Bibliography of Publications by Paul B. Sears (1891-1990)

Author Institution: Department of Biology, Denison universityAuthor Institution: Department of Pathology, The Ohio State UniversityPaul B. Sears authored or coauthored more than 550 publications from 1914 to 1988. They included journal articles, abstracts or complete papers presented at meetings, book chapters, books, magazine articles, letters, many book reviews and editorials. Subjects discussed ranged from entomology and cytology to palynology/paleoecology to many aspects of ecology, conservation and conservation education. Numbers of publications peaked in several years of the 1950s, ranging from 20 to 30 per year. This bibliography is largely complete, but items may well have been missed because Sears was so prolific. This listing was current circa 2005

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK

Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting in multiple schwannomas and meningiomas. There are no FDA approved therapies for these tumors and their relentless progression results in high rates of morbidity and mortality. Through a combination of high throughput screens, preclinical in vivo modeling, and evaluation of the kinome en masse, we identified actionable drug targets and efficacious experimental therapeutics for the treatment of NF2 related schwannomas and meningiomas. These efforts identified brigatinib (ALUNBRIG®), an FDA-approved inhibitor of multiple tyrosine kinases including ALK, to be a potent inhibitor of tumor growth in established NF2 deficient xenograft meningiomas and a genetically engineered murine model of spontaneous NF2 schwannomas. Surprisingly, neither meningioma nor schwannoma cells express ALK. Instead, we demonstrate that brigatinib inhibited multiple tyrosine kinases, including EphA2, Fer and focal adhesion kinase 1 (FAK1). These data demonstrate the power of the de novo unbiased approach for drug discovery and represents a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies

Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas

Objectives/Hypothesis: Recent studies indicate that vestibular schwannomas (VSs) rely on phosphatidylinositol 3-kinase/AKT activation to promote cell proliferation and survival; therefore, targeting AKT may provide new therapeutic options. We have previously shown that AR42, a novel histone deacetylase inhibitor, potently suppresses VS growth in vitro at doses correlating with AKT inactivation. The objectives of the current study were translational: 1) to examine the end biologic effects of AR42 on tumor growth in vivo, 2) to validate AKT as its in vivo molecular target, 3) to determine whether AR42 penetrates the blood-brain barrier (BBB), and 4) to study the pharmacotoxicity profile of AR42. Study Design: In vivo mouse studies. Methods: AR42 was dosed orally in murine schwannoma allografts and human VS xenografts. Magnetic resonance imaging was used to quantify changes in tumor volume, and intracellular molecular targets were analyzed using immunohistochemistry. BBB penetration was assayed, and both blood-chemistry measurements and histology studies were used to evaluate toxicity. Results: Growth of schwannoma implants was dramatically decreased by AR42 at doses correlating with AKT dephosphorylation, cell cycle arrest, and apoptosis. AR42 penetrated the BBB, and wild-type mice fed AR42 for 6 months behaved normally and gained weight appropriately. Blood-chemistry studies and organ histology performed after 3 and 6 months of AR42 treatment demonstrated no clinically significant abnormalities. Conclusions: AR42 suppresses schwannoma growth at doses correlating with AKT pathway inhibition. This orally bioavailable drug penetrates the BBB, is well tolerated, and represents a novel candidate for translation to human VS clinical trials. © 2011 The American Laryngological, Rhinological, and Otological Society, Inc

AR42, a novel histone deacetylase inhibitor, as a potential therapy for vestibular schwannomas and meningiomas

Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease that results in the formation of bilateral vestibular schwannomas (VSs) and multiple meningiomas. Treatment options for NF2-associated tumors are limited, and to date, no medical therapies are FDA approved. The ideal chemotherapeutic agent would inhibit both VS and meningiomas simultaneously. The objectives of this study are (1) to test the efficacy of AR42, a novel histone deacetylase inhibitor, to inhibit VS and meningioma growth and (2) to investigate this drug\u27s mechanisms of action. Primary cultures of human VS and meningioma cells were established. Nf2-deficient mouse schwannoma and benign human meningioma Ben-Men-1 cells were also cultured. Cells were treated with AR42, and the drug\u27s effects on proliferation and the cell cycle were analyzed using a methanethiosulfonate assay and flow cytometry, respectively. Human phospho-kinase arrays and Western blots were used to evaluate the effects of AR42 on intracellular signaling. The in vivo efficacy of AR42 was investigated using schwannoma xenografts. Tumor volumes were quantified using high-field, volumetric MRI, and molecular target analysis was performed using immunohistochemistry. AR42 inhibited the growth of primary human VS and Nf2-deficient mouse schwannoma cells with a half maximal inhibitory concentration (IC50) of 500 nM and 250-350 nM, respectively. AR42 also inhibited primary meningioma cells and the benign meningioma cell line, Ben-Men-1, with IC50 values of 1.5 mM and 1.0 mM, respectively. AR42 treatment induced cell-cycle arrest at G2 and apoptosis in both VS and meningioma cells. Also, AR42 exposure decreased phosphorylated Akt in schwannoma and meningioma cells. In vivo treatment with AR42 inhibited the growth of schwannoma xenografts, induced apoptosis, and decreased Akt activation. The potent growth inhibitory activity of AR42 in schwannoma and meningioma cells suggests that AR42 should be further evaluated as a potential treatment for NF2-associated tumors. © 2011 The Author(s)

The Pedagogical Value of Polling: A Coordinated 2012 Exit Poll Project across Diverse Classrooms

Several previous studies have demonstrated that student exit polling has educational value and promotes civic engagement (Berry and Robinson 2012, Evans and Lagergren 2007, Lelieveldt and Rossen 2009, and others). The authors of this paper have created assignments and an instructor\u27s manual on running student exit polls in undergraduate courses. Three institutions used these assignments during the fall 2012 semester. Working together, these instructors created an opportunity for their students to participate collaboratively with others in survey design and data analysis. This effort further provided assessment data on the effectiveness of this pedagogical approach for student engagement outside of the classroom in different communities and course contexts. Student surveys measured the impact that this experience had on their understanding of their own community, their relationship to the national community, their understanding of survey methodology, and descriptive statistics. Do students learn more about their community or the scientific process? Does it matter whether the course is designed primarily around politics, statistics, or public opinion? This paper addresses these questions and how these effects vary across different types of students and classrooms