, 2009). Yeon et al. (2011) showed that feral cats Felis catus produce vocalizations with higher energy distributions, F1 and peak frequencies in affiliative compared with agonistic situations. However, the ‘affiliative’ situation in this case was an approach by a familiar caretaker, and it is not clear how positive

or intense this experience was for feral cats. Pond et al. (2010) found spectral differences between vocalizations produced in two situations of similar arousal and different valence using Hidden Markov Models, but the shifts in individual vocal parameters are not detailed in this study. There is also evidence for a shift towards low frequencies during positive situations. Jovanovic & Gouzoules (2001) and Scheumann et al. (2007) showed that infant Rhesus monkeys and gray mouse lemurs selleckchem produce different kinds of calls during positive contexts (‘coos’ and ‘purr’ respectively) compared with negative contexts. ‘Coos’ and ‘purr’ are both characterized by low frequencies. Fichtel, Hammerschmidt & Jürgens (2001) found that in squirrel monkeys Saimiri sciureus, call level of ‘negativity’ (aversion) is generally

correlated with longer duration, higher F0 contour, energy distribution, peak frequency, dominant frequency band contour, wider frequency range, and more noise. However, it is not clear how much of this variance is explained by arousal or valence. Tame and aggressive silver foxes Vulpes vulpes differ in their reactions to humans; tame foxes show a decrease and aggressive foxes selleck chemical an increase in peak frequency during approach (Gogoleva et al., 2010a), suggesting that low-peak frequencies reflects positive emotions. Soltis et al. (2011) found that African elephant rumbles produced in a positive situation have lower F0, H1–H2 and narrower F0 range than those produced in a negative situation. However, because the shifts in these parameters occurring between the neutral and positive contexts were similar (i.e. same direction),

yet less intense, than the shifts exhibited between the neutral and negative contexts, the authors suggested that their results MCE公司 were more consistent with an effect of emotional arousal than valence. Similarly, the variations between contexts in vocal parameters found by Collins et al. (2011) in Weddell seals were more consistent with the expression of emotional arousal. Therefore, the only parameter shift that is supported by three studies, without any opposite shift, is duration, with positive situations characterized by shorter vocalizations (Table 4). There are some good examples in the literature of vocal expression of positive emotions: purr, laughter and rat ultrasonic 50-Hz vocalizations. Felid purrs are low pitched vocalizations (mean F0 = 26.

Our APPCI model had a significantly better predictive performance compared to the FI, APRI, GPI, and APGPI models, respectively. Conclusions CP levels were negatively and indirectly correlated with inflammation and fibrosis stages in CHB patients. Our model used routine laboratory variables along with CP to accurately predict liver fibrosis in CHB. Disclosures: The following people have nothing to disclose: Da-wu Zeng, Jing Dong, Yu-rui Liu, Yue-Yong Zhu, Su

LIN, Jing Chen, Jia-ji Jiang Background: HBeAg and HBcAg share an identical sequence of 149 amino-acids. Hence, they FDA-approved Drug Library in vivo are collectively called Hepatitis B virus core-related antigens (HBcrAg). HBcrAg levels have been shown to correlate with both HBsAg and HBV DNA in Asian patients infected with HBV genotypes B and C. Moreover HBcrAg but not HBsAg levels were independently associated with the development of HCC in Japanese patients. The aim of this study was to investigate the performance of an HBcrAg assay in European patients mainly infected with HBV genotypes A and D. Methods:

