TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage.

Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2 regulates the 5' exonuclease activity of its binding partner, Apollo, a member of the metallo-beta-lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome ends. Genetic data indicate that DNA topoisomerase 2alpha acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1, TOP2alpha, and TOP2beta at telomeres. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres.

Capability of four sigmoidoscopy-based screening strategies to predict proximal neoplasia in an asymptomatic Chinese population.

BACKGROUND AND AIM: A proper colonoscopy referral criterion is essential for flexible sigmoidoscopy-based colorectal cancer screening. We aimed to compare the predictive capability of four existing criteria to detect proximal neoplasia (PN) and advanced proximal neoplasia (APN) in a Chinese population. METHODS: Asymptomatic Chinese participants aged 50-75 years, who received screening colonoscopy, were consecutively recruited. The four criteria included (i) UK flexible sigmoidoscopy; (ii) Italian Screening for COlon REctum; (iii) NORwegian Colorectal Cancer Prevention trial; and (iv) US clinical index. The sensitivity, specificity, positive/negative predictive value, and the number of subjects needed to screen (NNS)/refer (NNR) to detect one APN/PN were examined. The area under receiver operating characteristic curve was evaluated. RESULTS: Among 5833 subjects, 749 (12.8%) and 151 (2.6%) cases were found to have PN and APN, respectively. US criteria achieved the highest sensitivity for PN (49%) and APN (66%), while UK criteria attained the highest specificity (93%) for PN/APN. The lowest NNS was required by US criteria for PN (16 vs 19-38) and APN (58 vs 69-86), while the lowest NNR was required by UK criteria for PN (3.2 vs 4.0-4.8) and APN (7 vs 10-16). The receiver operating characteristic of all four criteria was 0.57-0.61 for PN and 0.68-0.70 for APN. CONCLUSIONS: Among all the four criteria, US criteria had the highest sensitivity and lowest NNS, while UK criteria achieved the highest specificity and lowest NNR. Their limited discriminatory capability highlighted the need for a new score to predict PN/APN in Chinese populations.

Diagnostic yield is not influenced by the timing of screening endoscopy: morning versus afternoon.

BACKGROUND: Previous studies have shown the colonoscopy quality affected by the endoscopist's fatigue. This study was aimed to evaluate this potential factor in a colorectal cancer-screening cohort of Chinese patients. METHODS: The attendances at department of gastroenterology for colorectal cancer screening between 2013 and 2015 were retrospectively analyzed. The procedure time-of-day and hours elapse were recorded. The primary outcome was defined as adenoma detection rate (ADR). RESULTS: A total of 1342 screening colonoscopies were performed by 19 gastroenterologists in the study. Detection rates were 7.7% for all polyps and 20.0% for adenomas. Time-of-day was not significantly associated with ADR. With time elapsing, the first climax for ADR was presented at 09:00-10:00, and persistently rose again after the lunch break. Significant inclined trend in ADR was noted for each hour blocks of a full day (p = .0021). CONCLUSIONS: The procedure time-of-day, morning versus afternoon, did not affect the diagnostic efficacy of screening endoscopy in Chinese patients.

Decreased MIZ1 Expression in Severe Experimental Acute Pancreatitis: A Rat Study.

AIM: We tested our hypothesis that Myc-interacting zinc finger protein 1 (MIZ1), a cell cycle regulator, suppressed inflammation, and therefore, represented a useful prognostic marker in patients with acute necrotizing pancreatitis (ANP) complicated by acute lung injury. METHODS: Sprague-Dawley rats were randomly divided into control and ANP groups at different time points. The MIZ1 protein expression was measured by Western blot and ELISA, and confirmed using immunohistochemistry. The severity of pancreatic and lung injury was evaluated by the injury score and wet/dry weight ratio. The severity of disease was evaluated by serum C-reactive protein (CRP). The MPO activity of lung tissue amylase levels and the degree of inflammation were evaluated by serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression. The risk due to multiple factors was investigated by relationship analysis. RESULTS: The serum levels of CRP, amylase, TNF-α, and IL-6 were gradually increased at 6, 24, and 48 h in ANP when compared with the control rats. The MIZ1 expressions were greatly decreased in ANP rats, especially at 24 h. Statistical analysis showed that there were time-dependent differences in ANP rats when compared with control rats (6 vs. 24 or 48 h, P < 0.01). MIZ1 showed close negative correlation with the degree of pancreatic and lung injury, serum amylase, CRP, TNF-α, and IL-6 (P < 0.01, respectively). CONCLUSION: The decreasing MIZ1 expression was closely correlated with inflammatory response, and development of ANP. Decreasing MIZ1 levels indicate a risk for ANP.

VEGF-C expression is associated with the poor survival in gastric cancer tissue.

Vascular endothelial growth factor-C (VEGF-C) is considered as a prime mediator of lymphangiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF-C overexpression and the clinical outcome in patients with gastric cancer, but yielded conflicting results. Electronic databases updated to July 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF-C overexpression and survival of patients with gastric cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 13 studies that evaluated the correlation between VEGF-C overexpression and survival in patients with gastric cancer. Combined hazard ratios suggested that VEGF-C overexpression had an unfavorable impact on overall survival (OS) (hazard ratio (HR) = 1.38, 95% confidence interval (CI) = 1.08-1.68), but not disease-free survival (DFS) (HR = 1.25, 95% CI = 0.89-1.62) in patients with gastric cancer. No significant heterogeneity (P = 0.132) was observed among 11 studies for OS and among 5 studies for DFS (P = 0.105). VEGF-C overexpression indicates a poor prognosis for overall survival, but not disease-free survival in patients with gastric cancer.

miR-34a regulates cisplatin-induce gastric cancer cell death by modulating PI3K/AKT/survivin pathway.

The purposes of this study were to determine the expression profiles of microRNA-34a (miR-34a) in human gastric cancer cell line (SGC-7901) and cisplatin-resistant cell lines (SGC-7901/DDP), and to establish the correlation between miR-34a expression profile and the sensitivity of human gastric cancer cell to cisplatin-based pattern, thereby providing new methods and strategies for treating gastric cancer. Gastric cancer cell line (SGC-7901) and cisplatin-resistant cell line (SGC-7901/DDP) were cultivated in vitro, respectively. Quantitative real-time PCR (qRT-PCR) and Western blot were utilized to determine the expression profiles of miR-34a and survivin in both gastric cancer cell lines. With miR-34a mimic and miR-34a inhibitor transfected into SGC-7901 and SGC-7901/DDP for 48 h, post-transfection changes of miR-34a expression was determined; the effects of miR-34a ectopic expression on the viability of cisplatin-induce gastric cancer cell were assayed by the MTT method. The effects of miR-34a ectopic expression on apoptosis of cisplatin-induce gastric cancer cell were determined by Annexin V/propidium iodide (PI) double staining method and flow cytometry. The effects of miR-34a ectopic expression on the AKT and p-AKT expression of cisplatin-induce gastric cancer cells were determined by Western blot and flow cytometry with the PI3K pathway inhibitor Wortmannin. As shown by qRT-PCR and Western blot analyses, the expression of miR-34a in cisplatin-resistant cell lines decreased significantly in comparison to that of SGC-7901 cell line (p < 0.05), while significant up-regulation of survivin expression was also observed (p < 0.05). Compared with the control group, the expression of miR-34a increased significantly in SGC-7901 cells transfected with miR-34a mimic for 48 h (p < 0.01). After miR-34a inhibitor transfection, the expression of miR-34a decreased significantly (p < 0.05). The viability of cisplatin-induce gastric cancer cells increased significantly (p < 0.05) with significant decrease of apoptosis after miR-34a expression inhibition, as demonstrated by MTT and flow cytometry with miR-34a over-expression, the viability of cisplatin-induce gastric cancer cells decreased significantly (p < 0.05), with significant apoptosis increase (p < 0.05). As shown by Western blot and flow cytometry, in comparison to the control group, Wortmannin could inhibit miR-34a inhibitor and DDP induced up-regulation of p-AKT significantly (p < 0.05) and stimulated apoptosis. In conclusion, miR-34a expression was down-regulated in cisplatin-resistant cell lines. miR-34a over-expression could improve the sensitivity of gastric cancer cells against cisplatin-based chemotherapies, with PI3K/AKT/survivin signaling pathway possibly involved in the mechanism.

