The RECQL helicase prevents replication fork collapse during replication stress

Most tumors lack the G1/S phase checkpoint and are insensitive to antigrowth signals. Loss of G1/S control can severely perturb DNA replication as revealed by slow replication fork progression and frequent replication fork stalling. Cancer cells may thus rely on specific pathways that mitigate the deleterious consequences of replication stress. To identify vulnerabilities of cells suffering from replication stress, we performed an shRNA-based genetic screen. We report that the RECQL helicase is specifically essential in replication stress conditions and protects stalled replication forks against MRE11-dependent double strand break (DSB) formation. In line with these findings, knockdown of RECQL in different cancer cells increased the level of DNA DSBs. Thus, RECQL plays a critical role in sustaining DNA synthesis under conditions of replication stress and as such may represent a target for cancer therapy

Thoracic aortic surgery: An overview of 40 years clinical practice

Objective: The objective of our study was to report on the total experience in thoracic aortic surgery over a 40-year time period for a single institution. Methods: All 1075 patients who underwent surgery for thoracic aortic pathology from 1972 to 2011 (n = 1159) were included. Patient, procedural, and follow-up information was obtained from hospital records and the civil registry. Patients were grouped into 4 categories: acute type A dissection (n = 261), other ascending aortic/arch surgery (n = 626), descending aortic surgery (n = 175), and thoracoabdominal surgery (n = 97). Risk factors for early and late mortality and the incidence of reoperations were analyzed. Results: The annual number of operations increased significantly over time. In all 4 patient groups, early mortality (in hospital or within 30 days of operation) decreased significantly over time to 15.3% in group 1, 1.9% in group 2, 0% in group 3, and 10.5% in group 4 during the contemporary time period 2007 to 2011. Overall actuarial survival was 54.3% (95% confidence interval, 50.7-57.9) after 10 years and 27.8% (95% confidence interval, 26.4-38.3) after 20 years. Late survival improved over time, but was reduced compared with the general population and was related predominantly to preexisting risk factors. In 80 patients, 111 reoperations were necessary, most frequently in group 1 patients and in patients with connective tissue disease. Conclusions: Thora cic aortic operations were performed increasingly during a 40-year time period. Early mortality decreased and late survival increased significantly in all patient groups. A significant proportion of patients required multiple operations