Thus, whilst useful in terms of generating hypotheses, the results of this more recent review are also inconclusive with respect to confirming the relative immunogenicity between plasma-derived www.selleckchem.com/products/jq1.html and recombinant FVIII products.

Early in 2013, a study by the European Pediatric Network for Hemophilia Management (PedNet) and Research of Determinants of Inhibitor Development (RODIN) was published [14]. This multicentre, observational (mainly prospective, partially retrospective) cohort study evaluated 574 consecutive patients with severe haemophilia A (FVIII activity < 0.01 U mL−1) born between 1 January 2000 and 1 January 2010, making it the largest study to date in PUPs at high risk of developing inhibitors. Over a total of 29 679 exposure days, inhibitory antibodies developed in 177 of the children for a cumulative

incidence of 32.4%. Interestingly, and in contrast to the systematic reviews discussed above [7, 13], no difference was found in the risk of inhibitor development between plasma-derived and recombinant products (adjusted hazard ratio 0.96 [95% CI 0.62–1.49]). Although the study provided useful new evidence in relation to the use of recombinant products, it also has some important limitations. Patients were not assigned randomly to FVIII products and there was no apparent use of scores to account for differences in the propensity of various Inhibitor Library in vitro products to be associated selleck screening library with inhibitor development [15]. The number of children treated with pdFVIII was small, involving only 4018 exposure days compared with 25 661 exposure days for patients treated

with rFVIII. Many patients treated with plasmatic FVIII received monoclonal products that contain only traces of VWF, but results were combined with those of patients receiving VWF-rich products. Finally, as with all studies, there is risk of a type 2 error, i.e. finding no difference when a difference does in fact exist. As is the case with the systematic reviews, the results of this study cannot be considered conclusive and the ‘jury is still out’ with regard to the relative risk of inhibitor development in PUPs treated with plasma-derived or recombinant FVIII concentrates. Switching among FVIII products has also been suggested as a risk factor for inhibitor development. In their cohort of PUPs, the PedNet/RODIN investigators found no increased risk of inhibitor development in patients who switched vs. those who did not switch FVIII products (adjusted hazard ratio 0.99 [95% CI 0.63–1.56]) [14]. The haemophiliac population also contains a small group of previously treated patients (PTPs) who initially respond to FVIII but develop inhibitors upon further exposure. Inhibitor development in PTPs treated with any type of FVIII concentrate was investigated in a systematic review of 33 independent cohorts of PTPs [16].

In vivo plasmacytoid DC depletion was accomplished using 120G8 (200 μg; Imgenex, San Diego, CA).26 In selected experiments, the novel immune-modulator VAG539 (30 mg/kg, Novartis, Basel, Switzerland) was used to partially inactivate DC.27 To deplete Gr1+ cells, RB6-8C5 was employed (150 μg/day; Monoclonal Antibody Core Facility, Sloan-Kettering Institute, New York, NY). For in vivo NK cell depletions, 100 μL of a 1:5 dilution of anti-asialo GM1 (Wako Chemical, Richmond, VA) was injected intraperitoneally 3 days prior to APAP treatment. In selected experiments, antibodies

directed against IFN-α (1 μg, F18, Sigma), TNF-α (200 μg, AB-410, R&D, Minneapolis, MN), IL-6 (200 μg, AB-406, R&D), or MCP-1 (50 μg, AB-479, R&D) were administered in vivo before APAP challenge. Changes in serum FK228 in vivo liver enzymes, including ALT, aspartate aminotransferase (AST), were determined using the Olympus AU400 Chemistry Analyzer (Center Valley, PA). In survival experiments, animals were euthanized when they were moribund and death was imminent. Animal procedures were approved by the New York University School of Medicine Animal Care and Use Committee. Liver DC were isolated as described.25 Briefly, immediate postmortem laparotomy was performed and the portal vein was MDX-1106 cannulated and infused with 1% Collagenase IV (Sigma-Aldrich). Hepatectomy was then performed and livers mechanically minced

before incubation with Collagenase IV at 37° for 10 minutes. Low-speed (30g) centrifugation was performed find more to exclude the pelleted hepatocytes followed by high-speed (300g) centrifugation to isolate the hepatic nonparenchymal cells (NPCs). The NPC were then further enriched over a 40% Optiprep