Expression and regulatory function of miRNA-34a in targeting survivin in gastric cancer cells.

We aimed to investigate the expression of microRNA-34a (miR-34a) in human gastric cancer cells and to evaluate the effects of miR-34a, acting via its gene survivin, on gastric cancer cell HGC-27 to provide potential new strategies for treating gastric cancer. In vitro cultures of the human gastric cancer cell lines MGC80-3, HGC-27, NCI-N87, and SGC-7901 and the normal human gastric epithelial cell line GES-1 were established. The expression of miR-34a in each gastric cancer cell line and GES-1 normal human gastric epithelial cell line was detected using quantitative real-time polymerase chain reaction (qRT-PCR). After the HGC-27 cells were transfected with a miR-34a mimic for 48 h, the changes in the expression levels of miR-34a were detected using qRT-PCR. The effect of miR-34a on HGC-27 cell viability was measured using a tetrazolium-based colorimetric [-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT)] assay. Flow cytometry was used to analyze the effects of miR-34a on HGC-27 cell proliferation. Annexin V/propidium iodide double staining and flow cytometry were used to analyze the effects of miR-34a on HGC-27 cell apoptosis. A Transwell invasion chamber was used to detect the effects of miR-34a on HGC-27 cell invasion. Finally, western blotting was used to analyze the effects of miR-34a on survivin protein expression. The qRT-PCR test determined that miR-34a expression in gastric cancer cells was significantly reduced compared to the normal gastric epithelial cell line GES-1 (p < 0.01). Compared to the control group, cellular miR-34a expression levels were significantly increased in HGC-27 human gastric carcinoma cells after transfection with a miR-34a mimic for 48 h (p < 0.01). The MTT assay demonstrated that after overexpressing miR-34a in HGC-27 cells, cellular viability was significantly reduced (p < 0.05). Flow cytometry analysis determined that upon miR-34a overexpression, the proliferation index decreased significantly (p < 0.05), and cellular apoptosis was significantly increased (p < 0.01). The Transwell invasion chamber assay illustrated that after increasing the expression of miR-34a, the number of cells passing through the Transwell chamber was significantly reduced (p < 0.01). Based on western blotting, compared with the control group, survivin protein expression levels were significantly decreased in the HGC-27 cells transfected with the miR-34a mimic for 48 h (p < 0.01). In conclusion, the expression level of miR-34a was downregulated in human gastric cancer cell lines. miR-34a can negatively regulate survivin protein expression and inhibit gastric cancer cell proliferation and invasion. Therapeutically enhancing miR-34a expression or silencing the survivin gene may benefit patients with gastric cancer.

RNA-seq analysis revealed genes associated with neuropathic pain induced by chronic compressive injury in interferon regulatory factors 4 knockout mice.

OBJECTIVE: To explore the differential expression of genes between wild-type chronic compressive injury (CCI) mice (WT-CCI) and interferon regulatory factors 4 (IRF4) knockout CCI mice (KO-CCI) by RNA-seq analysis of the mouse spinal cord. METHODS: RNA-seq analysis of the spinal cord tissue of the chronic sciatic nerve ligation mice and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used. RESULTS: A total of 104 genes were up-regulated and 116 genes were down-regulated in spinal cord of the mice in IRF4 knockout (KO-CCI) group compared with that in the wild-type CCI (WT-CCI) group. There were 1472 differentially expressed genes in the biological process group, 62 differentially expressed genes in the cellular component group, and 163 differentially expressed genes in the molecular function group in KO-CCI mice. A total of 14 genes related to inflammatory reactions were differentially expressed. Real-time PCR results confirmed that Pparg and Grpr mRNA expression was up-regulated and Arg 1 and Ccl11 mRNA expression was down-regulated in the KO-CCI group. CONCLUSION: IRF4 is involved in neuropathic pain in CCI mice, IRF4 may participate in neuropathic pain by regulating Grpr, Mas1, Galr3, Nos2, Arg1, Ccl11, Ptgs2, S100a8, Pparg, Cd40, Has2, Gpr151, Il123a, Capns2, Ankrd1, Ccnb1, and Nppb genes.

