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Melanoma Research

Maria Chiara Scaini, Jacopo Pigozzo, Marco Pizzi, Mariangela Manicone, Vanna Chiarion-Sileni, Pamela Zambenedetti, Massimo Rugge, Paola Zanovello, Elisabetta Rossi, Rita Zamarchi, Antonela Facchinetti
The management of metastatic melanoma is a difficult matter. Nevertheless, the advent of target therapy has significantly improved patient outcome, provided that tumor molecular characteristics become available: the detection of drug-resistant clones can contribute to understanding the reasons for resistance onset, influencing the choice of subsequent therapy. This work aimed to provide a possible explanation for the early resistance to vemurafenib developed by a patient with melanoma, and concurrently to assess the extent, and role, of the tumor clonal heterogeneity...
September 14, 2018: Melanoma Research
Xiong Tingfeng, Pan Fuqiang, Li Dong
Genes in the S100 family are abnormally expressed in a variety of tumor cells and are associated with clinical pathology, but their prognostic value in melanoma patients has not yet been fully elucidated. In this study, we extracted and profiled S100 family mRNA expression data and corresponding clinical data from the Gene Expression Omnibus database to analyze how expression of these genes correlates with clinical pathology. Compared with normal skin, S100A1, S100A13, and S100B were expressed at significantly higher levels in melanoma samples...
September 13, 2018: Melanoma Research
Ahmad Tarhini, Sameer R Ghate, Raluca Ionescu-Ittu, Ameur M Manceur, Briana Ndife, Philippe Jacques, François Laliberté, Antonio Nakasato, Rebecca Burne, Mei Sheng Duh
Surgery is the mainstay treatment for operable nonmetastatic melanoma, but recurrences are common and limit patients' survival. This study aimed to describe real-world patterns of treatment and recurrence in patients with melanoma and to quantify healthcare resource utilization (HRU) and costs associated with episodes of locoregional/distant recurrences. Adults with nonmetastatic melanoma who underwent melanoma lymph node surgery were identified from the Truven Health MarketScan database (1 January 2008 to 31 July 2017)...
September 13, 2018: Melanoma Research
Shalin Shah, Jason J Luke, Heather A Jacene, Tianqi Chen, Anita Giobbie-Hurder, Nageatte Ibrahim, Elizabeth L Buchbinder, David F McDermott, Keith T Flaherty, Ryan J Sullivan, Donald P Lawrence, Patrick A Ott, F Stephen Hodi
Uveal melanoma (UM) is a rare form of melanoma without effective therapy. The biology of UM relies on several heat-shock protein 90 (Hsp90)-dependent molecules such as MET, MEK and AKT, making Hsp90 inhibition a rational approach. Patients with stage IV UM, measurable disease, and no previous chemotherapy were eligible. Patients received either ganetespib 200 mg weekly (cohort A) or 150 mg twice a week (cohort B). Primary endpoint response rate (RR) was assessed by RECIST. A total of 17 patients were accrued for this study, with seven in cohort A and 10 in cohort B...
September 11, 2018: Melanoma Research
Teofila Seremet, Simon Planken, Julia K Schwarze, Yanina Jansen, Laura Vandeweerd, Robbe van den Begin, Ioannis Tsechelidis, Danielle Lienard, Véronique Del Marmol, Bart Neyns
Monoclonal antibodies that block the programmed death-1 (anti-PD-1) or cytotoxic T-lymphocyte antigen-4 (CTLA-4) immune checkpoint receptors (pembrolizumab, nivolumab, ipilimumab, or the combination of nivolumab with ipilimumab) are approved treatment option for patients with advanced melanoma. Over half of all patients are refractory to these immunotherapies and are in need of alternative or complementary treatment options. Talimogene laherparepvec (T-VEC) is a first-in-class intralesionally delivered oncolytic immunotherapy, which has proven efficacy in the treatment of advanced melanoma...
September 11, 2018: Melanoma Research
Luisa Christensen, Jeffrey Scott, Jeremy Bordeaux
Advances in the field of molecular genetics have led to the development of multiple tests capable of identifying genetic changes within cutaneous melanoma. Although the majority of these tests are currently used for diagnostic purposes, their potential use as prognostic tools is rapidly emerging. A new 31-gene expression profile test has been developed that promises to accurately predict metastatic risk in patients with early-stage cutaneous melanoma. Although current data are promising, many questions remain in terms of its potential effects in patient care...
September 11, 2018: Melanoma Research
Andréia C de Melo, Alberto J A Wainstein, Antonio C Buzaid, Luiz C S Thuler
The current research aimed to understand melanoma epidemiology in Brazil and to evaluate temporal trends in incidence and mortality. The data came from Brazilian Hospital Cancer Registries, Population Based Cancer Registries, and the National Mortality Information System from 2000 to 2014. Descriptive statistics were used for epidemiological and clinical characteristics. To describe trends in change in incidence and mortality rates, the Average Annual Percentage Change (AAPC) was calculated. Between 2000 and 2013, in men, the median incidence rate rose from 2...
