Perp blocking peptide

Effects related to offshore contamination have been observed in gadoid species in the North Sea, but uncertainties regarding exposure conditions have led to the need for environmentally relevant exposure studies. In the current study, Atlantic cod (Gadus morhua) were sampled at regular intervals during an 11-month continuous or pulsed water-borne exposure to a mixture of produced water components. There was variation in time to female maturation between and within treatment groups; although differences were not significant, there was a tendency towards delayed maturation in intermittently exposed females not seen in continuously exposed females. Physiological parameters such as condition factor, liver somatic index, gonadosomatic index, or hematocrit did not appear to be affected by the treatments. A range of toxicologically relevant genes were differentially expressed in the exposed fish, including AhR-responsive genes (CYP1A, UDP-GT) and genes relevant to immune function (complement C3, MHC 1, CYP27B), apoptosis (PERP), and oxidative stress (hepcidin, serotransferrin, glutathione peroxidase). Although powerful in their depiction of the complexity of cellular responses to environmental stressors, the use of molecular tools should be accompanied by biochemical and physiological endpoints, and results should be holistically interpreted in terms of individual health and function.

Background PERP (p53 apoptosis effector related to PMP22) localizes to desmosomes and suppresses squamous cell carcinoma development. Loss of PERP leads to worse local control in head and neck squamous cell carcinoma (HNSCC), likely by destabilizing desmosomes. We evaluated PERP loss at HNSCC surgical margins as a predictor of local relapse. Methods Combining discovery (n = 17) and validation (n = 31) cohorts, we examined membranous PERP protein expression by immunohistochemistry in surgical mucosal margins with competing risk analysis of the relationship between local relapse and PERP expression. Results Of the 44 analyzable patients, the 2-year cumulative incidence of local relapse was 44.4% for the PERP-negative group and 16.4% for the PERP-positive group (P= .01). A trend toward worse progression-free survival (P= .09) and overall survival (P= .06) was observed with loss of PERP. Conclusions PERP loss at surgical margins is associated with higher risk of local recurrence in HNSCC, warranting further evaluation in a larger prospective study.