Pigment Cell Research via MedWorm.com MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Pigment Cell Research' source. Tue, 07 Feb 2012 08:49:01 +0100 GWAS in Melanoma: Off to a Good Start http://www.medworm.com/index.php?rid=5626234&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00981.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5626234 Mon, 23 Jan 2012 05:00:00 +0100 5626234 The genetics of uveal melanoma: an emerging framework for targeted therapy http://www.medworm.com/index.php?rid=5626233&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00979.x This article will review the genetic findings in uveal melanoma over the past two decades and suggest important areas for future work.© 2012 John Wiley & Sons A/S (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5626233 Mon, 23 Jan 2012 05:00:00 +0100 5626233 MicroRNAs and signaling, complex interaction by feedback loops http://www.medworm.com/index.php?rid=5626232&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00980.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5626232 Mon, 23 Jan 2012 05:00:00 +0100 5626232 Functional Expression of Voltage‐Gated Calcium Channels in Human Melanoma http://www.medworm.com/index.php?rid=5618249&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00978.x AbstractThe expression of voltage‐gated calcium channels (VGCCs) has not been reported previously in melanoma cells, in spite of the increasing evidences for a role of VGCCs in tumorigenesis and tumour progression. To address this issue we have performed an extensive RT‐PCR analysis of VGCCs expression in human melanocytes and a range of melanoma cell lines and biopsies. In addition, we have tested the functional expression of these channels upon application of Ca2+ imaging techniques, and examined their relevance in the viability and proliferation of the melanoma cells. Our results show that control melanocytes and melanoma cells express channel isoforms belonging to the Cav1 and Cav2 gene families. Importantly, the expression of low voltage‐activated Cav3 (T‐type) channels is res... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5618249 Thu, 19 Jan 2012 05:00:00 +0100 5618249 The Yin‐Yang of RAF inhibitors http://www.medworm.com/index.php?rid=5605683&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00947.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5605683 Thu, 19 Jan 2012 05:00:00 +0100 5605683 Highly penetrant melanoma in a zebrafish model is independent of ErbB3b signaling http://www.medworm.com/index.php?rid=5605682&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00973.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5605682 Mon, 16 Jan 2012 05:00:00 +0100 5605682 Reviewing the somatic genetics of melanoma: from current to future analytical approaches http://www.medworm.com/index.php?rid=5605681&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00975.x This article will review the catalog of mutations identified in melanoma through a variety of approaches, including the use of unbiased exome and whole‐genome next generation sequencing platforms, as well discuss complementary strategies for identifying driver mutations. The promise of personalised medicine afforded by better understanding these mutation events should provide impetus for increased activity and rapid advances in this field. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5605681 Mon, 16 Jan 2012 05:00:00 +0100 5605681 Targeting Sphingosine Kinase‐1 To Inhibit Melanoma http://www.medworm.com/index.php?rid=5579188&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00970.x This study shows that elevated sphingosine‐1‐phosphate (S‐1‐P) levels resulting from increased activity of sphingosine kinase‐1 (SPHK1) occur in advanced melanomas. Targeting SPHK1 using siRNA decreased anchorage dependent and independent growth as well as sensitized melanoma cells to apoptosis inducing agents. Pharmacological SPHK1 inhibitors SKI‐I but not SKI‐II decreased S‐1‐P content, elevated ceramide levels, caused a G2‐M block and induced apoptotic cell death in melanomas. Targeting SPHK1 using siRNA or the pharmacological agent called SKI‐I, decreased the levels of pAKT. Furthermore, SKI‐I inhibited the expression of CYCLIN D1 protein and increased the activity of caspase‐3/7, which in turn led to the degradation of PARP. In animals, SKI‐I but not SKI‐... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5579188 Wed, 11 Jan 2012 05:00:00 +0100 5579188 Genetic and Molecular Characterization of Uveal Melanoma Cell Lines http://www.medworm.com/index.php?rid=5579187&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00971.x We report the mutation status of relevant melanoma genes, expression levels of proteins of interest and DNA fingerprinting of a panel of uveal melanoma cell lines used in the research community. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5579187 Wed, 11 Jan 2012 05:00:00 +0100 5579187 Duplication of CXC chemokine genes on chromosome 4q13 in a melanoma‐prone family http://www.medworm.com/index.php?rid=5579189&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00969.x SummaryCopy 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 without known segregating mutations using genome‐wide comparative genomic hybridization (CGH) tiling arrays. We identified a duplicated region on chromosome 4q13 in germline DNA of all melanoma patients in a melanoma‐prone family with three affected siblings. We confirmed the duplication using quantitative PCR and a custom‐made CGH array design spanning the 4q13 region. The duplicated region contains 10 genes, most of which encode CXC chemokines. Among them... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5579189 Mon, 09 Jan 2012 05:00:00 +0100 5579189 En route to a new in vivo diagnostic of malignant pigmented melanoma http://www.medworm.com/index.php?rid=5626235&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00966.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5626235 Thu, 05 Jan 2012 05:00:00 +0100 5626235 En route to a new in vivo diagnostics of malignant pigmented melanoma http://www.medworm.com/index.php?rid=5570494&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00966.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5570494 Thu, 05 Jan 2012 05:00:00 +0100 5570494 Glutamatergic Signaling in Cellular Transformation http://www.medworm.com/index.php?rid=5626231&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00983.x The role of the glutamatergic system in cancer cell homeostasis has expanded exponentially over the last decade. Once thought to participate only in synaptic transmission and neuronal excitability, the presence of functional glutamate receptors have since been demonstrated in peripheral tissues. Most notable is the implication of glutamate receptors in the pathophysiology of various human malignancies. We previously described the oncogenic properties of metabotropic glutamate receptor 1 (Grm1), a G‐protein coupled receptor in melanoma development in vivo. TG‐3, a transgenic mouse line developed spontaneous melanoma with 100% penetrance in the absence of any known stimuli. Stable Grm1‐mouse melanocytic clones display transformed phenotypes in vitro and were aggressively tumorigenic in... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5626231 Sun, 01 Jan 2012 05:00:00 +0100 5626231 Delving into somatic variation in sporadic melanoma http://www.medworm.com/index.php?rid=5618248&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00976.x AbstractMelanoma, the most aggressive form of skin cancer, has increased in incidence more rapidly than any other cancer. The completion of the human genome project and advancements in genomics technologies has allowed us to investigate genetic alterations of melanoma at a scale and depth that is unprecedented. Here, we survey the history of the different approaches taken to understand the genomics of melanoma ‐ from early candidate genes, to gene families, to genome wide studies. The new era of whole exome and whole genome sequencing has paved the way for an in depth understanding of melanoma biology, identification of new therapeutic targets and development of novel personalized therapies for melanoma. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5618248 Sun, 01 Jan 2012 05:00:00 +0100 5618248 Small molecule screening identifies targetable zebrafish pigmentation pathways http://www.medworm.com/index.php?rid=5605680&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00977.x SummarySmall molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish, and investigate the effects of a few of these compounds in further detail. We identified and confirmed 57 compounds that altered pigment cell patterning, number, survival or differentiation. Additional tissue targets and toxicity of small molecules are also discussed. Given that the majority of cell types, including pigment cells, are conserved between zebrafish and other vertebrates, we present these chemicals as molecular tools to study developmental processes of pigment cells in living animals, and ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5605680 Sun, 01 Jan 2012 05:00:00 +0100 5605680 Striping by striding: synthetic approaches toward pattern formation http://www.medworm.com/index.php?rid=5579186&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00972.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5579186 Sun, 01 Jan 2012 05:00:00 +0100 5579186 Stem cell niche: from concept to reality http://www.medworm.com/index.php?rid=5570493&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2012.00967.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5570493 Sun, 01 Jan 2012 05:00:00 +0100 5570493 Identification of differentially expressed genes in matched formalin‐fixed paraffin‐embedded primary and metastatic melanoma tumor pairs http://www.medworm.com/index.php?rid=5535391&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00965.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5535391 Sat, 24 Dec 2011 02:14:17 +0100 5535391 β‐catenin in metastatic melanoma ‐ The smoking gun reloaded http://www.medworm.com/index.php?rid=5521967&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00964.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5521967 Wed, 21 Dec 2011 01:13:15 +0100 5521967 β‐catenin in metastatic melanoma – the smoking gun reloaded http://www.medworm.com/index.php?rid=5579190&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00964.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5579190 Mon, 19 Dec 2011 05:00:00 +0100 5579190 On the edge http://www.medworm.com/index.php?rid=5513617&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00940.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5513617 Sun, 18 Dec 2011 01:38:30 +0100 5513617 Role and Therapeutic Potential of PI3K‐mTOR Signaling in De Novo Resistance to BRAF Inhibition http://www.medworm.com/index.php?rid=5513615&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00950.x SummaryBRAF inhibition is highly active in BRAF‐mutant melanoma, but the degree and duration of responses is quite variable. Improved understanding of the mechanisms of de novo resistance may lead to rational therapeutic strategies with improved efficacy. Proteomic analysis of BRAF‐mutant, PTEN‐wild‐type human melanoma cell lines treated with PLX4720 demonstrated that sensitive and de novo resistant lines exhibit similar RAS‐RAF‐MEK‐ERK pathway inhibition, but the resistant cells exhibited durable activation of S6 and P70S6K. Treatment with the mTOR inhibitor rapamycin blocked activation of P70S6K and S6, but it also increased activation of AKT and failed to induce cell death. Combined treatment with rapamycin and PX‐866, a PI3K inhibitor, blocked the activation of S6 and A... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5513615 Sun, 18 Dec 2011 01:38:19 +0100 5513615 Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype http://www.medworm.com/index.php?rid=5513616&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00949.x SummaryThe mitogen activated protein kinase (MAPK) pathway is important in melanoma. In this pathway, DUSP6 phosphatase negatively controls activation of ERK kinase. Through comparison of melanoma signalling pathways between immortal mouse melanocytes and their tumourigenic derivatives, retrieved from mouse xenografts, we identified a molecularly distinct subtype of melanoma, characterized by reduced ERK activity and increased DUSP6 expression. Overexpression of DUSP6 enhanced anchorage‐independent growth and invasive ability of immortal mouse melanocytes, suggesting that increased DUSP6 expression contributes to melanoma formation in the mouse xenografts. In contrast, reduced tumourigenicity was observed after DUSP6 overexpression in human melanoma cells. A minority of thick human prima... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5513616 Thu, 15 Dec 2011 05:00:00 +0100 5513616 Elevated Expression of Rad18 Regulates Melanoma Cell Proliferation http://www.medworm.com/index.php?rid=5484785&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00948.x SummaryThe E3 ligase Rad18 is a key regulator for the lesion bypass pathway which plays an important role in genomic stability. However, the status of Rad18 expression in melanoma is not known. Using melanoma tissue microarray (TMA), we showed that nuclear Rad18 expression was upregulated in primary and metastatic melanoma compared to dysplastic nevi. Rad18 expression was significantly reduced in sun‐exposed sites compared to the sun‐protected sites. Strong Rad18 expression correlated with worse 5‐year patient survival and was an independent prognostic factor for melanoma found in the sun‐protected sites. Furthermore, we showed that melanoma cell proliferation and the expression of pAkt and cyclin D1 were reduced upon Rad18 knockdown. We for the first time showed that Rad18 is sign... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5484785 Tue, 06 Dec 2011 05:00:00 +0100 5484785 Site dependent actinic skin damage as risk factor for melanoma in a central European population http://www.medworm.com/index.php?rid=5484784&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00946.x SummarySun exposure is causal for melanoma but is subject to bias of recall so that it is difficult to dissect the role of particular patterns of sun exposure. In this hospital‐based case‐control study (n=1991), we aimed to analyze pigmentation traits and signs of actinic damage at different anatomic locations as markers of melanoma risk in central European patients. Although all signs of actinic damage (freckling, wrinkling and solar lentigos) were significantly associated with melanoma risk in multivariate logistic regression models adjusting for age and sex, the strongest associations were observed for the dorsal parts of the body: adjusted odds ratios [OR] were 4.22 for wrinkling on the neck, 3.43 for solar lentigos and 3.37 for freckling on the back (all P<0.001), respectively.... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5484784 Thu, 01 Dec 2011 05:00:00 +0100 5484784 Dysregulation of Melanocyte Function by Th17‐related Cytokines: Significance of Th17 Cell Infiltration in Autoimmune Vitiligo Vulgaris http://www.medworm.com/index.php?rid=5474569&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00945.x SummaryThe aim of this study was to show CD4+IL‐17A+Th17 cells infiltrate into vitiligo skin and to investigate whether the proinflammatory cytokines related to Th17 cells influence the melanocyte enzymatic activity and cell fate. An immunohistochemical analysis showed Th17 cells infiltration in 7 of 23 vitiligo skin samples in addition to CD8+ cells on the reticular dermis. An in vitro analysis showed the expression of MITF and downstream genes to be downregulated by the treatment with IL‐17A, IL‐1β, IL‐6 and TNF‐α. The treatment with these cytokines also induced morphological shrinking in melanocyte, resulting in a decreased melanin production. In view of local cytokine network in the skin, IL‐17A dramatically induced IL‐1β, IL‐6 and TNF‐α production in skin residen... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5474569 Thu, 01 Dec 2011 05:00:00 +0100 5474569 Carcinogen treatment in mouse selectively expressing activated N‐RasQ61K in melanocytes recapitulates metastatic cutaneous melanoma development http://www.medworm.com/index.php?rid=5455243&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00944.x SummaryThe incidence of melanoma has significantly increased and a better understanding its pathogenesis and development of new therapeutic strategies are urgently needed. Here we describe a murine model of metastatic cutaneous melanoma using C57BL/6 mice expressing a mutated human N‐Ras gene under the control of a tyrosinase promoter (TyrRas). These mice were topically exposed to 7,12‐ dimethylbenzanthracene (DMBA) for brief exposure periods. Cutaneous melanoma developed at the site of exposure on average by 19 weeks of age and in 80% of mice. Importantly, as in humans, melanoma development was associated with subsequent metastasis to tumor‐draining lymph nodes. Critically, such metastatic behavior is transplantable, as intradermal inoculation of melanoma cells from TyrRas‐DMBA mi... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5455243 Wed, 30 Nov 2011 02:06:00 +0100 5455243 NLRP1, a regulator of innate immunity associated with vitiligo http://www.medworm.com/index.php?rid=5448415&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00942.x AbstractSome familial forms of the dermatological condition vitiligo have recently been linked to polymorphisms in the innate immunity gene, NLRP1. Here we review what is currently known about the mechanisms that regulate activation of the NLRP1 protein and the downstream effects of NLRP1 on pathways impacting inflammation and apoptosis. How polymorphic variants of the NLRP1 gene contribute to the pathogenesis of vitiligo remains mysterious, requiring further investigation. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5448415 Sun, 27 Nov 2011 03:05:19 +0100 5448415 Meeting report from the 2011 International Melanoma Congress, Tampa, Florida http://www.medworm.com/index.php?rid=5448416&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00943.x AbstractThe 2011, 8th International Congress of the Society for Melanoma Research was held in conjunction with the 5th Meeting of the Interdisciplinary Melanoma/Skin Cancer Centres, the 2nd Melanoma update for Primary Care Physicians, Surgeons, Oncologists and Dermatologists and the 4th Melanoma Pathology Symposium of the International Melanoma Pathology Working Group in Tampa, Florida, USA. The four meetings attracted over 685 attendees and covered the breadth of basic melanoma biology all the way through to the clinical management of melanoma and other skin cancers. The major focus of discussions this year was upon the resistance of melanoma patients to BRAF inhibitors and novel strategies for the preclinical and clinical management of therapeutic escape. Overall, it was felt that the me... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5448416 Fri, 25 Nov 2011 05:00:00 +0100 5448416 List of referees for Volume 24 http://www.medworm.com/index.php?rid=5438888&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00924.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5438888 Thu, 24 Nov 2011 01:33:49 +0100 5438888 The three M’s: melanoma, microphthalmia‐associated transcription factor and microRNA http://www.medworm.com/index.php?rid=5438887&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00931.x SummaryStudies examining intratumor heterogeneity have indicated that several cancer types, including melanoma, can display phenotypic plasticity, corresponding to their capacity to undergo transient reversible cellular changes. Conceptual models constructed to explain the process of cancer propagation differ in their treatment of intratumor heterogeneity. Recent observations of reversible phenotypic heterogeneity in melanoma have led to the proposal of a novel ‘phenotypic plasticity’ model of cancer propagation. Microphthalmia‐associated transcription factor (MITF), the melanocyte ‘lineage‐specific’ transcription factor, has emerged as one of the central players in melanoma phenotypic plasticity. Here we discuss the conceptual models suggested to explain the relations between ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5438887 Thu, 24 Nov 2011 01:33:39 +0100 5438887 P‐REX1, a Rac guanine exchange factor, links melanocyte development and melanoma progression http://www.medworm.com/index.php?rid=5438886&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00934.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5438886 Thu, 24 Nov 2011 01:33:37 +0100 5438886 Microphthalmia‐associated transcription factor, melanoma, and renal carcinoma: the small ubiquitin‐like modifier connection http://www.medworm.com/index.php?rid=5438885&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00925.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5438885 Thu, 24 Nov 2011 01:33:31 +0100 5438885 Research – endure! http://www.medworm.com/index.php?rid=5438884&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00932.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5438884 Thu, 24 Nov 2011 01:33:28 +0100 5438884 Book Review http://www.medworm.com/index.php?rid=5438883&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00941.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5438883 Thu, 24 Nov 2011 01:33:01 +0100 5438883 Absorbing black bodies: melanosomes come of age http://www.medworm.com/index.php?rid=5493261&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00941.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5493261 Wed, 23 Nov 2011 05:00:00 +0100 5493261 Nick Hayward http://www.medworm.com/index.php?rid=5419776&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00936.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5419776 Wed, 16 Nov 2011 05:00:00 +0100 5419776 General strategy to analyse coat colour phenotypes in mice http://www.medworm.com/index.php?rid=5419775&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00912.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5419775 Wed, 16 Nov 2011 05:00:00 +0100 5419775 MEK–ERK and heparin‐susceptible signaling pathways are involved in cell‐cycle entry of the wound edge retinal pigment epithelium cells in the adult newt http://www.medworm.com/index.php?rid=5419774&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00935.x SummaryThe onset mechanism of proliferation in mitotically quiescent retinal pigment epithelium (RPE) cells is still obscure in humans and newts, although it can be a clinical target for manipulating both retinal diseases and regeneration. To address this issue, we investigated factors or signaling pathways involved in the first cell‐cycle entry of RPE cells upon retinal injury using a newt retina‐less eye‐cup culture system in which the cells around the wound edge of the RPE exclusively enter the cell cycle. We found that MEK–ERK signaling is necessary for their cell‐cycle entry, and signaling pathways whose activities can be modulated by heparin, such as Wnt‐, Shh‐, and thrombin‐mediated pathways, are capable of regulating the cell‐cycle entry. Furthermore, we found tha... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5419774 Tue, 25 Oct 2011 04:00:00 +0100 5419774 The Three M’s: Melanoma, MITF and MicroRNA http://www.medworm.com/index.php?rid=5332853&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00931.x AbstractStudies examining intratumor heterogeneity have indicated that several cancer types, including melanoma, can display phenotypic plasticity, corresponding to their capacity to undergo transient reversible cellular changes. Conceptual models constructed to explain the process of cancer propagation differ in their treatment of intratumor heterogeneity. Recent observations of reversible phenotypic heterogeneity in melanoma,haveled the proposal ofa novel ‘phenotypic plasticity’ model of cancer propagation. Microphthalmia‐associated transcription factor (MITF), the melanocyte ‘lineage‐specific’ transcription factor, has emerged as one of the central players in melanoma phenotypic plasticity.Here we discuss the conceptual models proposed to explain the relations between MITF a... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5332853 Mon, 17 Oct 2011 04:00:00 +0100 5332853 Is proteomics starting to deliver on biomarkers discovery http://www.medworm.com/index.php?rid=5332852&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00930.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5332852 Mon, 17 Oct 2011 04:00:00 +0100 5332852 Glutamate Receptors: Emerging Players in Melanomagenesis http://www.medworm.com/index.php?rid=5332851&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00926.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5332851 Mon, 17 Oct 2011 04:00:00 +0100 5332851 A new mutation with STAGgering effects http://www.medworm.com/index.php?rid=5332850&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00928.