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https://www.readbyqxmd.com/read/29433557/metastatic-uveal-melanoma-showing-durable-response-to-anti-ctla-4-and-anti-pd-1-combination-therapy-after-experiencing-progression-on-anti-pd-1-therapy-alone
#1
Muhammad Zubair Afzal, Rodwell Mabaera, Keisuke Shirai
BACKGROUND: Uveal melanoma accounts for 85% of the ocular melanomas and has an increased risk of hematogenous spread, most commonly to the liver. After curative intent therapy like surgery and radiation, fifty percent of patients present with distant metastasis. Metastatic uveal melanoma (MUM) does not harbor typically targetable mutations, e.g., BRAF as in cutaneous melanoma. As a result, there is no proven therapy for MUM. Various chemotherapy and immunotherapy regimens have been tried and only partial response (PR) is the best that has been achieved in most of the cases...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29416875/patterns-of-bap1-protein-expression-provide-insights-into-prognostic-significance-and-the-biology-of-uveal-melanoma
#2
Neil Farquhar, Sophie Thornton, Sarah E Coupland, Judy M Coulson, Joseph J Sacco, Yamini Krishna, Heinrich Heimann, Azzam Taktak, Colleen M Cebulla, Mohamed H Abdel-Rahman, Helen Kalirai
Uveal melanoma (UM) is a rare aggressive intraocular tumour with a propensity for liver metastases, occurring in ∼50% of patients. The tumour suppressor BAP1 is considered to be key in UM progression. Herein, we present the largest study to date investigating cellular expression patterns of BAP1 protein in 165 UMs, correlating these patterns to prognosis. Full clinical, histological, genetic, and follow-up data were available for all patients. BAP1 gene sequencing was performed on a subset of 26 cases. An independent cohort of 14 UMs was examined for comparison...
January 2018: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/29409899/a-12-year-study-of-slotted-palladium-103-plaque-radiation-therapy-for-choroidal-melanoma-near-touching-or-surrounding-the-optic-nerve
#3
Abhilasha Maheshwari, Paul T Finger
PURPOSE: To present our 12-year experience with low energy photon, slotted eye plaque radiation therapy. DESIGN: Retrospective interventional case series METHODS: SETTING: The New York Eye Cancer Center. STUDY POPULATION: Fifty-two consecutive patients with uveal melanomas near, touching or surrounding the optic disc. INTERVENTION: Slotted eye plaque radiation therapy. MAIN OUTCOME MEASURES: change in visual acuity, local tumor control, radiation side effects, eye salvage and systemic metastases...
January 31, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29344493/comparison-of-gene-expression-profiling-and-chromosome-3-analysis-by-fluorescent-in-situ-hybridization-and-multiplex-ligation-probe-amplification-in-fine-needle-aspiration-biopsy-specimens-of-uveal-melanoma
#4
Michael A Klufas, Elizabeth Richter, Sujit Itty, Christian Moreno, Colin A McCannel, Tara A McCannel
Purpose: The aim of this paper was to assess the concordance between results of DecisionDx-UM specific gene expression profiling (GEP) and fluorescence in situ hybridization (FISH) for chromosome 3 analysis, and between DecisionDx-UM GEP and multiplex ligation probe amplification (MLPA) in uveal melanoma undergoing intraoperative fine-needle aspiration biopsy (FNAB) for metastatic prognostication during brachytherapy. Methods: We retrospectively reviewed consecutive patients diagnosed with posterior uveal melanoma who underwent intraoperative FNAB prior to placement of an iodine-125 radioactive plaque between 2012 and 2014...
December 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/29344481/choroidal-melanoma-mimicker-a-case-of-metastatic-clear-cell-renal-cell-carcinoma
#5
Chris B Komanski, Shaina M Rubino, Jacob C Meyer, Craig M Greven
Choroidal melanoma is the most common primary intraocular malignancy, yet metastatic disease remains the most common malignancy of the eye. Differentiating these entities is essential as treatment, systemic associations, and prognosis vary dramatically between the two. Established diagnostic criteria are accurate for the diagnosis of uveal melanoma. Yet, metastatic disease may be misdiagnosed as a uveal melanoma in rare cases. We report a case of metastatic clear-cell renal cell carcinoma masquerading as uveal melanoma...
November 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/29338117/nestin-expression-in-primary-and-metastatic-uveal-melanoma-possible-biomarker-for-high-risk-uveal-melanoma
#6
Luna Djirackor, Dilem Shakir, Helen Kalirai, Goran Petrovski, Sarah E Coupland
PURPOSE: Nestin, a member of the intermediate filament protein family, has been described as a putative cancer stem cell marker (CSC) in uveal melanoma and poor prognostic factor in a variety of tumours, including cutaneous melanoma. In this study, we examined the expression of nestin in primary (PUM) and metastatic uveal melanoma (MUM) samples, and correlated the findings with histological, clinical and survival data. METHODS: Nestin expression was assessed by immunohistochemistry in 141 PUM and 26 MUM samples; 11 PUM cases were matched with their corresponding metastases...
