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Pigment Cell & Melanoma Research

Gabriel E Bertolesi, Sarah McFarlane
Melanopsin photopigments, Opn4x and Opn4m, were evolutionary selected to "see the light" in systems that regulate skin colour change. In this review, we analyze the roles of melanopsins, and how critical evolutionary developments, including the requirement for thermoregulation and ultraviolet protection, the emergence of a background adaptation mechanism in land-dwelling amphibian ancestors, and the loss of a photosensitive pineal gland in mammals, may have helped sculpt the mechanisms that regulate light-controlled skin pigmentation...
December 14, 2017: Pigment Cell & Melanoma Research
Pierre Sohier, Léa Legrand, Zackie Aktary, Christine Grill, Véronique Delmas, Florence Bernex, Edouard Reyes-Gomez, Lionel Larue, Béatrice Vergier
Genetically engineered mouse models offer essential opportunities to investigate the mechanisms of initiation and progression in melanoma. Here we report a new simplified histopathology classification of mouse melanocytic lesions in Tyr::NRASQ61K derived models, using an interactive decision tree that produces homogeneous categories. Reproducibility for this classification system was evaluated on a panel of representative cases of murine melanocytic lesions by pathologists and basic scientists. Reproducibility, measured as inter-rater agreement between evaluators using a modified Fleiss' kappa statistic revealed a very good agreement between observers...
December 10, 2017: Pigment Cell & Melanoma Research
Douglas B Johnson, Merrida A Childress, Zachary R Chalmers, Garrett M Frampton, Siraj M Ali, Samuel M Rubinstein, David Fabrizio, Jeffrey S Ross, Sohail Balasubramanian, Vincent A Miller, Philip J Stephens, Jeffrey A Sosman, Christine M Lovly
BRAF and MEK inhibitors have improved clinical outcomes in advanced, BRAFV600 - mutated melanomas. Acquired resistance occurs in most patients, with numerous and diverse drivers. We obtained pre-treatment and progression biopsies from a patient who progressed on dabrafenib and trametinib. In addition to a preserved BRAFV600E mutation, an internal deletion (rearrangement) of BRAF was observed in the progression sample. This deletion involved exons 2-8, which includes the Ras-binding domain, and is analogous to previously documented BRAF fusions and splice variants known to reactivate RAS-RAF-MEK-ERK signaling...
November 24, 2017: Pigment Cell & Melanoma Research
Shosuke Ito, Shiho Miyake, Shoji Maruyama, Itaru Suzuki, Stéphane Commo, Yukiko Nakanishi, Kazumasa Wakamatsu
We previously reported a constant ratio of the benzothiazole-pheomelanin marker thiazole-2,4,5-tricarboxylic acid (TTCA) to the eumelanin marker pyrrole-2,3,5-tricaboxylic acid (PTCA) in eumelanic, black human hair. A constant level (20-25%) of benzothiazole-type pheomelanin was recently demonstrated in human skin with varying concentrations of melanin. Therefore, in this study, we aimed to investigate the origin of pheomelanin markers in black to brown human hair by developing a method to remove protein components from hair by heating with 6 M HCl at 110°C for 16 h...
November 24, 2017: Pigment Cell & Melanoma Research
Xiaoyin Ma, Jiajia Hua, Guoxiao Zheng, Fang Li, Chunbao Rao, Huirong Li, Jing Wang, Li Pan, Ling Hou
Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death associated protein like-1 DAPL1 cell-autonomously suppresses RPE proliferation in vivo and in vitro. Here we show in human RPE cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF is, however, mediated predominantly by (-) MITF, one of two alternative splice isoforms of MITF that lacks six residues located upstream of the DNA binding basic domain...
November 24, 2017: Pigment Cell & Melanoma Research
Jenny Hj Lee, Megan Lyle, Alexander M Menzies, Matthew Mk Chan, Serigne Lo, Arthur Clements, Matteo S Carlino, Richard F Kefford, Georgina V Long
This study evaluated patterns of response as discerned by comprehensive metastasis-specific analysis in metastatic melanoma patients receiving anti-PD-1 antibodies. Bi-dimensional measurements of every metastasis in patients enrolled in the KEYNOTE-001 trial at a single institution were obtained at baseline and throughout treatment. Twenty-seven evaluable patients had 399 baseline metastases measurable on CT imaging. Complete response (CR) which occurred in 52.6% of metastases was smaller (mean 223mm(2) vs...
November 24, 2017: Pigment Cell & Melanoma Research
Hanine Barek, Manickam Sugumaran, Shosuke Ito, Kazumasa Wakamatsu
Melanin from several insect samples were isolated and subjected to chemical degradation and HPLC analysis for melanin markers. Quantification of different melanin markers reveals that insect melanins are significantly different from that of the mammalian epidermal melanins. The eumelanin produced in mammals are derived from the oxidative polymerization of both 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid. The pheomelanin is formed by the oxidative polymerization of cysteinyldopa. Thus dopa is the major precursor for both eumelanin and pheomelanin in mammals...
