title: Preclinical evaluation of herpes simplex virus armed with granulocyte-macrophage colony-stimulating factor in pancreatic carcinoma.
abstract: OBJECTIVE
  To investigate the therapeutic efficacy and mechanisms of action of oncolytic-herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating factor (HSV(GM-CSF)) in pancreatic carcinoma.
  
  
  METHODS
  Tumor blocks were homogenized in a sterile grinder in saline. The homogenate was injected into the right armpit of each mouse. After vaccination, the mice were randomly assigned into four groups: a control group, a high dose HSV(GM-CSF) group [1 × 10⁷ plaque forming units (pfu)/tumor], a medium dose HSV(GM-CSF) group (5 × 10⁶ pfu/tumor) and a low dose HSV(GM-CSF) group (5 × 10⁵ pfu/tumor). After initiation of drug administration, body weights and tumor diameters were measured every 3 d. Fifteen days later, after decapitation of the animal by cervical dislocation, each tumor was isolated, weighed and stored in 10% formaldehyde solution. The drug effectiveness was evaluated according to the weight, volume and relative volume change of each tumor. Furthermore, GM-CSF protein levels in serum were assayed by enzyme-linked immunosorbent assays at 1, 2, 3 and 4 d after injection of HSV(GM-CSF).
  
  
  RESULTS
  Injection of the recombinant mouse HSV encoding GM-CSF resulted in a significant reduction in tumor growth compared to the control group, and dose-dependent effects were observed: the relative tumor proliferation rates of the low dose, medium dose and high dose groups on 15 d after injection were 45.5%, 55.2% and 65.5%, respectively. The inhibition rates of the tumor weights of the low, middle, and high dose groups were 41.4%, 46.7% and 50.5%, respectively. Furthermore, the production of GM-CSF was significantly increased in the mice infected with HSV(GM-CSF). The increase in the GM-CSF level was more pronounced in the high dose group compared to the other two dose groups.
  
  
  CONCLUSIONS
  Our study provides the first evidence that HSV(GM-CSF) could inhibit the growth of pancreatic cancer. The enhanced GM-CSF expression might be responsible for the phenomenon.
authors: Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
authors: Hao
authors: H
authors: Liu
authors: Shou-Jun
authors: SJ
authors: Yuan
authors: Ying-Tai
authors: YT
authors: Chen
authors: Yi-Bin
authors: YB
authors: Xie
authors: Liang
authors: L
authors: Cui
authors: Wei-Zhi
authors: WZ
authors: Yang
authors: De-Xuan
authors: DX
authors: Yang
authors: Yan-Tao
authors: YT
authors: Tian
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050130:Oncolytic Virotherapy; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D047368:Tumor Burden
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Animal test; Gene therapy; Herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating factor; Pancreatic carcinoma
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