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dc.contributor.authorDwyer, Róisín M.
dc.contributor.authorBergert, Elizabeth R.
dc.contributor.authorO'Connor, Michael K.
dc.contributor.authorGendler, Sandra J.
dc.contributor.authorMorris, John C.
dc.date.accessioned2019-09-04T12:39:08Z
dc.date.available2019-09-04T12:39:08Z
dc.date.issued2006-06-15
dc.identifier.citationDwyer, Róisín M., Bergert, Elizabeth R., O'Connor, Michael K., Gendler, Sandra J., & Morris, John C. (2006). Adenovirus-Mediated and Targeted Expression of the Sodium–Iodide Symporter Permits In Vivo Radioiodide Imaging and Therapy of Pancreatic Tumors. Human Gene Therapy, 17(6), 661-668. doi: 10.1089/hum.2006.17.661en_IE
dc.identifier.issn1557-7422
dc.identifier.urihttp://hdl.handle.net/10379/15389
dc.description.abstractPancreatic cancer is the fourth leading cause of cancer death in the United States. It is highly aggressive with no uniformly effective chemotherapy available for metastatic disease. The sodium–iodide symporter (NIS) is a transmembrane protein responsible for uptake of iodide into cells. The presence of NIS in thyroid cells permits diagnostic imaging and therapy of thyroid tumors, using radioiodide. Previous studies from this laboratory reported mucin-1 (MUC1)-driven expression of NIS in cancer cells. MUC1 overexpression has also been reported in 90% of pancreatic tumors. In this study Ad5/MUC1/NIS was used to infect pancreatic cancer cells both in vitro and in vivo, to investigate the potential for radioiodide imaging and ablation of this disease. In vitro studies revealed a 43-fold increase in iodide uptake in NIS-transduced cells compared with controls. In vivo imaging revealed effective iodide uptake and retention at the site of NIS-transduced tumors, with optimal uptake (13% of injected dose) observed 5 hr after iodide administration. Intravenous delivery was performed to investigate potential hepatotoxicity of the construct in the event of virus leakage. Intravenous injection of Ad5/CMV/NIS resulted in robust iodide uptake throughout mouse liver, whereas no uptake was detected in the liver of animals given Ad5/MUC1/NIS intravenously. Administration of therapeutic doses of 131I resulted in significant regression of NIS-transduced tumors, with a mean 50% reduction in volume within 10 weeks of therapy (p < 0.0001). The ability to target NIS expression to pancreatic cancer, which has such limited treatment options, may be highly beneficial and warrants further investigation.en_IE
dc.description.sponsorshipFunding for this work was received from the Prospect Creek Foundation, a Mayo Foundation Prostate Cancer SPORE grant (CA91956), the Mayo Breast Cancer Program, and the Molecular Medicine Program of the Mayo Clinic College of Medicine.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherMary Ann Lieberten_IE
dc.relation.ispartofHuman Gene Therapyen
dc.subjectNISen_IE
dc.subjectMUC1en_IE
dc.subjectradioiodideen_IE
dc.subjectgene therapyen_IE
dc.subjectpancreatic canceren_IE
dc.titleAdenovirus-mediated and targeted expression of the sodium-iodide symporter permits in vivo radioiodide imaging and therapy of pancreatic tumorsen_IE
dc.date.updated2019-08-16T10:22:16Z
dc.identifier.doi10.1089/hum.2006.17.661
dc.local.publishedsourcehttps://doi.org/10.1089/hum.2006.17.661en_IE
dc.description.peer-reviewedpeer-reviewed
dc.internal.rssid1167634
dc.local.contactRóisín Dwyer, Surgery, Nui Galway. 3008 Email: roisin.dwyer@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
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