Improving outcomes in colorectal cancer requires more accurate in vivo modelling of the disease in humans, allowing more reliable pre-clinical assessment of potential therapies. Novel imaging techniques are necessary to improve the longitudinal assessment of disease burden in these models, reducing the number of animals required for translational studies. This report describes the development of an immune-competent syngeneic orthotopic murine model of colorectal cancer, utilising caecal implantation of CT26 cells stably transfected with the luciferase gene into immune-competent BALB/c mice, allowing serial bioluminescent imaging of cancer progression. Luminescence in the stably transfected CT26 cell line, after pre-conditioning in the flank of a BALB/c mouse, accurately reflected cell viability and resulted in primary caecal tumours in five of eight (63%) mice in the initial pilot study following caecal injection. Luminescent signal continued to increase throughout the study period with one mouse (20%) developing a liver metastasis. Histopathological assessment confirmed tumours to be consistent with a poorly differentiated adenocarcinoma. We have now performed this technique in 68 immune-competent BALB/c mice. There have been no complications from the procedure or peri-operative deaths, with primary tumours developing in 44 (65%) mice and liver metastases in nine (20%) of these. This technique provides an accurate model of colorectal cancer with tumours developing in the correct microenvironment and metastasising to the liver with a similar frequency to that seen in patients presenting with colorectal cancer, with serial bioluminescent reducing the murine numbers required in studies by removing the need for cull for assessment of disease burden.

中文翻译：

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大肠癌的原位同基因鼠模型的开发，用于转化研究。

改善结直肠癌的结局需要对人类疾病进行更准确的体内建模，从而可以对潜在疗法进行更可靠的临床前评估。为了改善这些模型中疾病负担的纵向评估，减少转化研究所需的动物数量，必须使用新颖的成像技术。这份报告描述了结直肠癌的一种免疫能力强的同基因原位鼠模型的开发，该模型利用经荧光素酶基因稳定转染的CT26细胞盲肠植入免疫力强的BALB / c小鼠体内，从而实现了癌症进展的连续生物发光成像。在BALB / c小鼠腹侧进行预处理后，稳定转染的CT26细胞系中的发光，在盲肠注射后的初始初步研究中，该实验准确地反映了细胞活力并在八只小鼠中的五只（63％）中导致了原发性盲肠肿瘤。在整个研究期间，发光信号持续增加，一只小鼠（20％）发生肝转移。组织病理学评估证实肿瘤与低分化腺癌一致。现在，我们已经在68只具有免疫功能的BALB / c小鼠中进行了这项技术。没有因手术或围手术期死亡而引起的并发症，其中44例（65％）小鼠发生了原发性肿瘤，其中9例（20％）发生了肝转移。