A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo

dc.contributor.authorFueyo, J.en
dc.contributor.authorGomez-Manzano, C.en
dc.contributor.authorAlemany, R.en
dc.contributor.authorLee, P. S.en
dc.contributor.authorMcDonnell, T. J.en
dc.contributor.authorMitlianga, P.en
dc.contributor.authorShi, Y. X.en
dc.contributor.authorLevin, V. A.en
dc.contributor.authorYung, W. K.en
dc.contributor.authorKyritsis, A. P.en
dc.date.accessioned2015-11-24T19:40:11Z
dc.date.available2015-11-24T19:40:11Z
dc.identifier.issn0950-9232-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/24313
dc.rightsDefault Licence-
dc.subjectAdenoviridae/*geneticsen
dc.subjectAnimalsen
dc.subject*Gene Therapyen
dc.subjectGlioma/*therapyen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectMice, Inbred BALB Cen
dc.subjectMice, Nudeen
dc.subjectMutationen
dc.subjectRetinoblastoma Protein/*physiologyen
dc.subjectS Phaseen
dc.subjectTumor Cells, Cultureden
dc.subjectVirus Replicationen
dc.titleA mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivoen
heal.abstractEffective anti cancer strategies necessitate the use of agents that target tumor cells rather than normal tissues. In this study, we constructed a tumor-selective adenovirus, Delta24, that carries a 24-bp deletion in the E1A region responsible for binding Rb protein. Immunoprecipitation analyses verified that this deletion rendered Delta24 unable to bind the Rb protein. However, titration experiments in 293 cells demonstrated that the Delta24 adenovirus could replicate in and lyse cancer cells with great efficiency. Lysis of most human glioma cells was observed within 10 - 14 days after infection with Delta24 at 10 PFU/cell. In vivo, a single dose of the Delta24 virus induced a 66.3% inhibition (P<0.005) and multiple injections, an 83.8% inhibition (P<0.01) of tumor growth in nude mice. However, normal fibroblasts or cancer cells with restored Rb activity were resistant to the Delta24 adenovirus. These results suggest that the E1A-mutant Delta24 adenovirus may be clinically and therapeutically useful against gliomas and possibly other cancers with disrupted Rb pathway.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1038/sj.onc.1203251-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/10644974-
heal.journalNameOncogeneen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2000-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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