{"id":115967,"date":"2014-01-07T00:00:00","date_gmt":"2014-01-07T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/acquired-resistance-to-bcl-2-inhibitors-in-lymphomas\/"},"modified":"2014-01-07T00:00:00","modified_gmt":"2014-01-07T00:00:00","slug":"acquired-resistance-to-bcl-2-inhibitors-in-lymphomas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/navarra\/acquired-resistance-to-bcl-2-inhibitors-in-lymphomas\/","title":{"rendered":"Acquired resistance to bcl-2 inhibitors in lymphomas"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Melissa Andrea Rieger Menanteau <\/strong><\/h2>\n<p>La adquisici\u00f3n de resistencia a terapias dirigidas es uno de los principales obst\u00e1culos para la terapia contra el c\u00e1ncer. Recientemente, un compuesto bh3-mim\u00e9tico selectivo de la prote\u00edna bcl2 llamado abt-199 mostr\u00f3 resultados prometedores en el tratamiento de tumores dependientes a dicha prote\u00edna. Dada la alta afinidad del abt-199 por bcl2, estudiamos los posibles mecanismos que podr\u00edan conferir resistencia tras el tratamiento con abt-199 con el objetivo de anticipar su ocurrencia en la cl\u00ednica.  se establecieron dos modelos de resistencia en linfomas tras la exposici\u00f3n continua a abt-199. En las c\u00e9lulas de linfoma murino resistentes que expresan bcl2, identificamos dos mutaciones missense en el dominio bh3 de bcl2. Ambas mutaciones, f101c y f101l, impidieron la uni\u00f3n de abt-199 al dominio bh3, evitando la activaci\u00f3n de la apoptosis mitocondrial. En l\u00edneas celulares humanas de linfoma resistentes se encontr\u00f3 una mutaci\u00f3n missense en el dominio transmembrana c-terminal de la prote\u00edna pro-apopt\u00f3tica bax (g179e). Dicha mutaci\u00f3n impide la uni\u00f3n de bax a la membrana de la mitocondria y bloquea la apoptosis inducida por abt-199 en modelos in vitro e in vivo. Adem\u00e1s, la mutaci\u00f3n g179e de bax induce resistencia no solo a compuestos bh3 mim\u00e9ticos, sino que tambi\u00e9n a otros f\u00e1rmacos antineopl\u00e1sicos. Nuestro estudio muestra que la adquisici\u00f3n de mutaciones en la familia de prote\u00ednas de bcl2 es un nuevo mecanismo de resistencia a la apoptosis en c\u00e1ncer. Estos resultados anticipan el posible desarrollo de mutaciones como estas en pacientes tratados con abt-199 y proveen una base para prevenir su ocurrencia y dise\u00f1ar compuestos que permitan sobrepasar la resistencia adquirida.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Acquired resistance to bcl-2 inhibitors in lymphomas<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Acquired resistance to bcl-2 inhibitors in lymphomas <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Melissa Andrea Rieger Menanteau <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 01\/07\/2014<\/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>Jos\u00e9 \u00e1ngel Mart\u00ednez Climent<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: africa Garcia orad <\/li>\n<li>carlo Carolis (vocal)<\/li>\n<li>Carlos Manuel Panizo santos (vocal)<\/li>\n<li>Jos\u00e9 Luis Fern\u00e1ndez luna (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Melissa Andrea Rieger Menanteau La adquisici\u00f3n de resistencia a terapias dirigidas es uno de los principales obst\u00e1culos [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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