Fig 2: Anticancer effect of anticarin-β in PDX models of OS. (A) Ex vivo 3D assay using primary cells isolated from 3 PDX models of OS: SA3849 (post-chemotherapy), SA4061 (post-radiation), and SA4062 (lung metastasis). Dose–response curves of the inhibitory effect by dapagliflozin and anticarin-β are shown. (B, C) Small pieces (approximately 2–3 mm in diameter) PDX model SA4062 tumors were inoculated subcutaneously at the upper right flank region into NOD/SCID (n = 6, B) or NCG (n = 8, C) mice for tumor development. Groups were randomized when tumor volume reaches 100–150 mm3 and dosing was initiated at the same time. For peripheral blood mononuclear cell (PMBC) group (C), when mean tumor volume reaches 50–80 mm3, PBMC were inoculated. Mice were treated daily by intramuscular injection (i.m.) of vehicle control (100 μL) or anticarin-β (5 mg/kg), beginning 23 days after allograft. Graph indicates tumor growth by volume (W2 × L), assessed three times a week. Inset, image of tumors. Two-way t-test analysis of variance. Data represent mean ± SD, scale bars, 1 cm. ∗∗∗∗P < 0.0001, ∗∗∗P < 0.001. (D) Tumors from mice treated with anticarin-β or solvent were subjected to Western analysis for cleaved PARP (Clv-PARP), p-STAT3, and STAT3. The intensity of each band was quantified using ImageJ. The data are presented as mean ± SD, n = 6; ∗∗P < 0.01, ∗P < 0.05. (E) Tumors from NCG mice treated with PBMC + anticarin-β or PBMC + solvent were subjected to immunofluorescence analysis for CD3, CD68, and CD56. Anticarin-β significantly increased the infiltration of immune cells into tumor tissue. The data are presented as mean ± SD, ∗P < 0.05, ∗∗P < 0.01. Scale bar, 200 μm.

Fig 3: Efficacy of ICAM-1 CAR T Cells in an Intraperitoneal Xenograft Model(A) Whole-body bioluminescence image of SNU-638-engrafted NSG mice without treatment (no T), or treated with non-transduced T (NT) or low or high doses (LD or HD) of ICAM-1 CAR T cells. Mice were treated with T cells 5 days after tumor xenograft either by intravenous or intraperitoneal injection. LD, 1 × 106 CAR T cells; HD, 10 × 106 CAR T cells. (B) Quantitation of total body bioluminescence intensity. Data represent mean ± SD (n = 2–3). (C) Bioluminescence intensities on day 33 following xenograft. LD and HD cohorts were pooled for analysis. An unpaired, two-tailed t test was used for statistical comparisons. ∗p < 0.05, ∗∗p < 0.01. ns, not significant. (D) Kaplan-Meier survival curves. (E) Summary of body weight changes over time. Data represent mean ± SD (n = 2–3). (F) GFP images of tumors and gastrointestinal tracts acquired on day 85 post-xenograft. (G) Histologic images of H&E staining, GFP IHC, and CD3 IHC of tumor or spleen from mice treated with ICAM-1 CAR T cells.

Fig 4: Anti-PD-L1 antibody combined with radiotherapy facilitates T cell immune response in miR-21+/+ mice in vivo. miR-21+/+ mice were either treated or not treated with radiotherapy or radiotherapy+anti-PD-L1 antibody. (a) The number of CD3+CD8+ cells in the peripheral blood of miR-21+/+ mice following different treatment protocols detected by flow cytometry. (b) T lymphocyte apoptosis rate in peripheral blood of miR-21+/+ mice following different treatment protocols measured using Annexin V-FITC/PI. (c) Levels of IL-2 in the peripheral blood of miR-21+/+ mice following different treatment protocols measured using ELISA. (d) Levels of IFN-γ in peripheral blood of miR-21+/+ mice following different treatment protocols measured using ELISA. ∗p < 0.05 compared with miR-21+/+ mice without treatment; #p < 0.05 compared with miR-21+/+ mice treated with radiotherapy or anti-PD-L1 antibody. Each sample was evaluated three times independently. Data (mean ± standard deviation) from two groups were compared using independent sample t-test. The experiments were repeated 3 times independently.

Fig 5: PINK1 enhances the anti-inflammatory effect of BMSCs on the kidneys of IRI-AKI mice. a Representative image of immunohistochemical staining. × 400 and × 200, BAR: 100 μm. b CD3-positive cell counts (n = 6). c CD14-positive cell counts (n = 6). d CD20-positive cell counts (n = 6). e CD68-positive cell counts (n = 6). f Relative changes in the expression of IL-10 in peripheral blood (n = 6). g Relative changes in the expression of TNF-α in peripheral blood (n = 6). SEM, ###p < 0.001, ##p < 0.01 and #p < 0.05, compared with the IRI group; ***p < 0.001, **p < 0.01 and *p < 0.05, compared with among the groups