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Fig. 4 | Journal of Experimental & Clinical Cancer Research

Fig. 4

From: Piperlongumine conquers temozolomide chemoradiotherapy resistance to achieve immune cure in refractory glioblastoma via boosting oxidative stress-inflamation-CD8+-T cell immunity

Fig. 4

PL restores RT/TMZ-reduced ROS and augments oxidative damage in G422TN-tumor via reprograming ROS modulator genes. A Representative DHE staining of ROS levels in control, PL, RT/TMZ, RT/TMZ/PL, RT/TMZ/PL/GSH group of G422TN-mice. Upper panel: whole brain figures. Scale bar, 500 μm. Lower panel: partial graphs. Scale bar, 100 μm. (n = 3). B Statistical analysis of ROS levels in control, PL, RT/TMZ, RT/TMZ/PL, RT/TMZ/PL/GSH group of G422TN-mice. (n = 3). C Gene expression of ROS generating and scavenging genes of all samples, the bar above the heatmap represents the group information, and the bar on the right of the heatmap represents the category of genes. D Fold changes of gene expression of ROS generating and scavenging genes in different comparison (PL treatment vs. control, top) and (RT/TMZ/PL treatment vs. control, bottom). E qRT-PCR showing the mRNA expression of ROSgen (Duox2, Duox1, Ncf1, Ncf2) and ROSsca signature genes (Gpx2, Txnrd2, Gpx3, Fth1). (n = 3). F Enrichment plot of ranked genes illustrating the enrichment of oxidative stress in different condition including PL treatment vs. control, RT/TMZ treatment vs. control, and RT/TMZ/PL treatment vs. control. G The heatmap of genes related to oxidative stress. H and I Patient survival in high oxidative signature group vs. low oxidative signature group of TCGA (H) LGG&GBM dataset, and CGGA (I) LGG&GBM dataset. J The boxplot illustrating ssGSEA score of the oxidative signature induced by RT/TMZ/PL treatment in different glioma types of TCGA dataset (Student’s t-tests). K The boxplot illustrating ssGSEA score of the oxidative signature induced by RT/TMZ/PL treatment in different GBM subtypes of TCGA dataset (Student’s t-tests). L and M Correlation between Duox2 expression and the oxidative damage signature in bulk RNA sequencing data of animal models (L), and of CGGA database (M). (*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns, not statistically significant)

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