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Métodos Terapéuticos y Terapias MTCI
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1.
Cells ; 11(22)2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36429040

RESUMEN

Monitoring tumor growth dynamics is crucial for understanding cancer. To establish an in vitro method for the continuous assessment of patient-specific tumor growth, tumor organoids were generated from patients with intrahepatic CCA (iCCA). Organoid growth was monitored for 48 h by label-free live brightfield imaging. Growth kinetics were calculated and validated by MTS assay as well as immunohistochemistry of Ki67 to determine proliferation rates. We exposed iCCA organoids (iCCAOs) and non-tumor intrahepatic cholangiocyte organoids (ICOs) to sub-therapeutic concentrations of sorafenib. Monitoring the expansion rate of iCCAOs and ICOs revealed that iCCAO growth was inhibited by sorafenib in a time- and dose-dependent fashion, while ICOs were unaffected. Quantification of the proliferation marker Ki67 confirmed inhibition of iCCAO growth by roughly 50% after 48 h of treatment with 4 µM sorafenib. We established a robust analysis pipeline combining brightfield microscopy and a straightforward image processing approach for the label-free growth monitoring of patient-derived iCCAOs. Combined with bioanalytical validation, this approach is suitable for a fast and efficient high-throughput drug screening in tumor organoids to develop patient-specific systemic treatment options.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Organoides/patología , Sorafenib/farmacología , Sorafenib/uso terapéutico , Antígeno Ki-67 , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología
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