EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features.


BACKGROUND & AIMS:Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC), in part, may be owing to the presence of hepatic cancer cells with stem/progenitor features. METHODS:Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from 2 recently identified HCC subtypes (EpCAM(+) alpha-fetoprotein [AFP(+)] HCC and EpCAM(-) AFP(-) HCC). These subtypes differed in their expression of AFP, a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting was used to isolate EpCAM(+) HCC cells, which were tested for hepatic stem/progenitor cell properties. RESULTS:Gene expression and pathway analyses revealed that the EpCAM(+) AFP(+) HCC subtype had features of hepatic stem/progenitor cells. Indeed, the fluorescence-activated cell sorting-isolated EpCAM(+) HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in nonobese diabetic, severe combined immunodeficient mice. Activation of Wnt/beta-catenin signaling enriched the EpCAM(+) cell population, whereas RNA interference-based blockage of EpCAM, a Wnt/beta-catenin signaling target, attenuated the activities of these cells. CONCLUSIONS:Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM(+) cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/beta-catenin signaling components such as EpCAM.






Yamashita T,Ji J,Budhu A,Forgues M,Yang W,Wang HY,Jia H,Ye Q,Qin LX,Wauthier E,Reid LM,Minato H,Honda M,Kaneko S,Tang ZY,Wang XW




Has Abstract


2009-03-01 00:00:00














  • Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis.

    abstract:BACKGROUND & AIMS:The disruption of homeostasis between proliferation and apoptosis in the colonic epithelium contributes to the pathogenesis of human ulcerative colitis. Mice lacking the transcriptional corepressor myeloid translocation gene related-1 (Mtgr1) display impaired secretory cell lineage development in the ...


    pub_type: 杂志文章


    authors: Martinez JA,Williams CS,Amann JM,Ellis TC,Moreno-Miralles I,Washington MK,Gregoli P,Hiebert SW

    更新日期:2006-08-01 00:00:00

  • Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis.

    abstract::The results of a clinical trial comparing slow-release 5-aminosalicylic acid tablets (Pentasa) and enteric-coated sulfasalazine tablets (Salazopyrin) with regard to the efficacy of maintaining ulcerative colitis patients in remission for 12 mo and with regard to safety of treatment are reported. Seventy-five patients ...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Mulder CJ,Tytgat GN,Weterman IT,Dekker W,Blok P,Schrijver M,van der Heide H

    更新日期:1988-12-01 00:00:00

  • Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation.

    abstract:BACKGROUND & AIMS:Patients with irritable bowel syndrome with diarrhea (IBS-D) have increased mucosal serotonin (5-hydroxytryptamine [5-HT]) availability, possibly because immune activation reduces activity of the 5-HT transporter (SERT). We investigated the relationship between mucosal and platelet SERT and immune act...


    pub_type: 杂志文章


    authors: Foley S,Garsed K,Singh G,Duroudier NP,Swan C,Hall IP,Zaitoun A,Bennett A,Marsden C,Holmes G,Walls A,Spiller RC

    更新日期:2011-05-01 00:00:00

  • Oral cimetidine in reflux esophagitis: a double blind controlled trial.

    abstract::The efficacy of cimetidine (1.6 g per day) was evaluated using a double blind placebo-controlled trial in 24 patients with moderate or severe peptic reflux esophagitis. The results show that cimetidine is superior to placebo when using endoscopic and histological criteria. Improved patient symptomatology and lower ant...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Wesdorp E,Bartelsman J,Pape K,Dekker W,Tytgat GN

    更新日期:1978-05-01 00:00:00

  • Association Between Psychological Distress and Liver Disease Mortality: A Meta-analysis of Individual Study Participants.

    abstract:BACKGROUND & AIMS:Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with nonalcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with l...


    pub_type: 杂志文章,meta分析


    authors: Russ TC,Kivimäki M,Morling JR,Starr JM,Stamatakis E,Batty GD

    更新日期:2015-05-01 00:00:00

  • Silencing of USP18 potentiates the antiviral activity of interferon against hepatitis C virus infection.

    abstract:BACKGROUND & AIMS:Modulation of the host innate immune response is an attractive means of inhibiting hepatitis C virus (HCV) replication. Having previously determined that expression of the interferon-sensitive gene (ISG)15 protease USP18 is increased in the liver biopsy specimens of patients who do not respond to inte...


    pub_type: 杂志文章


    authors: Randall G,Chen L,Panis M,Fischer AK,Lindenbach BD,Sun J,Heathcote J,Rice CM,Edwards AM,McGilvray ID

    更新日期:2006-11-01 00:00:00

  • Hepatocellular Carcinomas With Mutational Activation of Beta-Catenin Require Choline and Can Be Detected by Positron Emission Tomography.

    abstract:BACKGROUND & AIMS:In one-third of hepatocellular carcinomas (HCCs), cancer cells have mutations that activate β-catenin pathway. These cells have alterations in glutamine, bile, and lipid metabolism. We investigated whether positron emission tomography (PET) imaging allows identification of altered metabolic pathways t...


    pub_type: 杂志文章


    authors: Gougelet A,Sartor C,Senni N,Calderaro J,Fartoux L,Lequoy M,Wendum D,Talbot JN,Prignon A,Chalaye J,Imbeaud S,Zucman-Rossi J,Tordjmann T,Godard C,Bossard P,Rosmorduc O,Amaddeo G,Colnot S

    更新日期:2019-09-01 00:00:00

  • Prospective evaluation of esophageal varices in primary biliary cirrhosis: development, natural history, and influence on survival.

    abstract::The aims of our prospective study were to determine the development and natural history of esophageal varices and variceal bleeding in patients with primary biliary cirrhosis. As part of a controlled clinical study, 265 patients with primary biliary cirrhosis who did not have esophageal varices at entry were followed ...


    pub_type: 杂志文章


    authors: Gores GJ,Wiesner RH,Dickson ER,Zinsmeister AR,Jorgensen RA,Langworthy A

    更新日期:1989-06-01 00:00:00

  • Antibodies against mitochondrial dehydrogenase complexes in primary biliary cirrhosis.

    abstract::Antimitochondrial antibodies, serological hallmarks of primary biliary cirrhosis, recently were found to be directed against the E2 subunits of mitochondrial dehydrogenase complexes (pyruvate, branched-chain ketoacid, and alpha-ketoglutarate dehydrogenases). The objectives of this study were to extend these findings a...


    pub_type: 杂志文章


    authors: Yoshida T,Bonkovsky H,Ansari A,Danner D

    更新日期:1990-07-01 00:00:00

  • Effect of substance P on somatostatin release from the isolated perfused rat stomach.

    abstract::The effect of substance P (SP) on the release of gastric somatostatinlike immunoreactivity (SLI) was studied. Substance P inhibited both basal SLI release and SLI release stimulated by gastric inhibitory polypeptide or 1-isoproterenol. This inhibitory action of SP was not blocked by atropine or hexamethonium, suggesti...


    pub_type: 杂志文章


    authors: Kwok YN,McIntosh CH,Pederson RA,Brown JC

    更新日期:1985-01-01 00:00:00

  • Obesity-induced lymphocyte hyperresponsiveness to chemokines: a new mechanism of Fatty liver inflammation in obese mice.

    abstract:BACKGROUND & AIMS:Hepatic lipid retention (steatosis) predisposes hepatitis. We investigated the mechanisms of lymphocyte homing to fatty liver and the role of lipopolysaccharide (LPS) in the onset of inflammation in ob/ob mice. METHODS:We decreased intestinal bacterial compounds by oral antibiotic treatment to test t...


    pub_type: 杂志文章


    authors: Bigorgne AE,Bouchet-Delbos L,Naveau S,Dagher I,Prévot S,Durand-Gasselin I,Couderc J,Valet P,Emilie D,Perlemuter G

    更新日期:2008-05-01 00:00:00

  • Optimizing anti-TNF treatment in inflammatory bowel disease.

    abstract::Infliximab, the chimeric monoclonal immunoglobulin (Ig)G1 antibody to tumor necrosis factor (TNF) has changed our therapy of Crohn's disease. Infliximab is indicated in refractory luminal and fistulizing Crohn's disease. In patients with luminal disease, a single intravenous (i.v.) dose of 5 mg/kg is efficacious; in f...


    pub_type: 杂志文章,评审


    authors: Rutgeerts P,Van Assche G,Vermeire S

    更新日期:2004-05-01 00:00:00

  • h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine.

    abstract:BACKGROUND & AIMS:Recently, the immediate early gene h-sgk was cloned as a hypertonicity-induced gene from human hepatoma cells. The aim of this study was to localize h-sgk messenger RNA (mRNA) expression in normal and inflamed intestinal mucosa and to identify potential transcriptional regulators. METHODS:h-sgk mRNA ...


    pub_type: 杂志文章


    authors: Waldegger S,Klingel K,Barth P,Sauter M,Rfer ML,Kandolf R,Lang F

    更新日期:1999-05-01 00:00:00

  • Hepcidin expression does not rescue the iron-poor phenotype of Kupffer cells in Hfe-null mice after liver transplantation.

