dc.contributor.author | Karakaş, Nihal | |
dc.contributor.author | Stuckey, Daniel | |
dc.contributor.author | Revai-Lechtich, Esther | |
dc.contributor.author | Shah, Khalid | |
dc.date.accessioned | 2021-06-17T07:34:55Z | |
dc.date.available | 2021-06-17T07:34:55Z | |
dc.date.issued | 2021 | en_US |
dc.identifier.citation | Karakaş, N., Stuckey, D., Revai-Lechtich, E. ve Shah, K. (2021). IL13R alpha 2-and EGFR-targeted pseudomonas exotoxin potentiates the TRAIL-mediated death of GBM cells. International Journal of Molecular Medicine, 48(1). https://dx.doi.org/10.3892/ijmm.2021.4978 | en_US |
dc.identifier.issn | 1107-3756 | |
dc.identifier.issn | 1791-244X | |
dc.identifier.uri | https://dx.doi.org/10.3892/ijmm.2021.4978 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12511/7208 | |
dc.description.abstract | Glioblastomas (GBMs) are refractory to current treatments and novel therapeutic approaches need to be explored. Pro-apoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is tumor-specific and has been shown to induce apoptosis and subsequently kill GBM cells. However, approximately 50% of GBM cells are resistant to TRAIL and a combination of TRAIL with other therapeutics is necessary to induce mechanism-based cell death in TRAIL-resistant GBMs. The present study examined the ability of the tumor cell surface receptor, interleukin (IL)-13 receptor alpha 2 (IL13R alpha 2)- and epidermal growth factor receptor (EGFR)-targeted pseudomonas exotoxin (PE) to sensitize TRAIL-resistant GBM cells and assessed the dual effects of interleukin 13-PE (IL13-PE) or EGFR nanobody-PE (ENb-PE) and TRAIL for the treatment of a broad range of brain tumors with a distinct TRAIL therapeutic response. Receptor targeted toxins upregulated TRAIL death receptors (DR4 and DR5) and suppressed the expression of anti-apoptotic FLICE-inhibitory protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP). This also led to the induction of the cleavage of caspase-8 and caspase-9 and resulted in the sensitization of highly resistant established GBM and patient-derived GBM stem cell (GSC) lines to TRAIL-mediated apoptosis. These findings provide a mechanism-based strategy that may provide options for the cell-mediated delivery of bi-functional therapeutics to target a wide spectrum of TRAIL-resistant GBMs. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Spandidos Publications Ltd | en_US |
dc.rights | info:eu-repo/semantics/embargoedAccess | en_US |
dc.subject | Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand | en_US |
dc.subject | Interleukin-13 Receptor | en_US |
dc.subject | Pseudomonas Exotoxin | en_US |
dc.subject | Glioblastoma | en_US |
dc.subject | Targeted Therapy | en_US |
dc.title | IL13R alpha 2-and EGFR-targeted pseudomonas exotoxin potentiates the TRAIL-mediated death of GBM cells | en_US |
dc.type | article | en_US |
dc.relation.ispartof | International Journal of Molecular Medicine | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı | en_US |
dc.authorid | 0000-0002-9096-1512 | en_US |
dc.identifier.volume | 48 | en_US |
dc.identifier.issue | 1 | en_US |
dc.relation.tubitak | info:eu-repo/grantAgreement/TUBITAK/SOBAG/RO1 CA138922 | |
dc.relation.tubitak | info:eu-repo/grantAgreement/TUBITAK/SOBAG/R01 CA201148 | |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.identifier.doi | 10.3892/ijmm.2021.4978 | en_US |
dc.identifier.wosquality | Q2 | en_US |
dc.identifier.scopusquality | Q1 | en_US |