September 10, 2018: Melanoma Research
Bei Zhao, Xiankui Cheng, Xiyuan Zhou
Inhibition of BRAF improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to BRAF inhibitor is inevitable, and the drug resistance mechanisms still remain to be elucidated. Here, BRAF mutant cells A375 and SK-MEL-28 were chosen and treated with BRAF inhibitor vemurafenib, and the results showed that the ERK signaling pathway was blocked in these cells. Then, vemurafenib-resistant cells were constructed, and we found that drug resistance-related gene P-gp was overexpressed in the two cell lines...
September 5, 2018: Melanoma Research
Isabelle Tromme, Laurine Sacré, Fatima Hammouch, Pauline Richez, Jean-Marie Degryse, Niko Speybroeck
About half of the melanomas are detected by patients but the mean thickness of such melanomas is higher than when diagnosed by physicians. Symptoms and signs described by patients are dynamic changes and pruritus, the appearance of a new lesion having been rarely investigated. These observations are documented for melanomas but not for benign naevi. To the best of our knowledge, this is the first study in which both melanomas and suspected excised naevi were included. The main objectives were to (a) analyse the value of the anamnestic predictors for melanoma versus non-melanoma and (b) calculate the influence of age on the most significant anamnestic predictors...
September 5, 2018: Melanoma Research
Anthony Nye, Justin D Collins, Caroline L Porter, Mary Montes de Oca, Kathryn George, Colin G Stafford, Christine M G Schammel, Samuel Horton, Steven D Trocha
Melanoma confers an estimated lifetime risk of one in 50 for 2016. Clinicopathologic staging and sentinel lymph node biopsy (SLNB) have been the standard of care for T2 and T3 lesions. Molecular biomarkers identified in the primary lesion suggestive of metastatic potential may offer a more conclusive prognosis of these lesions. Our purpose was to investigate molecular mutations in primary melanoma that were predictive for micrometastasis as defined by a positive sentinel lymph node (SLN) in a case-controlled manner: nine patients with negative SLN and nine with positive SLN...
September 1, 2018: Melanoma Research
Rachel Kang, Shari Lipner
In this study, we sought to objectively determine the accuracy and comprehensibility of online material with regard to subungual melanoma, a nail disease that is rare within the general population, yet has high incidence in certain patient groups, and carries a poorer prognosis than other forms of cutaneous melanoma. Because improved prognosis relies on early diagnosis, the dissemination of accurate, understandable information is an important factor in patient education and health. Using a pro forma designed to score website reliability, the accountability, quality, readability, display, support features, and transparency of the most commonly listed search engine hits related to subungual melanoma were analyzed...
August 30, 2018: Melanoma Research
Sally Y Tan, Julie Najita, Xiaoxue Li, Lauren C Strazzulla, Haili Dunbar, Mee-Young Lee, Virginia J Seery, Elizabeth I Buchbinder, Nicholas E Tawa, David F McDermott, Sandra J Lee, Michael B Atkins, Caroline C Kim
Under current AJCC staging criteria, stage IIC patients paradoxically have worse outcomes than IIIA patients despite the lack of nodal metastatic disease. This study sought to identify additional clinicopathologic characteristics correlated with worse patient outcomes. Retrospective chart review of stage IIC and IIIA melanoma patients were evaluated between 1995 and 2011 with clinical follow-up through 2015. Records were reviewed for demographics, clinical characteristics, and tumor pathology. Fisher's exact test and Wilcoxon's rank-sum test were used to assess group differences...
August 30, 2018: Melanoma Research
Panagiotis T Diamantopoulos, Sofia Stoungioti, Amalia Anastasopoulou, George Papaxoinis, Helen Gogas
Ophthalmological complications constitute a class effect of treatment with BRAF inhibitors. Encorafenib is a new BRAF inhibitor currently being tested in phase 3 clinical trials for advanced or metastatic melanoma as monotherapy or in combination with the MEK-inhibitor binimetinib. In this study, we present a case of severe bilateral panuveitis and neurosensory hearing loss in an elderly patient treated with encorafenib and binimetinib for metastatic BRAF-mutant melanoma. This constellation of findings is compatible with incomplete Vogt-Koyanagi-Harada (VKH) disease...
August 30, 2018: Melanoma Research
Cathy Yunjia Zhao, Shelley Ji Eun Hwang, Germana Consuegra, Shaun Chou, Pablo Fernandez-Peñas
Bullous disorders are rare adverse events associated with anti-programmed cell death-1 (anti-PD1) therapy. This paper presents two new cases of bullous disorders under anti-PD1 therapy and systematically reviewed the literature to foster a better understanding of the presentation and pathogenesis of bullous disorders under anti-PD1. A systematic review of the literature was completed using MEDLINE, Embase, PubMed and LILACS databases. We identified 29 cases of bullous disorders under anti-PD1 therapy, including our two new cases...
