Journal: Biomaterials

Article Title: Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials

doi: 10.1016/j.biomaterials.2025.123097

Figure Lengend Snippet: CO exposure increases MHC-I and PD-L1 expression in pancreatic cancer cells. Human and mouse pancreatic cancer cell lines were exposed to CO in the air at a concentration of 250 ppm for 48 hours before being harvested for analysis of gene and protein expression. (A) Log 10 -fold change in RNA levels for antigen processing and presentation proteins, MHC-I molecules, and PD-L1 in human pancreatic cancer cells (Panc1) exposed to CO relative to air. Data are means ± standard deviation. CO-treated samples; n=3; air-treated samples, n=3. (B) Gene set enrichment analysis of pathways that promote immunotherapy response and were upregulated in human pancreatic cancer cells (Panc1) exposed to CO relative to those exposed to air. Data are means ± standard deviation; CO-treated samples; n=3; air-treated samples, n=3. (C) Western blots from cell lysates obtained from human pancreatic cancer cells (Panc1) or mouse pancreatic cancer cells (KPC) exposed to CO or air. β-actin served as a loading control. (D) Flow cytometric analysis of Panc1 or KPC cells exposed to CO or air in the presence or absence of increasing concentrations of IFN-γ. Cells were analyzed for expression of MHC-I (HLA in humans; H2Kb in mice) or PD-L1. Results represent the mean ± standard deviation of 3 independent experiments. *, P<0.05; **, P<0.01; ***, P < 0.001; Panc1 with CO + IFN-γ, n=8; Panc1 with air + IFN-γ, n=8; KPC with CO + IFN-γ, n=8; KPC with air + IFN-γ, n=8; P values were determined by unpaired t-test.

Article Snippet: To generate syngeneic tumors, 3 × 10 6 KPC cells were injected into the right flank of C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA).

Techniques: Expressing, Concentration Assay, Standard Deviation, Western Blot, Control

Journal: Biomaterials

Article Title: Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials

doi: 10.1016/j.biomaterials.2025.123097

Figure Lengend Snippet: Enhanced anti-tumor effects for combined treatment with CO-GeMs and ICIs. (A) Volumes and weights of subcutaneous allograft pancreatic tumors. Once tumors reached a volume of approximately 100 mm 3 mice received intratumoral injection of CO-GeMs and anti-PD-1 antibody, alone and in combination, or with IgG control. Results represent the mean ± standard deviation of 7 mice/group. Statistical analysis on day 19 post initiation of treatment. *, P<0.05; **, P<0.01; ***, P < 0.001; P values determined by one-way ANOVA. (B) Representative immunohistochemical staining for CD8 and CD45 in tumors treated with anti-PD-1 antibody with or without CO-GeM exposure in mice treated as in (A). (C) Quantification of CD8+ and CD45+ cells in subcutaneous allograft tumors from mice treated as in (A). The results represent the mean ± standard deviation of 10 images/group. NS, not significant; *, p < 0.05, ***, P <0.001. P values were determined by one-way ANOVA. (D) Luciferase emission as determined by bioluminescence imaging and Kaplan-Meier survival curves of allograft hepatic metastases induced in C57BL/6J mice using luc-expressing KPC cells. Results represent mean ± standard deviation of 5–7 mice/group. IgG control, n=5; CO, n=6; anti-PD-1, n=7; anti-PD-1 + CO, n=7. P values were determined by one-way ANOVA. NS, not significant; *, p < 0.05; **, p < 0.01.

Article Snippet: To generate syngeneic tumors, 3 × 10 6 KPC cells were injected into the right flank of C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA).

Techniques: Injection, Control, Standard Deviation, Immunohistochemical staining, Staining, Luciferase, Imaging, Expressing

Journal: Nature Communications

Article Title: Metabolic characterization of the tumor microenvironment orchestrates therapeutic strategies and clinical outcomes in pancreatic cancer

doi: 10.1038/s41467-026-73702-z

Figure Lengend Snippet: A Cellular proportions of each TMS subtype, with immune cells and fibroblast fractions shown (mean ± SD, N = 148/116/196, p < 0.0001). B Venn diagram of intersecting metabolic features from metabolomic and transcriptomic analyses. C Ferroptosis-associated metabolic fluxes, pathways ( N = 148/312), and metabolites ( N = 75/115) between TMS1 and non-TMS1 (median, 25th–75th percentiles). D Enrichment of glutathione metabolism genes in TMS1 PDACs. E GSH/GSSG ratios between TMS1 ( N = 75) and non-TMS1 ( N = 115) PDACs (mean, 95% CI, p < 0.0001). F Normalized scores for glutathione, BH4, complex I-IV, CoQ10, fatty acids, and membrane lipids between TMS1 ( N = 148) and non-TMS1 ( N = 312) PDAC subtypes (mean ± SD). G GSH/GSSG ratios in organoids from TMS1 and non-TMS1 PDACs (mean ± SD, n = 3, biological replicates, p < 0.0001). Heatmap of fold change in MDA concentration before and after RSL-3 treatment. H Drug sensitivity (relative IC50) of five common PDAC chemotherapy regimens for TMS1 and non-TMS1 subtypes. I Workflow for calculating drug sensitivity using snRNA-seq data. Relative IC50 values for drugs in TMS1 ( N = 4) vs non-TMS1 PDAC cells ( N = 5). J Workflow for generating drug-resistant MIA PaCa-2 and KPC-0116 cells and comparing IC50 ratios to their parental cells. K GPX4 expression in resistant vs parental cells (loading control: β-actin). L Deregulation of ferroptosis-related proteins in chemotherapy-treated PDACs. M Workflow for generating PDPPCs (patient-derived primary PDAC cells) and drug sensitivity testing. N Synergy scores (ZIP method, mean ± SD, two-sided) for RSL-3 plus paclitaxel in TMS1 ( N = 7) and non-TMS1 ( N = 16) PDPPCs. O Bright-field image and viability curve of RSL-3 (100 nM) plus paclitaxel (2 nM) in TMS1 and non-TMS1 organoids ( n = 3, biological replicates, mean ± SD, p = 0.005, p = 0.002). P Tumor size change (CT imaging) in a PDAC patient, during AG regimen treatment (maximum diameter ratios, p < 0.0001). Q Bright-field images and viability of organoids treated with paclitaxel and/or RSL-3 ( n = 3, biological replicates, mean ± SD). Significance was determined by the two-sided Wilcoxon test ( C , E , F , I ), Kruskal–Wallis test ( A ), two-sided unpaired t -test ( G , N , H , L , O ), and the one-way ANOVA with Tukey’s multiple comparisons test ( Q ). Source data are provided as a Source Data file.

Article Snippet: Drug-resistant cell lines were established from MIA PaCa-2 and KPC cells by gradually exposing them to increasing concentrations of gemcitabine (MCE, HY-17026), oxaliplatin (MCE, HY-17371), paclitaxel (MCE, HY-B0015), irinotecan (MCE, HY-16562), and 5-fluorouracil (MCE, HY-90006) .

Techniques: Metabolomic, Membrane, Concentration Assay, Expressing, Control, Derivative Assay, Imaging