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5332850 Mon, 17 Oct 2011 04:00:00 +0100 5332850 Functional Defects of Peripheral Regulatory T Lymphocytes in Patients with Progressive Vitiligo http://www.medworm.com/index.php?rid=5312246&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00920.x SummaryAuto‐reactive cytotoxic T lymphocytes play a key role in the progressive loss or destruction of melanocytes in vitligo but the mechanism underlying the loss of self‐tolerance is unknown. A deregulation of regulatory T cell biology has been recently suggested. The analysis of the suppressive effects of peripheral T regulatory cells in vitiligo patients revealed a functional defect in 7 out of fifteen cases. This defect was strongly correlated with disease activity. The evaluation of the percentage of peripheral regulatory T lymphocytes did not reveal any intrinsic quantitative defect. Yet, a decrease in the percentage of such cells was noted in patients with progressive forms suggesting a recruitment of regulatory T cells from the peripheral blood to the site of injury. This was ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5312246 Tue, 11 Oct 2011 04:00:00 +0100 5312246 In vivo vitiligo induction and therapy model: double‐blind, randomized clinical trial http://www.medworm.com/index.php?rid=5378270&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00922.x In this study, we developed an in vivo vitiligo induction model to explore the underlying mechanisms leading to Koebner’s phenomenon and to evaluate the efficacy of therapeutic strategies. The model consisted of 12 pigmented test regions on the back of generalized vitiligo patients that were exposed to three Koebner induction methods: cryotherapy, 755 nm laser therapy, and epidermal abrasion. In addition, four cream treatments (pimecrolimus, tacrolimus, steroid and placebo) were randomly applied. Koebnerization was efficiently induced by all three induction methods. In general, cryotherapy was the best method of Koebner induction, followed by 755 nm laser therapy and epidermal abrasion. Reproducible results were obtained, which showed enhanced depigmented surface areas and higher amo... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5378270 Mon, 10 Oct 2011 04:00:00 +0100 5378270 Modelling melanoma in mice http://www.medworm.com/index.php?rid=5378269&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00923.x SummaryPhenotypic and molecular heterogeneity in human melanoma has impaired efforts to explain many of the clinically important features of melanoma. For example, many of the underlying mechanisms that might predict age‐of‐onset, time to metastasis and other key elements in melanoma progression remain unknown. Furthermore, melanoma staging used to predict outcome and treatment has not yet moved beyond a basic phenotypic classification. While molecularly targeted therapies show great promise for melanoma patients, establishing accurate animal models that recapitulate human cutaneous melanoma progression remains a priority. We examine the relevance of mice as models for human melanoma progression and for key molecular and histopathologic variants of melanoma. These mice may be used as p... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5378269 Mon, 10 Oct 2011 04:00:00 +0100 5378269 In vivo vitiligo induction and therapy model : double blind, randomized clinical trial http://www.medworm.com/index.php?rid=5302601&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00922.x In this study, we developed an in vivo vitiligo induction model to explore the underlying mechanisms leading to Koebner’s phenomenon and to evaluate the efficacy of therapeutic strategies. The model consisted of 12 pigmented test regions on the back of generalized vitiligo patients that were exposed to 3 Koebner induction methods: cryotherapy, 755nm laser therapy and epidermal abrasion. In addition, 4 cream treatments (pimecrolimus, tacrolimus, steroid and placebo) were randomly applied. Koebnerization was efficiently induced by all 3 induction methods. In general, cryotherapy was the best method of koebner induction, followed by 755nm laser therapy and epidermal abrasion. Reproducible results were obtained which showed enhanced depigmented surface areas and higher amounts of T lymphocyt... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302601 Mon, 10 Oct 2011 04:00:00 +0100 5302601 Inhibition of coding region determinant binding protein sensitizes melanoma cells to chemotherapeutic agents http://www.medworm.com/index.php?rid=5356903&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00921.x SummaryWe previously reported that malignant melanomas express high levels of the mRNA binding protein coding region determinant binding protein (CRD‐BP). This molecule is important for the activation of anti‐apoptotic pathways, a mechanism often linked to insensitivity to therapeutics. However, it is not known whether CRD‐BP plays a role in the resistance of melanomas to anti‐cancer treatment. Here we demonstrate that knockdown of CRD‐BP with a specific sh‐RNA enhances the effect of dacarbazine, temozolomide, vinblastine, and etoposide on both primary and metastatic melanoma cell lines. CRD‐BP down‐regulation contributes to cell sensitization by increasing apoptosis and diminishing melanoma cell growth in response to chemotherapeutic agents. Furthermore, inhibition of CRD... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5356903 Sat, 08 Oct 2011 04:00:00 +0100 5356903 Inhibition of CRD‐BP sensitizes melanoma cells to chemotherapeutic agents http://www.medworm.com/index.php?rid=5302603&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00921.x SummaryWe previously reported that malignant melanomas express high levels of the mRNA binding protein CRD‐BP. This molecule is important for the activation of anti‐apoptotic pathways, a mechanism often linked to insensitivity to therapeutics. However, it is not known whether CRD‐BP plays a role in the resistance of melanomas to anti‐cancer treatment. Here we demonstrate that knock‐down of CRD‐BP with a specific sh‐RNA enhances the effect of dacarbazine, temozolomide, vinblastine and etoposide on both primary and metastatic melanoma cell lines. CRD‐BP down‐regulation contributes to cell sensitization by increasing apoptosis and diminishing melanoma cell growth in response to chemotherapeutic agents. Furthermore, inhibition of CRD‐BP decreases MITF expression and reintro... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302603 Sat, 08 Oct 2011 04:00:00 +0100 5302603 PHGDH amplification and altered glucose metabolism in human melanoma http://www.medworm.com/index.php?rid=5302602&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00919.x SummarySince the seminal work of Otto Warburg, cancer cells have been known to import and consume increased amounts of glucose compared to most normal cells and to produce lactate even in the presence of oxygen. This switch to a fermentative metabolism is known as the Warburg effect (Warburg, 1924, Warburg, 1956). Why cancer cells engage in aerobic glycolysis despite the low ATP yield compared to the Krebs Cycle is not clearly understood. One explanation could be that cancer cell proliferation is not limited by ATP production, but rather by the ability of cells to synthesize the lipids, nucleic acids and proteins needed to produce biomass (Vander Heiden et al., 2009, Locasale et al., 2009, Deberardinis et al., 2008, DeBerardinis et al., 2008). This hypothesis is consistent with the observa... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302602 Sat, 08 Oct 2011 04:00:00 +0100 5302602 HSP70i is a Critical Component of the Immune Response Leading to Vitiligo http://www.medworm.com/index.php?rid=5302605&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00916.x SummaryHSP70i and other stress proteins have been used in anti‐tumor vaccines. This begs the question whether HSP70i plays a unique role in immune activation. We vaccinated inducible HSP70i (Hsp70‐1) knockout mice and wild‐type animals with optimized TRP‐1, a highly immunogenic melanosomal target molecule. We were unable to induce robust and lasting depigmentation in the Hsp70‐1 knockout mice, and in vivo cytolytic assays revealed a lack of CTL activity. Absence of T cell infiltration to the skin and maintenance of hair follicle melanocytes was observed. By contrast, depigmentation proceeded without interruption in mice lacking a tissue specific constitutive isoform of HSP70 (Hsp70‐2) vaccinated with TRP‐2. Next, we demonstrated that HSP70i was necessary and sufficient to acc... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302605 Thu, 06 Oct 2011 04:00:00 +0100 5302605 A Spoonful of Sugar Makes the Melanoma Go: The Role of Heparan Sulfate Proteoglycans in Melanoma Metastasis http://www.medworm.com/index.php?rid=5302604&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00918.x AbstractHeparan sulfate proteoglycans have been shown to regulate signaling in many systems and are of increasing interest in cancer. While not the only sugars to drive melanoma metastasis, HSPGs play important roles in driving metastatic signaling cascades in melanoma. The ability of these proteins to modulate ligand‐receptor interactions in melanoma has been quite understudied. Recent data from several groups indicates the importance of these ligands in modulating key signaling pathways including Wnt and FGF signaling. In this review, we summarize the current knowledge regarding the structure and function of these proteoglycans, and their role in melanoma. Understanding how heparan sulfate proteoglycans modulate signaling in melanoma could lead to new therapeutic approaches via the dam... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302604 Thu, 06 Oct 2011 04:00:00 +0100 5302604 Vitiligo as an inflammatory skin disorder: a therapeutic perspective http://www.medworm.com/index.php?rid=5429562&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00939.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5429562 Sat, 01 Oct 2011 04:00:00 +0100 5429562 Coding genes join the non‐coding world http://www.medworm.com/index.php?rid=5419773&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00938.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5419773 Sat, 01 Oct 2011 04:00:00 +0100 5419773 Can having fun protect you from obesity and its cancer risk? http://www.medworm.com/index.php?rid=5398291&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00937.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5398291 Sat, 01 Oct 2011 04:00:00 +0100 5398291 MEK‐ERK and heparin‐susceptible signaling pathways are involved in cell‐cycle entry of the wound edge retinal pigment epithelium cells in the adult newt http://www.medworm.com/index.php?rid=5356902&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00935.x SummaryThe onset mechanism of proliferation in mitotically quiescent retinal pigment epithelium (RPE) cells is still obscure in humans and newts, although it can be a clinical target for manipulating both retinal diseases and regeneration. To address this issue, we investigated factors or signalling pathways involved in the first cell‐cycle entry of RPE cells upon retinal injury using a newt retina‐less eye‐cup culture system in which the cells around the wound edge of the RPE exclusively enter the cell‐cycle. We found that MEK‐ERK signaling is necessary for their cell‐cycle entry, and signalling pathways whose activities can be modulated by heparin, such as Wnt‐, Shh‐ and thrombin‐mediated pathways, are capable of regulating the cell‐cycle entry. Furthermore, we found ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5356902 Sat, 01 Oct 2011 04:00:00 +0100 5356902 Oncogene‐induced senescence and melanoma: where do we stand? http://www.medworm.com/index.php?rid=5344933&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00933.x SummaryIn recent years, many groups have detected biomarkers of cellular senescence in a plethora of neoplastic lesions, in model systems and humans. Indeed, we have come to realize that oncogene‐induced senescence (OIS) acts as a potent barrier to oncogenic transformation, operating alongside cell death programs. We have begun to uncover some of its underlying principles, but many fundamental questions remain. In this perspective, some of the “knowns” and “unknowns” of OIS are discussed, with a focus on melanomagenesis. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5344933 Sat, 01 Oct 2011 04:00:00 +0100 5344933 CSPG4, a Potential Therapeutic Target, Facilitates Malignant Progression of Melanoma http://www.medworm.com/index.php?rid=5332849&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00929.x SummaryChondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified as a highly immunogenic tumor antigen on the surface of melanoma cells, is associated with melanoma tumor formation and poor prognosis in certain melanomas and several other tumor types. The complex mechanisms by which CSPG4 affects melanoma progression have started to be defined, in particular the association with other cell surface proteins and receptor tyrosine kinases and its central role in modulating the function of these proteins. CSPG4 is essential to the growth of melanoma tumors through its modulation of integrin function, and enhanced growth factor receptor‐regulated pathways including sustained activation of ERK 1,2. This activation of integrin, receptor tyrosine kinase and E... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5332849 Sat, 01 Oct 2011 04:00:00 +0100 5332849 The gluttonous side of malignant melanoma: Basic and clinical implications of macroautophagy http://www.medworm.com/index.php?rid=5312245&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00927.x SummaryTrue to their inherent aggressive behavior, melanomas keep impressing the melanoma community by their ability to bypass tumor suppressor mechanisms. Name a pathway with the potential to control cell survival, and melanoma cells will likely have it potentiated by multiple genetic or epigenetic alterations. In the context of progression and chemoresistance, large efforts have been dedicated to the identification of protective mechanisms associated with or linked to apoptotic death programs. These studies have guided the design of targeted anticancer strategies. Still, the promise for pro‐apoptotic inducers as lead compounds for drug development has yet to come to fruition. It was then a question of time to identify alternative modulators of cell viability. An ideal candidate that is... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5312245 Sat, 01 Oct 2011 04:00:00 +0100 5312245 2011 International Melanoma Congress http://www.medworm.com/index.php?rid=5302612&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00909.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302612 Sat, 01 Oct 2011 04:00:00 +0100 5302612 Erratum http://www.medworm.com/index.php?rid=5302611&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00911.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302611 Sat, 01 Oct 2011 04:00:00 +0100 5302611 Reply to Perris, Borghese, and Magro http://www.medworm.com/index.php?rid=5302610&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00897.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302610 Sat, 01 Oct 2011 04:00:00 +0100 5302610 Pitfalling in nanomedical targeting of melanoma: a ‘clinical’ case of misdelivered RNAi http://www.medworm.com/index.php?rid=5302609&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00888.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302609 Sat, 01 Oct 2011 04:00:00 +0100 5302609 Melanoma response and resistance – taking it to the tumor bank http://www.medworm.com/index.php?rid=5302608&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00890.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302608 Sat, 01 Oct 2011 04:00:00 +0100 5302608 The rush to publish http://www.medworm.com/index.php?rid=5302607&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00903.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302607 Sat, 01 Oct 2011 04:00:00 +0100 5302607 Modeling melanoma in mice http://www.medworm.com/index.php?rid=5302600&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00923.x AbstractPhenotypic and molecular heterogeneity in human melanoma has impaired efforts to explain many of the clinically important features of melanoma. For example, many of the underlying mechanisms that might predict age of onset, time to metastasis and other key elements in melanoma progression remain unknown. Furthermore, melanoma staging used to predict outcome and treatment has not yet moved beyond a basic phenotypic classification. While molecularly targeted therapies show great promise for melanoma patients, establishing accurate animal models that recapitulate human cutaneous melanoma progression remains a priority. We examine the relevance of mice as models for human melanoma progression and for key molecular and histopathologic variants of melanoma. These mice may be used as prec... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302600 Sat, 01 Oct 2011 04:00:00 +0100 5302600 NrF2/Keap1 as gatekeepers of redox homeostasis – do they prevent or cause cancer? http://www.medworm.com/index.php?rid=5312247&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00913.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5312247 Fri, 30 Sep 2011 04:00:00 +0100 5312247 General strategy to analyse melanoma in mice http://www.medworm.com/index.php?rid=5271133&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00907.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5271133 Thu, 29 Sep 2011 04:00:00 +0100 5271133 Dot Bennett http://www.medworm.com/index.php?rid=5258305&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00904.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5258305 Mon, 26 Sep 2011 04:00:00 +0100 5258305 Coat color dilution in mice because of inactivation of the melanoma antigen MART‐1 http://www.medworm.com/index.php?rid=5302606&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00910.x In conclusion, our results suggest that MART‐1 is a pigmentation gene that is required for melanosome biogenesis and/or maintenance. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5302606 Wed, 21 Sep 2011 04:00:00 +0100 5302606 Front seat and back seat drivers of melanoma metastasis http://www.medworm.com/index.php?rid=5220802&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00905.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5220802 Mon, 12 Sep 2011 04:00:00 +0100 5220802 Identification of a melanocyte‐specific, microphthalmia‐associated transcription factor‐dependent regulatory element in the intronic duplication causing hair greying and melanoma in horses http://www.medworm.com/index.php?rid=5247741&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00902.x SummaryGreying with age in horses is an autosomal dominant trait, characterized by hair greying, high incidence of melanoma and vitiligo‐like depigmentation. Previous studies have revealed that the causative mutation for this phenotype is a 4.6‐kb intronic duplication in STX17 (Syntaxin 17). By using reporter constructs in transgenic zebrafish, we show that a construct containing two copies of the duplicated sequence acts as a strong enhancer in neural crest cells and has subsequent melanophore‐specific activity during zebrafish embryonic development whereas a single copy of the duplicated sequence acts as a weak enhancer, consistent with the phenotypic manifestation of the mutation in horses. We further used luciferase assays to investigate regulatory regions in the duplication, to ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5247741 Tue, 30 Aug 2011 04:00:00 +0100 5247741 A DUB for MITF: no myth, some dubiety http://www.medworm.com/index.php?rid=5158199&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00900.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5158199 Fri, 19 Aug 2011 23:00:00 +0100 5158199 Melanoma response and resistance – taking it to the tumor bank http://www.medworm.com/index.php?rid=5130488&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.890.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5130488 Sun, 14 Aug 2011 23:00:00 +0100 5130488 L‐tyrosine and L‐dihydroxyphenylalanine as hormone‐like regulators of melanocyte functions http://www.medworm.com/index.php?rid=5191970&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00898.x SummaryThere is evidence that L‐tyrosine and L‐dihydroxyphenylalanine (L‐DOPA), besides serving as substrates and intermediates of melanogenesis, are also bioregulatory agents acting not only as inducers and positive regulators of melanogenesis but also as regulators of other cellular functions. These can be mediated through action on specific receptors or through non‐receptor‐mediated mechanisms. The substrate induced (L‐tyrosine and/or L‐DOPA) melanogenic pathway would autoregulate itself as well as regulate the melanocyte functions through the activity of its structural or regulatory proteins and through intermediates of melanogenesis and melanin itself. Dissection of regulatory and autoregulatory elements of this process may elucidate how substrate‐induced autoregulator... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5191970 Wed, 10 Aug 2011 23:00:00 +0100 5191970 Melanoma Cells in Distinct Growth Phases Retain Specific Invasive Qualities During Brain Metastasis in vivo http://www.medworm.com/index.php?rid=5282872&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00914.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5282872 Mon, 01 Aug 2011 04:00:00 +0100 5282872 NrF2/Keap1 as Gatekeepers of Redox Homeostasis ‐ Do They Prevent or Cause Cancer? http://www.medworm.com/index.php?rid=5271132&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00913.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5271132 Mon, 01 Aug 2011 04:00:00 +0100 5271132 Coat color dilution in mice due to inactivation of the melanoma antigen MART‐1 http://www.medworm.com/index.php?rid=5247740&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00910.x In conclusion, our results suggest that MART‐1 is a pigmentation gene which is required for melanosome biogenesis and/or maintenance. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5247740 Mon, 01 Aug 2011 04:00:00 +0100 5247740 The role of mitogen‐ and stress‐activated protein kinase pathways in melanoma http://www.medworm.com/index.php?rid=5220801&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00908.x AbstractRecent discoveries have increased our comprehension of the molecular signaling events critical for melanoma development and progression. Many oncogenes driving melanoma have been identified and most of them exert their oncogenic effects through the activation of the RAF/MEK/ERK mitogen‐activated protein kinase (MAPK) pathway. The JNK and p38 MAPK pathways are also important in melanoma but their precise role is not clear yet. This review summarizes our current knowledge on the role of the three main MAPK pathways ‐ ERK, JNK and p38 ‐ and their impact on melanoma biology. Although the results obtained with BRAF inhibitors in melanoma patients are impressive, several mechanisms of acquired resistance have emerged. To overcome this obstacle constitutes the new challenge in melan... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5220801 Mon, 01 Aug 2011 04:00:00 +0100 5220801 Sorting through the many opportunities for melanoma therapy http://www.medworm.com/index.php?rid=5205513&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00906.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5205513 Mon, 01 Aug 2011 04:00:00 +0100 5205513 Identification of a melanocyte‐specific, MITF‐dependent regulatory element in the intronic duplication causing hair greying and melanoma in horses http://www.medworm.com/index.php?rid=5181163&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00902.x SummaryGreying with age in horses is an autosomal dominant trait, characterized by hair greying, high incidence of melanoma and vitiligo‐like depigmentation. Previous studies have revealed that the causative mutation for this phenotype is a 4.6 kb intronic duplication in STX17 (Syntaxin 17). By using reporter constructs in transgenic zebrafish, we show that a construct containing two copies of the duplicated sequence acts as a strong enhancer in neural crest cells and has subsequent melanophore‐specific activity during zebrafish embryonic development whereas a single copy of the duplicated sequence acts as a weak enhancer, consistent with the phenotypic manifestation of the mutation in horses. We further used luciferase assays to investigate regulatory regions in the duplication, to re... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5181163 Sun, 31 Jul 2011 23:00:00 +0100 5181163 XXIst International Pigment Cell Conference (IPCC) http://www.medworm.com/index.php?rid=5158203&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00885.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5158203 Sun, 31 Jul 2011 23:00:00 +0100 5158203 Cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4) in isolated vitiligo: a genotype‐phenotype correlation http://www.medworm.com/index.php?rid=5158202&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00892.