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Uveal melanoma

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https://www.readbyqxmd.com/read/29332125/icg-001-exerts-potent-anticancer-activity-against-uveal-melanoma-cells
#1
Salma Kaochar, Jianrong Dong, Marie Torres, Kimal Rajapakshe, Fotis Nikolos, Christel M Davis, Erik A Ehli, Cristian Coarfa, Nicholas Mitsiades, Vasiliki Poulaki
Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic chemotherapies, thus creating an urgent need for novel therapeutics. In this study, we investigated the sensitivity of UM cells to ICG-001, a small molecule reported to suppress the Wnt/β-catenin-mediated transcriptional program. Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on cellular proliferation, migration, and gene expression. In vivo efficacy of ICG-001 was evaluated in a UM xenograft model...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29327717/combined-mutation-and-copy-number-variation-detection-by-targeted-next-generation-sequencing-in-uveal-melanoma
#2
Kyra N Smit, Natasha M van Poppelen, Jolanda Vaarwater, Robert Verdijk, Ronald van Marion, Helen Kalirai, Sarah E Coupland, Sophie Thornton, Neil Farquhar, Hendrikus-Jan Dubbink, Dion Paridaens, Annelies de Klein, Emine Kiliç
Uveal melanoma is a highly aggressive cancer of the eye, in which nearly 50% of the patients die from metastasis. It is the most common type of primary eye cancer in adults. Chromosome and mutation status have been shown to correlate with the disease-free survival. Loss of chromosome 3 and inactivating mutations in BAP1, which is located on chromosome 3, are strongly associated with 'high-risk' tumors that metastasize early. Other genes often involved in uveal melanoma are SF3B1 and EIF1AX, which are found to be mutated in intermediate- and low-risk tumors, respectively...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29317634/punctuated-evolution-of-canonical-genomic-aberrations-in-uveal-melanoma
#3
Matthew G Field, Michael A Durante, Hima Anbunathan, Louis Z Cai, Christina L Decatur, Anne M Bowcock, Stefan Kurtenbach, J William Harbour
Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when the aberrations associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) is the most common primary eye cancer and frequently leads to metastatic death, which is strongly linked to BAP1 mutations. Accordingly, UM is ideally suited for studying the clonal evolution of metastatic competence. Here we analyze sequencing data from 151 primary UM samples using a customized bioinformatic pipeline, to improve detection of BAP1 mutations and infer the clonal relationships among genomic aberrations...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316429/integrative-analysis-identifies-four-molecular-and-clinical-subsets-in-uveal-melanoma
#4
A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman
No abstract text is available yet for this article.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29313397/detection-of-extrascleral-extension-in-uveal-melanoma-with-histopathological-correlation
#5
Christopher K H Burris, Vasilios P Papastefanou, Caroline Thaung, Marie Restori, Amit K Arora, Mandeep S Sagoo, Victoria M L Cohen
PURPOSE: Uveal melanoma is the most common primary intraocular malignancy. Extrascleral extension (ESE) is rare, but associated with an increased rate of orbital recurrence and an overall poor prognosis. Clinical studies show low rates when compared with histological studies. Due to the prognostic importance of ESE, we sought to compare our clinical, intraoperative, and histological detection rates. DESIGN: A retrospective cross-sectional case series. METHODS: A list of eyes enucleated for uveal melanoma was compiled from the admissions records of the London Ocular Oncology Service during the 28-month period, i...
January 9, 2018: Orbit
https://www.readbyqxmd.com/read/29284076/percutaneous-hepatic-perfusion-with-melphalan-in-uveal-melanoma-a-safe-and-effective-treatment-modality-in-an-orphan-disease
#6
Ioannis Karydis, Alexandra Gangi, Matthew J Wheater, Junsung Choi, Iain Wilson, Kerry Thomas, Neil Pearce, Arjun Takhar, Sanjay Gupta, Danielle Hardman, Sean Sileno, Brian Stedman, Jonathan S Zager, Christian Ottensmeier
BACKGROUND: Metastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M-PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy. METHODS: Retrospective analysis of outcomes data of UM patients receiving M-PHP at two institutions was performed. Tumor response and toxicity were evaluated using RECIST 1...
