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Proliferation and the action of an anti-proliferative agent in Dupuytren's fibroblast cultures

Jemec, Barbara; (2000) Proliferation and the action of an anti-proliferative agent in Dupuytren's fibroblast cultures. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Dupuytren's disease (DD) is a common and disabling hand condition with proliferative and contractile properties. Treatment is surgical, but recurrence is common. Review of the literature suggested that Transforming Growth Factor β1 (TGFβ1) influenced myofibroblast differentiation, which was a cause of contraction and that DD shared certain characteristics with malignant tumours, which arise from an imbalance between proliferation and apoptosis. The hypothesis was therefore proposed that co-expression of the c-myc oncogene (mediates control of cell-cycle progression) and the bcl-2 gene (protects against apoptosis) results in an imbalance between proliferation and apoptosis in palmar fascia, leading to DD. It was furthermore suggested that the proliferation, differentiation and contractile properties of Dupuytren's disease may be inhibited by 5-fluorouracil in vitro. This was investigated utilising immunohistochemical methods in DD, non-diseased palmar fascia (NDF) from DD hands, carpal ligament (CL) and fibrosarcoma specimens, 30 day cell culture studies in DD, NDF and CL and 24 hour gel-contraction studies in DD. C-myc expression was elevated in primary DD and fibrosarcoma. Mib-1 antibody, measuring proliferation and bcl-2 were absent. C-myc expression in recurrent DD was found to be correlated to the total digital angle deformity. A single dose of 5-fluorouracil decreased proliferation for a longer time period in control DD and NDF fibroblasts than in CL. Also myofibroblast differentiation was continuously decreased in DD fibroblasts, incompletely in NDF, whilst CL was un-affected. TGFβ1 produced a general decrease in proliferation, amplified by 5-fluorouracil, and a sustained increase in myofibroblast differentiation in DD fibroblasts only, incompletely inhibited by 5-fluorouracil. 5-fluorouracil also decreased DD fibroblast contraction. These experiments demonstrated that DD is not caused by an imbalance between proliferation and apoptosis. However, 5-fluorouracil inhibited proliferation, differentiation and contraction of DD fibroblasts in vitro. It is therefore suggested that 5-fluorouracil may reduce contracture and recurrence in DD in vivo.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Proliferation and the action of an anti-proliferative agent in Dupuytren's fibroblast cultures
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Dupuytren's disease
URI: https://discovery.ucl.ac.uk/id/eprint/10102746
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