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Journal: Cell Reports Medicine
Article Title: Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer
doi: 10.1016/j.xcrm.2025.102158
Figure Lengend Snippet: RNA-seq analysis identified cell cycle inhibition as a synergistic strategy for Oba01 (A and B) Venn diagram showing the number and overlap of DEGs in 4 CRC PDXs treated with Oba01 vs. vehicle. (C) Multidimensional scaling of genetic dissimilarity across the 4 PDXs. (D) KEGG of DEG profiles in Oba01-treated vs. vehicle-treated groups. (E) GSEA analysis showing signaling pathway enrichment. FDR, false discovery rate; NES, normalized enrichment score. (F) Heatmap of cell cycle-related gene transcription in Oba01-treated samples. (G) CDK4 expression in primary CRC tumors and corresponding PDXs. Scale bars, 20 μm. (H and I) Protein and mRNA expression of CDK4 in CDK4-knockdown RKO and HCT116 cells. (J) Cell viability in Oba01-treated CDK4-knockdown RKO and HCT116 cells. (K) Antitumor activity of Abem in MSS and MSI-H PDXs. Abem were orally administered once a day until the end of the experiment. Data represent the mean ± SEM of ≥3 experiments. p values from one-way ANOVA. ns, non-significant. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001.
Article Snippet:
Techniques: RNA Sequencing, Inhibition, Expressing, Knockdown, Activity Assay
Journal: Cell Reports Medicine
Article Title: Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer
doi: 10.1016/j.xcrm.2025.102158
Figure Lengend Snippet: Anti-tumor effects of Oba01 combined with Abem on advanced MSS and MSI-H CRC PDXOs (A) Schematic illustrating PDXO (O) generation from corresponding PDXs (P) for drug screening. (B) IF staining of DR5 and CDK4 in PDXOs. Scale bars, 20 μm (C) Cluster dendrogram of CRC primary tumors (T), corresponding PDXs (P), and PDXOs (O) based on WES analysis. (D and E) Somatic mutation heatmaps (D) and mutation spectrum histogram (E). (F) Organoid growth with 50 μg/mL Oba01 plus 200 nM Abem treatment. (G) Heatmap of proteomic profiling in PDXOs with indicated treatments. (H) KEGG analysis of differentially expressed proteins between vehicle and combination groups ( n = 4). (I) Protein expression of the Notch signaling pathway in treated cell lines. (J) Organoids growth following indicated treatments. Oba01, 50 μg/mL; Abem, 200 nM; FLI-06, 2 μM. Data represent the mean ± SEM of ≥3 experiments. p values from one-way ANOVA. ns, non-significant. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001.
Article Snippet:
Techniques: Drug discovery, Staining, Mutagenesis, Expressing