti-VEGF.

&#x8840;&#x7BA1;&#x751F;&#x6210;&#x662F; tumourigenesis &#x53CA;&#x6291;&#x5236;&#x4F5C;&#x7528;&#x7684;&#x4E00;&#x4E2A;&#x5173;&#x952E;&#x7279;&#x70B9;&#x662F;&#x884C;&#x4E4B;&#x6709;&#x6548;&#x7684;&#x65B0;&#x578B;&#x6297;&#x764C;&#x836F;&#x7269;&#x6CBB;&#x7597;&#x5B66;&#x53D1;&#x5C55;&#x6218;&#x7565;&#x3002;&#x65E9;&#x671F;&#x8840;&#x7BA1;&#x751F;&#x6210;&#x7684;&#x4E00;&#x4E2A;&#x91CD;&#x8981;&#x65B9;&#x9762;&#x662F;&#x534F;&#x8C03;&#x4E00;&#x81F4;&#x7684;&#x8FC1;&#x79FB;&#xFF0C;&#x5E76;&#x901A;&#x8FC7;&#x7F3A;&#x6C27;&#x80BF;&#x7624;&#x7EC4;&#x7EC7;&#x8840;&#x7BA1;&#x5185;&#x76AE;&#x7EC6;&#x80DE;&#x7684;&#x5165;&#x4FB5;&#x3002;&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x8868;&#x660E;&#x6709;&#x8840;&#x7BA1;&#x5185;&#x76AE;&#x751F;&#x957F;&#x56E0;&#x5B50; (VEGF) &#x5728;&#x8840;&#x7BA1;&#x751F;&#x6210;&#x65B9;&#x9762;&#x53D1;&#x6325;&#x7740;&#x91CD;&#x8981;&#x7684;&#x4F5C;&#x7528;&#x3002;&#x6211;&#x4EEC;&#x8BBE;&#x6CD5;&#x8BC4;&#x4F30;&#x6297;&#x8840;&#x7BA1;&#x751F;&#x6210;&#x5F71;&#x54CD;&#x7684; Fsn0503&#xFF0C;&#x4E00;&#x79CD;&#x65B0;&#x578B;&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x6291;&#x5236;&#x6297;&#x4F53;&#xFF0C;&#x5F53;&#x4E0E;&#x6297; VEGF &#x8840;&#x7BA1;&#x53D1;&#x5C55;&#x76F8;&#x7ED3;&#x5408;&#x3002;

&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x6297;&#x4F53;&#x9488;&#x5BF9;&#x6291;&#x5236;&#x8840;&#x7BA1;&#x751F;&#x6210;&#xFF0C;&#x5E76;&#x534F;&#x540C;&#x589E;&#x5F3A;&#x4E86;&#x6297; VEGF&#x3002;

Angiogenesis is a key hallmark of tumourigenesis and its inhibition is a proven strategy for the development of novel anti-cancer therapeutics. An important aspect of early angiogenesis is the co-ordinated migration and invasion of endothelial cells through the hypoxic tumour tissue. Cathepsin S has been shown to play an important role in angiogenesis as has vascular endothelial growth factor (VEGF). We sought to assess the anti-angiogenic effect of Fsn0503, a novel cathepsin S inhibitory antibody, when combined with anti-VEGF on vascular development.

Antibody targeting of cathepsin S inhibits angiogenesis and synergistically enhances anti-VEGF.

L&#39;angiogen&egrave;se est qu&#39;une caract&eacute;ristique cl&eacute;e de la tumorigen&egrave;se et son inhibition est une strat&eacute;gie &eacute;prouv&eacute;e pour le d&eacute;veloppement de nouveaux m&eacute;dicaments anticanc&eacute;reux. Un aspect important de l&#39;angiogen&egrave;se pr&eacute;coce est la migration coordonn&eacute;e et l&#39;invasion des cellules endoth&eacute;liales &agrave; travers le tissu de tumeur hypoxique. Cathepsine S jouent un r&ocirc;le important dans l&#39;angiogen&egrave;se comme facteur de croissance endoth&eacute;lial vasculaire (VEGF) a &eacute;t&eacute; &eacute;tablie. Nous avons cherch&eacute; &agrave; &eacute;valuer l&#39;effet anti-angiog&eacute;nique de Fsn0503, un anticorps inhibiteurs de roman cathepsine S, lorsqu&#39;il est combin&eacute; avec des anti-VEGF sur d&eacute;veloppement vasculaire.

Anticorps ciblant de la cathepsine S inhibe l&#39;angiogen&egrave;se et synerg&eacute;tique anti-VEGF.

Angiogenese ist ein wichtige Kennzeichen der Tumourigenesis und seine Hemmung ist eine bew&auml;hrte Strategie f&uuml;r die Entwicklung von neuartigen Anti-Krebs-Therapeutika. Ein wichtiger Aspekt der fr&uuml;hen Angiogenese ist die koordinierte Migration und Invasion von Endothelzellen durch die Hypoxie Tumorgewebe. Kathepsin S hat sich gezeigt, eine wichtige Rolle in der Angiogenese zu spielen, wie vascular endothelial Growth Factor (VEGF) hat. Wir wollten den Anti-angiogenen Effekt der Fsn0503, ein neuartiger Kathepsin S hemmende Antik&ouml;rper, zu beurteilen, in Kombination mit Anti-VEGF auf vaskul&auml;re Entwicklung.

Antik&ouml;rper-targeting von Kathepsin S hemmt die Angiogenese und synergistisch verst&auml;rkt Anti-VEGF.

