Time resolved amplified FRET identifies protein kinase B activation state as a marker for poor prognosis in clear cell renal cell carcinoma

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usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="mUxTOOlC1T4yudhFSxY6bYuVczl5zTtoRZtags3s2fgYQhjQFZSGDIkR5QIuiSOY"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="mUxTOOlC1T4yudhFSxY6bYuVczl5zTtoRZtags3s2fgYQhjQFZSGDIkR5QIuiSOY"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="mUxTOOlC1T4yudhFSxY6bYuVczl5zTtoRZtags3s2fgYQhjQFZSGDIkR5QIuiSOY"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="mUxTOOlC1T4yudhFSxY6bYuVczl5zTtoRZtags3s2fgYQhjQFZSGDIkR5QIuiSOY"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> 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required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 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journal BBA clinical" data-pinger-ignore> BBA Clin </button><div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal BBA clinical"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22BBA+Clin%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22BBA+Clin%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=BBA Clin" data-ga-category="search" data-ga-action="journal_link" data-ga-label="BBA Clin"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22BBA+Clin%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="BBA Clin"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"BBA Clin"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"BBA Clin"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2017 Oct 13:8:97-102.</span> </div> <span class="citation-doi"> doi: 10.1016/j.bbacli.2017.10.002. </span> <span class="secondary-date"> eCollection 2017 Dec. </span> </div> <h1 class="heading-title"> Time resolved amplified FRET identifies protein kinase B activation state as a marker for poor prognosis in clear cell renal cell carcinoma </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Miles+J&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="James Miles">James Miles</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pharmacy and Pharmacology, University of Bath, UK." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Applebee+CJ&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Christopher J Applebee">Christopher J Applebee</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Leboucher+P&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Pierre Leboucher">Pierre Leboucher</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institut du Cerveau et de la Moelle épinière, Hôpital de la Pitié-Salpêtrière, Paris, France." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lopez-Fernandez+S&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sonia Lopez-Fernandez">Sonia Lopez-Fernandez</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lee+DJ&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dae-Jin Lee">Dae-Jin Lee</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Basque Centre for Applied Mathematics, Bilbao, Bizkaia, Spain." href="#full-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Guarch+R&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Rosa Guarch">Rosa Guarch</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology B, Complejo Hospitalario de Navarra, Pamplona, Spain." href="#full-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ward+S&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stephen Ward">Stephen Ward</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pharmacy and Pharmacology, University of Bath, UK." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Parker+PJ&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Peter J Parker">Peter J Parker</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Protein Phosphorylation Laboratory, The Francis Crick Institute, London, UK and Division of Cancer Studies, King's College London, London, UK." href="#full-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=L%C3%B3pez+JI&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jose I López">Jose I López</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Larijani+B&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Banafshé Larijani">Banafshé Larijani</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/29296589/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain.</li> <li data-affiliation-id="full-view-affiliation-2" id="full-view-affiliation-2" ><sup class="key">2</sup> Department of Pharmacy and Pharmacology, University of Bath, UK.</li> <li data-affiliation-id="full-view-affiliation-3" id="full-view-affiliation-3" ><sup class="key">3</sup> Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain.</li> <li data-affiliation-id="full-view-affiliation-4" id="full-view-affiliation-4" ><sup class="key">4</sup> Institut du Cerveau et de la Moelle épinière, Hôpital de la Pitié-Salpêtrière, Paris, France.</li> <li data-affiliation-id="full-view-affiliation-5" id="full-view-affiliation-5" ><sup class="key">5</sup> Basque Centre for Applied Mathematics, Bilbao, Bizkaia, Spain.</li> <li data-affiliation-id="full-view-affiliation-6" id="full-view-affiliation-6" ><sup class="key">6</sup> Department of Pathology B, Complejo Hospitalario de Navarra, Pamplona, Spain.</li> <li data-affiliation-id="full-view-affiliation-7" id="full-view-affiliation-7" ><sup class="key">7</sup> Protein Phosphorylation Laboratory, The Francis Crick Institute, London, UK and Division of Cancer Studies, King's College London, London, UK.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">29296589</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" 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data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"BBA Clin"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2017 Oct 13:8:97-102.</span> </div> <span class="citation-doi"> doi: 10.1016/j.bbacli.2017.10.002. </span> <span class="secondary-date"> eCollection 2017 Dec. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Miles+J&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="James Miles">James Miles</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pharmacy and Pharmacology, University of Bath, UK." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Applebee+CJ&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Christopher J Applebee">Christopher J Applebee</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Leboucher+P&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Pierre Leboucher">Pierre Leboucher</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institut du Cerveau et de la Moelle épinière, Hôpital de la Pitié-Salpêtrière, Paris, France." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lopez-Fernandez+S&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sonia Lopez-Fernandez">Sonia Lopez-Fernandez</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lee+DJ&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dae-Jin Lee">Dae-Jin Lee</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Basque Centre for Applied Mathematics, Bilbao, Bizkaia, Spain." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Guarch+R&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Rosa Guarch">Rosa Guarch</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology B, Complejo Hospitalario de Navarra, Pamplona, Spain." href="#short-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ward+S&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stephen Ward">Stephen Ward</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pharmacy and Pharmacology, University of Bath, UK." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Parker+PJ&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Peter J Parker">Peter J Parker</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Protein Phosphorylation Laboratory, The Francis Crick Institute, London, UK and Division of Cancer Studies, King's College London, London, UK." href="#short-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=L%C3%B3pez+JI&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jose I López">Jose I López</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Larijani+B&cauthor_id=29296589" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Banafshé Larijani">Banafshé Larijani</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Cell Biophysics Laboratory, Ikerbasque, Basque Foundation for Science, FASTBASE SOLUTIONS Ltd, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Biofísika Institute (UPV/EHU, CSIC), University of the Basque Country, Spain.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Department of Pharmacy and Pharmacology, University of Bath, UK.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> Institut du Cerveau et de la Moelle épinière, Hôpital de la Pitié-Salpêtrière, Paris, France.</li> <li data-affiliation-id="short-view-affiliation-5" id="short-view-affiliation-5" ><sup class="key">5</sup> Basque Centre for Applied Mathematics, Bilbao, Bizkaia, Spain.</li> <li data-affiliation-id="short-view-affiliation-6" id="short-view-affiliation-6" ><sup class="key">6</sup> Department of Pathology B, Complejo Hospitalario de Navarra, Pamplona, Spain.</li> <li data-affiliation-id="short-view-affiliation-7" id="short-view-affiliation-7" ><sup class="key">7</sup> Protein Phosphorylation Laboratory, The Francis Crick Institute, London, UK and Division of Cancer Studies, King's College London, London, UK.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">29296589</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC5744020&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5744020/" data-ga-category="full_text" data-ga-action="PMCID" > PMC5744020 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1016/j.bbacli.2017.10.002&id_type=DOI" href="https://doi.org/10.1016/j.bbacli.2017.10.002" data-ga-category="full_text" data-ga-action="DOI" > 10.1016/j.bbacli.2017.10.002 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/29296589/citations/" data-citation-style="nlm" data-pubmed-format-link="/29296589/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> <strong class="sub-title"> Purpose: </strong> Clear cell Renal Cell Carcinomas (ccRCC), the largest group of renal tumours, are resistant to classical therapies. The determination of the functional state of actionable biomarkers for the assessment of these adenocarcinomas is essential. The dysregulation of the oncoprotein, PKB/Akt has been linked with poor prognoses in human cancers. </p> <p> <strong class="sub-title"> Material & methods: </strong> We analysed the status of the PKB/Akt pathway in a representative tumour tissue microarray obtained from the primary tumours and their metastases in 60 ccRCC with long term follow up. We sought to define the evolution of this pathway from the primary tumour to the metastatic event and to know the impact of its functional state in tumour aggressiveness and patient survival. Two-site time resolved amplified FRET (A-FRET) was utilised for assessing the activation state of PKB/Akt and this was compared to conventional immunohistochemistry measurements. </p> <p> <strong class="sub-title"> Results: </strong> Activation state of PKB/Akt in primary tumours defined by A-FRET correlated with poorer overall survival (hazard ratio 0.228; <i>p</i> = 0.002). Whereas, increased protein expression of phosphoPKB/Akt, identified using classical immunohistochemistry, yielded no significant difference (hazard ratio 1.390; <i>p</i> = 0.548). </p> <p> <strong class="sub-title"> Conclusions: </strong> Quantitative determination of PKB/Akt activation in ccRCC primary tumours alongside other diagnostics tools could prove key in taking oncologists closer to an efficient personalised therapy in ccRCC patients. </p> <p> <strong class="sub-title"> General significance: </strong> The quantitative imaging technology based on Amplified-FRET can rapidly analyse protein activation states and molecular interactions. It could be used for prognosis and assess drug function during the early cycles of chemotherapy. It enables evaluation of clinical efficiency of personalised cancer treatment. </p> </div> <p> <strong class="sub-title"> Keywords: </strong> Amplified FRET; Biomarker activation; Clear cell renal cell carcinoma; Fret-FLIM; Prognosis; Protein kinase B (PKB/Akt). </p> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="fig-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/5744020/08329ab2f430/gr1.