-Pan

Archer

Aristizabal

Caporale

Connor

Cousens

Covey

Daly

Daniel

DeMartini

DiMasi

Ferlay

Fish

Gaeta

Gray

Griffiths

Haramati

Heyer

House

Jassim

Johnson

Kazerooni

Khan

Klein

Kola

Kozaki

Laurent

Leroux

Linnerth-Petrik

Lynch

Marland

Martin

Mase

Masi

Mazzone

Meeusen

Moore

Mueller

Murgia

Palmarini

Pang

Paoloni

Pozzi

Saji

Salvatori

Schreiber

Scott

Sharp

Shrimpton

Suau

Swischuk

Szymanska

Tomiyama

Vlachostergios

Wallace

Yang

Yeow

Youssef

Edinburgh Research Explorer

In vitro cell line and in vivo murine models have historically dominated pre-clinical cancer research. These models can be expensive and time consuming and lead to only a small percentage of anti-cancer drugs gaining a license for human use. Large animal models that reflect human disease have high translational value; these can be used to overcome current pre-clinical research limitations through the integration of drug development techniques with surgical procedures and anesthetic protocols, along with emerging fields such as implantable medical devices. Ovine pulmonary adenocarcinoma (OPA) is a naturally-occurring lung cancer that is caused by the jaagsiekte sheep retrovirus. The disease has similar histological classification and oncogenic pathway activation to that of human lung adenocarcinomas making it a valuable model for studying human lung cancer. Developing OPA models to include techniques used in the treatment of human lung cancer would enhance its translational potential, making it an excellent research tool in assessing cancer therapeutics. In this study we developed a novel OPA model to validate the ability of miniaturized implantable O2 and pH sensors to monitor the tumor microenvironment. Naturally-occurring pre-clinical OPA cases were obtained through an on-farm ultrasound screening programme. Sensors were implanted into OPA tumors of anesthetized sheep using a CT-guided trans-thoracic percutaneous implantation procedure. This study reports the findings from 9 sheep that received sensor implantations. Time taken from initial CT scans to the placement of a single sensor into an OPA tumor was 45 ± 5 min, with all implantations resulting in the successful delivery of sensors into tumors. Immediate post-implantation mild pneumothoraces occurred in 4 sheep, which was successfully managed in all cases. This is, to the best of our knowledge, the first description of the use of naturally-occurring OPA cases as a pre-clinical surgical model. Through the integration of techniques used in the treatment of human lung cancer patients, including ultrasound, general anesthesia, CT and surgery into the OPA model, we have demonstrated its translational potential. Although our research was tailored specifically for the implantation of sensors into lung tumors, we believe the model could also be developed for other pre-clinical applications.</p

Gray, Mark E.

Sullivan, Paul

Marland, Jamie R. K.

Greenhalgh, Stephen N.

Meehan, James

Gregson, Rachael

Clutton, R. Eddie

Cousens, Chris

Griffiths, David J.

Murray, Alan

Argyle, David

Heriot Watt Pure