Methods: We reviewed a total of 191 cases of SAP patients admitted to the intensive care unit

of Xijing hospital between Feb 2010 and Apr 2012. From the 191 cases, we identified the patients who received EPCD and classified them into the failure group and the success group according to whether EPCD failed. Failure of EPCD was defined as the need of additional surgery or death. We analyzed the feasibility, safety and efficacy of EPCD and the factors determining the failure of EPCD. Results: There were 17 necrotizing patients receiving EPCD. Thirteen of the 17 patients got gastrointestinal function recovered (GIF score < 2) within 3 days after early PCD. Of the 17 patients, 10 (59%) developed infectious complication, 7 (41%) with infected MI-503 purchase necrosis, 2 (12%) with bacteremia, 4 (24%) with pneumonia. Two (12%) patients

needed additional surgery. Two (12%) patients died. There were 4 patients in the failure group and 13 patients in the success group. APACHE-II STA-9090 datasheet score before EPCD was higher in the failure group than the success group (17.3 ± 7.1 vs. 10.5 ± 3.2, P = 0.015). Conclusion: EPCD of peripancreatic collections was feasible and safe in necrotizing pancreatitis. It might improve gastrointestinal function and reduce the rates of bacteremia, pneumonia, the need of surgery and death. It seemed that EPCD increased the risk of the infection of necrosis which could be easily controlled by conservative treatment. High APACHE-II score predicted the failure of EPCD. Our conclusion remains to be evaluated by further well-designed trials. Key Word(s): 1. Acute Pancreatitis; 2. gut failure; 3. Catheter Drainage; Presenting Author: XUJIE ZHANG Additional Authors: BIN XU, JUNJIE ZHU, QUANXIN FENG, CAILIN ZHU, BIN BAI, QINGCHUAN ZHAO Corresponding Author: QINGCHUAN ZHAO Affiliations: Fourth Military Medical University Objective: To our knowledge, the predictors

for the prognosis of acute pancreatitis still can not satisfy clinical practice. This study was to investigate whether 5-grade scoring system for assessment of gastrointestinal function (the Gastrointestinal Failure [GIF] scores) could be used to predict the mortality of patients with acute pancreatitis (AP). Methods: Two hundred 上海皓元 forty-one patients with AP admitted into the intensive care unit of the Xijing Hospital of Digestive Diseases from September 2008 to April 2012 were studied retrospectively. SOFA scores and GIF scores for the first 3 days were calculated. The AUC of ROC was used to evaluate the ability of SOFA scores, GIF scores and the combination of SOFA and GIF scores in predicting the mortality of AP patients. Results: A total of 235 patients were included in the final analysis. A high mean GIF score during the first 3 days was associated with a high rate of mortality. The combination of SOFA and GIF scores had the greatest AUC (0.849), significantly higher than SOFA scores (0.793, P = 0.002) alone. The AUC of GIF scores alone was 0.812.

45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0 × 10−16. As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared

DMXAA mw with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). Conclusion: We identified LY2157299 cell line four missense mutations associated with CHB, our results providing evidence for rare inborn genetic defects that contribute

to increased host susceptibility to CHB. (HEPATOLOGY 2012;56:1661–1670) Chronic hepatitis B (CHB) is a major global health issue particularly important in some developing countries. It can lead to cirrhosis, hepatic failure, and hepatocellular carcinoma. According to a national epidemiological survey for hepatitis B by the Chinese Ministry of Health in 2006, the hepatitis B surface antigen (HBsAg) seropositive rate was 7.18% for the general population MCE aged between 1 and 59 years (http://www.chinacdc.cn/dcbg/200804/t20080423_34870.htm), whereas in Guangdong province, where our study was conducted, the seropositive rate was 15.46% for the same-age population as indicated by a survey in 2009.1 In the search for genetic variants predisposing to CHB numerous candidate gene approaches have been performed. Based on the “common-variant common-disease” hypothesis2 two genome-wide association studies have been conducted and reported common variants in the HLA-DP and HLA-DQ predisposing to CHB.3, 4 However,

the possible roles of rare genetic variants (minor allele frequency <0.05) remain undescribed. The fast-progressing next-generation sequencing technology has proven an effective way to interrogate the whole exome (exome sequencing) or the whole genome (whole genome sequencing) and to unravel rare variants.5 In this study, exome sequencing was performed in a group of discovery patients and controls. Candidate genetic variants were selected and their association with CHB infection tested in a case-control study. The results were further analyzed by structural analyses of the mutant proteins. Gene expression studies were also performed for the associated gene, transmembrane protein 2.

45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0 × 10−16. As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared

selleck compound with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). Conclusion: We identified selleck kinase inhibitor four missense mutations associated with CHB, our results providing evidence for rare inborn genetic defects that contribute

to increased host susceptibility to CHB. (HEPATOLOGY 2012;56:1661–1670) Chronic hepatitis B (CHB) is a major global health issue particularly important in some developing countries. It can lead to cirrhosis, hepatic failure, and hepatocellular carcinoma. According to a national epidemiological survey for hepatitis B by the Chinese Ministry of Health in 2006, the hepatitis B surface antigen (HBsAg) seropositive rate was 7.18% for the general population 上海皓元医药股份有限公司 aged between 1 and 59 years (http://www.chinacdc.cn/dcbg/200804/t20080423_34870.htm), whereas in Guangdong province, where our study was conducted, the seropositive rate was 15.46% for the same-age population as indicated by a survey in 2009.1 In the search for genetic variants predisposing to CHB numerous candidate gene approaches have been performed. Based on the “common-variant common-disease” hypothesis2 two genome-wide association studies have been conducted and reported common variants in the HLA-DP and HLA-DQ predisposing to CHB.3, 4 However,

the possible roles of rare genetic variants (minor allele frequency <0.05) remain undescribed. The fast-progressing next-generation sequencing technology has proven an effective way to interrogate the whole exome (exome sequencing) or the whole genome (whole genome sequencing) and to unravel rare variants.5 In this study, exome sequencing was performed in a group of discovery patients and controls. Candidate genetic variants were selected and their association with CHB infection tested in a case-control study. The results were further analyzed by structural analyses of the mutant proteins. Gene expression studies were also performed for the associated gene, transmembrane protein 2.

Primary cultures of PTFs and CAFs isolated from human HCC tumors were immunophenotypically characterized by way of positive immunostaining for fibroblast markers and distinguished from tumor cells by negative staining for pan-cytokeratin, Hepar-1, E-cadherin, and α-fetoprotein (Supporting Fig. 1). Purity of the isolated fibroblast population, assessed by way of immunostaining, was >99%. Cells from passages 3-10 were used for all experiments. Full descriptions of additional Materials

and Methods are given in the Supporting Information. First, we stained HCC and matching peritumoral tissues with an anti–α-SMA antibody to detect stromal myofibroblasts.3 We found that α-SMA–positive cells were mostly present in the fibrotic septa of the peritumoral cirrhotic tissue, whereas in tumor tissues α-SMA–positive cells were mainly expressed within the tumor stroma (Fig. 1A). We then isolated and further characterized CAFs and PTFs Ceritinib mouse from 10 different patients using a panel of epithelial and mesenchymal antigens (Fig. 1B,C and Supporting Fig. 1A). Consistent with the microscopic observation, the HSP tumor number of vimentin-positive cells was similar in PTFs and CAFs preparations, whereas the number of α-SMA–positive

cells was much higher (P < 0.0001) in CAFs compared with PTFs (Fig. 1D and Supporting Fig. 1B). No staining was observed in either cell population for pan-cytokeratin, nor for other epithelial or vascular markers (Fig. 1C),

thus indicating the absence of contamination by other cell types. These results were reproducible medchemexpress in all the different preparations (six out of 10 are shown). The different expression of α-SMA between CAFs and PTFs also reveals different functions. CAFs display a greater ability to contract collagen gel (P < 0.0001) and to proliferate more efficiently over time up to 14 days (P < 0.001) compared with PTFs (Fig. 1 E,F and Supporting Fig. 1C,D). These results were consistently reproduced in all the different cell preparations. In coculture experiments, both CAFs and PTFs stimulated Huh7 proliferation with the same efficiency in a three-dimensional collagel gel after 4 (P < 0.05) and 7 (P < 0.05) days (Supporting Fig. 2). However, in the same experiments, the addition of α-bromomethylene phosphonate [BrP]-LPA, a pan-LPA inhibitor, blocked the proliferation rate of Huh7 cells (P < 0.05) stimulated by the presence of PTFs or CAFs (Fig. 2A). Notably, under the same experimental conditions, there was only a trend toward an increased proliferation of PLC/PRF/5 cells upon CAFs treatment, whereas BrP-LPA abolished the CAFs-dependent PLC/PRF/5 proliferation (Fig. 2B). In cell motility experiments, Huh7 cells migrated more efficiently in the presence of PTFs compared with control (P < 0.05), and even more efficiently in the presence of CAFs. However, the presence of BrP-LPA significantly inhibited tumor migration (P < 0.05) (Fig. 2C).

In summary, the stress-induced expression of MIC A/B and their recognition by diverse

NK PD-1 inhibiton cells may serve as a mechanism for the detection of damaged (for example, by fatty infiltration during NASH), infected, or malignantly transformed cells.44 In our present study, MIC A/B transcripts were detected in significant levels in patients with biopsy-proven NASH following bariatric surgery for obesity. Consistent with the PCR data, immunohistochemical analysis revealed that immunoreactivity of hepatic NK cells and MIC A/B was also enhanced in the livers of these patients. Immunohistochemically, MIC A/B revealed a diffuse tissue staining pattern. Due to loss of cell membrane integrity upon tissue injury, these stress-induced ligands may be internalized upon cellular stress as observed during fatty infiltration of the liver in NASH patients. The exact mechanisms remain to be clarified by further studies. In order to exclude the possibility that MIC A/B are up-regulated by obesity, we furthermore investigated a cohort of patients with NAFL and could demonstrate that the number of hepatic NK cells and transcripts for MIC B were significantly decreased

in this study population, which was accompanied by lower degrees of liver injury, hepatocyte apoptosis, and fibrosis. BVD-523 cell line Moreover, we found a significant positive correlation between MIC proteins and markers of disease severity in patients with NASH. Therefore, assessment of MIC A/B serum levels could be identified as a novel index to assess liver injury in NASH in a noninvasive fashion. Taken together, these results

indicate that MIC A/B are expressed on hepatocytes from patients with NASH and that their expression plays an important role in their susceptibility to NK cells during hepatic inflammation as mediated by fatty infiltration of the liver. Indeed, based on the crystal structure of the NKG2D-MIC A-complex, Zhang and colleagues synthesized 3 short peptides, mimicking functional α1 and 2 domain of MIC A, and demonstrated that MIC A–mimicking peptides might be useful for targeting the function of NK cells.45 medchemexpress In addition, Jinushi et al.46 demonstrated that NK-induced cytolysis was completely abolished by antibody-mediated masking of MIC A/B. MIC molecules can also be released from the cell surface by the activity of metalloproteinases, which can be inhibited by addition of a broad-spectrum metalloproteinase inhibitor.47 Metalloproteinases are known to be involved in tissue inflammation and repair.48 We recently demonstrated in a mouse model of murine obstructive cholestasis that administration of CTS-1027—a broad-spectrum matrix metalloproteinase inhibitor—significantly decreased liver injury, hepatocyte apoptosis, and fibrosis.49 This drug has already entered clinical trials evaluating the anti-inflammatory and antifibrogenic properties in hepatitis C.

This study was aimed at

evaluating their diagnostic value in PHC. Methods: Aptamers were incubated with serum specimens and then electrophoresed on polyacrylamide gel (PAGE) and stained with GelRed. The gray value of the free aptamer band in each specimen was measured. The gray ratio of each specimen to the aptamer control was calculated. A mathematical diagnostic model was created with multivariate logistic regression analysis of gray indicators. The area under the receiver operating characteristic curve (AUC) and diagnostic performance were used to evaluate the diagnostic value of aptamers for PHC. Results: Twelve aptamers were evaluated in 72 cases of PHC and 108 cases of non-PHC (the cases of cirrhosis, hepatitis

