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Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond

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TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.
Abstract
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.

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Dissertation

Translation of sphingosine-1-phosphate-dependent regulation of myogenic tone in human resistance arteries with heart failure

Sonya K. Hui
TL;DR: Results show molecular expression of S 1P signalling components and S1P signalling-dependent regulation of the myogenic response in human resistance arteries and demonstrate potential vascular bed or coronary artery disease-dependent differences.
Journal ArticleDOI

Sphingosine-1-phosphate alleviates irradiation-induced parotid injury in a miniature pig model

TL;DR: S1P may partially alleviate IR-induced parotid dysfunction by decreasing apoptosis of microvascular endothelial cells and maintaining the blood flow rate.

The Group IVA Cytosolic Phospholipase A2/C1P Interaction and Its Role in Eicosanoid Synthesis and Inflammation

TL;DR: The obtained results allowed us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals, not necessarily belonging to the same breeds.
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Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells.

TL;DR: In this paper, the authors explore the oncogenic functions of sphingosine kinase 1 in human cancers and summarize current research findings of SPHK1 signaling with a focus on breast cancer.
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High Circulating Sphingosine 1-Phosphate is a Risk Factor for Osteoporotic Fracture Independent of Fracture Risk Assessment Tool.

TL;DR: S1P is a consistent and significant risk factor of OF independent of FRAx, especially in subjects with osteopenia and low FRAX probability, and adding S1P levels to FRAZ probabilities improved the area under the receiver-operating characteristics curve (AUC) for OF.
References
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Journal ArticleDOI

STATs in cancer inflammation and immunity: a leading role for STAT3

TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
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Principles of bioactive lipid signalling: lessons from sphingolipids

TL;DR: An understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action is required to understand the mechanisms of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking.
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The many roles of histone deacetylases in development and physiology: Implications for disease and therapy

TL;DR: In this article, the expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programs of gene expression.
Journal Article

Heart-lung transplantation.

TL;DR: A broad overview of the various grounds upon which this difference is likely based and discuss recent advances in each area: 1) criteria for the selection of candidates and donors, 2) methods for ex-vivo preservation of donor organs, 3) technical execution of the operative procedure, and 4) prevention of postoperative infection as discussed by the authors.
Journal ArticleDOI

Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase

TL;DR: The identification of a small molecule called necrosulfonamide that specifically blocks necrosis downstream of RIP3 activation is reported, which implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3.
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