Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens.


BACKGROUND AND AIMS:Hepatocellular carcinoma (HCC) frequently results from synergism between chemical and infectious liver carcinogens. Worldwide, the highest incidence of HCC is in regions endemic for the foodborne contaminant aflatoxin B1 (AFB1) and hepatitis B virus (HBV) infection. Recently, gut microbes have been implicated in multisystemic diseases including obesity and diabetes. Here, the hypothesis that specific intestinal bacteria promote liver cancer was tested in chemical and viral transgenic mouse models. METHODS:Helicobacter-free C3H/HeN mice were inoculated with AFB1 and/or Helicobacter hepaticus. The incidence, multiplicity and surface area of liver tumours were quantitated at 40 weeks. Molecular pathways involved in tumourigenesis were analysed by microarray, quantitative real-time PCR, liquid chromatography/mass spectrometry, ELISA, western blot and immunohistochemistry. In a separate experiment, C57BL/6 FL-N/35 mice harbouring a full-length hepatitis C virus (HCV) transgene were crossed with C3H/HeN mice and cancer rates compared between offspring with and without H hepaticus. RESULTS:Intestinal colonisation by H hepaticus was sufficient to promote aflatoxin- and HCV transgene-induced HCC. Neither bacterial translocation to the liver nor induction of hepatitis was necessary. From its preferred niche in the intestinal mucus layer, H hepaticus activated nuclear factor-kappaB (NF-kappaB)-regulated networks associated with innate and T helper 1 (Th1)-type adaptive immunity both in the lower bowel and liver. Biomarkers indicative of tumour progression included hepatocyte turnover, Wnt/beta-catenin activation and oxidative injury with decreased phagocytic clearance of damaged cells. CONCLUSIONS:Enteric microbiota define HCC risk in mice exposed to carcinogenic chemicals or hepatitis virus transgenes. These results have implications for human liver cancer risk assessment and prevention.






Fox JG,Feng Y,Theve EJ,Raczynski AR,Fiala JL,Doernte AL,Williams M,McFaline JL,Essigmann JM,Schauer DB,Tannenbaum SR,Dedon PC,Weinman SA,Lemon SM,Fry RC,Rogers AB




Has Abstract


2010-01-01 00:00:00
















  • Global prevalence of Barrett's oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis.

    abstract:OBJECTIVES:Chronic gastro-oesophageal reflux might lead to the development of Barrett's oesophagus (BO) or even oesophageal adenocarcinoma. There has been no definitive systematic review and meta-analysis of data to estimate global prevalence of BO or oesophageal adenocarcinoma in individuals with gastro-oesophageal re...


    pub_type: 杂志文章


    authors: Eusebi LH,Cirota GG,Zagari RM,Ford AC

    更新日期:2020-07-30 00:00:00

  • Malignant histiocytosis of the intestine: the early histological lesion.

    abstract::A histological study of peroral jejunal biopsies and resection specimens from patients with malignant histiocytosis of the intestine (MHI) has revealed characteristic lesions consisting of intramucosal histiocytic aggregations which invade surface and crypt epithelium. These lesions are found in 'uninvolved' jejunal m...


    pub_type: 杂志文章


    authors: Isaacson P

    更新日期:1980-05-01 00:00:00

  • Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis.

    abstract:BACKGROUND:5-Lipoxygenase products play a part in inflammatory response. AIMS:The effect of intracolonic administration of zileuton (a 5-lipoxygenase inhibitor) on colonic damage and eicosanoid local release was assessed in a rat model of colitis. METHODS:Ninety rats with trinitrobenzenesulphonic acid induced colitis...


    pub_type: 杂志文章


    authors: Bertrán X,Mañé J,Fernández-Bañares F,Castellá E,Bartolí R,Ojanguren I,Esteve M,Gassull MA

    更新日期:1996-06-01 00:00:00

  • Evidence for a transmissible factor in Crohn's disease.

    abstract::The injection of rabbits' ileum with homogenates of both normal and Crohn's affected human bowel tissue gave Crohn's-like changes in 11 of 27 animals after six months, but 12 months after injection the rabbit bowel had reverted to normal. The addition of ampicillin to the homogenates prevented the appearance of these ...


    pub_type: 杂志文章


    authors: Donnelly BJ,Delaney PV,Healy TM

    更新日期:1977-05-01 00:00:00

  • Effect of ursodeoxycholic acid on methionine adenosyltransferase activity and hepatic glutathione metabolism in rats.

    abstract:BACKGROUND AND AIMS:Both bile salts and glutathione participate in the generation of canalicular bile flow. In this work, we have investigated the effect of different bile salts on hepatic glutathione metabolism. METHODS:Using the isolated and perfused rat liver, we studied hepatic glutathione content, and metabolism ...


