期刊
JOURNAL OF SURGICAL RESEARCH
卷 164, 期 2, 页码 248-255出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2009.02.023
关键词
bacterial therapy; pancreatic cancer; orthotopic model; nude mouse; red fluorescent protein; imaging
类别
资金
- National Institutes of Health, National Cancer Institute [CA119841, CA126023]
- U S Army Medical Research and Materiel Command, Department of Defense [W81XWH 06 1 0117]
Cancer of the exocrine pancreas is the fourth leading cause of cancer deaths in the United States Currently, surgical resection is the only hope for cure The majority of patients present with locally-advanced or metastatic disease The most common site for distant metastasis is the liver We report here a modified auxotrophic strain of S typhimurium that can target and inhibit the growth of liver metastasis in a mouse model of pancreatic cancer This strain of S typhimurium is auxotrophic (leucine arginine dependent) but apparently receives sufficient nutritional support from tumor tissue To increase tumor targeting ability and tumor killing efficacy, this strain was further modified by re-isolation from a tumor growing in a nude mouse and termed A1-R In the present study, we demonstrate the efficacy of locally- as well as systemically-administered A1-R on liver metastasis of pancreatic cancer Mice treated with A1-R given locally via intrasplenic injection or systemically via tail vein injection had a much lower hepatic and splenic tumor burden compared with control mice Systemic treatment with intravenous A1-R also increased survival time All results were statistically significant This study suggests the clinical potential of bacterial treatment of a critical metastatic target of pancreatic cancer (C) 2010 Elsevier Inc All rights reserved
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