Programmed death ligand-1 (PD-L1), encoded by the gene, is a target for immune checkpoint blockade; however, little is known about genomic alterations. A subset of small-cell lung cancer (SCLC) exhibits increased copy number of chromosome 9p24, on which resides; however, most SCLCs show low expression of PD-L1. We therefore examined whether is a target of recurrent genomic alterations. We examined somatic copy number alterations in two patient cohorts by quantitative real-time PCR in 72 human SCLC cases (cohort 1) and SNP array analysis in 138 human SCLC cases (cohort 2). Whole-genome sequencing revealed the detailed genomic structure underlying focal amplification. PD-L1 expression in amplified cases from cohorts 1 and 2 was further examined by transcriptome sequencing and immunohistochemical (IHC) staining. By examining somatic copy number alterations in two cohorts of primary human SCLC specimens, we observed 9p24 copy number gains (where resides) and focal, high-level amplification of We found evidence for genomic targeting of , suggesting selection during oncogenic transformation. amplification was caused by genomic rearrangements not affecting the open reading frame, thus leading to massively increased transcripts and high level expression of PD-L1. A subset (4/210, 1.9%) of human SCLC patient cases exhibits massive expression of PD-L1 caused by focal amplification of Such tumors may be particularly susceptible to immune checkpoint blockade..

Endoscopic submucosal dissection and preoperative assessment with EUS are effective for treating rectal carcinoid tumors and enabling en bloc resection.

ESD with a combination of small-caliber-tip transparent hood and flex knife is a safe endoscopic treatment for superficial esophageal neoplasias and enables large en bloc resection.

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Sepsis is a serious clinical problem. Negative regulation of innate immunity is associated with sepsis progression, but the underlying mechanisms remains unclear. Here we show that the receptor CD300f promotes disease progression in sepsis. CD300f −/− mice were protected from death after cecal ligation and puncture (CLP), a murine model of septic peritonitis. CD300f was highly expressed in mast cells and recruited neutrophils in the peritoneal cavity. Analysis of mice (e.g., mast cell-deficient mice) receiving transplants of wild-type or CD300f −/− mast cells or neutrophils indicated that CD300f deficiency did not influence intrinsic migratory abilities of neutrophils, but enhanced neutrophil chemoattractant production (from mast cells and neutrophils) in the peritoneal cavity of CLP-operated mice, leading to robust accumulation of neutrophils which efficiently eliminated Escherichia coli. Ceramide-CD300f interaction suppressed the release of neutrophil chemoattractants from Escherichia coli-stimulated mast cells and neutrophils. Administration of the reagents that disrupted the ceramide-CD300f interaction prevented CLP-induced sepsis by stimulating neutrophil recruitment, whereas that of ceramide-containing vesicles aggravated sepsis. Extracellular concentrations of ceramides increased in the peritoneal cavity after CLP, suggesting a possible role of extracellular ceramides, CD300f ligands, in the negative-feedback suppression of innate immune responses. Thus, CD300f is an attractive target for the treatment of sepsis.

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www.jacionline.org) 1 : only 11q13.1 (OVOL1) replicated in the AA population. Interestingly, OVOL1 was also one of the top significant genes showing transethnic effects after the MANTRA meta-analysis performed by Paternoster et al. 1 These results suggest that AD genetic factors described to date cannot be extrapolated to AA populations and specific genetic factors need to be uncovered. In conclusion, we have identified the first genome-wide significant association for AD in AAs and replicated the association in individuals of European ancestry. The top SNP at the locus, rs3811419, is an eQTL for THEM4, a gene previously associated with allergy 5 and FLG-AS1, a long noncoding RNA that overlaps the fillagrin gene. Although we provide replication of the association in individuals of European ancestry, replication in an independent AA sample and elucidation of the exact biological role of these variants in AD is needed. We thank all patients and control subjects for their participation in the study and the eMERGE phenotyping group and researchers.

The amount of chest tube drainage just after surgery and before oral intake was a useful predictor to help us decide on the need for early surgical intervention for postoperative chylothorax.