HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation.

Human hedgehog-interacting protein (HHIP), a negative regulator of hedgehog (HH) signaling pathway, has been reported to be dysregulated in many types of cancer, including gastric cancer. However, the inhibitory role of HHIP as well as the underlying molecular mechanism of HHIP regulation in gastric cancer haven't been fully elucidated yet. In this study, we demonstrated that HHIP overexpression significantly suppressed the proliferation and invasion of AGS cells evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays, respectively. Interestingly, methylation-specific polymerase chain reaction (MS-PCR, MSP) showed that HHIP overexpression dramatically decreased its de novo promoter methylation levels in AGS cells. Furthermore, HHIP expression was higher in adjacent non-cancerous tissue compared to matched gastric cancer tissue. High HHIP level was negatively correlated with metastasis (p = 0.035) but not local recurrence (p = 0.58). Taken together, our study suggested that HHIP can modulate gastric cancer progression and metastasis via regulation of its de novo promoter methylation levels in a feedback manner. Lower HHIP levels is positively associated with gastric cancer metastasis, which not only indicates HHIP could be served as a protective marker for gastric cancer, but also suggests restoring HHIP expression might be a potential therapeutic strategy for clinical treatment.

A comparative study of treatment of gastrointestinal stromal tumors with laparoscopic surgery: a retrospective study.

PURPOSE: The purpose of this study was to analyze the clinical efficacy and complications of endoscopic submucosal dissection (ESD) and laparoscopic resection of stromal tumors, and to explore the clinical value and complications of stromal tumors treated with ESD. METHODS: 146 patients with gastric stromal tumors (GSTs) treated in our hospital from January 2012 to January 2016 were retrospectively analyzed. Patients were divided into the ESD group and the laparoscopic surgery group (LS). The operation time, postoperative recovery time of diet, postoperative exhaust time, etc were observed and analyzed. All the measurement indexes were described as mean ± standard deviation. The t-test of two independent samples was used for the hypothesis test. Chi-square test was used for comparison of the percent data between the two groups and p<0.05 indicated significant difference. RESULTS: The postoperative diet recovery time, postoperative exhaust time, hospital stay and hospitalization cost of the ESD group were better compared with the LS group (p<0.001). There was no significant difference in operative time between the ESD and LS group (p>0.05), while the operation time in ESD group was longer than in the LS group (p<0.05). The operation time of gastric body and antrum stromal tumors was shorter than in the ESD group group (p<0.05). There were no significant differences in tumor diameter, mitotic number and Flether classification between the groups (p>0.05). No significant difference in the incidence of postoperative bleeding, incision infection and recurrence rate was noticeable between the groups (p>0.05). CONCLUSIONS: Endoscopic treatment of GSTs is safe and feasible, and may be better than laparoscopic resection.

NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins.

T cell receptor (TCR) and costimulatory receptor (CD28) signals cooperate in activating T cells, although understanding of how these pathways are themselves regulated is incomplete. We found that Homer2 and Homer3, members of the Homer family of cytoplasmic scaffolding proteins, are negative regulators of T cell activation. This is achieved through binding of nuclear factor of activated T cells (NFAT) and by competing with calcineurin. Homer-NFAT binding was also antagonized by active serine-threonine kinase AKT, thereby enhancing TCR signaling via calcineurin-dependent dephosphorylation of NFAT. This corresponded with changes in cytokine expression and an increase in effector-memory T cell populations in Homer-deficient mice, which also developed autoimmune-like pathology. These results demonstrate a further means by which costimulatory signals are regulated to control self-reactivity.