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World J Gastroenterol. 2013 Aug 21;19(31):5138-43. doi: 10.3748/wjg.v19.i31.5138.

Preclinical evaluation of herpes simplex virus armed with granulocyte-macrophage colony-stimulating factor in pancreatic carcinoma.

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  • 1Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.

Abstract

AIM:

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.

CONCLUSION:

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.

KEYWORDS:

Animal test; Gene therapy; Herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating factor; Pancreatic carcinoma

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