{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:53:16Z","timestamp":1760057596002,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["UIP-2019-04-6680","DOK-2020-01-9351"],"award-info":[{"award-number":["UIP-2019-04-6680","DOK-2020-01-9351"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Globally, bladder cancer is the sixth most frequently diagnosed cancer among men. Despite the increasing availability of immunomodulatory treatments for bladder cancer, the survival rates are still low, which calls for potential new drug-repurposing targets. This study aimed to investigate the effects of cromolyn, a mast cell (MC) stabilizer in allergic reactions, on a subcutaneous tumor model with a syngeneic mouse MB49 bladder cancer cell line. A concentration of 50 mg\/kg of cromolyn was daily administered intraperitoneally in a 4-day therapeutic protocol to mice with established tumors and in a continuous 11-day protocol which started one day prior to the subcutaneous injection of tumor cells. Therapeutic treatment demonstrated a marked downregulation of genes related to angiogenesis and upregulation of genes related to cytotoxic T-cell and NK cell activity. Conversely, continuous cromolyn treatment suppressed genes involved in immune cell recruitment and activation, as well as apoptotic and necroptotic pathways, leading to a greater tumor burden (+142.4 mg [95CI + 28.42, +256.4], p = 0.0158). The same pro-tumorigenic effect was found in mast cell-deficient mice (KitW-sh\/W-sh + 301.7 mg [95CI + 87.99, 515.4], p = 0.0079; Cpa3Cre\/+ +107.2 mg [95CI \u2212 39.37, +253.57], p = 0.1423), indicating that continuous cromolyn treatment mostly acts through the inhibition of mast cell degranulation. In summary, our results demonstrate the distinct effects of cromolyn on tumor progression, which depend on the protocol of cromolyn administration.<\/jats:p>","DOI":"10.3390\/ijms26041619","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T03:20:52Z","timestamp":1739503252000},"page":"1619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pro-Tumorigenic Effect of Continuous Cromolyn Treatment in Bladder Cancer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-8286","authenticated-orcid":false,"given":"Lucija","family":"Frankovi\u0107","sequence":"first","affiliation":[{"name":"Laboratory for Cancer Research, Department of Immunology and Medical Genetics, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-9381","authenticated-orcid":false,"given":"Marina","family":"Degoricija","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Biochemistry, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Gabela","sequence":"additional","affiliation":[{"name":"Laboratory for Cancer Research, Department of Immunology and Medical Genetics, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina","family":"Vilovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic Medicine and Cytology, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Anatomy, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-9979","authenticated-orcid":false,"given":"Jelena","family":"Korac-Prlic","sequence":"additional","affiliation":[{"name":"Laboratory for Cancer Research, Department of Immunology and Medical Genetics, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","unstructured":"(2024, May 27). 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