title: Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer.
abstract: OBJECTIVE
  To investigate the in vitro effects of suicide gene therapy system of herpes simplex virus thymidine kinase gene (HSV-TK) in combination with the treatment of nucleotide analog-ganciclovir (GCV) on human pancreatic cancer, and to provide a novel clinical therapeutic method for human pancreatic cancer.
  
  
  METHODS
  We used a replication defective recombinant retrovirus vector GINaTK (bearing HSV-TK gene) to make packaging cell PA317 produce progeny virions. We then transferred the HSV-TK gene to target cells SW1990 using these progeny virions, and treated these gene-modified tumor cells with GCV to study the sensitivity of the cells to GCV and their bystander effects by routine MTT-method.
  
  
  RESULTS
  Packaging cell PA317/TK was successfully constructed, and we acquired SW1990/TK through virus progeny infection. These gene-modified pancreatic cancer cells were sensitive to the treatment of GCV compared with unmodified tumor cells (t=4.15, n=10, P<0.0025). We also observed a remarkable bystander effect by mixing two kinds of cells at different ratio.
  
  
  CONCLUSIONS
  Our data demonstrate that HSV-TK/GCV suicide gene therapy system is effective for treating experimental human pancreatic cancer, which is largely resistant to the common therapies, so the suicide gene therapy system may be a potential treatment approach for pancreatic cancer.
authors.affiliation: Genetics Research Center, School of Basic-Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China. wjing18@sohu.com
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xiao-Xuan
authors.initials: XX
authors.lastname: Lu
authors.forename: Dao-Zhen
authors.initials: DZ
authors.lastname: Chen
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Li
authors.forename: Li-Shan
authors.initials: LS
authors.lastname: Zhang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015774:Ganciclovir / Q000627:therapeutic use*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000628:therapy*; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir