Journal: bioRxiv

Article Title: A Novel Therapeutic Approach: Notch Inhibition Enhances Radiotherapy and Checkpoint Blockade Therapy via Reprogramming of the Tumor Microenvironment

doi: 10.64898/2025.12.30.696685

Figure Lengend Snippet: (A). Tumor cells were implanted into the flank (1 x 10 6 9464D) or mammary fat pad (1 x 10 5 EO771) of C57BL/6 mice, enrolled when tumors reached 0.15-0.2mm 3 . Mice were treated as per the schema and sacrificed when tumors reached a size 1.5cm 3 . (B) The Kaplan-Meier survival curve of mice and tumor volume growth curve of 9464D tumor. Median Survival: Control 12d; IgG 10d; GSI 10d; aPD-1 10d; aPD-1+ GSI 10d; RT 37d; RT+ GSI 50d; RT+aPD-1 46d; RT+aPD-1+AL101 87d. Curve comparison by Log-rank (Mantel-Cox) test. P<0.0001. (C) The Kaplan-Meier survival curve of mice and tumor volume growth curve of EO771 tumor Median Survival: Control: 14d; IgG 14.5d; GSI 18.5d; aPD-1 15d; GSI+aPD-1 10d; RT 35d; RT+ GSI 41d; RT+aPD-1 43d; RT+aPD-1+ GSI 98.5d. Curve comparison by Log-rank (Mantel-Cox) test. P<0.0001. (D) Lungs were collected from EO771 tumor–bearing mice (n = 4–7 per group) treated as described above and sacrificed either at day 10 or at the survival endpoint. Tumor metastases were quantified using HALO image analysis, calculated as metastatic area divided by total lung area. Bars represent mean ± SD. *P<0.05, using one-way ANOVA followed by Tukey post-hoc comparisons.

Article Snippet: EO771 cells (purchased from ATCC) and the 9464D cells (derived from a TH-MYCN transgenic neuroblastoma mouse, obtained as a gift from Dr.

Techniques: Control, Comparison

Journal: bioRxiv

Article Title: A Novel Therapeutic Approach: Notch Inhibition Enhances Radiotherapy and Checkpoint Blockade Therapy via Reprogramming of the Tumor Microenvironment

doi: 10.64898/2025.12.30.696685

Figure Lengend Snippet: (A) UMAPs showing M1-like and M2-like macrophage states across treatments in 9464D tumor scRNA-seq. (B) Proportion of M1- and M2-like macrophages by treatment group (C) Expression of classical M1 (Il1b, Tnf) and M2 (Mrc1, Mgl2) markers. (D) M-MDSC module scores increase following RT + aPD-1 + GSI (E) Changes in the proportion of M1 and M2 macrophages subpopulation and Myeloid-derived suppressor cells (MDSC) subpopulations by flow cytometry in 9464D tumor (F) Changes in the proportion of M1 and M2 macrophages subpopulation and MDSC subpopulations by flow cytometry in EO771 tumor. Bars represent the mean. Each dot represents one animal. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 using one-way ANOVA followed by Tukey post-hoc comparisons.

Article Snippet: EO771 cells (purchased from ATCC) and the 9464D cells (derived from a TH-MYCN transgenic neuroblastoma mouse, obtained as a gift from Dr.

Techniques: Expressing, Derivative Assay, Flow Cytometry

Journal: bioRxiv

Article Title: A Novel Therapeutic Approach: Notch Inhibition Enhances Radiotherapy and Checkpoint Blockade Therapy via Reprogramming of the Tumor Microenvironment

doi: 10.64898/2025.12.30.696685

Figure Lengend Snippet: (A) Triple therapy enhances DC activation and antigen-presentation gene expression in 9464D tumor scRNA-seq. (B) Changes in the proportion of DC and CD103+DC proportion by flowcytometry in 9464D tumor. (C) Changes in the proportion of DC and CD103+DC proportion by flowcytometry in EO771 tumor. Bars represent mean, each dot represents one animal. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 using one-way ANOVA followed by Tukey post-hoc comparisons.

Article Snippet: EO771 cells (purchased from ATCC) and the 9464D cells (derived from a TH-MYCN transgenic neuroblastoma mouse, obtained as a gift from Dr.

