{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:35:34Z","timestamp":1790764534934,"version":"4.1.0"},"reference-count":34,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cytokine"],"published-print":{"date-parts":[[2020,4]]},"DOI":"10.1016\/j.cyto.2019.154984","type":"journal-article","created":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T12:29:08Z","timestamp":1579523348000},"page":"154984","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["Interleukin-2 chronotherapy for metastatic renal cell carcinoma: Results of a phase I-II study"],"prefix":"10.1016","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1169-2359","authenticated-orcid":false,"given":"Giovanni Lo","family":"Re","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide A.","family":"Santeufemia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Lo","family":"Re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Bortolus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Doretto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wally","family":"Marus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Buttazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliviero","family":"Lenardon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Falda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Piazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Sulfaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.cyto.2019.154984_b0005","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.cyto.2019.154984_b0010","unstructured":"J.N. Eble, G. Sauter, J.I. Epstein,I.A. Sesterhenn, eds. Tumors of the kidney. In: World Health Organization Classification of Tumors: Pathology and Genetics, Tumors of the Urinary System and Male Genital Organs. Lyon, France: IARC Press; 2004:9\u201343."},{"issue":"2","key":"10.1016\/j.cyto.2019.154984_b0015","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.juro.2015.02.013","article-title":"Pathological stage T3a significantly increases disease recurrence across all tumor sizes in renal cell carcinoma","volume":"194","author":"Chevinsky","year":"2015","journal-title":"J. Urol."},{"issue":"4","key":"10.1016\/j.cyto.2019.154984_b0020","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1053\/j.seminoncol.2013.05.004","article-title":"Adjuvant therapy in renal cell carcinoma-past, present, and future","volume":"40","author":"Janowitz","year":"2013","journal-title":"Semin. Oncol."},{"issue":"23","key":"10.1016\/j.cyto.2019.154984_b0025","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1056\/NEJMoa1611406","article-title":"S-TRAC investigators. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy","volume":"375","author":"Ravaud","year":"2016","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.cyto.2019.154984_b0030","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ctrv.2007.12.001","article-title":"Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review","volume":"34","author":"Gupta","year":"2008","journal-title":"Cancer Treat. Rev."},{"issue":"22","key":"10.1016\/j.cyto.2019.154984_b0035","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1200\/JCO.2008.20.1293","article-title":"Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma","volume":"27","author":"Motzer","year":"2009","journal-title":"J. Clin. Oncol."},{"issue":"8","key":"10.1016\/j.cyto.2019.154984_b0040","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1056\/NEJMoa1303989","article-title":"Pazopanib versus sunitinib in metastatic renal-cell carcinoma","volume":"369","author":"Motzer","year":"2013","journal-title":"N. Engl. J. Med."},{"issue":"19","key":"10.1016\/j.cyto.2019.154984_b0045","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","article-title":"Nivolumab versus everolimus in advanced renal-cell carcinoma","volume":"373","author":"Motzer","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"14","key":"10.1016\/j.cyto.2019.154984_b0050","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1056\/NEJMoa1712126","article-title":"Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N. Engl. J. Med."},{"issue":"16","key":"10.1016\/j.cyto.2019.154984_b0055","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1200\/JCO.2003.02.122","article-title":"Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer","volume":"21","author":"Yang","year":"2003","journal-title":"J. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.cyto.2019.154984_b0060","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1200\/JCO.2005.03.206","article-title":"Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma","volume":"23","author":"McDermott","year":"2005","journal-title":"J. Clin. Oncol."},{"issue":"2","key":"10.1016\/j.cyto.2019.154984_b0065","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.116.013441","article-title":"Systems chronotherapeutics","volume":"69","author":"Ballesta","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.cyto.2019.154984_b0070","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1146\/annurev.pharmtox.48.113006.094626","article-title":"Circadian timing in cancer treatments","volume":"50","author":"L\u00e9vi","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"issue":"2","key":"10.1016\/j.cyto.2019.154984_b0075","first-page":"1024","article-title":"Chrono-immunotherapy with interleukin-2 for treatment of metastatic renal cell carcinoma: a phase I-II study","volume":"2","author":"Lo Re","year":"2014","journal-title":"J. Immunol. Clin. Res."},{"issue":"4","key":"10.1016\/j.cyto.2019.154984_b0080","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/j.1365-2567.2010.03320.x","article-title":"The influence of regulatory T cells and diurnal hormone rhythms on T helper cell activity","volume":"131","author":"Bollinger","year":"2010","journal-title":"Immunology"},{"issue":"9","key":"10.1016\/j.cyto.2019.154984_b0085","doi-asserted-by":"crossref","first-page":"4454","DOI":"10.4049\/jimmunol.158.9.4454","article-title":"Effects of sleep and circadian rhythm on human circulating immune cells","volume":"158","author":"Born","year":"1997","journal-title":"J. Immunol."},{"issue":"1\u20136","key":"10.1016\/j.cyto.2019.154984_b0090","first-page":"431","article-title":"Circadian variations of interferon-induced enhancement of human natural killer (NK) cell activity","volume":"12","author":"Gatti","year":"1988","journal-title":"Cancer Detect. Prev."},{"issue":"12","key":"10.1016\/j.cyto.2019.154984_b0095","doi-asserted-by":"crossref","first-page":"6291","DOI":"10.4049\/jimmunol.1004030","article-title":"Circadian variation of the response of T cells to antigen","volume":"187","author":"Fortier","year":"2011","journal-title":"J. Immunol."},{"issue":"5","key":"10.1016\/j.cyto.2019.154984_b0100","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1097\/01.cji.0000170357.14962.9b","article-title":"Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy","volume":"28","author":"Upton","year":"2005","journal-title":"J. Immunother."},{"issue":"1","key":"10.1016\/j.cyto.2019.154984_b0105","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ygyno.2017.03.515","article-title":"Objective response rate is a possible surrogate endpoint for survival in patients with advanced, recurrent ovarian cancer","volume":"146","author":"Siddiqui","year":"2017","journal-title":"Gynecol. Oncol."},{"issue":"2","key":"10.1016\/j.cyto.2019.154984_b0110","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/cncr.23552","article-title":"High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006","volume":"113","author":"Klapper","year":"2008","journal-title":"Cancer"},{"issue":"3","key":"10.1016\/j.cyto.2019.154984_b0115","first-page":"273","article-title":"Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic renal cell cancer?","volume":"26","author":"Dillman","year":"2011","journal-title":"Cancer Biother. Radiopharm."},{"issue":"3","key":"10.1016\/j.cyto.2019.154984_b0120","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1200\/JCO.2004.06.132","article-title":"Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma","volume":"22","author":"Motzer","year":"2004","journal-title":"J. Clin. Oncol."},{"issue":"4","key":"10.1016\/j.cyto.2019.154984_b0125","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1200\/JCO.2005.05.179","article-title":"Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma","volume":"23","author":"Mekhail","year":"2005","journal-title":"J. Clin. Oncol."},{"issue":"34","key":"10.1016\/j.cyto.2019.154984_b0130","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1200\/JCO.2008.21.4809","article-title":"Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study","volume":"27","author":"Heng","year":"2009","journal-title":"J. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.cyto.2019.154984_b0135","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s40425-019-0567-3","article-title":"Overall survival by clinical risk category for high dose interleukin-2 (HD IL-2) treated patients with metastatic renal cell cancer (mRCC): data from the PROCLAIM registry","volume":"7","author":"Fishman","year":"2019","journal-title":"J. ImmunoTher. Cancer"},{"key":"10.1016\/j.cyto.2019.154984_b0140","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1749-6632.2000.tb05415.x","article-title":"Cooperation of pituitary hormone prolactin with interleukin-2 and interleukin-12 on production of interferon-gamma by natural killer and T cells","volume":"917","author":"Matera","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"8","key":"10.1016\/j.cyto.2019.154984_b0145","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/sj.bjc.6600860","article-title":"Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer","volume":"88","author":"Bauernhofer","year":"2003","journal-title":"Br. J. Cancer"},{"issue":"12","key":"10.1016\/j.cyto.2019.154984_b0150","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.1093\/annonc\/mds148","article-title":"Sex moderates circadian chemotherapy effects on survival of patients with metastatic colorectal cancer: a meta-analysis","volume":"23","author":"Giacchetti","year":"2012","journal-title":"Ann. Oncol."},{"issue":"4","key":"10.1016\/j.cyto.2019.154984_b0155","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.bbi.2003.09.014","article-title":"A regulatory role of prolactin, growth hormone, and corticosteroids for human T-cell production of cytokines","volume":"18","author":"Dimitrov","year":"2004","journal-title":"Brain Behav. Immun."},{"issue":"21","key":"10.1016\/j.cyto.2019.154984_b0160","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.1182\/blood-2008-11-190769","article-title":"Cortisol and epinephrine control opposing circadian rhythms in T cell subsets","volume":"113","author":"Dimitrov","year":"2009","journal-title":"Blood"},{"issue":"8","key":"10.1016\/j.cyto.2019.154984_b0165","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1200\/JCO.1996.14.8.2410","article-title":"Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy","volume":"14","author":"Fyfe","year":"1996","journal-title":"J. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.cyto.2019.154984_b0170","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40425-019-0522-3","article-title":"Therapy with high-dose interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition","volume":"7","author":"Buchbinder","year":"2019","journal-title":"J. ImmunoTher. Cancer"}],"container-title":["Cytokine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043466619304168?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043466619304168?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T20:54:00Z","timestamp":1760907240000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043466619304168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":34,"alternative-id":["S1043466619304168"],"URL":"https:\/\/doi.org\/10.1016\/j.cyto.2019.154984","relation":{},"ISSN":["1043-4666"],"issn-type":[{"value":"1043-4666","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Interleukin-2 chronotherapy for metastatic renal cell carcinoma: Results of a phase I-II study","name":"articletitle","label":"Article Title"},{"value":"Cytokine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cyto.2019.154984","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"154984"}}