{"id":11881,"date":"2001-02-07T00:00:00","date_gmt":"2001-02-07T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/terapia-genica-del-hepatocarcinoma-mediante-genes-quimiosensibilizantes-bajo-control-de-promotor-especifico-de-tumor-estudios-de-eficacia-y-toxicidad-en-modelos-experimentales-ortotopicos\/"},"modified":"2001-02-07T00:00:00","modified_gmt":"2001-02-07T00:00:00","slug":"terapia-genica-del-hepatocarcinoma-mediante-genes-quimiosensibilizantes-bajo-control-de-promotor-especifico-de-tumor-estudios-de-eficacia-y-toxicidad-en-modelos-experimentales-ortotopicos","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ciencias-medicas\/terapia-genica-del-hepatocarcinoma-mediante-genes-quimiosensibilizantes-bajo-control-de-promotor-especifico-de-tumor-estudios-de-eficacia-y-toxicidad-en-modelos-experimentales-ortotopicos\/","title":{"rendered":"Terapia genica del hepatocarcinoma mediante genes quimiosensibilizantes bajo control de promotor especifico de tumor: estudios de eficacia y toxicidad en modelos experimentales ortotopicos"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Guillem Genove Martinez <\/strong><\/h2>\n<p>El hcc constituye una formidable desafio terapeutico debido a la carencia de terapias eficientes para su tratamiento. La terapia genica se ha constituido en una herramienta muy prometedora en la lucha contra el cancer. De entre las diversas estrategias de terapia g\u00e9nica del cancer exploradas, la m\u00e1s utilizada consiste en la transferencia de genes quimosensibilizantes cuyo producto sensiblice a las celulas transducidas frente a la administraci\u00f3n de prof\u00e1rmacos. Si bien mediante esta maniobra se ha conseguido obtener remisiones tumorales, su aplicaci\u00f3n genera toxicidad hep\u00e1tica severa debido a la infecci\u00f3n del parenquima hep\u00e1tico y posterior expresi\u00f3n del transgen en los hepatocitos no tumorales. Por ello, se hace necesario restringir la expresion de los transgenes a las celulas tumorales. Dado que entre el 40 y el 60% de los hcc humanos reexpresan la proteina fetal afp, el promotor de la misma es un buen candidato para expresar de forma tumor-especifica el transgen de interes. En esta memoria hemos mostrado que la transferencia de gen hsv-tk bajo control del promotor afp sensibiliza el profarmaco gcv exclusivamente a aquellas lineas productoras de afp. Esta especificidad se mantiene in vivo, de forma que la administracion del vector adafptk y gcv en ratas sanas no genera hepatotoxicidad. Utilizado el vector en un modelo de hcc ortot\u00f3pico unifocal hemos obtenido un 40% de remisiones tumorales completas, e incrementos significativos en la supervivencia de los animales. La falta de expresi\u00f3n de afp por parte de los nodulos de menor tama\u00f1o en un modelo de hcc ortotopico multifocal fue la causa que no se obtuviera una buena respuesta antitumoral en ese modelo. La utilizaci\u00f3n del vector adafptk y gcv genera un efecto antitumoral significativamente mejor que el uso del vector adcmvtk, debido probablemente a una menor producci\u00f3n de proteina recombinante, lo cual genera una ralentizaci\u00f3n en la muerte celular que puede contribuir a recl<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Terapia genica del hepatocarcinoma mediante genes quimiosensibilizantes bajo control de promotor especifico de tumor: estudios de eficacia y toxicidad en modelos experimentales ortotopicos<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Terapia genica del hepatocarcinoma mediante genes quimiosensibilizantes bajo control de promotor especifico de tumor: estudios de eficacia y toxicidad en modelos experimentales ortotopicos <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Guillem Genove Martinez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 02\/07\/2001<\/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>Jes\u00fas M. Prieto Valtue\u00f1a<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: pilar Civeira murillo <\/li>\n<li>Santiago Ramon y cajal ag\u00ed\u00bceras (vocal)<\/li>\n<li>jordi Bruix tudo (vocal)<\/li>\n<li>bruno Sangro g\u00f3mez-acebo (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Guillem Genove Martinez El hcc constituye una formidable desafio terapeutico debido a la carencia de terapias eficientes [&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":[36483,36606,35,9,491,139,17749],"tags":[18316,38952,15059,38953,17764,36351],"class_list":["post-11881","post","type-post","status-publish","format-standard","hentry","category-biologia-molecular","category-biologia-molecular-de-microorganismos","category-ciencias-de-la-vida","category-ciencias-medicas","category-gastroenterologia","category-medicina-interna","category-navarra","tag-bruno-sangro-gomez-acebo","tag-guillem-genove-Martinez","tag-jesus-m-prieto-valtuena","tag-jordi-bruix-tudo","tag-pilar-civeira-murillo","tag-santiago-ramon-y-cajal-agieras"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/11881","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=11881"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/11881\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=11881"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=11881"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=11881"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}