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Uveal melanoma

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https://www.readbyqxmd.com/read/28529629/the-antihelminthic-drug-niclosamide-effectively-inhibits-the-malignant-phenotypes-of-uveal-melanoma-in-vitro-and-in-vivo
#1
Jingfeng Zhou, Bei Jin, Yanli Jin, Yizhi Liu, Jingxuan Pan
Uveal melanoma (UM) is a lethal intraocular malignancy with an average survival of only 2~8 months in patients with hepatic metastasis. Currently, there is no effective therapy for metastatic UM. Here, we reported that niclosamide, an effective repellence of tapeworm that has been approved for use in patients for approximately 50 years, exhibited strong antitumor activity in UM cells in vitro and in vivo. We showed that niclosamide potently inhibited UM cell proliferation, induced apoptosis and reduced migration and invasion...
2017: Theranostics
https://www.readbyqxmd.com/read/28529451/role-of-epigenetics-in-uveal-melanoma
#2
REVIEW
Yongyun Li, Renbing Jia, Shengfang Ge
Uveal melanoma (UM) is a severe human malignancy with a high mortality rate that demands continued research into new and alternative forms of prevention and treatment. The emerging field of epigenetics is beginning to unfold an era of contemporary approaches to reducing the risk and improving the clinical treatment of UM. Epigenetic changes have a high prevalence rate in cancer, are reversible in nature, and can lead to cancer characteristics even in mutation-free cells. The information contained in this review highlights and expands on the main mechanisms of epigenetic dysregulation in UM tumorigenesis, progression and metastasis, including microRNA expression, hypermethylation of genes and histone modification...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28520637/clinical-experience-of-stereotactic-radiosurgery-at-a-linear-accelerator-for-intraocular-melanoma
#3
Alena Furdova, Miron Sramka, Martin Chorvath, Gabriel Kralik, Robert Furda, Michal Gregus
Long-term results with linear accelerator LINAC-based stereotactic radiosurgery for intraocular uveal malignant melanoma were assessed. A retrospective study was carried out of patients with uveal melanoma after a 1-day session stereotactic radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2 to 1.6 cm). Tumors ranged in size from 2...
May 17, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28512868/metastasis-associated-microrna-expression-in-canine-uveal-melanoma
#4
M P Starkey, L Compston-Garnett, P Malho, K Dunn, R Dubielzig
BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumour in dogs. There is no effective means of predicting whether a tumour will metastasize. microRNA (miRNA) metastasis signatures have been identified for several human cancers, including UM. AIMS: In this study we investigated whether metastasizing and non-metastasizing canine UMs can be distinguished by miRNA expression levels. MATERIALS AND METHODS: miRNA microarray profiling was used to compare miRNA expression in 8 metastasizing and 12 non-metastasizing formalin-fixed, paraffin-embedded (FFPE) primary UM biopsies...
May 17, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28512236/focus-on-cutaneous-and-uveal-melanoma-specificities
#5
REVIEW
Charlotte Pandiani, Guillaume E Béranger, Justine Leclerc, Robert Ballotti, Corine Bertolotto
Cutaneous melanoma (CM) and uveal melanoma (UM) derive from cutaneous and uveal melanocytes that share the same embryonic origin and display the same cellular function. However, the etiopathogenesis and biological behaviors of these melanomas are very different. CM and UM display distinct landscapes of genetic alterations and show different metastatic routes and tropisms. Hence, therapeutic improvements achieved in the last few years for the treatment of CM have failed to ameliorate the clinical outcomes of patients with UM...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28508938/immunotherapy-for-the-treatment-of-uveal-melanoma-current-status-and-emerging-therapies
#6
REVIEW
Kimberly M Komatsubara, Richard D Carvajal
PURPOSE OF REVIEW: Uveal melanoma is a distinct subset of melanoma with a biology and treatment approach that is unique from that of cutaneous melanoma. Here we will review the current data evaluating immunotherapies in both the adjuvant and metastatic settings in uveal melanoma. RECENT FINDINGS: In the adjuvant setting, interferon demonstrated no survival benefit in uveal melanoma, and studies evaluating immune-based strategies such as vaccine therapy are ongoing...
July 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28505674/-novel-adjuvant-therapy-for-ocular-melanoma
#7
Jacobus J Bosch, Ludwig M Heindl
Background Malignant melanoma is the most common cancer of the eye in adults that originates either in the intra-ocular uveal tract or extra-ocular conjunctiva. Although the primary tumor can be treated successfully, no effective therapy for both metastatic conjunctival and uveal melanoma currently exits. Tumor-associated lymphangiogenesis and immune cell infiltration play a pivotal role in the development and therapeutic targeting of metastases. Project description Here, we provide an overview of current translational research on lymphangiogenesis and its therapeutic inhibition as well as modulation of immune cell infiltration by passive and active immunotherapy in melanoma of the eye...
May 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28503286/fulminant-hepatic-failure-due-to-metastatic-choroidal-melanoma
#8
Emmanuel Escobar-Valdivia, Roberto Monreal-Robles, Guillermo Delgado-García, Badir Hernández-Velazquez
BACKGROUND: Acute liver failure (ALF) as a consequence of metastatic disease is extremely uncommon. The liver is the most commonly affected organ by metastatic disease, but only a few cases of ALF in the setting of metastatic choroidal melanoma have been reported. CASE PRESENTATION: We describe the case of a 47-year-old man with right upper quadrant pain, progressive jaundice, and unintentional weight loss. He also reported that he had experienced reduced left visual acuity which progressed to blindness over 2 months...
2017: Caspian Journal of Internal Medicine
https://www.readbyqxmd.com/read/28495150/personalized-prognosis-of-uveal-melanoma-based-on-cytogenetic-profile-in-1059-patients-over-an-8-year-period-the-2017-harry-s-gradle-lecture
#9
Carol L Shields, Emil Anthony T Say, Murat Hasanreisoglu, Jarin Saktanasate, Brendan M Lawson, Jeffrey E Landy, Anjali U Badami, Meera D Sivalingam, Alexander J Hauschild, Robert J House, Zachary E Daitch, Arman Mashayekhi, Jerry A Shields, Arupa Ganguly
PURPOSE: To determine the personalized rate of uveal melanoma-related metastasis on the basis of individual tumor cytogenetic profile. DESIGN: Retrospective case series. PARTICIPANTS: A total of 1059 patients with uveal melanoma. METHODS: Fine-needle aspiration biopsy (FNAB) for DNA amplification and whole genome array-based assay were performed for analysis of chromosomes 3, 6, and 8. MAIN OUTCOME MEASURES: Melanoma-related metastasis...
May 7, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28494168/uveal-melanoma-risk-factors-a-systematic-review-of-meta-analyses
#10
Taylor Nayman, Cristina Bostan, Patrick Logan, Miguel N Burnier
PURPOSE: There is currently no clinical risk-assessment tool allowing identification of patients at risk for developing uveal melanoma (UM) who might benefit from regular screening. As a first step toward the elaboration of such a tool, we systematically reviewed UM risk factors already established by meta-analysis. METHODS: Two reviewers independently screened Pubmed, Medline, Embase, and Web of Science from their respective inception dates until July 2016 using a combination of keywords and MeSH terms...
May 11, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28489707/intravitreal-dexamethasone-ozurdex-implant-for-radiation-maculopathy-secondary-to-stereotactic-radiotherapy-for-posterior-uveal-melanoma
#11
Irem Koc, Sibel Kadayifcilar, Hayyam Kiratli, Bora Eldem
PURPOSE: To evaluate the efficacy of 0.7 mg intravitreal dexamethasone implant in the treatment of radiation maculopathy after stereotactic radiotherapy for posterior uveal melanoma. METHODS: Retrospective chart review of seven eyes of seven consecutive patients was performed. Extracted data included age, sex, initial and follow-up visual acuities and central macular thickness values, intraocular pressure, follow-up time, number of implants, and time elapsed from radiotherapy to implantation...
May 9, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28487752/brachytherapy-and-anterior-segment-imaging-in-iris-melanoma
#12
Jin Soo Andy Song, Adam A Dmytriw, Hesham Lakosha
A 40-year-old male presented to the ophthalmology clinic with a darkly pigmented infratemporal lesion in his right eye. The corrected visual acuity in both eyes was 6/6 and both pupils were equal and reactive. Slit lamp biomicroscopy showed a well-demarcated and heavily pigmented lesion in the peripheral iris between 6 and 8 o'clock. Ultrasound biomicroscopy (UBM) revealed a solid mass deriving from the iris stroma without ciliary body involvement, helping to classify the uveal melanoma and establishing the diagnosis of iris melanoma...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28486107/rasgrp3-mediates-mapk-pathway-activation-in-gnaq-mutant-uveal-melanoma
#13
Xu Chen, Qiuxia Wu, Philippe Depeille, Peirong Chen, Sophie Thornton, Helen Kalirai, Sarah E Coupland, Jeroen P Roose, Boris C Bastian
Constitutive activation of Gαq signaling by mutations in GNAQ or GNA11 occurs in over 80% of uveal melanomas (UMs) and activates MAPK. Protein kinase C (PKC) has been implicated as a link, but the mechanistic details remained unclear. We identified PKC δ and ɛ as required and sufficient to activate MAPK in GNAQ mutant melanomas. MAPK activation depends on Ras and is caused by RasGRP3, which is significantly and selectively overexpressed in response to GNAQ/11 mutation in UM. RasGRP3 activation occurs via PKC δ- and ɛ-dependent phosphorylation and PKC-independent, DAG-mediated membrane recruitment, possibly explaining the limited effect of PKC inhibitors to durably suppress MAPK in UM...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28485764/%C3%A3-kad-kunskap-om-familj%C3%A3-rt-melanom-och-de-bakom%C3%A2-liggande-generna
#14
Hildur Helgadottir, Kari Nielsen, Veronica Höiom
Increased knowledge on familial melanoma and the underlying genetics Approximately 5-10 % of all melanoma patients have close relatives with melanoma. 5-20% of melanoma families have germline mutations in the CDKN2A gene. Swedish CDKN2A mutation carriers have a young median age of onset of melanoma, increased risks of multiple primary melanoma and of tobacco-associated cancers in respiratory and upper digestive tissues, and also worse survival compared to non-carriers. In up to 80% of melanoma families no high risk melanoma associated germline mutations are found...
May 9, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28482042/bap1-mutations-in-high-grade-meningioma-implications-for-patient-care
#15
Ganesh M Shankar, Sandro Santagata
We have recently shown that the BAP1 (BRCA1-associated protein-1) tumor suppressor gene is inactivated in a subset of clinically-aggressive meningiomas that display rhabdoid histomorphology. Immunohistochemistry for BAP1 protein provides a rapid and inexpensive method for screening suspected cases. Notably, some patients with BAP1-mutant meningiomas have germline BAP1 mutations and the BAP1 tumor predisposition syndrome (BAP1-TPDS). It appears that nearly all patients with germline BAP1 mutations develop malignancies by age 55, most frequently uveal melanoma, cutaneous melanoma, pleural or peritoneal malignant mesothelioma or renal cell carcinoma, although other cancers have also been associated with the BAP1-TPDS...
May 8, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28459943/circulating-tumor-dna-changes-for-early-monitoring-of-anti-pd1-immunotherapy-a-proof-of-concept-study
#16
L Cabel, F Riva, V Servois, A Livartowski, C Daniel, A Rampanou, O Lantz, E Romano, M Milder, B Buecher, S Piperno-Neumann, V Bernard, S Baulande, I Bieche, J Y Pierga, C Proudhon, F C Bidard
BackgroundRecent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab, pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.Patients and methodsThis prospective pilot study was conducted in patients with non-small cell lung cancer, uveal melanoma or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie...
April 29, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28457288/the-use-of-semistructured-interviews-to-assess-quality-of-life-impacts-for-patients-with-uveal-melanoma
#17
Brianna C Kopp, R Trafford Crump, Ezekiel Weis
OBJECTIVE: There are limited studies on uveal melanoma and patient quality of life. However, the burden of implementing a patient-reported outcome measure to collect this information in a clinical setting is unknown. The objectives of this study were (i) to understand the issues of quality of life that are most important to patients undergoing treatment for uveal melanoma, (ii) to explore patient views on the European Organization for Research and Treatment of Cancer's (EORTC) ophthalmic oncology quality of life questionnaire (QLQ-OPT30), and (iii) to assess patient willingness to complete questionnaires measuring quality of life on an ongoing basis...
April 2017: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/28455241/in%C3%A2-vitro-and-in%C3%A2-vivo-anti-uveal-melanoma-activity-of-jsl-1-a-novel-hdac-inhibitor
#18
Yun Wang, Maoxing Liu, Yanli Jin, Sheng Jiang, Jingxuan Pan
Uveal melanoma (UM) is the most common intraocular malignant neoplasm in adults. Despite the availability of enucleation, radiation and chemotherapy, the prognosis of patients with metastasis remains poor. Therefore, novel effective therapies for patients with metastatic UM are urgently needed. In the present study, we demonstrated that JSL-1, a novel HDAC inhibitor, effectively inhibited the proliferation. JSL-1 induced apoptosis with increased expression of proapoptotic BH3-only protein BIM in UM cells. JSL-1 suppressed migration and invasion of UM cells with MMP-2 decreased...
April 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28448663/prame-as-a-potential-target-for-immunotherapy-in-metastatic-uveal-melanoma
#19
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
#20
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
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