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

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.

• Authors: 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
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 119 Issue 9 Pg. 7827-7833 (09 2018) ISSN: 1097-4644 [Electronic] United States
• PMID: 29932244 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Green Fluorescent Proteins
• Doxorubicin
• Receptor, Platelet-Derived Growth Factor alpha

Topics

• Aged
• Animals
• Body Weight
• Combined Modality Therapy
• Doxorubicin (administration & dosage, pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Gene Amplification
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Liposarcoma (drug therapy, genetics)
• Male
• Mice
• Random Allocation
• Receptor, Platelet-Derived Growth Factor alpha (genetics)
• Salmonella typhimurium (genetics, physiology)
• Sarcoma (drug therapy, genetics)
• Treatment Outcome
• Xenograft Model Antitumor Assays