Ideas and Consequences: Richard Weaver, Sharon Crowley, and Rhetorical Politics

Although it has been ten years since Sharon Crowley called for Richard M. Weaver\u27s exclusion from the canon of rhetorical history, Weaver\u27s rhetorical positions have never been stronger, utilized in movements such as the Tea Party and current conservative rhetoric. While Crowley (2001) argued that Weaver\u27s Platonism came from his reaction to Roosevelt\u27s politics, this archival study suggests that Weaver was much more pragmatic than his political pronouncements have led scholars, such as Crowley, to believe. Before Weaver wrote polemical works such as To Write the Truth, he operated within the constraints of the philosophically rigid institutional culture of neo-Aristotelianism, and the archival record demonstrates his attenuation to this rhetorical situation. The implications for these findings diminish the effectiveness of his appropriation by political movements that are based in foundationalistic rhetoric. These implications also demonstrate how rhetorical scholarship has utilized the polemical nature of Weaver\u27s writings in the advancement of the professionalization of the discipline. © 2013 Copyright Taylor & Francis Group, LLC

A phase II clinical trial of the Aurora and angiogenic kinase inhibitor ENMD-2076 for previously treated, advanced, or metastatic triple-negative breast cancer

Abstract Background Triple-negative breast cancer (TNBC) remains an aggressive breast cancer subtype with limited treatment options. ENMD-2076 is a small-molecule inhibitor of Aurora and angiogenic kinases with proapoptotic and antiproliferative activity in preclinical models of TNBC. Methods This dual-institution, single-arm, two-stage, phase II clinical trial enrolled patients with locally advanced or metastatic TNBC previously treated with one to three prior lines of chemotherapy in the advanced setting. Patients were treated with ENMD-2076 250 mg orally once daily with continuous dosing in 4-week cycles until disease progression or unacceptable toxicity occurred. The primary endpoint was 6-month clinical benefit rate (CBR), and secondary endpoints included progression-free survival, pharmacokinetic profile, safety, and biologic correlates in archival and fresh serial tumor biopsies in a subset of patients. Results Forty-one patients were enrolled. The 6-month CBR was 16.7% (95% CI, 6–32.8%) and included two partial responses. The 4-month CBR was 27.8% (95% CI, 14–45.2%), and the average duration of benefit was 6.5 cycles. Common adverse events included hypertension, fatigue, diarrhea, and nausea. Treatment with ENMD-2076 resulted in a decrease in cellular proliferation and microvessel density and an increase in p53 and p73 expression, consistent with preclinical observations. Conclusions Single-agent ENMD-2076 treatment resulted in partial response or clinical benefit lasting more than 6 months in 16.7% of patients with pretreated, advanced, or metastatic TNBC. These results support the development of predictive biomarkers using archival and fresh tumor tissue, as well as consideration of mechanism-based combination strategies. Trial registration ClinicalTrials.gov, NCT01639248. Registered on July 12, 2012