A novel form of cell-to-cell communication involving the formation and shedding of large vesicular structures, called microvesicles (MVs), from the surfaces of highly aggressive forms of human cancer cells has been attracting increasing amounts of attention. This is in large part due to the fact that MVs contain a variety of cargo that is not typically thought to be released from cells including cell-surface receptor tyrosine kinases, cytosolic and nuclear signaling proteins and RNA transcripts. MVs, by sharing their contents with other cells, can greatly impact cancer progression by increasing primary tumor growth,1–3 as well as by promoting the development of the pre-metastatic niche.4 We have recently shown that the small GTPase RhoA is critical for MV biogenesis in human cancer cells. Moreover, we have now obtained evidence that implicates the highly related small GTPases, Rac and Cdc42, in regulating the loading of specific cargo into MVs, as well as in the shedding of MVs from cancer cells. Thus, linking the Rho family of small GTPases to MV biogenesis has begun to shed some light on a new and unexpected way that these signaling proteins contribute to human cancer progression.

Pharmacists, with expertise in optimizing drug therapy outcomes, are valuable components of the healthcare team and are becoming increasingly involved in public health efforts. Pharmacists and pharmacy technicians in diverse community pharmacy settings can implement a variety of asthma interventions when they are brief, supported by appropriate tools, and integrated into the workflow. The Asthma Friendly Pharmacy (AFP) model addresses the challenges of providing patient-focused care in a community pharmacy setting by offering education to pharmacists and pharmacy technicians on asthma-related pharmaceutical care services, such as identifying or resolving medication-related problems; educating patients about asthma and medication-related concepts; improving communication and strengthening relationships between pharmacists, patients, and other healthcare providers; and establishing higher expectations for the pharmacist’s role in patient care and public health efforts. This article describes the feasibility of the model in an urban community pharmacy setting and documents the interventions and communication activities promoted through the AFP model.

SUMMARY

Rho GTPases impact a number of activities important for oncogenesis. Here we describe a small molecule inhibitor which blocks oncogenic transformation induced by various Rho GTPases in fibroblasts, and the growth of human breast cancer and B lymphoma cells, without affecting normal cells. We identify the target of this inhibitor to be the metabolic enzyme glutaminase, which catalyzes the hydrolysis of glutamine to glutamate. We show that transformed fibroblasts and breast cancer cells exhibit elevated glutaminase activity that is dependent on Rho GTPases and NFκB activity, and is blocked by the small molecule inhibitor. These findings highlight a previously unappreciated connection between Rho GTPase activation and cellular metabolism, and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation.

The binding of capped RNAs to the cap-binding complex (CBC) in the nucleus, and their dissociation from the CBC in the cytosol, represent essential steps in RNA-processing. Here we show how the nucleocytoplasmic transport proteins, importin-α and importin-β, play key roles in regulating these events. As a first step toward understanding the molecular basis for this regulation, we determined a 2.2 Å resolution x-ray structure for a CBC-importin-α complex that provides a detailed picture for how importin-α binds to the CBP80 subunit of the CBC. Through a combination of biochemical studies, x-ray crystallographic information, and small-angle scattering experiments, we then determined how importin-β binds to the CBC through its CBP20 subunit. Together, these studies enable us to propose a model describing how importin-β stimulates the dissociation of capped RNA from the CBC in the cytosol following its nuclear export.

The nuclear cap-binding complex (CBC), a heterodimer comprised of a 20 kDa subunit (CBP20) and an 80 kDa regulatory subunit (CBP80), binds to nascent RNA polymerase II transcripts and is important throughout different aspects of RNA metabolism. In a recent publication, using a combination of X-ray crystallographic information, mutagenesis studies, small-angle scattering experiments, analytical ultracentrifugation and in vivo assays, we presented evidence that importin-α and importin-β, two nucleocytoplasmic transport proteins, play key roles in regulating the binding of capped RNA by the CBC in cells. A model for how complexes between CBC and the importins cycle in and out of the nucleus and direct the proper positional binding and release of capped RNA is presented here and is discussed in light of recent publications.