التفاصيل البيبلوغرافية
| العنوان: |
Development of a patient-derived explant model for prediction of drug responses in endometrial cancer. |
| المؤلفون: |
Collins, Anna1 (AUTHOR), Miles, Gareth J.1 (AUTHOR), Powley, Ian R.1 (AUTHOR), Hew, Roger2 (AUTHOR), Pringle, J. Howard1 (AUTHOR), MacFarlane, Marion3 (AUTHOR), Pritchard, Catrin1 (AUTHOR) cap8@le.ac.uk, Moss, Esther L.1 (AUTHOR) em321@le.ac.uk |
| المصدر: |
Gynecologic Oncology. Feb2021, Vol. 160 Issue 2, p557-567. 11p. |
| مصطلحات موضوعية: |
*ENDOMETRIAL cancer, *IMMUNE checkpoint inhibitors, *PREDICTION models, *DRUG monitoring, *IMAGE analysis, *CULTURE media (Biology), *PEMBROLIZUMAB |
| مستخلص: |
To undertake a pilot study to develop a novel Patient-Derived-Explant (PDE) model system for use in endometrial cancer (EC) that is capable of monitoring differential drug responses in a pre-clinical setting. Fresh tumour was obtained post-hysterectomy from 27 patients with EC. Tumours were cut into 1–3 mm3 explants that were cultured at the air-liquid interface for 16–24 h in culture media. Explants were cultured in different media conditions to optimise viability. Explants were also treated with carboplatin/paclitaxel or pembrolizumab for 24 h and processed into histology slides. Multiplexed immunofluorescence for Ki67 (proliferation marker), cPARP (apoptosis marker) and CAM 5.2 (tumour mask) was performed followed by image analysis and quantitation of biomarker expression. EC samples are amenable to PDE culture with preserved histological architecture and PDE viability for up to 48 h, with the addition of autologous serum in culture media facilitating EC-PDE viability. Our PDE platform provides evidence of differential drug-response to conventional chemotherapeutics and immune checkpoint inhibition, and these responses can be assessed in the context of a preserved tumour microenvironment. Our PDE platform represents a rapid, low-cost pre-clinical model which can be easily integrated into drug development pipelines. PDE culture preserves original tumour architecture and enables evaluation of spatial relationships in the tumour microenvironment. PDE culture has the potential for personalised drug-testing in a pre-clinical setting which is increasingly important in an era of personalised medicine in the treatment of EC. • Endometrial cancer PDEs are viable for 48 h with optimised culture conditions. • EC-PDE culture preserves the tumour microenvironment and tumour heterogeneity. • EC-PDEs detect differential drug response to standard of care agents. • EC-PDEs are capable of detecting drug response to immune checkpoint inhibitors. • EC-PDEs represent a powerful pre-clinical model for drug response studies. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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