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. 2018 Oct 23;38(10):1734–1750. doi: 10.1038/s41388-018-0546-z

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© The Author(s) 2018

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. 6 — In vivo administration of Lck-I using an orthotopic xenograft model results in significant inhibition of tumor growth and downregulation of stemness gene expression. a 3D reconstruction of human glioblastoma xenograft tumors untreated (left panel) or treated with continuous local infusion of Lck-I (right panel) for 4 weeks. Red contours show the outline of the mouse brain and green shows the tumor area as reconstructed using Neurolucida software. b Comparison of the total tumor area between Lck-I-treated animals and controls. The results are plotted as mean values ± s.d. (*p < 0.0002, n = 16 animals, eight control and eight treated with Lck-I, calculated by two-tailed Student’s t-test). c Pie chart showing the number of downregulated genes in Lck-I-treated tumors that belong to five functional clusters: neuro-developmental genes, pseudopodia-specific genes, human cancer genes, human glioblastoma genes and CNS genes. Functional annotation was performed using the Broad Institute’s Gene Set Enrichment Analysis tool. d Radar chart displaying the overlap between the 743 downregulated genes in tumors treated with Lck-I and the various stem cell types in StemChecker. Significant overlap was observed with stemness signature genes expressed in neural stem cells (red) (p < 1.8 × 10^–12 calculated by the hypergeometric test and adjusted by the Bonferroni correction). e Radar chart displaying the overlap between the 743 downregulated genes in tumors treated with Lck-I and genes that are targeted by transcription factors linked to pluripotency and stem cell maintenance (StemChecker). This analysis showed significant overlap of the Lck-I-downregulated genes with Nanog-targeted genes (red) (p < 3.5 × 10^–4 calculated by the hypergeometric test and adjusted by the Bonferroni correction)