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Uveal melanoma

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https://www.readbyqxmd.com/read/28448663/prame-as-a-potential-target-for-immunotherapy-in-metastatic-uveal-melanoma
#1
Gülçin Gezgin, Sietse J Luk, Jinfeng Cao, Mehmet Dogrusöz, Dirk M van der Steen, Renate S Hagedoorn, Daniëlle Krijgsman, Pieter A van der Velden, Matthew G Field, Gregorius P M Luyten, Karoly Szuhai, J William Harbour, Ekaterina S Jordanova, Mirjam H M Heemskerk, Martine J Jager
Importance: Uveal melanoma (UM) is an intraocular primary malignant neoplasm that often gives rise to metastatic disease for which there are no effective therapies. A substantial proportion of UMs express the cancer-testis antigen PRAME (preferentially expressed antigen in melanoma), which can potentially be targeted by adoptive T-cell therapy. Objective: To determine whether there may be a rationale for PRAME-directed T-cell therapy for metastatic UM. Design, Setting, and Participants: An experimental study using a retrospective cohort of 64 patients with UM (median follow-up, 62 months) was conducted from January 8, 2015, to November 20, 2016, at the Leiden University Medical Center...
April 27, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28444874/prognostic-impact-of-chromosomal-aberrations-and-gnaq-gna11-and-bap1-mutations-in-uveal-melanoma
#2
Kjersti M Staby, Karsten Gravdal, Sverre J Mørk, Steffen Heegaard, Olav K Vintermyr, Jørgen Krohn
PURPOSE: To evaluate clinico-pathological and molecular prognostic factors in a well-defined series of posterior uveal melanoma (UM) with focus on chromosomal aberrations and mutations in the GNAQ, GNA11 and BRCA1-associated protein 1 (BAP1) genes. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue samples were obtained from 50 consecutive eyes enucleated for UM between 1993 and 2005. The material was tested for loss of chromosome 3 and gain of chromosome 8q gene signatures by selective molecular gene markers using multiplex ligation-dependent probe amplification (MLPA), and for DNA mutations in the GNAQ, GNA11 and BAP1 genes...
April 26, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28440333/immunotherapy-cul-til-vating-uveal-melanoma-regression
#3
Lisa Hutchinson
No abstract text is available yet for this article.
April 25, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28433129/swept-source-optical-coherence-tomography-angiography-imaging-in-a-case-of-uveal-melanoma
#4
Marco Pellegrini, Giovanni Staurenghi
No abstract text is available yet for this article.
May 2017: Ophthalmology
https://www.readbyqxmd.com/read/28432067/adoptive-t-cell-therapy-has-antitumor-activity-in-uveal-melanoma
#5
(no author information available yet)
Adoptive T-cell therapy achieved responses in 35% of patients with metastatic uveal melanoma.
April 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28429726/verteporfin-induced-formation-of-protein-cross-linked-oligomers-and-high-molecular-weight-complexes-is-mediated-by-light-and-leads-to-cell-toxicity
#6
Eleni K Konstantinou, Shoji Notomi, Cassandra Kosmidou, Katarzyna Brodowska, Ahmad Al-Moujahed, Fotini Nicolaou, Pavlina Tsoka, Evangelos Gragoudas, Joan W Miller, Lucy H Young, Demetrios G Vavvas
Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28409567/sf3b1-and-bap1-mutations-in-blue-nevus-like-melanoma
#7
Klaus G Griewank, Hansgeorg Müller, Louise A Jackett, Michael Emberger, Inga Möller, Johannes Ap van de Nes, Lisa Zimmer, Elisabeth Livingstone, Thomas Wiesner, Simone L Scholz, Ioana Cosgarea, Antje Sucker, Tobias Schimming, Uwe Hillen, Bastian Schilling, Annette Paschen, Henning Reis, Thomas Mentzel, Heinz Kutzner, Arno Rütten, Rajmohan Murali, Richard A Scolyer, Dirk Schadendorf
Blue nevi are melanocytic tumors originating in the cutaneous dermis. Malignant tumors may arise in association with or resembling blue nevi, so called 'blue nevus-like melanoma', which can metastasize and result in patient death. Identifying which tumors will behave in a clinically aggressive manner can be challenging. Identifying genetic alterations in such tumors may assist in their diagnosis and prognostication. Blue nevi are known to be genetically related to uveal melanomas (eg, both harboring GNAQ and GNA11 mutations)...
