Donigan Melissa, Norcross Laurie S, Aversa John, Colon Jimmie, Smith Joshua, Madero-Visbal Rafael, Li Shuan, McCollum Neal, Ferrara Andrea, Gallagher Joseph T, Baker Cheryl H
Cancer Research Institute of M. D. Anderson Cancer Center Orlando, Orlando, Florida 32806, USA.
J Surg Res. 2009 Jun 15;154(2):299-303. doi: 10.1016/j.jss.2008.05.028. Epub 2008 Jun 20.
This study was conducted to develop a modified murine model of colon cancer that is non-operative. Currently, the most accurate orthotopic murine model of colon cancer requires an invasive procedure involving cecal injection of colon cancer cells and therefore limits the ability to perform immunological studies subsequent to cecal resections.
Murine colon cancer (CT26) cells were injected submucosally into the distal, posterior rectum of BALB/c mice. Care was taken not to pass transmurally into the pelvic cavity. Different magnifications (10x versus 100x) were used for injection, and primary tumor growth and metastatic disease were studied.
In the initial study, 3/7 mice injected using 10x magnifications had notable, large tumor originating from the rectal wall, and histology revealed that all excised tumors were poorly differentiated adenocarcinoma. In the second study, 8/10 mice injected using 100x magnifications had notable tumor originating from the rectal well, and 4/8 mice had abnormal lung tissue with pathological evidence of hemorrhagic pulmonary edema. The use of 10x magnification resulted in 43% tumor take. In sharp contrast, 80% tumor take was observed with 100x magnification. The overall success of tumor take was 65% using the trans-anal rectal injection model.
Our modified orthotopic murine model of colon cancer offers an alternative non-operative murine model for colon cancer and is less invasive than the traditional orthotopic model (i.e., cecal injection). This model may allow for more accurate investigations of inflammation and immune responses to surgical intervention without the influence of previous abdominal surgery.
本研究旨在开发一种改良的非手术性小鼠结肠癌模型。目前，最准确的原位小鼠结肠癌模型需要进行侵入性操作，包括向盲肠注射结肠癌细胞，因此限制了在盲肠切除术后进行免疫学研究的能力。
将小鼠结肠癌细胞（CT26）黏膜下注射到BALB/c小鼠远端直肠后壁。注意不要穿透肠壁进入盆腔。注射时使用不同放大倍数（10倍与100倍），并研究原发性肿瘤生长和转移性疾病。
在初始研究中，7只使用10倍放大倍数注射的小鼠中有3只出现了源自直肠壁的明显大肿瘤，组织学检查显示所有切除的肿瘤均为低分化腺癌。在第二项研究中，10只使用100倍放大倍数注射的小鼠中有8只出现了源自直肠壁的明显肿瘤，8只小鼠中有4只肺部组织异常，有出血性肺水肿的病理证据。使用10倍放大倍数时肿瘤接种成功率为43%。与之形成鲜明对比的是，使用100倍放大倍数时观察到肿瘤接种成功率为80%。经肛门直肠注射模型的总体肿瘤接种成功率为65%。
我们改良的原位小鼠结肠癌模型为结肠癌提供了一种替代性非手术小鼠模型，且比传统原位模型（即盲肠注射）侵入性更小。该模型可能允许在不受先前腹部手术影响的情况下，更准确地研究炎症和对手术干预的免疫反应。
