Reperfusion injury and reactive oxygen species: The evolution of a concept☆
Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer, the primary clinical challenge remains that of preventing and combating metastatic spread. Surgical resection is the best treatment for colorectal metastases isolated to the liver. However, in rodent models, the hepatic ischemia-reperfusion (I/R) applied during the surgery accelerates the outgrowth of implanted tumors. Among the adverse effects of I/R on cellular function, several studies have demonstrated an over expression of the matrix metalloproteinase-9 (MMP-9) in the ischemic liver. Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma, the role of MMP-9 might be considered as a potential common mediator, favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.