Abstract
The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.
Highlights
Pancreatic cancer is one of the most aggressive malignant tumors with a 23 % 1-year survival rate and < 2 % 5-year survival rate
These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the patient-derived orthotopic xenograft (PDOX) model, suggesting its clinical potential
We demonstrate the efficacy of S. typhimurium A1-R following antiangiogenic therapy with bevacizumab/gemcitabine (BEV/GEM) in patientderived orthotopic xenograft (PDOX) and cell line nudemouse models of pancreatic cancer
Summary
Pancreatic cancer is one of the most aggressive malignant tumors with a 23 % 1-year survival rate and < 2 % 5-year survival rate. The two most commonly used chemotherapy drugs approved for the treatment of pancreatic cancer are gemcitabine (GEM) and 5-fluorouracil (5-FU). Overexpression of vascular endothelial growth factor (VEGF) and its receptors is associated with poor prognosis and increased metastatic potential [2, 3]. The strain targets and grows in tumors. In order to increase the tumor-targeting capability of A1, the strain was re-isolated after infection of a human colon tumor growing in nude mice. The tumor-isolated strain, termed S. typhimurium A1-R, had increased targeting for cells in vivo as well as in vitro [6]
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