title: Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin-2 gene.
abstract: BACKGROUND
  The 5-year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer-targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)-harboring lipocalin-2, is capable of treating pancreatic cancer.
  
  
  METHODS
  Tissue microarrays were constructed to detect the expression of lipocalin-2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin-2 was investigated in an analysis of correlations between lipocalin-2 expression and matched clinical characteristics. A lipocalin-2-expressing OV, ZD55-lipocalin-2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo.
  
  
  RESULTS
  Lipocalin-2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55-lipocalin-2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase-dependent apoptosis.
  
  
  CONCLUSIONS
  Higher lipocalin-2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55-lipocalin-2, which specifically expressed higher levels of lipocalin-2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations.
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. pfdbs1@yahoo.com.cn
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Zheng
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Jin
authors.forename: Dan-Song
authors.initials: DS
authors.lastname: Wang
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Liu
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Qin
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics*; D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D050130:Oncolytic Virotherapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; C117307:KRAS protein, human; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins