Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1-3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design. Studies in a panel of 40 HCC cell lines and 30 HCC PDX models showed that FGF19 expression is a predictive biomarker for H3B-6527 response. Moreover, coadministration of the CDK4/6 inhibitor palbociclib in combination with H3B-6527 could effectively trigger tumor regression in a xenograft model of HCC. Overall, our results offer preclinical proof of concept for H3B-6527 as a candidate therapeutic agent for HCC cases that exhibit increased expression of FGF19. .

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The effects of professional teacher dispositions on student development have been widely documented. Yet there is limited discussion of the impact of socially just dispositions. The present study critically examines the relationship between justice-oriented mind-sets in preservice teachers and their perceptions of teaching in urban schools. Using critical interpretive case study, we analyze a series of journal reflections from a diverse group of prospective teachers to determine whether exposure to service-learning opportunities within an urban school influenced their views about urban schools and students. As a result of the findings from the study, recommendations for teacher education are addressed.

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Through course readings, museum visits, focus group discussions, and reflections on clinical observation experiences, preservice teachers developed a fictitious educational setting (Courage High School) that incorporates critical, social justice practices and privileges the experiences and cultural backgrounds of all K-12 students. Participants presented a model for this school and how it would benefit specific student needs. From our classroom experiences, the authors developed recommendations for how future educators problematized ideas of courage, race, and diversity in developing Courage High School. The authors suggest that using museums as experiential pedagogical tools and offering authentic learning opportunities can encourage a critical, social justice orientation to teaching and may inspire future teachers to enact courage in their teaching practice.

Purpose The purpose of this study is to inquire into the effectiveness of authentic writing instruction embedded in a critical service-learning project in a middle school English Language Arts curriculum. Design/methodology/approach This paper analyzes middle school students’ survey responses before and after their participation in a critical service-learning project designed to engage students in authentic writing. Specifically, the paper considers students’ perspectives of community and writing as a result of their participation in the project. Findings Participants’ perspectives fell into three categories: audience influence, empowerment or personal knowledge to act and confidence in ideas. Originality/value These perspectives suggest a deviation from common findings regarding the benefits of authentic writing instruction, as the presence of an audience in this study often hindered student confidence in their abilities as writers and community change agents. Authors draw from the findings to offer recommendations to support teachers in effectively incorporating authentic writing practices and audiences into their instruction.

School districts in the U.S. are increasingly calling on content area and English as a Second Language (ESL) teachers to work together to plan and deliver instruction in classrooms with linguistically diverse students. Such programming presumes, however, that collaborative teaching dynamics are unproblematic. The aim of this article is to examine ESL and content area coteaching dyads at an urban high school in the U.S. southeast. Data were drawn from a year-long qualitative study of these classrooms and were analyzed using sociocultural perspectives on learning (Lave & Wenger, 1991; Lave, 1998). Findings highlight structural factors that inhibit the development of positive co-teaching relationships, including top-down decision-making, inadequate training for co-teaching, and lack of time for co-planning. Positive relationships were formed on the basis of shared personal and pedagogical visions, flexibility and adaptability. In addition to recommendations for school-level changes, implications of this study center on the need to prepare teacher candidates for collaborative teaching through cross-disciplinary coursework that includes opportunities to practice and reflect on co-teaching.