Soluble TREM-1, as a new ligand for the membrane receptor Robo2, promotes hepatic stellate cells activation and liver fibrosis.

Triggering receptor expressed on myeloid cells-1 (TREM-1) exists in two forms: a transmembrane form and a soluble form (sTREM-1). The levels of sTREM-1 are elevated in supernatants of activated HSCs. However, the role of sTREM-1 in HSC activation and liver fibrosis remains undefined. Previous studies have primarily focused on the transmembrane form of TREM-1; we innovatively observed the function of sTREM-1 as a ligand in liver fibrosis and screened its receptor. Here, recombinant sTREM-1 was used as a stimulator which induced HSC activation and further aggravated liver fibrosis. Then, screening for sTREM-1 interacting membrane receptors was performed using pull-down assay followed by mass spectrometry, and the membrane receptor roundabout guidance receptor 2 (Robo2) was identified as a candidate receptor for sTREM-1. The interaction between sTREM-1 and Robo2 was verified by pull-down and immunofluorescence. The role of Robo2 on sTREM-1-induced HSC activation and its downstream signal pathways was assessed by knockdown of Robo2 in LX-2 cells. Furthermore, HSC-specific knockdown of Robo2 was achieved in a mouse model of liver fibrosis by using a recombinant adeno-associated virus (AAV) vector to confirm the role of the receptor, and we proved that Robo2 knockdown inhibited the activation of HSC and liver fibrosis, which also led to the inactivation of Smad2/3 and PI3K/Akt pathways in sTREM-1-induced HSC activation and liver fibrosis. In conclusion, sTREM-1 acts as a new ligand of Robo2; the binding of sTREM-1 to Robo2 initiates the activation of the downstream Smad2/3 and PI3K/Akt signalling pathways, thereby promoting HSC activation and liver fibrosis.

Gastrointestinal tract specific gene GDDR inhibits the progression of gastric cancer in a TFF1 dependent manner.

The novel gene GDDR, also named trefoil factor interactions 1, is abundantly expressed in human gastric epithelial cells but significantly down-regulated in gastric cancer. In this study, we first demonstrated that GDDR was specifically expressed in the gastrointestinal tract epithelium, while suppressed in gastric cancer cells. Forced expression of GDDR suppressed the tumor growth as shown by MTT and xenograft assay. siRNA mediated TFF1 inhibition nearly blocked the growth inhibitory role of GDDR. In summary, our study suggested that gastrointestinal tract specific gene GDDR might inhibit gastric cancer growth in a TFF1 dependent manner.

[Intracorporeal hand-sewn technique used in totally laparoscopic colectomy].

OBJECTIVE: To evaluate the safety and feasibility of hand-sewn anastomosis in totally laparoscopic colectomy. METHODS: Clinical data of 19 consecutive patients with benign(n=5) or malignant colonic diseases(n=14, 4 ascending colon cancers, 2 transverse colon cancers, and 8 sigmoid colon cancers) treated with totally laparoscopic colectomy with a hand-sewn anastomosis were reviewed. All the procedures were performed by the same surgeon team including totally laparoscopic resection and hand-sewn anastomosis, ileocolic anastomosis after right hemicolectomy, and hand-sewn purse-string sutures in the colon. RESULTS: Hand-sewn anastomosis was performed for 11 patients and circular-stapled anastomosis with hand-sewn purse-string sutures was performed for other 8 patients. The mean hand-sewn anastomosis time was (49.5 ± 29.4) min, and the mean hand-sewn purse-string sutures time was (13.3 ± 5.5) min. No patients required conversion to laparoscopy-assisted or open surgery, and there were no postoperative complications related to anastomosis. One patient with transverse colon lipoma developed mild intra-abdominal infection after surgery and recovered after conservative treatment. CONCLUSION: Totally laparoscopic intracorporeal hand-sewn anastomosis or hand-sewn purse-string sutures for colectomy is feasible and safe when performed by experienced laparoscopic surgeons.

A case-control study of laparoscopy-assisted and open distal gastrectomy for advanced gastric cancer.

BACKGROUND: The application of laparoscopy-assisted gastric surgery has been increasing rapidly for the treatment of early gastric cancer. However, there were few reports of laparoscopic surgery in the management of advanced gastric cancer (AGC), especially with T3 depth of invasion. The aim of this study was to compare the technical feasibility and oncologic efficacy of laparoscopy-assisted distal gastrectomy (LADG) versus open distal gastrectomy (ODG) for advanced gastric cancer. METHODS: A retrospective case-control study was performed comparing LADG and ODG for AGC. Thirty-five consecutive patients with AGC undergoing LADG between August 2005 and December 2007 were enrolled and these patients were compared with 35 AGC patients undergoing ODG during the same period. RESULTS: Forty-two (60.0%) patients were T3 in terms of depth of invasion. Tumor location and histology were similar between the two groups. Operation time was significantly longer in the LADG group than in the ODG group. Estimated blood loss was significantly less in the LADG group. Hospital length of stay after LADG was significantly shorter than in the open group. Postoperative pain was significantly lower for laparoscopic patients. There were no significant differences in postoperative early and late complication and in the number of lymph nodes retrieved between the two groups, and the cumulative survival of the two groups was similar. CONCLUSION: Our data indicate that LADG for AGC, mostly with T3 depth of invasion, yields good oncologic outcomes including the similar early and late complication and the cumulative survival between the two groups after 50 months of follow-up. To be accepted as a choice treatment for advanced distal gastric cancer, well-designed prospective trial to assess long-term outcomes is necessary.