non obese diabetic  (Charles River Laboratories)

Journal: iScience

Article Title: Selective inhibition of ALDH1A3 impedes breast cancer growth and metastasis by blocking ALDH1A3-driven transcriptional programs

doi: 10.1016/j.isci.2026.114863

Figure Lengend Snippet: IP pharmacokinetics of CLM296 in female NOD-SCID mice (A and B) CLM296 serum concentrations versus time curve and PK parameters in female NOD-SCID mice treated with a single dose of 4 mg/kg CLM296 administered via IP injection and collected at set time points. Each point represents an individual mouse ( n = 4 per time point). (C) CLM296 organ concentrations versus time curve in female NOD-SCID mice treated with a single dose of 4 mg/kg CLM296 administered via IP injection. Each point represents an individual mouse ( n = 4 per time point). (D) CLM296 serum concentrations versus time curve in female NOD-SCID mice bearing MDA-MB-231 tumors with ALDH1A3 OE were treated with a single dose of 4 mg/kg CLM296 administered via IP injection. Each point represents an individual mouse ( n = 4 per time point). (E) CLM296 tumor concentrations versus time curve in female NOD-SCID mice bearing MDA-MB-231 tumors with ALDH1A3 OE with a single dose of 4 mg/kg CLM296 administered via IP injection. Each point represents an individual mouse ( n = 4 per time point). (F) CLM296 organ concentrations versus time curve in female NOD-SCID mice bearing MDA-MB-231 tumors with ALDH1A3 OE treated with a single dose of 4 mg/kg CLM296 administered via IP injection. Each point represents an individual mouse ( n = 4 per time point).

Article Snippet: Six to 12-week-old female non-obese diabetic severe combined immunodeficient (NOD-SCID) female mice (Charles River Laboratories, Senneville, QC) were used for all in vivo experiments.

Techniques: Drug discovery, Injection

Journal: iScience

Article Title: Selective inhibition of ALDH1A3 impedes breast cancer growth and metastasis by blocking ALDH1A3-driven transcriptional programs

doi: 10.1016/j.isci.2026.114863

Figure Lengend Snippet: Oral pharmacokinetics of CLM296 in MDA-MB-231 ALDH1A3 OE tumor-bearing female NOD-SCID mice (A and B) CLM296 serum concentrations versus time curve in female NOD-SCID mice bearing MDA-MB-231 tumors with ALDH1A3 OE were treated with a single dose of 4 mg/kg CLM296 administered via oral gavage. Each point represents an individual mouse ( n = 4 per time point). (C) CLM296 tumor concentrations versus time curve in female NOD-SCID mice bearing MDA-MB-231 tumors with ALDH1A3 OE treated with a single dose of 4 mg/kg CLM296 administered via oral gavage. Each point represents an individual mouse ( n = 4 per time point, note that at early time points, a few of the tumor samples were below the limit of detection and so are not shown in the graph). (D) CLM296 organ concentrations versus time curve in female NOD-SCID mice bearing MDA-MB-231 tumors with ALDH1A3 OE treated with a single dose of 4 mg/kg CLM296 administered via oral gavage. Each point represents an individual mouse ( n = 4 per time point).

Article Snippet: Six to 12-week-old female non-obese diabetic severe combined immunodeficient (NOD-SCID) female mice (Charles River Laboratories, Senneville, QC) were used for all in vivo experiments.

Techniques: Drug discovery

Journal: iScience

Article Title: Selective inhibition of ALDH1A3 impedes breast cancer growth and metastasis by blocking ALDH1A3-driven transcriptional programs

