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. 2022 Feb 28;13:1090. doi: 10.1038/s41467-022-28619-8

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Longitudinal µCT imaging of lung tumors in KT;Lkb1^XTR/XTR and KT;Lkb1^XTR/XTR;FLPo-ER^T2 mice. Treatment began within 1 to 6 weeks from initial detection of lung tumors. Tumors were tracked for an additional 6–10 weeks, and lung tissue was harvested at 28 weeks. VEH vehicle, TAM tamoxifen. b Changes in tumor volume. Red numbers indicate the number of tumors measured at a given time point. Bars correspond to the mean tumor volume relative to size at first detection. Error bars indicate standard deviation. Source data is displayed in Supplementary Fig. 6b. KT;Lkb1^XTR/XTR-tamoxifen, n = 10 tumors; KT;Lkb1^XTR/XTR;FLPo-ER^T2-vehicle, n = 9 tumors; KT;Lkb1^XTR/XTR;FLPo-ER^T2-tamoxifen, n = 10 tumors. c Representative µCT images of tumor-bearing lungs at treatment initiation (top) and after 10 weeks of treatment (bottom). d BrdU (top) and cleaved caspase 3 (CC3; bottom) detection by IHC within Lkb1 non-restored (left) and restored (right) lung tumors following 2 weeks of treatment with vehicle or tamoxifen. Inset image shows CC3 staining of involuting mammary gland. Scale bars = 100 µm. Images were acquired from a single experiment including multiple biological replicates as noted in e, f. e, f Quantification of BrdU⁺ (e) and CC3⁺ (f) cells within Lkb1-restored and non-restored tumors. Each dot represents a ×20 field. Red crossbars indicate the mean. In e, KT;Lkb1^XTR/XTR-vehicle, n = 60 fields; KT;Lkb1^XTR/XTR-tamoxifen, n = 60 fields; KT;Lkb1^XTR/XTR;FLPo-ER^T2-vehicle, n = 60 fields; KT;Lkb1^XTR/XTR;FLPo-ER^T2-tamoxifen, n = 80 fields. In f, KT;Lkb1^XTR/XTR-vehicle, n = 60 fields; KT;Lkb1^XTR/XTR-tamoxifen, n = 80 fields; KT;Lkb1^XTR/XTR;FLPo-ER^T2-vehicle, n = 80 fields; KT;Lkb1^XTR/XTR;FLPo-ER^T2-tamoxifen, n = 120 fields. One tissue section per mouse was analyzed. P values calculated by two-sided unpaired t test. HPF high-power field, VEH vehicle, TAM tamoxifen. g Serial ¹⁸F-FDG-PET/CT imaging. Tamoxifen treatment of KT;Lkb1^XTR/XTR, and KT;Lkb1^XTR/XTR;FLPo-ER^T2 mice began within 2 days of establishing baseline levels of ¹⁸F-FDG uptake (at least two measurements within 18–24 weeks after tumor initiation). ¹⁸F-FDG uptake was captured after 2 and 6 weeks of treatment, as well as at 12 weeks for restored mice. h Changes in ¹⁸F-FDG uptake in restored (n = 15 tumors) and non-restored (n = 22 tumors) tumors. Source data displayed in Supplementary Fig. 8c. P values calculated by two-sided unpaired t test.