{"id":114122,"date":"2013-03-05T00:00:00","date_gmt":"2013-03-05T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/effect-of-multitargeted-antifolate-on-human-metastatic-melanoma-cell-lines-molecular-pathways-and-resistance-mechanisms\/"},"modified":"2013-03-05T00:00:00","modified_gmt":"2013-03-05T00:00:00","slug":"effect-of-multitargeted-antifolate-on-human-metastatic-melanoma-cell-lines-molecular-pathways-and-resistance-mechanisms","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica-molecular\/effect-of-multitargeted-antifolate-on-human-metastatic-melanoma-cell-lines-molecular-pathways-and-resistance-mechanisms\/","title":{"rendered":"Effect of multitargeted antifolate on human metastatic melanoma cell lines. molecular pathways and resistance mechanisms"},"content":{"rendered":"

Tesis doctoral de Aitziber Buque Martinez <\/strong><\/h2>\n

El objetivo principal de este trabajo es determinar la actividad antitumoral del antifolato pemetrexed (mta) sobre modelos celulares de melanoma humano mediante la identificaci\u00f3n de las rutas de muerte celular que activa e identificar los mecanismos moleculares implicados en la resistencia al f\u00e1rmaco. Para ello se ha analizado el efecto de mta sobre la viabilidad celular tras la exposici\u00f3n a diferentes dosis del f\u00e1rmaco. Se han estudiado las rutas de muerte celular activadas mediante la observaci\u00f3n de cambios morfol\u00f3gicos empleando distintas t\u00e9cnicas de microscopia, cambios bioqu\u00edmicos mediante ensayos elisa, inmunofluorescencia y western blots y se ha estudiado el ciclo celular mediante citometr\u00eda de flujo. Por otro lado, se establecieron subl\u00edneas celulares resistentes a mta y a dacarbazina (tratamiento est\u00e1ndar actual) a partir de las l\u00edneas iniciales. Se analizaron marcadores moleculares implicados en la resistencia a ambas drogas mediante an\u00e1lisis de arrays de baja densidad y los resultados se validaron mediante t\u00e9cnicas de silenciamiento (sirna) y ensayos de expresi\u00f3n espec\u00edficos. Finalmente, se valor\u00f3 el potencial metast\u00e1tico de las cepas resistentes mediante el estudio de la capacidad de invasi\u00f3n y migraci\u00f3n, ensayo de la herida y zimogramas. Adem\u00e1s, se han determinado los niveles de integrinas implicadas en la adhesi\u00f3n celular mediante citometr\u00eda de flujo.Bas\u00e1ndonos en los resultados obtenidos se puede concluir que mta induce apoptosis por v\u00edas dependientes e independientes de caspasas en l\u00edneas celulares de melanoma humano. Durante el proceso apopt\u00f3tico mta induce la regulaci\u00f3n post-trascripcional de los efectores de la muerte celular. Esta regulaci\u00f3n es dependiente de p53, limitando la actividad del antifolato a c\u00e9lulas que muestren actividad de p53. De manera paralela, mta es capaz de actuar sobre la ruta mtor\/akt reforzando el est\u00edmulo apopt\u00f3tico. Finalmente, las c\u00e9lulas resistentes a mta presentan una menor capacidad de invasi\u00f3n que las c\u00e9lulas sensibles al f\u00e1rmaco. Adem\u00e1s, mta muestra actividad citot\u00f3xica contra c\u00e9lulas de melanoma resistentes a dacarbazina. Por todo ello, proponemos que mta cumple con los requisitos para ser tenido en cuenta como una posible opci\u00f3n de tratamiento para pacientes de melanoma metast\u00e1tico y\/o como tratamiento de segunda l\u00ednea en pacientes que desarrollen resistencia a dacarbazina.<\/p>\n

 <\/p>\n

Datos acad\u00e9micos de la tesis doctoral \u00abEffect of multitargeted antifolate on human metastatic melanoma cell lines. molecular pathways and resistance mechanisms<\/strong>\u00ab<\/h3>\n
    \n
  • T\u00edtulo de la tesis:<\/strong>\u00a0 Effect of multitargeted antifolate on human metastatic melanoma cell lines. molecular pathways and resistance mechanisms <\/li>\n
  • Autor:<\/strong>\u00a0 Aitziber Buque Martinez <\/li>\n
  • Universidad:<\/strong>\u00a0 Pa\u00eds vasco\/euskal herriko unibertsitatea<\/li>\n
  • Fecha de lectura de la tesis:<\/strong>\u00a0 03\/05\/2013<\/li>\n<\/ul>\n

     <\/p>\n

    Direcci\u00f3n y tribunal<\/h3>\n
      \n
    • Director de la tesis<\/strong>\n
        \n
      • Guillermo Lopez Vivanco<\/li>\n<\/ul>\n<\/li>\n
      • Tribunal<\/strong>\n
          \n
        • Presidente del tribunal: alejandro Tres sanchez <\/li>\n
        • guillermo Velasco d\u00edez (vocal)<\/li>\n
        • Jos\u00e9 Manuel Lopes — (vocal)<\/li>\n
        • Rafael Zalacain Jorge (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n

           <\/p>\n","protected":false},"excerpt":{"rendered":"

          Tesis doctoral de Aitziber Buque Martinez El objetivo principal de este trabajo es determinar la actividad antitumoral del antifolato pemetrexed […]<\/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":[849,160,115,12909],"tags":[226353,27351,18362,93432,226354,218931],"class_list":["post-114122","post","type-post","status-publish","format-standard","hentry","category-biologia-celular","category-bioquimica","category-bioquimica-molecular","category-pais-vasco-euskal-herriko-unibertsitatea","tag-aitziber-buque-Martinez","tag-alejandro-tres-sanchez","tag-guillermo-lopez-vivanco","tag-guillermo-velasco-diez","tag-jose-manuel-lopes","tag-rafael-zalacain-jorge"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/114122","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=114122"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/114122\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=114122"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=114122"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=114122"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}