August 30, 2018: Melanoma Research
Douglas S Swords, Robert H I Andtbacka, Tawnya L Bowles, John R Hyngstrom
Pelvic sentinel lymph nodes (SLNs) are commonly identified during inguinal SLN biopsy for melanoma, but retrieval is not uniform among surgeons/centers. Few studies have assessed rates of micrometastases in pelvic versus superficial inguinal SLNs. Previous studies suggested that presence of pelvic SLNs was predicted by aggressive pathologic features and that their presence portended a worse prognosis. The objectives of this study were to examine presurgical predictors of pelvic SLNs among patients undergoing inguinal SLN biopsy, assess rates of micrometastases in superficial inguinal versus pelvic SLNs, and determine whether presence of pelvic SLNs was associated with long-term outcomes...
August 29, 2018: Melanoma Research
István Kenessey, Zsófia Kramer, Lilla István, Mihály T Cserepes, Tamás Garay, Balázs Hegedűs, Judit Dobos, József Tímár, József Tóvári
Oncogenic activation of the epidermal growth factor receptor (EGFR) signaling pathway occurs in a variety of tumor types, albeit in human melanoma, the contribution of EGFR is still unclear. The potential role of EGFR was analyzed in four BRAF-mutant, one NRAS-mutant and one wild-type NRAS-BRAF-carrying human melanoma cell lines. We have tested clinically available reversible tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, irreversible EGFR-TKI pelitinib and a reversible experimental compound PD153035 on in-vitro proliferation, apoptosis, migration as well as in-vivo metastatic colonization in a spleen-liver model...
August 17, 2018: Melanoma Research
Marc Dumas, Pauline Laly, Jérémy Gottlieb, Laetitia Vercellino, Frédéric Paycha, Martine Bagot, Barouyr Baroudjian, Isabelle Madelaine, Nicole Basset-Seguin, Pirayeh Eftekhari, Cécile Pagès, Céleste Lebbé, Frédéric Lioté
Targeted therapies have markedly improved the survival of patients with melanoma. We report the case of two patients with advanced melanoma controlled by long-term MEK inhibitor or combination of BRAF and MEK inhibitors, who developed fractures related to severe osteopenia. A 48-year-old woman was treated by pimasertib after the failure of two lines of chemotherapy, and a 42-year-old man was treated by an association of BRAFi (dabrafenib) and MEKi (trametinib) after the failure of one line of chemotherapy. During follow-up, both complained of buttock pain, revealing primary fractures of the pelvis and lumbar vertebra...
August 17, 2018: Melanoma Research
Annie Herbert, Minjoung M Koo, Matthew E Barclay, David C Greenberg, Gary A Abel, Nick J Levell, Georgios Lyratzopoulos
The aim of this study was to examine temporal trends in overall and stage-specific incidence of melanoma. Using population-based data on patients diagnosed with melanoma in East Anglia, England, 1996-2015, we estimated age-standardized time trends in annual incidence rates for each stage at diagnosis. Negative binomial regression was used to model trends over time adjusted for sex, age group and deprivation, and to subsequently examine variation in stage-specific trends by sex and age group. The age-standardized incidence increased from 14 to 29 cases/100 000 persons (i...
August 13, 2018: Melanoma Research
Lisa M Hillen, Milan S Geybels, Dorit Rennspiess, Ivelina Spassova, Cathrin Ritter, Jürgen C Becker, Marjan Garmyn, Axel Zur Hausen, Joost Van den Oord, Véronique Winnepenninckx
The molecular properties of benign melanocytic lesions are poorly understood. Only a few studies have been carried out on specific nevi subtypes, including common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in melanoma-associated oncogenes are typically absent in SN. In the present study, mRNA expressions of 25 SN and 15 NCN were analyzed. Molecular profiling was performed using the RNA NanoString nCounter Gene Expression Platform (number of genes=770). Marker discovery was performed with a training set consisting of seven SN and seven NCN samples from the same patients, and validation was performed using a second set consisting of 18 SN and eight NCN samples...
August 7, 2018: Melanoma Research
Junya Yan, Xiaowen Wu, Jiayi Yu, Meng Ma, Huan Yu, Tianxiao Xu, Huan Tang, Longwen Xu, Jie Dai, Lu Si, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Jun Guo, Yan Kong
Patient-derived xenograft (PDX) models mostly retain the histological and genetic features of their donor tumors, which have been used for investigating various types of cancer. However, PDX models for melanoma, especially acral melanoma, are reported occasionally. We aimed to establish a large panel of melanoma PDX models representing the predominant Asian melanomas. Ninety-three fresh melanoma samples were implanted subcutaneously into nonobese diabetic/severe combined immunodeficiency mice. The histological and genetic characteristics were analyzed in both patient tumors and PDX models using immunohistochemistry, PCR amplification, and Sanger sequencing...
August 6, 2018: Melanoma Research
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