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Christopher Cheleuitte-Nieves

Publications and source records attributed to Christopher Cheleuitte-Nieves.

2 recordsLinked to original sources

Induction and characterization of neoplastic bladder tumors in a transgenic porcine model.

BACKGROUND: Large animal models of bladder cancer are lacking. OBJECTIVE: This study aimed to develop and characterize a transgenic porcine model of bladder cancer (BC) using Oncopigs expressing Cre-inducible KRASG12D and TP53R167H mutations. METHODS: Eleven female Oncopigs underwent tumor induction via three cystoscopic inoculation procedures: Procedure I (N = 3, 1 inoculation/pig), chemical dissolution of the glycosaminoglycan layer with N-Dodecyl-β-d-Maltoside DDM followed by adenoviral Cre-recombinase (AdCre) instillation; Procedure II (N = 4, 3 inoculation/pig), mechanical mucosal denudation followed by AdCre instillation; and Procedure III (N = 4, 3 inoculation/pig), cystoscopy-guided submucosal injection of AdCre. Animals were clinically monitored throughout follow-up (14-28 days). Tumor development was assessed on cystoscopy and ultrasonography, and pathologically, immunohistochemically (IHC), and genomically characterized. RESULTS: All pigs remained clinically healthy. Tumors developed at 59% (16/27) of inoculation sites: nine (33%) were neoplastic and seven (26%) were inflammatory. Procedure I achieved 100% neoplastic tumors and produced both non-muscle invasive (71%) and muscle-invasive (29%) tumors. Procedure II achieved 50% neoplastic tumors, all of which were muscle invasive (100%). Procedure III generated only inflammatory tumors. Histologically, neoplastic tumors were pathologically interpreted as urothelial cell carcinomas with sarcomatoid differentiation, with IHC confirming the presence of both epithelioid and sarcomatoid features with abundant mixed leukocytic infiltrates. Genomic analyses verified Cre-induced alterations alongside other mutations seen in human BC. CONCLUSIONS: We herein demonstrate an efficient and reproducible method for developing autochthonous neoplastic bladder tumors in Oncopigs that resemble human bladder cancer of varying stages. This large animal model facilitates the evaluation of novel surgical and intravesical therapies in BC.

bladder cancer

Armenian Hamsters (Nothocricetulus migratorius): A New Host Susceptible to Corynebacterium bovis Infection and Disease.

Corynebacterium bovis causes skin disease in immunocompromised mice and possibly rats. In 2022, scaly skin and mortality were observed in 7- to 11-d-old neonates (n = 8) from a primiparous Armenian (Nothocricetulus migratorius) hamster breeding pair in a newly established colony. C. bovis was detected by culture and PCR, and affected animals had moderate to severe acanthotic, hyperkeratotic lesions with intralesional C. bovis confirmed by in situ hybridization. Intrafollicular Demodex cricetuli mites, an ectoparasite found in all laboratory-maintained Armenian hamsters, were also identified in affected animals. To elucidate the role of D. cricetuli on C. bovis-associated disease and maintain adult hamsters without the need for sustained mite treatment, a D. cricetuli-free colony was generated by treating breeding pairs and their 1- to 3-d-old neonates with topical fluralaner (35 mg/kg), and a prospective study was undertaken to compare C. bovis-associated pup mortality in D. cricetuli-free and D. cricetuli-infested hamsters. During the ensuing 22 mo, 4 of 96 (4.2%) litters born exhibited C. bovis-associated disease and/or mortality. The litters were born to 4 different nulliparous breeding pairs (n = 47, 9%). Of the 4 affected litters, 2 were D. cricetuli-infested while 2 were D. cricetuli-free. C. bovis was routinely cultured with a variable bacterial burden that had no association with mortality or skin lesion severity from all hamsters, independent of their D. cricetuli status. The severity of histologic pathology appeared to correlate with clinical presentation and mortality in neonates. Whole genome sequencing was performed on 4 hamster C. bovis isolates, which revealed a close genetic association among the isolates as well as with previously characterized mouse and rat C. bovis isolates.

DSS, deep skin scrape