Plasma samples of 302 HBsAg positive patients, including selleck 124 (41%) HBeAg-positive samples, were tested for quantitative HBsAg levels (Abbott Architect) and HBV DNA (Cobas Taqman). In addition, HBcrAg was determined using the Lumipulse® G HBcrAg assay (Fujirebio), which measures HBeAg, HBcAg and the precore protein p22cr (aa28-150). Results: HBcrAg tested positive in 167 out of the 302 patients including all 124 HBeAg-positive and 43 out of 178 HBeAg-negative samples. A very robust 上海皓元医药股份有限公司 linearity of HBcrAg levels for up to 4 log dilutions was observed across HBV genotypes A, B, C and D. There was no significant difference in detection limits between HBV genotypes. HBcrAg showed a very high correlation with HBV DNA (Spearman correlation: r=0.88; linear regression r2=0.84;

p<0.0001) and a modest correlation with HBsAg levels (r=0.78; r2=0.47; p<0.0001). Correlation with HBV DNA was independent from HBV genotype A and D, and was also not influenced by HBeAg status. Conclusions: The HBcrAg assay shows a high accuracy across HBV genotypes A, B, C and D. Thus it can also be used in patients with HBV genotypes A and D. The clinical utility of HBcrAg testing to individualize management of patients with chronic HBV should be evaluated in further studies. Disclosures: Benjamin Maasoumy-Advisory Committees or Review Panels: Abbott Molecular; Speaking and Teaching: MSD, Roche Diagnostics, Roche Pharma Jerzy Jaroszewicz – Speaking and Teaching: Roche, Gilead, Abbott, MSD, BMS Michael P.

Study design characteristics.  There were a total

of 804 patients in the selected studies and the age ranged from 23 to 94 years. In 15 studies, the sex distribution was described: 385 patients were male and 321 patients were female. In all studies, imaging data were presented about the identification of patients; the reference standard was histopathologic analysis and clinical follow-up. Of all 16 studies, 10 studies28,30–34,36–38,41 enrolled patients Selleckchem MAPK Inhibitor Library prospectively, five studies27,29,35,39,40 enrolled patients retrospectively, and one study26 was unknown. Eight studies27,28,30–35 enrolled patients in a consecutive manner; the others26,29,36–41 were not in a consecutive manner or unknown. There were nine studies26,27,29,31,33–37,40 in which the MRI or PET/CT reviewer was blinded to other test results and clinical data. For DWI, all of the included studies26,29,30,32,33,35,36 used the 1.5T system.

There were three studies26,30,35 in which the average lesion size was over 30 mm. In the other four studies29,32,33,36 the average lesions size was less than 30 mm. For PET/CT, contrast enhanced PET/CT was used in four studies,27,28,31,40 and noncontrast enhanced PET/CT was used in seven Doxorubicin solubility dmso studies,27,31,34,37–39,41Table 1 presents the included datasets with the corresponding numbers of patients and reference numbers. A full list of all included articles with all relevant study characteristics and complete examination results is available on request from the authors of this article. Diagnostic accuracy

of 18 F-FDG PET and DWI.  When considering all 16 studies with data on pancreatic malignancy per patient, for PET/CT, the pooled sensitivity was 0.87 (95% CI, 0.82, 0.81) and specificity was 0.83 (95% CI, 0.71, 0.91). Overall, LR+ was 5.84 (95% CI, 4.59, 7.42) and LR− was 0.24 (95% CI, MCE 0.17, 0.33). For DWI, the pooled sensitivity was 0.85 (95% CI, 0.74, 0.92) and specificity was 0.91 (95% CI, 0.71, 0.98). LR+ was 9.53 (95% CI, 2.41, 37.65) and LR− was 0.17 (95% CI, 0.09, 0.32). SROC curves show the overall very good, but not excellent, diagnostic performance for PET/CT and DWI is shown in Figures 2 and 3, respectively. Subgroup analysis and meta-regression analysis. I2 is an index for heterogeneity: I2 = [Q − (k − 1)]/Q × 100%, where Q is the χ2 value of heterogeneity, and k is the number of studies included. Along with P < 0.05 for heterogeneity, I2 > 50% further indicates heterogeneity between studies. The heterogeneity in the sensitivity test and specificity test was highly significant (P < 0.05 and I2 > 50%), confirming that there was strong evidence of between-study heterogeneity both for PET/CT and DWI (Table 2). Therefore, a random effect model was used for the primary meta-analysis to obtain a summary estimate for sensitivity and specificity with 95% CI. To explore the possible source of heterogeneity, subgroup analyses were applied (Table 2).

