Rabbit Anti-Human STK11 (Phospho-Ser334) polyclonal antibody

Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radio-chemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2-IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups. (C)2015 AACR.

The high-energy requirement of the kidney and the importance of energy metabolism in renal physiology has been appreciated for decades, but only recently has there emerged a strong link between impaired renal energy metabolism and chronic kidney disease (CKD). The mechanisms underlying the association between changes in energy metabolism and progression of CKD, however, remain poorly understood. A new study from Qiu and colleagues reported in the Journal of Pathology has advanced this understanding by showing that, after renal injury, the energy sensor AMPK inhibits epithelial-mesenchymal transition and inflammation, processes important in the pathogenesis of CKD. Furthermore, this study identifies an interaction between AMPK and CK2.. as an important mechanism in the anti-fibrotic effect. CK2.. has previously been shown to interact with STK11 (also known as LKB1) to regulate cellular polarity. These findings are consistent with the known roles of the LKB1-AMPK pathway in sustaining cellular energy homeostasis and epithelial cell polarity, and add to growing evidence linking the suppression of energy metabolism to CKD. They emphasize the importance of energy metabolism in general and the LKB1-AMPK axis in particular as key investigational and therapeutic targets in the battle against CKD. Copyright (C) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.