Nonghua Lv

Combined use of AFP, CEA, CA125 and CAl9-9 improves the sensitivity for the diagnosis of gastric cancer

BackgroundThe detection of serum tumor marker becomes a common method for screening tumors. However, this method has not been widely used for routine gastric cancer screening. In this study we aimed to determine whether the combined use of tumor markers may increase the sensitivity for the diagnosis of gastric cancer.MethodsSerum AFP, CEA, CA125 and CA19-9 levels were measured in 149 patients with gastric cancer, 111 patients with benign gastric diseases and 124 healthy people, who visited the First Affiliated Hospital of Nanchang University from May 2011 to May 2012. Statistical analysis including receiver operating characteristic (ROC) curve, the area under the curve (AUC), and logistic regression analysis was performed to evaluate the diagnostic value of these markers on gastric cancer.ResultsSerum levels of CEA, CA125, and CA19-9 in gastric cancer group were higher than that in the benign gastric disease group and the healthy control group (P <0.005). The sensitivity of AFP, CEA, CA125 and CA19-9 in the diagnosis of gastric cancer was 4.7-20.8% individually, and increased to 40.3% in combination. By using optimal cut-off value, the sensitivity of CEA, CA125, and CA19-9 for the diagnosis of gastric cancer was improved. Especially, the sensitivity of CEA increased to 58.4% and the sensitivity of combined use of four markers increased to 69.1%. The age and gender had no effects on the diagnostic value of these markers.ConclusionsThe determination and application of optimal cut-off values based on ROC curve and logistic regression analysis could improve the diagnosis of gastric cancer based on common tumor markers.

SEVERE ACUTE PANCREATITIS IN CHINA: ETIOLOGY AND MORTALITY IN 1976 PATIENTS

Objectives: Many epidemiological studies have recently been published on acute pancreatitis; however, there is no known published report on pancreatitis in China. The present study aims to assess the etiology and mortality of severe acute pancreatitis in China. Methods: Fifteen medical centers located throughout mainland China were involved in this retrospective study. The medical records of 1976 patients, who were admitted to these centers with the diagnosis of severe acute pancreatitis from December 1990 to December 2005, were reviewed. Epidemiological, laboratory, radiological, and therapeutic data for each case were collected on a standardized form for analysis. Severity of pancreatitis was graded according to established criteria. Results: Of the 1976 patients (1028 men, 948 women; mean age, 56.2 ± 16.5 years; range, 9-94 years). Biliary tract disease (58.7%) was the main etiologic factor, whereas in 25.2%, the cause was identified as idiopathic. Endotherapy was performed in 9.1% of the severe biliary cases, but only in 33%, it was performed within 72 hours. The mean duration of hospitalization was 22.5 ± 21.4 days, and the overall mortality rate was 11.8%. Conclusions: In this retrospective study, biliary tract disease was the main etiologic factor of severe acute pancreatitis in China. The highest mortality occurred in severe idiopathic pancreatitis, and there was no clear relationship between mortality and age.

Derivation and Validation of a Prediction Rule for Estimating Advanced Colorectal Neoplasm Risk in Average-Risk Chinese

No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (≤3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese.

Aquaporin 5 promotes the proliferation and migration of human gastric carcinoma cells

Aquaporin 5 (AQP5) promotes the progression and invasion of several cancers, but its role in the tumorigenesis of human gastric carcinoma (GC) has not been clearly defined. Here, we investigated the potential functions of AQP5 in the proliferation and migration of human GC. RT-PCR and western blotting were used to detect the expression of AQP5 in human GC cell lines. Immunohistochemistry was applied to evaluate the expression of AQP5 in human GC tissues and corresponding normal tissues. Following ectopic overexpression of AQP5 or inhibition of AQP5 by its inhibitor, acetazolamide (AZA), cell proliferation and migration of AGS cells were analyzed by MTT assay, colony formation assay, and wound healing assay. Heterogeneous expression of AQP5 mRNA and protein was observed in human GC cell lines MKN45, MKN28, AGS, and SGC7901. AQP5 was up-regulated in GC tissues in comparison to corresponding normal tissues. AQP5 protein was mainly localized in the cell membrane. Overexpression of AQP5 was correlated with enhanced lymph node metastasis. In vitro, overexpression of AQP5 notably enhanced, while inhibition of AQP5 by AZA significantly attenuated the proliferation and migration of AGS cells. Our data indicate that AQP5 may play an important role in the tumorigenesis and progression of human GC and suggest that AQP5 is a potential therapeutic target against GC.

Gastroesophageal Reflux Disease Questionnaire (GerdQ) in real‐world practice: A national multicenter survey on 8065 patients

Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real‐world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China.

AMPK Inhibits the Stimulatory Effects of TGF-β on Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition

AMP-activated protein kinase (AMPK), an important downstream effector of the tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is well known to exert a preventive and inhibitory effect on tumorigenesis; however, its role in cancer progression and metastasis has not been well characterized. The present study investigates the potential roles of AMPK in inhibiting cancer-cell migration and epithelial-to-mesenchymal transition (EMT) by regulating the canonical transforming growth factor β (TGF-β) signaling pathway, an important promoting factor for cancer progression. Our results showed that activation of AMPK by metformin inhibited TGF-β–induced Smad2/3 phosphorylation in cancer cells in a dose-dependent manner. The effect of metformin is dependent on the presence of LKB1. A similar effect was obtained by expressing a constitutive active mutant of AMPKα1 subunit, whereas the expression of a dominant negative mutant of AMPKα1 or ablation of AMPKα subunits greatly enhanced TGF-β stimulation of Smad2/3 phosphorylation. As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion. In addition, metformin blocked TGF-β–induced inteleukin-6 expression through both LKB1-dependent and -independent mechanisms. Our results also indicate that activation of LKB1/AMPK inhibits TGF-β–stimulated cancer cell migration. Finally, TGF-β induction of EMT was inhibited by phenformin and enhanced by knockdown of LKB1 expression with shRNA. Together, our data suggest that AMPK could be a drug target for controlling cancer progression and metastasis.

Efficacy and safety of probiotics as adjuvant agents for Helicobacter pylori infection: A meta‑analysis

The aim of the present study was to determine whether probiotics could help to improve the eradication rates and reduce the side effects associated with anti-Helicobacter pylori treatment, and to investigate the optimal time and duration of probiotic administration during the treatment, thus providing clinical practice guidelines for eradication success worldwide. By searching Pubmed, Embase, the Cochrane Central Register of Controlled Trials and the Science Citation Index, all the randomized controlled trials (RCTs) comparing probiotics as adjuvant agents of anti-H. pylori standard triple-therapy regimens with placebo or no treatment were selected. Statistical analysis was performed with the Comprehensive Meta Analysis Software. Subgroup, meta-regression and sensitivity analyses were also carried out. Twenty-one RCTs involving a total of 3,814 participants met the inclusion criteria. The pooled eradication rates of the probiotic group were 80.3% (1,709/2,128) by intention-to-treat (ITT) and 83.8% (1,709/2,039) by pro-protocol analyses; the pooled relative risk (RR) by ITT for probiotic supplementation versus treatment without probiotics was 1.12 [95% confidence interval (CI), 1.06–1.19]. A reduced risk of overall H. pylori therapy-related adverse effects was also found with probiotic supplementation (RR, 0.60; 95% CI, 0.40–0.91). The subgroup analyses showed that probiotic supplementation prior and subsequent to the treatment regimen both improved eradication rates for H. pylori infection. Furthermore, probiotic treatment lasting >2 weeks and including Lactobacillus or multiple probiotic strains significantly enhanced the efficacy. In conclusion, supplementation with probiotics for H. pylori eradication may be effective in increasing eradication rates and decreasing therapy-related side effects. Probiotic administration prior or subsequent to therapy and for a duration of >2 weeks may increase the eradication efficacy.

Computed tomographic enterography adds value to colonoscopy in differentiating Crohn’s disease from intestinal tuberculosis: a potential diagnostic algorithm

