{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:06:42Z","timestamp":1782536802156,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2024-643"],"award-info":[{"award-number":["075-15-2024-643"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives. Damage of the gastrointestinal mucosa is a major side effect of the anticancer drug 5-fluorouracil (5-FU). Insight into the molecular pathogenesis of 5-FU-induced gut mucositis is expected to justify the strategies of prophylaxis. Methods. We analyzed intestinal specimens obtained from Balb\/c mice treated with 70 mg\/kg 5-FU daily for up to 6 days. Results. Manifestations of mucositis in the ileum and the colon included diarrhea, weight loss, and morphological lesions. The proteomic analysis revealed dozens of differentially expressed proteins governed by a set of master regulator proteins that regulated downstream pathways culminating in the complexes of specific transcription factors. Among the most important mechanisms of 5-FU-induced gut damage predicted by bioinformatics tools was stimulation of insulin-like growth factor 1 concomitant with inhibition of insulin receptor substrate 1, suggesting an involvement of the insulin pathway. Furthermore, the levels of 14-3-3\u03b3 protein and epinephrin B2 tyrosine kinase were interpreted as key inhibitory effects of 5-FU. These changes were detectable in the ileum as well as in the colon, pointing to the commonality of 5-FU responses across the gut. Conclusion. These results demonstrated a hierarchical network of gut injury mechanisms differentially regulated in the course of the emergence of 5-FU-induced mucositis.<\/jats:p>","DOI":"10.3390\/cancers16234025","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T04:04:04Z","timestamp":1733198644000},"page":"4025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proteomic Analysis Identifies Multiple Mechanisms of 5-Fluorouracil-Induced Gut Mucositis in Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Sergey M.","family":"Ivanov","sequence":"first","affiliation":[{"name":"Institute of Biomedical Chemistry, 119121 Moscow, Russia"},{"name":"Department of Bioinformatics, Pirogov Russian National Research Medical University, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4532-4274","authenticated-orcid":false,"given":"Victor G.","family":"Zgoda","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, 119121 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria A.","family":"Isakova","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint-Petersburg University, 199034 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubov S.","family":"Trukhanova","sequence":"additional","affiliation":[{"name":"Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7937-2621","authenticated-orcid":false,"given":"Vladimir V.","family":"Poroikov","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, 119121 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Shtil","sequence":"additional","affiliation":[{"name":"Blokhin National Medical Research Center of Oncology, 115522 Moscow, Russia"},{"name":"Institute of Cyber Intelligence Systems, National Research Nuclear University MEPhI, 115409 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1111\/jgh.16527","article-title":"Big data approach in the field of gastric and colorectal cancer research","volume":"39","author":"Cheung","year":"2024","journal-title":"J. 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