Anti-TIMP2 monoclonal antibody, clone 4H8

Background Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2* IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery. Methods A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72 h after CPB initiation. TIMP-2* IGFBP-7 concentration was measured in urine samples using the Astute 140 (R) meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000. Results A total of 94 infants with a mean age of 154.2 +/- 85.7 days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 +/- 7 h after CPB initiation. The concentration of TIMP-2* IGFBP-7 was significantly higher in patients with AKI at 12 h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2* IGFBP-7 concentration of >= 0.78 had a threefold higher odds of developing AKI than those with a TIMP-2* IGFBP-7 concentration of < 0.78 (95% confidence interval 1.47-6.11, p = 0.001). Conclusion These results demonstration that TIMP2* IGFBP-7 concentration can be used in infants to predict subsequent serum creatinine-defined AKI following CPB.

Curcumin is a natural compound extracted from turmeric (Curcuma longa), which has been reported to be a promising anti-cancer drug in various human cancers. However, the effects of combination treatment of curcumin with gemcitabine or docetaxel on pancreatic cancer remains elusive. In the present study, the combinatory effects of curcumin with either gemcitabine or docetaxel on the proliferation, apoptosis, migration as well as invasion of PC cells were investigated. Calcusyn software was used to determine whether curcumin has is synergistic with gemcitabine or docetaxel. Combination index values from combinational use were all lower than 1, indicating the synergism of curcumin with gemcitabine or docetaxel on PC cells in vitro. EdU assay showed that curcumin could enhance the ability of gemcitabine or docetaxel to inhibit the proliferation of PC cells. Furthermore, the results from transmission electron microscope, DAPI staining experiments and western blot analysis revealed that curcumin may trigger apoptosis of PC cells via PARP/caspase-3 signaling pathway and reinforced pro-apoptotic ability of either gemcitabine or docetaxel. In addition, curcumin exhibited marked suppressive ability on metastasis of PC cells by wound healing and matrigel-transwell assay. Mechanistically, upregulation of TIMP1/TIMP2 with concomitant downregulation of MMP2/MMP9/N-cadherin proteins may be involved in this process. In conclusion, curcumin showed synergistic anti-cancer effects with either gemcitabine or docetaxel on PC cells.