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7064. Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases.
作者: Xavier Verhelst.;Ana M Dias.;Jean-Frederic Colombel.;Severine Vermeire.;Hans Van Vlierberghe.;Nico Callewaert.;Salomé S Pinho.
来源: Gastroenterology. 2020年158卷1期95-110页
Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy.
7067. Time Trends in Adherence to Surveillance Intervals and Biopsy Protocol Among Patients With Barrett's Esophagus.
作者: Sachin Wani.;J Lucas Williams.;Srinadh Komanduri.;V Raman Muthusamy.;Nicholas J Shaheen.
来源: Gastroenterology. 2020年158卷3期770-772.e2页 7068. Identification of a γc Receptor Antagonist That Prevents Reprogramming of Human Tissue-resident Cytotoxic T Cells by IL15 and IL21.
作者: Cezary Ciszewski.;Valentina Discepolo.;Alain Pacis.;Nick Doerr.;Olivier Tastet.;Toufic Mayassi.;Mariantonia Maglio.;Asjad Basheer.;Laith Q Al-Mawsawi.;Peter H R Green.;Renata Auricchio.;Riccardo Troncone.;Thomas A Waldmann.;Nazli Azimi.;Yutaka Tagaya.;Luis B Barreiro.;Bana Jabri.
来源: Gastroenterology. 2020年158卷3期625-637.e13页
Gamma chain (γc) cytokines (interleukin [IL]2, IL4, IL7, IL9, IL15, and IL21) signal via a common γc receptor. IL2 regulates the immune response, whereas IL21 and IL15 contribute to development of autoimmune disorders, including celiac disease. We investigated whether BNZ-2, a peptide designed to inhibit IL15 and IL21, blocks these cytokines selectively and its effects on intraepithelial cytotoxic T cells.
7069. Identification and Validation of MicroRNA Profiles in Fecal Samples for Detection of Colorectal Cancer.
作者: Saray Duran-Sanchon.;Lorena Moreno.;Josep M Augé.;Miquel Serra-Burriel.;Míriam Cuatrecasas.;Leticia Moreira.;Agatha Martín.;Anna Serradesanferm.;Àngels Pozo.;Rosa Costa.;Antonio Lacy.;Maria Pellisé.;Juan José Lozano.;Meritxell Gironella.;Antoni Castells.
来源: Gastroenterology. 2020年158卷4期947-957.e4页
Screening for colorectal cancer (CRC) is effective in the population at average risk. The most extended strategy in organized programs involves the fecal immunochemical test, which is limited by low sensitivity for the detection of advanced adenomas (AAs). We aimed to identify microRNA (miRNA) signatures in fecal samples that identify patients with AAs or CRC and might be used in noninvasive screening.
7071. Pathways of Colorectal Carcinogenesis.
Colorectal cancer is a heterogeneous disease that develops via stepwise accumulation of well-characterized genetic and epigenetic alterations. We review the genetic changes associated with the development of precancerous colorectal adenomas and their progression to tumors, as well as the effects of defective DNA repair, chromosome instability, microsatellite instability, and alterations in the serrated pathway and DNA methylation. We provide insights into the different molecular subgroups of colorectal tumors that develop via each of these different mechanisms and their associations with patient outcomes.
7072. Therapeutic Targeting of the Colorectal Tumor Stroma.
作者: Wolf H Fridman.;Ian Miller.;Catherine Sautès-Fridman.;Annette T Byrne.
来源: Gastroenterology. 2020年158卷2期303-321页
Colorectal tumors have been classified based on histologic factors, genetic factors, and consensus molecular subtypes, all of which affect the tumor microenvironment. Elements of the tumor microenvironment serve as therapeutic targets and might be used as prognostic factors. For example, immune checkpoint inhibitors are used to treat tumors with microsatellite instability, and anti-angiogenic agents may be used in combination with other drugs to slow or inhibit tumor growth. We review the features of the colorectal tumor stroma that are associated with patient outcomes and discuss potential therapeutic agents that target these features.
