000125979 001__ 125979
000125979 005__ 20241125101137.0
000125979 0247_ $$2doi$$a10.3390/cancers15092457
000125979 0248_ $$2sideral$$a133537
000125979 037__ $$aART-2023-133537
000125979 041__ $$aeng
000125979 100__ $$0(orcid)0000-0001-5932-2889$$aLanas, Á.$$uUniversidad de Zaragoza
000125979 245__ $$aBiomarkers of response to low-dose aspirin in familial adenomatous polyposis patients
000125979 260__ $$c2023
000125979 5060_ $$aAccess copy available to the general public$$fUnrestricted
000125979 5203_ $$aBackground: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial. Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas. Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B2 generation ex vivo (serum TXB2). However, enhanced residual urinary 11-dehydro-TXB2 and urinary PGEM, primary metabolites of TXA2 and prostaglandin (PG)E2, respectively, were detected in association with incomplete acetylation of COX-1 in normal colorectal biopsies and adenomas. Proteomics of adenomas showed that Aspirin significantly modulated only eight proteins. The upregulation of vimentin and downregulation of HBB (hemoglobin subunit beta) distinguished two groups with high vs. low residual 11-dehydro-TXB2 levels, possibly identifying the nonresponders and responders to Aspirin. Conclusions: Although low-dose Aspirin appropriately inhibited the platelet, persistently high systemic TXA2 and PGE2 biosynthesis were found, plausibly for a marginal inhibitory effect on prostanoid biosynthesis in the colorectum. Novel chemotherapeutic strategies in FAP can involve blocking the effects of TXA2 and PGE2 signaling with receptor antagonists.
000125979 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI14-01218$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI17-01109
000125979 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000125979 590__ $$a4.5$$b2023
000125979 592__ $$a1.391$$b2023
000125979 591__ $$aONCOLOGY$$b78 / 322 = 0.242$$c2023$$dQ1$$eT1
000125979 593__ $$aOncology$$c2023$$dQ1
000125979 593__ $$aCancer Research$$c2023$$dQ2
000125979 594__ $$a8.0$$b2023
000125979 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000125979 700__ $$aTacconelli, S.
000125979 700__ $$aContursi, A.
000125979 700__ $$0(orcid)0000-0001-5813-3445$$aPiazuelo, E.$$uUniversidad de Zaragoza
000125979 700__ $$aBruno, A.
000125979 700__ $$aRonci, M.
000125979 700__ $$aMarcone, S.
000125979 700__ $$aDovizio, M.
000125979 700__ $$0(orcid)0000-0002-8678-4680$$aSopeña, F.$$uUniversidad de Zaragoza
000125979 700__ $$aFalcone, L.
000125979 700__ $$aMilillo, C.
000125979 700__ $$aMucci, M.
000125979 700__ $$aBallerini, P.
000125979 700__ $$aPatrignani, P.
000125979 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000125979 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000125979 773__ $$g15, 9 (2023), 2457 [21 pp.]$$pCancers$$tCancers$$x2072-6694
000125979 8564_ $$s3534490$$uhttps://zaguan.unizar.es/record/125979/files/texto_completo.pdf$$yVersión publicada
000125979 8564_ $$s2864665$$uhttps://zaguan.unizar.es/record/125979/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000125979 909CO $$ooai:zaguan.unizar.es:125979$$particulos$$pdriver
000125979 951__ $$a2024-11-22-12:01:21
000125979 980__ $$aARTICLE