His achievements, along with his relationship with many famous gastroenterologists, opened the door at Harvard Medical School and American Gastroenterological Association (AGA) for Japanese researchers. Professor Daniel Podolsky was then Chief of the GI unit of Massachusetts’ General Hospital in the

Harvard Medical School at that time, later becoming President of the AGA, and is now President of the University of Texas, Southwestern Medical Center. Podolsky helped Mamoru personally, as well as, through him, becoming a good friend of the Japanese Society of the Gastroenterology (JSGE). In April 2000, Dr Watanabe accepted the position of Professor and Chairman, Department of Gastroenterology and Hepatology at Tokyo Medical and Dental University, where he currently see more serves. He also leads two other clinical gastroenterology divisions, the Department of Endoscopy and the Advanced Clinical Center for Inflammatory Bowel Disease. At Tokyo Medical and Dental University, his work continues to have a tremendous impact and he and his team have met numerous challenges both in the research field and in clinical care. Dr Watanabe has used his expertise to mentor many co-investigators in clinical sciences and trials,

to advance basic research and the principles of evidence-based medicine. His extraordinary professional standards always provide inspiration to all those with whom he works. This has built up the Division of Gastroenterology at Tokyo Medical and Dental University with talented faculty members and gastroenterologists, comprising an unprecedented I-BET-762 mw intellectual environment. It is no surprise that his currently leading department has become an extremely popular

GI center for training and research among Japanese schools and institutes. Mamoru Watanabe’s research interests are in immune-modulating therapy for IBD, cellular and molecular biological aspects of IBD, mucosal immunology, molecular biological aspects of inflammation-related carcinogenesis, and regeneration and differentiation of intestinal epithelial cells. Most recently, he has turned his attention to intestinal epithelial stem cell biology. An STK38 early discovery was the recognition that interleukin (IL)-7 is an essential factor for the pathogenesis of IBD, being responsible for the persistence of chronic T cell-mediated colitis. Mamoru has shown that IL-7 is constitutively produced by intestinal goblet cells. He is the first scientist who found the critical role of IL-7 in mucosal immunology and this ground-breaking paper was published in the Journal of Clinical Investigation in 1995.[1] IL-7 transgenic mice develop colitis that mimics the histopathological characteristics of human IBD (J Exp Med 1998).[2] CD4+ T cells that express high levels of IL-7Rα reside in inflamed lamina propria (LP) (Journal of Immunology [JI] 2003, JI 2011) and IL-7–/– mice do not develop colitis (JI 2007).

When the subgroup analyses were carried out

according to gender, BAY 73-4506 nmr both the genotypes and allelic frequencies in the female NAFLD group were significantly different from those in controls (P < 0.05), while there was no significant difference between the two male groups (P > 0.05). These results suggested that the G/A variant at leptin gene -2548 is associated with increased susceptibility to NAFLD in women. The genotypic distributions and allelic frequencies of the PPAR-γ gene -161 C/T polymorphism in the NAFLD group were significantly different from those in the control group (P < 0.05), but the difference was not significant in the PGC-1α gene -482 G/S polymorphism (P > 0.05). Our findings suggested that the C/T variant in the PPAR-γ gene increased susceptibility to NAFLD, and that the G/S variant in the PGC-1α genes was not relevant. Gender analyses showed no significant difference. The genotypic distributions and allelic frequencies at promoter region -514 C/T of the hepatic lipase gene were significantly different across groups (P < 0.05), suggesting that the C/T variant in the hepatic lipase learn more gene decreased susceptibility to NAFLD. The subgroup analysis according to gender showed no significant difference. The genotypic distributions and allelic frequencies at 175 G/A in exon 8 of the PEMT gene were significantly different between the NAFLD and control groups (P < 0.05). The

results pointed to a relationship between the G/A variant in

the PEMT gene and susceptibility to NAFLD. Gender analysis showed no significant difference. Genetic influences on susceptibility to metabolic syndrome have been reported, but the conclusions are controversial, and the associations are unclear.7–9 As an example, a meta-analysis including 31 observational studies found conclusions in most reports that the TNF-α -308 G/A variant was not involved in the pathogenesis of metabolic syndrome.18 However, other studies show an association between this variant and metabolic syndrome.19 There is less disagreement about the adiponectin gene; almost all papers supported an association with metabolic syndrome occurrence.20–23 As NAFLD represents the hepatic manifestation of metabolic syndrome, there is substantial overlap in the pathogenesis Fossariinae of these two syndromes.10–12 Theoretically, many variations in candidate genes contribute to the pathogenesis of NAFLD: first, genes related to insulin resistance, such as adiponectin, resistin, insulin receptor, PPAR-γ, etc.; second, genes impacting hepatic lipid metabolism, such as hepatic lipase, leptin (or leptin receptor), adiponectin, microsomal triglyceride transfer protein (MTP), PEMT, PPAR-α, cytochrome P450 (CYP) 2E1 and 4A, etc.; third, cytokine-related genes, such as TNF-α, interleukin (IL)-10, etc.; fourth, genes impacting liver fibrosis, such as leptin, adiponectin, transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), angiotensinogen, etc.

