The patient survival was 4/6 (66.7%) with a graft survival of 3/6 (50%) at current follow-up. Case 1 has been doing well and been totally off

TPN 14 years after transplantation. Case 2 died 5 months due to Maraviroc datasheet overwhelming infection secondary to severe acute rejection. Case 3 died 6 weeks due to unknown etiology of cardiac failure. Cases 4 and 5 lost intestinal graft due to rejection 3 months and 10 years, respectively, after transplantation and are waiting for second transplantation. Case 6 received a blood-type incompatible graft from her father and experienced one episode of rejection 30 days after surgery. She is doing well at 9-month follow-up. Conclusion: Our experience suggests that living donor bowel transplantation is safe for the donors and is a valuable strategy in the treatment of irreversible intestinal failure. Careful patient selection and post-transplant care are essential for good long-term outcome. Key Word(s): 1. Transplantation; 2. Intestine; 3. Living donor; Presenting Author: LIANG ZHU Additional Authors: WEI SUN, YUNHONG WU, DEZHENG GONG, SHUZHUANG LI, BINHAO WANG, YA ZHANG, CHENGYAN CHU, XUMIN GUAN, FANG LI, LIMING WANG, ZHONG LIU, LILI GUAN, QIONG WU, BO YUAN, DEQIN YU, JINGZHOU MU, QIUYU CHEN, YUANHANG WU, ZIQI ZHAO, SHUHANG GAO, SIWEN LUO, SHUHAO ZHANG, YUAN ZOU Corresponding Author:

LIANG ZHU Affiliations: Adriamycin in vitro Department of Physiology, Dalian Medical University; College of Basic Medical Sciences; School of Public Health, Dalian Medical University; College of seven-year clinical medicine, Dalian Medical University; Department of Immunology, Dalian Medical University; General Surgery of the Second HospitalGeneral Surgery of the Second Hospital, Dalian Medical University; General Surgery of the First Affiliated Hospital, Dalian Medical University; Affiliated

Hospital, Peking University Health Science Center; College of five-year clinical medicine, Dalian Medical University Objective: Intestinal transplantation (IT) may eventually become PIK3C2G the definitive therapeutic modality for irreversible intestinal failure. However, the small intestinal graft injury limits the success and widespread use of IT. Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that exhibits striking intestinotropic properties. For the first time, we used the proteomic approach to investigate the effect of GLP-2 (Glucagon Like Peptide-2) on normal intestinal mucosa growth and transplantation intestinal mucosa recovery, and clarify its mechanisms. Methods: 90 male Wistar rats of inbred line were divided into four groups according to the table of random number: normal intestine group (group a), GLP-2 intervention group (group b), intestinal transplantation group (group c), intestinal transplantation with GLP-2 intervention group (group d).

In the study by Ziegler-Sagi et al.,99 orlistat reportedly improved ALT and steatosis by US, but its effect on liver histology could not be evaluated because the majority of patients did not undergo

a follow-up liver biopsy. However, in the study by Harrison et al.,100 orlistat did not improve body weight or liver histology. The best evidence for weight loss as a means to improve liver histology in NASH comes from a trial that randomized 31 obese persons with NASH to intensive lifestyle changes (diet, behaviour modification and 200 minutes a week of moderate physical activity for 48 weeks) selleckchem versus structured basic education alone.101 The intensive arm had 9.3% weight loss (versus 0.2% in the dietary counseling alone arm) and led to an improvement in steatosis, necrosis and inflammation, but not fibrosis. Importantly, participants with ≥ 7% weight loss had significant improvement

