Acceptability Dabrafenib price of such screening influenced by knowledge, perception and attitude of the people. The study was conducted to determine the knowledge, perception and attitude of Indonesia people toward CRC screening. Aim: this study are assessing the knowledge perception

and attitudes with regard to colorectal cancer screening. Method: Cross sectional study with an interview-based population survey carried out in adult ages 30-79 years old, the instrument was structured questionnaires consisting 9 chapters. This survey collected from health center in Depok and hospital in Sumatera and Java. Result: the result from 809 respondents collected indicates that there are 478 (59, 1%) female, 459 (56,7%) age >=50 years old, 611 (75,5%) high educated, 681 (84,2%) married, 458(56,6%) worked and 440 (54,4%) had income GSK1120212 in vitro > 1 million, 76 (9.4%) done cancer colorectal screening, 25 (26.6%) good knowledge, 34 (7.6%) had a positive perception and 76 (17.1%)

positive attitude and 74 (13,9%) respondent from hospital. Chi square analysis, respondent whom less knowledge have odds ratio 34,3

(95% CI ,12,7-92,5; P<0,0001) and respondent from hospital done CRC screening have odds ratio 22,34 (95% CI 5,442-91,22; P<0,0001). Conclusion: The knowledge, perception and attitude on colorectal cancer screening test still low in Indonesian people. Key Word(s): 1. CRC screening; 2. knowledge; 3. perception; attitude Presenting Author: RUPAM Thymidine kinase BHATTACHARYYA Additional Authors: G. LONGCROFT-WHEATON, P. BHANDARI Affiliations: Queen Alexandra Hospital, Portsmouth, United Kingdom Introduction: ESD enables en-bloc resection reducing recurrence rates, but is technically challenging with high complication rates and hence not widely practiced in the West. We have used a novel Knife Assisted Resection (KAR) technique. We aim to evaluate the outcome of KAR in treatment of large and refractory colonic polyps and identify polyp features that predict complications and recurrence after KAR. Methods: Cohort study of patients referred to our centre.

Vacuolar type is common. B.hominis growth curve present ‘S’ shape, went through three growth stages: incubation period, the logarithmic growth phase and stagnation. 3. Results of electron microscopic enzyme cytochemistry showed that the acid phosphatase enzyme, adenosine triphosphate

(ATP enzyme), thiamine pyrophosphate enzyme (TPP enzyme), peroxidase were be positive, glucose-6-phosphatase, cytochrome oxidase were negative. Conclusion: The, B.hominis contain part of the organelle marker enzyme. Key Word(s): 1. Blastocystis hominis; 2. organelle enzyme; 3. DMEM medium; 4. morphology; Presenting Author: HAO NING-BO Additional Authors: YANG SHI-MING Corresponding Navitoclax Author: YANG SHI-MING Affiliations: Department of Gastroenterology, XinQiao

Hospital Objective: The role of the MIF −173 G/C gene polymorphism in the incidence of inflammatory bowel disease (IBD) is controversial. Methods: We performed a meta-analysis including 2084 cases and 2284 controls for whom Alpelisib the MIF −173 G/C polymorphism was genotyped. Results: Results show MIF −173 G/C gene polymorphism are associated with IBD in both the recessive model (CC vs. GC+GG) and the codominant model (CC vs. GG). In the stratified analysis by ethnicity, a significantly increased risk was observed in Asians in the recessive model and codominant model. In the subgroups of ulcerative colitis (UC) and Crohn’s disease (CD), significant differences were observed in UC in the recessive model and the codominant model. In the stratified analysis of ethnicity for UC, significant differences were observed in Asians for the recessive model Conclusion: The current meta-analysis suggested that the MIF −173 G/C polymorphism contributed to the susceptibility of IBD, especially for UC in Immune system Asians. Key Word(s): 1. Macrophage migration; 2. G/C polymorphism; 3. IBD; 4. meta-analysis; Presenting Author: WEI HOU Additional Authors: WEI LU Corresponding Author: WEI HOU Affiliations: Tianjin Second People’s Hospital and Tianjin Institute of Hepatology Objective: Our previous work showed that GW182, a processing body (P-body) component,

is essential for hepatitis C virus (HCV) replication (HEPATOLOGY 2013;57:70–80). The aim of this study was to further investigate the expression and subcellular localization of recombinant GW182-RFP in human hepatocellular carcinoma cell line Huh7 cells. Methods: The TNRC6A (GW182) gene encompassing nucleotides 115–6000 (5886bp) (GenBank Accession No. NM_014494) was amplified using primers with engineered restriction sites to facilitate the fusion of TNRC6A ‘inframe’ to the N terminus of red fluorescent protein (RFP) in the pTagRFP-N vector (Everogen) to construct fusion protein expression plasmid termed pTNRC6A-RFP. Forward primer (5′-GCGAGCTCATGAGAGAATTGGAAGCTAAAG-3′) containing Sac I restriction site and reverse primer (5′-CGCCGCGGCATGGACTCTCCACCCCC-3′) containing Sac II restriction site were synthesized.

MPs

were characterized by Invitrox Sizing, Antigen Detection and Enumeration, a light-scattering technology that can enumerate MPs as small as 0.15 μm, and by flow cytometry. Procoagulant activity was assessed by a functional MP-tissue factor (MP-TF) assay. Sixteen patients (32%) died and 27 (54%) recovered without liver transplantation (LT). Total MPs (0.15-1.0 μm) were present in nearly 19-fold Cabozantinib nmr higher concentrations in ALI/ALF patients, compared to healthy controls (P < 0.0001). MP-TF assays revealed high procoagulant activity (9.05 ± 8.82 versus 0.24 ± 0.14 pg/mL in controls; P = 0.0008). MP concentrations (0.28-0.64 μm) were higher in patients with the SIRS and high-grade HE, and MPs in the 0.36-0.64-μm size range increased in direct proportion to SIRS severity (P < 0.001) and grade of HE (P < 0.002). Day 1 MPs (0.28-0.64

μm) correlated with laboratory predictors of death/LT (higher phosphate and creatinine; lower bicarbonate), and day 1 and 3 MPs were higher in patients who died or underwent LT, compared to spontaneous survivors (P ≤ 0.01). By flow cytometry, 87% of patients had circulating CD41+ MPs, indicating platelet origin. Conclusion: Highly procoagulant MPs of specific size ranges are associated with the SIRS, systemic complications, and adverse outcome of ALI/ALF. MPs may contribute to the multiorgan system failure and high mortality of ALF. (HEPATOLOGY 2013;) Acute liver failure (ALF), the clinical syndrome subsequent to acute liver injury (ALI), is characterized by coagulopathy, hepatic encephalopathy

(HE), and, frequently, death without liver transplantation (LT).1 An intense systemic inflammatory response L-NAME HCl syndrome (SIRS),2 often ABC294640 supplier in the absence of infection, predicts multiorgan system failure (MOSF) and death.3 Although proinflammatory cytokines originating from the necrotic liver may trigger the systemic complications of ALF, mediators of the syndrome are incompletely defined, and others with effects on vascular endothelium and hemostasis likely coexist.4 Although abnormalities in hemostasis are an invariable feature of ALF syndrome, patients rarely develop bleeding complications despite dramatically elevated international normalized ratio of prothrombin time (INR).5 Indeed, patients with ALF appear more prone to thrombotic, rather than bleeding, complications,6 and intrahepatic thrombosis may exacerbate the initial injury.7 Recently, we6, 8 and others9 have suggested that patients with ALF generally maintain normal or hypercoagulable global hemostasis, as determined by thromboelastography (TEG) and thrombin generation assays. Moreover, maximal clot strength by TEG increases in proportion to the number of SIRS components, possibly resulting from increased release of factor VIII and von Willebrand factor from activated/injured endothelial cells (ECs),10 providing a plausible explanation for the absence of bleeding, even in the most critically ill subjects with the highest INR.

A total of 1,536 cases and 2,074 controls, representing 95% of eligible cases and 98% of eligible controls, were enrolled and interviewed. At the same time, 4 mL of peripheral blood was obtained for serum analysis and DNA extraction. Surgically removed tumor samples of all cases were collected for analyzing XRCC4 protein

expression levels and TP53M. Additionally, for analyzing XRCC4 messenger RNA (mRNA) expression levels, 75 fresh cancerous tissuespecimens were also collected during May 2010-December 2010 according to the following criteria: amount of tumor component (at least 70% of tumor cells) and quality of material (i.e., absence of necrosis or hemorrhage). Thirty-seven cases and 29 controls, respectively, were excluded from the study because of extracted DNA being of low yield or quality and because of lack of information on viral infection status. Thus, 1,499 HCC patients (including 1,156 patients previously studied9) Palbociclib purchase and 2,045 controls (including 1,402 subjects previously studied9) were included for the final analysis. Those hepatitis B surface antigen (HBsAg) positive and anti-HCV positive in their peripheral serum were defined as groups infected with BAY 57-1293 concentration HBV and HCV. Liver cirrhosis was diagnosed by pathological examination, and stages of tumor were confirmed according to the tumor-nodes-metastasis

(TNM) staging system. In the present study, AFB1 exposure information consisted of exposure levels and years. In Guangxi, Chorioepithelioma because food-consumption types are relatively simple and limited to corn, peanuts, and rice, and AFB1 mainly contaminates these poorly stored foods, especially corn and peanuts, the years of participants having food contaminated by AFB1 were defined as AFB1 exposure years for subjects.11 Because of the abnormal distribution of exposure-years data and significantly different median value of exposure

years between HCC cases and controls, AFB1 exposure years were divided into three groups: short (<40 years), medium (40-48 years), and long (>48 years), according to median exposure years among controls (40 years) and cases (48 years). AFB1 exposure levels were ascertained according to serum AFB1 albumin (ALB) adducts levels of peripheral blood. AFB1 ALB adducts levels was tested using the comparative enzyme-linked immunosorbent assay (ELISA) as previously published.12 Because missense mutations in the coding region from SNPs lead to an amino acid change in the protein product, and might be associated with the structure and function of corresponding protein,13 we obtained 21 known SNPs in the coding region of XRCC4 using the Ensembl database (Supporting Table 1). For SNP genotypic analyses, laboratory personnel were blinded to case and control status. Genomic DNA was isolated from peripheral blood leukocytes using the standard phenol-chloroform extraction method.

A promoter assay and western blotting confirmed that peretinoin promoted the autophagy KU-57788 datasheet related-gene Atg16L1, and electron microscopy revealed increased autophagosome formation due to peretinoin. Atg16L1-transfected HepG2 cells showed suppressed expression of pStat3 and pNFkB. Recombinant IL-6 and palmitic acid induced expression of pSTAT3 and pNFkB in primary hepatocytes in vitro, whereas peretinoin dose-de-pendently suppressed the expression of these genes. Conclusion Peretinoin suppresses the

development of liver steatosis, inflammation, and tumorigenesis by activating Atg16L1-depen-dent autophagy. These results support the clinical efficacy of peretinoin for preventing HCC. Disclosures: Hikari Okada – Employment: Kanazawa University Shuichi Kaneko – Grant/Research Support: MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, Bayer Japan The following people have nothing to disclose: Masao Honda, SB203580 molecular weight Kai Takegoshi, Naoto Matsuzawa, Taro Yamashita, Yoshio Sakai, Toshinari Takamura, Takuji Tanaka Background and Aims: Cholangiocarcinoma (CCA) is a lethal

neoplasm originating from the biliary epithelium. Risk factors for CCA include liver inflammation and fibrosis. IL-33 has been shown to promote liver inflammation and fibrosis. The AKT cell survival and Hippo cell growth controlling pathways are involved in CCA carcinogenesis and progression. Yes-associated protein (YAP) is a major transcriptional factor of the Hippo pathway. Our aim was to generate a mouse model of CCA incorporating these oncogenic pathways mimicking the human disease. Methods: Ectopic oncogene expression in the biliary tract was accomplished by the Sleeping Beauty transposon transfection system with transduction of constitutively

active AKT and/or YAP. Intrabiliary injection of the transposon-transposase complex was coupled with lobar bile duct ligation in CL57/BL6 wild type or IL-6 −/− mice. After injection, mice were treated with either vehicle or IL-33 i.p. for three consecutive SDHB days. Mice were sacrificed on day 70 and examined for the presence of tumors and tumor burden. Results: Intrabiliary instillation of a sleeping beauty transposon-transposase complex expressing GFP revealed significant transduction of the cholangiocytes, but not hepatocytes, in the bile duct ligated lobe 7 days later; GFP transduction did not require IL-33 administration. Tumor development following intrabiliary instillation of AKT plus YAP, however, was augmented in animals treated with IL-33. Tumors developed in 60% of the animals receiving both oncogenes plus IL-33, but in only 20% of the mice transduced with the oncogenes alone (p<0.05).