We mimicked dietary exposures of obese children, utilizing a Westernized diet (WD) that was both high in dietary fat and contained high-fructose corn syrup (HFCS), to generate diet-induced obesity combined with a VitD depleted condition (WD+VDD). Our central hypothesis was that VDD contributes to IR, hepatic necroinflammation, and may result in NASH in diet-induced obesity. ALK, alkaline phosphatase; selleck GTT, glucose tolerance test; HFCS, high-fructose corn syrup; H&E, hematoxylin-eosin; HO-1, heme oxygenase-1;

IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α; IKKB, inhibitor of kappa B kinase; IL, interleukin; IR, insulin resistance; ITT, insulin tolerance test; JNK, c-Jun-N-terminal kinase; LFD, low-fat diet; LPS, lipopolysaccharide; LBP, LPS binding protein; MetS, metabolic syndrome; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD Activity Score; NASH, nonalcoholic steatohepatitis; NF-κB, nuclear factor kappa B; PPARγ, peroxisome proliferator activated receptor γ; SOCS3, suppression of cytokine signaling 3; TIRAP, Toll/interleukin-1 receptor adaptor protein; T2DM, type 2 diabetes mellitus; TLR, Toll-like receptor; TNFα, tumor necrosis factor α; VDD, vitamin D deficiency;

VitD, vitamin D; WD, Westernized diet. Weanling (25 days old at start of diets) male Sprague-Dawley rats (Charles River Z-VAD-FMK Laboratories, Wilmington, MA) were randomly assigned test groups and housed in pairs. Rats had a 12-hour light/dark cycle and provided ad libitum access to assigned diet and water. Additionally, WD (HFCS+HFD) groups had continuous access to a separate bottle with HFCS-55 (HFCS-55: 55% fructose, 45% glucose diluted with water to 12.5%, 0.375 kcal/mL solution). Custom rodent diets were purchased from Research Diets (New Brunswick, NJ), with 10% (LFD) or 45% (HFD) total kcal from fat (soybean oil and lard); similar amounts of maltodextrin, no sucrose, and 57% (LFD) or 22% (HFD) total kcal from cornstarch. Vitamin D3 content was either normal (1,000 IU Vitamin D3/4,057 kcal) or depleted

(25 IU Vitamin D3/4,057 kcal) adjusting the latter to approximately 30% of controls MCE公司 to mimic VDD in children without reaching levels that may create rickets.12-14 In VDD groups the ultraviolet section of light (290-315 nm) was filtered from the room. This strategy produced a reduction of 25(OH)D levels to 26% of normal after 14 days and reached 29% of normal at 70 days in VDD animals (95% confidence interval [CI]: 23%-36%, mean 25-(OH)D levels were 4.8 ± 1.3 ng/mL in VDD groups and 13.3 ± 0.6 ng/mL in controls (LFD) (see Supporting Fig. 1). Body weight and food intake measures were recorded daily. Blood was collected from trunk (final measures) following a 12-hour fast. After euthanizing the rats, livers and epididymal fat pads were quickly excised, weighed, and an aliquot was snap-frozen.

To further investigate the role of hepatic FXR in mediating bile acid regulation of biliary and fecal cholesterol content, we fed wild-type, liver-specific Fxr knockout (L-FXR-KO) and intestine-specific selleck compound Fxr knockout (I-FXR-KO) mice either a chow diet or a chow diet supplemented with 0.5% CA for 1 week. Deletion of the Fxr gene in the liver or the intestine

did not significantly alter hepatic cholesterol content (Fig. 6A). CA feeding significantly increased biliary cholesterol content by three-fold in wild-type, two-fold in I-FXR-KO mice, and approximately 0.3-fold in L-FXR-KO mice (Fig. 6B) suggesting that FXR-independent bile acid signaling may be also involved in biliary cholesterol secretion. CA feeding also resulted in a small but significant increase in biliary phospholipid levels in all three genotypes. This suggests that a bile acid effect on biliary phospholipid content may be independent of FXR (Fig. 6C). Gene expression analysis showed that CA feeding significantly induced ABCG5 and ABCG8 mRNA expression in the livers of wild-type mice and I-FXR-KO mice, but not in GSI-IX ic50 the livers of L-FXR-KO mice (Fig. 7A). In contrast, CA feeding had no effect on the mRNA expression of intestine ABCG5 and ABCG8 in mice of all three genotypes (Fig. 7B). These results further

