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

引用

World Journal of Gastroenterology 2013年第31期19卷 5138-5143页

作者： Hao Liu Shou-Jun Yuan Ying-Tai Chen Yi-Bin Xie Liang Cui Wei-Zhi Yang De-Xuan Yang Yan-Tao Tian Department of Abdominal Surgery Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Pharmacological and Toxi-cological Laboratory Institute of Radiation Medicine Medical Radiobiology Laboratory Cancer Hospital Chinese Academy of Medical Science Peking Union Medical College

AIM: To investigate the therapeutic efficacy and mechanisms of action of oncolytic-herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating factor(HSVGM-CSF) in pancreatic ***: Tumor blocks were homogenized in a sterile grinder in *** homogenate was injected into the right armpit of each *** vaccination,the mice were randomly assigned into four groups: a control group,a high dose HSVGM-CSFgroup [1 × 107plaque forming units(pfu)/tumor],a medium dose HSVGM-CSF group(5 × 106pfu/tumor) and a low dose HSVGM-CSF group(5 × 105pfu/tumor).After initiation of drug administration,body weights and tumor diameters were measured every 3 *** days later,after decapitation of the animal by cervical dislocation,each tumor was isolated,weighed and stored in 10% formaldehyde *** drug effectiveness was evaluated according to the weight,volume and relative volume change of each ***,GM-CSF protein levels in serum were assayed by enzyme-linked immunosorbent assays at 1,2,3 and 4 d after injection of ***: Injection of the recombinant mouse HSV encoding GM-CSF resulted in a significant reduction in tumor growth compared to the control group,and dosedependent 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%,*** inhibition rates of the tumor weights of the low,middle,and high dose groups were 41.4%,46.7% and 50.5%,***,the production of GM-CSF was significantly increased in the mice infected with *** increase in the GM-CSF level was more pronounced in the high dose group compared to the other two dose ***: Our study provides the first evidence that HSVGM-CSFcould inhibit the growth of pancreatic *** enhanced GM-CSF expression might be responsible for the phenomenon.

关键词： Pancreatic carcinoma Gene therapy Animal test herpes-simplex-virus encoding granulocytemacrophage colony-stimulating factor

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