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Uveal melanoma

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https://www.readbyqxmd.com/read/28812919/comparison-of-primary-and-secondary-enucleation-for-uveal-melanoma
#1
Chau M Pham, Philip L Custer, Steven M Couch
We investigated operative course and post-operative findings of patients undergoing primary enucleation for uveal melanoma versus those requiring secondary enucleation after brachytherapy. A retrospective chart review was performed with IRB approval on patients receiving treatment for uveal melanoma. Patients with enucleation as initial treatment and patients enucleated after plaque brachytherapy were analyzed for demographic data, operative course, and post-enucleation outcome. Further cause analysis for secondary enucleations was investigated...
August 16, 2017: Orbit
https://www.readbyqxmd.com/read/28810145/integrative-analysis-identifies-four-molecular-and-clinical-subsets-in-uveal-melanoma
#2
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
Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28809862/gnaq-and-gna11-mutations-and-downstream-yap-activation-in-choroidal-nevi
#3
M J C Vader, M C Madigan, M Versluis, H M Suleiman, G Gezgin, N A Gruis, J J Out-Luiting, W Bergman, R M Verdijk, M J Jager, P A van der Velden
BACKGROUND: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations. METHODS: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions...
August 15, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28801919/familial-associations-of-female-breast-cancer-with-other-cancers
#4
Guoqiao Zheng, Hongyao Yu, Akseli Hemminki, Asta Försti, Kristina Sundquist, Kari Hemminki
Familial risks of breast cancer (BC) are well established but whether BC clusters with other, i.e. discordant, cancers is less certain but of interest for the identification of common genetic and possible environmental factors contributing to a general cancer susceptibility. We apply a novel approach to search for familial associations of BC with other (discordant) cancers based on the Swedish Family-Cancer Database. Relative risks (RRs) were calculated for BC in families with increasing numbers of patients with discordant cancer X, and conversely, familial RRs for cancer X in families with increasing numbers of BC patients...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28793149/genotypic-and-phenotypic-features-of-bap1-cancer-syndrome-a-report-of-8-new-families-and-review-of-cases-in-the-literature
#5
Alexandra M Haugh, Ching-Ni Njauw, Jeffrey A Bubley, Anna Elisa Verzì, Bin Zhang, Emily Kudalkar, Timothy VandenBoom, Kara Walton, Brian L Swick, Raj Kumar, Huma Q Rana, Sarah Cochrane, Shelley R McCormick, Christopher R Shea, Hensin Tsao, Pedram Gerami
Importance: Patients with germline mutations in BAP1 may develop several flesh-colored melanocytic BAP1-mutated atypical intradermal tumors (MBAITs). These tumors generally develop earlier than other BAP1-associated tumors, highlighting an important role for dermatologists in identifying and screening patients with a history suggestive of a germline mutation. Objective: To describe 8 new families with germline mutations in BAP1 and provide a comprehensive review of reported cases...
August 9, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28791340/grb2-associated-binder-2-expression-and-its-roles-in-uveal-melanoma-invasion
#6
Meiling Chen, Yuehua Li, Xiuning Sun, Baogang Zhang, Wei Li, Shuxiao Wang, Xuetao Zhu, Feng Li, Lihong Shi
Uveal melanoma (UM) is characterized by high metastasis and poor prognosis. A more improved understanding of the metastatic mechanism in UM cells is essential for the design of molecular therapy. Grb2‑associated binder 2 (Gab2) has been reported to serve important roles in the progression of various types of human cancer. However, the role of Gab2 in the migration and invasion of UM remains unclear. The present study sought to further assess the expression of Gab2 in UM and the role of Gab2 in the invasion of UM cells...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28781888/a-gwas-in-uveal-melanoma-identifies-risk-polymorphisms-in-the-clptm1l-locus
#7
Lenha Mobuchon, Aude Battistella, Claire Bardel, Ghislaine Scelo, Alexia Renoud, Alexandre Houy, Nathalie Cassoux, Maud Milder, Géraldine Cancel-Tassin, Olivier Cussenot, Olivier Delattre, Céline Besse, Anne Boland, Jean-François Deleuze, David G Cox, Marc-Henri Stern
Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28781790/somatic-brca1-associated-protein-1-bap1-loss-is-an-early-and-rare-event-in-esophageal-adenocarcinoma
#8
Heike Loeser, Dirk Waldschmidt, Fabian Kuetting, Simon Schallenberg, Thomas Zander, Elfriede Bollschweiler, Arnulf Hoelscher, Katharina Weckermann, Patrick Plum, Hakan Alakus, Reinhard Buettner, Alexander Quaas