B and normal controls were all 36). The APO866 mouse free bands of aptamer incubated with PHC specimens were usually weaker than that of non-PHC specimens, and the results of gray measurement were accorded with them. The diagnostic value of gray ratio and diagnostic model were showed in the table 1 below. This is firstly reported that aptamers against PHC serum applied in the study of diagnosis of PHC, and also PAGE combined gray analysis was firstly introduced to evaluate the diagnostic value of the aptamers. Conclusion: The Selleck INK 128 aptamers against primary hepatic carcinoma serum are valuable in the diagnosis of primary hepatic carcinoma. Key Word(s): 1. Aptamer; 2. Serum; 3. Hepatoma; 4. Diagnosis; Aptamer Gray ratio Mathematical model AUC Sensitivity (%) Specificity medchemexpress (%) Accuracy (%) AUC Sensitivity (%) Specificity (%) Accuracy (%) AP-HCS-9-10 0.881 76.4 83.3 80.6 0.913 86.1 86.1 86.1 AP-HCS-9-26 0.749 56.9 81.5 71.7 0.845 73.6 77.8 76.1 AP-HCS-9-31 0.768 66.7 77.8 73.3 0.853 65.1 85.5 78.3 AP-HCS-9-74 0.885 72.2 88.9 82.2 0.949 88.9 89.8 89.4 AP-HCS-9-89 0.688 43.1 80.6 65.6 0.931 81.9 90.7 87.2 AP-HCS-9-90 0.893 85.2 84.7 84.4 0.965 90.7 90.3 90.6 AP-HCS-9-132 0.862 75.0 83.3 80.0 0.918 76.4 90.7 85.0

AP-HCS-11-3 0.816 63.9 88.0 78.3 0.939 83.3 86.1 85.0 AP-HCS-11-4 0.859 72.2 85.2 80.0 0.894 79.2 80.6 80.0 AP-HCS-11-5 0.859 73.6 77.8 76.1 0.916 79.2 88.0 84.4 AP-HCS-11-6 0.847 66.1 83.4 77.2 0.942 86.1 69.8 88.3 AP-HCS-11-8 0.795 66.7 81.5 75.6 0.827 66.7 78.7 73.9 AP-HCS-11-10 0.870 69.4 83.3 77.8 0.899 80.6 87.0 84.4 Presenting Author: SHI QIU Corresponding Author: SHI QIU Affiliations: Wuhan university Objective: To investigate the expression of liver-intestine (LI)-cadherin in hepatocellular Carcinoma (HCC) by tissues microarray and explore its relationship with pathologic features of HCC patients.

More recently, human-murine chimeric liver models have been developed for studying in vivo infection and evaluating therapeutics.[8] This strategy was further Selisistat clinical trial advanced by the recent development of humanized mice with both human hepatocytes and immune cells, which enabled both hepatitis virus infection and liver immunopathogenesis.[9, 10] We will focus on the update of mouse models for studying HBV/HCV infection, immunopathogenesis, and liver diseases. Transgenic mice expressing whole genome or individual genes of HBV have been widely used to investigate the mechanism of HBV replication, gene expression, and immunopathogenesis of HBV in a small-animal model.[11-15]

The immune system of the mice is tolerant to the viral antigen, and

therefore, most of the mice do not develop liver disease. Nonetheless, adoptive transfer of HBV-specific cytotoxic T lymphocytes (CTLs) or spleen cells from syngeneic mice provides a way for immunological study. HBV-transgenic mice with 1.3× of HBV genome can produce high level of infectious viral particles.[13] The viral particles produced in the mice are morphologically indistinguishable from virus derived from human, and they are infectious MG-132 mw when inoculated in chimpanzees.[16] No liver disease developed in these mice, suggesting that HBV was not directly cytopathic.[13] This transgenic mouse model was used to test the efficacy of HBV inhibitors,

including nucleoside analogs reverse transcriptase inhibitors, cytokines, and small interfering RNAs.[17-20] By adoptive transfer of hepatitis 上海皓元医药股份有限公司 B surface antigen (HBsAg)-specific CTLs into HBV-transgenic mice, people found that CTLs can inhibit HBV DNA replication by noncytolytic mechanisms via release of cytokines.[21] Transfer of HBsAg-specific CTLs into the mice can also lead to liver injury, and antigen-non-specific inflammatory cells recruited into the liver during the process can amplify the severity of liver damage.[22] Using HBV-transgenic severe combined immunodeficient (SCID) mice, Larkin et al. report that the mice clear the HBV virus from the serum and develop chronic liver disease after adoptive transfer of syngeneic splenocytes.[23] Report also shows that a subset of nonclassical natural killer T cells mediates acute hepatitis after transfer of splenocytes into the HBV-transgenic mice on the recombination activating gene (RAG)−/− or T-cell receptor (TCR)-α−/− background.[24] The development of transgenic mice expressing individual genes of HBV allowed investigators to explore the role of certain viral proteins in vivo. Transgenic mice that overexpress HBsAg along with pre-S polypeptide accumulate the surface antigen in the endoplasmic reticulum (ER). These mice display low levels of hepatocellular injury and can eventually progressed to HCC.

