An immunocompetent rectal cancer model to study radiation therapy

用于研究放射疗法的免疫功能健全的直肠癌模型

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作者:Jin K Kim ,Chao Wu ,Michael Del Latto ,Yajing Gao ,Seo-Hyun Choi ,Maria Kierstead ,Charles-Etienne Gabriel Sauvé ,Canan Firat ,Almudena Chaves Perez ,Jussi Sillanpaa ,Chin-Tung Chen ,Kayla E Lawrence ,Philip B Paty ,Francisco M Barriga ,John E Wilkinson ,Jinru Shia ,Charles L Sawyers ,Scott W Lowe ,Julio García-Aguilar ,Paul B Romesser ,J Joshua Smith

Abstract

We describe a mouse model of rectal cancer (RC) involving rapid tumor organoid engraftment via orthotopic transplantation in an immunocompetent setting. This approach uses simple mechanical disruption to allow engraftment, avoiding the use of dextran sulfate sodium. The resulting RC tumors invaded from the mucosal surface and metastasized to distant organs. Histologically, the tumors closely resemble human RC and mirror remodeling of the tumor microenvironment in response to radiation. This murine RC model thus recapitulates key aspects of human RC pathogenesis and presents an accessible approach for more physiologically accurate, preclinical efficacy studies.

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