Activation of Wnt signaling has been implicated in gastric tumorigenesis, although mutations in APC (adenomatous polyposis coli), CTNNB1 (b-catenin) and AXIN are seen much less frequently in gastric cancer (GC) than in colorectal cancer. In the present study, we investigated the relationship between activation of Wnt signaling and changes in the expression of secreted frizzled-related protein (SFRP) family genes in GC. We frequently observed nuclear b-catenin accumulation (13/15; 87%) and detected the active form of b-catenin in most (12/16; 75%) GC cell lines. CpG methylation-dependent silencing of SFRP1, SFRP2 and SFRP5 was frequently seen among GC cell lines (SFRP1, 16/16, 100%; SFRP2, 16/ 16, 100%; SFRP5, 13/16, 81%) and primary GC specimens (SFRP1, 42/46, 91%; SFRP2, 44/46, 96%; SFRP5, 30/46, 65%), and treatment with the DNA methyltransferase inhibitor 5-aza-2 0 -deoxycytidine rapidly restored SFRP expression. Ectopic expression of SFRPs downregulated T-cell factor/lymphocyte enhancer factor transcriptional activity, suppressed cell growth and induced apoptosis in GC cells. Analysis of global expression revealed that overexpression of SFRP2 repressed Wnt target genes and induced changes in the expression of numerous genes related to proliferation, growth and apoptosis in GC cells. It thus appears that aberrant SFRP methylation is one of the major mechanisms by which Wnt signaling is activated in GC.

Interpretation: Although the number of patients is limited, our results show that the antibody response against the first SARS-CoV-2 infection in symptomatic patients is typical of that observed in an acute viral infection.

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Background and aims Needle tract seeding after preoperative endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) for pancreatic body and tail cancer has been reported. This study aimed to investigate the long‐term outcomes, including the needle tract seeding ratio, of patients undergoing distal pancreatectomy for pancreatic body and tail cancer diagnosed preoperatively by EUS‐FNA. Methods This retrospective, observational cohort study assessed patients from three university hospitals and 11 tertiary referral centers. All patients who underwent distal pancreatectomy for invasive cancer of the pancreatic body and tail between January 2006 and December 2015 were identified and reviewed. Needle tract seeding rate, recurrence‐free survival (RFS), and overall survival (OS) were evaluated. Results Of the 301 total patients analyzed, 176 underwent preoperative EUS‐FNA (EUS‐FNA group) and 125 did not (non‐EUS‐FNA group). The median follow‐up periods of the EUS‐FNA group and non‐EUS‐FNA group were 32.8 and 30.1 months. Six patients (3.4%) in the EUS‐FNA group were diagnosed as having needle tract seeding. The 5‐year cumulative needle tract seeding rate estimated using Fine and Gray's method was 3.8% (95% CI 1.6–7.8%). The median RFS or OS was not significantly different between the EUS‐FNA group and the non‐EUS‐FNA group (23.7 vs 16.9 months: P = 0.205; 48.0 vs 43.9 months: P = 0.392). Conclusion Although preoperative EUS‐FNA for pancreatic body and tail cancer has no negative effect on RFS or OS, needle tract seeding after EUS‐FNA was observed to have a non‐negligible rate. (UMIN000030719)