Effect of shRNA-based knockdown of btg1 on glucocorticoid-evoked cell cycle arrest and apoptosis of CEM-C7-15 human leukemia cells

Includes bibliographical references (leaves 56-60)BTG 1 (B-cell Translocation Gene 1) has been identified as an anti-proliferative protein that has a role in G1 cell cycle arrest leading to T-lymphocyte cell apoptosis. The gene, btg1 has been previously shown by microarray analysis to be upregulated by glucocorticoids (GCs) in the GC-sensitive CEM-C7-14 cells and not in the GC-resistant sister clone CEM-Cl-15. This suggests btg1 is involved in the apoptosis signaling pathway induced by GCs. (See more in text.

Introduction: Compiling ‘Endangered Knowledge’

This essay introduces a special issue of KULA on the subject of ‘endangered knowledge,’ comprising 22 essays by 34 authors working across a wide array of disciplines and fields. Guest editors Samantha MacFarlane, Rachel Mattson, and Bethany Nowviskie have assembled a collection of scholarly articles, pedagogical reflections, and project reports that take up theoretical and practical considerations of archival salvage and erasure, the persistence of the public record, indigenous knowledge, and the politics of loss. The special issue explores endangerment as a critical category of analysis for records, data, collections, languages, ecosystems, and networks

Discovery and Optimization of Quinazolinone-pyrrolopyrrolones as Potent and Orally Bioavailable Pan-Pim Kinase Inhibitors

The high expression of proviral insertion site of Moloney murine leukemia virus kinases (Pim-1, -2, and -3) in cancers, particularly the hematopoietic malignancies, is believed to play a role in promoting cell survival and proliferation while suppressing apoptosis. The three isoforms of Pim protein appear largely redundant in their oncogenic functions. Thus, a pan-Pim kinase inhibitor is highly desirable. However, cell active pan-Pim inhibitors have proven difficult to develop because Pim-2 has a low <i>K</i>_m for ATP and therefore requires a very potent inhibitor to effectively block the kinase activity at cellular ATP concentrations. Herein, we report a series of quinazolinone-pyrrolopyrrolones as potent and selective pan-Pim inhibitors. In particular, compound <b>17</b> is orally efficacious in a mouse xenograft model (KMS-12 BM) of multiple myeloma, with 93% tumor growth inhibition at 50 mg/kg QD upon oral dosing