L&#39;angiogenesi &egrave; che una caratteristica chiave della tumorigenesi e la sua inibizione &egrave; una collaudata strategia per lo sviluppo di nuove terapie anti-cancro. Un aspetto importante dell&#39;angiogenesi precoce &egrave; la coordinata migrazione e invasione delle cellule endoteliali attraverso il tessuto tumorale ipossica. Catepsina S ha dimostrato di svolgere un ruolo importante nell&#39;angiogenesi come fattore di crescita endoteliale vascolare (VEGF). Abbiamo cercato di valutare l&#39;effetto anti-angiogenico della Fsn0503, un anticorpo inibitore catepsina romanzo S, quando combinato con anti-VEGF sullo sviluppo vascolare.

Anticorpo targeting della catepsina S inibisce l&#39;angiogenesi e migliora in sinergia anti-VEGF.

&#x8840;&#x7BA1;&#x65B0;&#x751F; tumourigenesis &#x3068;&#x963B;&#x5BB3;&#x306E;&#x4E3B;&#x8981;&#x7279;&#x5FB4;&#x65B0;&#x898F;&#x6297;&#x304C;&#x3093;&#x6CBB;&#x7642;&#x85AC;&#x306E;&#x958B;&#x767A;&#x306E;&#x305F;&#x3081;&#x306E;&#x5B9F;&#x8A3C;&#x6E08;&#x307F;&#x306E;&#x6226;&#x7565;&#x3067;&#x3059;&#x3002;&#x65E9;&#x671F;&#x306E;&#x8840;&#x7BA1;&#x65B0;&#x751F;&#x306E;&#x91CD;&#x8981;&#x306A;&#x5074;&#x9762;&#x306F;&#x3001;&#x30B3;&#x30FC;&#x30C7;&#x30A3;&#x30CD;&#x30FC;&#x30C8;&#x306E;&#x79FB;&#x884C;&#x3068;&#x4F4E;&#x9178;&#x7D20;&#x6027;&#x816B;&#x760D;&#x7D44;&#x7E54;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x8840;&#x7BA1;&#x5185;&#x76AE;&#x7D30;&#x80DE;&#x306E;&#x4FB5;&#x5165;&#x3067;&#x3059;&#x3002;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x8840;&#x7BA1;&#x5185;&#x76AE;&#x5897;&#x6B96;&#x56E0;&#x5B50; (VEGF) &#x304C;&#x3042;&#x308A;&#x3001;&#x8840;&#x7BA1;&#x65B0;&#x751F;&#x306B;&#x304A;&#x3051;&#x308B;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3059;&#x3053;&#x3068;&#x304C;&#x793A;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x3001;&#x8840;&#x7BA1;&#x306E;&#x958B;&#x767A;&#x6297; VEGF &#x3068;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x308B;&#x3068; Fsn0503&#x3001;&#x5C0F;&#x8AAC;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x306E;&#x6291;&#x5236;&#x6027;&#x6297;&#x4F53;&#x306E;&#x6297;&#x8840;&#x7BA1;&#x65B0;&#x751F;&#x52B9;&#x679C;&#x3092;&#x8A55;&#x4FA1;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x6C42;&#x3081;&#x305F;&#x3002;

&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x306E;&#x6297;&#x4F53;&#x3092;&#x30BF;&#x30FC;&#x30B2;&#x30C3;&#x30C8;&#x8840;&#x7BA1;&#x65B0;&#x751F;&#x3092;&#x963B;&#x5BB3;&#x3057;&#x3066;&#x76F8;&#x4E57;&#x7684;&#x6297; VEGF &#x3092;&#x9AD8;&#x3081;&#x307E;&#x3059;&#x3002;

&#xC2E0;&#xC0DD; tumourigenesis &#xBC0F; &#xADF8; &#xC5B5;&#xC81C;&#xC758; &#xC8FC;&#xC694; &#xD2B9;&#xC9D5;&#xC740; &#xC0C8;&#xB85C;&#xC6B4; &#xD56D; &#xC554; &#xCE58;&#xB8CC;&#xC81C; &#xAC1C;&#xBC1C;&#xC744; &#xC704;&#xD55C; &#xC785;&#xC99D; &#xB41C; &#xC804;&#xB7B5; &#xC774;&#xB2E4;. &#xCD08;&#xAE30; &#xC2E0;&#xC0DD;&#xC758; &#xC911;&#xC694; &#xD55C; &#xCE21;&#xBA74;&#xC740; &#xACF5;&#xB3D9;-ordinated &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158;&#xACFC; hypoxic &#xC885;&#xC591; &#xC870;&#xC9C1; &#xB0B4; &#xD53C; &#xC138;&#xD3EC;&#xC758; &#xCE68;&#xACF5;. Cathepsin S &#xD608;&#xAD00; &#xB0B4; &#xD53C; &#xC131;&#xC7A5; &#xC778;&#xC790; (VEGF)&#xAC00; &#xD608;&#xAD00; &#xC2E0;&#xC0DD;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xBCF4;&#xC5EC;&#xC654;&#xB2E4;. &#xC6B0;&#xB9AC; &#xD608;&#xAD00; &#xAC1C;&#xBC1C;&#xC5D0; &#xC548;&#xD2F0;-VEGF&#xC640; &#xACB0;&#xD569; &#xB420; &#xB54C; Fsn0503, &#xC18C;&#xC124; cathepsin S &#xC5B5;&#xC81C; &#xD56D; &#xCCB4;&#xC758; &#xC548;&#xD2F0; angiogenic &#xC601;&#xD5A5;&#xC744; &#xD3C9;&#xAC00; &#xD558;&#xACE0;&#xC790; &#xD588;&#xB2E4;.