confirmed the role of liver FXR in mediating the bile acid induction of ABCG5/G8 expression in the liver. 上海皓元医药股份有限公司 CA strongly repressed CYP7A1 mRNA expression in wild-type mice as expected, but surprisingly had a much weaker effect in L-FXR-KO mice (Fig. 7C), even though loss of liver Fxr abolished CA induction of hepatic SHP, whereas loss of intestine Fxr completely abolished intestine FGF15 induction (Fig. 7D,E). The attenuated

repression of CYP7A1 by CA in L-FXR-KO mice may be due to abolished SHP induction in the liver. Taken together, these results suggest that redundant pathways mediate bile acid repression of the Cyp7a1 gene. This study demonstrated that induction of CYP7A1 had profound effects on hepatic cholesterol synthesis, uptake, catabolism, and secretion, but hepatic cholesterol homeostasis is maintained to prevent hypercholesterolemia. Increased CYP7A1 expression promotes biliary and fecal cholesterol secretion without affecting intestine cholesterol absorption in Cyp7a1-tg mice. Induction of CYP7A1 increases CDCA in the bile acid pool, which is the most efficacious ligand of FXR that induces expression of hepatic, but not the intestinal cholesterol transporters ABCG5/ABCG8 and SR-B1, and the hepatic bile acid efflux transporter BSEP. Thus, bile acid synthesis is directly linked to biliary bile acid and cholesterol secretion, but not intestinal cholesterol absorption. In a previous study, lowering circulating cholesterol levels in Cyp7a1-tg mice was attributed to compensatory up-regulation of LDL-mediated uptake of cholesterol, which is converted to bile acids in the liver.

The availability of a highly effective treatment with a very low rate of bleeding-related mortality (3%) even in high-risk patients might call into question the need for primary prophylaxis for variceal bleeding. Thus, the need for (and adverse effects of) regular endoscopic procedures and years of drug therapy could be avoided, and this would probably improve patients’ quality of life. In this context, the knowledge that primary prophylaxis Small molecule library cell assay delayed neither the occurrence of varices nor the first occurrence of variceal bleeding is important.6

Furthermore, in patients who receive early TIPS for their first variceal bleeding, the role of secondary prophylaxis in the prevention of rebleeding will be limited. In these patients, drugs and endoscopic treatments might be primarily applied as temporary measures to stop bleeding until TIPS implantation is performed.

According to this study, early TIPS placement might be beneficial only in a minority of patients with variceal bleeding. Thus, only 63 of 359 patients (17.5%) with acute variceal bleeding were randomly allocated to the treatment groups: 18 refused to participate; 112 had Child-Pugh class A or B cirrhosis without active bleeding on endoscopy; and 166 Acalabrutinib manufacturer were excluded for various reasons, such as isolated gastric variceal bleeding, Child-Pugh scores greater than 13 points, previous failure to respond to treatment with drugs and endoscopic band ligation, age greater than 75 years, portal vein thrombosis, hepatocellular carcinoma, and renal failure. However, MCE in everyday practice, many of the patients excluded from this randomized study might be considered good candidates for early TIPS treatment. In particular, patients with gastric variceal bleeding, patients with renal failure, and patients who have failed to respond to previous medical treatment might benefit from the early use of TIPS. Patients older than 75 years might also be regarded as good candidates for early TIPS placement because they have poor tolerance for rebleeding. In addition, the general exclusion of patients with hepatocellular

carcinoma from early TIPS treatment might not be justified. TIPS could have a place as a palliative treatment in patients with an adequate prognosis and an increased risk of rebleeding. The largest group excluded from the study was the group of patients with Child-Pugh class A or B disease without active bleeding on endoscopy (31%). Because of the 97% survival rate at 6 weeks in patients with Child-Pugh class B or C disease, we might suggest that the survival of patients with Child-Pugh class A or B disease who received early TIPS placement would be close to 100%, which could hardly be improved by any other treatment. In addition, rebleeding after TIPS placement would be a rare occurrence in such patients, and thus secondary prevention could be avoided.

