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IRSN, Institut de radioprotection et de sûreté nucléaire

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Enhancing Nuclear Safety


Research

Publications

Role of endothelium in radiation-induced damage to healthy tissue

Fabien MILLIAT, thèse de doctorat de l'Université Paris VI, 194p., soutenue le 02 mai 2007.

Document type > *Mémoire/HDR/Thesis

Keywords > radiotherapy

Research Unit > IRSN/DRPH/SRBE/LRPAT, IRSN/DRPH/SRBE/LRTE

Authors > MILLIAT Fabien

Publication Date > 02/05/2007

Summary

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy . The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibrogenic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibrogenic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells.


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