in steatosis, lobular inflammation, ballooning, and NAFLD Activity Score (NAS).101 There was a similar pattern in the study by Harrison et al.,100 where participants who lost > 5% body weight improved steatosis, whereas individuals with ≥ 9% weight loss had significant improvement in steatosis, lobular inflammation, ballooning, and NAS. A number of recent studies used MR spectroscopy to assess changes Selleckchem ABT-263 in hepatic fat in response to lifestyle modification. The results from these studies using a variety of interventions, either by diet alone81, 83, 84, 89, 92, 93 or in combination with OSBPL9 different exercise prescriptions,82, 85-88, 92, 94 have consistently reported a significant reduction in liver fat by an average of ∼40% (ranging from 20% to 81%). The degree of hepatic fat reduction was proportional to the intensity of the lifestyle intervention and generally required

a body weight loss between ∼5 to 10%.82, 88, 92 The effect of exercise without dietary modification on hepatic steatosis was investigated in four studies using MR spectroscopy.102-105 Exercise programs consisted of 2-3 sessions a week of 30-60 minutes over a period of 6 to 12 weeks. In all but one study101 liver fat content diminished without a significant change in body weight. Recommendations 16. Weight loss generally reduces hepatic steatosis, achieved either by hypocaloric diet alone or in conjunction with increased physical activity. (Strength – 1, Evidence – A) 17. Loss of at least 3-5% of body weight appears necessary to improve steatosis, but a greater weight loss (up to 10%) may be needed to improve necroinflammation. (Strength – 1, Evidence – B) 18. Exercise alone in adults with NAFLD may reduce hepatic steatosis but its ability to improve other aspects of liver histology remains unknown. (Strength – 1, Evidence – B) Several studies investigated the effect of metformin on aminotransferases and liver histology in patients with NASH. Early small, open-label studies demonstrated a reduction in insulin resistance and aminotransferases106-108 but no significant improvement in liver histology.

[15, 16] HCV-induced modulations of lipid metabolism include increased cellular triglyceride and cholesterol storage to facilitate viral replication.[15-17] Furthermore,

both cholesterol[18] and lipoprotein[19, 20] receptors have been implicated as HCV entry factors. Viral particle assembly and secretion also use components of the very-low density lipoprotein (VLDL) pathway.[21] Given this intimate link between HCV and hepatic metabolism, we examined the role of miR-27 in HCV pathogenesis and, herein, establish its role in HCV-induced hepatic steatosis. The pFK-I389luc/NS3-3′/5.1 PI3K Inhibitor Library clinical trial plasmid containing the HCV subgenomic replicon (genotype 1b isolate Con1, GenBank accession no. AJ242654) and the NS5B active site mutant replicon were kind gifts from Dr. Ralf Bartenschlager (Institute of Hygiene, University of Heidelberg, Heidelberg, Germany). The

Huh7.5 cell line stably expressing the full-length HCV genotype 1b replicon with a S2204I adaptive mutation in NS5A (Huh7.5-FGR) was a kind gift from Dr. Charles M. Rice (Rockefeller University, New York, NY) and Apath (St. Louis, MO). Imaged cells were washed twice with phosphate-buffered saline (PBS), followed by a 15-minute incubation at room temperature with fixing solution (4% formaldehyde, 4% sucrose, 1 mL). The fixed cells were washed twice with PBS for 3 minutes and learn more then stored at 4°C in PBS prior to imaging. The imaging and subsequent quantitative voxel analysis of TG content was performed as described.[22, 23] Lipid droplet (LD) sizing/counting was performed using ImageJ (NIH, Bethesda, MD). Liver frozen sections (at 4 μm thickness) were fixed in 4% freshly made paraformaldehyde for 30 minutes, followed by 5 minutes Vasopressin Receptor PBS rinse to remove excess paraformaldehyde. Fixed slides were then permeabilized in PBS containing 0.5% Triton X-100 for 10 minutes and blocked in PBS with 10% normal goat serum for 1 hour. The 1/100 diluted primary rabbit monoclonal antibody specifically recognizing human Cytokeratin 18 (CK-18) (Abcam, Cambridge, MA) was applied to the liver sections

