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  1 / 3647 MEDLINE  
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[PMID]:29240458
[Au] Autor:Xu B; Ma R; Ren H; Qian J
[Ad] Endereço:Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital, Fudan University , Shanghai, China .
[Ti] Título:Genome-Wide Analysis of Uveal Melanoma Metastasis-Associated LncRNAs and Their Functional Network.
[So] Source:DNA Cell Biol;37(2):99-108, 2018 Feb.
[Is] ISSN:1557-7430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Up to 50% of primary UM cases will develop distant metastasis, but no effective therapies are currently available. The present study aimed to characterize the expression profile of the long noncoding RNAs (lncRNAs) and screen the potential metastasis-associated lncRNAs in UM. A genome-wide analysis of the transcriptome was performed on 11 primary UM tissues (6 metastasized and 5 nonmetastasized) through RNA sequencing. A total of 40,878 lncRNAs were detected in UM, 4,983 of which were novel candidates. We identified 329 differentially expressed lncRNAs (DELs) and 802 differentially expressed mRNAs (DEMs) by comparing the transcriptome profile between metastasized and nonmetastasized UM group. The DEL-DEM coexpression network revealed that the RP11-551L14.4, TCONS_00004101, and TCONS_00004845 DELs had the highest connectivity with the DEMs, coexpressed with 225, 28, and 10 DEMs, respectively, whereas the SPOCD1, PEA15, and SLC44A3 DEMs were most closely connected with the DELs, and were coexpressed with 89, 27, and 22 DELs, respectively. Moreover, 17 and 743 DEMs were targeted by the DELs through cis- or trans-action, respectively. These targeted DEMs were significantly enriched in D-Arginine and D-ornithine metabolism and glycerolipid metabolism of Kyoto Encyclopedia of Genes and Genomes pathways, and enriched in bradykinin receptor activity and haptoglobin binding of gene ontology biological processes. Quantitative real-time PCR confirmed the sequencing data. These findings have provided new insights into the molecular mechanism of UM metastasis and paved the way for further investigations regarding lncRNA in UM.
[Mh] Termos MeSH primário: Melanoma/metabolismo
RNA Longo não Codificante/metabolismo
Neoplasias Uveais/metabolismo
[Mh] Termos MeSH secundário: Regulação Neoplásica da Expressão Gênica
Ontologia Genética
Redes Reguladoras de Genes
Estudo de Associação Genômica Ampla
Seres Humanos
Melanoma/genética
Melanoma/secundário
RNA Longo não Codificante/genética
Transcriptoma
Neoplasias Uveais/genética
Neoplasias Uveais/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Long Noncoding)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1089/dna.2017.4015


  2 / 3647 MEDLINE  
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[PMID]:29317634
[Au] Autor:Field MG; Durante MA; Anbunathan H; Cai LZ; Decatur CL; Bowcock AM; Kurtenbach S; Harbour JW
[Ad] Endereço:Bascom Palmer Eye Institute, Sylvester Comprehensive Cancer Center and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida, 33136, USA.
[Ti] Título:Punctuated evolution of canonical genomic aberrations in uveal melanoma.
[So] Source:Nat Commun;9(1):116, 2018 01 09.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when the aberrations associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) is the most common primary eye cancer and frequently leads to metastatic death, which is strongly linked to BAP1 mutations. Accordingly, UM is ideally suited for studying the clonal evolution of metastatic competence. Here we analyze sequencing data from 151 primary UM samples using a customized bioinformatic pipeline, to improve detection of BAP1 mutations and infer the clonal relationships among genomic aberrations. Strikingly, we find BAP1 mutations and other canonical genomic aberrations usually arise in an early punctuated burst, followed by neutral evolution extending to the time of clinical detection. This implies that the metastatic proclivity of UM is "set in stone" early in tumor evolution and may explain why advances in primary treatment have not improved survival.
[Mh] Termos MeSH primário: Melanoma/genética
Proteínas Supressoras de Tumor/genética
Ubiquitina Tiolesterase/genética
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Análise por Conglomerados
Variações do Número de Cópias de DNA
Metilação de DNA
Evolução Molecular
Seres Humanos
Mutação
Sequenciamento Completo do Exoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Tumor Suppressor Proteins); EC 3.1.2.15 (BAP1 protein, human); EC 3.4.19.12 (Ubiquitin Thiolesterase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02428-w


