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Sleeve gastrectomy (SG) inhibits tumor growth in an orthotopic diabetic mouse model of anaplastic thyroid cancer (ATC)
Andrei Moscalu
1, Bixiao Zhao
1, Cullen F. Roberts
1, Justine A. Barletta
2, Ali Tavakkoli
1, Eric G. Sheu
1, Matthew A. Nehs
1 1Department of Surgery, Brigham and Women's Hospital, Boston, MA
2Department of Pathology, Brigham and Women's Hospital, Boston, MA
Introduction: ATC 5-year survival is <5% and its median survival only 5-months. Type-2-diabetes (T2D) is associated with decreased survival in patients with ATC, and thus T2D-associated hyperglycemia and insulin resistance may be driving this worsened disease outcome. We therefore hypothesized that SG and/or the ketogenic diet (KD) would improve tumor burden in an orthotopic diabetic mouse model of ATC.
Methods: Fifty, 4-week-old, male recombination-activating-gene-2-protein-knockout (RAG-2 KO) mice were reared on a high-fat-diet (HFD), followed by implantation of 500,000 human ATC cells into the right thyroid lobe at 11-weeks and 11-days after, randomized to: HFD-Sham, HFD-SG, KD-Sham, and KD-SG. Oral-glucose-tolerance-tests were performed at 2-weeks postop. The experiment was terminated 46-days from tumor implant, when fasting glucose and insulin were measured, ATC tumors harvested, and tumor volume calculated.
Results: In both HFD and KD fed mice, SG yielded a significant weight loss (Fig.1A); a >27% improvement in glucose tolerance, p<0.01, (Fig.1-B&C); a lower overnight-fasting-glucose, p<0.0001, (Fig.1D), and Homeostatic-Model-Assessment-for-Insulin-Resistance (HOMA-IR), p<0.01, (Fig.-1E), compared to Sham. Tumor volume was significantly reduced in HFD-SG mice (121 mm³) compared to HFD-Sham (364 mm³), p<0.001. Additionally, tumor volume was significantly reduced in KD-SG mice (90 mm³) compared to KD-Sham (217 mm³), p<0.001(Fig.-1F).
Conclusion: Sleeve gastrectomy inhibited tumor growth in an orthotopic mouse model of ATC in diabetic mice, HFD and KD fed mice.
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