scholarly journals Predictive role of human equilibrative nucleoside transporter 1 in patients with pancreatic cancer treated by curative resection and gemcitabine-only adjuvant chemotherapy

2017 ◽  
Vol 14 (1) ◽  
pp. 599-606 ◽  
Author(s):  
Toru Aoyama ◽  
Keisuke Kazama ◽  
Yohei Miyagi ◽  
Masaaki Murakawa ◽  
Koichiro Yamaoku ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Curative Resection ◽  
Nucleoside Transporter ◽  
Equilibrative Nucleoside Transporter ◽  
Predictive Role

Use of human equilibrative nucleoside transporter 1 to predict survival after adjuvant gemcitabine chemotherapy in resected pancreatic adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 224-224
Author(s):  
S. Morinaga ◽  
N. Yamamoto ◽  
M. Shiozawa ◽  
H. Tamagawa ◽  
M. Ueno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Cells ◽  
Pancreatic Adenocarcinoma ◽  
Curative Resection ◽  
Staining Intensity ◽  
Nucleoside Transporter ◽  
Prognostic Information ◽  
Positive Tumor Cell ◽  
Equilibrative Nucleoside Transporter

224 Background: Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic adenocarcinoma. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for 2′, 2′-difluoro-2deoxycytidine (gemcitabine) uptake into cells. The aim of this study was to determine the outcomes according to the expression of hENT1 in tumor cells in patients treated with adjuvant gemcitabine chemotherapy after curative resection. Methods: We studied 27 pancreatic adenocarcinoma patients treated with gemcitabine adjuvant chemotherapy after curative resection and 8 gemcitabine naïve patients between 2006 and 2008. The hENT expressions were assessed using immunohistochemistry. The staining intensity of hENT1 protein was assigned a score from 0 to 3 based on staining with 0: no staining, 1: weakly positive, 2: moderately positive, 3: strongly positive. The percentage of positive tumor cells was scored as follows, 0: no positive tumor cell; 1: < 50% positive cells, 2: 51-80% positive cells, 3: > 81% positive cells. The hENT1 score was obtained by calculating the sum of these two scores. Each patients received adjuvant chemotherapy by either protocols as follows; GEM 1,000 mg/m2biweekly × 12 (6 months) or GEM 1,000 mg/m2Days 1,8,15; every 4 weeks for 6 months. Results: 11 patients were assigned to low hENT1 expression group (hENT1 score <4) and 16 patients to high hENT1 group (hENT1 score 4,5,6). The median DFS was 7.3 months (95% CI, 3.6-11.1) in the low hENT1 group, and 9.3 months (95% CI, 4.2-14.5) in the high hENT1 group. The median OS was 11.8 months (95% CI, 6.9- 16.6) in the low hENT1 group, and 22.2 months (95% CI, 11.5-32.9). The high hENT1 group had significantly longer DFS (Log-rank, p=0.04) and OS (p=0.02). In the gemcitabine naïve patients after curative resection, neither DFS nor OS correlated with hENT1 expression. Conclusions: In the pancreatic cancer patients treated with adjuvant gemcitabine chemotherapy after curative resection, both DFS and OS correlated with hENT1 expression. The expression of hENT1 may provides prognostic information and predictive for benefit from gemcitabine in these patients. No significant financial relationships to disclose.

scholarly journals Novel Strategy with Gemcitabine for Advanced Pancreatic Cancer

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shuji Komori ◽  
Shinji Osada ◽  
Kazuhiro Yoshida
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Metabolic Enzymes ◽  
Interindividual Variation ◽  
Nucleoside Transporter ◽  
Standard Drug ◽  
Equilibrative Nucleoside Transporter ◽  
Nucleotide Pools ◽  
Novel Strategy

5-fluorouracil (5-FU) is widely used in chemotherapy for gastric and colorectal cancer, but gemcitabine (GEM), and not 5-FU, is approved as a standard drug for use in pancreatic cancer. Interindividual variation in the enzyme activity of the GEM metabolic pathway can affect the extent of GEM metabolism and the efficacy of GEM chemotherapy. Human equilibrative nucleoside transporter 1 (hENT1) is recognized as a major transporter of GEM into cells. In addition, a factor that activates hENT1 is the inhibition of thymidylate synthase (TS), one of the 5-FU metabolic enzymes; TS inhibition mediates depleting intracellular nucleotide pools, resulting in the activation of the salvage pathway mediated through hENT1. In this paper, the role of 5-FU in GEM-based chemotherapy for pancreatic cancer is discussed with special emphasis on enzymes involved in the 5-FU and GEM metabolic pathways and in the correlation between GEM responsiveness and the expression of 5-FU and GEM metabolic enzymes.