BACKGROUND Crohns disease and intestinal tuberculosis (ITB) are chronic granulomatous disorders that are difficult to distinguish. Computed tomographic enterography (CTE) yields striking findings for Crohns disease in the small bowel but its role in differentiating Crohns from ITB is undefined. This prospective study aimed to investigate the value of CTE for differential diagnosis between Crohns disease and ITB. PATIENTS AND METHODS 105 consecutive patients (67 Crohns, 38 ITB) who underwent CTE and colonoscopy were enrolled. CTE findings and colonoscopic parameters were compared between Crohns disease and ITB by blinded reviewers. Based on univariate and multiple logistic regression analyses, a diagnostic algorithm combining colonoscopy and CTE was formulated. and its performance validated on 60 new patients (40 Crohns, 20 ITB). RESULTS On univariate analysis of CTE findings, proximal small-bowel involvement, asymmetrical mural thickening, segmental small-bowel lesions, mural stratification, the comb sign, and mesentery fibrofatty proliferation were significantly more common in Crohns disease, whereas mesenteric lymph node change (calcification or central necrosis) and focal ileocecal lesions were more common in ITB. On multivariate analysis, segmental small-bowel involvement (odds ratio [OR] 0.104, 95 % confidence interval [95 %CI] 0.022 - 0.50), and comb sign (OR 0.02, 95 %CI 0.003 - 0.26) were independent predictors of Crohns. Combining CTE and colonoscopic findings increased the accuracy of diagnosing either Crohns disease or ITB from 66.7 % (70/105) to 95.2 % (100/105) in the development set (P < 0.001). Sensitivity, specificity, and area under the curve for receiver-operating characteristic (ROC) in the validation dataset were 92.5 %, 80 %, and 0.862 (95 %CI 0.75 - 0.98), respectively. CONCLUSIONS CTE adds unique information to colonoscopy in differential diagnosis between Crohns disease and ITB, allowing correct diagnosis in most patients.

Suppression of growth and migration by blocking the hedgehog signaling pathway in gastric cancer cells

PurposePrevious studies have indicated that Hedgehog signaling is essential for gastric cancer development, but its precise role is still unclear. The aim of this study was to clarify the role of Hedgehog signaling in gastric cancer development.MethodsThe expression of key Hedgehog signaling components in clinical samples of sequential gastric cancer stages was assessed by immunohistochemistry. The roles and regulatory mechanisms of Hedgehog signaling in human gastric cancer cells and normal gastric epithelial cells were investigated using multiple cell biological approaches and cDNA microarray analyses.ResultsHedgehog signaling was found to be abnormally activated in a ligand-independent manner during gastric cancer development. Gli1 over-expression and reduced SuFu expression were found to be typical events in gastric cancer tissues. Gli1 over-expression was found to correlate with a poorly differentiated histology, advanced clinical stage, membrane serosa infiltration and lymph node metastasis in patients with gastric cancer. Data obtained from multiple cell biological assays showed that human gastric cancer cells require active Hedgehog signaling for survival, proliferation, migration and colony formation. N-Shh treatment significantly enhanced the migration, invasion and colony formation of gastric cancer cells. Moreover, the results of cDNA microarray analyses indicated that after treatment with cyclopamine or GANT61 (inhibitors of Hedgehog signaling), differentially expressed genes in gastric cancer cells were enriched in the apoptosis and MAPK pathways. Inhibitors of the Hedgehog pathway were found to suppress gastric cancer cell growth via apoptosis induction.ConclusionsOur findings indicate a vital role of the activated Hedgehog signaling pathway in promoting gastric initiation and progression. The Hedgehog signaling pathway may serve as a target for gastric cancer therapy.

SMAD7: a timer of tumor progression targeting TGF-β signaling

In the context of cancer, transforming growth factor β (TGF-β) is a cell growth suppressor; however, it is also a critical inducer of invasion and metastasis. SMAD is the important mediator of TGF-β signaling pathway, which includes receptor-regulated SMADs (R-SMADs), common-mediator SMADs (co-SMADs), and inhibitory SMADs (I-SMADs). I-SMADs block the activation of R-SMADs and co-SMADs and thus play important roles especially in the SMAD-dependent signaling. SMAD7 belongs to the I-SMADs. As an inhibitor of TGF-β signaling, SMAD7 is overexpressed in numerous cancer types and its abundance is positively correlated to the malignancy. Emerging evidence has revealed the switch-in-role of SMAD7 in cancer, from a TGF-β inhibiting protein at the early stages that facilitates proliferation to an enhancer of invasion at the late stages. This role change may be accompanied or elicited by the tumor microenvironment and/or somatic mutation. Hence, current knowledge suggests a tumor-favorable timer nature of SMAD7 in cancer progression. In this review, we summarized the advances and recent findings of SMAD7 and TGF-β signaling in cancer, followed by specific discussion on the possible factors that account for the functional changes of SMAD7.