MC/9 cells were cultured for 1 hour with rIL-10 (0.25 ng/mL) or rIL-9 (Sigma; 12.5 U/mL) previously incubated for 1 hour with or without peptides (100 μg/mL) or anti-IL-10 neutralizing antibody (eBioscience) (1 μg/mL). Then cells were harvested and phospho-STAT-3 (signal transducer and activator of transcription 3) and actin content was determined by immunoblot as described.22 Blood was obtained from the Blood Bank of Navarra after informed consent. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. Peripheral blood mononuclear cells (PBMCs) (2 × 105 cells/well) were stimulated in RPMI 1640 CM in 96-well plates with the Toll-like receptor 9 (TLR9) oligodeoxinucleotide

ligand CpG 221623 (Sigma-Genosys) (5 μg/mL) for pDC analysis, or with a monolayer of 2 × 104 irradiated control or CD40L-expressing BHK cells24 (kindly provided by H. Engelmann; Munich, Germany) Ensartinib purchase for mDC analysis, with or without recombinant HCV core protein (2.5 μg/mL) (BioDesign; Memphis, TN). IL-10-binding peptides (100 μg/mL) or anti-IL-10 antibody were added simultaneously to some wells in triplicate. Two days later, supernatants were harvested and enzyme-linked immunosorbent assay (ELISA) was used to measure content of IFN-α (Mabtech, CT99021 mw Sweden), IL-12 and IL-10 (BD-Biosciences,

San Diego, CA). Human monocyte-derived DC (MoDC) (105 cells/well), prepared as described,25 were stimulated with lipopolysaccharide (LPS) (1 μg/mL). Murine bone marrow-derived DC (BMDC) were prepared as described21 from C57BL/6 or HHD mice (transgenic for human HLA-A2.1 and beta-2 microglobulin molecules; a gift of Dr. F. Lemonnier, Institute Pasteur, Paris, France). Animals received humane care, maintained in pathogen-free conditions, and treated according to guidelines of our Institution PDK4 Review Board. Murine BMDC were cultured at 106 cells/mL with LPS (0.5 μg/mL) and peptide

1073-1081 (10 μg/mL) or were infected with a recombinant adenovirus encoding HCV NS3 (AdNS3) as described.21 In all cases, cells were cultured with or without IL-10 peptide inhibitors (100 μg/mL) for 24 hours, harvested, washed, and used for in vitro stimulation experiments or immunization, in the case of murine DC. To measure IL-12 production by human mDC, PBMC were stimulated with CD40L as described above, and monensin (BD-Biosciences) was added for the last 4 hours of culture. Then cells were stained with a cocktail of FITC-labeled anti-CD3, -CD14, -CD16, -CD19, -CD20, and -CD56, PerCP-labeled anti-HLA-DR and APC-labeled anti-CD11c antibodies (all from BD-Biosciences). After fixation and permeabilization, PE-labeled anti-IL-12 antibodies (Miltenyi, Germany) were added and IL-12 production was analyzed in the mDC population, gated as Lin-HLA-DR+CD11c+. Cells were acquired in a FACSCalibur flow cytometer (BD-Biosciences) and analyzed with Flowjo software (Tree Star, Ashland, OR).