[1] To eliminate HCV, which establishes chronic infection in ~80% of infected individuals, interferon (IFN)-based treatments have been developed. The treatment of first choice at present for IFN-naïve patients of HCV genotype 1 with high viral load in Japan is pegylated interferon (PEG IFN), ribavirin

(RBV) and telaprevir (TVR) triple therapy, if it can be tolerated.[2] Although the sustained virological response (SVR) rate is much improved by the triple therapy, it is poorly tolerated due to a number of adverse events. Anemia is often a critical barrier to successful treatment for chronic hepatitis C patients on IFN therapy with RBV, forcing reduction or discontinuation of RBV administration. To overcome this obstacle, several groups reported employment find more of human recombinant erythropoietin (EPO) administration to alleviate anemia and thereby complete the therapy without RBV reduction in patients under IFN/RBV or PEG IFN/RBV combination therapy.[3-8] Most of the reports describe the successful role of EPO as an alternative to RBV dose reduction, and meta-analysis demonstrates that EPO administration can considerably enhance SVR with no adverse event due to EPO.[9] In triple therapy, Rucaparib purchase anemia develops more frequently than in PEG IFN/RBV combination therapy, consequently resulting in poor adherence to RBV.[10,

11] Thus far, little is known about the efficacy of EPO to RBV-induced anemia in the triple therapy. In the present study, we examined whether EPO administration can alleviate anemia in hepatitis C patients on IFN therapy receiving both RBV and TVR, as observed in the PEG IFN/RBV combination therapy. The patients were given human recombinant epoetin-α at a dose of 12 000 or 24 000 IU/week, which is a relatively low dose compared with those used in previous reports, determined according

to the hemoglobin (Hb) decline from the baseline. The average adherence of the patients with EPO administration to RBV during the triple therapy phase was 97.5%, which was clearly higher than that of the phase III study of triple therapy,[10, 11] and no adverse event was observed. These findings indicate that low-dose EPO administration facilitates RBV adherence and can 上海皓元医药股份有限公司 be a favorable alternative to RBV dose reduction. THE OBJECTIVE OF this study was to determine the safety of EPO administration and find whether it could prevent dose reduction of RBV due to anemia in triple therapy. Twenty-two patients (15 men and seven women, mean age of 56 years [range, 31–70]) with HCV genotype 1 infection and 5.0 log10 IU/mL or higher HCV RNA level were enrolled. All patients gave their informed consent before participating in the study. The study was approved by the ethics committee of Osaka National Hospital and conducted in accordance with good clinical practice and the Declaration of Helsinki. All patients received PEG IFN-α-2b (PegIntron; MSD, Tokyo, Japan) at a dose of 1.5 μg/kg/week s.c.

Presenting Author: LINGYUN ZHANG Additional Authors: YU LAN, QI WANG Corresponding Author: YU LAN Affiliations: Jishuitan hospital Objective: This study was to find out the pathogenesis and guide the treatment of dysphagia by the analysis of the high-resolution manometry inspections of Ruxolitinib the patients with non-organic esophageal obstruction dysphagia. Methods: 42 patients (age 22∼79, 13 male) with dysphagia diagnosed from March, 2010 to May, 2012

were observed. Of the patients, 7 cases were with diabetes mellitus (DM), 9 cases were with connective tissue disorder (CTD), and 22 cases were with gastroesophageal reflux disease (GERD). All the patients received upper gastrointestinal endoscopy examination, and the cases with organic obstruction were excluded. Then, they received the examination selleck chemicals of solid-state high-resolution manometry. The manometric protocol included a 5-min assessment of low esophageal sphincter pressure (LESP) and ten 5-mL water swallows. We observed the esophageal body pressure, pressurization front velocity (PFV), LESP and LES relaxation pressure (RP) of every swallow. When the swallow was with the pressure of proximal esophageal body 12∼180 mmHg, of the distal 30∼180 mmHg and PFV < 8 cm/s, we considered the swallow as normal.