Esophageal cancer is the eighth most common malignant tumor worldwide, and the number of incidences of esophageal adenocarcinoma is increasing in the Western world. Despite improvements in perioperative treatment, the overall survival rate of patients with esophageal adenocarcinoma remains poor. Breast cancer type 1 susceptibility protein (BRCA1)-associated protein (BAP1) is located on chromosome 3p21, and it is an enzyme with ubiquitin carboxyl hydrolase activity that regulates cell growth. It interacts with BRCA1, and the nuclear localization of BAP1 is required for its tumor suppressor function...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28778073/expression-of-ezh2-in-uveal-melanomas-patients-and-associations-with-prognosis
#9
Ying Cheng, Ying Li, Xin Huang, Wenbin Wei, Yi Qu
PURPOSE: To analyze the prognostic value and potential target for therapeutic intervention of enhancer of zeste homologue 2 (EZH2) in uveal melanomas (UM) patients. METHOD: We analyzed EZH2 expression in 89 primary UM patients by immuno- histochemistry to observe the clinicopathological and prognostic value of EZH2. RESULTS: The high levels of mitoses count and Ki67 labeling index had significant correlation with overexpression EZH2 (R = 0...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28767411/sigma-1-and-sigma-2-receptor-ligands-induce-apoptosis-and-autophagy-but-have-opposite-effect-on-cell-proliferation-in-uveal-melanoma
#10
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)...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766683/pristimerin-effectively-inhibits-the-malignant-phenotypes-of-uveal-melanoma-cells-by-targeting-nf%C3%A2-%C3%AE%C2%BAb-pathway
#11
Biao Zhang, Jing Zhang, Jingxuan Pan
Uveal melanoma (UM) is a highly aggressive intraocular malignancy that lacks any effective targeted-therapy. Neither survival nor prognosis has been improved for the past decades in patients with metastatic UM. NF‑κB pathway is reported to be abnormally activated in UM. However, the role of NF‑κB pathway as a potential therapeutical target in UM remains unclear. Here, the effect of pristimerin, a potent inhibitor of NF‑κB pathway, on UM cells in terms of growth, apoptosis, motility, invasion and cancer stem-like cells (CSCs) was evaluated in vitro...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28763558/radiation-maculopathy-after-proton-beam-therapy-for-uveal-melanoma-optical-coherence-tomography-angiography-alterations-influencing-visual-acuity
#12
Alexandre Matet, Alejandra Daruich, Leonidas Zografos
Purpose: To analyze microvascular and structural changes in radiation maculopathy and their influence on visual acuity (VA), using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: This was a retrospective analysis of consecutive patients with radiation maculopathy, 12 months or more after proton-beam irradiation for uveal melanoma, imaged with fluorescein angiography, OCT, and OCTA. Clinical parameters potentially affecting VA were recorded, including OCTA-derived metrics: foveal avascular zone (FAZ) area, vascular density, and local fractal dimension of the superficial (SCP) and deep capillary plexuses (DCP)...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28759124/recent-advances-in-uveal-melanoma-treatment
#13
REVIEW
Beatriz Álvarez-Rodríguez, Alfonso Latorre, Christian Posch, Álvaro Somoza
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recent advances in the understanding of molecular characteristics helped to determine which tumors are most likely to progress. About 50% of patients carrying genetic alterations such as chromosomal aberrations and mutations are at significant risk for metastatic disease of which the majority will succumb to UM within few months. Currently, there is no effective treatment for metastatic uveal melanoma, and we hope this review will encourage researchers and clinicians to work to find a better standard of care...
July 31, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28757700/brachytherapy-and-anterior-segment-imaging-in-iris-melanoma
#14
Jin Soo Andy Song, Adam A Dmytriw, Hesham Lakosha
Ultrasound biomicroscopy (UBM) remains a potent tool in the diagnosis and characterization of uveal lesions. In the setting of malignancy, it can confirm both placement of and response to brachytherapy. We present a case of iris melanoma with aggressive BAP-1 mutation, treated successfully with I-131 brachytherapy which was both characterized and followed with UBM and thereafter discuss the current state of these modalities.
May 2017: Oman Journal of Ophthalmology
https://www.readbyqxmd.com/read/28749709/lncrna-hoxa11-as-exerts-oncogenic-functions-by-repressing-p21-and-mir-124-in-uveal-melanoma
#15
Qinkang Lu, Na Zhao, Guiping Zha, Huiyun Wang, Qihu Tong, Shuanghua Xin
Long noncoding RNAs (lncRNAs) have been reported to play vital roles in various human cancers. The aim of this study was to explore the critical role of lncRNA HOXA11-AS in uveal melanoma (UM) progression. Briefly, we found that HOXA11-AS is overexpressed in UM tissues and cells; HOXA11-AS could regulate UM cell growth, invasion, and apoptosis. Mechanistically, RNA immunoprecipitation demonstrated that HOXA11-AS could simultaneously interact with enhancer of zeste homolog 2 (EZH2) to suppress its target p21 protein expression...
July 27, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28744147/evaluation-of-p53-gene-expression-and-prognosis-characteristics-in-uveal-melanoma-cases
#16
Haojie Liu, Ming Zhou
OBJECTIVE: The objective of this study was to evaluate the correlation between the expression of p53 gene and the prognosis after local excision in uveal melanoma. MATERIALS AND METHODS: Real-time polymerase chain reaction (RT-PCR) test and Western blot were used to detect the expression of p53 in C918, MUM-2B, and D78 cell lines at the levels of messenger RNA (mRNA) and protein. Immunohistochemistry staining was done in the tissues of 68 patients, which were diagnosed with uveal melanoma...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28743137/-surgical-methods-in-the-treatment-of-uveal-melanoma
#17
Georgios Blatsios, Gertrud Haas, Claus Zehetner, Nikolaos E Bechrakis
Significant advancements have been made in the last decades in the treatment of uveal melanoma. Radiation therapy can achieve, depending on the method, local tumour control in up to 98% of cases. Surgical modalities have been implemented in the ocular therapy for uveal melanoma either to treat/prevent radiation complications, such as so-called toxic tumour syndrome, or to primarily treat the tumour with or without adjunctive radiotherapy. These include endoresection and transscleral resection for melanomas of the choroid/ciliary body or irido-trabeculo-cyclectomy for melanomas of the iris-ciliary body...
July 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28737763/melanoma-subtypes-demonstrate-distinct-pd-l1-expression-profiles
#18
Genevieve J Kaunitz, Tricia R Cottrell, Mohammed Lilo, Valliammai Muthappan, Jessica Esandrio, Sneha Berry, Haiying Xu, Aleksandra Ogurtsova, Robert A Anders, Alexander H Fischer, Stefan Kraft, Meg R Gerstenblith, Cheryl L Thompson, Kord Honda, Jonathan D Cuda, Charles G Eberhart, James T Handa, Evan J Lipson, Janis M Taube
PD-L1 expression in the tumor immune microenvironment is recognized as both a prognostic and predictive biomarker in patients with cutaneous melanoma, a finding closely related to its adaptive (IFN-γ-mediated) mechanism of expression. Approximately 35% of cutaneous melanomas express PD-L1, however, the expression patterns, levels, and prevalence in rarer melanoma subtypes are not well described. We performed immunohistochemistry for PD-L1 and CD8 on 200 formalin-fixed paraffin-embedded specimens from patients with acral (n=16), mucosal (n=36), uveal (n=103), and chronic sun-damaged (CSD) (n=45) melanomas (24 lentigo maligna, 13 'mixed' desmoplastic, and 8 'pure' desmoplastic melanomas)...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28730086/peptidome-profiling-of-human-serum-of-uveal-melanoma-patients-based-on-magnetic-bead-fractionation-and-mass-spectrometry
#19
Xiang-Yu Shi, Qing Li, Wen-Bin Wei, Li-Ming Tao
AIM: To find new biomarkers for uveal melanoma (UM) by analyzing the serum peptidome profile. METHODS: Proteomic spectra in patients with UM before and after operation were analyzed and compared with those of healthy controls. Magnetic affinity beads were used to capture serum peptides and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer were used to compile serum peptide profiles. RESULTS: A panel of 49 peptides were differentially expressed between UM patients and controls, of which 33 peptides were of higher intensities in patient group and 16 peptides were of higher intensities in control group...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28728954/ultrasound-histopathological-and-genetic-features-of-uveal-melanoma-in-a-mexican-mestizo-population
#20
S Delgado, A Rodriguez Reyes, L Mora Rios, A Dueñas-González, L Taja-Chayeb, E Moragrega Adame
OBJECTIVE: To describe the ultrasound, histopathological and genetic characteristics of uveal melanoma in a Mexican-Mestizo population. MATERIAL AND METHODS: A total of 39 enucleated eyes with a histopathological diagnosis of uveal melanoma were assessed by describing the clinical findings, and ultrasound, histopathological and genetic features. RESULTS: A high correlation was observed between tumour height measurement using ultrasound and histopathology...
July 17, 2017: Archivos de la Sociedad Española de Oftalmología
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