We establish in this study that PLA2GXIIB is an HNF-4α target gene. We demonstrate that HNF-4α binds to a response element on the PLA2GXIIB promoter. Moreover, HNF-4α agonists induce PLA2GXIIB expression in human hepatocarcinoma cells. Importantly, PLA2GXIIB-null mice accumulate triglyceride, cholesterol, and fatty acids in the liver and develop severe hepatosteatosis resembling some of the phenotypes of liver-specific HNF-4α–null mice. These defects are in part due to compromised hepatic very low-density

lipoprotein secretion. Finally, adenovirus-mediated overexpression of HNF-4α elevates Selleck BMS-907351 serum triglyceride level in wild-type but not PLA2GXIIB-null mice. Conclusion: Collectively, these evidences suggest that HNF-4α is a key physiological PLA2GXIIB transcriptional regulator and that PLA2GXIIB is a novel mediator of triglyceride metabolism in the liver. (HEPATOLOGY 2011;53:458-466) Hepatocyte nuclear factor-4 alpha (HNF-4α) was initially identified as a transcriptional factor required for liver-specific gene expression.1 Coenzyme A (CoA) derivatives of certain fatty acids can bind to the ligand-binding domain of HNF-4α and activate the receptor,2 suggesting that HNF-4α activity is subjected to modulation by metabolic and nutritional

signals. HNF-4α regulates the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase (PEPCK)3 and glucose-6-phosphatase (G6P),4 through binding to hormone response elements on their promoters and recruiting coactivators such as peroxisome proliferator-activated Navitoclax cell line receptor γ coactivator-1α (PGC-1α) to their promoters.5 In addition, HNF-4α and PGC-1α regulate the expression of lipoproteins and packaging enzymes such as microsomal triglyceride transfer protein (MTP) that are involved in very low-density lipoprotein much (VLDL) secretion. Significantly, liver-specific HNF-4α-null (HNF4αLivKO) mice suffer from severe defects in lipid homeostasis

with hepatosteatosis and reduced serum triglyceride (TG) and cholesterol levels.6 Phospholipases A2 are enzymes that catalyze the hydrolysis of glycerophospholipids at the Sn2 position to release free fatty acids such as arachidonic acid and lysophospholipids that are precursors of signaling molecules.7 In particular, arachidonic acid and its metabolites leukotrienes and prostaglandins are key inflammatory regulators. On the basis of their protein structures and biochemical properties, the superfamily of PLA2 can be divided into five principal kinds of enzyme: cytosolic PLA2s (cPLA2s), Ca2+-independent PLA2s (iPLA2s), lysosomal PLA2s, platelet activating factor acetylhydrolases, and secreted PLA2s (sPLA2s). Secreted PLA2s have relatively low molecular masses of 14-19 kDa, a large number of disulfides, and similar Ca2+-dependent catalytic mechanism. Mammalian sPLA2s include GIB, GIIA, GIIC, GIID, GIIE, GIIF, GIII, GV, GX, GXIA, GXIB, GXIIA, and GXIIB.

003). All six HBV isolates that could be sequenced were of genotype

A/subgenotype A1. Four of these six HBV isolates contained mutations associated with lamivudine resistance in the DNA polymerase (two with L180M/M204V and two with rt173V/180M/204V) and a specific substitution (Y100C) in the HBV small surface protein. Conclusions:  HBV isolates with the identified substitutions have the potential to spread silently by nosocomial transmission within the hemodialysis unit. These results have potential implications for the management of patients with occult HBV infection undergoing hemodialysis. “
“Since the introduction of antiretroviral therapy (ART) in the mid-1990s, AIDS-related death has been dramatically reduced, and hepatitis-C-virus (HCV)-related liver failure or hepatocellular carcinoma has currently become the leading cause of death in HIV/HCV co-infected patients. Liver STA-9090 mouse transplantation may be one of the treatments of choices in such cases, but the indications for transplantation, perioperative management including both HIV and HCV treatments, immunosuppression and the prevention/treatment of infectious complications are all still topics of debate. With the improved understanding of the viral behaviors of both HIV and HCV and the development of novel strategies, especially to avoid drug

interactions between ART and immunosuppression, liver transplantation has become a realistic treatment for HIV/HCV co-infected patients. IN

JAPAN, IN the late 1980s, contaminated buy PLX3397 blood production of coagulation factor for hemophilia caused co-infection of HIV and hepatitis C virus (HCV). Actually, greater than 90% of HIV-infected patients have HCV as well.[1] After antiretroviral therapy (ART) was introduced in the late 1990s, successful control of HIV was achieved in most cases and death due to AIDS was dramatically reduced, but HCV-related death due to liver failure or hepatocellular carcinoma became a serious problem, not only in Japan, but all over the world.[2-6] In such cases, triclocarban liver transplantation (LT) is the only treatment option to achieve long-term survival, but several modifications of perioperative management are required. In this review, the outcome and the points of management of LT for HIV/HCV co-infected patients were reviewed. THE REPORTED OUTCOMES of LT for HIV and HIV/HCV co-infected patients from Western countries after the introduction of ART are summarized in Table 1.[7-11] In general, most reports concluded that the results were worse than in the cases with HCV mono-infection, with a 3-year survival of approximately 60–70%. In Japan, the Tokyo group reported six cases of living donor liver transplantation (LDLT) between 2001 and 2004, of whom four died.