April 14, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28404670/intravitreal-dexamethasone-implant-in-radiation-induced-macular-oedema
#8
Luisa Frizziero, Raffaele Parrozzani, Sara Trainiti, Elisabetta Pilotto, Giacomo Miglionico, Serena Pulze, Edoardo Midena
AIMS: To evaluate the efficacy and duration of activity of a single intravitreal dexamethasone implant in patients affected by radiation maculopathy. METHODS: Thirteen consecutive eyes of 13 patients affected by radiation maculopathy secondary to eye irradiation for a primary uveal melanoma (Iodine-125 brachytherapy) and treated with a single intravitreal 0.7 mg dexamethasone implant were retrospectively evaluated. Each patient underwent full ophthalmological examination, including fluorescein angiography and spectral domain optical coherence tomography (SD-OCT), even in en-face modality...
April 12, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28399342/uveal-melanoma-treatment-and-prognostication
#9
Mehmet Dogrusöz, Martine J Jager, Bertil Damato
Approximately 90% of uveal melanoma develop in the choroid, with the remainder arising in the ciliary body or the iris. The treatment of uveal melanoma is aimed at conserving the eye and useful vision, and, if possible, preventing metastatic disease. Enucleation is now reserved for tumors that are large and/or involve the optic disc, having largely been replaced by various forms of radiotherapy (plaque brachy-therapy, proton beam or stereotactic radiotherapy) and laser therapy. Whereas iridectomy and iridocyclectomy are widely performed, transscleral exoresection of choroidal tumors is performed only in a few centers because it requires special skills and hypotensive anesthesia...
March 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28399339/uveal-melanoma-identifying-immunological-and-chemotherapeutic-targets-to-treat-metastases
#10
Martine J Jager, Mehmet Dogrusöz, Scott E Woodman
Uveal melanoma is an intraocular malignancy that, depending on its size and genetic make-up, may lead to metastases in up to 50% of cases. Currently, no therapy has been proven to improve survival. However, new therapies exploiting immune responses against metastases are being developed. The primary tumor is well characterized: tumors at high risk of developing metastases often contain macrophages and lymphocytes. However, these lymphocytes are often regulatory T cells that may suppress immune response. Currently, immune checkpoint inhibitors have shown marked efficacy in multiple cancers (eg, cutaneous melanoma) but do not yet improve survival in uveal melanoma patients...
March 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28395881/adopting-a-new-stance-on-immunotherapy-for-uveal-melanoma
#11
Kimberly M Komatsubara, Richard D Carvajal
No abstract text is available yet for this article.
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28395880/treatment-of-metastatic-uveal-melanoma-with-adoptive-transfer-of-tumour-infiltrating-lymphocytes-a-single-centre-two-stage-single-arm-phase-2-study
#12
Smita S Chandran, Robert P T Somerville, James C Yang, Richard M Sherry, Christopher A Klebanoff, Stephanie L Goff, John R Wunderlich, David N Danforth, Daniel Zlott, Biman C Paria, Arvind C Sabesan, Abhishek K Srivastava, Liqiang Xi, Trinh H Pham, Mark Raffeld, Donald E White, Mary Ann Toomey, Steven A Rosenberg, Udai S Kammula
BACKGROUND: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma...
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28391358/genetic-evolution-of-uveal-melanoma-guides-the-development-of-an-inflammatory-microenvironment
#13
Gülçin Gezgin, Mehmet Dogrusöz, T Huibertus van Essen, Wilhelmina G M Kroes, Gregorius P M Luyten, Pieter A van der Velden, Vonn Walter, Robert M Verdijk, Thorbald van Hall, Sjoerd H van der Burg, Martine J Jager
Uveal melanoma (UM) is characterized by a number of genetic aberrations that follow a certain chronology and are tightly linked to tumor recurrence and survival. Loss of chromosome 3, bi-allelic loss of BAP1 expression, and gain in chromosome 8q have been associated with metastasis formation and death, while loss of chromosome 3 has been associated with the influx of macrophages and T cells. We used a set of genetically-classified UM to study immune infiltration in the context of their genetic evolution. We show in two independent cohorts that lack of BAP1 expression is associated with an increased density of CD3(+) T cells and CD8(+) T cells...
April 8, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28387434/incidence-of-secondary-glaucoma-after-treatment-of-uveal-melanoma-with-robotic-radiosurgery-versus-brachytherapy
#14
Jakob Siedlecki, Veronika Reiterer, Simon Leicht, Paul Foerster, Karsten Kortüm, Ulrich Schaller, Siegfried Priglinger, Christoph Fuerweger, Alexander Muacevic, Kirsten Eibl-Lindner
PURPOSE: Different modalities of radiation therapy nowadays allow for effective treatment of uveal melanoma combined with the advantage of eye preservation. However, this advantage can secondarily be impaired by radiation-related side effects. After local recurrence, secondary glaucoma (SG) has been described as second most frequent complication leading to need of enucleation. This study compares the incidence of SG after conventional Ruthenium (Ru)-106 brachytherapy (BT) versus CyberKnife robotic radiosurgery (RRS) which has been gaining importance lately as an efficient treatment option offering improved patient comfort...
