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. 1. Introduction A growing amount of evidence highlights the role of the acetylsalicylate aspirin for the chemoprevention of sporadic colorectal cancer (CRC) [1–4]. Similarly, aminosalicylates such as sulfasalazine, mesalazine, and others have been shown to reduce the risk for colitis-associated colorectal cancer (CAC) in patients with inflammatory bowel disease [5]. In addition, recent data also propose an improved outcome for patients treated with aspirin following the diagnosis of CRC [6]. This is of great importance, as colorectal neoplasia remains one of the leading causes of cancer-related morbidity and mortality in industrialized countries [7]. The effects of aspirin and aminosalicylates are largely attributed to the inhibition of cyclooxygenase-1 (COX-1) and -2. These enzymes convert arachidonic acid to prostaglandin PGH2, a precursor molecule for various proinflammatory prostaglandins and eicosanoids. Especially COX-2 has been shown to be responsible for the tumor promoting effects, whereas COX-1 is involved in tissue homeostasis and platelet function [8]. In fact, COX-2 expression is elevated in almost up to 90 percent of sporadic carcinomas and also 40 percent of colonic adenomas, while expression in healthy colonic
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