Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis.


OBJECTIVE:Gastric cancer is the third leading cause of cancer death worldwide and infection by Helicobacter pylori is the strongest risk factor. We have reported increased epidermal growth factor receptor (EGFR) phosphorylation in the H. pylori-induced human carcinogenesis cascade, and association with DNA damage. Our goal was to determine the role of EGFR activation in gastric carcinogenesis. DESIGN:We evaluated gefitinib, a specific EGFR inhibitor, in chemoprevention of H. pylori-induced gastric inflammation and cancer development. Mice with genetically targeted epithelial cell-specific deletion of Egfr (EfgrΔepi mice) were also used. RESULTS:In C57BL/6 mice, gefitinib decreased Cxcl1 and Cxcl2 expression by gastric epithelial cells, myeloperoxidase-positive inflammatory cells in the mucosa and epithelial DNA damage induced by H. pylori infection. Similar reductions in chemokines, inflammatory cells and DNA damage occurred in infected EgfrΔepi versus Egfrfl/fl control mice. In H. pylori-infected transgenic insulin-gastrin (INS-GAS) mice and gerbils, gefitinib treatment markedly reduced dysplasia and carcinoma. Gefitinib blocked H. pylori-induced activation of mitogen-activated protein kinase 1/3 (MAPK1/3) and activator protein 1 in gastric epithelial cells, resulting in inhibition of chemokine synthesis. MAPK1/3 phosphorylation and JUN activation was reduced in gastric tissues from infected wild-type and INS-GAS mice treated with gefitinib and in primary epithelial cells from EfgrΔepi versus Egfrfl/fl mice. Epithelial EGFR activation persisted in humans and mice after H. pylori eradication, and gefitinib reduced gastric carcinoma in INS-GAS mice treated with antibiotics. CONCLUSIONS:These findings suggest that epithelial EGFR inhibition represents a potential strategy to prevent development of gastric carcinoma in H. pylori-infected individuals.






Sierra JC,Asim M,Verriere TG,Piazuelo MB,Suarez G,Romero-Gallo J,Delgado AG,Wroblewski LE,Barry DP,Peek RM Jr,Gobert AP,Wilson KT




Has Abstract


2018-07-01 00:00:00
















  • Hepatocellular carcinoma: clinical frontiers and perspectives.

    abstract::Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and...


    pub_type: 杂志文章,评审


    authors: Bruix J,Gores GJ,Mazzaferro V

    更新日期:2014-05-01 00:00:00

  • Development and validation of a rapid, generic measure of disease control from the patient's perspective: the IBD-control questionnaire.

    abstract:INTRODUCTION:The use of patient reported outcome measures to support routine inflammatory bowel disease (IBD) care is not widespread and suggests that existing questionnaires lack relevance to day-to-day decisions or are too cumbersome to administer. We developed a simple, generic tool for capturing disease control fro...


    pub_type: 杂志文章


    authors: Bodger K,Ormerod C,Shackcloth D,Harrison M,IBD Control Collaborative.

    更新日期:2014-07-01 00:00:00

  • Determinants of perception of heartburn and regurgitation.

    abstract:BACKGROUND AND AIMS:It is not known why some reflux episodes evoke symptoms and others do not. We investigated the determinants of perception of gastro-oesophageal reflux. METHODS:In 32 patients with symptoms suggestive of gastro-oesophageal reflux, 24 hour ambulatory pH and impedance monitoring was performed after ce...


    pub_type: 杂志文章


    authors: Bredenoord AJ,Weusten BL,Curvers WL,Timmer R,Smout AJ

    更新日期:2006-03-01 00:00:00

  • Bile acid composition regulates GPR119-dependent intestinal lipid sensing and food intake regulation in mice.

    abstract:OBJECTIVES:Lipid mediators in the GI tract regulate satiation and satiety. Bile acids (BAs) regulate the absorption and metabolism of dietary lipid in the intestine, but their effects on lipid-regulated satiation and satiety are completely unknown. Investigating this is challenging because introducing excessive BAs or ...


    pub_type: 杂志文章


    authors: Higuchi S,Ahmad TR,Argueta DA,Perez PA,Zhao C,Schwartz GJ,DiPatrizio NV,Haeusler RA

    更新日期:2020-09-01 00:00:00

  • CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer.

    abstract:OBJECTIVE:Adaptive immune resistance mediated by the cytokine interferon gamma (IFNG) still constitutes a major problem in cancer immunotherapy. We develop strategies for overcoming IFNG-mediated adaptive immune resistance in pancreatic ductal adenocarcinoma cancer (PDAC). DESIGN:We screened 429 kinase inhibitors for ...