pylori eradication rates between probiotic and HSP inhibitor placebo group (45.5 vs 37.5%; p = NS) [71]. In a study of our group, aimed to evaluate the efficacy of probiotics to reduce antibiotic side effects, we found no differences in the eradication rates according to the presence/absence of the probiotic: treatment was successful in 17 of 20 patients supplemented

with L. reuteri ATCC 55730 (SD2112) as compared to 16 of 20 patients in the placebo group (85 vs 80%; p = NS) [72]. Recently, in a double-blind placebo-controlled randomized clinical trial performed in 66 children no difference was found with respect to H. pylori eradication rates between children receiving standard triple therapy supplemented with L. rhamnosus GG or placebo (69 vs 68%; p = NS) [77]. Pooled data, derived from children and adults’ studies Selleckchem Staurosporine on more than 1900 treated patients, show eradication

rates of 82.5% (95%CI: 80.1–84.7%) in patients with probiotic supplementation as compared to 73.7% (95%CI: 71–76.4%) in patients receiving placebo (RR: 1.11; 95%CI: 1.07–1.17). These data do not represent convincing evidence to support the use of probiotics as an adjunct with the aim of increasing the H. pylori eradication rate. Nevertheless, further studies are needed to clarify their role in this particular issue. The major limit to establish whether a probiotic is able to significantly increase the eradication rate is represented by the power of the study. Indeed, due to the high eradication rates that we mostly achieve with standard antibiotic treatment, to detect a 10% increase in eradication (secondary to the use of a probiotic strain), given a power of al least 80% and an alpha error level of 5%, 150 patients in each arm are needed to be enrolled. In our own experience on 40 adults, we were able to demonstrate a favorable effect of L. reuteri ATCC 55730 (SD2112) on dyspeptic symptoms

induced by H. pylori [56]. In this study, L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale (GSRS) as compared to pre-treatment value (7.9 ± 4.1 vs 11.8 ± 8.5; p < .05) that was not observed before in patients receiving placebo (9.7 ± 8.7 vs 11.4 ± 9.7; p < NS) [56]. Not all probiotic strains are able do decrease dyspeptic symptoms [53] suggesting that the effect is strain specific. No data are available in the pediatric age. Bacterial resistance and antibiotic’ side-effects represent the most frequent cause for anti-H. pylori treatment failure in clinical practice [9]. Several studies evaluated whether probiotic supplementation might help to prevent or reduce drug-related side effects during H. pylori eradication therapy in adults [61,63,64,66,68,69,72–75,78–80]. All showed that diarrhea, nausea and taste disturbances were significantly reduced by probiotics and overall they were superior to placebo for side effect prevention.

Park, Moon Young Kim, Soon Koo Baik, Yun Soo Kim, Ju Hyun Kim, Jung Il Lee, Jin-Woo Lee, Sun P. Hong, Soon Ho Um INTRODUCTION:Chronic hepatitis B (CHB) infection is a common cause of hepatocellular carcinoma (HCC).Nucleos(t)ide analogues (NA) are effective in suppressing viral replication and decreasing the inflammatory response in the liver,but their effect on progression to HCC is unclear.This study examines the factors affecting development of HCC in patients receiving long-term NA therapy.

METHODS:CHB patients,who received at least 12 months of NA therapy,were enrolled in the study.The patients who diagnosed with HCC before they have completed the first 12 selleck months of treatment were excluded.Clinical and biochemical findings, stage of fibrosis and type of NA treatment were recorded .The patients were screened for HCC at every 6 months by USG and AFP. A drug with a higher genetic barrier against resistance was added or switched,if HBVDNA negativity could not be achieved or genotypic resistance/virological breakthrough developed during treatment. Lamivudine and adefovir were accepted to be low genetic barrier drugs,while entecavir and tenofovir click here were defined

as high genetic barrier drugs. RESULTS:661 patients with genotype D CHB infection (71% male,mean age 50±12 years,71% HBeAg (-) ) were enrolled in the study.66% of patients were pre-cirrhotic, while 34% were cirrhotic.The median duration of NA treatment was 48 months (1 2 – 1 94 months). HCC developed in a total of 57 (8.6%) patients.The cumulative incidence of HCC was significantly higher Tolmetin in patients with cirrhosis than in those without (p<0.001).Also it tended to be higher in patients with decom-pensated cirrhosis compared to those with compensated cirrhosis.Cumulative HCC incidence in cirrhotic and CHB patients were 2.3% vs.0.2% at 1st year, 8.3% vs.0.5

% at 2nd year, 14.8% vs. 1.4% 3rd year and 22.9% vs.2.6% at 5th year, respectively (log-rank,p<0.001 ).The median time for HCC development during NA treatment was 36 months.In univariate Cox regression analyses,factors associated with HCC development were found to be male sex (p=0.002), cirrhosis (p<0.001),alcohol (p=0.02),HBeAg negativity (p=0.001),low genetic barrier drug regimen (p<0.001),resistance/virological breakthrough (p=0.002) and diabetes (p=0.03).In a multivariate analysis,cirrhotic liver (p<0.001), low genetic barrier drug regimens (p=0.02) and resistance-virological breakthrough (p=0.04) were independent factors associated with HCC development.

, 2007), additional cognitive tasks of attention, memory and executive function were also implemented. Nine individuals (2 women, 7 men; Mage = 38.4 years; SD = 17.3; Range 17–69 year) with TBI were selected from patients currently hospitalized at the regional hospital Hammel Neurocenter, a highly specialized rehabilitation centre for people with acquired brain damage, on the basis of medical evidence that they had sustained moderate-to-severe TBI. Six of the TBI participants suffered a severe TBI, defined by a post-resuscitation score of 8 or less on the Glasgow Coma Scale (GCS; Teasdale & Jennett, 1974). The remaining

three participants suffered a moderate TBI classified by GCS scores between 9 and 12 (n = 2) or by a GCS score higher than 12 accompanied by a positive neuroimaging finding and neurosurgery. All participants experienced an extended period of post-traumatic amnesia (PTA) https://www.selleckchem.com/PD-1-PD-L1.html (MPTA = 19.33; SD = 16.84; TSA HDAC nmr Range 2–56 days), assessed by medical records and clinical questioning of the participants. TBI participants were assessed between 39 and 117 days after injury (M = 64.33; SD = 22.26). All patients were screened on intake, and participants with aphasia or whose gravity of comprehension, attention, and behavioural problems would invalidate the assessment were excluded. None of the participants suffered from any pre-injury,

psychiatric, or neurological disorders or had any history of prior substance abuse. Five TBI participants suffered their head injuries as a result of a motor vehicle 3-mercaptopyruvate sulfurtransferase accident, three incurred injury from a fall and one TBI participant experienced a blow to the head. Computed tomography (CT) or Magnetic Resonance Imaging (MRI) showed a predominance of diffuse and frontal lobe lesions. The comparison group consisted of nine healthy participants (4 women, 5 men, Mage = 30.67 years; SD = 12.35; Range =  20–57 year), with no history of neurological or psychiatric disorder, or substance abuse recruited on a voluntary basis. There was no significant difference between groups in age (t(16)=1.10, p = .29)

and premorbid IQ, as estimated by the Danish adaptation of the National Adult Reading Test (DART; Dalsgaard, 1998; (t(10.73) = −1.10, p = .30). Although not significant, there was a greater age-range in the TBI group, due to one patient being much older (69 years old). Excluding this patient did not change the results, and we therefore chose to include all of the patients regardless of age. The control group included slightly more women (4 of 9) compared with the patients (2 of 9), but this difference was not significant (Fischer’s exact test, p = .62). The controls had on average spent more years in school than the TBI participants (t(8) = −6.11, p < .001), but when examining formal level of education [no education (incl.

Recently, intestinal microbiota analysis revealed that patients with NASH had a lower percentage of Bacteroidetes compared to healthy control, consistent with previous observations made in alcoholic patients.[38] Such correlations are strongly suggestive of the notion

that gut microbiota products promote NAFLD. In accordance, mice maintained on high-fat/simple carbohydrate, i.e., “modern Western,” diets exhibit increased intestinal permeability, elevated levels of serum endotoxin, and modestly elevated levels of proinflammatory cytokines that correlate with various aspect of metabolic syndrome including NAFLD.[39, 40] Increased levels of serum endotoxin may reflect increased permeability and the fairly large shifts Doxorubicin nmr in gut microbiota composition that occur in mice in response to diets designed to mimic Western diets. Evidence that NAFLD is actually driven by responses Dabrafenib nmr to endotoxin and other microbial products include observations that, in mice, diet-induced metabolic syndrome is absent in germfree conditions and that ablation of innate immune signaling by deleting TLR4 ameliorates disease, while the absence of MyD88, which plays a central role in TLR/NLR signaling, appears to eliminate it entirely.[41-43] Similarly, the suppressor of cytokine signaling 1 (SOCS1) protein, a negative-feedback regulator in cytokine signaling induced upon TLR stimulation,

