The effect of 5-fluorouracil on Dupuytren fibroblast proliferation and differentiation
| Autor: | Duncan A. McGrouther, Roy Sanders, Barbara Jemec, P. J. Smith, C. Linge, Adriaan O. Grobbelaar |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Pathology medicine.medical_specialty Cell division Antimetabolites Cellular differentiation medicine.medical_treatment Drug Evaluation Preclinical Cell Count Myofibrils Recurrence medicine Humans Orthopedics and Sports Medicine Fibroblast Cells Cultured Aged Chemotherapy business.industry Cell Differentiation General Medicine Fascia Fibroblasts Middle Aged musculoskeletal system Dupuytren Contracture body regions medicine.anatomical_structure Chemotherapy Adjuvant Cell culture Case-Control Studies Female Surgery Fluorouracil Contracture medicine.symptom business Myofibroblast Cell Division |
| Zdroj: | Chirurgie de la Main. 19:15-22 |
| ISSN: | 1297-3203 |
| DOI: | 10.1016/s1297-3203(00)73455-x |
| Popis: | INTRODUCTION: Dupuytren's disease is a proliferative disease with contractile properties, prone to recur after surgery. Intra-operatively applied 5-fluorouracil has been used to avoid scar problems in the eye after glaucoma filtration surgery and was therefore investigated as a means to inhibit proliferation and myofibroblast differentiation in Dupuytren fibroblasts in vitro. METHOD: Primary cell lines were obtained by explants from Dupuytren's tissue (n = 6), non-diseased palmar fascia from patients with Dupuytren's disease (n = 3) and carpal ligament from patients undergoing carpal tunnel release (n = 3). The effect of 5-fluorouracil on proliferation was assessed by cell counting. Myofibroblast differentiation, an intergral part of Dupuytren's contracture, was investigated by staining for alpha smooth muscle actin, a marker for contractile cells, using immunohisto-chemical methods. RESULTS: A single exposure to 5-fluorouracil caused a sustained inhibition of proliferation in Dupuytren's and non-diseased fascia cultures, whilst the effect on carpal ligament cultures was transient. Untreated Dupuytren's fibroblasts exhibited the highest myofibroblast differentiation, whilst differentiation in non-diseased fascia cultures was shown to be proportional to cell density and virtually non-existent in carpal ligament cultures. After 5-fluorouracil exposure, the differentiation was significantly reduced in Dupuytren's fibroblasts cultures, reduced at high cell densities in non-diseased fascia and unchanged in carpal ligament cell cultures. DISCUSSION: 5-fluorouracil inhibits both proliferation and myofibroblast differentiation in Dupuytren's cell cultures and may have a potential use as an adjuvant treatment to Dupuytren surgery in order to reduce the rate of recurrence and contracture. |
| Databáze: | OpenAIRE |
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