***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Purpose : Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic adenocarcinoma and its use in combination with radiotherapy is under exploration . Human equilibrative nucleoside transporter 1 ( hENT1 ) and human concentrative nucleoside transporter ( hCNT ) 1 and 3 are the major transporters responsible for 2′,2′-difluoro-2-deoxycytidine ( gemcitabine ) uptake into cells . The aim of this study was to determine patients ' outcome according to the expression of hENT1 and hCNT3 in tumoral cells after postoperative gemcitabine-based chemoradiation regimen . Experimental Design : We studied tumor blocks from 45 pancreatic adenocarcinoma patients treated with gemcitabine-based chemoradiation after curative resection  and assessed hENT1 and hCNT3 expression using immunohistochemistry . Results : When adjusted for the effects of lymph node ratio and tumor diameter , patients with high hENT1 expression had significantly longer disease-free survival and overall survival ( OS ) than patients with low expression , whereas high hCNT3 expression was only associated with longer OS . In a combined analysis , patients with two favorable prognostic factors ( hENT1high/hCNT3high expression ) had a longer survival ( median OS , 94.8 months ) than those having one ( median OS , 18.7 months ) or no ( median OS , 12.2 months ) favorable prognostic factor . Conclusions : Pancreatic adenocarcinoma patients with a high expression of hENT1 and hCNT3 immunostaining have a significantly longer survival after adjuvant gemcitabine-based chemoradiation . These biomarkers deserve prospect i ve evaluation in patients receiving gemcitabine-based adjuvant therapy Purpose : Gemcitabine monotherapy is the st and ard palliative chemotherapy for pancreatic adenocarcinoma .  Gemcitabine requires plasma membrane nucleoside transporter proteins to efficiently enter cells and exert it cytotoxicity . In vitro studies have demonstrated that deficiency of human equilibrative nucleoside transporter 1 ( hENT1 ) , the most widely abundant and distributed nucleoside transporter in human cells , confers resistance to gemcitabine toxicity , but the distribution and abundance of nucleoside transporters in normal and malignant pancreatic tissue is unknown . Experimental Design : We studied tumor blocks from normal pancreas and 21 Alberta patients with gemcitabine-treated pancreatic cancer .  Immunohistochemistry on the formalin-fixed , paraffin-embedded tissues was performed with specific hENT1 and human Concentrative Nucleoside Transporter 3 monoclonal antibodies and scored by a pathologist blinded to clinical outcomes . Results : hENT1 was detected in normal Langerhan cells and lymphocytes but not in normal gl and ular elements . Patients in whom all adenocarcinoma cells had detectable hENT1 had significantly longer median survivals from gemcitabine initiation than those for whom hENT1 was absent in a proportion ( 10 to 100 % ) of adenocarcinoma cells ( median survival , 13 versus 4 months , P = 0.01 ) . Immunohistochemistry for human Concentrative Nucleoside Transporter 3 revealed moderate to high-intensity staining in all adenocarcinoma tissue sample s. Conclusions : Patients with pancreatic adenocarcinoma with uniformly detectable hENT1 immunostaining have a significantly longer survival after gemcitabine chemotherapy than tumors without detectable hENT1 . Immunohistochemistry for hENT1 shows promise as a molecular predictive assay to appropriately select patients for palliative gemcitabine chemotherapy but requires formal validation in prospect i ve , r and omized trials BACKGROUND Human equilibrative nucleoside transporter 1 ( hENT1 ) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection . METHODS Microarrays from 434 patients r and omized to chemotherapy in the ESPAC-3 trial ( plus controls from ESPAC-1/3 ) were stained with the 10D7G2 anti-hENT1 antibody . Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score ( 48 ) . High and low hENT1-expressing groups were compared using Kaplan-Meier curves , log-rank tests , and Cox proportional hazards models . All statistical tests were two-sided . RESULTS Three hundred eighty patients ( 87.6 % ) and 1808 cores were suitable and included in the final analysis . Median overall survival  for gemcitabine-treated patients ( n = 176 ) was 23.4 ( 95 % confidence interval [ CI ] = 18.3 to 26.0 ) months vs 23.5 ( 95 % CI = 19.8 to 27.3 ) months for 176 patients treated with 5-fluorouracil/folinic acid ( χ(2 ) 1=0.24 ; P = .62 ) . Median survival for patients treated with gemcitabine was 17.1 ( 95 % CI = 14.3 to 23.8 ) months for those with low hENT1 expression vs 26.2 ( 95 % CI = 21.2 to 31.4 ) months for those with high hENT1 expression ( χ(2)₁= 9.87 ; P = .002 ) . For the 5-fluorouracil  group , median survival was 25.6 ( 95 % CI = 20.1 to 27.9 ) and 21.9 ( 95 % CI = 16.0 to 28.3 ) months for those with low and high hENT1 expression , respectively ( χ(2)₁ = 0.83 ; P = .36 ) . hENT1 levels were not predictive of survival for the 28 patients of the observation group ( χ(2)₁ = 0.37 ; P = .54 ) . Multivariable analysis  confirmed hENT1 expression as a predictive marker in gemcitabine-treated ( Wald χ(2 ) = 9.16 ; P = .003 ) but not 5-fluorouracil-treated ( Wald χ(2 ) = 1.22 ; P = .27 ) patients . CONCLUSIONS Subject to prospect i ve validation , gemcitabine should not be used for patients with low tumor hENT1 expression BACKGROUND High expression of human equilibrative nucleoside transporter 1 ( hENT1 ) is considered to predict survival in patients treated with adjuvant gemcitabine for pancreatic cancer . A st and ard evaluation system for immunohistochemical analysis ( antibody , scoring system ) has not yet been established . METHODS CONKO-001 , a prospect i ve r and omised phase III study investigated the role of adjuvant gemcitabine ( gem ) as compared to observation ( obs ) . Tumour sample s of 156 patients were analysed by immunohistochemistry with the rabbit monoclonal antibody SP120 ( Ventana Medical Systems ) for expression of hENT1 . Kaplan-Meier analyses for median disease-free survival ( DFS ) and overall survival ( OS ) were performed in dependence of hENT1 expression measured analogously to Farrell et al. 2009 and Poplin et al. 2013 . RESULTS For the 88 gem and 68 obs patients , median DFS/OS was 12.9/22.7 months and 6.2/19.1 months . High hENT1 expression was not associated with improved median DFS ( Farrell : no hENT1 22.2 months , low hENT1 13.7 months , high hENT1 12.1 months , p=0.248 ; Poplin : low hENT1 13.2 months versus high hENT1 11.5 months , p=0.5 ) or median OS ( Farrell : no hENT1 21.7 months , low hENT1 24.7 months , high hENT1 19.5 , p=0.571 ; Poplin : low hENT1 24.4 months versus high hENT1 19.7 months , p=0.92 ; ) in the gem group or in the obs group ( median DFS Farrell : no hENT1 5.1 months , low hENT1 6.2 months , high hENT1 7.5 months , p=0.375 ; Poplin : low hENT1 6.2 months versus high hENT1 5.9 months , p=0.83 ; median OS Farrell : no hENT1 20.2months , low hENT1 17.7 months , high HENT1 19.1 months , p=0.738 ; Poplin : low hENT1 17.7 months versus high hENT1 20.4 months , p=0.65 ) measured by the Farrell or Poplin Score . CONCLUSIONS We can not confirm a predictive role of hENT1 measured by the clone SP120 rabbit antibody in our study population . Reproducible st and ard procedures are urgently needed prior to the implementation or exclusion of hENT1 as a predictive biomarker in the treatment of pancreatic cancer . TRIAL REGISTRATION IS RCT N34802808 Pancreatic cancer is one of the most lethal cancers , where curative surgical resections are rare and less than 5 % of patients experience long-term survival . Despite numerous clinical trials , improvements in the systemic treatment of this disease have been limited . Gemcitabine , a nucleoside analogue , is still considered the st and ard of care chemotherapy for most patients in the advanced disease setting . To exert its cytotoxic effects , gemcitabine must enter cells via nucleoside transporters , most notably human equilibrative nucleoside transporter 1 ( hENT1 ) . Increasingly strong evidence suggests hENT1 is a prognostic biomarker in gemcitabine-treated pancreatic cancer , and may well be a predictive biomarker of gemcitabine efficacy . In this review , we synthesize the literature surrounding hENT1 in pancreatic cancer , identify the key outst and ing questions , and suggest strategies to prospect ively evaluate the clinical utility of hENT1 in future clinical studies AIMS The human equilibrative nucleoside transporter 1 ( hENT1 ) expression level in pancreatic ductal adenocarcinoma ( PDAC ) may predict survival in gemcitabine-treated patients after resection . These results have been obtained with a murine anti-hENT1 antibody ( 10D7G2 ) that is not commercially available . Another antibody , which is rabbit-derived ( SP120 ) , appears to have no predictive value in local , advanced or metastatic PDAC . We aim ed to study whether the two antibodies are equivalent . METHODS AND RESULTS We compared hENT1 expression with both antibodies in resected PDAC . The results were correlated with overall survival ( OS ) following gemcitabine treatment . Tissues from two sets of patients ( n = 147 each ) were stained with SP120 by the use of different equipment , with an amplification technique being used for set 2 . The rate of ' hENT1 high ' cases was lower with SP120 ( set 1 , 7 % versus 48 % ; set 2 , 11 % versus 38 % ) . With the amplification technique , the rate of hENT1 high cases was globally similar between both antibodies . However , concordance between the antibodies was found in only 50 % of cases . High hENT1 expression was predictive of OS only with 10D7G2 ( hazard ratio 0.49 ; 95 % confidence interval 0.24 - 0.98 ; P = 0.045 ) . CONCLUSIONS The two antibodies are not equivalent . Further prospect i ve studies seem to be warranted before hENT1 testing for PDAC is used in daily practise BACKGROUND The role of human equilibrative nucleoside transporter 1 ( hENT1 ) as a predictive biomarker for gemcitabine efficacy in advanced pancreatic cancer remains unclear to date . PATIENTS AND METHODS AIO-PK0104 was a German multicenter phase III trial comparing gemcitabine/erlotinib followed by capecitabine ( GEC ) with capecitabine/erlotinib followed by gemcitabine ( CEG ) in advanced pancreatic cancer . Archival tumour tissue from 169 of the 274 eligible study patients was available for a central and st and ardised immunohistochemistry staining for hENT1 expression using the SP120 rabbit monoclonal anti-hENT1 antibody . Within a retrospective translational subgroup analysis , biomarker data were correlated with efficacy end-points . RESULTS Thirty-nine out of 130 fresh-cut slides were scored as hENT1(high ) ( 30 % ) , whereas 91 sample s were classified as hENT1(low ) ( 70 % ) . For the 62 patients r and omised to CEG median overall survival was estimated with 6.4 months in the hENT1(low ) compared to 6.9 months in the hENT1(high ) subgroup ( Hazard Ratio ( HR ) 0.88 , 95 % confidence interval ( CI ) 0.48 - 1.61 , p=0.67 ) . For the 68 patients r and omised to GEC survival was 5.7 months in the hENT1(low ) compared to 4.4 months in the hENT1(high ) subgroup ( HR 1.16 , 95 % CI 0.69 - 1.96 , p=0.57 ) . In 101 patients receiving gem 
    Output:
    
Conclusion : Expression of hENT1 is a suitable prognostic biomarker in patients undergoing adjuvant gemcitabine‐based chemotherapy .