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1.
Clin. transl. oncol. (Print) ; 16(8): 725-731, ago. 2014. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-126560

RESUMO

PURPOSE: We sought to study the microRNA regulation of epithelial mesenchymal transition (EMT), the acquisition of migratory, mesenchymal-like properties of epithelial cells, in cancer of unknown primary (CUP). PATIENTS AND METHODS: We studied the global expression profile of 982 microRNAs by means of microarray technology in 68 CUP cases immunohistochemically characterised as EMT-positive (n = 5 by % of cells or n = 10 by a semiquantitative H-score) or EMT-negative. RESULTS: EMT-suppressive miRNAs such as miR-203 and members of the miR-200 family (miR-200a,b,c and miR-141) presented a 2.45 to 3.64-fold lower expression level in the EMT-positive cases without, however, reaching statistical significance. MiR-205, a squamous tissue-specific marker, was very variable in the data set. Excluding CUP cases with squamous cell histology, miR-205, miR-203 and the miR-200 family exhibited a trend of downregulation in EMT-positive cases. A similar pattern of miRNA expression was detected when the comparison took place between EMT-positive vs EMT-negative cases according to the H-score. Moreover, miR-203, miR-205 and miR-200c were numerically downregulated in those tumours with high expression of the EMT marker N-cadherin. CONCLUSIONS: The EMT-suppressive miR-203 and miR-200 family were consistently but non-significantly downregulated in CUP with the EMT phenotype. A larger study is warranted to further explore the role of microRNAs in CUP (AU)


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Assuntos
Humanos , Masculino , Feminino , Neoplasias Primárias Desconhecidas/classificação , Neoplasias Primárias Desconhecidas/diagnóstico , RNA , Análise Serial de Proteínas/instrumentação , Análise Serial de Proteínas/métodos , Condrossarcoma Mesenquimal/diagnóstico , Transição Epitelial-Mesenquimal , Transição Epitelial-Mesenquimal/efeitos da radiação , Análise Serial de Proteínas/normas , Análise Serial de Proteínas , Metástase Neoplásica
2.
Clin Transl Oncol ; 16(8): 725-31, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24282096

RESUMO

PURPOSE: We sought to study the microRNA regulation of epithelial mesenchymal transition (EMT), the acquisition of migratory, mesenchymal-like properties of epithelial cells, in cancer of unknown primary (CUP). PATIENTS AND METHODS: We studied the global expression profile of 982 microRNAs by means of microarray technology in 68 CUP cases immunohistochemically characterised as EMT-positive (n = 5 by % of cells or n = 10 by a semiquantitative H-score) or EMT-negative. RESULTS: EMT-suppressive miRNAs such as miR-203 and members of the miR-200 family (miR-200a,b,c and miR-141) presented a 2.45 to 3.64-fold lower expression level in the EMT-positive cases without, however, reaching statistical significance. MiR-205, a squamous tissue-specific marker, was very variable in the data set. Excluding CUP cases with squamous cell histology, miR-205, miR-203 and the miR-200 family exhibited a trend of downregulation in EMT-positive cases. A similar pattern of miRNA expression was detected when the comparison took place between EMT-positive vs EMT-negative cases according to the H-score. Moreover, miR-203, miR-205 and miR-200c were numerically downregulated in those tumours with high expression of the EMT marker N-cadherin. CONCLUSIONS: The EMT-suppressive miR-203 and miR-200 family were consistently but non-significantly downregulated in CUP with the EMT phenotype. A larger study is warranted to further explore the role of microRNAs in CUP.


Assuntos
Transição Epitelial-Mesenquimal/genética , MicroRNAs/análise , Neoplasias Primárias Desconhecidas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Fenótipo
3.
Curr Med Chem ; 18(11): 1629-39, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21428884

RESUMO

Despite declining incidence in developed countries, gastric cancer is still the second cause of cancer death worldwide, while proximal gastric cancer is increasing in incidence. Cytotoxic combinations of platinum salts, fluoropyrimidines with or without taxanes or anthracyclines improved response rates but failed to improve the median survival of patients with advanced gastric cancer beyond the 12-month benchmark. Novel rationally designed therapies targeting molecular aberrations which are tumour-specific and pivotal for tumour survival, are urgently needed in order to improve patient outcome. Angiogenic mediators, transmembrane receptors, signal transduction molecules, transcription factors, epigenetic regulators and other biomolecules are among potential targets being modulated by monoclonal antibodies or small molecules in current phase I, II and III clinical trials. To date, only the addition of trastuzumab, an anti-HER2 monoclonal antibody combined with chemotherapy has yielded a clinically meaningful survival improvement in patients with advanced gastric cancer overexpressing HER2.


Assuntos
Terapia de Alvo Molecular/métodos , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Gerenciamento Clínico , Humanos
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