title: Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.
abstract: BACKGROUND
  Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC.
  
  
  METHODS
  The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription-polymerase chain reactions and examined for correlations with GEM sensitivity.
  
  
  RESULTS
  The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively).
  
  
  CONCLUSIONS
  hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Eto
authors.forename: H
authors.initials: H
authors.lastname: Kawakami
authors.forename: M
authors.initials: M
authors.lastname: Kuwatani
authors.forename: T
authors.initials: T
authors.lastname: Kudo
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Kawahata
authors.forename: A
authors.initials: A
authors.lastname: Takasawa
authors.forename: M
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuno
authors.forename: M
authors.initials: M
authors.lastname: Asaka
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C499374:NOTCH3 protein, human; D012333:RNA, Messenger; D000071656:Receptor, Notch3; D051880:Receptors, Notch; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine