Journal: iScience

Article Title: Patient-derived organoid xenografts model esophageal cancer cachexia and enable assessment of anti-inflammatory drug repositioning

doi: 10.1016/j.isci.2026.114638

Figure Lengend Snippet: Macrophage-targeted therapy (PLX3397) alleviates cachexia in PDOX models (A) Flow cytometry analysis of dissociated PDOX tumors from solvent-treated control and PLX3397-treated mice, identifying macrophages as H-2Kd+ and F4/80+. The quantitative summary (right) confirms significant macrophage depletion by PLX3397. (B) Immunohistochemistry (IHC) staining for macrophage markers Cd68 and Cd206, illustrating a reduction in total and M2-like macrophages following PLX3397 treatment. (C) RT-qPCR analyses of bulk RNA from tumor and host tissues, confirming decreased expression of macrophage-related markers post-treatment. (D) Functional evaluation of PLX3397’s anti-cachexia efficacy in ET1, ET3, ET13, and ET24 PDOX lines, demonstrating improved body weight and forelimb grip strength in PLX3397-treated mice (orange) relative to controls (blue).

Article Snippet: • Pexidartinib (PLX3397): PLX3397 (MedChemExpress) was prepared in the same vehicle as above.

Techniques: Flow Cytometry, Solvent, Control, Immunohistochemistry, Quantitative RT-PCR, Expressing, Functional Assay

Journal: iScience

Article Title: Patient-derived organoid xenografts model esophageal cancer cachexia and enable assessment of anti-inflammatory drug repositioning

doi: 10.1016/j.isci.2026.114638

Figure Lengend Snippet: PLX3397 reduces inflammation and preserves adipose tissue integrity in PDOX-bearing mice (A) Representative images of inguinal adipose tissue from ET24-bearing mice, showing reduced wasting in PLX3397-treated mice compared with controls. Images were selected to illustrate the representative phenotype, excluding extreme outliers. (B) Quantitative summary of inguinal adipose tissue sizes after PLX3397 treatment across PDOX models: (control = 79333, 95% CI [52111–106556]; PLX3397 = 124900, 95% CI [101700–148100]). (C) Evaluation of the anti-tumor efficacy of PLX3397, showing minimal effects on tumor size in treated (orange) versus control (blue) groups. (D) Plasma IL-6 cytokine levels measured by ELISA, illustrating reduced systemic inflammation in PLX3397-treated mice (ET1 and ET13): NTB = 22.72, 95% CI [14.82–30.62]; ET1 Control = 66.3, 95% CI [46.58–86.02]; ET1 PLX3397 = 25.22, 95% CI [18.29–32.16]; ET13 Control = 110.14, 95% CI [50.06–170.22]; ET13 PLX3397 = 38.18, 95% CI [30.53–45.82]. (E) Plasma GDF15 cytokine levels (ELISA) significantly reduced following PLX3397 treatment: control = 3.10, 95% CI [2.75–3.45]; PLX3397 = 2.60, 95% CI [2.44–2.77]. (F) RT-qPCR analysis revealing reduced expression of cachexia-related genes Tnf in tumor, Prplah/Atgl in adipose tissue, Il1a and Il1b in liver, and Tgfb in brain tissues post-PLX3397 treatment, indicative of systemic anti-inflammatory effects. (G) Representative H&E images showing histopathological differences in adipose tissue between PLX3397-treated and control mice. Control mice displayed adipocyte necrosis, marked inflammatory infiltration, and multilocular adipocytes with small lipid droplets, whereas treated mice showed preserved adipose morphology. Scale bars, 100 μm . (H) Gene set enrichment analysis (GSEA) using Gene Ontology Biological Process pathways, indicating significant downregulation of macrophage-associated and cachectic cytokine receptor signaling pathways (IL-1β, IL-6, IL-10, TNF) in PLX3397-treated mice relative to controls, suggesting reduced macrophage-driven inflammatory signaling. Results shown as mean ± 95% CI. Statistical significance is labeled as: ###, adjusted p value < 0.01, ##, adjusted p value < 0.01; #, adjusted p value < 0.05; ∗∗∗, p value < 0.001; ∗∗, p value < 0.01; ∗, p value < 0.05; marginally significant (ms), p value < 0.1; n.s., not statistically significant.

Article Snippet: • Pexidartinib (PLX3397): PLX3397 (MedChemExpress) was prepared in the same vehicle as above.

Techniques: Control, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, Quantitative RT-PCR, Expressing, Protein-Protein interactions, Labeling