{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:50:42Z","timestamp":1792842642061,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,5,20]],"date-time":"2018-05-20T00:00:00Z","timestamp":1526774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA206104"],"award-info":[{"award-number":["R21CA206104"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Photochem & Photobiology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"Abstract<\/jats:title>\n \n Aminolevulinate\u2010based photodynamic therapy (\n ALA<\/jats:styled-content>\n \u2010\n PDT<\/jats:styled-content>\n ) selectively eliminates diseased tissues primarily through the induction of intrinsic apoptotic pathway.\n ALA<\/jats:styled-content>\n \u2010\n PDT<\/jats:styled-content>\n is a first\u2010line therapy for actinic keratosis, however, it is less effective for cutaneous T\u2010cell lymphoma (\n CTCL<\/jats:styled-content>\n ). We have previously demonstrated that the resistance of\n CTCL<\/jats:styled-content>\n to apoptosis correlates with decreased expression of death receptors such as\n FAS<\/jats:styled-content>\n , and that methotrexate functions as an epigenetic regulator that reestablishes the susceptibility of\n CTCL<\/jats:styled-content>\n to extrinsic pathway apoptosis. We showed previously that\n MTX<\/jats:styled-content>\n augments the effectiveness of\n PDT<\/jats:styled-content>\n by sensitizing cells to apoptosis by induction of apoptotic factors, a process we call \u201cepigenetically enhanced\u201d\n PDT<\/jats:styled-content>\n (\n \n e<\/jats:italic>\n PDT\n <\/jats:styled-content>\n ). Here, in\n CTCL<\/jats:styled-content>\n cell lines, leukemic\n CTCL<\/jats:styled-content>\n cells, and normal blood T cells, we analyzed multiple components of the\n FAS<\/jats:styled-content>\n ,\n TRAIL<\/jats:styled-content>\n , and\n TNF<\/jats:styled-content>\n families using multispectral imaging of immunostained cytopreparations, a quantitative technique with five\u2010fold greater sensitivity than standard immunocytology.\n \n e<\/jats:italic>\n PDT\n <\/jats:styled-content>\n induced significantly greater\n FAS<\/jats:styled-content>\n ,\n FASL<\/jats:styled-content>\n ,\n TRAIL<\/jats:styled-content>\n \u2010R1 & \u2010R2, and\n TNF<\/jats:styled-content>\n \u03b1<\/jats:italic>\n levels than standard\n PDT<\/jats:styled-content>\n . This correlated with significantly greater induction of extrinsic pathway apoptosis and\/or overall apoptosis in all\n CTCL<\/jats:styled-content>\n samples. There was no appreciable effect on normal T cells. These data set the stage for clinical trials of\n \n e<\/jats:italic>\n PDT\n <\/jats:styled-content>\n as a novel localized treatment of CTCL.\n <\/jats:p>","DOI":"10.1111\/php.12925","type":"journal-article","created":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T03:46:13Z","timestamp":1524195973000},"page":"1058-1065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Epigenetically Enhanced PDT Induces Significantly Higher Levels of Multiple Extrinsic Pathway Apoptotic Factors than Standard\n PDT<\/scp>\n , Resulting in Greater Extrinsic and Overall Apoptosis of Cutaneous T\u2010cell Lymphoma"],"prefix":"10.1111","volume":"94","author":[{"given":"Katrin A.","family":"Salva","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Wisconsin Madison WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology Stanford University Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziba","family":"Rahbar","sequence":"additional","affiliation":[{"name":"Department of Dermatology Stanford University Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Wisconsin Madison WI"},{"name":"VA Medical Center Madison WI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.1992.tb04222.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.12.6977"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/1011-1344(92)85108-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0738-081X(02)00266-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8635(05)70458-7"},{"key":"e_1_2_6_7_1","first-page":"145","article-title":"Current evidence and applications of photodynamic therapy in dermatology","volume":"7","author":"Wan M. 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