Search

Background: Due to the low incidence of malignant tracheoesophageal fistula and the paucity of relevant clinical studies, the benefits of stent implantation have not been well documented. It remains unclear which factors may affect fistula closure. Methods: Between January 2015 and January 2021, 344 patients who were diagnosed with malignant tracheoesophageal fistula at Zhongda Hospital, Southeast University, were retrospectively enrolled. Demographic and clinical data were collected. Risk factors for fistula closure identified by univariate analysis were further analyzed using multivariable logistic regression. Results: A total of 288 patients were analyzed in this study, of which 94 were treated conservatively, 170 were treated with an esophageal stent, and 24 were treated with a tracheal stent. Among them, the delta Karnofsky's performance status score values (after 2 weeks/before treatment [p = 0.0028], after 1 month/before treatment [p = 0.0103]) were significantly different between conservative and stent treatment. There was a significant reduction of pneumonia incidence in the stenting group (33.53%) compared to the conservative treatment group (77.05%) after one month (p <0.0001). In addition, the closure of fistulas was influenced by four independent risk factors: 1) treatment methods (p < 0.0001), 2) fistula size (p = 0.0003), 3) preoperative white blood cell count (p = 0.0042), and 4) preoperative Karnofsky's performance status score (p = 0.0001). Conclusions: Stent implantation has become an effective method for treating malignant tracheoesophageal fistula compared to conservative treatment. Additionally, stent implantation, smaller fistula size, lower preoperative white blood cell count, and higher preoperative Karnofsky's performance status score suggest a better outcome. [ABSTRACT FROM AUTHOR]

Background: The clinical significance of insulin-like growth factor-II mRNA-binding protein-3 (IGF2BP3) in esophageal high-grade intraepithelial neoplasia (HGIN) is not clear. This study was designed to characterize the expression of IGF2BP3 in HGIN. Patients and methods: IGF2BP3 expression was evaluated by Western blot analyses in 12 cases and by immunohistochemistry (IHC) in 112 cases. The associations between IGF2BP3 expression in HGIN and the clinicopathological parameters were examined. Results: Moderate to strong IGF2BP3 expression was present in HGIN samples. Using IHC, it was found that IGF2BP3 was positive in 68 (60.71%) cases. Intense IHC of IGF2BP3 in HGIN was associated with a deeper lesion depth, and the lesion depth was the only predictor of the positive expression of IGF2BP3. Conclusion: Our results suggested that IGF2BP3 may be a supplementary tissue marker for preoperative diagnosis of HGIN. [ABSTRACT FROM AUTHOR]

Background: Aberrant expression of miR-224 is associated with tumor development and progression. This study investigated the role of miR-224 in esophageal squamous cell carcinoma (ESCC) ex vivo and in vitro. Methods: A total of 103 esophageal intraepithelial neoplasia, ESCC tissue specimens, and their matched distant normal tissues were collected to test miR-224 expression using qRT-PCR analysis. Western blot was used to quantify the level of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and PHLPP2 in ESCC tissues. Cell viability, apoptosis, invasion, and colony formation assays were used to assess the altered phenotypes of esophageal cancer cell lines after miR-224 expression or inhibition. A luciferase reporter assay was used to confirm miR-224 binding to PHLPP1 and PHLPP2 mRNA. Results: miR-224 was significantly overexpressed in esophageal intraepithelial neoplasia and ESCC tissues, while the expression of PHLPP1 and PHLPP2 proteins, the target genes of miR-224, was downregulated in ESCC tissues. miR-224 expression was associated with advanced clinical TNM stage, pathologic grade, and the level of PHLPP1 and PHLPP2 proteins in ESCC tissues. Ectopic overexpression of miR-224 promoted proliferation, migration, and invasion, but suppressed apoptosis of ESCC cells. miR-224 was able to bind to the 3' untranslated region (3'-UTR) of PHLPP1 and PHLPP2 mRNA to suppress their expression. Conclusions: The current study demonstrated that miR-224 acts as an oncogenic miRNA in ESCC, possibly by targeting PHLPP1 and PHLPP2. [ABSTRACT FROM AUTHOR]

Background: Aberrant expression of miR-224 is associated with tumor development and progression. This study investigated the role of miR-224 in esophageal squamous cell carcinoma (ESCC) ex vivo and in vitro. Methods: A total of 103 esophageal intraepithelial neoplasia, ESCC tissue specimens, and their matched distant normal tissues were collected to test miR-224 expression using qRT-PCR analysis. Western blot was used to quantify the level of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and PHLPP2 in ESCC tissues. Cell viability, apoptosis, invasion, and colony formation assays were used to assess the altered phenotypes of esophageal cancer cell lines after miR-224 expression or inhibition. A luciferase reporter assay was used to confirm miR-224 binding to PHLPP1 and PHLPP2 mRNA. Results: miR-224 was significantly overexpressed in esophageal intraepithelial neoplasia and ESCC tissues, while the expression of PHLPP1 and PHLPP2 proteins, the target genes of miR-224, was downregulated in ESCC tissues. miR-224 expression was associated with advanced clinical TNM stage, pathologic grade, and the level of PHLPP1 and PHLPP2 proteins in ESCC tissues. Ectopic overexpression of miR-224 promoted proliferation, migration, and invasion, but suppressed apoptosis of ESCC cells. miR-224 was able to bind to the 3′ untranslated region (3′-UTR) of PHLPP1 and PHLPP2 mRNA to suppress their expression. Conclusions: The current study demonstrated that miR-224 acts as an oncogenic miRNA in ESCC, possibly by targeting PHLPP1 and PHLPP2. [ABSTRACT FROM AUTHOR]

Background: Esophageal carcinoma is one of the most common malignancies with high cancer-related morbidity and mortality worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate a wide variety of cellular processes, and also play an important role in the development and progression of cancers. In a previous microarray study, we demonstrated that miR-130b was upregulated in esophageal squamous cell carcinoma (ESCC) tissues. However, the biologic functions and the molecular mechanism of miR-130b in ESCC remain to be elucidated. Methods: qRT-PCR assays were used to quantify miR-130b expression levels in ESCC samples. Novel targets of miR-130b were identified via a bioinformatics search and confirmed using a dual-luciferase reporter system. Western blotting and qRT-PCR assays were used to quantify the expression of the target gene PTEN (phosphatase and tensin homolog) and the downstream effector, Akt. ESCC cells over- or underexpressing miR-130b were analyzed for in vitro biologic functions. Results: High levels of miR-130b were identified in 20 ESCC samples following comparison with adjacent non-neoplastic tissues. We confirmed that miR-130b interacted with the 3'-untranslated region of PTEN, and that an increase in the expression level of miR-130b negatively affected the protein level of PTEN. However, the dysregulation of miR-130b had no obvious impact on PTEN mRNA. As Akt is a downstream effector of PTEN, we explored if miR-130b affected Akt expression, and found that miR-130b indirectly regulated the level of phosphorylated Akt, while total Akt protein remained unchanged. Overexpression of miR-130b increased the proliferation of ESCC cells and enhanced their ability to migrate and invade. In contrast, the proliferation, migration, and invasion of ESCC cells were weakened when miR-130b expression was suppressed, which was reversed by PTEN-targeted siRNA. Conclusion: The results indicate that miR-130b plays an oncogenic role in ESCC cells by repressing PTEN expression and Akt phosphorylation, which would be helpful in developing miRNA-based treatments for ESCC. [ABSTRACT FROM AUTHOR]

