Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

AIM: To investigate the expression of PTEN/MMAC1/TEP1 and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated. RESULTS: PTEN expression significantly decreased (t= 3.98, P<0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P<0.01) in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t=1.95, P<0.05) whereas VEGF expression (t = 2.37, P<0.05) and MVD (t= 3.28, P<0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P<0.01), invasion depth (t= 1.95, P<0.05) and age (t= 4.69, P<0.01). MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t=3.69, P<0.01), and there was a negative correlation betweenPTEN expression and MVD (γ=-0.363, P<0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P<0.01), lymph node metastasis (t= 2.31, P<0.05) and TNM stage (t= 3.04, P<0.01). MVD in VEGF-positive gaslyic cancer was significantly higher than that in VEGF-negative gastric cancer (t=4.62, P<0.01), and there was a positive correlation between VEGF expression of and MVD (y = 0.512, P<0.05). VEGF expression in PTEN-negative gaslyic cancer was significantly stronger than that in PTEN-positive gastric cancer (t=2.61, P<0.05), and there was a significantly negative correlation between the expression of VEGF and PTEN (γ=-0.403, P<0.05).CONCLUSION: Our results imply that inactivation of PTEN gene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer. PTEN-related angiogenesis might be attributed to its up-regulation of VEGF expression. PTEN and VEGF could be used as the markers reflecting the biologic behaviors of tumor and viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers.

Modified techniques of heterotopic total small intestina transplantation in rats

AIM: To establish a successful model of heterotopictotal small intestinal transplantation (SIT) in rats inorder to reduce the complications and increase thesurvival rate.METHODS: A total of 196 Wistar rats underwentheterotopic SIT with microsurgical technique. Technicalmodifications included shortening fasting time andsupplying energy before surgery, administering optimalvolume of crystalloid fluid to the donor and recipientduring surgical procedures, reducing mechanical andischemic injuries to donor intestine, revascularizingsmall intestinal graft with a combination ofconventional aorta to aorta anastomosis and a cuffedportal vein to left renal vein anastomosis which resultedin an acceptably short warm ischemic time, and alsoan adequate blood supply and drainage of the graft.RESULTS: The average time for the donor surgery was86min±20min, the mean operative time for therecipient was 115min±20min and warm ischemia timewas shortened to 40min±5min. There was a shorterrevascularizing time of the graft, the abdominal aorta(AA) to AA anastomosis being 21min±10min, and thecuffed portal vein (PV) to the renal vein anastomosisbeing 5min±5min.The one-week survival rate of 98 ratswith SIT was 88.78% (87/98), without thrombosis andstenosis of anastomosis. The longest survival time ofrecipient rats was more than 389 days after SIT, therats were maintaining normal weight, with perfectintestinal function and intact intestinal histology.CONCLUSION: These modified techniques for SIT wouldremarkably reduce the complications and improve survival rate in rats, which provided a potentially more consistent and practical model for experimental andclinical studies.

Clinical evidence of growth hormone for patients undergoing abdominal surgery: Meta-analysis of randomized controlled trials

AIM: To assess the effectiveness and safety of perioperative growth hormone (GH) in patients undergoing abdominal surgery.METHODS: We searched the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in February 2003. No language restrictions were applied. Randomized controlled trials (RCT) comparing GH with placebo in patients undergoing abdominal surgery were extracted and evaluated.Methodological quality was evaluated using the Jadad scale.RESULTS: Eighteen trials involving 646 patients were included. The combined results showed that GH had a positive effect on improving postoperative nitrogen balance (standardized mean difference [SMD] = 3.37, 95%CI [2.46, 4.27], P＜0.00001), and decreasing the length of hospital stay (weighted mean difference [WMD] = -2.07,95%CI [-3.03, -1.11], P = 0.00002), and reducing the duration of postoperative fatigue syndrome (SMD = -1.83,95%CI [-2.37, -1.30], P＜0.00001), but it could increase blood glucose levels (WMD = 0.91, 95%CI [0.56, 1.25],P＜0.00001).CONCLUSION: GH for patients undergoing abdominal surgery is effective and safe, if blood glucose can be controlled well. Further trials are required with a sufficient size to account for clinical heterogeneity and to measure other important outcomes such as infection, morbidity,mortality, fluid retention, immunomodulatory effects, and tumor recurrence.

Effects of n-3 fatty acid,fructose-1,6-diphosphate and glutamine on mucosal cell proliferation and apoptosis of small bowel graft after transplantation in rats

AIM: To evaluate the effects of n-3 fatty acids (n-3FA),fructose-l,6-diphosphate (FDP) and glutamine (GLN) on mucosal cell proliferation and apoptosis of small bowel graft.METHODS: One hundred and ninety-six inbred strain Wistar rats were grouped as donors and recipients, and underwent heterotopic small bowel transplantation (SBT). n-3FA, FDP and GLN were administered via gastric tube as well as venous infusion for 10 days before and after surgery, respectively.The proliferation and apoptosis of mucosal cells were analyzed with flow cytometry and in situ cell death detection kits.RESULTS: Apparent apoptosis and minor proliferation of mucosal cells of small bowel graft after transplantation were observed. A higher mucosal cell proliferative index and lower apoptotic index were found in all small bowel grafts after supplying with n-3FA, FDP and GLN.CONCLUSION: Nutritional support with n-3FA, FDP and GLN promotes mucosal cell proliferation significantly, and prevents mucosal cell from undergoing apoptosis with different degrees. These regulatory effects on the apoptosis alter the structure and absorption function of transplanted small bowel favorably.