Educational leadership during a decade of medical curricular innovation and renewal.

Background: The past decade has witnessed successful expansion, distribution and curricular renewal at the University of British Columbia (UBC) medical school. The expansion and distribution of the medical program doubled enrollment and established the first North American medical school training students across multiple geographical locations. The more recent competency-based curriculum renewal demonstrates sustained innovation within UBC medicine.

High ceramide content liposomes with in vivo antitumor activity.

Background: The pro-apoptotic activity of ceramide lipids has made this an exciting new target for therapeutic manipulation. While approaches using exogenous application of short-chain ceramides and modulation of endogenous ceramide levels via manipulation of metabolic pathways have been explored, controlled delivery of natural ceramide has not been previously reported. In this paper we describe the formulation of novel liposomes containing high levels of natural ceramide in the lipid bilayer for the purpose of controlled ceramide delivery.

Intracellular delivery of ceramide lipids via liposomes enhances apoptosis in vitro.

Ceramide lipids have emerged as important intracellular signalling molecules that mediate diverse cellular effects, of which programmed cell death, or apoptosis, has attracted significant interest. Although the exact mechanism(s) by which ceramides trigger apoptosis is not fully understood, there is considerable evidence that they are key mediators of this response. Exogenously applied, cell-permeable ceramides have been shown to induce apoptosis when incubated with cells in culture.

Development of an in vitro drug release assay that accurately predicts in vivo drug retention for liposome-based delivery systems.

The therapeutic activity of numerous drugs can be dramatically improved by liposomal encapsulation. However, this requires that liposomes retain their encapsulated drugs following systemic administration. Often, in vitro drug release assays do not accurately predict the liposomal drug retention properties observed in vivo.

P-glycoprotein modulates ceramide-mediated sensitivity of human breast cancer cells to tubulin-binding anticancer drugs.

Alterations in metabolism of ceramide (Cer) to the noncytotoxic metabolite glucosylceramide have been implicated in the multidrug resistance (MDR) phenomenon. This observation has been made with tumor cells that also overexpress P-glycoprotein (Pgp), raising the possibility that Pgp plays a role in regulating Cer metabolism. We investigated the effect of the glucosylceramide synthase inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on the chemosensitivity of two wild-type and multidrug-resistant human breast tumor cell lines.