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Topical application of bleaching phenols; in-vivo studies and mechanism of action relevant to melanoma treatment.
MedLine Citation:
PMID:  21317816     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Skin depigmentation represents a well-established treatment for extensive vitiligo and may likewise be suited to prevent tumor recurrences and as a prophylactic treatment of familial melanoma, as common bleaching agents are cytotoxic to melanocytes. Effective melanoma prevention requires a bleaching agent-induced loss of exposed melanocytes supported by an immune response to distant pigment cells. Studies on human explant cultures treated with depigmenting agents such as 4-tertiary butyl phenol (4-TBP) or monobenzyl ether of hydroquinone (MBEH) showed a significant increase in the migration of Langerhans cells toward the dermis only upon treatment with MBEH, thus suggesting selective elicitation of an immune response. To assess the depigmenting potential of bleaching agents in vivo, 4-TBP and MBEH were topically applied to C57BL/6 wild type as well as k14-SCF transgenic, epidermally pigmented mice. MBEH-induced significant skin depigmentation in both strains was not observed upon treatment with 4-TBP. Cytokine expression patterns in skin treated with MBEH support activation of a Th1-mediated immune response corresponding to an influx of T cells and macrophages. Importantly, despite insensitivity of tumor cells to MBEH-induced cytotoxicity, significantly retarded tumor growth was observed in B16 challenged k14-SCF mice pretreated with MBEH, likely due to an abundance of cytotoxic T cells accompanied by an increased expression of Th1 and Th17 cytokines. These data support the use of MBEH as a prophylactic treatment for melanoma.
Authors:
Vidhya Hariharan; Timothy Toole; Jared Klarquist; Jeffrey Mosenson; Jack B Longley; I Caroline Le Poole
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-11
Journal Detail:
Title:  Melanoma research     Volume:  -     ISSN:  1473-5636     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
aMolecular and Cellular Biochemistry Graduate Program, Loyola University Chicago bStritch School of Medicine cDepartments of Pathology, Microbiology and Immunology/Oncology Institute dCell Biology, Neurobiology and Anatomy Graduate Program, Loyola University Chicago eDepartment of Dermatology, University of Wisconsin at Madison, Wisconsin, Illinois, USA.
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