Document Detail


Pathogenetic mechanisms in radiation fibrosis.
MedLine Citation:
PMID:  20888056     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Deregulation of normal regenerative responses to physical, chemical and biological toxins in susceptible individuals leads to abnormal remodelling of extracellular matrix with pathological fibrosis. Processes deregulated after radiotherapy have much in common with processes associated with fibrotic diseases affecting the heart, skin, lungs, kidneys, gastro-intestinal tract and liver. Among the secreted factors driving fibrosis, transforming growth factor beta 1 (TGFβ1) produced by a wide range of inflammatory, mesenchymal and epithelial cells converts fibroblasts and other cell types into matrix-producing myofibroblasts. Even if required for the initiation of fibrosis, inflammation and the continued stimulus of TGFβ1 may not be needed to maintain it. After myofibroblast activation, collagen production can be perpetuated independently of TGFβ1 by autocrine induction of a cytokine called connective tissue growth factor. The role of inflammation, the origins and activation of myofibroblasts as biosynthetic cells and the downstream pathways of extracellular matrix synthesis in common fibrotic states are reviewed. Oxidative stress, hypoxia and microvascular damage are also considered, before examining the same processes in the context of radiotherapy. One of the main uncertainties is the relevance of very early events, including inflammatory responses in blood vessels, to fibrosis. Despite the power of animal models, including genetic systems, the potential contribution of research based on human tissue samples has never been greater. A closer interaction between scientists researching fibrosis and radiation oncologists holds enormous promise for therapeutic advances.
Authors:
John Yarnold; Marie-Catherine Vozenin Brotons
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Publication Detail:
Type:  Journal Article     Date:  2010-09-29
Journal Detail:
Title:  Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology     Volume:  97     ISSN:  1879-0887     ISO Abbreviation:  Radiother Oncol     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8407192     Medline TA:  Radiother Oncol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  149-61     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Academic Radiotherapy Unit, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK. john.yarnold@icr.ac.uk
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