Similarly to human hepatocellular carcinoma, tumors are characterized by a further increase in miR-221 expression and a concomitant inhibition

of its target protein-coding genes (i.e., cyclin-dependent kinase inhibitor [Cdkn]1b/p27, Cdkn1c/p57, and B-cell lymphoma 2–modifying factor). To validate the tumor-promoting effect of miR-221, we showed that in vivo delivery of anti-miR-221 find more oligonucleotides leads to a significant reduction of the number and size of tumor nodules. Conclusions: This study not only establishes that miR-221 can promote liver tumorigenicity, but it also establishes a valuable animal model to perform preclinical investigations for the use of anti-miRNA approaches aimed at liver cancer therapy. (HEPATOLOGY 2012;56:1025–1033) Several studies revealed that the expression of microRNAs (miRNAs) is deregulated in human hepatocellular carcinoma (HCC), in comparison with non-neoplastic liver tissues, as reviewed recently.1

Trametinib Among these, microRNA-221 (miR-221) emerged as consistently up-regulated. In HCC, miR-221 is up-regulated in approximately 70%-80% of cases.2 Its up-regulation in glioblastoma, pancreatic, kidney, bladder, colon, stomach, prostate, and thyroid cancer strengthened its importance in tumorigenesis.2-11 The hypothesized tumor-promoting activity was supported by functional and molecular evidence. Forced expression of miR-221 in HCC cells could induce an increase in growth, proliferation, migration, and invasion capabilities in vitro.2, 10, 12 Conversely, anti-miR-221 oligonucleotides could inhibit in vitro growth DNA Damage inhibitor of liver cancer cells.13 Importantly, the promotion of tumor progression in vivo and the shortening of animal survival was observed when miR-221 was introduced into c-myc-immortalized P53−/− liver progenitor cells, which were implanted into irradiated nude mice.13 Surprisingly, the almost identical miR-222 miRNA, which shares the same seed sequence of miR-221, did not accelerate tumorigenesis in this model system. At the molecular

level, miR-221 was shown to affect several cancer pathways by modulating multiple gene targets, which included the cyclin-dependent kinase inhibitors CDKN1B/p277,11 and CDKN1C/p57,2,10 the pro-apoptotic protein B-cell lymphoma 2-modifying factor (BMF),14 the inhibitor of the phosphoinositide 3-kinase pathway phosphatase and tensin homolog (PTEN),12 the DNA damage-inducible transcript 4 (DDIT4), a tumor suppressor that modulates kinase activity of mammalian target of rapamycin (mTOR),13 the tissue inhibitor of metalloproteinase 3 (TIMP3).12 From a clinical point of view, it was shown that higher levels of miR-221 in HCC correlated with higher tumor stage and metastasis15 and were associated with multifocal tumors and a shorter time to recurrence after surgical treatment.

04 versus before embolization). Eight patients of 37 were still in need of nonabsorbable antibiotics compared to 17 before embolization. One patient was successfully transplanted after embolization because of persisting bouts of encephalopathy. Univariate analysis of a wide spectrum of biochemical and clinical parameters identified sex, time interval between diagnosis of HE and SPSS, serum albumin, International Normalized Ratio (INR), the presence of ascites preembolization, hemoglobin level, Child and MELD score (all with P < 0.05) as predictors of HE recurrence CDK inhibitor post-SPSS-embolization. After weighing these different variables to exclude multicollinearity,

logistic regression ascertained the following parameters to be predictive of HE recurrence BI 6727 mw postembolization: sex (odds ratio [OR] 0.06, 95% confidence interval [CI] 0.005-0.971, P = 0.048) and MELD preembolization (OR 1.52, 95% CI 1.073-2.180, P = 0.019). We further evaluated the discrimination ability of the MELD score in predicting HE recurrence after SPSS embolization by using the area under ROC curve. The MELD score showed good accuracy

to discriminate between patients with recurrence or not (95% CI = 0.637- 0.914, P < 0.0001). Using the Youden index, the best cutoff point for the MELD score was 11 with a sensitivity and specificity of 68.4% and 77.6%, respectively (Fig. 5). Overall there were eight early procedure-related complications, of which seven were mild and symptomatically treated (one cutaneous infection at the puncture site, one contrast-induced nephropathy, three hematomas limited to the puncture site, and two self-limiting episodes of fever). One patient had a capsular bleeding due to a transhepatic approach complicated with hypovolemic shock for which surgical hemostasis was needed. All complications were nonlethal and without permanent