doi: 10.1016/j.isci.2026.114863

Figure Lengend Snippet: CLM296 reduces ALDH1A3-mediated tumor growth and metastasis of MDA-MB-231 cells in NOD-SCID mice. (A) Tumor growth and weight of MDA-MB-231 vector control tumor-bearing female NOD-SCID mice treated with 0 mg/kg ( n = 9), 0.4 mg/kg CLM296 ( n = 10), or 4 mg/kg CLM296 ( n = 10), or ALDH1A3 OE tumor-bearing mice treated with 0 mg/kg ( n = 9), 0.4 mg/kg ( n = 10), or 4 mg/kg ( n = 9) CLM296. Treatment with CLM296 began once palpable tumors developed (indicated by the arrow, day 15) in the tumor volume plot, which demonstrates weekly caliper measurements. The tumor weight plot shows final tumor weight from the harvested tumors at endpoint. Tumor volume and weight significance were analyzed with two-way ANOVA with multiple comparisons post-test and p value < 0.05 = ∗, <0.01 = ∗∗, <0.001 = ∗∗∗, <0.0001 = ∗∗∗∗, ns, not significant. In the tumor volume graph, each point represents the mean of each group and error bars represent standard error of the mean (SEM). In the tumor weight graph, each point represents an individual mouse, and error bars represent SEM. (B) RNA extracted from the harvested tumors was analyzed via RT-qPCR for DHRS3 and RARβ expression. Significance was analyzed with two-way ANOVA with multiple comparisons post-test and p value < 0.05 = ∗, <0.01 = ∗∗, <0.001 = ∗∗∗, <0.0001 = ∗∗∗∗, ns, not significant. Each point represents an individual mouse and error bars represent SEM. (C) Body weights of the mice were measured weekly. Arrow indicates start of CLM296 IP injections. Each point represents the mean of each group and error bars represent SEM. (D) Serum creatinine and ALT of MDA-MB-231 vector control or ALDH1A3 OE tumor-bearing mice when treated daily with CLM296 via IP injection for 26 days. Significance was analyzed with two-way ANOVA with multiple comparisons post-test and p value < 0.05 = ∗, <0.01 = ∗∗, <0.001 = ∗∗∗, <0.0001 = ∗∗∗∗, ns, not significant. Each point represents an individual mouse and error bars represent SEM. (E) Transwell invasion assays were completed with vector control and ALDH1A3 OE MDA-MB-231 cells treated with or without 100 nM CLM296. FBS was used as a chemoattractant. Significance was determined by one-way ANOVA followed by Tukey’s multiple comparisons test and p value < 0.05 = ∗, <0.01 = ∗∗, <0.001 = ∗∗∗, <0.0001 = ∗∗∗∗, ns, not significant. Each point represents a separate n ( n = 6), and error bars represent SD. (F) Representative images of H&E-stained mouse lung sections from the second in vivo experiment taken from mice bearing MDA-MB-231 ALDH1A3 OE tumors treated with or without 4 mg/kg CLM296 ( n = 5 per group; 1 independent experiment). Arrows indicate metastatic lesions. (G) Quantification of MDA-MB-231 ALDH1A3 OE cells in the lung lobes of each mouse by RT-qPCR using human specific GAPDH primers. The horizontal line represents the limit of detection in the assay at 10 MDA-MB-231 per mouse lung lobe. Significance was analyzed with a one-way unpaired t test, and p value < 0.05 = ∗. Each point represents an individual mouse ( n = 9), and error bars represent SEM.

Article Snippet: Six to 12-week-old female non-obese diabetic severe combined immunodeficient (NOD-SCID) female mice (Charles River Laboratories, Senneville, QC) were used for all in vivo experiments.

Techniques: Plasmid Preparation, Control, Quantitative RT-PCR, Expressing, Injection, Staining, In Vivo

Journal: bioRxiv

Article Title: Synthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes

doi: 10.64898/2026.03.06.710219

Figure Lengend Snippet: a, Experimental design: Female Non-Obese Diabetic (NOD) mice were implanted with the scaffolds at 4 weeks of age. Scaffold based immunological niches (INs) were explanted at early (∼6 weeks), intermediate (∼11-15 weeks), and late (∼16-20 weeks) stages to characterize immune and transcriptomic changes in diabetic progressors (blood glucose ≥250 mg/dl) versus non-progressors (normoglycemic). b, Blood glucose levels per mice over time: By 30 weeks, the progressors mice developed hyperglycemia (blood glucose ≥250mg/dl), while the non-progressors remained normoglycemic). c-f, Intraperitoneal Glucose Tolerance Test (IPGTT) in progressor (n-5) vs non-progressor (n=4) at c, early, d, intermediate, e, late stage and f, AUC for progressor vs non-progressor across each stage. Statistical analysis was performed using multiple unpaired t-tests with single pooled variance. Data are shown as mean ± SEM. g–n, Immune cell composition in the IN analyzed by flow cytometry as fraction of CD45+ immune cells: g, Myeloid cells h, macrophages i, M2-like macrophages (CD206⁺CD163⁺) j, PD-L1⁺ k, T cells, l, CD4⁺ T cells, m, CD8⁺ T cells, n, PD-1⁺ CD4⁺ T cells as a fraction of total immune cells. Statistical analysis was performed using a mixed-effects model with the Geisser-Greenhouse correction, followed by Tukey’s multiple-comparison test, with individual variances computed for each comparison. Data are shown as mean ± SEM (n = 5-14 per group). o–q, Differential Gene Expression Analysis of IN transcriptomics across disease stages: Volcano plots of DEGs (p ≤ 0.05, |log₂FC| ≥ 1) in progressors vs non-progressors at o, early (n = 16-24 per group), p, intermediate (n = 10 per group), and q, late (n = 4-10 per group) stages. Axes were constrained for visualization (log₂FC: -8 to 8; -log 10 (p): 0 to 6). r, Genset enrichment analysis across disease stages: Dotplot of selected enriched pathways in progressor vs non-progressor (FDR ≤ 0.1, |NES| ≥ 1 in at least one stage). s, Venn Diagrams showing limited overlap between of IN based early stage T1D DEGs with IN based DEGs from 4T1 Breast cancer and Experimental Autoimmune Encephalomyelitis model t, Double Volcano Plot showing fold changes of IN based early stage DEGs in spontaneous NOD T1D model compared to IN DEGs from Adoptive Transfer T1D model. Genes colored show differential expression (p ≤ 0.05, |log₂FC| ≥ 1). Axes were constrained to ±5 log₂FC for visualization.

Article Snippet: Female non-obese diabetic (NOD/ShiLtJ, strain #001976; The Jackson Laboratory) mice were used due to their higher incidence of type 1 diabetes ( ).

Techniques: Flow Cytometry, Comparison, Gene Expression, Transcriptomics, Adoptive Transfer Assay, Quantitative Proteomics