January 16, 2018: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29333944/mir-155-promotes-uveal-melanoma-cell-proliferation-and-invasion-by-regulating-ndfip1-expression
#7
Jing Peng, Honglei Liu, Cuihong Liu
MicroRNAs refer to small RNA molecules that destroy the messenger RNA by binding on them inhibiting the production of protein. However, the role of miR-155 in uveal melanoma metastasis remains largely unknown. In this study, we found that miR-155 was upregulated in both uveal melanoma cells and tissues. Transfection of miR-155 mimic into uveal melanoma cells led to an increase in cell growth and invasion; in contrast, inhibition of miR-155 resulted in opposite effects. Also, we identified Nedd4-family interacting protein 1 as a direct target of miR-155, and the expression of Nedd4-family interacting protein 1 was inhibited by miR-155...
December 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29327717/combined-mutation-and-copy-number-variation-detection-by-targeted-next-generation-sequencing-in-uveal-melanoma
#8
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
#9
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/29275868/ruthenium-brachytherapy-for-uveal-melanomas-factors-affecting-the-development-of-radiation-complications
#10
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
#11
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/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/29219931/bilateral-uveal-metastases-secondary-to-prostate-adenocarcinoma
#14
Katherine J Cochran, James R Gray, Anthony A Meluch, David A Reichstein
PURPOSE: To report a patient with bilateral uveal metastases secondary to previously quiescent prostate adenocarcinoma with a 22-month follow-up. METHODS: Retrospective chart review was performed for this patient. RESULTS: Androgen deprivation therapy and external beam radiation therapy were shown to manage ocular symptoms in a sixty-nine-year-old man previously diagnosed with adenocarcinoma of the prostate. CONCLUSION: Uveal metastases can be the first site of systemic metastasis even long after initial diagnosis and treatment of prostate adenocarcinoma; the 17 years between this patient's treatment for adenocarcinoma and commencement of his ocular symptoms is the longest interval reported...
December 5, 2017: Retinal Cases & Brief Reports
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
#15
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/29198096/prognostic-factors-and-decision-tree-for-long-term-survival-in-metastatic-uveal-melanoma
#16
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
https://www.readbyqxmd.com/read/29187428/clinical-histopathological-and-cytogenetic-prognosticators-in-uveal-melanoma-a-comprehensive-review
#17
REVIEW
Tomasz Berus, Agnieszka Halon, Anna Markiewicz, Jolanta Orlowska-Heitzman, Bozena Romanowska-Dixon, Piotr Donizy
Uveal melanoma is the most prevalent primary intraocular cancer in adults. Although it accounts for only 5% of all melanomas, it is responsible for 13% of deaths due to this type of cancer. A wide variety of therapeutic options of primary tumor is available and progress in its management is noticeable. The fact still remains, however, that almost half of patients develop metastases which may be due to practically undetectable cancer spread present as early as at diagnosis of the primary focus. Metastatic disease is uniformly fatal despite systemic therapy...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29185395/pd-l1-expression-in-tumor-metastasis-is-different-between-uveal-melanoma-and-cutaneous-melanoma
#18
Asad Javed, David Arguello, Curtis Johnston, Zoran Gatalica, Mizue Terai, Ryan M Weight, Marlana Orloff, Michael J Mastrangelo, Takami Sato
AIM: To compare PD-L1 expression between metastatic uveal melanoma (MUM) and metastatic cutaneous melanoma (MCM). MATERIALS & METHODS: A total of 295 MCM and 78 MUM specimens were analyzed for tumor cell PD-L1 expression. Additionally, 91 MCM and 45 MUM specimens were analyzed for PD-1 expression on tumor-infiltrating lymphocytes. RESULTS:  A total of 77/295 (26.1%) MCM specimens expressed PD-L1 as compared to 4/78 (5.1%) MUM specimens (p < 0...
December 2017: Immunotherapy
https://www.readbyqxmd.com/read/29184418/fgf2-promotes-metastasis-of-uveal-melanoma-cells-via-store-operated-calcium-entry
#19
Yanyan Wang, Xiuli Bao, Zhiyong Zhang, Yi Sun, Xiyuan Zhou
Uveal melanoma (UM), the most common primary intraocular malignancy in adults, is highly metastatic and associated with dismal prognosis. Fibroblast growth factor 2 (FGF2) has been shown to induce cell proliferation and angiogenesis of melanoma and other malignancies. However, the expression of FGF2 in UM and its effects on melanoma cell migration are not well known. In this study, we found FGF2 expression was related to UM histological subtype and presence of metastasis. In vitro experiments showed that FGF2 treatment caused increased horizontal and vertical migration and F-actin cytoskeleton assembly as well as decreased adhesive activity of MUM2B cells, together with increased intracellular calcium concentration and expression of ORAI1 and STIM1 - two key regulatory proteins of store-operated calcium entry (SOCE)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29142760/outcomes-of-primary-endoresection-for-choroidal-melanoma
#20
Andre A C Vidoris, Andre Maia, Marcia Lowen, Melina Morales, Jordan Isenberg, Bruno F Fernandes, Rubens N Belfort
Purpose: To review long time treatment results in patients with small or medium sized choroidal melanoma who underwent surgical tumor endoresection as a primary treatment when plaque radiotherapy was unable and patients declined enucleation. Materials and methods: Patients were evaluated for best corrected visual acuity (BCVA), and underwent biomicroscopy, indirect ophthalmoscopy, retinography and ultrasound as well as the usual systemic workup. Study inclusion required the absence of scleral invasion or metastasis and an anterior margin not exceeding the pars plana or the ciliary body...
2017: International Journal of Retina and Vitreous
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