The recent emergence of immunotherapies is transforming cancer treatments. Although many cancer immunotherapies are finding enormous success for treating hematologic tumors, a major obstacle for the treatment of solid tumors is localizing immune cells to the tumor site. Therefore, we have developed a technology that is capable of directing immune cell migration. Specifically, we have packaged chemokines, signaling molecules that promote immune cell migration, inside polyethylene glycol decorated-liposomes. The release profiles of chemokines and other large molecules from the liposomes have been examined in serum-containing media. We have demonstrated that the liposomes are able to release chemokines to induce immune cell migration. Additionally, these liposomes have been shown in vitro to limit cancer cell growth through increased immune cell recruitment. This strategy of encapsulating chemokines within liposomes paves the way for additional cancer immunotherapies and chemokine-based therapies.
Sodium fluoroacetate (1080) is a highly toxic metabolic poison that has the potential because of its lack of defined color, odor, and taste and its high water solubility to be intentionally or unintentionally ingested through food adulteration. Although the mechanism of action for 1080 has been known since the 1950's, no known antidote exists. In an effort to better understand the cardiopulmonary impacts of 1080, we utilized whole-body plethysmography and telemeterized Sprague-Dawley rats which allowed for the real-time measurement of respiratory and cardiac parameters following exposure using a non-invasive assisted-drinking method. Overall, the animals showed marked depression of respiratory parameters over the course of 24 hours post-exposure and the development of hemorrhage in the lung tissue. Tidal volume was reduced by 30% in males and 60% in females at 24 hours post-exposure, and respiratory frequency was significantly depressed as well. In telemeterized female rats, we observed severe cardiac abnormalities, highlighted by a 50% reduction in heart rate, 75% reduction in systolic blood pressure, and a 3.5-fold lengthening of the QRS interval over the course of 24 hours. We also observed a reduction in core body temperature of nearly 15°C. Our study was able to describe the severe and pronounced effects of sodium fluoroacetate poisoning on cardiopulmonary function, the results of which indicate that both tissue specific and systemic deficits contribute to the toxicological progression of 1080 intoxication and will need to be accounted for when developing any potential countermeasure for 1080 poisoning.
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