Abstract:
:Melanoma incidence continues to rise at an alarming rate while effective systemic therapies remain very limited. Microphthalmia-associated transcription factor (MITF) is required for development of melanocytes and is an amplified oncogene in a fraction of human melanomas. Microphthalmia-associated transcription factor also plays an oncogenic role in human clear cell sarcomas, which typically exhibit melanoma-like features. Although pharmacologic suppression of MITF is of potential interest in a variety of clinical settings, it is not known to contain intrinsic catalytic activity capable of direct small molecule inhibition. An alternative drug-targeting strategy is to identify and interfere with lineage-restricted mechanisms required for its expression. Here, we report that multiple histone deacetylase (HDAC)-inhibitor drugs potently suppress MITF expression in melanocytes, melanoma and clear cell sarcoma cells. Although HDAC inhibitors may affect numerous cellular targets, we observed suppression of skin pigmentation by topical drug application as well as evidence of anti-melanoma efficacy in vitro and in mouse xenografts. Consequently, HDAC inhibitor drugs are candidates to play therapeutic roles in targeting conditions affecting the melanocyte lineage.
journal_name
Pigment Cell Melanoma Resjournal_title
Pigment cell & melanoma researchauthors
Yokoyama S,Feige E,Poling LL,Levy C,Widlund HR,Khaled M,Kung AL,Fisher DEdoi
10.1111/j.1755-148X.2008.00480.xsubject
Has Abstractpub_date
2008-08-01 00:00:00pages
457-63issue
4eissn
1755-1471issn
1755-148Xpii
PCR480journal_volume
21pub_type
杂志文章abstract::Neurofibromatosis type 1 (NF1) is a frequent genetic disease leading to the development of Schwann cell-derived neurofibromas or melanocytic lesions called café-au-lait macules (CALMs). The molecular mechanisms involved in CALMs formation remain largely unknown. In this report, we show for the first time pathophysiolo...
journal_title:Pigment cell & melanoma research
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doi:10.1111/pcmr.12369
更新日期:2015-07-01 00:00:00
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journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12534
更新日期:2016-11-01 00:00:00
abstract::Genome-wide association studies (GWAS) have become a widely used approach for genetic association studies of various human traits. A few GWAS have been conducted with the goal of identifying novel loci for pigmentation traits, melanoma, and non-melanoma skin cancer. Nevertheless, the phenotype variation explained by t...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2012.01023.x
更新日期:2012-09-01 00:00:00
abstract::The aim of present study was to evaluate CD4(+) /CD8(+) ratio and CD4(+) CD25(hi) FoxP3(+) Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4(+) /CD8(+) ratio and Tregs in 82 patients and 50 controls. CD8(+) T-cell counts were signific...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12105
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2011.00939.x
更新日期:2012-01-01 00:00:00
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12779
更新日期:2019-09-01 00:00:00
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journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2011.00837.x
更新日期:2011-04-01 00:00:00
abstract::Acral melanoma is a rare melanoma subtype with distinct epidemiological, clinical and genetic features. To determine if acral melanoma cell lines are representative of this melanoma subtype, six lines were analysed by whole-exome sequencing and array comparative genomic hybridisation. We demonstrate that the cell line...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2012.01016.x
更新日期:2012-07-01 00:00:00
abstract::We examined nevi and melanomas in 10 xeroderma pigmentosum (XP) patients with defective DNA repair. The lesions had a lentiginous appearance with markedly increased numbers of melanocytes. Using laser capture microdissection, we performed DNA sequencing of 18 benign and atypical nevi and 75 melanomas (melanoma in situ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12226
更新日期:2014-05-01 00:00:00
abstract::There are many techniques for evaluating melanosome transfer to keratinocytes but the spectrophotometric quantification of melanosomes incorporated by keratinocyte phagocytosis has not been previously reported. Here we describe a new method that allows the spectrophotometric visualization of melanosome uptake by norma...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2009.00640.x
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abstract::NDRG2 (N-myc downstream-regulated gene 2) is a candidate tumor suppressor implicated in control of glioblastoma proliferation and dendritic cell differentiation. The microphthalmia-associated transcription factor (Mitf) plays a crucial role in the melanocyte lineage and in melanoma by controlling survival, differentia...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2008.00503.x
更新日期:2008-12-01 00:00:00
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2011.00825.x
更新日期:2011-04-01 00:00:00
abstract::Oncogenic BRAF and NRAS mutations drive human melanoma initiation. We used transgenic zebrafish to model NRAS-mutant melanoma, and the rapid tumor onset allowed us to study candidate tumor suppressors. We identified P38α-MAPK14 as a potential tumor suppressor in The Cancer Genome Atlas melanoma cohort of NRAS-mutant m...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12925
更新日期:2020-09-10 00:00:00
abstract::Binding of melanocortin peptide agonists to the melanocortin-1 receptor of melanocytes results in eumelanin production, whereas binding of the agouti signalling protein inverse agonist results in pheomelanin synthesis. Recently, a novel melanocortin-1 receptor ligand was reported. A β-defensin gene mutation was found ...
journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2010.00806.x
更新日期:2011-04-01 00:00:00
abstract::The 4th international melanoma congress of the Society for Melanoma Research (SMR), organized by Marianne Berwick (University of New Mexico), Paul Chapman (Memorial Sloan-Kettering Cancer Center), Rene Gonzalez (University of Colorado) and Ze'ev Ronai (Burnham Institute), was held at the Marriott Hotel in downtown New...
journal_title:Pigment cell & melanoma research
pub_type:
doi:10.1111/j.1755-148X.2007.00437.x
更新日期:2008-02-01 00:00:00
abstract::Converging lines of evidence from varied scientific disciplines suggest that cutaneous melanomas comprise biologically distinct subtypes that arise through multiple causal pathways. Understanding the respective relationships of each subtype with etiologic factors such as UV radiation and constitutional factors is the ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2011.00880.x
更新日期:2011-10-01 00:00:00
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2008.00514.x
更新日期:2008-12-01 00:00:00
abstract::Giant congenital melanocytic nevi may be symptomatically isolated or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71-year-old patient with a giant congenital melanocytic nevus (CMN) of the lower back, buttocks, and thighs was asympto...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12685
更新日期:2018-05-01 00:00:00
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
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journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2012.00989.x
更新日期:2012-05-01 00:00:00
abstract::RS-4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD) was reported to induce leukoderma of the skin. To explore the mechanism underlying that effect, we previously showed that oxidation of RD with mushroom tyrosinase produces RD-quinone, which is converted to secondary quinone products, and we suggested that those quino...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12363
更新日期:2015-05-01 00:00:00
abstract::Copy number variations (CNVs) have been shown to contribute substantially to disease susceptibility in several inherited diseases including cancer. We conducted a genome-wide search for CNVs in blood-derived DNA from 79 individuals (62 melanoma patients and 17 spouse controls) of 30 high-risk melanoma-prone families w...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2012.00969.x
更新日期:2012-03-01 00:00:00