Human tissue biobanking encompasses a wide range of activities and study designs and is critical for application of a wide range of new technologies (-“omics”) to the discovery of molecular patterns of disease and for implementation of novel biomarkers into clinical trials. Pathology is the cornerstone of hospital-based tissue biobanking. Pathologists not only provide essential information identifying the specimen but also make decisions on what should be biobanked, making sure that the timing of all operations is consistent with both the requirements of clinical diagnosis and the optimal preservation of biological products. This document summarizes the conclusions of a Pathology Expert Group Meeting within the European Biological and Biomolecular Research Infrastructure (BBMRI) Program. These recommendations are aimed at providing guidance for pathologists as well as for institutions hosting biobanks on how to better integrate and support pathological activities within the framework of biobanks that fulfill international standards.
Angiogenesis is a promising target for the therapy of several diseases including cancer. This study was undertaken to characterize the antiangiogenic properties of a series of original dual thromboxane A 2 (TXA 2 ) inhibitors derived from torasemide, a marketed loop diuretic with TXA 2 antagonistic properties, by evaluating their effects on human endothelial cell migration, adhesion, and viability in vitro, as well as in the ex vivo rat aortic ring assay. All drugs tested exhibited a marked affinity toward human platelet TXA 2 receptor, significantly prevented platelet aggregation induced by U-46,619, a stable TXA 2 receptor agonist, and inhibited platelet TXA 2 synthase without affecting cyclooxygenase (COX)-1 or COX-2 enzymatic activities. These dual TXA 2 inhibitors dose dependently inhibited endothelial cell migration in chemotaxis assays using vascular endothelial growth factor (VEGF) as a chemoattractant but failed to affect cell adhesion and viability. The highest rates of cell migration inhibition were obtained with original compounds BM-567 and BM-573 (50.3 and 59.4% inhibition, respectively) when used at the final concentration of 10 M. In addition, pretreatment of endothelial cells with these two drugs significantly prevented U-46,619-induced intracellular Ca 2ϩ pool mobilization, thus suggesting a mechanistic link between inhibition of the TXA 2 pathway and reduced endothelial cell migration. Treatment of rat aortic explants with U-46,619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F 2 ) significantly enhanced vessel sprouting whereas aortic rings treated with some of the compounds, including BM-567 (N-n-pentyl-NЈ-[2-(cyclohexylamino)-5-nitrobenzenesulfonyl]urea) and BM-573 (N-tert-butyl-NЈ-[5-nitro-2-p-toluylaminobenzenesulfonyl]urea), showed a significant decrease in vessel sprouting, which was not reversed by the addition of VEGF. These data suggest that our original dual TXA 2 inhibitors bear antiangiogenic properties, mainly by inhibiting endothelial cell migration. Angiogenesis, a process by which new blood vessels are formed from preexisting vascular networks, occurs both in physiologic conditions, including wound healing, organ regeneration, ovulation, menstruation, and placenta formation, and in pathologic situations, such as rheumatoid arthritis, osteoarthritis, psoriatic skin disease, endometriosis, preeclampsia, diabetic retinopathy, and tumor growth. At the cellular level, angiogenesis is characterized by the transition of endothelial cells from a quiescent state into a metabolically active, proliferative and migrative state. This activation coincides with important changes in the metabolism of endothelial cells and their expression of numerous enzymes. Among these, cyclooxygenase
Aside from ethical considerations, the primary requirement for usage of human tissues in basic or translational research is the thorough characterization of tissues. The second, but equally essential, requirement is that tissues be collected, processed, annotated, and preserved in optimal conditions. These requirements put the pathologist at the center of tissue banking activities and of research aimed at discovering new biomarkers. Pathologists not only provide information identifying the specimen but also make decisions on what materials should be biobanked, on the preservation conditions, and on the timeline of events that precede preservation and storage. This central position calls for increased recognition of the role of the pathologist by the biomolecular community and places new demands on the pathologist's workload and scope of scientific activities. These questions were addressed by an Expert Group Meeting of the European Biological and Biomolecular Research Infrastructure (BBMRI). While detailed recommendations are published elsewhere (Bevilacqua et al., Virchows Archivs, 2010, in press), this article outlines the strategic and technological issues identified by the Expert Group and identifies ways forward for better integration of pathology in the current thrust for development of biomarker-based "personalized medicine."
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.