    pub_type: 杂志文章


    authors: Huang J,Chen P,Liu K,Liu J,Zhou B,Wu R,Peng Q,Liu ZX,Li C,Kroemer G,Lotze M,Zeh H,Kang R,Tang D

    更新日期:2020-08-14 00:00:00

  • A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits.

    abstract:BACKGROUND:Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis. AIMS:To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbi...


    pub_type: 杂志文章


    authors: Osman MO,Kristensen JU,Jacobsen NO,Lausten SB,Deleuran B,Deleuran M,Gesser B,Matsushima K,Larsen CG,Jensen SL

    更新日期:1998-08-01 00:00:00

  • Screening SMAD1, SMAD2, SMAD3, and SMAD5 for germline mutations in juvenile polyposis syndrome.

    abstract:BACKGROUND AND AIMS:Juvenile polyps occur in several Mendelian disorders, whether in association with gastrointestinal cancer alone (juvenile polyposis syndrome, JPS) or as part of known syndromes (Cowden, Gorlin, and Bannayan-Zonana) in association with developmental abnormalities, dysmorphic features, or extraintesti...


    pub_type: 杂志文章


    authors: Bevan S,Woodford-Richens K,Rozen P,Eng C,Young J,Dunlop M,Neale K,Phillips R,Markie D,Rodriguez-Bigas M,Leggett B,Sheridan E,Hodgson S,Iwama T,Eccles D,Bodmer W,Houlston R,Tomlinson I

    更新日期:1999-09-01 00:00:00

  • Psychological and sex features of delayed gut transit in functional gastrointestinal disorders.

    abstract:BACKGROUND:The relation of demographic and psychological factors to the presence and extent of gut transit impairment in the functional gastrointestinal disorders has received little attention. AIMS:To compare the psychosocial and demographic features of patients with functional gastrointestinal disorders and delayed ...


    pub_type: 杂志文章


    authors: Bennett EJ,Evans P,Scott AM,Badcock CA,Shuter B,Höschl R,Tennant CC,Kellow JE

    更新日期:2000-01-01 00:00:00

  • Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium.

    abstract:BACKGROUND:In normal gastric epithelium, MUC5AC is detected in superficial epithelium associated with Lewis type 1 antigens and MUC6 is detected in antral glands with Lewis type 2. Therefore, the stomach constitutes an excellent model to examine the role of glycosyltransferases in determining the specificity of apomuci...


    pub_type: 杂志文章


    authors: López-Ferrer A,de Bolós C,Barranco C,Garrido M,Isern J,Carlstedt I,Reis CA,Torrado J,Real FX

    更新日期:2000-09-01 00:00:00

  • Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

    abstract::Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either g...


    pub_type: 杂志文章


    authors: Spiller RC,Trotman IF,Adrian TE,Bloom SR,Misiewicz JJ,Silk DB

    更新日期:1988-08-01 00:00:00

  • Lithogenic bile in patients with ileal dysfunction.

    abstract::Ileal disease or resection causes bile salt malabsorption and a reduction in the bile salt content of bile. Since cholesterol solubility requires adequate bile salt concentrations, depletion of the bile salt content of bile might, therefore, jeopardize cholesterol solubility and predispose to cholesterol gallstone for...


    pub_type: 杂志文章


    authors: Dowling RH,Bell GD,White J

    更新日期:1972-06-01 00:00:00

  • Effect of sodium taurocholate on gastric secretion in patients with duodenal ulceration.

    abstract::The effect of sodium taurocholate instillation on the stimulated stomachs of patients with duodenal ulceration has been investigated. Instillation into the stomach of sodium taurocholate significantly reduced pentagastrin stimulated volume and outputs of both acid and sodium, with no change in the calculated volume of...


    pub_type: 杂志文章


    authors: Lewin MR,Pifano E,Daniel RD,Boulos PB,Clark CG

    更新日期:1983-01-01 00:00:00

  • Protein kinase C inhibits cyclic adenosine monophosphate generation by histamine and truncated glucagon like peptide 1 in the human gastric cancer cell line HGT-1.

    abstract::The HGT-1 gastric cancer cell line was used to determine the actions of protein kinase C on the stimulation of adenylate cyclase by the human histamine H2 receptor, and the receptors for gastric inhibitory polypeptide and truncated glucagon like peptide 1 (TGLP-1). Suspensions of HGT-1 cells were preincubated with the...


    pub_type: 杂志文章


    authors: McKenna P,Williams JM,Gespach CP,Hanson PJ

    更新日期:1993-07-01 00:00:00

  • Extramedullary haemopoiesis in the small bowel.

    abstract::A patient with myelofibrosis developed repeated gastrointestinal haemorrhage from the small intestine, which was found to be infiltrated with extramedullary haemopoiesis. Nineteen months later he presented with subacute intestinal obstruction; radiology and laparotomy documented progressive infiltration of the small b...


    pub_type: 杂志文章


    authors: Sharma BK,Pounder RE,Cruse JP,Knowles SM,Lewis AA

    更新日期:1986-07-01 00:00:00

  • Incidences, temporal trends and risks of hospitalisation for gastrointestinal bleeding in new or chronic low-dose aspirin users after treatment for Helicobacter pylori: a territory-wide cohort study.

    abstract:OBJECTIVE:The risk of GI bleeding (GIB) in aspirin users after Helicobacter pylori (HP) eradication remains poorly defined. We characterised the incidences and temporal trends of hospitalisations for all GIB in aspirin users after HP eradication therapy. DESIGN:Based on a territory-wide health database, we identified ...


    pub_type: 杂志文章


    authors: Guo CG,Cheung KS,Zhang F,Chan EW,Chen L,Wong IC,Leung WK

    更新日期:2020-03-01 00:00:00

  • Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid.

    abstract::Cholestasis of pregnancy is associated with increased fetal morbidity and mortality and should be treated actively. The significance attached to pruritus in pregnancy is often minimal, but it is a cardinal symptom of cholestasis of pregnancy, which may have no other clinical features. Eight women with previous cholest...


    pub_type: 杂志文章


    authors: Davies MH,da Silva RC,Jones SR,Weaver JB,Elias E

    更新日期:1995-10-01 00:00:00

  • USF1 defect drives p53 degradation during Helicobacter pylori infection and accelerates gastric carcinogenesis.

    abstract:OBJECTIVE:Helicobacter pylori (Hp) is a major risk factor for gastric cancer (GC). Hp promotes DNA damage and proteasomal degradation of p53, the guardian of genome stability. Hp reduces the expression of the transcription factor USF1 shown to stabilise p53 in response to genotoxic stress. We investigated whether Hp-me...


    pub_type: 杂志文章


    authors: Costa L,Corre S,Michel V,Le Luel K,Fernandes J,Ziveri J,Jouvion G,Danckaert A,Mouchet N,Da Silva Barreira D,Torres J,Camorlinga M,D'Elios MM,Fiette L,De Reuse H,Galibert MD,Touati E

    更新日期:2020-09-01 00:00:00

  • Effects of chronic oral cimetidine on apparent liver blood flow and hepatic microsomal enzyme activity in man.

    abstract::Cimetidine 200 mg three times daily and 400 mg at night was given to 10 subjects for four weeks. Apparent liver blood flow was measured by indocyanine green clearance and microsomal enzyme activity by antipyrine clearance, before and after cimetidine. There was no reduction in indocyanine green clearance but antipyrin...


    pub_type: 杂志文章


    authors: Daneshmend TK,Ene MD,Parker G,Roberts CJ

    更新日期:1984-02-01 00:00:00

  • Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery.

    abstract::The major end products of fermentation, short chain fatty acids (acetate, propionate, butyrate) were measured in portal and peripheral venous blood after the caecal instillation of lactulose at surgery in patients undergoing elective cholecystectomy. Blood samples for short chain fatty acid measurement were taken befo...


    pub_type: 杂志文章


    authors: Peters SG,Pomare EW,Fisher CA

    更新日期:1992-09-01 00:00:00

  • Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells).

    abstract:BACKGROUND:Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. OBJEC...


    pub_type: 杂志文章


    authors: Puthia M,Storm P,Nadeem A,Hsiung S,Svanborg C

    更新日期:2014-01-01 00:00:00

  • Comparison of magnetic resonance imaging colonography with conventional colonoscopy for the assessment of intestinal inflammation in patients with inflammatory bowel disease: a feasibility study.

    abstract:AIM:Magnetic resonance imaging (MRI) based colonography represents a new imaging tool which has mainly been investigated for polyp screening. To evaluate this approach for patients with inflammatory bowel disease (IBD), we compared MRI based colonography with conventional colonoscopy for assessing the presence and exte...


    pub_type: 杂志文章


    authors: Schreyer AG,Rath HC,Kikinis R,Völk M,Schölmerich J,Feuerbach S,Rogler G,Seitz J,Herfarth H

    更新日期:2005-02-01 00:00:00

  • Detection of small hepatocellular carcinomas in cirrhotic livers using iodised oil computed tomography.

    abstract:BACKGROUND:The detection of hepatocellular cancers (HCC) is a major role of preoperative imaging in patients with end stage liver disease being considered for orthotopic liver transplantation (OLT). AIMS:To assess the sensitivity of iodised oil computed tomography (IOCT). PATIENTS AND METHODS:A prospective evaluation...


