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Cun Wang, Hui Wang, Cor Lieftink, Aimee du Chatinier, Dongmei Gao, Guangzhi Jin, Haojie Jin, Roderick L Beijersbergen, Wenxin Qin, René Bernards
OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and a major leading cause of cancer-related deaths worldwide. Several therapeutic options like sorafenib and regorafenib provide only modest survival benefit to patients with HCC. This study aims to identify novel druggable candidate genes for patients with HCC. DESIGN: A non-biased CRISPR (clustered regularly interspaced short palindromic repeats) loss-of-function genetic screen targeting all known human kinases was performed to identify vulnerabilities of HCC cells...
September 13, 2019: Gut
Pim J Koelink, Felicia M Bloemendaal, Bofeng Li, Liset Westera, Esther W M Vogels, Manon van Roest, Anouk K Gloudemans, Angelique B van 't Wout, Hannelie Korf, Séverine Vermeire, Anje A Te Velde, Cyriel Y Ponsioen, Geert Ram D'Haens, J Sjef Verbeek, Terrence L Geiger, Manon E Wildenberg, Gijs R van den Brink
OBJECTIVE: Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined. DESIGN: We used human peripheral blood monocytes and mouse bone marrow-derived macrophages to study IL-10 production and CD206+ regulatory macrophage differentiation...
September 10, 2019: Gut
Eszter Hegyi, Anna Zsófia Tóth, Áron Vincze, Andrea Szentesi, Péter Hegyi, Miklós Sahin-Tóth
No abstract text is available yet for this article.
September 10, 2019: Gut
Colin J Rees, Tim M Trebble, Christian Von Wagner, Zoe Clapham, Paul Hewitson, Hugh Barr, Simon Everett, Helen Griffiths, Manu Nayar, Kofi Oppong, Stuart Riley, John Stebbing, Siwan Thomas-Gibson, Roisin Bevan
No abstract text is available yet for this article.
September 10, 2019: Gut
Zaid S Ardalan, Miles P Sparrow, Jane G Muir, Peter R Gibson
No abstract text is available yet for this article.
September 6, 2019: Gut
Rebecca L Siegel, Lindsey A Torre, Isabelle Soerjomataram, Richard B Hayes, Freddie Bray, Thomas K Weber, Ahmedin Jemal
OBJECTIVE: Early-onset colorectal cancer (CRC) is increasing in the USA despite rapid declines in older ages. Similar patterns are reported in Australia and Canada, but a comprehensive global analysis of contemporary data is lacking. DESIGN: We extracted long-term data from Cancer Incidence in Five Continents and supplemental sources to report on worldwide CRC incidence rates and trends by age (20-49 years and ≥50 years) through diagnosis year 2012 or beyond (Australia, Finland, New Zealand, Norway, Sweden, USA)...
September 5, 2019: Gut
Neal Shahidi, Michael J Bourke
No abstract text is available yet for this article.
September 3, 2019: Gut
Kecheng Liu, Mengbin Qin, Jiean Huang
No abstract text is available yet for this article.
September 3, 2019: Gut
Kevin A Bockerstett, Scott A Lewis, Kyle J Wolf, Christine N Noto, Nicholas M Jackson, Eric L Ford, Tae-Hyuk Ahn, Richard J DiPaolo
OBJECTIVE: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a regenerative lesion in the gastric mucosa and is a potential precursor to intestinal metaplasia/gastric adenocarcinoma in a chronic inflammatory setting. The goal of these studies was to define the transcriptional changes associated with SPEM at the individual cell level in response to acute drug injury and chronic inflammatory damage in the gastric mucosa. DESIGN: Epithelial cells were isolated from the gastric corpus of healthy stomachs and stomachs with drug-induced and inflammation-induced SPEM lesions...
September 3, 2019: Gut
Matteo Ghisa, Massimo Rugge, Matteo Fassan, Fabio Farinati, Edoardo Savarino
No abstract text is available yet for this article.
August 31, 2019: Gut
Min-Soo Kim, Yoonhee Kim, Hyunjung Choi, Woojin Kim, Sumyung Park, Dongjoon Lee, Dong Kyu Kim, Haeng Jun Kim, Hayoung Choi, Dong-Wook Hyun, June-Young Lee, Eun Young Choi, Dong-Sup Lee, Jin-Woo Bae, Inhee Mook-Jung
OBJECTIVE: Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer's disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive. DESIGN: Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT ) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis...
August 30, 2019: Gut
Xiafei Hong, Sitan Qiao, Fuqiang Li, Wenze Wang, Rui Jiang, Huanwen Wu, Hao Chen, Lulu Liu, Junya Peng, Jing Wang, Congwei Jia, Xiaolong Liang, Hongmei Dai, Jialin Jiang, Taiping Zhang, Quan Liao, Menghua Dai, Lin Cong, Xianlin Han, Dan Guo, Zhiyong Liang, Dongjing Li, Zetian Zheng, Chen Ye, Siliang Li, Yupei Zhao, Kui Wu, Wenming Wu
OBJECTIVE: Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs. DESIGN: The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium...
August 28, 2019: Gut
Melinda Y Hardy, Amy K Russell, Catherine Pizzey, Claerwen M Jones, Katherine A Watson, Nicole L La Gruta, Donald J Cameron, Jason A Tye-Din
OBJECTIVE: Barley and rye are major components of the Western diet, and historic feeding studies indicate that they cause clinical effects in patients with coeliac disease (CD). This toxicity has been attributed to sequence homology with immunogenic wheat sequences, but in adults with CD, these cereals stimulate unique T cells, indicating a critical contribution to gluten immunity independent of wheat. Clinical and immune feeding studies with these grains in children with CD are sparse...
August 28, 2019: Gut
Kin Seng Liem, Scott Fung, David K Wong, Colina Yim, Seham Noureldin, Jiayun Chen, Jordan J Feld, Bettina E Hansen, Harry L A Janssen
OBJECTIVE: Although most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, we evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy. DESIGN: Patients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks...
August 28, 2019: Gut
Carlo Senore, Marco Zappa, Cinzia Campari, Sergio Crotta, Paola Armaroli, Arrigo Arrigoni, Paola Cassoni, Rossana Colla, Mario Fracchia, Fabrizio Gili, Grazia Grazzini, Roberto Lolli, Patrizia Menozzi, Lorenzo Orione, Salvatore Polizzi, Stefano Rapi, Emilia Riggi, Tiziana Rubeca, Romano Sassatelli, Carmen Visioli, Nereo Segnan
OBJECTIVE: To estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer-CRC-or advanced adenoma). DESIGN: Prospective cohort of subjects aged 50-69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy. METHODS: All programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces)...
August 27, 2019: Gut
Julien Kirchgesner, Nynne Nyboe Andersen, Fabrice Carrat, Tine Jess, Laurent Beaugerie
OBJECTIVE: Patients with IBD are at increased risk of acute arterial events. Antitumour necrosis factor (TNF) agents and thiopurines may, via their anti-inflammatory properties, lower the risk of acute arterial events. The aim of this study was to assess the impact of thiopurines and anti-TNFs on the risk of acute arterial events in patients with IBD. DESIGN: Patients aged 18 years or older and affiliated to the French national health insurance with a diagnosis of IBD were followed up from 1 April 2010 until 31 December 2014...
August 24, 2019: Gut
Yiwei Xiao, Kuixia Sun, Zhongping Duan, Zhixiu Liu, Yi Li, Ling Yan, Yarong Song, Huaibin Zou, Hui Zhuang, Jie Wang, Jie Li
OBJECTIVE: This study was performed to explore the correlation between the characteristics of hepatitis B virus (HBV) quasispecies in HBV-infected pregnant women and the risk of immunoprophylaxis failure for their infants. DESIGN: In this prospective nested case-control study, the characteristics of HBV quasispecies in mothers whose infants were immunoprophylaxis success (control group) and those whose infants were immunoprophylaxis failure (case group) were analysed by the clone-based sequencing of full-length HBV genome and next-generation sequencing (NGS) of "a" determinant region, and were compared between the two groups...
August 24, 2019: Gut
Jialing Shen, Mengnuo Chen, Derek Lee, Cheuk-Ting Law, Lai Wei, Felice Ho-Ching Tsang, Don Wai-Ching Chin, Carol Lai-Hung Cheng, Joyce Man-Fong Lee, Irene Oi-Lin Ng, Carmen Chak-Lui Wong, Chun-Ming Wong
OBJECTIVE: Facilitates Chromatin Transcription (FACT) complex is a histone chaperone participating in DNA repair-related and transcription-related chromatin dynamics. In this study, we investigated its oncogenic functions, underlying mechanisms and therapeutic implications in human hepatocellular carcinoma (HCC). DESIGN: We obtained HCC and its corresponding non-tumorous liver samples from 16 patients and identified FACT complex as the most upregulated histone chaperone by RNA-Seq...
August 22, 2019: Gut
John Joseph McGoran, Sudarshan R Kadri, Catherine Moreman, Peter Wurm
No abstract text is available yet for this article.
August 20, 2019: Gut
Jiajia Zhang, Charles Haines, Alastair J M Watson, Andrew R Hart, Mary Jane Platt, Drew M Pardoll, Sara E Cosgrove, Kelly A Gebo, Cynthia L Sears
BACKGROUND: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking. OBJECTIVE: To assess the association between oral antibiotic use and CRC risk. DESIGN: A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012. RESULTS: 28 980 CRC cases and 137 077 controls were identified...
August 19, 2019: Gut
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