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dc.contributor.authorHossain, Jubayeren_US
dc.contributor.authorLatif, Md Abdulen_US
dc.contributor.authorYstaas, Lars Andreas Rømoen_US
dc.contributor.authorNinzima, Sandraen_US
dc.contributor.authorRiecken, Kristofferen_US
dc.contributor.authorMuller, Arnauden_US
dc.contributor.authorAzuaje, Fransiscoen_US
dc.contributor.authorVareecal Joseph, Justinen_US
dc.contributor.authorTalasila, Krishna Mukharjien_US
dc.contributor.authorGhimire, Jiwanen_US
dc.contributor.authorFehse, Borisen_US
dc.contributor.authorBjerkvig, Rolfen_US
dc.contributor.authorMiletic, Hrvojeen_US
dc.date.accessioned2020-05-28T11:36:05Z
dc.date.available2020-05-28T11:36:05Z
dc.date.issued2019
dc.PublishedHossain J, Latif MA, Ystaas LAR, Ninzima S, Riecken K, Muller A, Azuaje F, Vareecal Joseph J, Talasila KM, Ghimire J, Fehse B, Bjerkvig R, Miletic H. Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma. Neuro-Oncology. 2019;21(7):890-900eng
dc.identifier.issn1522-8517
dc.identifier.issn1523-5866
dc.identifier.urihttps://hdl.handle.net/1956/22396
dc.description.abstractBackground: Suicide gene therapy for malignant gliomas has shown encouraging results in the latest clinical trials. However, prodrug application was most often restricted to short-term treatment (14 days), especially when replication-defective vectors were used. We previously showed that a substantial fraction of herpes simplex virus thymidine kinase (HSV-TK) transduced tumor cells survive ganciclovir (GCV) treatment in an orthotopic glioblastoma (GBM) xenograft model. Here we analyzed whether these TK+ tumor cells are still sensitive to prodrug treatment and whether prolonged prodrug treatment can enhance treatment efficacy. Methods: Glioma cells positive for TK and green fluorescent protein (GFP) were sorted from xenograft tumors recurring after suicide gene therapy, and their sensitivity to GCV was tested in vitro. GBM xenografts were treated with HSV-TK/GCV, HSV-TK/valganciclovir (valGCV), or HSV-TK/valGCV + erlotinib. Tumor growth was analyzed by MRI, and survival as well as morphological and molecular changes were assessed. Results: TK-GFP+ tumor cells from recurrent xenograft tumors retained sensitivity to GCV in vitro. Importantly, a prolonged period (3 mo) of prodrug administration with valganciclovir (valGCV) resulted in a significant survival advantage compared with short-term (3 wk) application of GCV. Recurrent tumors from the treatment groups were more invasive and less angiogenic compared with primary tumors and showed significant upregulation of epidermal growth factor receptor (EGFR) expression. However, double treatment with the EGFR inhibitor erlotinib did not increase therapeutic efficacy. Conclusion: Long-term treatment with valGCV should be considered as a replacement for short-term treatment with GCV in clinical trials of HSV-TK mediated suicide gene therapy.en_US
dc.language.isoengeng
dc.publisherOxford University Presseng
dc.titleLong-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastomaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2020-01-16T07:01:29Z
dc.description.versionacceptedVersionen_US
dc.rights.holderCopyright 2019 The Author(s). All rights reserved
dc.identifier.doihttps://doi.org/10.1093/neuonc/noz060
dc.identifier.cristin1743548
dc.source.journalNeuro-Oncology


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