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. 2023 Dec 13;14:8095. doi: 10.1038/s41467-023-43630-3

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© The Author(s) 2023

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a Effects of either NFD or WFD on GNE-617 (GNE) therapeutic effects. Volumes of Lu-139 tumors at day 12 are shown relative to baseline (day 0) volumes. Each bar represents a tumor. n = 8 (Normal diet groups) or 6 (NFD and WFD) tumors. P<0.0001 (Normal diet vs NFD, GNE-617); P<0.0001 (NFD vs WFD). b NAD levels in Lu-139 tumors from mice treated with NFD, NAMPTi (GNE) or both (Combo). Each symbol represents one tumor. n = 4 (CTRL), 6 (NFD) or 8 (all others) tumors. P = 0.9034 (CTRL vs NFD); P<0.0001 (CTRL vs GNE); P = 0.0016 (GNE vs Combo). c Growth curves of SCLC (Lu-139), SCPC (NCI-H660) and NEPCa (KUCaP13) xenograft tumors in mice treated with vehicle (CTRL), GNE-617 alone (GNE) or GNE-617 plus NFD (Combo). KUCaP13 graph also includes results from mice treated only with NFD. n = 6 (CTRL and GNE) or 8 (GNE/NFD) Lu-139 tumors; n = 6 (CTRL), 5 (GNE) or 9 (GNE/NFD) NCI-H660 tumors; n = 4 (CTRL), 6 (GNE and NFD) or 10 (GNE/NFD) KUCaP13 tumors. P = 0.0002 (CTRL vs GNE/NFD, day 36, Lu-139); P = 0.0335 (GNE vs GNE/NFD, day 36, Lu-139); P <0.0001 (CTRL vs GNE/NFD, day 53, NCI-H660); P = 0.0065 (GNE vs GNE/NFD, day 53, NCI-H660); P = 0.0053 (CTRL vs GNE/NFD, day 28, KUCaP13); P = 0.0005 (NFD vs GNE/NFD, day 28, KUCaP13); P = 0.0074 (GNE vs GNE/NFD, day 28, KUCaP13). d Analyses using two structurally dissimilar NAMPT inhibitors (GNE-617 and TLM-118). (left) Compound structures. (right panels) Growth curves of 87-5 SCLC tumors in mice treated with NFD, a NAMPTi (GNE-617 or TLM-118) or a combination of NFD + the indicated NAMPTi. n = 10 (CTRL, NAMPTi), 7 (NFD) or 12 (Combo) tumors in GNE-617 experiments; n = 8 tumors in TLN-118 experiments. P = 0.0029 (NAMPTi vs Combo, day 53, GNE-617); P = 0.0364 (NAMPTi vs Combo, day 56, TLM-118). Data are presented as mean plus the SEM. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 as determined by one-way ANOVA with a post hoc test (a–c) or by two-tailed t test (d). ns. not significant. Source data are provided as a Source Data file.