&#xD56D; &#xCCB4; &#xD0C0;&#xAC9F;&#xD305; cathepsin S&#xC758; &#xC2E0;&#xC0DD;&#xC744; &#xC5B5;&#xC81C; &#xD558; &#xACE0; synergistically &#xC548;&#xD2F0; VEGF&#xB97C; &#xD5A5;&#xC0C1; &#xC2DC;&#xD0B5;&#xB2C8;&#xB2E4;.

&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x662F;&#x5377;&#x5165; tumourigenesis &#x5165;&#x4FB5;&#x548C;&#x8840;&#x7BA1;&#x751F;&#x6210;&#x4E2D;&#x7684;&#x5173;&#x952E;&#x89D2;&#x8272;&#x4E0E;&#x6EB6;&#x9176;&#x4F53;&#x534A;&#x80F1;&#x6C28;&#x9178;&#x86CB;&#x767D;&#x9176;&#x3002;&#x6211;&#x4EEC;&#x5148;&#x524D;&#x5DF2;&#x8868;&#x660E;&#x7279;&#x5B9A;&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x4F7F;&#x7528;&#x5355;&#x514B;&#x9686;&#x6297;&#x4F53; (Fsn0503) &#x7684;&#x6291;&#x5236;&#x4F5C;&#x7528;&#x963B;&#x6B62;&#x5927;&#x80A0;&#x764C;&#x80BF;&#x7624;&#x751F;&#x957F;&#x548C;&#x8840;&#x7BA1;&#x751F;&#x6210;&#x7684;&#x3002;&#x6211;&#x4EEC;&#x8C03;&#x67E5;&#x662F;&#x5426;&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x8868;&#x8FBE;&#x6C34;&#x5E73;&#x53D7;&#x5316;&#x7597;&#x7684;&#x80BF;&#x7624;&#x7EC6;&#x80DE;&#x9006;&#x8F6C;&#x5F55;-&#x805A;&#x5408;&#x9176;&#x94FE;&#x53CD;&#x5E94;&#x3002;&#x6211;&#x4EEC;&#x4F7F;&#x7528;&#x5927;&#x80A0;&#x764C;&#x5F02;&#x79CD;&#x79FB;&#x690D;&#x6A21;&#x578B;&#xFF0C;&#x7814;&#x7A76;&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x6291;&#x5236; CPT-11 &#x5446;&#x677F;&#x5730;&#x7ED9;&#x836F;&#x65B9;&#x6848;&#x7ED3;&#x5408;&#x4F7F;&#x7528; Fsn0503 &#x7684;&#x6CBB;&#x7597;&#x6548;&#x76CA;&#x3002;&#x6211;&#x4EEC;&#x5206;&#x6790;&#x5BF9;&#x80BF;&#x7624;&#x8FDB;&#x5C55;&#x548C; vascularisation &#x80BF;&#x7624;&#x7EFC;&#x5408;&#x6CBB;&#x7597;&#x7684;&#x5F71;&#x54CD;&#x7684;&#x80BF;&#x7624;&#x514D;&#x75AB;&#x7EC4;&#x7EC7;&#x5316;&#x5B66;&#x67D3;&#x8272;&#x6CD5;&#x3002;&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x8868;&#x8FBE;&#x6C34;&#x5E73;&#x662F;&#x5728; HCT116&#xFF0C;LoVo&#xFF0C;Colo205 &#x7EC6;&#x80DE;&#x682A;&#x548C;&#x8110; CPT-11 &#x4F53;&#x5916;&#x66B4;&#x9732;&#x540E;&#x7684;&#x4E0A;&#x8C03;&#x3002;&#x884C;&#x653F; Fsn0503 CPT-11 &#x7ED3;&#x5408;&#x5927;&#x5927;&#x51CF;&#x6BD2;&#x4E0E; CPT-11 &#x5355;&#x7ED3;&#x76F4;&#x80A0;&#x764C; HCT116 &#x5F02;&#x79CD;&#x79FB;&#x690D;&#x6A21;&#x578B;&#x4E2D;&#x7684;&#x80BF;&#x7624;&#x751F;&#x957F;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x80BF;&#x7624; vascularisation &#x7684;&#x5206;&#x6790;&#x8868;&#x660E;&#x8FD9;&#x4E5F;&#x5927;&#x5927;&#x53D7;&#x5230;&#x7EC4;&#x5408;&#x6CBB;&#x7597;&#x3002;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x8868;&#x660E; CPT-11 &#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x6291;&#x5236;&#x7ED3;&#x5408;&#x63D0;&#x9AD8;&#x5316;&#x7597;&#x7684;&#x7597;&#x6548;&#x3002;&#x8FD9;&#x4E2A;&#x7406;&#x7531;&#x53EF;&#x80FD;&#x6709;&#x4E34;&#x5E8A;&#x5E94;&#x7528;&#x4E2D;&#x8FDB;&#x4E00;&#x6B65;&#x8BC4;&#x4F30;&#x540E;&#x7ED3;&#x76F4;&#x80A0;&#x764C;&#x7684;&#x6CBB;&#x7597;&#x3002;

&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x7531; Fsn0503 &#x7684;&#x6291;&#x5236;&#x4F5C;&#x7528;&#x63D0;&#x9AD8;&#x5927;&#x80A0;&#x764C;&#x5316;&#x7597;&#x7684;&#x7597;&#x6548;&#x3002;

