{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:32:04Z","timestamp":1790789524242,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T00:00:00Z","timestamp":1410307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2015,1,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Standard biomarker testing of a single macroscopic disease site is unlikely to be sufficient because of tumor heterogeneity. A focus on examining global biomarker expression or activity, particularly in microscopic residual chemotherapy\u2010resistant disease, is needed for the appropriate selection of targeted therapies. This study was aimed at establishing a technique for the assessment of biomarkers of ovarian cancer peritoneal spread.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>An in\u2010house developed fluorescent imaging device was used to detect the expression of the c\u2010Met oncogene in ovarian cancer. A modified cyanine 5\u2013tagged peptide, GE137, with a high in vitro affinity for the human c\u2010Met protein, was tested in a panel of ovarian cancer cell lines. Finally, the feasibility of detecting submillimeter ovarian cancer cell peritoneal metastases in vivo was tested through the intravenous injection of GE137 into mice with tumor xenografts.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Using optical imaging it was possible to detect c\u2010Met expression in submillimeter peritoneal metastases that were freshly excised from a human high\u2010grade serous ovarian cancer. GE137 selectively bound to the c\u2010Met tyrosine kinase without activating survival signaling pathways (AKT or extracellular signal\u2010regulated kinase phosphorylation) downstream of c\u2010Met. GE137 specifically accumulated in SKOv3 ovarian cancer cells expressing c\u2010Met via clathrin\u2010mediated endocytosis and emitted a fluorescent signal that lasted for at least 8 hours in tumor xenografts in vivo with a sustained high signal\u2010to\u2010noise ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Our results suggest that intraoperative optical imaging could provide a new paradigm for selecting cancer patients for appropriate targeted therapies, particularly after initial chemotherapy. <jats:bold><jats:italic>Cancer<\/jats:italic> 2015;121:202\u201313.<\/jats:bold> \u00a9 <jats:italic>2014 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.29029","type":"journal-article","created":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T15:34:34Z","timestamp":1410363274000},"page":"202-213","source":"Crossref","is-referenced-by-count":14,"title":["Toward operative in vivo fluorescence imaging of the c\u2010<scp>M<\/scp>et proto\u2010oncogene for personalization of therapy in ovarian cancer"],"prefix":"10.1002","volume":"121","author":[{"given":"Shujuan","family":"Liu","sequence":"first","affiliation":[{"name":"Weatherall Institute of Molecular Medicine University of Oxford Oxford United Kingdom"},{"name":"Nuffield Department of Obstetrics and Gynaeoclogy Women's Centre, John Radcliffe Hospital Oxford United Kingdom"},{"name":"Department of Obstetrics and Gynecology, Xijing Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine University of Oxford Oxford United Kingdom"},{"name":"Nuffield Department of Obstetrics and Gynaeoclogy Women's Centre, John Radcliffe Hospital Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Volpi","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Oxford Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"El\u2010Kasti","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine University of Oxford Oxford United Kingdom"},{"name":"Nuffield Department of Obstetrics and Gynaeoclogy Women's Centre, John Radcliffe Hospital Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Klotz","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine University of Oxford Oxford United Kingdom"},{"name":"Nuffield Department of Obstetrics and Gynaeoclogy Women's Centre, John Radcliffe Hospital Oxford United 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