Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric caner by systematically reviewing the risk of the original studies. Thirty-nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta-analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL-1B-511T, 231C, 13954T and IL-1RN*2 was 1.26 (95% confidence interval (CI): 1.03-1.55), 1.00 (95% CI: 0.82-1.22), 1.37 (95% CI: 0.94-2.00) and 1.20 (95% CI: 1.01-1.41), respectively. A stratified analysis showed that IL-1B-511T was associated with an increased risk of gastric cancer (intestinal type) (OR 5 1.76, 95% CI: 1.12-2.57). Moreover, IL-1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR 5 1.30, 95% CI: 1.09-1.54). In conclusion, IL-1B-511 and IL-1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer. ' 2006 Wiley-Liss, Inc.

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Aims: To test the usefulness of upper gastrointestinal investigations and quality of life assessment in Chinese patients with non‐cardiac chest pain. Methods: Seventy‐eight consecutive patients with non‐cardiac chest pain underwent upper endoscopy. Eight patients had upper gastrointestinal pathology (10%). The remaining 70 patients received acid perfusion test, oesophageal manometry and 24‐h ambulatory oesophageal pH (n=65)/manometry (n=61), and the results were compared with those of healthy controls (n=20). Symptoms and quality of life (SF‐36) were assessed by standard validated questionnaire. Results: Significant acid reflux symptoms were present in five (5/70, 7%) patients. Abnormal 24‐h oesophageal pH, indicating gastro‐oesophageal reflux, was found in 19 (19/65, 29%) patients. The percentage of simultaneous contractions was higher and the percentage peristalsis was lower in patients with non‐cardiac chest pain when compared with normal subjects by 24‐h ambulatory manometry. Patients with non‐cardiac chest pain had a lower SF‐36 score when compared to controls. Conclusions: Typical acid reflux symptoms are uncommon in Chinese patients with non‐cardiac chest pain, but abnormal 24‐h pH results, indicating gastro‐oesophageal reflux, were found in 29% of patients. Ineffective contractions were more frequently found in patients with non‐cardiac chest pain by 24‐h ambulatory manometry, which may have a bearing on the impaired quality of life in such patients. Upper gastrointestinal investigations are useful for the evaluation of Chinese patients with non‐cardiac chest pain.

Aim: To test the efficacy of omeprazole, furazolidone and amoxicillin triple therapy for the treatment of Helicobacter pylori infection after failure of standard first‐line therapy recommended by the Asia‐Pacific Consensus on the management of H. pylori infection. Methods: Patients with failed H. pylori eradication received omeprazole, 20 mg, furazolidone, 100 mg, and amoxicillin, 1 g, all twice daily for 1 week. Endoscopy (CLO test, histology and culture) was performed before treatment. Post‐treatment H. pylori status was determined by 13C‐urea breath test 6 weeks later. Results: Fifty patients were recruited. Resistance to metronidazole, clarithromycin and both drugs was in the range of 50–64%, 60–75% and 40–50%, respectively, after failure of first‐line therapy. Amoxicillin resistance was not found. The intention‐to‐treat and per protocol H. pylori eradication rates were 52% and 53%, respectively. Patients with double resistance to metronidazole and clarithromycin showed the lowest eradication rate (38%), which was significantly lower than that of patients with sensitive strains (88%). Side‐effects were minimal and compliance was excellent (98%). Conclusions: One‐week omeprazole, furazolidone and amoxicillin rescue therapy achieved a high eradication rate in strains sensitive to metronidazole and clarithromycin. This is a cheap and safe rescue regimen when guided by pre‐treatment sensitivity testing.

It has been found that expression of 15-lipoxygenase-1 (15-LOX-1) and its main product, 13-S-hydroxyoctadecadienoic acid (13-S-HODE), are decreased in human colorectal and esophageal cancers and that non-steroidal anti-inflammatory drugs (NSAIDs) can therapeutically induce 15-LOX-1 expression to trigger apoptosis in those cancer cells. We found that a specific cyclooxygenase-2 (COX-2) inhibitor SC-236 similarly induced apoptosis in gastric cancer cells. In the present study, we tested whether SC-236 induced apoptosis through up-regulation of 15-LOX-1 in gastric cancer. We found that: (i) SC-236 inhibited growth of gastric cancer cells mainly by inducing apoptosis; (ii) SC-236 induced 15-LOX-1 expression and increased endogenous 13-S-HODE product, instead of 15-S-HETE during apoptosis; (iii) SC-236 did not affect expression of COX-1, COX-2, 5-LOX and 12-LOX; and (iv) 15-LOX-1 inhibition suppressed SC-236 induced apoptosis. These findings demonstrated that SC-236 induced apoptosis in gastric cancer cells via up-regulation of 15-LOX-1, and 13-S-HODE. These are potential and new targets for prevention and treatment of gastric cancer.

