Abstract:
OBJECTIVE:To develop gene expression profiles that characterise KRAS-, BRAF- or PIK3CA-activated- tumours, and to explore whether these profiles might be helpful in predicting the response to the epidermal growth factor receptor (EGFR) pathway inhibitors better than mutation status alone. DESIGN:Fresh frozen tumour samples from 381 colorectal cancer (CRC) patients were collected and mutations in KRAS, BRAF and PIK3CA were assessed. Using microarray data, three individual oncogenic and a combined model were developed and validated in an independent set of 80 CRC patients, and in a dataset from metastatic CRC patients treated with cetuximab. RESULTS:175 tumours (45.9%) harboured oncogenic mutations in KRAS (30.2%), BRAF (11.0%) and PIK3CA (11.5%). Activating mutation signatures for KRAS (75 genes), for BRAF (58 genes,) and for PIK3CA (49 genes) were developed. The development of a combined oncogenic pathway signature-classified tumours as 'activated oncogenic', or as 'wildtype-like' with a sensitivity of 90.3% and a specificity of 61.7%. The identified signature revealed other mechanisms that can activate ERK/MAPK pathway in KRAS, BRAF and PIK3CA wildtype patients. The combined signature is associated with response to cetuximab treatment in patients with metastatic CRC (HR 2.51, p<0.0009). CONCLUSION:A combined oncogenic pathway signature allows the identification of patients with an active EGFR-signalling pathway that could benefit from downstream pathway inhibition.
journal_name
Gutjournal_title
Gutauthors
Tian S,Simon I,Moreno V,Roepman P,Tabernero J,Snel M,van't Veer L,Salazar R,Bernards R,Capella Gdoi
10.1136/gutjnl-2012-302423subject
Has Abstractpub_date
2013-04-01 00:00:00pages
540-9issue
4eissn
0017-5749issn
1468-3288pii
gutjnl-2012-302423journal_volume
62pub_type
杂志文章相关文献
GUT文献大全abstract::The response of lymphocytes from peripheral blood and mesenteric lymph nodes to stimulation with phytohaemagglutinin in vitro has been studied in eight patients suffering from active Crohn's disease. Patients with Crohn's disease exhibited reduced responses when compared with similar studies performed in control subje...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.14.1.20
更新日期:1973-01-01 00:00:00
abstract::A dodecapeptide of A-gliadin, which shares amino acid homologies with the E1b protein of adenovirus 12, was used to produce murine monoclonal antibodies. Five monoclonal antibodies were produced and were screened by enzyme linked immunosorbant assay, immunodot assay, and immunoblotting. The antibodies were tested agai...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.33.11.1504
更新日期:1992-11-01 00:00:00
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...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.34.8.1091
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND:Hypersensitivity of gastric afferent pathways may play an aetiological role in symptoms of functional dyspepsia. AIMS:To determine whether patients with severe organic dyspepsia (associated with tissue irritation/injury) and those with functional dyspepsia (no detectable tissue irritation) differ in their p...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.42.6.814
更新日期:1998-06-01 00:00:00
abstract:OBJECTIVE:We aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC). DESIGN:Large cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational s...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2018-317632
更新日期:2019-07-01 00:00:00
abstract::Options for managing the common bile duct during laparoscopic cholecystectomy include routine peroperative cholangiography and selected preoperative endoscopic retrograde cholangiopancreatography (ERCP). The use of these methods was reviewed in 350 patients with symptomatic gall stones referred for laparoscopic cholec...
journal_title:Gut
pub_type: 杂志文章,多中心研究
doi:10.1136/gut.35.7.991
更新日期:1994-07-01 00:00:00
abstract::Liver regeneration is the common mechanism whereby a patient recovers form a liver injury. In the western world, ethanol is the single most important aetiological factor associated with liver disease, and it appears crucial to determine if ethanol interferes with liver regeneration. We studied the response to a 70% he...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.23.1.8
更新日期:1982-01-01 00:00:00
abstract::Progress in the management of hepatocellular carcinoma (HCC) has been slow and has limited impact on outcome. Most patients with HCC have two diseases--chronic liver disease and HCC--and complex interactions between the two have major implications for diagnosis and prognosis as well as the management of HCC. The disea...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gut.51.4.459
更新日期:2002-10-01 00:00:00
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...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2011-300207
更新日期:2012-04-01 00:00:00
abstract::A case is described of non-necrotizing, epithelioid cell granulomatous synovitis of the ankle of a 22-year-old man with Crohn's disease. It appears to be the first published example of granulomatous arthritis in association with Crohn's disease. ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.13.4.257
更新日期:1972-04-01 00:00:00
abstract::Little is known about chronic constipation in infants, toddlers, and preschool children and longterm outcome after treatment. The symptoms of 174 children < or = 4 years of age, who were evaluated for chronic constipation, are reported in this study together with the long-term outcome in 90 of them. Initial symptoms w...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.34.10.1400
更新日期:1993-10-01 00:00:00
abstract::A patient presented with pruritus and recent elevation of aminotransferases. The case fulfilled most of the criteria for the diagnosis of autoimmune hepatitis and achieved clinical and complete biochemical response to steroid therapy. However, the liver biopsy specimen revealed an unusual histological pattern consisti...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.41.2.269
更新日期:1997-08-01 00:00:00
abstract::The effects of the methyl ester analogue of prostaglandin E1, misoprostol, on gastric epithelial cell proliferation were investigated in six dogs given 300 micrograms/kg/day of misoprostol orally for 11 weeks and in six control dogs given placebo for 11 weeks. Misoprostol treatment resulted in a 36% increase in stomac...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.30.3.316
更新日期:1989-03-01 00:00:00
abstract:OBJECTIVE:Guidelines mandate expert pathology review of Barrett's oesophagus (BO) biopsies that reveal dysplasia, but there are no evidence-based standards to corroborate expert reviewer status. We investigated BO concordance rates and pathologist features predictive of diagnostic discordance. DESIGN:Pathologists (n=5...
