{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T05:21:40Z","timestamp":1761110500719,"version":"3.30.1"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aust J Dermatology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/Objective<\/jats:title><jats:p>Ingenol mebutate gel is approved for actinic keratosis field therapy, but little has been published as a treatment of basal cell carcinoma (BCC). Our objective is to characterise the histopathological changes and the infiltrating cell populations to better understand its mechanism of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen patients with various BCC subtypes were prospectively evaluated and treated once daily for two consecutive days with ingenol mebutate gel 0.05% under occlusion. Patients were randomised to two arms: the first arm was biopsied between the third and the tenth day after treatment initiation (\u2018early immune response\u2019), and the second arm was biopsied at day 30 after treatment initiation (\u2018late immune response\u2019). The immunopathology was evaluated by immunohistochemistry: anti\u2010CD3, anti\u2010CD4, anti\u2010CD8, anti\u2010CD20, anti\u2010CD56, anti\u2010CD68, anti\u2010Bcl\u20102, anti\u2010CASP3, anti\u2010FoxP3, anti\u2010GrzB and anti\u2010TIA\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten BCCs were in complete remission after 2\u00a0years of follow\u2010up. The early immune response was characterised by a quick recruitment of T lymphocytes, macrophages and natural killer cells. At later time\u2010points, T\u2010regulatory cells and some pro\u2010apoptotic markers were detected. Treatment\u2010related adverse events were described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ingenol mebutate gel produces a transient immuno\u2010inflammatory response and an important necrosis reaction in BCCs. Larger studies will be required to determine the maximum effective tolerated dose of ingenol mebutate gel for BCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ajd.13229","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T08:21:12Z","timestamp":1579162872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterisation of the inflammatory response triggered by topical ingenol mebutate 0.05% gel in basal cell carcinoma"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7070-3110","authenticated-orcid":false,"given":"M\u00aa Reyes","family":"Garc\u00eda\u2010de\u2010la\u2010Fuente","sequence":"first","affiliation":[{"name":"Department of Dermatology University Hospital Arnau de Vilanova Lleida Spain"},{"name":"Lleida Institute for Biomedical Research Dr. Pifarr\u00e9 Foundation (IRBLleida) Lleida Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1975-2598","authenticated-orcid":false,"given":"Maria","family":"Santacana","sequence":"additional","affiliation":[{"name":"Lleida Institute for Biomedical Research Dr. Pifarr\u00e9 Foundation (IRBLleida) Lleida Spain"},{"name":"Department of Pathology University Hospital Arnau de Vilanova Lleida Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1768-9310","authenticated-orcid":false,"given":"Joan","family":"Verdaguer","sequence":"additional","affiliation":[{"name":"Lleida Institute for Biomedical Research Dr. Pifarr\u00e9 Foundation (IRBLleida) Lleida Spain"},{"name":"Immunology Unit Department of Experimental Medicine University of  Lleida Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0876-5425","authenticated-orcid":false,"given":"Felip","family":"Vilardell","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospital Arnau de Vilanova Lleida Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3505-4901","authenticated-orcid":false,"given":"Eloi","family":"Gar\u00ed","sequence":"additional","affiliation":[{"name":"Lleida Institute for Biomedical Research Dr. Pifarr\u00e9 Foundation (IRBLleida) Lleida Spain"},{"name":"Department of Basic Medical Sciences University of  Lleida Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6573-2507","authenticated-orcid":false,"given":"Josep Manel","family":"Casanova","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital Arnau de Vilanova Lleida Spain"},{"name":"Lleida Institute for Biomedical Research Dr. Pifarr\u00e9 Foundation (IRBLleida) Lleida Spain"},{"name":"Department of Medicine University of Lleida Lleida Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_6_2_1","DOI":"10.1684\/ejd.2014.2271"},{"doi-asserted-by":"publisher","key":"e_1_2_6_3_1","DOI":"10.1007\/s40257-014-0070-z"},{"doi-asserted-by":"publisher","key":"e_1_2_6_4_1","DOI":"10.1016\/j.jid.2017.09.033"},{"doi-asserted-by":"publisher","key":"e_1_2_6_5_1","DOI":"10.1111\/dth.12148"},{"doi-asserted-by":"publisher","key":"e_1_2_6_6_1","DOI":"10.1111\/j.1440-0960.2010.00626.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_7_1","DOI":"10.1111\/j.1365-2133.2010.10184.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_8_1","DOI":"10.5021\/ad.2016.28.6.796"},{"doi-asserted-by":"publisher","key":"e_1_2_6_9_1","DOI":"10.1111\/dth.12438"},{"doi-asserted-by":"publisher","key":"e_1_2_6_10_1","DOI":"10.1111\/dth.12399"},{"doi-asserted-by":"publisher","key":"e_1_2_6_11_1","DOI":"10.2147\/CCID.S109531"},{"key":"e_1_2_6_12_1","first-page":"S3","article-title":"Ingenol mebutate topical gel A status report on clinical use beyond actinic keratosis","volume":"9","author":"Del Rosso JQ","year":"2016","journal-title":"J. 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