    pub_type: 杂志文章


    authors: Rodríguez-Ortigosa CM,Cincu RN,Sanz S,Ruiz F,Quiroga J,Prieto J

    更新日期:2002-05-01 00:00:00

  • Mesalazine and thymoquinone attenuate intestinal tumour development in Msh2(loxP/loxP) Villin-Cre mice.

    abstract:OBJECTIVE:Lynch syndrome is caused by germline mutations in DNA mismatch repair genes leading to microsatellite instability (MSI) and colorectal cancer. Mesalazine, commonly used for the treatment of UC, reduces MSI in vitro. Here, we tested natural compounds for such activity and applied mesalazine and thymoquinone in...


    pub_type: 杂志文章


    authors: Kortüm B,Campregher C,Lang M,Khare V,Pinter M,Evstatiev R,Schmid G,Mittlböck M,Scharl T,Kucherlapati MH,Edelmann W,Gasche C

    更新日期:2015-12-01 00:00:00

  • Immunological studies in patients with Crohn's disease.

    abstract::An investigation of immunological parameters was conducted in 38 patients with Crohn's disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and ...


    pub_type: 杂志文章


    authors: MacPherson BR,Albertini RJ,Beeken WL

    更新日期:1976-02-01 00:00:00

  • Expression of cyclooxygenase 1 and 2 by human gastric endothelial cells.

    abstract:BACKGROUND:Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and cause gastric ulceration. NSAIDs also impair granulation tissue angiogenesis and healing of established gastric ulcers in humans. The mechanism whereby NSAIDs inhibit granulation tissue angiogenesis is unknown but may involve inh...


    pub_type: 杂志文章


    authors: Hull MA,Thomson JL,Hawkey CJ

    更新日期:1999-10-01 00:00:00

  • A ne method for studying gut transit times using radioopaque markers.

    abstract::A simple technique for measuring gastrointestinal transit times using radioopaque pellets of barium-impregnated polythene has been developed and validated. A normal range has been established by studying 25 normal subjects; all passed the first marker within three days and most passed 80% of the markers within five da...


    pub_type: 杂志文章


    authors: Hinton JM,Lennard-Jones JE,Young AC

    更新日期:1969-10-01 00:00:00

  • Site of the abnormal stimulus of gastric secretion after small bowel exclusion.

    abstract::In dogs with either vagally innervated or denervated pouches, the acid responses to a standard meal, a meal which bypassed the greater part of the small bowel, and a meal introduced directly into the small intestine were measured before and after exclusion of 75% of the small bowel.After intestinal exclusion an increa...


    pub_type: 杂志文章


    authors: Buxton B,Wasunna AE,Saunders J,Gillespie IE

    更新日期:1972-07-01 00:00:00

  • Evaluation of indium scintigraphy in patients with active inflammatory bowel disease.

    abstract::Recent reports have indicated a possible role for 111Indium leucocyte scintigraphy in the management of patients with acute inflammatory bowel disease. Our experience with this technique in 15 patients (nine with ulcerative colitis, six with Crohn's disease) is described. Perfect agreement was not obtained between sci...


    pub_type: 杂志文章


    authors: Buxton-Thomas MS,Dickinson RJ,Maltby P,Hunter JO,Wraight EP

    更新日期:1984-12-01 00:00:00

  • Calcium in milk and fermentation by yoghurt bacteria increase the resistance of rats to Salmonella infection.

    abstract::Calcium in milk products stimulates gastric acid secretion and inhibits the cytolytic activity of intestinal contents. Based on these effects, it was hypothesised that calcium might lessen the severity of food borne intestinal infections. The possible differential effects of a low calcium milk and normal milk products...


    pub_type: 杂志文章


    authors: Bovee-Oudenhoven I,Termont D,Dekker R,Van der Meer R

    更新日期:1996-01-01 00:00:00

  • Real time high resolution magnetic resonance imaging for the assessment of gastric motility disorders.

    abstract:BACKGROUND:The aim of this study was to evaluate whether patients with increased or decreased gastric motility can be differentiated from healthy volunteers by means of real time magnetic resonance imaging (MRI). PATIENTS AND METHODS:Ten healthy volunteers, 10 patients with gastroparesis, and 10 patients with function...


    pub_type: 杂志文章


    authors: Ajaj W,Goehde SC,Papanikolaou N,Holtmann G,Ruehm SG,Debatin JF,Lauenstein TC

    更新日期:2004-09-01 00:00:00

  • No evidence of persistent mumps virus infection in inflammatory bowel disease.