Background Esophageal carcinoma is one of the most common malignancies with high cancer-related morbidity and mortality worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate a wide variety of cellular processes, and also play an important role in the development and progression of cancers. In a previous microarray study, we demonstrated that miR-130b was upregulated in esophageal squamous cell carcinoma (ESCC) tissues. However, the biologic functions and the molecular mechanism of miR-130b in ESCC remain to be elucidated. Methods qRT-PCR assays were used to quantify miR-130b expression levels in ESCC samples. Novel targets of miR-130b were identified via a bioinformatics search and confirmed using a dual-luciferase reporter system. Western blotting and qRT-PCR assays were used to quantify the expression of the target gene PTEN (phosphatase and tensin homolog) and the downstream effector, Akt. ESCC cells over- or underexpressing miR-130b were analyzed for in vitro biologic functions. Results High levels of miR-130b were identified in 20 ESCC samples following comparison with adjacent non-neoplastic tissues. We confirmed that miR-130b interacted with the 3'-untranslated region of PTEN, and that an increase in the expression level of miR-130b negatively affected the protein level of PTEN. However, the dysregulation of miR-130b had no obvious impact on PTEN mRNA. As Akt is a downstream effector of PTEN, we explored if miR-130b affected Akt expression, and found that miR-130b indirectly regulated the level of phosphorylated Akt, while total Akt protein remained unchanged. Overexpression of miR-130b increased the proliferation of ESCC cells and enhanced their ability to migrate and invade. In contrast, the proliferation, migration, and invasion of ESCC cells were weakened when miR-130b expression was suppressed, which was reversed by PTEN-targeted siRNA. Conclusion The results indicate that miR-130b plays an oncogenic role in ESCC cells by repressing PTEN expression and Akt phosphorylation, which would be helpful in developing miRNA-based treatments for ESCC. [ABSTRACT FROM AUTHOR]

Background Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. Methods A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Results Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. Conclusions The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between MDM2 SNP309 (T > G) and gastric cancer have reported conflicting results. Thus, the aim of this study was to investigate whether MDM2 SNP309 is associated with susceptibility and prognosis of gastric carcinoma in Chinese patients. Methods: Total of 574 gastric carcinoma cases and 574 age- and sex-matched healthy controls were included. MDM2 polymorphism was detected by PCR- RFLP and infection of Helicobacter pylori (H. pylori) by a validated serology test. The functionality of MDM2 SNP309, with or without H. pylori lipopolysaccharide (LPS), was examined by dual-luciferase assay. Kaplan-Meier survival curves were used to evaluate survival. Additional, a meta-analysis was conducted to verity the findings. Results: MDM2 SNP309G/G genotype was associated with an increased risk of gastric carcinoma when compared with T/T genotype or T carriers (both P < 0.01), and a joint effect between MDM2 SNP309G/G and H. pylori infection was observed to intensify gastric carcinoma risk. SNP309G/G was identified as an independent marker of poor overall survival of carcinoma. In vitro, the luciferase assay further showed an increased transcriptional activity of SNP309G allele compared with SNP309T allele, and the function of polymorphism T309G in MDM2 gene promoter was intensified by H. pylori LPS. Pooled results from the meta-analysis confirmed that SNP309G/G genotype had a significantly increased risk of gastric carcinoma compared with T/T genotype or T carriers, consistent with the case- control findings. Conclusions: MDM2 SNP309G allele is associated with an increased risk and poor prognosis of gastric carcinoma in Chinese patients. Additional, there is a joint effect of MDM2 SNP309G/G allele and H. pylori infection on gastric carcinoma development, which may attribute to H. pylori LPS. [ABSTRACT FROM AUTHOR]

Background: It has been previously reported that IL-22, one of the cytokines secreted by Th17 cells, demonstrates both a protective and inflammatory promotion effect in inflammatory bowel disease (IBD) through STAT3 signaling activation. We sought to investigate the role of IL-22 expression in colon cancer (CC). Methods: The expression of IL-22 and related molecules were detected in human CC, the detail function and mechanism of IL-22 were investigated by in vivo and in vitro model. Results: Our results demonstrated significant upregulation of IL-22 in human CC tumor infiltrated leukocytes (TILs) compared to peripheral lymphocytes. Moreover, our findings demonstrated that IL-22 expression was significantly higher in ulcerative colitis (UC) tissues versus normal colon tissues. Both IL-22 receptor a1 (IL-22RA1) and IL-23 were highly expressed in CC and UC tissues compared to normal controls. TILs exhibiting various IL-22 expression levels isolated from CC patients were demonstrated to enhance tumor growth and metastasis co-transplanted with Hct- 116 cells underwent subcutaneous transplantation in mice model. Tumor growth and metastasis was promoted by STAT3 phosphorylation and upregulation of its downstream genes such as Bcl-xl, CyclinD1, and VEGF. In vitro studies confirmed the anti-apoptotic and pro-proliferation effect of IL-22 according to the BrdU cooperation assay and peroxide induced apoptosis analysis with or without the presence of IL-22. Conclusion: In this study we demonstrated that excessive IL-22 in the CC and UC microenvironment leads to tumor growth, inhibition of apoptosis, and promotion of metastasis depend on STAT3 activation. [ABSTRACT FROM AUTHOR]