scholarly journals The role of the equilibrative nucleoside transporter 1 on tissue and fetal distribution of ribavirin in the mouse

2016 ◽  
Vol 37 (6) ◽  
pp. 336-344 ◽  
Author(s):  
Christopher J. Endres ◽  
Aaron M. Moss ◽  
Kazuya Ishida ◽  
Rajgopal Govindarajan ◽  
Jashvant D. Unadkat
Keyword(s):  
Nucleoside Transporter ◽  
Equilibrative Nucleoside Transporter

Su1644 Human Equilibrate Nucleoside Transporter 1 Expression Predicts Survival of Pancreatic Cancer Patients Trated With Gemcitabine-Based Adjuvant Chemotherapy After Resection

2013 ◽  
Vol 144 (5) ◽  
pp. S-1080
Author(s):  
Toshiyuki Moriya ◽  
Shigemi Fuyama ◽  
Yukinori Kamio ◽  
Koichiro Ozawa ◽  
Shigeo Hasegawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Nucleoside Transporter

The predictive role of CA 19–9 kinetics for time-to-progression (TTP) and overall survival (OS) in patients receiving palliative first-line chemotherapy for advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15637-e15637
Author(s):  
M. Haas ◽  
S. Boeck ◽  
P. Stieber ◽  
R. P. Laubender ◽  
H. Buchner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
First Line ◽  
Predictive Role ◽  
Pre Treatment ◽  
Line Chemotherapy

e15637 Background: Previous studies showed contradictory results for a predictive role of CA 19–9 kinetics during chemotherapy in patients (pts) with pancreatic cancer (PC). Methods: We performed a retrospective, multicenter study in order to evaluate the role of CA 19–9 as a biomarker for TTP and OS in PC. Main inclusion criteria: histological confirmed diagnosis of PC, treatment with first-line chemotherapy for advanced disease, pre-treatment CA 19–9 level of > 5.2 U/ml. As CA 19–9 measurements were conducted in different laboratories using different commercial assays, we defined a subgroup of pts where CA 19–9 was assessed exclusively by the Elecsys assay (Roche Diagnostics). For the analysis of CA 19–9 kinetics, at least one follow-up measurement between day 20 and 64 during first-line chemotherapy had to be available. Pts were divided into two subgroups of CA 19–9 responders and non-responders by cut-offs of a 25% and 50% decline, respectively. OS and TTP were estimated with the Kaplan-Meier-Method, differences between the subgroups were analyzed by using the log-rank test. Results: One hundred and eighty-six pts were included, 83 of them were tested with the Elecsys method. Median age was 63 years, 90 % of the pts were treated within prospective clinical trials. Median pre-treatment CA 19–9 was 1076 U/ml (range 5.7–100,000 U/ml), the median bilirubin was 0.6 mg/dl. Median OS and TTP were 9.8 months (mo) and 5.4 mo, respectively. In univariate analysis, pts with a CA 19–9 decline of at least 25% during chemotherapy lived significantly longer (11.9 mo vs. 8.2 mo, p=0.003) and had a significantly prolonged TTP (5.8 mo vs. 4.4 mo, p=0.018) than those with a lower decline or even CA 19–9 increase. Data for the Elecsys-measurements were comparable (OS: 13.4 mo vs. 8.6 mo, p=0.004; TTP: 7.0 mo vs. 2.6 mo, p=0.003). None of the analyses demanding a CA 19–9 drop of at least 50% reached the level of statistical significance. Conclusion: An early CA 19–9 decline of 25% during first-line chemotherapy may predict OS and TTP in pts with advanced PC. Innovative statistical methods are required to improve our understanding of the utility of CA 19–9 as a predictive biomarker in PC. [Table: see text]

Human Equilibrative Nucleoside Transporter 1 Levels Predict Response to Gemcitabine in Patients With Pancreatic Cancer

2009 ◽  
Vol 136 (1) ◽  
pp. 187-195 ◽  
Author(s):  
James J. Farrell ◽  
Hany Elsaleh ◽  
Miguel Garcia ◽  
Raymond Lai ◽  
Ali Ammar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Nucleoside Transporter ◽  
Equilibrative Nucleoside Transporter
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