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Efficacy of Salmonella typhimurium A1‐R Versus Chemotherapy on a Pancreatic Cancer Patient‐Derived Orthotopic Xenograft (PDOX)
Author(s) -
Hiroshima Yukihiko,
Zhao Ming,
Maawy Ali,
Zhang Yong,
Katz Matthew H.G.,
Fleming Jason B.,
Uehara Fuminari,
Miwa Shinji,
Yano Shuya,
Momiyama Masashi,
Suetsugu Atsushi,
Chishima Takashi,
Tanaka Kuniya,
Bouvet Michael,
Endo Itaru,
Hoffman Robert M.
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24769
Subject(s) - pancreatic cancer , gemcitabine , chemotherapy , medicine , pancreatic tumor , cancer , cancer research , green fluorescent protein , pathology , oncology , biology , biochemistry , gene
The aim of this study is to determine the efficacy of tumor‐targeting Salmonella typhimurium A1‐R (A1‐R) on pancreatic cancer patient‐derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID‐NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)‐expressing stroma for the purpose of imaging the tumor after passage to non‐transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1‐R or standard chemotherapy, including gemcitabine (GEM), which is first‐line therapy for pancreatic cancer, for comparison of efficacy. A1‐R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control ( P = 0.011), with comparable efficacy of GEM, CDDP, and 5‐FU. Histopathological response to treatment was defined according to Evans's criteria and A1‐R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1‐R is effective against a very low‐passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1‐1 will have clinical activity in pancreatic cancer, a highly lethal and treatment‐resistant disease and may be most effectively used in combination with other agents. J. Cell. Biochem. 115: 1254–1261, 2014. © 2014 Wiley Periodicals, Inc.