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A novel RET inhibitor with potent efficacy against medullary thyroid cancer in vivo
dc.contributor.author | Samadi, Abbas K. | |
dc.contributor.author | Mukerji, Ridhwi | |
dc.contributor.author | Shah, Anuj | |
dc.contributor.author | Timmermann, Barbara N. | |
dc.contributor.author | Cohen, Mark S. | |
dc.date.accessioned | 2017-04-19T20:50:55Z | |
dc.date.available | 2017-04-19T20:50:55Z | |
dc.date.issued | 2010-12 | |
dc.identifier.citation | Samadi, Abbas K. et al. “A Novel RET Inhibitor with Potent Efficacy against Medullary Thyroid Cancer in Vivo.” Surgery 148.6 (2010): 1228–1236. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23747 | |
dc.description.abstract | BackgroundMost medullary thyroid carcinomas (MTC) recur or progress despite optimal surgical resection. Current targeted-therapies show promise but lack durable efficacy and tolerability. The purpose of this study was to build upon previous in vitro work and evaluate Withaferin A (WA), a novel RET inhibitor, in a metastatic murine model of MTC.Methods5 million DRO-81-1 human MTC-cells injected in the left posterior neck of Nu/Nu mice uniformly generated metastases to the liver, spleen, and/or lungs. Treatment with WA (8mg/kg/day i.p.×21 days) was started for tumors >100 mm3. Endpoints were survival, tumor>1500 mm3, decreased bodyweight, or body score (all measured thrice weekly).ResultsAll controls (saline; n=5) died or deteriorated from metastatic disease by 7 weeks post injection. All treated animals were alive,(WA; n=5), having tumor regression and growth-delay without toxicity or weight-loss at 6 wks post treatment; p<0.01. Tumor cells treated with WA demonstrated inhibition of total and phospho-RET levels by Western-Blot analysis in a dose-dependent manner (almost complete inhibition with 5uM WA treatment) as well as potent inhibition of phospho-ERK and phospho-AKT levels.ConclusionsWithaferin A is a novel natural-product RET-inhibitor with efficacy in a metastatic murine model of MTC. Further long-term efficacy/toxicity studies are warranted to evaluate this compound for clinical translation. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.title | A novel RET inhibitor with potent efficacy against medullary thyroid cancer in vivo | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Timmerman, Barbara N. | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1016/j.surg.2010.09.026 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.