Possible dissemination of conjunctival melanoma along tear flow path.
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ABSTRACT:
SUBMITTER: Kubota T
PROVIDER: S-EPMC5956803 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Possible dissemination of conjunctival melanoma along tear flow path.
Kubota Toshinobu T Kawasaki Tomonori T
American journal of ophthalmology case reports 20180223
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Project description:Rare earth elements (REE) are known to be emerging contaminants in hydrosphere, but roles of hydrous manganese oxyhydroxides (HMO) in REE transport in groundwater remains unknown. In this study, groundwater was sampled along a flow path in the North China Plain to determine the behavior of REE surface complexation to HMO by a modeling and field study approach. Results show that the proportion of neodymium (Nd) complexed by HMO ranges from 0.2% to 95.8%, and from 0.3% to 99.6% in shallow groundwater and deep groundwater, respectively. The amount of complexed REE increases along the flow path. REE bound to HMO exhibit decreasing trends with increasing atomic number. The process was determined to be independent of pH, HMO content, and metal loading. This finding further demonstrates HMO-REE complexation plays a key role in transport of REE in groundwater through preferential scavenging of light REE (LREE) over heavy REE (HREE). Nevertheless, carbonate ligands appear to be robust competitors in reducing the amount of REE sorbed to HMO when solution pH rises above 8.0. Assuming that 50% of Mn concentration occurs as HMO, the amount of complexed REE was predicted to show a more marked decrease in LREE compared to that of HREE.
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Project description:NanoString data on 12 conjunctival melanomas and mucosal melanoma The objective was to compare conjunctival melanoma with other mucosal melanomas at the RNA level using NanoString expression analysis of FFPE material.
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Project description:The first aim of this study was to clarify whether cigarette smoking affects tear secretion, goblet cell density, and tear MUC5AC concentration. The second purpose was to evaluate the correlations of conjunctival goblet cell density with tear MUC5AC concentration and other ocular surface evaluation factors. This cross-sectional study included 88 office workers. All subjects were required to fill in dry eye and smoking questionnaires, in addition to ocular surface evaluation. Tear wash fluid was collected from inferior fornix, and conjunctival epithelium was obtained by impression cytology. Tear MUC5AC concentration was quantified using enzyme-linked immunoassay, and conjunctival goblet cell density was counted after Periodic-acid Schiff staining. Tear MUC5AC concentration had significant positive correlation with conjunctival goblet cell density (r = 0.181, P = 0.03). In current smokers, Schirmer I test value, goblet cell density and tear MUC5AC concentration were significantly lower than non-smokers. Pack-years of smoking have significant negative correlation with goblet cell density (r = -0.174, P = 0.036) and tear MUC5AC concentration (r = -0.183, P = 0.028). We concluded that smoking might decrease tear secretion, goblet cell density and tear MUC5AC concentration. In addition, MUC5AC concentration in tears depends on goblet cell density in the conjunctiva among office workers.
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Project description:Conjunctival and mucosal melanoma
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Project description:Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes: BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM.
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Project description:PurposeTo assess the role of the canonical Wnt pathway via activation of β-catenin in tumor progression of conjunctival melanoma.Methodsβ-Catenin localization was assessed by immunohistochemistry in 43 conjunctival nevi, 48 primary acquired melanoses (PAM; conjunctival melanocytic intraepithelial neoplasia), and 44 conjunctival melanomas. Activation of the canonical or the noncanonical Wnt pathway was tested in vitro in 4 conjunctival melanoma cell lines with stimulation of either Wnt5a or Wnt3a. Wound healing assays were performed with Wnt5a.ResultsNuclear β-catenin expression was found in 16% of the nevi, in 15% of the melanomas, and in 4% of the PAM. Membranous β-catenin expression was identified in all the nevi and PAM and in 97.7% of the melanomas. In vitro, Wnt5a stimulation in the 4 conjunctival melanomas and in 1 skin melanoma cell line did not induce nuclear translocation of β-catenin, nor did it increase cell motility in the wound healing assays. Wnt3a stimulation did not induce nuclear localization of β-catenin in any of the cell lines tested.ConclusionsIn conjunctival melanoma, nuclear localization and activation of β-catenin appear to be limited, suggesting that inhibition of ARF6, responsible for β-catenin activation, in subsets of skin melanoma may not represent a treatment option for this tumor. In vitro, Wnt3a or Wnt5a did not induce nuclear β-catenin localization.
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Project description:Importance:Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood. Objective:To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES). Design, Setting, and Participants:Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011. These samples were analyzed at a tertiary academic ocular oncology referral center using a customized bioinformatic pipeline. Main Outcomes and Measures:Sample analyses were designed to detect driver mutations, chromosome copy number aberrations, and mutation signatures. Results:The study’s 5 patients ranged in age from 51 to 77 years. Four of the 5 were female, and all were white. Mutations were detected in known oncogenes, including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC. None of the mutations associated with uveal melanoma were found. All samples demonstrated a C→T mutation signature typical of UV-induced DNA damage. The most common CNA was a gain in chromosome 6p. Conclusions and Relevance:In these 5 patients, WES allowed identification of mutations that can be targeted with therapy and supported the role of UV light in CM pathogenesis. These findings indicate a need for larger studies to evaluate the diagnostic, prognostic, and therapeutic value of WES for CM.
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Project description:BackgroundConjunctival melanoma is rare in adults and rarer in children. We systematically reviewed the presentation, diagnostic and management strategies as well as outcomes for conjunctival melanoma in children and adolescents.MethodsThe following databases were searched: Medline, Embase, Web of Science and Scopus for cases of conjunctival melanoma occurring in children and adolescents < 18 years of age.ResultsSeventeen studies with 32 patients (18 males) were identified. The median age at presentation was 11 years (range 4-18 years). Most patients were white. Most patients presented with a conjunctival mass or naevus with a recent history of growth or change. Excision biopsy provided diagnosis and management for all cases. Adjuvant chemotherapy and radiotherapy were also used. One patient had metastatic disease at diagnosis and 3 developed metastatic disease (range 1-10 months). Two patients died from disease and one was alive with metastatic disease. Two patients had disease recurrence. Outcomes were observed to be better where diagnosis was made earlier and "no-touch" excision biopsy was performed in an appropriate specialist setting.ConclusionsConjunctival melanoma occurs rarely in children and adolescents. Surgery is the mainstay of management. The prognosis is guarded in metastatic disease due to the small sample size and limited follow-up.
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Project description:Conjunctival malignant melanoma is a pigmented lesion of the ocular surface. It is an uncommon but potentially devastating tumor that may invade the local tissues of the eye, spread systemically through lymphatic drainage and hematogenous spread, and recur in spite of treatment. Despite its severity, the rarity of available cases has limited the evidence for diagnosis and management. This review will provide an overview of the epidemiology, presentation, diagnosis, management, and surveillance of conjunctival melanoma, with an emphasis on recent advances in biological therapies to treat this disease.
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