April 7, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28377140/early-outcomes-of-uveal-melanoma-treated-with-intraoperative-ultrasound-guided-brachytherapy-using-custom-built-plaques
#15
Anne W Tann, Bin S Teh, Sarah B Scarboro, Gary D Lewis, Maria E Bretana, Porshea C Croft, Yuval Raizen, E Brian Butler, Ryan S Kim, Patricia Chevez-Barrios, Amy C Schefler
PURPOSE: To report early outcomes of patients with uveal melanoma treated with Eye Physics iodine-125 episcleral plaque therapy using modern biopsy techniques and intraoperative ultrasound guidance at our institution. METHODS AND MATERIALS: A retrospective chart review was conducted for 48 consecutive patients with uveal melanoma who were treated with Eye Physics plaque brachytherapy performed by 1 ocular oncologist. All patients underwent intraoperative ultrasound for image guidance of plaque placement...
January 7, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28376556/-uveal-melanoma-cell-under-oxidative-stress-influence-of-vegf-and-vegf-inhibitors
#16
M Dithmer, A M Kirsch, L Gräfenstein, F Wang, H Schmidt, S E Coupland, S Fuchs, J Roider, A K Klettner
Background The role of oxidative stress in cancer is complex. While the pathological alterations induced by oxidative stress may be involved in the induction of tumours, in the late stages of tumour development, it can facilitate the loss of tumour cells and might even prevent metastasis. Tumour cells show metabolic alterations, often inducing an increased production of reactive oxygen species, which makes these cells particularly vulnerable to additional oxidative stress. This is an important mode of action in the use of many chemotherapeutics and in the application of ionizing radiation...
April 4, 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28365241/adjuvant-ab-interno-tumor-treatment-after-proton-beam-irradiation
#17
Ira Seibel, Aline I Riechardt, Jens Heufelder, Dino Cordini, Antonia M Joussen
PURPOSE: This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. DESIGN: Retrospective cohort study METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. RESULTS: A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95...
March 29, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28362882/sex-disparity-in-survival-of-patients-with-uveal-melanoma-better-survival-rates-in-women-than-in-men-in-south-korea
#18
San Jun Park, Chang-Mo Oh, Bora Yeon, Hyunsoon Cho, Kyu Hyung Park
Purpose: The purpose of this study was to determine the survival rate of patients with uveal melanoma and sex disparity in this rate in South Korea. Methods: We extracted incident uveal melanoma patients using the Korea Central Cancer Registry (KCCR) database, which covered the entire population from 1999 to 2012 in South Korea. We estimated all-cause survival probabilities and cancer-specific survival probabilities of patients with uveal melanoma and compared these probabilities between subgroups (sex, tumor site, age at diagnosis, etc...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28356703/differential-responses-of-choroidal-melanocytes-and-uveal-melanoma-cells-to-low-oxygen-conditions
#19
Cindy Weidmann, Jade Pomerleau, Laurence Trudel-Vandal, Solange Landreville
PURPOSE: Tissue culture is traditionally performed at atmospheric oxygen concentration (21%), which induces hyperoxic stress, as endogenous physiologic oxygen tension found in tissues varies between 2% and 9%. This discrepancy may lead to misinterpretation of results and may explain why effects observed in vitro cannot always be reproduced in vivo and vice versa. Only a few studies have been conducted in low physiologic oxygen conditions to understand the development and differentiation of cells from the eye...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28350816/multi-channel-mri-segmentation-of-eye-structures-and-tumors-using-patient-specific-features
#20
Carlos Ciller, Sandro De Zanet, Konstantinos Kamnitsas, Philippe Maeder, Ben Glocker, Francis L Munier, Daniel Rueckert, Jean-Philippe Thiran, Meritxell Bach Cuadra, Raphael Sznitman
Retinoblastoma and uveal melanoma are fast spreading eye tumors usually diagnosed by using 2D Fundus Image Photography (Fundus) and 2D Ultrasound (US). Diagnosis and treatment planning of such diseases often require additional complementary imaging to confirm the tumor extend via 3D Magnetic Resonance Imaging (MRI). In this context, having automatic segmentations to estimate the size and the distribution of the pathological tissue would be advantageous towards tumor characterization. Until now, the alternative has been the manual delineation of eye structures, a rather time consuming and error-prone task, to be conducted in multiple MRI sequences simultaneously...
2017: PloS One
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