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Effective treatment of squamous cell carcinomas with ingenol mebutate gel in immunologically intact SKH1 mice
Journal article   Open access   Peer reviewed

Effective treatment of squamous cell carcinomas with ingenol mebutate gel in immunologically intact SKH1 mice

S J Cozzi, T T Le, Steven Ogbourne, C James and A Suhrbier
Archives of Dermatological Research, Vol.305(1), pp.79-83
2013
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https://doi.org/10.1007/s00403-012-1270-0View
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Abstract

ingenol mebutate squamous cell carcinoma mouse model
Ingenol mebutate has recently been approved by the Federal Drug Administration (USA) as a topical treatment for actinic keratoses. Herein, we describe the efficacy of ingenol mebutate for the topical treatment of squamous cell carcinoma (SCC) using a wild-type mouse model (SKH1) and the UV-induced mouse SCC cell line, T7. Daily treatment for 2 days with 0.25 % ingenol mebutate gel produced a cure rate of 70 %, with 0 % for placebo gel. Electron microscopy revealed swelling of cancer cell mitochondria within 1 h, with disruption of the inner mitochondrial membranes evident at 6 h post treatment. Primary necrosis of cancer cells was clearly evident by 24 h. Treatment was associated with local haemorrhage and a prodigious neutrophil infiltrate, with anti-T7 antibodies also detected. This is the first report of the successful treatment of SCC tumours with ingenol mebutate gel in wild-type mice, and supports the view that ingenol mebutate induces primary necrosis and activates the immune system.

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