Background:Previous studies implicated that IL23R and IL17 genes play an important role in autoimmune inflammation. Genome-wide association studies have also identified multiple single nucleotide polymorphisms (SNPs) in the IL23R gene region associated with inflammatory bowel diseases. This study examined the association of IL23R and IL17A gene SNPs with ulcerative colitis susceptibility in a population in China. Methodology:A total of 270 ulcerative colitis and 268 healthy controls were recruited for the analyses of 23 SNPs in the IL23R and IL17A regions. Genomic DNA was extracted and analysis of these 23 SNPs using ligase detection reaction allelic (LDR) technology. Genotype and allele associations were calculated using SPSS 13.0 software package. Principal Findings: Compared to the healthy controls, the variant alleles IL23R rs7530511, and rs11805303 showed a statistically significant difference for ulcerative colitis susceptibility (0.7% vs 3.3%, P = 0.002; 60.4% vs 53.2%, P = 0.0017, respectively). The linkage disequilibrium (LD) patterns of these SNPs were measured and three LD blocks from the SNPs of IL23R and one block from those of IL17A were identified. A novel association with ulcerative colitis susceptibility occurred in haplotypes of IL23R (Block1 H3 P = 0.02; Block2 H2 P = 0.019; Block3 H4 P = 0.029) and IL17A (H4 P = 0.034). Pair-wise analyses showed an interaction between the risk haplotypes in IL23R and IL17A (P = 0.014). Conclusions:Our study demonstrated that rs7530511, and rs11805303 of IL23R were significantly associated with ulcerative colitis susceptibility in the Chinese population. The most noticeable finding was the linkage of IL23R and IL17A gene region to ulcerative colitis risk due to the gene-gene interaction. [ABSTRACT FROM AUTHOR]

Background: Bismuthyl ecabet is a combination of sulfodehydroabietic acid and bismuth, which forms a new type of salt that is useful in treating peptic ulcers and gastritis. Objective: This study was designed to assess the safety and tolerability of bismuthyl ecabet suspension in healthy Chinese subjects. Methods: For the study 77 volunteers were randomized into single- or multiple dose groups for oral administration of bismuthyl ecabet 200-1600 mg once daffy or 1200 mg twice daily for 7 days. Safety and tolerability were assessed by adverse events, physical examination and serum biochemistry. Results: In both the single- and multiple-dose studies, no severe adverse events were observed in any of the volunteers. The main adverse events caused by the drug in single-dose groups were an increase in serum alanine transaminase (ALT), γ-glutamyl transpeptidase, blood urea nitrogen, total bilirubin and skin rash. The numbers of adverse events judged to be possibly related to the drug were 2/18 in the 400mg, 2/18 in the 800mg, 1/8 in the 1200mg, and none in the 200 or 1600mg dose groups. In the multiple-dose studies, an increased serum ALT and aspartate transaminase (AST) was found in one subject after 7 days of administration of the drug. All serum biochemistry returned to normal levels and skin rash resolved after 7 days without any special treatment. Conclusion: Bismuthyl ecabet was shown to be safe and well tolerated in healthy Chinese subjects. The oral dosing regimen selected for subsequent phase II/III clinical trials was 800 mg twice daily. [ABSTRACT FROM AUTHOR]

