Modeling human choroidal melanoma xenograft growth in immunocompromised rodents to assess treatment efficacy

在免疫缺陷啮齿动物中模拟人脉络膜黑色素瘤异种移植瘤的生长,以评估治疗效果

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Abstract

PURPOSE: To evaluate potential treatments of primary uveal melanoma in rodent xenograft models, it is necessary to track individual tumor growth during treatment. Previously, high-frequency ultrasound (HF-US) was used to measure tumor volume in nude rats for up to 2 weeks. This study tests the hypothesis that HF-US can be used to repeatedly measure tumor volume for at least a month in both nude rat and severe combined immunodeficiency (SCID) mouse xenograft models of human uveal melanoma, with the goal of modeling tumor growth to evaluate treatment efficacy. METHODS: C918 human uveal melanoma spheroids were implanted in the choroids of six nude rats and six severe combined immunodeficiency mice. OCM-1 human uveal melanoma spheroids were implanted in six nude rats. Every 4-7 days thereafter for up to 5 weeks, HF-US images of the tumor-bearing eye were captured every 100 or 250 μm. Tumor areas were measured on each image and integrated to calculate volume. Tumor growth was modeled using a logistic curve, and parameters characterizing growth, including the time to reach a target volume (t(T)), were evaluated as potential measures of treatment efficacy. RESULTS: Tumor volume could be measured for up to 5 weeks in all models, and the logistic curve described the growth well. The parameter t(T) was shown to be a suitable endpoint to evaluate treatments. CONCLUSIONS: HF-US is a practical method to track uveal melanoma growth in the same nude rat or SCID mouse for up to a month. Such growth data can be used to evaluate treatments in these xenograft models.

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