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Mol Ther ; 23(9): 1486-96, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26061649

RESUMO

Circulating tumor cells (CTCs) are rare cells and valuable clinical markers of prognosis of metastasis formation and prediction of patient survival. Most CTC analyses are based on the antibody-based detection of a few epithelial markers; therefore miss an important portion of mesenchymal cancer cells circulating in blood. In this work, we selected and identified DNA aptamers as specific affinity probes that bind to lung adenocarcinoma cells derived from postoperative tissues. The unique feature of our selection strategy is that aptamers are produced for lung cancer cell biomarkers in their native state and conformation without previous knowledge of the biomarkers. The aptamers did not bind to normal lung cells and lymphocytes, and had very low affinity to A549 lung adenocarcinoma culture. We applied these aptamers to detect CTCs, apoptotic bodies, and microemboli in clinical samples of peripheral blood of lung cancer and metastatic lung cancer patients. We identified aptamer-associated protein biomarkers for lung cancer such as vimentin, annexin A2, annexin A5, histone 2B, neutrophil defensin, and clusterin. Tumor-specific aptamers can be produced for individual patients and synthesized many times during anticancer therapy, thereby opening up the possibility of personalized diagnostics.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Aptâmeros de Nucleotídeos , Biomarcadores Tumorais , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Aptâmeros de Nucleotídeos/química , Proteínas de Transporte/metabolismo , Linhagem Celular , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Gradação de Tumores , Período Pós-Operatório , Ligação Proteica , Técnica de Seleção de Aptâmeros
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