December 28, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29281872/prognoses-and-clinical-outcomes-of-primary-and-recurrent-uveal-melanoma
#7
Jee Hung Kim, Su-Jin Shin, Soo Jin Heo, Eun-Ah Choe, Chang-Gon Kim, Minkyu Jung, Ki Chang Keum, Jin Sook Yoon, Sung Chul Lee, Sang Joon Shin
Purpose: Uveal melanoma has a very poor prognosis despite successful local primary tumor treatment. In this study, we investigated prognostic factors that more accurately reflected the likelihood of recurrence and survival and delineated a prognostic model that could effectively identify different risk groups based on initial clinical parameters. Materials and Methods: Prognostic factors associated with distant recurrence, recurrence-free survival (RFS), progression-free survival (PFS), and OS from distant recurrence to death (OS2) were analyzed in 226 patients with stage I-III uveal melanoma who underwent primary local therapy...
December 28, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29280938/choroidal-tumor-biopsy-a-review-of-the-current-state-and-a-glance-into-future-techniques
#8
Avni P Finn, Miguel A Materin, Prithvi Mruthyunjaya
PURPOSE: To review the indications for and the methods of obtaining biopsies in eyes with uveal melanoma. In addition, this review provides recommendations for avoiding biopsy-related complications and discusses the future directions of biopsy techniques for uveal melanoma. METHODS: This review is based on a presentation by the authors (PM and MM) at the 2017 Duke Advanced Vitreoretinal Surgery Course and an extensive literature review using PubMed. RESULTS: Transscleral and transvitreal fine-needle aspiration biopsy, and transvitreal vitrectomy-assisted biopsy techniques are described...
December 26, 2017: Retina
https://www.readbyqxmd.com/read/29275868/ruthenium-brachytherapy-for-uveal-melanomas-factors-affecting-the-development-of-radiation-complications
#9
Monica M Pagliara, Luca Tagliaferri, Luigi Azario, Jacopo Lenkowicz, Angela Lanza, Rosa Autorino, Carmela G Caputo, Maria A Gambacorta, Vincenzo Valentini, Maria A Blasi
PURPOSE: To investigate how treatment complications are related to dosimetric parameters after ruthenium-106 brachytherapy for uveal melanoma, in a large, clinically homogeneous population. METHODS AND MATERIALS: A retrospective review was performed to evaluate patients affected by small and medium size uveal melanoma, treated with ruthenium-106 brachytherapy from December 2006 to December 2014. We excluded tumors with posterior margin within 1 mm from the edge of the optic disc and foveola...
December 21, 2017: Brachytherapy
https://www.readbyqxmd.com/read/29244840/high-expression-of-lncrna-pvt1-independently-predicts-poor-overall-survival-in-patients-with-primary-uveal-melanoma
#10
Haiming Xu, Jingwen Gong, Hui Liu
The plasmacytoma variant translocation 1 gene (PVT1) plays an oncogenic role in the initiation and progression of multiple cancers. In this study, by using deep-sequencing data and follow-up data in the Cancer Genome Atlas-Uveal melanomas (TCGA-UVM), we assessed the association between the expression of PVT1 and clinicopathological characteristics of patients with uveal melanoma, the mechanism of its dysregulation and its prognostic value. Results showed that high PVT1 expression group had a higher proportion of epithelioid cell dominant disease (a more malignant histological subtype than spindle cell dominant disease) and more cases of extrascleral extension (a risk factor for metastasis) compared with the low PVT1 expression group...
