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.read more
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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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
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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
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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.