    abstract:BACKGROUND & AIMS:Hemochromatosis is a common hereditary disease caused by mutations in HFE and characterized by increased absorption of iron in the intestine. However, the intestine does not appear to be the site of mutant HFE activity in the disease; we investigated the role of the liver-the source of the iron regula...


    pub_type: 杂志文章


    authors: Garuti C,Tian Y,Montosi G,Sabelli M,Corradini E,Graf R,Ventura P,Vegetti A,Clavien PA,Pietrangelo A

    更新日期:2010-07-01 00:00:00

  • Early diagnosis of pancreatic infection by computed tomography-guided aspiration.

    abstract::We performed 92 computed tomography-guided percutaneous needle aspirations of pancreatic inflammatory masses in 60 patients suspected of harboring pancreatic infection. Thirty-six patients (60%) were found by Gram stain and culture to have a total of 41 separate episodes of pancreatic infection. Among 42 aspirates jud...


    pub_type: 杂志文章


    authors: Gerzof SG,Banks PA,Robbins AH,Johnson WC,Spechler SJ,Wetzner SM,Snider JM,Langevin RE,Jay ME

    更新日期:1987-12-01 00:00:00

  • Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study.

    abstract::One hundred Chinese patients who received induction cytotoxic therapy for malignant lymphoma were prospectively studied to determine the incidence, morbidity, mortality, and predisposing factors for reactivation of hepatitis B virus replication during cytotoxic therapy. In 18 (67%) hepatitis B surface antigen-positive...


    pub_type: 杂志文章


    authors: Lok AS,Liang RH,Chiu EK,Wong KL,Chan TK,Todd D

    更新日期:1991-01-01 00:00:00

  • Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites.

    abstract:BACKGROUND/AIMS:Cirrhotic patients are predisposed to develop spontaneous bacteremias and/or peritonitis, mainly caused by enteric bacteria. The aim of this study was to investigate if bacterial translocation, which is the passage of bacteria from the intestinal lumen to regional lymph nodes and/or the systemic circula...


    pub_type: 杂志文章


    authors: Garcia-Tsao G,Lee FY,Barden GE,Cartun R,West AB

    更新日期:1995-06-01 00:00:00

  • Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas.

    abstract::Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical a...


    pub_type: 杂志文章


    authors: Lupinacci RM,Goloudina A,Buhard O,Bachet JB,Maréchal R,Demetter P,Cros J,Bardier-Dupas A,Collura A,Cervera P,Scriva A,Dumont S,Hammel P,Sauvanet A,Louvet C,Delpéro JR,Paye F,Vaillant JC,André T,Closset J,Emile JF

    更新日期:2018-03-01 00:00:00

  • Tissue transglutaminase does not affect fibrotic matrix stability or regression of liver fibrosis in mice.

    abstract:BACKGROUND & AIMS:The ubiquitous cross-linking enzyme tissue transglutaminase (TG2) has been implicated in irreversible collagen stabilization in liver fibrosis, although functional evidence is lacking. We studied the contribution of TG2 to hepatic fibrotic matrix stability, as well as liver fibrosis progression and re...


    pub_type: 杂志文章


    authors: Popov Y,Sverdlov DY,Sharma AK,Bhaskar KR,Li S,Freitag TL,Lee J,Dieterich W,Melino G,Schuppan D

    更新日期:2011-05-01 00:00:00

  • Increased frequency of transient lower esophageal sphincter relaxation induced by gastric distention in reflux patients with hiatal hernia.

    abstract:BACKGROUND & AIMS:This study aimed to determine if hiatal hernia influences vulnerability to reflux and transient lower esophageal sphincter relaxation (tLESR) during gastric distention in patients with gastroesophageal reflux disease (GERD). METHODS:Eight normal subjects and 15 patients with GERD were studied. A meta...


    pub_type: 杂志文章


    authors: Kahrilas PJ,Shi G,Manka M,Joehl RJ

    更新日期:2000-04-01 00:00:00

  • Bone disease in cholestatic liver disease.

    abstract::Osteopenia in the form of osteoporosis is a common clinical problem associated with chronic cholestatic liver disease, and clinical morbidity from atraumatic fractures is increasing as more patients with PBC and PSC undergo successful liver transplantation. In the absence of symptomatic fractures, the clinical diagnos...


    pub_type: 杂志文章,评审


    authors: Hay JE

    更新日期:1995-01-01 00:00:00

  • Pancreatitis in Children.

    abstract::Acute, acute recurrent, and chronic forms of pancreatitis have been increasingly diagnosed in children in the past 2 decades. Risk factors in the pediatric group are broad and appear to be strikingly different compared with the adult cohort. However, the disease burden and impact on quality of life are surprisingly si...


