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Pigment Cell & Melanoma Research

Nhu T Nguyen, David E Fisher
Ultraviolet radiation (UVR) has numerous effects on skin, including DNA damage, tanning, vitamin D synthesis, carcinogenesis, and immunomodulation. Keratinocytes containing damaged DNA secrete both α-melanocyte-stimulating hormone (α-MSH), which stimulates pigment production by melanocytes, and the opioid β-endorphin, which can trigger addiction-like responses to UVR. The pigmentation (tanning) response is an adaptation that provides some delayed protection against further DNA damage and carcinogenesis, while the opioid response may be an evolutionary adaptation for promoting sun-seeking behavior to prevent vitamin D deficiency...
July 17, 2018: Pigment Cell & Melanoma Research
Ken Okamura, Masahiro Hayashi, Osamu Nakajima, Michihiro Kono, Yuko Abe, Yutaka Hozumi, Tamio Suzuki
Oculocutaneous albinism (OCA) type 4 is one of the most common types of albinism among Japanese population. In some patients who were clinically diagnosed with OCA, we have found a heterozygous pathological mutation in the coding region of SLC45A2, the gene responsible for OCA4, not leading to a DNA-based diagnosis. In this study, we evaluated pathological variants in the promoter region of SLC45A2 in these patients. The results indicated that the majority of the patients had a 4-bp deletion in the said region (c...
July 17, 2018: Pigment Cell & Melanoma Research
Mitchell E Fane, Richard A Sturm
No abstract text is available yet for this article.
July 17, 2018: Pigment Cell & Melanoma Research
Jonathan M Eby, Angela R Smith, Timothy P Riley, Cormac Cosgrove, Christian M Ankney, Steven W Henning, Chrystal M Paulos, Elizabeth Garrett-Mayer, Rosalie M Luiten, Michael I Nishimura, Brian M Baker, I Caroline Le Poole
To study the contribution of T-cell receptors (TCR) to resulting T cell responses, we studied three different human αβ TCRs, reactive to the same gp100-derived peptide presented in the context of HLA-A*0201. When expressed in primary CD8 T cells, all receptors elicited classic antigen-induced IFN-γ responses, which correlated with TCR affinity for peptide-MHC in the order T4H2>R6C12>SILv44. However, SILv44 elicited superior IL-17A release. Importantly, in vivo, SILv44-transgenic T cells mediated superior anti-tumor responses to 888-A2+ human melanoma tumor cells upon adoptive transfer into tumor-challenged mice while maintaining IL-17 expression...
July 15, 2018: Pigment Cell & Melanoma Research
Tatiana P Rogasevskaia, Robert T Szerencsei, Ali H Jalloul, Frank Visser, Robert J Winkfein, Paul P M Schnetkamp
NCKX5 is a bidirectional K+ -dependent Na+ -Ca2+ exchanger, which belongs to the SLC24A gene family. In particular, the A111T mutation of NCKX5 has been associated with reduced pigmentation in European populations. In contrast to other NCKX isoforms, which function in the plasma membrane (PM), NCKX5 has been shown to localize either in the trans-Golgi network (TGN) or in melanosomes. Moreover, sequences responsible for retaining its intracellular localization are unknown. This study addresses two major questions: (i) clarification of intracellular location of NCKX5 and (ii) identification of sequences that retain NCKX5 inside the cell...
July 7, 2018: Pigment Cell & Melanoma Research
Stefano Masi, Georgios Georgiopoulos, Simone Ribero, Stefano Taddei, Veronique Bataille, Claire J Steves
The presence of a skin-brain connection whereby alterations in the skin can inform on mechanisms underlying neurodegenerative diseases is increasingly recognized. In this study, we used a discovery (n = 321) and replication (n = 147) sample from the Twins UK population to test the association between naevus count and memory function, and its mediation by telomeres. Memory function was assessed in 1999 and 2009 using the paired associates learning test (PAL), while naevus count and leucocyte telomere length (LTL, assessed by the terminal restriction fragment assay) were measured once...
June 28, 2018: Pigment Cell & Melanoma Research
Valerie Fock, Sigurdur Runar Gudmundsson, Hilmar Orn Gunnlaugsson, Jon August Stefansson, Vivien Ionasz, Alexander Schepsky, Jade Viarigi, Indridi Einar Reynisson, Vivian Pogenberg, Matthias Wilmanns, Margret Helga Ogmundsdottir, Eirikur Steingrimsson
Microphthalmia-associated transcription factor (MITF) is a member of the basic helix-loop-helix leucine zipper (bHLH-Zip) family and functions as the master regulator of the melanocytic lineage. MITF-M is the predominant isoform expressed in melanocytes and melanoma cells, and, unlike other MITF isoforms, it is constitutively nuclear. Mutational analysis revealed three karyophilic signals in the bHLH-Zip domain of MITF-M, spanning residues 197-206, 214-217, and 255-265. Structural characterization of the MITF protein showed that basic residues within these signals are exposed for interactions in the absence of DNA...
June 25, 2018: Pigment Cell & Melanoma Research
Zeinab Kasraian, Sandra Trompezinski, Muriel Cario-André, Fanny Morice-Picard, Cécile Ged, Marie-Laure Jullie, Alain Taieb, Hamid Reza Rezvani
Skin pigmentation abnormalities are manifested in several disorders associated with deficient DNA repair mechanisms such as nucleotide excision repair (NER) and double-strand break (DSB) diseases, a topic that has not received much attention up to now. Hereditary disorders associated with defective DNA repair are valuable models for understanding mechanisms that lead to hypo- and hyperpigmentation. Owing to the UV-associated nature of abnormal pigmentary manifestations, the outcome of the activated DNA damage response (DDR) network could be the effector signal for alterations in pigmentation, ultimately manifesting as pigmentary abnormalities in repair-deficient disorders...
June 25, 2018: Pigment Cell & Melanoma Research
Mitchell E Fane, Yash Chhabra, Aaron G Smith, Richard A Sturm
The POU domain family of transcription factors play a central role in embryogenesis and are highly expressed in neural crest cells and the developing brain. BRN2 is a class III POU domain protein that is a key mediator of neuroendocrine and melanocytic development and differentiation. While BRN2 is a central regulator in numerous developmental programs, it has also emerged as a major player in the biology of tumourigenesis. In melanoma, BRN2 has been implicated as one of the master regulators of the acquisition of invasive behaviour within the phenotype switching model of progression...
May 21, 2018: Pigment Cell & Melanoma Research
Grace Tharmarajah, Ulrich Eckhard, Fagun Jain, Giada Marino, Anna Prudova, Oscar Urtatiz, Helmut Fuchs, Martin H de Angelis, Christopher M Overall, Catherine D Van Raamsdonk
The mouse tail has an important role in the study of melanogenesis, because mouse tail skin can be used to model human skin pigmentation. To better understand the development of melanocytes in the mouse tail, we cloned two dominant ENU-generated mutations of the Adamts9 gene, Und3 and Und4, which cause an unpigmented ring of epidermis in the middle of the tail, but do not alter pigmentation in the rest of the mouse. Adamts9 encodes a widely expressed zinc metalloprotease with thrombospondin type 1 repeats with few known substrates...
May 21, 2018: Pigment Cell & Melanoma Research
Vijayasaradhi Setaluri
No abstract text is available yet for this article.
July 2018: Pigment Cell & Melanoma Research
Shosuke Ito, Misa Agata, Kotono Okochi, Kazumasa Wakamatsu
RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, is known to induce leukoderma in some consumers. To explore the mechanism underlying this effect, we previously showed that the oxidation of RD with mushroom or human tyrosinase produces cytotoxic quinone oxidation products and RD-eumelanin exerts a potent pro-oxidant activity. Cellular antioxidants were oxidized by RD-eumelanin with a concomitant production of H2 O2 . In this study, we examined whether this pro-oxidant activity of RD-eumelanin is enhanced by ultraviolet A (UVA) radiation because most RD-induced leukoderma lesions are found in sun-exposed areas...
July 2018: Pigment Cell & Melanoma Research
Joshua Arbesman, Sairekha Ravichandran, Pauline Funchain, Cheryl L Thompson
Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1...
July 2018: Pigment Cell & Melanoma Research
Janice M Mehnert, Ann W Silk, J H Lee, Liesel Dudek, Byeong-Seon Jeong, Jiadong Li, Jason M Schenkel, Evita Sadimin, Michael Kane, Hongxia Lin, Weichung J Shih, Andrew Zloza, Suzie Chen, James S Goydos
Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg PO bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1-positive tumors were enrolled. No objective responses were observed, and accrual was stopped. Stable disease was noted in six (46%) patients, with one patient on study for 42 weeks. Riluzole was well tolerated, with fatigue (62%) as the most common adverse event...
July 2018: Pigment Cell & Melanoma Research
Nikolay Ogryzko, Yi Feng
No abstract text is available yet for this article.
July 2018: Pigment Cell & Melanoma Research
Richard A Sturm, David L Duffy
No abstract text is available yet for this article.
July 2018: Pigment Cell & Melanoma Research
Oscar Maiques, Carla Barceló, Anaïs Panosa, Jordi Pijuan, Jose L Orgaz, Irene Rodriguez-Hernandez, Clara Matas-Nadal, Gemma Tell, Ramón Vilella, Angels Fabra, Susana Puig, Victoria Sanz-Moreno, Xavier Matias-Guiu, Carles Canti, Judit Herreros, Rosa M Marti, Anna Macià
Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) are overexpressed in melanoma cells and play an important role in melanoma progression. Importantly, TTCC pharmacological blockers reduce proliferation and deregulate autophagy leading to apoptosis. Here, we analyze the role of autophagy during migration/invasion of melanoma cells. TTCC Cav3...
July 2018: Pigment Cell & Melanoma Research
Raffaella Micillo, Mariagrazia Iacomino, Marco Perfetti, Lucia Panzella, Kenzo Koike, Gerardino D'Errico, Marco d'Ischia, Alessandra Napolitano
To inquire into the role of the carboxyl group as determinant of the properties of 5,6-dihydroxyindole melanins, melanins from aerial oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and its DHICA methyl ester (MeDHICA) were comparatively tested for their antioxidant activity. MALDI MS spectrometry analysis of MeDHICA melanin provided evidence for a collection of intact oligomers. EPR analysis showed g-values almost identical and signal amplitudes (ΔB) comparable to those of DHICA melanin, but spin density was one order of magnitude higher, with a different response to pH changes...
July 2018: Pigment Cell & Melanoma Research
Eulalie Lasseaux, Claudio Plaisant, Vincent Michaud, Perrine Pennamen, Aurelien Trimouille, Laetitia Gaston, Solène Monfermé, Didier Lacombe, Caroline Rooryck, Fanny Morice-Picard, Benoît Arveiler
Albinism is a clinically and genetically heterogeneous disease characterized by variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity impedes the establishment of phenotype-genotype correlations. To obtain a precise diagnosis, we screened the 19 known albinism genes in 990 index patients using targeted next-generation sequencing (NGS) and high-resolution comparative genomic hybridization. A molecular diagnosis was obtained in 72...
July 2018: Pigment Cell & Melanoma Research
Yuan Lu, Mikki Boswell, William Boswell, Susanne Kneitz, Michael Hausmann, Barbara Klotz, Janine Regneri, Markita Savage, Angel Amores, John Postlethwait, Wesley Warren, Manfred Schartl, Ronald Walter
Comparative analysis of human and animal model melanomas can uncover conserved pathways and genetic changes that are relevant for the biology of cancer cells. Spontaneous melanoma in Xiphophorus interspecies backcross hybrid progeny may be informative in identifying genes and functional pathways that are similarly related to melanoma development in all vertebrates, including humans. To assess functional pathways involved in the Xiphophorus melanoma, we performed gene expression profiling of the melanomas produced in interspecies BC1 and successive backcross generations (i...
July 2018: Pigment Cell & Melanoma Research
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