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      Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models

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          Abstract

          Imaging of clinically relevant preclinical animal models is critical to the development of personalized therapeutic strategies for endometrial carcinoma. Although orthotopic patient-derived xenografts (PDXs) reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by the lack of appropriate imaging modalities. Here, we describe molecular imaging of a near-infrared fluorescently labeled monoclonal antibody targeting epithelial cell adhesion molecule (EpCAM) as an in vivo imaging modality for visualization of orthotopic endometrial carcinoma PDX. Application of this near-infrared probe (EpCAM-AF680) enabled both spatio-temporal visualization of development and longitudinal therapy monitoring of orthotopic PDX. Notably, EpCAM-AF680 facilitated imaging of multiple PDX models representing different subtypes of the disease. Thus, the combined implementation of EpCAM-AF680 and orthotopic PDX models creates a state-of-the-art preclinical platform for identification and validation of new targeted therapies and corresponding response predicting markers for endometrial carcinoma.

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          Most cited references40

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          Interrogating open issues in cancer precision medicine with patient-derived xenografts

          This Opinion article discusses progress and challenges in using patient-derived xenograft (PDX) models in cancer precision medicine. It is primarily co-authored by members of the EurOPDX Consortium and as such highlights the merits of shared PDX resources.
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            Markers for individualised therapy in endometrial carcinoma.

            Most endometrial carcinomas are diagnosed at an early stage. Still, 15-20% of these carcinomas recur with limited effect of systemic therapies in metastatic disease. Improved ability to target surgical and systemic therapies to well selected patient populations will increase the likelihood of benefits. Retrospective studies have identified several markers for lymph-node metastasis and poor prognosis. No new targeted treatments are available in the clinic, but recent comprehensive molecular characterisations of tumours have identified drugs targeting the PI3K/PTEN/AKT/mTOR pathway and fibroblast growth factor receptor (FGFR) 2 as promising for further studies, also reflected in current clinical trials investigating endometrial carcinoma. A more systematic approach to integration of biomarkers in surgical trials and clinical trials of therapeutics, earlier characterisation and standardisation of diagnostic imaging and biomarker assessment, and prospective implementation studies are needed for clinical implementation. We summarise the present knowledge regarding biomarkers in endometrial carcinoma, assessing how such markers could be applied to address key clinical challenges for the treatment of this disease. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis.

              In the staging of endometrial cancer, controversy remains regarding the role of sentinel lymph node mapping compared with other nodal assessment strategies.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                06 February 2020
                February 2020
                : 12
                : 2
                : 370
                Affiliations
                [1 ]Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway; tina.fonnes@ 123456uib.no (T.F.); Elin.Strand@ 123456helse-bergen.no (E.S.); hege.berg@ 123456uib.no (H.F.B.); Line.Bjorge@ 123456uib.no (L.B.); camilla.krakstad@ 123456uib.no (C.K.)
                [2 ]Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway
                [3 ]Center for Nuclear Medicine/PET, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway; kristine.eldevik.fasmer@ 123456helse-bergen.no
                [4 ]Department of Biomedicine, University of Bergen, 5021 Bergen, Norway; heidi.espedal@ 123456uib.no (H.E.); kristinasortland@ 123456hotmail.com (K.S.)
                [5 ]Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway; ingunn.stefansson@ 123456uib.no
                [6 ]Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway; ingfrid.helene.salvesen.haldorsen@ 123456helse-bergen.no
                [7 ]Section for Radiology, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway
                Author notes
                [* ]Correspondence: Emmet.Mc.Cormack@ 123456uib.no ; Fax: +47-55-97-29-50
                Author information
                https://orcid.org/0000-0002-5894-8967
                https://orcid.org/0000-0002-1712-6609
                https://orcid.org/0000-0002-0190-8999
                https://orcid.org/0000-0001-9313-7564
                https://orcid.org/0000-0002-0174-8139
                Article
                cancers-12-00370
                10.3390/cancers12020370
                7072497
                32041116
                148c70ff-6df2-4b0b-8881-296f6f43ac5a
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 January 2020
                : 05 February 2020
                Categories
                Article

                endometrial carcinoma,epithelial cell adhesion molecule,near-infrared fluorescent imaging,patient-derived xenografts,orthotopic mouse model

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