It has been suggested that tumor cells produce IL-8 as an autocrine growth factor, which promote tumor growth, tissue invasion and metastatic spread.7 Previous studies have revealed that highly metastatic solid tumors such as prostate,

Our preliminary data suggest that these two polymorphisms may be useful molecular markers to predict clinical outcome in metastatic CRC patients treated with cetuximab and that they may indicate a role of ADCC of cetuximab.

Dysregulation of human epidermal growth factor receptor (ErbB/HER) pathways by over-expression or constitutive activation can promote tumor processes including angiogenesis and metastasis and is associated with poor prognosis in many human malignancies. In addition to cancer, ErbB signaling has also been implicated in cardiovascular and neurodegenerative diseases. Conversely, inhibition of ErbB pathways with targeted agents, such as monoclonal antibodies (MoAbs) or tyrosine kinase inhibitors (TKIs), blocks cell cycle progression, inhibits the production of pro-angiogenic factors and induces apoptosis in numerous in vitro and xenograft models. Accordingly, the ErbB receptor family with their most prominent members EGFR and HER-2 represents validated targets for anti-cancer therapy, and anti-ErbB MoAbs (cetuximab, panitumumab, and trastuzumab) and TKIs (gefitinib, erlotinib, and lapatinib) have now been approved for the treatment of advanced colorectal cancer, squamous cell carcinoma of the head and neck, advanced non-small-cell lung cancer, as well as pancreatic and breast cancer. Although results have been encouraging, more work remains to be done.

Objective: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). Background: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). Methods: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). Results: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59–78) years, recipient age: 62 (IQR: 55–65) years, labMELD: 15 (IQR: 9–25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221–828) vs 796 (IQR: 477–1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12–56) vs 52 (IQR: 35–98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4–8) vs 8 (IQR: 5–18) days, P = 0.045; 20 (IQR: 16–27) vs 36 (IQR: 23–62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). Conclusion: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.