Cover & Contents

SPIRIT figure showing schedule of events in cohort 2 of the trial. (PDF 180 kb

Additional file 5: of Tropomyosin Receptor Antagonism in Cylindromatosis (TRAC), an early phase trial of a topical tropomyosin kinase inhibitor as a treatment for inherited CYLD defective skin tumours: study protocol for a randomised controlled trial

SPIRIT figure showing schedule of events in cohort 1 of the trial. (PDF 140 kb

Ku55933 and NU7441 altered CaP cell lines cell cycle and increased apoptosis.

<p><b>LNCaP (A&C)</b> and <b>PC3 (B&D)</b> cells were incubated with Ku55933 (10 µM) and/or NU7441 (1 µM) before being exposed to the indicated doses of IR or doxorubicin for 48 h and then stained with PI and analysed directly on FACscan. Data is a representative three independent experiments. <b>LNCaP (E)</b> and <b>PC3 (F)</b> cells were treated as described above and stained with FITC-conjugated anti caspase 3 antibody before direct analysis on FACScan. Results are the mean of three independent experiments ± SD.</p

Ku55933 and NU7441 increased DNA DSB in CaP cell lines.

<p><b>LNCaP (A&C)</b> and <b>PC3 (B&D)</b> cells were treated with 10 Gy or 1 µM doxorubicin following 1 h incubation with Ku55933 (10 µM) and/or NU7441 (1 µM) and stained with FITC-conjugated H2AX antibody before being analysed directly on FACscan. Results are the mean of at least 5 independent experiments±SEM. <b>PC3 (E)</b> cells were treated as above for 24 h and analysed using comet assay, 50 cells were counted per arm treatment. Results are the mean of 3 independent experiments ± SEM.</p

Ku55933 and/or NU7441 sensitised CaP cells to IR or doxorubicin.

<p><b>LNCaP (A&B)</b> or <b>PC3 (C&D)</b> cells were seeded in different densities and left to attach before 1 h incubation with varying concentration of Ku55933 or NU7441 prior to irradiation 1 Gy or 10 nM doxorubicin treatment for 24 h (<i>P</i><0.001). <b>LNCaP (E&F)</b> or <b>PC3 (G&H)</b> cells were seeded in different densities and left to attach before 1 h incubation with Ku55933 (10 µM) or NU7441 (1 µM) prior to treatment with varying IR doses or doxorubicin concentration for 24 h (<i>P</i><0.001). All results are the mean of three independent experiments ± SEM.</p

Nile red staining of lipids.

<p>A) DMSO. B) 250 nM DEX. C) 3.2 μM PBDE mixture. D) 25.5 μM PBDE mixture. E) 3 μM DE-71. F) 12 μM DE-71. G) 1.5 μM BDE-47. H) 12 μM BDE-47. I) Percentage of adipocytes present following differentiation.</p