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  1. Article: Targeting the integrated stress response in hematologic malignancies.

    Nwosu, Gus O / Powell, Jason A / Pitson, Stuart M

    Experimental hematology & oncology

    2022  Volume 11, Issue 1, Page(s) 94

    Abstract: While numerous targeted therapies have been recently adopted to improve the treatment of hematologic malignancies, acquired or intrinsic resistance poses a significant obstacle to their efficacy. Thus, there is increasing need to identify novel, ... ...

    Abstract While numerous targeted therapies have been recently adopted to improve the treatment of hematologic malignancies, acquired or intrinsic resistance poses a significant obstacle to their efficacy. Thus, there is increasing need to identify novel, targetable pathways to further improve therapy for these diseases. The integrated stress response is a signaling pathway activated in cancer cells in response to both dysregulated growth and metabolism, and also following exposure to many therapies that appears one such targetable pathway for improved treatment of these diseases. In this review, we discuss the role of the integrated stress response in the biology of hematologic malignancies, its critical involvement in the mechanism of action of targeted therapies, and as a target for pharmacologic modulation as a novel strategy for the treatment of hematologic malignancies.
    Language English
    Publishing date 2022-11-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2669066-4
    ISSN 2162-3619
    ISSN 2162-3619
    DOI 10.1186/s40164-022-00348-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sphingolipids as multifaceted mediators in ovarian cancer.

    Pitman, MelissaR / Oehler, Martin K / Pitson, Stuart M

    Cellular signalling

    2021  Volume 81, Page(s) 109949

    Abstract: Ovarian cancer is the most lethal gynaecological malignancy. It is commonly diagnosed at advanced stage when it has metastasised to the abdominal cavity and treatment becomes very challenging. While current standard therapy involving debulking surgery ... ...

    Abstract Ovarian cancer is the most lethal gynaecological malignancy. It is commonly diagnosed at advanced stage when it has metastasised to the abdominal cavity and treatment becomes very challenging. While current standard therapy involving debulking surgery and platinum + taxane-based chemotherapy is associated with high response rates initially, the large majority of patients relapse and ultimately succumb to chemotherapy-resistant disease. In order to improve survival novel strategies for early detection and therapeutics against treatment-refractory disease are urgently needed. A promising new target against ovarian cancer is the sphingolipid pathway which is commonly hijacked in cancer to support cell proliferation and survival and has been shown to promote chemoresistance and metastasis in a wide range of malignant neoplasms. In particular, the sphingosine kinase 1-sphingosine 1-phosphate receptor 1 axis has been shown to be altered in ovarian cancer in multiple ways and therefore represents an attractive therapeutic target. Here we review the roles of sphingolipids in ovarian cancer progression, metastasis and chemoresistance, highlighting novel strategies to target this pathway that represent potential avenues to improve patient survival.
    MeSH term(s) Animals ; Female ; Humans ; Lysophospholipids/genetics ; Lysophospholipids/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Signal Transduction ; Sphingosine/analogs & derivatives ; Sphingosine/genetics ; Sphingosine/metabolism ; Sphingosine-1-Phosphate Receptors/genetics ; Sphingosine-1-Phosphate Receptors/metabolism
    Chemical Substances Lysophospholipids ; Neoplasm Proteins ; Sphingosine-1-Phosphate Receptors ; sphingosine 1-phosphate (26993-30-6) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-) ; Sphingosine (NGZ37HRE42)
    Language English
    Publishing date 2021-02-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1002702-6
    ISSN 1873-3913 ; 0898-6568
    ISSN (online) 1873-3913
    ISSN 0898-6568
    DOI 10.1016/j.cellsig.2021.109949
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2579: Show issues Location:
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  3. Article ; Online: Modification of the tumour microenvironment

    Pitson, Stuart M / Powell, Jason A

    Oncotarget

    2018  Volume 9, Issue 57, Page(s) 30938–30939

    Language English
    Publishing date 2018-07-24
    Publishing country United States
    Document type News ; Comment
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.25793
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  4. Article: Targeting the Sphingolipid System as a Therapeutic Direction for Glioblastoma.

    Tea, Melinda N / Poonnoose, Santosh I / Pitson, Stuart M

    Cancers

    2020  Volume 12, Issue 1

    Abstract: Glioblastoma (GBM) is the most commonly diagnosed malignant brain tumor in adults. The prognosis for patients with GBM remains poor and largely unchanged over the last 30 years, due to the limitations of existing therapies. Thus, new therapeutic ... ...

    Abstract Glioblastoma (GBM) is the most commonly diagnosed malignant brain tumor in adults. The prognosis for patients with GBM remains poor and largely unchanged over the last 30 years, due to the limitations of existing therapies. Thus, new therapeutic approaches are desperately required. Sphingolipids are highly enriched in the brain, forming the structural components of cell membranes, and are major lipid constituents of the myelin sheaths of nerve axons, as well as playing critical roles in cell signaling. Indeed, a number of sphingolipids elicit a variety of cellular responses involved in the development and progression of GBM. Here, we discuss the role of sphingolipids in the pathobiology of GBM, and how targeting sphingolipid metabolism has emerged as a promising approach for the treatment of GBM.
    Language English
    Publishing date 2020-01-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12010111
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  5. Article ; Online: Accelerated Closure of Diabetic Wounds by Efficient Recruitment of Fibroblasts upon Inhibiting a 14-3-3/ROCK Regulatory Axis.

    Johan, M Zahied / Pyne, Natasha T / Kolesnikoff, Natasha / Poltavets, Valentina / Esmaeili, Zahra / Woodcock, Joanna M / Lopez, Angel F / Cowin, Allison J / Pitson, Stuart M / Samuel, Michael S

    The Journal of investigative dermatology

    2024  

    Abstract: Chronic non-healing wounds negatively impact quality of life and are a significant financial drain on health systems. The risk of infection that exacerbates comorbidities in patients necessitates regular application of wound care. Understanding the ... ...

    Abstract Chronic non-healing wounds negatively impact quality of life and are a significant financial drain on health systems. The risk of infection that exacerbates comorbidities in patients necessitates regular application of wound care. Understanding the mechanisms underlying impaired wound healing are therefore a key priority to inform effective new-generation treatments. In this study, we demonstrate that 14-3-3-mediated suppression of signaling through ROCK is a critical mechanism that inhibits the healing of diabetic wounds. Accordingly, pharmacological inhibition of 14-3-3 by topical application of the sphingo-mimetic drug RB-11 to diabetic wounds on a mouse model of type II diabetes accelerated wound closure more than 2-fold than vehicle control, phenocopying our previous observations in 14-3-3ζ-knockout mice. We also demonstrate that accelerated closure of the wounded epidermis by 14-3-3 inhibition causes enhanced signaling through the Rho-ROCK pathway and that the underlying cellular mechanism involves the efficient recruitment of dermal fibroblasts into the wound and the rapid production of extracellular matrix proteins to re-establish the injured dermis. Our observations that the 14-3-3/ROCK inhibitory axis characterizes impaired wound healing and that its suppression facilitates fibroblast recruitment and accelerated re-epithelialization suggest new possibilities for treating diabetic wounds by pharmacologically targeting this axis.
    Language English
    Publishing date 2024-04-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2024.03.032
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    In stock of ZB MED Cologne/Königswinter

    Ui VI Zs.124: Show issues Location:
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  6. Article: Regulation of sphingosine kinase and sphingolipid signaling.

    Pitson, Stuart M

    Trends in biochemical sciences

    2011  Volume 36, Issue 2, Page(s) 97–107

    Abstract: Bioactive sphingolipids, including ceramide, sphingosine and sphingosine 1-phosphate are important regulators of many cellular processes, including cell survival, proliferation, differentiation, migration and immune responses. Although the levels of ... ...

