PIM-induced phosphorylation of Notch3 promotes breast cancer tumorigenicity in a CSL-independent fashion.

Dysregulation of the developmentally important Notch signaling pathway is implicated in several types of cancer, including breast cancer. However, the specific roles and regulation of the four different Notch receptors have remained elusive. We have previously reported that the oncogenic PIM kinases phosphorylate Notch1 and Notch3.

Targetability Validation of Peptide-Functionalized Mesoporous Silica Nanoparticles in the Presence of Serum Proteins.

Demonstration of receptor-mediated targeting of nanoparticles to specific organs and/or cell types is an integral aim in many bionanomedicine development projects. However, engagement of targeted receptors with ligands on nanocarriers, which is the cornerstone of the active targeting concept, is challenging to study under biologically relevant conditions and thus often stays overlooked. In this work, we utilize an in-house established bioassay for targetability validation of mesoporous silica nanoparticles (MSNs), functionalized with high-affinity peptide ligands to somatostatin receptors via protective group chemistry, ensuring the correct orientation of the peptide's pharmacophore.

iGIST-A Kinetic Bioassay for Pertussis Toxin Based on Its Effect on Inhibitory GPCR Signaling.

Detection of pertussis toxin (PTX) activity is instrumental for the development and manufacturing of pertussis vaccines. These quality and safety measures require thousands of mice annually. Here, we describe nterference in α-mediated ignal ransduction (iGIST), an animal-free kinetic bioassay for detection of PTX, by measuring its effect on inhibitory G protein-coupled receptor (GPCR) signaling.

Targeting Somatostatin Receptors By Functionalized Mesoporous Silica Nanoparticles - Are We Striking Home?

The concept of delivering nanoformulations to desired tissues by means of targeting membrane receptors of high local abundance by ligands anchored to the nanocarrier has gained a lot of attention over the last decade. Currently, there is no unanimous opinion on whether surface functionalization of nanocarriers by targeting ligands translates into any real benefit in terms of pharmacokinetics or treatment outcomes. Having examined the published nanocarriers designed to engage with somatostatin receptors, we realized that in the majority of cases targetability claims were not supported by solid evidence of targeting ligand-targeted receptor coupling, which is the very crux of a targetability concept.