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="758" data-image-height="573" data-image-alt="Fig. 1" data-pmc-id="PMC5744020" data-figure-id="f0005"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/5744020/147dbc9d049d/gr1.gif" alt="Fig. 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="758"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="573"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 1 </p> </strong> <div class="figure-caption-contents"><p> Schematic overview of the Protein… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 1 </p> </strong> <div class="figure-caption-contents"><p> Schematic overview of the Protein Kinase B signalling pathway. Protein Kinase B (PKB/Akt)… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 1 </strong> <div class="figure-caption-contents">Schematic overview of the Protein Kinase B signalling pathway. Protein Kinase B (PKB/Akt) is part of the AGC kinase super family. Upon the binding of a growth factor receptor to a receptor tyrosine kinase, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P<sub>2</sub>) is phosphorylated, by phosphoinositide 3-kinase (PI3K) to phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P<sub>3</sub>). This recruits PKB and phosphoinositide-dependent protein kinase 1 (PDK1) to the plasma membrane. PDK1 phosphorylates threonine-308 to partially active it and mTORC2 phosphorylates Ser473 for full activation.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="fig-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/5744020/04be3d97fafe/gr2.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="758" data-image-height="884" data-image-alt="Fig. 2" data-pmc-id="PMC5744020" data-figure-id="f0010"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/5744020/e53cb27d82d1/gr2.gif" alt="Fig. 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="758"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="884"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 2 </p> </strong> <div class="figure-caption-contents"><p> PKB/Akt activation is higher in… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 2 </p> </strong> <div class="figure-caption-contents"><p> PKB/Akt activation is higher in metastatic ccRCC tumours in FFPE TMAs. A, Low-(left)… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 2 </strong> <div class="figure-caption-contents">PKB/Akt activation is higher in metastatic ccRCC tumours in FFPE TMAs. A, Low-(left) and high-(right) grade ccRCCs B, the intensity images (corresponding to protein expression levels) of PKB/Akt and pAkt expression levels do not yield differences. Lifetime maps however do yield significant differences between primary and metastatic ccRCC samples. C, PKB/Akt activation state determined by A-FRET from primary to metastatic tumours for each patient. Patients 9 and 31 have higher Akt activation in their primary tumours D, the Box and Whisker plots show an increase in PKB/Akt activation from the non-tumour control tissue to the primary ccRCC cores with a significant difference of (<i>p</i> = 3.81 × 10<sup>− 5</sup>). Each point on the Box and Whisker plot indicates the activation state of the primary and metastatic tumours of each patient. A larger increase in activation is shown from primary cores to metastatic cores. <i>P</i> values are shown between significantly different groups.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="fig-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/5744020/82be1f7b6972/gr3.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="711" data-image-height="829" data-image-alt="Fig. 3" data-pmc-id="PMC5744020" data-figure-id="f0015"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/5744020/32ceddd8a51f/gr3.gif" alt="Fig. 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="711"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="829"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 3 </p> </strong> <div class="figure-caption-contents"><p> PKB/Akt activation state correlates with… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 3 </p> </strong> <div class="figure-caption-contents"><p> PKB/Akt activation state correlates with poor overall survival in ccRCC. A, shows the… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 3 </strong> <div class="figure-caption-contents">PKB/Akt activation state correlates with poor overall survival in ccRCC. A, shows the survival outcomes related to PKB/Akt activation as determined by A-FRET (left panel) or by conventional IHC (right panel). A highly significant difference was observed between the upper quartile of FRET Efficiency and the lower 3 quartiles FRET Efficiency. No difference was detected when survival is determined by IHC intensity of the activation state of PKB/Akt. B, Both A-FRET and IHC detections did not relate to grading (High H and Low L) <i>p</i> = 0.709 and <i>p</i> = 0.968. C, A-FRET and IHC measurements did not show significant correlations between staging (confined, c, versus non-confined, n, primary tumours) <i>p</i> = 0.774 and <i>p</i> = 0.065 respectively.</div> </figcaption> </figure> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/35114593/" ref="article_id=35114593&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="35114593" data-ga-label=""> Quantification of protein-protein interactions and activation dynamics: A new path to predictive biomarkers. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Larijani B, Miles J.</span> <span class="docsum-authors short-authors">Larijani B, et al.</span> <span class="docsum-journal-citation full-journal-citation">Biophys Chem. 2022 Apr;283:106768. doi: 10.1016/j.bpc.2022.106768. 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Time resolved amplified FRET identifies protein kinase B activation state as a marker for poor prognosis in clear cell renal cell carcinoma - PubMed