{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:41:29Z","timestamp":1783464089383,"version":"3.55.0"},"reference-count":164,"publisher":"IMR Press","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: It is commonly believed that cancer development is irreversible, organ-specific as well as systemic malignant disorder, often associated with harmful oxidative stress and inflammation. However, there are also well-documented cases of spontaneous cancer regression, the causative mechanisms of which are not understood. It is known that inflammation is a negative pathophysiological process that may support the development of cancer, but it is also believed that the immune system as well as oxidative stress play important roles in prevention of cancer development and defense against tumor progression. Hence, in animal models spontaneous regression of cancer could be mediated by rapid inflammatory response of granulocytes, acting against cancer mostly as innate immune response. In addition, the administration of granulocytes at the site of solid tumors can lead to tumor regression or can slow down tumor growth and extend the overall survival of animals. In both cases, similar to the radiotherapy, surgery and various chemotherapies, oxidative stress occurs generating lipid peroxidation product 4-hydroxynonenal (4-HNE). This \u201csecond messenger of free radicals\u201d acts as growth regulating signaling molecule that exerts relatively selective cytotoxicity against cancer cells. Conclusions: We hypothesize that abundant inflammation and metabolic changes caused by cancer and oxidative stress producing of 4-HNE may be crucial mechanisms for spontaneous cancer regression.<\/jats:p>","DOI":"10.31083\/j.fbl2704119","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T09:21:14Z","timestamp":1649928074000},"source":"Crossref","is-referenced-by-count":14,"title":["Spontaneous Regression of Cancer: Revealing Granulocytes and Oxidative Stress as the Crucial Double-edge Sword"],"prefix":"10.31083","volume":"27","author":[{"given":"Neven","family":"\u017darkovi\u0107","sequence":"first","affiliation":[{"name":"Laboratory for Oxidative Stress (LabOS), Division of Molecular Medicine, Rudjer Boskovic Institute, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morana","family":"Jaganjac","sequence":"first","affiliation":[{"name":"Laboratory for Oxidative Stress (LabOS), Division of Molecular Medicine, Rudjer Boskovic Institute, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamelija","family":"\u017darkovi\u0107","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Zagreb School of Medicine, HR-1000 Zagreb, Croatia"},{"name":"Department of Pathology, Clinical Hospital Centre Zagreb, HR-1000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"G\u0119gotek","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bia\u0142ystok, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Skrzydlewska","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bia\u0142ystok, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. 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