906P - Microfluidic maintenance of ovarian tumour biopsies for the study of hypercoaguability during chemotherapy

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Ovarian Cancer
Supportive Care
Presenter Amy Dawson
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors A. Dawson1, J.B. Lutz2, K. Date2, Y. Dou2, M. Flynn3, A. Maraveyas4, J. Greenman2, L. Madden2
  • 1School Of Biological, Biomedical And Environmental Sciences, University of Hull, HU6 7RX - Kingston upon Hull/GB
  • 2Science And Engineering, University of Hull, HU6 7RX - Kingston upon Hull/GB
  • 3Department Of Gynaecological Oncology, Castle Hill Hospital, HU16 2AZ - Cottingham/GB
  • 4Clinical Oncology, Castle Hill Hospital, HU16 2AZ - Cottingham/GB

Abstract

Aim

High incidences of venous thromboembolism (VTE) are associated with cancer and the risk of VTE has been shown to be increased with chemotherapy. The observed pro-coagulant state is thought to be driven primarily by tumour cell-derived microparticles (MP) expressing surface tissue factor (TF), which may be released from the tumour in response to chemotherapy, however other mechanisms may also contribute. Current in vivo animal models of ovarian cancer have severe limitations and soothe aim of this study was to develop a microfluidic device on which individual tumour samples can be tested to monitor the behaviour of the tumour, and to identify factors that may contribute to hypercoaguability.

Methods

Ovarian tumour biopsies (2-3 mm3) obtained from newly-presenting, chemotherapy-naïve patients were placed within a microfluidic device (on-chip) with constant perfusion of cell culture media. Viability was determined over several days using a lactate dehydrogenase (LDH) release assay on media samples. Media was also analysed for procoagulant potential using a pro-thrombin time (PT) clotting assay. Blood plasma samples from the same patients were analysed for PT time and also for TF-positive MP (TFMP) levels using flow cytometry.

Results

Ex-vivo ovarian tumour tissue (n = 20) was successfully maintained on-chip for up to 160h with minimal LDH release. Data obtained following paclitaxel drug treatment of ovarian tumour tissue on-chip indicated that there was an increased procoagulant activity in some samples. PT of plasma samples from the same ovarian cancer patients showed a near logarithmic relationship with the levels of TFMP detected in plasma where increased TFMP concentrations resulted in faster PT (n = 11, p < 0.05).

Conclusions

Tumour tissue was successfully maintained within a microfluidic system that enabled analysis of the tissue in response to chemotherapy treatment. It may therefore prove a useful tool in investigating data from both in vivo work and clinical studies that document the link between chemotherapy, VTE and MP.

Disclosure

All authors have declared no conflicts of interest.