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.
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.
AntiCancer, Inc., San Diego, CA, USA. Department of Surgery, University of California San Diego, San Diego, CA, USA. Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yukihiko
Y
Hiroshima
AntiCancer, Inc., San Diego, CA, USA.
Yong
Y
Zhang
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Takashi
T
Murakami
Department of Surgery, University of California San Diego, San Diego, CA, USA.
Ali
A
Maawy
AntiCancer, Inc., San Diego, CA, USA. Department of Surgery, University of California San Diego, San Diego, CA, USA.
Shinji
S
Miwa
AntiCancer, Inc., San Diego, CA, USA. Department of Surgery, University of California San Diego, San Diego, CA, USA.
Mako
M
Yamamoto
AntiCancer, Inc., San Diego, CA, USA. Department of Surgery, University of California San Diego, San Diego, CA, USA.
Shuya
S
Yano
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Sho
S
Sato
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Masashi
M
Momiyama
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Ryutaro
R
Mori
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Ryusei
R
Matsuyama
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Takashi
T
Chishima
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Kuniya
K
Tanaka
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yasushi
Y
Ichikawa
Department of Surgery, University of California San Diego, San Diego, CA, USA.
Michael
M
Bouvet
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Itaru
I
Endo
AntiCancer, Inc., San Diego, CA, USA.
Ming
M
Zhao
AntiCancer, Inc., San Diego, CA, USA. Department of Surgery, University of California San Diego, San Diego, CA, USA.
Robert M
RM
Hoffman
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D010190:Pancreatic Neoplasms / Q000382:microbiology / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction; D012480:Salmonella Infections; D012486:Salmonella typhimurium; D042461:Vascular Endothelial Growth Factor A; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A