The abnormal swallow included hypotensive (<5-cm defect in the domain of subnormal pressure), failed (> 5-cm defect in the domain of subnormal pressure), rapidly conducted (PFV ≥ 8 cm/s), hypertensive (contraction

pressure of the esophageal body ≥180 mmHg). Normal esophageal motility was difined as: PFV < 8 cm/s in > 90% of swallows, normal contraction pressure in > 70% of swallows, LESP 10–45 mmHg and RP < 8 mmHg. Abnormal esophageal motilities included impaired LES relaxation (RP ≥ 8 mmHg), nutcracker esophagus (hypertensive contraction pressure in ≥30% and non-rapidly conducted in > 90% of wallows), esophageal spasm (rapidly conducted in > 20% of swallows), peristaltic dysfunction, and others. Peristaltic dysfunction included two types: Mild: 30%~70% of the swallows were MCE hypotensive contractions; severe: ≥70% were hypotensive contractions. Results:  13 (30%)cases were with normal esophageal motility. 12 (28.6%)cases were with impaired LES relaxation. Among the 12 cases, 3 cases were achalasia with failed or rapidly conducted contraction; 5 cases were with hypertensive contractions at 5 cm above LES in 20%∼30% of swallows; 3 cases were with hypotensive contraction at 10 cm above LES in 10%∼60% of swallows; 1 case was with failed contraction in proximal esophagus. 2 (4.8%)cases were with nutcracker esophagus; 3 (7.1%)cases were with esophageal spasm; 7 (16.7%)cases were with mild peristaltic dysfunction; 4 (9.5%)cases were with severe peristaltic dysfunction; 1 case was with only lower LESP. Table 1 showed the patients with different esophageal motilities and diseases.

Presenting Author: LINGYUN ZHANG Additional Authors: YU LAN, QI WANG Corresponding Author: YU LAN Affiliations: Jishuitan hospital Objective: This study was to find out the pathogenesis and guide the treatment of dysphagia by the analysis of the high-resolution manometry inspections of Fulvestrant chemical structure the patients with non-organic esophageal obstruction dysphagia. Methods: 42 patients (age 22∼79, 13 male) with dysphagia diagnosed from March, 2010 to May, 2012

were observed. Of the patients, 7 cases were with diabetes mellitus (DM), 9 cases were with connective tissue disorder (CTD), and 22 cases were with gastroesophageal reflux disease (GERD). All the patients received upper gastrointestinal endoscopy examination, and the cases with organic obstruction were excluded. Then, they received the examination selleck products of solid-state high-resolution manometry. The manometric protocol included a 5-min assessment of low esophageal sphincter pressure (LESP) and ten 5-mL water swallows. We observed the esophageal body pressure, pressurization front velocity (PFV), LESP and LES relaxation pressure (RP) of every swallow. When the swallow was with the pressure of proximal esophageal body 12∼180 mmHg, of the distal 30∼180 mmHg and PFV < 8 cm/s, we considered the swallow as normal.

The abnormal swallow included hypotensive (<5-cm defect in the domain of subnormal pressure), failed (> 5-cm defect in the domain of subnormal pressure), rapidly conducted (PFV ≥ 8 cm/s), hypertensive (contraction