Cathepsin S tumourigenesis&#xC5D0; &#xCE68;&#xACF5;&#xACFC; &#xC2E0;&#xC0DD;&#xC758; &#xC8FC;&#xC694; &#xC5ED;&#xD560;&#xACFC; &#xC5F0;&#xB8E8; lysosomal cysteine &#xB2E8;&#xBC31;&#xC9C8; &#xC774;&#xB2E4;. &#xC6B0;&#xB9AC;&#xAC00; &#xC774;&#xC804;&#xC5D0; Cathepsin S &#xB2E8;&#xC77C; &#xD074;&#xB860; &#xD56D; &#xCCB4; (Fsn0503)&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xD2B9;&#xC815; &#xC5B5;&#xC81C; &#xB300; &#xC7A5; &#xC554; &#xC885;&#xC591; &#xC131;&#xC7A5;&#xACFC; &#xC2E0;&#xC0DD; vivo&#xC5D0;&#xC11C; &#xCC28;&#xB2E8; &#xAC83;&#xC73C;&#xB85C; &#xB098;&#xD0C0;&#xB0AC;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC; &#xC870;&#xC0AC; &#xC5EC;&#xBD80; Cathepsin S &#xC2DD; &#xB808;&#xBCA8; RT-PCR&#xC5D0; &#xC758;&#xD574; &#xC778;&#xAC04;&#xC758; &#xC554; &#xC138;&#xD3EC; &#xB77C;&#xC778;&#xC5D0; &#xD654;&#xD559; &#xC694;&#xBC95;&#xC5D0; &#xC758;&#xD574; &#xC601;&#xD5A5;&#xC744; &#xBC1B;&#xC558;&#xB2E4;. &#xB300; &#xC7A5; &#xB1CC;&#xC885;&#xC591; &#xBAA8;&#xB378;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC;, &#xC6B0;&#xB9AC; Cathepsin S &#xC5B5;&#xC81C; CPT 11 metronomic &#xD22C;&#xC57D; &#xCC98;&#xBC29;&#xC744; &#xD568;&#xAED8;&#xC5D0;&#xC11C; fsn0503&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xCE58;&#xB8CC; &#xD61C;&#xD0DD;&#xC744; &#xC870;&#xC0AC; &#xD588;&#xB2E4;. &#xC6B0;&#xB9AC; immunohistochemical &#xC885;&#xC591;&#xC758; &#xC5BC;&#xB8E9;&#xC5D0; &#xC758;&#xD574; &#xC885;&#xC591;&#xC758; &#xC9C4;&#xD589; &#xBC0F; &#xC885;&#xC591; vascularisation &#xCF64;&#xBE44;&#xB124;&#xC774;&#xC158; &#xCE58;&#xB8CC;&#xC758; &#xD6A8;&#xACFC; &#xBD84;&#xC11D;. Cathepsin S &#xC2DD; &#xC218;&#xC900;&#xC740; HCT116, LoVo, Colo205 &#xC140; &#xB77C;&#xC778; &#xBC0F; CPT 11 &#xCCB4; &#xC678;&#xC5D0; &#xB178;&#xCD9C; &#xB41C; &#xD6C4; Huvecs&#xC5D0;&#xC5D0;&#xC11C;&#xB294; upregulated&#xC785;&#xB2C8;&#xB2E4;. CPT 11&#xC640; &#xD568;&#xAED8;&#xC5D0;&#xC11C; fsn0503&#xC758; &#xAD00;&#xB9AC;&#xB294; &#xD06C;&#xAC8C; CPT-11 &#xD63C;&#xC790; &#xB300; &#xC7A5; HCT116 &#xB1CC;&#xC885;&#xC591; &#xBAA8;&#xB378;&#xC5D0; &#xBE44;&#xD574; &#xC885;&#xC591; &#xC131;&#xC7A5;&#xC744; &#xAC10;&#xC1E0;. &#xB610;&#xD55C;, &#xC885;&#xC591; vascularisation&#xC758; &#xBD84;&#xC11D; &#xBC1D;&#xD600;&#xC774; &#xB610;&#xD55C; &#xD06C;&#xAC8C; &#xC870;&#xD569; &#xCE58;&#xB8CC;&#xC5D0; &#xC758;&#xD574; &#xC911;&#xB2E8; &#xB418;&#xC5C8;&#xB2E4;. &#xC774; &#xACB0;&#xACFC; &#xBCF4;&#xC5EC; CPT 11 Cathepsin S &#xC800;&#xD574; &#xC870;&#xD569; &#xD654;&#xD559; &#xC694;&#xBC95;&#xC758; &#xCE58;&#xB8CC; &#xD6A8;&#xACFC; &#xD5A5;&#xC0C1; &#xC2DC;&#xD0B5;&#xB2C8;&#xB2E4;. &#xC774; &#xADFC;&#xAC70; &#xCD94;&#xAC00; &#xD3C9;&#xAC00; &#xC2DC; &#xB300; &#xC7A5; &#xC554; &#xCE58;&#xB8CC;&#xC5D0; &#xC784;&#xC0C1; &#xC751;&#xC6A9;&#xC744; &#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

Fsn0503&#xC5D0; &#xC758;&#xD574; Cathepsin S&#xC758; &#xC5B5;&#xC81C; &#xB300; &#xC7A5; carcinomas&#xC5D0; &#xD654;&#xD559; &#xC694;&#xBC95;&#xC758; &#xD6A8;&#xB2A5;&#xC744; &#xD5A5;&#xC0C1; &#xC2DC;&#xD0B5;&#xB2C8;&#xB2E4;.

Cathepsin S is a lysosomal cysteine protease implicated in tumourigenesis with key roles in invasion and angiogenesis. We have previously shown that the specific inhibition of Cathepsin S using a monoclonal antibody (Fsn0503) blocks colorectal carcinoma tumour growth and angiogenesis inÂ vivo. We investigated whether Cathepsin S expression levels were affected by chemotherapy in human cancer cell lines by RT-PCR. Using colorectal xenograft models, we examined the therapeutic benefit of Cathepsin S inhibition using Fsn0503 in combination with a metronomic dosing regimen of CPT-11. We analysed the effects of the combination therapy on tumour progression and on tumour vascularisation by immunohistochemical staining of tumours. Cathepsin S expression levels are upregulated in HCT116, LoVo, Colo205 cell lines and HUVECs after exposure to CPT-11 inÂ vitro. The administration of Fsn0503 in combination with CPT-11 significantly attenuated tumour growth in comparison to CPT-11 alone in colorectal HCT116 xenograft models. Furthermore, analysis of tumour vascularisation revealed that this was also significantly disrupted by the combination treatment. These results show that the combination of Cathepsin S inhibition with CPT-11 enhances the therapeutic effect of the chemotherapy. This rationale may have clinical application in the treatment of colorectal cancer upon further evaluation.

Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas.

Cathepsine S est une prot&eacute;ase de cyst&eacute;ine lysosomale impliqu&eacute;e dans la tumorigen&egrave;se avec des r&ocirc;les principaux dans l&#39;invasion et de l&#39;angiogen&egrave;se. Nous avons d&eacute;j&agrave; montr&eacute; que l&#39;inhibition sp&eacute;cifique de la cathepsine S utilisant un anticorps monoclonal (Fsn0503) bloque la croissance de tumeur carcinome colorectal et angiogen&egrave;se in vivo. Nous avons examin&eacute; si les niveaux d&#39;expression de la cathepsine S ont &eacute;t&eacute; affect&eacute;es par chimioth&eacute;rapie dans les lign&eacute;es cellulaires canc&eacute;reuses humaines par RT-PCR. &Agrave; l&#39;aide des mod&egrave;les de x&eacute;nogreffes colorectal, nous avons examin&eacute; les bienfaits th&eacute;rapeutiques de l&#39;inhibition de la cathepsine S avec Fsn0503 en combinaison avec un sch&eacute;ma posologique m&eacute;tronomique de CPT-11. Nous avons analys&eacute; les effets de la th&eacute;rapie de combinaison sur la progression tumorale et sur la vascularisation de la tumeur par coloration immunohistochimique des tumeurs. Niveaux d&#39;expression de la cathepsine S sont surexprim&eacute;s dans HCT116, LoVo, lign&eacute;es de cellules Colo205 et HUVECs apr&egrave;s exposition au CPT-11 in vitro. L&#39;administration de la Fsn0503 en combinaison avec le CPT-11 a significativement att&eacute;nu&eacute; la croissance tumorale par rapport aux seuls dans des mod&egrave;les de x&eacute;nogreffes HCT116 colorectal CPT-11. En outre, l&#39;analyse de la vascularisation tumorale a r&eacute;v&eacute;l&eacute; que c&#39;&eacute;tait aussi significativement perturb&eacute; par la polyth&eacute;rapie. Ces r&eacute;sultats montrent que la combinaison de l&#39;inhibition de la cathepsine S avec CPT-11 augmente l&#39;effet th&eacute;rapeutique de la chimioth&eacute;rapie. Ce raisonnement peut avoir une application clinique dans le traitement du cancer colorectal sur une &eacute;valuation plus pouss&eacute;e.

L&#39;inhibition de la cathepsine S par Fsn0503 am&eacute;liore l&#39;efficacit&eacute; de la chimioth&eacute;rapie des carcinomes colorectaux.

Kathepsin S ist eine lysosomale Cystein-Protease mit Schl&uuml;sselrollen in Invasion und Angiogenesis in Tumourigenesis verwickelt. Wir haben bereits gezeigt, dass die spezifische Hemmung der Cathepsin-S mit einen monoklonalen Antik&ouml;rper (Fsn0503) kolorektales Karzinom Tumorwachstum und Angiogenesis in vivo blockiert. Wir wurde untersucht, ob Kathepsin S Ausdruck Niveaus von Chemotherapie in menschlichen Krebszelllinien durch RT-PCR betroffen waren. Mit Dick-Xenograft-Modellen, haben wir den therapeutischen Nutzen der Kathepsin S Hemmung mit Fsn0503 in Kombination mit metronomischer Dosierung von CPT-11 gepr&uuml;ft. Analysieren wir die Auswirkungen der Kombinationstherapie auf Tumorprogression und Tumor-Vaskularisation von Immunohistochemical Beflecken von Tumoren. Kathepsin S Ausdruck Niveaus sind in HCT116, LoVo, Colo205-Zelllinien und HUVECs nach Exposition mit CPT-11 in-vitro-herraufreguliert. Die Verwaltung des Fsn0503 in Kombination mit CPT-11 abgeschw&auml;cht deutlich Tumorwachstum im Vergleich zu CPT-11 allein in Dick-HCT116 Xenograft-Modelle. Dar&uuml;ber hinaus ergab die Analyse der Tumor Vaskularisierung, dass dies durch die Kombinationsbehandlung auch erheblich gest&ouml;rt wurde. Diese Ergebnisse zeigen, dass die Kombination von Kathepsin S Hemmung mit CPT-11 den therapeutischen Effekt der Chemotherapie erh&ouml;ht. Diese Begr&uuml;ndung kann klinische Anwendung in der Behandlung von Darmkrebs auf weitere Auswertungen haben.