Establishment of an animal model of sciatic nerve injury induced by local anesthetics.

Peripheral neurotoxicity injury caused by local anesthetics is a common complication of clinical anesthesia. The study of its mechanism is helpful to prevent and treat the neurotoxic injury of local anesthetics. Previous studies on peripheral neurotoxicity injury caused by local anesthetics have mainly focused on in vitro cell experiments. Due to the lack of an animal model of peripheral neurotoxicity damage caused by local anesthetics, there are few in vivo experimental studies regarding this topic. Herein, 1% ropivacaine hydrochloride was injected into the sciatic nerve by direct incision and exposure of the sciatic nerve to create a local anesthetic neurotoxic injury model. The results showed that 1% ropivacaine hydrochloride could reduce the lower limb motor score and mechanical paw withdrawal threshold in mice 48 hours after injection. Pathological sections showed that 48 hours after treatment with 1% ropivacaine hydrochloride, the sciatic nerve showed increased axonal edema and degeneration, edema between nerve fiber bundles, increased degeneration of axon and myelin sheath vacuoles, edema of nerve bundle membrane and local degeneration and necrosis, and a large number of inflammatory cells around the nerve adventitia were soaked. The above results show that under open vision, 1% ropivacaine hydrochloride can cause injury to the sciatic nerve after 48 h of treatment, which can simulate the neurotoxic damage of local anesthetics. This animal model provides a research tool for studying the mechanism of neurotoxic injury caused by local anesthetics.

Risk Factors of Silicosis Progression: A Retrospective Cohort Study in China.

Background: Silicosis poses a threat to workers' health due to the irreversible lung lesions. Design: A retrospective cohort study. Methods: A total of 259 patients [80 worked with artificial stone (AS), 179 with non-artificial stone (non-AS)] with confirmed silicosis were included in this study. Forty-one of AS and 91 of non-AS had approximately 2 years' follow-up records [lung function tests and high-resolution computer tomography (HRCT)]. Compared with the first records, increased, densified, or newly emerging lesions in lung HRCT images were judged as progression of the disease. Cox proportional hazards models were used to determine the risk factors. Kaplan-Meier survival curve and log-rank test were used to compare prognostic factors for cumulative risk of progression. Results: In 132 patients with median follow-up of 24.0 months (IQR, 13.8, 24.9), 66 patients showed progression, in them, 36 (87.8%) were from AS group and 30 (32.9%) from non-AS group. Working experience of AS processing (hazard ratio, 5.671; 95% CI, 3.048-10.550) and complicated silicosis in CT images (hazard ratio, 2.373; 95% CI, 1.379-4.082) were the main risk factors associated with progression. Forced vital capacity decreased after 1-year (241.5 vs. 55.2 mL) and 2-year (328.1 vs. 68.8 mL) follow-up in the two groups (AS vs. non-AS). History of anti-tuberculosis medication, chest oppression and pain, ground-glass opacity, pleural abnormalities, and restrictive pulmonary dysfunction were more frequently found on HRCT images in the AS group than non-AS group. Lung functions (DLCO, %) were lower in the current/former smokers than the non-smokers (P < 0.05) in AS patients. Conclusion: Prevention and protection rules are needed to be enforced in the occupation involving AS processing; smoking may be associated with declined lung function in AS patients.

Hypermethylation-mediated reduction of LMX1A expression in gastric cancer.