injury or morbidity. With regard to long-term complications, we observed no significant aggravation of portal hypertension during follow-up. More specifically, there was no increase postembolization in the number of patients with gastroesophageal varices (48.6 versus 52%, P = 0.94) or with portal hypertensive gastropathy (50 versus 66%, P = 0.18). Two patients developed de novo esophageal varices (grade 1 and grade 2, respectively). Overall, one patient with preexisting varices experienced a nonfatal variceal bleeding SB-3CT at 55 months postembolization which was managed by combined pharmacological and endoscopic intervention. There was no difference with respect to the number of patients with ascites (13/37 pre- and 15/37 postembolization, P = 0.92). In the postembolization group, 6 of 15 patients developed de novo ascites (of which five were patients with recurrent HE). From these 15 patients, seven were in need of large-volume paracentesis (of which six were also nonresponders to embolization) and two developed spontaneous bacterial peritonitis during follow-up.

4A). Moreover, a previous report has suggested that C-Jun protein

is overexpressed in human HCC, as assessed by IHC.18 Therefore, we examined the protein expression of C-Jun in full-length HBx- and HBxΔC1-expressing HepG2 cells. There was an observable induction of C-Jun protein in HBxΔC1-expressing cells, as compared to full-length HBx-expressing or vector control cells (Fig. 4B). Similarly, C-Jun protein was overexpressed in HBxΔC1-expressing cells, as compared to full-length HBx expressing cells Luminespib supplier in the Tet-On HepG2 cell system (Supporting Fig. 3C). Furthermore, with the ChIP assay, a significant amount of C-Jun protein interacted with the MMP10 promoter in HBxΔC1-expressing Tet-Off HepG2 cells, as compared to full-length HBx-expressing or vector control cells (Fig. 4C). Taken together, these Opaganib results indicate that HBxΔC1 is able to increase both C-Jun protein expression and transcriptional activity, resulting in enhanced MMP10 transcription in HepG2 cells. Evidence from previous studies suggests that HBV genomic DNA integration or mutation leads to COOH truncation of the HBx protein in human HCC.6-8, 19 However, such integration or mutation is uncommon in corresponding nontumorous liver tissues. In our present

study, 46% (23 of 50) of human HCC tissues contained COOH-truncated HBx DNA. The result was consistent with that of a recent study showing that 79% of human HCCs from China had COOH-truncated HBx transcript in tumor tissues.7 These lines of evidence indicate that COOH-truncation of HBx is frequent in HCC. Furthermore, upon clinicopathological correlation, we found that the presence of COOH-truncated HBx in HCC tumors was associated with venous invasion. So, the presence of COOH-truncated HBx appears to have clinical significance.

Because of the Non-specific serine/threonine protein kinase growth-suppressive and toxic effects of HBx on host cells, it has been difficult to establish a stable cell line with HBx expression.20 In the present study, we successfully established the Tet-Off HBx expression system in HepG2 cells that efficiently and effectively allowed controlled expression of HBx. Such inducible systems have also been used by other groups, but they worked only with full-length HBx and not on COOH-truncated HBx.21, 22 We then attempted to delineate the mechanistic basis of our observed association between the presence of natural COOH-truncated HBx and venous invasion in human HCCs by assessing cell-invasive ability in vitro. We chose the previously widely reported COOH-truncated form of HBx, with a breakpoint at 130 aa (HBxΔC1)6, 8, 15 for our cell model because breakpoint between 125 and 135 aa was the major form of truncation (47.8% of the 23 cases) (Supporting Fig. 1). With the cell-invasion assay, we observed enhanced HepG2 cell invasiveness with both full-length HBx and HBxΔC1, but more so with HBxΔC1 in the inducible expression system.

Briefly, AGS cells were treated with a mixture of lipofectamine and plasmid DNA in a ratio of 1 : 3 for 4 hours. Thereafter, the serum-free medium was aspirated and cells were grown in Ham’s

