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Endomicroscopic Imaging of COX-2 Activity in Murine Sporadic and Colitis-Associated Colorectal Cancer

机译:内镜显微镜成像的小鼠散发性和结肠炎相关的大肠癌COX 2活性。

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Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC.
机译:尽管有几项研究提出了阿司匹林对结直肠癌(CRC)的化学预防作用,但由于其不良副作用,因此不建议一般使用阿司匹林。由于阿司匹林的保护作用与COX-2的表达增加有关,例如,在共聚焦内窥镜检查过程中,COX-2的分子成像可以确定可能受益于阿司匹林治疗的患者。在该试验性试验中,我们使用共聚焦显微镜在小鼠中使用了COX-2特异性荧光探针检测结肠炎相关性和散发性CRC。在将COX-2探针注射到荷瘤的APCmin小鼠或暴露于结肠炎相关癌的AOM + DSS模型的小鼠后,可以通过体内荧光成像验证COX-2的肿瘤特异性上调。与健康对照组的正常黏膜相比,肿瘤组织的随后共聚焦成像显示出表达COX-2的细胞数量增加。在肿瘤细胞和浸润性基质细胞中亚细胞分辨率可检测到COX-2-表达。这些发现提出了概念证明,并建议在结肠直肠癌监视内窥镜检查中使用CLE检测COX-2表达。这可以改善CRC患者的化学预防的早期发现和分层。

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