    Abstract Bioactive sphingolipids, including ceramide, sphingosine and sphingosine 1-phosphate are important regulators of many cellular processes, including cell survival, proliferation, differentiation, migration and immune responses. Although the levels of these bioactive sphingolipids are regulated by complex pathways subject to spatial and temporal control, the sphingosine kinases have emerged as critical central regulators of this system and, as a consequence, they have received substantial recent attention as potential therapeutic targets for cancer and a range of other conditions. Deciphering the molecular mechanisms that regulate both the activity and subcellular localization of these enzymes is vital for understanding the control of bioactive sphingolipid generation and action, and has clear implications for therapeutic strategies targeting these enzymes.
    MeSH term(s) Animals ; Cells/enzymology ; Humans ; Isoenzymes/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Signal Transduction ; Sphingolipids/metabolism
    Chemical Substances Isoenzymes ; Sphingolipids ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-)
    Language English
    Publishing date 2011-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2010.08.001
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1207: Show issues Location:
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  7. Article: Validation of commercially available sphingosine kinase 2 antibodies for use in immunoblotting, immunoprecipitation and immunofluorescence.

    Neubauer, Heidi A / Pitson, Stuart M

    F1000Research

    2016  Volume 5, Page(s) 2825

    Abstract: Sphingosine kinase 2 (SK2) is a ubiquitously expressed lipid kinase that has important, albeit complex and poorly understood, roles in regulating cell survival and cell death. In addition to being able to promote cell cycle arrest and apoptosis under ... ...

    Abstract Sphingosine kinase 2 (SK2) is a ubiquitously expressed lipid kinase that has important, albeit complex and poorly understood, roles in regulating cell survival and cell death. In addition to being able to promote cell cycle arrest and apoptosis under certain conditions, it has recently been shown that SK2 can promote neoplastic transformation and tumorigenesis
    Language English
    Publishing date 2016-12-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2699932-8
    ISSN 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.10336.2
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  8. Article: Author Correction: Targeting sphingolipid metabolism as an approach for combination therapies in haematological malignancies.

    Lewis, Alexander C / Wallington-Beddoe, Craig T / Powell, Jason A / Pitson, Stuart M

    Cell death discovery

    2021  Volume 7, Issue 1, Page(s) 170

    Language English
    Publishing date 2021-06-18
    Publishing country United States
    Document type Published Erratum
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-020-00380-1
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  9. Article ; Online: The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism.

    Pitman, Melissa R / Lewis, Alexander C / Davies, Lorena T / Moretti, Paul A B / Anderson, Dovile / Creek, Darren J / Powell, Jason A / Pitson, Stuart M

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 454

    Abstract: Sphingosine 1-phosphate (S1P) is a signaling lipid that has broad roles, working either intracellularly through various protein targets, or extracellularly via a family of five G-protein coupled ... ...

    Abstract Sphingosine 1-phosphate (S1P) is a signaling lipid that has broad roles, working either intracellularly through various protein targets, or extracellularly via a family of five G-protein coupled receptors
    MeSH term(s) HEK293 Cells ; Humans ; Kinetics ; Oxidoreductases/chemistry ; Oxidoreductases/genetics ; Oxidoreductases/metabolism ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Pyridines/chemistry ; Pyridines/pharmacology ; Sphingolipids/metabolism ; Sphingosine-1-Phosphate Receptors/antagonists & inhibitors ; Sphingosine-1-Phosphate Receptors/genetics ; Sphingosine-1-Phosphate Receptors/metabolism
    Chemical Substances JTE 013 ; Pyrazoles ; Pyridines ; S1PR2 protein, human ; S1PR4 protein, human ; Sphingolipids ; Sphingosine-1-Phosphate Receptors ; Oxidoreductases (EC 1.-) ; dihydroceramide desaturase (EC 1.3.1.-)
    Language English
    Publishing date 2022-01-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-04009-w
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  10. Article ; Online: Sphingolipids--who's controlling who in disease?

    Bonder, Claudine S / Pitson, Stuart M

    Immunology and cell biology

    2015  Volume 93, Issue 9, Page(s) 767–768

    MeSH term(s) Animals ; Cell Movement/immunology ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Female ; Humans ; Male ; Neutrophils/immunology ; Sphingosine N-Acyltransferase/immunology
    Chemical Substances Sphingosine N-Acyltransferase (EC 2.3.1.24)
    Language English
    Publishing date 2015-08-04
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1038/icb.2015.70
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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.175: Show issues Location:
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