(Sigma-Aldrich) density gradient. To purify the DC population, NPCs were incubated with 1 μg of anti-FcγRIII/II (2.4G2, Fc block; Monoclonal Antibody Core Facility, Sloan-Kettering Institute) per 106 cells, labeled with fluorescently conjugated anti-CD11c and anti-MHC II (both BD Biosciences, Franklin Lakes, NJ), and FACS sorted using a MoFlo cell sorter (Beckman Coulter, Fullerton, CA). Splenocytes were prepared by mechanical disruption and specific cellular subgroups were purified by FACS. For in vitro T-cell proliferation assays, peptide-pulsed DC (3 × 104) were added to CD8+OT-I TCR-transgenic T cells (1 × 105) specific for Ova257-264, or CD4+OT-II TCR-transgenic T cells specific for Ova323-339 in 96-well plates for 48-72 hours before pulsing with 3H-thymidine as described.25 DCs were loaded with the relevant Ova peptide (10 μg/mL; AnaSpec, San Jose, CA) for 90 minutes before co-culture with respective T cells. In selected experiments, VAF347 (5 mM, Novartis), a low-molecular-weight compound that binds the aryl hydrocarbon receptor was used to prevent DC induction of CD4+ T cells.28 Western blotting was performed as described.29 Livers were minced in PBS with Protease Inhibitor cocktail (Roche, Pleasanton, CA) and homogenized.

Such limitations can affect the standard of management provided to patients. It is important for these hospitals to frequently evaluate disease

management especially when there are advancements. This enables issues to be identified and practice modified accordingly. The aim of this study is to assess the standard of hepatitis C management in a regional hospital in the setting http://www.selleckchem.com/products/bmn-673.html of recent advancements in management. Methods: A retrospective analysis of patients undergoing hepatitis C management in a regional hospital from September 2011 until May 2014 was conducted. The management team consisted of one full time gastroenterologist and 2 HCV nurse specialists covering a population of 250 thousand, many of whom are from remote rural areas. Medical records were examined to obtain data. Patients underwent an initial psychiatric assessment and most had a fibroscan or liver biopsy before starting treatment. Patients were divided into 2 genotype specific groups (genotype 1 and genotypes 2&3). These groups were further subdivided depending on whether treatment was completed or not. Genotype 1 received either double therapy (interferon and riboviran) or triple therapy (interferon, riboviran and teleprovir or Boceprevir). Genotypes

2 & 3 received only double therapy. Reasons for not completing were analyzed as well XL184 in vivo as the cure and relapse rates. Results: A total of 61 patients were treated. 41% (21) had genotype 1, whilst 59% (36) had genotypes 2 and 3. Median age was 44 years old. 15 patients (24%) did not complete the treatment (7 in Genotype 1 and 8 in genotypes 2&3). Genotype 1: 18 completed treatment (72%), selleckchem 4 of which were on double therapy. Six patients (33%) were null responders (1/4 double therapy and 5/14 triple therapy). Of the 12 responders (66%), 6 had confirmed cure at 6 month review, but unfortunately another 6 were lost to follow up (un-contactable or refused blood test). Of the 7 non-completers (28%), 4 were non-compliant, 1 withdrew and 2 experienced side effects of severe skin

rash, uncontrollable drop in Hb or severe abdominal pain. Genotypes 2&3: 28 completed treatment (78%). Three patients (11%) were null responders. Of the 25 responders (89%), 15 had confirmed cure at 6 month review, 3 relapsed and unfortunately 7 were lost to follow up (un-contactable or refused blood test). Of the 8 non-completers (22%), 2 were non-compliant and 6 experienced side effects of severe skin rash, significant psychiatric illness, vomiting and uncontrollable low platelets. Conclusion: This study identified a high response rate in treatment regimes for all genotypes studied at a regional hospital. However it was lower than expected for genotype 1 particularly in the initial stages of triple therapy. Of interest, the side effect profile of triple therapy was found to be no more than that of double therapy.