F12 medium with 10% fetal bovine serum for 24 hours. The coverslips were then washed thrice with 1X phosphate buffer saline and fixed in 4% paraformaldehyde and probed with anti-rabbit HP0986 antibody. This was followed by 1 hour incubation with peroxidase-conjugated goat anti-rabbit IgG. Slides were washed and mounted with Vectashield mounting medium containing DAPI Sirolimus (Invitrogen). Expression vector pEGFPN-1 without any insert was used as negative control. Two tailed student t-test was used to demonstrate the level of secretion of IL-8 in treated cells when compared with untreated cells. Further, Mann–Whitney’s U test was carried out to compare antibody responses. All the data were expressed

as mean ± SEM. p values of less than .05 were read as statistically significant. To investigate the in vitro expression of HP0986 in H. pylori clinical isolates and to confirm it as a virulence marker linked to disease outcome, we checked the epidemiologic consistency of HP0986 across the Malaysian patient population selected by us (see in methods). Firstly, we performed PCR-based detection of HP0986 using the genomic DNA isolated from all (n = 110) H. pylori isolates and with the help of gene specific primers as described earlier [14]. Among the 110 clinical isolates, HP0986 gene p38 MAPK signaling pathway was found in 31% (n = 34) of the samples. To investigate if PCR-based detection of HP0986 also entails expression of HP0986, a quantitative real time PCR was

performed on the above 34 isolates so as to analyze the in vitro expression of the gene. Galeterone A single primer set, complementary to a highly conserved region, which specifically amplifies HP0986 was used to perform the in vitro expression analysis. This precluded the possibility of any primer mismatches. The mRNA expression of HP0986 was recorded as cycle threshold relative to the strain P12 of H. pylori. (Fig. 1). Our results revealed that the presence of HP0986 genotypes corroborated with the in vitro expression of HP0986. The prevalence of HP0986 in the clinical samples varied among three ethnic groups and it was highest among the Indian origin patients (88%) followed by Chinese (10%) and Malay subjects (2%). This demonstrated that there was a differential prevalence of HP0986 in H. pylori clinical isolates corresponding to different ethnic groups in Malaysia. We analyzed the expression of HP0986 mRNA in gastric biopsy specimens and the analysis of relative HP0986 transcript levels was performed by quantitative RT PCR. On a pilot scale, relative mRNA was measured only in 10 gastric biopsy specimens. These 10 biopsy specimens were different from the 110 clinical isolates used for in vitro expression analysis.

6 (P < 0.001). The presence of ascites was a significant prognostic factor in CPB7 patients (hazard ratio 2.262; P = 0.016). OS of CPB7 patients without ascites was similar to that of CPA6 patients (4.6 months) and was significantly longer than that of CPB7 patients with ascites (2.5 months; P = 0.027). OS of CPB7 patients with ascites was similar to that of CPB8–9 patients. CP score was more important than CP class in predicting the outcome of sorafenib therapy in patients with advanced HCC. Among the CP score components, presence of ascites was a significant prognostic factor, especially in CPB7 patients. "
“Hepatocellular carcinoma (HCC) is associated with poor survival

for patients and few effective treatment Selleck Everolimus options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver’s unique affinity for small nucleic acids, miRNA-based therapy has been proposed in the treatment of liver disease. Thus, there is an urgent need

to identify and characterize aberrantly expressed miRNAs in HCC. In our study, we profiled miRNA expression changes in de novo liver tumors driven by MYC and/or RAS, two canonical oncogenes activated in a majority of human HCCs. We identified an up-regulated learn more miRNA megacluster comprised of 53 miRNAs on mouse chromosome 12qF1 (human homolog 14q32). This miRNA megacluster is up-regulated in all three transgenic liver models and in a subset of human HCCs. An unbiased functional analysis of all miRNAs within this cluster was performed. We found that miR-494 is overexpressed in human HCC and aids in transformation by regulating the G1/S cell cycle transition through targeting of the Mutated in Colorectal Cancer tumor suppressor. miR-494 inhibition in human HCC cell lines decreases cellular transformation, Phosphoprotein phosphatase and anti-miR-494 treatment of primary MYC-driven liver tumor

formation significantly diminishes tumor size. Conclusion: Our findings identify a new therapeutic target (miR-494) for the treatment of HCC. (Hepatology 2014;58:202–215) “
“IgG4 reactions consisting of marked infiltration by immunoglobulin G4 (IgG4)-positive plasma cells in affected organs is found in cancer patients as well as patients with IgG4-related diseases. Notably, extrahepatic cholangiocarcinomas accompanying marked IgG4 reactions clinicopathologically mimic IgG4-related sclerosing cholangitis. The regulatory cytokine interleukin (IL)-10 is thought to induce the differentiation of IgG4-positive cells. In this study, to clarify the mechanism of the IgG4 reaction in extrahepatic cholangiocarcinoma, we investigated nonprofessional antigen-presenting cells (APCs) generating IL-10–producing regulatory T cells (anergy T cells) and Foxp3-positive regulatory cells producing IL-10.