ArticleGastroenterology2021
Dicarbonyl Electrophiles Mediate Inflammation-Induced Gastrointestinal Carcinogenesis.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Tooth loss and infrequent brushing significantly elevate gastric cancer risk: an updated systematic review and meta-analysis with heterogeneity exploration.Frontiers in medicine · 2026Pooled it
- Safety and Efficacy of Eflornithine in Patients with Gastric Precancerous Lesions: A Double-Blinded, Randomized Clinical Trial.Cancer prevention research (Philadelphia, Pa.) · 2026Trial
- Pulmonary arterial hypertension from a translational perspective: Bridging pathophysiology and treatment.Chinese medical journal · 2026Review
- Spermine oxidase promotes Helicobacter pylori-mediated gastric carcinogenesis through acrolein production.Oncogene · 2025Article
- Alterations in polyamine metabolism induced by the pathogen Helicobacter pylori: Implications for gastric inflammation and carcinogenesis.Methods in enzymology · 2025Article
- The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice.Amino acids · 2024Article
- Translational Utility of Organoid Models for Biomedical Research on Gastrointestinal Diseases.Stem cell reviews and reports · 2024Review
- Analysis of the effect of hypusination in myeloid cells on colitis and colitis-associated cancer.Heliyon · 2024Article
- Molecular mechanism of MLCK1 inducing 5-Fu resistance in colorectal cancer cells through activation of TNFR2/NF-κB pathway.Discover oncology · 2024Article
- Tumor therapy by targeting extracellular hydroxyapatite using novel drugs: A paradigm shift.Cancer medicine · 2024Article
- Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification.Gastroenterology · 2023Article
- Inflammation Biomarker Response to Oral 2-Hydroxybenzylamine (2-HOBA) Acetate in Healthy Humans.Inflammation · 2023Article
- Organoids: Construction and Application in Gastric Cancer.Biomolecules · 2023Review
- Electrophilic reactive aldehydes as a therapeutic target in colorectal cancer prevention and treatment.Oncogene · 2023Article
- Intestinal Lymphatic Dysfunction in Kidney Disease.Circulation research · 2023Review
- HyperCys: A Structure- and Sequence-Based Predictor of Hyper-Reactive Druggable Cysteines.International journal of molecular sciences · 2023Article
- The nutraceutical electrophile scavenger 2-hydroxybenzylamine (2-HOBA) attenuates gastric cancer development caused by Helicobacter pylori.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Protein adduction causes non-mutational inhibition of p53 tumor suppressor.Cell reports · 2023Article
- Article
- Inflammation, Lymphatics, and Cardiovascular Disease: Amplification by Chronic Kidney Disease.Current hypertension reports · 2022Review
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsInflammation in the gastrointestinal tract may lead to the development of cancer. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules. Thus, we sought to determine the role of dicarbonyl electrophiles in inflammation-associated carcinogenesis.
methodsThe formation of isoLG adducts was analyzed in the gastric tissues of patients infected with Helicobacter pylori from gastritis to precancerous intestinal metaplasia, in human gastric organoids, and in patients with colitis and colitis-associated carcinoma (CAC). The effect on cancer development of a potent scavenger of dicarbonyl electrophiles, 5-ethyl-2-hydroxybenzylamine (EtHOBA), was determined in transgenic FVB/N insulin-gastrin (INS-GAS) mice and Mongolian gerbils as models of H pylori-induced carcinogenesis and in C57BL/6 mice treated with azoxymethane-dextran sulfate sodium as a model of CAC. The effect of EtHOBA on mutations in gastric epithelial cells of H pylori-infected INS-GAS mice was assessed by whole-exome sequencing.
resultsWe show increased isoLG adducts in gastric epithelial cell nuclei in patients with gastritis and intestinal metaplasia and in human gastric organoids infected with H pylori. EtHOBA inhibited gastric carcinoma in infected INS-GAS mice and gerbils and attenuated isoLG adducts, DNA damage, and somatic mutation frequency. Additionally, isoLG adducts were elevated in tissues from patients with colitis, colitis-associated dysplasia, and CAC as well as in dysplastic tumors of C57BL/6 mice treated with azoxymethane-dextran sulfate sodium. In this model, EtHOBA significantly reduced adduct formation, tumorigenesis, and dysplasia severity.
conclusionsDicarbonyl electrophiles represent a link between inflammation and somatic genomic alterations and are thus key targets for cancer chemoprevention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.