Inhibiting Aberrant Signal Transducer and Activator of Transcription Protein Activation with Tetrapodal, Small Molecule Src Homology 2 Domain Binders: Promising Agents against Multiple Myeloma

The signal transducer and activator of transcription (STAT) proteins represent a family of cytoplasmic transcription factors that regulate a pleiotropic range of biological processes. In particular, Stat3 protein has attracted attention as it regulates the expression of genes involved in a variety of malignant processes, including proliferation, survival, migration, and drug resistance. Multiple myeloma (MM) is an incurable hematologic malignancy that often exhibits abnormally high levels of Stat3 activity. Although current treatment strategies can improve the clinical management of MM, it remains uniformly incurable with a dismal median survival time post-treatment of 3–4 years. Thus, novel targeted therapeutics are critically needed to improve MM patient outcomes. We herein report the development of a series of small molecule Stat3 inhibitors with potent anti-MM activity <i>in vitro</i>. These compounds showed high-affinity binding to Stat3’s SH2 domain, inhibited intracellular Stat3 phosphorylation, and induced apoptosis in MM cell lines at low micromolar concentrations

Networks of violence in the production of young women's trajectories and subjectivities

© 2016 Feminist Review. This paper focuses on the deployment and interdependence of different expressions of gendered and classed violence in shaping the choices, trajectories and subjectivities of young women on vocational beauty therapy courses. It takes as its premise the understanding that, far from simply being an aberrant expression of interpersonal or intergroup aggression, violence is embedded in social life in multiple and complex ways, reverberating through women's lives to reproduce disadvantage and subordination. The paper draws on theoretical and empirical investigations of the interrelationships between structural, direct and symbolic expressions of violence and asks what this literature can offer in challenging normative, often individualised, conceptions of violence. Drawing on an ethnographic case study of National Vocational Qualification (NVQ) beauty therapy courses and the young women undertaking them, I explore the accounts of students and their tutors on becoming and being 'beauty girls'. I consider what these accounts might tell us about how forms of symbolic and interpersonal violence intersect with, reproduce and legitimise the violence involved in unequal and unjust socio-economic structures. I argue that the ways in which different forms of violence mutually reinforce each other at a micro-level produce an embodied 'sense of limits' that ultimately reproduces the structural violence of gendered and classed inequalities. The examples given illustrate both a 'chronology of violence' in young women's lives, and the way in which those lives can be understood, at least in part, as embedded in and shaped by networks of violence. Finally, I briefly consider examples of dissent and resistance, the conditions under which they might be possible and the ways in which, through the interplay of different forms of violence, they might also be curtailed