title: Automated image analysis of intra-tumoral and peripheral endocrine organ vascular bed regression using 'Fibrelength' as a novel structural biomarker.
abstract: The study of vascular modulation has received a great deal of attention in recent years as knowledge has increased around the role of angiogenesis within disease contexts such as cancer. Despite rapidly expanding insights into the molecular processes involved and the concomitant generation of a number of anticancer vascular modulating chemotherapeutics, techniques used in the measurement of structural vascular change have advanced more modestly, particularly with regard to the preclinical quantification of off-target vascular regression within systemic, notably endocrine, blood vessels. Such changes translate into a number of major clinical side effects and there remains a need for improved preclinical screening and analysis. Here we present the generation of a novel structural biomarker, which can be incorporated into a number of contemporary image analysis platforms and used to compare tumour versus systemic host tissue vascularity. By contrasting the measurements obtained, the preclinical efficacy of vascular modulating chemotherapies can be evaluated in light of the predicted therapeutic window. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: PathCelerate Ltd, The BioHub, Alderley Park, Mereside, Alderley Edge, Cheshire, UK.
authors.forename: Adam
authors.identifier: 0000-0003-0772-7627
authors.initials: A
authors.lastname: Hargreaves
authors.affiliation: Oraclebio Ltd, BioCity Scotland, North Lanarkshire, Scotland, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Bigley
authors.affiliation: University of Surrey, 3660 Office of the Vice-Provost, Guildford, Surrey, UK.
authors.forename: Shirley
authors.initials: S
authors.lastname: Price
authors.affiliation: AstraZeneca PLC, Oncology iMED, Alderley Edge, Cheshire, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Kendrew
authors.affiliation: AstraZeneca PLC, Oncology iMED, Alderley Edge, Cheshire, UK.
authors.forename: Simon T
authors.initials: ST
authors.lastname: Barry
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D004703:Endocrine System / Q000098:blood supply*; D005260:Female; D007091:Image Processing, Computer-Assisted; D008175:Lung Neoplasms / Q000098:blood supply* / Q000473:pathology; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Endocrine organs; adrenal gland; fibrelength; image analysis; microvessel density; vascular modulation