Development of a long term, ex vivo, patient-derived explant model of endometrial cancer.

Autor: van der Woude H; Department of Obstetrics, Gynaecology and Women's Health, University of Otago, Wellington, New Zealand., Phan K; Department of Obstetrics, Gynaecology and Women's Health, University of Otago, Wellington, New Zealand., Kenwright DN; Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand., Goossens L; Medical Photography, Capital, Coast and Hutt Valley, Wellington, New Zealand., Hally KE; Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand., Currie MJ; Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand., Kokkinos J; Pancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, Australia., Sharbeen G; Pancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, Australia., Phillips PA; Pancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, Australia., Henry CE; Department of Obstetrics, Gynaecology and Women's Health, University of Otago, Wellington, New Zealand.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Apr 18; Vol. 19 (4), pp. e0301413. Date of Electronic Publication: 2024 Apr 18 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0301413
Abstrakt: Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 van der Woude et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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