No abstract

BackgroundA model to predict chemotherapy response would provide a marked clinical benefit, enabling tailored treatment of oesophageal cancer, where less than half of patients respond to the routinely administered chemotherapy.MethodsCancer cells were established from tumour biopsies taken from individual patients about to undergo neoadjuvant chemotherapy. A 3D-tumour growth assay (3D-TGA) was developed, in which cancer cells were grown with or without supporting mesenchymal cells, then subjected to chemo-sensitivity testing using the standard chemotherapy administered in clinic, and a novel emerging HDAC inhibitor, Panobinostat.RESULTSIndividual patients cancer cells could be expanded and screened within a clinically applicable timescale of 3 weeks. Incorporating mesenchymal support within the 3D-TGA significantly enhanced both the growth and drug resistance profiles of the patients cancer cells. The ex vivo drug response in the presence, but not absence, of mesenchymal cells accurately reflected clinical chemo-sensitivity, as measured by tumour regression grade. Combination with Panobinostat enhanced response and proved efficacious in otherwise chemo-resistant tumours.ConclusionsThis novel method of establishing individual patient oesophageal cancers in the laboratory, from small endoscopic biopsies, enables clinically-relevant chemo-sensitivity testing, and reduces use of animals by providing more refined in vitro models for pre-screening of drugs. The 3D-TGA accurately predicted chemo-sensitivity in patients, and could be developed to guide tailored patient treatment. The incorporation of mesenchymal cells as the stromal cell component of the tumour micro-environment had a significant effect upon enhancing chemotherapy drug resistance in oesophageal cancer, and could prove a useful target for future drug development.

No abstract

(2016) The influence of nanotexturing of poly(lactic-co-glycolic acid) films upon human ovarian cancer cell attachment. Nanotechnology, 27 (25) A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. KEYWORDS Nanotexturing, human ovarian cancer cell, poly(lactic-co-glycolic acid), films ABSTRACT In this study, we have produced nanotextured poly(lactic-co-glycolic acid) (PLGA) films by using polystyrene (PS) particles as a template to make a polydimethylsiloxane (PDMS) mold against which PLGA is solvent cast. Biocompatible, biodegradable and nanotextured PLGA films were prepared with PS particles of diameter of 57, 99, 210, and 280 nm that produced domes of the same dimension in the PLGA surface. The effect of the particulate monolayer templating method was investigated to enable preparation of the films with uniformly ordered surface nanodomes. 2Cell attachment of a human ovarian cancer cell line (OVCAR3) alone and co-cultured with mesenchymal stem cells (MSC) was evaluated on flat and topographically nano-patterned surfaces. Cell numbers were observed to increase on the nanotextured surfaces compared to nontextured surfaces both with OVCAR3 cultures and OVCAR3-MSC co-cultures at 24 and 48 hour time points.

No abstract