pressure of the esophageal body ≥180 mmHg). Normal esophageal motility was difined as: PFV < 8 cm/s in > 90% of swallows, normal contraction pressure in > 70% of swallows, LESP 10–45 mmHg and RP < 8 mmHg. Abnormal esophageal motilities included impaired LES relaxation (RP ≥ 8 mmHg), nutcracker esophagus (hypertensive contraction pressure in ≥30% and non-rapidly conducted in > 90% of wallows), esophageal spasm (rapidly conducted in > 20% of swallows), peristaltic dysfunction, and others. Peristaltic dysfunction included two types: Mild: 30%~70% of the swallows were MCE公司 hypotensive contractions; severe: ≥70% were hypotensive contractions. Results:  13 (30%)cases were with normal esophageal motility. 12 (28.6%)cases were with impaired LES relaxation. Among the 12 cases, 3 cases were achalasia with failed or rapidly conducted contraction; 5 cases were with hypertensive contractions at 5 cm above LES in 20%∼30% of swallows; 3 cases were with hypotensive contraction at 10 cm above LES in 10%∼60% of swallows; 1 case was with failed contraction in proximal esophagus. 2 (4.8%)cases were with nutcracker esophagus; 3 (7.1%)cases were with esophageal spasm; 7 (16.7%)cases were with mild peristaltic dysfunction; 4 (9.5%)cases were with severe peristaltic dysfunction; 1 case was with only lower LESP. Table 1 showed the patients with different esophageal motilities and diseases.

That β-catenin failed to combine with TCF4 and the following inhibitory expression of their downstream factors might play a key role in the decrease of invasion and proliferation ability of SGC-7901 cell in vivo and in vitro as showed above. Conclusion: This study demonstrates that FH535 can inhibit proliferation and invasion

learn more of human gastric adenocarcinoma cell line SGC-7901 in vivo and in vitro. Further, these phenomena may relate to the lower expression of c-Myc and cyclin-D1. Key Word(s): 1. FH535; 2. gastric neopasia; 3. cell prolifration; 4. cell invation; Presenting Author: YING SHAO Additional Authors: SHENG-TAO ZHU, PENG LI, YONG-JUN WANG, YONG-DONG WU, BANG-WEI CAO, SHU-TIAN ZHANG Corresponding Author: YING SHAO Affiliations: Friendship Hospital, Capital Medical University; Friendship Hospital, Capital medical

University; Friendship Hospital, Captital Medical University Objective: Overexpression of cyclooxygenase-2 (COX-2) is associated with the carcinogenesis of esophageal squamous cell carcinoma (ESCC). Bioinformatic analysis showed that miR-26a and miR-144 could bind to 3′ UTR of COX-2. In this study, we planned to investigate the functions and mechanisms of two miRNAs in ESCC. Methods: Eleven ESCC cell lines, one immotalized esophageal cell (Het-1A), 30 pairs ESCC and corresponding non-tumour tissues, and BALB/c nude mice were selected to study. Real-time PCR was used for detecting miRNAs in tissue samples and cell lines, western blot for COX-2 protein in cell lines. CCK8, transwell chamber assay and flow cytometry were used to Small Molecule Compound Library detect the functional change of ESCC cell lines after being overexpressed these miRNAs by constructing stable over-expression clones. Dual luciference reporter gene assay were used to verify that miR-26a and miR-144 could target COX-2 in ESCC. ESCC cell lines that were stably transfected with miR-26a, miR-144 and miR-26a-144 were injected into subcutaneous or tail veil of nude mice. 上海皓元 The

volume of tumour or numbers of tumour nodules formed on the liver surfaces were calculated. Results: The expression level of two miRNAs were down-regμlated in both ESCC cell lines and ESCC tissues. MiR-26a and miR-144 could inhibit the metastasis of ESCC both in vivo and in vitro. Cluster vector of miR-26a and miR-144 could enhance the inhibitive metastasis effect of miR-26a or miR-144 and had inhibitive proliferation effect on ESCC, while miR-144 or 26a did not have inhibitive effect on proliferation in ESCC. The inhibitive effect of miR-26a and miR-144 on ESCC was partly through COX-2 pathway. Conclusion: MiR-26a and miR-144 could inhibit the development and progression of ESCC through inhibiting COX-2 pathway. MiR-26a and miR-144 had better inhibitive effect on the development and progression of ESCC by constructing cluster vector of miR-144 and miR-26a. Key Word(s): 1. ESCC; 2. Cyclooxygenase-2; 3. miR-26a; 4.