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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.

  • Author(s): Hiroshima, Yukihiko;
  • Zhang, Yong;
  • Murakami, Takashi;
  • Maawy, Ali;
  • Miwa, Shinji;
  • Yamamoto, Mako;
  • Yano, Shuya;
  • Sato, Sho;
  • Momiyama, Masashi;
  • Mori, Ryutaro;
  • Matsuyama, Ryusei;
  • Chishima, Takashi;
  • Tanaka, Kuniya;
  • Ichikawa, Yasushi;
  • Bouvet, Michael;
  • Endo, Itaru;
  • Zhao, Ming;
  • Hoffman, Robert M
  • et al.
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.

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