Multipotent Capacity of Immortalized Human Bronchial Epithelial Cells

While the adult murine lung utilizes multiple compartmentally restricted progenitor cells during homeostasis and repair, much less is known about the progenitor cells from the human lung. Translating the murine stem cell model to humans is hindered by anatomical differences between species. Here we show that human bronchial epithelial cells (HBECs) display characteristics of multipotent stem cells of the lung. These HBECs express markers indicative of several epithelial types of the adult lung when experimentally tested in cell culture. When cultured in three different three-dimensional (3D) systems, subtle changes in the microenvironment result in unique responses including the ability of HBECs to differentiate into multiple central and peripheral lung cell types. These new findings indicate that the adult human lung contains a multipotent progenitor cell whose differentiation potential is primarily dictated by the microenvironment. The HBEC system is not only important in understanding mechanisms for specific cell lineage differentiation, but also for examining changes that correlate with human lung diseases including lung cancer

Detection of Fcγ receptors on human endothelial cells stimulated with cytokines tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)

This investigation was conducted to detect Fcγ receptors (FcγR) on cytokine-stimulated human endothelial cells (EC) by measuring anti-FcγR MoAb binding with an ELISA. TNF-α and IFN-γ significantly increased the expression of FcγR type II (FcγRII) and type III (FcγRIII) on aortic EC. Simultaneous treatment with both cytokines had a synergistic effect and pretreatment of EC with IFN-γ augmented the effect of TNF-α. The greatest effect was the increase (up to four-to-six-fold) in expression of FcγRII found by the simultaneous treatment of aortic EC with both cytokines. The receptors were expressed on the cell surface and showed receptor capping after incubation at 37°C. This study showed that the inflammatory cytokines TNF-α and IFN-γ enhanced low-affinity FcγR expression on human EC in vitro. The expression of FcγR may contribute to the specific localization of circulating immune complexes on blood vessels in areas of vasculitis

IDH2 mutations define a unique subtype of breast cancer with altered nuclear polarity.

Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. Cancer Res; 76(24); 7118-29. ©2016 AACR

Top manager effects on buprenorphine adoption in outpatient substance abuse treatment programs.

To examine the influence of top managers\u27 characteristics on the adoption of buprenorphine for opioid dependence among U.S. outpatient substance abuse treatment units, this investigation analyzed a cross-sectional national study of 547 such units in the 2004-2005 wave of the Drug Abuse Treatment System Survey. Administrators reported their demographics, training, and treatment orientation, as well as features of the unit and its pattern of use of buprenorphine. Nationally, 15.8% of programs offered any buprenorphine services. Greater adoption of buprenorphine correlated with directors\u27 younger age, longer tenure, male gender, and weaker endorsement of abstinence as the most important treatment goal. Availability of naltrexone and medical services also correlated positively with buprenorphine adoption. The authors conclude that leaders\u27 characteristics are related to the adoption of innovative practices in addiction treatment programs. Future work should examine whether leadership development for community addiction programs might speed up the diffusion of buprenorphine and other innovative, evidence-based practices