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Enhancing Nuclear Safety


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Study of the respective role of TGF-beta1 and CTGF in cases of radiation enteritis and inhibition of CTGF as an anti-fibrogenic strategy

Valérie HAYDONT, doctorate thesis of the University of Paris XI, 234p., defended on the 6th December 2006.

Document type > *Mémoire/HDR/Thesis

Keywords > fibrosis, irradiation, NUCLEA

Research Unit > UPRES (Radiosensitivity of tumors and healthy tissues)

Authors > HAYDONT Valérie

Publication Date > 06/12/2006

Summary

Delayed radiation enteritis is an intestinal fibrosis induced by accidental or therapeutic radiation for pelvic and abdominal cancer treatments. Studies of molecular mechanisms involved in the development and maintenance of fibrosis have showed the respective contribution of CTGF, low TGF-β1 concentrations and Rho/ROCK pathway. Thus, based on the relationship between CTGF, TGF-β1 and Rho pathway, 2 therapeutics strategies have been develop. First, a pravastatin curative gift leads to a fibrolysis involving an inhibition of Rho and in cascade a reduction of CTGF expression and extracellular matrix deposition. The data suggest that reversal of established radiation fibrosis in the gut is possible. Second, a pravastatin prophylactic gift prevents the installation of a chronic fibrosis but does not protect the tumor. On the base of these results, the radiation therapy department of the Institut Gustave Roussy will soon initiate 2 clinical trials.


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