{"id":104065,"date":"2010-04-10T00:00:00","date_gmt":"2010-04-10T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/implications-of-complement-activation-in-the-efficacy-of-the-monoclonal-antibody-cetuximab-against-lung-cancer-cells\/"},"modified":"2010-04-10T00:00:00","modified_gmt":"2010-04-10T00:00:00","slug":"implications-of-complement-activation-in-the-efficacy-of-the-monoclonal-antibody-cetuximab-against-lung-cancer-cells","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-celular\/implications-of-complement-activation-in-the-efficacy-of-the-monoclonal-antibody-cetuximab-against-lung-cancer-cells\/","title":{"rendered":"Implications of complement activation in the efficacy of the monoclonal antibody cetuximab against lung cancer cells"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Yi-fan Hsu <\/strong><\/h2>\n<p>Background:  cetuximab, an antibody targeting the epidermal growth factor receptor (egfr), increases survival in patients with advanced egfr-positive non-small cell lung cancer when administrated in combination with chemotherapy. In this study, we investigated the role of complement activation in the antitumor mechanism of this therapeutic drug.   results:  egfr-expressing lung cancer cell lines were able to bind cetuximab and initiate complement activation by the classical pathway, irrespective of the mutational status of egfr. This activation led to deposition of complement components and increase in complement-mediated cell death. The influence of complement activation on the activity of cetuximab in vivo was evaluated in xenografts of a549 lung cancer cells on nude mice. A549 cells express wild-type egfr and have a kras mutation. Cetuximab activity against a549 xenografts was highly dependent on complement activation, since complement depletion completely abrogated the antitumor efficacy of cetuximab. Moreover, cetuximab activity was significantly higher on a549 cells in which a complement inhibitor, factor h, was genetically downregulated.  conclusions:  we demonstrate for the first time that the in vivo antitumor activity of cetuximab can be associated with a complement-mediated immune response. These results may have important implications for the development of new cetuximab-based therapeutic strategies and for the identification of markers that predict clinical response.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Implications of complement activation in the efficacy of the monoclonal antibody cetuximab against lung cancer cells<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Implications of complement activation in the efficacy of the monoclonal antibody cetuximab against lung cancer cells <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Yi-fan Hsu <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 04\/10\/2010<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Rub\u00e9n Pio Os\u00e9s<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 Luis Gonz\u00e1lez larriba <\/li>\n<li>Mar\u00eda mercedes Garayoa berrueta (vocal)<\/li>\n<li>sergio Portal n\u00fa\u00f1ez (vocal)<\/li>\n<li>alfonso Calvo gonzalez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Yi-fan Hsu Background: cetuximab, an antibody targeting the epidermal growth factor receptor (egfr), increases survival in patients 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