Steatosis and ethanol consumption are considered key hits for the development of ALD. 1-4 Mitochondrial damage, selleckchem up-regulation of nitric oxide synthase-2 (NOS2) and generation of reactive oxygen and nitrogen species (ROS and RNS) condition cell viability, inflammation, and fat deposition in ALD. Thus, understanding the

molecular mechanisms of pathological nitric oxide (NO·) production by NOS2 is of great relevance to prevent ethanol hepatotoxicity. NOS2 catalyzes the nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-dependent oxygenation of L-arginine to NO· and L-citrulline. 5 Although the Nos2 gene lies quiescent under physiological conditions, cytokines, ROS, growth factors, and, most important, ethanol, initiate and sustain its activation. 2 Overexpressing NOS2 mediates mitochondrial damage as it occurs in ALD. 6 Previous work has shown that NOS2 is required for ALD due to generation of NO·-derived prooxidants. 7, 8 Indeed, ethanol hepatotoxicity was blunted in Nos2−/− mice as well as by a NOS2 inhibitor in wildtype (WT) mice. 7 The urea cycle is a metabolic pathway in which ammonia is converted to urea in the liver. The urea cycle enzymes along with the L-citrulline/NO· cycle catalyze de novo biosynthesis

of L-arginine, which also serves as a substrate for NO· synthesis by NOS2. Five reactions occur within a STA-9090 purchase functional complex or metabolon between the mitochondria and the cytosol (Supporting Fig. 1, green line): 2ATP + HCO + NH Carbamoyl phosphate + 2ADP + Pi (Carbamyl phosphate synthase-1, CPS1); Carbamyl phosphate + Ornithine Citrulline + Pi (Ornithine transcarbamylase, OTC); Citrulline + Aspartate + ATP

Argininosuccinate + AMP + PPi (ASS); Argininosuccinate Arginine + Fumarate (Argininosuccinate lyase, ASL); Arginine + H2O Ornithine + Urea (Arginase-1, ARG1) Although ASS and ASL are usually considered in the context of their contribution to the urea cycle, in conjunction with NOS2 they endow cells with a salvage pathway, the L-citrulline/NO· cycle (Supporting Fig. 1, red line) that continually generates L-arginine from L-citrulline for sustained NO· production. Physiological levels of L-arginine do not suffice to saturate NOS2 and changes in L-arginine bioavailability contribute to regulate NO· production. selleck chemicals llc Patients with type-I citrullinemia—an autosomal recessive urea cycle disorder due to Ass deficiency—develop hyperammonemia due to inefficient protein catabolism. 9, 10 Genetic disorders in the urea cycle cause steatosis and amino acid imbalance; however, the mechanism for these events is unknown. Hyperammonemia, changes in the concentration of amino acids and a decline in urea synthesis, occur in ALD patients. 11, 12 The role of the L-citrulline/NO· cycle in the liver, the potential role of ASS as an enzymatic “switch” to provide a substrate for NOS2-induced activity, and the subsequent excess of NO· biosynthesis in ALD is still to be defined.

15, 16 Accumulating evidence suggests that the formation of apoB100-BLp17 and apoB48-BLp18, 19 is accomplished sequentially. The two-step model

postulates that the initial product is a primordial particle, formed during apoB translation in the endoplasmic reticulum (ER). It is clear that microsomal TG transfer protein is involved in the early stage (first step) of apoB lipidation. However, the mechanism involved in the later stage (second step) is still not well understood. We have unexpectedly found that PLTP deficiency causes a significant impairment in hepatic secretion of VLDL.20 Likewise, it has been reported that animals overexpressing PLTP exhibit hepatic LBH589 VLDL overproduction.21 Associations of plasma PLTP activity with elevated apoB levels22 have been found in humans, as well. In a recent study, Masson et al.23 found that human PLTP transgenic rabbits showed a significant increase of BLp, but not of HDL cholesterol, in the circulation. These animals demonstrated increased atherosclerotic lesions after a high-fat diet feeding compared with controls. Luminespib in vivo Nevertheless, the surprising discovery that PLTP

affects BLp secretion from the liver must be explored fully. The liver is one of the major sites of lipoprotein production and degradation, as well as PLTP expression. To investigate the role of PLTP in lipoproteins homeostasis, we initially planned to prepare a liver-specific KO mouse model using the Cre-Loxp system under the control of an albumin promoter. Finally, we created a unique mouse model that expresses PLTP acutely and specifically in the liver, with a PLTP-null background. We studied lipoprotein metabolism, VLDL secretion, and VLDL lipidation in these animals, concluding that liver PLTP-mediated VLDL production is one of the driving forces for plasma lipoprotein metabolism. AdV, adenovirus; apo, apolipoprotein; BLp, apoB-containing lipoproteins; CETP, this website cholesteryl ester transfer protein; ER, endoplasmic reticulum;