and incubated at 4°C overnight. The next day liver sections were incubated in secondary antibody cocktail, including Alexa Fluor 488-conjugated goat antirabbit and DAPI, for 1 hour in the dark. After 3 washes of PBS, slides were immersed in Oil Red O working solution (freshly prepared in 30% triethyl-phosphate),[24] for 30 minutes in the dark, followed by 3 rinses with distilled water. Finally, slides were rinsed in the dark for 10 minutes, air dried, mounted with prolong gold mounting medium (Invitrogen), and coverslipped. Samples were examined with a Leica TCS SP5 confocal microscope. Oil Red O staining of lipids was visualized at far-red wavelength: 633 (ex) and 647 (em). Images were processed using LAS AF Lite software.

Following the removal of ∼99% of the sea otters, Enhydra lutris, from the ecosystem, changes to the benthic communities resulted in widespread losses to most of the region’s kelp beds and corresponding increases in the prevalence of urchin barrens. Within the urchin barrens, the few kelps that have remained are exposed

to elevated light, nutrients and currents, all of which may enhance their physiological condition and thus result in greater fecundity. To explore this further, we examined patterns of sporophyte fecundity in the dominant canopy-forming kelp, Eualaria fistulosa, in both urchin barrens and in nearby kelp beds at seven Aleutian Islands spanning a range of 800 km. We found PLX4032 that the average weight of E. fistulosa sporophyll bundles was significantly greater on sporophytes occurring in the urchin barrens than in the nearby kelp beds. Furthermore, the average number of zoospores released per cm2 of sporophyll area was

also significantly greater in individuals from the urchin barrens than the nearby kelp beds. When these two metrics were combined, our results suggest that individual E. fistulosa sporophytes occurring in the urchin barrens may produce as many as three times more zoospores than individual E. fistulosa sporophytes occurring in the nearby kelp beds, and thus they may contribute disproportionately Maraviroc cell line to the following year’s sporophyte recruitment in both urchin barrens and the adjacent kelp beds. “
“Inferring how the Pleistocene climate oscillations have repopulated the extant

population structure of Chondrus crispus Stackh. in the North Atlantic Ocean is important both for our understanding of the glacial episode promoting diversification and for the conservation and development of marine organisms. C. crispus is an ecologically and commercially important red seaweed with broad distributions in the North Atlantic. Here, we employed both partial mtDNA Cox1 and nrDNA internal transcribed spacer region 2 (ITS2) sequences to explore the genetic structure of 17 C. crispus populations from this area. Twenty-eight and 30 haplotypes were inferred from these two markers, respectively. Analysis of molecular variance (AMOVA) and of Farnesyltransferase the population statistic ΦST not only revealed significant genetic structure within C. crispus populations but also detected significant levels of genetic subdivision among and within populations in the North Atlantic. On the basis of high haplotype diversity and the presence of endemic haplotypes, we postulate that C. crispus had survived in Pleistocene glacial refugia in the northeast Atlantic, such as the English Channel and the northwestern Iberian Peninsula. We also hypothesize that C. crispus from the English Channel refugium repopulated most of northeastern Europe and recolonized northeastern North America in the Late Pleistocene. The observed phylogeographic pattern of C.

28 This makes it extremely Endocrinology antagonist difficult to delineate which shedding events are involved in obesity-associated pathologies. Because the biological significance of TNFR1 shedding in NAFLD and insulin resistance was unclear, we aimed to unravel the extent

to which it controls the initiation of NAFLD and the progression towards NASH, as well as its role in the development of insulin resistance. We used knockin mutant mice expressing nonsheddable TNFR1s (p55Δns mice), which have been shown to exhibit persistent expression of the receptor at the cell surface. This dominant mutation leads to a spontaneous inflammatory response resulting in enhanced antibacterial host defenses, increased susceptibility to endotoxic shock, exacerbated TNF-dependent arthritis, and in a mild form of chronic hepatitis.29 Using this gain-of-function approach, we demonstrated PI3K Inhibitor Library ic50 that the inability of TNFR1 shedding did not result in obesity, insulin resistance, or hepatic steatosis in mice. However, p55Δns mice showed a rapid progression towards NASH. Our data therefore suggest that activation of TNFR1 ectodomain shedding does not safeguard against the development

