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Open AccessJournal ArticleDOI

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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Book ChapterDOI

Sphingosine-1-phosphate and Sphingosine-1-phosphate receptors in the cardiovascular system: pharmacology and clinical implications.

TL;DR: In this article , the authors summarized the available information on S1P receptors in the cardiovascular system and discussed their potential for treating cardiovascular conditions and/or their role on the clinical pharmacology of drugs so far approved for non-cardiovascular conditions.
Journal ArticleDOI

Inhibition of Tumors in Mice Models by a Synthetic Ceramide-analog AD2725

TL;DR: In animal studies, treatment with AD2725 resulted in a significant reduction of the tumor volume and weight, and a significantly prolonged survival of the treated mice, indicating that use of suitable synthetic analogs that most probably elevate the ceramide levels may have beneficial anti-cancer therapeutic effects.
Book ChapterDOI

The Emerging Role of Sphingolipids in Cancer Stem Cell Biology

TL;DR: There is emerging evidence to suggest that sphingolipids and alterations in sphingoipid metabolism contribute to cancer stem cell biology.
Journal ArticleDOI

Integrated Metabonomics and Network Pharmacology to Reveal the Action Mechanism Effect of Shaoyao Decoction on Ulcerative Colitis

TL;DR: Wang et al. as discussed by the authors explored the mechanism of SYD in the treatment of mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through metabolomics and network pharmacology, and verify through molecular docking and immunohistochemistry, so as to provide a scientific basis for the role of SyD in treating UC.
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.
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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