Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer

Gothard, Lone; Cornes, Paul; Earl, Judith; Hall, Emma; MacLaren, Julie-Ann; Mortimer, Peter; Peacock, John; Peckitt, Clare; Woods, Mary; Yarnold, John

doi:10.1016/j.radonc.2004.09.013

Cited by 98 publications

(55 citation statements)

References 12 publications

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“…Five-micrometer paraffin-embedded sections were stained with Masson trichrome and the collagen deposition was quantified by Image J software. 7 Lesions were scored dystrophic when Research.…”

Section: Methodsmentioning

confidence: 99%

Pravastatin Inhibits the Rho/CCN2/Extracellular Matrix Cascade in Human Fibrosis Explants and Improves Radiation-Induced Intestinal Fibrosis in Rats

Haydont

Bourgier

Pocard

et al. 2007

Clinical Cancer Research

127

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Purposes: Intestinal complications after radiotherapy are caused by transmural fibrosis and impair the quality of life of cancer survivors. Radiation fibrosis was considered permanent and irreversible, but recently, its dynamic nature was shown, providing new opportunities for the development of antifibrotic therapies. Among these new targets, we identified the Rho/ROCK pathway and thought to investigate whether pravastatin treatment inhibits Rho pathway activation and elicits an antifibrotic action. Experimental Design: Rho and ROCK activities were monitored in human explants presenting radiation fibrosis remodeling after incubation with pravastatin. Subsequent modulation of CCN2, type I collagen, and fibronectin expression were assessed ex vivo and in intestinal smooth muscle cells derived from radiation enteropathy. Then, the therapeutic relevance of the antifibrotic action of pravastatin was explored in vivo in a rat model of chronic radiation fibrosis (19 Gy X-rays) treated with 30 mg/kg/d pravastatin in the drinking water. Results:The results obtained with human explants show that pravastatin specifically inhibits Rho activity in submucosal mesenchymal cells. Pravastatin also elicits ROCK inhibition, and subsequent CCN2 production in human explants and smooth muscle cells isolated from radiation enteropathy. Inhibition of type I collagen and fibronectin does occur, showing that pravastatin modulates the secretory phenotype of mesenchymal cells. Lastly, curative pravastatin administration improves radiation enteropathy in rats. This structural improvement is associated with decreased deposition of CCN2 and subsequent decreased extracellular matrix deposition. Conclusion: Targeting established fibrosis with pravastatin is an efficient and safe antifibrotic strategy in radiation-induced enteropathy, and is easily transferable into the clinic.

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Section: Methodsmentioning

confidence: 99%

Pravastatin Inhibits the Rho/CCN2/Extracellular Matrix Cascade in Human Fibrosis Explants and Improves Radiation-Induced Intestinal Fibrosis in Rats

Haydont

Bourgier

Pocard

et al. 2007

Clinical Cancer Research

127

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“…Therefore, successful strategies to improve patient well being must separate sensation from actual limb volume. Incremental improvements in therapeutic manoeuvres will require a precise and reproducible method of measuring limb volume [25].…”

Section: Prevalence Of Lymphedemamentioning

confidence: 99%

Measurement of limb volume: Laser scanning versus volume displacement

McKinnon

Wong

Temple

et al. 2007

Journal of Surgical Oncology

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“…Recently, PTX has been of interest in radiation oncology for the improvement of tumor perfusion and tumor oxygenation [9][10][11][12]. In several clinical and experimental studies, PTX was also shown to diminish the severity of late radiation injury, however, it remains to be shown whether PTX is beneficial in the prevention of early radiation injury [12][13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Preventive Effect of Pentoxifylline on Acute Radiation Damage via Antioxidant and Anti-inflammatory Pathways

Hepgül

Tanrikulu

Ünalp³

et al. 2009

Dig Dis Sci

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Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer

Cited by 98 publications

References 12 publications

Pravastatin Inhibits the Rho/CCN2/Extracellular Matrix Cascade in Human Fibrosis Explants and Improves Radiation-Induced Intestinal Fibrosis in Rats

Pravastatin Inhibits the Rho/CCN2/Extracellular Matrix Cascade in Human Fibrosis Explants and Improves Radiation-Induced Intestinal Fibrosis in Rats

Measurement of limb volume: Laser scanning versus volume displacement

Preventive Effect of Pentoxifylline on Acute Radiation Damage via Antioxidant and Anti-inflammatory Pathways

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