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Pigment Cell & Melanoma Research

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https://www.readbyqxmd.com/read/29781575/brn2-a-pouerful-driver-of-melanoma-phenotype-switching-and-metastasis
#1
REVIEW
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 behavior within the phenotype-switching model of progression...
May 21, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29781574/melanocyte-development-in-the-mouse-tail-epidermis-requires-the-adamts9-metalloproteinase
#2
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
https://www.readbyqxmd.com/read/29778085/braf-and-mek-inhibitor-therapy-eliminates-nestin-expressing-melanoma-cells-in-human-tumors
#3
Deon B Doxie, Allison R Greenplate, Jocelyn S Gandelman, Kirsten E Diggins, Caroline E Roe, Kimberly B Dahlman, Jeffrey A Sosman, Mark C Kelley, Jonathan M Irish
Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAFV 600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM...
May 19, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29741814/drosophila-melanogaster-has-the-enzymatic-machinery-to-make-the-melanic-component-of-neuromelanin
#4
Hanine Barek, Alexey Veraksa, Manickam Sugumaran
In Drosophila, the same set of genes that are used for cuticle pigmentation and sclerotization are present in the nervous system and are responsible for neurotransmitter recycling. In this study, we carried out biochemical analysis to determine if insects have the enzymatic machinery to make melanic component of neuromelanin. We focused our attention on two key enzymes of melanogenesis, namely phenoloxidase and dopachrome decarboxylase/tautomerase. Activity staining of the proteins isolated from the Drosophila larval brain tissue, separated by native polyacrylamide gel electrophoresis indicated the presence of these two enzymes...
May 9, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29738114/oncogenic-signaling-in-uveal-melanoma
#5
REVIEW
John J Park, Russell J Diefenbach, Anthony M Joshua, Richard F Kefford, Matteo S Carlino, Helen Rizos
Uveal melanoma is the most common primary cancer of the eye, and despite rapidly emerging insights into the molecular profile of this disease, prognosis of patients with metastatic uveal melanoma remains poor with mortality rates unchanged in over 35 years. Early genetic events activate G protein-coupled receptor signaling in nearly all uveal tumors via mutually exclusive mutations in the GNAQ, GNA11, CYSLTR2, or PLCB4 genes. A multitude of signaling cascades downstream of G protein activation, including protein kinase C and mitogen-activated protein kinase activity, are actionable, and many ongoing clinical trials are targeting these pathways...
May 8, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29738111/raman-spectroscopy-quantification-of-eumelanin-subunits-in-natural-unaltered-pigments
#6
Ismael Galván, Cuauhtemoc Araujo-Andrade, Mónica Marro, Pablo Loza-Alvarez, Kazumasa Wakamatsu
Eumelanins are large polymers composed of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Reactive oxygen species generation is higher during the synthesis of DHI than during the synthesis of DHICA; thus, the production of eumelanins with high relative DHI contents may compromise the viability of cells and organisms. Here, we show that dispersive Raman spectroscopy allows a noninvasive direct detection and quantification of DHI and DHICA in unaltered eumelanins that can be applied to the analysis of natural pigments in biological tissues...
May 8, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29665313/refinement-of-the-endogenous-epitope-tagging-technology-allows-the-identification-of-a-novel-nras-binding-partner-in-melanoma
#7
Michal Alon, Rafi Emmanuel, Nouar Qutob, Anna Bakhman, Victoria Peshti, Alexandra Brodezki, David Bassan, Mickey Kosloff, Yardena Samuels
The NRAS oncoprotein is highly mutated in melanoma. However, to date, no comprehensive proteomic study has been reported for NRAS. Here, we utilized the endogenous epitope tagging (EET) approach for the identification of novel NRAS binding partners. Using EET, an epitope tag is added to the endogenously expressed protein, via modification of its genomic coding sequence. Existing EET systems are not robust, suffer from high background, and are labor-intensive. To this end, we present a polyadenylation signal-trap construct for N'-tagging that generates a polycistronic mRNA with the gene of interest...
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29665239/fbxw7-regulates-a-mitochondrial-transcription-program-by-modulating-mitf
#8
Franco Abbate, Brateil Badal, Karen Mendelson, Iraz T Aydin, Madhavika N Serasinghe, Ramiz Iqbal, Jarvier N Mohammed, Alexander Solovyov, Benjamin D Greenbaum, Jerry E Chipuk, Julide T Celebi
FBXW7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor-suppressive function have not been fully elucidated. We leveraged two distinct RNA sequencing datasets: human melanoma cell lines (n = 10) with control versus silenced FBXW7 and a cohort of human melanoma tumor samples (n = 51) to define the transcriptomic fingerprint regulated by FBXW7. Here, we report that loss of FBXW7 enhances a mitochondrial gene transcriptional program that is dependent on MITF in human melanoma and confers poor patient outcomes...
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29665231/estrogen-returns-to-the-stage-in-melanoma
#9
Jennifer L McQuade, Michael A Davies
No abstract text is available yet for this article.
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29603877/concordance-of-somatic-mutational-profile-in-multiple-primary-melanomas
#10
Nikki R Adler, Catriona A McLean, Rory Wolfe, John W Kelly, Grant A McArthur, Andrew Haydon, Thien Tra, Nicholas Cummings, Victoria J Mar
This study aimed to determine the frequency and concordance of BRAF and NRAS mutation in tumours arising in patients with multiple primary melanoma (MPM). Patients with MPM managed at one of three tertiary referral centres in Melbourne, Australia, from 2010 to 2015 were included. Incident and subsequent melanomas underwent mutation testing. Cohen's kappa (κ) coefficient assessed agreement between incident and subsequent primary melanomas for both BRAF and NRAS mutation status (mutant versus wild-type). Mutation testing of at least two primary tumours from 64 patients was conducted...
March 30, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29603875/toll-like-receptors-2-and-3-enhance-melanogenesis-and-melanosome-transport-in-human-melanocytes
#11
Saaya Koike, Kenshi Yamasaki, Takeshi Yamauchi, Mai Inoue, Ryoko Shimada-Ohmori, Kenichiro Tsuchiyama, Setsuya Aiba
Because little is known about how the innate immune response influences skin pigmentation, we examined whether Toll-like receptor (TLR) agonists participate in melanogenesis and melanosome transportation. We observed that TLR2/2 agonist HKLM and TLR3 agonist Poly(I:C) increased the amount of extracellular melanin from primary human epidermal melanocytes. HKLM, but not Poly(I:C), increased the melanogenic genes such as tyrosinase and dopachrome tautomerase. Poly(I:C) increased the expression of Rab27A, a molecule that facilitates melanosome transport to perimembranous actin filament...
March 30, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29582573/regulation-of-melanocyte-stem-cell-behavior-by-the-niche-microenvironment
#12
REVIEW
Huirong Li, Ling Hou
Somatic stem cells are regulated by their niches to maintain tissue homeostasis and repair throughout the lifetime of an organism. An excellent example to study stem cell/niche interactions is provided by the regeneration of melanocytes during the hair cycle and in response to various types of injury. These processes are regulated by neighboring stem cells and multiple signaling pathways, including WNT/β-catenin, KITL/KIT, EDNs/EDNRB, TGF-β/TGF-βR, α-MSH/MC1R, and Notch signaling. In this review, we highlight recent studies that have advanced our understanding of the molecular crosstalk between melanocyte stem cells and their neighboring cells, which collectively form the niche microenvironment, and we focus on the question of how McSCs/niche interactions shape the responses to genotoxic damages and mechanical injury...
March 26, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29337423/the-next-generation-of-melanocyte-data-genetic-epigenetic-and-transcriptional-resource-datasets-and-analysis-tools
#13
Stacie K Loftus
The number of melanocyte- and melanoma-derived next generation sequence genome-scale datasets have rapidly expanded over the past several years. This resource guide provides a summary of publicly available sources of melanocyte cell derived whole genome, exome, mRNA and miRNA transcriptome, chromatin accessibility and epigenetic datasets. Also highlighted are bioinformatic resources and tools for visualization and data queries which allow researchers a genome-scale view of the melanocyte.
May 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29316280/giant-congenital-melanocytic-nevus-with-vascular-malformation-and-epidermal-cysts-associated-with-a-somatic-activating-mutation-in-braf
#14
Heather C Etchevers, Christian Rose, Birgit Kahle, Helmuth Vorbringer, Frédéric Fina, Pauline Heux, Irina Berger, Benjamin Schwarz, Stéphane Zaffran, Nicolas Macagno, Sven Krengel
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 asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts then developed within it...
May 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29272074/prevalence-of-vitiligo-in-brazil-a-population-survey
#15
LETTER
Caio Cesar Silva de Castro, Hélio A Miot
No abstract text is available yet for this article.
May 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29239123/seeing-the-light-to-change-colour-an-evolutionary-perspective-on-the-role-of-melanopsin-in-neuroendocrine-circuits-regulating-light-mediated-skin-pigmentation
#16
REVIEW
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 analyse 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...
May 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29224244/a-histopathological-classification-system-of-tyr-nras-q61k-murine-melanocytic-lesions-a-reproducible-simplified-classification
#17
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::NRASQ 61K 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...
May 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29171936/braf-internal-deletions-and-resistance-to-braf-mek-inhibitor-therapy
#18
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, BRAFV 600 -mutated melanomas. Acquired resistance occurs in most patients, with numerous and diverse drivers. We obtained pretreatment and progression biopsies from a patient who progressed on dabrafenib and trametinib. In addition to a preserved BRAFV 600E 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...
May 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29171182/acid-hydrolysis-reveals-a-low-but-constant-level-of-pheomelanin-in-human-black-to-brown-hair
#19
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-tricarboxylic 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 hr...
May 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29171181/regulation-of-cell-proliferation-in-the-retinal-pigment-epithelium-differential-regulation-of-the-death-associated-protein-like-1-dapl1-by-alternative-mitf-splice-forms
#20
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...
May 2018: Pigment Cell & Melanoma Research
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