The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis. Here, we identify cell-surface autoantigens using an expression cloning system. A cDNA library of endothelial cells is retrovirally transfected into a rat myeloma cell line from which AECA-positive clones are sorted with flow cytometry. Four distinct AECA-positive clones are isolated, and endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) are identified as endothelial autoantigens. Autoantibodies against EPCR and SR-BI are detected in 34.6% and 36.5% of cases, respectively, with minimal overlap (3.8%). Autoantibodies against EPCR are also detected in ulcerative colitis, the frequent comorbidity of TAK. In mechanistic studies, EPCR and SR-BI function as negative regulators of endothelial activation. EPCR has also an effect on human T cells and impair Th17 differentiation. Autoantibodies against EPCR and SR-BI block the functions of their targets, thereby promoting pro-inflammatory phenotype.
TCthe Northern Japan Gastric Cancer Study Consortium
the Northern Japan Gastric Cancer Study Consortium
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Paradoxically, Helicobacter pylori–positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP–negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome. A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death–ligand 1 (PD-L1) and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse-free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Among 491 patients that were analyzed, 175 (36%) and 316 (64%) patients were HP+ and HP−, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction=.049) and PD-L1 (P =.02). HP+ patients in the PD-L1- group had statistically higher 5-year OS and RFS than HP- patients (81% vs 68%; P =.0011; hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.303 to 0.751, and 76% vs 63%; P =.001; HR = 0.508, 95% CI = 0.335 to 0.771, respectively). The 5-year OS and RFS was also statistically higher for HP+ compared with HP- patients in the "PD-L1- and S-1–r educed" group (86% vs 46%; P =.001; HR = 0.205, 95% CI = 0.07 to 0.602, and 83% vs 34%; P =.001; HR = 0.190, 95% CI = 0.072 to 0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival. This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.
A web-based dose computation system, WAZA-ARI, is being developed for patients undergoing X-ray CT examinations. The system is implemented in Java on a Linux server running Apache Tomcat. Users choose scanning options and input parameters via a web browser over the Internet. Dose coefficients, which were calculated in a Japanese adult male phantom (JM phantom) are called upon user request and are summed over the scan range specified by the user to estimate a normalised dose. Tissue doses are finally computed based on the radiographic exposure (mA s) and the pitch factor. While dose coefficients are currently available only for limited CT scanner models, the system has achieved a high degree of flexibility and scalability without the use of commercial software.
14 November 2014 in International Journal of Clinical Oncology