Convection Enhanced Delivery in the Setting of High-Grade Gliomas.

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood-brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

Endpoint in ovarian cancer xenograft model predicted by nighttime motion metrics.

Despite several therapeutics showing promise in nonclinical studies, survival from ovarian cancer remains poor. New technologies are urgently needed to optimize the translation of nonclinical studies into clinical successes. While most nonclinical settings utilize subjective measures of physiological parameters, which can hamper the accuracy of the results, this study assessed the physical activity of mice in real time using an objective, non-invasive, cloud-based, digital vivarium monitoring platform. An initial range-finding study in which varying numbers of ovarian cancer cells were inoculated in mice was conducted to characterize disease progression using digital metrics such as motion and breathing rate. Data from the range-finding study were used to establish a motion threshold (MT) that might predict terminal endpoint. Using the MT, the efficacies of cisplatin and OS2966, an anti-CD29 antibody, were assessed. Results showed that MT predicted terminal endpoint significantly earlier than traditional parameters and correlated with therapeutic efficacy. Thus, continuous motion monitoring sensitively predicts terminal endpoint in nonclinical ovarian cancer models and could be applicable for drug efficacy testing.

Structure, formation and catalytic studies of a meso-palladioporphyrin intermediate in a Heck reaction.

A meso-palladioporphyrin intermediate was isolated from a Heck reaction between an iodoporphyrin and a non-activated olefin using a Pd(PPh3)2Cl2/Et3N system; its structure was characterized by NMR, MS and X-ray crystallography. Studies on its formation indicate that the Pd(II) catalyst was reduced in situ by Et3N with the assistance of water. The catalytic activity of the intermediate was confirmed by stoichiometric and catalytic reactions using a more reactive olefin, ethyl acrylate.

Site-specific prodrug release using visible light.

Using a photosensitization-singlet oxygenation-dioxetane cleavage strategy, a photodynamic prodrug system has been developed, whereby drugs bearing carbonyl groups can first be attached to a photosensitizer to give a photosensitizer-drug complex and then released from the complex upon visible light irradiation. Visible light, which has good penetration through tissue, generates singlet oxygen via the photosensitizer, which then releases the prodrug when and where required. With this system, drug mimics and methyl esters of NSAIDs have been successfully incorporated with photosensitizers related to verteporfin and then released by visible light illumination in high to quantitative yields within minutes.