Research Papers:

Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cell line mouse models

Yukihiko Hiroshima, Yong Zhang, Takashi Murakami, Ali Maawy, Shinji Miwa, Mako Yamamoto, Shuya Yano, Sho Sato, Masashi Momiyama, Ryutaro Mori, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Ming Zhao and Robert M. Hoffman _

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Oncotarget. 2014; 5:12346-12357. https://doi.org/10.18632/oncotarget.2641

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Yukihiko Hiroshima1,2,3, Yong Zhang1, Takashi Murakami3, Ali Maawy2, Shinji Miwa1,2, Mako Yamamoto1,2, Shuya Yano1,2, Sho Sato3, Masashi Momiyama3, Ryutaro Mori3, Ryusei Matsuyama3, Takashi Chishima3, Kuniya Tanaka3, Yasushi Ichikawa3, Michael Bouvet2, Itaru Endo3, Ming Zhao1 and Robert M. Hoffman1,2

1 AntiCancer, Inc., San Diego, CA, USA

2 Department of Surgery, University of California San Diego, San Diego, CA, USA

3 Yokohama City University Graduate School of Medicine, Yokohama, Japan


Robert M. Hoffman or Ming Zhao, email:

Keywords: Pancreatic cancer, Salmonella typhimurium A1-R, patient-derived orthotopic xenograft (PDOX), orthotopic, nude mice, GFP, VEGF, anti-angiogenic therapy, bevacizumab, gemcitabine

Received: September 17, 2014 Accepted: October 28, 2014 Published: October 28, 2014


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.

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