Oncotarget

Research Papers:

Chemotherapy sensitivity testing on ovarian cancer cells isolated from malignant ascites

Judith E. den Ouden, Guido J.R. Zaman, Jelle Dylus, Antoon M. van Doornmalen, Winfried R. Mulder, Yvonne Grobben, Wilhelmina E. van Riel, Joanne A. de Hullu, Rogier C. Buijsman and Anne M. van Altena _

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Oncotarget. 2020; 11:4570-4581. https://doi.org/10.18632/oncotarget.27827

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Abstract

Judith E. den Ouden1, Guido J.R. Zaman2, Jelle Dylus2, Antoon M. van Doornmalen2, Winfried R. Mulder2, Yvonne Grobben2, Wilhelmina E. van Riel2, Joanne A. de Hullu1, Rogier C. Buijsman2 and Anne M. van Altena1

1 Radboud Institute for Health Sciences, Radboud University Medical Center, Obstetrics and Gynecology, Nijmegen, The Netherlands

2 Netherlands Translational Research Center B.V., Oss, The Netherlands

Correspondence to:

Anne M. van Altena,email: Anne.vanAltena@radboudumc.nl

Keywords: ovarian cancer; chemotherapy sensitivity; prediction; ascites; proliferation assays

Received: April 08, 2020     Accepted: November 12, 2020     Published: December 08, 2020

Copyright: © 2020 den Ouden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Background: In epithelial ovarian cancer (EOC), 15–20% of the tumors do not respond to first-line chemotherapy (paclitaxel with platinum-based therapy), and in recurrences this number increases. Our aim is to determine the feasibility of cell proliferation assays of tumor cells isolated from malignant ascites to predict in vitro chemotherapy sensitivity, and to correlate these results with clinical outcome.

Materials and Methods: Ascites was collected from twenty women with advanced EOC. Cell samples were enriched for tumor cells and EOC origin was confirmed by intracellular staining of CK7, surface staining of CA125 and EpCAM, and HE4 gene expression. In vitro sensitivity to chemotherapy was determined in cell proliferation assays using intracellular ATP content as an indirect measure of cell number. In vitro drug response was quantified by calculation of the drug concentration at which cell growth was inhibited with 50%. Clinical outcome was determined using post-treatment CA125 level.

Results: Cell samples of twenty patients were collected, of which three samples that failed to proliferate were excluded in the analysis (15%). Three other samples were excluded, because clinical outcome could not be determined correctly. In twelve of the fourteen remaining cases (86%) in vitro drug sensitivity and clinical outcome corresponded, while in two samples (14%) there was no correspondence.

Conclusions: Our study demonstrates the feasibility of drug sensitivity tests using tumor cells isolated from ascites of advanced EOC patients. Larger observational studies are required to confirm the correlation between the in vitro sensitivity and clinical outcome.


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