HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network

Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neural tissue. Here we show that HES6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for transcription factors such as E2F1. In the clinical setting, we have uncovered a HES6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted by inhibition of PLK1 with restoration of sensitivity to castration. We have therefore shown for the first time the critical role of HES6 in the development of CRPC and identified its potential in patient-specific therapeutic strategies.

Vergilius Redivivus: Studies in Joseph Addison's Latin Poetry

J.W. Binns, Modern Language Review 101.2 (2006), 504-5:
‘This book is an important contribution to the study of Anglo-Latin poetry in the late seventeenth and early eighteenth centuries … ’Haan provides an able and authoritative account …, setting the poems in their contexts, and providing for each a very clear and penetrating analysis which traces the classical well-springs that lie behind much of Addison’s Latin writing, and also calls attention to non-traditional elements’.