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  1 / 42219 MEDLINE  
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[PMID]:29408272
[Au] Autor:Saif I; Kasmi Y; Allali K; Ennaji MM
[Ad] Endereço:Team of Virology, Oncology and Medical Biotechnologies, Laboratory of Virology, Microbiology, Quality and Biotechnologies/ETB, Faculty of Science sand Technologies-Mohammedia, Hassan II University of Casablanca, Morocco.
[Ti] Título:Prediction of DNA methylation in the promoter of gene suppressor tumor.
[So] Source:Gene;651:166-173, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The epigenetics methylation of cytosine is the most common epigenetic form in DNA sequences. It is highly concentrated in the promoter regions of the genes, leading to an inactivation of tumor suppressors regardless of their initial function. In this work, we aim to identify the highly methylated regions; the cytosine-phosphate-guanine (CpG) island located on the promoters and/or the first exon gene known for their key roles in the cell cycle, hence the need to study gene-gene interactions. The Frommer and hidden Markov model algorithms are used as computational methods to identify CpG islands with specificity and sensitivity up to 76% and 80%, respectively. The results obtained show, on the one hand, that the genes studied are suspected of developing hypermethylation in the promoter region of the gene involved in the case of a cancer. We then showed that the relative richness in CG results from a high level of methylation. On the other hand, we observe that the gene-gene interaction exhibits co-expression between the chosen genes. This let us to conclude that the hidden Markov model algorithm predicts more specific and valuable information about the hypermethylation in gene as a preventive and diagnostics tools for the personalized medicine; as that the tumor-suppresser-genes have relative co-expression and complementary relations which the hypermethylation affect in the samples studied in our work.
[Mh] Termos MeSH primário: Biologia Computacional/métodos
Ilhas de CpG
Metilação de DNA
Genes Supressores de Tumor
Regiões Promotoras Genéticas
[Mh] Termos MeSH secundário: Algoritmos
DNA de Neoplasias
Conjuntos de Dados como Assunto
Epistasia Genética
Seres Humanos
Cadeias de Markov
Modelos Genéticos
Neoplasias/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Neoplasm)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


  2 / 42219 MEDLINE  
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[PMID]:29177308
[Au] Autor:Fang K; Wu S; Dong G; Wu Y; Chen S; Liu J; Wang W; Sheng C
[Ad] Endereço:School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. China. wwang@unm.edu.
[Ti] Título:Discovery of IDO1 and DNA dual targeting antitumor agents.
[So] Source:Org Biomol Chem;15(47):9992-9995, 2017 Dec 06.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The development of small molecules for cancer immunotherapy is highly challenging and indoleamine 2,3-dioxygenase 1 (IDO1) represents a promising target. Inspired by the synergistic effects between IDO1 inhibitors and traditional antitumor chemotherapeutics, the first orally active dual IDO1 and DNA targeting agents were designed by the pharmacophore fusion strategy. The bifunctional hybrids exhibited enhanced IDO1 enzyme inhibitory activity and in vitro cytotoxicity as compared to IDO1 inhibitor 1-methyl-tryptophan and DNA alkylating agent melphalan. In a murine LLC tumor model, the dual targeting agents demonstrated excellent antitumor efficacy, highlighting the advantages of this novel design strategy to improve the efficacy of small molecule cancer immunotherapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
DNA de Neoplasias/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores
Melfalan/farmacologia
Triptofano/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Descoberta de Drogas
Ensaios de Seleção de Medicamentos Antitumorais
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Seres Humanos
Imunoterapia
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
Melfalan/síntese química
Melfalan/química
Camundongos
Estrutura Molecular
Neoplasias Experimentais/tratamento farmacológico
Relação Estrutura-Atividade
Triptofano/síntese química
Triptofano/química
Triptofano/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-methyltryptophan); 0 (Antineoplastic Agents); 0 (DNA, Neoplasm); 0 (Enzyme Inhibitors); 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 0 (indoleamine 2,3-dioxygenase 1, human); 8DUH1N11BX (Tryptophan); Q41OR9510P (Melphalan)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1039/c7ob02529g


  3 / 42219 MEDLINE  
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[PMID]:28460452
[Au] Autor:Lin Z; Neiswender J; Fang B; Ma X; Zhang J; Hu X
[Ad] Endereço:State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China.
[Ti] Título:Value of circulating cell-free DNA analysis as a diagnostic tool for breast cancer: a meta-analysis.
[So] Source:Oncotarget;8(16):26625-26636, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The aim of this study was to systematically evaluate the diagnostic value of cell free DNA (cfDNA) for breast cancer. RESULTS: Among 308 candidate articles, 25 with relevant diagnostic screening qualified for final analysis. The mean sensitivity, specificity and area under the curve (AUC) of SROC plots for 24 studies that distinguished breast cancer patients from healthy controls were 0.70, 0.87, and 0.9314, yielding a DOR of 32.31. When analyzed in subgroups, the 14 quantitative studies produced sensitivity, specificity, AUC, and a DOR of 0.78, 0.83, 0.9116, and 24.40. The 10 qualitative studies produced 0.50, 0.98, 0.9919, and 68.45. For 8 studies that distinguished malignant breast cancer from benign diseases, the specificity, sensitivity, AUC and DOR were 0.75, 0.79, 0.8213, and 9.49. No covariate factors had a significant correlation with relative DOR. Deek's funnel plots indicated an absence of publication bias. MATERIALS AND METHODS: Databases were searched for studies involving the use of cfDNA to diagnose breast cancer. The studies were analyzed to determine sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the summary receiver operating characteristic (SROC). Covariates were evaluated for effect on relative DOR. Deek's Funnel plots were generated to measure publication bias. CONCLUSIONS: Our analysis suggests a promising diagnostic potential of using cfDNA for breast cancer screening, but this diagnostic method is not yet independently sufficient. Further work refining qualitative cfDNA assays will improve the correct diagnosis of breast cancers.
[Mh] Termos MeSH primário: Biomarcadores Tumorais
Neoplasias da Mama/diagnóstico
Neoplasias da Mama/genética
Ácidos Nucleicos Livres
DNA de Neoplasias
[Mh] Termos MeSH secundário: Área Sob a Curva
Neoplasias da Mama/sangue
Bases de Dados Genéticas
Detecção Precoce de Câncer/métodos
Feminino
Seres Humanos
Biópsia Líquida
Viés de Publicação
Curva ROC
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Cell-Free Nucleic Acids); 0 (DNA, Neoplasm)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15775


  4 / 42219 MEDLINE  
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[PMID]:29484962
[Au] Autor:Kumar M; Choudhury Y; Ghosh SK; Mondal R
[Ad] Endereço:1 Department of Biotechnology, Assam University, Silchar, India.
[Ti] Título:Application and optimization of minimally invasive cell-free DNA techniques in oncogenomics.
[So] Source:Tumour Biol;40(2):1010428318760342, 2018 Feb.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The conventional method of measuring biomarkers in malignant tissue samples has already given subversive growth in cancer diagnosis, prognosis, and therapy selection. However, the regression and heterogeneity associated with tumor tissue biopsy have urged for the development of an alternative approach. Considering the limitations, cell-free DNA has emerged as a surrogate alternative, facilitating preoperative chemoradiotherapy (p < 0.0001) treatment response in rectal cancer and detection of biomarker in lung cancer. This potential of cell-free DNA in several other cancers has yet to be explored based on clinical relevance by optimizing the preanalytical factors. This review has highlighted the crucial parameters from blood collection to cell-free DNA analysis that has a significant impact on the accuracy and reliability of clinical data. The quantity of cell-free DNA is also a limiting factor. Therefore, a proper preanalytical factor for blood collection, its stability, centrifugation speed, and plasma storage condition are to be optimized for developing cancer-specific biomarkers useful for clinical purpose. Liquid biopsy-based origin of cell-free DNA has revolutionized the area of cancer research. Lack of preanalytical and analytical procedures may be considered for identification of novel biomarkers through next-generation sequencing of tumor-originated cell-free DNA in contradiction to tissue biopsy for cancer-specific biomarkers.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Ácidos Nucleicos Livres/genética
DNA de Neoplasias/genética
Mutação
Neoplasias/genética
[Mh] Termos MeSH secundário: Genômica
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Seres Humanos
Neoplasias/diagnóstico
Neoplasias/terapia
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Cell-Free Nucleic Acids); 0 (DNA, Neoplasm)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180228
[St] Status:MEDLINE
[do] DOI:10.1177/1010428318760342