7074. Chromosome Engineering of Human Colon-Derived Organoids to Develop a Model of Traditional Serrated Adenoma.
作者: Kenta Kawasaki.;Masayuki Fujii.;Shinya Sugimoto.;Keiko Ishikawa.;Mami Matano.;Yuki Ohta.;Kohta Toshimitsu.;Sirirat Takahashi.;Naoki Hosoe.;Shigeki Sekine.;Takanori Kanai.;Toshiro Sato.
来源: Gastroenterology. 2020年158卷3期638-651.e8页
Traditional serrated adenomas (TSAs) are rare colorectal polyps with unique histologic features. Fusions in R-spondin genes have been found in TSAs, but it is not clear whether these are sufficient for TSA development, due to the lack of a chromosome engineering platform for human tissues. We studied the effects of fusions in R-spondin genes and other genetic alterations found in TSA using CRISPR-Cas9-mediated chromosome and genetic modification of human colonic organoids.
7076. Does Colon Polyp Surveillance Improve Patient Outcomes?
Colon polyp surveillance now accounts for 25% of all colonoscopies performed. The evidence that colonoscopy surveillance reduces colorectal cancer (CRC) incidence or mortality is weak. The biology of the baseline lesions and quality of the baseline exam are two primary factors contributing to post-colonoscopy CRC. Prior recommendations for surveillance were based largely on the likelihood that patients with adenomas would develop advanced adenomas, a surrogate for CRC. There is now evidence that baseline colonoscopy findings are strongly associated with the risk of incidence or death from CRC. This evidence provides a basis for updated evidence-based recommendations for surveillance. In addition, there is also growing evidence that the quality of the baseline exam is an important predictor of the likelihood of developing post-colonoscopy CRC.
7077. Predominantly Antibiotic-resistant Intestinal Microbiome Persists in Patients With Pouchitis Who Respond to Antibiotic Therapy.
作者: Vadim Dubinsky.;Leah Reshef.;Nir Bar.;Danielle Keizer.;Noam Golan.;Keren Rabinowitz.;Lihi Godny.;Karin Yadgar.;Keren Zonensain.;Hagit Tulchinsky.;Uri Gophna.;Iris Dotan.
来源: Gastroenterology. 2020年158卷3期610-624.e13页
Pouchitis that develops in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis is usually treated with antibiotics. Some patients have recurrence of flares, or become antibiotic-dependent, and require repeated courses or prolonged periods of antibiotic therapy. We investigated microbial factors associated with response to antibiotic treatment and development of antibiotic dependence in patients with pouchitis.
7079. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease.
作者: Aleksejs Sazonovs.;Nicholas A Kennedy.;Loukas Moutsianas.;Graham A Heap.;Daniel L Rice.;Mark Reppell.;Claire M Bewshea.;Neil Chanchlani.;Gareth J Walker.;Mandy H Perry.;Timothy J McDonald.;Charlie W Lees.;J R Fraser Cummings.;Miles Parkes.;John C Mansfield.;Peter M Irving.;Jeffrey C Barrett.;Dermot McGovern.;James R Goodhand.;Carl A Anderson.;Tariq Ahmad.; .
来源: Gastroenterology. 2020年158卷1期189-199页
Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.
7080. Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis.
作者: Ikuo Hirano.;Evan S Dellon.;Jennifer D Hamilton.;Margaret H Collins.;Kathryn Peterson.;Mirna Chehade.;Alain M Schoepfer.;Ekaterina Safroneeva.;Marc E Rothenberg.;Gary W Falk.;Yehudith Assouline-Dayan.;Qiong Zhao.;Zhen Chen.;Brian N Swanson.;Gianluca Pirozzi.;Leda Mannent.;Neil M H Graham.;Bolanle Akinlade.;Neil Stahl.;George D Yancopoulos.;Allen Radin.
来源: Gastroenterology. 2020年158卷1期111-122.e10页
Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL) 4 receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE.
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