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1.
Can J Ophthalmol ; 57(2): 105-111, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33839068

RESUMEN

OBJECTIVE: Advancements in the treatment of uveal melanoma have not improved survival; therefore, identifying modifiable risk factors is critical to improving outcomes. This study aims to investigate the association between sunlamp use and the development of uveal melanoma. DESIGN: This study is designed as a meta-analysis. METHODS: Literature was searched and reviewed through the MEDLINE (with both OVID and PubMed), EMBASE, MD Consult, and Web of Science databases. These databases were searched from 1966 to 2019 using the following keywords to identify articles examining risk factors for uveal melanoma: ultraviolet, sun, sunlight, uveal melanoma, eye cancer, eye melanoma, nevus, and risk factor. All articles were evaluated for inclusion based on methodology and data reporting association between sunlamp use and uveal melanoma. The Meta-analysis of Observational Studies in Epidemiology guidelines and the Newcastle-Ottawa Scale were used to assess data quality and validity. A random effects model was employed. RESULTS: A total of 5 studies, enrolling a total of 1753 uveal melanoma cases and 3399 controls were included in this meta-analysis. The results of this study showed a positive association between sunlamp use and uveal melanoma (odds ratio = 2.15; 95% confidence interval 1.27-3.64). Meta-regression of between study heterogeneity did not reveal a statistically significant association when publication year, site latitude, melanoma tissue location (specifically, inclusion of iris tumors), or control type (population versus clinic) were evaluated. CONCLUSION: This meta-analysis identified a statistically significant association between sunlamp use and uveal melanoma, supporting sunlamp use as a modifiable risk factor for uveal melanoma.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Neoplasias de la Úvea , Humanos , Melanoma/epidemiología , Melanoma/etiología , Factores de Riesgo , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología
2.
Sci Rep ; 11(1): 22244, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34782661

RESUMEN

Cutaneous melanoma could be treated by immunotherapy, which only has limited efficacy on uveal melanoma (UM). UM immunotyping for predicting immunotherapeutic responses and guiding immunotherapy should be better understood. This study identified molecular subtypes and key genetic markers associated with immunotherapy through immunosignature analysis. We screened a 6-immune cell signature simultaneously correlated with UM prognosis. Three immune subtypes (IS) were determined based on the 6-immune cell signature. Overall survival (OS) of IS3 was the longest. Significant differences of linear discriminant analysis (LDA) score were detected among the three IS types. IS3 with the highest LDA score showed a low immunosuppression. IS1 with the lowest LDA score was more immunosuppressive. LDA score was significantly negatively correlated with most immune checkpoint-related genes, and could reflect UM patients' response to anti-PD1 immunotherapy. Weighted correlation network analysis (WGCNA) identified that salmon, purple, yellow modules were related to IS and screened 6 prognostic genes. Patients with high-expressed NME1 and TMEM255A developed poor prognosis, while those with high-expressed BEX5 and ROPN1 had better prognosis. There was no notable difference in OS between patients with high-expressed LRRN1 and ST13 and those with low-expressed LRRN1 and ST13. NME1, TMEM255A, Bex5 and ROPN1 showed potential prognostic significance in UM.


Asunto(s)
Biomarcadores de Tumor/genética , Inmunomodulación/genética , Melanoma/etiología , Melanoma/mortalidad , Transcriptoma , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/mortalidad , Análisis por Conglomerados , Biología Computacional/métodos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Proteínas de Punto de Control Inmunitario/genética , Proteínas de Punto de Control Inmunitario/metabolismo , Melanoma/metabolismo , Melanoma/terapia , Anotación de Secuencia Molecular , Terapia Molecular Dirigida , Modelos de Riesgos Proporcionales , Curva ROC , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/terapia
3.
Digit J Ophthalmol ; 26(3): 27-30, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33867879

RESUMEN

Uveal melanoma size is a significant predictor of tumor metastasis. Although the relationship between antivascular endothelial growth factors (VEGF) and uveal melanoma growth has been studied, results are paradoxical, and the relationship remains controversial. We report the case of a 65-year-old man who presented with elevated intraocular pressure in his right eye, neovascularization of his iris, and significant corneal edema, which obscured the view of the angle. Given his history of proliferative diabetic retinopathy, he was diagnosed with neovascular glaucoma and subsequently received an intravitreal injection of bevacizumab and underwent Ahmed valve insertion. This was complicated by postoperative hyphema. Two and a half months postoperatively, a mass involving the inferior iris and ciliary body became visible, and fine-needle aspiration biopsy confirmed uveal melanoma. Seven weeks after diagnosis, the tumor's largest basal diameter had increased from 2.51 mm to 18.0 mm, and apical height increased from 6.23 mm to 11.0 mm. His right eye was enucleated. Histopathological analysis showed discontinuous invasion next to the Ahmed valve. Tumor progression after injection raises the possibility that in some untreated uveal melanomas, accelerated growth may occur following exposure to anti-VEGF agents.


Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Bevacizumab/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Glaucoma Neovascular/tratamiento farmacológico , Melanoma/patología , Neoplasias de la Úvea/patología , Anciano , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico por imagen , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Enucleación del Ojo , Angiografía con Fluoresceína , Humanos , Presión Intraocular , Inyecciones Intravítreas , Masculino , Melanoma/diagnóstico por imagen , Melanoma/etiología , Microscopía Acústica , Neoplasias de la Úvea/diagnóstico por imagen , Neoplasias de la Úvea/etiología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
4.
Hematol Oncol Clin North Am ; 35(1): 85-98, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33759775

RESUMEN

Extracutaneous melanomas (ECMs) represent a heterogeneous group of melanoma subtypes characterized by distinct clinical and biological features from cutaneous melanoma. These subtypes share an aggressive natural history with high mortalities compared with nonacral cutaneous melanoma (NACM). Although recent advances in NACM have made significant improvements in morbidity and mortality, ECMs continue to lag behind. As the pathogenesis and molecular features of these rare subtypes continue to emerge, therapeutic research has aimed to closing the gap.


Asunto(s)
Melanoma , Neoplasias de la Úvea , Terapia Combinada , Progresión de la Enfermedad , Femenino , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Femeninos/epidemiología , Neoplasias de los Genitales Femeninos/etiología , Neoplasias de los Genitales Femeninos/terapia , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/etiología , Melanoma/terapia , Membrana Mucosa/patología , Metástasis de la Neoplasia , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/epidemiología , Neoplasias del Recto/etiología , Neoplasias del Recto/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/terapia , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/terapia
5.
Int J Oncol ; 57(6): 1262-1279, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33173970

RESUMEN

Uveal melanoma is the most common type of intraocular cancer with a low mean annual incidence of 5­10 cases per million. Tumours are located in the choroid (90%), ciliary body (6%) or iris (4%) and of 85% are primary tumours. As in cutaneous melanoma, tumours arise in melanocytes; however, the characteristics of uveal melanoma differ, accounting for 3­5% of melanocytic cancers. Among the numerous risk factors are age, sex, genetic and phenotypic predisposition, the work environment and dermatological conditions. Management is usually multidisciplinary, including several specialists such as ophthalmologists, oncologists and maxillofacial surgeons, who participate in the diagnosis, treatment and complex follow­up of these patients, without excluding the management of the immense emotional burden. Clinically, uveal melanoma generates symptoms that depend as much on the affected ocular globe site as on the tumour size. The anatomopathological study of uveal melanoma has recently benefited from developments in molecular biology. In effect, disease classification or staging according to molecular profile is proving useful for the assessment of this type of tumour. Further, the improved knowledge of tumour biology is giving rise to a more targeted approach to diagnosis, prognosis and treatment development; for example, epigenetics driven by microRNAs as a target for disease control. In the present study, the main epidemiological, clinical, physiopathological and molecular features of this disease are reviewed, and the associations among all these factors are discussed.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biomarcadores de Tumor/antagonistas & inhibidores , Melanoma/terapia , Procedimientos Quirúrgicos Oftalmológicos/métodos , Neoplasias de la Úvea/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Quimioradioterapia Adyuvante/métodos , Coroides/patología , Cuerpo Ciliar/patología , Ensayos Clínicos como Asunto , Epigénesis Genética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Incidencia , Iris/patología , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/etiología , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Terapia Molecular Dirigida/métodos , Terapia Neoadyuvante/métodos , Pronóstico , Factores de Riesgo , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología
6.
Int J Mol Sci ; 21(19)2020 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-32998469

RESUMEN

Uveal melanoma (UM) is a global disease which especially occurs in elderly people. Its incidence varies widely between populations, with the highest incidence among Caucasians, and a South-to-North increase in Europe. As northern Europeans often have blond hair and light eyes, we wondered whether iris colour may be a predisposing factor for UM and if so, why. We compared the distribution of iris colour between Dutch UM patients and healthy Dutch controls, using data from the Rotterdam Study (RS), and reviewed the literature regarding iris colour. We describe molecular mechanisms that might explain the observed associations. When comparing a group of Dutch UM patients with controls, we observed that individuals from Caucasian ancestry with a green/hazel iris colour (Odds Ratio (OR) = 3.64, 95% Confidence Interval (CI) 2.57-5.14) and individuals with a blue/grey iris colour (OR = 1.38, 95% CI 1.04-1.82) had a significantly higher crude risk of UM than those with brown eyes. According to the literature, this may be due to a difference in the function of pheomelanin (associated with a light iris colour) and eumelanin (associated with a brown iris colour). The combination of light-induced stress and aging may affect pheomelanin-carrying melanocytes in a different way than eumelanin-carrying melanocytes, increasing the risk of developing a malignancy.


Asunto(s)
Envejecimiento/genética , Iris/efectos de la radiación , Melaninas/efectos de la radiación , Melanocitos/efectos de la radiación , Melanoma/epidemiología , Neoplasias de la Úvea/epidemiología , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Estudios de Cohortes , Color del Ojo/fisiología , Femenino , Humanos , Incidencia , Iris/anatomía & histología , Iris/metabolismo , Luz/efectos adversos , Masculino , Melaninas/biosíntesis , Melanocitos/metabolismo , Melanocitos/patología , Melanoma/etnología , Melanoma/etiología , Melanoma/patología , Persona de Mediana Edad , Países Bajos/epidemiología , Oportunidad Relativa , Neoplasias de la Úvea/etnología , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/patología , Población Blanca
9.
Clin Cancer Res ; 25(7): 2206-2218, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30563937

RESUMEN

PURPOSE: Uveal melanoma (UM) is the most prevalent and lethal intraocular malignancy in adults. Here, we examined the importance of hypoxia in UM growth and tested the antitumor effects of arylsulfonamide 64B, an inhibitor of the hypoxia-induced factor (HIF) pathway in animal models of UM and investigated the related mechanisms. EXPERIMENTAL DESIGN: UM cells were implanted in the uvea of mice eyes and mice systemically treated with 64B. Drug effect on primary eye tumor growth, circulating tumor cells, metastasis formation in liver, and survival were examined. 64B effects on UM cell growth, invasion and hypoxia-induced expression of C-X-C chemokine receptor type 4 (CXCR4) and mesenchymal-epithelial transition factor (c-Met) were measured. Luciferase reporter assays, chromatin immunoprecipitation, co-immunoprecipitation, and cellular thermal shift assays were used to determine how 64B interferes with the HIF transcriptional complex. RESULTS: Systemic administration of 64B had potent antitumor effects against UM in several orthotopic mouse models, suppressing UM growth in the eye (∼70% reduction) and spontaneous liver metastasis (∼50% reduction), and extending mice survival (P < 0.001) while being well tolerated. 64B inhibited hypoxia-induced expression of CXCR4 and c-Met, 2 key drivers of tumor invasion and metastasis. 64B disrupted the HIF-1 complex by interfering with HIF-1α binding to p300/CBP co-factors, thus reducing p300 recruitment to the MET and CXCR4 gene promoters. 64B could thermostabilize p300, supporting direct 64B binding to p300. CONCLUSIONS: Our preclinical efficacy studies support the further optimization of the 64B chemical scaffold toward a clinical candidate for the treatment of UM.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/metabolismo , Melanoma/etiología , Melanoma/metabolismo , Proteínas Proto-Oncogénicas c-met/genética , Receptores CXCR4/genética , Sulfonamidas/farmacología , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/metabolismo , Animales , Biomarcadores de Tumor , Biopsia , Línea Celular Tumoral , Modelos Animales de Enfermedad , Proteína p300 Asociada a E1A/metabolismo , Humanos , Neoplasias Hepáticas/secundario , Melanoma/tratamiento farmacológico , Melanoma/patología , Ratones , Pronóstico , Unión Proteica , Proteínas Proto-Oncogénicas c-met/metabolismo , Receptores CXCR4/metabolismo , Sulfonamidas/química , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/patología , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Cancer Metastasis Rev ; 37(2-3): 335-345, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30094568

RESUMEN

Uveal melanoma is a rare, but deadly, form of eye cancer that arises from melanocytes within the uveal tract. Although advances have emerged in treatment of the primary tumour, patients are still faced with vision loss, eye enucleation and lethal metastatic spread of the disease. Approximately 50% of uveal melanoma patients develop metastases, which occur most frequently in the liver. Metastatic patients encounter an extremely poor prognosis; as few as 8% survive beyond 2 years. Understanding of the genetic underpinnings of this fatal disease evolved in recent years with the identification of new oncogenic mutations that drive uveal melanoma pathogenesis. Despite this progress, the lack of successful therapies or a proven standard-of-care for uveal melanoma highlights the need for new targeted therapies. This review focuses on the recently identified CYSLTR2 oncogenic mutation in uveal melanoma. Here, we evaluate the current status of uveal melanoma and investigate how to better understand the role of this CYSLTR2 mutation in the disease and implications for patients harbouring this mutation.


Asunto(s)
Melanoma/etiología , Melanoma/metabolismo , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Receptores de Leucotrienos/genética , Receptores de Leucotrienos/metabolismo , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/metabolismo , Animales , Biomarcadores de Tumor , Carcinogénesis , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad , Variación Genética , Xenoinjertos , Humanos , Melanoma/tratamiento farmacológico , Melanoma/epidemiología , Terapia Molecular Dirigida , Pronóstico , Transducción de Señal , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/epidemiología
11.
JAMA Ophthalmol ; 136(5): 543-547, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29596556

RESUMEN

Importance: Patients with myotonic dystrophy (MD) have an increased risk of malignancy including uveal melanoma. This case series further explores the association between these 2 diseases. Objective: To describe a cohort of patients with uveal melanoma associated with MD, including a case of iris melanoma, and MD-associated uveal melanoma in relatives. Design, Setting, and Participants: Retrospective case series at 3 tertiary referral centers (Wills Eye Hospital, Philadelphia, Pennsylvania; Mayo Clinic, Rochester, Minnesota; and Moorfields Eye Hospital, London, England), between January 1, 2000, and August 31, 2017. The study included 6 patients with MD and uveal melanoma. Main Outcomes and Measures: Melanoma response to treatment and development of metastatic disease. Results: There were 6 patients, 4 men and 2 women, with MD and uveal melanoma. The mean patient age at melanoma diagnosis was 47 years (median, 43 years; range, 30-67 years), and the tumor involved the choroid in 5 patients (83%) and iris in 1 patient (17%). The diagnosis of MD was known since young adulthood in 2 patients (33%) and was discovered in adulthood in 4 patients (67%). The main clinical features of MD included muscle weakness (n = 5; 83%), myotonia (n = 4; 67%), polychromatic cataract (n = 4; 67%), complications with general anesthesia (n = 4; 67%), myalgia (n = 3; 50%), cardiac arrhythmia (n = 2; 33%), and frontal baldness (n = 2; 33%). Genetic testing revealed MD type 1 (4 of 4 tested patients), and 2 patients demonstrated positive family history of MD with classic clinical features and preferred no testing. Melanoma treatment included plaque radiotherapy (n = 4; 67%), photodynamic therapy (n = 1; 17%), and declined treatment (n = 1; 17%). At follow-up of 6, 6, 41, 42, and 87 months (5 patients), findings included melanoma regression (4 of 5 tumors), melanoma recurrence (1 of 5 tumors), and no metastatic disease (5 of 5 patients). Conclusions and Relevance: Six adult patients with MD demonstrated uveal melanoma involving the choroid or iris, emphasizing the association between these 2 diseases. Further research seems warranted to explore the pathogenesis of uveal melanoma in MD. These findings support the consideration of ophthalmic examination for uveal melanoma in patients with MD.


Asunto(s)
Melanoma/etiología , Distrofia Miotónica/complicaciones , Neoplasias de la Úvea/etiología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Distrofia Miotónica/diagnóstico , Estudios Retrospectivos , Neoplasias de la Úvea/diagnóstico
12.
Curr Eye Res ; 42(8): 1085-1093, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28494168

RESUMEN

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. Eligible studies were meta-analyses or systematic reviews providing pooled odds ratios (ORs) of risk factors for UM development or sufficient information to calculate them. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews tool. RESULTS: Four meta-analyses with a mean methodological quality score of 65.9% (min: 54.5%; max: 72.7%) were included. The following significant risk factors were identified: atypical cutaneous nevi (OR 2.82, 95% CI 1.10-7.26), welding (OR 2.05, 95% CI 1.20-3.51), occupational cooking (OR 1.81, 95% CI 1.33-2.46), fair skin color (OR 1.80, 95% CI 1.31-2.47), light eye color (OR 1.75, 95% CI 1.31-2.34), common cutaneous nevi (OR 1.74, 95% CI 1.27-2.39), propensity to sunburn (OR 1.64, 95% CI 1.29-2.09), iris nevi (OR 1.53, 95% CI 1.03-2.27), and cutaneous freckles (OR 1.27, 95% CI 1.09-1.49). Non-significant factors included outdoor leisure activity, occupational sunlight exposure, latitude of birth, and hair color. CONCLUSION: Moderate quality of evidence determined nine significant risk factors for developing UM. Knowledge of these variables will assist researchers in the elaboration of a formal risk-assessment tool allowing clinicians to estimate susceptibility to the disease and necessity of regular screening.


Asunto(s)
Tamizaje Masivo/métodos , Melanoma , Exposición Profesional/efectos adversos , Medición de Riesgo , Úvea/patología , Neoplasias de la Úvea , Salud Global , Humanos , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/etiología , Morbilidad/tendencias , Factores de Riesgo , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología
13.
Eye (Lond) ; 31(2): 241-257, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27911450

RESUMEN

Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival.


Asunto(s)
Melanoma , Neoplasias de la Úvea , Distribución por Edad , Terapia Combinada , Humanos , Incidencia , Iridectomía/métodos , Melanoma/epidemiología , Melanoma/etiología , Melanoma/patología , Melanoma/terapia , Radiocirugia/métodos , Radioterapia/métodos , Factores de Riesgo , Distribución por Sexo , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Rayos Ultravioleta/efectos adversos , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/terapia
14.
Semin Ophthalmol ; 32(4): 514-516, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27082038

RESUMEN

PURPOSE: To describe a case of a ciliochoroidal melanoma arising from the site of a scleral buckle. DESIGN: Observational case report. METHOD: A 69-year-old female was referred for evaluation of decreased vision and occasional floaters in the left eye for two months. Eight years previously, she had undergone vitrectomy and scleral buckling for rhegmatogenous retinal detachment repair in the same eye. Clinical examination revealed an elevated, pigmented choroidal mass in the inferonasal periphery at the crest of the scleral buckle. Clinical and ultrasonographic features were consistent with ciliochoroidal melanoma. RESULTS: The patient underwent Iodine-125 brachytherapy with plaque placement directly on the scleral buckle. Intraoperative ultrasonography confirmed accurate plaque position. Appropriate tumor response was demonstrated at serial follow up-evaluations; however, over 48 months, the patient developed gradual decline in vision secondary to radiation retinopathy. CONCLUSION: Choroidal melanomas may arise from the same location as a scleral buckle and local tumor control with brachytherapy can be achieved without manipulation or removal of the buckle element. However, we encourage orbital surgeons to consider the radiation attenuating effect of silicone, found in the buckle, in order to prevent undertreatment of these melanomas.


