Showing papers in "Pharmacology & Therapeutics in 2014"

TL;DR: Novel approaches to PI3K/AKT/mTOR pathway inhibition together with a better understanding of prognostic and predictive markers have the potential to significantly improve the future care of cancer patients in the current era of personalized cancer medicine.

TL;DR: A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH.

TL;DR: This work reviews the current evidence of molecular disturbances present in the diabetic heart, and their role in the development of diabetes-induced impairments in myocardial function and structure, and incorporates both the contribution of increased reactive oxygen species production and reduced antioxidant defenses to diabetic cardiomyopathy.

TL;DR: Interleukin-6 antagonism has been shown to be a potential therapy for these disorders refractory to conventional drugs, and new strategies, such as combination of IL-6 blockade with inhibition of other signaling pathways, may further improve IL- 6-targeted immunotherapy of human diseases.

TL;DR: A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis, and other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial.

TL;DR: Artemisinins have demonstrated cytotoxic effects against a variety of cancer cells by inducing cell cycle arrest, promoting apoptosis, preventing angiogenesis, and abrogating cancer invasion and metastasis, and it is likely that artemisinin drugs will become a major armamentarium combating a number of human diseases beyond malaria.

TL;DR: This review focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand-receptor interaction by monoclonal antibodies (mAbs).

TL;DR: This review will focus on the cardiac ventricular contractile and relaxation kinetics of humans and animal models in order to illustrate these differences.

TL;DR: Strong evidence indicates n-3 PUFAs are beneficial as a dietary supplement in certain diseases such as rheumatoid arthritis; however for other conditions such as asthma, the data are less robust.

TL;DR: It is demonstrated that H2 reacts with strong oxidants such as hydroxyl radical in cells, and its potential for preventive and therapeutic applications is proposed, indicating its promising potential for clinical use against many diseases.

TL;DR: Various approaches recently proposed in the literature to inhibit HMGB1 and the related inflammatory processes are described, especially focusing on the block of RAGE-HMGB1 signaling.

TL;DR: The angiogenic factors found in the MSC secretome and their therapeutic mode of action in pathologies caused by limited blood vessel formation will be summarized and the application of MSC as a vehicle to deliver drugs and/or genes in (anti-)angiogenesis will be discussed.

TL;DR: This review focuses on relatively recently identified mechanisms of action of HDACI, with particular emphasis on those that relate to the DNA damage response (DDR), and discusses synergistic strategies combining HDACIs with several novel targeted agents that disrupt the DDR or antagonize anti-apoptotic proteins that could have implications for the future use ofHDACIs in patients with cancer.

TL;DR: The role of the MEK pathway in carcinogenesis and its therapeutic potential in cancer patients is examined and the known mechanisms of resistance to MEKi and emerging strategies to overcome it are highlighted.

TL;DR: The latest advances in understanding the way in which MAO inhibitors affect the release of the monoamine neurotransmitters dopamine, noradrenaline and serotonin in the CNS are described, with an accent on the importance of these effects for the clinical actions of the drugs.

TL;DR: Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease, and reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body.

TL;DR: Conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies are reviewed.

TL;DR: Genetic and in-vitro and animal studies indicate that elevated LDL cholesterol levels cause atherosclerosis without a major inflammatory component, whereas an inflammatory component of Atherosclerosis is driven by elevated remnant cholesterol levels.

TL;DR: This paper examines the different recent theories proposed for GPCR activation and shows that they are all indeed parts of the same process, and are intrinsically related through their effect on the central hydrophobic core of GPCRs.

TL;DR: Critical evaluation of the current scientific preclinical literature suggests that small molecule modulators of nociceptin opioid peptide receptors (NOP) might be useful in the treatment of diseases related to these biological functions and that antagonism of NOP receptors will produce anti-obesity and antidepressant activities in humans.

TL;DR: Research in Met prognostics and predictors of drug response is now shifting toward more sophisticated methodologies suitable for development as validated and effective biomarkers that can be partnered with therapeutics to improve patient survival.

TL;DR: This review provides an update on recent progress in CTC isolation and molecular characterization technologies and covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies.

TL;DR: The roles of XIAP, cI AP1, and cIAP2 in regulation of cell death and survival, and the design and development of small-molecule SMAC mimetics as novel cancer treatments are discussed.

TL;DR: How the different constituents of the cAMP pathway are targeted and participate in the formation of cAMP compartmentalized signaling events is discussed, with a particular focus on the nucleus, the sarcoplasmic reticulum and the mitochondria.

TL;DR: There is evidence of the existence of large monogenetic functional polymorphisms affecting pharmacokinetics and suggesting a potential use of UGT polymorphisms for the individualization of drug therapy.

TL;DR: Evidence that inhibition of glycogen synthase kinase-3 (GSK3) ameliorates cognitive deficits in a wide variety of animal models of CNS diseases, including Alzheimer's disease, Fragile X syndrome, Down syndrome, Parkinson's Disease, spinocerebellar ataxia type 1, traumatic brain injury, and others is reviewed.

TL;DR: This review is intended to provide information on the current progress of CHK1 inhibitors in pre-clinical and clinical development and will focus on mechanisms of single-agent activity and potential strategies for patient tailoring and combinations with non-genotoxic agents.

TL;DR: Developments in lipidomics including methodology, bioinformatics/statistics, insights into disease pathophysiology, the effect of therapeutic interventions, the role of large clinical outcome trials in validating lipidomic approaches to patient management and potential applications in clinical practice are covered.

TL;DR: The current knowledge on the metabolic effects of the NP system is reviewed and potential therapeutic applications are discussed, holding the potential to be amenable to therapeutical intervention against pandemic diseases such as obesity, insulin resistance, and arterial hypertension.

TL;DR: The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems that lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops.