Journal: Translational Oncology

Article Title: A RIPK2 activity signature in prostate cancer: Modulation by RIPK2 inhibition and clinical association

doi: 10.1016/j.tranon.2026.102819

Figure Lengend Snippet: Ponatinib progressively suppresses the RIPK2 activity signature in vivo. (A) Schematic of the in vivo experimental design. Male immunodeficient SCID/Beige mice bearing ∼200 mm 3 subcutaneous (s.c.) 22Rv1 xenograft tumors were treated daily with ponatinib (Pon, 6 mg/kg) or vehicle (Veh) control by oral gavage for 3 or 7 days. Created with BioRender.com. (B) Tumor weights of 22Rv1 xenografts harvested after 3 or 7 days of treatment (n = 3 mice per group). (C) Immunoblot images (left) and corresponding densitometric quantification (right) of the indicated proteins in xenograft tumor lysates (n = 3). (D) Grouped dot plot showing log 2 -transformed fold changes (Log 2 FC) of the indicated RIPK2 signature genes in xenograft tumors relative to vehicle controls (n = 3). (E) Swarm plot of RIPK2 qPCR signature scores in xenografts (n = 3). Solid lines represent the mean signature scores. Nominal P-values were calculated using an unpaired two-tailed Student’s t-test. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns, not significant.

Article Snippet: A total of 100 μL of the cell suspension was injected subcutaneously into one flank of 6-week-old male SCID/Beige mice (n = 12; Charles River, #CRL:250; CB17.Cg-Prkdc scid Lyst bg-J /Crl).

Techniques: Activity Assay, In Vivo, Control, Western Blot, Transformation Assay, Two Tailed Test

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Figure Lengend Snippet: SCID mice were infected intravenously with 1.0×10 6 CFU per animal of either Mabs ATCC 19977 WT, the dosRS KO mutant or the dosRS complemented mutant. AMK and AZI treatment of each group of mice began 28 d after infection, upon establishment of chronic infection. As of d 28, mice were treated daily (7 d/week) for 28 d with saline (gavage), AMK (150 mg/kg, subcutaneous injection) or AZI (200 mg/kg, gavage). Groups of mice were ethically euthanized on d 2, 28 and 56, and lungs and spleens were taken for bacterial enumeration (CFU). For each bacterial strain, the CFU results represent the average of 5 mice per time point, and bacterial loads are expressed as Log 10 CFU (± SEM). Asterisks denote statistically significant differences between antibiotic-treated WT and mutant- or complemented mutant-infected mice pursuant to the Student’s t -test (p* < 0.05; p** < 0.005).

Article Snippet: Fox Chase severe combined immunodeficiency (SCID) Beige mice were ordered from Charles River (North Wilmington, MA, USA).

Techniques: Infection, Mutagenesis, Saline, Injection

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Figure Lengend Snippet: ( A ) Exposure of OZ439 in Mabs ATCC 19977-infected SCID mice. In the acute model, mice received OZ439 orally (200 mg/kg) every other d for 14 d. In the chronic model, mice received OZ439 orally (50 mg/kg) every other d for 28 d. Shown are the averages (± SD) of lung and plasma concentrations 2 and 48 hs after the last dosing. Two mice were used per time point in the acute model. Four mice were used per time point in the chronic model. ( B ) Therapeutic efficacy testing in an acute SCID mouse model of MABSC infection. Mice (n=5 mice/group) were infected intratracheally with 1.0×10 6 CFUs of WT Mabs ATCC 19977. On d 12 post-infection, during the acute phase of infection, mice were treated daily (7 d/week) for 14 d, or every other day for OZ439, with vehicle used in the formulation of OZ439 (HPMC-SV), OZ439, AMK, AZI, IMI, CFZ, and the same four antibiotic treatments in combination with OZ439. See text for more details about the treatments. Bacterial loads were determined in the lungs, liver and spleen on d 2, 12 and 26. ( C ) Therapeutic efficacy testing in a chronic SCID mouse model of MABSC infection. Mice (five animals per group) were infected intravenously with 1.0×10 6 CFUs of WT Mabs ATCC 19977. On d 28 post-infection, upon establishment of chronic infection, mice were treated daily (7 d/week) for 28 d, or every other day for OZ439, with formulation vehicle, OZ439, AMK, AZI, IMI and CFZ, and the same four antibiotics in combination with OZ439. See text for more details about the treatments. Bacterial loads were determined in the lungs, liver, and spleen on d 2, 28 and 56. In ( B ) and ( C ), asterisks denote statistically significant differences between antibiotic-treated and antibiotic+OZ439-treated mice, or untreated and OZ439-treated mice pursuant to the Student’s t -test (*p < 0.05; **p < 0.005; ***p < 0.0005).

Article Snippet: Fox Chase severe combined immunodeficiency (SCID) Beige mice were ordered from Charles River (North Wilmington, MA, USA).

Techniques: Drug discovery, Infection, Clinical Proteomics, Formulation