{"id":14605,"date":"2018-03-09T09:01:22","date_gmt":"2018-03-09T09:01:22","guid":{"rendered":""},"modified":"2018-03-09T09:01:22","modified_gmt":"2018-03-09T09:01:22","slug":"estudio-precla%c2%adnico-de-la-toxicidad-del-tratamiento-combinado-de-un-vector-adenoviral-que-contiene-el-gen-de-la-timida%c2%adk-kinasa-adtk-y-ganciclovir-en-ratas-sanas-y-en-un-modelo-de-hepatoca","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ciencias-medicas\/estudio-precla%c2%adnico-de-la-toxicidad-del-tratamiento-combinado-de-un-vector-adenoviral-que-contiene-el-gen-de-la-timida%c2%adk-kinasa-adtk-y-ganciclovir-en-ratas-sanas-y-en-un-modelo-de-hepatoca\/","title":{"rendered":"Estudio precl\u00ednico de la toxicidad del tratamiento combinado de un vector adenoviral que contiene el gen de la timid\u00edk kinasa (adtk) y ganciclovir en ratas sanas y en un modelo de hepatocarcinoma unifocal"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Ana Gloria Gil Royo <\/strong><\/h2>\n<p>La terapia g\u00e9nica som\u00e1tica se encuentra en una fase de desarrollo intenso. el proceso de trasferencia de material gen\u00e9tico puede realizarse mediante vectores adenovirales. Una de las estrategias m\u00e1s estudiadas para el tratamiento del c\u00e1ncer es la utilizaci\u00f3n de \u00abgenes suicidas\u00bb que codifican enzimas capaces de trasformar f\u00e1rmacos inactivos en derivados con actividad citot\u00f3xica, entre ellos el sistema adtk\/ganciclovir. Los resultados de eficacia precl\u00ednicos han sido prometedores; no obstante, se asocia a efectos t\u00f3xicos cuyas caracter\u00edsticas se establecen en este trabajo de investigaci\u00f3n.  para el estudio de los efectos t\u00f3xicos agudos y largo plazo, se administra adtk\/gcv en ratas wistar, mediante administraci\u00f3n sist\u00e9mica y se complementa con el estudio de los efectos t\u00f3xicos tras la administraci\u00f3n intratumoral en un modelo experimental de hepatocarcinoma unifocal.  la coadministraci\u00f3n del adenovirus adtk y del gcv resulta imprescindible para que el sistema produzca graves efectos t\u00f3xicos agudos, caracterizados por toxicidad hep\u00e1tica y linfoide. Se observa un da\u00f1o de aparici\u00f3n muy precoz, de intensidad variable consistente en una hepatitis aguda colest\u00e1sica severa, que condiciona una insuficiencia hep\u00e1tica, y en una depleci\u00f3n linfoide generalizada. Los efectos t\u00f3xicos dependen de la dosis y v\u00eda de administraci\u00f3n del vector, y de la forma de administraci\u00f3n del gcv.  en este estudio muestra que el pretratamiento con adtk disminuye la toxicidad del tratamiento combinado sin impedir la trasferencia eficaz del transg\u00e9n y se determinan par\u00e1metros toxicol\u00f3gicos de inter\u00e9s.  en los animales que sobreviven al tratamiento, estos efectos t\u00f3xicos tienden a us remisi\u00f3n de forma espont\u00e1nea pero lenta. El estudio histol\u00f3gico del h\u00edgado muestra un proceso de reparaci\u00f3n, cuyo \u00abfallo\u00bb desencadena en uno de los animales tratados el desarrollo de un colangiocarcinoma.  el tratamiento no produce toxicidad relevante a l<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio precl\u00ednico de la toxicidad del tratamiento combinado de un vector adenoviral que contiene el gen de la timid\u00edk kinasa (adtk) y ganciclovir en ratas sanas y en un modelo de hepatocarcinoma unifocal<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio precl\u00ednico de la toxicidad del tratamiento combinado de un vector adenoviral que contiene el gen de la timid\u00edk kinasa (adtk) y ganciclovir en ratas sanas y en un modelo de hepatocarcinoma unifocal <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Ana Gloria Gil Royo <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 15\/12\/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> Idoate Gastearena Miguel Angel<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Edurne Cenarruzabeitia Sagarminaga <\/li>\n<li>Juan  Antonio Amiguet Garc\u00eda (vocal)<\/li>\n<li>Arturo Ramon Anadon Navarro (vocal)<\/li>\n<li>Adela Lopez De Cerain Salsamendi (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Ana Gloria Gil Royo La terapia g\u00e9nica som\u00e1tica se encuentra en una fase de desarrollo intenso. el [&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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