journal_title:Gut
pub_type: 杂志文章,多中心研究
doi:10.1136/gutjnl-2019-318985
更新日期:2020-05-01 00:00:00
abstract:AIMS:To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda. PATIENTS:Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites. METHODS:Stools and biopsy specimens were examined for enteropathogens....
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.43.3.350
更新日期:1998-09-01 00:00:00
abstract::T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the exp...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.34.10.1452
更新日期:1993-10-01 00:00:00
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...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.27.7.873
更新日期:1986-07-01 00:00:00
abstract::Fifteen patients with severe intractable irritable bowel syndrome previously reported as successfully treated with hypnotherapy, have now been followed up for a mean duration of 18 months. All patients remain in remission although two have experienced a single relapse overcome by an additional session of hypnotherapy....
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.28.4.423
更新日期:1987-04-01 00:00:00
abstract::A 45 year old man is described with Whipple's disease who presented with weight loss, lethargy, and ascites. He subsequently developed fever and a mass in the neck, but died despite antibiotic treatment and nutritional support. Necropsy showed extraintestinal lymphoma. ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.34.11.1627
更新日期:1993-11-01 00:00:00
abstract::Lymphocytic gastritis is a new histopathological entity characterised by a dense lymphocytic infiltration of surface and pit gastric epithelium. Previous retrospective work has suggested that lymphocytic gastritis is related to an endoscopic form of gastropathy comprising enlarged folds, nodules and erosions, commonly...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.31.3.282
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:Suicide gene therapy consists of the transfer into tumour cells of a "suicide" gene that can convert a non-toxic compound into a lethal drug. Expression of the cytosine deaminase gene leads to the conversion of the non-toxic compound 5-fluorocytosine to 5-fluorouracil. We have recently shown that "suicide ce...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.50.3.387
更新日期:2002-03-01 00:00:00
abstract::The value of the bipolar electrocoagulator in the haemostasis of bleeding ulcers is controversial. We have therefore investigated the effect of different coagulation times on vessel weld strength achieved by the bipolar device. Welds were then made in vessels of known diameter using a standard 10F endoscopic haemostat...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.32.2.188
更新日期:1991-02-01 00:00:00
abstract::By prolonged immunization of an inbred rat strain with isologous liver homogenate in Freund's complete adjuvant a low grade autoimmune ;cholangitis' with periductular fibrosis has been demonstrated. The lesion could be transferred to isogeneic animals by serial spleen cell injections and was associated with mild but v...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.12.6.458
更新日期:1971-06-01 00:00:00
abstract::Upper gastrointestinal function in response to a mixed nutrient meal was evaluated in hyperthyroid patients, both before and after therapy, and in healthy controls. Gastric secretion, gastric emptying, and pancreatic secretion were all normal and normally integrated postprandially in the hyperthyroid patients. Bile ac...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.21.8.695
更新日期:1980-08-01 00:00:00
abstract::Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited d...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gut.52.suppl_2.ii31
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Treatment of Helicobacter pylori infection prevents duodenal ulcer relapse. It has not been established if treatment of the infection heals duodenal ulcer. AIM:To test the hypothesis that treatment of the infection was associated with healing of duodenal ulcer. METHODS:A randomised, double blind placebo co...
journal_title:Gut
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/gut.41.1.43
更新日期:1997-07-01 00:00:00
abstract:OBJECTIVE:Chronic pancreatitis is a progressive inflammatory disorder of the pancreas characterised by permanent destruction of acinar cells. Mutations in the chymotrypsinogen C (CTRC) gene have been linked to the development of chronic pancreatitis. The aim of the present study was to explore whether CTRC mutants indu...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2009.198903
更新日期:2010-03-01 00:00:00
abstract::The purpose of this single blind controlled multicentre trial was to compare the relative effectiveness of pirenzepine and cimetidine in healing endoscopically proven duodenal ulcers. One hundred and twenty six patients with duodenal ulcer were treated with a daily dose of 100 mg pirenzepine (50 mg each before breakfa...
journal_title:Gut
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/gut.25.2.206
更新日期:1984-02-01 00:00:00
abstract::The carrier rate of hepatitis B virus (HBV) in black Africans averages 10.4% throughout the continent. Even within each country, however, there may be wide variations. HBV carriage in black Africans is largely established in early childhood, mostly through horizontal transmission. Perinatal transmission also occurs bu...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gut.38.suppl_2.s31
更新日期:1996-01-01 00:00:00
abstract::Alcohol tolerance has been studied in 10 patients after proximal gastric vagotomy and six patients after truncal vagotomy and antrectomy. No difference in alcohol tolerance was found before and after proximal gastric vagotomy, while an increased rate of absorption with higher blood levels of alcohol were found after t...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.16.12.966
更新日期:1975-12-01 00:00:00