Involving patients and their tissues in the research pathway is crucial for future heath innovations. There are many challenges including sustainability, logistical organisation whilst maintaining robust ethical oversight. For over a decade, TAPb has developed to become a research infrastructure to facilitate patient-centric studies across the research pipeline (from bench science, translation to human tissue and the sample component of interventional clinical trials). The TAPb platform groups researchers across academic, commercial and clinical trial sectors, and clinical services. This spreads the costs of the core team, and introduces capacity to provide specialised research services in an incremental way. TAPb is a not-for-profit, full cost recovery model that has been implemented across 7 patient clinical services within the Royal Free London NHS Foundation Trust. It supports an office of 6 fulltime staff, complemented by a number (currently about 7) part-time staff, to reflect the fluctuations in research demand. The researcher journey starts with TAPb linking NHS standard of care and research requirements to aid study design and feasibility. TAPb then provides suitable ethics and project management to develop timescales and delivery methodologies according to evolving research requirements, throughout the delivery phase. Samples and link-anonymised clinical data, and disease interpretation is provided to place samples in the correct research context. This presentation will provide an overview of the important steps which TAPb office have learnt which can make the infrastructure sustainable. Some examples of the significant research impact will be given as an illustration.

P055 Table 1 Association between CE/HD scope and dysplasia detection Abstracts A42 Gut 2021;70(Suppl 3):A1–A76 on S etem er 4, 2023 by gest. P rocted by coright. http/gut.bm jcom / G t: frst pulished as 10.113utjnl-2021-B A S L.63 on 17 S etem er 221. D ow nladed fom

Purpose Sonodynamic therapy (SDT) is emerging as a cancer treatment alternative with significant advantages over conventional therapies, including its minimally invasive and site-specific nature, its radical antitumour efficacy with minimal side effects, and its capacity to raise an antitumour immune response. The study explores the efficacy of SDT in combination with nanotechnology against pancreatic ductal adenocarcinoma. Methods A nanoparticulate formulation (HPNP) based on a cathepsin B-degradable glutamate-tyrosine co-polymer that carries hematoporphyrin was used in this study for the SDT-based treatment of PDAC. Cathepsin B levels in BxPC-3 and PANC-1 cells were correlated to cellular uptake of HPNP. The HPNP efficiency to induce a sonodynamic effect at varying ultrasound parameters, and at different oxygenation and pH conditions, was investigated. The biodistribution, tumour accumulation profile, and antitumour efficacy of HPNP in SDT were examined in immunocompetent mice carrying bilateral ectopic murine pancreatic tumours. The immune response profile of excised tumour tissues was also examined. Results The HPNP formulation significantly improved cellular uptake of hematoporphyrin for both BxPC-3 and PANC-1 cells, while increase of cellular uptake was positively correlated in PANC-1 cells. There was a clear SDT-induced cytotoxicity at the ultrasound conditions tested, and the treatment impaired the capacity of both BxPC-3 and PANC-1 cells to form colonies. The overall acoustic energy and pulse length, rather than the power density, were key in eliciting the effects observed in vitro. The SDT treatment in combination with HPNP resulted in 21% and 27% reduction of the target and off-target tumour volumes, respectively, within 24 h. A single SDT treatment elicited an antitumour effect that was characterized by an SDT-induced decrease in immunosuppressive T cell phenotypes. Conclusion SDT has significant potential to serve as a monotherapy or adjunctive treatment for inoperable or borderline resectable PDAC.

P055 Table 1 Association between CE/HD scope and dysplasia detection Abstracts A42 Gut 2021;70(Suppl 3):A1–A76 on S etem er 2, 2021 by gest. P rocted by coright. http/gut.bm jcom / G t: frst pulished as 10.113utjnl-2021-B A S L.63 on 17 S etem er 221. D ow nladed fom

Structural and mechanical differences between cancerous and healthy tissue give rise to variations in macroscopic properties such as visual appearance and elastic modulus that show promise as signatures for early cancer detection. Atomic force microscopy (AFM) has been used to measure significant differences in stiffness between cancerous and healthy cells owing to its high force sensitivity and spatial resolution, however due to absorption and scattering of light, it is often challenging to accurately locate where AFM measurements have been made on a bulk tissue sample. In this paper we describe an image registration method that localizes AFM elastic stiffness measurements with high-resolution images of haematoxylin and eosin (H\&E)-stained tissue to within 1.5 microns. Color RGB images are segmented into three structure types (lumen, cells and stroma) by a neural network classifier trained on ground-truth pixel data obtained through k-means clustering in HSV color space. Using the localized stiffness maps and corresponding structural information, a whole-sample stiffness map is generated with a region matching and interpolation algorithm that associates similar structures with measured stiffness values. We present results showing significant differences in stiffness between healthy and cancerous liver tissue and discuss potential applications of this technique.

Background. Prostaglandin El (PGE1) is known to protect the liver from I/R, however, the mechanism of cytoprotection is not well understood. This study investigates the effect of intraportal infusion of PGE1 in a warm liver ischemia/reperfusion (I/R) model on cytokines, adhesion molecules and liver structure.Materials and methods. Twenty dogs underwent laparotomy under general anesthesia. PGE1 (0.02 mu g\kg\min) was perfused through the portal vein in the PGE1 group (n = 10), or a similar volume of Ringer's solution in the control group (n = 10) for 15 min. Liver ischemia was induced by hepatic artery and portal vein occlusion and PGE1 was infused via the portal vein for 60 min. The occlusion was released and PGE1 infusion recommenced for 30 min. Blood and liver biopsies were sampled at baseline, 60 min ischemia, and 30 min reperfusion. and assessed for transaminases, cytokines, adhesion molecules, and electron microscopy.Results. PGE1 infusion significantly reduced transaminases TNF-alpha, sICAM-1, sP-selectin, and sE-selectin on ischemia and reperfusion. PGE1 reduced hepatocytic degeneration, portal and central ICAM-1 expression, central and sinusoidal VCAM-1 expression, portal and central P-selectin expression, and portal and sinusoidal E-selectin expression on reperfusion.Conclusion. Intraportal PGE1 infusion reduced I/R injury and was associated with down-regulation of ICAM-1, VCAM-1, P-selectin, and E-selectin on reperfusion. (c) 2007 Elsevier Inc. All rights reserved.