TY - JOUR
T1 - Tumor-targeting Salmonella typhimurium A1-R combined with recombinant methioninase and cisplatinum eradicates an osteosarcoma cisplatinum-resistant lung metastasis in a patient-derived orthotopic xenograft (PDOX) mouse model
T2 - decoy, trap and kill chemotherapy moves toward the clinic
AU - Igarashi, Kentaro
AU - Kawaguchi, Kei
AU - Kiyuna, Tasuku
AU - Miyake, Kentaro
AU - Miyake, Masuyo
AU - Li, Shukuan
AU - Han, Qinghong
AU - Tan, Yuying
AU - Zhao, Ming
AU - Li, Yunfeng
AU - Nelson, Scott D.
AU - Dry, Sarah M.
AU - Singh, Arun S.
AU - Elliott, Irmina A.
AU - Russell, Tara A.
AU - Eckardt, Mark A.
AU - Yamamoto, Norio
AU - Hayashi, Katsuhiro
AU - Kimura, Hiroaki
AU - Miwa, Shinji
AU - Tsuchiya, Hiroyuki
AU - Eilber, Fritz C.
AU - Hoffman, Robert M.
N1 - Funding Information:
National Cancer Institute (grant number CA213649).
Publisher Copyright:
© 2018 Taylor & Francis.
PY - 2018/3/19
Y1 - 2018/3/19
N2 - In the present study, a patient-derived orthotopic xenograft (PDOX) model of recurrent cisplatinum (CDDP)-resistant metastatic osteosarcoma was treated with Salmonella typhimurium A1-R (S. typhimurium A1-R), which decoys chemoresistant quiescent cancer cells to cycle, and recombinant methioninase (rMETase), which selectively traps cancer cells in late S/G 2 , and chemotherapy. The PDOX models were randomized into the following groups 14 days after implantation: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks). G4, S. typhimurium A1-R (5 × 10 7 CFU/100 μl, i.v., weekly, for 2 weeks); G5, S. typhimurium A1-R (5 × 10 7 CFU/100 μl, i.v., weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G6, S. typhimurium A1-R (5 × 10 7 CFU/100 μl, i.v., weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks) and CDDP (6 mg/kg, i.p. injection, weekly, for 2 weeks). On day 14 after initiation, all treatments except CDDP alone, significantly inhibited tumor growth compared to untreated control: (CDDP: p = 0.586; rMETase: p = 0.002; S. typhimurium A1-R: p = 0.002; S. typhimurium A1-R combined with rMETase: p = 0.0004; rMETase combined with both S. typhimurium A1-R and CDDP: p = 0.0001). The decoy, trap and kill combination of S. typhimurium A1-R, rMETase and CDDP was the most effective of all therapies and was able to eradicate the metastatic osteosarcoma PDOX.
AB - In the present study, a patient-derived orthotopic xenograft (PDOX) model of recurrent cisplatinum (CDDP)-resistant metastatic osteosarcoma was treated with Salmonella typhimurium A1-R (S. typhimurium A1-R), which decoys chemoresistant quiescent cancer cells to cycle, and recombinant methioninase (rMETase), which selectively traps cancer cells in late S/G 2 , and chemotherapy. The PDOX models were randomized into the following groups 14 days after implantation: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks). G4, S. typhimurium A1-R (5 × 10 7 CFU/100 μl, i.v., weekly, for 2 weeks); G5, S. typhimurium A1-R (5 × 10 7 CFU/100 μl, i.v., weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G6, S. typhimurium A1-R (5 × 10 7 CFU/100 μl, i.v., weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks) and CDDP (6 mg/kg, i.p. injection, weekly, for 2 weeks). On day 14 after initiation, all treatments except CDDP alone, significantly inhibited tumor growth compared to untreated control: (CDDP: p = 0.586; rMETase: p = 0.002; S. typhimurium A1-R: p = 0.002; S. typhimurium A1-R combined with rMETase: p = 0.0004; rMETase combined with both S. typhimurium A1-R and CDDP: p = 0.0001). The decoy, trap and kill combination of S. typhimurium A1-R, rMETase and CDDP was the most effective of all therapies and was able to eradicate the metastatic osteosarcoma PDOX.
KW - PDOX
KW - Salmonella typhimurium A1-R
KW - cisplatinum
KW - decoy
KW - kill
KW - lung
KW - metastasis
KW - methioninase
KW - osteosarcoma
KW - resistance
KW - trap
UR - http://www.scopus.com/inward/record.url?scp=85045148127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045148127&partnerID=8YFLogxK
U2 - 10.1080/15384101.2018.1431596
DO - 10.1080/15384101.2018.1431596
M3 - Article
C2 - 29374999
AN - SCOPUS:85045148127
VL - 17
SP - 801
EP - 809
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 6
ER -