Heterogeneity among studies was assessed. Subgroup analyses were performed according to the source of bleeding (esophageal/gastric), type of stents (covered/bare), and patient selection (high-risk/unselected). Results: Results: Six of 558 identified articles were eligible in the meta-analysis, including 3 randomized and 3 non-randomized studies. TIPS was superior to medical/endoscopic therapy to control acute bleeding (OR = 0.33, 95%CI:0.14-0.76;

P = 0.009), to prevent variceal rebleeding (OR = 0.21, 95%CI:0.12-0.38; P < 0.00001), to improve overall survival (HR = 0.55, 95%CI:0.38-0.81; P = 0.002), GSK3235025 chemical structure and to decrease the incidence of bleeding-related death (OR = 0.19, 95%CI:0.06-0.59; P = 0.004). No significant heterogeneity among studies was observed in the 4 meta-analyses. These benefits of TIPS became more significant in the subgroup meta-analyses of studies regarding TIPS with covered stents for acute esophageal variceal bleeding in high-risk patients.

Additionally, results of meta-analysis didn’t show a significantly higher incidence of post-treatment hepatic encephalopathy in patients treated with TIPS (OR = 1.37, 95%CI:0.63-2.99; P = 0.43). Conclusion: Conclusions: Use of TIPS with covered stents should be shifted to an earlier time in high-risk patients with acute esophageal variceal bleeding. Additional well-designed randomized controlled trials should be warranted to confirm this conclusion in the setting of acute gastric variceal bleeding or non-high-risk patients. DZNeP manufacturer Key Word(s): 1. Transjugular intrahepatic portosystemic shunt; 2. Variceal bleeding; Presenting Author: NAZIM ARAIN Corresponding Author: NAZIM ARAIN Affiliations: lnh Objective: we aimed to determine

the seroprevalence of anti-HAV antibodies in patients with CLD with or without hepatocelular carcinoma in our region. we aimed to determine the seroprevalence of anti-HAV antibodies in patients with CLD with or without hepatocelular carcinoma in our region. Methods: Patients with CLD ( n = 104) attending the Gastroenterology outpatient and in patient of Liaquat national hospital Karachi, Pakistan, between January 2012 to February 2013 were enrolled. The eligibility criteria included patients with established diagnosis of chronic liver disease of any etiologies medchemexpress with or without hepatocellular carcinoma. The patients with history of HAV vaccination were excluded from this study. The patients were classified into the following groups according to age: Group A: 20 to 40 years; Group B: 41 to 60 years; Group C: greater than 60 years of age. Results: Out of total 104 patients. 68(65.4%) were male and 36(34.6%) were females. The distribution of etiologies for chronic liver disease was HCV in 47 patients (45.2%), HBV in 17 patients (16.3%), hepatocellular carcinoma with HBV/HCV in 13 patients (12.5%), HBV + HDV in 8 patients (7.7%) and other causes of CLD in 19 patients (18.3%).

Our study is the first to identify the important role of thrombin in OPN-dependent HCC metastasis. Previous studies have shown that thrombin-induced modification can lead to changes in OPN activity.7-10, 12, 14

