title: Treatment of brain glioblastoma multiforme with pcDNA3.1-Egr. 1p-p16 combined with gamma knife radiation: an experimental study on nude mice.
abstract: BACKGROUND
  High post-operative recurrence and poor prognosis are likely to be related to the infiltrative growth of the glioblastoma multiforme (GBM).
  
  
  OBJECTIVE
  The primary objective of this study is to investigate the possible synergistic effect of the combined treatment of gamma knife radio-surgery (GKRS) and gene therapy for GBM and secondary objective is to explore the role of GKRS for the temporal and spatial regulation of the gene expression.
  
  
  METHODS
  The study performed on 70 nude mice and randomly divided into seven groups. Subcutaneous injection of human GBM tumor cells (T98G) was carried out to establish the animal models. Various doses of liposome-mediated pcDNA3.1-Egr. 1p-p16 recombinant plasmid were transfected through intra-tumor injection. GKRS was scheduled following the plasmid transfection. Tumor volumes were measured every 4 days after the treatment. Subcutaneous tumor nodule specimens were collected to analyze the cell apoptosis and p16 gene expression using terminal-deoxynucleoitidyl transferase mediated nick end labeling staining and reverse transcription-polymerase chain reaction. Tumor volumes, levels of cell apoptosis and p16 gene expression were compared between groups.
  
  
  RESULTS
  Rates of tumor growth were significantly lower in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS groups than that in the remaining groups 28 days following the GKRS management. The p16mRNA expression was noted in both of the pcDNA3.1-Egr. 1p-p16 plasmid group and the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with marginal-dose of 20 Gy group. The level of messenger ribonucleic acid expression was higher in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with the marginal-dose of 20 Gy group, with a markedly increased apoptotic and necrotic cells, than that in the pcDNA3.1-Egr. 1p-p16 plasmid group.
  
  
  CONCLUSIONS
  In animal studies, pcDNA3.1-Egr. 1p-p16 in combination with GKRS is a preferable management option for the GBM to the sole use of GKRS or gene therapy. It may be a novel approach for the treatment of human patient with GBM.
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Wenke
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Wang
authors.initials: W
authors.lastname: Xing
authors.forename: Shi
authors.initials: S
authors.lastname: Yujun
authors.forename: Zhong
authors.initials: Z
authors.lastname: Qi
authors.forename: Ren
authors.initials: R
authors.lastname: Haibo
authors.forename: Wang
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D016634:Radiosurgery; D014162:Transfection; D016896:Treatment Outcome
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051766:Early Growth Response Protein 1; D009363:Neoplasm Proteins