Asunto(s)
Neoplasias de la Coroides/etiología , Cuerpo Ciliar/patología , Melanoma/etiología , Complicaciones Posoperatorias , Desprendimiento de Retina/cirugía , Curvatura de la Esclerótica/efectos adversos , Neoplasias de la Úvea/etiología , Anciano , Biopsia con Aguja Fina , Neoplasias de la Coroides/diagnóstico , Neoplasias de la Coroides/terapia , Terapia Combinada , Femenino , Humanos , Melanoma/diagnóstico , Melanoma/terapia , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/terapia
15.
Biomed Res Int ; 2016: 4521807, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27366747

RESUMEN

Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field.


Asunto(s)
Melanoma/patología , Neoplasias de la Úvea/patología , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Isoinjertos , Neoplasias Hepáticas/secundario , Melanoma/etiología , Melanoma/secundario , Ratones , Ratones Transgénicos , Trasplante de Neoplasias , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/secundario
16.
Cancer ; 122(15): 2299-312, 2016 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-26991400

RESUMEN

Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society.


Asunto(s)
Melanoma/diagnóstico , Melanoma/terapia , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/terapia , Aberraciones Cromosómicas , Terapia Combinada , Detección Precoz del Cáncer , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Melanoma/epidemiología , Melanoma/etiología , Mutación , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Investigación , Resultado del Tratamiento , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología
17.
Retin Cases Brief Rep ; 10(2): 168-70, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26444522

RESUMEN

PURPOSE: To describe two cases of choroidal hemorrhage caused by optic disk drusen-induced choroidal neovascularization simulating uveal melanoma. METHODS: Observational case reports of two patients and brief review of the literature. RESULTS: Two patients were referred with pigmented juxtapapillary lesions concerning for choroidal melanoma. Multimodal imaging revealed the presence of optic disk drusen with overlying choroidal neovascular membranes and peripapillary choroidal hemorrhage. Both patients were treated with antivascular endothelial growth factor and the lesions resolved. CONCLUSION: In the setting of diagnostic uncertainty, careful multimodal imaging can assist in distinguishing between malignant choroidal melanoma and a benign simulating lesion. Optic disk drusen with associated neovascularization and hemorrhage should be included in the list of pseudomelanomas.


Asunto(s)
Coroides/patología , Neovascularización Coroidal/complicaciones , Melanoma/etiología , Drusas del Disco Óptico/complicaciones , Disco Óptico/patología , Neoplasias de la Úvea/etiología , Anciano , Anciano de 80 o más Años , Coroides/irrigación sanguínea , Neovascularización Coroidal/diagnóstico , Diagnóstico Diferencial , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Masculino , Melanoma/diagnóstico , Drusas del Disco Óptico/diagnóstico , Tomografía de Coherencia Óptica , Neoplasias de la Úvea/diagnóstico , Agudeza Visual
18.
Pigment Cell Melanoma Res ; 28(2): 135-47, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25113308

RESUMEN

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed.


Asunto(s)
Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/patología , Investigación Biomédica , Ensayos Clínicos como Asunto , Humanos , Melanoma/etiología , Melanoma/inmunología , Estadificación de Neoplasias , Transducción de Señal , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/inmunología
20.
Photochem Photobiol ; 90(1): 15-21, 2014 01.
Artículo en Inglés | MEDLINE | ID: mdl-23981010

RESUMEN

Uveal melanoma is the most frequent intraocular cancer and the second most common form of melanoma. It metastasizes in half of the patients and the prognostic is poor. Although ultraviolet (UV) radiation is a proven risk factor for skin melanoma, the role of UV light in the etiology of uveal melanoma is still contradictory. We have compared epidemiological and genetic evidences of the potential role of UV radiation in uveal melanoma with data on cutaneous melanoma. Even though frequently mutated genes in skin melanoma (e.g. BRAF) differ from those found in uveal melanoma (i.e. GNAQ, GNA11), their mutation pattern bears strong similarities. Furthermore, we provide new results showing that RAC1, a gene recently found harboring UV-hallmark mutation in skin melanoma, is also mutated in uveal melanoma. This article aims to review the work done in the last decades to understand the etiology of uveal melanoma and discuss new avenues, which shed some light on the potential role of UV exposure in uveal melanoma.


Asunto(s)
Melanoma/epidemiología , Melanoma/etiología , Rayos Ultravioleta , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología , Humanos , Melanoma/genética , Mutación , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/genética , Neoplasias de la Úvea/genética , Melanoma Cutáneo Maligno
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