Hemmung der Kathepsin S durch Fsn0503 erh&ouml;ht die Wirksamkeit der Chemotherapie bei kolorektalen Karzinomen.

Catepsina S &egrave; una proteasi lisosomiale cisteina implicata nella tumorigenesi con ruoli chiave nell&#39;invasione e l&#39;angiogenesi. In precedenza abbiamo dimostrato che l&#39;inibizione specifica della catepsina S utilizzando un anticorpo monoclonale (Fsn0503) blocca la crescita del tumore carcinoma del colon-retto e l&#39;angiogenesi in vivo. Abbiamo valutato se i livelli di espressione catepsina S sono stati colpiti dalla chemioterapia in linee di cellule tumorali umane mediante RT-PCR. Utilizzando modelli xenoinnesto del colon-retto, abbiamo esaminato il beneficio terapeutico dell&#39;inibizione catepsina S con Fsn0503 in combinazione con un regime di dosaggio metronomico di CPT-11. Abbiamo analizzato gli effetti della terapia di combinazione sulla progressione tumorale e sulla vascolarizzazione tumorale di colorazione immunoistochimica dei tumori. Livelli di espressione di catepsina S sono sovraregolati nella HCT116, LoVo, linee cellulari Colo205 e HUVECs dopo esposizione a CPT-11 in vitro. L&#39;amministrazione di Fsn0503 in combinazione con CPT-11 significativamente attenuato crescita tumorale rispetto a CPT-11 solo in modelli di xenoinnesto HCT116 del colon-retto. Inoltre, l&#39;analisi della vascolarizzazione tumorale ha rivelato che questo &egrave; stato anche significativamente interrotta dal trattamento di combinazione. Questi risultati mostrano che la combinazione di inibizione catepsina S con CPT-11 migliora l&#39;effetto terapeutico della chemioterapia. Questa logica pu&ograve; avere applicazioni cliniche nel trattamento del cancro del colon-retto su un&#39;ulteriore valutazione.

Inibizione della catepsina S da Fsn0503 migliora l&#39;efficacia della chemioterapia nel carcinoma del colon-retto.

&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S tumourigenesis &#x3067;&#x6D78;&#x6F64;&#x3068;&#x8840;&#x7BA1;&#x65B0;&#x751F;&#x306E;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3068;&#x95A2;&#x4E0E;&#x306B;&#x304A;&#x3051;&#x308B;&#x30EA;&#x30BD;&#x30BE;&#x30FC;&#x30E0;&#x6027;&#x30B7;&#x30B9;&#x30C6;&#x30A4;&#x30F3;&#x30D7;&#x30ED;&#x30C6;&#x30A2;&#x30FC;&#x30BC; &#x30D7;&#x30ED;&#x30C6;&#x30A2;&#x30FC;&#x30BC;&#x3067;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x4EE5;&#x524D;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; &#x30E2;&#x30CE;&#x30AF;&#x30ED;&#x30FC;&#x30CA;&#x30EB;&#x6297;&#x4F53; (Fsn0503) &#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066; S &#x306E;&#x7279;&#x7570;&#x7684;&#x963B;&#x5BB3;&#x5927;&#x8178;&#x764C;&#x816B;&#x760D;&#x306E;&#x5897;&#x6B96;&#x304A;&#x3088;&#x3073;&#x8840;&#x7BA1;&#x65B0;&#x751F; in vivo &#x3067;&#x30D6;&#x30ED;&#x30C3;&#x30AF;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x3001;RT-pcr &#x6CD5;&#x306B;&#x3088;&#x308B;&#x3072;&#x3068;&#x764C;&#x7D30;&#x80DE;&#x306B;&#x304A;&#x3051;&#x308B;&#x5316;&#x5B66;&#x7642;&#x6CD5;&#x306B;&#x3088;&#x308B;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x8868;&#x73FE;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x304C;&#x5F71;&#x97FF;&#x3092;&#x53D7;&#x3051;&#x305F;&#x304B;&#x3069;&#x3046;&#x304B;&#x3092;&#x8ABF;&#x67FB;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x5927;&#x8178; xenograft &#x30E2;&#x30C7;&#x30EB;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x3001;Fsn0503 &#x30E1;&#x30C8;&#x30ED;&#x30CE;&#x30FC;&#x30E0;&#x6295;&#x4E0E;&#x30EC;&#x30B8;&#x30E1;&#x30F3;&#x3067; cpt-11 &#x306E;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x6291;&#x5236;&#x306E;&#x6CBB;&#x7642;&#x52B9;&#x679C;&#x3092;&#x691C;&#x8A0E;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x6211;&#x3005; &#x306F;&#x816B;&#x760D;&#x306E;&#x514D;&#x75AB;&#x7D44;&#x7E54;&#x5316;&#x5B66;&#x7684;&#x67D3;&#x8272;&#x306B;&#x3088;&#x308A;&#x816B;&#x760D;&#x9032;&#x884C;&#x3057;&#x816B;&#x760D; vascularisation &#x4F75;&#x7528;&#x7642;&#x6CD5;&#x306E;&#x52B9;&#x679C;&#x3092;&#x5206;&#x6790;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x8868;&#x73FE;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x306F;&#x3001;HCT116&#x3001;LoVo, Colo205 &#x7D30;&#x80DE;&#x682A;&#x3068;&#x6BD4;&#x8F03; CPT 11 in vitro &#x66DD;&#x9732;&#x5F8C;&#x3067;&#x4EA2;&#x9032;&#x3067;&#x3059;&#x3002;Fsn0503 &#x306E;&#x7BA1;&#x7406;&#x306E;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B; CPT 11 &#x3067;&#x306F;&#x3001;&#x5927;&#x5E45;&#x306B;&#x816B;&#x760D;&#x5897;&#x6B96; CPT 11 &#x5927;&#x8178; HCT116 xenograft &#x30E2;&#x30C7;&#x30EB;&#x3067;&#x5358;&#x72EC;&#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066;&#x6E1B;&#x8870;&#x3057;&#x307E;&#x3059;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x816B;&#x760D; vascularisation &#x306E;&#x89E3;&#x6790;&#x3053;&#x308C;&#x3082;&#x5927;&#x5E45;&#x306B;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x51E6;&#x7406;&#x306B;&#x3088;&#x3063;&#x3066;&#x4E2D;&#x65AD;&#x3055;&#x308C;&#x305F;&#x3053;&#x3068;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x963B;&#x5BB3; CPT 11 &#x3068;&#x306E;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x304C;&#x3001;&#x5316;&#x5B66;&#x7642;&#x6CD5;&#x306E;&#x6CBB;&#x7642;&#x52B9;&#x679C;&#x3092;&#x9AD8;&#x3081;&#x308B;&#x3053;&#x3068;&#x304C;&#x793A;&#x5506;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x306E;&#x7406;&#x8AD6;&#x7684;&#x6839;&#x62E0;&#x306F;&#x3055;&#x3089;&#x306A;&#x308B;&#x8A55;&#x4FA1;&#x306B;&#x57FA;&#x3065;&#x3044;&#x3066;&#x5927;&#x8178;&#x764C;&#x306E;&#x6CBB;&#x7642;&#x306B;&#x304A;&#x3051;&#x308B;&#x81E8;&#x5E8A;&#x5FDC;&#x7528;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x306B;&#x3088;&#x308B; Fsn0503 &#x306E;&#x6291;&#x5236;&#x306B;&#x304A;&#x3051;&#x308B;&#x5927;&#x8178;&#x764C;&#x5316;&#x5B66;&#x7642;&#x6CD5;&#x306E;&#x6709;&#x52B9;&#x6027;&#x304C;&#x5411;&#x4E0A;&#x3057;&#x307E;&#x3059;&#x3002;

