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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/27340

Title: Identifying Pharmacological Therapeutics for Aggressive Fibromatosis
Authors: Hong, Helen
Advisor: Alman, Benjamin
Department: Laboratory Medicine and Pathobiology
Keywords: aggressive fibromatosis
beta-catenin
wnt signaling
mouse model
Issue Date: 30-May-2011
Abstract: Aggressive fibromatosis is a fibroproliferative tumour that can occur as a sporadic lesion or a manifestation in FAP patients. Tumours are characterized by the stabilization of beta-catenin. Current therapies have yet to offer complete success for primary and recurrent tumours, and there remains a need for more effective therapeutic strategies. In this work, we demonstrate the anti-neoplastic and beta-catenin modulating capacities of Nefopam, a currently approved analgesic agent. We found that Nefopam was able to decrease cell viability and proliferation as well as total beta-catenin levels in human aggressive fibromatosis tumour cells in vitro. Furthermore, Nefopam reduced the number of tumours formed in the Apc+/Apc1638N aggressive fibromatosis mouse model. We also demonstrated that androgens contribute to the development of tumours and could also modulate beta-catenin levels as indicated in Testosterone-treated orchidectomized Apc+/Apc1638N mice. Together, this work suggests that Nefopam and androgen signaling-blocking agents are potential candidates to effectively manage aggressive fibromatosis.
URI: http://hdl.handle.net/1807/27340
Appears in Collections:Master

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