of hepatic steatosis, obesity, or insulin resistance, although it is pivotal in attenuating the progression towards NASH. ADAM17, ADAM metallopeptidase domain17; ALT, alanine aminotransferase, AST, aspartate transaminase; Bfl1, BCL2-related protein A1; Cd11b, integrin, alpha M (Mac 1); Cd68, cluster of differentiation 68; Ciap, cellular inhibitors of

apoptosis; Col1a1, collagen type 1 alpha 1; HFD, high-fat diet; Il1β, interleukin-1β; Il6, interleukin-6; LDLR, low density lipoprotein receptor; MCD-diet, methionine choline-deficient diet; Mcp1, monocyte chemotactic Dichloromethane dehalogenase protein-1; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; Mmp9, matrix metallopeptidase; NF-κB, nuclear factor kappa B; OGTT, oral glucose tolerance test; p55ΔNS/+, TNFR1 nonsheddable heterozygous mice; p55ΔNS/ΔNS, TNFR1 nonsheddable homozygous mice; PBS, phosphate-buffered saline; Ppia, peptidylprolyl isomerase A (cyclophilin A); RT-PCR, real-time polymerase chain reaction; TACE, TNFα converting enzyme; TG, triglycerides; Timp1, tissue inhibitor of metalloproteinase 1; TNF, tumor necrosis factor; TNFR1, TNF receptor 1; TNFR1ns, TNFR1 nonsheddable; Traf1, TNFR-associated factor 1; wildtype mice, p55+/+. Mice containing the TNFR1 nonsheddable mutation heterozygously and homozygously (referred to as p55Δns/+ and p55Δns/Δns mice, respectively) and their wildtype littermates (p55+/+)29 in a C57Bl/6 background were purchased from the European Mouse Mutant Archive (EMMA, Monterotondo Scalo, Italy) and crossed into a C57Bl/6 background for at least 10 generations.

13 There is difficulty discerning and dissecting out the number of individual factors that may contribute collectively to liver damage

in patients receiving antiretroviral therapy. Several drugs are combined in a given HAART regimen making difficult the attribution of hepatotoxicity to a particular drug. Moreover, HIV-infected patients may be receiving concurrent medications with potential for liver toxicity as well, such as antimycobacterial drugs, lipid-lowering agents, antifungals, antibiotics, and anticonvulsants. It is also difficult to make comparisons among reported cohorts, because individuals often differ on the factors predisposing to elevations of liver enzymes, like the presence/absence of concurrent viral hepatitis. Biochemical, pharmacokinetic/dynamic, and pathological correlations selleck compound of HAART hepatotoxicity have been poorly characterized, which makes it often difficult to determine the true incidence of drug-induced liver injury. In many instances, the hepatotoxic potential of a drug has been recognized only after post-marketing experience with the drug. Chronic viral hepatitis has been consistently reported to increase the risk of severe HAART hepatotoxicity (relative risk = 2.1).14 There is an estimated 2.7-fold to 5-fold increased risk of severe alanine aminotransferase (ALT) elevation on HAART with hepatitis C virus (HCV) coinfection.15-17

Chronic hepatitis B virus (HBV) infection appears to also carry a higher risk, with a 9.2 hazard risk of grade 4 liver enzyme elevations reported in one study.17 The same authors PF-01367338 ic50 also observed that discontinuing lamivudine, an antiretroviral also active against HBV, was a factor associated with aminotransferase elevation in HIV/HBV-coinfected patients (hazard risk = 6.8 for grade 4 liver toxicity).17 The presence of underlying liver inflammation as reflected by elevated ALT at baseline has been also identified as a risk factor for HAART liver toxicity.16, 17 Isolated

studies have identified additional host factors including older age, female sex, thrombocytopenia, renal insufficiency, high HIV RNA levels, increased body mass index, and non-black ethnicity.15-18 Aside from host factors, several individual antiretrovirals or classes have been independently Vasopressin Receptor associated with HAART hepatotoxicity, such as nevirapine, protease inhibitors, high doses of ritonavir (≥600 mg/day), and prolonged zidovudine or stavudine exposure.14, 17, 18 Alcohol use and concurrent hepatotoxic medications are additional factors identified.15, 16, 18 Lastly, an increase in CD4 cell counts of >50 cells/mm3 after HAART initiation was associated with almost two-fold increased risk of severe ALT elevation in one study.14 Other risk factors individual to each pathogenic mechanism are covered within its corresponding section. A major challenge for mechanistic classifications is that the pathogenesis of drug hepatotoxicity is poorly understood in many instances.

13 There is difficulty discerning and dissecting out the number of individual factors that may contribute collectively to liver damage

in patients receiving antiretroviral therapy. Several drugs are combined in a given HAART regimen making difficult the attribution of hepatotoxicity to a particular drug. Moreover, HIV-infected patients may be receiving concurrent medications with potential for liver toxicity as well, such as antimycobacterial drugs, lipid-lowering agents, antifungals, antibiotics, and anticonvulsants. It is also difficult to make comparisons among reported cohorts, because individuals often differ on the factors predisposing to elevations of liver enzymes, like the presence/absence of concurrent viral hepatitis. Biochemical, pharmacokinetic/dynamic, and pathological correlations ICG-001 of HAART hepatotoxicity have been poorly characterized, which makes it often difficult to determine the true incidence of drug-induced liver injury. In many instances, the hepatotoxic potential of a drug has been recognized only after post-marketing experience with the drug. Chronic viral hepatitis has been consistently reported to increase the risk of severe HAART hepatotoxicity (relative risk = 2.1).14 There is an estimated 2.7-fold to 5-fold increased risk of severe alanine aminotransferase (ALT) elevation on HAART with hepatitis C virus (HCV) coinfection.15-17

Chronic hepatitis B virus (HBV) infection appears to also carry a higher risk, with a 9.2 hazard risk of grade 4 liver enzyme elevations reported in one study.17 The same authors Romidepsin concentration also observed that discontinuing lamivudine, an antiretroviral also active against HBV, was a factor associated with aminotransferase elevation in HIV/HBV-coinfected patients (hazard risk = 6.8 for grade 4 liver toxicity).17 The presence of underlying liver inflammation as reflected by elevated ALT at baseline has been also identified as a risk factor for HAART liver toxicity.16, 17 Isolated

studies have identified additional host factors including older age, female sex, thrombocytopenia, renal insufficiency, high HIV RNA levels, increased body mass index, and non-black ethnicity.15-18 Aside from host factors, several individual antiretrovirals or classes have been independently Parvulin associated with HAART hepatotoxicity, such as nevirapine, protease inhibitors, high doses of ritonavir (≥600 mg/day), and prolonged zidovudine or stavudine exposure.14, 17, 18 Alcohol use and concurrent hepatotoxic medications are additional factors identified.15, 16, 18 Lastly, an increase in CD4 cell counts of >50 cells/mm3 after HAART initiation was associated with almost two-fold increased risk of severe ALT elevation in one study.14 Other risk factors individual to each pathogenic mechanism are covered within its corresponding section. A major challenge for mechanistic classifications is that the pathogenesis of drug hepatotoxicity is poorly understood in many instances.

Our findings demonstrate potent bile acid-mediated suppression of hepatic CSAD mRNA levels and induction with cholestyramine-induced enterohepatic bile acid depletion (Fig. 2b). Higher CSAD mRNA abundance with cholestyramine feeding suggests that, under physiological conditions, enterohepatic bile acids exert tonic suppression of CSAD mRNA levels and that CSAD mRNA is not simply suppressed by bile acids at supraphysiologic concentrations. Though we did not directly measure the impact of cholesterol

feeding on hepatic CSAD selleck screening library mRNA levels, the lack of response to LXR agonist treatment (T-0901317) (Fig. 5c) suggests that alterations in cholesterol flux likely would not regulate CSAD mRNA via LXR at the transcriptional level. Farnesoid X receptor and SHP play a canonical role AZD2014 chemical structure in regulating cholate synthesis.[1] Physiological activation of FXR by enterohepatic bile acids induces expression of SHP, which in turn binds to the orphan nuclear receptors LHR-1 and HNF4α, and potentially other promoter-bound elements, inhibiting transcription of CYP7A1.[1] Previous studies have demonstrated that CYP7A1 gene expression is decreased by FXR agonist treatment[24] and is higher in both Fxr−/− and Shp−/− mice[2, 7, 8, 24] in which the feedback loop has been genetically disrupted. In the current study, we utilize both pharmacological and genetic approaches to establish that SHP and FXR are also key components

of bile acid-mediated suppression of CSAD mRNA level. A role for FXR was established by the finding that GW4064, a FXR agonist, potently suppresses hepatic CSAD mRNA levels (Fig. 3a). A role for SHP in this feedback loop was established by the finding that CSAD abundance is dramatically increased in Shp−/− mice (Fig. 4a). Taken together, these results demonstrate that hepatic CSAD mRNA abundance else is regulated through genetic mechanisms shared with CYP7A1 (Fig. 6). Though FXR and SHP are central to CYP7A1 gene expression, the existence of an SHP-independent pathway has been demonstrated by using Shp−/− mice.[7,

8] This is now understood to include the FGF15/19 pathway and signaling via FGFR4/β-klotho with activation of c-Jun N-terminal kinase[9, 25] and transcriptional repression of CYP7A1. Inagaki et al. showed that the FGF15/FGFR4 signaling cooperates with SHP to repress CYP7A1 in liver although FGF19 reduced CYP7A1 mRNA levels without increasing SHP mRNA levels[9] indicating that the FXR/FGF19 pathway is also SHP-independent. The current findings indicate that hepatic CSAD mRNA level is not regulated by FGF19 administration despite potent suppression of CYP7A1 level (Fig. 5a). In addition, activation of LXR did not result in altered hepatic CSAD mRNA abundance. This divergence in response implies that while CYP7A1 and CSAD mRNA respond similarly to dietary bile acid supplementation, and are both regulated by FXR and SHP, there are important differences in some of the mediators involved.

To explore the roles of TF, we used stable transfect antisense TF (anti-TF) technology to silence TF in gastric cancer cell line SGC7901 with high level expression of TF and detection antitumor effects in vitro and in vivo. Methods: Antisense TF designed for human TF was stable transfected into SGC7901 cells. The expression of TF was detected by reverse transcription PCR and western blot. Adriamycin cell line Cell proliferation was measured by MTT assay. Cell apoptosis was assessed by flow cytometry. The metastatic potential of SGC7901 cells was determined by wound healing, transwell assays. In vivo the effect of anti-TF on the

growth of gastric cancer xenografts in nude mice was detected. Results: Anti-TF can reduced the TF expression mRNA and protein in the SGC7901 cells. Reduce the TF in SGC7901 cells resulted is suppression of cell proliferation, invasion and metastasis induced cell apoptosis. Intratumoral injection of stable transfec anti-TF gastric cancer cells suppressed the tumor growth in vivo model of gastric cancer. Conclusion: Inhibited of the TF using antisense could provide a potential

approach for gene therapy against gastric cancer. Key Word(s): 1. check details gastric cancer; 2. tissue factor; 3. gene therapy; Presenting Author: BIN WANG Additional Authors: DONGFENG CHEN Corresponding Author: BIN WANG Affiliations: Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China Objective: Cancer stem cell (CSC) was proposed to fuel the malignant and metastatic growth gastric cancer (GC), one of the most common malignancies of the digestive tract. However, the identity of this critical subpopulation of GC cells in primary human gastric cancers remains elusive Methods: we show that Lgr5, a well-established stem cell marker of the gastrointestinal epithelium, was expressed in GC tissue

Results: Using an optimized culture system for pyloric gland stem cells, Lgr5 was demonstrated to identify tumorsphere initiating GC Cytidine deaminase cells that showed extensive self-renewing ability. Lgr5+ cells were endowed with multilineage potential both in vitro and in vivo, even at single cell level. Lgr5+ cells enriched robust tumor initiating capacity which could be maintained upon serial transplantation in NOD/SCID mice. Importantly, knockdown of Lgr5 attenuated self-renewal of tumorigenicity of gastric CSC, through a mechanism involving downregulation of Wnt/β-catenin signaling Conclusion: These results provided evidences for the first time that Lgr5 marked and sustained self-renewing and tumor propagating cells in GC, which might facilitate development of novel therapeutic modalities for GC. Key Word(s): 1. Gastric Cancer; 2. Cancer Stem Cells; 3. Lgr5; 4.

To explore the roles of TF, we used stable transfect antisense TF (anti-TF) technology to silence TF in gastric cancer cell line SGC7901 with high level expression of TF and detection antitumor effects in vitro and in vivo. Methods: Antisense TF designed for human TF was stable transfected into SGC7901 cells. The expression of TF was detected by reverse transcription PCR and western blot. Atezolizumab chemical structure Cell proliferation was measured by MTT assay. Cell apoptosis was assessed by flow cytometry. The metastatic potential of SGC7901 cells was determined by wound healing, transwell assays. In vivo the effect of anti-TF on the

growth of gastric cancer xenografts in nude mice was detected. Results: Anti-TF can reduced the TF expression mRNA and protein in the SGC7901 cells. Reduce the TF in SGC7901 cells resulted is suppression of cell proliferation, invasion and metastasis induced cell apoptosis. Intratumoral injection of stable transfec anti-TF gastric cancer cells suppressed the tumor growth in vivo model of gastric cancer. Conclusion: Inhibited of the TF using antisense could provide a potential

approach for gene therapy against gastric cancer. Key Word(s): 1. selleck compound gastric cancer; 2. tissue factor; 3. gene therapy; Presenting Author: BIN WANG Additional Authors: DONGFENG CHEN Corresponding Author: BIN WANG Affiliations: Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China Objective: Cancer stem cell (CSC) was proposed to fuel the malignant and metastatic growth gastric cancer (GC), one of the most common malignancies of the digestive tract. However, the identity of this critical subpopulation of GC cells in primary human gastric cancers remains elusive Methods: we show that Lgr5, a well-established stem cell marker of the gastrointestinal epithelium, was expressed in GC tissue

Results: Using an optimized culture system for pyloric gland stem cells, Lgr5 was demonstrated to identify tumorsphere initiating GC IKBKE cells that showed extensive self-renewing ability. Lgr5+ cells were endowed with multilineage potential both in vitro and in vivo, even at single cell level. Lgr5+ cells enriched robust tumor initiating capacity which could be maintained upon serial transplantation in NOD/SCID mice. Importantly, knockdown of Lgr5 attenuated self-renewal of tumorigenicity of gastric CSC, through a mechanism involving downregulation of Wnt/β-catenin signaling Conclusion: These results provided evidences for the first time that Lgr5 marked and sustained self-renewing and tumor propagating cells in GC, which might facilitate development of novel therapeutic modalities for GC. Key Word(s): 1. Gastric Cancer; 2. Cancer Stem Cells; 3. Lgr5; 4.