Fig 1: Human plasma and mouse serum studies Chemokine expressions in the BOECs treated with autologous plasma. Fold changes in gene expressions of CXCL10, CXCL11, CXCL12, CCL20, and CX3CL1 in NAFLD (n = 10) BOECs were normalized to healthy (n = 12) BOECs. Results are indicated by mean ± SD. *P < 0.05; **P < 0.01; ****P < 0.0001; ns—not significant (Mann–Whitney test).Plasma concentrations of CXCL10 and CXCL12 in healthy and NAFLD subjects. Box-whisker plots indicate median (middle line), 25th, 75th percentile (box), and the lowest/highest data points (whiskers). ns—not significant (Mann–Whitney test).Serum CXCL12 concentrations of wild-type C57BL/6J mice placed on LIDPAD or control diet for 12 and 16 weeks (n = 5 mice), determined by ELISA. Data presented as box-whisker plots of median (middle line), 25th, 75th percentile (box), and the lowest/highest data points (whiskers). ns—not significant (two-way ANOVA).
Fig 2: Antitumor acitivity of crizotinib combined with anlotinib in H3122CR-derived xenograft model. A Schematic diagram of anlotinib reversing crizotinib resistance by inhibition of angiogenesis via JAK2/STAT3-CCL20-VEGFA/IL6 axis; B Inhibition effect of anlotinib combined with crizotinib on H3122CR compared with anlotinib or crizotinib monotherapy; C Timeline of the treatment in mice; D Measurements of subcutaneous tumor volumes in the control, crizotinib monotherapy, anlotinib monotherapy, and crizotinib combined with anlotinib groups (n = 24); E Tumors were obtained after mice were sacrificed on Day 26; F Measurement of tumor weight at the end of the experiment; G Body weight growth curves of nude mice during the treatment; H Body weight minus tumor weight was analyzed at the end of the experiment. *p < 0.05, **p < 0.01, ***p < 0.001, ns not significant
Fig 3: CCL20 and CCL24 involved in crizotinib resistance. A 10 chemokines mRNA expression in H3122CR compared with H3122 (Control); B 4 chemokines protein expression in H3122 and H3122CR cell supernatants; C The mRNA and protein expression of 4 chemokines after si-RNA treatment compared with si-negative control (si-NC); D–F Effect of CCL2, CCL20, CCL24, and CX3CL1 knockdown on (D) cell proliferation of H3122CR; (E) cell cycle distribution of H3122CR; F half maximal inhibitory concentration (IC50) of crizotinib in H3122CR. * p < 0.05, ** p < 0.01, *** p < 0.001, ns: not significant
Fig 4: CCL20 may induce crizotinib resistance by activation of angiogenesis via JAK2/STAT3-CCL20-VEGFA/IL6 axis. A a) Tube formation of HUVECs cultured in H3122 culture medium (CM), H3122CR CM, H3122 CM supplemented with human recombinant CCL20, and H3122 CM supplemented with rhCCL24. b) Tube formation of HUVECs cultured in the CM of H3122CR transfected with si-negative control (si-NC), si-CCL20, and si-CCL24. The number of tubes and capillary length were analyzed to evaluate angiogenic activity of CCL20 and CCL24; B, C Knockdown of CCL20 suppressed the protein expression of CCL2, IL6, and VEGFA in H3122CR compared with si-NC (Control); D STAT3 was upregulated in H3122CR compared with H3122; E, F Stattic inhibited the JAK2/STAT3 pathway and the protein expression of CCL20 and VEGFA in H3122CR. GAPDH served as a loading control. *p < 0.05, **p < 0.01, ***p < 0.001, ns not significant
Fig 5: Plasma chemokines reflect and predict crizotinib response in EML4-ALK positive non-small cell lung cancer patients. A Forest plots of multivariant COX analysis results for progression-free survival (PFS) and overall survival (OS); B Kaplan–Meier curves of PFS and OS for CCL20 concentration; C Heatmap of 7 significant chemokines between patients with PFS shorter than 6 months (NR, n = 32) and longer than 12 months (R, n = 15); D Box plots of 7 significant chemokines expression comparing responders (R, n = 15) and non-responders (NR, n = 32); E Plasma CCL20 and CCL15 levels in baseline samples and samples after disease progression (PD)
Supplier Page from Abcam for Human MIP-3 alpha ELISA Kit (CCL20)