Background and Aim: To study the low-molecular-weight metabolites in blood plasma of patients with the progressive disease, gastric cancer, and to characterize different stages from chronic superficial gastritis (CSG) to chronic atrophic gastritis (CAG), intestinal metaplasia (IM), gastric dysplasia (DYS) and finally gastric cancer (GC). Methods: We applied gas chromatography time-of-flight mass spectrometry (GC/TOF-MS) to determine metabolites levels in plasma obtained from 80 patients including 19 with CSG, 13 with CAG, 10 with IM, 15 with DYS and 22 with GC (nine preoperation and 13 postoperation). Principal component analysis (PCA) and statistics were used to differentiate the stages and to identify the markers of gastric cancer. Results: Totally, 223 peaks were detected in GC/TOF-MS and 72 compounds were authentically identified. CSG showed distinct difference from the other groups of CAG, IM, DYS and GC, whose plots clustered closely. IM clustered closely to GC, suggesting similar metabolic patterns of them. Fifteen identified metabolites contributed most to the differentiating between CSG and GC, and characterized different stages of GC. Statistics revealed elevated levels of 2-Hydroxybutyrate, pyroglutamate, glutamate, asparagine, azelaic acid, ornithine, urate, 11-eicosenoic acid, 1-monohexadecanoylglycerol and g-tocopherol, while downregulation of creatinine, threonate in GC group, indicating that GC patients were obviously involved in oxidative stress, and perturbed metabolism of amino acids and fatty acids. Conclusion: The metabolic phenotype of CSG is significantly different from GC, while that of IM is similar to it. The discriminatory metabolites characterizing progressive stages from CSG to GC might be the potential markers to indicate a risk of GC. [ABSTRACT FROM AUTHOR]

