{"id":111816,"date":"2018-03-11T10:38:27","date_gmt":"2018-03-11T10:38:27","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/preclinical-studies-of-pharmacological-mapk-pathway-regulation-in-breast-cancer\/"},"modified":"2018-03-11T10:38:27","modified_gmt":"2018-03-11T10:38:27","slug":"preclinical-studies-of-pharmacological-mapk-pathway-regulation-in-breast-cancer","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-celular\/preclinical-studies-of-pharmacological-mapk-pathway-regulation-in-breast-cancer\/","title":{"rendered":"Preclinical studies of pharmacological mapk pathway regulation in breast cancer"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Irene Gonz\u00e1lez Navarrete <\/strong><\/h2>\n<p>El c\u00e1ncer de mama supone un problema de salud p\u00fablica a nivel mundial. Los avances en los \u00faltimos a\u00f1os han llevado al diagn\u00f3stico precoz de la enfermedad y a una mejora en la supervivencia. Sin embargo, la mortalidad sigue siendo elevada y el c\u00e1ncer metast\u00e1sico sigue siendo incurable. Por lo tanto, es necesario mejorar el tratamiento del c\u00e1ncer de mama, tanto con la identificaci\u00f3n de biomarcadores que permitan monitorizar la progresi\u00f3n de la enfermedad y predecir la respuesta a un determinado tratamiento, como con la personalizaci\u00f3n de los tratamientos en funci\u00f3n de caracter\u00edsticas individuales de cada tumor. De entre estas caracter\u00edsticas, el estado de las distintas v\u00edas de se\u00f1alizaci\u00f3n implicadas en el crecimiento celular, la supervivencia y la apoptosis es de gran inter\u00e9s. Las v\u00edas de las mapks (erk1\/2, jnk y p38) son importantes reguladoras de estos procesos y se han visto involucradas en la biolog\u00eda tumoral.  diversas terapias antitumorales pueden modular las v\u00edas de las mapks, ya sea de manera directa o indirecta, pero sus efectos est\u00e1n pobremente caracterizados. En este trabajo hemos estudiado la regulaci\u00f3n de las mapks por tres f\u00e1rmacos antitumorales distintos (doxorubicina [un inhibidor de la topoisomerasa], lapatinib [un inhibidor tirosina cinasa dual de egfr y her2] y ro5126766 [el primer inhibidor dual de raf y mek]), centr\u00e1ndonos en la v\u00eda de erk1\/2 y en mkp-1, una fosfatasa que desfosforila las mapks. Los tres f\u00e1rmacos provocaron la down-modulaci\u00f3n de mkp-1, tanto in vitro como ex vivo. El mecanismo por el cual la doxorubicina alcanz\u00f3 esta down-modulaci\u00f3n fue a trav\u00e9s de la reducci\u00f3n de los niveles de marn de mkp-1, mientras que en el caso de lapatinib y ro5126766 fue a trav\u00e9s de una mayor degradaci\u00f3n de mkp-1 por el proteasoma. Tambi\u00e9n analizamos los efectos de la combinaci\u00f3n de doxorubicina y lapatinib en las l\u00edneas celulares de c\u00e1ncer de mama bt-474 y sk-br-3, y encontramos un efecto sin\u00e9rgico en la combinaci\u00f3n secuencial doxorubicina + lapatinib.  hemos caracterizado tambi\u00e9n los efectos celulares y moleculares producidos por el tratamiento con ro5126766 en un panel de l\u00edneas celulares de c\u00e1ncer de mama y tambi\u00e9n ex vivo. Solamente la l\u00ednea celular mda-mb-231 (de fenotipo triple-negativo) result\u00f3 sensible al tratamiento con este f\u00e1rmaco. Ro5126766 indujo apoptosis y parada de ciclo celular en g1, y tambi\u00e9n un aumento inesperado en la quimiotaxis de estas c\u00e9lulas, aunque no indujo cambios en su capacidad invasiva.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Preclinical studies of pharmacological mapk pathway regulation in breast cancer<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Preclinical studies of pharmacological mapk pathway regulation in breast cancer <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Irene Gonz\u00e1lez Navarrete <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pompeu fabra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 21\/11\/2011<\/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>Joan Albanell Mestres<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: joaquim Bellmunt vilaplana <\/li>\n<li>ander Urruticoechea ribate (vocal)<\/li>\n<li>  (vocal)<\/li>\n<li>  (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Irene Gonz\u00e1lez Navarrete El c\u00e1ncer de mama supone un problema de salud p\u00fablica a nivel mundial. Los [&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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[849,1027,18712],"tags":[138314,222669,50544,222670],"class_list":["post-111816","post","type-post","status-publish","format-standard","hentry","category-biologia-celular","category-oncologia","category-pompeu-fabra","tag-ander-urruticoechea-ribate","tag-irene-gonzalez-navarrete","tag-joan-albanell-mestres","tag-joaquim-bellmunt-vilaplana"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/111816","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=111816"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/111816\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=111816"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=111816"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=111816"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}