Current drug targets
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Current drug targets · Jan 2017
ReviewProgress in Therapies for Myocardial Ischemia Reperfusion Injury.
Experimental studies of acute myocardial infarction have revealed that up to half of the final infarct size may be due to reperfusion injury rather than the initial ischemic incident. Research over the past three decades has deepened our understanding of the molecular mechanisms underlying ischemic reperfusion injury and several therapeutic strategies to decrease the incidence and severity of reperfusion injury have been explored. ⋯ Studies demonstrate that nonpharmacological and pharmacological conditioning can be used together as part of a multifaceted approach to improve clinical outcomes in patients with ischemic heart disease.
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Current drug targets · Jan 2017
ReviewHematoma Expansion Following Intracerebral Hemorrhage: Mechanisms Targeting the Coagulation Cascade and Platelet Activation.
Hematoma expansion (HE), defined as a greater than 33% increase in intracerebral hemorrhage (ICH) volume within the first 24 hours, results in significant neurological deficits, and enhancement of ICH-induced primary and secondary brain injury. An escalation in the use of oral anticoagulants has led to a surge in the incidences of oral anticoagulation-associated ICH (OAT-ICH), which has been associated with a greater risk for HE and worse functional outcomes following ICH. The oral anticoagulants in use include vitamin K antagonists, and direct thrombin and factor Xa inhibitors. ⋯ Recent studies have found that reduced platelet activity may be more effective in predicting ICH risk, hemorrhage expansion, and outcomes, than antiplatelet agents, and activating platelets may thus be a novel target for ICH therapy. This review explores how dysfunctions or alterations in the coagulation and platelet cascades can lead to, and/or exacerbate, hematoma expansion following intracerebral hemorrhage, and describe the mechanisms behind these effects and the drugs that induce them. We also discuss potential future therapy aimed at increasing platelet activity after ICH.
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Current drug targets · Jan 2016
ReviewPharmacological Correction of Cystic Fibrosis: Molecular Mechanisms at the Plasma Membrane to Augment Mutant CFTR Function.
In the late 1980s, a loss-of-function mutation in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel was identified to be the primary cause of cystic fibrosis (CF); a fatal multiple-organ disorder that mostly affects Caucasians. To date, approximately 2000 genetic mutations have been identified in the CFTR gene (http://www.genet.sickkids.on.ca/cftr/app). The most common cause of morbidity and mortality in persons with CF is a progressive deterioration in lung function leading ultimately to respiratory collapse. ⋯ It is necessary to understand the biology of F508del-CFTR post-ER and at the plasma membrane where the protein might also confront the modifiers and how we can incorporate these components into CF therapeutics. Additionally, the notion that CF individuals would eventually benefit from more of a personalized medicine is becoming increasingly accepted. Here, we review how CF therapeutics may be simplified by understanding the complexities of rescued F508del-CFTR biology and eventually move toward more personalized medicine for patients suffering with CF.
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Current drug targets · Jan 2016
ReviewEmerging Immunotargets and Immunotherapies in Prostate Cancer.
Innate and adaptive immunity are both involved in prostate cancer (PCa) carcinogenesis and progression. On this scenario, several immunotherapeutic approaches have been proposed and are presently under extensive investigation in PCa patients. Among emerging immune targets, immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), anti-Programmed death-1 (PD-1) and anti-Programmed death-ligand-1 (PD-L1) agents seem to represent the most promising candidate for these patients, together with oncolytic viruses and vaccines, used alone or in combined strategies. In this review, we focused on emerging immunotherapeutic approaches in patients with PCa, showing the rational for their association with current standard therapies including anti-androgen agents, chemo- or radiation therapy.
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Current drug targets · Jan 2015
ReviewTargets Involved in Cardioprotection by the Non-Anesthetic Noble Gas Helium.
Research data from the past decade indicate that noble gases like xenon and helium exert profound cardioprotection when applied before, during or after organ ischemia. Of all noble gases, especially helium, has gained interest in the past years because it does not have an anesthetic "side effect" like xenon, allowing application of this specific gas in numerous clinical ischemia/reperfusion situations. ⋯ Investigations in animals as well as in humans have proven that this noble gas is not completely inert and can induce several biological effects. Though the underlying molecular mechanisms of helium-induced cardiac protection are still not yet fully understood, recently different signaling pathways have been elucidated.