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Uveal melanoma

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https://www.readbyqxmd.com/read/28103611/phase-ii-randomised-discontinuation-trial-of-the-met-vegf-receptor-inhibitor-cabozantinib-in-metastatic-melanoma
#1
Adil Daud, Harriet M Kluger, Razelle Kurzrock, Frauke Schimmoller, Aaron L Weitzman, Thomas A Samuel, Ali H Moussa, Michael S Gordon, Geoffrey I Shapiro
BACKGROUND: A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma. METHODS: Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS)...
January 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28101347/clinical-presentation-and-management-of-uveal-melanoma
#2
Abelardo Rodríguez, Alfonso Dueñas-Gonzalez, Sarai Delgado-Pelayo
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The majority of the patients are Caucasian (97.8%) and aged 50-80 years. Choroidal melanoma is the predominant type (86.3%). The clinical presentation may range from no symptoms over various types of visual disturbances to visual loss. Examination includes slit-lamp biomicroscopy, indirect ophthalmoscopy and diagnostic testing, such as B-scan ultrasonography. A number of patients with posterior UM are treated with plaque radiation therapy or enucleation...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28074614/mutation-analysis-and-gene-expression-profiling-of-ocular-melanomas-in-cats
#3
J G Rushton, R Ertl, D Klein, B Nell
Feline ocular melanomas show a high malignant behaviour, but adjunctive therapies are non-existent. The aim of this pilot study was to determine, whether feline ocular melanomas harbour mutations comparable to mutations in human melanomas and to evaluate the gene expression status of genes known to be involved in initiation and progression of human melanomas. Mutation hotspot regions of several genes of feline ocular melanomas were analysed by DNA sequencing and RNA expression levels of the respective genes and others were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR)...
January 11, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28069617/ocular-oncology-advances-in-retinoblastoma-uveal-melanoma-and-conjunctival-melanoma
#4
REVIEW
Marina Vasalaki, Ido D Fabian, M Ashwin Reddy, Victoria M L Cohen, Mandeep S Sagoo
BACKGROUND: Retinoblastoma, uveal and conjunctival melanomas are important malignancies within the remit of ocular oncology. Outlined are the diagnostic features and management principles, as well as advancements in the field and current challenges. SOURCES OF DATA: Original papers, reviews and guidelines. AREAS OF AGREEMENT: Most eyes with retinoblastoma (International Intraocular Retinoblastoma Classification (IIRC) Group A-D) are salvaged, whereas advanced cases (Group E) remain a challenge...
January 8, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28062663/a-population-based-analysis-of-germline-bap1-mutations-in-melanoma
#5
Sally J O'Shea, Carla Daniela Robles-Espinoza, Lauren McLellan, Jeanine Harrigan, Xavier Jacq, James Hewinson, Vivek Iyer, Will Merchant, Faye Elliott, Mark Harland, D Timothy Bishop, Julia Newton-Bishop, David J Adams
Germline mutation of the BRCA1 associated protein-1 (BAP1) gene has been linked to uveal melanoma, mesothelioma, meningioma, renal cell carcinoma and basal cell carcinoma. Germline variants have also been found in familial cutaneous melanoma pedigrees, but their contribution to sporadic melanoma has not been fully assessed. We sequenced BAP1 in 1,977 melanoma cases and 754 controls and used deubiquitinase assays, a pedigree analysis, and a histopathological review to assess the consequences of the mutations found...
January 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28060147/myomelanocytic-choroidal-tumor-cytopathologic-diagnosis
#6
Ian M Jaffee, Devron H Char
PURPOSE: Establishing the correct diagnosis of a growing choroidal tumor can be difficult. METHODS: Clinical examination and ultrasound of a patient followed for what was thought to be a uveal melanoma. Fine-needle biopsy established the correct diagnosis. RESULTS: We demonstrate that fine-needle biopsy can correctly identify a very rare tumor, a myomelanocytic neoplasm. CONCLUSION: Myomelanocytic choroidal tumors can be diagnosed on fine-needle biopsy...
January 2, 2017: Retina
https://www.readbyqxmd.com/read/28059929/hepatic-progression-free-and-overall-survival-after-regional-therapy-to-the-liver-for-metastatic-melanoma
#7
Andrea M Abbott, Matthew P Doepker, Youngchul Kim, Matthew C Perez, Cassandra Gandle, Kerry L Thomas, Junsung Choi, Ravi Shridhar, Jonathan S Zager
OBJECTIVES: Regional therapy for metastatic melanoma to the liver represents an alternative to systemic therapy. Hepatic progression-free survival (HPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. MATERIALS AND METHODS: A retrospective review of patients with liver metastases from cutaneous or uveal melanoma treated with yttrium-90 (Y90), chemoembolization (CE), or percutaneous hepatic perfusion (PHP) was conducted. RESULTS: Thirty patients (6 Y90, 10 PHP, 12 CE, 1 PHP then Y90, 1 CE then PHP) were included...
January 4, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28056132/prognostic-implications-of-the-largest-basal-tumor-diameter-vs-the-tnm-staging-system-in-association-with-the-gene-expression-profile-for-uveal-melanoma
#8
Tero T Kivelä, Paul T Finger
No abstract text is available yet for this article.
January 5, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28056125/prognostic-implications-of-the-largest-basal-tumor-diameter-vs-the-tnm-staging-system-in-association-with-the-gene-expression-profile-for-uveal-melanoma-reply
#9
https://www.readbyqxmd.com/read/28048976/repeat-episcleral-plaque-brachytherapy-clinical-outcomes-in-patients-treated-for-locally-recurrent-posterior-uveal-melanoma
#10
Benjamin King, Vanessa M Morales-Tirado, Henry G Wynn, Brad T Gao, Matthew T Ballo, Matthew W Wilson
PURPOSE: Report the outcomes of survival, local control, visual acuity and eye retention in patients treated with repeat episcleral plaque brachytherapy (EPBT) for locally recurrent posterior uveal melanoma (PUM). DESIGN: Retrospective, interventional case series METHODS: Setting: Institutional Patient Population: 1201 patients that underwent Iodine-125 (I-125) EPBT as primary treatment for PUM between 1985 and 2015 Inclusion criteria: Development of locally recurrent disease and retreatment with I-125 EPBT Observation Procedures: Clinical records review Main Outcome Measures: Visual acuity, Kaplan-Meier estimates of survival, local control, metastasis and loss of the eye over the duration of follow up RESULTS: Twenty-seven patients (13 men) met our inclusion criteria...
December 31, 2016: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28048872/we-fg-bra-10-radiodosimetry-of-a-novel-alpha-particle-therapy-targeted-to-uveal-melanoma-absorbed-dose-to-organs-in-mice
#11
Christopher J Tichacek, Narges K Tafreshi, Mikalai M Budzevich, Epifanio Ruiz, Thaddeus J Wadas, Mark L McLaughlin, Eduardo G Moros, David L Morse
PURPOSE: The melanocortin-1 receptor (MC1R) is expressed in 94% of uveal melanomas and is described as an ideal target for this untreatable disease. MC1RL is a high affinity MC1R specific peptidomimetic ligand that can serve as a scaffold for therapeutic conjugates such as alpha particle emitting isotopes. The purpose of this study was to assess normal tissue distribution and risk as a result of using the DOTA chelator conjugated to MC1RL to deliver (225) Ac: MC1RL-DOTA-(225) Ac. METHODS: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-(225) Ac radiopharmaceutical with an average initial administered activity of 2...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28043154/prognostic-value-of-apoptosis-inducing-factor-in-uveal-melanoma
#12
V Krasnik, A Furdova, Z Svetlosakova, D Kobzova, H Gergisakova, L Feketeova, M Svetlosak, A Barta, P Babal
In malignant tumors including uveal melanoma there is a continuous effort in search for additional and relevant factors with predictive value and possible therapeutic indications. In the present work we evaluated the 5-year mortality in a group of patients with surgically treated uveal melanoma and its relation to selected demographic, clinical and histopathological parameters, including the expression of apoptosis inducing factor (AIF) in the neoplastic tissue.We analyzed retrospectively the clinical data of patients with uveal melanoma treated surgically (enucleation, endoresection, exenteration) in the period from 2001 to 2007 (n=54)...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28018148/epigenetics-and-common-ophthalmic-diseases
#13
REVIEW
Wendy Li, Ji Liu, Jennifer A Galvin
The study of ocular diseases and epigenetic dysregulation is an emerging area of research. The knowledge from the epigenetic mechanisms of DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs regarding the pathogenesis of ocular diseases will be helpful for improved treatment modalities for our patients. In particular, we focus upon the how epigenetic regulatory mechanisms impact five common ocular diseases: age related macular degeneration, age-related cataract, pterygium, retinoblastoma, and uveal melanoma...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018010/uveal-melanoma-cell-lines-where-do-they-come-from-an-american-ophthalmological-society-thesis
#14
Martine J Jager, J Antonio Bermudez Magner, Bruce R Ksander, Sander R Dubovy
PURPOSE: To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. METHODS: Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. RESULTS: Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota...
August 2016: Transactions of the American Ophthalmological Society
https://www.readbyqxmd.com/read/28012237/sporadic-melanotic-schwannoma-with-overlapping-features-of-melanocytoma-bearing-a-gna11-mutation-in-an-adolescent-girl
#15
Christina Tatsi, Flora Bacopoulou, Charalampos Lyssikatos, Elena Belyavskaya, Fabio R Faucz, Constantine A Stratakis
Melanotic schwannoma (MS) is a soft tissue neoplasm that shares histologic features with melanocytic tumors and schwannomas. A type of MS, called psammomatous MS (PMS), is associated with Carney complex (CNC), which is caused by PRKAR1A mutations. Other pigmented neoplasms, such as uveal melanomas and melanocytomas (MCs), are associated with genetic defects in other genes including GNA11. We report an adolescent female with a large sporadic mesenteric MS with complex histologic findings reminiscent of both PMS and MC...
December 24, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28003967/immune-oppression-array-elucidating-immune-escape-and-survival-mechanisms-in-uveal-melanoma
#16
Fang Hou, Qi-Ming Huang, Dan-Ning Hu, Jost B Jonas, Wen-Bin Wei
AIM: To examine the genetic profile of primary uveal melanoma (UM) as compared to UM in immune escape. METHODS: Dendritic cells (DC) loaded with lysates of UM cells of high metastatic potential were used to stimulate CTLs(CTLs). When CTLs co-cultured with the UM cells, most UM cells could be eliminated. Survival UM cells grew slowly and were considered to be survival variants and examined by a microarray analysis. These differential genes were analyzed further with Venn Diagrams and functions related to immune escape...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28000887/lentiviral-mediated-overexpression-of-kctd12-inhibits-the-proliferation-of-human-uveal-melanoma-ocm-1-cells
#17
Lifu Luo, Jizhe Cui, Zhitong Feng, Yana Li, Mengdi Wang, Yong Cai, Yazhen Wu, Jingji Jin
Human potassium channel tetramerization domain containing 12 (KCTD12, also known as Pfetin) is a member of the KCTD family which consists of 26 members. It has been reported that KCTD12 regulates agonist potency and kinetics of GABAB receptor signaling. Proteomic analysis indicates that KCTD12 may be a potential biomarker for the diagnosis and prognosis of gastrointestinal stromal tumors. However, little has been reported concerning the role of KCTD12 in the other tumor types. In the present study, we designed and subcloned N-terminally Flag-tagged human KCTD12 into the pLVX‑Puro vector...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27993792/network-guided-modelling-allows-tumor-type-independent-prediction-of-sensitivity-to-all-trans-retinoic-acid
#18
M Bolis, E Garattini, G Paroni, A Zanetti, M Kurosaki, T Castrignano', S K Garattini, F Biancardi, M M Barzago, M Gianni', M Terao, L Pattini, M Fratelli
BACKGROUND: All-trans retinoic acid (ATRA) is a differentiating agent used in the treatment of acute-promyelocytic-leukemia and it is under-exploited in other malignancies despite its low systemic toxicity. A rational/personalized use of ATRA requires development of predictive tools allowing identification of sensitive cancer types and responsive individuals. MATERIALS AND METHODS: RNA-Sequencing data for 10080 patients and 33 different tumor-types were derived from the TCGA and Leucegene datasets and completely re-processed...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27987156/immunotherapy-of-uveal-melanoma-vaccination-against-cancer
#19
Mirko Kummer, Beatrice Schuler-Thurner
Uveal melanoma is the most frequently occurring primary intraocular tumor in adults, with an incidence of about 5 out of 100,000 per year, the incidence rising with increasing age (Lipski, Klin Monbl Augenheilkd 230:1005-1019, 2013; Metz et al., Klin Monbl Augenheilkd 230:686-691, 2013; Singh and Topham, Ophthalmology 110:956-961, 2003). Often diagnosed late due to a lack of early symptoms, this kind of melanoma is associated with a poor prognosis. Approximately 50 % of the patients develop distant metastases (Lipski, Klin Monbl Augenheilkd 230:1005-1019, 2013; Metz et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27974237/copy-number-variation-analysis-and-methylome-profiling-of-a-gnaq-mutant-primary-meningeal-melanocytic-tumor-and-its-liver-metastasis
#20
Heidi V N Küsters-Vandevelde, Vibeke Kruse, Tom Van Maerken, Tom Boterberg, Rolph Pfundt, David Creytens, Caroline Van den Broecke, Trudi C Machielsen, Christian Koelsche, Andreas von Deimling, Benno Küsters, Patricia J T A Groenen, Pieter Wesseling, Willeke A M Blokx
Primary meningeal melanocytic tumors have genetic similarities with uveal melanomas, including GNAQ or GNA11 mutations. While BAP1 mutations and loss of chromosome 3 have adverse prognostic meaning in uveal melanoma, genetic alterations associated with metastasis have not been investigated in primary meningeal melanocytic tumors. We describe a 43-year-old female with a GNAQ-mutated, BAP1-wt melanocytic tumor originating in the parietal brain region and liver metastases 4years after initial diagnosis. After repeated surgery and chemotherapy she was treated with the immunomodulatory agent ipilimumab...
December 11, 2016: Experimental and Molecular Pathology
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