{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:44:59Z","timestamp":1791665099697,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carol Davila University of Medicine and Pharmacy, Bucharest"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Hypoxia was intensively studied in cancer during the last few decades, being considered a characteristic of the tumor microenvironment. The aim of the study was to evaluate the capacity of tumor cells to adapt to the stress generated by limited oxygen tissue in cutaneous melanoma. We developed a case\u2013control prospective study that included 52 patients with cutaneous melanoma and 35 healthy subjects. We focused on identifying and monitoring hypoxia, the dynamic of nitric oxide (NO) serum metabolites and posttranslational metabolic disorders induced by NO signaling according to the clinical, biological and tumoral characteristics of the melanoma patients. Our study showed high levels of hypoxia-inducible factor-1a (HIF-1a) and hypoxia-inducible factor-2a (HIF-2a) in the melanoma patients. Hypoxia-inducible factors (HIFs) control the capacity of tumor cells to adapt to low levels of oxygen. Hypoxia regulated the nitric oxide synthase (NOS) expression and activity. In the cutaneous melanoma patients, disorders in NO metabolism were detected. The serum levels of the NO metabolites were significantly higher in the melanoma patients. NO signaling influenced the tumor microenvironment by modulating tumoral proliferation and sustaining immune suppression. Maintaining NO homeostasis in the hypoxic tumoral microenvironment could be considered a future therapeutic target in cutaneous melanoma.<\/jats:p>","DOI":"10.3390\/jpm12101646","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T01:43:11Z","timestamp":1665279791000},"page":"1646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hypoxia-Nitric Oxide Axis and the Associated Damage Molecular Pattern in Cutaneous Melanoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Corina Daniela","family":"Ene","sequence":"first","affiliation":[{"name":"\u201cCarol Davila\u201d Nephrology Hospital, 010731 Bucharest, Romania"},{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilinca","family":"Nicolae","sequence":"additional","affiliation":[{"name":"Dermatology Department, \u201cVictor Babes\u201d Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/s41598-022-05161-7","article-title":"Hypoxia-induced HIF1\u03b1 activation regulates small extracellular vesicle release in human embryonic kidney cells","volume":"12","author":"Romero","year":"2022","journal-title":"Sci. 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