Catepsina S es una proteasa de ciste&iacute;na lisosomal implicado en la tumorig&eacute;nesis con papeles claves en la invasi&oacute;n y la angiog&eacute;nesis. Previamente hemos demostrado que la inhibici&oacute;n espec&iacute;fica de catepsina S usando un anticuerpo monoclonal (Fsn0503) bloquea el crecimiento del tumor carcinoma colorrectal y angiog&eacute;nesis en vivo. Investigamos si los niveles de expresi&oacute;n de catepsina S fueron afectados por la quimioterapia en l&iacute;neas celulares de c&aacute;ncer humano por RT-PCR. Usando modelos de xenoinjerto colorrectal, examinamos el beneficio terap&eacute;utico de la inhibici&oacute;n de la catepsina S usando Fsn0503 en combinaci&oacute;n con un r&eacute;gimen de dosis metron&oacute;mica de CPT-11. Se analizaron los efectos de la terapia de combinaci&oacute;n en la progresi&oacute;n del tumor y en la vascularizaci&oacute;n del tumor por tinci&oacute;n inmunohistoqu&iacute;mica de tumores. Los niveles de expresi&oacute;n de catepsina S son alza en HCT116, LoVo, l&iacute;neas de celulares Colo205 y HUVECs despu&eacute;s de la exposici&oacute;n a CPT-11 in vitro. La administraci&oacute;n de Fsn0503 en combinaci&oacute;n con CPT-11 aten&uacute;a significativamente crecimiento tumoral en comparaci&oacute;n con el CPT-11 solo en modelos de xenoinjerto HCT116 colorrectales. Adem&aacute;s, el an&aacute;lisis de la vascularizaci&oacute;n del tumor revel&oacute; que esto fue interrumpido tambi&eacute;n significativamente por el tratamiento combinado. Estos resultados demuestran que la combinaci&oacute;n de la inhibici&oacute;n de la catepsina S con CPT-11 realza el efecto terap&eacute;utico de la quimioterapia. Este razonamiento puede tener aplicaci&oacute;n cl&iacute;nica en el tratamiento del c&aacute;ncer colorrectal en evaluaci&oacute;n adicional.

Inhibici&oacute;n de la catepsina S por Fsn0503 mejora la eficacia de la quimioterapia en carcinomas colorrectales.

AG-045572 (CMPD1, 1 a) is a nonpeptidic gonadotropin-releasing hormone (GnRH) antagonist that has been investigated for the treatment of sex hormone-related diseases. In the context of systematic studies on sila-substituted drugs, the silicon analogue disila-AG-045572 (1 b) and its derivative 2 were prepared in multi-step syntheses and characterized by elemental analyses (C, H, N), NMR spectroscopic studies (1H, 13C, 29Si), and single-crystal X-ray diffraction. The pharmacological properties of compounds 1 a, 1 b, and 2 were compared in terms of their in vitro potency at cloned human and rat GnRH receptors. Compounds 1 a and 2 were also examined in regard to their pharmacokinetics and in vivo efficacy in both castrated rat (luteinizing hormone (LH) suppression) and intact rat (testosterone suppression) models. The efficacy and pharmacokinetic profiles of 1 a and its silicon-containing analogue 2 appear similar, indicating that replacement of the 5,6,7,8-tetrahydronaphthalene ring system by the 1,3-disilaindane skeleton led to retention of efficacy. Therefore, the silicon compound 2 represents a novel drug prototype for the design of potent, orally available GnRH antagonists suitable for once-daily dosing.

