Tumor-targeting Salmonella typhimurium A1-R arrests a doxorubicin-resistant PDGFRA-amplified patient-derived orthotopic xenograft mouse model of pleomorphic liposarcoma

被引:13
作者
Kiyuna, Tasuku [1 ,2 ,3 ]
Tome, Yasunori [3 ]
Murakami, Takashi [1 ,2 ]
Zhao, Ming [1 ]
Miyake, Kentaro [1 ,2 ]
Igarashi, Kentaro [1 ,2 ]
Kawaguchi, Kei [1 ,2 ]
Miyake, Masuyo [1 ,2 ]
Oshiro, Hiromichi [1 ,2 ]
Higuchi, Takashi [1 ,2 ]
Li, Yunfeng [4 ]
Dry, Sarah M. [4 ]
Nelson, Scott D. [4 ]
Russell, Tara A. [5 ]
Eckardt, Mark A. [6 ]
Singh, Arun S. [7 ]
Kanaya, Fuminori [3 ]
Eilber, Fritz C. [5 ]
Hoffman, Robert M. [1 ,2 ]
机构
[1] AntiCancer Inc, 7917 Ostrow St, San Diego, CA 92111 USA
[2] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA
[3] Univ Ryukyus, Grad Sch Med, Dept Orthoped Surg, 207 Uehara, Nishihara, Okinawa 9030215, Japan
[4] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Div Surg Oncol, 10833 LeConte Ave,Rm 54-140 CHS, Los Angeles, CA 90095 USA
[6] Yale Sch Med, Dept Surg, New Haven, CT USA
[7] Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA 90095 USA
关键词
green fluorescent protein; patient-derived orthotopic xenograft; PDGFRA amplification; pleomorphic liposarcoma; Salmonella typhimurium A1-R; soft-tissue sarcoma; tumor targeting; SUBCUTANEOUS ECTOPIC MODEL; HUMAN PANCREATIC-CANCER; SOFT-TISSUE SARCOMA; HUMAN COLON-CANCER; ANTI-CEA ANTIBODY; FUS-ERG FUSION; EWINGS-SARCOMA; PDOX MODEL; NUDE-MICE; COMBINATION;
D O I
10.1002/jcb.27183
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pleomorphic liposarcoma (PLPS) is a recalcitrant soft-tissue sarcoma (STS) subtype in need of transformative therapy. We have previously established a patient-derived orthotopic xenograft (PDOX) model, of PLPS with PDGFRA amplification, using surgical orthotopic implantation. In the current study, the PLPS PDOX model was randomized into 3 groups of 7 mice each: untreated control; doxorubicin (DOX)-treated; and treated with Salmonella typhimurium A1-R (S. typhimurium A1-R) expressing green fluorescent protein (GFP). Tumor volume and body weight were monitored during the treatment period. The PLPS PDOX was resistant to DOX. In contrast, the PLPS PDOX was highly sensitive to S. typhimurium A1-R. There was no significant body-weight loss among these 3 groups. Fluorescence imaging demonstrated that S. typhimurium A1-R-GFP was very effective to target the PLPS PDOX tumor. The current study demonstrates that a PLPS PDOX, resistant to first-line therapy DOX, was highly sensitive to tumor targeting S. typhimurium A1-R.
引用
收藏
页码:7827 / 7833
页数:7
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Kiyuna T, TISSUE CELL