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Pigment Cell & Melanoma Research

Eleonora Leucci, Pierre Close, Jean-Christophe Marine
During tumor progression cancer cells are constantly challenged by intrinsic oncogene-induced and extrinsic micro-environmental stress signals such as hypoxia, nutrient deprivation, oxidative and genotoxic stress. Under these suboptimal growth conditions cancer cells activate an Integrative Stress Response (ISR), which results in a transient decrease in energy consumption followed by a cellular adaptation phase and possibly recovery, if the environmental conditions become more favorable. Translation is a very high energy-consuming process; it is therefore not surprising that to minimize energy consumption cancer cells turn down global protein synthesis rates while reprograming translation towards specific transcripts required for survival and adaptation...
February 21, 2017: Pigment Cell & Melanoma Research
Emily Clement, Ikrame Lazar, Catherine Muller, Laurence Nieto
Over the last decade, it has become increasingly clear that adipose tissue, and particularly adipocytes, contribute to tumor progression. Obesity, an ever-increasing worldwide phenomenon, exacerbates this effect. The influence of obesity on melanoma remains poorly studied, although recent data does underline an association between the two diseases in both humans and murine models. Herein, we review the impact of obesity on melanoma incidence and progression and discuss the underlying mechanisms known to be involved...
February 21, 2017: Pigment Cell & Melanoma Research
Stuart Gordon Jarrett, Katharine Marie Carter, John August D'Orazio
UV radiation is a major environmental risk factor for the development of melanoma by causing DNA damage and mutations. Resistance to UV damage is largely determined by the capacity of melanocytes to respond to UV injury by repairing mutagenic photolesions. The nucleotide excision repair (NER) pathway is the major mechanism by which cells correct UV photodamage. This multi-step process involves the basic steps of damage recognition, isolation, localized strand unwinding, assembly of a repair complex, excision of the damage-containing strand 3' and 5' to the photolesion, synthesis of a sequence-appropriate replacement strand and finally ligation to restore continuity of genomic DNA...
February 13, 2017: Pigment Cell & Melanoma Research
Makoto Goda
The chameleon sand tilefish Hoplolatilus chlupatyi displays rapid color changes in integument from blue to red. Our microscopic observations revealed that the rapid color changes were generated by motile activities of novel dermal iridophores. In the cytoplasm of the iridophores, we observed very thin reflecting platelets, resembling damselfish-type iridophores, but the platelets were arranged and distributed in a limited area near the cell membrane. Our pharmacological evaluation revealed that increasing K(+) ions in the perfusion medium led to a rapid color change of the iridophores from blue to red within 0...
February 13, 2017: Pigment Cell & Melanoma Research
Robert N Kelsh, Kleio Petratou
Pigment patterns throughout the animal kingdom repeatedly utilise shared motifs (solid spots, hollow spots, stripes in different orientations), begging the question of whether these are generated by the same or different mechanisms in each case. Although intuitively this might seem unlikely, a whole body of work on mathematical modelling of these patterns suggests that, in theory at least, all such patterns could share an underlying mechanism. Within the mammals, one such motif is alternating longitudinal dark and light stripes, whether the supremely contrasting facial stripes of European Meles meles and American Badgers Taxidea taxus or the more subtle and more numerous stripes of the head, flanks and back of chipmunks, Tamias...
February 9, 2017: Pigment Cell & Melanoma Research
Stacie K Loftus, Laura L Baxter, Julia C Cronin, Temesgen D Fufa, William J Pavan
Hypoxia and HIF1α signaling direct tissue-specific gene responses regulating tumor progression, invasion and metastasis. By integrating HIF1α knockdown and hypoxia-induced gene expression changes, this study identifies a melanocyte-specific, HIF1α-dependent / hypoxia-responsive gene expression signature. Integration of these gene expression changes with HIF1α ChIP-Seq analysis identifies 81 HIF1α direct target genes in melanocytes. The expression levels for ten of the HIF1α direct targets - GAPDH, PKM, PPAT, DARS, DTWD1, SEH1L, ZNF292, RLF, AGTRAP, and GPC6 - are significantly correlated with reduced time of Disease Free Status (DFS) in melanoma by logistic regression (P-value =0...
February 6, 2017: Pigment Cell & Melanoma Research
Ronan Crépin, David Gentien, Angeline Duché, Audrey Rapinat, Cecile Reyes, Fariba Némati, Gérald Massonnet, Didier Decaudin, Selma Djender, Sandrine Moutel, Klervi Desrumeaux, Nathalie Cassoux, Sophie Piperno-Neumann, Sebastian Amigorena, Franck Perez, Sergio Roman Roman, Ario de Marco
Monoclonal antibodies specific for biomarkers expressed on the surface of uveal melanoma (UM) cells would simplify the immune-capture and genomic characterization of heterogeneous tumor cells originated from patient derived xenografts (PDXs). Antibodies against four independent tumor antigens were isolated by panning a nanobody synthetic library. Such antibodies enabled flow-cytometry-based sorting of distinct cell sub-populations from UM PDXs and to analyze their genomic features. The complexity and specificity of the biochemical and genomic biomarker combinations mirrored the UM tumor polyclonality...
January 31, 2017: Pigment Cell & Melanoma Research
Lisa Koetz-Ploch, Douglas Hanniford, Igor Dolgalev, Elena Sokolova, Judy Zhong, Marta Díaz-Martínez, Emily Bernstein, Farbod Darvishian, Keith T Flaherty, Paul B Chapman, Hussein Tawbi, Eva Hernando
Melanoma patients with BRAF(V)(600E) -mutant tumors display striking responses to BRAF inhibitors (BRAFi); however, almost all invariably relapse with drug-resistant disease. Here we report that microRNA-125a (miR-125a) expression is upregulated in human melanoma cells and patient tissues upon acquisition of BRAFi resistance. We show that miR-125a induction confers resistance to BRAF(V)(600E) melanoma cells to BRAFi by directly suppressing pro-apoptotic components of the intrinsic apoptosis pathway, including BAK1 and MLK3...
January 31, 2017: Pigment Cell & Melanoma Research
Henri Montaudié, Michael Cerezo, Philippe Bahadoran, Coralie Roger, Thierry Passeron, Laurent Machet, Jean-Philippe Arnault, Laurence Verneuil, Eve Maubec, François Aubin, Florence Granel, Damien Giacchero, Véronique Hofman, Jean-Philippe Lacour, Allegra Maryline, Robert Balotti, Stéphane Rocchi
Targeted therapies and immunotherapies have significantly improved the prognosis of patients with advanced melanoma (Long et al., 2015; Robert et al., 2015a; Robert et al., 2015b; Ascierto et al., 2015). Unfortunately, treatment failure due to primary and secondary drug resistance are still observed and therefore there is an urgent need to identify new anti-melanoma agents. The oral anti-diabetic drug metformin belongs to the family of biguanides and it is the most widely used antidiabetic drug in the world...
January 25, 2017: Pigment Cell & Melanoma Research
Valerie Fock, Eiríkur Steingrímsson
Microphthalmia-associated transcription factor (MITF) is pivotal for the development of different cell lineages such as melanocytes, retinal pigment epithelial (RPE) cells and osteoclasts. Most of the information on the role of MITF has come from studying the many different mutations at the mouse microphthalmia (mi) locus. Mice that are heterozygous for the original Mitf(mi) allele exhibit a white belly spot, whereas homozygotes are completely white, microphthalmic, deaf and osteopetrotic (Steingrimsson et al...
January 24, 2017: Pigment Cell & Melanoma Research
Nicola Thompson, David Adams, Marco Ranzani
Great progress has been made in the treatment of melanoma through use of targeted therapies and immunotherapy. One approach that has not been fully explored is synthetic lethality, which exploits somatically acquired changes, usually driver mutations, to specifically kill tumour cells. We outline the various approaches that may be applied to identify synthetic lethal interactions and define how these interactions may drive drug discovery efforts. This article is protected by copyright. All rights reserved.
January 17, 2017: Pigment Cell & Melanoma Research
Roy Rabbie, Mamun Rashid, Ana M Arance, Marcelo Sánchez, Gemma Tell-Marti, Miriam Potrony, Carles Conill, Remco van Doorn, Stefan Dentro, Nellele A Gruis, Pippa Corrie, Vivek Iyer, Carla Daniela Robles-Espinoza, Joan A Puig-Butille, Susana Puig, David J Adams
Melanoma in young children is rare, however its incidence in adolescents and young adults is rising. We describe the clinical course of a 15-year-old female diagnosed with AJCC stage IB non-ulcerated primary melanoma, who died from metastatic disease four years after diagnosis despite three lines of modern systemic therapy. We also present the complete genomic profile of her tumour and compare this to a further series of 13 adolescent melanomas, and 275 adult cutaneous melanomas. A somatic BRAF(V)(600E) mutation and a high mutational load equivalent to that found in adult melanoma, and composed primarily of C>T mutations was observed...
January 17, 2017: Pigment Cell & Melanoma Research
Peter A Johansson, Antonia Pritchard, Ann-Marie Patch, James S Wilmott, John V Pearson, Nicola Waddell, Richard A Scolyer, Graham J Mann, Nicholas K Hayward
Whole-genome sequencing of matched germline and tumour pairs in a well characterised cohort of melanoma patients allowed investigation of associations between melanoma body site, age at melanoma onset and MC1R variant status with overall mutation burden and specific base pair changes observed in the corresponding melanoma. We observed statistically significant associations between mutation burden in melanoma and body site, age at onset and MC1R genotype, for both ultraviolet radiation (UVR) signature changes (C>T and CC>TT) and non-UVR base pair substitutions, as well as with overall variant load...
