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Publications

Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery.

By:
Contributors: Andries Zijlstra Research Group, John D. Lewis Research Group, Desmond Pink, PhD
PLoS One. 2012;7(3):e33760. doi: 10.1371/journal.pone.0033760. Epub 2012 Mar 29.

Abstract

The leaky, heterogeneous vasculature of human tumors prevents the even distribution of systemic drugs within cancer tissues. However, techniques for studying vascular delivery systems in vivo often require complex mammalian models and time-consuming, surgical protocols. The developing chicken embryo is a well-established model for human cancer that is easily accessible for tumor imaging. To assess this model for the in vivo analysis of tumor permeability, human tumors were grown on the chorioallantoic membrane (CAM), a thin vascular membrane which overlays the growing chick embryo. The real-time movement of small fluorescent dextrans through the tumor vasculature and surrounding tissues were used to measure vascular leak within tumor xenografts. Dextran extravasation within tumor sites was selectively enhanced an interleukin-2 (IL-2) peptide fragment or vascular endothelial growth factor (VEGF). VEGF treatment increased vascular leak in the tumor core relative to surrounding normal tissue and increased doxorubicin uptake in human tumor xenografts. This new system easily visualizes vascular permeability changes in vivo and suggests that vascular permeability may be manipulated to improve chemotherapeutic targeting to tumors.

PubMed

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Dr. Nawaid Usmani and team receive funding for their PRIME study!

The PRIME Study – Prevention and Intervention for MEtabolic syndrome:

Androgen deprivation therapy (ADT), and newer manipulations of androgen receptor signaling have improved outcomes for advanced prostate cancer (PCa) patients.  The toxicities of ADT are many, including an increased risk of developing metabolic syndrome (MS; defined as at least 3 of: hyperglycemia; abdominal obesity; hypertriglyceridemia; reduced HDL cholesterol; and/or hypertension). MS is associated with an increased risk of diabetes, cardiovascular disease mortality, stroke mortality, and all-cause mortality.  The prevalence of MS in men receiving ADT is at least 50% and contributes to decreased quality of life and increased non-cancer-related mortality.  Metformin holds promise as a countermeasure to MS development, and also has been shown to suppress PCa growth in pre-clinical models.

We hypothesize that the addition of metformin to ADT will reduce the rates of MS in men with advanced PCa, diminishing important toxicities of a therapy universally used in advanced disease.

We propose a double-blind, randomized phase III study of metformin or placebo in men with PCa starting intermittent ADT. The primary endpoint is the difference in MS rates at 1 year.  Other aims include evaluation of the influence of metformin on: individual MS components at additional time points; mean serum insulin levels and measures of insulin resistance; weight and quality of life.

A finding that metformin reduces MS incidence and/or has other benefits would change practice, as it would provide a practical and inexpensive strategy to reduce toxicity of an intervention employed in most men with advanced PCa.

- Catalina Vasquez