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https://www.readbyqxmd.com/read/28713672/bap1-a-tumor-suppressor-gene-driving-malignant-mesothelioma
#1
REVIEW
Mitchell Cheung, Joseph R Testa
Like cancer generally, malignant mesothelioma (MM) is a genetic disease at the cellular level. DNA copy number analysis of mesothelioma specimens has revealed a number of recurrent sites of chromosomal loss, including 3p21.1, 9p21.3, and 22q12.2. The key inactivated driver genes located at 9p21.1 and 22q12.2 were discovered two decades ago as being the tumor suppressor loci CDKN2A and NF2, respectively. Only relatively recently was the BAP1 gene determined to be the driver gene at 3p21.1 that is somatically inactivated...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28700778/frequent-gnaq-gna11-and-eif1ax-mutations-in-iris-melanoma
#2
Simone L Scholz, Inga Möller, Henning Reis, Daniela Süßkind, Johannes A P van de Nes, Sonia Leonardelli, Bastian Schilling, Elisabeth Livingstone, Tobias Schimming, Annette Paschen, Antje Sucker, Rajmohan Murali, Klaus-Peter Steuhl, Dirk Schadendorf, Henrike Westekemper, Klaus G Griewank
Purpose: The most common malignant intraocular tumors with a high mortality in adults are uveal melanomas. Uveal melanomas arise most frequently in the choroid or ciliary body (97%) and rarely in the iris (3%). Whereas conjunctival and posterior uveal (ciliary body and choroidal) melanomas have been studied in more detail genetically, little data exist regarding iris melanomas. Methods: In our study, we genetically analyzed 19 iris melanomas, 8 ciliary body melanomas, 3 ring melanomas, and 4 iris nevi...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28692599/cavitary-choroidal-metastasis-from-clear-cell-renal-cell-carcinoma
#3
Bernadete Ayres, Tanya McClendon, Hakan Demirci
PURPOSE: To report the clinical, funduscopic, and echographic features of a choroidal metastatic tumor from a clear cell renal cell carcinoma presenting with intralesional cavitation. CASE REPORT: An 81-year-old man with history of clear cell renal cell carcinoma presented with blurred vision. A clinical examination including standardized ultrasound was performed, which revealed a choroidal mass with cystic-like cavitation. The patient underwent brachytherapy with regression of the tumor...
July 7, 2017: Optometry and Vision Science: Official Publication of the American Academy of Optometry
https://www.readbyqxmd.com/read/28690979/presentation-treatment-and-prognosis-of-secondary-melanoma-within-the-orbit
#4
Anna M Rose, Sophie Cowen, Channa N Jayasena, David H Verity, Geoffrey E Rose
BACKGROUND: Ocular melanoma is a rare but often deadly malignancy that arises in the uvea, conjunctiva, or orbit. Uveal melanoma is the most common type, with conjunctival melanoma being the second most frequently observed. Melanoma accounts for 5-10% of metastatic or secondary orbital malignancies, but only a minute proportion of primary orbital neoplasia. The aim of this study was to characterize the clinical presentation, treatment, and prognosis in patients presenting with melanoma metastatic to, or secondary within, the orbit...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28680759/parallel-profiling-of-immune-infiltrate-subsets-in-uveal-melanoma-versus-cutaneous-melanoma-unveils-similarities-and-differences-a-pilot-study
#5
Yong Qin, Mariana Petaccia de Macedo, Alexandre Reuben, Marie-Andrée Forget, Cara Haymaker, Chantale Bernatchez, Christine N Spencer, Vancheswaran Gopalakrishnan, Sujan Reddy, Zachary A Cooper, Orenthial J Fulbright, Renjith Ramachandran, Arely Wahl, Esteban Flores, Shawne T Thorsen, Rene J Tavera, Claudius Conrad, Michelle D Williams, Michael T Tetzlaff, Wei-Lien Wang, Dan S Gombos, Bita Esmaeli, Rodabe N Amaria, Patrick Hwu, Jennifer A Wargo, Alexander J Lazar, Sapna P Patel
The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8(+) T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679643/endogenous-heat-shock-protein-induction-with-or-without-radiofrequency-ablation-or-cryoablation-in-patients-with-stage-iv-melanoma
#6
Evidio Domingo-Musibay, James M Heun, Wendy K Nevala, Matthew Callstrom, Thomas Atwell, Evanthia Galanis, Lori A Erickson, Svetomir N Markovic
LESSONS LEARNED: Percutaneous thermal ablation combined with in situ granulocyte-macrophage colony-stimulating factor cytokine therapy was technically feasible and well tolerated.No significant clinical or immunologic responses were seen. BACKGROUND: Melanoma tumor-derived heat-shock proteins (HSPs) and HSP-peptide complexes can elicit protective antitumor responses. The granulocyte-macrophage colony-stimulating factor (GM-CSF) chemokine can also promote uptake and processing by professional antigen presenting cells (APCs)...
July 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28673748/late-solitary-extraocular-recurrence-from-previously-resected-iris-melanoma
#7
Ido Didi Fabian, Caroline Thaung, Lamis AlHarby, Karen Sisley, Hardeep S Mudhar, Rachel E Doherty, Andrew W Stacey, Amit K Arora, Victoria M L Cohen, Mandeep S Sagoo
PURPOSE: To report on cases of late extraocular relapse of previously resected iris melanoma, without concurrent intraocular recurrence. DESIGN: Retrospective case series. METHODS: A retrospective chart review of 4 patients diagnosed with late subconjunctival relapse of previously resected iris melanoma. RESULTS: Three females and one male underwent iris tumour resection and presented to our service with suspicious conjunctival lesions at a median of 22 years later (mean: 21)...
June 30, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28672400/comparison-of-alternative-tumor-size-classifications-for-posterior-uveal-melanomas
#8
COMPARATIVE STUDY
Cassandra C Skinner, James J Augsburger, Bret D Augsburger, Zelia M Correa
Purpose: Determine which posterior uveal melanoma (PUM) size classification with three categories has the best prognostic discrimination. Methods: Single-institution study of 424 consecutive patients with PUM. The tumor's largest basal diameter (LBD), smallest basal diameter (SBD), and thickness (TH) were estimated by fundus mapping and ultrasonography. Tumors were assigned to "small," "medium," or "large" size categories defined by 11 different classifications (Linear LBD, Rectangular LBD × TH, Cubic LBD × SBD × TH, Warren Original, Warren Modified, Augsburger, COMS Original, COMS Revised, TNM 2002, and modified TNM 2010 classification [a,b])...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28665870/molecular-prognostics-for-uveal-melanoma
#9
Michael I Seider, Prithvi Mruthyunjaya
PURPOSE: To review laboratory methods, currently available commercial tests, caveats and clinical tips regarding prognostic analysis of uveal melanoma tissue. METHODS: A review of the literature was performed focused on the genetic abnormalities found in uveal melanoma cells, their correlation to the development of metastases, the validity of various laboratory approaches in their detection, and the existing commercially available tests for uveal melanoma prognostication...
June 29, 2017: Retina
https://www.readbyqxmd.com/read/28655639/inflammatory-cell-infiltrates-in-advanced-metastatic-uveal-melanoma
#10
Yamini Krishna, Conni McCarthy, Helen Kalirai, Sarah E Coupland
Current treatments for metastatic uveal melanoma (mUM) are limited and rarely prolong patient survival. Immunotherapy trials for mUM are few, and to-date have demonstrated only marginal success. High densities of tumour-associated-macrophages (TAMs) and infiltrating T-lymphocytes (TILs) in primary UM are associated with poor prognosis. Little is known about the immune microenvironment of mUM. Our aim was to examine the presence and distribution of TAMs and TILs in mUM within the liver. Whole tissue-sections of liver mUM (n=35) were examined by immunohistochemistry...
June 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28648699/prognostic-factors-and-outcomes-in-metastatic-uveal-melanoma-treated-with-programmed-cell-death-1-or-combined-pd-1-cytotoxic-t-lymphocyte-antigen-4-inhibition
#11
Markus V Heppt, Lucie Heinzerling, Katharina C Kähler, Andrea Forschner, Michael C Kirchberger, Carmen Loquai, Markus Meissner, Friedegund Meier, Patrick Terheyden, Beatrice Schell, Rudolf Herbst, Daniela Göppner, Felix Kiecker, David Rafei-Shamsabadi, Sebastian Haferkamp, Margit A Huber, Jochen Utikal, Mirjana Ziemer, Irmgard Bumeder, Christiane Pfeiffer, Susanne G Schäd, Christoph Schmid-Tannwald, Julia K Tietze, Thomas K Eigentler, Carola Berking
BACKGROUND: Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. PATIENTS AND METHODS: Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28645290/establishment-of-an-orthotopic-patient-derived-xenograft-mouse-model-using-uveal-melanoma-hepatic-metastasis
#12
Ken Kageyama, Masahiro Ohara, Kengo Saito, Shinji Ozaki, Mizue Terai, Michael J Mastrangelo, Paolo Fortina, Andrew E Aplin, Takami Sato
BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment...
June 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28640512/a-major-responder-to-ipilimumab-and-nivolumab-in-metastatic-uveal-melanoma-with-concomitant-autoimmunity
#13
Pui Ying Chan, Peter Hall, Gordon Hay, Victoria M L Cohen, Peter W Szlosarek
The use of immune checkpoint inhibition has led to major improvements in outcome for patients with metastatic cutaneous melanoma. The combination of ipilimumab and nivolumab has demonstrated greater activity over single agent immunotherapy in phase III trials. Clinical trials of combination CTLA-4 and PD-1 inhibition are underway in uveal melanoma, for which there are currently no data. Here, we present the case of a 74-year-old male patient with metastatic uveal melanoma, who was treated with a combination of ipilimumab and nivolumab...
June 22, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28640204/fucoidan-does-not-exert-anti-tumorigenic-effects-on-uveal-melanoma-cell-lines
#14
Michaela Dithmer, Anna-Maria Kirsch, Elisabeth Richert, Sabine Fuchs, Fanlu Wang, Harald Schmidt, Sarah E Coupland, Johann Roider, Alexa Klettner
BACKGROUND: The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. METHODS: The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL-1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA...
June 22, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28639409/anti-pd-1-antibodies-in-metastatic-uveal-melanoma-a-treatment-option
#15
Carolin Bender, Alexander Enk, Ralf Gutzmer, Jessica C Hassel
Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti-PD-1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals...
July 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28630054/slc45a2-a-melanoma-antigen-with-high-tumor-selectivity-and-reduced-potential-for-autoimmune-toxicity
#16
Jungsun Park, Amjad H Talukder, Seonah Lim, Kwanghee Kim, Ke Pan, Brenda Melendez, Sherille D Bradley, Kyle Jackson, Jahan S Khalili, Junmei Wang, Caitlin Creasy, Bih-Fang Pan, Scott E Woodman, Chantale Bernatchez, David Hawke, Patrick Hwu, Kyung-Mi Lee, Jason Roszik, Gregory Lizee, Cassian Yee
Cytotoxic T lymphocyte (CTL)-based immunotherapies have had remarkable success at generating objective clinical responses in patients with advanced metastatic melanoma.  Although the melanocyte differentiation antigens (MDAs) MART-1, PMEL, and tyrosinase were among the first melanoma tumor-associated antigens identified and targeted with immunotherapy, expression within normal melanocytes of the eye and inner ear can elicit serious autoimmune side effects, thus limiting their clinical potential as CTL targets...
June 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28618948/tissue-specific-significance-of-bap1-gene-mutation-in-prognostic-prediction-and-molecular-taxonomy-among-different-types-of-cancer
#17
Xiang-Yu Wang, Zheng Wang, Jian-Bo Huang, Xu-Dong Ren, Dan Ye, Wen-Wei Zhu, Lun-Xiu Qin
BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28614305/bap1-regulates-ip3r3-mediated-ca-2-flux-to-mitochondria-suppressing-cell-transformation
#18
Angela Bononi, Carlotta Giorgi, Simone Patergnani, David Larson, Kaitlyn Verbruggen, Mika Tanji, Laura Pellegrini, Valentina Signorato, Federica Olivetto, Sandra Pastorino, Masaki Nasu, Andrea Napolitano, Giovanni Gaudino, Paul Morris, Greg Sakamoto, Laura K Ferris, Alberto Danese, Andrea Raimondi, Carlo Tacchetti, Shafi Kuchay, Harvey I Pass, El Bachir Affar, Haining Yang, Paolo Pinton, Michele Carbone
BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1(+/-)) developed one and often several BAP1(-/-) malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28609317/characteristics-of-melanoma-in-japan-a-nationwide-registry-analysis-2011-2013
#19
Taro Tomizuka, Kenjiro Namikawa, Takahiro Higashi
The distribution and incidence of melanoma vary among different races and ethnic groups. This study aimed to investigate the characteristics of cutaneous melanoma, mucosal melanoma, uveal melanoma, and melanoma of unknown primary (MUP) origin in a Japanese population. We studied these four types of melanoma in patients registered in Hospital Based Cancer Registries in Japan from 2011 to 2013. A total of 5566 patients with melanoma were identified. The distribution of sex, age, primary site, and clinical stage was analyzed...
June 12, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28599335/-current-diagnosis-of-choroidal-nevi
#20
J Lüke, S Grisanti, A Tura
Despite the diversity of techniques for documentation and diagnostics of choroidal nevi, the differential diagnosis, especially regarding small uveal melanomas, remains difficult. In many cases, frequent controls to exclude growth or for the detection of an unchanged appearance are recommended. This article reviews-under consideration of the actual literature-different diagnostic techniques for documentation and differentiation of choroidal nevi.
June 9, 2017: Klinische Monatsblätter Für Augenheilkunde
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