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. The effect of rofecoxib or octreotide on proliferation of gastric cancer cell line was determined by 3 H-thymidine ribotide incorporation. The TdT-mediated dUTP nick endlabeling 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 the 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% ؎ 6.45%) of the xenografts as compared with that of using rofecoxib alone (46.60% ؎ 3.42%); the difference was very significant (p < 0.001). Rofecoxib could inhibit the activity of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice. Our results indicate that combination of rofecoxib and octreotide significantly enhances the antiproliferative effect in gastric adenocarcinoma, which might have potential therapeutic value. © 2004 Wiley-Liss, Inc. Key words: rofecoxib; octreotide; gastric adenocarcinoma; cyclooxygenase-2The poor prognosis of unresectable gastric adenocarcinoma and the various disappointing therapeutic modalities make further investigation of new therapeutic approach for advanced gastric cancer of primary importance. Accumulative evidence has shown that overexpression of cyclooxygenase-2 (COX-2) in gastric adenocarcinoma might play a crucial role in invasive tumor growth and offer a new strategy against cancer by the use of COX-2 inhibitors. [1][2][3][4] The inhibitive effect of aspirin or rofecoxib, a higher selective COX-2 inhibitor 5 on the proliferation of gastric cancer, has been observed in our previous studies. 6,7 Various studies have demonstrated that the growth of normal cells and malignant tumor may be regulated by gut peptides. 8,9 In the stomach, besides the known inhibitory function of somatostatin (SST) on acid secretion, it has been suggested that the analogues of SST could be candidates for arresting the growth of gastric adenocarcinoma. Previous data from the literature have shown that the mean tumor volume in nude mice treated with octreotide, an analogue of SST, was significantly lower than that of control group with an inhibitory rate of 60.6%. 6,10 The antineoplastic action of octreotide is thought to be mediated through the receptors for S...
Inhibition of sequential molecular events in MAPK pathway may interpret the mechanisms underlying the effect of octreotide on the growth of gastric adenocarcinoma.
BackgroundWireless esophageal pH monitoring system is an important approach for diagnosis of gastroesophageal reflux disease (GERD), the aim of this study is to test the tolerability and utility of the first wireless esophageal pH monitoring system made in China, and evaluate whether it is feasible for clinical application to diagnose GERD.MethodsThirty patients from Department of Gastroenterology of The First Affiliated Hospital of Chongqing Medical University who were suspected GERD underwent JSPH-1 pH capsule. The capsule was placed 5 cm proximal to the squamocolumnar junction (SCJ) by endoscopic determination, the data was recorded consecutively for 48 hours. Then all pH data was downloaded to a computer for analysis. The discomforts reported by patients were recorded.Results30 patients were placed JSPH-1 pH capsule successfully and completed 24-hour data recording, 29 patients completed 48-hour data recording. One patient complained of chest pain and required endoscopic removal. No complications and interference of daily activities were reported during data monitoring or follow-up period. 48-hour pH monitoring detected 15 patients of abnormal acid exposure, on day1 detected 9 patients, the difference had statistical significance (P<0.01). Positive symptom index (SI) was identified in 3 patients with normal pH data in both 24-hours. In total, 48-hour monitoring increased diagnosis of GERD in 9 patients.Conclusion48-hour esophageal pH monitoring with JSPH-1 wireless pH monitoring system is safe, well tolerated and effective. It can be feasible for clinical application to diagnose GERD.
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