Professor of Comparative Medicine University of Georgia Athens, GA, United States
Abstract:
Background: Bladder cancer, particularly high-grade Urothelial Carcinoma (UC), poses significant treatment challenges in humans and canines due to its high lethality. Canines are valuable models for studying human UC due to their similar histologic and molecular characteristics and biological behavior. Recent research aims to enhance treatment efficacy by combining radiation therapy with subsequent chemotherapy. With their complex cellular architecture, canine UC urine-derived organoids are more accurate in predicting treatment responses than conventional 2D cell lines.
Objective: This study aimed to evaluate individual in vitro variation in cytotoxicity response to sequential radiation and chemotherapy compared to cisplatin monotherapy using urine-derived canine UC organoid cell lines.
Methods: Canine UC organoid cell lines from two patients were isolated, expanded, plated (10,000 cells/well), and irradiated (5, 9, or 15 Gy) 24 hours after seeding. Following 72 hours of incubation, the organoids were treated with cisplatin (10, 25, 50, or 100 µM) with untreated cells as controls. Metabolic activity was measured after one week using Presto Blue. Histological analysis including immunohistochemistry to assess apoptosis (Caspase 3/7) and proliferation (Ki-67) were performed.
Results: Using radiation with subsequent chemotherapy induced greater cytotoxicity than cisplatin monotherapy, and differential IC50s were observed between the two patients (IC50: ranging from 10-50 µM; 5-9 Gy).
Conclusion: Significant individual variation in cytotoxicity was observed in in vitro radiation/chemotherapy protocol responses. This highlights the possibility of interpatient variation in therapeutic response and the importance of developing personalized treatment strategies to optimize therapeutic outcomes.
