S. Delanian and J. Lefaix, The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway, Radiotherapy and Oncology, vol.73, issue.2, pp.119-131, 2004.
DOI : 10.1016/j.radonc.2004.08.021

P. Gervaz, P. Morel, and M. Vozenin-brotons, Molecular Aspects of Intestinal Radiation-Induced Fibrosis, Current Molecular Medicine, vol.9, issue.3, pp.273-280, 2009.
DOI : 10.2174/156652409787847164

S. Delanian and J. Lefaix, Current Management for Late Normal Tissue Injury: Radiation-Induced Fibrosis and Necrosis, Seminars in Radiation Oncology, vol.17, issue.2, pp.99-107, 2007.
DOI : 10.1016/j.semradonc.2006.11.006

M. Hauer-jensen, J. Wang, and J. Denham, Bowel injury: current and evolving management strategies, Semin Radiat Oncol, vol.13, issue.3, pp.357-371, 2003.

M. Anscher, The Irreversibility of Radiation-Induced Fibrosis: Fact or Folklore?, Journal of Clinical Oncology, vol.23, issue.34, pp.8551-8552, 2005.
DOI : 10.1200/JCO.2005.03.6194

L. Fajardo, The pathology of ionizing radiation as defined by morphologic patterns, Acta Oncologica, vol.96, issue.1, pp.13-22, 2005.
DOI : 10.1080/02841860510007440

M. Vozenin-brotons, F. Milliat, J. Sabourin, A. De-gouville, A. Francois et al., Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression, International Journal of Radiation Oncology*Biology*Physics, vol.56, issue.2, pp.561-572, 2003.
DOI : 10.1016/S0360-3016(02)04601-1

G. Grotendorst, H. Okochi, and N. Hayashi, A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene, Cell Growth Differ, vol.7, issue.4, pp.469-480, 1996.

A. Leask, A. Holmes, C. Black, and D. Abraham, Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts, J Biol Chem, issue.15, pp.27813008-13015, 2003.

C. Bourgier, V. Haydont, F. Milliat, A. Francois, V. Holler et al., Inhibition of Rho kinase modulates radiation induced fibrogenic phenotype in intestinal smooth muscle cells through alteration of the cytoskeleton and connective tissue growth factor expression, Gut, vol.54, issue.3, pp.336-343, 2005.
DOI : 10.1136/gut.2004.051169

V. Haydont, D. Mathe, C. Bourgier, J. Abdelali, J. Aigueperse et al., Induction of CTGF by TGF-??1 in normal and radiation enteritis human smooth muscle cells: Smad/Rho balance and therapeutic perspectives, Radiotherapy and Oncology, vol.76, issue.2, pp.219-225, 2005.
DOI : 10.1016/j.radonc.2005.06.029

M. Vozenin-brotons, F. Milliat, C. Linard, C. Strup, A. Francois et al., Gene Expression Profile in Human Late Radiation Enteritis Obtained by High-Density cDNA Array Hybridization, Radiation Research, vol.161, issue.3, pp.161299-311, 2004.
DOI : 10.1667/RR3128

V. Haydont and C. Bourgier, Vozenin-Brotons MC: Rho/ROCK pathway as a molecular target for modulation of intestinal radiation-induced toxicity

C. Strup-perrot, D. Mathe, C. Linard, D. Violot, F. Milliat et al., Global gene expression profiles reveal an increase in mRNA levels of collagens, MMPs, and TIMPs in late radiation enteritis, AJP: Gastrointestinal and Liver Physiology, vol.287, issue.4
DOI : 10.1152/ajpgi.00088.2004

V. Haydont, B. Riser, J. Aigueperse, and M. Vozenin-brotons, Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-??1, AJP: Cell Physiology, vol.294, issue.6, pp.294-1332, 2008.
DOI : 10.1152/ajpcell.90626.2007

A. Ridley, Rho GTPases and cell migration, J Cell Sci, vol.114, pp.2713-2722, 2001.

E. Vieu and N. Hernandez, Actin's latest act: polymerizing to facilitate transcription?, Nature Cell Biology, vol.21, issue.7, pp.650-651, 2006.
DOI : 10.1083/jcb.200507101

M. Boerma, Q. Fu, J. Wang, D. Loose, A. Bartolozzi et al., Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin, Blood Coagulation & Fibrinolysis, vol.19, issue.7, pp.709-718, 2008.
DOI : 10.1097/MBC.0b013e32830b2891

J. Greenwood, L. Steinman, and S. Zamvil, Statin therapy and autoimmune disease: from protein prenylation to immunomodulation, Nature Reviews Immunology, vol.116, issue.5, pp.358-370, 2006.
DOI : 10.1038/nri1839

V. Haydont, O. Gilliot, S. Rivera, C. Bourgier, A. Francois et al., Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection, International Journal of Radiation Oncology*Biology*Physics, vol.68, issue.5, pp.681471-1482, 2007.
DOI : 10.1016/j.ijrobp.2007.03.044

J. Wang, M. Boerma, Q. Fu, A. Kulkarni, L. Fink et al., Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism, International Journal of Radiation Oncology*Biology*Physics, vol.68, issue.5, pp.681483-1490, 2007.
DOI : 10.1016/j.ijrobp.2007.03.036

J. Williams, E. Hernady, C. Johnston, C. Reed, B. Fenton et al., Effect of Administration of Lovastatin on the Development of Late Pulmonary Effects after Whole-Lung Irradiation in a Murine Model, Radiation Research, vol.161, issue.5, pp.161560-567, 2004.
DOI : 10.1667/RR3168

V. Monceau, N. Pasinetti, C. Schupp, F. Pouzoulet, P. Opolon et al., Modulation of the Rho/ROCK Pathway in Heart and Lung after Thorax Irradiation Reveals Targets to Improve Normal Tissue Toxicity, Current Drug Targets, vol.11, issue.11, pp.111395-1404, 2010.
DOI : 10.2174/1389450111009011395

Y. Ikawa, P. Ng, K. Endo, M. Kondo, S. Chujo et al., Neutralizing monoclonal antibody to human connective tissue growth factor ameliorates transforming growth factor????????induced mouse fibrosis, Journal of Cellular Physiology, vol.155, issue.3, pp.680-687, 2008.
DOI : 10.1002/jcp.21449

A. Abdollahi, M. Li, G. Ping, C. Plathow, S. Domhan et al., Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis, The Journal of Experimental Medicine, vol.63, issue.6, pp.925-935, 2005.
DOI : 10.1097/01.rli.0000138134.89050.a5

K. Vuorinen, F. Gao, T. Oury, V. Kinnula, and M. Myllarniemi, IMATINIB MESYLATE INHIBITS FIBROGENESIS IN ASBESTOS-INDUCED INTERSTITIAL PNEUMONIA, Experimental Lung Research, vol.79, issue.7, pp.357-373, 2007.
DOI : 10.1038/sj.leu.2404207

J. Gordon and R. Spiera, Targeting tyrosine kinases: a novel therapeutic strategy for systemic sclerosis, Current Opinion in Rheumatology, vol.22, issue.6, pp.690-695, 2010.
DOI : 10.1097/BOR.0b013e32833f1105

M. Gaugler, V. Vereycken-holler, C. Squiban, M. Vandamme, M. Vozenin-brotons et al., Pravastatin Limits Endothelial Activation after Irradiation and Decreases the Resulting Inflammatory and Thrombotic Responses, Radiation Research, vol.163, issue.5, pp.479-487, 2005.
DOI : 10.1667/RR3302

P. Noble, C. Albera, W. Bradford, U. Costabel, M. Glassberg et al., Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials, The Lancet, vol.377, issue.9779, pp.3771760-1769, 2011.
DOI : 10.1016/S0140-6736(11)60405-4

URL : https://hal.archives-ouvertes.fr/hal-00873255

L. Richeldi, U. Costabel, M. Selman, D. Kim, D. Hansell et al., Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis, New England Journal of Medicine, vol.365, issue.12, pp.3651079-1087, 2011.
DOI : 10.1056/NEJMoa1103690

S. Delanian, S. Balla-mekias, and J. Lefaix, Striking Regression of Chronic Radiotherapy Damage in a Clinical Trial of Combined Pentoxifylline and Tocopherol, Journal of Clinical Oncology, vol.17, issue.10, pp.3283-3290, 1999.
DOI : 10.1200/JCO.1999.17.10.3283

S. Delanian, R. Porcher, S. Balla-mekias, and J. Lefaix, Randomized, Placebo-Controlled Trial of Combined Pentoxifylline and Tocopherol for Regression of Superficial Radiation-Induced Fibrosis, Journal of Clinical Oncology, vol.21, issue.13, pp.2545-2550, 2003.
DOI : 10.1200/JCO.2003.06.064

S. Delanian, J. Depondt, and J. Lefaix, Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: A phase II trial, Head & Neck, vol.19, issue.2, pp.114-123, 2005.
DOI : 10.1002/hed.20121

S. Delanian, R. Porcher, J. Rudant, and J. Lefaix, Kinetics of Response to Long-Term Treatment Combining Pentoxifylline and Tocopherol in Patients With Superficial Radiation-Induced Fibrosis, Journal of Clinical Oncology, vol.23, issue.34, pp.8570-8579, 2005.
DOI : 10.1200/JCO.2005.02.4729

H. Letur-konirsch, F. Guis, and S. Delanian, Uterine restoration by radiation sequelae regression with combined pentoxifylline-tocopherol: a phase II study, Fertility and Sterility, vol.77, issue.6, pp.1219-1226, 2002.
DOI : 10.1016/S0015-0282(02)03120-5

P. Haddad, B. Kalaghchi, and F. Amouzegar-hashemi, Pentoxifylline and vitamin E combination for superficial radiation-induced fibrosis: A phase II clinical trial, Radiotherapy and Oncology, vol.77, issue.3, pp.324-326, 2005.
DOI : 10.1016/j.radonc.2005.09.014

A. Hille, H. Christiansen, O. Pradier, R. Hermann, B. Siekmeyer et al., Effekt einer Kombinationstherapie aus Pentoxifyllin und Tocopherol auf die strahleninduzierte Proktitis/Enteritis, Strahlentherapie und Onkologie, vol.181, issue.9, pp.606-614, 2005.
DOI : 10.1007/s00066-005-1390-y

L. Gothard, P. Cornes, S. Brooker, J. Earl, J. Glees et al., Phase II study of vitamin E and pentoxifylline in patients with late side effects of pelvic radiotherapy, Radiotherapy and Oncology, vol.75, issue.3, pp.75334-341, 2005.
DOI : 10.1016/j.radonc.2005.02.002

S. Delanian, M. Martin, A. Bravard, C. Luccioni, and J. Lefaix, Cu/Zn superoxide dismutase modulates phenotypic changes in cultured fibroblasts from human skin with chronic radiotherapy damage, Radiotherapy and Oncology, vol.58, issue.3, pp.325-331, 2001.
DOI : 10.1016/S0167-8140(00)00332-7

M. Vozenin-brotons, V. Sivan, N. Gault, C. Renard, C. Geffrotin et al., Antifibrotic action of Cu/Zn SOD is mediated by TGF-??1 repression and phenotypic reversion of myofibroblasts, Free Radical Biology and Medicine, vol.30, issue.1, pp.30-42, 2001.
DOI : 10.1016/S0891-5849(00)00431-7

J. Lefaix, S. Delanian, M. Vozenin, J. Leplat, Y. Tricaud et al., Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and ??-tocopherol: an experimental study, International Journal of Radiation Oncology*Biology*Physics, vol.43, issue.4, pp.839-847, 1999.
DOI : 10.1016/S0360-3016(98)00419-2

N. Ledee-bataille, F. Olivennes, J. Lefaix, G. Chaouat, R. Frydman et al., Combined treatment by pentoxifylline and tocopherol for recipient women with a thin endometrium enrolled in an oocyte donation programme, Human Reproduction, vol.17, issue.5, pp.1249-1253, 2002.
DOI : 10.1093/humrep/17.5.1249

M. Boerma, K. Roberto, and M. Hauer-jensen, Prevention and Treatment of Functional and Structural Radiation Injury in the Rat Heart by Pentoxifylline and Alpha-Tocopherol, International Journal of Radiation Oncology*Biology*Physics, vol.72, issue.1, pp.170-177, 2008.
DOI : 10.1016/j.ijrobp.2008.04.042

S. Delanian, C. Chatel, R. Porcher, J. Depondt, and J. Lefaix, Complete Restoration of Refractory Mandibular Osteoradionecrosis by Prolonged Treatment with a Pentoxifylline-Tocopherol-Clodronate Combination (PENTOCLO): A??Phase II Trial, International Journal of Radiation Oncology*Biology*Physics, vol.80, issue.3, pp.832-839, 2011.
DOI : 10.1016/j.ijrobp.2010.03.029

S. Delanian, J. Lefaix, T. Maisonobe, F. Salachas, and P. Pradat, Significant clinical improvement in radiation-induced lumbosacral polyradiculopathy by a treatment combining pentoxifylline, tocopherol, and clodronate (Pentoclo), Journal of the Neurological Sciences, vol.275, issue.1-2, pp.164-166, 2008.
DOI : 10.1016/j.jns.2008.08.004

A. Azzi, R. Gysin, P. Kempna, A. Munteanu, Y. Negis et al., Vitamin E Mediates Cell Signaling and Regulation of Gene Expression, Annals of the New York Academy of Sciences, vol.318, issue.part 2, pp.86-95, 2004.
DOI : 10.1196/annals.1331.009

R. Ricciarelli, P. Maroni, N. Ozer, J. Zingg, and A. Azzi, Age-dependent increase of collagenase expression can be reduced by ??-tocopherol via protein kinase C inhibition, Free Radical Biology and Medicine, vol.27, issue.7-8, pp.729-737, 1999.
DOI : 10.1016/S0891-5849(99)00007-6

A. Akeson, C. Woods, L. Mosher, C. Thomas, and R. Jackson, Inhibition of IL-1?? expression in THP-1 cells by probucol and tocopherol, Atherosclerosis, vol.86, issue.2-3, pp.261-270, 1991.
DOI : 10.1016/0021-9150(91)90222-O

M. Chojkier, K. Houglum, K. Lee, and M. Buck, Long-and short-term D-alphatocopherol supplementation inhibits liver collagen alpha1(I) gene expression, Am J Physiol, vol.275, issue.6, pp.1480-1485, 1998.

S. Devaraj, A. Chan, and . Jr, ??-Tocopherol Supplementation Decreases Plasminogen Activator Inhibitor-1 and P-Selectin Levels in Type 2 Diabetic Patients, Diabetes Care, vol.25, issue.3, pp.524-529, 2002.
DOI : 10.2337/diacare.25.3.524

L. Villacorta, A. Graca-souza, R. Ricciarelli, J. Zingg, and A. Azzi, alpha-Tocopherol Induces Expression of Connective Tissue Growth Factor and Antagonizes Tumor Necrosis Factor-alpha-Mediated Downregulation in Human Smooth Muscle Cells, Circulation Research, vol.92, issue.1, pp.104-110, 2003.
DOI : 10.1161/01.RES.0000049103.38175.1B

B. Horvath, Z. Marton, R. Halmosi, T. Alexy, L. Szapary et al., In Vitro Antioxidant Properties of Pentoxifylline, Piracetam, and Vinpocetine, Clinical Neuropharmacology, vol.25, issue.1, pp.37-42, 2002.
DOI : 10.1097/00002826-200201000-00007

B. Berman and M. Duncan, Pentoxifylline Inhibits Normal Human Dermal Fibroblast In Vitro Proliferation, Collagen, Glycosaminoglycan, and Fibronectin Production, and Increases Collagenase Activity, Journal of Investigative Dermatology, vol.92, issue.4, pp.605-610, 1989.
DOI : 10.1111/1523-1747.ep12712140

B. Berman and M. Duncan, Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin, British Journal of Dermatology, vol.1, issue.3, pp.339-346, 1990.
DOI : 10.1001/archderm.125.10.1390

M. Duncan, A. Hasan, and B. Berman, Pentoxifylline, Pentifylline, and Interferons Decrease Type I and III Procollagen mRNA Levels in Dermal Fibroblasts: Evidence for Mediation by Nuclear Factor 1 Down-Regulation, Journal of Investigative Dermatology, vol.104, issue.2
DOI : 10.1111/1523-1747.ep12612819

R. Janknecht, N. Wells, and T. Hunter, TGF-beta -stimulated cooperation of Smad proteins with the coactivators??CBP/p300, Genes & Development, vol.12, issue.14, pp.2114-2119, 1998.
DOI : 10.1101/gad.12.14.2114

C. Pouponnot, L. Jayaraman, and J. Massague, Physical and Functional Interaction of SMADs and p300/CBP, Journal of Biological Chemistry, vol.273, issue.36, pp.22865-22868, 1998.
DOI : 10.1074/jbc.273.36.22865

M. Schiller, F. Verrecchia, and A. Mauviel, Cyclic adenosine 3',5'-monophosphate- elevating agents inhibit transforming growth factor-beta-induced SMAD3/4-dependent transcription via a protein kinase A-dependent mechanism, Oncogene, issue.55, pp.228881-8890, 2003.
URL : https://hal.archives-ouvertes.fr/inserm-00147460

C. Laurent, J. Pouget, and P. Voisin, Modulation of DNA Damage by Pentoxifylline and ??-Tocopherol in Skin Fibroblasts Exposed to Gamma Rays, Radiation Research, vol.164, issue.1, pp.63-72, 2005.
DOI : 10.1667/RR3383