{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:30:46Z","timestamp":1787236246884,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T00:00:00Z","timestamp":1388361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Novel insights into intra\u2010cellular signalling involved in pemphigus vulgaris (\n                    <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content>\n                    ), an autoimmune blistering disease of skin and mucous membranes, are now revealing new therapeutic approaches such as the chemical inhibition of\n                    <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content>\n                    \u2010associated signals in conjunction with standard immunosuppressive therapy. However, extensive inhibition of signalling molecules that are required for normal tissue function and integrity may hamper this approach. Using a neonatal\n                    <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content>\n                    mouse model, we demonstrate that epidermal blistering can be prevented in a dose\u2010dependent manner by clinically approved\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    inhibitors erlotinib and lapatinib, but only up to approximately 50% of normal\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    activity. At lower EGFR activity, blisters again aggravated and were highly exacerbated in mice with a conditional deletion of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    <\/jats:italic>\n                    . Statistical analysis of the relation between\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    activity and the extent of skin blistering revealed the best fit with a non\u2010linear, V\u2010shaped curve with a median break point at 52%\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    activity (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.0005). Moreover, lapatinib (a dual\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    \/ErbB2 inhibitor) but not erlotinib significantly reduced blistering in the oral cavity, suggesting that signalling mechanisms differ between\n                    <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content>\n                    predilection sites. Our results demonstrate that future clinical trials evaluating\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    \/ErbB2 inhibitors in\n                    <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content>\n                    patients must select treatment doses that retain a specific level of signal molecule activity. These findings may also be of relevance for cancer patients treated with\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    inhibitors, for whom skin lesions due to extensive\n                    <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                    inhibition represent a major threat.\n                  <\/jats:p>","DOI":"10.1111\/exd.12290","type":"journal-article","created":{"date-parts":[[2013,11,27]],"date-time":"2013-11-27T03:12:05Z","timestamp":1385521925000},"page":"33-38","source":"Crossref","is-referenced-by-count":38,"title":["<scp>EGFR<\/scp>\n                    inhibitors erlotinib and lapatinib ameliorate epidermal blistering in pemphigus vulgaris in a non\u2010linear,\n                    <scp>V<\/scp>\n                    \u2010shaped relationship"],"prefix":"10.1111","volume":"23","author":[{"given":"Beyza S.","family":"Sayar","sequence":"first","affiliation":[{"name":"Molecular Dermatology Institute of Animal Pathology University of Bern Bern Switzerland"},{"name":"DermFocus University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"R\u00fcegg","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Institute Vetsuisse Faculty University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enno","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Luebeck Luebeck Germany"},{"name":"Comprehensive Center for Inflammation Medicine University of Luebeck Luebeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sibilia","sequence":"additional","affiliation":[{"name":"Department of Medicine I Institute of Cancer Research Department of Medicine I Comprehensive Cancer Center Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Siffert","sequence":"additional","affiliation":[{"name":"Molecular Dermatology Institute of Animal Pathology University of Bern Bern Switzerland"},{"name":"DermFocus University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja M.","family":"Suter","sequence":"additional","affiliation":[{"name":"Molecular Dermatology Institute of Animal Pathology University of Bern Bern Switzerland"},{"name":"DermFocus University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Galichet","sequence":"additional","affiliation":[{"name":"Molecular Dermatology Institute of Animal Pathology University of Bern Bern Switzerland"},{"name":"DermFocus University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane J.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Molecular Dermatology Institute of Animal Pathology University of Bern Bern Switzerland"},{"name":"DermFocus University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.4049\/jimmunol.159.4.2010","volume":"159","author":"Ishii K","year":"1997","journal-title":"J. Immunol."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12337524"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.111"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701248"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016309789869065"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601224"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.00893.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602973103"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12088"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2012.01441.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.172874"},{"key":"e_1_2_8_13_1","unstructured":"RubensteinD S WerthV StroberBet\u00a0al.http:\/\/clinicaltrials.gov\/2008."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080392"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5252"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.299"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.2170"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2005.10.010"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2009-0118"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.12.046"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2007.00557.x"},{"key":"e_1_2_8_22_1","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2013"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1545"},{"key":"e_1_2_8_24_1","volume-title":"segmented: an R Package to Fit Regression Models with broken\u2010line relationships","author":"Muggeo V M"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930600971836"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611365200"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.12-7-756"},{"key":"e_1_2_8_28_1","first-page":"4838","volume":"57","author":"Moyer J D","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2008.08.008"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005886"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506119200"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1142.b"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014211"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fexd.12290","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.12290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T12:41:19Z","timestamp":1695559279000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.12290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,30]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1111\/exd.12290"],"URL":"https:\/\/doi.org\/10.1111\/exd.12290","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,30]]}}}