Local iontophoretic administration of cytotoxic therapies to solid tumors

Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of −0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors

Movescapes and eco‐evolutionary movement strategies in marine fish: Assessing a connectivity hotspot

Data from the Integrated Tracking of Aquatic Animals in the Gulf of Mexico (iTAG) network, and sister networks, were used to evaluate fish movements in the Florida Keys—an extensive reef fish ecosystem just north of Cuba connecting the Atlantic Ocean and Gulf of Mexico. We analysed ~2 million detections for 23 species, ranging from reef fish such as Nassau grouper (Epinephelus striatus, Serranidae) to migratory apex predators such as white sharks (Carcharodon carcharias, Lamnidae). To facilitate comparisons across species, we used an eco‐evolutionary movement strategy framework that identified measurable movement traits and their proximate and ultimate drivers. Detectability was species‐specific and quantified with a detection potential index. Life stages detected in the study area varied by species and residency varied with life stage. Four annual movement types were identified as follows: high site‐fidelity residents, range residents, seasonal migrants and general migrants. The endangered smalltooth sawfish (Pristis pectinata, Pristidae), a seasonal migrant, exhibited the greatest within‐ecosystem connectivity. Site attachment, stopover and deep‐water migration behaviours differed between individuals, species and annual movement types. All apex predators were migratory. General migrants were significantly larger than fish in the other movement types, a life‐history and movement trait combination that is common but not exclusive, as many small pelagics also migrate. Most teleosts exhibited movements associated with spawning. As concerns grow over habitat and biodiversity loss, multispecies movescapes, such as presented here, are expected to play an increasingly important role in informing ecosystem‐based and non‐extractive fisheries management strategies

Regional-scale variability in the movement ecology of marine fishes revealed by an integrative acoustic tracking network

Marine fish movement plays a critical role in ecosystem functioning and is increasingly studied with acoustic telemetry. Traditionally, this research has focused on single species and small spatial scales. However, integrated tracking networks, such as the Integrated Tracking of Aquatic Animals in the Gulf of Mexico (iTAG) network, are building the capacity to monitor multiple species over larger spatial scales. We conducted a synthesis of passive acoustic monitoring data for 29 species (889 transmitters), ranging from large top predators to small consumers, monitored along the west coast of Florida, USA, over 3 yr (2016-2018). Space use was highly variable, with some groups using all monitored areas and others using only the area where they were tagged. The most extensive space use was found for Atlantic tarpon Megalops atlanticus and bull sharks Carcharhinus leucas. Individual detection patterns clustered into 4 groups, ranging from occasionally detected long-distance movers to frequently detected juvenile or adult residents. Synchronized, alongshore, long-distance movements were found for Atlantic tarpon, cobia Rachycentron canadum, and several elasmobranch species. These movements were predominantly northbound in spring and southbound in fall. Detections of top predators were highest in summer, except for nearshore Tampa Bay where the most detections occurred in fall, coinciding with large red drum Sciaenops ocellatus spawning aggregations. We discuss the future of collaborative telemetry research, including current limitations and potential solutions to maximize its impact for understanding movement ecology, conducting ecosystem monitoring, and supporting fisheries management