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dc.contributor.authorMiles, James
dc.contributor.authorApplebee, Christopher J.
dc.contributor.authorLeboucher, Pierre
dc.contributor.authorLópez Fernández, Sonia
dc.contributor.authorLee, Dae-Jin
dc.contributor.authorGuarch, Rosa
dc.contributor.authorWard, Stephen G.
dc.contributor.authorParker, Peter J.
dc.contributor.authorLópez Fernández de Villaverde, José Ignacio ORCID
dc.contributor.authorLarijani, Banafshé ORCID
dc.date.accessioned2018-06-14T12:02:26Z
dc.date.available2018-06-14T12:02:26Z
dc.date.issued2017-12
dc.identifier.citationBBA Clinical 8 : 97-102 (2017)es_ES
dc.identifier.issn2214-6474
dc.identifier.urihttp://hdl.handle.net/10810/27526
dc.description.abstractPurpose: 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. Material & methods: 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 (AFRET) was utilised for assessing the activation state of PKB/Akt and this was compared to conventional immunohistochemistry measurements. Results: Activation state of PKB/Akt in primary tumours defined by A-FRET correlated with poorer overall survival (hazard ratio 0.228; p=0.002). Whereas, increased protein expression of phosphoPKB/Akt, identified using classical immunohistochemistry, yielded no significant difference (hazard ratio 1.390; p=0.548). Conclusions: 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. General significance: 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.es_ES
dc.description.sponsorshipWe also acknowledge the support of the Ikerbasque Foundation of Science; the Spanish Ministry of Economy for the grants [grant number BFU 2011-28566] to B.L.; Basque Government through the BERC 360 2014- 2017; the Spanish Ministry of Economy and Competitiveness MINECO and FEDER: BCAM Severo Ochoa excellence accreditation SEV-2013-0323 to DJL.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/BFU 2011-28566es_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/SEV-2013-0323es_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectclear cell renal cell carcinomaes_ES
dc.subjectprotein kinase b (pkb/akt)es_ES
dc.subjectamplified fretes_ES
dc.subjectprognosises_ES
dc.subjectfret-flimes_ES
dc.subjectbiomarker activationes_ES
dc.subjectbreast-canceres_ES
dc.subjectAKT/PKBes_ES
dc.subjectPTENes_ES
dc.titleTime resolved amplified FRET identifies protein kinase B activation state as a marker for poor prognosis in clear cell renal cell carcinomaes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holder2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).es_ES
dc.rights.holderAtribución-NoComercial-SinDerivadas 3.0 España*
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2214647417300363?via%3Dihubes_ES
dc.identifier.doi10.1016/j.bbacli.2017.10.002
dc.departamentoesEspecialidades médico-quirúrgicases_ES
dc.departamentoeuMedikuntza eta kirurgia espezialitateakes_ES


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2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Except where otherwise noted, this item's license is described as 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).