• Login
    View Item 
    •   Home
    • Hospital Research
    • Leinster
    • Coombe Women & Infants University Hospital
    • View Item
    •   Home
    • Hospital Research
    • Leinster
    • Coombe Women & Infants University Hospital
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Map of Submissions

    Home Page
    UlsterN
    4708
    UlsterS
    4708
    Connacht
    1606
    Munster
    48
    Leinster
    426

    Browse

    All of Lenus, The Irish Health RepositoryCommunitiesTitleAuthorsDate publishedSubjectsThis CollectionTitleAuthorsDate publishedSubjects

    My Account

    LoginRegister

    About

    About LenusDirectory of Open Access JournalsOpen Access Publishing GuideNational Health Library & Knowledge ServiceGuide to Publishers' PoliciesFAQsTerms and ConditionsVision StatementRIAN Pathways to Irish ResearchHSE position statement on Open AccessNational Open Research Forum (NORF)Zenodo (European Open Research repository)

    Statistics

    Display statistics

    The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    journalpone0100816.pdf
    Size:
    12.01Mb
    Format:
    PDF
    Download
    Authors
    d'Adhemar, Charles J
    Spillane, Cathy D
    Gallagher, Michael F
    Bates, Mark
    Costello, Katie M
    Barry-O'Crowley, Jacqui
    Haley, Kathryn
    Kernan, Niamh
    Murphy, Ciara
    Smyth, Paul C
    O'Byrne, Ken
    Pennington, Stephen
    Cooke, Aoife A
    Ffrench, Brendan
    Martin, Cara M
    O'Donnell, Dearbhaile
    Hennessy, Bryan
    Stordal, Britta
    Finn, Stephen
    McCann, Amanda
    Gleeson, Noreen
    D'Arcy, Tom
    Flood, Brian
    O'Neill, Luke A J
    Sheils, Orla
    O'Toole, Sharon
    O'Leary, John J
    Show allShow less
    Issue Date
    2014
    MeSH
    Aged
    Antineoplastic Agents, Phytogenic
    Cell Line, Tumor
    Cystadenocarcinoma, Serous
    Drug Resistance, Neoplasm
    Female
    Gene Expression Regulation, Neoplastic
    Genotype
    Humans
    Immunohistochemistry
    MicroRNAs
    Middle Aged
    Myeloid Differentiation Factor 88
    Neoplasms, Glandular and Epithelial
    Neoplastic Stem Cells
    Ovarian Neoplasms
    Paclitaxel
    Phenotype
    Prognosis
    RNA, Small Interfering
    Signal Transduction
    Survival Analysis
    Toll-Like Receptor 4
    Show allShow less
    
    Metadata
    Show full item record
    Citation
    The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer. 2014, 9 (6):e100816 PLoS ONE
    Journal
    PloS one
    URI
    http://hdl.handle.net/10147/559447
    DOI
    10.1371/journal.pone.0100816
    PubMed ID
    24977712
    Abstract
    The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.
    Item Type
    Article
    Language
    en
    ISSN
    1932-6203
    Sponsors
    Funding: This work was supported by Cancer Research Ireland (grant reference number ICS CRP09OLE), the Meath foundation, The Royal City of Dublin Hospital Trust, BDI-2 (10/CE/B1821), the Emer Casey foundation, the Irish Cancer Society, and a Marie Curie European Union grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0100816
    Scopus Count
    Collections
    Coombe Women & Infants University Hospital

    entitlement

    Related articles

    • NSAID-activated gene 1 mediates pro-inflammatory signaling activation and paclitaxel chemoresistance in type I human epithelial ovarian cancer stem-like cells.
    • Authors: Kim KH, Park SH, Do KH, Kim J, Choi KU, Moon Y
    • Issue date: 2016 Nov 1
    • The role of the MAD2-TLR4-MyD88 axis in paclitaxel resistance in ovarian cancer.
    • Authors: Bates M, Spillane CD, Gallagher MF, McCann A, Martin C, Blackshields G, Keegan H, Gubbins L, Brooks R, Brooks D, Selemidis S, O'Toole S, O'Leary JJ
    • Issue date: 2020
    • Atractylenolide-I sensitizes human ovarian cancer cells to paclitaxel by blocking activation of TLR4/MyD88-dependent pathway.
    • Authors: Huang JM, Zhang GN, Shi Y, Zha X, Zhu Y, Wang MM, Lin Q, Wang W, Lu HY, Ma SQ, Cheng J, Deng BF
    • Issue date: 2014 Jan 23
    • FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients.
    • Authors: Tassi RA, Todeschini P, Siegel ER, Calza S, Cappella P, Ardighieri L, Cadei M, Bugatti M, Romani C, Bandiera E, Zanotti L, Tassone L, Guarino D, Santonocito C, Capoluongo ED, Beltrame L, Erba E, Marchini S, D'Incalci M, Donzelli C, Santin AD, Pecorelli S, Sartori E, Bignotti E, Odicino F, Ravaggi A
    • Issue date: 2017 May 8
    • The inflammatory microenvironment in epithelial ovarian cancer: a role for TLR4 and MyD88 and related proteins.
    • Authors: Li Z, Block MS, Vierkant RA, Fogarty ZC, Winham SJ, Visscher DW, Kalli KR, Wang C, Goode EL
    • Issue date: 2016 Oct
    National Health Library & Knowledge Service | Health Service Executive | Dr Steevens' Hospital | Dublin 8 | Ireland
    lenus@hse.ie | Tel +353 (1) 6352558
    DSpace software copyright © 2002-2017  DuraSpace
    Contact Us | Disclaimer
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.