  3 / 3647 MEDLINE  
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[PMID]:29185101
[Au] Autor:Nguyen BT; Kim RS; Bretana ME; Kegley E; Schefler AC
[Ad] Endereço:Retina Consultants of Houston, 6560 Fannin Street, Suite 750, Houston, TX, 77030, USA.
[Ti] Título:Association between traditional clinical high-risk features and gene expression profile classification in uveal melanoma.
[So] Source:Graefes Arch Clin Exp Ophthalmol;256(2):421-427, 2018 Feb.
[Is] ISSN:1435-702X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP). METHODS: This was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD). A novel point system was created to grade the high-risk clinical features of each tumor. Further analyses were performed to assess the degree of association between GEP and each individual risk factor, total clinical risk score, vascularity, internal reflectivity, American Joint Committee on Cancer (AJCC) tumor stage classification, apical tumor height/thickness, and LBD. RESULTS: Of the 83 total patients, 41 were classified as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical tumor height/thickness ≥ 2 mm were not statistically significantly associated with GEP class. Lack of drusen/RPE changes demonstrated a trend toward statistical association with GEP class 2 compared to class 1A/1B. LBD and advancing AJCC stage was statistically associated with higher GEP class. CONCLUSIONS: In this cohort, AJCC stage classification and LBD were the only clinical features statistically associated with GEP class. Clinicians should use caution when inferring the growth potential of melanocytic lesions solely from traditional funduscopic and ultrasonographic risk factors without GEP data.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Perfilação da Expressão Gênica/métodos
Melanoma/genética
Estadiamento de Neoplasias
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Biomarcadores Tumorais/biossíntese
Biópsia por Agulha Fina
Corioide/metabolismo
Corioide/patologia
Feminino
Seguimentos
Seres Humanos
Masculino
Melanoma/classificação
Melanoma/diagnóstico
Meia-Idade
Prognóstico
Estudos Retrospectivos
Transcriptoma
Neoplasias Uveais/classificação
Neoplasias Uveais/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1007/s00417-017-3856-x


  4 / 3647 MEDLINE  
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[PMID]:29244840
[Au] Autor:Xu H; Gong J; Liu H
[Ad] Endereço:Department of Ophthalmology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
[Ti] Título:High expression of lncRNA PVT1 independently predicts poor overall survival in patients with primary uveal melanoma.
[So] Source:PLoS One;12(12):e0189675, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The plasmacytoma variant translocation 1 gene (PVT1) plays an oncogenic role in the initiation and progression of multiple cancers. In this study, by using deep-sequencing data and follow-up data in the Cancer Genome Atlas-Uveal melanomas (TCGA-UVM), we assessed the association between the expression of PVT1 and clinicopathological characteristics of patients with uveal melanoma, the mechanism of its dysregulation and its prognostic value. Results showed that high PVT1 expression group had a higher proportion of epithelioid cell dominant disease (a more malignant histological subtype than spindle cell dominant disease) and more cases of extrascleral extension (a risk factor for metastasis) compared with the low PVT1 expression group. 61 out of 80 cases (76.3%) of primary uveal melanoma had PVT1 amplification in TCGA-UVM. In addition, PVT1 expression was strongly and negatively correlated with its methylation status (Pearson's r = -0.712, Spearman's r = -0.806). By performing univariate and multivariate analysis, we found that high PVT1 expression was an independent predictor of poor OS in patients with uveal melanoma (HR: 12.015, 95%CI: 1.854-77.876, p = 0.009). Based on these findings, we infer that PVT1 expression is modulated by both DNA amplification and methylation and its expression might serve as a valuable and specific prognostic biomarker in terms of OS in uveal melanoma.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Melanoma/genética
RNA Longo não Codificante/genética
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Masculino
Melanoma/patologia
Meia-Idade
Prognóstico
Úvea/metabolismo
Úvea/patologia
Neoplasias Uveais/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (PVT1 long-non-coding RNA, human); 0 (RNA, Long Noncoding)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189675


  5 / 3647 MEDLINE  
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[PMID]:29187428
[Au] Autor:Berus T; Halon A; Markiewicz A; Orlowska-Heitzman J; Romanowska-Dixon B; Donizy P
[Ad] Endereço:The Clinical Ward of Ophthalmology, Fourth Military Clinical Hospital with Polyclinic, Wroclaw, Poland tberus@4wsk.pl.
[Ti] Título:Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma - A Comprehensive Review.
[So] Source:Anticancer Res;37(12):6541-6549, 2017 12.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Uveal melanoma is the most prevalent primary intraocular cancer in adults. Although it accounts for only 5% of all melanomas, it is responsible for 13% of deaths due to this type of cancer. A wide variety of therapeutic options of primary tumor is available and progress in its management is noticeable. The fact still remains, however, that almost half of patients develop metastases which may be due to practically undetectable cancer spread present as early as at diagnosis of the primary focus. Metastatic disease is uniformly fatal despite systemic therapy. Prediction of metastasis is crucial for prognosis. It also allows targeting of emerging new therapeutic methods to the appropriate group of patients. The Authors reviewed literature concerning epidemiology and etiopathogenesis of uveal melanoma, and its clinical, histopathological and cytogenetic prognosticators.
[Mh] Termos MeSH primário: Citogenética
Melanoma/genética
Patologia Clínica
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Aberrações Cromossômicas
Regulação Neoplásica da Expressão Gênica
Predisposição Genética para Doença/genética
Seres Humanos
Melanoma/patologia
Mutação
Prognóstico
Neoplasias Uveais/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


  6 / 3647 MEDLINE  
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[PMID]:27860480
[Au] Autor:Horkovicová K; Markus J; Krcová I; Babál P; Kobzová D; Smolková B
[Ti] Título:[THE BRAF MUTATION AND THE POSSIBILITIES OF UVEAL MELANOMA METASTASING PROGNOSTIC MARKERS IDENTIFICATION].
[Ti] Título:MUTÁCIA BRAF A MOZNOSTI IDENTIFIKÁCIE PROGNOSTICKÝCH MARKEROV METASTÁZOVANIA UVEÁLNEHO MELANÓMU..
[So] Source:Cesk Slov Oftalmol;72(4):149-156, 2016.
[Is] ISSN:1211-9059
[Cp] País de publicação:Czech Republic
[La] Idioma:cze
[Ab] Resumo:AIM: The aim is to assess the BRAF gene mutations in patients with posterior uveal melanoma. MATERIAL AND METHODS: Retrospective analysis of the group of patients with malignant melanoma of the uvea, who were indicated to enucleation between 1.1 2015 to 1.3.2016. We analyzed stage of uveal melanoma, volume, cell type and BRAF gene mutations. RESULTS: In clinical study of 20 patients after enucleation due to uveal melanoma at the Department of Ophthalmology in Bratislava, patient age was ranged from 22 to 89 years with a median of 62 years. In 14 patients (70 %) enucleation was the primary treatment and in 6 patients (30 %) enucleation was after irradiation (brachytherapy, Leksell gama knife, linear accelerator). In 17 cases (85 %) the mutation of the BRAF gene was negative and in 3 cases the sample was not assessable for the BRAF mutation. CONCLUSION: BRAF gene mutation is confirmed by several studies found in malignant melanoma of the skin. The histopathology findings in our group did not confirmed our theory, that since the uveal melanoma itself has the similar origin as skin melanoma, should also contain a BRAF mutation.Key words: malignant melanoma of the uvea, mutation of the BRAF gene, chromosomal abnormalities as a prognostic factor.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Melanoma/genética
Mutação
Proteínas Proto-Oncogênicas B-raf/genética
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Braquiterapia
Análise Mutacional de DNA
Enucleação Ocular
Feminino
Seres Humanos
Masculino
Melanoma/patologia
Melanoma/cirurgia
Meia-Idade
Metástase Neoplásica/genética
Prognóstico
Estudos Retrospectivos
Neoplasias Cutâneas/genética
Neoplasias Cutâneas/patologia
Neoplasias Uveais/patologia
Neoplasias Uveais/cirurgia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE


  7 / 3647 MEDLINE  
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[PMID]:29059311
[Au] Autor:Mori T; Sukeda A; Sekine S; Shibata S; Ryo E; Okano H; Suzuki S; Hiraoka N
[Ad] Endereço:Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
[Ti] Título:SOX10 Expression as Well as BRAF and GNAQ/11 Mutations Distinguish Pigmented Ciliary Epithelium Neoplasms From Uveal Melanomas.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5445-5451, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Adenocarcinomas or adenomas derived from pigmented ciliary epithelium (APCE) are exceptionally rare ocular tumors. These tumors have pigmented and epithelioid features, and some APCEs are negative for keratin markers and positive for melanocytic markers. It is especially difficult to distinguish APCEs from uveal melanoma (UM). Accordingly, we examined protein expression and genetic mutations associated with APCE to facilitate diagnosis. Methods: Five APCE and 11 UM samples were obtained from patients during surgical resection at our institute. APCE and UM ocular structures were compared comprehensively. Protein expression and genetic alterations involved in malignant melanoma were evaluated. Results: SOX10 was expressed diffusely in all 11 UMs and in surrounding uveal or choroidal melanocytes, but not in the APCEs or nontumorous pigmented epithelia. Additionally, the expression patterns of cytokeratins and melanocytic markers differed between UMs and APCEs. We identified BRAF V600E mutations in four of five APCE samples, but not in the 11 UM samples. Moreover, GNAQ or GNA11 mutations were found in 10 of the 11 UM samples, but not in APCE samples. NRAS mutations were not observed in either tumor group examined. Conclusions: APCE is a separate entity distinguished from UM by the absence of SOX10 expression and presence of the BRAF V600E mutation. These results have implications for diagnosis, providing a means to distinguish between UM and APCE.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Corpo Ciliar/patologia
Melanoma/genética
Mutação
Proteínas de Neoplasias/genética
Epitélio Pigmentado Ocular/patologia
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/diagnóstico
Adenocarcinoma/genética
Adenoma/diagnóstico
Adenoma/genética
Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Análise Mutacional de DNA
Feminino
Subunidades alfa de Proteínas de Ligação ao GTP/genética
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética
Regulação Neoplásica da Expressão Gênica/fisiologia
Seres Humanos
Imuno-Histoquímica
Masculino
Melanócitos/metabolismo
Melanoma/diagnóstico
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Microscopia Eletrônica de Transmissão
Meia-Idade
Reação em Cadeia da Polimerase
Proteínas Proto-Oncogênicas B-raf/genética
Fatores de Transcrição SOXE/genética
Neoplasias Uveais/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (GNA11 protein, human); 0 (GNAQ protein, human); 0 (GTP-Binding Protein alpha Subunits); 0 (Neoplasm Proteins); 0 (SOXE Transcription Factors); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171024
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22362


  8 / 3647 MEDLINE  
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[PMID]:29049740
[Au] Autor:Doherty RE; Sisley K; Hammond DW; Rennie IG; Cross NA
[Ad] Endereço:Academic Unit of Ophthalmology and Orthoptics, Department of Oncology and Metabolism, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom.
[Ti] Título:Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5387-5395, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and approximately half of those diagnosed will die of metastasis. This study investigates whether UM progression is driven by a subpopulation of stem-like cells, termed "cancer stem cells" (CSCs). Methods: Expression of postulated stem cell markers aldehyde dehydrogenase (ALDH), CD44, and CD133 was analyzed in UM cell lines and primary UM short-term cultures (STCs) established from tumor samples. Additionally, the notion of a "cellular hierarchy" within UM was investigated. Finally, the phenomenon of phenotypic plasticity in response to environmental factors was explored. Results: We demonstrate that expression of ALDH, CD44, and CD133 does not select for a subpopulation of stem-like cells in either UM cell lines or UM STCs. Furthermore, there is an absence of a cellular hierarchy in cell lines and all cells in culture are able to drive tumor progression. Last, we show that established UM cell lines and UM STCs are plastic in nature and switch their phenotype in response to environmental stimuli. Conclusions: We hypothesize that this capacity to undergo phenotypic plasticity may be a consequence of neural crest lineage and renders the exploration of the CSC hypothesis extremely challenging in UM.
[Mh] Termos MeSH primário: Plasticidade Celular
Melanoma/patologia
Células-Tronco Neoplásicas/patologia
Neoplasias Uveais/patologia
[Mh] Termos MeSH secundário: Antígeno AC133/metabolismo
Aldeído Desidrogenase/metabolismo
Biomarcadores Tumorais/metabolismo
Linhagem Celular Tumoral
Citometria de Fluxo
Seres Humanos
Receptores de Hialuronatos/metabolismo
Melanoma/metabolismo
Células-Tronco Neoplásicas/metabolismo
Fenótipo
Ensaio Tumoral de Célula-Tronco
Neoplasias Uveais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AC133 Antigen); 0 (Biomarkers, Tumor); 0 (CD44 protein, human); 0 (Hyaluronan Receptors); 0 (PROM1 protein, human); EC 1.2.1.3 (Aldehyde Dehydrogenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22272


  9 / 3647 MEDLINE  
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[PMID]:29049739
[Au] Autor:Thariat J; Jacob S; Caujolle JP; Maschi C; Baillif S; Angellier G; Mathis T; Rosier L; Carnicer A; Hérault J; Salleron J
[Ad] Endereço:Institution, Department of Radiation Oncology-Proton Therapy, Nice, France.
[Ti] Título:Cataract Avoidance With Proton Therapy in Ocular Melanomas.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5378-5386, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: The lens is a radiosensitive organ. Any dose of cephalic irradiation can give rise to radiation-induced cataracts. Contrary to other forms of radiotherapy, proton therapy (PT) can spare all or part of the lens due to accurate dose deposition. We investigated whether a lens-sparing approach was relevant to avoid cataracts in uveal melanoma patients. Methods: Patients were referred for PT from onco-ophthalmologists of private and academic institutions. Patients without preexisting cataracts or implants were entered in a prospective database. Dose thresholds responsible for cataracts were investigated in volumes of lens or lens periphery. Lens opacifications and de novo vision-impairing cataracts (VICs) had biannual follow up by ophthalmologists blinded to lens dose. Correlations between dose-volume relationships and VICs were assessed using univariate/multivariate regressions. Results: Between 1991 and 2015, 1696 uveal melanoma patients were consecutively treated with PT. After a median follow up of 48 months, 14.4% and 8.7% of patients had cataracts and VIC within median times of 19 and 28 months, respectively. Median values of mean lens and lens periphery doses were 1.1 (radiobiologically effective [RBE] dose in photon-equivalent grays [GyRBE]) and 6.5 GyRBE, respectively. The lens received no dose in 25% of the patients. At an irradiated lens volume of ≤5%, there was no significantly increased risk for VIC below a dose of 10 GyRBE. Conclusions: A lens-sparing approach is feasible and results not only in reduced need for cataract surgery but also in better fundus-based tumor control. Reassessment of radioprotection rules for lens dose thresholds may follow.
[Mh] Termos MeSH primário: Catarata/prevenção & controle
Melanoma/radioterapia
Terapia com Prótons
Lesões por Radiação/prevenção & controle
Neoplasias Uveais/radioterapia
[Mh] Termos MeSH secundário: Catarata/diagnóstico
Catarata/epidemiologia
Feminino
Seres Humanos
Incidência
Cristalino/patologia
Cristalino/efeitos da radiação
Masculino
Meia-Idade
Estudos Prospectivos
Lesões por Radiação/diagnóstico
Lesões por Radiação/epidemiologia
Dosagem Radioterapêutica
Planejamento da Radioterapia Assistida por Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22557


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Fotocópia
[PMID]:28982892
[Au] Autor:Psinakis F; Katseli A; Koutsandrea C; Frangia K; Florentin L; Apostolopoulou D; Dimakopoulou K; Papakonstantinou D; Georgopoulou E; Brouzas D
[Ad] Endereço:1st Department of Ophthalmology, National and Kapodistrian University of Athens, Athens, Greece.
[Ti] Título:Uveal Melanoma: and Mutations in a Greek Population.
[So] Source:Anticancer Res;37(10):5719-5726, 2017 10.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Uveal melanoma is the most common primary adult intraocular malignancy. It is known to have a strong metastatic potential, fatal for the vast majority of patients. In recent years, meticulous cytogenetic and molecular profiling has led to precise prognostication, that unfortunately is not matched by advancements in adjuvant therapies. G Protein subunits alpha Q (GNAQ) and alpha 11 (GNA11) are two of the major driver genes that contribute to the development of uveal melanoma. Understanding their prognostic significance can allow tailored management and facilitate their use in the on-going quest of targeted uveal melanoma therapies. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens were obtained from 47 patients of Greek origin, with uveal melanoma. GNAQ and GNA11 genes were screened for mutations in exons 4 and 5, by polymerase chain reaction and Sanger sequencing. RESULTS: The overall mutation frequency of GNAQ/GNA11 genes was 42.4%. A novel mutation c.625_626delinsGC was identified in GNA11. No correlation was observed between the mutation status and metastasis occurrence or overall survival time of patients. CONCLUSION: Mutations in GNAQ and GNA11 genes in this Greek population present frequencies that qualify them as potential targets for customized therapy.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética
Subunidades alfa de Proteínas de Ligação ao GTP/genética
Mutação
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Análise Mutacional de DNA
Feminino
Predisposição Genética para Doença
Grécia
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Taxa de Mutação
Fenótipo
Prognóstico
Fatores de Risco
Fatores de Tempo
Neoplasias Uveais/mortalidade
Neoplasias Uveais/patologia
Neoplasias Uveais/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (GNA11 protein, human); 0 (GNAQ protein, human); 0 (GTP-Binding Protein alpha Subunits); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE



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