    abstract:BACKGROUND AND AIM:There is controversy regarding whether paramyxovirus infection is causally associated with inflammatory bowel disease (IBD). The latest cohort study claimed that atypical measles and mumps infections in childhood may be risk factors for later IBD. This study was conducted to clarify the validity of a...


    pub_type: 杂志文章


    authors: Iizuka M,Saito H,Yukawa M,Itou H,Shirasaka T,Chiba M,Fukushima T,Watanabe S

    更新日期:2001-05-01 00:00:00

  • Effect of histamine on the growth of human gastrointestinal tumours: reversal by cimetidine.

    abstract::The proliferative effects of histamine were examined on the human gastric tumour cell lines; MKN45, the gastrin producing subline, MKN45G, and the colorectal lines; LoVo and C170. The proliferation of MKN45 as assessed by 75[Se] selenomethionine uptake and cell counts was increased by histamine concentrations of 10(-7...


    pub_type: 杂志文章


    authors: Watson SA,Wilkinson LJ,Robertson JF,Hardcastle JD

    更新日期:1993-08-01 00:00:00

  • Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease.

    abstract:OBJECTIVE:The aetiology of Crohn's disease (CD) has been related to nucleotide-binding oligomerisation domain containing 2 (NOD2) and ATG16L1 gene variants. The observation of bacterial DNA translocation in patients with CD led us to hypothesise that this process may be facilitated in patients with NOD2/ATG16L1-variant...


    pub_type: 杂志文章


    authors: Gutiérrez A,Scharl M,Sempere L,Holler E,Zapater P,Almenta I,González-Navajas JM,Such J,Wiest R,Rogler G,Francés R

    更新日期:2014-02-01 00:00:00

  • Leadership training to improve adenoma detection rate in screening colonoscopy: a randomised trial.

    abstract:OBJECTIVE:Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared the effect of leadership training versus feedback only on colonoscopy quality in a countrywide randomised trial. DESIGN:40 colonoscopy...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Kaminski MF,Anderson J,Valori R,Kraszewska E,Rupinski M,Pachlewski J,Wronska E,Bretthauer M,Thomas-Gibson S,Kuipers EJ,Regula J

    更新日期:2016-04-01 00:00:00

  • Hydrogen sulphide and the hyperdynamic circulation in cirrhosis: a hypothesis.

    abstract::Cirrhosis is associated with the development of a hyperdynamic circulation, which is secondary to the presence of systemic vasodilatation. Several mechanisms have been postulated to be involved in the development of systemic vasodilatation, including increased synthesis of nitric oxide, hyperglucagonaemia, increased c...


    pub_type: 杂志文章,评审


    authors: Ebrahimkhani MR,Mani AR,Moore K

    更新日期:2005-12-01 00:00:00

  • First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying.

    abstract:BACKGROUND:Ethanol undergoes a first pass metabolism (FPM) in the stomach and liver. Gastric FPM of ethanol primarily depends on the activity of gastric alcohol dehydrogenase (ADH). In addition, the speed of gastric emptying (GE) may modulate both gastric and hepatic FPM of ethanol. AIMS:To study the effect of modulat...


    pub_type: 杂志文章


    authors: Oneta CM,Simanowski UA,Martinez M,Allali-Hassani A,Parés X,Homann N,Conradt C,Waldherr R,Fiehn W,Coutelle C,Seitz HK

    更新日期:1998-11-01 00:00:00

  • Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition.

    abstract:BACKGROUND AND AIMS:The authors have previously isolated a putative oncogene, eukaryotic initiation factor 5A2 (EIF5A2) from 3q26. In this study, EIF5A2 was characterised for its role in colorectal carcinoma (CRC) aggressiveness and underlying molecular mechanisms. METHODS:The expression dynamics of EIF5A2 were examin...


    pub_type: 杂志文章


    authors: Zhu W,Cai MY,Tong ZT,Dong SS,Mai SJ,Liao YJ,Bian XW,Lin MC,Kung HF,Zeng YX,Guan XY,Xie D

    更新日期:2012-04-01 00:00:00

  • Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden.

    abstract:OBJECTIVE:Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD). DESIGN:In a binational, population-based cohort study from Sweden and De...


    pub_type: 杂志文章


    authors: Axelrad JE,Olén O,Sachs MC,Erichsen R,Pedersen L,Halfvarson J,Askling J,Ekbom A,Sørensen HT,Ludvigsson JF

    更新日期:2021-02-01 00:00:00

  • Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis.

    abstract:BACKGROUND AND AIMS:Extrahepatic manifestations of HCV are responsible for morbidity and mortality in many chronically infected patients. New, interferon-free antiviral treatment regimens, which present the opportunity to treat all HCV-infected patients, call for a better understanding of the benefits of treating non-c...