November 21, 2017: Pigment Cell & Melanoma Research
Jannett Nguyen, Tiffany Alexander, Hong Jiang, Natasha Hill, Zied Abdullaev, Svetlana D Pack, Amy P Hsu, Steven M Holland, Dennis D Hickstein, Eric A Engels, Isaac Brownell
GATA2 deficiency is a recently described genetic disorder affecting hematopoietic stem cells and is associated with immunodeficiency, cutaneous findings, and hematologic malignancy. The risk of non-hematologic malignancies is unclear. To explore the incidence and clinical course of melanoma in GATA2 deficient patients we conducted a retrospective chart review of 71 patients with GATA2 deficiency. We identified two patients with melanoma, including an invasive melanoma presenting as a graft-versus-tumor effect following bone marrow transplantation...
November 20, 2017: Pigment Cell & Melanoma Research
Matthew J Wongchenko, Antoni Ribas, Brigitte Dréno, Paolo A Ascierto, Grant A McArthur, Jorge D Gallo, Isabelle A Rooney, Jessie Hsu, Hartmut Koeppen, Yibing Yan, James Larkin
The prognostic significance of programmed death ligand-1 (PD-L1) on treatment outcomes in patients receiving BRAF with or without MEK inhibitors is not well understood. This retrospective exploratory analysis evaluated the association of tumour PD-L1 expression with progression-free survival (PFS) and overall survival (OS) among 210 patients in the coBRIM trial treated with cobimetinib plus vemurafenib or placebo plus vemurafenib. In the vemurafenib cohort, there was a trend of increased PFS and OS in those with PD-L1(+) melanoma, with hazard ratios (HRs) (PD-L1(+) versus PD-L1(-) ) of 0...
November 20, 2017: Pigment Cell & Melanoma Research
Cathy Yunjia Zhao, Shaun Chou, Rose Congwei Liu, Pablo Fernandez-Peñas
The advent of targeted therapies using BRAF or MEK inhibitors (BRAFi or MEKi) or their combinations (BiMiC) as well as checkpoint immunotherapies based on antibodies to CTLA4 or PD1 has recently brought about a drastic revolution in the treatment of advanced cancers, in particular of melanoma. These therapies are, however, not without side effects. Many of them involve the skin and range from keratosis to squamous cell carcinomas under BRAFi monotherapy and from lichenoid reactions to vitiligo under immunotherapies...
November 13, 2017: Pigment Cell & Melanoma Research
Jisu Park, Hyejung Jung, Kyuri Kim, Kyung-Min Lim, Ji-Young Kim, Eek-Hoon Jho, Eok-Soo Oh
Although L-tyrosine is well known for its melanogenic effect, the contribution of D-tyrosine to melanin synthesis was previously unexplored. Here, we reveal that, unlike L-tyrosine, D-tyrosine dose-dependently reduced the melanin contents of human MNT-1 melanoma cells and primary human melanocytes. In addition, 500 μM of D-tyrosine completely inhibited 10 μM L-tyrosine-induced melanogenesis, and both in vitro assays and L-DOPA staining MNT-1 cells showed that tyrosinase activity is reduced by D-tyrosine treatment...
November 9, 2017: Pigment Cell & Melanoma Research
Marwa Abdallah, Medhat El-Mofty, Tag Anbar, Hoda Rasheed, Samia Esmat, Amira Al-Tawdy, Marwa M Fawzy, Dalia Abdel-Halim, Rehab Hegazy, Heba Gawdat, Dalia Bassiouny, Mona A Ibrahim, Iman Sany, Mahy El-Bassiouny, Mohamed Khalil, Abeer Abdel-Aziz, Zeinab M El Maadawi, Wedad Z Mostafa
This cross-sectional multicenter study aimed to evaluate serum CXCL-10, as an activity marker for vitiligo and compare it with other putative serum and tissue markers. Serum CXCL-10 was compared to interferon gamma (IFN-γ), interleukin 6 (IL-6) and IL-17 using ELISA in 55 non-segmental vitiligo patients (30 active and 25 stable) and 30 healthy controls. Marginal skin biopsy was taken for immunohistochemical evaluation of CD8+T-cells and CXCL-10 +ve cells. Serum levels of CXCL-10, IL-17 and IL-6 were elevated in all vitiligo patients compared to controls (P<0...