Objective: Whether gastric atrophy (GA) and intestinal metaplasia (IM) are reversible after the eradication of Helicobacter pylori remains controversial. The purpose of this meta-analysis was to systematically review histological alterations in GA and IM by comparing histological scores before and after H. pylori eradication. Methods: English-language articles in the medical literature containing information about the association between infection with H. pylori and gastric premalignant lesions (i.e. GA and IM) were identified by searching the Medline, PubMed, and EMBASE databases with suitable key words up to December 2009. Review Manager 4.2.8 was used for the meta-analysis. Results: Twelve studies containing a total of 2,658 patients were included in the first meta-analysis. Before treatment, 2,648 patients had antrum GA, 2,401 patients had corpus GA, 2,582 patients had antrum IM, and 2,460 patients had corpus IM. Comparing the histological alterations before and after H. pylori eradication, the pooled weighted mean difference (WMD) with 95% CI for antral GA was 0.12 (0.00-0.23), p = 0.06. For corpus GA, the pooled WMD was 0.32 (0.09-0.54), p = 0.006. For antral IM, the pooled WMD was 0.02 (-0.12-0.16), p = 0.76, and for corpus IM, the pooled WMD was -0.02 (-0.05-0.02), p = 0.42. Conclusion: Our study shows that eradication of H. pylori results in significant improvement in GA in the corpus but not in the antrum; it also does not improve gastric mucous IM. Consequently, all patients with GA in the corpus should be tested for H. pylori infection, and eradication therapy should be prescribed for H. pylori-positive patients in those with GA in corpus. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aim: The use of prophylactic antibiotics to prevent infection and reduce mortality in patients with acute necrotizing pancreatitis (ANP) remains controversial. The aim of this study is to perform a systematic review of the data from randomized controlled trials to compare prophylactic antibiotic treatment of patients with ANP versus placebo. Methods: A computerized literature search was conducted using Medline, PubMed, EMBase and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant articles published in English from January 1990 to March 2010. MeSH terms and keywords used to identify articles included 'antibiotic', 'pancreatitis', and 'randomized'. Outcome measures were infected pancreatic necrosis (IPN), mortality, nonpancreatic infection (NPN) and need for surgical intervention. Results: Nine trials involving 564 patients were included. Analysis suggested that IPN was significantly reduced by treatment with antibiotics (RR 0.73, 95% CI 0.54-0.98, p = 0.04). Mortality (p = 0.1), NPN (p = 0.07), and need for surgical intervention (p = 0.17) were not significantly reduced by antibiotic treatment. Subsequent subgroup analysis confirmed that antibiotics were statistically superior to controls in reducing of infected necrosis (p = 0.003) and also mortality (p = 0.02) in single-blinded randomized controlled trials. Conclusion: Prophylactic antibiotic treatment reduced occurrence of IPN, but did not affect mortality, NPN, or surgical intervention in patients with ANP. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Some studies have reported that Toll-like receptor 4 (TLR4) D299G and T399I polymorphisms are associated with increased Crohn’s disease (CD) and ulcerative colitis (UC) risk in the Caucasian population. However, the results have been inconsistent. Methods: A systemic review of the published data (16 studies with 8,387 cases and 7,013 controls for D299G; 8 studies with 3,881 cases and 1,861 controls for T399I) was undertaken and a meta-analysis was performed to test whether TLR4 D299G and T399I polymorphisms were associated with CD or UC susceptibility and whether 299Gly carriage was associated with phenotypes of CD patients. Results: The TLR4 299Gly allele showed a significant association with CD and UC in the Caucasian population (OR 1.29, 95% CI 1.08–1.54, and OR 1.28, 95% CI 1.08–1.51, respectively). Similar association was detected between the T399I polymorphism and susceptibility to CD and UC (OR 1.37, 95% CI 1.12–1.68, and OR 1.46, 95% CI 1.13–1.88, respectively). However, no significant association was identified between CD phenotypes and 299Gly carriage. Conclusion: The meta-analysis showed that TLR4 D299G and T399I confer a significant risk for developing CD and UC in Caucasians. Additional well-powered studies of the association between TLR4 variants and UC are needed. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Human cervical cancer oncoprotein 1 (HCCR-1), reported as a negative regulator of p53, is overexpressed in a variety of human cancers. However, it is yet unknown whether HCCR-1 plays any role in pancreatic cancer development. The aim of this study was to investigate the effect of epidermal growth factor on the expression of HCCR in pancreatic cancer cells, and to explore if PI3K/Akt/mTOR signaling pathway mediated this expression. Methods: A polyclonal antibody against HCCR protein was raised by immunizing Balb/c mice with the purified recombinant protein pMBPc-HCCR. Tissue samples were constructed on a tissue chip, and the expression of HCCR was investigated by immunohistochemistry assay and Western blotting. Pancreatic cell line, PANC-1 cells were stably transfected with plasmids containing sense-HCCR-1 fragment and HCCR siRNA fragment. MTT and transwell assay were used to investigate the proliferation and invasion of stable tansfectants. The specific inhibitor of PI3K and mTOR was used to see if PI3K/mTOR signal transduction was involved in the induction of HCCR gene expression. A Luciferase assay was used to see if Akt can enhance the HCCR promoter activity. Results: HCCR was up-regulated in pancreatic tumor tissues (mean Allred score 4.51 ± 1.549 vs. 2.87 ± 2.193, P < 0.01), especially with high expression in poorly differentiated pancreatic cancer. The growth of cells decreased in HCCR-1 siRNA transfected cells compared with vector transfectants. The number of invasion cells was significantly lower in HCCR-1 siRNA transfected cells (24.4 ± 9.9) than that in vector transfectants (49.1 ± 15.4). Treatment of PANC-1 cells with epidermal growth factor increased HCCR protein level in a dose- and time-dependent manner. However, application of LY294002 and rapamycin caused a dramatic reduction of epidermal growth factor-induced HCCR expression. Over-expression of exogenous constitutively active Akt increased the HCCR promoter activity; in contrast, dominant negative Akt decreased the promoter activity. Conclusions: EGF-induced HCCR-1 over-expression is mediated by PI3K/AKT/mTOR signaling which plays a pivotal role in pancreatic tumor progression, suggesting that HCCR-1 could be a potential target for cancer therapeutics. [ABSTRACT FROM AUTHOR]