Techniques: Activation Assay, Immunopeptidomics, Gene Expression

Journal: bioRxiv

Article Title: A Novel Therapeutic Approach: Notch Inhibition Enhances Radiotherapy and Checkpoint Blockade Therapy via Reprogramming of the Tumor Microenvironment

doi: 10.64898/2025.12.30.696685

Figure Lengend Snippet: 9464D cells or EO771 were implanted into NCr nude mice and treated per the schema in . Mice were sacrificed when tumors reached a size >1.5 cm 3 . (A) The Kaplan-Meier survival curve of mice and tumor volume growth curve of athymic nude mice 9464D tumor. (B) The Kaplan-Meier survival curve of mice and tumor volume growth curve, as well as lung metastasis of athymic nude mice EO771 tumor. Comparison by Log-rank (Mantel-Cox) test and one-way ANOVA.

Article Snippet: EO771 cells (purchased from ATCC) and the 9464D cells (derived from a TH-MYCN transgenic neuroblastoma mouse, obtained as a gift from Dr.

Techniques: Comparison

Journal: Materials Today Bio

Article Title: Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1

doi: 10.1016/j.mtbio.2025.102492

Figure Lengend Snippet: MDSCs promoted migration and invasion of HR + breast cancer cells (A-B) Volcano plot and KEGG analysis of significantly regulated genes in MDSCs high within the TCGA BC cohort (n = 676). (C) GSEA enrichment plot for the epithelial-mesenchymal transition pathway in patients with high MDSCs infiltration in the TCGA BC cohort. (D–F) Distribution of FPKM values for three EMT-related genes in the TCGA BC cohort between MDSCs high and MDSCs low groups. (G) Schematic illustration of co-incubation of MDSCs and E0771 cells. (H) Transwell assays were conducted to assess migration and invasion of HR + breast cancer cells (E0771) after co-culturing with MDSCs. (I–J) The mRNA and protein abundances of E-cadherin, Snail, and Slug in E0771 cells were evaluated using qRT-PCR and Western blot following co-cultivation with MDSCs. n = 3. Data represents mean ± SD. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001002E

Article Snippet: The E0771 cell (ATCC, CRL-3461) was sourced from the American Type Culture Collection and maintained in DMEM media, supplemented with 10 % fetal bovine serum.

Techniques: Migration, Incubation, Quantitative RT-PCR, Western Blot

Journal: Materials Today Bio

Article Title: Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1

doi: 10.1016/j.mtbio.2025.102492

Figure Lengend Snippet: The MDSCs-derived exosomal miR-155-5p promoted migration and invasion of breast cancer cells (A) Schematic illustration of co-incubation of MDSC-derived exosomes (MDSCs-exo) and E0771 cells. (B) Transwell assays to evaluate migration and invasion capacity of E0771 cells after co-culturing with MDSC-derived exosomes. (C–D) The mRNA and protein levels of E-cadherin, Snail, and Slug in E0771 after co-culturing with MDSC-derived exosomes were assessed by qRT-PCR and Western blot. n = 3. (E) Volcano plot showing significantly regulated miRNAs in MDSCs high from the TCGA BC cohort (n = 676). (F–G) The 11 significantly upregulated miRNAs in MDSCs high breast cancer samples were determined by qRT-PCR in E0771 cells co-cultured with MDSC-derived exosomes. (H) Pre-treatment of MDSCs with GW4869 prior to co-culture significantly reduced miR-155-5p levels in E0771 cells. n = 3. (I) The miR-155-5p mimics (50 nM) significantly enhanced migration and invasion of E0771 cells. (J–K) qRT-PCR and Western blot was used to assess the mRNA and protein levels of miR-155-5p, E-cadherin, Snail, and Slug in E0771 cells after transfection of miR-155-5p mimics. n = 3. Data represents mean ± SD. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001.

Article Snippet: The E0771 cell (ATCC, CRL-3461) was sourced from the American Type Culture Collection and maintained in DMEM media, supplemented with 10 % fetal bovine serum.