Silicon analogues of the nonpeptidic GnRH antagonist AG-045572: syntheses, crystal structure analyses, and pharmacological characterization.

&#x6297;&#x4F53;&#x9776;&#x5411;&#x7684;&#x7EC4;&#x7EC7;&#x86CB;&#x767D;&#x9176; S &#x8BF1;&#x5BFC;&#x6297;&#x4F53;&#x4F9D;&#x8D56;&#x7684;&#x7EC6;&#x80DE;&#x6BD2;&#x4F5C;&#x7528;&#x3002;

Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity.

Anticorps ciblant de cathepsine S induit la cytotoxicit&eacute; cellulaire d&eacute;pendante des anticorps.

Antik&ouml;rper gezielt Kathepsin s induziert Antik&ouml;rper-abh&auml;ngige zellul&auml;re Zytotoxizit&auml;t.

Anticorpo targeting della catepsina S induce citotossicit&agrave; cellulare anticorpo-dipendente.

&#x6297;&#x4F53;&#x30AB;&#x30C6;&#x30D7;&#x30B7;&#x30F3; S &#x306E;&#x30BF;&#x30FC;&#x30B2;&#x30C6;&#x30A3;&#x30F3;&#x30B0;&#x6297;&#x4F53;&#x4F9D;&#x5B58;&#x6027;&#x7D30;&#x80DE;&#x969C;&#x5BB3;&#x3092;&#x8A98;&#x5C0E;&#x3057;&#x307E;&#x3059;&#x3002;

Cathepsin S&#xC758; &#xB300;&#xC0C1;&#xC73C;&#xB85C; &#xD56D; &#xCCB4; &#xD56D; &#xCCB4; &#xC758;&#xC874; &#xC138;&#xD3EC; &#xB3C5;&#xC131; &#xC138;&#xD3EC; &#xC720;&#xB3C4; &#xD569;&#xB2C8;&#xB2E4;.

Anticuerpos dirigidos contra la catepsina S induce la citotoxicidad celular dependiente de anticuerpos.

Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously assessed the impact of cigarette smoke (CS) seen as perturbations of biological processes in human nasal and bronchial organotypic epithelial culture models. Here, we report our further assessment using in vitro human oral organotypic epithelium models. We exposed the buccal and gingival organotypic epithelial tissue cultures to CS at the air-liquid interface. CS exposure was associated with increased secretion of inflammatory mediators, induction of cytochrome P450s activity and overall weak toxicity in both tissues. Using microarray technology, gene-set analysis and a novel computational modeling approach leveraging causal biological network models, we identified CS impact on xenobiotic metabolism-related pathways accompanied by a more subtle alteration in inflammatory processes. Gene-set analysis further indicated that the CS-induced pathways in the in vitro buccal tissue models resembled those in the in vivo buccal biopsies of smokers from a published dataset. These findings support the translatability of systems responses from in vitro to in vivo and demonstrate the applicability of oral organotypical tissue models for an impact assessment of CS on various tissues exposed during smoking, as well as for impact assessment of reduced-risk products.

In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures.

Exposure to cigarette smoke (CS) is linked to the development of respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. Although animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. We report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures that mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Despite the similar cellular staining and cytokine secretion in both tissue types, the transcriptomic analyses in the context of biological network models identified similar and diverse biological processes that were impacted by CS-exposed nasal and bronchial cultures. Our results demonstrate that nasal and bronchial tissue cultures are appropriate in vitro models for the assessment of CS-induced adverse effects in the respiratory system and promising alternative to animal experimentation.

The response of human nasal and bronchial organotypic tissue cultures to repeated whole cigarette smoke exposure.

Only a few exposure systems are presently available that enable cigarette smoke exposure of living cells at the air-liquid interface, of which one of the most versatile is the Vitrocell® system (Vitrocell® Systems GmbH). To assess its performance and optimize the exposure conditions, we characterized a Vitrocell® 24/48 system connected to a 30-port carousel smoking machine. The Vitrocell® 24/48 system allows for simultaneous exposure of 48 cell culture inserts using dilution airflow rates of 0-3.0 L/min and exposes six inserts per dilution. These flow rates represent cigarette smoke concentrations of 7-100%.

Article	Year
Antibody targeting of cathepsin S inhibits angiogenesis and synergistically enhances anti-VEGF. PloS one\| PubMed ID: 20824056	2010
Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas. Biochimie\| PubMed ID: 21896304	2012
Silicon analogues of the nonpeptidic GnRH antagonist AG-045572: syntheses, crystal structure analyses, and pharmacological characterization. ChemMedChem\| PubMed ID: 21953839	2011
Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity. Molecular cancer\| PubMed ID: 22168338	2011
In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures. Toxicology mechanisms and methods\| PubMed ID: 25046638	2014
The response of human nasal and bronchial organotypic tissue cultures to repeated whole cigarette smoke exposure. International journal of toxicology\| PubMed ID: 25297719	2014
Characterization of the Vitrocell® 24/48 in vitro aerosol exposure system using mainstream cigarette smoke. Chemistry Central journal\| PubMed ID: 25411580	2014

Diana Kuehn

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