Tigilanol Tiglate-Mediated Margins: A Comparison With Surgical Margins in Successful Treatment of Canine Mast Cell Tumours

Abstract

Tigilanol tiglate (TT) is a novel small molecule registered as a veterinary pharmaceutical for intratumoural treatment of canine mast cell tumours (MCTs). The drug has a multifactorial mode of action resulting in rapid destruction of the treated tumour by haemorrhagic necrosis and subsequent slough of the necrotic tumour to reveal a tissue deficit that is left to heal by second intention with minimal to no veterinary intervention. Here we introduce the concept of TT-mediated margins, the calculated margin of tissue loss analogous to surgically applied margins to help clinicians conceptualise tissue deficits formed following tumour destruction by TT relative to surgical excision. We used data from 51 dogs that were recurrence-free 12 months after a single administered TT dose into a single target MCT <10 cm3 in volume in a randomised, controlled clinical trial in the USA. We calculated TT-mediated margins based on length of the longest axis of (i) the tumour prior to treatment and (ii) the maximum tissue deficit formed 7–14 days after TT treatment. We compared these TT-mediated margins for each tumour to two surgical approaches to MCT excision in general practise: modified proportional margins (with 2 cm upper limit) and 3 cm fixed margins. For most dogs, TT-mediated margins were less than half the length of the margins calculated for the two surgical approaches in removing the same tumour. There was a trend for TT-mediated margins to increase with increasing tumour volume. Nonetheless, even for the larger tumours in this study (>2 cm3 volume), 50% of TT-mediated margins were less than half the length of the two surgical margins. Eighteen cases were lower limb MCTs, sites often surgically challenging in veterinary practise. On these lower limbs, TT-mediated margins were less than half the length of the corresponding proportional margins in 56% of cases and larger than proportional margins in only two cases. This study suggests that, in many cases, smaller and more targeted margins could be expected when treating MCTs <10 cm3 volume with TT compared with surgical excision. TT-mediated margins are a novel approach to conceptualise tissue deficits after intratumoural TT treatment.

Clinical, histopathological, and molecular characterization of canine pigmented viral plaques

“…None of the cases were treated with tiginalol glycate, which is currently only commercially available as an intratumoral treatment for canine mast cell tumors. 6,9 Azithromycin was proposed as medical treatment for canine papillomatosis and was later used to treat PVPs in dogs without any effect on the size or number of lesions. Similarly, azithromycin was found to be uneffective in a single case in this series and it is reasonable that it could be abandoned, although a proper efficacy study in PVPs is lacking.…”

“…1a-d). Single lesions were distributed over the head (6), trunk (3), and limbs (3); the exact localization was not reported for 1 dog. The most common site of multiple grouped viral plaques was the abdomen (9 cases as single site, 6 cases with multiple sites including the abdomen).…”

An Engineered Heat-Inducible Expression System for the Production of Casbene in Nicotiana benthamiana

“…Our research focused on the production of the gem-dimethylcyclopropyl class of bioactive casbene-derived diterpenoids from Euphorbiaceae species, using Nicotiana benthamiana as a plant platform to synthesize these exogenous molecules [12]. Tiglianol tigliate is for example a casbene-derived veterinary pharmaceutical, registered to treat mast cell tumors in dogs [13]. However, it is currently only extracted from Fontainea picrosperma seeds, a sub-canopy tree native to a restricted area of the Queensland rainforest [14].…”