Background: Activation of integrins may improve cell retention rates in stem cell transplantation. Results:The first small molecule agonist of integrin ␣4␤1 is generated and enhances cell adhesion mechanisms in vitro. Conclusion:The agonist binds at the subunit interface, inducing ligand binding with consequent displacement of compound. Significance: The agonist may improve progenitor cell retention as an adjunct to cell-based therapy.

Background:The disruption of endothelial barrier function by tumor cells was studied. Results: The attachment of tumor cells to endothelial cells leads to the disorganization of endothelial adherens junction. Conclusion: Interaction of tumor cells with endothelial cells alters endothelial signaling and facilitates cancer cell diapedesis. Significance: This study introduces new therapeutic targets for treating metastatic breast cancer.

No abstract

Inflammation drives the degradation of atherosclerotic plaque, yet there are no non-invasive techniques available for imaging overall inflammation in atherosclerotic plaques, especially in the coronary arteries. To address this, we have developed a clinically relevant system to image overall inflammatory cell burden in plaque. Here, we describe a targeted contrast agent (THI0567-targeted liposomal-Gd) that is suitable for magnetic resonance (MR) imaging and binds with high affinity and selectivity to the integrin α4β1(very late antigen-4, VLA-4), a key integrin involved in recruiting inflammatory cells to atherosclerotic plaques. This liposomal contrast agent has a high T1 relaxivity (~2 × 105 mM−1s−1 on a particle basis) resulting in the ability to image liposomes at a clinically relevant MR field strength. We were able to visualize atherosclerotic plaques in various regions of the aorta in atherosclerosis-prone ApoE−/− mice on a 1 Tesla small animal MRI scanner. These enhanced signals corresponded to the accumulation of monocyte/macrophages in the subendothelial layer of atherosclerotic plaques in vivo, whereas non-targeted liposomal nanoparticles did not demonstrate comparable signal enhancement. An inflammatory cell-targeted method that has the specificity and sensitivity to measure the inflammatory burden of a plaque could be used to noninvasively identify patients at risk of an acute ischemic event.

No abstract