Objective: CYP2C19 polymorphisms have been inconsistently reported to associate with the efficacy of proton pump inhibitor (PPI)-based triple therapies for eradicating Helicobacter pylori infection. The aim of this meta-analysis was to determine whether CYP2C19 polymorphism affect H. pylori eradication rates obtained with first-line PPI-based triple therapies. Methods: A systematic literature search was conducted up to July 2007 using Medline, PubMed, EMBase, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, CNKI (Chinese), and Wanfang (Chinese) digital database. MeSH terms and keywords included proton pump inhibitor, omeprazole, lansoprazole, rabeprazole, pantoprazole, or esomeprazole, cytochromeP4502C19 or CYP2C19, and Helicobacter pylori or H. pylori. Twenty articles met the inclusion criteria, and were included in the meta-analysis by using Review Manager 4.2.8. Results: Eradication rates were significantly different between poor metabolizers (PM) and heterozygous extensive metabolizers (HetEM) (odds ratio (OR) = 1.73, p = .002) and between PM and homozygous extensive metabolizers (HomEM) (OR = 2.79, p < .0001). Moreover, eradication rates were also significant difference between HetEM and HomEM (OR = 2.00, p < .0001). Triple omeprazole and lansoprazole therapies achieved higher H. pylori eradication rates in PM than in HomEM (OR = 4.28, p = .0005 for omeprazole and OR = 3.06, p = .001 for lansoprazole), and higher in HetEM than those in HomEM (OR = 3.22, p < .0001 for omeprazole and OR = 1.95, p = .040 for lansoprazole). Rabeprazole therapies had no significant effect on H. pylori eradication rates (between PM and HomEM, OR = 1.35, p = .610 and between HetEM and HomEM, OR = 1.57, p = .190). No significant difference in H. pylori eradication rates between PM and HetEM was observed in the three individual PPI therapies. Conclusion: The efficacy of omeprazole- and lansoprazole-based first-line triple therapies at the standard doses is dependent on CYP2C19 genotype status, which appears not to affect the efficacy of the regimens including rabeprazole. [ABSTRACT FROM AUTHOR]

Abstract  The aim of the study was to investigate the effects of rebamipide on symptom, histology, endogenous prostaglandin, and mucosal oxygen free radicals in chronic erosive gastritis (CEG) patients by using sucralfate as a control. The trial also examined whether Helicobacter pylori infection would affect rebamipide-induced protection. A total of 453 endoscopy-confirmed CEG patients from 11 hospitals in China were enrolled in the study. They randomly received either rebamipide (100 mg t.i.d) or sucralfate (1.0 t.i.d) for 8 weeks with a ratio of 3:1. Per-protocol analysis (n = 415) showed the accumulated symptom score in the rebamipide group dropped from 5.54 ± 0.97 to 0.80 ± 0.47 after 8 weeks (P P 2) contents in rebamipide-treated subjects mucosa (225.4 ± 18.3 pg/g versus 266.7 ± 14.7 pg/g) compared with that in sucralfate group after 8 weeks of treatment. Malondialdehyde (MDA) contents were significantly depressed both in the trial and control group. When Helicobacter pylori infection was considered, no statistically difference was found in the effect of rebamipide on either symptom or inflammation scores. In conclusion, Rebamipide demonstrated a stronger suppressive effect on the mucosal inflammation in chronic erosive gastritis than sucralfate. The gastroprotection induced by rebamipide is not influenced by H. pylori infection, which indicates its usage in the treatment of H. pylori-associated CEG. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Helicobacter pylori is higher in developing countries. The aim of this study was to investigate the prevalence and risk factors of H. pylori infection in areas with high prevalence of gastric cancer in Jiangsu Province, China. Methods: A prospective epidemiologic survey of H. pylori infection was accomplished in a natural population of 1457 individuals in Xiangshui and Gaoyou counties, Jiangsu Province, China. Questionnaires and laboratory tests for H. pylori infection (13C-urea breath test and serum IgG antibodies to H. pylori) were used and performed, respectively. Result: Among 1371 subjects who completed questionnaires and H. pylori detection, 851 (62%) were H. pylori positive. The prevalence reached a peak at the age of 30–40 years (67%). There was no sex difference. The annual family income level was shown to be positively correlated with the risk of H. pylori infection. The prevalence of H. pylori infection was also associated with family size, education level, and several diet-related factors, such as the number of times cooked rice and potatoes eaten per week, and a family history of stomach diseases. Compared to nonsymptomatic individuals, people with dyspeptic symptoms (nausea, vomiting, and belching) presented a low prevalence of H. pylori infection. No association between H. pylori prevalence and smoking or drinking was found. Using multivariate logistic regression analysis, annual family income and education level were the independent predictors for H. pylori infection. Conclusion: High prevalence of H. pylori infection was found in areas with a high risk of gastric cancer and was related to several risk factors. The underlying mechanisms need to be further investigated. [ABSTRACT FROM AUTHOR]