    pub_type: 杂志文章,评审


    authors: Uc A,Husain SZ

    更新日期:2019-05-01 00:00:00

  • Unusual thoracoabdominal duplication associated with pancreaticopleural fistula.

    abstract::The clinical case is presented of a 16-yr-old patient with thoracoabdominal duplication that communicated with the main pancreatic duct and the right pleural cavity and resulted in pancreaticopleural fistula. Although abdominal duplications communicating with the pancreas have been described before, to our knowledge, ...


    pub_type: 杂志文章


    authors: Fitzgibbons RJ Jr,Nugent FW,Ellis FH Jr,Braasch JW,Scholz FJ

    更新日期:1980-08-01 00:00:00

  • HCl-induced cell edema in rabbit esophageal epithelium: a bumetanide-sensitive process.

    abstract:BACKGROUND & AIMS:The morphology of acid damage to esophageal epithelium is characterized by marked cell (swelling) edema. This observation suggests that, in the process of acid damage, an increase in osmotic forces develops within the cell that accounts for the increase in cell water. The aim of this study was to docu...


    pub_type: 杂志文章


    authors: Tobey NA,Cragoe EJ Jr,Orlando RC

    更新日期:1995-08-01 00:00:00

  • Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. A cholescintigraphic study.

    abstract::We studied gallbladder bile flow before, during, and after cholesterol gallstone formation in the prairie dog using infusion cholescintigraphy with 99mTc-diethyl iminodiacetic acid. In 18 fasting animals partitioning of bile between gallbladder and intestine was determined every 15 min for 140 min, and gallbladder res...


    pub_type: 杂志文章


    authors: Pellegrini CA,Ryan T,Broderick W,Way LW

    更新日期:1986-01-01 00:00:00

  • Increased colonic mucosal angiotensin I and II concentrations in Crohn's colitis.

    abstract::To define a potential role for the angiotensin system in Crohn's colitis, the colonic mucosal levels of angiotensin I and II were measured in endoscopic biopsy samples from patients with active Crohn's colitis (n = 20), ulcerative colitis (n = 13), other forms of colitis (n = 3), and normal controls (n = 17). Colonic ...


    pub_type: 杂志文章


    authors: Jaszewski R,Tolia V,Ehrinpreis MN,Bodzin JH,Peleman RR,Korlipara R,Weinstock JV

    更新日期:1990-06-01 00:00:00

  • Monozygotic triplets with Crohn's disease of the colon.

    abstract::Female monozygotic triplets all developed Crohn's disease within a period of 11 mo. The monozygosity was demonstrated by analysis of 24 genetic markers of different chromosomal localization. Crohn's disease was diagnosed using clinical, radiologic, and endoscopic findings. Histologic evaluation of bowel tissue was con...


    pub_type: 杂志文章


    authors: Purrmann J,Bertrams J,Borchard F,Miller B,Cleveland S,Stolze T,Strohmeyer G

    更新日期:1986-12-01 00:00:00

  • Activated ATF6 Induces Intestinal Dysbiosis and Innate Immune Response to Promote Colorectal Tumorigenesis.

    abstract:BACKGROUND & AIMS:Activating transcription factor 6 (ATF6) regulates endoplasmic reticulum stress. We studied whether ATF6 contributes to the development of colorectal cancer (CRC) using tissue from patients and transgenic mice. METHODS:We analyzed data from 541 patients with CRC in The Cancer Genome Atlas database fo...


    pub_type: 杂志文章


    authors: Coleman OI,Lobner EM,Bierwirth S,Sorbie A,Waldschmitt N,Rath E,Berger E,Lagkouvardos I,Clavel T,McCoy KD,Weber A,Heikenwalder M,Janssen KP,Haller D

    更新日期:2018-11-01 00:00:00

  • Management Strategies to Improve Outcomes of Patients With Inflammatory Bowel Diseases.

    abstract::Strategies for management of inflammatory bowel diseases are shifting from simple control of symptoms toward full control of these diseases (clinical and endoscopic remission), with the final aim of blocking their progression and preventing bowel damage and disability. New goals have been proposed for treatment, such ...


    pub_type: 杂志文章,评审


    authors: Colombel JF,Narula N,Peyrin-Biroulet L

    更新日期:2017-02-01 00:00:00

  • Inflammasomes in intestinal inflammation and cancer.

    abstract::Inflammasomes are multi-protein complexes that mediate activation of caspase-1, which promotes secretion of the proinflammatory cytokines interleukin-1β and interleukin-18 and pyroptosis, a form of phagocyte cell death induced by bacterial pathogens. Members of the Nod-like receptor family (including Nlrp1, Nlrp3, and...


    pub_type: 杂志文章,评审


    authors: Chen GY,Núñez G

    更新日期:2011-12-01 00:00:00