Techniques: Derivative Assay, Migration, Incubation, Quantitative RT-PCR, Western Blot, Cell Culture, Co-Culture Assay, Transfection

Journal: Materials Today Bio

Article Title: Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1

doi: 10.1016/j.mtbio.2025.102492

Figure Lengend Snippet: miR-155-5p promoted migration and invasion of breast cancer cells by directly inhibiting SIRT1 (A) Venn diagram showing potential miR-155-5p target genes by TargetScan and miRTarBase. (B–E) TRPS1, SIRT1, MYB and RCOR1 exhibit marked downregulation in miR-155-5p high group from the TCGA BC cohort (n = 676). (F–H) qPCR and Western blot confirmed that miR-155-5p mimics and inhibitor significantly regulate the expression level of SIRT1. n = 3. (I–J) Dual-luciferase assay verified direct binding of miR-155-5p to the 3′-UTR of SIRT1. n = 3. (K) Transwell assays were conducted to evaluate how SIRT1 overexpression modulates the metastatic potential of miR-155-5p mimic-transfected E0771 cells. (L) The mRNA changes of EMT-related markers after SIRT1 overexpression in E0771 cells transfected with miR-155-5p mimics were detected by qPCR. n = 3. Data represents mean ± SD. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001.

Article Snippet: The E0771 cell (ATCC, CRL-3461) was sourced from the American Type Culture Collection and maintained in DMEM media, supplemented with 10 % fetal bovine serum.

Techniques: Migration, Western Blot, Expressing, Luciferase, Binding Assay, Over Expression, Transfection

Journal: Materials Today Bio

Article Title: Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1

doi: 10.1016/j.mtbio.2025.102492

Figure Lengend Snippet: SIRT1 deficiency was detected in MDSCs high HR + breast cancer tissues and promoted the EMT process (A) SIRT1 was downregulated in MDSCs high breast cancer tissues of TCGA BC cohort (n = 676). (B–C) qPCR and Western blot confirmed the mRNA and protein levels of EMT-related markers after SIRT1 overexpression in E0771 cells co-cultured with MDSCs. n = 3. (D) Transwell assays to detect the effects of SIRT1-overexpression on migration and invasion of E0771 cells co-cultured with MDSCs. n = 3. (E–F) Representative mIHC images and quantification analysis showed the expression of SIRT1 and Snail in human breast tissue samples fron Xinchao BC cohort (n = 67), as well as T cell infiltration. Data represents mean ± SD. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001.

Article Snippet: The E0771 cell (ATCC, CRL-3461) was sourced from the American Type Culture Collection and maintained in DMEM media, supplemented with 10 % fetal bovine serum.

Techniques: Western Blot, Over Expression, Cell Culture, Migration, Expressing

Journal: Materials Today Bio

Article Title: Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1

doi: 10.1016/j.mtbio.2025.102492

Figure Lengend Snippet: MDSCs promoted the growth and EMT of PIK3CA MUT HR + breast cancer via activating the miR-155-5p/SIRT1 axis (A) In the TCGA BC cohort (n = 676), elevated MDSC infiltration showed a positive association with PIK3CA mutations. (B) High MDSC infiltration combined with PIK3CA MUT revealed increased miR-155-5p expression in the TCGA BC cohort. (C) The mRNA levels of miR-155-5p, SIRT1 and EMT-related markers in PIK3CA MUT HR + breast cancer cells after co-culturing with MDSCs. n = 3. (D) Western blot analysis of SIRT1 and EMT-related markers in PIK3CA MUT HR + breast cancer cells after co-culturing with MDSCs. (E–G) General view of tumor volume, tumor weight, body weight from mice bearing PIK3CA WT and PIK3CA MUT E0771 xenografts (n = 3) treated with PBS and cobomarsen. (H–I) The mRNA level of miR-155-5p and the protein levels of SIRT1 and EMT-related markers in the above groups. Data represents mean ± SD. ∗∗ P < 0.01, ∗∗∗ P < 0.001.

Article Snippet: The E0771 cell (ATCC, CRL-3461) was sourced from the American Type Culture Collection and maintained in DMEM media, supplemented with 10 % fetal bovine serum.

Techniques: Expressing, Western Blot

Journal: Materials Today Bio

Article Title: Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1

doi: 10.1016/j.mtbio.2025.102492

Figure Lengend Snippet: TME-responsive polymeric micelles cobomarsen@alpelisib-MSPM was synthesized and characterized (A) Schematic illustration for the preparation process for cobomarsen@alpelisib-MSPM. (B–D) Particle size distribution, TEM image and Zeta potential of alpelisib@MSPM, cobomarsen@MSPM and cobomarsen@alpelisib-MSPM. n = 3. Scale bar: 100 nm. (E) Cumulative release curve of alpelisib from alpelisib@MSPM at different pH values in vitro . n = 3. (F) The expression of miR-155-5p in PIK3CA MUT E0771 cells after treated with different concentrations of cobomarsen@MSPM. n = 3. (G) The viability of E0771 cells following treatment with NC@MSPM. n = 3. Data represents mean ± SD.