FPLC, fast protein liquid chromatography; GFP, green fluorescent protein; HDL, high-density lipoprotein; KO, knockout; PCR, polymerase chain reaction; PERPP, post-ER presecretory proteolysis; PLTP, phospholipid transfer protein; SDS-PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis; TG, triglycerides; TLC, thin-layer chromatography; VLDL, very low-density lipoprotein; WT, wild-type. To prepare PLTP-Flox mice, a 9.16-kb region used to construct the targeting vector was first subcloned from a positively identified C57BL/6 (RPCI23) BAC clone. The region was designed so that the short homology arm extended about 1.68 kb (3′ to exon 3), and the long homology arm extended about 6.85 kb (5′ to exon 2). The loxP and FRT double-flanked Neo cassette was inserted on the 3′ side of exon 3, and the single loxP site was inserted at the 5′ side of exon 2. (Fig. 1A). All mice used in this study were aged 12-16 weeks, with a C57BL/6J genetic background.

Under informed consent, 1 8 cases Napabucasin price switched to Peg IFN a-2a plus adefovir, 5 continued therapy with telbivudine, 1 1 refused to receive treatment and 10 followed the suggestion to stopped treatment. The durations of treatment are from 48 to 96 weeks. Results Among 1 8 cases switched to Peg IFN a-2a plus adefovir, 15(83.3%) achieved complete virological response (HBV DNA<20IU/ml),

9(50%) achieved HBeAg clearance or sero-conversion with HBV DNA<20IU/ml, 5(27.8%) achieved HBsAg clearance(HBsAg <0.05IU/ml) or seroconversion with HBeAg loss and HBV DNA<20IU/ml, 1 did not achieve virological response, and 2 lost to follow-up. 3 patients who achieved HBsAg seroconversion had stopped antiviral therapy GPCR & G Protein inhibitor with HBsAb titers greater than 300IU/L persistently. Conclusions Based on postpartum ALT elevation, decrease of HBeAg titer and reduction of HBV DNA, switching to IFN-based regimen may achieve high rates of response after childbirth in pregnant HBV carriers who

received nucleoside analogs for PTMCT . The mechanism may be associated with recovery of immune function after childbirth and enhancement of immune function by antiviral therapy in the third trimester of pregnancy. Disclosures: The following people have nothing to disclose: Junfeng Lu, Xinyue Chen, Yali Liu, Hongwei Zhang, Lina Ma, Hua Zhang Switch in HBV genotypes is well known on interferon therapy. Whether prolonged Tenofovir therapy introduces genotype switches in patients (pts) during treatment is not known. Eighty-Eight chronic hepatitis B pts with raised ALT (>1.5 x ULN) and histologically proven chronic hepatitis, this website receiving tenofovir as per protocol were followed up every 6 months. HBV genotypes were studied if pts had at least two follow-ups (n=67) . Of these pts, 17 were treatment exposed (Lamivudine 12, Adefovir 3, Lamivudine + Adefovir 2). HBV Polymerase/surface region sequences from 67 pts were subjected to phylogenetic,

recombination analysis and inter-genotype (change of genotype), intra-genotype (change of subgenotype), recombination were determined in follow-up samples and compared to baseline. Majority of pts were male (n 58). Median HBV DNA was 3.1×106 IU/ml. HBeAg was +ve in 38 (56.7%). At baseline, HBV genotypes were : A 14 (20.8%), D 52 (77.6%) and C 1 (1.5%) with predominance of sub-genotype A1, C1 and D1. Twenty-two of 67 (32.8%) pts experienced inter-genotype switches. Six pts experienced switch in genotype at 6 months and 7 at 1 year, 3 at 1.5 year, 4 at 2 year and 2 pts at 2.5 years. The trend of genotype switch was more often detected from A to D [13 (92.8%), baseline HBeAg +ve: 9; HBeAg -ve 4] as compared to genotype D to A [9 (17.3%) baseline HBeAg +ve: 2; HBeAg -ve: 7] (P <0.002). Of 22 pts, in 3 change in HBeAg coincided with genotype switch i.e. [HBeAg +ve, Genotype A converted to HBeAg -ve, genotype D in one ], [HBeAg -ve, genotype D reverted to HBeAg +ve, genotype A in 2 pts].