Thus, investigating the role of thrombin in the OPN-mediated pathway is helpful in understanding the mechanisms by which OPN regulates the proliferation and metastasis of HCC, and in the development of a potential therapeutic target to block OPN function and control HCC metastasis.6 Previous studies have also indicated that thrombin click here expression is associated with a more malignant cancer phenotype.15, 16 In this study we demonstrated for the first time that the thrombin expression was significantly correlated with metastatic potential of HCC, postoperative tumor recurrence, and poor prognosis of HCC patients. This finding is supported by the fact that a high thrombin expression was significantly associated with the aggressive histopathological characteristics of HCC, such as large tumor size, vascular invasion, Selleckchem LDK378 and high TNM staging. The prognostic value of thrombin was further confirmed to be independent of the other clinicopathological characteristics of HCC in multivariate analysis. This indicates that thrombin may serve as an independent predictor for tumor recurrence and prognosis

of HCC patients. Interestingly, the correlations of thrombin to the HCC prognosis were different in patients with various OPN expression levels. Thrombin expression was closely associated with tumor recurrence and survival in HCC patients with higher OPN levels; however, this association was not significant in those patients with lower OPN expression. The HCC patients with thrombin+/OPN+ have the poorest prognosis. These findings MCE provide more evidence to support the fact that thrombin makes a substantial contribution, together with OPN, to HCC malignancy. To further explore the role of thrombin in

the OPN-mediated HCC metastasis, we used exogenous thrombin to treat HCC cell lines in vitro, and found that thrombin could only promote proliferation and adhesion of HCC cells with OPN overexpression (PLC-OPN). We also compared the effects of N-terminal and C-terminal fragments with intact OPN on cell growth and adhesion, and found that the OPN N-terminal fragment increased the rate of proliferation and adhesion of HCC cells to an even higher degree than intact OPN. These results suggest that OPN is necessary for the effects of thrombin on the proliferation and adhesion of HCC cells; in the other words, thrombin affects HCC malignancy through the functional roles of OPN pathway. Previous reports have shown that proteolytic modification of OPN by thrombin cleavage not only enhances the accessibility of the binding motif (RGD) for αvβ3 integrins,11 but also reveals the cryptic binding site SVVYGLR in the N-terminal of β1-containing integrins.

Our study is the first to identify the important role of thrombin in OPN-dependent HCC metastasis. Previous studies have shown that thrombin-induced modification can lead to changes in OPN activity.7-10, 12, 14

Thus, investigating the role of thrombin in the OPN-mediated pathway is helpful in understanding the mechanisms by which OPN regulates the proliferation and metastasis of HCC, and in the development of a potential therapeutic target to block OPN function and control HCC metastasis.6 Previous studies have also indicated that thrombin Opaganib manufacturer expression is associated with a more malignant cancer phenotype.15, 16 In this study we demonstrated for the first time that the thrombin expression was significantly correlated with metastatic potential of HCC, postoperative tumor recurrence, and poor prognosis of HCC patients. This finding is supported by the fact that a high thrombin expression was significantly associated with the aggressive histopathological characteristics of HCC, such as large tumor size, vascular invasion, selleckchem and high TNM staging. The prognostic value of thrombin was further confirmed to be independent of the other clinicopathological characteristics of HCC in multivariate analysis. This indicates that thrombin may serve as an independent predictor for tumor recurrence and prognosis

of HCC patients. Interestingly, the correlations of thrombin to the HCC prognosis were different in patients with various OPN expression levels. Thrombin expression was closely associated with tumor recurrence and survival in HCC patients with higher OPN levels; however, this association was not significant in those patients with lower OPN expression. The HCC patients with thrombin+/OPN+ have the poorest prognosis. These findings MCE公司 provide more evidence to support the fact that thrombin makes a substantial contribution, together with OPN, to HCC malignancy. To further explore the role of thrombin in

the OPN-mediated HCC metastasis, we used exogenous thrombin to treat HCC cell lines in vitro, and found that thrombin could only promote proliferation and adhesion of HCC cells with OPN overexpression (PLC-OPN). We also compared the effects of N-terminal and C-terminal fragments with intact OPN on cell growth and adhesion, and found that the OPN N-terminal fragment increased the rate of proliferation and adhesion of HCC cells to an even higher degree than intact OPN. These results suggest that OPN is necessary for the effects of thrombin on the proliferation and adhesion of HCC cells; in the other words, thrombin affects HCC malignancy through the functional roles of OPN pathway. Previous reports have shown that proteolytic modification of OPN by thrombin cleavage not only enhances the accessibility of the binding motif (RGD) for αvβ3 integrins,11 but also reveals the cryptic binding site SVVYGLR in the N-terminal of β1-containing integrins.