Article Snippet: The E0771 cell (ATCC, CRL-3461) was sourced from the American Type Culture Collection and maintained in DMEM media, supplemented with 10 % fetal bovine serum.

Techniques: Synthesized, Zeta Potential Analyzer, In Vitro, Expressing

Journal: Materials Today Bio

Article Title: Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1

doi: 10.1016/j.mtbio.2025.102492

Figure Lengend Snippet: Cobomarsen@alpelisib-MSPM suppressed tumor growth and reversed MDSCs-related TME remodeling by inhibiting the activation of miR-155-5p/SIRT1 axis in PIK3CA MUT HR + breast cancer (A) Schematic illustration of the therapy process in vivo . (B–F) General view of tumor mass, tumor volume, tumor weight, tumor inhibition ratio and body weight from mice bearing PIK3CA MUT E0771 xenografts (n = 3) treated with PBS, alpelisib, cobomarsen, alpelisib + cobomarsen, alpelisib@MSPM, cobomarsen@MSPM and cobomarsen@alpelisib-MSPM. (G–H) Percentage of MDSCs and CD3 + CD8 + T cells in the above groups. n = 3. (I–J) The mRNA and protein levels of miR-155-5p, SIRT1 and EMT-related markers in the above groups. n = 3. Data represents mean ± SD. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001.

Article Snippet: The E0771 cell (ATCC, CRL-3461) was sourced from the American Type Culture Collection and maintained in DMEM media, supplemented with 10 % fetal bovine serum.

Techniques: Activation Assay, In Vivo, Inhibition

Journal: Advanced Science

Article Title: Mapping the Tissue‐of‐Origins of Mesenchymal Stromal Cells in Injury Repair

doi: 10.1002/advs.202509533

Figure Lengend Snippet: BM‐MSC‐derived myofibroblasts or CAFs were not detected in distal tissue fibrosis or tumors. A) Confocal imaging of kidney sections from normal and UUO‐induced renal fibrotic Pdgfra creER ;Sp7 dre ;R26 ZT1 mice treated with tamoxifen at 2 months old. Myofibroblasts were indicated with anti‐Col1 antibody staining. B) Confocal imaging of lung sections from normal and bleomycin‐induced pulmonary fibrotic Pdgfra creER ;Sp7 dre ;R26 ZT1 mice treated with tamoxifen at 2 months old. Myofibroblasts were indicated with anti‐Col1 antibody staining. C) Confocal imaging of liver sections from normal and CCl 4 ‐induced liver fibrotic Pdgfra creER ;Sp7 dre ;R26 ZT1 mice treated with tamoxifen at 2 months old. Myofibroblasts were indicated with anti‐Col1 antibody staining. D) Confocal imaging of liver sections from normal and DDC‐induced liver fibrotic Pdgfra creER ;Sp7 dre ;R26 ZT1 mice treated with tamoxifen at 2 months old. Myofibroblasts were indicated with anti‐Col1 antibody staining. E–H) Quantification of the percentages of DAPI + Col1 + myofibroblasts that were ZsGreen + and tdTomato + in renal fibrosis (E), pulmonary fibrosis (F), CCl 4 ‐induced liver fibrosis (G) and DDC‐induced liver fibrosis (H). n = 5 mice from 4 independent experiments. I) Confocal imaging of E0771‐induced subcutaneous tumors from Pdgfra creER ;Sp7 dre ;R26 ZT1 mice treated with tamoxifen at 2 months old. Cancer associated fibroblasts (CAFs) were indicated with anti‐Col1 antibody staining. J) Confocal imaging of normal colons and AOM/DSS‐induced colorectal cancer from Pdgfra creER ;Sp7 dre ;R26 ZT1 mice treated with tamoxifen at 2 months old. CAFs were indicated with anti‐Col1 antibody staining. K,L) Quantification of the percentages of DAPI + Col1 + CAFs that were ZsGreen + and tdTomato + in subcutaneous tumors (K) and colorectal cancer (L). n = 3 mice from 3 independent experiments.

Article Snippet: The E0771 mouse breast cancer cell line (CRL‐3461, RRID:CVCL_GR23) was obtained from the American Tissue Type Collection (ATCC) in 2018.

Techniques: Derivative Assay, Imaging, Staining