Abstract: Our previous studies indicated that cyclooxygenase-2 inhibitor or octreotide could suppress the proliferation of gastric adenocarcinoma in vitro or in vivo. The present study was aimed to find whether rofecoxib combined with octreotide could enhance the inhibitive effects on the growth of gastric cancer or not. The effect of rofecoxib or octreotide on proliferation of gastric cancer cell line was determined by 3H-thymidine ribotide incorporation. The TdT-mediated dUTP nick end labeling assay was used to detect the apopotosis. To determine their synergic antineoplastic effects, the interaction between rofecoxib and octreotide on SGC-7901 cell was evaluated by the median effect plot. After orthotopical implantion of xenografts of human gastric cancer in stomach, nude mice were given rofecoxib plus octreotide for 8 weeks. Cyclooxygenase-2 in gastric cancer tissues was measured by immunohistochemistry. Combination of rofecoxib and octreotide presented synergistic effect (combination index <1) in majority of responses. The inhibitory rate for xenografts in nude mice was 89.7% in rofecoxib group. Combination of rofecoxib and octreotide enhanced inhibitory rate to 98.8%. The combination greatly increased the apoptotic index (78.20%

Objective: Octreotide and aspirin have shown the growth inhibition for some tumors. However, the effects of these non-cytotoxitic agents on gastric adenocarcinoma are still largely unknown. The effects of combination of octreotide and aspirin on the growth of gastric cancer were investigated. Methods: Proliferation of gastric cancer cell line affected with octreotide or aspirin was determined by 3H-thymidine incorporation. After xenografts of human gastric cancer were implanted orthotopically in stomach, nude mice were administrated octreotide plus aspirin for 8 weeks. The mRNA of somatostatin receptor in the tissues of gastric carcinoma was detected by reverse transcription polymerase chain reaction technique. Cyclooxygenase-2 in gastric cancer tissues was measured by immunohistochemistry. Results: Both octreotide and aspirin significantly reduced the 3H-thymidine incorporation of gastric cancer cells. Xenografts in situ were found in all stomachs of nude mice except two nude mice in combination group. Either size or weight of tumors treated by octreotide or aspirin was significantly reduced when compared to that of control. The combination group showed the best inhibition in tumor growth. The inhibition rate for tumor was 60.6% in octreotide group, 39.3% in aspirin group and 85.6% in the combination group respectively. No severe side effect was observed in all of treatment groups. Somatostatin receptor-2 and 3 were expressed in the transplanted gastric adenocarcinomas. Aspirin could down regulate the strong expression of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice. Conclusions： Combination of octreotide and aspirin significantly enhanced the anti-proliferative effect in gastric cancer through mediation of somatosatin receptors and suppression of cyclooxygenase-2.

Abstract Objective: This study was undertaken to evaluate the changes of the activity of the intestinal mucosal mast cells (IMMC) in multiple organ failure (MOF). Methods: Rat model of the MOF was induced by intraperitoneal injection of zymosan. Both the functional alteration and the pathological morphology of essential organs, including small intestine, liver, kidney and the lungs, were examined, or visualized by light microscopy. The histamine and tumor necrosis factor α (TNF-α) in plasma and small intestinal tissue were detected by the fluorimetric assay and Enzyme-linked immunoadsordent assay, respectively. The ultra structure changes of the IMMC from MOF rat were evaluated by a transmission electronic microscope. Results: Zymosan induced obvious inflammatory morphology and functional impairment in the essential organs in the rats, which is indicative of characteristic changes in the MOF. It showed a significant decreased level of histamine in the intestinal tissue of the MOF rats when compared with the normal controls (11.63±1.97 vs 8.67±1.16 ng/g protein, P<0.01), whereas the plasma histamine level no significant changes. TNF-α level elevated apparently in both intestinal tissue and plasma in MOF rats. Furthermore, the increased number and degranulation of IMMC in the gut tissue were obvious in the MOF rats. Conclusion: These results suggested that the histamine and TNF-α, released from irrelevantly activated IMMC, may play an important role in the development of MOF.