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Studies have indicated the role of HSF1 (heat-shock transcription factor 1) in repressing the transcription of some nonheat shock genes. XAF1 (XIAP-associated factor 1) was an inhibitor of apoptosis-interacting protein with the effect of antagonizing the cytoprotective role of XIAP. XAF1 expression was lower in gastrointestinal cancers than in normal tissues with the mechanism unclear. Here we showed that gastrointestinal cancer tissues expressed higher levels of HSF1 than matched normal tissues. The expression of XAF1 and HSF1 was negatively correlated in gastrointestinal cancer cell lines. Stress stimuli, including heat, hypo-osmolarity, and H 2 O 2 , significantly suppressed the expression of XAF1, whereas the alteration of HSF1 expression negatively correlated with XAF1 expression. We cloned varying lengths of the 5-flanking region of the XAF1 gene into luciferase reporter vectors, and we evaluated their promoter activities. A transcription silencer was found between the ؊592-and ؊1414-nucleotide region that was rich in nGAAn/nTTCn elements (where n indicates G, A, T, or C). A high affinity and functional HSF1-binding element within the ؊862/؊821-nucleotide region was determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Inactivation of this "heat-shock element" by either site-directed mutation or an HSF1 inhibitor, pifithrin-␣, restored the promoter activity of the silencer structure. Moreover, pretreatment with antioxidants suppressed HSF1 binding activity and increased the transcriptional activity and expression of XAF1. These findings suggested that endogenous stress pressure in cancer cells sustained the high level expression of HSF1 and subsequently suppressed XAF1 expression, implicating the synergized effect of two anti-apoptotic protein families, HSP and inhibitors of apoptosis, in cytoprotection under stress circumstances.Heat-shock proteins (HSPs) 2 are conserved molecules present in all prokaryotes and eukaryotes (1, 2). The expression of these proteins is very low under normal physiological conditions and can be induced by stress factors, including physiological (growth factors, oxidative stress, and hormonal stimulation), environmental (heat shock, heavy metals, and ultraviolet radiation), or pathological stimuli (inflammation and autoimmune reactions and viral, bacteriological, or parasitic infections) (3, 4). Some stress factors, such as oxidative stress, have been considered as tumorigenic agents at low concentrations (5, 6). The main function of HSPs is to operate as an intracellular chaperone for aberrantly folded or mutated proteins and to provide cytoprotection against the stress conditions (31). For this reason, the presence of a cellular stress response in cancer cells reduces their sensitivity to chemical stress caused by insufficient tumor perfusion of chemotherapeutic agents (2).Heat-shock transcription factors (HSFs or HSTFs) were originally characterized as regulators of the expression of the heat-shock protein, through binding to specific s...

Background: The proportion of duodenal ulcers not associated with Helicobacter pylori infection or the use of non‐steroidal anti‐inflammatory drugs (NSAIDs) is increasing. Aim: To identify the clinical and endoscopic characteristics of non‐H. pylori, non‐NSAID duodenal ulcers. Methods: Clinical and endoscopic data and H. pylori status were prospectively collected from consecutive patients who underwent upper endoscopy from 1997 to 1999. Patients with duodenal ulcers were identified, and those with non‐H. pylori, non‐NSAID duodenal ulcers were analysed further. Results: A total of 11 717 upper endoscopies were performed in 8344 patients. Of these, 1153 (14%) had duodenal ulcers. Of 599 patients with active ulcers and known H. pylori status, 104 (17%) had ulcers not associated with H. pylori or the use of NSAIDs, 393 (66%) had ulcers associated with H. pylori alone, 51 (8.5%) had ulcers associated with the use of NSAIDs alone and 51 (8.5%) had ulcers associated with both. Multivariate logistic regression analysis revealed that the presence of concomitant diseases (odds ratio=15.0; 95% confidence interval, 8.64–25.9; P < 0.001) and the absence of epigastric pain/discomfort (odds ratio=0.52; 95% confidence interval, 0.29–0.91; P=0.022) were independent predictors for non‐H. pylori, non‐NSAID duodenal ulcers. Conclusions: Non‐H. pylori, non‐NSAID duodenal ulcers exhibit certain distinct clinical and endoscopic characteristics. The presence of concomitant diseases is an important predictive factor.