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dc.contributor.authorHingtgen, Shawn
dc.contributor.authorKasmieh, Randa
dc.contributor.authorElbayly, Elizabeth
dc.contributor.authorNesterenko, Irina
dc.contributor.authorFigueiredo, Jose-Luiz
dc.contributor.authorDash, Rupesh
dc.contributor.authorSarkar, Devanand
dc.contributor.authorHall, David
dc.contributor.authorKozakov, Dima
dc.contributor.authorVajda, Sandor
dc.contributor.authorFisher, Paul B.
dc.contributor.authorShah, Khalid A.
dc.date.accessioned2013-03-21T20:42:51Z
dc.date.issued2012
dc.identifier.citationHingtgen, Shawn, Randa Kasmieh, Elizabeth Elbayly, Irina Nesterenko, Jose-Luiz Figueiredo, Rupesh Dash, Devanand Sarkar, David Hall, Dima Kozakov, Sandor Vajda, Paul B. Fisher, and Khalid Shah. 2012. A first-generation multi-functional cytokine for simultaneous optical tracking and tumor therapy. PLoS ONE 7(7): e40234.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10456185
dc.description.abstractCreating new molecules that simultaneously enhance tumor cell killing and permit diagnostic tracking is vital to overcoming the limitations rendering current therapeutic regimens for terminal cancers ineffective. Accordingly, we investigated the efficacy of an innovative new multi-functional targeted anti-cancer molecule, SM7L, using models of the lethal brain tumor Glioblastoma multiforme (GBM). Designed using predictive computer modeling, SM7L incorporates the therapeutic activity of the promising anti-tumor cytokine MDA-7/IL-24, an enhanced secretory domain, and diagnostic domain for non-invasive tracking. In vitro assays revealed the diagnostic domain of SM7L produced robust photon emission, while the therapeutic domain showed marked anti-tumor efficacy and significant modulation of p38MAPK and ERK pathways. In vivo, the unique multi-functional nature of SM7L allowed simultaneous real-time monitoring of both SM7L delivery and anti-tumor efficacy. Utilizing engineered stem cells as novel delivery vehicles for SM7L therapy (SC-SM7L), we demonstrate that SC-SM7L significantly improved pharmacokinetics and attenuated progression of established peripheral and intracranial human GBM xenografts. Furthermore, SC-SM7L anti-tumor efficacy was augmented in vitro and in vivo by concurrent activation of caspase-mediated apoptosis induced by adjuvant SC-mediated S-TRAIL delivery. Collectively, these studies define a promising new approach to treating highly aggressive cancers, including GBM, using the optimized therapeutic molecule SM7L.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0040234en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394792/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectNeuroscienceen_US
dc.subjectDevelopmental Neuroscienceen_US
dc.subjectNeural Stem Cellsen_US
dc.subjectNeuroimagingen_US
dc.subjectMedicineen_US
dc.subjectClinical Research Designen_US
dc.subjectAnimal Models of Diseaseen_US
dc.subjectDrugs and Devicesen_US
dc.subjectDrug Research and Developmenten_US
dc.subjectDrug Discoveryen_US
dc.subjectPharmacokineticsen_US
dc.subjectDrug Distributionen_US
dc.subjectPharmacodynamicsen_US
dc.subjectOncologyen_US
dc.subjectCancer Treatmenten_US
dc.subjectCytokine Therapyen_US
dc.subjectGene Therapyen_US
dc.subjectCancer Preventionen_US
dc.titleA First-Generation Multi-Functional Cytokine for Simultaneous Optical Tracking and Tumor Therapyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorShah, Khalid A.
dc.date.available2013-03-21T20:42:51Z
dc.identifier.doi10.1371/journal.pone.0040234*
dash.contributor.affiliatedShah, Khalid


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