    pub_type: 杂志文章,meta分析


    authors: Cacoub P,Desbois AC,Comarmond C,Saadoun D

    更新日期:2018-11-01 00:00:00

  • Alkyl halides, super hydrogen production and the pathogenesis of pneumatosis cystoides coli.

    abstract:BACKGROUND AND AIMS:The colons of patients with pneumatosis cystoides coli produce excessive H2. Exposure to alkyl halides could explain this. Six consecutive patients who had pneumatosis cystoides coli while taking chloral hydrate (1-5+ g/day) are reported. Patients 2 and 3 were investigated after they had ceased chlo...


    pub_type: 杂志文章


    authors: Florin TH

    更新日期:1997-12-01 00:00:00

  • Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

    abstract:OBJECTIVES:Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN:Retrospective multinational study including SCN diagnosed between 1990 and 2014. ...


    pub_type: 杂志文章


    authors: Jais B,Rebours V,Malleo G,Salvia R,Fontana M,Maggino L,Bassi C,Manfredi R,Moran R,Lennon AM,Zaheer A,Wolfgang C,Hruban R,Marchegiani G,Fernández Del Castillo C,Brugge W,Ha Y,Kim MH,Oh D,Hirai I,Kimura W,Jang JY

    更新日期:2016-02-01 00:00:00

  • Intestinal permeability in patients with Crohn's disease and their first degree relatives.

    abstract::It has been reported that intestinal permeability to polyethylene glycol 400 is increased in patients with Crohn's disease and their apparently unaffected first degree relatives. Because of the implications that these findings have for the aetiology of Crohn's disease these studies were repeated. Patients with Crohn's...


    pub_type: 杂志文章


    authors: Teahon K,Smethurst P,Levi AJ,Menzies IS,Bjarnason I

    更新日期:1992-03-01 00:00:00

  • Direct measurement of acid permeation into rat oesophagus.

    abstract:BACKGROUND AND AIMS:The early responses of the oesophageal mucosa to acid perfusion may predict subsequent pathology. Mucosal responses to luminal acid may result either from acid permeating through the mucosa or from other unknown transduction mechanisms. In order to better understand the dynamics of acid permeation i...


    pub_type: 杂志文章


    authors: Tanaka S,Chu S,Hirokawa M,Montrose MH,Kaunitz JD

    更新日期:2003-06-01 00:00:00

  • Saccharomyces boulardii upgrades cellular adaptation after proximal enterectomy in rats.

    abstract:BACKGROUND:Saccharomyces boulardii is a non-pathogenic yeast which exerts trophic effects on human and rat small intestinal mucosa. AIMS:To examine the effects of S boulardii on ileal adaptation after proximal enterectomy in rats. METHODS:Wistar rats, aged eight weeks, underwent 60% proximal resection or transection ...


    pub_type: 杂志文章


    authors: Buts JP,De Keyser N,Marandi S,Hermans D,Sokal EM,Chae YH,Lambotte L,Chanteux H,Tulkens PM

    更新日期:1999-07-01 00:00:00

  • Hydrogen peroxide induced adenosine diphosphate ribosyl transferase (ADPRT) response in patients with inflammatory bowel disease.

    abstract::The sample population in this initial case control study of the adenosine diphosphate ribosyl transferase (ADPRT) response of inflammatory bowel disease patients included: 23 patients with ulcerative colitis (UC)-active and inactive, 13 patients with Crohn's disease (CD)-active and inactive, 14 first degree relatives ...


    pub_type: 杂志文章


    authors: Markowitz MM,Rozen P,Pero RW,Tobi M,Miller DG

    更新日期:1988-12-01 00:00:00

  • NAD metabolism fuels human and mouse intestinal inflammation.

    abstract:OBJECTIVE:Nicotinamide phosphoribosyltransferase (NAMPT, also referred to as pre-B cell colony-enhancing factor or visfatin) is critically required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD) supply catalysing the rate-limiting step of the NAD salvage pathway. NAMPT is strongly upregulated i...


    pub_type: 杂志文章


    authors: Gerner RR,Klepsch V,Macheiner S,Arnhard K,Adolph TE,Grander C,Wieser V,Pfister A,Moser P,Hermann-Kleiter N,Baier G,Oberacher H,Tilg H,Moschen AR

    更新日期:2018-10-01 00:00:00

  • Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis.

    abstract:OBJECTIVE:Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dy...


    pub_type: 杂志文章


    authors: Huang W,Booth DM,Cane MC,Chvanov M,Javed MA,Elliott VL,Armstrong JA,Dingsdale H,Cash N,Li Y,Greenhalf W,Mukherjee R,Kaphalia BS,Jaffar M,Petersen OH,Tepikin AV,Sutton R,Criddle DN

    更新日期:2014-08-01 00:00:00