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5158202 Sun, 31 Jul 2011 23:00:00 +0100 5158202 UV tanning – the problem that does not go away http://www.medworm.com/index.php?rid=5158201&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00886.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5158201 Sun, 31 Jul 2011 23:00:00 +0100 5158201 GLI2 and M‐MITF transcription factors control exclusive gene expression programs and inversely regulate invasion in human melanoma cells http://www.medworm.com/index.php?rid=5158200&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00893.x SummaryWe recently identified GLI2, the most active of GLI transcription factors, as a direct TGF‐β/SMAD target, whose expression in melanoma cells is associated with increased invasiveness and metastatic capacity. In this work, we provide evidence that high GLI2 expression is inversely correlated with that of the melanocyte‐specific transcription factor M‐microphthalmia transcription factor (M‐MITF) and associated transcriptional program. GLI2‐expressing cell lines were characterized by the loss of M‐MITF‐dependent melanocytic differentiation markers and reduced pigmentation. The balance between M‐MITF and GLI2 expression did not correlate with the presence or absence of BRAF‐activating mutations, but rather was controlled by two distinct pathways: the TGF‐β pathway,... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5158200 Sun, 31 Jul 2011 23:00:00 +0100 5158200 Cellular and clinical report of new Griscelli syndrome type III cases http://www.medworm.com/index.php?rid=5158198&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00901.x We report the first cellular studies on GSIII melanocytes, which demonstrated that MLPH(R35W) causes perinuclear aggregation of melanosomes in melanocytes, typical for GS. Additionally, co‐immunoprecipitation assays showed that MLPH(R35W) lost its interaction with RAB27A, indicating pathogenicity of the R35W mutation. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5158198 Sun, 31 Jul 2011 23:00:00 +0100 5158198 Embryonic stem‐cell‐preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells http://www.medworm.com/index.php?rid=5138409&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00891.x SummaryThe cancer microenvironment affects cancer cell proliferation and growth. Embryonic stem (ES)‐preconditioned 3‐dimensional (3‐D) culture of cancer cells induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration in skin melanoma. However, the mechanism has not yet been clarified. Using the ES‐preconditioned 3‐D microenvironment model, we provide evidence showing that the ES microenvironment inhibits proliferation and anchorage‐independent growth of SK‐MEL‐28 melanoma cells. We also found that the ES microenvironment suppresses telomerase activity and thereby induces senescence in SK‐MEL‐28 cells. Furthermore, we observed that gremlin, an antagonist of BMP4, is secreted from ES cells and plays an impor... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5138409 Fri, 22 Jul 2011 23:00:00 +0100 5138409 Melanoma Response and Resistance—Taking It to the Tumor Bank http://www.medworm.com/index.php?rid=5057634&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00890.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5057634 Fri, 22 Jul 2011 23:00:00 +0100 5057634 2,4,6‐Octatrienoic acid is a novel promoter of melanogenesis and antioxidant defence in normal human melanocytes via PPAR‐γ activation http://www.medworm.com/index.php?rid=5118312&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00887.x SummaryGiven the importance of the tanning response in protecting human skin from the harmful effects of UV radiation, one important research priority is to identify novel molecules that are capable of promoting pigmentation and/or antioxidant defence. Parrodienes share some structural features with carotenoids and retinoids, stimulate cell antioxidant defence and counteract senescence‐like phenotype in fibroblasts. We selected the parrodiene‐derivative 2,4,6‐octatrienoic acid (Octa) to study its impact on key parameters of melanogenesis and antioxidant defence in organ‐cultured human skin and in normal human melanocytes. Octa promoted melanogenesis by up‐regulating tyrosinase and microphthalmia‐associated transcription factor expression. This correlated with an increase of mel... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5118312 Sun, 17 Jul 2011 23:00:00 +0100 5118312 2,4,6‐octatrienoic acid, is a novel promoter of melanogenesis and antioxidant defence in normal human melanocytes via PPARγ activation http://www.medworm.com/index.php?rid=5050020&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00887.x SummaryGiven the importance of the tanning response in protecting human skin from the harmful effects of UV radiation, one important research priority is to identify novel molecules that are capable of promoting pigmentation and/or antioxidant defence. Parrodienes share some structural features with carotenoids and retinoids, stimulate cell antioxidant defence and counteract senescence‐like phenotype in fibroblasts. Thefore, we selected the parrodiene‐derivative, 2,4,6‐octatrienoic acid (Octa), to study its impact on key parameters of melanogenesis and antioxidant defence in organ‐cultured human skin and in normal human melanocytes (NHMs). We demonstrated that Octa promoted melanogenesis by up‐regulating tyrosinase and microphthalmia‐associated transcription factor (MITF) expre... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5050020 Sun, 17 Jul 2011 23:00:00 +0100 5050020 If you can’t beat me, join me: collaborating oncogenes circumventing senescence and causing cancer http://www.medworm.com/index.php?rid=4992278&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00883.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4992278 Thu, 30 Jun 2011 23:00:00 +0100 4992278 The Melanomas: A synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin http://www.medworm.com/index.php?rid=4975521&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00880.x Summary: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 first necessary step towards developing refined prevention strategies for the specific forms of melanoma. Furthermore, classifying this disease precisely into biologically distinct subtypes is the key to developing mechanism‐based treatments, as highlighted by recent discoveries. In this review, we outline the historical developments that underpin our understanding of melanoma heterogeneity, and we do this from the perspectives of clinical presentation, histopathol... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4975521 Sun, 26 Jun 2011 23:00:00 +0100 4975521 FoxP3 expression on melanoma cells is related to early visceral spreading in melanoma patients treated by electrochemotherapy http://www.medworm.com/index.php?rid=5095412&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00879.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5095412 Tue, 21 Jun 2011 23:00:00 +0100 5095412 Contribution of susceptibility gene variants to melanoma risk in families from the Veneto region of Italy http://www.medworm.com/index.php?rid=5007700&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00876.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5007700 Tue, 14 Jun 2011 23:00:00 +0100 5007700 Contribution of susceptibility gene variants to melanoma risk in families from the Veneto region of Italy. http://www.medworm.com/index.php?rid=4933543&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00876.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4933543 Tue, 14 Jun 2011 23:00:00 +0100 4933543 Targeting Leucine addiction and autophagy in melanoma http://www.medworm.com/index.php?rid=4933542&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00877.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4933542 Tue, 14 Jun 2011 23:00:00 +0100 4933542 Transcriptional signatures of full‐spectrum and non‐UVB‐spectrum solar irradiation in human skin http://www.medworm.com/index.php?rid=5138408&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00899.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5138408 Tue, 31 May 2011 23:00:00 +0100 5138408 L‐tyrosine and L‐DOPA as hormone‐like regulators of melanocytes functions http://www.medworm.com/index.php?rid=5125581&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00898.x SummaryEvidence reveals that L‐tyrosine and L‐DOPA, besides serving as substrates and intermediates of melanogenesis, are also bioregulatory agents acting not only as inducers and positive regulators of melanogenesis but also as regulators of other cellular functions. These can be mediated through action on specific receptors or through non‐receptor mediated mechanisms. The substrate induced (L‐tyrosine and/or L‐DOPA) melanogenic pathway would autoregulate itself as well as it would regulate the melanocyte functions through activity of its structural or regulatory proteins and through intermediates of melanogenesis and melanin itself. Dissection of regulatory and autoregulatory elements of this process may elucidate how substrate induced autoregulatory pathways have evolved from ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5125581 Tue, 31 May 2011 23:00:00 +0100 5125581 The Fundamental Building Blocks of Red Human Hair Pheomelanin are Isoquinoline‐Containing Dimers http://www.medworm.com/index.php?rid=5118311&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00896.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5118311 Tue, 31 May 2011 23:00:00 +0100 5118311 Induction of senescence in melanoma: thinking outside the cell http://www.medworm.com/index.php?rid=5107204&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00895.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5107204 Tue, 31 May 2011 23:00:00 +0100 5107204 Serine Biosynthesis: Fuel for the Melanoma Cell Growth Engine http://www.medworm.com/index.php?rid=5095411&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00894.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5095411 Tue, 31 May 2011 23:00:00 +0100 5095411 GLI2 and M‐MITF control exclusive gene expression programs and inversely regulate invasion in human melanoma cells http://www.medworm.com/index.php?rid=5085817&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00893.x In this report, we provide evidence that GLI2 and M‐MITF have an exclusive expression pattern in melanoma cells and demonstrate that GLI2 and M‐MITF antagonize each other and control melanoma cell invasion in an opposite manner. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5085817 Tue, 31 May 2011 23:00:00 +0100 5085817 Cytotoxic T‐Lypmhocyte Associated Antigen‐4 (CTLA‐4) in Vitiligo: A Genotype‐Phenotype Correlation http://www.medworm.com/index.php?rid=5069179&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00892.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5069179 Tue, 31 May 2011 23:00:00 +0100 5069179 Embryonic stem cell‐preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells http://www.medworm.com/index.php?rid=5057633&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00891.x SummaryThe cancer microenvironment affects cancer cell proliferation and growth. Embryonic stem (ES)‐preconditioned 3‐dimensional (3‐D) culture of cancer cells induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration in skin melanoma. However, the mechanism has not yet been clarified. Using the ES‐preconditioned 3‐D microenvironment model, we provide evidence showing that the ES microenvironment inhibits proliferation and anchorage‐independent growth of SK‐MEL‐28 melanoma cells. We also found that the ES microenvironment suppresses telomerase activity and thereby induces senescence in SK‐MEL‐28 cells. Furthermore, we observed that gremlin, an antagonist of BMP4, is secreted from ES cells and plays an impor... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5057633 Tue, 31 May 2011 23:00:00 +0100 5057633 The Pleiotropic Roles of Autophagy Regulators in Melanogenesis http://www.medworm.com/index.php?rid=5050019&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00889.x SummaryMelanin pigments protect the skin and eyes from toxic insults and are critical for the normal functioning of multiple organ systems including the skin, eyes, and brain. Biochemical and genetic studies in both human and mice have revealed the molecular machinery that controls the transcription of genes encoding enzymes that produce melanin and the trafficking of these enzymes to the melanosome, a lysosome‐related organelle dedicated to melanin synthesis. Recent functional genomic studies have identified a role for genes previously known to regulate autophagy, a cellular process that facilitates nutrient recycling during starvation, in the biogenesis of melanosomes in vitro and in vivo. In this review, we describe the pleiotropic roles of autophagy regulators in multiple vesicle tra... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5050019 Tue, 31 May 2011 23:00:00 +0100 5050019 UBE3A Regulates MC1R Expression: A Link to Hypopigmentation in Angelman Syndrome http://www.medworm.com/index.php?rid=5007699&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00884.x SummaryAngelman syndrome (AS) is a neurogenetic disorder caused by the lack of functional ubiquitin‐protein ligase E3A (UBE3A) that acts as an E3 ligase in the ubiquitin‐proteosomal degradation pathway and/or as a transcriptional coactivator. Besides neurological deficit, hypopigmentation is another phenotype associated with AS patients currently attributed towards the hemizygosity of the type II oculocutaneous albinism (OCA2) gene. Here we show that the melanocortin‐1‐receptor (MC1R) is down‐regulated in the skin of the Ube3a(‐/‐) mice. Luciferase‐reporter assay shows that UBE3A is able to induce MC1R promoter activity. Using chromatin immunoprecipitation assay, Ube3a was observed to be physically associated with the Mc1r promoter. Deletion of the E box/SP1 element in the ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=5007699 Tue, 31 May 2011 23:00:00 +0100 5007699 Identification of DNA repair gene Ercc1 as a novel target in melanoma http://www.medworm.com/index.php?rid=4992277&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00882.x SummaryIncreased expression of DNA repair genes contributes to the extreme resistance shown by melanoma to conventional DNA‐damaging chemotherapeutics. One such chemotherapeutic effective against a range of other cancers, but not melanoma, is cisplatin. The DNA repair protein, ERCC1, is needed to remove cisplatin‐induced DNA damage. We have shown that ERCC1 is essential for melanoma growth and resistance to cisplatin in a mouse xenograft model. Untreated xenografts of our transformed Ercc1‐proficient melanocyte cell line grew very rapidly as malignant melanoma. Cisplatin treatment caused initial shrinkage of xenografts, but cisplatin‐resistant regrowth soon followed. Cells reisolated into culture had two‐fold elevated levels of ERCC1 compared to both input cells and cells reisola... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4992277 Tue, 31 May 2011 23:00:00 +0100 4992277 Constitutive activation of the ETS‐1‐miR‐222 circuitry in metastatic melanoma http://www.medworm.com/index.php?rid=4975520&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00881.x SummaryMicroRNAs‐221 and ‐222 are highly up‐regulated in several solid tumors, including melanomas. We demonstrate that the proto‐oncogene ETS‐1, involved in the pathogenesis of cancers of different origin, is a transcriptional regulator of miR‐222 by direct binding to its promoter region. Differently from 293FT cells or early stage melanomas, where not phosphorylated ETS‐1 represses miR‐222 transcription, in metastatic melanoma the constitutively Thr‐38 phosphorylated fraction of ETS‐1 induces miR‐222. Despite its stepwise decreased expression along with melanoma progression, the oncogenic activity of ETS‐1 relies on its RAS/RAF/ERK‐dependent phosphorylation status more than on its total amount. To close the loop, we demonstrate ETS‐1 as a direct target of miR... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4975520 Tue, 31 May 2011 23:00:00 +0100 4975520 FoxP3 expression on melanoma cells is related to early visceral spreading in melanoma patients treated by electrochemotherapy. http://www.medworm.com/index.php?rid=4959824&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00879.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4959824 Tue, 31 May 2011 23:00:00 +0100 4959824 Monobenzone‐induced depigmentation: from enzymatic blockade to autoimmunity http://www.medworm.com/index.php?rid=4952540&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00878.x AbstractAutoimmune side‐effects such as vitiligo regularly occur during melanoma immunotherapy. Vitiligo development being associated with a superior prognosis, the active induction of vitiligo in melanoma patients can be a useful tactic. The potent skin‐depigmenting agent monobenzone can be successfully used for this purpose. Until recently however, the mechanism of action behind monobenzone‐induced skin depigmentation was unclear. Lately, the mechanistic basis for the augmented immunogenicity of monobenzone‐exposed pigmented cells has been unveiled, and their active role in the induction of autoimmune T‐cell‐mediated vitiligo has become apparent. Here, we provide an immunological framework in which we condense this knowledge to an integrated theory of the generation of monobe... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4952540 Tue, 31 May 2011 23:00:00 +0100 4952540 Meeting report from the 2011 International Expert Meeting on Large Congenital Melanocytic Nevi and Neurocutaneous Melanocytosis, Tübingen http://www.medworm.com/index.php?rid=4933541&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00875.x AbstractAn unconventional symposium on the subject of pathogenetic, clinical, and therapeutic aspects of large and giant congenital melanocytic nevi and neurocutaneous melanocytosis, was held at the University of Tübingen, Germany, on May 6‐7, 2011. Exchanges were made between physicians from a wide range of clinical disciplines, including pathology, dermatology, plastic and pediatric surgery, neurosurgery, pediatric neurology and genetics; basic scientists in cell and developmental biology; psychologists; and an unprecedented gathering of international patient advocacy group representatives. This diversity of outlooks brought fresh perspectives to the discussions about current scientific and therapeutic advances in the field of these rare congenital diseases and their oncogenic associa... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4933541 Tue, 31 May 2011 23:00:00 +0100 4933541 Niche work when you can get it: Collagen XVII and the melanocyte stem cell http://www.medworm.com/index.php?rid=4883260&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00874.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4883260 Tue, 31 May 2011 23:00:00 +0100 4883260 Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma. http://www.medworm.com/index.php?rid=4871744&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00873.x SummaryThe effect of NRAS mutations on the pathological features and clinical outcomes in patients with cutaneous melanoma was compared to tumors containing BRAFV600E mutations and tumors wild‐type for both (WT). Clinical outcome data was obtained from a prospective cohort of 249 patients. Mutations involving NRAS and BRAFV600E were detected by PCR and were sequence verified. Cox proportional hazards regression was performed to relate NRAS and BRAF mutations to clinical outcome. 75% of NRAS mutations occurred in tumors >1mm thick (BRAFV600E 40%, WT 34%). 75% of NRAS mutations had >1 mitosis/mm2 (BRAFV600E 40%, WT 55%). When compared to WT, multivariate analysis of melanoma specific survival (MSS) identified NRAS mutations as an adverse prognostic factor (HR 2.96; p=0.04) but not BR... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4871744 Sat, 28 May 2011 02:40:24 +0100 4871744 Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma http://www.medworm.com/index.php?rid=4959825&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00873.x SummaryThe effect of NRAS mutations on the pathological features and clinical outcomes in patients with cutaneous melanoma was compared with that of tumors containing BRAFV600E mutations and tumors wild type for both (WT). Clinical outcome data were obtained from a prospective cohort of 249 patients. Mutations involving NRAS and BRAFV600E were detected by PCR and were sequence verified. Cox proportional hazards regression was performed to relate NRAS and BRAF mutations to clinical outcome. Seventy‐five percentage of NRAS mutations occurred in tumors >1 mm thick (BRAFV600E 40%, WT 34%); 75% of NRAS mutations had >1 mitosis/mm2 (BRAFV600E 40%, WT 55%). When compared to WT, multivariate analysis of melanoma‐specific survival (MSS) identified NRAS mutations as an adverse prognostic... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4959825 Wed, 25 May 2011 23:00:00 +0100 4959825 Glutathione S‐transferase M1/T1 gene polymorphisms and vitiligo in a Mediterranean population http://www.medworm.com/index.php?rid=4952541&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00872.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4952541 Wed, 25 May 2011 23:00:00 +0100 4952541 Glutathione S‐transferase M1/T1 gene polymorphisms and vitiligo in a Mediterranean population. http://www.medworm.com/index.php?rid=4871745&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00872.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4871745 Wed, 25 May 2011 23:00:00 +0100 4871745 Differential LEF1 and TCF4 expression is involved in melanoma cell phenotype switching. http://www.medworm.com/index.php?rid=4847713&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00871.x SUMMARYRecent observations suggest that melanoma cells drive disease progression by switching back‐and‐forth between phenotypic states of proliferation and invasion. Phenotype switching has been linked to changes in Wnt signalling and we therefore looked for cell phenotype‐specific differences in the levels and activity of β‐catenin and its LEF/TCF co‐factors. We found that while cytosolic β‐catenin distribution is phenotype‐specific (membrane‐associated in proliferative cells and cytosolic in invasive cells), its nuclear distribution and activity is not. Instead, the expression patterns of two β‐catenin co‐factors, LEF1 and TCF4, are both phenotype‐specific and inversely‐correlated. LEF1 is preferentially expressed by differentiated/proliferative phenotype cells... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4847713 Sat, 21 May 2011 05:55:21 +0100 4847713 The phosphatidyl inositol 3‐kinase pathway is central to the pathogenesis of Kit‐activated melanoma http://www.medworm.com/index.php?rid=4841086&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00870.x SummaryMouse Kit L575P, the orthologue of human KIT L576P, a common KIT mutation found in human melanoma, was expressed in an immortalized but non‐transformed mouse Ink4a‐Arf‐deficient melanocyte cell line. The resultant Ink4a‐Arf deficient Kit L575P expressing melanocytes exhibited increased proliferation, the ability to grow in soft agar, and increased migration. When these cells were injected subcutaneously into NOD/SCID/gamma(c) mice, melanomas arose in 5 of 7 (71%) mice. 1 of 7 mice (14%) injected with these cells developed metastatic disease. Evaluation of signal transduction pathways downstream of constitutively activated Kit L575P revealed striking activation of the phosphatidyl inositol 3‐kinase (PI3K) pathway. Inhibition of the PI3K pathway pharmacologically or genetica... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4841086 Thu, 19 May 2011 23:39:58 +0100 4841086 Differential LEF1 and TCF4 expression is involved in melanoma cell phenotype switching http://www.medworm.com/index.php?rid=4920889&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00871.x SummaryRecent observations suggest that melanoma cells drive disease progression by switching back and forth between phenotypic states of proliferation and invasion. Phenotype switching has been linked to changes in Wnt signalling, and we therefore looked for cell phenotype‐specific differences in the levels and activity of β‐catenin and its LEF/TCF co‐factors. We found that while cytosolic β‐catenin distribution is phenotype‐specific (membrane‐associated in proliferative cells and cytosolic in invasive cells), its nuclear distribution and activity is not. Instead, the expression patterns of two β‐catenin co‐factors, LEF1 and TCF4, are both phenotype‐specific and inversely correlated. LEF1 is preferentially expressed by differentiated/proliferative phenotype cells and ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4920889 Thu, 19 May 2011 23:00:00 +0100 4920889 Suppression of α5 gene expression is closely related to the tumorigenic properties of uveal melanoma cell lines http://www.medworm.com/index.php?rid=4933544&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00869.x SummaryCancer aggressiveness is related to the ability of cancer cells to escape the anchorage dependency toward the extracellular matrix, a process regulated by the integrin α5β1 and its ligand fibronectin. Here, we characterized the expression of the α5 gene in human uveal melanoma cell lines with distinct tumorigenic properties and investigated some of the mechanisms underlying the variations of their malignancy. Strong and weak expression of α5 was observed in cells with no (T108/T115) and high (T97/T98) tumorigenic properties, respectively. Expression and DNA binding of the transcription factors Sp1, activator protein 1 (AP‐1) (both acting as activators), and nuclear factor I (NFI) (a strong repressor) to the α5 promoter were demonstrated in all cell lines. A reduced expression... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4933544 Tue, 17 May 2011 23:00:00 +0100 4933544 Effective inhibition of melanoma by BI‐69A11 is mediated by dual targeting of the AKT and NF‐κB pathways http://www.medworm.com/index.php?rid=4902046&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00867.x SummaryIn melanoma, the activation of pro‐survival signaling pathways, such as the AKT and NF‐κB pathways, is critical for tumor growth. We have recently reported that the AKT inhibitor BI‐69A11 causes efficient inhibition of melanoma growth. Here, we show that in addition to its AKT inhibitory activity, BI‐69A11 also targets the NF‐κB pathway. In melanoma cell lines, BI‐69A11 inhibited TNF‐α‐stimulated IKKα/β and IκB phosphorylation as well as NF‐κB reporter gene expression. Furthermore, the effective inhibition of melanoma growth by BI‐69A11 was attenuated upon NF‐κB activation. Mechanistically, reduced NF‐κB signaling by BI‐69‐A11 is mediated by the inhibition of sphingosine kinase 1, identified in a screen of 315 kinases. Significantly, we demonstra... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4902046 Tue, 17 May 2011 23:00:00 +0100 4902046 Effective inhibition of melanoma by BI‐69A11 is mediated by dual targeting of the AKT and NF‐κB pathways. http://www.medworm.com/index.php?rid=4841089&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00867.x SummaryIn melanoma, the activation of pro‐survival signaling pathways, such as the AKT and NF‐κB pathways, are critical for tumor growth. We have recently reported that the AKT inhibitor BI‐69A11 causes efficient inhibition of melanoma growth. Here, we show that in addition to its AKT inhibitory activity, BI‐69A11 also targets the NF‐κB pathway. In melanoma cell lines, BI‐69A11 inhibited TNF‐α‐stimulated IKKα/β and IκB phosphorylation as well as NF‐κB reporter gene expression. Furthermore, the effective inhibition of melanoma growth by BI‐69A11 was attenuated upon NF‐κB activation. Mechanistically, reduced NF‐κB signaling by BI‐69‐A11 is mediated by the inhibition of sphingosine kinase 1, identified in a screen of 315 kinases. Significantly, we demonstr... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4841089 Tue, 17 May 2011 23:00:00 +0100 4841089 Melanoma Researchers Have a Reason to GRIN: Melanoma Yields More of Its Secrets to Exome Sequencing http://www.medworm.com/index.php?rid=4841088&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00868.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4841088 Tue, 17 May 2011 23:00:00 +0100 4841088 Suppression of α5 gene expression is closely related to the tumorigenic properties of uveal melanoma cell lines. http://www.medworm.com/index.php?rid=4841087&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00869.x SummaryCancer aggressiveness is related to the ability of cancer cells to escape the anchorage dependency toward the extracellular matrix, a process regulated by the integrin α5β1 and its ligand fibronectin. Here, we characterized the expression of the α5 gene in human uveal melanoma cell lines with distinct tumorigenic properties and investigated some of the mechanisms underlying the variations of their malignancy. Strong and weak expression of α5 was observed in cells with no (T108/T115) and high (T97/T98) tumorigenic properties, respectively. Expression and DNA binding of the transcription factors Sp1, AP‐1 (both acting as activators) and NFI (a strong repressor) to the α5 promoter were demonstrated in all cell lines. A reduced expression of AP‐1 combined to a dramatic increase... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4841087 Tue, 17 May 2011 23:00:00 +0100 4841087 Many are called, few are chosen http://www.medworm.com/index.php?rid=4828631&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00859.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4828631 Tue, 17 May 2011 11:42:33 +0100 4828631 Separating melanins into their primary colors: quantifying contributions from eumelanin and pheomelanin http://www.medworm.com/index.php?rid=4828630&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00866.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4828630 Tue, 17 May 2011 11:42:29 +0100 4828630 Microenvironment & Immunology Epac1 promotes melanoma metastasis via modification of heparan sulfate http://www.medworm.com/index.php?rid=4820529&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00863.x SummaryOur previous report suggested the potential role of the exchange protein directly activated by cyclic AMP (Epac) in melanoma metastasis via heparan sulfate (HS)‐mediated cell migration. In order to obtain conclusive evidence that Epac1 plays a critical role in modification of HS and melanoma metastasis, we extensively investigated expression and function of Epac1 in human melanoma samples and cell lines. We have found that, in human melanoma tissue microarray, protein expression of Epac1 was higher in metastatic melanoma than in primary melanoma. In addition, expression of Epac1 positively correlated with that of N‐sulfated HS, and N‐deacetylase/N‐sulfotransferase‐1 (NDST‐1), an enzyme that increases N‐sulfation of HS. Further, an Epac agonist increased, but ablation o... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4820529 Mon, 18 Apr 2011 23:00:00 +0100 4820529 BRCA1 is a new MITF target gene http://www.medworm.com/index.php?rid=4733649&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00862.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4733649 Mon, 18 Apr 2011 23:00:00 +0100 4733649 Integumental reddish‐violet coloration owing to novel dichromatic chromatophores in the teleost fish, Pseudochromis diadema http://www.medworm.com/index.php?rid=4788869&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00861.x SummaryIn the reddish‐violet parts of the skin of the diadema pseudochromis Pseudochromis diadema, we found novel dichromatic chromatophores with a reddish pigment and reflecting platelets. We named these novel cells ‘erythro‐iridophores’. In standard physiological solution, erythro‐iridophores displayed two hues, red and dark violet when viewed with an optical microscope under ordinary transmission light and epi‐illumination optics, respectively. Under transmission electron microscopy, however, we observed no typical red chromatosomes, i.e., erythrosomes, in the cytoplasm. High‐performance thin‐layer chromatography (HPTLC) analysis of the pigment eluted from the erythro‐iridophores indicated that carotenoid is the main pigment generating the reddish color. Furthermore, w... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4788869 Sun, 17 Apr 2011 23:00:00 +0100 4788869 Integumental reddish‐violet coloration due to novel dichromatic chromatophores in the teleost fish, Pseudochromis diadema. http://www.medworm.com/index.php?rid=4723495&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00861.x SummaryIn the reddish‐violet parts of the skin of the diadema pseudochromis Pseudochromis diadema, we found novel dichromatic chromatophores with a reddish pigment and reflecting platelets. We named these novel cells “erythro‐iridophores”. In standard physiological solution, erythro‐iridophores displayed two hues, red and dark violet when viewed with an optical microscope under ordinary transmission light and epi‐illumination optics, respectively. Under transmission electron microscopy, however, we observed no typical red chromatosomes, i.e., erythrosomes, in the cytoplasm. High‐performance thin layer chromatography (HPTLC) analysis of the pigment eluted from the erythro‐iridophores, indicated that carotenoid is the main pigment generating the reddish color. Furthermore, wh... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4723495 Sun, 17 Apr 2011 23:00:00 +0100 4723495 Junctional Adhesion Molecules are required for melanoma cell lines transendothelial migration in vitro http://www.medworm.com/index.php?rid=4683960&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00856.x AbstractOne of the main steps of metastasis is extravasation, a phenomenon well described in lymphocytes, but remaining to be fully uncovered for melanoma. Junctional Adhesion Molecules (JAMs) are controlling the transendothelial migration of leukocytes. To date the role of the JAM proteins, notably JAM‐A and JAM‐C, has not been examined in melanoma. Here, we compared two melanoma tumor cell lines, A375 and SLM8 cells, the A375 cell line being four times more efficient than the SLM8 cells in the crossing of the endothelial monolayer. We evidence the differential expression of JAM‐A and JAM‐C in these cell lines with JAM‐C mainly expressed in the A375 cell line, and JAM‐A detected preferentially in the SLM8 cells. To further dissect the respective roles of these proteins, we use... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4683960 Tue, 05 Apr 2011 23:00:00 +0100 4683960 MicroRNA‐155 Targets the SKI Gene in Human Melanoma Cell Lines http://www.medworm.com/index.php?rid=4683959&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00857.x SummaryThe SKI protein is a transcriptional co‐regulator over‐expressed in melanoma. Experimentally induced down‐regulation of SKI inhibits melanoma cell growth in vitro and in vivo. Micro‐RNAs (miRNAs) negatively modulate gene expression, and have been implicated in oncogenesis. We previously showed that microRNA‐155 (miR‐155) is down‐regulated in melanoma cells as compared with normal melanocytes, and that its ectopic expression impairs proliferation and induces apoptosis. Here, we investigated whether miR‐155 could mediate melanoma growth inhibition via SKI gene silencing. Luciferase reporter assays demonstrated that miR‐155 interacted with SKI 3’UTR and impaired gene expression. Transfection of melanoma cells with miR‐155 reduced SKI levels, while inhibition of en... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4683959 Tue, 05 Apr 2011 23:00:00 +0100 4683959 Inter‐Observer Concordance for the Recognition of Angiotropism in Human Melanoma http://www.medworm.com/index.php?rid=4683962&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00854.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4683962 Mon, 04 Apr 2011 23:00:00 +0100 4683962 Melanocyte stem cells: A melanocyte reservoir in hair follicles for hair and skin pigmentation http://www.medworm.com/index.php?rid=4683961&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00855.x SummaryMost mammals are coated with pigmented hair. Melanocytes in each hair follicle produce melanin pigments for the hair during each hair cycle. The key to understanding the mechanism of cyclic melanin production is the melanocyte stem cell (MelSC) population, previously known as “amelanotic melanocytes”. The MelSC population resides in the hair follicle bulge‐subbulge area, the lower‐most permanent portion of the hair follicle, which serves as a melanocyte reservoir for skin and hair pigmentation. MelSCs form a stem cell system within individual hair follicles and provide a “hair pigmentary unit” for each cycle of hair pigmentation. This review focuses on the identification of MelSCs and their characteristics and explains the importance of the MelSC population in the mechan... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4683961 Mon, 04 Apr 2011 23:00:00 +0100 4683961 The stepwise two‐photon excited melanin fluorescence is a unique diagnostic tool for the detection of malignant transformation in melanocytes http://www.medworm.com/index.php?rid=4775154&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00853.x SummaryMalignant transformation of melanocytes is associated with changes in melanogenesis. Therefore, fluorescence of melanin may be an informative indicator of this process. But the conventionally excited autofluorescence of melanin in skin tissue is ultra‐weak and its main part in the visible spectral region is hidden by the much stronger fluorescence from other endogenous fluorophores. Here, using a new mode of stepwise two‐photon excitation, melanin‐dominated fluorescence spectra of pigmented skin lesions are reported. From these, pure melanin fluorescence spectra of normal pigmented skin, melanocytic nevi and malignant pigmented melanoma were analyzed. They show distinctly different spectral shapes: melanoma gave a characteristic fingerprint with a fluorescence band peaking at ... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4775154 Fri, 01 Apr 2011 23:00:00 +0100 4775154 UV‐tanning behavior: a problem that doesn’t go away http://www.medworm.com/index.php?rid=4775153&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00865.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4775153 Thu, 31 Mar 2011 23:00:00 +0100 4775153 Usefulness of Alkaline Hydrogen Peroxide Oxidation to Analyze Eumelanin and Pheomelanin in Various Tissue Samples: Application to Chemical Analysis of Human Hair Melanins http://www.medworm.com/index.php?rid=4758544&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00864.x SummaryEumelanin and pheomelanin in tissue samples can be specifically measured as the markers pyrrole‐2,3,5‐tricarboxylic acid (PTCA) and 4‐amino‐3‐hydroxyphenylalanine after acidic permanganate oxidation and hydroiodic acid hydrolysis, respectively. Those degradation methods, although widely applied, are not easily performed in most laboratories. To overcome this difficulty, we developed alkaline H2O2 oxidation in 1M K2CO3 that produces, in addition to the eumelanin marker PTCA, thiazole‐2,4,5‐tricarboxylic acid (TTCA) and thiazole‐4,5‐dicarboxylic acid (TDCA) as markers for pheomelanin and pyrrole‐2,3‐dicarboxylic acid (PDCA) as a marker for 5,6‐dihydroxyindole‐derived eumelanin. Those 4 degradation products can be easily separated by HPLC and analyzed with ult... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4758544 Thu, 31 Mar 2011 23:00:00 +0100 4758544 Epac1 Promotes Melanoma Metastasis via Modification of Heparan Sulfate http://www.medworm.com/index.php?rid=4733648&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00863.x SummaryOur previous report suggested the potential role of the exchange protein directly activated by cyclic AMP (Epac) in melanoma metastasis via heparan sulfate (HS)‐mediated cell migration. In order to obtain conclusive evidence that Epac1 plays a critical role in modification of HS and melanoma metastasis, we extensively investigated expression and function of Epac1 in human melanoma samples and cell lines. We have found that, in human melanoma tissue microarray, protein expression of Epac1 was higher in metastatic melanoma than in primary melanoma. In addition, expression of Epac1 positively correlated with that of N‐sulfated HS, and N‐deacetylase/N‐sulfotransferase‐1 (NDST‐1), an enzyme which increases N‐sulfation. Further, an Epac agonist increased, and ablation of Epa... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4733648 Thu, 31 Mar 2011 23:00:00 +0100 4733648 Expression of human endogenous retrovirus K is stimulated by ultraviolet radiation in melanoma http://www.medworm.com/index.php?rid=4723494&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00860.x In this study we investigated effects of ultraviolet radiation (UVR) on the expression of human endogenous retrovirus type K (HERV‐K) in melanoma cells and non‐melanoma cells in vitro. Solely in melanoma cell lines, irradiation with UVB (200 mJ cm−2) resulted in a significant transcriptional activation of the retroviral pol gene as well as in an enhanced expression of the retroviral envelope protein (env). In addition, UVB treatment induced the production of retroviral particles in the supernatants of melanoma cell lines. This data indicates that HERV‐K expression can be activated by UVB irradiation and suggests an involvement of HERV‐K in UVR‐related melanoma pathogenesis. (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4723494 Thu, 31 Mar 2011 23:00:00 +0100 4723494 Constitutive Smad linker phosphorylation in melanoma: A mechanism of resistance to Transforming Growth Factor‐β‐mediated growth inhibition http://www.medworm.com/index.php?rid=4683958&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00858.x In this study, we investigated a mechanism of resistance involving a regulatory domain, called linker region, in Smad2 and Smad3, main downstream effectors of TGFβ. Melanoma cells in culture and in tumor samples exhibited constitutive Smad2 and Smad3 linker phosphorylation. Treatment of melanoma cells with the MEK1/2 inhibitor, U0126, or the two pan‐CDK and GSK3 inhibitors, Flavopiridol and R547, resulted in decreased linker phosphorylation of Smad2 and Smad3. Overexpression of the linker phosphorylation‐resistant Smad3 EPSM mutant in melanoma cells resulted in an increase in expression of p15INK4B and p21WAF1, as compared with cells transfected with wild‐type Smad3. In addition, the cell numbers of EPSM Smad3‐expressing melanoma cells were significantly reduced compared to wild... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4683958 Thu, 31 Mar 2011 23:00:00 +0100 4683958 The stepwise two photon excited melanin fluorescence is a unique diagnostic tool for the detection of malignant transformation in melanocytes http://www.medworm.com/index.php?rid=4669974&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00853.x ABSTRACTMalignant transformation of melanocytes is associated with changes in melanogenesis. Therefore, fluorescence of melanin may be an informative indicator of this process. But the conventionally excited autofluorescence of melanin in skin tissue is ultra‐weak and its main part in the visible spectral region is hidden by the much stronger fluorescence from other endogeneous fluorophores. Here, using a new mode of stepwise two‐photon excitation, melanin‐dominated fluorescence spectra of pigmented skin lesions are reported. From these, pure melanin fluorescence spectra of normal pigmented skin, of melanocytic nevi as well as of malignant pigmented melanoma were analyzed. They show distinctly different spectral shapes: melanoma gave a characteristic fingerprint with a fluorescence b... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4669974 Thu, 31 Mar 2011 23:00:00 +0100 4669974 Evolution in Action: Highlighting a Role for the Agouti Gene in Development? http://www.medworm.com/index.php?rid=4663732&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00852.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4663732 Thu, 31 Mar 2011 23:00:00 +0100 4663732 Melanocytes and melanoma: hooked on elongation http://www.medworm.com/index.php?rid=4658179&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00846.x (Source: Pigment Cell Research) Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4658179 Tue, 29 Mar 2011 23:00:00 +0100 4658179 Botanicals for the prevention and treatment of cutaneous melanoma http://www.medworm.com/index.php?rid=4626672&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00851.x AbstractCutaneous melanoma, a cancer of melanocytes, when detected at later stages is arguably one of the most lethal cancers and the cause of more years of lost life than any other cancer among young adults. There is no standard therapy for advanced‐stage melanoma and the median survival time for patients with metastatic melanoma is less than one year. An urgent need for novel strategies against melanoma has directed research towards development of new chemotherapeutic and biologic agents that can target the tumor by several different mechanisms. Recently, several dietary agents are being investigated for their role in the prevention and treatment of various forms of cancer and may represent the future modality of the treatment. Here, we have reviewed emerging data on botanicals that ar... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4626672 Thu, 24 Mar 2011 05:08:41 +0100 4626672 Malignancy without immortality? Evidence for cellular immortalization as a late event in melanoma progression http://www.medworm.com/index.php?rid=4614982&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00850.x SummaryCell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β‐galactosidase, nuclear p16 and heterochromatic foci/aggregates. However melanoma cultures also showed featu... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4614982 Mon, 21 Mar 2011 19:04:07 +0100 4614982 Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression http://www.medworm.com/index.php?rid=4733650&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00850.x SummaryCell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β‐galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed fea... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4733650 Mon, 21 Mar 2011 00:00:00 +0100 4733650 Melanoma cell invasiveness is regulated by miR‐211 suppression of the BRN2 transcription factor. http://www.medworm.com/index.php?rid=4605650&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00849.x SummaryTo identify microRNAs potentially involved in melanomagenesis we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR‐211. We focused on this pigment cell enriched miRNA as it is derived from the MITF‐regulated gene, TRPM1 (melastatin). We find that miR‐211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR‐211, including POU3F2 (BRN2). Inhibition of miR‐211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR‐211 represses BRN2 in differentiated cells. Over‐expression of miR‐211 in melan... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4605650 Fri, 18 Mar 2011 06:13:44 +0100 4605650 N‐glycosylation of the human melanocortin 1 receptor. Occupancy of glycosylation sequons and functional role. http://www.medworm.com/index.php?rid=4600338&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00848.x SummaryThe melanocortin 1 receptor (MC1R), a major determinant of skin pigmentation and phototype, mediates the actions of α melanocyte‐stimulating hormone on melanocytes and is critical for melanocyte proliferation and differentiation. MC1R has two putative N‐glycosylation targets, Asn15 and Asn29. It has been shown that MC1R is a glycoprotein with an unusual sensitivity to endoglycosidase H digestion. However, the occupancy and functional importance of each specific glycosylation sequon remains unknown. We demonstrate that MC1R is N‐glycosylated at Asn15 and Asn29, with structurally and functionally different glycan chains. N‐glycosylation is not necessary for high affinity agonist binding or functional coupling, but has a strong effect on the availability of MC1R molecules on t... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4600338 Thu, 17 Mar 2011 04:18:07 +0100 4600338 Melanoma cell invasiveness is regulated by miR‐211 suppression of the BRN2 transcription factor http://www.medworm.com/index.php?rid=4683963&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00849.x SummaryTo identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR‐211. We focused on this pigment‐cell‐enriched miRNA as it is derived from the microphthalmia‐associated transcription factor (MITF)‐regulated gene, TRPM1 (melastatin). We find that miR‐211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR‐211, including POU3F2 (BRN2). Inhibition of miR‐211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR‐211 represses BRN2 in diffe... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4683963 Thu, 17 Mar 2011 00:00:00 +0100 4683963 Dermis‐derived stem cells: A source of epidermal melanocytes and melanoma? http://www.medworm.com/index.php?rid=4591837&cid=s_32031_171_f&fid=32031&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1755-148X.2011.00847.x AbstractHuman multipotent dermal stem cells (DSC) have been isolated and propagated from the dermal region of neonatal foreskin. DSC can self‐renew, express the neural crest stem cell markers NGFRp75 and nestin, and are capable of differentiating into a wide variety of cell types including mesenchymal and neuronal lineages and melanocytes, indicative of their neural crest origin. When placed in the context of reconstructed skin, DSCs migrate to the basement membrane zone and differentiate into melanocytes. These findings, combined with the identification of NGFRp75‐positive cells in the dermis of human foreskin, which are devoid of hair, suggest that DSC may be a self‐renewing source of extrafollicular epidermal melanocytes. In this review we discuss the properties of DSC, the pathwa... Pigment Cell Research journals http://www.medworm.com/rss/comments.php?id=4591837 Wed, 16 Mar 2011 00:22:14 +0100 4591837