plays a protective role in liver injury, since SOCS1-deficient mice display fulminant hepatitis, characterized by hepatic Cediranib (AZD2171) inflammation, fatty degeneration, and hepatocyte necrosis.[44-46] Thus, overall, these findings suggest that the dramatically increased incidence of NAFLD may,

in part, result from increased consumption of Western diets causing increased activation of proinflammatory signaling due to increased intestinal permeability and/or changing in microbiota composition. A recent study supports the former possibility. Specifically, this study examined mice on a HFD that did and did not develop steatosis, and observed changes in microbiota composition that correlated with this phenotypic difference.[47] Transfer of the microbiota from the steatotic mice to germfree mice promoted development of HFD-induced steatosis relative to germfree mice given the microbiota of nonsteatotic mice. Such steatosis correlated with dysglycemia, suggesting that the altered microbiota was broadly promoting metabolic syndrome. The alterations in gut microbiota involved alterations in numerous bacterial species. As reviewed elsewhere, increased proinflammatory signaling can be a direct cause of liver disease and other aspects of metabolic syndrome.[48] Effects of proinflammatory signaling on metabolism include dysregulating appetite control, thus amplifying events that can drive NAFLD/metabolic syndrome. Inflammation can also alter gut microbiota composition.

METHODS: Colon carcinoma CT26 cells, expressing HSF1, HSP70 and HSP90, were used to assess shRNA-HSF1-nanoliposomal uptake, toxic-ity/efficiency by employing immunofluorescence, Q-PCR and protein analysis. In vitro sub-lethal heat experiments were performed to mimic radiofrequency ablation and this by using different time points and temperatures. An orthotopic murine model of coloncarcinoma cancer – liver metastasis was used to analyze HSF1 expression during tumour formation. Radiofre-quency ablation (RFA) in small animals was optimized Sotrastaurin clinical trial to investigate the HSF1-induced-and

related signaling pathways in the treatment of liver metastasis. RESULTS: shRNA-HSF1-nanolipo-somes were taken up by 99 procent of cells without inducing cytotoxicity. Sub-lethal heat treatment of 45 and 50 degrees Celsius induced p-ERK, p-AKT and HSF1-related proteins at different timepoints investigated and this coincided with a nuclear to cytosolic shift of HSF1, HSP70/90, AKT and ERK. Apoptosis was significantly induced only after 10 days post-heat treatment. In vivo, see more tumours highly expressed HSF1, HSP70/90, AURBK and p-ERK and p-AKT. Radiofrequency-ablated tumours showed an increase in HSF1 and HSP70/90 protein expression after 6 and 10 days post-RFA, suggesting the involvement of HSF1 during the process

of tumour recurrence. CONCLUSION: This study demonstrates that HSF1 is highly expressed in CRC liver metastasis and suggest its possible involvement in tumour recurrence after employing radiofrequency ablation. Disclosures: Claudio Amabile – Employment: H.S. Hospital Service SpA Nevio Tosoratti – Employment:

HS HOSPITAL SERVICE SpA Simone Cassarino – Employment: H.S. Hospital Service SpA Mark Kester – Stock Shareholder: those Keystone Nano Inc Massimo Pinzani – Advisory Committees or Review Panels: Intercept Pharmaceutical, Silence Therapeutic, Abbot; Consulting: UCB; Speaking and Teaching: Gilead, BMS The following people have nothing to disclose: Francesca Zanieri, Vinicio Car-loni, Sara Omenetti, Sriram Saravanan Shanmuga Velandy, Krista Rombouts Background/Aims: Hepatitis E virus (HEV), a hepatotropic virus has shown the property of self-assembly through its N-terminally truncated ORF2 (Nt-ORF2). Recent studies have demonstrated virus-like particles (VLPs) as a drug-delivery vehicle. In this study, we developed HEV-LPs generation system based on Huh7 cells and confirmed liver-specific penetration of the HEV-LPs. Moreover, we established a HEV-LP disassembly/reassembly system to charge therapeutic agents into the VLPs. Methods: In order to deliver CMV promoter derived-Nt-ORF2 gene into Huh7 cells, we used Bac-to-Bac system.