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RESEARCH PRODUCT

Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC)

Luigi ChiusaCarol E CassJohn R. MackeyEnrico VasileRaymond LaiAndrea D. ManazzaAlice GiacobinoMichele CaragliaDaniele SantiniGiacomo Giulio BaldiAlfredo FalconeSergio RizzoVincenzo CatalanoGiuseppe ToniniBruno VincenziGaia SchiavonAntonio Russo

subject

Oncologymedicine.medical_specialtyPathologyCancer ResearchAntimetabolites Antineoplasticmedicine.medical_treatmentEquilibrative nucleoside transporter 1DeoxycytidineEquilibrative Nucleoside Transporter 1Statistical significanceInternal medicineDrug DiscoveryMedicineHumansHENT1PharmacologyChemotherapyUnivariate analysisPredictive markerBiliary tract cancer; Gemcitabine; HENT1; Predictive factor; Drug Discovery3003 Pharmaceutical Science; Pharmacology; Cancer Researchbiologybusiness.industryDrug Discovery3003 Pharmaceutical ScienceCancermedicine.diseaseImmunohistochemistryGemcitabineGemcitabineBiliary Tract NeoplasmsOncologybiology.proteinImmunohistochemistryBiliary tract cancerbusinessPredictive factormedicine.drug

description

Background and aim: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. Materials and Methods: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. Results: Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) (p=0.0394; HR 2.902, 95%CI 1.053-7.996). The median TTP was 6.33 versus 2.83 months, respectively in patients with positive versus negative hENT1 staining. Moreover, patients with positive hENT1 expression showed a longer median overall survival when compared with patients with low hENT1 expression (14 versus 7 months, respectively), but this difference did not reach the statistical significance (p=0.128). Conclusions: Therefore, hENT1 may be a relevant predictive marker of benefit from gemcitabine-based therapies in patients with advanced BTC. © 2011 Bentham Science Publishers Ltd.

10.2174/156800911793743600http://hdl.handle.net/11573/1641798