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Downregulation of scar Fibroblasts by Antineoplastic Drugs: A Potential Treatment for Fibroproliferative Disorders

surgical science 2016年第6期7卷 258-271页

作者： M. Georgina Uberti Yvonne N. Pierpont Rajat Bhalla Karan Desai Martin C. Robson Wyatt G. Payne Institute for Tissue Regeneration Repair & Rehabilitation Bay Pines V.A. Healthcare System Bay Pines USA Division of Plastic surgery University of South Florida Tampa USA

The various fibroproliferative disorders affecting humans have in common excess fibroblast activity and persistent overexpression or dysregulated activity of transforming growth factor beta (TGF-β). Cancer has many similar characteristics. Antineoplastic drugs can downregulate fibroblast activity and cytokine growth factors. This study evaluates the effect of six antineoplastic drugs on keloid and dupuytren’s disease fibroblasts. Keloid, normal scar, dupuytren’s affected palmar fascia, and normal palmar fascia fibroblasts were grown and seeded into Fibroblast Populated Collagen Lattices (FPCLs). The FPCLs were treated with one of six antineoplastic drugs or left untreated as controls. At 7 days, supernatants were extracted from all FPCLs and assayed for expression of Transforming Growth Factor beta (TGF)-βsub>1sub> and TGF-βsub>2sub>. All six antineoplastic drugs significantly inhibited FPCL contraction in both fibroproliferative conditions compared with the untreated controls (p βsub>1sub> and TGF-βsub>2sub> expression was downregulated in the supernatants of all FPCLs by the drug exposure. Cytotoxicity did not occur in these studies and was not the reason for the results. Although antineoplastic drugs can have significant side effects when given systemically, these results may be minimized when given to small areas involved in fibroproliferative scarring or when given topically or intralesionally. These in vitro results suggest that antineoplastic drugs may have a utility for treating various fibroproliferative disorders and warrant further investigation.

关键词： scar Fibroblasts Antineoplastic Drugs Fibroproliferative Disorders dupuytren’s disease Keloid

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