A theory of venturing: A critical realist explanation of why my father is not like Richard Branson

This article presents a theory of venturing using a critical realist approach. Venturing is presented as an outcome of reflexive engagement between individuals and circumstances, where opportunity is perceived in relation to some idiosyncratically defined value. Traditionally, venturing has been considered as necessarily involving financial value orientation. Removing the primacy of financial ambitions affords better explanation of real-life business activity. Venturing is presented also as temporally informed and informing through a lifetime, and thus it influences ongoing work choices, including further venturing. The benefits to theory and practice are outlined, including informing support of disparate venturing and of entrepreneurship as a specific type

Differential Effects of Genistein on Prostate Cancer Cells Depend on Mutational Status of the Androgen Receptor

Blocking the androgen receptor (AR) activity is the main goal of therapies for advanced prostate cancer (PCa). However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent) activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A) mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L) stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy