TNFR2 promotes pancreatic cancer proliferation, migration, and invasion via the NF-κB signaling pathway.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant disease with low overall survival; chemotherapy and immunotherapy have limited efficacy. Tumor necrosis factor receptor 2 (TNFR2), a type II transmembrane protein, contributes to the development and progression of several tumors. In this study, we elucidated the effect and molecular mechanisms of TNFR2. METHOD: We used The Cancer Genome Atlas and the Genotype-Tissue Expression database to compare the expression of the TNFR2 gene between normal and malignant pancreatic tissue. Using immunohistochemical staining, we divided the patients into high and low-expression groups, then investigated clinicopathologic data and survival curves of pancreatic cancer patients. We measured TNFR2 protein expression in PANC-1 and ASPC-1 pancreatic cancer cells subjected to TNFR2 small interfering RNA or negative control treatment. We performed proliferation, invasion, and migration assays to study the biological effects of TNFR2 in PDAC. The molecular mechanisms were validated using western blotting. RESULTS: TNFR2 was more highly expressed in PDAC cells and tissues than controls. Abundant expression of TNFR2 was associated with aggressive clinicopathologic characteristics and poor outcomes. Overexpression of TNFR2 promoted PDAC cell proliferation, migration, and invasion in vitro. Mechanistically, TNFR2 binds to TNF-α and activates the NF-κB signaling pathway. CONCLUSION: TNFR2 is a prognostic marker that facilitates the proliferation, migration, and invasion of PDAC via the NF-κB signaling pathway. TNFR2 may become a therapeutic target.

Early outcomes of primary repair versus reconstruction for acute anterior cruciate ligament injury: A systematic review and meta-analysis.

BACKGROUND: Contemporary techniques for repair of acute anterior cruciate ligament (ACL) rupture have been receiving renewed interest recently because of reports of good outcomes. METHODS: A literature search of PUBMED, MEDLINE, EMBASE, and the Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only RCTs published in English and comparing clinical outcomes of ACL repair versus reconstruction were included. Outcomes were evaluated using the International Knee Documentation Committee subjective score, Lysholm score, Tegner activity scale, visual analog scale pain score, anterior laxity, Lachman test, hop tests, knee injury and osteoarthritis outcome score, extension deficit, revision rate, and re-rupture rate. Statistical analysis was performed with Review Manager 5.4 and Stata 14.0. Two-tailed P < .05 was considered statistically significant. RESULTS: Four RCTs (with a total of 293 patients) that met the eligibility criteria were included in this review. Over short-term follow-up, none of the studies found significant differences between the repair groups and reconstruction groups with respect to International Knee Documentation Committee, Lysholm, Tegner, visual analog scale, anterior laxity, Lachman test, re-rupture rate, extension deficit, and performance of 3 hop tests (P > .05). In both groups, the hop tests scores were >90%. CONCLUSION: ACL repair and ACL reconstruction appear to provide comparable short-term outcomes. The low revision rate after primary repair is encouraging. For patients with ACL injury, current repair techniques such as dynamic intraligamentary stabilization and bridge-enhanced ACL repair may be an effective alternative to reconstruction.