    pub_type: 杂志文章


    authors: Saada J,Bhattacharya S,Dhillon AP,Dick R,Burroughs AK,Rolles K,Davidson BR

    更新日期:1997-09-01 00:00:00

  • Chronic painless pancreatitis.

    abstract::This paper describes four patients whose chief symptoms were steatorrhoea and loss of weight. Despite the absence of a history of abdominal pain investigations showed that these patients had chronic pancreatitis, which responded to medical treatment. The pathological findings in two of these cases and in six which cam...


    pub_type: 杂志文章



    更新日期:1962-09-01 00:00:00

  • Massive hepatic resection for the carcinoid syndrome.

    abstract::Removal of the right lobe of the liver which was occupied largely by metastases, together with resection of ileal primary tumours, brought about complete remission of symptoms and signs in a 43-year-old man with a six-year history of the carcinoid syndrome. Investigations should be orientated toward surgery. When prac...


    pub_type: 杂志文章


    authors: Zeegen R,Rothwell-Jackson R,Sandler M

    更新日期:1969-08-01 00:00:00

  • Trypsinogen variants in pancreatic juice of healthy volunteers, chronic alcoholics, and patients with pancreatitis and cancer of the pancreas.

    abstract::Polyacrylamide gel electrophoresis of pure pancreatic juice from 14 healthy normal subjects, 11 chronic alcoholics without detectable pancreatic disease, 15 patients with pancreatitis, and two with cancer of the pancreas consistently demonstrated the presence of two variants of trypsinogen with different electrophoret...


    pub_type: 杂志文章


    authors: Rinderknecht H,Renner IG,Carmack C

    更新日期:1979-10-01 00:00:00

  • Pectin and complications after gastric surgery: normalisation of postprandial glucose and endocrine responses.

    abstract::Pectin has been shown to minimise the fall in blood glucose seen in patients who are troubled by hypoglycaemia attacks after gastric surgery. We therefore performed 50 g glucose tolerance tests with and without 14.5 g pectin on 11 post-gastric surgery patients. After pectin, the high postprandial levels of glucose, in...


    pub_type: 杂志文章


    authors: Jenkins DJ,Bloom SR,Albuquerque RH,Leeds AR,Sarson DL,Metz GL,Alberti KG

    更新日期:1980-07-01 00:00:00

  • The effect of heritability and host genetics on the gut microbiota and metabolic syndrome.

    abstract:OBJECTIVE:Metabolic syndrome (MetS) arises from complex interactions between host genetic and environmental factors. Although it is now widely accepted that the gut microbiota plays a crucial role in host metabolism, current knowledge on the effect of host genetics on specific gut microbes related to MetS status remain...


    pub_type: 杂志文章


    authors: Lim MY,You HJ,Yoon HS,Kwon B,Lee JY,Lee S,Song YM,Lee K,Sung J,Ko G

    更新日期:2017-06-01 00:00:00

  • Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates.

    abstract:OBJECTIVE AND DESIGN:The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6-9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mu...


    pub_type: 杂志文章


    authors: Sievers CK,Zou LS,Pickhardt PJ,Matkowskyj KA,Albrecht DM,Clipson L,Bacher JW,Pooler BD,Moawad FJ,Cash BD,Reichelderfer M,Vo TN,Newton MA,Larget BR,Halberg RB

    更新日期:2017-12-01 00:00:00

  • Race-dependent association of sulfidogenic bacteria with colorectal cancer.

    abstract:OBJECTIVE:Colorectal cancer (CRC) incidence is higher in African Americans (AAs) compared with non-Hispanic whites (NHWs). A diet high in animal protein and fat is an environmental risk factor for CRC development. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC. Hy...


    pub_type: 杂志文章,多中心研究


    authors: Yazici C,Wolf PG,Kim H,Cross TL,Vermillion K,Carroll T,Augustus GJ,Mutlu E,Tussing-Humphreys L,Braunschweig C,Xicola RM,Jung B,Llor X,Ellis NA,Gaskins HR

    更新日期:2017-11-01 00:00:00

  • Mechanism and specificity of increased amylase/creatinine clearance ratio in pancreatitis.

    abstract::The amylase/creatinine clearance ratio (Cam/Ccr ratio) was determined in 239 subjects. In 87 hospitalised patients without pancreatic disease (controls) the Cam/Ccr ratio was 3.02 +/- 0.69 (mean +/- ISD). The ratio was above the normal range in all patients with acute pancreatitis but was normal in those with chronic ...


    pub_type: 杂志文章


    authors: Marten A,Beales D,Elias E

    更新日期:1977-09-01 00:00:00