Journal: EMBO Molecular Medicine

Article Title: Targeting aurora kinases limits tumour growth through DNA damage-mediated senescence and blockade of NF-κB impairs this drug-induced senescence

doi: 10.1002/emmm.201201378

Figure Lengend Snippet: A,B. Biopsy tumour tissues from 19 melanoma patients were implanted into nude mice and when tumours formed they were passaged by implantation into treatment groups ( n ≥ 4 mice per group). Tumour-bearing mice received MLN8054 (60 mg/kg) or vehicle alone ( A ), MLN8237 (30 mg/kg) or vehicle alone ( B ), once daily by oral gavage for 2–6 weeks depending on their response to the treatment or the tumour volume. Mean tumour volumes ± SEM are shown for patient V13 ( A ) or V35 ( B ) as representative patient tumours. C. Hs294T melanoma cells were injected subcutaneously into nude mice (2 × 10 6 cells per mouse). After 1 week, tumour-bearing mice were treated with vehicle control or MLN8237 (30 mg/kg) once daily for 28 days. Tumour volume was then evaluated to determine response to the drug. Mean tumour volumes ± SEM for five mice per treatment group are shown. D. Tissue microarray (TMA) slides from patient melanoma tumour implants growing on mice treated with vehicle control or MLN8237 were stained for pAURKA (T-288) (red), alpha tubulin (green) and DAPI (blue) to identify cells with p-AURKA associated with the nuclear spindle microtubule complex (yellow) (see insert enlargement in upper panel). E. Histological features of the H&E stained patient melanoma tissues from mice treated with vehicle or MLN8237. F. Ki67 (proliferation marker) staining of patient tissues from mice treated with MLN8237 or vehicle control.

Article Snippet: Aurora kinase inhibitors MLN8054 and MLN8237 (Alisertib) were obtained from Millennium Pharmaceuticals, Inc.

Techniques: Injection, Control, Microarray, Staining, Marker