December 26, 2016: Pigment Cell & Melanoma Research
Kyriakos Orfanidis, Petra Wäster, Katarzyna Lundmark, Inger Rosdahl, Karin Öllinger
Malignant melanoma might develop from melanocytic nevi in which the growth-arrested state has been broken. We analyzed the gene expression of young and senescent human melanocytes in culture and compared the gene expression data with a dataset from nevi and melanomas. A concordant altered gene expression was identified in 84 genes when comparing the growth-arrested samples with proliferating samples. TUBB3, which encodes the microtubule protein tubulin β-3, showed a decreased expression in senescent melanocytes and nevi and was selected for further studies...
December 26, 2016: Pigment Cell & Melanoma Research
Nima Mesbah Ardakani, Connull Leslie, Fabienne Grieu-Iacopetta, Wei-Sen Lam, Charley Budgeon, Michael Millward, Benhur Amanuel
Heterogeneity of BRAF mutation in melanoma has been a controversial subject. Quantitative data on BRAF allele frequency (AF) is sparse and the potential relationship with response to BRAF inhibitors (BRAFi) in patients with metastatic melanoma is unknown. We quantitatively measured BRAF AF in a cohort of treatment naïve metastatic melanoma samples by pyrosequencing and correlated with survival data in patients treated with BRAFi as part of their clinical care. 52 samples from 50 patients were analysed. BRAF V600E mutations were detected in 71...
December 21, 2016: Pigment Cell & Melanoma Research
Laura Vibert, Gerardo Aquino, Ines Gehring, Tatiana Subkhankulova, Thomas F Schilling, Andrea Rocco, Robert N Kelsh
A role for Wnt signaling in melanocyte specification from neural crest is conserved across vertebrates, but possible ongoing roles in melanocyte differentiation have received little attention. Using a systems biology approach to investigate the gene regulatory network underlying stable melanocyte differentiation in zebrafish highlighted a requirement for a positive feedback loop involving the melanocyte master regulator Mitfa. Here we test the hypothesis that Wnt signaling contributes to that positive feedback...
December 15, 2016: Pigment Cell & Melanoma Research
Yueting Wu, Wentao Deng, Emily Chambers McGinley, David J Klinke
As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T cell function, a key mechanism for anti-tumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T cell proliferation. In contrast, Cloudman S91 exosomes promoted T cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells...
December 8, 2016: Pigment Cell & Melanoma Research
Eduardo Nagore, Diana Reyes-Garcia, Barbara Heidenreich, Zaida Garcia-Casado, Celia Requena, Rajiv Kumar
Mutations in the promoter of the telomerase reverse transcriptase gene (TERT) are one of the most prevalent somatic alterations in melanomas that occur at early stages of the disease (Heidenreich et al., 2014; Horn et al., 2013; Shain et al., 2015). Those mutations increase TERT expression by creating new binding motifs for Ets transcription factors which ultimately increase telomerase activity (Horn et al., 2013). Moreover, melanomas harbouring TERT promoter mutations display aggressive characteristics and associate with worse disease-free and melanoma-specific survival, particularly in presence of the BRAF or NRAS mutations (Griewank et al...
December 8, 2016: Pigment Cell & Melanoma Research
Naoki Oiso, Kazuko Sakai, Kazuto Nishio, Akira Kawada
Mosaicism in human skin results in different cutaneous patterns: the narrow lines of Blaschko (type 1a), the broad lines of Blaschko (type 1b), the checkerboard pattern (type 2), the phylloid pattern (type 3), and a patchy pattern without midline separation (type 4) (Happle, 1993). The phylloid pattern is characterized by an arrangement of pigmentary disturbances reminiscent of floral ornamentsor a Jugendstil painting (Happle, 1993). Phylloid hypomelanosis is characterized by congenital hypopigmented macules following the phylloid pattern...
December 8, 2016: Pigment Cell & Melanoma Research
Celia Requena, Barbara Heidenreich, Rajiv Kumar, Eduardo Nagore
The differential diagnosis between benign and malignant lesions in the field of spitzoid tumors can often be a challenge, and in some cases almost impossible. Significance of this differential diagnosis is due to its clinical implications; an erroneous diagnosis of spitzoid melanoma for a Spitz nevus can result in unnecessary treatment, which would not be required in the latter case. In recent years, diagnosis of atypical spitzoid tumor is preferred for lesions with features between benign and unequivocally malignant tumors...
December 8, 2016: Pigment Cell & Melanoma Research
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