LMX1A is epigenetically inactivated in cervical cancer. However, the expression and methylation status of LMX1A in gastric cancer tissues remains unknown. In the present study, we found that the expression of LMX1A was significantly decreased in gastric cancer tissues compared with normal tissues. A statistically significant inverse association was found between the LMX1A methylation status and expression of LMX1A in tumor tissues (P = 0.008). Restoration of LMX1A induced cell apoptosis and suppressed anchorage-independent growth, suggesting LMX1A may be a potential biomarker for gastric cancer.

Down-regulation of NDRG2 gene expression in human colorectal cancer involves promoter methylation and microRNA-650.

The expression of N-myc downstream-regulated gene 2 (NDRG2) is present in normal tissues but low or undetectable in various cancers and thus poses a potential tumor suppressor gene. However, the expression of NDRG2 in colorectal tissues remains unknown. Here, our results showed that NDRG2 was down-regulated in colorectal cancer compared to benign colorectal tissues by using immunohistochemical staining and semi-quantitative RT-PCR analyses. Bisulfite sequencing analysis showed that the reduced NDRG2 expression was accompanied by de novo DNA methylation at the NDRG2 promoter. We also found that microRNA-650 (miR-650) targets a homologous DNA region in the promoter region of the NDRG2 gene and represses its expression at the transcriptional level. Reporter assay with 3'untranslated region of NDRG2 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-650, providing strong evidence that miR-650 is a direct regulator of NDRG2. In conclusion, these results suggest that NDRG2 expression is regulated by promoter methylation and miR-650 in human colorectal cancer cells, and endogenous small noncoding RNA induced control of transcription may be a potential system for expressional regulation in human colorectal cancer cells.

Serum interleukin-33 levels in patients with gastric cancer.

BACKGROUND: Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines, and it is closely related to IL-18, one of the best characterized members of the IL-1 family. It's been demonstrated that elevated levels of IL-18 are involved in a wide variety of tumors, especially in gastric cancer. AIMS: The purpose of this study was to determine the correlations between serum IL-33 levels and the clinicopathologic features in gastric cancer patients. METHODS: Serum samples were collected from 68 patients with gastric cancer and 57 controls. Serum IL-33 levels were measured by ELISA. Classical tumor markers of CEA and CA19-9 levels were routinely detected by chemiluminescence immunoassay. Western blot analysis was used to detect IL-33 expression in gastric cancer tissue samples and cell lines. The relationship between serum levels of IL-33 and clinical characteristics in patients was analyzed. RESULTS: IL-33 levels in the serum of gastric cancer patients were significantly elevated in comparison with that of healthy volunteers. Furthermore, higher serum levels of IL-33 in gastric cancer patients were found to correlate with several poor prognostic factors like depth of invasion, distant metastasis and advanced stage (stage III/IV). On the other hand, serum IL-33 levels did not correlate with CEA and CA19-9. The expression of IL-33 protein was upregulated in carcinoma tissues in comparison with matched normal tissues, and no statistically significant difference was found between the four gastric cancer cell lines and human gastric epithelial cell line GES-1. CONCLUSIONS: Serum IL-33 may be a useful biomarker for predicting the prognosis of gastric cancer.

Epigenetic inactivation and tumor suppressor activity of HAI-2/SPINT2 in gastric cancer.

Hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2) encodes Kunitz-type protease inhibitor that regulates HGF activity. Inspection of the human HAI-2/SPINT2 locus uncovered a large and dense CpG island within the 5' region of this gene. Analysis of cultured human gastric tumor lines indicated that HAI-2/SPINT2 expression is either undetectable or in low abundance in several lines; however, enhanced gene expression was measured in cells cultured on the DNA demethylating agent 5-aza-2'-deoxycytidine. Bisulfite DNA sequencing confirmed the densely methylated HAI-2/SPINT2 promoter region. Forced expression of HAI-2/SPINT2 induced cell apoptosis, suppressed anchorage independent growth in vitro and tumor growth in vivo. We investigated HAI-2/SPINT2 aberrant methylation in patients with gastric cancer. The HAI-2/SPINT2 methylation was found preferentially in cancerous tissues (30 of 40, 75%) compared with nontumor tissues (no methylation was detected), indicating that this aberrant characteristic is common in gastric malignancies. In conclusion, epigenetic inactivation of HAI-2/SPINT2 is a common event contributing to gastric carcinogenesis and may be a potential biomarker for gastric cancer.

Upregulation and CpG island hypomethylation of the TRF2 gene in human gastric cancer.

The telomere-binding protein TRF2 regulates both telomere protection and telomere length. The fact that TRF2 is up-regulated in some tumors indicates that TRF2 plays a role in cancer. However, the role of TRF2 in gastric cancer has not been fully understood. The aim of this study is to evaluate the expression pattern of TRF2 in gastric cancer and examine the potential mechanism of TRF2 regulation. Our study revealed that the expression of TRF2 analyzed by immunohistochemistry was significantly higher in gastric cancers compared to noncancerous tissues. Moreover, TRF2 methylation was detected in six of 30 (20%) primary gastric cancers and 18 of 30 (60%) paired normal tissues, and the downregulation of TRF2 was strongly correlated with the methylation status (P < 0.001). Our results suggest that hypomethylation might contribute to the upregulation of TRF2 in gastric cancers and this overexpression may play a role in the pathogenesis of gastric cancers.

Therapeutic endoscopy of localized gastric varices: pretherapy screening and posttreatment evaluation with MDCT portography.

BACKGROUND: Gastric varices are a major cause of gastrointestinal bleeding in patients with portal hypertension. Whatever therapeutic method is used, hemodynamic changes in the portal systemic shunt should be assessed. In this study, we used multi-detector row CT portography as a screening and assessment tool. METHODS: A total of 85 patients with gastroscopy-confirmed gastroesophageal varices underwent multi-detector row CT portography. Patients through multi-detector row CT portography screening were recommended to therapeutic endoscopy. Multi-detector row CT portography was carried out in these patients one week before treatment and one month after treatment. The cross-sectional areas of the left gastric vein, main portal vein, superior mesenteric vein and splenic vein were measured by advanced vessel analysis software before and after treatment. Data was subjected to statistical test. RESULTS: Of the 85 patients who underwent multi-detector row CT portography screening, 17 had localized gastric varices with a solitary afferent vein and were recommended for therapeutic endoscopy. The changes in cross-sectional areas of the left gastric vein, main portal vein, superior mesenteric vein, and splenic vein before and after the treatment were of significant statistical difference. CONCLUSIONS: Multi-detector row CT portography is an effective screening and evaluating tool for therapeutic endoscopy.

Gastric xanthelasma may be a warning sign of intestinal metaplasia: A cross­sectional study.

Certain conflicting conclusions have been drawn that gastric xanthelasma is related to H. pylori, atrophic gastritis, intestinal metaplasia, and early gastric cancer. The aim of this study was to examine the relationship between gastric xanthelasma and upper gastrointestinal (GI) endoscopic or pathological features. A cross­sectional study was completed. A total of 8,634 patients who underwent stomach biopsy and who had no gastrectomy history were enrolled in the study. The patients were divided into two groups according to the presence or absence of gastric xanthelasma. The relationship between gastric xanthelasma and demographic characteristics (including age and sex), endoscopic features (including peptic ulcer, bile reflux, and gastric poly), or pathological features (including atrophy, intestinal metaplasia, H. pylori, dysplasia, and gastric cancer) was analyzed. Age/sex matched analysis was also performed to exclude the influence of age and sex. The results revealed that out of the 8,634 patients, 3.54% patients had xanthelasma. Gastric xanthelasma was significantly associated with age (55.76 vs. 49.17 years, P<0.0001), duodenal ulcer (OR 0.860, 95% CI 0.369­0.923), atrophy (OR 1.839, 95% CI 1.432­2.362), and intestinal metaplasia (OR 3.296, 95% CI 2.612­4.159). Binary logistic analysis revealed that age (OR 1.027, 95% CI 1.017­1.037) and intestinal metaplasia (OR 2.700, 95% CI 2.090­3.487) were independently related to gastric xanthelasma. Age/sex matched control binary logistic analysis revealed that gastric xanthelasma was significantly associated with presence of intestinal metaplasia (OR 2.338, 95% CI 1.659­3.297). There was no difference in the number (P=0.427) and location (P>0.05) of gastric xanthelasma for intestinal metaplasia. In conclusion, gastric xanthelasma may be an independent endoscopic warning sign of intestinal metaplasia.

