ABSTRACT
Objective: To explore the clinicopathological characteristics and prognostic factors of gastric neuroendocrine neoplasm (NEN). Methods: Clinicopathological parameters and follow-up data collected from 117 patients with gastric NEN at Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2017 were reviewed, classified, and graded according to World Health Or-ganization (WHO) 2010 classification. Clinicopathological characteristics of different types and grades of gastric NEN were compared and survival analysis was performed. Results: Among the 117 cases confirmed as gastric NEN, this entire cohort comprised 13 cases (11.1%) of neuroendocrine tumor (NET) G1, 6 cases (5.1%) of NET G2, 57 cases (48.7%) of neuroendocrine carcinoma (NEC), and 41 cases (35.1%) of mixed adenoneuroendocrine carcinoma (MANEC). Gastric NET G1 and G2 typically consisted of multiple small tumors with shallow invasion and infrequent lymphatic and distant metastases at early stages at the time of diagnosis. The treatment of patients with gastric NET included endoscopic submucosal dissection and radical surgical resection. Precursor neuroendocrine lesions were detected in most cases. The patients with gastric NET G1 and G2 had a good prognosis. Gastric NEC and MANEC mostly consisted of single large tumors with deep infiltration, and common lymphatic and distant metastases at advanced stages when the diagnoses were confirmed. All the patients with gastric NEC and MANEC underwent surgical resection, and most received adjuvant therapy. Histopathological changes of gastric NEC were characterized by large cells and poorly differentiated tumors, while gastric MANEC had various forms of neuroendocrine and adenocarcinoma components. The prognosis of patients with gastric NEC and MANEC was poor for both; however, the predictors of progression-free survival and overall survival were different between gastric NEC and MANEC. Conclusions: Gastric NEN are a group of heterogeneous tumors with different clinicopathological features and prognosis. More multicenter studies with large sample sizes are still needed to improve the classification of gastric NEN and explore the prognostic factors.
ABSTRACT
Objective To investigate the vasorelaxant effect and possible mechanism of niclosamide ethanolamine (NEN)on isolated rat coronary artery(RCA). Methods Wire myograph was used to record myogenic tone of vessels. The vasorelaxant effect of NEN was studied in RCA precontracted with either KCl or U46619. Study of related inhibitors was performed to investigate possible involvement of potassium channels and the mitogen-activated protein kinase(MAPK) signaling pathway in vasorelaxation. The effect of NEN on Ca2+mobilization was determined by observing vasoconstrictor-induced contractions in tissue solution deprived of Ca2+followed by Ca2+restoration. Results NEN(0.5-3.0 μmol/L) relaxed RCA precontracted with KCl or U46619 in a concentration-dependent manner. MAPK inhibitors(PD98059 and SB239063)reduced the relaxant effect of NEN,while the potassium-channel blockers(tetraethylamine,4-aminopyridine, BaCl2,and glibenclamide)did not significantly affect relaxation. NEN specifically inhibited the contraction component dependent on extracellular Ca2+influx in vessels stimulated with KCl and U46619, with a negligible effect on the component dependent on intracellular Ca2+release. Conclusions NEN exhibits vasodilator properties in RCA. Inhibition of extracellular Ca2+influx and activation of the MAPK signaling pathway may be involved in NEN-induced RCA vasorelaxation.