Epidermal growth factor receptor-dependent PI3K-activation promotes restitution of wounded human gastric epithelial monolayers

Restitution is a crucial event during the healing of superficial injury of the gastric mucosa involving epithelial cell sheet movement into the damaged area. We demonstrated that growth factors promote the restitution of human gastric epithelial cells. However, the intracellular signaling pathways that transmit extracellular cues as well as regulate basal and growth factor-stimulated gastric epithelial cell migration are still unclear. Herein, confluent human gastric epithelial cell monolayers (HGE-17) or primary cultures of gastric epithelial cells were wounded with a razor blade and the migration response was analyzed in presence or absence of TGFalpha or of pharmacological inhibitors of signaling proteins. Kinase activation profile analysis and phase-contrast microscopy were also performed in parallel. We report that ERK1/2 and Akt activities are rapidly stimulated following wounding of HGE-17 cells. Treatment of confluent HGE-17 cells or primary cultures of gastric epithelial cells with the phosphatidylinositol 3-kinase inhibitor LY294002, but not the MEK1 inhibitor, PD98059, significantly inhibits basal and TGFalpha-induced migration following wounding. Conversely, treatment of wounded HGE-17 cells with phosphatidylinositol(3,4,5)-triphosphate is sufficient to stimulate basal cell migration by 235%. In addition, pp60c-src kinase activity and tyrosine phosphorylation of epidermal growth factor receptors (EGFR) are also rapidly enhanced after wounding and pharmacological inhibition of both these activities strongly attenuates basal and TGFalpha-induced migration as well as Akt phosphorylation levels. In conclusion, the present results indicate that EGFR-dependent PI3K activation promotes restitution of wounded human gastric epithelial monolayers.     

Le traitement chirurgical des tumeurs endocrines digestives

Surgery is the only curative treatment for localized gastrointestinal endocrine tumors. It plays a major role in therapeutic strategy. It meets the oncological principles of treatment. It must take into consideration the site of the tumor, its extension and its secretory nature. In well-differentiated endocrine tumors according to WHO classification, surgery must be indicated, not only for the primary tumor but also for the metastasis, particularly liver metastasis. The primary gastrointestinal endocrine tumors (functional or non functional) are mainly pancreatic in origin but also can be situated in small bowel, appendix, colon, or rectum. Surgery is part of a comprehensive approach discussed in multidisciplinary meeting.     

Small fibronectin fragments induce endothelium-dependent vascular relaxations

Strips of rabbit thoracic aorta precontracted with phenylephrine relaxed when exposed to selected synthetic peptides derived from the cell attachment domain of fibronectin. The relaxations elicited by both acetylcholine and the hexapeptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) were dependent on the presence of an intact endothelium, were resistant to indomethacin, and were inhibited by hemoglobin. The structure-activity relationship of four oligopeptides derived from fibronectin was in fair agreement with their ability to prevent fibronectin-mediated cell adhesion in other experimental systems. Human plasma fibronectin (up to 2.3 microM) did not relax this preparation and did not prevent the relaxant effect of the synthetic hexapeptide GRGDSP. On the rabbit isolated mesenteric artery, the relaxations induced by GRGDSP were significantly inhibited by indomethacin treatment, suggesting a contribution of locally produced prostaglandins. The displacement of fibronectin by soluble peptides from its binding sites on endothelial cells may result in significant pharmacologic responses, probably resulting from perturbations of the endothelial cell membranes.