  5 / 42219 MEDLINE  
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[PMID]:27771279
[Au] Autor:Miyamoto DT; Lee RJ
[Ad] Endereço:Massachusetts General Hospital Cancer Center, Boston, MA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: dmiyamoto@mgh.harvard.edu.
[Ti] Título:Cell-free and circulating tumor cell-based biomarkers in men with metastatic prostate cancer: Tools for real-time precision medicine?
[So] Source:Urol Oncol;34(11):490-501, 2016 11.
[Is] ISSN:1873-2496
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The recent expansion of therapeutic options for the treatment of metastatic prostate cancer highlights the need for precision medicine approaches to enable the rational selection of appropriate therapies for individual patients. In this context, circulating biomarkers in the peripheral blood are attractive as readily accessible tools for predicting and monitoring therapeutic response. In the case of circulating tumor cells and circulating tumor DNA, they may also serve as a noninvasive means of assessing molecular aberrations in tumors at multiple time points before and during therapy. These so-called "liquid biopsies" can provide a snapshot view of tumor molecular architecture and may enable clinicians to monitor the molecular status of tumors as they evolve during treatment, thus allowing for individualized precision therapeutic decisions for patients over time. In this review, we outline recent progress in the field of circulating biomarkers in metastatic prostate cancer and evaluate their potential for enabling this vision of real-time precision medicine.
[Mh] Termos MeSH primário: Adenocarcinoma/secundário
Biomarcadores Tumorais/sangue
DNA de Neoplasias/sangue
Células Neoplásicas Circulantes/química
Medicina de Precisão/métodos
Neoplasias da Próstata/sangue
[Mh] Termos MeSH secundário: Adenocarcinoma/sangue
Adenocarcinoma/tratamento farmacológico
Adenocarcinoma/genética
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Ensaios Clínicos como Assunto
Sistemas de Computação
Dosagem de Genes
Seres Humanos
Masculino
Estudos Multicêntricos como Assunto
Mutação
Proteínas de Neoplasias/sangue
Proteínas de Neoplasias/genética
Medicina de Precisão/tendências
Prognóstico
Neoplasias da Próstata/tratamento farmacológico
Neoplasias da Próstata/genética
Receptores Androgênicos/sangue
Receptores Androgênicos/genética
Análise de Célula Única
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (AR protein, human); 0 (Biomarkers, Tumor); 0 (DNA, Neoplasm); 0 (Neoplasm Proteins); 0 (Receptors, Androgen)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161106
[St] Status:MEDLINE


  6 / 42219 MEDLINE  
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[PMID]:28471108
[Au] Autor:Zhang MW; Fujiwara K; Che X; Zheng S; Zheng L
[Ad] Endereço:The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
[Ti] Título:DNA methylation in the tumor microenvironment.
[So] Source:J Zhejiang Univ Sci B;18(5):365-372, 2017 May.
[Is] ISSN:1862-1783
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth. Here we summarize recent studies about how DNA methylation affects tumorigenesis through regulating tumor-associated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers.
[Mh] Termos MeSH primário: Carcinogênese/genética
Metilação de DNA/genética
DNA de Neoplasias/genética
Regulação Neoplásica da Expressão Gênica/genética
Neoplasias/genética
Neoplasias/patologia
Microambiente Tumoral/genética
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Modelos Genéticos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (DNA, Neoplasm)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1631/jzus.B1600579


  7 / 42219 MEDLINE  
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[PMID]:29372685
[Au] Autor:Fialkova V; Vidomanova E; Balharek T; Marcinek J; Kudela E; Hanysova S; Visnovsky J; Dobrota D; Hatok J
[Ad] Endereço:Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. hatok@jfmed.uniba.sk.
[Ti] Título:DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients.
[So] Source:Gen Physiol Biophys;36(5):521-529, 2017 Dec.
[Is] ISSN:0231-5882
[Cp] País de publicação:Slovakia
[La] Idioma:eng
[Ab] Resumo:DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients. The aim of our study was to examine the promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid endometrial cancer patients, precancerous lesions and healthy tissue from various normal menstrual cycle phases using a unique pre-designed methylation platform. We observed as the first a significant difference in promoter DNA methylation status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05) during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of normal menstrual cycle. The results of our study indicate that deregulation of mitochondrial apoptotic pathway can considerably contributes to the apoptosis resistance development and may be helpful in identifying of new potent biomarkers in endometrial cancer.
[Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/genética
Apoptose/genética
Metilação de DNA/genética
DNA de Neoplasias/genética
Neoplasias do Endométrio/genética
Epigênese Genética/genética
Lesões Pré-Cancerosas/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Carcinogênese/genética
Feminino
Predisposição Genética para Doença/genética
Seres Humanos
Meia-Idade
Polimorfismo de Nucleotídeo Único/genética
Eslováquia
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); 0 (DNA, Neoplasm)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.4149/gpb_2017032


  8 / 42219 MEDLINE  
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[PMID]:29372684
[Au] Autor:Murín R; Vidomanová E; Kowtharapu BS; Hatok J; Dobrota D
[Ad] Endereço:Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. murin@jfmed.uniba.sk.
[Ti] Título:Role of S-adenosylmethionine cycle in carcinogenesis.
[So] Source:Gen Physiol Biophys;36(5):513-520, 2017 Dec.
[Is] ISSN:0231-5882
[Cp] País de publicação:Slovakia
[La] Idioma:eng
[Ab] Resumo:Alterations in enzymatic activities underlying the cellular capacity to maintain functional S-adenosylmethionine (SAM) cycle are associated with modified levels of its constituents. Since SAM is the most prominent donor of methyl group for sustaining the methylation pattern of macromolecules by methyltransferases, its availability is an essential prerequisite for sustaining the methylation pattern of nucleic acids and proteins. In addition, increased intracellular concentrations of S-adenosylhomocysteine and homocysteine, another two constituents of SAM cycle, exerts an inhibitory effect on the enzymatic activity of methyltranferases. While methylation pattern of DNA and histones is considered as an important regulatory hallmark in epigenetically regulated gene expression, amended methylation of several cellular proteins, including transcription factors, affects their activity and stability. Indeed, varied DNA methylome is a common consequence of disturbed SAM cycle and is linked with molecular changes underlying the transformation of the cells that may underlay the carcinogenesis. Here we summarize the recent evidences about the impact of disturbed SAM cycle on carcinogenesis.
[Mh] Termos MeSH primário: Carcinogênese/genética
Carcinogênese/metabolismo
DNA de Neoplasias/genética
Epigênese Genética/genética
Neoplasias/genética
Neoplasias/metabolismo
S-Adenosilmetionina/metabolismo
[Mh] Termos MeSH secundário: Animais
Metilação de DNA/genética
Regulação Neoplásica da Expressão Gênica/genética
Seres Humanos
Modelos Genéticos
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (DNA, Neoplasm); 7LP2MPO46S (S-Adenosylmethionine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.4149/gpb_2017031


  9 / 42219 MEDLINE  
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[PMID]:29385200
[Au] Autor:Rout ED; Burnett RC; Labadie JD; Yoshimoto JA; Avery AC
[Ad] Endereço:Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
[Ti] Título:Preferential use of unmutated immunoglobulin heavy variable region genes in Boxer dogs with chronic lymphocytic leukemia.
[So] Source:PLoS One;13(1):e0191205, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, and immunoglobulin heavy variable region (IGHV) gene mutational status is an important prognostic marker. IGHV mutational status has not been previously examined in canine CLL. We sequenced the IGHV-D-J rearrangements from 55 canine patients with CLL, including 36 non-Boxer and 19 Boxer dogs. The majority of non-Boxers (75%) had mutated IGHV genes, whereas the majority of Boxers (79%) had unmutated IGHV genes. IGHV3-41 and IGHV3-67 gene usage was significantly higher in Boxers with CLL compared to non-Boxers. Additionally, 11 Boxers with large B-cell lymphoma and the normal IGHV repertoire of six control dogs (three Boxers and three non-Boxers) were sequenced. IGHV3-41 was preferentially used in Boxers with other forms of lymphoma and without lymphoproliferative disease. However, preferential use of unmutated IGHV genes was unique to Boxers with CLL, suggesting Boxers may be a valuable model to investigate unmutated CLL.
[Mh] Termos MeSH primário: Doenças do Cão/genética
Doenças do Cão/imunologia
Genes de Cadeia Pesada de Imunoglobulina
Região Variável de Imunoglobulina/genética
Leucemia Linfocítica Crônica de Células B/veterinária
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Estudos de Casos e Controles
Análise Mutacional de DNA
DNA de Neoplasias/genética
Cães
Feminino
Rearranjo Gênico de Cadeia Pesada de Linfócito B
Leucemia Linfocítica Crônica de Células B/genética
Leucemia Linfocítica Crônica de Células B/imunologia
Masculino
Mutação
Homologia de Sequência do Ácido Nucleico
Especificidade da Espécie
Éxons VDJ
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Neoplasm); 0 (Immunoglobulin Variable Region)
[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:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191205


  10 / 42219 MEDLINE  
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[PMID]:29324814
[Au] Autor:Topcagic J; Feldman R; Ghazalpour A; Swensen J; Gatalica Z; Vranic S
[Ad] Endereço:Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina, Sarajevo, Bosnia and Herzegovina.
[Ti] Título:Comprehensive molecular profiling of advanced/metastatic olfactory neuroblastomas.
[So] Source:PLoS One;13(1):e0191244, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Olfactory neuroblastoma (ONB) is a rare, locally aggressive, malignant neoplasm originating in the olfactory epithelium in the nasal vault. The recurrence rate of ONB remains high and there are no specific treatment guidelines for recurrent/metastatic ONBs. This study retrospectively evaluated 23 ONB samples profiled at Caris Life Sciences (Phoenix, Arizona) using DNA sequencing (Sanger/NGS [Illumina], n = 15) and gene fusions (Archer FusionPlex, n = 6), whole genome RNA microarray (HumanHT-12 v4 beadChip, Illumina, n = 4), gene copy number assays (chromogenic and fluorescent in situ hybridization), and immunohistochemistry. Mutations were detected in 63% ONBs including TP53, CTNNB1, EGFR, APC, cKIT, cMET, PDGFRA, CDH1, FH, and SMAD4 genes. Twenty-one genes were over-expressed and 19 genes under-expressed by microarray assay. Some of the upregulated genes included CD24, SCG2, and IGFBP-2. None of the cases harbored copy number variations of EGFR, HER2 and cMET genes, and no gene fusions were identified. Multiple protein biomarkers of potential response or resistance to classic chemotherapy drugs were identified, such as low ERCC1 [cisplatin sensitivity in 10/12], high TOPO1 [irinotecan sensitivity in 12/19], high TUBB3 [vincristine resistance in 13/14], and high MRP1 [multidrug resistance in 6/6 cases]. None of the cases (0/10) were positive for PD-L1 in tumor cells. Overexpression of pNTRK was observed in 67% (4/6) of the cases without underlying genetic alterations. Molecular alterations detected in our study (e.g., Wnt and cKIT/PDGFRA pathways) are potentially treatable using novel therapeutic approaches. Identified protein biomarkers of response or resistance to classic chemotherapy could be useful in optimizing existing chemotherapy treatment(s) in ONBs.
[Mh] Termos MeSH primário: Estesioneuroblastoma Olfatório/genética
Cavidade Nasal
Neoplasias Nasais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/metabolismo
Variações do Número de Cópias de DNA
DNA de Neoplasias/genética
Estesioneuroblastoma Olfatório/metabolismo
Estesioneuroblastoma Olfatório/secundário
Feminino
Perfilação da Expressão Gênica
Fusão Gênica
Seres Humanos
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Masculino
Meia-Idade
Terapia de Alvo Molecular
Mutação
Recidiva Local de Neoplasia/genética
Recidiva Local de Neoplasia/metabolismo
Recidiva Local de Neoplasia/terapia
Neoplasias Nasais/metabolismo
Neoplasias Nasais/terapia
Estudos Retrospectivos
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (DNA, Neoplasm)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191244



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