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

Tasuku Kiyuna, Yasunori Tome, Takashi Murakami, Ming Zhao, Kentaro Miyake, Kentaro Igarashi, Kei Kawaguchi, Masuyo Miyake, Hiromichi Oshiro, Takashi Higuchi, Yunfeng Li, Sarah M. Dry, Scott D. Nelson, Tara A. Russell, Mark A. Eckardt, Arun S. Singh, Fuminori Kanaya, Fritz C. Eilber, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7827-7833
Number of pages7
JournalJournal of Cellular Biochemistry
Volume119
Issue number9
DOIs
Publication statusPublished - 2018 Sep
Externally publishedYes

Keywords

  • PDGFRA amplification
  • Salmonella typhimurium A1-R
  • green fluorescent protein
  • patient-derived orthotopic xenograft
  • pleomorphic liposarcoma
  • soft-tissue sarcoma
  • tumor targeting

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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