November 1, 2017: Pigment Cell & Melanoma Research
Gabriela Vilas Bôas Gomez, José Augusto Rinck-Junior, Cristiane de Oliveira, Dennis Henrique Leandro da Silva, Ronei Luciano Mamoni, Gustavo Jacob Lourenço, Aparecida Machado de Moraes, Carmen Silvia Passos Lima
This study aimed to evaluate whether PD1.1 (c.-606G>A), PD1 (c.627+252C>T), PD1.5 (c.804C>T) and PD1.9 (c.644C>T) single nucleotide polymorphisms of PDCD1 gene influence the risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Individuals with phototype I or II and PD1 CC genotype were under 5.89-fold increased risk of developing CM. PD1.5 TT genotype increased PDCD1 expression (2.49 vs. 1.28 arbitrary units, P= 0.03) and PD1.5 CT or TT genotype and allele T increased PD1 expression in TCD4(+) lymphocytes (16...
November 1, 2017: Pigment Cell & Melanoma Research
Karine A Cohen-Solal, Howard L Kaufman, Ahmed Lasfar
Resistance to targeted therapy in cancer is often coupled with the acquisition of a pro-invasive phenotype by tumors cells and a highly permissive tumor microenvironment promoting drug resistance. Transcription factors are frequently shown as major points of convergence of multiple dysregulated receptors and signaling pathways in cancer. Several transcription factors are now incriminated as drivers of both drug resistance and invasiveness. We focused this review on critical transcription factors playing a causal role in both the resistance to BRAF V600E targeted therapy and the pro-invasive behavior of melanoma cells...
November 1, 2017: Pigment Cell & Melanoma Research
Sheera Rosenbaum, Andrew Aplin
A new wave of immunotherapies has considerably expanded treatment options for cutaneous melanoma patients. One strategy for boosting the anti-tumor immune response is to block inhibitory immune checkpoint proteins that restrain immune cells. Utilizing this strategy, FDA-approved immune checkpoint inhibitors targeting CTLA-4 (ipilimumab) and PD-1/PD-L1 (nivolumab, pembrolizumab) alone or in combination enhance existing immune responses and have increased patient survival and response durability. This article is protected by copyright...
October 25, 2017: Pigment Cell & Melanoma Research
Ken Okamura, Yuko Abe, Yuta Araki, Kazumasa Wakamatsu, Mariko Seishima, Takafumi Umetsu, Atsushi Kato, Masakazu Kawaguchi, Masahiro Hayashi, Yutaka Hozumi, Tamio Suzuki
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), a bleeding tendency and ceroid deposition. Most of the causative genes for HPS encode subunits of the biogenesis of lysosome-related organelles complex (BLOC). In this study, we identified one patient each with HPS4, HPS6 and HPS9 by whole-exome sequencing. Next, we analyzed hair samples from the three patients and representative patients with HPS1 and controls using electron microscopy and chemical methods...
October 20, 2017: Pigment Cell & Melanoma Research
Peter Dietrich, Anja Katrin Bosserhoff
MicroRNAs (miRs) were originally described as non-coding RNA molecules that mediate the inhibition of translation of their target genes by binding to distinctive, now called canonical, MicroRNA Response Elements (MREs). After binding to MREs, which are usually located near the 3'UTR of their target mRNA, a complex protein machinery (RNA-induced silencing complex, RISC) mediates mRNA decay and/or the inhibition of translation initiation (Mione and Bosserhoff, 2015). However, the diversity of microRNA regulation and function has greatly expanded over the last several years, and more non-canonical functions of miRs are emerging...
October 19, 2017: Pigment Cell & Melanoma Research
Grant M Fischer, Y N Vashisht Gopal, Jennifer L McQuade, Weiyi Peng, Ralph J DeBerardinis, Michael A Davies
Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There is also data to support that the metabolic phenotypes of melanoma cells depend upon contributions from both intrinsic oncogenic pathways and extrinsic factors in the tumor microenvironment. This review summarizes current understanding of the metabolic processes that promote cutaneous melanoma tumorigenesis and progression, the regulation of cancer cell metabolism by the tumor microenvironment, and the impact of metabolic pathways on targeted and immune therapies...
October 19, 2017: Pigment Cell & Melanoma Research
Linli Zhou, Kun Yang, Spencer Dunaway, Zalfa Abdel-Malek, Thomas Andl, Ana Luisa Kadekaro, Yuhang Zhang
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs...
October 17, 2017: Pigment Cell & Melanoma Research
Sue Kyung Kim, Seung-Jae Oh, Se-Yeon Park, Woo-Jung Kim, You-Sun Kim, You Chan Kim
Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles and whitening, on aged skin. In this study, we investigated the mechanism underlying the whitening effects of PDT on melanocytes (MCs) in vitro and in vivo. Exposure of MCs to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. Interestingly, melanogenesis was also inhibited by exposing MCs to conditioned media of PDT-treated keratinocytes or dermal fibroblasts...
October 17, 2017: Pigment Cell & Melanoma Research
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