SHIP2 controls PtdIns(3,4,5)P3 and PKB activity in response to oxidative stress

Reactive oxygen species (ROS) are known to be involved in redox signalling pathways that may contribute to normal cell function as well as disease progression. The tumour suppressor PTEN and the inositol 5-phosphatase SHIP2 are critical enzymes in the control of PtdIns(3,4,5)P(3) level. It has been reported that oxidants, including those produced in cells such as macrophages, can activate downstream signalling via the inactivation of PTEN. The present study evaluates the potential impact of SHIP2 on phosphoinositides in cells exposed to sodium peroxide. We used a model of SHIP2 deficient mouse embryonic fibroblasts (MEFs) stimulated by H(2)O(2): at 15 min, PtdIns(3,4,5)P(3) was markedly increased in SHIP2 -/- cells as compared to +/+ cells. In contrast, no significant increase in PtdIns(3,4)P(2) could be detected at 15 or 120 min incubation of the cells with H(2)O(2) (0.6 mM). PKB activity was also upregulated in SHIP2 -/- cells as compared to +/+ cells in response to H(2)O(2). SHIP2 add back experiments in SHIP2 -/- cells confirm its critical role as a lipid phosphatase in the control of PtdIns(3,4,5)P(3) level in response to H(2)O(2). We conclude that SHIP2 lipid phosphatase activity plays an important role in the metabolism PtdIns(3,4,5)P(3) which is demonstrated in oxygen stressed cell

Sixteen-year follow-up of Barrett's esophagus, endoscopically treated with argon plasma coagulation.

OBJECTIVE: The thermal destruction of non-dysplastic Barrett&#8217;s esophagus (BE) and its replacement by squamous epithelium is an attractive, but unproven strategy to avoid further development of dysplasia or cancer. The goal of this study was to estimate the persistence of restoration of squamous epithelium and the risk of cancer in BE that was eradicated using argon plasma coagulation (APC) in the absence of high-grade dysplasia, 16 years after its&nbsp;application. DESIGN: We followed 32 patients with BE who underwent eradication of metaplastic epithelium using APC, up to 16 years&nbsp;later. RESULTS: At the end of the initial treatment, 25 of 32 patients (78%) had complete endoscopic eradication, there was partial squamous re-epithelialization in four patients (13%) and it was absent in three patients (9%). We observed buried metaplastic glands under new squamous epithelium in 6 of the 25 patients who had complete endoscopic eradication. At follow-up, sustained complete endoscopic eradication was observed in 16 of 32 patients (50%), partial eradication in 11 of 32 patients (35%); there were two patients (6%) lost to follow-up and three patients (9%) developed esophageal adenocarcinoma. Two of the latest cases arose from the buried glands under neosquamous epithelium after complete eradication and one arose from a small remaining Barrett&#8217;s&nbsp;segment. CONCLUSIONS: We observed long-term re-epithelialization in the majority of patients who had previously had complete eradication of Barrett&#8217;s esophagus. This did not provide protection against cancer development, as the incidence of cancers arising from buried glands or from residual Barrett&#8217;s esophagus was similar to that observed in patients undergoing no specific&nbsp;treatment.</p