Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

Guidelines for management of ischaemic stroke and transient ischaemic attack 2008

This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation

ANT and politics:working in and on the world

Actor-network theory (ANT) comes from Science, Technology and Society (STS), a discipline that is distinctive because it thinks theoretically through a rich tradition of qualitative case studies. This means that while it is possible to define ANT in a series of abstract bullet points, attempts to do so miss most of the point. Words aren’t enough. You need to practise it. For this reason this paper draws on an ANT-inflected ethnography of farming. For related reasons we also work dialogically, because in ANT theory doesn’t pre-exist, waiting to be applied. Instead it is created, recreated, explored and tinkered with in particular research practices. Hence we argue that ANT is best understood as a sensibility to features of the world that aren’t quite those of standard social science: to the heterogeneous materialities, relationalities and uncertainties of the practices that compose the world. And, as we have also tried to show, this is a sensibility that has political consequences. ANT works on the assumption that other worlds are possible, then it tries to articulate them. The hope is that if we can craft appropriate tools for articulation it will be possible to know and make space for different and better social arrangements