[Abstract]: Multiple organ failure (MOF) is the most serious result followed by trauma and infection. Our previous study has shown that activated intestinal mucosal mast cells (IMMC) may play an important role in the development of MOF. Somatostatin (SST), one of gut peptides, is an important regulator in the neuro-endocrine-immune network. However, the effects of SST on IMMC especially in the case of MOF remain unclear. Objective: This study was aimed to investigate the effect of SST on the activity of IMMC in the development of MOF. Methods: The rat model of MOF was established by injection of zymosan. Thirty minutes after the injection of zymosan, SST at 2.3ng/Kg/h or 0.023ng/Kg/h was injected respectively through tail veins. The concentration of histamine and tumor necrosis factor-α (TNF-α) in plasma and intestine tissue were measured. The pathological alterations of essential organ including intestine, liver, kidney and lung were studied under light microscope. Their corresponding functions were reflected with alanine aminotransferase (ALT), cretinine (Cr) and oxygen pressure (PO2). In addition, the ultra structure of the IMMC was observed under a transmission electronic microscope. Results: Compared with the controlled rats, the rats injected with SST (2.3ng/Kg/h) showed less serious inflammatory response under light microscope. ALT and Cr were decreased 53% and 60% respectively. However, PO2 was increased 50%. The histamine level in the intestinal tissue from rats treated with SST remarkably increased (8.60±0.50 to 14.50±1.08 ng/g protein), while the plasma histamine level did not show any significant changes. Exdogeneous SST also resulted in lower level of TNF-α in intestine but no changes in plasma. Furthermore, degranulation of IMMC from the rats treated with SST was less obvious. Conclusions: SST may prevent from or arrest the development of MOF through suppression of inflammatory mediators releasing such as histamine and TNF-α.

Objectives: Somatostatin and its analogues may suppress the growth of various tumor cells. However, the effect of octreotide on growth of gastric adenocarcinoma is still largely unknown. This study was to explore if octreotide could inhibit the growth of gastric adenocarcinoma and the probable mechanisms behind the effects. Methods: Proliferation of gastric cancer cell line affected with octreotide was determined by 3H-thymidine incorporation. After xenografts of human gastric cancer were implanted orthotopically in stomach, nude mice were administrated octreotide for 8 weeks. The mRNA of somatostatin receptor in the SGC-7901 cells was detected by reverse transcription polymerase chain reaction technique. Extrcellular signal-regulated protein kinase and c-Fos in gastric cancer tissues were measured by immunohistochemistry and western blot. Activator protein-1 binding activity was examined by electrophoretic mobility sift assay. Results: 3H-thymidine incorporation into SGC-7901 cells was significantly decreased by octreotide in a manner of concentration dependence. Either size or weight of tumors treated with octreotide was significantly reduced in vivo. The inhibition rate for tumor was 62.3% in octreotide group. The genes of somatostatin receptor 2 and 3 were expressed in SGC-7901 gastric cancer cell lines. Extracellular signal-regulated protein kinase and the c-Fos protein level were decreased in gastric adenocarcinoma treated with octreotide. Moreover, the fetal calf serum stimulated activator protein-1 binding activity could be suppressed by octreotide potentially. Conclusions: Inhibition of sequential molecular events in MAPK pathway may interpret the mechanisms behind the suppressive effect of octreotide on the growth of gastric adenocarcinoma.

Objective: To study the effect of somatostatin analogue octreotide on the invasion and metastasis of gastric cancer in vitro and in vivo. Methods: Using membrane invasion culture system alone or coated with matrigel, we observed the effect of octreotide on blocking migration and invasion of gastric carcinoma cells. Nude mice implanted orthotopically with SGC-7901 human stomach carcinoma were given injections of octreotide for 8 weeks. MMP-2 was detected by gelatin zymography or RT-PCR. The microvascular density and VEGF expression were examined by immunohistochemical staining with factor VIII antibody and VEGF antibody. Results: Octreotide significantly inhibit migration(49.8

Objective: To investigate effects of Aspirin on the growth of gastric cancer in vitro and in vivo. Methods: The effects of aspirin on the proliferation of SGC-7901 cells were measured by 3H-thymidine incorporation into DNA and cell cycle analysised by flow cytometric analysis, separately. COX-2 protein was examed in SGC-7901 cells by immunohistochemistry. The expression of c-Fos and AP-1 activity were detected by immunoblotting and EMSA separately. Results: Aspirin significantly decreased 3H-thymidine incorporation into SGC-7901 cells. Among concentration of 1

Objective: To investigate the effects of somatostatin analogue octreotide on the proliferation and apoptosis of human hepatocellular carcinoma (HCC) cell line as well as the growth of HCC xenografts in nude mice. Methods The effects of octreotide on the proliferation and apoptosis of SMMC-7721 HCC cells was measured by 3H-thymidine incorporation into DNA and the TdT-mediated dUTP nick end labeling assay (TUNEL) or flow cytometric assay separately. Nude mice bearing xenografts of the cell line were treated with octreotide or saline as a control daily until eight weeks after tumor implantation. Results Incubation with octreotide decreased 3H-thymidine incorporation into DNA of SMMC-7721 cells by～50% at a concentration of 1μM. The inhibit effect of octreotide showed a concentration dependence. After 96h incubation, total cell count was decreased 52.2% compared with control. When cells were treated by octreotide at 1×10-6mol/L for 24 hours, the apoptosis rates was (15.2±2.4)%. At necropsy, in mice given octreotide, the mean tumor weight were significantly lower than that of control group(0.27±0.05 vs 0.85±0.37,P<0.01). The inhibition rate of tumor in vivo at 2 months was 68.2%. Conclusion Octreotide is effective in inhibiting growth of HCC both in vivo and in vitro significantly. The mechanisms of antineoplastic effect action may involved in inhibiting DNA synthesize and inducing apoptosis of tumor cells.

To observe the effect of vasoactive intestinal peptide(VIP) or somatostatin (SST) on the lymphocytes traffic in gut-associated lymphoid tissues in rat, 18 rats were divided into three groups at random. VIP and SST were continuously infused from femoral vein at a dose of 60 pmol/h for 7 h. It was found that the lymphocytes in intestinal lymph collected in 5 hours were significantly reduced after VIP and SST administration(P<0.05). Although the volume decreasing of intestinal lymph was happened in all groups, no significant changes in lymph flow were observed in control and treat groups. The percentages of CD8+ cells in intestinal lymph of rat treated by VIP or SST was markedly lower than that in control group (P<0.05). Finally, either VIP or SST infusion reduced CD8+ cells in the small intestinal mucosa when compared with control. It concludes that either VIP or SST not only reduces lymphocytes, especially CD8+ cells traffic from intestinal mucosa immune system to other organs and systemic immune system but also suppresses the homing of CD8+lymphocytes into intestinal mucosa immune system in rats.

Objective: To observe the effect of VIP or SST on the lymphocyte homing to the intestinal tract. Methods: Intestinal lymph were collected from mesenteric lymphatic duct of rats. Intestinal lymphocytes, which had been incubated with VIP or SST, were labeled with 51Cr and then were infused into blood circulation of rats. The 51Cr-intestinal lymphocytes in organs (or tissues)were determined with γ-counter. Results: About 10% of 51Cr-intestinal lymphocytes homed to intestinal tract within 1 h at normal physiological state. The distribution of 51Cr-intestinal lymphocytes treated with either VIP or SST in mesenteric node (1.83% or1.56%) and in Peyer's patches (1.85% or 1.60%) were significantly lower than that of control group (3.83%, 3.85%), P<0.05. VIP or SST did not show remarkable affection on the homing of 51Cr-intestinal lymphocytes to diffusive lymphatic tissue in small intestine when compared with control. Conclusion: Either VIP or SST reduces the homing of intestinal lymphocytes to mesenteric nodes and Peyer's patches in rats.