Multitarget stool DNA test compared with fecal occult blood test for colorectal cancer screening.

Patient screening is important for early diagnosis of colorectal cancer (CRC). The present study aimed to compare the multitarget stool DNA (mt-sDNA) test with the fecal occult blood test (FOBT) for CRC screening. A total of 151 individuals were screened using colonoscopy, mt-sDNA and FOBT for the detection of CRC and adenoma. The results of the mt-sDNA test and FOBT were compared with colonoscopy to examine their sensitivity and specificity. Subsequently, the sensitivity and specificity of the mt-sDNA test were compared with those of FOBT in CRC and large adenoma. Stool samples were collected from patients with CRC (n=50) or large adenoma (n=51), as well as from normal controls (n=50). The mt-sDNA test outperformed FOBT in detecting CRC with a sensitivity of 90.0% (45/50) vs. 42.0% (21/50), advanced adenoma with a sensitivity of 70.6% (36/51) vs. 19.6% (10/51), stage I-III CRC with a sensitivity of 91.9% (34/37) vs. 29.7% (11/37), and stage IV CRC with a sensitivity of 84.6% (11/13) vs. 76.9% (10/13). In addition, the mt-sDNA test exhibited a specificity of 94.0% (47/50) in detecting CRC, which was superior to FOBT with a specificity of 90.0% (45/50). Therefore, the mt-sDNA test may have higher sensitivity and specificity compared with FOBT in diagnosing both CRC and advanced adenoma.

Frequent promoter hypermethylation and transcriptional downregulation of BTG4 gene in gastric cancer.

The BTG4 gene belongs to the BTG family of genes endowed with antiproliferative properties. In this study, we have found that BTG4 undergoes promoter CpG island hypermethylation-associated inactivation in gastric cancer and 5'-aza-2'-deoxycytidine (DAC) treatment restores BTG4 expression. We also found BTG4 levels were significantly reduced in primary gastric cancer but not in normal gastric tissues. BTG4 reexpression in gastric cancer causes growth inhibition of colony assays and nude mice. Taken together, our data support BTG4 as a candidate tumor suppressor gene that is epigenetically silenced in the majority of gastric cancers.

Stat3 is involved in angiotensin II-induced expression of MMP2 in gastric cancer cells.

The expression of matrix metalloproteinase-2 (MMP2) has been linked with tumor invasion, angiogenesis, and metastasis. It has been reported that angiotensin II (Ang II) can induce MMP2 expression in gastric cancer cells. However, the molecular basis for Ang II regulates MMP2 expression in gastric cancer cells remains unclear. The aim of our study is to explore whether angiotensin II could induce MMP2 expression mediated through the Stat signaling pathway and its potential mechanism. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-binding assays was employed to determine the DNA-STAT binding activity. MMP2 and VEGF expression was analyzed with real-time PCR and Western blots. To examine the role of Stat3 in angiotensin II-induced MMP2 expression, A JAK-specific inhibitor and AG490 were used. Angiotensin II activated STAT-DNA binding activity in dose-dependent manners in gastric cancer cells. AG490 markedly inhibited angiotensin II-induced Stat3 activation and the expression of MMP2 and VEGF in gastric cancer cells. These results indicate that Stat3 may at least in part mediate angiotensin II-induced MMP2 mRNA expression in human gastric cancer cells. The activation of the JAK/Stat3 signaling pathway plays an important role in the progression of gastric cancer and that blockade of JAK/Stat3 signals may provide a novel therapeutic strategy for gastric cancer.