2017: PloS One
https://www.readbyqxmd.com/read/29242243/an-infrared-dye-conjugated-virus-like-particle-for-the-treatment-of-primary-uveal-melanoma
#11
Rhonda C Kines, Isabella Varsavsky, Sanghamitra Choudhary, Debaditya Bhattacharya, Sean Spring, Roger J McLaughlin, Shin J Kang, Hans E Grossniklaus, Demitrios G Vavvas, Stephen Monks, John R MacDougall, Elisabet de Los Pinos, John T Schiller
The work outlined herein describes AU-011, a novel recombinant papillomavirus-like particle (VLP) drug conjugate and its initial evaluation as a potential treatment for primary uveal melanoma. The VLP is conjugated with a phthalocyanine photosensitizer, IRDye 700DX, that exerts its cytotoxic effect through photo-activation with a near-infrared laser. We assessed the anti-cancer properties of AU-011 in vitro utilizing a panel of human cancer cell lines and in vivo using murine subcutaneous and rabbit orthotopic xenograft models of uveal melanoma...
December 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29240458/genome-wide-analysis-of-uveal-melanoma-metastasis-associated-lncrnas-and-their-functional-network
#12
Binbin Xu, Ruiqi Ma, Hui Ren, Jiang Qian
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Up to 50% of primary UM cases will develop distant metastasis, but no effective therapies are currently available. The present study aimed to characterize the expression profile of the long noncoding RNAs (lncRNAs) and screen the potential metastasis-associated lncRNAs in UM. A genome-wide analysis of the transcriptome was performed on 11 primary UM tissues (6 metastasized and 5 nonmetastasized) through RNA sequencing. A total of 40,878 lncRNAs were detected in UM, 4,983 of which were novel candidates...
December 14, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29233905/neddylation-blockade-diminishes-hepatic-metastasis-by-dampening-cancer-stem-like-cells-and-angiogenesis-in-uveal-melanoma
#13
Yanli Jin, Ping Zhang, Yun Wang, Bei Jin, Jingfeng Zhou, Jing Zhang, Jingxuan Pan
PURPOSE: Liver metastasis is the major and direct cause of death in patients with uveal melanoma (UM). There is no effective therapy for patients with metastatic UM. Improved treatments of hepatic metastatic patients with UM were urgently needed. Inspired by readily detectable key components in neddylation pathway in UM cells, we aimed at exploring whether neddylation pathway was a therapeutic target for liver metastatic UM. EXPERIMENTAL DESIGN: Expression of key proteins in neddylation pathway in UM was detected by Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunohistochemical staining...
December 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29219254/primary-bilateral-uveal-melanoma-a-population-based-study-and-systematic-review
#14
Jeffrey F Scott, Ritva Vyas, Jessica Galvin, Erica Gotow, Lori Fiessinger, Adam T Gerstenblith, Meg R Gerstenblith
IMPORTANCE: Primary bilateral uveal melanoma is a rare and incompletely described entity. It is not known how these patients compare to those with unilateral uveal melanoma. BACKGROUND: We sought to comprehensively characterize and compare patients with primary bilateral and unilateral uveal melanoma. DESIGN: Retrospective, population-based and systematic review. PARTICIPANTS: Patients with bilateral (N=52) and unilateral uveal melanoma (N=8915)...
December 8, 2017: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/29209985/frequent-and-yet-unreported-gnaq-and-gna11-mutations-are-found-in-uveal-melanomas
#15
Bjoern Schneider, Katrin Riedel, Andrey Zhivov, Maja Huehns, Heike Zettl, Rudolf F Guthoff, Anselm Jünemann, Andreas Erbersdobler, Annette Zimpfer
Malignant melanoma of the uvea is the most common primary malignant tumor in the eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters. Tumor tissue was microdissected followed by amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by Sanger sequencing. A total of 64.4 GNA11/GNAQ mutations, including ten yet unreported, were found. Two cases showed multiple mutations...
December 5, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29207628/sigma-1-and-sigma-2-receptor-ligands-induce-apoptosis-and-autophagy-but-have-opposite-effect-on-cell-proliferation-in-uveal-melanoma
#16
Lucia Longhitano, Carlo Castruccio Castracani, Daniele Tibullo, Roberto Avola, Maria Viola, Giuliano Russo, Orazio Prezzavento, Agostino Marrazzo, Emanuele Amata, Michele Reibaldi, Antonio Longo, Andrea Russo, Nunziatina Laura Parrinello, Giovanni Li Volti
Uveal melanoma is the most common primary intraocular tumor in adults, with about 1200-1500 new cases occurring per year in the United States. Metastasis is a frequent occurrence in uveal melanoma, and outcomes are poor once distant spread occurs and no clinically significant chemotherapeutic protocol is so far available. The aim of the present study was to test the effect of various σ1 and σ2 receptor ligands as a possible pharmacological strategy for this rare tumor. Human uveal melanoma cells (92.1) were treated with various concentrations of different σ2 ligands (haloperidol and haloperidol metabolite II) and σ1 ligand ((+)-pentazocine) at various concentrations (1, 10 and 25 μM) and time points (0, 4 h, 8 h, 24 h and 48 h)...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29206651/novel-therapeutic-strategies-and-targets-in-advanced-uveal-melanoma
#17
Vivian Chua, Andrew E Aplin
PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. RECENT FINDINGS: Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1)...
December 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29206102/eif1a-residues-implicated-in-cancer-stabilize-translation-preinitiation-complexes-and-favor-suboptimal-initiation-sites-in-yeast
#18
Pilar Martin-Marcos, Fujun Zhou, Charm Karunasiri, Fan Zhang, Jinsheng Dong, Jagpreet Nanda, Neelam Sen, Mercedes Tamame, Michael Zeschnigk, Jon R Lorsch, Alan G Hinnebusch
The translation pre-initiation complex (PIC) scans the mRNA for an AUG codon in favorable context, and AUG recognition stabilizes a closed PIC conformation. The unstructured N-terminal tail (NTT) of yeast eIF1A deploys five basic residues to contact tRNAi, mRNA, or 18S rRNA exclusively in the closed state. Interestingly, EIF1AX mutations altering the human eIF1A NTT are associated with uveal melanoma (UM). We found that substituting all five basic residues, and seven UM-associated substitutions, in yeast eIF1A suppresses initiation at near-cognate UUG codons and AUGs in poor context...
December 5, 2017: ELife
https://www.readbyqxmd.com/read/29204166/patterns-of-care-and-survival-outcomes-after-treatment-for-uveal-melanoma-in-the-post-coms-era-2004-2013-a-surveillance-epidemiology-and-end-results-analysis
#19
Yuan James Rao, Julia Sein, Shahed Badiyan, Julie K Schwarz, Todd DeWees, Perry Grigsby, Prabakar Kumar Rao
Purpose: The Collaborative Ocular Melanoma Study (COMS) established modern treatment recommendations for uveal melanoma. We aim to evaluate patterns of care and survival outcomes in the time after COMS. Material and methods: The retrospective study population includes 2,611 patients in the SEER database treated for uveal melanoma between 2004-2013. Patients stage were T1-4N0M0. Data analyzed included age, clinical stage, tumor size, race, and treatment. Treatments included enucleation (EN) and globe preserving therapy (GPT), which consisted of limited surgical resection or ablation (LSRA), external beam radiation (EBRT), or brachytherapy (BT)...
October 2017: Journal of Contemporary Brachytherapy
https://www.readbyqxmd.com/read/29198096/prognostic-factors-and-decision-tree-for-long-term-survival-in-metastatic-uveal-melanoma
#20
Daniel Lorenzo, María Ochoa, Josep Maria Piulats, Cristina Gutiérrez, Luis Arias, Jaum Català, María Grau, Judith Peñafiel, Estefanía Cobos, Pere Garcia-Bru, Marcos Javier Rubio, Noel Padrón-Pérez, Bruno Dias, Joan Pera, Josep Maria Caminal
Purpose: The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. Materials and Methods: The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion...
December 4, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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