• Admin Login
    View Item 
    •   Home
    • Research Institute in Healthcare Science
    • Research Institute in Healthcare Science
    • View Item
    •   Home
    • Research Institute in Healthcare Science
    • Research Institute in Healthcare Science
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of WIRECommunitiesTitleAuthorsIssue DateSubmit DateSubjectsTypesJournalDepartmentPublisherThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsTypesJournalDepartmentPublisher

    Administrators

    Admin Login

    Local Links

    AboutThe University LibraryOpen Access Publications PolicyDeposit LicenceCOREWIRE Copyright and Reuse Information

    Statistics

    Display statistics

    MGMT methylation status and expression level do not correlate with sensitivity to CCNU in short-term cultures derived from malignant astrocytoma

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Warr, Tracy
    Poh, R.
    Suarez-Merino, Blanca
    Ward, Samantha
    Warren, Phil
    Darling, John L.
    Thomas, David G.
    Issue Date
    2005
    
    Metadata
    Show full item record
    Other Titles
    In: Abstracts from the World Federation of Neuro-Oncology Second Quadrennial Meeting and the Sixth Meeting of the European Association for Neuro-Oncology: May 5–8, 2005, Edinburgh, UK. No.308
    Abstract
    Adjuvant chemotherapy using DNA-damaging agents has largely failed to make a significant impact on the outcome of patients with malignant astrocytoma. One of the primary mechanisms of resistance to nitrosureas such as CCNU is mediated through O6-methylguanine-DNA methyltrans-ferase (MGMT). This DNA repair enzyme removes the cytotoxic alkyl adducts from O6-guanine, and hence the level of MGMT activity in tumor cells is related to their sensitivity to nitroureas. It has been proposed that functional inactivation of MGMT through hypermethylation of the gene promotor region could be predictive of chemosensitivity. We have previously reported differential sensitivity to CCNU in a panel of 17 short-term cultures derived from malignant astrocytoma. In this study, we determined the methylation status of MGMT using methylation-specific PCR in these 17 cultures. We also assessed the amounts of MGMT mRNA and protein present in each culture using real-time quantitative PCR and immunohistochemistry with a commercial antibody against MGMT. There was good correlation between MGMT promotor methylation and presence of MGMT mRNA and protein in all but 2 cases. In both these cultures, mRNA and protein were not detected even though the MGMT promotor was unmethylated. However, there was no correlation between sensitivity to CCNU and MGMT status. In the 2 most resistant cultures, the MGMT gene was methylated and was not expressed. Similarly, in 4/5 of the most sensitive cultures, MGMT was unmethylated, and in 2 of these cases, there was commensurate MGMT expression. However, in the remaining 2 cultures, MGMT expression was not detected, indicating that an alternative mechanism to gene methylation is responsible for MGMT inactivation. This study highlights that the resistance of malignant astrocytoma to nitroureas may be more complex than simple reliance on MGMT activity and prediction of response to such agents by MGMT methylation status should be used with caution.
    Citation
    Neuro-oncology, 7: 360
    Publisher
    Society for Neuro-Oncology and Duke University Press
    Journal
    Neuro-oncology
    URI
    http://hdl.handle.net/2436/30197
    DOI
    10.1215/S1152851705200388
    Additional Links
    https://academic.oup.com/neuro-oncology/article/7/3/279/1069729
    Type
    Conference contribution
    Language
    en
    Description
    Abstracts from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Duke University Press.
    ISSN
    1522-8517
    ae974a485f413a2113503eed53cd6c53
    10.1215/S1152851705200388
    Scopus Count
    Collections
    Research Institute in Healthcare Science

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    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.