{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:15:22Z","timestamp":1788156922521,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"MINECO","doi-asserted-by":"publisher","award":["FIS PI18\/00708"],"award-info":[{"award-number":["FIS PI18\/00708"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Dermatologic Therapy"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Vitamin D (VD) serum levels, and keratinocytic basal expression of vitamin D receptor (VDR) before treatment of actinic keratoses (AK) have been previously reported as possible biomarkers of the response of AK to treatments. We intended to evaluate the association between these and other serum and immunohistochemical parameters with the response of AK to treatment with topical ingenol mebutate (IM). Twenty\u2010five patients with AK on the head were treated with topical IM 0.015% gel once daily for 3\u2009days. Biopsies were taken at baseline and 6\u2009weeks after treatment. Immunohistochemical staining was performed for VDR, P53, Ki67, Aurora B, Survivin and \u03b2\u2010catenin. Basal serum 25(OH)D levels were determined. IM was more effective for KIN I and II AKs than in KIN III, and histological responders showed significantly higher serum VD levels (30.278 [SD 8.839] ng\/mL) than nonresponders (21.14 [SD 7.079] ng\/mL,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.023). In addition, mean basal expression of VDR (45.63 [SD 16.105] %) increased significantly (57.92 [SD 14.738] %,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.003) after treatment with IM. A significant decrease after treatment in the expression of several markers of aggressiveness and progression to squamous cell carcinoma, namely P53, Ki\u201067, aurora B kinase and survivin, was also observed. Our results support a relationship between VD status and the response of AK to treatment with topical IM, suggesting that its previous correction to proper serum levels in VD\u2010deficient patients could improve the response of AK to the treatment.\n                  <\/jats:p>","DOI":"10.1111\/dth.15949","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T22:44:35Z","timestamp":1666219475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Influence of serum vitamin D level in the response of actinic keratosis to ingenol mebutate"],"prefix":"10.1155","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-8364","authenticated-orcid":false,"given":"Ricardo Moreno\u2010Alonso","family":"de Celada","sequence":"first","affiliation":[{"name":"Department of Dermatology Hospital Universitario del Henares  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0523-2076","authenticated-orcid":false,"given":"Tamara","family":"Gracia\u2010Caza\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hospital Universitario Miguel Servet  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-0081","authenticated-orcid":false,"given":"Laura","family":"Najera\u2010Botello","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Universitario Puerta de Hierro\u2010Majadahonda  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Cerro\u2010Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hospital Universitario Miguel Servet  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-2887","authenticated-orcid":false,"given":"Angeles","family":"Juarranz","sequence":"additional","affiliation":[{"name":"Department of Biology Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9282-4784","authenticated-orcid":false,"given":"Salvador","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties Instituto Ram\u00f3n y Cajal de Investigaciones Sanitarias, Universidad de Alcal\u00e1  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8034-3617","authenticated-orcid":false,"given":"Yolanda","family":"Gilaberte","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hospital Universitario Miguel Servet  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"European Medicines Agency.EMA review of Picato concludes medicine's risks outweigh its benefits. Accessed May 07 2020.https:\/\/www.ema.europa.eu\/en\/news\/emareview-picato-concludes-medicines-risks-outweigh-its-benefits."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.04.001"},{"key":"e_1_2_9_4_1","first-page":"7","article-title":"The vitamin D receptor: a tumor suppressor in skin","volume":"11","author":"Bickle D","year":"2011","journal-title":"Discov Med"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-55580-0_19"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0385"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1111170"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14054"},{"issue":"3","key":"e_1_2_9_9_1","first-page":"442","article-title":"Squamous cell carcinoma developed after ingenol mebutate therapy: a possible consequence of the treatment?","volume":"153","author":"Maglie R","year":"2018","journal-title":"G Ital Dermatol Venereol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annder.2018.04.007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14852"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15528"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13831"},{"issue":"3","key":"e_1_2_9_14_1","first-page":"199","article-title":"Ki\u201067 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies","volume":"1","author":"Gerdes J","year":"1990","journal-title":"Semin Cancer Biol"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10270.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215537"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15965"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.697"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-021-03669-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9020398"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00166"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers5041426"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-46227-7_14"}],"container-title":["Dermatologic Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dth.15949","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dth.15949","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dth.15949","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:36:46Z","timestamp":1788154606000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dth.15949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":22,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/dth.15949"],"URL":"https:\/\/doi.org\/10.1111\/dth.15949","archive":["Portico"],"relation":{},"ISSN":["1396-0296"],"issn-type":[{"value":"1396-0296","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10,31]]},"assertion":[{"value":"2022-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15949"}}