A dock derived compound against laminin receptor (37 LR) exhibits anti-cancer properties in a prostate cancer cell line model.

Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37 LR). 37/67 LR is a strong clinical correlate for progression, aggression, and chemotherapeutic relapse of several cancers including breast, prostate, and colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further increased by its ability to transduce physiochemical and mechanosensing signals in endothelial cells and modulate angiogenesis. Recently, it was demonstrated that 37/67 LR modulates the anti-angiogenic potential of the secreted glycoprotein pigment epithelium-derived factor (PEDF). Restoration of PEDF balance is a desirable therapeutic outcome, and we sought to identify a small molecule that could recapitulate known signaling properties of PEDF but without the additional complications of peptide formulation or gene delivery safety validation. We used an in silico drug discovery approach to target the interaction interface between PEDF and 37 LR. Following cell based counter screening and binding validation, we characterized a hit compound's anti-viability, activation of PEDF signaling-related genes, anti-wound healing, and anti-cancer signaling properties. This hit compound has potential for future development as a lead compound for treating tumor growth and inhibiting angiogenesis.

Strategies for reducing inflammation and promoting bone repair in arthritis.

Chronic forms of arthritis encompass many joint inflammatory disorders, including rheumatoid arthritis (RA), an autoimmune inflammatory disease, and osteoarthritis (OA), typically a 'wear and tear' condition that is now known to also have an inflammatory etiology. The impact of inflammation in the disease prognosis and joint degradation due to impaired repair mechanisms has long been recognized for RA, and now also for OA. Both forms of arthritis are prevalent chronic health conditions, and despite recent advances, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. There is an urgent need to develop and test new drugs that selectively target inflamed joints and to control articular inflammation while preventing healthy tissue damage. The therapeutics developed for RA might be useful for OA, since studies in humans and animal models demonstrate a key role for chronic, low-grade inflammation in the pathogenesis of OA. In this review, we discuss current and emerging new therapies for management of inflammation and promotion of cartilage and/or bone repair in RA and OA.

Sonodelivery Facilitates Sustained Luciferase Expression from an Episomal Vector in Skeletal Muscle.

Successful gene delivery to skeletal muscle is a desirable goal, not only for treating muscle diseases, but also for immunization, treatment of metabolic disorders, and/or delivering gene expression that can treat systemic conditions, such as bone metastatic cancer, for example. Although naked DNA uptake into skeletal muscle is possible, it is largely inefficient in the absence of additional chemical or physical delivery methods. We describe a system for delivery of non-viral or plasmid DNA to skeletal muscle using ultrasound-assisted sonoporation of a nanoplex combining plasmid DNA and a branched polymer based on poly(cyclooctene-graft-oligopeptide). The materials and methods described herein promise to advance the field of sonodelivery and of gene delivery to muscle for therapeutic applications since a simple system is presented that enables long-term gene expression in vivo with the promise of a minimal inflammatory gene expression profile.