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4081. Identification of Reduced ERAP2 Expression and a Novel HLA Allele as Components of a Risk Score for Susceptibility to Liver Injury Due to Amoxicillin-Clavulanate.
作者: Paola Nicoletti.;Andrew Dellinger.;Yi Ju Li.;Huiman X Barnhart.;Naga Chalasani.;Robert J Fontana.;Joseph A Odin.;Jose Serrano.;Andrew Stolz.;Amy S Etheridge.;Federico Innocenti.;Olivier Govaere.;Jane I Grove.;Camilla Stephens.;Guruprasad P Aithal.;Raul J Andrade.;Einar S Bjornsson.;Ann K Daly.;M Isabel Lucena.;Paul B Watkins.; .; .; .
来源: Gastroenterology. 2023年164卷3期454-466页
Drug-induced liver injury (DILI) due to amoxicillin-clavulanate (AC) has been associated with HLA-A∗02:01, HLA-DRB1∗15:01, and rs2476601, a missense variant in PTPN22. The aim of this study was to identify novel risk factors for AC-DILI and to construct a genetic risk score (GRS).
4085. Race and Ethnicity, Stage-Specific Mortality, and Cancer Treatment in Esophageal and Gastric Cancers: Surveillance, Epidemiology, and End Results (2000-2018).
作者: Omonefe O Omofuma.;Michael B Cook.;Christian C Abnet.;M Constanza Camargo.
来源: Gastroenterology. 2023年164卷3期473-475.e4页 4087. PTEN Deficiency Facilitates Exosome Secretion and Metastasis in Cholangiocarcinoma by Impairing TFEB-mediated Lysosome Biogenesis.
作者: Tian-Yi Jiang.;Yuan-Yuan Shi.;Xiao-Wen Cui.;Yu-Fei Pan.;Yun-Kai Lin.;Xiao-Fan Feng.;Zhi-Wen Ding.;Chun Yang.;Ye-Xiong Tan.;Li-Wei Dong.;Hong-Yang Wang.
来源: Gastroenterology. 2023年164卷3期424-438页
In eukaryotes, the ubiquitin-proteasome system and the autophagy-lysosome pathway are essential for maintaining cellular proteostasis and associated with cancer progression. Our previous studies have demonstrated that phosphatase and tensin homolog (PTEN), one of the most frequently mutated genes in human cancers, limits proteasome abundance and determines chemosensitivity to proteasome inhibitors in cholangiocarcinoma (CCA). However, whether PTEN regulates the lysosome pathway remains unclear.
4090. Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth and Metabolic Reprogramming Leading to Chemoresistance.
作者: Sumeet Solanki.;Katherine Sanchez.;Varun Ponnusamy.;Vasudha Kota.;Hannah N Bell.;Chun-Seok Cho.;Allison H Kowalsky.;Michael Green.;Jun Hee Lee.;Yatrik M Shah.
来源: Gastroenterology. 2023年164卷3期376-391.e13页
Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear.
4094. Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression.
作者: Verawan Boonsanay.;Mohammed H Mosa.;Mario Looso.;Dieter Weichenhan.;Fatih Ceteci.;Lorenz Pudelko.;Andre Lechel.;Christian S Michel.;Carsten Künne.;Henner F Farin.;Christoph Plass.;Florian R Greten.
来源: Gastroenterology. 2023年164卷2期214-227页
Epigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.
4095. Hepatocyte Kctd17 Inhibition Ameliorates Glucose Intolerance and Hepatic Steatosis Caused by Obesity-induced Chrebp Stabilization.
作者: Ah-Reum Oh.;Yelin Jeong.;Junjie Yu.;Dao Thi Minh Tam.;Jin Ku Kang.;Young Hoon Jung.;Seung-Soon Im.;Sang Bae Lee.;Dongryeol Ryu.;Utpal B Pajvani.;KyeongJin Kim.
来源: Gastroenterology. 2023年164卷3期439-453页
Obesity predisposes to type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD), but underlying mechanisms are incompletely understood. Potassium channel tetramerization domain-containing protein 17 (Kctd17) levels are increased in livers from obese mice and humans. In this study, we investigated the mechanism of increased Kctd17 and whether it is causal to obesity-induced metabolic complications.
4096. N-glycosylation Regulates Intrinsic IFN-γ Resistance in Colorectal Cancer: Implications for Immunotherapy.
作者: Julia Krug.;Gabriele Rodrian.;Katja Petter.;Hai Yang.;Svetlana Khoziainova.;Wei Guo.;Alan Bénard.;Susanne Merkel.;Susan Gellert.;Simone Maschauer.;Monika Spermann.;Maximilian Waldner.;Peter Bailey.;Christian Pilarsky.;Andrea Liebl.;Philipp Tripal.;Jan Christoph.;Elisabeth Naschberger.;Roland Croner.;Vera S Schellerer.;Christoph Becker.;Arndt Hartmann.;Thomas Tüting.;Olaf Prante.;Robert Grützmann.;Sergei I Grivennikov.;Michael Stürzl.;Nathalie Britzen-Laurent.
来源: Gastroenterology. 2023年164卷3期392-406.e5页
Advanced colorectal carcinoma (CRC) is characterized by a high frequency of primary immune evasion and refractoriness to immunotherapy. Given the importance of interferon (IFN)-γ in CRC immunosurveillance, we investigated whether and how acquired IFN-γ resistance in tumor cells would promote tumor growth, and whether IFN-γ sensitivity could be restored.
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