Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients

Abstract

Background. The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involvedingemcitabineintracellularuptake.Thisstudyinvestigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Methods. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells.The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals(CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Results. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%)

Brain Metastases from Biliary Tract Cancer: A Monocentric Retrospective Analysis of 450 Patients

“…Chemotherapy is well established for the first line with platinum-gemcitabine combination but not for the further lines [6,7] , though radical resection remains the only potentially curative treatment [8] . The role of adjuvant strategies in this pathology remains unclear [9][10][11] . Unfortunately, most patients present an advanced disease at the diagnosis and their prognosis is poor.…”

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

“…118,119 Among these transporters, hENT1 is a major transporter involved in gemcitabine cellular uptake. 120 In fact, hENT1 has been reported as a vital predictive marker of tumor response to gemcitabine-based therapy. 32,121,122 Clinical data showed that cancer patients with a decreased tumor expression of hENT1 have a significantly lower survival rate after gemcitabine treatment than those with tumors that express a higher level of hENT1.…”

hENT-1 Expression and Localization Predict Outcome After Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients

“…In the May 2016 issue of The Oncologist , Brandi et al [1] explored the expression and localization of human equilibrative nucleoside transporter 1 (hENT-1) in paraffin-embedded tissues from radically resected cholangiocarcinoma patients. They highlighted the prognostic role of this transporter and identified hENT-1 as a potential biomarker to predict outcome after adjuvant therapy with gemcitabine [1].…”

“…They highlighted the prognostic role of this transporter and identified hENT-1 as a potential biomarker to predict outcome after adjuvant therapy with gemcitabine [1]. …”