Time to progression

(TTP) and overall survival were estimated by the Kaplan-Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (±18) Gy. According to EASL criteria, complete responses were determined in 3% of Selleckchem RO4929097 patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue-syndrome. Conclusion: Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted. (HEPATOLOGY

2010;52:1741-1749) Hepatocellular carcinoma (HCC) is a global health problem with increasing incidence worldwide. Today, therapy of HCC follows defined treatment algorithms and the most commonly used algorithm has been proposed by the Barcelona Liver Cancer Clinic (BCLC).1 Standard therapy for patients with larger tumor sizes and no macrovascular invasion is transarterial chemoembolization Nutlin-3 supplier (TACE). TACE has been shown to prolong survival

in patients with BCLC stage B (intermediate stage),2 but has failed to show survival benefit in patients find more with advanced HCC, even in those patients with adequate hepatic functional reserve.3 Therefore, in the current adaptation of the BCLC treatment algorithm the therapy of choice for advanced HCC is systemic treatment with sorafenib.4 This multikinase inhibitor has recently been shown to prolong survival in patients with advanced HCC in a randomized, controlled phase III trial,5 and is the first drug ever approved for the treatment of HCC. Due to the adverse effect profile of sorafenib, many patients can only tolerate a reduced dose or must discontinue the medication. This fact causes an ongoing effort to develop a locoregional treatment approach for patients with advanced HCC that is effective, but with a more acceptable/favorable toxicity profile than systemic therapy. Microsphere-related transarterial application of radioactive agents into malignant tumors represents a new generation of therapeutics in interventional oncology, even though the first reports of this approach were published decades ago. The main reasons for the delayed acceptance of this method were the safety issues caused by pulmonal and gastrointestinal deposition of radioactive microspheres.

Time to progression

(TTP) and overall survival were estimated by the Kaplan-Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (±18) Gy. According to EASL criteria, complete responses were determined in 3% of Pexidartinib patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue-syndrome. Conclusion: Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted. (HEPATOLOGY

2010;52:1741-1749) Hepatocellular carcinoma (HCC) is a global health problem with increasing incidence worldwide. Today, therapy of HCC follows defined treatment algorithms and the most commonly used algorithm has been proposed by the Barcelona Liver Cancer Clinic (BCLC).1 Standard therapy for patients with larger tumor sizes and no macrovascular invasion is transarterial chemoembolization GSK1120212 manufacturer (TACE). TACE has been shown to prolong survival

in patients with BCLC stage B (intermediate stage),2 but has failed to show survival benefit in patients click here with advanced HCC, even in those patients with adequate hepatic functional reserve.3 Therefore, in the current adaptation of the BCLC treatment algorithm the therapy of choice for advanced HCC is systemic treatment with sorafenib.4 This multikinase inhibitor has recently been shown to prolong survival in patients with advanced HCC in a randomized, controlled phase III trial,5 and is the first drug ever approved for the treatment of HCC. Due to the adverse effect profile of sorafenib, many patients can only tolerate a reduced dose or must discontinue the medication. This fact causes an ongoing effort to develop a locoregional treatment approach for patients with advanced HCC that is effective, but with a more acceptable/favorable toxicity profile than systemic therapy. Microsphere-related transarterial application of radioactive agents into malignant tumors represents a new generation of therapeutics in interventional oncology, even though the first reports of this approach were published decades ago. The main reasons for the delayed acceptance of this method were the safety issues caused by pulmonal and gastrointestinal deposition of radioactive microspheres.

29 However, based on our current observation, it is plausible that OATP1B1 functions as a key pathway in the network for modulation of hepatic bile acid concentration through its ability to mediate the sodium-independent hepatic uptake of bile acids and thereby enhance bile acid sensing through FXR and modulation of target gene expression. It seems noteworthy that another hepatic OATP capable of bile acid uptake, OATP1B3,29 has been shown to also be positively regulated by FXR.17, 18 Indeed, in human hepatocytes,

we were able to confirm that treatment with CDCA results in OATP1B3 induction (Fig. 7). However, unlike OATP1B1, OATP1B3 Tyrosine Kinase Inhibitor Library mw does not appear to be regulated by LXRα (Fig. 7). We hypothesize that regulation of the bile acid transporters is multifactorial and includes several components (Fig. 8). Protein kinase A exhibits cyclic adenosine monophosphate (cAMP)-dependent catalytic activity and is involved in the regulation click here of several intracellular processes, including

the activity of transcription factors such as HNF4α as well as OATP1B1.30 HNF4α not only regulates OATP1B1, but also the expression of NTCP (SLC10A1), the sodium-dependent transporter for bile acids.31, 32 Introducing an additional factor to this network of OATP1B1 expression is the G protein–coupled receptor TGR5, which induces intracellular cAMP levels upon binding of bile acids.33 Thus, increased bile acid levels would reduce the expression of both bile acid transporters through suppression of HNF4α activity and expression of the transporters

that facilitate the uptake of bile acid FXR ligands. This notion is supported by findings showing that cAMP protects against hepatocellular apoptosis induced by hydrophilic bile acids such as GCDCA,34 although expression selleck inhibitor and function of TGR5 in human hepatocytes is controversial.35, 36 There are reports suggesting moderate but functional expression of TGR5 in hepatocytes.29 In terms of LXRα, there has been significant progress using LXRα as a therapeutic target to treat metabolic disorders and atherosclerosis.37 Indeed, our observed effects of an LXRα agonist in human hepatocytes suggest that such a strategy might result in the induction of hepatic drug transporters such as OATP1B1 (Fig. 6), which for drugs such as the statin class of HMG-Co-A reductase inhibitors would result in a higher liver concentration of the drug while lowering systemic exposure. This may be viewed as a therapeutically beneficial effect of LXRα. Given the importance of regulated conversion of cholesterol to bile acids by LXRα target genes, regulation of OATP1B1 by LXRα is consistent with an important physiological role of OATP1B1 to hepatic cholesterol and bile acid homeostasis In conclusion, we show for the first time that OATP1B1 is dual nuclear receptor–regulated through the actions of the bile acid sensor FXR and the cholesterol sensor LXRα, but not by the typical xenobiotic receptors such as PXR and CAR.

Key Word(s): 1. cancer; 2. liver; 3. alcohol; 4. dolichol; Presenting Author: HAO WU Additional Authors: YING ZHOU, RUYI XUE,

TAOTAO LIU, LING DONG, XIZHONG Rucaparib in vitro SHEN Corresponding Author: HAO WU Affiliations: Zhongshan Hospital; Public Health College, Fudan University Objective: Hepatocellular carcinoma (HCC) is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Biomarkers that discriminate HCC from normal are important but are limited. Methods: In the present study, we present a metabolomic method of using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to investigate the metabolic difference between the malignant and non-malignant tissues in hepatocellular carcinoma patients (n = 30). The accuracy of UPLC-MS profiles and alpha-fetoprotein

(AFP) levels were compared for their use in HCC diagnosis. Results: Seventeen potential biomarkers were identified and suggested that there were significant disturbances of key metabolic pathways in HCC patients. A diagnostic model was constructed with a combination of the marker metabolites or together with alphafetoprotein (AFP). By multivariate statistics and receiver operating characteristic curves analysis yielded the strongest separation between the two groups. Conclusion: We conclude that the metabolomic profile of HCC tissue was different BTK inhibitor supplier from normal, and that the selected tissue metabolites could probably be applied for clinical diagnosis. Key Word(s): 1. metabolomics; 2. HCC; 3. biomarker; 4. UPLC-MS; Presenting Author: HUAHONG XIE Additional Authors: HONGBO ZHANG, KAICHUN WU, DAIMING FAN Corresponding Author: HUAHONG XIE Affiliations: Xijing Hospital of

Digestive Diseases Objective: To detect the effects and mechanisms of COX-2 selective inhibitor, celecoxib on cell cycle of HCC cells with different COX-2 expression. Methods: Cell cycle distributions in HepG2 cells transfected with HBx gene (HepG2-X cell), which was proved to be with high COX-2 expression, and control cells (HepG2-PC cell) with or without treatment of celecoxib were analyzed by flow cytometer. RT-PCR and Western blot were used to detect cell cycle related moleculars, including p21waf1, p27kip1, CyclinA, CyclinB, CyclinD1, CyclinD2, CycinD3, CycinE, CDK1, CDK2, see more CDK4, CDK6. Results: Flow cytometry showed that celecoxib caused a concentration-dependent decrease in the number of cells in the S and G2/M phase in both HepG2-X and HepG2-PC cells, but without significant differences at cell cycle changes between these two cell clones. CyclinA, CyclinD1, CDK1 and CDK2 expressions were decreased while the expressions of p21Waf1 and p27Kip1 were induced in a dose-dependent manner in cells after treated with celecoxib. But no alternations with CyclinB, CyclinD2, CycinD3, CyclinE, CDK4, and CDK6 were observed in celecoxib treated cells.