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Background Cyclooxygenase‐2 (COX‐2) is an inducible enzyme with catalytic activity for biosynthesis of prostaglandins which are the key mediators of inflammation. COX‐2 is also the therapeutic target for widely used non‐steroidal anti‐inflammatory drugs (NSAIDs). However, the involvement of COX‐2 in xenotransplantation (eg, pig‐to‐non‐human primate) remains poorly recognized. Methods We investigated the mechanisms that regulate COX‐2 expression and the effects of COX‐2 on porcine aortic endothelial cell (PAEC) viability using in vitro pig‐to‐primate xenotransplantation model and in vivo pig‐to‐mouse cellular transplant model. Regulation of COX‐2 expression was assessed by real‐time quantitative polymerase chain reaction (qPCR) and Western blotting. The effects of inhibition or downregulation of COX‐2 on PAEC viability were assessed by propidium iodide (PI)‐Annexin V staining and Cell Counting Kit‐8 assay. Results Human serum triggered robust COX‐2 expression in PAECs in a dose‐ and time‐dependent manner. Induction of COX‐2 expression by human serum was partially through activation of both canonical and non‐canonical nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κb) signaling and increasing intracellular calcium. Cytokines like tumor necrosis factor alpha (TNF‐α), interleukin 1 beta (IL‐1β), IL‐17, were able to induce COX‐2 expression. Selective inhibition of COX‐2 by celecoxib dramatically decreased PAEC death in vitro and in vivo as defined by propidium iodide (PI)‐Annexin V staining. Consistently, downregulation of COX‐2 expression by NF‐κb inhibitors or calcium chelator BAPTA decreased human serum‐induced PAEC death as well. Silencing of COX‐2 expression by small interfering RNA (siRNA) protected PAEC viability when transplanted under kidney capsule of C57BL/6 mice. Conclusions Taken together, our data suggest that COX‐2 is highly induced in PAECs by xenogenic serum and associated with human antibody‐mediated complement‐dependent cytotoxicity. COX‐2 might be a potential therapeutic target to improve xenotransplantation.

Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case–control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches conducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast cancer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confidence interval (CI) = 0.04–0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13–0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77–7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues respectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; therefore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis.

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