J Transl Med
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Clinical Trial
Gastrointestinal delivery of propofol from fospropofol: its bioavailability and activity in rodents and human volunteers.
Propofol is a safe and widely used intravenous anesthetic agent, for which additional clinical uses including treatment of migraine, nausea, pain and anxiety have been proposed (Vasileiou et al. Eur J Pharmacol 605:1-8, 2009). However, propofol suffers from several disadvantages as a therapeutic outside anesthesia including its limited aqueous solubility and negligible oral bioavailability. The purpose of the studies described here was to evaluate, in both animals and human volunteers, whether fospropofol (a water soluble phosphate ester prodrug of propofol) would provide higher propofol bioavailability through non-intravenous routes. ⋯ These data suggest potential utility of oral administration of fospropofol for various therapeutic indications previously considered for propofol.
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Interleukin-12 (IL-12) has long been considered to be effective in triggering an anticancer immune response, however, the dosage has been limited by potential systemic immunotoxicity. Since focused ultrasound (FUS) has been confirmed to temporally and locally open the blood-brain barrier (BBB), the purpose of this study was to elucidate the possibility of combining FUS-induced BBB opening with IL-12 delivery to enhance the anticancer immunological response for glioma treatment. ⋯ This study provides evidence that FUS-BBB opening can enhance immune-modulating agent delivery to the brain, which improve the anticancer immune response in brain tumor treatment.
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Monoclonal antibodies (mAb) that block programmed death (PD)-1 signaling pathway hold great potential as a novel cancer immunotherapy. Recent evidence suggests that combining with conventional, targeted or other immunotherapies, these mAb can induce synergistic antitumor responses. In this study, we investigated whether Trabectedin (ET-743), a novel anticancer agent currently used for treating relapsed ovarian cancer, can synergize with anti (α)-PD-1 mAb to increase antitumor activity in the murine ID8 ovarian cancer model. ⋯ This study provides the evidence that α-PD-1 mAb can produce a synergistic antitumor efficacy when combined with Trabectedin, a clinically available anticancer agent, supporting a direct translation of this combination strategy in clinic for the treatment of ovarian cancer.
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Chronic diseases (CD) are generating a dramatic societal burden worldwide that is expected to persist over the next decades. The challenges posed by the epidemics of CD have triggered a novel health paradigm with major consequences on the traditional concept of disease and with a profound impact on key aspects of healthcare systems. ⋯ The current manuscript describes main features of the project design and the strategies put in place for its development, as well the expected outcomes during the project life-span. Moreover, the manuscript serves as introductory and unifying chapter of the different papers associated to the Supplement describing the characteristics, tools and the objectives of Synergy-COPD.
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The use of information and communication technologies to manage chronic diseases allows the application of integrated care pathways, and the optimization and standardization of care processes. Decision support tools can assist in the adherence to best-practice medicine in critical decision points during the execution of a care pathway. ⋯ Specialized decision support can be offered as a complementary service to existing policies of integrated care for chronic-disease management. The CDSS was able to issue recommendations that have a high degree of accuracy to support COPD case-finding. Integration into healthcare providers' work-flow can be achieved seamlessly through the use of a modular design and service-oriented architecture that connect to existing health information systems.