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Sci Rep ; 10(1): 16876, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037240

RESUMO

The establishment of clinically relevant models for tumor metastasis and drug testing is a major challenge in cancer research. Here we report a physiologically relevant assay enabling quantitative analysis of metastatic capacity of tumor cells following implantation into the chorioallantoic membrane (CAM). Engraftment of as few as 103 non-small cell lung cancer (NSCLC) and prostate cancer (PCa) cell lines was sufficient for both primary tumor and metastasis formation. Standard 2D-imaging as well as 3D optical tomography imaging were used for the detection of fluorescent metastatic foci in the chick embryo. H2228- and H1975-initiated metastases were confirmed by genomic analysis. We quantified the inhibitory effect of docetaxel on LNCaP, and that of cisplatin on A549- and H1299-initiated metastatic growths. The CAM assay also mimicked the sensitivity of ALK-rearranged H2228 and EGFR-mutated H1975 NSCLC cells to tyrosine kinase inhibitors crizotinib and gefitinib respectively, as well as sensitivity of LNCaP cells to androgen-dependent enzalutamide therapy. The assay was suggested to reconstitute the bone metastatic tropism of PCa cells. We show that the CAM chick embryo model may be a powerful preclinical platform for testing and targeting of the metastatic capacity of cancer cells.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Membrana Corioalantoide , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/genética , Neoplasias da Próstata/patologia , Animais , Benzamidas , Embrião de Galinha , Cisplatino/farmacologia , Crizotinibe/farmacologia , Docetaxel/farmacologia , Gefitinibe/farmacologia , Masculino , Células Neoplásicas Circulantes , Nitrilas , Feniltioidantoína/análogos & derivados , Feniltioidantoína/farmacologia
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