PurposeEpithelial to mesenchymal transition (EMT) can contribute to gastric cancer (GC) progression and recurrence following therapy. Tumor-associated neutrophils (TANs) are associated with poor outcomes in a variety of cancers. However, it is not clear whether TANs interact with the EMT process during GC development.MethodsImmunohistochemistry was performed to examine the distribution and levels of CD66 + neutrophils in samples from 327 patients with GC. CD66b + TANs were isolated either directly from GC cell suspensions or were conditioned from healthy donor peripheral blood polymorphonuclear neutrophils (PMNs) stimulated with tumor tissue culture supernatants (TTCS) and placed into co-culture with MKN45 or MKN74 cells, after which migration, invasion and EMT were measured. Interleukin-17a (IL-17a) was blocked with a polyclonal antibody, and the STAT3 pathway was blocked with the specific inhibitor AG490.ResultsNeutrophils were widely distributed in gastric tissues of patients with GC and were enriched predominantly at the invasion margin. Neutrophil levels at the invasion margin were an independent predictor of poor disease-free survival (DFS) and disease-specific survival (DSS). IL-17a + neutrophils constituted a large portion of IL-17a-producing cells in GC, and IL-17a was produced at the highest levels in co-culture compared with that in TANs not undergoing co-culture. TANs enhanced the migration, invasion and EMT of GC cells through the secretion of IL-17a, which activated the Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3) pathway in GC cells, while deprivation of IL-17a using a neutralizing antibody or inhibition of the JAK2/STAT3 pathway with AG490 markedly reversed these TAN-induced phenotypes in GC cells induced by TANs.ConclusionsNeutrophils correlate with tumor stage and predict poor prognosis in GC. TANs produce IL-17a, which promotes EMT of GC cells through JAK2/STAT3 signalling. Blockade of IL-17a signalling with a neutralizing antibody inhibits TAN-stimulated activity in GC cells. Therefore, IL-17a-targeted therapy might be used to treat patients with GC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1003-0) contains supplementary material, which is available to authorized users.
In the field of management psychology, the matching of employees and leaders can help improve enterprise performance. Then, in the field of sustainable development, can human aspects enhance green product development performance? Does the match between leaders and employees help to advance this improvement? A survey questionnaire was used to collect data for this study; 52 leaders and their 214 employees were contacted. The findings of this study revealed that green transformational leadership is positively related to green product development performance. Besides, both green transformational leadership and individual green values have positive influences on green psychological climate, which leads to the promotion of green product development performance in the organization. Further, when green transformational leadership matches employees with green values, it is more conducive to create green psychological climate in the organization, thereby improving the green products development performance. The implications for practitioners are discussed on the basis of the empirical findings.
Background and study aims: Qualified esophagogastroduodenoscopy (EGD) is a prerequisite for detecting upper gastrointestinal lesions especially early gastric cancer (EGC). Our previous report showed that artificial intelligence system could monitor blind spots during EGD. Here, we updated the system to a new one (named ENDOANGEL), verified its effectiveness on improving endoscopy quality and pre-tested its performance on detecting EGC in a multi-center randomized controlled trial.
Patients and methods: ENDOANGEL was developed using deep convolutional neural networks and deep reinforcement learning. Patients undergoing EGD examination in 5 hospitals were randomly assigned to ENDOANGEL-assisted (EA) group or normal control (NC) group. The primary outcome was the number of blind spots. The second outcome includes performance of ENDOANGEL on predicting EGC in clinical setting.
Results: 1,050 patients were recruited and randomized. 498 and 504 patients in EA and NC groups were respectively analyzed. Compared with NC, the number of blind spots was less (5.382±4.315 vs. 9.821±4.978, p<0.001) and the inspection time was prolonged (5.400±3.821 min vs. 4.379±3.907 min, p<0.001) in EA group. In the 498 patients from EA group, 196 gastric lesions with pathological results were identified. ENDOANGEL correctly predicted all 3 EGC (1 mucosal carcinoma and 2 high-grade neoplasia) and 2 advanced gastric cancer, with a per-lesion accuracy of 84.69%, sensitivity of 100% and specificity of 84.29% for detecting GC.
Conclusions: The results of the multi-center study confirmed that ENDOANGEL is an effective and robust system to improve the quality of EGD and has the potential to detect EGC in real time.
When stage matched, SRC patients had a similar survival to NSRC patients. Curative resection is recommended to improve the prognosis of patients with SRC.
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