Suppression of human glioma growth by adenovirus-mediated Rb gene transfer

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dc.contributor.authorFueyo, J.en
dc.contributor.authorGomez-Manzano, C.en
dc.contributor.authorYung, W. K.en
dc.contributor.authorLiu, T. J.en
dc.contributor.authorAlemany, R.en
dc.contributor.authorBruner, J. M.en
dc.contributor.authorChintala, S. K.en
dc.contributor.authorRao, J. S.en
dc.contributor.authorLevin, V. A.en
dc.contributor.authorKyritsis, A. P.en
dc.date.accessioned2015-11-24T18:49:37Z
dc.date.available2015-11-24T18:49:37Z
dc.identifier.issn0028-3878-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/17986
dc.rightsDefault Licence-
dc.subjectAdenoviridae/*geneticsen
dc.subjectAnimalsen
dc.subjectCell Cycle/physiologyen
dc.subjectCell Division/physiologyen
dc.subjectDisease Progressionen
dc.subjectGene Expression Regulation, Neoplastic/physiologyen
dc.subject*Gene Transfer Techniquesen
dc.subject*Genes, Retinoblastomaen
dc.subjectGenetic Vectorsen
dc.subjectGlioblastoma/*therapyen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectMice, Nudeen
dc.subjectPhosphorylationen
dc.subjectTransplantation, Heterologousen
dc.subjectTumor Cells, Cultureden
dc.titleSuppression of human glioma growth by adenovirus-mediated Rb gene transferen
heal.abstractOBJECTIVE: This study was conducted to obtain evidence that restoration of the retinoblastoma protein function may have therapeutic application for gliomas. BACKGROUND: The development of glioblastoma multiforme involves progressive inactivation of several tumor suppressor genes. Abnormalities of the retinoblastoma tumor suppressor gene are found in the majority of cancers, including at least 30% of malignant gliomas. No final evidence has been produced about the role of Rb in suppressing glioma growth. METHODS: To address this question, the Ad5CMV-Rb adenovirus carrying a 3.2-kb cDNA of the Rb gene was constructed. Expression of the exogenous protein was assessed by immunoblot and immunohistochemistry analyses. Growth curve assays were used to evaluate the effect of the Rb protein on glioma cell growth. Flow-cytometry analyses were used to analyze the phenotype of the cell cycle after the transfer of Rb. Human glioma xenografts implanted subcutaneously in nude mice were used for the tumorigenicity assay. RESULTS: After the transfer of Rb, 80% of the treated cells expressed high levels of the retinoblastoma protein for at least 7 days. Within 5 days of treatment, the cells lost the neoplastic morphology and showed marked growth suppression. The majority of the Rb-expressing cells were arrested in the G1 phase of the cell cycle. In addition, the restoration of the retinoblastoma activity rendered the human glioma cells unable to form tumors in nude mice. CONCLUSIONS: These findings provide direct evidence that inactivation of the retinoblastoma protein is a critical event in gliomas, and suggest that the restoration of wild-type retinoblastoma activity in these tumors may have therapeutic utility.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/9595979-
heal.journalNameNeurologyen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate1998-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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